A bilateral series involving basic hypergeometric functions

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替罗非班在急性进展性脑梗死中应用

现代医学Modern Medical Journal2020，Aug ；48（8）：966-970［收稿日期］2020-03-23［修回日期］2020-08-11［作者简介］尹其舵（1982－），男，安徽巢湖人，主治医师。

E -mail ：Yqd19820815@163．com［通信作者］吴清阳E -mail ：qingyangwumd@163．com［引文格式］尹其舵，李正侠，耿万杰，等．替罗非班在急性进展性脑梗死中应用［J ］．现代医学，2020，48（8）：966-970．·论著·替罗非班在急性进展性脑梗死中应用尹其舵1，李正侠1，耿万杰1，吴清阳2（1．安徽省阜阳市太和县人民医院神经内科，安徽阜阳236600；2．南京医科大学附属无锡市人民医院影像科，江苏无锡214023）［摘要］目的：探讨替罗非班联合阿司匹林、氯吡格雷对急性进展性脑梗死患者的临床疗效、生活质量ADL 评分、神经功能缺损NIHSS 评分的影响。

方法：前瞻性分析90例急性进展性脑梗死患者，随机分为观察组和对照组，各45例。

对照组给予服用阿司匹林、氯吡格雷治疗，观察组在经替罗非班联合治疗（24 72）h 后贯续服用阿司匹林及氯吡格雷。

比较2组患者治疗后临床疗效、NIHSS 评分（24h 、72h 、7d 及14d ）、ADL 评分及不良反应发生率。

结果：观察组总有效率为88．99%，高于对照组的71．11%（P ＜0．05）；观察组治疗后NIHSS 评分低于对照组，且观察组治疗后与治疗前ADL 评分差值高于对照组（P ＜0．05）；不良反应发生率：观察组为13．85%，对照组为7．69%（P ＞0．05）。

结论：替罗非班联合阿司匹林、氯吡格雷能有效地改善急性进展性脑梗死患者脑组织血流，提高患者生活质量，改善神经功能，安全性较好。

［关键词］急性进展性脑梗死；替罗非班；NIHSS 评分；生活质量［中图分类号］Ｒ743．3［文献标识码］A［文章编号］1671-7562（2020）08-0966-05doi ：10．3969/j．issn．1671-7562．2020．08．006Effect of tirofiban in patients with acute cerebral infarctionYIN Qiduo 1，LI Zhengxia 1，GENG Wanjie 1，WU Qingyang 2（1．Department of Neurology ，Taihe County People ＇s Hospital ，Fuyang 236600，China ；2．Department of Ｒadiology ，the Affiliated Wuxi People ＇s Hospital of Nanjing Medical University ，Wuxi 214023，China ）［Abstract ］Objective ：To study the clinical efficacy of tirofiban combined with aspirin and clopidogrel on scores ofDaily Living Ability Scale （ADL ）and National Institute of Health Stroke Scale （NIHSS ）in patients with acute pro-gressive cerebral infarction．Methods ：90patients with acute progressive cerebral infarction admitted to our hospi-tal from July 2018to July 2019were randomly divided into observation group and control group （45cases ）．The control group was treated with aspirin and clopidogrel ，on top of which the observation group was given tirofiban．The clinical efficacy ，ADL ，NIHSS and adverse reactions between the two groups were statistically analyzed．Ｒesults ：The total effective rate was 88．89%in the observation group ，71．11%in the control group （P ＜0．05）．In the observation group ，the NIHSS were lower than those during the time of 24h ，72h ，7d and 14d ，respectively （P ＜0．05）and meanwhile ，the differentials of ADL between post treatment and prior treatment were high than those in the control group （P ＜0．05）．The incidence of adverse reactions was 13．85%in the observation group ，7．69%in the control group （P ＞0．05）．Conclusion ：Tirofiban combined with aspirin and clopidogrel has a cura-tive effect in acute progressive cerebral infarction ，improving the brain microcirculation blood flow and nerve func-tion ，enhancing life quality of patients ，and ensuring the safety of the therapy．［Key words ］acute progressive stroke ；tirofiban ；score of NIHSS ；quality of life·669·急性脑梗死是临床常见的一种脑血管疾病，病理生理学基础为脑血供突然中断，可导致脑组织坏死，神经元细胞、星形胶质细胞、胶质细胞不同程度损伤，是出现致残、致死的严重脑血管疾病之一。

1994 Optimal use of the SCE-UA global optimization method for calibrating watershed models

Qingyun Duan a, Soroosh Sorooshian *'b, Vijai K. Gupta b
aNWS/NOAA, 1325 East West Highway, Silver Spring, MD 20910, USA bDepartment of Hydrology and Water Resources, The University of Arizona, Tucson, AZ 85721, USA
Table 1 Summary of the five major characteristics complicating the optimization problem in CRR model calibration 1. 2. 3. 4. 5. Regions of attraction Minor local optima Roughness Sensitivity Shape More than one main convergence region Many small 'pits' in each region Rough response surface with discontinuous derivatives Poor and varying sensitivity of response surface in region of optimum and non-linear parameter interaction Non-convex response surface with long curved ridges
* Corresponding author. 0022-1694/94/$07.00 © 1994 - Elsevier Science B.V. All rights reserved SSDI 0022-1694(94)02467-P

【精品】翻译综合

一个抑制肿瘤的连续模型-------艾丽斯H伯杰，阿尔弗雷德G. Knudson 与皮埃尔保罗潘多尔菲今年，也就是2011 年，标志着视网膜母细胞瘤的统计分析的第四十周年，首次提供了证据表明，肿瘤的发生，可以由两个突变发起。

这项工作提供了“二次打击”的假说，为解释隐性抑癌基因（TSGs）在显性遗传的癌症易感性综合征中的作用奠定了基础。

然而，四十年后，我们已经知道，即使是部分失活的肿瘤抑制基因也可以致使肿瘤的发生。

在这里，我们分析这方面的证据，并提出了一个关于肿瘤抑制基因功能的连续模型来全方位的解释肿瘤抑制基因在癌症过程中的突变。

虽然在1900 年之前癌症的遗传倾向已经被人认知，但是，是在19 世纪曾一度被忽视的孟德尔的遗传规律被重新发现之后，癌症的遗传倾向才更趋于合理化。

到那时，人们也知道，肿瘤细胞中的染色体模式是不正常的。

接下来对癌症遗传学的理解做出贡献的人是波威利，他提出，一些染色体可能刺激细胞分裂，其他的一些染色体 a 可能会抑制细胞分裂，但他的想法长期被忽视。

现在我们知道，这两种类型的基因，都是存在的。

在这次研究中，我们总结了后一种类型基因的研究历史，抑癌基因（TSGs），以及能够支持完全和部分失活的肿瘤抑制基因在癌症的发病中的作用的证据。

我们将抑制肿瘤的连续模型与经典的“二次打击”假说相结合，用来说明肿瘤抑制基因微妙的剂量效应，同时我们也讨论的“二次打击”假说的例外，如“专性的单倍剂量不足”，指出部分损失的抑癌基因比完全损失的更具致癌性。

这个连续模型突出了微妙的调控肿瘤抑制基因表达或活动的重要性，如微RNA（miRNA）的监管和调控。

最后，我们讨论了这种模式在┲⒌恼锒虾椭瘟乒讨械挠跋臁！岸未蚧鳌奔偎?第一个能够表明基因的异常可以导致癌症的发生的证据源自1960 年费城慢性粒细胞白血病细胞的染色体的发现。

后来，在1973 年，人们发现这个染色体是是第9 号和第22 号染色体异位的结果，并在1977 年，在急性早幼粒细胞白血病患者中第15 号和第17 号染色体易位被识别出来。

Spike-and-Wave Oscillations Based on the Properties of

Spike-and-Wave Oscillations Based on the Properties of GABABReceptorsAlain DestexheNeurophysiology Laboratory,Department of Physiology,Laval University,Que´bec G1K7P4,CanadaNeocortical and thalamic neurons are involved in the genesis ofgeneralized spike-and-wave(SW)epileptic seizures.The cellu-lar mechanism of SW involves complex interactions between intrinsic neuronalﬁring properties and multiple types of synap-tic receptors,but because of the complexity of these interac-tions the exact details of this mechanism are unclear.In this paper these types of interactions were investigated by using biophysical models of thalamic and cortical neurons.It is shownﬁrst that,because of the particular activation properties of GABABreceptor-mediated responses,simulatedﬁeld poten-tials can display SW waveforms if cortical pyramidal cells and interneurons generate prolonged discharges in synchrony, without any other assumptions.Here the“spike”component coincided with the synchronousﬁring,whereas the“wave”component was generated mostly by slow GABAB-mediated Kϩcurrents.Second,the model suggests that intact thalamic circuits can be forced into aϳ3Hz oscillatory mode by corti-cothalamic feedback.Here again,this property was attributableto the characteristics of GABAB-mediated inhibition.Third,in the thalamocortical system this property can lead to general-izedϳ3Hz oscillations with SWﬁeld potentials.The oscillation consisted of a synchronous prolongedﬁring in all cell types, interleaved with aϳ300msec period of neuronal silence,sim-ilar to experimental observations during SW seizures.This model suggests that SW oscillations can arise from thalamo-cortical loops in which the corticothalamic feedback indirectlyevokes GABAB-mediated inhibition in the thalamus.This mech-anism is shown to be consistent with a number of different experimental models,and experiments are suggested to test its consistency.Key words:computational models;thalamus;cerebral cortex; epilepsy;absence;intrinsic properties;low-threshold spikes; spindle oscillations;thalamocorticalGeneralized spike-and-wave(SW)patterns characterize the hu-man electroencephalogram during several types of epilepsy as well as in animal models of absence seizures.Initially suggested by Jasper and Kershman(1941),the possible involvement of the thalamus in SW seizures was shown by recordings of thalamic nuclei in humans during absence attacks(Williams,1953;Prevett et al.,1995).An important role for the thalamus also is supported by electrophysiological recordings in experimental models of SW seizures,which show that cortical and thalamic cellsﬁre pro-longed discharges in phase with the“spike”component,whereas the“wave”is characterized by a silence in all cell types(Pollen, 1964;Steriade,1974;Avoli et al.,1983;McLachlan et al.,1984; Buzsa´ki et al.,1990;Inoue et al.,1993).Electrophysiological recordings also indicate that spindle oscillations,which are gen-erated by thalamic circuits(Steriade et al.,1990,1993),can be transformed gradually into SW discharges,and all manipulations that promote or antagonize spindles have the same effect on SW (Kostopoulos et al.,1981a,b;McLachlan et al.,1984).Finally,it has been demonstrated that SW patterns disappear after thalamic lesions or after inactivation of the thalamus(Pellegrini et al., 1979;Avoli and Gloor,1981;Vergnes and Marescaux,1992).A series of pharmacological results suggests that GABAB re-ceptors play a critical role in the genesis of SW discharges in rats, because GABA B agonists exacerbate seizures whereas GABA B antagonists suppress them(Hosford et al.,1992;Snead,1992;Puigcerver et al.,1996;Smith and Fisher,1996).The anti-absence drug clonazepam seems to act by diminishing GABA B-mediated IPSPs in thalamocortical(TC)cells,reducing their tendency to burst in synchrony(Huguenard and Prince,1994a;Gibbs et al., 1996).In ferret thalamic slices,spindle oscillations can be trans-formed into slowerϳ3Hz oscillations after blocking GABA A receptors,and,like SW,these oscillations are suppressed by GABA B receptor antagonists(von Krosigk et al.,1993).These experiments could be replicated by computational models of thalamic circuits(Destexhe and Sejnowski,1995;Destexhe et al., 1996a;Golomb et al.,1996).Although these results could suggest a thalamic origin of SW seizures involving GABA B-mediated mechanisms,clear evidence suggests a determinant role for the cortex:thalamic injections of high doses of GABA A antagonists such as penicillin(Ralston and Ajmone-Marsan,1956;Gloor et al.,1977)or bicuculline(Steriade and Contreras,1998)led to3–4Hz oscillations,with no sign of SW discharge.On the other hand,injection of the same drugs to the cortex,with no change in the thalamus,resulted in seizure activity with SW patterns(Gloor et al.,1977;Steriade and Con-treras,1998).These experiments show that both cortical and thalamic neu-rons are necessary to generate SW rhythms and that both GABA A and GABA B receptors are actively involved,but the exact mechanisms are unclear.In this paper a thalamocortical loop mechanism for the genesis of SW oscillatory patterns was investigated by the use of computational models that were based on the complex intrinsicﬁring properties of thalamic and cortical neurons(see Llina´s,1988)and the properties particular to each receptor type(Destexhe et al.,1998b).Received June15,1998;revised Aug.13,1998;accepted Aug.17,1998.This research was supported by the Medical Research Council of Canada(MT-13724).We thank D.Contreras and N.Kopell for comments on this manuscript.Correspondence should be addressed to Dr.Alain Destexhe at the above address.Copyright©1998Society for Neuroscience0270-6474/98/189099-13$05.00/0The Journal of Neuroscience,November1,1998,18(21):9099–9111MATERIALS AND METHODSAll models that are shown here were based on biophysical representa-tions of the ionic mechanisms underlying synaptic currents,ﬁeld poten-tial generation,intrinsic ﬁring properties,and network behavior.The modeling methods that were used to simulate these various aspects are described successively.Synaptic currents.Postsynaptic currents mediated by glutamate AMPA and NMDA receptors as well as by GABAergic GABA A and GABA B receptors were simulated by kinetic models of postsynaptic receptors (Destexhe et al.,1994,1998b).When a spike occurred in the presynaptic cell,a brief pulse of transmitter concentration (0.5m M during 0.3msec)was simulated in the synaptic cleft,and binding of the transmitter to postsynaptic receptors occurred according to simple open/closed kinet-ics,leading to a transient increase of the postsynaptic current described by the following equation (Destexhe et al.,1994):I syn ϭg៮syn m ͑V ϪE syn ͒and (1)dmdtϭ␣͓T ͔͑1Ϫm ͒Ϫ␤m ,(2)where I syn is the postsynaptic current,៮g syn is the maximal conductance,m is the fraction of open receptors,E syn is the reversal potential,[T ]is the transmitter concentration in the cleft,and ␣and ␤are forward and backward binding rate constants of T to open the receptors.This scheme was used to simulate AMPA,NMDA,and GABA A types of receptors,with the following parameters:E syn ϭ0mV,␣ϭ0.94ϫ106M Ϫ1s Ϫ1,␤ϭ180s Ϫ1for AMPA receptors;E syn ϭ0mV,␣ϭ11ϫ104M Ϫ1s Ϫ1,␤ϭ6.6s Ϫ1for NMDA receptors;and E syn ϭϪ80mV,␣ϭ20ϫ106M Ϫ1s Ϫ1,␤ϭ160s Ϫ1for GABA A receptors.These parameters were obtained by ﬁtting the model to postsynaptic currents recorded experi-mentally (see Destexhe et al.,1998b).In addition,NMDA receptors had a voltage-dependent term corresponding to an extracellular Mg 2ϩcon-centration of 2m M [Jahr and Stevens (1990);see Destexhe et al.(1998b)for the details of implementation].The modeling of slow GABA B receptor-mediated inhibition required a more complex scheme to capture the nonlinear properties of this type of interaction (Destexhe and Sejnowski,1995).The activation properties of GABA B receptors were based on the following steps:(1)the binding of GABA on the GABA B receptor,leading to the activated receptor;(2)the activated GABA B receptor catalyzes the activation of G-proteins in the intracellular side;(3)the binding of activated G-proteins to open K ϩchannels.These steps are described by the following equations:I GABA B ϭg៮GABA B s ns n ϩK D͑V ϪE K ͒,(3)drdtϭK 1͓T ͔͑1Ϫr ͒ϪK 2r ,and (4)dsdtϭK 3r ϪK 4s ,(5)where [T ]is the GABA concentration in the synaptic cleft,r is the fraction of GABA B receptors in the activated form,s is the normalized G-protein concentration in activated form,៮g GABA B is the maximal postsynaptic conductance of K ϩchannels,K D is the dissociation constant of G-protein binding on K ϩchannels,V is the postsynaptic membrane potential,and E K is the equilibrium potential for K ϩ.The ﬁtting of this model to experimental GABA B responses led to the following values of parameters (Destexhe et al.,1998b):K D ϭ100,K 1ϭ9ϫ104M Ϫ1s Ϫ1,K 2ϭ1.2s Ϫ1,K 3ϭ180s Ϫ1,and K 4ϭ34s Ϫ1,with n ϭ4binding sites.Field potentials.Extracellular ﬁeld potentials were calculated from postsynaptic currents in single-compartment models according to the model of Nunez (1981):V ext ϭR e 4␲͸jI j r j,(6)where V ext is the electrical potential at a given extracellular site,R e ϭ230⍀cm is the extracellular resistivity,I j is the postsynaptic current,and r j is the distance between the site of generation of I j and the extracellular site.Field potentials were calculated from a single cell receiving 200sim-ulated synapses (100excitatory synapses had AMPA and NMDA recep-tor types,and 100inhibitory synapses had GABA A and GABA B recep-tors;see the scheme in Fig.1B ).In this case,trains of presynaptic action potentials were generated individually for each synapse.To avoid possi-ble artifactual effects because of the coincident timing of action potentials at different synapses,a random time jitter of Ϯ1msec was included in the timing of each presynaptic action potential.Intrinsic currents.Intrinsic voltage-dependent or calcium-dependent currents were modeled by kinetic models of the Hodgkin and Huxley (1952)type.These intrinsic membrane currents were described by the following generic equation:I int ϭg៮int m N h M ͑V ϪE int ͒,(7)dmdtϭ␣m ͑1Ϫm ͒Ϫ␤m m ,and (8)dhdtϭ␣h ͑1Ϫh ͒Ϫ␤h h ,(9)where I int is the intrinsic membrane current,៮g int is the maximal conduc-tance,and E int is the reversal potential.The gating properties of the current were dependent on N activation gates and M inactivation gates,with m and h representing the fraction of gates in open form,and with respective rate constants ␣m ,␤m ,␣h ,and ␤h .Rate constants were dependent on either membrane voltage (V )or intracellular calcium concentration.Thalamocortical work models were based on single-compartment representations of thalamic and cortical neurons.The thalamocortical network was simulated with four cell types:cortical pyramidal cells (PY),cortical interneurons (IN),thalamic reticular cells (RE),and thalamocortical (TC)cells.Cortical cells represent layer VI of the cerebral cortex,in which PY cells constitute the major source of corticothalamic ﬁbers.Because corticothalamic PY cells receive a signif-icant proportion of their excitatory synapses from ascending thalamic axons (Hersch and White,1981;White and Hersch,1982),these cells mediate a monosynaptic excitatory feedback loop (thalamus–cortex–thalamus)that has been modeled here.Each layer of cells has been arranged in one dimension (connectivity is schematized in Fig.4A ).This one-dimensional network model with four cell types is a greatly simpli-ﬁed representation of the multilayered structure of the thalamocortical system,but no additional complexity was required.The cellular models had intrinsic and synaptic currents described by the membrane equation:C m V˙i ϭϪg L ͑V i ϪE L ͒Ϫ͸jI int jiϪ͸kI syn ki ,(10)where V i is the membrane potential,C m ϭ1␮F /cm 2is the speciﬁc capacity of the membrane,g L is the leakage conductance,and E L is the leakage reversal potential.Intrinsic and synaptic currents are representedby I int ji and I syn ki,respectively.The synaptic currents I syn ki ,from presynaptic cell k to postsynaptic cell i ,were simulated by activating a short pulse of transmitter when cell k ﬁred an action potential (see above).The receptor types present in synaptic connections between cells depended on the cell type.All exci-tatory connections (TC 3RE,TC 3IN,TC 3PY,PY 3PY,PY 3IN,PY 3RE,PY 3TC)were mediated by AMPA receptors;some inhibitory connections (RE 3TC,IN 3PY)were mediated by a mixture of GABA A and GABA B receptors,whereas intra-RE connections were mediated by GABA A receptors.Simulations also were performed with NMDA recep-tors added to all excitatory connections (with maximal conductance set to 25%of that of AMPA),and no appreciable difference was observed.They therefore were not included in the present ﬁgures.The total synaptic conductance on each neuron was the same for cells of the same type and was expressed as the sum over all individual synaptic conduc-tances of the same connection type.The total conductances correspond-ing to the reference state,displaying spindle oscillations,were 0.2␮S (AMPA,TC 3RE),0.2␮S (GABA A ,RE 3RE),0.02␮S (GABA A ,RE 3TC),0.04␮S (GABA B ,RE 3TC),0.6␮S (AMPA,PY 3PY),0.2␮S (AMPA,PY 3IN),0.15␮S (GABA A ,IN 3PY),0.03␮S (GABA B ,IN 3PY),1.2␮S (AMPA,PY 3RE),0.01␮S (AMPA,PY 3TC),1.2␮S (AMPA,TC 3PY),and 0.4␮S (AMPA,TC 3IN).The connectivity between thalamic and cortical layers was topograph-ic:within the thalamus and within cortex,each axon contacted the 11nearest neighbors to the presynaptic cell.The axonal divergence was of 21cells for projections between thalamus and cortex.The connection9100J.Neurosci.,November 1,1998,18(21):9099–9111Destexhe •GABA B -Based Mechanism for Spike and Wavetopology,values of synaptic conductances,and robustness of the network were described in detail in a previous study(Destexhe et al.,1998a). All intrinsic membrane currents I int ji were described by a variant of the Hodgkin and Huxley(1952)model(Eqs.7–9).All cell types had Naϩand Kϩcurrents for generating action potentials,for which the kinetics was taken from Traub and Miles(1991).Additional currents conferred to each cell type the most salient features of its intrinsicﬁring patterns. Thalamic cells produced bursts of action potentials because of the pres-ence of a T-current(see inset in Fig.3A).In TC cells,in addition to I T, the presence of I h conferred oscillatory properties.The upregulation of I h by intracellular Ca2ϩled to waxing and waning properties of these oscillations,as detailed in previous models(Destexhe et al.,1993,1996a, 1998a).In RE cells the T-current was of slower kinetics,as modeled previously(Destexhe et al.,1996b).Models for cortical cells were kept as simple as possible to reproduce their repetitiveﬁring properties(see inset in Fig.4A).IN cells contained no other current than was necessary for action potentials,producing similarﬁring patterns to“fast-spiking”cells (Connors and Gutnick,1990).PY cells had one additional slow voltage-dependent Kϩcurrent(I M)generating adapting trains of action poten-tials,similar to“regular-spiking”pyramidal cells(Connors and Gutnick, 1990).The conductance values and the activation properties of all in-trinsic membrane currents were identical to a previous study(Destexhe et al.,1998a).Field potentials were calculated from network simulations.In this case only cortical pyramidal cells were considered and were arranged equi-distantly in one dimension(intercellular distance of20␮m).Thenﬁeld potentials at a given extracellular site were calculated from postsynaptic currents:V extϭR e4␲͸i,k I syn ki r i,(11)where r i is the distance between each PY cell and the extracellular site. In some cases the contribution of the voltage-dependent current I M in ﬁeld potentials was evaluated according to the relation:V extϭR e4␲͸i͑I M iϩ¥k I syn ki͒r i,(12)where I M i is the voltage-dependent Kϩcurrent responsible for adaptation of repetitiveﬁring in the i th PY cells.All models were simulated by using NEURON(Hines and Carnevale, 1997)and were run on a Sparc-20workstation(Sun Microsystems, Mountain View,CA).RESULTSThe mechanism underlying a slow oscillation similar to SW is explained in three steps:(1)the nonlinear activation properties of GABA B responses can lead to the generation of SW waveforms in ﬁeld potentials;(2)intact thalamic circuits can be forced into a ϳ3Hz oscillation by corticothalamic feedback;(3)the combina-tion of these two factors can generateϳ3Hz oscillations with SW ﬁeld potentials in thalamocortical networks.These points are considered successively.The nonlinear activation properties ofGABABresponsesA property consistently observed for GABAB responses is that they require high stimulus intensities to be evoked,as shown in hippocampal(Dutar and Nicoll,1988;Davies et al.,1990)and thalamic slices(Kim et al.,1997).This property can be repro-duced under certain nonlinearity assumptions in the G-protein transduction mechanisms evoked by GABA B receptors;assuming that the binding of four G-proteins is required to activate Kϩchannels is enough to provide a nonlinear stimulus dependence similar to GABA B responses(Destexhe and Sejnowski,1995). The multiplicity of binding sites of G-proteins is indeed in agree-ment with the tetrameric structure of Kϩchannels(Hille,1992)and the cooperativity evidenced in the activation of GABA B responses(Sodickson and Bean,1996).The nonlinear stimulus dependence in the model of GABA B currents is illustrated in Figure1A.An isolated presynaptic spike could not evoke detectable GABA B current(Fig.1A1),in agree-ment with the absence of GABA B-mediated miniature events (Otis and Mody,1992;Thompson and Gahwiler,1992;Thomp-son,1994).However,a burst of5–10high-frequency spikes is a very powerful means of evoking GABA B responses(Fig.1A2). The latter feature is consistent with the observation that GABA B responses appear only under high-intensity stimulus conditions (Dutar and Nicoll,1988;Davies et al.,1990)and the evidence that bursts of high-frequency action potentials are an ideal presynaptic signal to evoke GABA B currents(Huguenard and Prince,1994b; Kim et al.,1997).In the model this property is obtained from the fact that a sufﬁcient level of G-proteins must be accumulated to evoke signiﬁcant Kϩcurrent.Possible role of GABAB-mediated currents in generating spike-and-waveﬁeld potentialsThe possible role of the particular activation properties of GABA B currents in generating SW patterns was investigated by simulatingﬁeld potentials from the postsynaptic currents gener-ated by100excitatory synapses(AMPA and NMDA receptors) and100inhibitory synapses(GABA A and GABA B receptors;see scheme in Fig.1B and Materials and Methods).With presynaptic trains consisting of single spikes,the voltage showed mixed EPSP/ IPSP sequences,and theﬁeld potential was dominated by nega-tive deﬂections(Fig.1C1).By contrast,bursts of high-frequency presynaptic spikes produced mixed EPSP/IPSPs,followed by large GABA B-mediated IPSPs in the cell(Fig.1C2).In this case the fast EPSP/IPSPs generated spikyﬁeld potentials,followed by a slow positive wave caused by GABA B currents.This simple simulation therefore shows that,if excitatory and inhibitory cells generate high-frequency discharges in synchrony and if GABA B receptors are present,sufﬁcient conditions are brought together to generateﬁeld potential waveforms consisting of interleaved spikes and waves.The effect of various parameters on the morphology of simu-lated SW complexes was investigated in Figure2A.When excita-tory synapses discharged earlier than inhibitory synapses(2and5 msec latency),the spike component was enhanced.Spike and wave components also were inﬂuenced by synaptic conductances. AMPA and NMDA conductances affected primarily the negative peak of the spike component(Fig.2B,top trace),whereas the positive peak was inﬂuenced mostly by GABA A conductances (Fig.2B,middle trace).GABA B conductances had few effects on the spike component but mostly affected the wave(Fig.2B, bottom trace).Intact thalamic circuits can be forced intoϳ3Hz oscillations because of GABAB-mediated currentsTo investigate how this type ofﬁeld potentials can be generated by the thalamocortical system,weﬁrst turn to the behavior of thalamic circuits,and,more particularly,we turn to how they are controlled by the cortex.An important behavior of thalamic networks is their propensity to generate oscillations such as the 7–14Hz spindle oscillations(Steriade et al.,1993;von Krosigk et al.,1993).Although these oscillations are generated in the thal-amus,the neocortex has been shown to trigger them powerfully (Steriade et al.,1972;Roy et al.,1984;Contreras and Steriade, 1996),and the corticothalamic feedback has been shown to exert a decisive control over thalamic oscillations(Contreras et al.,1996).Destexhe•GABA B-Based Mechanism for Spike and Wave J.Neurosci.,November1,1998,18(21):9099–91119101In computational models,reproducing this cortical control re-quired more powerful corticothalamic EPSPs on RE cells as compared with TC cells (Destexhe et al.,1998a).In these condi-tions the excitation of corticothalamic cells led to mixed EPSPs and IPSPs in TC cells in which the IPSP was dominant,consistent with experimental observations (Burke and Sefton,1966;De-sche ˆnes and Hu,1990).If cortical EPSPs and IPSPs from RE cells were of comparable conductance,cortical feedback could not evoke oscillations in the thalamic circuit because of shunting effects between EPSPs and IPSPs (Destexhe et al.,1998a).The most likely reason for these experimental and modeling evidences for “IPSP dominance”in TC cells is that RE cells are extremely sensitive to cortical EPSPs (Contreras et al.,1993),probably because of a powerful T-current in dendrites (Destexhe et al.,1996b).In addition,cortical synapses contact only the distal dendrites of TC cells (Liu et al.,1995)and probably are attenu-ated for this reason.Taken together,these data suggest that corticothalamic feedback operates mainly by eliciting bursts in RE cells,which in turn evoke powerful IPSPs on TC cells that in large part overwhelm the direct cortical EPSPs.The effect of corticothalamic feedback on the thalamic circuit is depicted in Figure 3A :simulated cortical EPSPs evoked bursts in RE cells (Fig.3B,arrow ),which recruited TC cells via IPSPs,and triggered a ϳ10Hz oscillation in the circuit.During the oscilla-tion TC cells rebounded after GABA A -mediated IPSPs once every two cycles,and RE cells discharged only a few spikes,evoking GABA A -mediated IPSPs in TC cells with no signiﬁcant GABA B currents (Fig.3B ).These features are typical of spindle oscillations (Steriade et al.,1993;von Krosigk et al.,1993).Repetitive stimulation of the same thalamic circuit at 3Hz with larger intensity (14spikes every 333msec)entrained the system into a different type of oscillatory behavior (Fig.3C ).All cell types were entrained to discharge in synchrony at ϳ3Hz.On the other hand,repetitive stimulation at 3Hz with low intensity produced spindle oscillations (Fig.3D )similar to those in Figure 3A .Strong-intensity stimulation at 10Hz led to quiescence in TC cells (Fig.3E )because of sustained GABA B currents,similar to a previous analysis [Lytton et al.(1997),their Fig.12].These simulations indicate that strong corticothalamic feed-back at 3Hz can force thalamic circuits in a different type of oscillation.Cortical EPSPs force RE cells to ﬁre large bursts (Fig.3C,arrows ),fulﬁlling the conditions needed to activate GABA B responses (see Fig.1A ).The consequence is that TC cells were “clamped”at hyperpolarized levels by GABA B IPSPs during ϳ300msec before they could rebound.The nonlinear properties of GABA B responses are therefore responsible for the coexist-ence between two types of oscillations in the same circuit:mild corticothalamic feedback recruits the circuit in ϳ10Hz spindle oscillations,whereas strong feedback at 3Hz could force the intact circuit at the same frequency because of the nonlinear activation properties of intrathalamic GABA Bresponses.Figure 1.Simulation of spike and wave in ﬁeld poten-tials,based on the properties of GABA B receptors.A ,Nonlinear activation properties of GABA B receptors.If the binding of four G-proteins is needed to activate the K ϩchannels associated with GABA B receptors,then GABA B -mediated inhibitory responses are dependent on the number of presynaptic action potentials.A1,With a single presynaptic spike no GABA B response was detectable.A2,A burst of presynaptic spikes led to sufﬁcient accumulation of G-proteins to generate the slow IPSP.B ,Scheme for the model of local ﬁeld po-tentials.Excitatory and inhibitory presynaptic trains of action potentials were generated to stimulate various postsynaptic receptor types (AMPA,NMDA,GABA A ,and GABA B ).One hundred synapses of each type were simulated,and the synaptic currents were integrated into a single compartment model and used to calculate the extracellular ﬁeld potential at a distance of 5␮m from the simulated neuron.C ,Field potentials gener-ated by single spikes and bursts of spikes.With single spikes (C1)the mixed EPSP/IPSP sequence led to neg-ative deﬂections in the ﬁeld potentials.With bursts of spikes (C2)the fast spiky components alternate with slow positive deﬂections,similar to spike-and-wave pat-terns.These slow positive waves are attributable to the activation of GABA B -mediated currents (arrows ).Con-ductance values are 4,1,1.5,and 4nS for individual AMPA,NMDA,GABA A ,and GABA B synapses,respectively.9102J.Neurosci.,November 1,1998,18(21):9099–9111Destexhe •GABA B -Based Mechanism for Spike and WaveSuppression of intrathalamic GABA A -mediated inhibition does not generate spike and waveThe impact of this mechanism at the network level was explored using a thalamocortical network consisting in different layers of cortical and thalamic cells (see details in Materials and Methods).The network included thalamic TC and RE cells and a simpliﬁed representation of the deep layers of the cortex with pyramidal cells and interneurons (Fig.4A ).In control conditions (Fig.4B )the network generated synchronized spindle oscillations with cellular discharges in phase between in all cell types,as observed experimentally (Contreras and Steriade,1996).TC cells dis-charged on average once every two cycles after GABA A -mediated IPSPs,whereas all other cell types discharged approx-imately at every cycle at ϳ10Hz,consistent with the typical features of spindle oscillations observed intracellularly (Steriade et al.,1990;von Krosigk et al.,1993).The simulated ﬁeld poten-tials displayed successive negative deﬂections at ϳ10Hz (Fig.4B ;in agreement with the pattern of ﬁeld potentials during spindle oscillations)(Steriade et al.,1990).Consistent with the analysis of Figure 1C1,this pattern of ﬁeld potentials was generated by the limited discharge in PY cells,which ﬁred approximately one spike per oscillation cycle.When GABA A receptors were suppressed in thalamic cells in this model,with cortical inhibition intact,spindle oscillations were transformed into slower oscillation patterns at 3–5Hz (Fig.4C ).In this case there was an increase in synchrony,as indicated by the TC cells that ﬁred at every cycle of the oscillation.RE cells generated prolonged burst discharges,leading to GABA B -mediated IPSPs in TC cells and,consequently,to a slow oscilla-tion frequency.The ﬁeld potentials consisted of successive neg-ative deﬂections (Fig.4C,bottom )similar to that of spindles.This pattern of ﬁeld potentials was generated by PY cells that dis-charged approximately single spikes at each cycle of the oscilla-tion (similar to Fig.1C1).This simulation therefore suggests that removing intrathalamic GABA A -mediated inhibition affects the oscillation frequency but does not generate SW,because pyrami-dal cells are still under the strict control of cortical fast inhibition.This is in agreement with in vivo injections of bicuculline into the thalamus,which reported slow oscillations with increased tha-lamic synchrony,but no SW patterns in the ﬁeld potentials (Ral-ston and Ajmone-Marsan,1956;Steriade and Contreras,1998).Suppression of intracortical GABA A -mediated inhibition leads to spike and waveOn the other hand,the alteration of GABA A receptors in the cortex had a considerable impact in generating SW.When GABA A -mediated inhibition was reduced in the cortex,with no change in thalamic inhibitory mechanisms,then spindle oscilla-tions transformed into 2–3Hz SW-like discharges (Fig.5).With intracortical fast inhibition decreased by 50%,increased occur-rences of prolonged high-frequency discharges were seen during spindle oscillations (Fig.5A ).In ﬁeld potentials these events tended to generate large-amplitude negative deﬂections,followed by small-amplitude positive waves (Fig.5A,bottom ).With totally suppressed GABA A -mediated inhibition in the cortex,the network generated a slow oscillation at 2–3Hz,with ﬁeld potentials similar to SW (Fig.5B ).Field potentials displayed one or several negative/positive sharp deﬂections,followed by a slowly developing positive wave (Fig.5B,bottom ).During the spike all cells ﬁred prolonged high-frequency discharges in syn-chrony,whereas the wave was coincident with neuronal silence in all cell types.This portrait is typical of experimental recordings of cortical and thalamic cells during SW patterns (Pollen,1964;Steriade,1974;Avoli et al.,1983;McLachlan et al.,1984;Buzsa ´ki et al.,1990;Inoue et al.,1993).Some TC cells stayed hyperpo-larized during the entire oscillation (second TC cell in Fig.5B ),as also was observed experimentally (Steriade and Contreras,1995).A similar oscillation arose if GABA A receptors were suppressed in the entire network (data not shown).These simulations thus indicate that spindles can be trans-formed into an oscillation with ﬁeld potentials displaying SW and that this transformation can occur by the alteration of cortical inhibition with no change in the thalamus,in agreement with SW discharges obtained experimentally by diffuse application of di-luted penicillin onto the cortex (Gloor et al.,1977).The mecha-nism of the ϳ3Hz oscillation of this model depends on a thalamocortical loop in which both cortex and thalamus are nec-essary,but none of them generates the 3Hz rhythmicity alone (see next sectionbelow).Figure 2.Factors determining the morphology of simulated spike-and-wave complexes.A ,Effect of a latency between the ﬁring of excitatory and inhibitory synapses.Control ,Simulation is identical to Figure 1C2.If excitatory synapses discharged earlier than inhibitory synapses (2and 5msec latency),the spike component was enhanced.B ,Effect of synaptic receptor types.The 5msec latency simulation from A was repeated here with different values for synaptic conductances.A 90%reduction of AMPA/NMDA conductances (top trace ),GABA A conductances (middle trace ),or GABA B conductances (bottom trace )affected the morphology of the SW patterns.The right column shows the last complexes at higher resolution.Destexhe •GABA B -Based Mechanism for Spike and WaveJ.Neurosci.,November 1,1998,18(21):9099–91119103。

大肠杆菌高产L丙氨酸

APPLIED GENETICS AND MOLECULAR BIOTECHNOLOGYProduction of L-alanine by metabolically engineered Escherichia coliXueli Zhang&Kaemwich Jantama&J.C.Moore&K.T.Shanmugam&L.O.IngramReceived:23May2007/Revised:13August2007/Accepted:16August2007/Published online:15September2007 #Springer-Verlag2007Abstract Escherichia coli W was genetically engineered to produce L-alanine as the primary fermentation product from sugars by replacing the native D-lactate dehydroge-nase of E.coli SZ194with alanine dehydrogenase from Geobacillus stearothermophilus.As a result,the heterolo-gous alanine dehydrogenase gene was integrated under the regulation of the native D-lactate dehydrogenase(ldhA) promoter.This homologous promoter is growth-regulated and provides high levels of expression during anaerobic fermentation.Strain XZ111accumulated alanine as the primary product during glucose fermentation.The methyl-glyoxal synthase gene(mgsA)was deleted to eliminate low levels of lactate and improve growth,and the catabolic alanine racemase gene(dadX)was deleted to minimize conversion of L-alanine to D-alanine.In these strains,re-duced nicotinamide adenine dinucleotide oxidation during alanine biosynthesis is obligately linked to adenosine triphosphate production and cell growth.This linkage provided a basis for metabolic evolution where selection for improvements in growth coselected for increased glycolytic flux and alanine production.The resulting strain, XZ132,produced1,279mmol alanine from120g l−1 glucose within48h during batch fermentation in the mineral salts medium.The alanine yield was95%on a weight basis(g g−1glucose)with a chiral purity greater than99.5%L-alanine.Keywords Alanine.Fermentation.E.coli.Evolution. GlycolysisIntroductionWorldwide production of L-alanine has been estimated at 500tons per year(Ikeda2003).In pharmaceutical and veterinary applications,L-alanine is used with other L-amino acids as a pre-and postoperative nutrition therapy(Hols et al.1999).Alanine is also used as a food additive because of its sweet taste(Lee et al.2004).The use of L-alanine is limited in part by the current high cost.L-Alanine is pro-duced commercially by the enzymatic decarboxylation of L-aspartic acid using immobilized cells or cell suspensions of Pseudomonas dacunhae as a biocatalyst with a yield greater than90%(Shibatani et al.1979).The substrate for this enzymatic production process,L-aspartate,is usually pro-duced from fumarate by enzymatic catalysis with aspartate ammonia-lyase.Fumaric acid is produced primarily from petroleum,a nonrenewable feedstock.An efficient fermen-tative process with a renewable feedstock such as glucose offers the potential to reduce L-alanine cost and facilitate a broad expansion of the alanine market into other products.Alanine is a central intermediate(Fig.1)and an essential component of cellular proteins.Most microorganisms produce alanine only for biosynthesis using a glutamate–pyruvate transaminase(Hashimoto and Katsumata1998). Some organisms such as Arthrobacter oxydans(Hashimoto and Katsumata1993;Hashimoto and Katsumata1998; Hashimoto and Katsumata1999),Bacillus sphaericus (Ohashima and Soda1979),and Clostridium sp.P2Appl Microbiol Biotechnol(2007)77:355–366DOI10.1007/s00253-007-1170-yElectronic supplementary material The online version of this article (doi:10.1007/s00253-007-1170-y)contains supplementary material, which is available to authorized users.X.Zhang:J.C.Moore:K.T.Shanmugam:L.O.Ingram(*) Department of Microbiology and Cell Science,University of Florida,Box110700,Gainesville,FL32611,USAe-mail:ingram@K.JantamaDepartment of Chemical Engineering,University of Florida, Gainesville,FL32611,USA(Orlygsson et al.1995)produce alanine from pyruvate and ammonia using an reduced nicotinamide adenine dinucleo-tide (NADH)-linked alanine dehydrogenase (ALD).How-ever,fermentations are slow,and yields from the best natural producers are typically 60%or less because of coproduct formation (Hashimoto and Katsumata 1998;Table 1).Plasmid-borne genes encoding NADH-linked ALD have been tested as an approach to develop improved biocatalysts with varying degrees of success (Table 1).Engineered strains of Zymomonas mobilis CP4expressing the B.sphaericus alaD gene produced low levels of racemic alanine during the anaerobic fermentation of 5%glucose (Uhlenbusch et al.1991).A native chromosomal lactate dehydrogenase gene (ldhA )-deleted strain of Lactococcus lactis containing a mutation in alanine racemase was engineered in a similar fashion and produced 12.6g l −1L -alanine from 1.8%glucose (Hols et al.1999).An Escherichia coli aceF ldhA double mutant containing pTrc99A-alaD plasmid produced 32g l −1racemic alanine in 27h during a two-stage (aerobic and anaerobic)fermentation with a yield of 0.63g alanine g −1glucose (Lee et al.2004).With further gene deletions and process optimization,the racemic alanine titer wasincreasedFig.1Alanine pathway in recombinant E.coli .a Native and recom-binant fermentation pathways.The foreign gene,G.stearothermophilus alaD ,is shown in bold .G.stearothermophilus alaD coding region and transcriptional terminator were integrated into the native ldhA gene under transcriptional control of the ldhA promoter.Solid stars represent deletions of native genes in XZ132.Note that the native biosynthetic route for alanine production is omitted for simplicity.ackA Acetate kinase,adhE alcohol/aldehyde dehydrogenase,alaD alanine dehydro-genase (Geobacillus stearothermophilus XL-65-6),aldA aldehyde dehydrogenase A,aldB aldehyde dehydrogenase B,alr alanine race-mase 1,dadX alanine racemase 2,frd fumarate reductase,gloA glyoxalase I,gloB glyoxalase II,gloC glyoxalase III,ldhA D -lactate dehydrogenase,mdh malate dehydrogenase,mgsA methylglyoxal synthase,pflB pyruvate –formate lyase,ppc phosphoenolpyruvate carboxylase,pta phosphate acetyltransferase.b Coupling of ATP production and growth to NADH oxidation and L -alanine production.Glucose is metabolized to pyruvate,ATP,and NADH.Energy conserved in ATP is utilized for growth and homeostasis,regenerating ADP.NADH is oxidized by alanine formation allowing glycolysis and ATP production to continueT a b l e 1C o m p a r i s o n o f a l a n i n e -p r o d u c i n g s t r a i n sO r g a n i s m s M o d i f i e d p r o p e r t yM e d i a ,s u b s t r a t e a n d p r o c e s s c o n d i t i o n sT i m e (h )A l a n i n e (g l −1)Y i e l d (%)L -A l a n i n ep u r i t y (%)R e f e r e n c e E .c o l i X Z 132I n t e g r a t e d G .s t e a r o t h e r m o p h i l u s a l a D ;Δp f l ,Δa c k A ,Δa d h E ,Δl d h A ,Δm g s A ,Δd a d XM i n e r a l m e d i u m ,b a t c h ,g l u c o s e 120g l −148.0114.095>99T h i s s t u d yA r t h r o b a c t e r o x y d a n s H A P -1M i n e r a l m e d i u m ,t w o -s t a g e f e d -b a t c h ,g l u c o s e 150g l −1120825560.0H a s h i m o t o a n d K a t s u m a t a 1998A .o x y d a n s D A N 75A l a n i n e r a c e m a c e d e f i c i e n tM i n e r a l m e d i u m ,t w o -s t a g e f e d -b a t c h ,g l u c o s e 150g l −1,0.2g l −1D -a l a n i n e120775198H a s h i m o t o a n d K a t s u m a t a 1998E c o l i A L 1(p O B P 1)P l a s m i d w i t h A .o x y d a n s H A P -1a l a D M i n e r a l m e d i u m ,g l u c o s e 20g l −1,l i m i t e d o x y g e n40841N o t r e p o r t e dK a t s u m a t a a n d H a s h i m o t o 1996C o r y n e b a c t e r i u m g l u t a m i c u m A L 107(p O B P 107)P l a s m i d w i t h A .o x y d a n s H A P -1a l a DC o r n s t e e p l i q u o r ,g l u c o s e 200g l −1,4g l −1D L -a l a n i n e ,l i m i t e d o x y g e n 707136>99K a t s u m a t a a n d H a s h i m o t o 1996Z y m o m o n a s m o b i l i s C P 4(p Z Y 73)P l a s m i d w i t h B .s p h a e r i c u s I F O 3525a l a D M i n e r a l s a l t s m e d i u m ,s i m p l e b a t c h ,g l u c o s e 50g l −126816N o t r e p o r t e dU h l e n b u s c h e t a l .1991L a c t o c o c c u s l a c t i s N Z 3950(p N Z 2650)P l a s m i d w i t h B .s p h a e r i c u s I F O 3525a l a D Δl d h AR i c h m e d i u m (M 17),g l u c o s e 18g l −117137085–90H o l s e t a l .1999L .l a c t i s P H 3950(p N Z 2650)P l a s m i d w i t h B .s p h a e r i c u s I F O 3525a l a D Δl d h A ,Δa l rR i c h m e d i u m (M 17),g l u c o s e 18g l −1,0.2g l −1D -a l a n i n e 17N o t k n o w nN o t k n o w n >99H o l s e t a l .1999E .c o l i A L S 887(p T r c 99A -a l a D )P l a s m i d w i t h B .s p h a e r i c u s I F O 3525a l a D Δl d h A ,Δa c e FY e a s t e x t r a c t ,t w o -s t a g e b a t c h ,g l u c o s e 50g l −1,a e r o b i c a i r 1l m i n −1273263N o t r e p o r t e d L e e e t a l .2004E .c o l i A L S 929(p T r c 99A -a l a D )P l a s m i d w i t h B .s p h a e r i c u s I F O 3525a l a D Δp f l ,Δp p s ,Δp o x B ,Δl d h A ,Δa c e E FY e a s t e x t r a c t a n d c a s a m i n o a c i d s ,t w o -s t a g e b a t c h (a e r o b i c c e l l g r o w t h a n d a n a e r o b i c f e r m e n t a t i o n )223486N o t r e p o r t e d S m i t h e t a l .2006E .c o l i A L S 929(p T r c 99A -a l a D )P l a s m i d w i t h B .s p h a e r i c u s I F O 3525a l a D Δp f l ,Δp p s ,Δp o x B ,Δl d h A ,Δa c e E FY e a s t e x t r a c t a n d c a s a m i n o a c i d s ,t w o -s t a g e f e d -b a t c h (a e r o b i c c e l l g r o w t h a n d a n a e r o b i c f e r m e n t a t i o n )4888100N o t r e p o r t e d S m i t h e t a l .2006to88g l−1in a more complex process with yields ap-proaching the theoretical maximum(Smith et al.2006). However,this strain produced only racemic alanine,utilized multicopy plasmids requiring antibiotic selection,and required complex media with a complex multistage fermen-tation process(Smith et al.2006).In this study,we developed novel biocatalysts that pro-duce chirally pure L-alanine in batch fermentations without using plasmid-containing biocatalysts,antibiotics,or com-plex nutrients.The resulting strains are based on a deriva-tive of E.coli W(strain SZ194)that produces D-lactate (Zhou et al.2006b).The ldhA gene in SZ194was replaced with a single,chromosomally integrated copy of the ALD gene from the thermophile,Geobacillus stearothermophilus XL-65-6(formerly B.stearothermophilus;Lai and Ingram 1993).After additional deletions of alanine racemase (dadX)and methylglyoxal synthase(mgsA)and metabolic evolution,the resulting strain produced L-alanine at high titers(over1M)and yields in batch fermentations using the mineral salts medium.Materials and methodsStrains,plasmids,media,and growth conditionsThe strains and plasmids used in this study are listed in Table2.Strain SZ194was previously engineered from a derivative of E.coli W(ATCC9637)and served as a starting point for constructions(Zhou et al.2006b).G. stearothermophilus XL-65-6(Lai and Ingram1993)was used for cloning the ALD gene.During sequencing of chro-mosomal genes,we discovered a20-year-old error in culture labeling.Strain SZ194,the parent used to construct the alanine strains,is a derivative of E.coli W(ATCC9637). Other constructs for ethanol production and lactate produc-tion that have been reported previously as derivatives of E. coli B are now known to be derivates of E.coli W(ATCC 9637).Primers used in this study are listed in Table3.During strain construction,cultures were grown aerobi-cally at30,37,or39°C in Luria broth(10g l−1Difco tryptone,5g l−1Difco yeast extract,and5g l−1NaCl) containing2%(w/v)glucose or5%(w/v)arabinose. Ampicillin(50mg l−1),tetracycline(12.5mg l−1), kanamycin(50mg l−1),or chloramphenicol(40mg l−1) were added as needed.For initial tests of fermentative alanine production,strains were grown without antibiotics at37°C in NBS mineral salts medium(Causey et al.2004) supplemented with100mM ammonia sulfate,1mM betaine,and2%(w/v)glucose.Fermentation experiments (2–12%sugar)were carried out in NBS medium and AM1 medium(Martinez et al.2007).Broth was maintained at pH 7by the automatic addition of5M NH4OH.Genetic methodsStandard methods were used for genomic deoxyribonucleic acid(DNA)extraction(Qiagen,Valencia,CA),polymerase chain reaction(PCR)amplification(Stratagene,La Jolla CA,and Invitrogen,Carlsbad,CA),transformation,plas-mid extration(Qiagen),and restriction endonuclease diges-tion(New England Biolabs,Ipswich,MA).Methods for foreign gene(alaD)integration and for chromosomal gene (mgsA and dadX)deletion are described below.DNA sequencing was provided by the University of Florida Interdisciplinary Center for Biotechnology Research.The Biocyc and Metacyc databases(Karp et al.2005)were instrumental in the design and completion of these studies. Cloning the alanine dehydrogenase gene alaD from G. stearothermophilus XL-65-6and detection of the enzyme activityThe primers for amplifying alaD from G.stearothermophilus XL-65-6were designed based on the alaD sequence of G. stearothermophilus strain10.The forward primers(5′–3′GGAAAAA GGAGGAAAAAGTG ATGAAGATCGG CATT)included the ribosomal-binding region(bold)and the amino terminus(italicized).The reverse primer(5′–3′GAA GGAGTTGATCATTGTTTAACGAGAGAGG)was down-stream from the putative transcriptional terminator region (Table3).ALD was verified in clones using an activity stain (Kuroda et al.1990).E.coli TOP10F′harboring plasmids containing alaD was grown on Luria–Bertani(LB)plates at 37°C,then transferred to a Whatman7.0-cm filter paper. The filter was immersed in10mM potassium phosphate buffer(pH7.2)and incubated for20min at80°C for lysis of the cells and denaturation of the E.coli proteins.The dried filter paper was assayed in a reaction mixture containing50mM L-alanine,50mM Tris–HCl buffer (pH9.0),0.625mM NAD+,0.064mM phenazine metho-sulfate,and0.24mM nitro blue tetrazolium.The cells with ALD appeared as blue spots on the filter.Integration of alaD into E.coli SZ194The alaD gene was integrated into the chromosomal ldhA gene of SZ194.The fragment(Sma I–Kpn I,1.7kb)con-taining a tet gene flanked by two FRT sites was isolated from pLOI2065and cloned into pLOI4211between a unique Bam HI site(Klenow-treated)and Kpn I site to produce plasmid pLOI4213(6.0kb).In this plasmid,transcription of alaD and tet are oriented in the same direction.The Apa I(treated with T4DNA polymerase to produce a blunt end)–Kpn I fragment(2.2kb)containing alaD and tet was isolated from pLOI4213and cloned into pLOI2395Table2 E.coli strains and plasmids used in this studyRelevant characteristics Source or referenceStrainsSZ194plfB frd adhE ackA deletions Zhou et al.2006bXZ103-110SZ194,ldhA::FRT-tet-FRT::This studyG.stearothermophilus alaDXZ111XZ105,ldhA::G.stearothermophilus alaD This studyXZ112XZ111,metabolic evolution in NBS medium with2%glucose This studyXZ113XZ112,metabolic evolution in NBS medium with5%glucose This studyXZ115XZ113,metabolic evolution in NBS medium with8%glucose This studyXZ121XZ115,mgsA deletion This studyXZ123XZ121,metabolic evolution in NBS medium with8%glucose This studyXZ126XZ123,dadX deletion This studyXZ129XZ126,metabolic evolution in NBS medium with8%glucose This studyXZ130XZ129,metabolic evolution in AM1medium with8%glucose This studyXZ131XZ130,metabolic evolution in AM1medium with10%glucose This studyXZ132XZ131,metabolic evolution in AM1medium with12%glucose This studyPlasmidspCR2.1-TOPO bla kan;TOPO TA cloning vector InvitrogenDatsenko and Wanner2000pKD46Blaγβexo(Red recombinase),temperature conditionalpSC101repliconpFT-A Bla flp,temperature conditional pSC101replicon Posfai et al.1997pEL04cat-sacB targeting cassette Lee et al.2001;Thomason et al.2005 pLOI2224kan;R6K conditional integration vector Martinez-Morales et al.1999pLOI2065bla;FRT-tet-FRT cassette Zhou et al.2003bpLOI2395bla;ldhA franked by two Asc I site Zhou et al.2003apLOI3421 1.8kbp SmaI fragment containing aac Wood et al.2005pLOI4151bla cat;cat-sacB cassette This studyalaD integrationThis studypLOI4211bla kan alaD;alaD(PCR)from G.stearothermophilus XL-65-6cloned into pCR2.1-TOPO vectorpLOI4213bla kan;alaD-FRT-tet-FRT Kpn I-Sma I fragment(FRT-tet-FRT)This studyfrom pLOI2065cloned into Kpn I-BamH I(blunted)site of pLOI4211This studypLOI4214bla kan;ldhA’-alaD-FRT-tet-FRT-ldhA”Apa I(blunted)-Kpn I fragment(alaD-FRT-tet-FRT)from pLOI4213cloned into ldhA at Hinc II-Kpn Isites of pLOI2395This studypLOI4215kan;ldhA’-alaD-FRT-tet-FRT-ldhA”Asc I fragment(ldhA’-alaD-FRT-tet-FRT-‘ldhA)from pLOI4214cloned into Asc I sites of pLOI2224mgsA deletionThis studypLOI4228bla kan;yccT’-mgsA-helD’(PCR)from E.coli W clonedinto PCR2.1-TOPO vectorThis studypLOI4229cat-sacB cassette PCR amplified from pLOI4151(Eco RV digested)cloned into mgsA in pLOI4228This studypLOI4230PCR fragment amplified from pLOI4228(using mgsA-1/mgsA-2primers),kinase treated,and self-ligateddadX deletionThis studypLOI4216bla kan;dadA’-dadX-cvrA’(PCR)from E.coli W clonedinto PCR2.1-TOPO vectorpLOI4218cat-sacB cassette PCR amplified from pLOI4151(Eco RV digested)This studycloned into dadX in pLOI4216This studypLOI4220PCR fragment amplified from pLOI4216(using dadX-4/dadX-5primers),kinase treated,and self-ligated(Hinc II to Kpn I sites)to produce pLOI4214(6.5kb).In this plasmid,ldhA ,alaD ,and tet genes are transcribed in the same direction.The Asc I fragment (4.3kb)containing these three genes was isolated from pLOI4214and cloned into the R6K integration vector pLOI2224to produce pLOI4215(6.2kb).Plasmid pLOI4215contains resistance genes for both tetracycline and kanamycin (Fig.2).The Asc I fragment (4.3kb)containing ldhA ,alaD ,and tet genes was isolated from pLOI4215,further cut by Xmn I to eliminate any remaining uncut plasmid DNA,and electroporated into SZ194containing the Red recombinase plasmid pKD46(Datsenko and Wanner 2000).Integrants were selected for tetracycline resistance,confirmed by sensitivity to kanamycin and ampicillin and by PCR analysis using the primers of ldhA and its neighboring genes ydbH and hslJ (Table 3).Deletion of mgsA and dadX genesA modified method for deleting E.coli chromosomal genes was developed using two steps of homologous recom-bination (Thomason et al.2005).With this method,no antibiotic genes or scar sequences remain on the chromo-some after gene deletion.In the first recombination,part of the target gene was replaced by a DNA cassette containing a chloramphenicol resistance gene (cat )and levansucrase gene (sacB ).In the second recombination,the cat –sacBcassette was removed by selection for resistance to sucrose.Cells containing the sacB gene accumulate levan during incubation with sucrose and are killed.Surviving recombi-nants are highly enriched for loss of the cat –sacB cassette.A new cassette was constructed as a template to facilitate gene deletions.The cat –sacB region was amplified from pEL04(Lee et al.2001;Thomason et al.2005)by PCR using the JM catsacB up Nhe I and JM catsacB down Nhe I primers (Table 3),digested with Nhe I,and ligated into the corresponding site in pLOI3421to produced pLOI4151.The cat –sacB cassette was amplified by PCR using pLOI4151as a template with the cat -up2and sacB -down2primers (Eco RV site included in each primer),digested with Eco RV ,and used in subsequent ligations.The mgsA gene and neighboring 500-bp regions (yccT ′–mgsA –helD ′,1,435bp)were amplified using the mgsA -up and mgsA -down primers and cloned into the pCR 2.1-TOPO vector (Invitrogen)to produce plasmid pLOI4228.A 1,000-fold diluted plasmid preparation of this plasmid served as a template for inside-out amplification using the mgsA -1and mgsA -2primers (both within the mgsA gene and facing outward).The resulting 4,958-bp fragment containing the replicon was ligated to the Eco RV-digested cat –sacB cassette from pLOI4151to produce pLOI4229(Fig.3a).This 4,958-bp fragment was also used to construct a second plasmid,pLOI4230(Fig.3b),by phosphorylation and self-ligation.In pLOI4230,the central region of mgsA is deleted (yccT ′–mgsA ′–mgsA ″–helD ′).After digestion of pLOI4229and pLOI4230with Xmn I (within the vector),each served as a template for amplifica-tion using the mgsA -up and mgsA -down primers to produce linear DNA for integration step 1(yccT ′–mgsA ′–cat –sacB –mgsA ″–helD ′)and step II (yccT ′–mgsA ′–mgsA ″–helD ′),respectively.After electroporation of the step 1fragment into XZ115containing pKD46(Red recombinase)and 2h ofTable 3Primers used in this study Primers SequencealaD -forward GGAAAAAGGAGGAAAAAGTGATGAA GATCGGCATTalaD -reverse GAAGGAGTTGATCATTGTTTAACGA GAGAGGldhA -forward AGTACCTGCAACAGGTGAAC ldhA -reverse CAGGCGACGGAATACGTCAT ldhA -up (ydbH )CTGATAACGCAGTTGCTGGA ldhA -down (hslJ )TTCATTAAATCCGCCAGCTTJM catsacB up NheI TTAGCTAGCATGTGACGGAAGATC ACTTCGJM catsacB down NheI CCGCTAGCATCAAAGGGAAAACTGT CCATATcat -up2AGAGAGGATATCTGTGACGGAAGAT CACTTCGsacB -down2AGAGAGGATATCGAATTGATCCGGT GGATGACmgsA -up CAGCTCATCAACCAGGTCAA mgsA -down AAAAGCCGTCACGTTATTGG mgsA -1AGCGTTATCTCGCGGACCGT mgsA -2AAGTGCGAGTCGTCAGTTCC dadX -up AGGCTACTCGCTGACCATTC dadX -down GGTTGTCGGTGACCAGGTAG dadX -4TGGGCTATGAGTTGATGTGC dadX -5CTGTATCGGACGGGTCATCTFig.2Integration vector used for chromosomal insertion of G.stearothermophilus alaD into E.coli ldhA .Sequence encoding the N-terminal and C-terminal regions are designated ldhA ′and ldhA ″,respectivelyincubation at 30°C to allow expression and segregation,recombinants were selected for chloramphenicol (40mg l −1)and ampicillin (50mg l −1)resistance in Luria broth at 30°C (18h).Three clones were selected,grown in Luria broth containing ampicillin and 5%(w/v)arabinose (to induce expression of red recombinase),and prepared for electro-poration.After electroporation with the step 2fragment,cells were incubated at 30°C for 4h and then transferred into a 250-ml flask containing 100ml of modified LB (100mM 3-(N -morpholino)propanesulfonic acid [MOPS]buffer added and NaCl omitted)containing 10%sucrose.After overnight incubation (30°C),clones were selected on modified LB plates (no NaCl;100mM MOPS added)containing 6%sucrose (39°C,16h).Resulting clones were tested for loss of ampicillin and chloramphenicol resistance.Construction was confirmed by PCR using the mgsA-up/down primer set.A clone containing a deletion in the central region of mgsA was selected and designated XZ121.The dadX gene was deleted in a manner analogous to that used to delete the mgsA gene.Primers for dadX deletion are shown in Table 3,and the corresponding plasmids are shown in Table 2.FermentationNBS mineral salts medium (Causey et al.2004)with 1mM betaine (Zhou et al.2006a )was used in the initial fermentation (pH 7.0).Preinoculum was grown by inocu-lating three colonies into a 250ml flask (100ml NBS medium,2%glucose,and 100mM ammonium sulfate).After 16h (37°C,120rpm),this preinoculum was diluted into 500-ml fermentation fleakers containing 300ml NBS medium (2–8%glucose,100mM ammonium sulfate,and 1mM betaine)with 33mg cell dry weight (CDW)l −1.In early experiments,pH was maintained at 7.0by automat-ically adding 2M potassium hydroxide.In later experi-ments,5M ammonium hydroxide was used to maintain pH,and a low salt medium,AM1(Martinez et al.2007),was used to replace the NBS medium for fermentation (8–12%glucose).AM1medium contains much less salt and has been optimized for E.coli .Metabolic evolutionCells from pH-controlled fermentations were serially transferred at 24-h intervals to facilitate metabolic evolution through competitive,growth-based selection (Fig.1b).At the beginning,sequentially transferred cultures were inoc-ulated with an initial density of 33mg CDW l −1.As growth increased,the inoculum was changed to a 1:100dilution and subsequently to a 1:300dilution.Periodically,clones were isolated from these experiments,assigned new strain designations,and frozen for storage.AnalysesCell mass was estimated by measuring the optical density at anic acids and glucose concentrations were mea-sured by high-performance liquid chromatography (HPLC,Underwood et al.2002).Analysis of fermentation products by mass spectroscopy and amino acid analyzer were provided by the University of Florida Interdisciplinary Center for Bio-technology Research.Alanine was found to be the predominant product.The alanine concentration and isomeric purity were further measured by HPLC using the Chiralpak MA(+)chiral column (Chiral Technologies,West Chester,PA).ResultCloning of the alanine dehydrogenase geneALD is found in Bacillus (and Geobacillus )species where it plays a pivotal role in energy generation during sporulation (Ohashima and Soda 1979;Kuroda et al.1990).ALD from B.sphaericus IFO3525has beenwidelyFig.3Plasmids used to delete mgsA .Plasmid pLOI4229(a )was used to delete the mgsA gene and insert the cat-sacB cassette in the first recombina-tion step.Plasmid pLOI4230(b )was used to remove the cat-sacB cassette to create a deletion devoid of foreign sequence.Se-quence encoding the N-terminal and C-terminal regions are des-ignated mgsA ′and mgsA ″,respectivelyused with varying degrees of success to engineer alanine production in recombinant bacteria(Uhlenbusch et al. 1991;Hols et al.1999;Lee et al.2004;Smith et al.2006). Selection of the B.sphaericus IFO3525is presumed to be due in part to the high specific activity(Ohashima and Soda 1979).In contrast,we have selected a thermostable ALD from the thermophile,G.stearothermophilus XL-65-6, based on our prior experience in expressing genes from this organism in recombinant E.coli(Burchhardt and Ingram 1992;Lai and Ingram1993;Lai and Ingram1995).The ribosomal-binding region,coding region,and tran-scriptional terminator of alaD were amplified from G. stearothermophilus XL-65-6and sequenced(EF154460in GenBank).The deduced amino acid sequence was identical to that reported for Geobacillus kaustophilus HTA426and very similar to G.stearothermophilus strain10(99%iden-tity)and G.stearothermophilus strain IFO12550(94% identity).The nucleotide sequence(65%identity)and the deduced ALD amino acid sequence(74%identity)were quite different from the B.sphaericus IFO3525gene,the gene pre-viously used for alanine production in recombinant bacteria.Modification of E.coli W for homoalanine productionE.coli W strain SZ194(pflB frdBC adhE ackA)was previously constructed to produce only D-lactic acid.All major fermentation pathways except lactate have been blocked in this strain by gene deletions(Fig.1a).To convert this strain to the production of alanine,part of the native ldhA-coding region was replaced by a DNA fragment containing the ribosomal-binding region,coding region,and transcriptional terminator of alaD from G. stearothermophilus XL-65-6.The promoterless alaD was oriented in the same direction as ldhA to allow expression from the native ldhA promoter(Fig.2).After electroporation,approximately500colonies were recovered with tetracycline resistance and sensitivity to kana-mycin,consistent with a double-crossover event.These colo-nies were further examined by PCR using ldhA forward and reverse primer set(Table3).Only eight colonies of the500 tested were correct based on an analysis of PCR fragments. These eight colonies were further verified using primer sets for alaD,ldhA forward and alaD reverse,alaD forward and ldhA reverse,and ldhA outside primers(Table3)and de-signated XZ103,XZ104,XZ105,XZ106,XZ107,XZ108, XZ109,and XZ110,respectively.These eight strains were initially tested in15-ml screw-cap tubes containing NBS medium with2%glucose and100mM ammonium sulfate, which were filled to the brim.Strain XZ105appeared to grow faster than the other strains(37°C for48h)and was selected for further development.XZ105was transformed with pFT-A,which contains an inducible flippase(FLP)recombinase(Martinez-Morales et al.1999;Posfai et al.1997).The chromosomal FRT-flanked tet gene in XZ105was removed by inducing the FLP recombinase.After growing in39°C to eliminate the temperature-sensitive plasmid pFT-A,resulting strain was designated XZ111.Expression of G.stearothermophilus alaD in XZ111is transcriptionally regulated by the ldhA promoter,the same promoter that regulates the production of lactate dehydrogenase(dominant fermentation pathway) in native E.coli.pH-controlled batch fermentation for alanine production Alanine production by strain XZ111was tested in500-ml fermentation vessels containing300ml NBS medium, 20g l−1glucose,100mM ammonium sulfate,and1mM betaine.Broth pH was automatically controlled by adding 2N potassium hydroxide.After96h,181mM alanine was produced.The alanine yield from total glucose was 81%(g/g),and84%based on glucose that had been metabo-lized.The chiral purity of L-alanine was96.1%(Table4). Very low levels of other products(lactate,succinate,ace-tate,ethanol)were present,typically below1mM.This result demonstrated that the integrated G.stearothermophilus alaD gene as a single chromosomal copy under the control of the native ldhA promoter can provide sufficient levels of ALD to support E.coli growth from the production of alanine as the sole fermentation product.Metabolic evolution of strain XZ111Although XZ111could accumulate alanine as the primary product,incubation times were long,and volumetric productivity was limited.When using a high-glucose concentration(80g l−1),growth and alanine productivity were further reduced(Table4).In this strain,adenosine triphosphate(ATP)production and growth are tightly coupled to NADH oxidation and alanine production by ALD(Fig.1b).This coupling provided a basis for strain improvement by selecting for increased growth during serial cultivation,i.e.,metabolic evolution.Cells with increased growth because of spontaneous mutations will successively displace their parents while coselecting for increased alanine productivity.Serial transfers of XZ111were carried out at24-h intervals in NBS mineral salts medium with1mM betaine.Cultures were first transferred in the medium containing20g l−1 glucose,and the pH was controlled by automatically adding 2N potassium hydroxide.However,after ten transfers to strain XZ112,little improvement was observed(data not shown).Because ammonia is essential for alanine pro-duction,it was thought that ammonia may be limiting for fermentation.Two normals potassium hydroxide containing 1N ammonia carbonate and5N ammonia hydroxide alone。

长筒弹力袜与中筒弹力袜在小腿段浅静脉曲张患者中的疗效比较及其对血流动力学的影响研究

中国现代医生2020年11月第58卷第33期•临床研究-长筒弹力袜与屮筒弹力袜在小腿段浅静脉曲张患者屮的疗效比较及其对血流动力学的影响研究甄杰生广东省台山市人民医院肝胆乳腺甲状腺血管外科，广东台山529200［摘要］目的探讨长筒弹力袜与中筒弹力袜在小腿段浅静脉曲张患者中的疗效比较及其对血流动力学的影响研究。

方法选取2015年1月-2019年11月我院收治的小腿段浅静脉曲张患者157例，所有患者均接受大隐静脉高位结扎剥脱术治疗，依据术后使用的医用弹力袜长度不同进行分组，对照组78例,研究组79例，对所有患者的临床资料进行回顾性分析。

对照组应用中筒弹力袜，研究组应用长筒弹力袜。

比较两组临床治疗总有效率及相关血流动力学指标。

结果研究组辅助治疗总有效率为98.7%.,显著高于对照组的89.7%(P<0.05)。

研究组隐股交界远端股静脉的反流时间为(2.6±0.9)s，显著短于对照组的(4.1±0.5)s(P<0.05),研究组股静脉内径为(10.5±0.4)m m,显著低于对照组的(14.4±0.7)mm(P<0.05)。

结论小腿段浅静脉曲张患者在大隐静脉高位结扎剥脱术后使用医用弹力袜，可起到十分显著有效的辅助效果，且长筒弹力袜的辅助效果更加理想,可更为显著地改善患者患肢的血流动力学指标水平。

［关键词］静脉曲张；大隐静脉；弹力袜;血流动力学［中图分类号］R82［文献标识码］B［文章编号］1673-9701渊2020冤33-0123-03Comparative observation on the curative effect of long-barreled compression stockings and middle-barreled compression stockings in patients with superficial varicose veins of the calf and the effect on hemodynamicsZHEN JieshengDeparLmenL of HepaLobiliary,BreasL and Thyroid and Vascular Surgery,People's HospiLal of Taishan CiLy in Guangdong Province,Taishan529200,China［Abstract］Objective To invesLigaLe Lhe comparaLive observaLion on Lhe curaLive effecL of long-barreled compression sLockings and middle-barreled compression sLockings in paLienLs wiLh superficial varicose veins of Lhe calf and Lhe sLudy of Lheir effecLs on hemodynamics.Methods A LoLal of157paLienLs wiLh superficial varicose veins of Lhe calf who were admiLLed Lo our hospiLal from January2015Lo November2019were selecLed.All paLienLs received high saphenous vein ligaLion and sLripping,and were grouped according Lo Lhe lengLh of Lhe medical compression sLockings afLer Lhe operaLion,including78cases in Lhe conLrol group,and79cases in Lhe sLudy group.The clinical daLa of all paLienLs were reLrospecLively analyzed.The conLrol group used middle-barreled compression sLockings,and Lhe sLudy group used long-barreled compression sLockings.The clinical LreaLmenL LoLal efficiency and Lhe relevanL hemodynamic indexes be-Lween Lhe Lwo groups were observed and compared.Results The LoLal effective raLe of adjuvanL Lherapy in Lhe sLudy group was98.7%,which was significanLly higher Lhan89.7%in Lhe conLrol group(P<0.05).The reflux Lime of Lhe disLal femoral vein of Lhe saphenous femoral juncLion in Lhe sLudy group was(2.6±0.9)s,which was significantly shorLer Lhan(4.1±0.5)s of Lhe conLrol group(P<0.05).The inLernal diameLer of Lhe femoral vein in Lhe sLudy group was(10.5±0.4)mm,which was significanLly lower Lhan(14.4±0.7)mm of Lhe conLrol group(P<0.05).Conclusion The use of medical compression sLockings afLer Lhe high ligaLion and sLripping of Lhe greaL saphenous vein in paLienLs wiLh superficial varicose veins of Lhe calf can play a very significanL and effecLive auxiliary effecL,and Lhe long-barreled elasLic sLockings has more ideal auxiliary effecL,which can more significantly improve Lhe hemodynamic index level of Lhe paLienL's affecLed limb.［Key words］Varicose veins;GreaL saphenous vein;Compression sLockings;Hemodynamics•临床研究・中国现代医生2020年11月第58卷第33期下肢浅静脉曲张中最常见的一种就是大隐静脉曲张,主要是指下肢浅静脉发生瓣膜关闭不全,导致静脉中的血液发生反流，瘀滞远端静脉血管［1］。

English words and their origin - Arizona State University

English words and their origin:Learning from historyElly van Gelderenellyvangelderen@1 The nature of English vocabulary: a double set of wordsWhat’s the point?-different formality-euphemisms-spelling problemsWhere do the words come from?Figure 1: OriginsCore and Periphery:(Williams 1975)Figure 2: Core and Periphery2 How did it happen?Figure 4: Just one set of migrations Major Influence: French and LatinLatin loans:Some estimate that between 1500 and 1660 nearly 27,000 new words enter the language (Garner 1982: 151; Wermser 1976: 23).Not all of the new words survive into Modern English. Some of my favorite rejected words are:adminiculation …aid‟, anacephalize …to summarize‟, eximious …excellent‟,illecebrous …alluring‟, ingent …immense‟, and honorificabilitudinitatibus. Minor Influence: Other languagesobvious meanings within ……‟)languages3 What's the use of a `double’ vocabulary?perspire - sweatdonate - givenarrate/describe - tellobtain - getarrive - comeliberty - freedomadolescent - boy/girlAre native speakers aware? YES, to some extentAttitudes regarding `inkhorn terms':George Orwell:-Never use a foreign phrase, a scientific word or a jargon word if you can think of an everyday English equivalent.-Never use a long word where a short one will do.-If it is possible to cut a word out, always cut it out.AND?4 Is English still borrowing?Yes, but lots of compounds, alphabet-soup, etc: `turning inwards' (Minkova & Stockwell 2007)5 Resources: the OED!/lib/resources/db/oed.htmEtymologyFirst date!Language of origin6 ExercisesA Guess which words are Latin or French in:a. A word is deadb. Fire and IceWhen it is said, Some say the world will end in fire, Some say. Some say in ice.I say it just From what I‟ve tasted of desireBegins to live I hold with those who favor fire.That day.But if it had to perish twice,I think I know enough of hateTo say that for destruction iceIs also greatAnd would suffice.Poems by Emily Dickinson and Robert FrostB Simple Search in the OED1: Do a simple search for `tree'. Which of the 12 instances would you click on? Is it a loanword? What other languages is it related to?2: Still using simple search, use a wildcard, e.g. ? means one letter: br?ng or s?ng. Do any words start with y and end in z? Use *.Advanced Search3: Using Advanced Search, look how many instances of `ain't' there are in the entire OED.4: Find all the words that first came in in 1960.5:F irst look up `assasination' in simple search; then in the full text. Difference? 6: Which words derive from Arabic? Search in etymologies!7: How often is Shakespeare quoted?Tables and figures in this handout are taken from the below, unless otherwise marked: Gelderen, Elly van 2006 A History of the English Language. Amsterdam: John Benjamins.。

当代研究生英语第七单元 B课文翻译

价格的利润生物公司正在吞噬可改变动物DNA序列的所有专利。

这是对阻碍医学研究发展的一种冲击。

木匠认为他们的贸易工具是理所当然的。

他们买木材和锤子后，他们可以使用木材和锤子去制作任何他们所选择的东西。

多年之后来自木材厂和工具储藏室的人并没有任何进展，也没有索要利润份额。

对于那些打造明日药物的科学家们来说，这种独立性是一种罕见的奢侈品。

发展或是发现这些生物技术贸易中的工具和稀有材料的公司，对那些其他也用这些工具和材料的人进行了严格的监控。

这些工具包括关键基因的DNA序列，人类、动物植物和一些病毒的基因的部分片段，例如，HIV,克隆细胞，酶，删除基因和用于快速扫描DNA样品的DNA 芯片。

为了将他们这些关键的资源得到手，医学研究人员进场不得不签署协议，这些协议可以制约他们如何使用这些资源或是保证发现这些的公司可以得到最终结果中的部分利益。

许多学者称这抑制了了解和治愈疾病的进程。

这些建议使Harold得到了警示，Harold是华盛顿附近的美国国家卫生研究院的院长，在同年早期，他建立了一个工作小组去调查此事。

由于他的提早的调查，下个月出就能发布初步的报告。

来自安阿伯密歇根大学的法律教授，该工作组的主席Rebecea Eisenberg说，她们的工作组已经听到了好多研究者的抱怨，在它们中有一份由美国联合大学技术管理组提交的重量级的卷宗。

为了帮助收集证据，NIH建立了一个网站，在这个网站上研究者们可以匿名举报一些案件，这些案件他们相信他们的工作已经被这些限制性许可证严重阻碍了。

迫使研究人员在出版之前需要将他们的手稿展示给公司的这一保密条款和协议是投诉中最常见的原因之一。

另一个问题是一些公司坚持保有自动许可证的权利，该许可证是有关利用他们物质所生产的任何未来将被发现的产品，并且这些赋予他们对任何利用他们的工具所赚取的利润的支配权利的条款也有保有的权利。

Eisenberg说：“如果你不得不签署了许多这样的条款的话，那真的是一个大麻烦”。

有效市场假说(英文)

Characteristic Example
Overconfidence Investors have unrealistically narrow range forecasts for future stock-market index levels. Overconfidence leads to overtrading and greater losses (Barber and Odean, 2001).
July 3rd 2012
Mark Largan | Current Issues in Finance | MSc in Finance and Management
Behavioural finance
Behavioural psychologists have tried to explain why and how investors might be irrational.
July 3rd 2012
Mark Largan | Current Issues in Finance | MSc in Finance and Management
Behavioural finance
Behavioural finance also argues that the ‘there is no free lunch’ argument which applies to rational pricing in an efficient market can also apply to an inefficient market.
July 3rd 2012
Mark Largan | Current Issues inБайду номын сангаасFinance | MSc in Finance and Management

计量经济学中英文词汇对照

Common variance Common variation Communality variance Comparability Comparison of bathes Comparison value Compartment model Compassion Complement of an event Complete association Complete dissociation Complete statistics Completely randomized design Composite event Composite events Concavity Conditional expectation Conditional likelihood Conditional probability Conditionally linear Confidence interval Confidence limit Confidence lower limit Confidence upper limit Confirmatory Factor Analysis Confirmatory research Confounding factor Conjoint Consistency Consistency check Consistent asymptotically normal estimate Consistent estimate Constrained nonlinear regression Constraint Contaminated distribution Contaminated Gausssian Contaminated normal distribution Contamination Contamination model Contingency table Contour Contribution rate Control

遗传育种相关名词中英文对照

中英文对照的分子育种相关名词3'untranslated region (3'UTR) 3'非翻译区5'untranslated region (5; UTR) 5'非翻译区A chromosome A 染色体AATAAA 多腺苷酸化信号aberration 崎变abiogenesis 非生源说accessory chromosome 副染色体accessory nucleus 副核accessory protein 辅助蛋白accident variance 偶然变异Ac-Ds system Ac-Ds 系统acentric chromosome 无着丝粒染色体acentric fragment 无着丝粒片段acentric ring 无着丝粒环achromatin 非染色质acquired character 获得性状acrocentric chromosome 近端着丝粒染色体acrosyndesis 端部联会activating transcription factor 转录激活因子activator 激活剂activator element 激活单元activator protein( AP)激活蛋白activator-dissociation system Ac-Ds 激活解离系统active chromatin 活性染色质active site 活性部位adaptation 适应adaptive peak 适应顶峰adaptive surface 适应面addition 附加物addition haploid 附加单倍体addition line 附加系additive effect 加性效应additive gene 加性基因additive genetic variance 加性遗传方差additive recombination 插人重组additive resistance 累加抗性adenosine 腺昔adenosine diphosphate (ADP )腺昔二鱗酸adenosine triphosphate( ATP)腺昔三憐酸adjacent segregation 相邻分离A-form DNA A 型DNAakinetic chromosome 无着丝粒染色体akinetic fragment 无着丝粒片断alien addition monosomic 外源单体生物alien chromosome substitution 外源染色体代换alien species 外源种alien-addition cell hybrid 异源附加细胞杂种alkylating agent 焼化剂allele 等位基因allele center 等位基因中心allele linkage analysis 等位基因连锁分析allele specific oligonucleotide(ASO)等位基因特异的寡核苷酸allelic complement 等位（基因）互补allelic diversity 等位（基因）多样化allelic exclusion 等位基因排斥allelic inactivation 等位（基因）失活allelic interaction 等位（基因）彼此作用allelic recombination 等位（基因）重组allelic replacement 等位（基因）置换allelic series 等位（基因）系列allelic variation 等位（基因）变异allelism 等位性allelotype 等位（基因）型allohaploid 异源单倍体allopatric speciation 异域种alloploidy 异源倍性allopolyhaploid 异源多倍单倍体allopolyploid 异源多倍体allosyndesis 异源联会allotetraploid 异源四倍体alloheteroploid 异源异倍体alternation of generation 世代交替alternative transcription 可变转录alternative transcription initiation 可变转录起始Alu repetitive sequence, Alu family Alu 重复序列，Alu 家族ambiguous codon 多义密码子ambisense genome 双义基因组ambisense RNA 双义RNAaminoacyl-tRNA binding site氨酰基tRNA接合位点aminoacyl-tRNA synthetase 氨酰基tRNA连接酶amixis 无融合amorph 无效等位基因amphipolyploid 双多倍体amplicon 扩增子amplification 扩增amplification primer 扩增引物analysis of variance 方差分析anaphase (割裂）后期anaphase bridge (割裂）后期桥anchor cell 锚状细胞androgamete 雄配子aneuhaploid 非整倍单倍体aneuploid 非整倍体animal genetics 动物遗传学annealing 复性antibody 抗体anticoding strand 反编码链anticodon 反密码子anticodon arm 反密码子臂anticodon loop 反密码子环antiparallel 反向平行antirepressor 抗阻抑物antisense RNA 反义RNAantisense strand 反义链apogamogony 无融合结实apogamy 无配子生殖apomixis 无融合生殖arm ratio (染色体)臂比artificial gene人工基因artificial selection 人工选择asexual hybridization 无性杂交asexual propagation 无性繁殖asexual reproduction 无性生殖assortative mating 选型交配asynapsis 不联会asynaptic gene 不联会基因atavism 返祖atelocentric chromosome 非端着丝粒染色体attached X chromosome 并连X 染色体attachment site 附着位点attenuation 衰减attenuator 衰减子autarchic gene 自效基因auto-alloploid 同源异源体autoallopolyploid 同源异源多倍体autobivalent 同源二阶染色体auto-diploid 同源二倍体；自体融合二倍体autodiploidization 同源二倍化autoduplication 自体复制autogenesis自然发生autogenomatic 同源染色体组autoheteroploidy 同源异倍性autonomous transposable element 自主转座单元autonomously replicating sequence(ARS)自主复制序列autoparthenogenesis 自发单性生殖autopolyhaploid 同源多倍单倍体autopolyploid 同源多倍体autoradiogram 放射自显影图autosyndetic pairing 同源配对autotetraploid 同源四倍体autozygote 同合子auxotroph 营养缺陷体B chromosome B 染色体B1，first backcross generation 回交第一代B2，second backcross generation 回交第二代back mutation 答复突变backcross 回交backcross hybrid 回交杂种backcross parent 回交亲本backcross ratio 回交比率background genotype 背景基因型bacterial artification chromosome( BAC )细菌人工染色体Bacterial genetics 细菌遗传学Bacteriophage 噬菌体balanced lethal 平衡致死balanced lethal gene 平衡致死基因balanced linkage 平衡连锁balanced load 平稳负荷balanced polymorphism 平衡多态现象balanced rearrangements 平稳重组balanced tertiary trisomic 平稳三级三体balanced translocation 平稳异位balancing selection 平稳选择band analysis 谱带分析banding pattern (染色体)带型basal transcription apparatus 基础转录装置base analog 碱基类似物base analogue 类減基base content 减基含量base exchange 碱基交换base pairing mistake 碱基配对错误base pairing rules 碱基配对法则base substitution 减基置换base transition 减基转换base transversion 减基颠换base-pair region 碱基配对区base-pair substitution 碱基配对替换basic number of chromosome 染色体基数behavioral genetics 行为遗传学behavioral isolation 行为隔离bidirectional replication 双向复制bimodal distribution 双峰散布binary fission 二割裂binding protein 结合蛋白binding site 结合部位binucleate phase 双核期biochemical genetics 生化遗传学biochemical mutant 生化突变体biochemical polymorphism 生化多态性bioethics 生物伦理学biogenesis 生源说bioinformatics 生物信息学biological diversity 生物多样性biometrical genetics 生物统计遗传学（简称生统遗传学) bisexual reproduction 两性生殖bisexuality 两性现象bivalent 二价体blending inheritance 混合遗传blot transfer apparatus 印迹转移装置blotting membrane 印迹膜bottle neck effect 瓶颈效应branch migration 分支迁移breed variety 品种breeding 育种，培育;繁衍，生育breeding by crossing 杂交育种法breeding by separation 分隔育种法breeding coefficient 繁衍率breeding habit 繁殖习性breeding migration 生殖回游，繁衍回游breeding period 生殖期breeding place 繁衍地breeding population 繁殖种群breeding potential繁衍能力，育种潜能breeding range 繁衍幅度breeding season 繁衍季节breeding size 繁衍个体数breeding system 繁衍系统breeding true 纯育breeding value 育种值broad heritability 广义遗传率bulk selection 集团选择C0，acentric 无着丝粒的Cl,monocentric 单着丝粒C2, dicentric双着丝粒的C3,tricentric 三着丝粒的candidate gene 候选基因candidate-gene approach 候选基因法Canpbenmodel坎贝尔模型carytype染色体组型，核型catabolite activator protein 分解活化蛋白catabolite repression 分解代谢产物阻遏catastrophism 灾变说cell clone 细胞克隆cell cycle 细胞周期cell determination 细胞决定cell division 细胞割裂cell division cycle gene(CDC gene) 细胞割裂周期基因ceU division lag细胞割裂延迟cell fate 细胞命运cell fusion 细胞融合cell genetics 细胞的遗传学cell hybridization 细胞杂交cell sorter细胞分类器cell strain 细胞株cell-cell communication 细胞间通信center of variation 变异中心centimorgan(cM) 厘摩central dogma 中心法则central tendency 集中趋势centromere DNA 着丝粒DNAcentromere interference 着丝粒干扰centromere 着丝粒centromeric exchange ( CME)着丝粒互换centromeric inactivation 着丝粒失活centromeric sequence( CEN sequence)中心粒序列character divergence 性状趋异chemical genetics 化学遗传学chemigenomics 化学基因组学chiasma centralization 交叉中化chiasma terminalization 交叉端化chimera异源嵌合体Chi-square (x2) test 卡方检验chondriogene 线粒体基因chorionic villus sampling 绒毛膜取样chromatid abemition染色单体畸变chromatid break染色单体断裂chromatid bridge 染色单体桥chromatid interchange 染色单体互换chromatid interference 染色单体干涉chromatid segregation 染色单体分离chromatid tetrad 四分染色单体chromatid translocation 染色单体异位chromatin agglutination 染色质凝聚chromosomal aberration 染色体崎变chromosomal assignment 染色体定位chromosomal banding 染色体显带chromosomal disorder 染色体病chromosomal elimination 染色体消减chromosomal inheritance 染色体遗传chromosomal interference 染色体干扰chromosomal location 染色体定位chromosomal locus 染色体位点chromosomal mutation 染色体突变chromosomal pattern 染色体型chromosomal polymorphism 染色体多态性chromosomal rearrangement 染色体质量排chromosomal reproduction 染色体增殖chromosomal RNA 染色体RNA chromosomal shift 染色体变迁，染色体移位chromosome aberration 染色体畸变chromosome arm 染色体臂chromosome association 染色体联合chromosome banding pattern 染色体带型chromosome behavior 染色体动态chromosome blotting 染色体印迹chromosome breakage 染色体断裂chromosome bridge 染色体桥chromosome coiling 染色体螺旋chromosome condensation 染色体浓缩chromosome constriction 染色体缢痕chromosome cycle 染色体周期chromosome damage 染色体损伤chromosome deletion 染色体缺失chromosome disjunction 染色体分离chromosome doubling 染色体加倍chromosome duplication 染色体复制chromosome elimination染色体丢失chromosome engineering 染色体工程chromosome evolution 染色体进化chromosome exchange 染色体互换chromosome fusion 染色体融合chromosome gap 染色体间隙chromosome hopping 染色体跳移chromosome interchange 染色体互换chromosome interference 染色体干与chromosome jumping 染色体跳查chromosome knob 染色体结chromosome loop 染色体环chromosome lose染色体丢失chromosome map 染色体图chromosome mapping 染色体作图chromosome matrix 染色体基质chromosome mutation染色体突变chromosome non-disjunction染色体不分离chromosome paring染色体配对chromosome polymorphism 染色体多态性chromosome puff染色体疏松chromosome rearrangement染色体质量排chromosome reduplication 染色体再加倍chromosome repeat染色体质量叠chromosome scaffold 染色体支架chromosome segregation 染色体分离chromosome set 染色体组chromosome stickiness染色体粘性chromosome theory of heredity 染色体遗传学说chromosome theory of inheritance 染色体遗传学说chromosome thread 染色体丝chromosome walking 染色体步查chromosome-mediated gene transfer 染色体中介基因转移chromosomology 染色体学CIB method CIB法;性连锁致死突变显现频率检测法circular DNA 环林DNAcis conformation 顺式构象cis dominance 顺式显性cis-heterogenote顺式杂基因子cis-regulatory element 顺式调剂兀件cis-trans test 顺反考试cladogram 进化树cloning vector 克隆载体C-meiosis C减数割裂C-metaphase C 中期C-mitosis C有丝割裂code degeneracy 密码简并coding capacity编码容量coding ratio 密码比coding recognition site 密码识别位置coding region 编码区coding sequence 编码序列coding site 编码位置coding strand 密码链coding triplet 编码三联体codominance 共显性codon bias 密码子偏倚codon type 密码子型coefficient of consanguinity 近亲系数coefficient of genetic determination 遗传决定系数coefficient of hybridity 杂种系数coefficient of inbreeding 近交系数coefficient of migration 迁移系数coefficient of relationship 亲缘系数coefficient of variability 变异系数coevolution 协同进化coinducer 协诱导物cold sensitive mutant 冷灵敏突变体colineartiy 共线性combining ability 配合力comparative genomics 比较基因组学competence 感受态competent cell感受态细胞competing groups 竞争类群competition advantage 竞争优势competitive exclusion principle 竞争排斥原理complementary DNA (cDNA)互补DNA complementary gene 互补基因complementation test 互补考试complete linkage 完全连锁complete selection 完全选择complotype 补体单元型composite transposon 复合转座子conditional gene 条件基因conditional lethal 条件致死conditional mutation 条件突变consanguinity 近亲consensus sequence 共有序列conservative transposition 保守转座constitutive heterochromatin 组成型染色质continuous variation 持续变异convergent evolution 趋同进化cooperativity 协同性coordinately controlled genes 协同操纵基因core promoter element 核心启动子core sequence 核心序列co-repressor协阻抑物correlation coefficient相关系数cosegregation 共分离cosuppression 共抑制cotranfection 共转染cotranscript共转录物cotranscriptional processing共转录进程cotransduction 共转导cotransformation 共转化cotranslational secrection 共翻译分泌counterselection 反选择coupling phase 互引相covalently closed circular DNA(cccDNA)共价闭合环状DNA covariation 相关变异criss-cross inheritance 交叉遗传cross 杂交crossability 杂交性crossbred 杂种cross-campatibility 杂交亲和性cioss-infertility 杂交不育性crossing over 互换crossing-over map 互换图crossing-over value 互换值crossover products 互换产物crossover rates 互换率crossover reducer 互换抑制因子crossover suppressor 互换抑制因子crossover unit 互换单位crossover value 值crossover-type gamete 互换型配子C-value paradox C 值悖论cybrid 胞质杂种cyclin 细胞周期蛋白cytidme 胞苷cytochimera 细胞嵌合体cytogenetics 细胞遗传学cytohet 胞质杂合子cytologic 细胞学的cytological map 细胞学图cytoplasm细胞质cytoplasmic genome 胞质基因组cytoplasmic heredity 细胞质遗传cytqplasmic incompatibility 细胞质不亲和性cytoplasmic inheritance 细胞质遗传cytoplasmic male sterility 细胞质雄性不育cytoplasmic mutation 细胞质突变cytofdasmic segregation 细胞质分离cytoskeleton 细胞骨架Darwin 达尔文Darwinian fitness 达尔文适合度Darwinism 达尔文学说daughter cell 子细胞daughter chromatid 子染色体daughter chromosome 子染色体deformylase 去甲酰酶degenerate code 简并密码degenerate primer 简并引物degenerate sequence 简并序列degenerated codon 简并密码子degeneration 退化degree of dominance 显性度delayed inheritance 延迟遗传deletant 缺失体deletion 缺失deletion loop 缺失环deletion mapping 缺失作图deletion mutation 缺失突变denatured DNA 变性DNA denatured protein 变性蛋白denaturing gel 变性胶denaturing gel electrophoresis 变性凝胶电泳denaturing gradient polyacrylamide gel 变性聚丙稀酰胺凝胶density gradient centrifugation 密度梯度离心density gradient separation 密度梯度分离deoxyribonucleic acid-dependent DNA polymerase 依托于DNA的DNA聚合酶derived line 衍生系derived type 衍生类型developmental genetics 发育遗传学developmental pathway 发育途径dicentric bridge 双粒染色体桥dicentric chromosome 双着丝粒染色体differential staining technique 显带技术differentiation center 分化中心dihaploid 双单倍体,dihybrid 双因子杂种dihybrid cross 双因子杂交dimorphism 二态性diploidization 二倍化diploidize 二倍化diploidized haploid 二倍化的单倍体direct cross 正交direct repeat 同向重复（序列）direct selection 正选择directed mutagenesis 正向突变discontinuous variation 不持续变异distant hybrid 远缘杂种distant hybridization 远缘杂交diversity center 多样性中心diversity curve 多样性曲线diversity gene ( D gene) D 基因diversity indices 多样性指数diversity of species 种的多样性diversity region ( D region) D 区；多变区DNA alkylation DNA 烧化DNA amplification DNA 扩增DNA amplification in vitro DNA 体外扩增DNA amplification polymorphism DNA 扩增多态性DNA breakage DNA 断裂DNA database DNA 数据库DNA degradation DNA 降解DNA denaturation DNA 变性DNA detection DNA 检测DNA distortion DNA 变形DNA duplex DNA 双链体DNA duplicase DNA 复合酶DNA element DNA 单元DNA evolution DNA 进化DNA fingerprint DNA 指纹DNA fingerprinting DNA 指纹分析DNA homology DNA 同源性DNA hybridization DNA 杂交DNA jumping technique DNA 跳查技术DNA melting DNA 解链DNA methylation DNA 甲基化DNA modification DNA 修饰DNA modification restriction system DNA 修饰限制系统DNA nicking DNA 切口形成DNA oxidation DNA 氧化DNA packaging DNA 包装DNA pairing DNA 配对DNA pitch DNA 螺距DNA polymorphism DNA 多态性DNA probe DNA 探针DNA puff DNA 泡DNA purification DNA 纯化DNA recombination DNA 重组DNA redundant 多余DNADNA repair DNA 修复DNA replication DNA 复制DNA replication enhancer DNA 复制增强子DNA replication origin DNA 复制起点DNA replication site DNA 复制点DNA sealase DNA 连接酶DNA sequence analysis DNA 序列分析DNA sizing gene DNA大小决定基因DNA strand exchange DNA 链互换DNA strand separation DNA 链分离DNA strand transfer protein DNA 链转移蛋白DNA template DNA 模板DNA thermal cycler DNA 热循环仪DNA topoisomerase DNA 拓扑异构酶DNA transcript DNA 转录物DNA transposon DNA 转座子DNA twist DNA 扭曲DNA typing DNA 分型DNA untwisting DNA 解旋DNA unwinding enzyme DNA 解旋酶DNA unwinding protein DNA 解旋蛋白DNA-agar technique DNA 琼脂技术DNAase I footprinting DNA 酶I 足迹法DNAase-free reagent 无DNA 酶试剂DNA-binding domain DNA 结合域DNA-binding motif DNA 结合基序DNA-binding protein DNA 结合蛋白DNA-polymerase DNA 聚合酶DNA-protein complex DNA -蛋白质复合体DNA-protein interaction DNA _ 蛋白质彼此作用DNA-restriction enzyme DNA 限制酶DNA-RNA hybrid DNA-RNA 杂交体DNase-free 不含DNA 酶的dominance 显性dominance type 优势型dominance variance 显性方差dominant allele 显性等位基因dominant effect 显性效应dominant gene 显性基因dominant gene mutation 显'性基因突变dominant lethal 显性致死dominant phenotype 显性表型donor DNA 供体DNAdonor organism 供体生物dosage compensation 剂量补偿作用dotting blotting 点溃法double crossing over 双互换double fertilization 汉受精duplicate genes 重复基因duplication 重复duplicon 重复子dyad 二分体dynamic selection 动态选择ecological genetics 生态遗传学ecological isolation 生态隔离ecological niche 生态小境ectopic expression 异位表达ectopic integration 异位整合effective population size 有效群体大小embryoid 胚状体embryonic stem cells( ES cells)胚胎干细胞endocrine signal 内分泌信号endogamy 近亲繁殖endomitosis 核内有丝割裂endonuclease 内切核酸酶endopolyploidy 核内多倍体environment 环境environmental variance 环境方差environmental variation 环境变异epigenesis 后成说epigenetic inheritance 后生遗传epigenetically silenced 后生沉默episome 附加体epistasis 上位性epistatic dominance 超显性epistatic gene 上位基因equal segregation 均等分离equational division 均等割裂equilibrium population 平衡群体Expressed Sequence T ag(EST)表达序列标签euchromatin 常染色质euchromatin常染色质eugenics 优生学euhaploid 整单倍体eukaryote 真核生物eukaryotic chromosome 真核染色体eukaryotic cell 真核细胞eukaryotic organism 真核生物eukaryotic vector 真核载体euphenics 优型学euploid 整倍体evolutional load 进化负荷evolutionary divergence 进化趋异evolutionary genetics 进化遗传学evolutionaiy rate 进化速率excision repair 切除修复exconjugant 接合后体excretion vector 分泌型载体exit site 萌生点exogenote 外基因子exogenous gene 外源基因exonuclease 外切核酸酶expression cloning 表达克隆expression library 表达文库expression mutation 表达突变expression plasmid 表达质粒expression product 表达产物expression screening 表达挑选extinguisher loci 消失基因座，灭绝基因座extirpated species 绝迹种extrachromosomal inheritance 染色体外遗传extra-chromosome 超数染色体，额外染色体extranuclear inheritance 核外遗传F1 generation F1代，子一代F2 generation F2 代，子二代facultative heterochromatin 兼性异染色质familial trait 家族性状family selection 家系选择feedback suppression 反馈抑制female gamete 雌配子fertility factor 致育因子filial generation 子代fingerprint 指纹finite population 有限群体first division segregation 第一次分裂分离first division segregation pattern 第一次割裂分离模式flanking sequence 侧翼序列flow cytometry 流式细胞仪fluorescence in situ hybridization ( FISH )荧光原位杂交fluorescent primer 荧光引物fluorescent probe 荧光探针formyl methionine (fMet)甲酰甲硫氨酸foot printing 足迹法foreign DNA 外源DNAforward genetics 正向遗传学forward mutation 正向突变forward primer 正向引物founder effect 成立者效应four strand double crossing over 四线双交换full-sib 全同胞functional genomics 功能基因组学functional RNA 功能RNAgain-of-function mutation 功能获得性突变gamete 配子gametic 配子的gametic incompatibility 配子不亲和性gametic lethal 配子致死gametic linkage 配子连锁gametic meiosis 配子减数分裂gametic ratio 配子分离比gametoclonal variation 配子无性系变异gametophyte 配子体G-band G带；中期染色体带GC box GC 框GC tailing GC 加尾gel electrophoresis 凝胶电泳gemetic sterility 配子不育gene activation 基因激活gene activity 基因活性gene amplification 基因扩增gene analysis 基因分析gene arrangement 基因排列gene balance 基因平稳gene basis 基因基础gene batteries 基因群gene block 基因区段gene carrier 基因携带者gene center theory 基因中心学说gene cluster 基因簇gene combination 基因重组gene complex 基因复合体gene content 基因含量gene conversion 基因转换gene distribution 基因散布gene diversity 基因多样性gene dosage 基因剂量gene dosage compensation 基因剂量补偿gene dosage effect 基因剂量效应gene duplication 基因重复gene element 基因元件gene exchange 基因交流gene expression 基因表达gene expression system 基因表达系统gene family 基因家族gene fixation 基因固定gene flow 基因流gene frequency 基因频率gene fusion 基因融合gene inactivation 基因失活gene inoculation 基因接种gene interaction 基因相互作用gene isolation 基因分离gene knockout 基因敲除gene knock-out 基因失效法gene linkage 基因连锁gene localization 基因定位gene location 基因位置gene locus 基因位点gene magnification 基因扩增gene manipulation 基因操作gene map 基因图谱gene mapping 基因作图gene multiplication 基因重复gene mutation 基因突变gene mutation rate 基因突变频率gene order 基因顺序gene organization 基因组构gene pool 基因库gene position effect 基因位置效应gene probe 基因探针gene product 基因产物gene rearrangement 某因重排gene reassortment 基因从头配对gene replication 基因复制gene repression 基因抑制gene resortment 基因重配gene silencing 基因沉默gene splicing 基因剪接gene string 基因线gene structure 基因结构gene substitute 基因置换gene substitution 基因置换gene suppression 基因抑制gene synthesis 基因合成gene tagged 基因标签gene tagging 基因标签gene targeting 基因导向，基因寻靶gene transfer 基因转移gene transfer agent 基因传递因子gene transfer vector 基因转移载体gene transposition 基因转座genealogical classification 系谱分类genera 属general transcription factor ( GTF )通用转录因子generalized transduction 普遍性转导generation 世代generative cell 生殖细胞generative reproduction 有性繁衍generic coefficient 种属系数generic cross 属间杂交generic name 属名genes in common 一起基因gene-specific transcription factor 基因特异性转录因子genetic ablation 基因缺损genetic advance 遗传进度genetic algebra 遗传代数genetic analysis 遗传分析genetic background 遗传背景genetic balance 遗传平稳genetic block 遗传性阻碍genetic compensation 遗传补偿genetic complementation 遗传互补genetic composition 遗传组成genetic continuity 遗传连续性genetic control 遗传控制genetic covariance 遗传协方差genetic cross 杂交genetic database 遗传数据库genetic death 遗传性死亡genetic deficiency 遗传缺损genetic deformity 基因变型genetic determinant 遗传决定因子genetic dimorphism 遗传二型现象genetic distance 遗传距离genetic divergence 遗传趋异genetic diversity 遗传多样性genetic dominance 遗传优势genetic donor 基因供体genetic drift 遗传漂变genetic element遗传因子，遗传成份genetic engineering 遗传工程genetic equilibrium 遗传平衡genetic erosion 遗传冲洗，遗传蚀变genetic expression 遗传表达genetic extinction 遗传灭绝genetic facilitation 遗传增进作用genetic factor 遗传因子genetic feedback 遗传反馈genetic fingerprint 遗传指纹genetic fingerprinting 遗传指纹分析genetic fitness 遗传适合度genetic flexibility 遗传可塑性genetic gain 遗传获得量genetic heterogeneity 遗传异质性genetic homology 遗传同源genetic immunity 遗传免疫genetic imprinting 遗传印记genetic inertia 遗传惰性genetic information 遗传信息genetic inoculation 基因接种genetic instability 遗传不稳定性genetic continuity 遗传连续性genetic control 遗传控制genetic covariance 遗传协方差genetic cross 杂交genetic database 遗传数据库genetic death 遗传性死亡genetic deficiency 遗传缺损genetic deformity 基因变型genetic determinant 遗传决定因子genetic dimorphism 遗传二型现象genetic distance 遗传距离genetic divergence 遗传趋异genetic diversity 遗传多样性genetic dominance 遗传优势genetic donor 基因供体genetic drift 遗传漂变genetic element遗传因子，遗传成份genetic engineering 遗传工程genetic equilibrium 遗传平衡genetic erosion 遗传冲洗，遗传蚀变genetic expression 遗传表达genetic extinction 遗传灭绝genetic facilitation 遗传增进作用genetic factor 遗传因子genetic feedback 遗传反馈genetic fingerprint 遗传指纹genetic fingerprinting 遗传指纹分析genetic fitness 遗传适合度genetic flexibility 遗传可塑性genetic gain 遗传获得量genetic heterogeneity 遗传异质性genetic homology 遗传同源genetic immunity 遗传免疫genetic imprinting 遗传印记genetic inertia 遗传惰性genetic information 遗传信息genetic inoculation 基因接种genetic instability 遗传不稳定性genetic interaction 遗传彼此作用genetic isolating factor 遗传隔离因子genetic isolation 遗传隔离genetic knock-out experiment 基因失效试验genetic linkage 遗传连锁genetic linkage map 遗传连锁图谱genetic load 遗传负荷genetic manipulation 遗传操作genetic map 遗传图谱genetic mapping 遗传作图genetic marker 遗传标记genetic masking 基因组掩饰genetic material 遗传物质genetic mobilization 遗传转移genetic modification 遗传修饰genetic module 遗传组件genetic nomenclature 遗传命名法genetic parameter 遗传参数genetic polarity 遗传极性genetic polymorphism 遗传多样性genetic population 遗传群体genetic potential 遗传潜力genetic process 遗传进程genetic property 遗传特'性genetic ratio 遗传比genetic reactivation 遗传复活genetic reassortment 遗传重排genetic recipient 基因受体genetic recombination 遗传重组genetic regulation 遗传调剂genetic relationship 亲缘关系genetic repair mechanism 遗传修复机制genetic replication 遗传复制genetic risk 遗传危险性genetic screening 遗传筛查genetic segregation 遗传分离genetic selection 遗传选择genetic sex 遗传性别genetic shift 遗传漂移genetic stability 遗传稳定性genetic sterility 遗传性不育genetic strain 遗传品系genetic suppression 遗传抑制genetic switch 遗传开关genetic system 遗传体系genetic transcription 遗传转录genetic transformation 遗传转换genetic translation 遗传翻译genetic transmission 遗传传递genetic typing 遗传分型genetic unit 遗传单位genetic value 遗传值genetic variability 遗传变异性genetic variance 遗传方差genetic vulnerability 遗传易损性genetic“hot spot” 遗传“热点”genetical marker 遗传标记genetical non-disjunction 遗传不分离genetical population 遗传群体genetically heterogeneous 遗传异质的genetically modified organism 基因修饰生物genetics correction 遗传修正genetics of resistance 抗性遗传genetype 基因型genic balance 基因平稳genome allopolyploid基因组异质多倍体genome amplification 基因组扩增genome evolution 基因组进化genome mapping 基因组作图genome project 基因组计划genome rearrangement 基因组重排genome sequencing 基因组测序genomic exclusion 基因组排斥genomic fingerprinting 基因组指纹分析genomic footprinting 基因组足迹分析genomic imprinting 基因组印记genomic instability 基因组不稳固性genomic library 基因组文库genomic walking 基因组步查genotypic frequency 基因型频率genotypic ratio 基因型比值genotypic value 基因型值genotypic variance 基因型方差geographic speciation 地理型新种形成geographical isolation 地理隔离geographical polymorphism 地理多态现象germ layer 胚层germ line 种系germ nucleus 生殖核germ plasm 种质germinal mutation 生殖细胞突变germ-line gene therapy 种系基因医治giant chromosome 巨型染色体global homology 整体同源性global region 全局调剂子globular protein 球蛋白group selection 集团选择growth factor 生长因子GT-AG rule mRNA剪接识别信号规那么gynandromorphy 雌雄嵌合体hairpin loop 发夹环hairpin structure 发夹结构half life 半寿期half sib mating 半同胞交配haplogenotypic 单倍基因型的haploid 单倍体haploidization 单倍体化haplotype 单元型hapostatic gene 下位基因Hardy-Weinberg equilibrium 哈迪-温伯格平稳heat shock gene 热激基因heat sock protein 热激蛋白heavy chain 重链helical structure 螺旋结构。

BinomialLinkFunctions：二项链接功能

beetles killed were noted. The data are in the
following table:
Example (continued)
> beetle<-read.table("BeetleData.txt",header=TRUE)
> head(beetle)
Dose Num.Beetles Num.Killed
(Intercept) -34.935
2.648 -13.19 <2e-16 ***
Dose
19.728
1.487 13.27 <2e-16 ***
--Signif. codes: 0 ‘***’ 0.001 ‘**’ 0.01 ‘*’ 0.05 ‘.’ 0.1 ‘ ’ 1
(Dispersion parameter for binomial family taken to be 1)
yi

i 1
n
e
xi T ˆ
• Logit:
pˆ i
• Probit:
pˆ i ( xiT ˆ )
• C Log Log:
pˆ i 1 exp{ exp[ xiT ˆ ]}
1 e
xi T ˆ
Differences in Link Functions
probLowerlogit <- vector(length=1000)
family = binomial) > summary(logitmodel)
> probitmodel<-glm(cbind(Num.Killed,Num.Beetles-Num.Killed) ~ Dose, data = beetle,

医学未折叠蛋白元件英语

医学未折叠蛋白元件英语The intricate world of medicine has long been shaped by the fundamental principles of biochemistry and molecular biology. At the heart of this dynamic interplay lies the enigmatic realm of unfolded protein elements, a domain that has captivated the attention of researchers and clinicians alike. These unique protein structures, often referred to as intrinsically disordered proteins or IDPs, have emerged as a pivotal area of study in the pursuit of understanding and addressing various medical conditions.Traditionally, the study of proteins has been dominated by the notion that a protein's function is intrinsically linked to its well-defined three-dimensional structure. However, the discovery of IDPs has challenged this conventional wisdom, revealing a remarkable diversity in the ways proteins can adopt and utilize their structural properties to perform a multitude of crucial biological functions. Unlike their folded counterparts, IDPs lack a stable tertiary structure, existing instead as dynamic and flexible ensembles that can adapt to a wide range of environmental conditions and interactions.This structural flexibility endows IDPs with a remarkable versatility, allowing them to participate in a vast array of cellular processes, from signal transduction and transcriptional regulation to protein-protein interactions and cellular signaling pathways. By eschewing the constraints of a fixed structure, IDPs can engage in a dynamic dance of conformational changes, enabling them to bind to multiple targets and perform diverse roles within the complex tapestry of the living cell.The significance of IDPs in the realm of medicine cannot be overstated. These unfolded protein elements have been implicated in a wide range of pathological conditions, from neurodegenerative disorders to cancer and infectious diseases. In the case of neurodegenerative diseases, such as Alzheimer's and Parkinson's, the aggregation and misfolding of IDPs, such as tau and α-synuclein, have been identified as key contributors to the development and progression of these devastating conditions. Understanding the underlying mechanisms that govern the behavior of these unfolded proteins has become a crucial area of research, as it holds the promise of unlocking new therapeutic avenues and strategies for intervention.Similarly, in the field of oncology, IDPs have emerged as pivotal players in the complex landscape of cancer biology. Many cancer-related proteins, such as p53 and Myc, are intrinsically disordered,and their structural flexibility allows them to engage in a dynamic interplay with a diverse array of cellular partners, ultimately influencing the hallmarks of cancer, including uncontrolled cell growth, evasion of apoptosis, and metastatic potential. By targeting these unfolded protein elements, researchers are exploring novel approaches to cancer treatment, seeking to disrupt the delicate balance that sustains the malignant phenotype.Beyond their role in disease pathogenesis, IDPs have also garnered attention for their potential as therapeutic targets and biomarkers. The unique structural and functional properties of these unfolded proteins offer opportunities for the development of targeted interventions, such as small-molecule inhibitors or allosteric modulators, that can selectively engage and modulate their behavior. Additionally, the presence and patterns of IDP expression in various disease states have been investigated as potential diagnostic and prognostic indicators, paving the way for more personalized and effective clinical management strategies.The study of unfolded protein elements in medicine is not without its challenges, however. The inherent complexity and dynamic nature of IDPs pose significant hurdles in terms of structural characterization, functional elucidation, and therapeutic targeting. Traditional structural biology techniques, designed for well-folded proteins, often struggle to capture the nuances of IDP behavior, necessitatingthe development of specialized methods and analytical tools.Despite these challenges, the scientific community has made remarkable strides in advancing our understanding of IDPs and their implications in human health and disease. Cutting-edge technologies, such as advanced spectroscopic techniques, computational modeling, and single-molecule approaches, have enabled researchers to delve deeper into the intricate world of unfolded protein elements, revealing their intricate roles in cellular processes and their potential as therapeutic targets.As the field of IDP research continues to evolve, the promise of unlocking new frontiers in medicine becomes increasingly tangible. By unraveling the mysteries of these unfolded protein elements, scientists and clinicians alike are poised to unveil innovative diagnostic strategies, develop targeted therapies, and ultimately improve the lives of patients suffering from a wide range of medical conditions. The journey ahead is filled with both challenges and opportunities, but the potential impact of this burgeoning field on the future of healthcare is truly transformative.。

Let Dbeanonemptysubsetof R.Onecancheckthateveryelementof D

FORMALIZED MATHEMATICSVolume9,Number3,2001University of BiałystokThe Urysohn LemmaJózef Białas ŁódźUniversity Yatsuka Nakamura Shinshu UniversityNaganoSummary.This article is the third part of a paper proving the funda-mental Urysohn Theorem concerning the existence of a real valued continuousfunction on a normal topological space.The paper is divided into two parts.Intheﬁrst part,we describe the construction of the function solving thesis of theUrysohn Lemma.The second part contains the proof of the Urysohn Lemma innormal space and the proof of the same theorem for compact space.MML Identiﬁer:URYSOHN3.The notation and terminology used here have been introduced in the following papers:[15],[10],[7],[8],[4],[1],[9],[6],[12],[16],[17],[13],[14],[2],[3],[11], and[5].Let D be a non empty subset of R.One can check that every element of D is real.One can prove the following proposition(1)Let T be a non empty topological space.Suppose T is a T4space.LetA,B be subsets of T.Suppose A=∅and A is closed and B is closed andA∩B=∅.Let n be a natural number.Then there exists a function G fromdyadic(n)into2the carrier of T such that for all elements r1,r2of dyadic(n)if r1<r2,then G(r1)is open and G(r2)is open and G(r1)⊆G(r2)andA⊆G(0)and B=ΩT\G(1).Let T be a non empty topological space,let A,B be subsets of T,and let n bea natural number.Let us assume that T is a T4space and A=∅and A is closedand B is closed and A∩B=∅.A function from dyadic(n)into2the carrier of T is said to be a drizzle of A,B,n if it satisﬁes the condition(Def.1).(Def.1)Let r1,r2be elements of dyadic(n).Suppose r1<r2.Then it(r1)is open and it(r2)is open and it(r1)⊆it(r2)and A⊆it(0)and B=ΩT\it(1).631c 2001University of BiałystokISSN1426–2630632józef białas and yatsuka nakamuraOne can prove the following propositions:(2)Let T be a non empty topological space.Suppose T is a T4space.LetA,B be subsets of T.Suppose A=∅and A is closed and B is closed andA∩B=∅.Let n be a natural number and D be a drizzle of A,B,n.Then A⊆D(0)and B=ΩT\D(1).(3)Let T be a non empty topological space.Suppose T is a T4space.LetA,B be subsets of T.Suppose A=∅and A is closed and B is closed andA∩B=∅.Let n be a natural number and G be a drizzle of A,B,n.Then there exists a drizzle F of A,B,n+1such that for every element rof dyadic(n+1)if r∈dyadic(n),then F(r)=G(r).Let A,B be non empty sets,let F be a function from N into A˙→B,and let n be a natural number.Then F(n)is a partial function from A to B.Next we state the proposition(4)Let T be a non empty topological space,A,B be subsets of T,andn be a natural number.Then every drizzle of A,B,n is an element ofDYADIC˙→2the carrier of T.Let A,B be non empty sets,let F be a function from N into A˙→B,and let n be a natural number.Then F(n)is an element of A˙→B.One can prove the following proposition(5)Let T be a non empty topological space.Suppose T is a T4space.LetA,B be subsets of T.Suppose A=∅and A is closed and B is closedand A∩B=∅.Then there exists a sequence F of partial functions fromDYADIC into2the carrier of T such that for every natural number n holdsF(n)is a drizzle of A,B,n and for every element r of dom F(n)holdsF(n)(r)=F(n+1)(r).Let T be a non empty topological space and let A,B be subsets of T.Let us assume that T is a T4space and A=∅and A is closed and B is closed and A∩B=∅.A sequence of partial functions from DYADIC into2the carrier of T is said to be a rain of A,B if it satisﬁes the condition(Def.2).(Def.2)Let n be a natural number.Then it(n)is a drizzle of A,B,n and for every element r of dom it(n)holds it(n)(r)=it(n+1)(r).Let x be a real number.Let us assume that x∈DYADIC.The functor InfDyadic x yields a natural number and is deﬁned by:(Def.3)x∈dyadic(0)iﬀInfDyadic x=0and for every natural number n such that x∈dyadic(n+1)and x/∈dyadic(n)holds InfDyadic x=n+1.The following propositions are true:(6)For every real number x such that x∈DYADIC holds x∈dyadic(InfDyadic x).(7)For every real number x such that x∈DYADIC and for every naturalnumber n such that InfDyadic x n holds x∈dyadic(n).the urysohn lemma633(8)For every real number x such that x∈DYADIC and for every naturalnumber n such that x∈dyadic(n)holds InfDyadic x n.(9)Let T be a non empty topological space.Suppose T is a T4space.LetA,B be subsets of T.Suppose A=∅and A is closed and B is closedand A∩B=∅.Let G be a rain of A,B and x be a real number.Ifx∈DYADIC,then for every natural number n holds G(InfDyadic x)(x)=G(InfDyadic x+n)(x).(10)Let T be a non empty topological space.Suppose T is a T4space.LetA,B be subsets of T.Suppose A=∅and A is closed and B is closed andA∩B=∅.Let G be a rain of A,B and x be a real number.Supposex∈DYADIC.Then there exists an element y of2the carrier of T such thatfor every natural number n if x∈dyadic(n),then y=G(n)(x).(11)Let T be a non empty topological space.Suppose T is a T4space.LetA,B be subsets of T.Suppose A=∅and A is closed and B is closed andA∩B=∅.Let G be a rain of A,B.Then there exists a function F fromDOM into2the carrier of T such that for every real number x holds(i)if x∈R<0,then F(x)=∅,(ii)if x∈R>1,then F(x)=the carrier of T,and(iii)if x∈DYADIC,then for every natural number n such that x∈dyadic(n)holds F(x)=G(n)(x).Let T be a non empty topological space and let A,B be subsets of T.Let us assume that T is a T4space and A=∅and A is closed and B is closed and A∩B=∅.Let R be a rain of A,B.The functor Tempest R yielding a function from DOM into2the carrier of T is deﬁned by the condition(Def.4).(Def.4)Let x be a real number such that x∈DOM.Then(i)if x∈R<0,then(Tempest R)(x)=∅,(ii)if x∈R>1,then(Tempest R)(x)=the carrier of T,and(iii)if x∈DYADIC,then for every natural number n such that x∈dyadic(n)holds(Tempest R)(x)=R(n)(x).Let X be a non empty set,let T be a topological space,let F be a function from X into2the carrier of T,and let x be an element of X.Then F(x)is a subset of T.One can prove the following three propositions:(12)Let T be a non empty topological space and A,B be subsets of T.Suppose T is a T4space and A=∅and A is closed and B is closed andA∩B=∅.Let G be a rain of A,B and r be a real number.If r∈DOM,then for every subset C of T such that C=(Tempest G)(r)holds C isopen.(13)Let T be a non empty topological space and A,B be subsets of T.Suppose T is a T4space and A=∅and A is closed and B is closed andA∩B=∅.Let G be a rain of A,B and r1,r2be real numbers.Suppose634józef białas and yatsuka nakamurar1∈DOM and r2∈DOM and r1<r2.Let C be a subset of T.IfC=(Tempest G)(r1),then C⊆(Tempest G)(r2).(14)Let T be a non empty topological space,A,B be subsets of T,G be arain of A,B,and p be a point of T.Then there exists a subset R of R suchthat for every set x holds x∈R if and only if the following conditions aresatisﬁed:(i)x∈DYADIC,and(ii)for every real number s such that s=x holds p/∈(Tempest G)(s).Let T be a non empty topological space,let A,B be subsets of T,let R bea rain of A,B,and let p be a point of T.The functor Rainbow(p,R)yielding asubset of R is deﬁned by:(Def.5)For every set x holds x∈Rainbow(p,R)iﬀx∈DYADIC and for every real number s such that s=x holds p/∈(Tempest R)(s).Let T,S be non empty topological spaces,let F be a function from the carrier of T into the carrier of S,and let p be a point of T.Then F(p)is a point of S.One can prove the following propositions:(15)Let T be a non empty topological space,A,B be subsets of T,G be arain of A,B,and p be a point of T.Then Rainbow(p,G)⊆DYADIC.(16)Let T be a non empty topological space,A,B be subsets of T,and Rbe a rain of A,B.Then there exists a map F from T into R1such thatfor every point p of T holdsif Rainbow(p,R)=∅,then F(p)=0and for every non empty subset S ofR such that S=Rainbow(p,R)holds F(p)=sup S.Let T be a non empty topological space,let A,B be subsets of T,and let R be a rain of A,B.The functor Thunder R yielding a map from T into R1is deﬁned by the condition(Def.6).(Def.6)Let p be a point of T.Then if Rainbow(p,R)=∅,then(Thunder R)(p)= 0and for every non empty subset S of R such that S=Rainbow(p,R)holds(Thunder R)(p)=sup S.Let T be a non empty topological space,let F be a map from T into R1, and let p be a point of T.Then F(p)is a real number.One can prove the following propositions:(17)Let T be a non empty topological space,A,B be subsets of T,G be arain of A,B,p be a point of T,and S be a non empty subset of R.SupposeS=Rainbow(p,G).Letℓ1be an extended real number.Ifℓ1=1,then sup S and sup S ℓ1.R(18)Let T be a non empty topological space.Suppose T is a T4space.LetA,B be subsets of T.Suppose A=∅and A is closed and B is closed andA∩B=∅.Let G be a rain of A,B,r be an element of DOM,and p be athe urysohn lemma635point of T.If(Thunder G)(p)<r,then p∈(Tempest G)(r).(19)Let T be a non empty topological space.Suppose T is a T4space.LetA,B be subsets of T.Suppose A=∅and A is closed and B is closedand A∩B=∅.Let G be a rain of A,B and r be a real number.Supposer∈DYADIC∪R>1and0<r.Let p be a point of T.If p∈(Tempest G)(r),then(Thunder G)(p) r.(20)Let T be a non empty topological space.Suppose T is a T4space.LetA,B be subsets of T.Suppose A=∅and A is closed and B is closedand A∩B=∅.Let G be a rain of A,B,n be a natural number,and r1be an element of DOM.If0<r1,then for every point p of T such thatr1<(Thunder G)(p)holds p/∈(Tempest G)(r1).(21)Let T be a non empty topological space.Suppose T is a T4space.LetA,B be subsets of T.Suppose A=∅and A is closed and B is closed andA∩B=∅.Let G be a rain of A,B.Then(i)Thunder G is continuous,and(ii)for every point x of T holds0 (Thunder G)(x)and(Thunder G)(x) 1and if x∈A,then(Thunder G)(x)=0and if x∈B,then(Thunder G)(x)=1.(22)Let T be a non empty topological space.Suppose T is a T4space.LetA,B be subsets of T.Suppose A=∅and A is closed and B is closed andA∩B=∅.Then there exists a map F from T into R1such that(i)F is continuous,and(ii)for every point x of T holds0 F(x)and F(x) 1and if x∈A,then F(x)=0and if x∈B,then F(x)=1.(23)Let T be a non empty topological space.Suppose T is a T4space.LetA,B be subsets of T.Suppose A is closed and B is closed and A∩B=∅.Then there exists a map F from T into R1such that(i)F is continuous,and(ii)for every point x of T holds0 F(x)and F(x) 1and if x∈A,then F(x)=0and if x∈B,then F(x)=1.(24)Let T be a non empty topological space.Suppose T is a T2space andcompact.Let A,B be subsets of T.Suppose A is closed and B is closedand A∩B=∅.Then there exists a map F from T into R1such that(i)F is continuous,and(ii)for every point x of T holds0 F(x)and F(x) 1and if x∈A,then F(x)=0and if x∈B,then F(x)=1.References[1]Grzegorz Bancerek.The fundamental properties of natural numbers.Formalized Mathe-matics,1(1):41–46,1990.636józef białas and yatsuka nakamura[2]Józef Białas.Inﬁmum and supremum of the set of real numbers.Measure theory.For-malized Mathematics,2(1):163–171,1991.[3]Józef Białas.Series of positive real numbers.Measure theory.Formalized Mathematics,2(1):173–183,1991.[4]Józef Białas.Properties of the intervals of real numbers.Formalized Mathematics,3(2):263–269,1992.[5]Józef Białas and Yatsuka Nakamura.Dyadic numbers and T4topological spaces.Forma-lized Mathematics,5(3):361–366,1996.[6]Leszek Borys.Paracompact and metrizable spaces.Formalized Mathematics,2(4):481–485,1991.[7]Czesław Byliński.Functions and their basic properties.Formalized Mathematics,1(1):55–65,1990.[8]Czesław Byliński.Functions from a set to a set.Formalized Mathematics,1(1):153–164,1990.[9]Czesław Byliński.Partial functions.Formalized Mathematics,1(2):357–367,1990.[10]Agata Darmochwał.Compact spaces.Formalized Mathematics,1(2):383–386,1990.[11]Agata Darmochwałand Yatsuka Nakamura.Metric spaces as topological spaces-funda-mental concepts.Formalized Mathematics,2(4):605–608,1991.[12]Beata Padlewska and Agata Darmochwał.Topological spaces and continuous functions.Formalized Mathematics,1(1):223–230,1990.[13]Beata Perkowska.Functional sequence from a domain to a domain.Formalized Mathe-matics,3(1):17–21,1992.[14]Zinaida Trybulec.Properties of subsets.Formalized Mathematics,1(1):67–71,1990.[15]Zinaida Trybulec and HalinaŚwięczkowska.Boolean properties of sets.Formalized Ma-thematics,1(1):17–23,1990.[16]Edmund Woronowicz.Relations and their basic properties.Formalized Mathematics,1(1):73–83,1990.[17]Edmund Woronowicz.Relations deﬁned on sets.Formalized Mathematics,1(1):181–186,1990.Received February16,2001。

Estimating Class Priors in Domain Adaptation for Word Sense Disambiguation

Estimating Class Priors in Domain Adaptation for Word Sense DisambiguationYee Seng Chan and Hwee Tou NgDepartment of Computer ScienceNational University of Singapore3Science Drive2,Singapore117543chanys,nght@.sgAbstractInstances of a word drawn from differentdomains may have different sense priors(the proportions of the different senses ofa word).This in turn affects the accuracyof word sense disambiguation(WSD)sys-tems trained and applied on different do-mains.This paper presents a method toestimate the sense priors of words drawnfrom a new domain,and highlights the im-portance of using well calibrated probabil-ities when performing these estimations.By using well calibrated probabilities,weare able to estimate the sense priors effec-tively to achieve signiﬁcant improvementsin WSD accuracy.1IntroductionMany words have multiple meanings,and the pro-cess of identifying the correct meaning,or sense of a word in context,is known as word sense disambiguation(WSD).Among the various ap-proaches to WSD,corpus-based supervised ma-chine learning methods have been the most suc-cessful to date.With this approach,one would need to obtain a corpus in which each ambiguous word has been manually annotated with the correct sense,to serve as training data.However,supervised WSD systems faced an important issue of domain dependence when using such a corpus-based approach.To investigate this, Escudero et al.(2000)conducted experiments using the DSO corpus,which contains sentences drawn from two different corpora,namely Brown Corpus(BC)and Wall Street Journal(WSJ).They found that training a WSD system on one part(BC or WSJ)of the DSO corpus and applying it to the other part can result in an accuracy drop of12% to19%.One reason for this is the difference in sense priors(i.e.,the proportions of the different senses of a word)between BC and WSJ.For in-stance,the noun interest has these6senses in the DSO corpus:sense1,2,3,4,5,and8.In the BC part of the DSO corpus,these senses occur with the proportions:34%,9%,16%,14%,12%,and 15%.However,in the WSJ part of the DSO cor-pus,the proportions are different:13%,4%,3%, 56%,22%,and2%.When the authors assumed they knew the sense priors of each word in BC and WSJ,and adjusted these two datasets such that the proportions of the different senses of each word were the same between BC and WSJ,accuracy im-proved by9%.In another work,Agirre and Mar-tinez(2004)trained a WSD system on data which was automatically gathered from the Internet.The authors reported a14%improvement in accuracy if they have an accurate estimate of the sense pri-ors in the evaluation data and sampled their train-ing data according to these sense priors.The work of these researchers showed that when the domain of the training data differs from the domain of the data on which the system is applied,there will be a decrease in WSD accuracy.To build WSD systems that are portable across different domains,estimation of the sense priors (i.e.,determining the proportions of the differ-ent senses of a word)occurring in a text corpus drawn from a domain is important.McCarthy et al.(2004)provided a partial solution by describing a method to predict the predominant sense,or the most frequent sense,of a word in a ing the noun interest as an example,their method will try to predict that sense1is the predominant sense in the BC part of the DSO corpus,while sense4 is the predominant sense in the WSJ part of thecorpus.In our recent work(Chan and Ng,2005b),we directly addressed the problem by applying ma-chine learning methods to automatically estimate the sense priors in the target domain.For instance, given the noun interest and the WSJ part of the DSO corpus,we attempt to estimate the propor-tion of each sense of interest occurring in WSJ and showed that these estimates help to improve WSD accuracy.In our work,we used naive Bayes as the training algorithm to provide posterior proba-bilities,or class membership estimates,for the in-stances in the target domain.These probabilities were then used by the machine learning methods to estimate the sense priors of each word in the target domain.However,it is known that the posterior proba-bilities assigned by naive Bayes are not reliable,or not well calibrated(Domingos and Pazzani,1996). These probabilities are typically too extreme,of-ten being very near0or1.Since these probabil-ities are used in estimating the sense priors,it is important that they are well calibrated.In this paper,we explore the estimation of sense priors byﬁrst calibrating the probabilities from naive Bayes.We also propose using probabilities from another algorithm(logistic regression,which already gives well calibrated probabilities)to esti-mate the sense priors.We show that by using well calibrated probabilities,we can estimate the sense priors more ing these estimates im-proves WSD accuracy and we achieve results that are signiﬁcantly better than using our earlier ap-proach described in(Chan and Ng,2005b).In the following section,we describe the algo-rithm to estimate the sense priors.Then,we de-scribe the notion of being well calibrated and dis-cuss why using well calibrated probabilities helps in estimating the sense priors.Next,we describe an algorithm to calibrate the probability estimates from naive Bayes.Then,we discuss the corpora and the set of words we use for our experiments before presenting our experimental results.Next, we propose using the well calibrated probabilities of logistic regression to estimate the sense priors, and perform signiﬁcance tests to compare our var-ious results before concluding.2Estimation of PriorsTo estimate the sense priors,or a priori proba-bilities of the different senses in a new dataset,we used a confusion matrix algorithm(Vucetic and Obradovic,2001)and an EM based algorithm (Saerens et al.,2002)in(Chan and Ng,2005b). Our results in(Chan and Ng,2005b)indicate that the EM based algorithm is effective in estimat-ing the sense priors and achieves greater improve-ments in WSD accuracy compared to the confu-sion matrix algorithm.Hence,to estimate the sense priors in our current work,we use the EM based algorithm,which we describe in this sec-tion.2.1EM Based AlgorithmMost of this section is based on(Saerens et al., 2002).Assume we have a set of labeled data D with n classes and a set of N independent instancesfrom a new data set.The likelihood of these N instances can be deﬁned as:(1) Assuming the within-class densities, i.e.,the probabilities of observing given the class,do not change from the training set D to the new data set,we can deﬁne:.To determine the a priori probability estimates of the new data set that will max-imize the likelihood of(1)with respect to, we can apply the iterative procedure of the EM al-gorithm.In effect,through maximizing the likeli-hood of(1),we obtain the a priori probability es-timates as a by-product.Let us now deﬁne some notations.When we apply a classiﬁer trained on D on an instance drawn from the new data set D,we get ,which we deﬁne as the probability of instance being classiﬁed as class by the clas-siﬁer trained on D.Further,let us deﬁneas the a priori probabilities of class in D.This can be estimated by the class frequency of in D.We also deﬁne and as es-timates of the new a priori and a posteriori proba-bilities at step s of the iterative EM procedure.As-suming we initialize,then for each instance in D and each class,the EMalgorithm provides the following iterative steps:(3) where Equation(2)represents the expectation E-step,Equation(3)represents the maximization M-step,and N represents the number of instances in D.Note that the probabilities andin Equation(2)will stay the same through-out the iterations for each particular instance and class.The new a posteriori probabilities at step s in Equation(2)are simply the a posteriori probabilities in the conditions of the labeled data,,weighted by the ratio of the new priors to the old priors. The denominator in Equation(2)is simply a nor-malizing factor.The a posteriori and a priori proba-bilities are re-estimated sequentially dur-ing each iteration s for each new instance and each class,until the convergence of the esti-mated probabilities.This iterative proce-dure will increase the likelihoodof(1)at each step.2.2Using A Priori EstimatesIf a classiﬁer estimates posterior class probabili-ties when presented with a new instance from D,it can be directly adjusted according to estimated a priori probabilities on D:(5) where S=denotes the set of poste-rior probability values for class,and S denotes the posterior probability of class as-signed by the classiﬁer for instance.Based on,we can imagine that we have bins,where each bin is associated with a speciﬁc value.Now,distribute all the instances in the new dataset D into the bins according to their posterior probabilities.Let B,for,denote the set of instances in bin. Note that B B B=. Now,let denote the proportion of instances with true class label in B.Given a well calibrated algorithm,by deﬁnition and Equation(5) can be rewritten as:B BReplace with mevaluation on the nouns of SENSEV AL-2English lexical sample task(Kilgarriff,2001).In another recent evaluation on the nouns of SENSEV AL-2English all-words task(Chan and Ng,2005a), promising results were also achieved using exam-ples gathered from parallel texts.Due to the po-tential of parallel texts in addressing the issue of scalability,we also drew training data for our ear-lier sense priors estimation experiments(Chan and Ng,2005b)from parallel texts.In addition,our parallel texts training data represents a natural do-main difference with the test data of SENSEV AL-2English lexical sample task,of which91%is drawn from the British National Corpus(BNC). As part of our experiments,we followed the ex-perimental setup of our earlier work(Chan and Ng,2005b),using the same6English-Chinese parallel corpora(Hong Kong Hansards,Hong Kong News,Hong Kong Laws,Sinorama,Xinhua News,and English translation of Chinese Tree-bank),available from Linguistic Data Consortium. To gather training examples from these parallel texts,we used the approach we described in(Ng et al.,2003)and(Chan and Ng,2005b).We then evaluated our estimation of sense priors on the nouns of SENSEV AL-2English lexical sam-ple task,similar to the evaluation we conducted in(Chan and Ng,2005b).Since the test data for the nouns of SENSEV AL-3English lexical sample task(Mihalcea et al.,2004)were also drawn from BNC and represented a difference in domain from the parallel texts we used,we also expanded our evaluation to these SENSEV AL-3nouns.4.3Choice of WordsResearch by(McCarthy et al.,2004)highlighted that the sense priors of a word in a corpus depend on the domain from which the corpus is drawn.A change of predominant sense is often indicative of a change in domain,as different corpora drawn from different domains usually give different pre-dominant senses.For example,the predominant sense of the noun interest in the BC part of the DSO corpus has the meaning“a sense of concern with and curiosity about someone or something”. In the WSJ part of the DSO corpus,the noun in-terest has a different predominant sense with the meaning“aﬁxed charge for borrowing money”, reﬂecting the business andﬁnance focus of the WSJ corpus.Estimation of sense priors is important when there is a signiﬁcant change in sense priors be-tween the training and target dataset,such as when there is a change in domain between the datasets. Hence,in our experiments involving the DSO cor-pus,we focused on the set of nouns and verbs which had different predominant senses between the BC and WSJ parts of the corpus.This gave us a set of37nouns and28verbs.For experi-ments involving the nouns of SENSEV AL-2and SENSEV AL-3English lexical sample task,we used the approach we described in(Chan and Ng, 2005b)of sampling training examples from the parallel texts using the natural(empirical)distri-bution of examples in the parallel texts.Then,we focused on the set of nouns having different pre-dominant senses between the examples gathered from parallel texts and the evaluation data for the two SENSEV AL tasks.This gave a set of6nouns for SENSEV AL-2and9nouns for SENSEV AL-3.For each noun,we gathered a maximum of500 parallel text examples as training data,similar to what we had done in(Chan and Ng,2005b).5Experimental ResultsSimilar to our previous work(Chan and Ng, 2005b),we used the supervised WSD approach described in(Lee and Ng,2002)for our exper-iments,using the naive Bayes algorithm as our classiﬁer.Knowledge sources used include parts-of-speech,surrounding words,and local colloca-tions.This approach achieves state-of-the-art ac-curacy.All accuracies reported in our experiments are micro-averages over all test examples.In(Chan and Ng,2005b),we used a multiclass naive Bayes classiﬁer(denoted by NB)for each word.Following this approach,we noted the WSD accuracies achieved without any adjustment,in the column L under NB in Table1.The predictions of these naive Bayes classiﬁers are then used in Equation(2)and(3)to estimate the sense priors,before being adjusted by these esti-mated sense priors based on Equation(4).The re-sulting WSD accuracies after adjustment are listed in the column EM in Table1,representing the WSD accuracies achievable by following the ap-proach we described in(Chan and Ng,2005b). Next,we used the one-against-all approach to reduce each multiclass problem into a set of binary class problems.We trained a naive Bayes classiﬁer for each binary problem and calibrated the prob-abilities from these binary classiﬁers.The WSDClassiﬁer NB NBcalL EM EMDSO nouns46.145.851.146.748.749.5SE2nouns62.462.363.553.955.758.8True L EM L11.6 5.3(45.7%)10.3 3.9(37.9%)3.0 1.2(40.0%)3.7 3.0(81.1%) Table2:Relative accuracy improvement based on cali-brated probabilities.accuracies of these calibrated naive Bayes classi-ﬁers(denoted by NBcal)are given in the column L under NBcal.1The predictions of these classiﬁers are then used to estimate the sense priors, before being adjusted by these estimates based on Equation(4).The resulting WSD accuracies after adjustment are listed in column EM in Table 1.The results show that calibrating the proba-bilities improves WSD accuracy.In particular, EM achieves the highest accuracy among the methods described so far.To provide a basis for comparison,we also adjusted the calibrated prob-abilities by the true sense priors of the test data.The increase in WSD accuracy thus ob-tained is given in the column True L in Table 2.Note that this represents the maximum possi-ble increase in accuracy achievable provided we know these true sense priors.In the col-umn EM in Table2,we list the increase in WSD accuracy when adjusted by the sense pri-ors which were automatically estimated us-ing the EM procedure.The relative improvements obtained with using(compared against us-ing)are given as percentages in brackets. As an example,according to Table1for the DSO verbs,EM gives an improvement of49.5% 46.9%=2.6%in WSD accuracy,and the rela-tive improvement compared to using the true sense priors is2.6/10.3=25.2%,as shown in Table2.Dataset EMDSO nouns0.586DSO verbs0.602SE2nouns0.307SE3nouns0.6321Though not shown,we also calculated the accuracies of these binary classiﬁers without calibration,and found them to be similar to the accuracies of the multiclass naive Bayes shown in the column L under NB in Table1.Method comparison DSO verbs SE3nouns NBcal-EM vs.NB-EMNBcal-EM vs.NB-EMNBcal-EM vs.NBcal-EMTable4:Paired t-tests between the various methods for the4datasets.sense priors.To gauge how well the sense pri-ors are estimated,we measure the KL divergence between the true sense priors and the sense pri-ors estimated by using the predictions of(uncal-ibrated)multiclass naive Bayes,calibrated naive Bayes,and logistic regression.These results are shown in Table3and the column EM shows that using the predictions of logistic regression to estimate sense priors consistently gives the lowest KL divergence.Results of the KL divergence test motivate us to use sense priors estimated by logistic regression on the predictions of the naive Bayes classiﬁers. To elaborate,weﬁrst use the probability estimates of logistic regression in Equations(2) and(3)to estimate the sense priors.These estimates and the predictions of the calibrated naive Bayes classiﬁer are then used in Equation(4)to obtain the adjusted predictions. The resulting WSD accuracy is shown in the col-umn EM under NBcal in Table1.Corre-sponding results when the predictionsof the multiclass naive Bayes is used in Equation (4),are given in the column EM under NB. The relative improvements against using the true sense priors,based on the calibrated probabilities, are given in the column EM L in Table2. The results show that the sense priors provided by logistic regression are in general effective in fur-ther improving the results.In the case of DSO nouns,this improvement is especially signiﬁcant.6.2Signiﬁcance TestPaired t-tests were conducted to see if one method is signiﬁcantly better than another.The t statistic of the difference between each test instance pair is computed,giving rise to a p value.The results of signiﬁcance tests for the various methods on the4 datasets are given in Table4,where the symbols “”,“”,and“”correspond to p-value0.05, (0.01,0.05],and0.01respectively.The methods in Table4are represented in the form a1-a2,where a1denotes adjusting the pre-dictions of which classiﬁer,and a2denotes how the sense priors are estimated.As an example,NBcal-EM speciﬁes that the sense priors es-timated by logistic regression is used to adjust thepredictions of the calibrated naive Bayes classiﬁer, and corresponds to accuracies in column EM under NBcal in Table1.Based on the signiﬁ-cance tests,the adjusted accuracies of EM and EM in Table1are signiﬁcantly better than their respective unadjusted L accuracies,indicat-ing that estimating the sense priors of a new do-main via the EM approach presented in this paper signiﬁcantly improves WSD accuracy compared to just using the sense priors from the old domain. NB-EM represents our earlier approach in (Chan and Ng,2005b).The signiﬁcance tests show that our current approach of using calibrated naive Bayes probabilities to estimate sense priors, and then adjusting the calibrated probabilities by these estimates(NBcal-EM)performs sig-niﬁcantly better than NB-EM(refer to row2 of Table4).For DSO nouns,though the results are similar,the p value is a relatively low0.06. Using sense priors estimated by logistic regres-sion further improves performance.For example, row1of Table4shows that adjusting the pre-dictions of multiclass naive Bayes classiﬁers by sense priors estimated by logistic regression(NB-EM)performs signiﬁcantly better than using sense priors estimated by multiclass naive Bayes (NB-EM).Finally,using sense priors esti-mated by logistic regression to adjust the predic-tions of calibrated naive Bayes(NBcal-EM) in general performs signiﬁcantly better than most other methods,achieving the best overall perfor-mance.In addition,we implemented the unsupervised method of(McCarthy et al.,2004),which calcu-lates a prevalence score for each sense of a word to predict the predominant sense.As in our earlier work(Chan and Ng,2005b),we normalized the prevalence score of each sense to obtain estimated sense priors for each word,which we then usedto adjust the predictions of our naive Bayes classi-ﬁers.We found that the WSD accuracies obtained with the method of(McCarthy et al.,2004)are on average1.9%lower than our NBcal-EM method,and the difference is statistically signiﬁ-cant.7ConclusionDifferences in sense priors between training and target domain datasets will result in a loss of WSD accuracy.In this paper,we show that using well calibrated probabilities to estimate sense priors is important.By calibrating the probabilities of the naive Bayes algorithm,and using the probabilities given by logistic regression(which is already well calibrated),we achieved signiﬁcant improvements in WSD accuracy over previous approaches. ReferencesEneko Agirre and David Martinez.2004.Unsuper-vised WSD based on automatically retrieved exam-ples:The importance of bias.In Proc.of EMNLP04. Miriam Ayer,H.D.Brunk,G.M.Ewing,W.T.Reid, and Edward Silverman.1955.An empirical distri-bution function for sampling with incomplete infor-mation.Annals of Mathematical Statistics,26(4). Yee Seng Chan and Hwee Tou Ng.2005a.Scaling up word sense disambiguation via parallel texts.In Proc.of AAAI05.Yee Seng Chan and Hwee Tou Ng.2005b.Word sense disambiguation with distribution estimation.In Proc.of IJCAI05.Pedro Domingos and Michael Pazzani.1996.Beyond independence:Conditions for the optimality of the simple Bayesian classiﬁer.In Proc.of ICML-1996. Gerard Escudero,Lluis Marquez,and German Rigau.2000.An empirical study of the domain dependence of supervised word sense disambiguation systems.In Proc.of EMNLP/VLC00.Adam Kilgarriff.2001.English lexical sample task description.In Proc.of SENSEVAL-2.Yoong Keok Lee and Hwee Tou Ng.2002.An empir-ical evaluation of knowledge sources and learning algorithms for word sense disambiguation.In Proc.of EMNLP02.Diana McCarthy,Rob Koeling,Julie Weeds,and John Carroll.2004.Finding predominant word senses in untagged text.In Proc.of ACL04.Rada Mihalcea,Timothy Chklovski,and Adam Kilgar-riff.2004.The senseval-3english lexical sample task.In Proc.of SENSEVAL-3.George ler,Martin Chodorow,Shari Landes, Claudia Leacock,and Robert G.Thomas.1994.Using a semantic concordance for sense identiﬁca-tion.In Proc.of ARPA Human Language Technol-ogy Workshop.Andrew Y.Ng and Michael I.Jordan.2001.On dis-criminative vs.generative classiﬁers:A comparison of logistic regression and naive Bayes.In Proc.of NIPS14.Hwee Tou Ng and Hian Beng Lee.1996.Integrating multiple knowledge sources to disambiguate word sense:An exemplar-based approach.In Proc.of ACL96.Hwee Tou Ng,Bin Wang,and Yee Seng Chan.2003.Exploiting parallel texts for word sense disambigua-tion:An empirical study.In Proc.of ACL03. Alexandru Niculescu-Mizil and Rich Caruana.2005.Predicting good probabilities with supervised learn-ing.In Proc.of ICML05.Tim Robertson,F.T.Wright,and R.L.Dykstra.1988.Chapter1.Isotonic Regression.In Order Restricted Statistical Inference.John Wiley&Sons.Marco Saerens,Patrice Latinne,and Christine De-caestecker.2002.Adjusting the outputs of a clas-siﬁer to new a priori probabilities:A simple proce-dure.Neural Computation,14(1).Slobodan Vucetic and Zoran Obradovic.2001.Clas-siﬁcation on data with biased class distribution.In Proc.of ECML01.Bianca Zadrozny and Charles Elkan.2002.Trans-forming classiﬁer scores into accurate multiclass probability estimates.In Proc.of KDD02.Jian Zhang and Yiming Yang.2004.Probabilistic score estimation with piecewise logistic regression.In Proc.of ICML04.。

Multiple-valued Logic

Multiple-valued LogicPeter H.Schmitt Daniele MundiciLotﬁZadeh(editors)Dagstuhl-Seminar-Report(Seminar9744)27.10.–31.10.1997This Dagstuhl Seminar brought together approximately60researchers cover-ing the full spectrum of the current research on many-valued logics,ranging from mathematical foundations to computational issues and applications.Sev-eral young researchers could attend this meeting,and have fruitful interactions with more established researchers from Japan,South and North America,and from an exceptionally large number of European countries.Their contributions may be classiﬁed under the following four headings.Enhancement of the theoretical basis.Despite its long tradition,work on foundational issues in many-valued logics still spawns new and thrilling prob-lems and results.The rich and intriguing properties of the algebraic counterparts of many-valued logic should beﬁrstly mentioned in this context.This algebraic perspective was strongly represented in this seminar.In the same spirit,albeit in a diﬀerent setting,several talks dealt with fuzzy set theory,and their relations with rule based control.Automated deduction:theory and tools.As a focal point in thisﬁeld one must also mention the current research on complete and sound proof systems –in particular for inﬁnitely-valued logics.Two notable examples are given by L ukasiewicz logic and by product logic.As amply discussed during the Dagstuhl seminar,the calculi corresponding to these logics require far reaching general-izations of the classical techniques arising from Hilbert-style systems,Gentzen systems and resolution.A recurring theme in thisﬁeld is the use of formulas with regular sets of signs.Modelling and reasoning with incomplete and uncertain knowledge. Many-valued calculi are often encountered,for instance,in possibility theory and possibilistic logic.They provide a natural framework for manipulating preference criteria between various interpretations.They alsoﬁnd use in clarifying many entrenched situations in non-monotonic reasoning.In this context we should also mention such topics as the logical manipulation of uncertainty factors,which were the main concern of a number of talks in the Dagstuhl meeting.Applications.Applications of many-valued logics–both in the inﬁnitely-valued and in theﬁnitely-valued case–are an important source of motivation for future research.During this seminar important talks focused on applications in hardware design and veriﬁcation,unit commitment in power systems,and in biomedical engineering.This Seminar was also a workshop/conference in the COST Action#15on “Many-valued Logics for Computer Science Applications”,the only existing Eu-ropean Action on Computer Science issues.One of the objectives of this Action was the dissemination of knowledge accumulated and produced within the project to the worldwide scientiﬁc community outside the COST action itself.This objective has been very successfully accomplished with this Dagstuhl seminar.Daniele MundiciPeter H.Schmitt2Abstracts of the TalksIn the order in which the talks were given.W alter Carnielli–Non-deterministic Semantics5 Matthias Baaz–Analytic Calculi for Many-valued Logics5Hiroakira Ono–Many-valued Logics as Logics without the Contraction Rule6Reiner H¨a hnle–Proof Theory of Many-valued Logic and Hardware Design7Gonzalo Escalada-Imaz–Determining the Truth Degree in Real Time Settings7Peter Vojt´aˇs–Many-valued Logic Programming and Abduction8Rasim Egri–A New Fuzzy Approach to Unit Commitment in Power Sys-tems9Hans J¨u rgen Ohlbach–How to Augment a Logical System with a Boolean Algebra Component9Christian Ferm¨u ller–Finite-valued Logics and Classical Proof Theory10Agata Ciabattoni–Cut-free Proof Systems for Logics of Weak Excluded Middle10Ewa Orlowska–Many-valued Substitutivity Principles11 Felip Many`a–Solving the SAT-problem in Regular CNF-formulas11 Siegfried Weber–Conditional Objects Based on MV-algebras12 Ulrich H¨o hle–Singletons and Fuzzy Partitions12 Antonio Di Nola–One Chain Generated Varieties of MV-algebras13Zbigniew Stachniak–From Inferentially and Referentially Finitely-valued Systems to Resolution14Dirk Van Heule and Albert Hoogewijs–The Partial Predicate Cal-culus.A Three-valued Object Logic for the Theorem Prover Isabelle15Erik Rosenthal–A Linear Resolution Rule for Annotated Logics163Petr H´a jek–Takeuti-Titani Logic Revisited16Marc Roubens–Some Basic Fuzzy Set Algebraic Operations Revisted17 Bernard de Baets–Residuation in Fuzzy Set Theory18 Radko Mesiar–Universal Operations in Fuzzy Logic19 Jeffrey Paris–Semantics for Fuzzy Logic19 Patrik Eklund–What is the Role of Logic in Biomedical Engineering?20 Esko Turunen–BL-algebras of Basic Fuzzy Logic21 Costas A.Drossos–Non-standard Methods in Many-valued Logics22Luisa Iturrioz–Non-functionally Complete n-Valued Systems Semanti-cally Based on Posets22Teresa Alsinet Bernado–Fuzzy Uniﬁcation23 Didier Dubois–Fuzzy Logic=Many-valuedness+Partial Belief24 Elena Tsiporkova–Possibility Theory in Modal Logic25Stephan Lehmke–A Comparison of Particular Logics of Graded Incom-plete Truth and Graded Incomplete Knowledge26Brunella Gerla–The Ulam Game and MV-entropy27Stefano Aguzzoli–McNaughton Functions of One Variable for Automated Deduction in L ukasiewicz Logics27Manuel Ojeda Aciego–The TAS Reduction Method in MVL:A TAS Theorem Prover for Three-valued Logic28Neil Murray–Parameterized Prime Implicant/Implicate Computations for Regular Logics284Walter Carnielli,Campinas(Brazil)Non-deterministic SemanticsThis talk introduces a new form of combining semantics,with the double intention of,ﬁrst,to oﬀer alternative semantic interpretations to certain less understood logic systems,and second,to combine simple logics so as to obtain other logics with richer structure.Let L be a propositional language.By a non-deterministic semantic frame-work for L we mean a pair ND= T,M where T is a collection of transformations (called translations)from L to a family of languages Lλ∈Λgoverned by a set of axioms or conditions,and M={Mλ∈Λ}is a class of basic models,where Lλand Mλhave the same type of similarity of L.It is possible then to deﬁne a non-deterministic forcing relation based on ND, generalizing from the conceptual framework of possible-worlds semantics(viewing the transformations in ND as abstractions of possible worlds,and the conditions on translations in ND as abstractions of accessibility relations).We discuss three example-cases of non-deterministic semantics,stressing the role of many-valued matrices as basic models:theﬁrst one,showing how to as-sociate multi-valued semantics to logics having non-truth-functional connectives (as in the paraconsistent logics),the second showing how to give interpretations to certain many-valued logics in terms of classes of logics having lower number of truth-values,and the third showing how to combine Kripke models to form new logics.Although the investigated examples involve just aﬁnite set of basic models in M,it is very natural to extend these deﬁnitions in terms of pre-sheaves of structures,with interesting consequences.In particular,a challenging problem is to deﬁne appropriate algebraic operations reﬂecting this construction,which would obtain new algebraic counterparts for the logics involved.Matthias Baaz,Vienna(Austria)Analytic Calculi for Many-valued LogicsThis lecture describes the impact of proof theoretic investigations on many-valued logics using three examples:1.Theﬁrst-order variant of Avron’s Hypersequent Calculus for inﬁnitely val-ued G¨o del logic makes it possible to gain a clear understanding of the properties of the completeness proof of Takeuti-Titani.2.The identiﬁcation of fragments of Hajek’s Basic Logic BL with Urquat’slogic C and its extensions by residuation makes it easy to analyze deriva-tions in BL and to demonstrate the independence of the“commutativity5of the minimum”-axiom from the other axioms of BL.A further proof-theoretic analysis of BL leads to an analytic formalization and consequently to decidability.3.The possibility to deal with inﬁnitary calculi/derivations in an eﬀective wayis connected to quantiﬁer elimination of the underlying metatheory. Hiroakira Ono,Ishikawa(Japan)Many-valued Logics as Logics without the Contraction RuleLogics lacking some or all of structural rules,when they are formulated in sequent calculi,are called substructural logics.The class of substructural logics includes Lambek calculus,logics without the contraction rule(BCK logics),linear logic, relevant logics and so on.The study of substructural logics will enable us to discuss these diﬀerent kinds of logics within a uniform framework.Now,it is expected to be one of the central topics in non-classical logic.Here,we are trying to develop a general theory of logics without the contrac-tion rule,i.e.,extensions of the intuitionistic logic without the contraction rule, FL ew(see e.g.[1,2]for the details).Our main tool is to use algebras which are related to the logic FL ew,which are known as residuated lattices.First,we will develop a basic algebraic study of residuated lattices and will show that models of L ukasiewicz’s many-valued logics and the model of product logic(from fuzzy set theory)come out naturally from their algebraic properties.Then we will discuss neighbours of the classical logic over FL ew.By applying J´o nsson’s Lemma,we can give a criterion for a logic to be a neighbour of the classical logic.As a consequence,we can show that there are inﬁnitely many neighbours of the classical logic,each of which is diﬀerent from any of L ukasiewicz m+1-valued logic with a prime number m.By discussing many-valued logics in such a broader context,we will be able to give a clearer view of them.Moreover,this approach will contribute to build-ing a bridge between the study of substructural logics and that of many valued logics and fuzzy logic.For,though many of the results on the former logics are apparently related to the latter,as we have sketched in the above,they are some-times unknown in the study of the latter logics.The whole contents of our study will appear in our forthcoming paper“Logics without the contraction rule and residuated lattices”.References[1]H.Ono and Y.Komori:Logics without the contraction rule.Journal of SymbolicLogic,50:169–201,1985.[2]H.Ono:Semantics for substructural logics.In K.Doˇs en and P.Schroeder-Heister(eds.):Substructural Logic,pp.259–291,Clarendon Press,Oxford,1993.6Reiner H¨a hnle,Karlsruhe(Germany)Proof Theory of Many-valued Logic and Hardware DesignWe show that tableau and sequent rules for many-valued logics are closely related to many-valued decision diagrams and generalized formula decompositions as used in logic design and hardware veriﬁcation.Although some tools and methods used in linear optimization,automated theorem proving,logic design and hardware veriﬁcation are common,distinct notation is used and there seems to be a negligible amount of communication among these communities.We endavour to show where parallels occur,but also where diﬀering points of view lead to a diﬀerent emphasis,thereby establishing a basic concordance.Gonzalo Escalada-Imaz,Barcelona(Spain)Determining the Truth Degree in Real Time SettingsUntil the beginning of this decade,controlling real-world industrial processes was done by classical control theory.However,currently it is widely accepted that whenever the mathematical model of the process is complex,Classical control theory fails to design a suitable controller.Given this fact,and the capital relevance of controlling industrial processes,a fragment of the AI research community has turned its attention to this promising ﬁeld.The goal consists in designing KBS-based controllers to work within the strong conditions that have to be met in real time settings(RTS),imposed by the dynamic evolution process.Controllers working in RTS must remain continuously active because each time the process state changes,a control signal must be produced in a bounded time(reactivity property).Also,some kind of temporal and approximated rea-soning is needed in order to follow the inherently dynamic nature of the process and to deal with inexact information.Our approach approximating reasoning relies on regular multiple-valued logic (RML)which enables to capture vague,imprecise and partial information.Thus, our KBS is based on RML rules enriched pertinently with a temporal structure to reason about time and so,to follow the dynamic changes of the process.Finally,the underlaying general model of the controller is an AND-connector tree where with each node a truth degree is associated.The truth degree of a father AND-connector is obtained by a function whose arguments are the truth degrees of the AND-connector’s sibling nodes.A compiler running oﬀ-line obtains a table data structure tied to each AND-connector.These tables have the crucial feature that,for each conﬁguration of the truth values modeling the current state of the process,the truth value degree of each father AND-connector is computed in O(1)time from the child nodes.This7performance together with the O(1)complexity of the bottom-up propagation of truth values ensures the reactivity condition.As aﬁnal remark,we add that the proposed controller has been inspired by a real-world application framework,a pediatric intensive care unit.Peter Vojt´aˇs,Koˇs ice(Slovakia)Many-valued Logic Programming and AbductionIn our talk we present declarative and procedural semantics of many-valued def-inite logic programming(MVDLP)and prove its completeness.In order toﬁt real world data and multiple agent behaviour,our connectives are arbitrary and subject of learning/approximation.First decision is that our program consists of implications of formA←∨([&1(B1,&2(B2,B3))],[&3(C1,&4(C2,C3))]).cf=a∈[0,1]So we skip the clausal notation in DNF(because in arbitrary many-valued logics the formula¬B∨A needs not to be equivalent to B→A;for another ap-proach see work of Mundici).Diﬀerent&i’s in the body correspond to diﬀerent nature of datas,depending,e.g.,on diﬀerent user environments and/or stereo-types.∨in the body serves to aggregate singleﬁndings to the global conﬁdence. Note that rule is equipped with a conﬁdence factor,hence our programs are fuzzy theories in the sense of Pavelka,Nov´a k and H´a jek.The deduction is based on backward usage of many-valued modus ponens(B,x),(B→A,y)Rasim Egri,Ankara(Turkey)with Ismet ErkmenA New Fuzzy Approach to Unit Commitment in Power SystemsIn this study,a new approach to solve Unit Commitment,one of the basic prob-lems in power systems,using fuzzy set theory is proposed.Unit Commitment procedure provides the most economic and feasible schedules of“on”and“oﬀ”time periods for the generating units in a power system for the near future.A generation schedule is feasible if the schedule successfully meets various opera-tional constraints of the system.However,due to the uncertainties coming from the nature of the problem,like the unknown demand and the unit production cost,an exact analytic solution is diﬃcult to obtain.Therefore these uncertain-ties are modeled using fuzzy logic in our approach.The performance and the sensitivity of the proposed technique are tested on a sample power system;the results are compared with the ones that are optained by the well established Dynamic Programming method.It is observed that the performance and the robustness of the proposed method is as good as the Dynamic Programming method.Considering the linguistic simplicity and the computational eﬃciency of the proposed technique,it can be said that it is a potential alternative for solving the Unit Commitment problem in power systems.The present extension to this study is on the tuning of the fuzzy logic controller and the application of the new technique to a real power system,namely the Turkish Power System.Hans J¨u rgen Ohlbach,London(UK)with Jana Koehler,Freiburg(Germany)How to Augment a Logical System with a Boolean Algebra Compo-nentWe investigate how to augment a given logical system,for example an arithmetical equation solver,with a Boolean component.The atomic decomposition technique proposed in this talk reduces reasoning about the Boolean component in the combined system to reasoning in the pure basic system only.A typical instance of this scheme is a linear programming system which is to be augmented with reasoning about cardinalities of sets,or other functions mapping sets to integers.The sets and their set-theoretic relationships are axiomatized with propositional logic.Atomic decomposition then reduces reasoning about numerical attributes of these sets to arithmetic equation solving.References[1]H.J.Ohlbach and J.Koehler:How to Augment a Logical System with a BooleanAlgebra Component.To appear in W.Bibel and P.H.Schmitt(eds.):Automated9Deduction–A Basis for Applications,volume III,Kluwer,Dordrecht. Christian Ferm¨u ller,Vienna(Austria)Finite-valued Logics and Classical Proof TheoryWe report on joint work of the VGML(Vienna Group in Many-valued Logics) consisting of M.Baaz,C.G.Ferm¨u ller,G.Salzer,and R.Zach.Finitely-valued logics are used as a tool to illuminate classic concepts of proof theory.Claiming that there exists a systematic relation between two concepts like the classical sequent calculus LK and natural deduction for classical logic,is a void statement as long as one does not consider broad classes of concepts of which the ones to be compared are just particular instances.We use the family of allﬁnitely-valued logics with arbitrary truth functional connectives and distribution quantiﬁers as basis to substantiate the claim that important concepts of Gentzen-style proof theory can be“derived”from each other.In particular we consider •the relation between many-placed sequents and multi-conclusional natural deduction systems,•truth tables and operators for reducing cuts with corresponding types of cut-formulas,and•the relation between the well-known syntactical restriction that turns LK into LJ,on the one hand,and Kripke semantics for logics of intuitionistic type,on the other hand.Tools like signed resolution allow to automatize the various translations of con-cepts.The system Multlog demonstrates this strikingly:Given anyﬁnite set of truth tables as input Multlog outputs various types of calculi along with soundness and completeness proofs as a L A T E X documents.Agata Ciabattoni,Bologna(Italy)with Dov Gabbay,London(UK),and Nicola Olivetti,Torino(Italy) Cut-free Proof Systems for Logics of Weak Excluded MiddleIn this talk we explore logics which arise from well known systems by weakening the excluded-middle principle.In particular,we introduce cut-free hypersequent calculi for the LQ logic,obtained by adding to Intuitionistic Logic the weak law of the excluded middle,that is¬A∨¬¬A,and for systems,called W n,obtained by adding to aﬃne Linear Logic(without exponential connectives)the n-weak law of the excluded middle,that is¬A∨(A⊕···⊕A)(n−1times).For n=3,the system W n coincides with3-valued L ukasiewicz Logic;for n>3,it is a proper subsystem of n-valued L ukasiewicz Logic.Then,our calculi can be seen as a10step forward in order toﬁnd hypersequent calculi,in which the cut-elimination theorem holds,forﬁnitely-valued L ukasiewicz Logics.Ewa Orlowska,Warsaw(Poland)with Mihir Chakraborty,Calcutta(India)Many-valued Substitutivity PrinciplesWe consider two families of many-valued logics:logics whose many-valuedness is numerical and logics with non-numerical many-valuedness.These classes of logics include,among others,many-valued information logics,Rosser-Turquette logic,fuzzy logic.For several logics from each of the two groups we propose a semantics for the identity predicate and we prove validity of the underlying substitutivity principles.We also discuss substitutivity principles that hold for p-compatible identities in algebraic theories and substitutivity principles in E-uniﬁcation theory.Felip Many`a,Lleida(Spain)with Ram´o n B´e jar,Lleida(Spain),and Gonzalo Escalada-Imaz, Barcelona(Spain)Solving the SAT-problem in Regular CNF-formulasFirst of all,we present a Davis-Putnam-style satisﬁability checking procedure for regular propositional formulas in conjunctive normal form(CNF-formulas). For the sake of eﬃciency,we have equipped the procedure with a suitable data structure for representing formulas.This data structure allows,for example,to detect the existence of unit clauses in constant time and to apply the regular unit clause rule with a linear-time worst-case complexity.Second,we deﬁne several regular branching rules:An optimized version of H¨a nhle’s branching rule,a regular version of the positive clause rule and a branch-ing rule based on the concept of maximal set of truth values.Third,we describe a generator of random k-SAT instances of the satisﬁability problem in regular CNF-formulas.Fourth,we show the experimental results obtained after executing an imple-mentation of the algorithm on a distribution family of randomly generated regular 3-SAT instances:It turns out that for3truth values and60propositional vari-ables,near the ratio C/V=6.17–where C and V are,respectively,the number of clauses and propositional variables–weﬁnd the hardest instances.The num-ber of nodes of the proof tree generated by the procedure increases exponentially near this ratio and quickly decreases beyond than.For5truth values and60 propositional variables,we observe the same eﬀects near the ratio C/V=8.17.11Finally,we show that the2-satisﬁability problem in regular CNF-formulas can be solved in polynomial time using a reﬁnement of the proof procedure proposed. Siegfried Weber,Mainz(Germany)Conditional Objects Based on MV-algebrasAbstract not available.Ulrich H¨o hle,Wuppertal(Germany)Singletons and Fuzzy PartitionsLet M=(L,≤,∗)be a GL-monoid[1,Section5]satisfying the additional dis-tributivity lawα∗( i∈Iβi)= i∈I(α∗βi)for allα∈L and all{βi|i∈I}⊆L. Typical examples are complete Heyting algebras or complete MV-algebras.The M-valued interpretation of the formalized theory of identity and existence[2,Sub-section3.2]leads to the following concept of MV-valued sets(X,E)where X is a non-empty set and E:X×X−→L is a map(so-called M-valued equality on X)subjected to the following axioms(E1)E(x,y)≤E(x,x)∧E(y,y)(Strictness) (E2)E(x,y)=E(y,x)(Symmetry) (E3)E(x,y)∗(E(y,y)→E(y,z))≤E(x,z)(Transitivity) A subset{f i|i∈I}of L X is called an L-fuzzy partition of the universe X iﬀ{f i|i∈I}satisﬁes the following disjointness condition:(( ℓ∈I fℓ(x))→f i(x))∗f j(x)≤x∈X[E(f i)∗( y∈X f i(y)→f j(y))]∧[E(f j)∗( y∈X f j(y)→f i(y))]where E(g)=∨{g(x)|x∈X}.Then the following theorem holds[2,Theo-rem4.2.2]:A subset Z={f i|∈I}of L X is an L-fuzzy partition of X iﬀthere exists an M-valued equality E on X such that•Every map f i∈Z is a singleton of(X,E),•E(x,x)= i∈I f i(x)for all x∈X.12References[1]U.H¨o hle:Commutative,residuated L-monoids.In U.H¨o hle and E.P.Klement(eds.):Non-classical Logics and Their Applications to Fuzzy Subsets,pp.53–106, Kluwer,Boston,1995.[2]U.H¨o hle:On the fundamentals of fuzzy set theory.J.Math.Anal.Appl.,201:786–826,1996.Antonio Di Nola,Naples(Italy)with Ada LettieriOne Chain Generated Varieties of MV-algebrasMV-algebras constitute a generalization of Boolean Algebras and arise from the many-valued logic of L ukasiewicz in the same manner as boolean algebras arise from two-valued logics.An MV-algebra is an algebraic structure A=(A,⊕,∗,0)such that(A,⊕,0) is an abelian monoid and the following identities hold:x∗∗=x;x⊕0∗=0∗; (x∗⊕y)∗⊕y=(y∗⊕x)∗⊕x.If we set x⊗y=(x∗⊕y∗)∗,x∧y=(x⊕y∗)⊗y,and x∨y=(x⊗y∗)⊕y, for every x,y∈A,then(A,∨,∧,0,1)is a bounded distributive lattice,which is called the reduct of A and denoted by L(A).Boolean algebras coincide with MV-algebras satisfying the additional identity x⊕x=x.Let A be an MV-algebra. The set B(A)={x∈A|x⊕x=x}is a boolean algebra.Actually it is the greatest boolean subalgebra of A.The variety△⇛of all MV-algebras coincides with the variety HSP[0,1]gen-erated by the MV-algebra deﬁned on the real unit[0,1]as follows: x⊕y=min(1,x+y),x⊗y=max(0,x+y−1),x∗=1−x.The main results presented here,are the following:1.A characterization of the sub-varieties satisfying the amalgamation prop-erty;actually,they are those that have exactly one generator.2.There exists a categorical equivalence between the sub-variety generated byaﬁnite chain MV-algebra with n elements and the category whose objects are pairs(B,R n)where B=(B,+,·,−,0,1)is a boolean algebra and R n⊆B n such that:i)If(b0,b1,...,b n−1)∈R n,then b0≥b1≥···≥b n−1;ii)If(b0,b1,...,b n−1)∈R n,then(b n−2,...,iii)If(b0,b1,...,b n−1),(c0,c1,...,c n−1)∈R n,then(b0+c0,...b k+c k+ i+j=k−1b i·c j,...b n−1+c n−1+ i+j=n−2b i·c j)is an element of R n;iv)(b,b,...,b)∈R n for all b∈B.3.Every relation R n can be represented by a boolean algebra B and a vectorof ideals of B.4.A characterization of the automorphisms of B(A)which can be extendedto automorphisms of A.5.Following I.R.Goodman,H.T.Nguyen,and E.A.Walker,we introducethe notion of Abstract Conditional MV-Space,as an MV-algebra having the reduct lattice to be an Abstract Conditional Space.These seem to be the suitable algebraic structures coping with the notion of conditional events in the framework of L ukasiewicz logic.Indeed we provide a characterization of such a class of MV-algebras.6.Finally we characterize the group of automorphisms of an n-valued algebra. Zbigniew Stachniak,Toronto(Canada)From Inferentially and Referentially Finitely-valued Systems to Res-olutionAre there many-valued logics or just logics with many-valued semantics?Is the semantic apparatus of many truth-values a distinctive feature of many-valued logic or is it the intended interpretation of an applied language,a philosophical commitment,that necessitates the choice of multiple-valued interpretation for the language?These issues seem to be still unresolved in spite of almost80years of continuous research in the area of many-valued logics.In the maze of opinions concerning the deﬁning features for the class of many-valued logics,there is still one path that can be explored.The bivalent nature of classical logic is clearly represented in the theses of this calculus.Other logical systems(such as Le´s niewski’s Protothetic or Ontology)are formalized in such a way as to make the intended interpretation of an applied language evident from the start,at the proof theoretic level.14In this talk we are concerned with the search for a proof-theoretical evidence ofﬁnite-valuedness within the class of cumulative inference systems.We deﬁne and investigate the notion of an inferentially many-valued inference system.In this deﬁnition we try to capture the idea of the proof-theoretical representation of truth-functional many-valued semantics.We contrast the notion of inferential many-valuedness with semantic(or referential)many-valuedness.Although the notions of inferential and referential many-valuedness do not coincide,standard(i.e.,structural and compact)inferentially or referentially ﬁnitely-valued logics are resolution logic in the sense of[1].Hence,every such system P has a resolution counterpart,i.e.,there exists a deductive proof system based on the(non-clausal)resolution principle which is refutationally equivalent to P.References[1]Z.Stachniak:Resolution Proof Systems:An Algebraic Theory.Kluwer AcademicPublishers,1996.Dirk Van Heule and Albert Hoogewijs,Gent(Belgium)The Partial Predicate Calculus.A Three-valued Object Logic for the Theorem Prover IsabelleIn this talk we deﬁne the3-valued Partial Predicate Calculus(PPC)as an object logic for the generic theorem prover Isabelle.We will focus on the propositional logic.It will be necessary to add some new deﬁnitions and rules to the semantics of PPC in order to use the proving mechanisms of Isabelle in natural deduction style.The truth-tables for the logical operators negation(¬)and conjunction(∧) correspond to Kleene’s notation.The logical operators are extended with a non-monotone operator∆to express the deﬁnedness(∆α≡T)or undeﬁnedness (∆α≡F)of a formula.¬T FT U UT F UT F U FU F UThe deﬁnition of validity and consequence diﬀers from most other3-valued logics. In PPC,a valuation is a mapping V:Form P P C→{T,F,U}with Form P P C being the well-formed formulas of PPC.M is a model for a set of formulasΣiﬀfor allγ∈Σ:V(γ)≡T.A formulaαis valid for a model M(M|=α)iﬀV(α)∈{T,U}.A formula is valid iﬀit is valid for all models of PPC.A formula15。

bilateralabnorma...

Anatomical Science International (2004) 79, 95–97Case ReportBilateral abnormal anterior bellies of digastric musclesSenem T uran-Ozdemir, Ibrahim Hakan Oygucu and Ilker Mustafa KafaDepartment of Anatomy, Faculty of Medicine, Uludag University, Bursa, TurkeyAbstractDuring dissection of the submental region of a male cadaver, we encountered an abnormal digastric muscle on both sides. Two muscle bundles, both of which fused with mylohyoid muscle close to the midline, were observed on the right side. The anterior one originated from the digastric fossa and its length and width were 27 and 9 mm, respectively. The posterior accessory belly originated from the right intermediate tendon and it was 32 mm in length and 11 mm wide. On the left side, there was a single accessory bundle that originated from the left intermediate tendon and inserted into the mylohyoid raphe at the fusion point of the right accessory bundles. The length and width of this belly were 29 and 9 mm, respectively. The remaining suprahyoid muscles of both sides were normal. Anatomical variations of digastric muscle have to be considered in the imaging procedures of the soft tissue masses in the submental region.Key words:abnormal, digastric muscle, submental region.IntroductionThe digastric muscle has two bellies united by an intermediate rounded tendon, which attaches to the hyoid bone. The muscle runs from the mastoid notch to the mandibular symphysis (Williams et al ., 1989). The anterior belly of the digastric muscle and the mylohyoid muscle develop from the ﬁrst branchial arch and appear by the 4th week of intrauterine life, where the posterior belly originates from the second arch (Moore, 1988).The anterior bellies of the digastric muscles divide the region between the hyoid bone and the mandible into two triangles: the submandibular and submental triangles (Hollinshead, 1982). The submental triangle consists of various amounts of adipose tissue and submental lymph nodes and the anterior bellies of the digastric muscles form the lateral margins of the this triangle. Abnormalities of the digastric muscles commonly occur in this triangle and, therefore, have to be considered in imaging procedures of soft tissue masses and in operations involving this region.The present study demonstrates a bilateral anom-aly of the anterior bellies of the digastric muscles,which is rare in the Turkish population.Case ReportDuring the gross anatomy dissection for medical students, a case of bilateral variation of digastricmuscles was found in a male cadaver and photographs were taken (Fig. 1; for a schematic representation,see Fig. 2). The anterior bellies of the digastric mus-cles had accessory muscle bundles on both sides.Two muscle bundles, both of which fused with the mylohyoid muscle close to the midline, were observed on the right side. The anterior one originated from the digastric fossa and its length and width were 27and 9 mm, respectively. The posterior accessory belly originated from the right intermediate tendon and was 32 mm in length and 11 mm wide. On the left side, there was a single accessory bundle that origin-ated from the left intermediate tendon and inserted into the mylohyoid raphe at the fusion point of the right accessory bundles. The length and width of thisCorrespondence: Dr Senem Turan-Ozdemir, Department of Anatomy, Faculty of Medicine, Uludag University, 16059 Bursa, Turkey.Email:****************.trReceived 9 April 2003; accepted 10 October 2003.Figure 1.Photograph of the suprahyoid region showing abnormal accessory anterior bellies (asterisks). (1), anterior bellies of digastric muscles.96S. T uran-Ozdemir et al.belly were 29 and 9 mm, respectively. It was also observed that accessory bellies were innervated by mylohyoid nerves of the corresponding sides (data not shown).The posterior bellies of the digastric muscles, the mylohyoid muscle and the remaining suprahyoid muscles of both sides were normal.DiscussionVarious types of digastric muscle abnormalities have been classiﬁed and well documented in previous ana-tomical studies (Zlabek, 1933; Yamada, 1935). Zlabek (1933) ﬁrst classiﬁed abnormal digastric muscles according to their phylogenetic and ontogenetic developments. Yamada (1935) added further weight to the classiﬁcation by describing six different types of abnormal digastric muscle anterior bellies. More recently, Fujimura et al.(2003) have proposed that the attachment position of muscle should be con-sidered in the classiﬁcation of an abnormal digastric muscle.Many authours have reported cases with abnor-mal digastric muscles (Celik et al., 1992, 1993; Traini, 1993; Sargon & Celik, 1994; Sarikcioglu et al., 1998; Holibková & Machálek, 1999; Peker et al., 2000; Celik et al., 2002). Bilateral anomalies of digastric muscles are reported to be more rare than unilateral anoma-lies (T estut & Laterjet, 1948; Traini, 1993; Holibková & Machálek, 1999; Peker et al., 2000). Traini (1993) described a four-belly digastric muscle that lay in the submental triangle and attached to the mylohyoid raphe; one belly inserted into the mandible, whereas the other three bellies blended with the anterior belly of the same side. Holibková and Machálek (1999) reported two anomalies of the anterior bellies of digastric muscles. Enlargement of the anterior bellies of digastric muscles has been demonstrated in a cadaver by Celik et al. (1992). In a clinical study, Connell and Shamoun (1997) encountered excess digastric muscle bulk in several cases. They observed that the large digastric muscle become apparent, bulging through the overlying platysma in a case lying in the supine position with the head ﬂexed.In the present case, we observed asymmetric accessory digastric muscles between the left and right digastric muscle and this case was a ‘mixed type’ according to the classiﬁcation of Yamada (1935). Although, the variation of the digastric muscle described in the present case has already been reported in the Japanese population (Yamada, 1935), it was not observed in a study of 99 Turkish cadavers (Sargon et al., 1999). Therefore, the incidence of this variation appears to be rare in the Turkish population.The digastric muscle normally depresses the man-dible and can elevate the hyoid bone. In addition, this muscle serves as an accessory muscle for extreme opening of the mouth (Connell & Shamoun, 1997). The digastric muscle has dual innervations from the trigeminal and facial nerves, which innervate the anter-ior and posterior bellies, respectively. In the present case, we observed that accessory anterior bellies are innervated by the mylohyoid nerve of the corres-ponding side.Bilateral symmetry is a very important criterion in the radiological evaluation of the submental region. Variations of digastric muscles can be easily con-fused with a pathological condition, such as a tumor or lymph nodes. New imaging modalities, such as computed tomography and magnetic resonance imag-ing, are both useful for the evaluation of anatomical and pathological lesions of the ﬂoor of the mouth.As a result, anatomical variations in digastric muscles may affect diagnostic and surgical pro-cedures involving the submental region, such as rhytidectomy, submental lipectomy, or the musculo-cutaneous or muscular ﬂap of the digastric muscle (Connell & Shamoun, 1997). These types of anomalies should be considered during surgical procedures involving this region.ReferencesCelik HH, Yilmaz E, Atasever A, Durgun B, Taner D (1992) Bilateral anatomical anomaly of anterior bellies of digastric muscles. Acta Anat Nippon67, 650–1.Celik HH, Yilmaz E, Atasever A, Durgun B, Taner D (1993) Observation of anomalous triplication of unilateral anterior digastric muscle. Clin Anat6, 353–5.Celik HH, Aldur MM, Ozdemir B, Aksit MD (2002) Abnormal digastric muscle with unilateral quadriﬁcation of the anterior belly. Clin Anat15, 32–4.Connell BF, Shamoun JM (1997) The signiﬁcance of digastric muscle contouring for rejuvenation of the submental area of the face. Plast Reconstr Surg99, 1586–90.Fujimura A, Onodera M, Feng X-Y et al.(2003) Abnormal anterior belly of the digastric muscle: A proposal for the classiﬁcation of abnormalities. Anat Sci Int78, 186–9.Figure 2.Schematic drawing of the submental region. (1), anterior bellies of digastric muscles; (2), posterior bellies of digastric muscles; asterisks, abnormal accessory anterior bellies.Anatomical variation of digastric muscles97Holibková A, Machálek L (1999) A report on anomalies of digastric muscle. Acta Univ Palacki Olomuc Fac Med142, 57–9.Hollinshead WH (1982) Anatomy for Surgeons, 3rd edn, Vol. 1.Harper & Row, Maryland.Moore KL (1988) The Developi ng Human: Cli ni cally Ori ented Embryology, 4th edn. WB Saunders, Philadelphia.Peker T, Turgut HB, Anil A (2000) Bilateral anomaly of anterior bellies of digastric muscles. Surg Radiol Anat22, 119–21.Sargon MF, Celik HH (1994) An abnormal digastric muscle with three bellies. Surg Radiol Anat16, 215–16.Sargon MF, Onderoglu S, Sürücü HS, Bayramoglu A, Demiryürek D, Oztürk H (1999) Anatomic study of complex anomalies of the digastric muscle and review of the litera-ture. Okajimas Folia Anat Jpn75, 305–14.Sarikcioglu L, Demir S, Oguz N, Sindel M (1998) An abnormal digastric muscle with three accessory bellies and one ﬁbrous band. Surg Radiol Anat20, 453–4.Testut L, Laterjet A (1948) Traite D’anatomie Humaine, 9th edn.G. Doin et Cie, Paris.Traini M (1993) Bilateral accessory digastric muscles. Anat Clin 5, 199–200.Williams PL, Warwick R, Dyson M, Bannister LH (1989) Gray’s Anatomy, 37th edn. Churchill Livingstone, New York. Yamada S (1935) Beobachtungen über den Venter anterior des Musculus digastricus mandibulae bei japanishen Erwachsenen und Foeten. Acta Anat Nippon8, 303–47 (in Japanese with an English abstract).Zlabek K (1933) Contribution a la connaissance des anomalies du ventre anterieur du digastrique de l’Homme. Arch Anat Histol Embryol16, 357–406.。

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2. A bilateral summation
We will now state the main result of the paper. Throughout, we use the standard notation of [GR]. The base q is assumed to satisfy 0 < |q| < 1. We denote by r+1φr not only the convergent basic hypergeometric series, but also its analytic continuation to C \ R≥1; cf. [GR, §4.5].
(1)
∞
2φ1
n=−∞
a, b; q, xqn c
2φ1
d, e; q, yqn f
tn,
which appeared as matrix elements of quantum SU(1, 1) representations. Several special cases were considered, with diﬀerent, very technical, proofs (some of these proofs were found by Mizan Rahman, see the appendix to [KS]).
1. Introduction
The object of the present paper is to study bilateral series of a type that ﬁrst appeared in the work of Koelink and Stokman [KS], in the context of harmonic analysis on the SU(1, 1) quantum group. They needed to compute sums of the form
(2)
abde = cf, f x = dey
(and thus also cy = abx), the sum in (1) can be expressed as the sum of two 8W7 series, or, alternatively, as the sum of three balanced 4φ3 series. From the quantum algebraic viewpoint, which was only brieﬂy mentioned in [KR], this computes a general class of matrix elements for the strange, the complementary and the principal unitary series of quantum SU(1, 1). The proof in [KR] is similar to, though not an extension of, one of Rahman’s proofs in [KS]. In particular, it is quite technical and involves rather non-obvious applications of q-series transformations.
(5)
∞
k+1φk
n=−∞
a1, . . . , ak+1 ; q, xqn b1, . . . , bk
l+1φl
c1, . . . , cl+1 ; q, yqn d1, . . . , dl
tn
=
(q, xt, q/xt, a1, . . . , ak+1, b1/t, . . . , bk/t; q)∞ (t, x, q/x, a1/t, . . . , ak+1/t, b1, . . . , bk; q)∞
Our main tool is the following lemma from [KR], where it was used only in the case k = 5. Here we need the general case.
Lemma 2.2. For
(6) and x ∈ C \ R>0 one has
Dedication: This paper would not have been written without the pioneering contributions of Mizan Rahman. I’m happy to know him, not only through his work as a master of identities, but also as a genuinely kind and helpful person. It is a pleasure to dedicate this paper to him as a small token of my appreciation.
In joint work with Koelink [KR], we gave an extension of the summation formulas from [KS], with a uniﬁed proof. Namely, we showed that under natural conditions of convergence and the assumption
the roles of k+1φk and l+1φl gives an alternative expression for the series, which is valid when (4) is replaced by the condition |qxd1 · · · dl| < |yc1 · · · cl+1|. These two expressions are related by [GR, (4.10.10)].
In [KR], we computed the sum when k = l = 1 and, crucially to the methods
used there, (2) holds. The latter condition means exactly that the three 4φ3 series on the right-hand side of (5) are balanced. In this case Theorem 2.1 reduces to [KR,
× k+l+2φk+l+1
t, qt/b1, qt/a1, .
. .
. .
. ,
, qt/bk, c1, . . . , cl+1 qt/ak+1, d1, . . . , dl
;
q,
qyb1 · · · bk xa1 · · · ak+1
+ (q, a1x, q/a1x, yt/a1, qa1/yt, a2, . . . , ak+1, b1/a1, . . . , bk/a1; q)∞ (x, q/x, y, q/y, t/a1, a2/a1, . . . , ak+1/a1, b1, . . . , bk; q)∞
× (c1, . . . , cl+1, a1d1/t, . . . , a1dl/t; q)∞ (a1c1/t, . . . , a1cl+1/t, d1, . . . , dl; q)∞
× k+l+2φk+l+1
a1, qa1/b1, . . . , qa1/bk, a1c1/t, . . . , a1cl+1/t qa1/t, qa1/a2, . . . , qa1/ak+1, a1d1/t, . . . , a1dl/t
;
q,
qyb1 · · · bk xa1 · · · ak+1
+ idem(a1; a2, . . . , ak+1).
Here, idem(a1; a2, . . . , ak+1) denotes the sum of the k terms obtained by interchanging a1 with each of a2, . . . , ak+1. As is customary, we implicitly assume that the parameters are such that one never divides by zero. Note also that interchanging
arXiv:math/0302114v1 [math.CA] 11 Feb 2003
A BILATERAL SERIES INVOLVING BASIC HYPERGEOMETRIC FUNCTIONS
HJALMAR ROSENGREN
Dedicated to Mizan Rahman
Abstract. We prove a summation formula for a bilateral series whose terms are products of two basic hypergeometric functions. In special cases, series of this type arise as matrix elements of quantum group representations.
1991 Mathematics Subject Classiﬁcation. 33D15. 1
2
HJALMAR ROSENGREN
Our aim is to use Stokman’s method not only to give a simple proof of the summation formula in [KR], but also to give a far-reaching extension of this identity.