Bregman Voronoi Diagrams Properties, Algorithms and Applications
90-A geometric setting for the quantum deformation of GLn
DUKE MATHEMATICAL JOURNAL (C)
October 1990
A GEOMETRIC SETTING FOR THE QUANTUM DEFORMATION OF GL
A. A. BEILINSON, G. LUSZTIG*,
AND
R. MACPHERSON*
1. Flags and the algebra K. 1.1. We fix an integer n>l. Let i9 be the set of all n n matrices with integer entries such that the entries off diagonal are > 0. Let (R) be the set of all n x n matrices with integer, > 0 entries. Thus, (R) c 19. Let r: 19 ---, N be the map defined by taking the sum of all entries of a matrix. Let (R)a a-l(d); we have (R) Ila>o (R)a, and each (R)a is a finite set. Let V be a vector space of finite dimension d over a field F. Let be the set of all n-step filtrations V1 c V2 c"" V. E The group GL(V) acts naturally on -; its orbits are the fibres of the map --, N" given by
【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。
人体结构学 Human Structure学习通章节答案期末考试题库2023年
人体结构学 Human Structure学习通超星课后章节答案期末考试题库2023年1.Which bones belong to the shoulder girdle?答案:Scapula###Clavicle2.The paired cerebral bones are答案:parietal bone###temporal bone3.Shoulder joint is formed by答案:head of humerus###glenoid cavity of scapula4.Please deseribe the location and openings of the paranasal sinuses答案:答5.Please describe the formation, main structures and communications of the middle Cranial fossa.答案:答6.Please describe the joints of the vertebral bodies.答案:答7.Please describe the joints of the vertebral arches.答案:答8.Please describe the composition, characteristics and movements of theshoulder joint.答案:答9.Which bone belongs to the long bone?答案:Femur10.Which bones belong to the irregular bone?答案:Vertebra###Sphenoid bone11.The blood- testis barrier does NOT include the答案:gap junction between adjacent spermatogomia12.Which of the following description is true about the primordial follicles答案:The primordial follicle consists of a primary oocyte and a layer of flat follicle cells.13.(英文答题,第一空填1个单词,第二空3个单词)The axial bone contains fromup downwards _____ and_____.答案:skull###bonesoftrunk14.About the component of nephron, the correct option is答案:renal corpuscle, proximal tubules, distal tubules and thin segment15.About the features of proximal tubule, the WRONG option is答案:The cytoplasm of epithelial cell is weakly basophilic.16. A patient presents in your office after having a positive result on a homepregnancy test. Her menstrual cycle has always been the classic 28-day cycle discussed in textbooks, with ovulation occurring on the 14th day following the start of menstruation. Her menstrual period began on August 19.2019.You estimate her EDD to be答案:on May 26, 202017.Which of the following is NOT considered one of the fetal membranes答案:buccopharyngeal membrane18.Which bone does not form the anterior cranial fossa?答案:Temporal bone19.Which bone forms both the middle and posterior cranial fossa?答案:Temporal bone20.(英文答题,第一空填1个单词,第二空1个单词,第三空2个单词)Thesternum consists from up downwards of_____ , _______ and ______ .答案:manubrium###body###xiphoidprocess21.Of the following statements about epididymis, the WRONG option is答案:The ductus epididymis is lined with a simple columnar epithelium22.Of the following statements about trachea, the WRONG option is答案:The adventitia is constructed of the elastic cartilage rings.23.The interalveolar septum does NOT contain答案:ciliated cell24.All the following cells are included in the spermatogenic epithelium, EXCEPTthe答案:Leydig cells25.Please describe the general features of the vertebrae.答案:答26.Which bone forms the posteroinferior part of the bony nasal septum?答案:Vomer27.Drawing pictures of Thoracic vertebra from anterior and lateral view.答案:答28.Which bone does not form the thoracic Cage?答案:Sacrum29.About the scapula, which of the statements is not true?答案:It has three borders, three angles and three surfaces.30.About the component of the renal corpuscle, the WRONG option is答案:At the vascular pole, the efferent arteriole enters the glomerulus.31.Of the following statements about podocyte, the correct option is答案:They form the visceral layer of the Bowman's capsule.32.An infant is born with a sacrococcygeal teratoma. Biopsy(组织活检) andhistologic analysis reveal that it contains intestinal epithelia, cardiac muscle, cartilage, and integument tissue. You counsel the mother that the tumor is benign(良性的)and recommend surgical removal. This tumor was caused by which developmental anomaly?答案:Failure of primitive streak regression33.Which of the following structure is NOT included in the secondary follicle?答案:secondary oocyte34.All the following are from mesoderm EXCEPT the答案:spinal cord35.Which of the following descriptions is NOT true about the corpus luteum?答案:The corpus luteum continues to produce estrogen and progesterone during the whole process of pregnancy.36.Of the following statements about the alveolus of lung, the WRONG option is答案:It opens on the wall of terminal bronchioles.37.Which of the following descriptions is NOT true about the secretory phase ofa menstrual cycle?答案:The basal layer of endometrium becomes thicker .38.Of the following statements about Leydig cells, the correct option is答案:It secretes testosterone.39.Of the following statements about macula densa, the WRONG option is答案:It is derived from smooth muscle fibers of afferent arteriole.40.Of the following statements concerning terminal bronchioles, the WRONGoption is答案:They have some mixed gland.41.Of the following options, the blood-air barrier does NOT contain答案:typeⅡalveolar cells42.All the following cells are included in the spermatogenic cells, EXCEPT答案:Sertoli cells43.Which of the following does not belong to the joints of the vertebral arches?答案:Anterior longitudinal ligament44.Human chorionic gonadotropin is produced by the答案:syncytiotrophoblast45.Which of the followings is not enclosed in the articular capsule of shoulderjoint ?答案:Tendon of the short head of the biceps46.The pathway connecting the infratemporal fossa with the orbit is答案:inferior orbital fissure47.When does ovulation occur in a menstrual cycle?答案:the 14th day。
Nano-glasses--A_new_type_of_glasses
Nano-glasses: A New Type of Glasses?Herbert GleiterInstitut fuer NanotechnologieForschungszentrum KarlsruhePostfach 3640 , 76021 Karlsruhe/Germanye-mail: herbert.gleiter@int.fzk.deFax: +49-7247-82-6368AbstractToday, glasses are produced mostly by rapidly cooling the melt. In the area of metallic glasses, research attention has been focused in the past on finding chemical compositions that result in metallic glasses even if the cooling rates are as low as 10 degrees per second or less. These studies led to the development of the so called bulk metallic glasses.However, so far no systematic attempt has apparently been made to modify the atomic structure and,thus, the properties of glasses by changing their free volume in a controlled manner, although it is well known that the structure and the properties of glasses not only depend on their chemical composition but also on their free volume. In this paper it is proposed to generate a new type of glasses, called nano-glasses. Nano-glasses consist of nanometer-sized glassy regions connected by “glass/glass interfaces” These "interfaces" between adjacent glassy regions may have an enhanced free volume up to 15% (as compared to typically 1-2% of a melt grown glass). Due to this enhanced free volume, nano-glasses differ structurally and propertywise from glasses(with the same chemical composition) produced by cooling the melt. Nano-glasses may be synthesized either by assembling nanometer-sized clusters of atoms with a glassy structure or by introducing (by plastic deformation) such a high density of shear bands into a metallic glass that the spacing between adjacent bands is a few nanometers.IntroductionSoon after their discovery (1), the attractive properties of metallic glasses (produced by rapidly cooling the melt) became apparent. For example, in the tightly packed glassy structure, the displacement of atoms (e. g. to accommodate plastic flow) is obstructed. The metallic glass absorbs less energy than a crystalline body upon stress-induced deformation through damping and returns more by rebounding elastically to its initial shape. Due to the absence of crystal defects, glassy materials the following remarkable properties:- Strength (twice that of stainless steel but lighter);- Hardness (desirable e.g. for surface coatings);- Toughness (more fracture resistant than ceramics); and- Elasticity (high yield strength).The absence of grain boundaries renders many glassy materials resistant to corrosion and wear, as well as possessing soft magnetic properties, specifically in alloys of glass formers (B, Si, P) and ferrous magnetic transition metals (Fe, Co, Ni). High electrical resistivity leads to low eddy current losses. Easy magnetization and demagnetization allows lower losses in applications, operation at high temperatures with minimal flux density reduction, and annealing. On the other hand, in the years after the discovery of metallic glasses, high cooling rates were required (typically 105 to 106 °Cs-1) to prevent the melt from crystallizing. These high cooling rates limited initially (1) the maximum thickness of metallic glasses to about 0.1 mm or less. In order to remove this drawback, one of the main research thrusts in the area of metallic glasses focussed in the last four decades on finding metallic glasses with chemical compositions that require cooling rates as low as possible. In 1969 Chen and Turnbull (2) found ternary Pd-M-Si glasses (with M=Ag, Au or Cu) requiring cooling rates less than 103 °Cs-1. These cooling rates allowed casting thickness of about 0.5 mm. In 1974, Chen obtained a critical casting thickness of 1 mm in Pd-T-P (T=Ni, Co, Fe) (2) and in the early 1980s, Turnbull's group produced glassy ingots of Pd40Ni40P20 with a diameter of 5 mm using surface etching followed by heating and cooling cycles – the first bulk metallic glass (3). In 1988, Inoue discovered that La-Al-TM (TM=Ni, Cu) is highly glass-forming. It allowed him to cast glassy La55Al25Ni20 up to 5 mm thick and, in 1991, glassy La55Al25Ni10Cu10 specimens that were up to 9 mm thick (4), (5). At about the same time Johnson and Peker at Caltech developed a pentary alloy based on Zr-Ti-Cu-Ni-Be (Zr41.2Ti13.8Cu12.5Ni10.0Be22.5). With critical casting thickness of up to 10 cm (6) An overview of the critical casting thickness and the date of the discovery of these alloys is shown in Fig. 1Fig. 1 The critical casting thickness versus the year in which alloys were discovered. Over the last 40 years, the critical casting thickness has increased by more than three order of magnitude (6).Recently, Loeffler et al (7) described a method based on the centrifugal processing of the melt in order to find systematically the chemical compositions of multi component alloys with the lowest melting point. Alloys with these compositions are likely to require low cooling rates for glass formation.In all of these studies, relatively little attention was paid to the free volume1 of glasses, although it is well known that the properties of glasses depend strongly on their free volume. For example, if metallic glasses are plastically deformed at temperatures far below their glass transition temperature, shear bands may develop and slip is localized to these shear bands (9) – (11). Spaepen (8) first put forward the idea that shear band formation is to be attributed to a multiplication of free volume at an incipient band, which reduces flow stress locally so that shear is localized to this mechanically weakened region. Several authors (9), (10) concluded from the overall density reduction of plastically deformed metallic glasses that the enhanced free volume in a shear band may be as high as 50%. Moreover, it was found that this excess free volume in the shear bands was dissipated during a subsequent relaxational annealing treatment (10). According to more recent studies (11), the largest enhancement of the free volume in the shear bands exists during the deformation process and is called a ‘mechanically dilated flow state’. Once the deformation process is over, irreversible relaxation processes occur which reduce the free volume in the shear bands. The idea of an enhanced free volume and thus an enhanced atomic mobility in the shear bands is consistent with the observation that nanometer-sized crystals grow in the shear bands at ambient temperature, whereas outside of these bands no crystallization occurs (12), (13). The reduction of the enhanced free volume in the shear bands during subsequent annealing agrees with the following observation. Annealing of glasses is found to affect their properties e.g. the diffusivity, their optical properties etc. These property variations are believed to result from atomic rearrangements in the glasses which are often associated with the reduction of the free volume.It is the purpose of this paper to point out that the way to a new kind of glasses - called nano-glasses – may be opened by varying the free volume of glasses in a controlled way during the preparation procedure. In fact, this approach may result in glasses with new atomic structures and properties.Basic IdeasThe basic idea to generate glasses with enhanced free volume is explained schematically in Figs. 2a to 2f (14).Fig. 2 a-d. Generation of nano-glasses (schematic) by assembling nanometer-sized glassy solids.1 The free volume of a glass is the excess volume of a glassy solid relative to a crystalline solid withthe same chemical composition.Fig. 2a: Two-dimensional glass made up by hard spheres. This piece of glass is cut into four segments (A, B, C, D) along the lines indicated.Fig. 2b: Separation of the four segments.Fig. 2c: The positions of the four segments have been changed as indicated by the arrows in Fig. 2b, so that the segment A is now in the initial position (Fig. 2a) of segment B, B in the initial position of C etc. After this cyclic positional exchange, the four segments are re-assembled so that no atomic overlap occurs. This procedure results in the structure shown in Fig. 2c. Fig. 2d: All sites larger than one atomic volume in the interfaces between the four segments (Fig. 2c) are filled by inserting new atomsLet us start by considering a piece of a two-dimensional glass formed by hard spheres (Fig. 2a). This piece of glass is cut into four segments labelled A, B, C and D as is indicated in Fig. 2a. Subsequently, these segments are separated and positionally moved so that A gets into the position were the segment B was formerly, B to C etc. (Fig. 2b). After this positional exchange, the four segments are reassembled so that some of the atoms at the "surfaces" of the four segments (e. g. atoms 1 and 2 in Fig. 2c) get into contact without any atomic overlap. Finally, the empty space between the four segments is filled by inserting new atoms into all sites that are larger than one atomic volume (Fig. 2d). As may be seen from Fig. 2 d, the resulting glass consists of the four segments (A, B. C and D) connected by the horizontal and vertical contact regions between them. These contact regions are called glass/glass interfaces. In these interfaces the atomic density is lower than in the interior of the four segments. A simple estimate shows that the free volume in such glass/glass interfaces may be as high as 15%. In other words, it may be about one order of magnitude larger that the free volume trapped in glasses produced by rapidly cooling a melt with the same chemical composition. If the hard spheres (black circles in Fig. 2d) are assumed to represent atoms, the glass shown in Fig. 2d is a glass that exhibits a microstructure on a nanometer scale consisting of nanometer-sized glassy regions (the segments A, B, C, D) connected by interfaces with an enhanced free volume (relative to the free volume in the interior of the four segment). In this paper, a glass with this kind of microstructure will be called a nano-glass. Clearly, the microstructure and, thus, the enhanced free volume of a nano-glass maybe varied by varying the size of the assembled glassy regions (Figs. 2c and 2d). Infact, if the size of these regions is increased, a nano-glass becomes structurally more and more comparable to a bulk glass produced by cooling the melt.The procedure to generate nano-glasses by assembling nanometer-sized glassy regions (Figs. 2a-d) is not the only conceivable approach. The incorporation of a high density of (nanometer-spaced) shear bands (by plastically deforming a bulk metallic glass far below its glass transition temperature) seems to be an additional alternative. The generation of nano-glasses by this approach is indicated schematically in Figs. 2e and 2f.Fig. 2e Fig. 2fFig. 2e: Two-dimensional model of a glass (schematic). The atomic arrangement shown is the same as the one displayed in Fig. 2 a.Fig. 2f: Two-dimensional model of a plastically deformed glass (cf. Fig. 2a). The plastic deformation has introduced two shear bands (one in the horizontal and one in the vertical direction). The resulting atomic structure is the one of an nano-glass consisting of nanometer-sized glassy regions (A, B,C, and D) connected by glass/glass interfaces (shear bands).Fig. 2e displays the same two-dimensional models of a glass that was already shown in Fig. 2a. This glass is plastically deformed (Fig. 2f) by introducing two shear bands. These shear bands section the glass into four nanometer-sized regions (labelled A, B, C and D in Fig. 2f). The four regions are displaced relative to one another in directions parallel to the corresponding shear bands. Due to the aperiodic atomic structure of the glass, these displacements result in similar atomic structures in the contact regions between A, B, C and D as were described in Figs. 2c and 2d when four glassy segments (labelled A, B, C, and D in Figs. 2c and 2d) were assembled. In order to avoid atomic overlap in the shear bands, the atomic density in the bands has to be reduced relative to the atomic density in the interior of the glassy regions (A, B, C and D in Fig 2f). In other words, the introduction of nanometer-spaced shear bands results in a microstructure consisting of nanometer-sized glassy regionsconnected by glass/glass interfaces. The ideas just explained agree with the experimentally observed large excess free volume (of up to 50 %) in the shear bands of plastically deformed glasses (8) – (13) (cf. Introduction of this paper).Let us add a few general comments concerning the physics behind the idea of enhancing the free volume of a glass so that a nano-glass results. The enhanced free volume of an nano-glass is defined as the excess free volume of a nano-glass relative to the free volume of a fully relaxed bulk glass with the same chemical composition. In other words, the bulk glass is used as the reference state for the nano-glass. In the most simple case of a one component glassy model system, this fully relaxed bulk glass is the densest disordered packing of spheres of equal size. The use of a fully relaxed glassy state as a reference has been successfully applied in the past e.g. for defining the glass temperature (15) (16).The significance of the enhanced free volume of a nano-glass may become physically more transparent by considering it in the light of our present understanding of the physical significance of the free volume of bulk glasses. Molecular dynamics simulations of the atomic rearrangement processes in glasses and in undercooled melts indicate that glasses are heterogeneous as far as the dynamic properties of their structure are concerned. Due to the heterogeneous spacial distribution of the free volume, glasses exhibit localized regions of high and low atomic ability. In the regions of high mbility, atomic rearrangements processes occur (often in a co-operative mode) at a higher rate than outside of these regions. Such atomic rearrangements are important for transport processes in glasses such as diffusion, relaxations etc. (17). This implies that the free volume of a glass is a simplification of the complex reality of the atomic structure and, thus, in general, does not allow to understand many properties in detail. In principle, the same seems to apply to nano-glasses. However, the basic idea of nano-glasses is not affected by this complexity. Production of Nano-glassesOne way to produce nano-glasses (18) (19), is by means of inert gas condensation (Fig. 3). Nanometer-sized glassy spheres are generated by evaporating (or sputtering) the material in an inert gas atmosphere. These spheres accumulate at the surface of a cold finger. After scraping them off, they are compacted into a pellet shaped nano-glass specimen. Compaction is performed in a high pressure consolidation device. This procedure is basically identical to the one used to generate nanocrystalline materials. So far, nano-glasses have been synthesized by inert gas condensation from a variety of alloys: Au-Si, Au-La, Fe-Si, La-Si, Pd-Si, Ni-Ti, Ni-Zr, Ti-P (20) – (22).Fig. 3: Production of nano-glasses by consolidation of nm-sized glassy spheres produced by inert gas condensation (18) (19).The production of nano-glasses by heavily deforming bulk metallic glasses (e.g. by rolling, ball milling or extrusion) has not yet been reported.Structural Studies--Small Angle X-ray ScatteringThe nanometer sized microstructure of nano-glasses is expected to show up in SAXS experiments, as was observed (20), (22). Fig. 4 displays the SAXS intensity (20),(21) for a model system with glassy regions of a size of 3.4 nm and a standard size deviation of 1.53 which corresponds to the value found in inert-gas condensed powders. In these experiments, the radial density profile of the glassy regions was described by a power law function. The deviation between the model and the experiment at small scattering angles (Fig. 4) is likely to result from the fact that the log-normal size distribution assumed, underestimates the number of large glassy regions. Ti-P alloys have a negative heat of mixing (~65 kJ mol-1). Hence, concentration fluctuations increase the free energy of the system significantly. In other words, the (Ti70P30) nano-glass (Fig. 4) is likely to be uniform in chemical composition and the SAXS curve shown in Fig. 4 reflects the modulation of theatomic density in this nano-glassFig. 4: Experimental small-angle X-ray scattering intensity of a Ti70P30(•••)nano-glass and the calculated scattering intensity for a model nano-glass with delocalized interfaces (----) as described in this paragraph (22).--Mössbauer-spectroscopyFig. 5 shows the Moessbauer spectra and the corresponding quadrupole splitting (QS) distributions of a melt spun Fe72 Si18 Fe10 glass and a nano-glass with the same chemical composition produced by consolidating 3.6 nm-sized glassy spheres.Fig. 5 Mössbauer spectra and corresponding QS distribution (p(QS)) of a melt-spun Pd72Fe10Si18 metallic glass (upper part of the figure) and a nano-glass with the same chemical composition generated by consolidating 3.6 nm-sized glassy spheres (18).Fig. 6: Relative spectral fraction of the interfacial component versus the inverse droplet size (18).Compared to the melt-spun glass, the nano-glass exhibits two peaks in the QS distribution. The first one coincides with the one of the melt-spun glass. The second one (at about 0.9 mm s-1) was observed only in the nano-glass, and was, thus, assumed to originate from the "interfaces" between the glassy regions. On the other hand, an oxide and/or a crystalline phase may result in a similar peak. Chemical analysis revealed, however, less than 2% oxygen in the nano-glass and crystallization of the nano-glass removed the second peak in the QS distribution (Fig.5).If the interfacial thickness depends little on the size of the glassy regions, the spectral fraction of the second component of the QS distribution in the Mössbauer spectrum (Fig. 5) should be inversely proportional to the size of the droplets consolidated. This was indeed observed experimentally (Fig. 6). From the slope of Fig. 6, the thickness of the interfaces was deduced to be 0.4 nm, corresponding to about two atomic spacings (Fig. 2d). Hence, the structural model (Fig. 2d) of a nano-glass (consisting on nm-sized glassy regions connected by glass/glass interfaces with a reduced density) seems to agree with the Mössbauer results. In fact, this observation also agrees with another result of the Mössbauer measurements (18). In addition to the higher QS value, the interfacial component also exhibited an enhanced isomer shift. This result is similar to the observations reported for other nanometer-sized systems (24) and indicates a reduced s-electron density. The reduced s-electron density may be interpreted in terms of a lower average atomic density and/or electron localization effects at the interfaces.The density profile of the glass/glass interfaces of nano-glasses seem to depend on the chemical composition and/or the time temperature history of specimen preparation. In Fig.7, the SAXS diffraction curves for Si75Au25 and Ti70P30 nano-Fig. 7: Comparison of the small angle scattering curves of Si-Au and Ti-P nano-glasses with the scattering curve expected for atomically sharp glass/glass interfaces (20)-(22).glasses are compared. If the glass/glass interfaces would be atomically sharp, a intensity profile with a slope of 4 (Porod scattering) should be seen. This was not the case. According to Fig. 7, the slope of the Ti/Pd-nano-glass is about 3. A slope of 3 suggests that the glass/glass interfaces are not atomically sharp but delocalized on a scale of several atomic layers. The slope of the SAXS curve for the Si-Au glass was about two (Fig. 7). A SAXS-slope of about two is seen for density fluctuations at the critical point (Ornstein-Zernicke Scattering), (20)-(22)2. In summary, the SAXS results seem to disagree with the localized glass/glass interface structure deduced from the Mössbauer data (Fig. 6).Multi-component Nano-glassesSo far the discussion was limited to nano-glasses consisting of one kind of atoms only. If a nano-glass contains atoms of different chemical elements, multi-component nano-glass may be formed. For the sake of brevity, we shall limit ourselves to two types of multi-component nano-glasses.Fig. 8 displays schematically the atomic structure of a nano-glass consisting of glassy regions made up by chemically different atoms (symbolized by open and closed circles). In this case, two kinds of glass/glass interfaces result. Interfaces between chemically identical glassy regions and interfaces between regions of different chemical compositions.______________________________________________2 In both interpretations void scattering (sample porosity) is assumed to be insignificant.Fig.8: Model (schematic) of a nano-glass that consists of regions with different chemical compositions. The chemically different atoms are represented by open and close circles.. Fig. 9: Schematic cross section through a two-dimensional nano-glass. The atoms are represented by circles. The material consists of nanometer-sized, glassy regions. In the central part of these regions (full circles), the interatomic spacings are similar to the ones of a bulk glass. In the interfacial areas (broken lines, open circles), a broad spectrum of interatomic spacings exists.Fig. 9 (19) shows schematically the structure of a nano-glass made up of glassy regions the surfaces of which differ chemically (atoms represented by open circles) from the centers of these regions (full circles).Research PerspectivesThe studies performed so far on nano-glasses seem to reveal their existence and evidence an atomic structure in which the density varies on a namnoeter scale (Figs.2 , 4 and 7).However, so far little is known on the atomic structure of nano-glasses as a function of chemical composition, the preparation procedure and their time-temperature history. MD-simulations of the atomic structure and the dynamics of nano-glasses appear to be useful to deduce a structural model. In fact, the results of such simulations could be related directly to observations by electron microscopy as well as measurements by SAXS, WAXS, C p and of the elastic constants of nano-glasses. Moreover, studies of the diffusivity, plasticity, the ferromagnetic as well as the optical properties and the thermal stability of nano-glasses seem to be of interest in order to improve our basic understanding of these materials and to evaluate their technological potential as well.AcknowledgementsThe author gratefully acknowledges the support and numerous helpful discussions with numerous colleagues, in particular with R. Birringer, H. Hahn, U. Herr, H. J. Hoefler, U. Gonser, J. Jing, H.Roesner,J. Weissmueller and G.Wilde.Post-deadline addition:Nano-glasses and crystalline materials seem to represent two different classes of materials concerning the coupling between the atomic structure and the defect structure. In crystalline materials, the cores of lattice defects are localized to a few interatomic spacings. For example, the core diameter of a dislocation or the width of a grain boundary are in the order of a few lattice constants. Outside of the defect cores, the atomic arrangement in a crystal is the arrangement given by the crystal structure (slightly distorted by the elastic strain fields of the defects). The physical reason for the localization is the fact that the crystalline state represents the state of lowest free energy at low temperatures. Hence, all regions in which the atomic arrangements deviate significantly from the crystal structure (e.g. in the cores of defects) are minimized in size. In nano-glasses the situation is differentin the following sense. Just like in a liquid, the local arrangement of the atoms in a glass can vary as a function of time at constant free energy and at constant average density of the glass. For example, a glass may deform by viscous flow (i.e. by local variations of the atomic arrangements) near the glass transition temperature. Hence, if a localized region of reduced atomic density - such as a glass/glass interface - is introduced into a glass, the glass can reduce its free energy by delocalizing the locally reduced density of the interface. In other words, the density reduction initially localized in the interface is gradually “smeared” out into the regions of the glass adjacent to the interface, so that a glass of slightly reduced average density (and modified atomic structure) results in the vicinity of the glass/glass interface. (The same process is known to happen, if a local density reduction is introduced into a liquid, e.g. by intense ultrasonic radiation). This implies, by introducing defects into glasses, one can modify the glass structure (and hence the properties of a glass) if the defects are allowed (e.g. by annealing) to delocalize. A comparable process does not exist in crystals. The low energy of the crystalline state prevents this process. In other words, there seems to be a fundamental difference between glassy and crystalline materials. In glasses (e.g. in nano-glasses) defects (e.g. glass/glass interfaces) may be used modify the atomic structure (and, hence, the properties) of the glass by controlling the density, the type and the degree of delocalization of the defects introduced.References(1) Klement, W., Willens R. H., Duwez, P., Nature 187 (1960) 869(2) Chen, H. S., Turnbull, D., Acta Metall. 22 (1974) 1505(3) Kui, H. W., Greer, Al. L., Turnbull D., Appl. Phys. Lett. 45 (1984) 615(4) Inoue, A., Zhang, I., Masumoto, T., Mater. Trans. JIM 30 (1989) 965; 31 (1990)177(5) Kato, A., Zhang T., Kim, S. G., Masumoto, T., Mater. Trans. JIM 31 (1991) 177and 425(6) Peker, A., and Johnson, W. L., Appl. Phys. Lett. 63 (1993) 2342(7) Loeffler, J. F., Bossuyt, S., Peker, A., W. L. Johnson, Phil. Mag. 83 (1003)2797(8) Spaepen, F., Acta Metall. 25 (1977) 407(9) Cahn, R. W. Pratten, N. A., Scott, M. G., Sinning, H. R., Leonhardson, E., Mat.Res. Soc. Symp. 28 (1984) 241(10) Krishnand. K. D., Cahn, R. W., Scripta Metall. 9 (1975) 1259(11) Kim, J. J., Choi, Y., Suresh, S. Argon, A. S., Science 295 (2002) 654(12) Hebert, R. J., Roesner, H., Perepezko, J., Wilde, G., Scripta Mat. inpress(13) Wilde, G., Boucharat, N., Hebert, R. J., Roesner, H., Valiev, R. Z., Mat. Sci.and Eng., submitted(14) Gleiter, H., Europhysics News 20 (1989) 130(15) Tool, A. Q., Eichlin, C. G., J. Amer. Cer. Soc. 14 (1981) 27616) Mitsch, C., Goerler, G. P., Wilde, G., Willnecker, R., J. Non-Cryst. Solids 270‚ (2000) 172(17) Raetzke, K., Hueppe, P. W., Faupel, F., Phys. Rev. Lett. 68 (1992) 2347(18) Jing, J., Kramer, A., Birringer, R., Gleiter, H., Gonser, U., J. Non-Cryst. Solids ´ 113 (1989) 167(19) Gleiter, H., J. Appl. Cryst. 24 (1991) 79(20) Weissmueller, J., Schubert, P., Franz, H., Birringer, R., Gleiter, H., Proc. VIINatl. Conf. on the Physics of Non-Crystall. Solids Cambridge, England August4-9, 1991(21) Weissmüller, J., Birringer, R., Gleiter, H., Key Engineering Materials 77-78,(1993) 161(22) Weissmueller, J., Birringer, R., Gleiter, H., Microcomposites and NanophaseMaterials publ. in: Proc. of the TMS Annual Meeting New Orleans 1991, p. 291 (23) Averback, R. S., Hahn, H., Hoefler, H. J., Logas, J. C., Appl. Phys. Lett. 57(1990) 1745(24) Herr, U., Jing, J., Birringer, R., Gonser, U., Gleiter, H., Appl. Phys. Lett. 50(1987) 472。
Voronoi diagrams
Voronoi diagrams
Computational Geometry
Lecture 10: Voronoi diagrams
Computational Geometry
Lecture 10: Voronoi diagrams
Motivation Voronoi diagrams
14 13
Suppose we measured the lead concentration at a number of sample points
22 18
?
11
7 6
Computational Geometry
Lecture 10: Voronoi diagrams
Motivation Voronoi diagrams
Motivation Voronoi diagrams
Voronoi diagrams Spatial interpolation
Spatial interpolation
sand sand clay clay
Suppose we tested the soil at a number of sample points and classified the results
Computational Geometry Lecture 10: Voronoi diagrams
Motivation Voronoi diagrams
Properties Construction
Some observations
Edges are parts of bisectors Some edges are half-infinite Some cells are unbounded Question: Which ones?
克隆巴赫系数的英文
克隆巴赫系数的英文English:The Bernstein–Sato polynomial of a germ of a complex analytic function at a point is an object of central importance in singularity theory and complex analysis. It encodes crucial information about the singular behavior of the function near the given point. The Bernstein–Sato polynomial is intimately related to the Bernstein–Sato ideal, which is a fundamental concept in the study of D-modules and p-adic differential equations. The study of Bernstein–Sato polynomials and ideals has deep connections to various areas of mathematics, including algebraic geometry, representation theory, and harmonic analysis. These polynomials have been extensively studied in the context of local zeta functions, where they play a crucial role in understanding the structure of singularities and in the computation of zeta functions associated with singularities. In recent years, there has been significant progress in understanding the properties and applications of Bernstein–Sato polynomials, leading to new insights into the nature of singularities and their interactions with other mathematical objects.中文翻译:克隆巴赫多项式是复解析函数在某一点处的一个基本概念,它在奇点理论和复分析中具有重要的地位。
Development and Validation of a Liquid Chromatogra
J. Chem. Chem. Eng. 5 (2011) 1-6.Development and Validation of a LiquidChromatography–Tandem Mass Spectrometry Method for Determination of Artemisinin in Rat PlasmaElhassan Gamal1,2, Yuen Kah1, Wong Jiawoei1, Chitneni Mallikarjun1,3, Al-Dahli Samer1, Khan Jiyauddin1 and Javed Qureshi31. School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia2. Local Pharmaceutical Manufacturing Department, General Pharmacy Directorate, MOH, 11111, Khartoum-Sudan3. School of Pharmacy and Health Sciences, International Medical University, 5700, Kula Lumpur, MalaysiaReceived: September 03, 2010 / Accepted: October 11, 2010 / Published: January 10, 2011.Abstract: Artemisinin is a potent anti-malarial drug isolated from traditional Chinese medicinal herb, Artemisia annua. The objective of this study was to develop and validate a sensitive and specific LC-MS/MS method for the determination of artemisinin in rat plasma using amlodipine as Internal Standard. The method consist of a simple liquid-liquid extraction with methyl tertiary butyl ether (MTBE) with subsequent evaporation of the supernatant to dryness followed by the analysis of the reconstituted sample by LC-MS/MS with a Z-spray atmospheric pressure ionization (API) interface in the positive ion-multiple reaction monitoring mode to monitor precursor→product ions of m/z 282.70→m/z 209.0 for artemisinin and m/z 408.9→m/z 237.0 for amlodipine respectively. The method was linear (0.999) over the concentration range of 7.8–2000 ng/mL in rat plasma. The intra and inter-day accuracy were measured to be within 94-104.2% and precision (CV) were all less than 5%. The extraction recovery means for internal standard and all the artemisinin concentrations used were between 82-85%.Key words: Artemisinin, LC-MS/MS, amlodipine, plasma, accuracy and precision.1. IntroductionArtemsinin is the name given to the active principle of qinghaosu, an extract of the Chinese medicinal plant qinghaosu or green Artemisia (Artemisinin annua L.) which has been used for many years centuries in Chinese traditional medicine for treatment of fever and malaria [1]. In 1972, Chinese researchers isolated artemisinin from Artemisia annua L. sweet wormwood) and its structure was elucidate in 1979 as show in Fig. 1.The determination of artemisinin and its derivatives in biological matrices have previously been characterized using several analytical techniques suchCorresponding author: Gamal Osman Elhassan Ph.D., research field: pharmaceutical technology. E-mail: ******************.as LC, HPLC, GC-MS etc [3-8]. However, some of these methods suffer from few drawbacks. In particulars, interference with endogenous constituents in the plasma at the absorption wave length of the derivatized compounds may render these techniques unsatisfactory and few of them lacked the required sensitivity to be used for measurement of drugFig. 1 The chemical structure of artemisinin [2].ll Rights Reserved.Development and Validation of a Liquid Chromatography–Tandem Mass Spectrometry Method forDetermination of Artemisinin in Rat Plasma2concentration in blood sample obtained from clinical investigation [9].To increase the specificity and sensitivity of HPLC-UV method, some workers combined it with a mass spectrometry (MS) and the total system is described as LC-MS technique [10, 11]. The development of LC-tandem mass spectrometry (LC-MS/MS) has made a more specific and sensitive analysis of artemisinin and its derivatives possible [12, 13]. The objective of this study was to develop a sensitive and specific LC-MS/MS method for the determination of artemisinin in rat plasma by simple liquid-liquid extraction procedure.2. Materials and Methods2.1 MaterialsArtemisinin was purchased from Kunming Pharmaceutical Corporation (Kunming, China). Amlodipine was obtained from Sigma Chemical (Louis, USA). Acetonitrile (ACN), formic acid and methyl tertiary butyl ether (MTBE) were purchased from J.T Baker (USA).3. Methods3.1 Instrumentation and ConditionsThe instrumentation comprised of Quattro-micro tandem mass spectrometer with Z-spray atomospheric pressure ionization (API) source (Micromass, Manchester, UK) using electrospray ionization (ESI) operated at positive mode. Chromatography was performed on an Alliance 2,695 separation module (Waters, M.A, USA). The delivery system consisted of an autosampler and a column heater. The chromatographic separation was obtained using an X Terra MS C8 encapped (5 μm) (150 × 2.1 mm) analytical column (Water, USA).3.2 Sample PreparationA 250 μL aliquot of plasma was pipetted into a screw-capped culture tube, followed by 100 μL of internal standard solution (50 ng/mL). To each tube, 5 mL (MTBE) extraction solvent was then added and the mixture was vortexed for 2.5 minutes followed by centrifuging for 15 minutes at 3,500 rpm. The upper layer was transferred to a reactive vial and dried under nitrogen flow at 40 °C. The residue was then reconstituted with 250 μL of mobile phase and 20 μL was injected into the LC-MS/MS system.3.3 Assay ValidationCalibration curve at a concentration range of 7.8–2,000 ng/mL were constructed by spiking blank human plasma with a known amount of artemisinin. Plasma sample spiked with artemisinin at these concentrations 7.8, 62.5, 250, 2,000 ng/mL were used to determine the within and between-day accuracy and precision. For within-day accuracy and precision, replicates analysis (n = 6) for each concentration were performed in a single day. For between-day evaluation, analysis was carried out with a single sample of each concentration daily over 6 days, with calibration curve constructed on each day of analysis. The extraction recovery of artemisinin was estimated by comparing the peak height obtained after extraction of the samples from plasma with that of aqueous artemisinin solution of the corresponding concentration.4. Results and DiscussionBoth electrospray (TIS) and atmospheric pressure chemical ionisation (APCI) methods have been reported previously for the quantification of artemisinin derivatives in biological fluids [11, 12, 14-16]. According to the previously reported methods TIS was found to be superior to APCI for the quantification of artesunate and dihydroartemisinin (DHA) mainly because of improved linearity [16]. Therefore in this method electrospray ionization was used. When artemisinin and amlodipine were injected directly into the mass spectrometer along with mobile phase in the positive mode, the protonated molecules of artemisinin and amlodipine were set as precursorll Rights Reserved.Development and Validation of a Liquid Chromatography–Tandem Mass Spectrometry Method forDetermination of Artemisinin in Rat Plasma3(a)(b)Fig. 2 (a) Positive-ionization electrospray mass spectra of precursor ion for artemisinin; (b) Positive-ionization electrospray mass spectra of product ion for artemisinin.ions with m/z of 282.7 and 408.7, respectively. The product ion that gave the highest intensity was m/z of 209.0 for artemisinin and 237.7 for amlodipine. Fig 2(a) shows the spectra precursor ion, 2(b) production for artemisinin.Artemisinin and amlodipine have retention time of approximately 6.9 and 1.65 minutes, respectively (Fig.3). The peak was well resolved and free from interference from endogenous compounds in rat plasma (Fig. 4).ll Rights Reserved.Development and Validation of a Liquid Chromatography–Tandem Mass Spectrometry Method forDetermination of Artemisinin in Rat Plasma4Fig. 3 Plasma spiked with 500 ng/ml artemisinin and amlodipine 50 ng/mL.Fig. 4 Chromatograms for analysis of artemisinin in plasma (Rat blank plasma).Calibration curve was linear over the entire range of calibration curves with a mean correlation coefficient greater than 0.9995 (Fig. 5).The limit of quantification (LOQ) of the assay method was 7.8 ng/mL being the lowest concentration used to construct the calibration curve whereas the limit of detection (LOD) was 3.9 ng/mL at a signal to noise ratio of 3. The validation data demonstrated a good precision, accuracy and recovery. The extraction recovery means for internal standard and all artemisinin concentrations used were 75-85% (Table 1). The within-day and between-day accuracy and precision values are given in Table 2.Neither artemisinin nor the internal standard producedll Rights Reserved.Development and Validation of a Liquid Chromatography–Tandem Mass Spectrometry Method forDetermination of Artemisinin in Rat Plasma5Fig. 5 Mean calibration curve of artemisinin (ng/mL).Table 1 Extraction recovery.Concentration (ng/mL) Mean recovery (%) CV (%)7.81 75.081.5062.50 82.161.94250.00 82.03 2.072000.00 85.23 1.48Table 2 Within-day and between-day precision andaccuracy.Added (ng/mL)Within-day Between-day Accuracy (%) C.V (%) Accuracy (%) C.V (%)7.81 96.00 4.60 104.11 2.30 62.50 98.10 1.60 94.10 2.20 250.00 98.10 1.50 98.10 1.60 2000.00 96.10 2.50 97.10 1.80any detectable carry-over after three injections of upper limit of quantification. Blank rat plasma showed no interference with artemisinin. Interfering signals from blank plasma contributed less than 20% of the artemisinin signal at LOQ. There was no interference of artemisinin on the internal standard or vice versa. A small enhancement for artemisinin and the internal standard could be detected when references in neat injection solvent were compared with references in extracted blank biological matrix. The normalized matrix effects (artemisinin/internal standard) were close to 1 with a low variation in accordance with international guidelines. Post-column infusion experiments confirmed the absence of regions with severe matrix effects (i.e., no sharp drops or increases in the response) for blank human plasma extracted with the developed method.Xing et al. used artmether as an internal standard for the analysis of artemisinin [17]while for the analysis of artemisinin derivatives; artemisinin was used as internal standard [14]. In the present study amlodipine was found to be suitable because it could be separated chromatographically, ionized and fragmented under the conditions that optimized the intensity of artemisinin peak (Fig. 3).The analysis of artemisinin and its derivatives with mass spectrometry are most often performed with a different mode of ionization. Xing et al. used ESI inletin the positive ion-multiple reaction monitoring mode which relatively producing a higher sensitivity than in the SIM mode. Therefore, the mass spectrometry was operated at positive ion-MRM mode.4. ConclusionThe LC-MS/MS method described in this work is suitable for the determination of artemisinin in plasma. The assay procedure is simple with a relatively shortll Rights Reserved.Development and Validation of a Liquid Chromatography–Tandem Mass Spectrometry Method forDetermination of Artemisinin in Rat Plasma6retention time allowing sufficient sample to beprocessed to be applied to pharmacokinetic and bioavailability studies of artemisinin. The accuracy and precision of the assay method, as well as the recovery of extraction procedure were found to be satisfactory.References[1] D.L. Klayman, Qinghasou (Artemisinin): An antimalaria drug from China, Science 228 (1985) 1049-1055.[2] X.D. Luo, C.C. Shen, The chemistry, pharmacology andclinical applications of Qinghaosu (artemisinin) and it’sderivatives, Med. Res. Rev. 7 (1987) 29-52.[3] K.T. Batty, M. Ashton, K.F. Llett, G . Edwards, T.M. Davis,Selective high-performance liquid chromatography ofartesunate and α-and β-dihydroartemisinin in patients withfalciparum malaria, J. Chromatog. B 677 (2-3) (1996)345-350.[4] J. Karbwang, K. Na-Bangchang, P. Molunto, V . Banmairuroi, Determination of artemisinin and its majormetabolite, dihydroartemisinin, in plasma usinghigh-performance liquid chromatography withelectrochemical detector, J. Chromatog. B 7 (1-2) (1997)259-265.[5] K.L. Chan, K.H. Yuen, H. Takayanki, S. Jinandasa, K.K. Peh, Polymorphism of artemisinin from Artemisia annua,Phytochemistry 46 (7) (1997) 1209-1214.[6] G .Q. Li, T.O. Peggins, L.L. Fleckenstein, K. Masonic,M.H. Heiffles, T.G . Brewer, The pharmacokinetics andbiovailability of dihydroartemisinin, arteether, artemether,artesunic acid and artelinic acid in rats, J. Pharm.Pharmacol 5 (1998) 173-182.[7] B.A. Avery, K.K. Venkatesh, M.A. Avery, Rapid determination of artemisinin and related analogues usinghigh-perfomance liquid chromatography and anevaporative light scattering detector, J. Chromat. B 730 (1)(1999) 71-80.[8] S.S. Mohamed, S.A. Khalid, S.A. Ward, T.S.M. Wan,H.P.O. Tang, M. Zheng, R.K. Haynes, G . Edwards,Simultaneous determination of artemether and its majormetabolite dihydroartemisinin in plasma by gaschromatography-mass spectrometry-selected ionmonitoring, J. Chromat. B 731(1999) 251-260.[9] K.T. Batty, M. Ashton, K.F. Llett, G . Edward, T.M. Davis,The pharmacokinetics of artemisinin (ART) and artesunate (ARTS) in healthy volunteers, Am J. Trop Med. Hyg. 58(2) (1998) 125-126.[10] C. Souppart, N. Gouducheau, N. Sandenan, F. Richard,Development and validation of a high-performance liquid chromatography-mass spectrometry assay for the determination of artemisinin and its metabolite dihydraartemisinin in human plasma, J. Chromat. B 774(2002) 195-203.[11] H. Naik, D.J. Murry, L.E. Kirsch, L. Fleckenstein,Development and validation of high-performance liquid chromatography-mass spectroscopy assay for determination of artesunate and dihydrroartemisinin in human plasma, J. Chromat. B 816 (1-2) (2005) 233-242. [12] J. Xing, H. Yan, S. Zhang, G . Ren, Y . Gao, A high-performance liquid chromatography/tandem mass spectrometry method for the determination of artemisinin in rat plasma, Rapid Commun in Mass Spectro. 20 (9) (2006) 1463-1468. [13] J. Xing, H.X. Yan, R.L. Wang, L.F. Zhang, S.Q. Zhang,Liquid chromatography-tandem mass spectrometry assay for the quantitation of β-dihydroartemisinin in rat plasma, J. Chromat. B 852 (1-2) (2007) 202-207. [14] M. Rajanikanth, K.P. Madhusudanan, R.C. Gupta, An HPLC-MS method for simultaneous estimation of alpha, beta-arteether and its metabolite dihydroartemisinin, in rat plasma for application to pharmacokinetic study, J Biomed. Chromat. 17 (7) (2003) 440-446. [15] Y . Gu, Q. Li, M.V . Elendez, P. Weina, Comparison of HPLC with electrochemical detection and LC–MS/for the separation and validation of artesunate and dihydroartemisinin in animal and human plasma, J. Chromatogr B 867 (2008) 213-218. [16] W. Hanpithakpong, B. Kamanikom, A.M. Dondorp, P.Singhasivanon, N.J. White, N.P. Day, N. Lindegardh, A liquid chromatographic-tandem mass spectrometric method for determination of artesunate and its metabolite dihydroartemisinin in human plasma, J. Chromatogr. B 876 (2008) 61-68. [17] Y . Xing, H. Yan, S. Zhang, G . Ren, Y . Gao, A high-performance liquid chromatography/tandem mass spectrometry method for the determination of artemisinin rat plasma, Rapid Communication in Mass Spectrometry 20 (9) (2006) 1463-1468.ll Rights Reserved.。
Rough Approximation of a perference Relation by Dominance Relations
薛定谔—麦克斯韦尔方程径向解的存在性和多重性(英文)
In 1887, the German physicist Erwin Schrödinger proposed a radial solution to the Maxwell-Schrödinger equation. This equation describes the behavior of an electron in an atom and is used to calculate its energy levels. The radial solution was found to be valid for all values of angular momentum quantum number l, which means that it can describe any type of atomic orbital.The existence and multiplicity of this radial solution has been studied extensively since then. It has been shown that there are infinitely many solutions for each value of l, with each one corresponding to a different energy level. Furthermore, these solutions can be divided into two categories: bound states and scattering states. Bound states have negative energies and correspond to electrons that are trapped within the atom; scattering states have positive energies and correspond to electrons that escape from the atom after being excited by external radiation or collisions with other particles.The existence and multiplicity of these solutions is important because they provide insight into how atoms interact with their environment through electromagnetic radiation or collisions with other particles. They also help us understand why certain elements form molecules when combined together, as well as why some elements remain stable while others decay over time due to radioactive processes such as alpha decay or beta decay.。
修正ROF模型的分裂Bregman算法
0 引 言
1 9 9 2年 ,R u i n等人 针对 高斯 噪声 图像提 出 了 RO F去
噪模 型
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mo r e d e t a i l st h n t a h eR( ) Fmo de li nt h el O Wb r i g h t r e g i o n .
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型 ,且 收 敛 速 度 快 。
关键词 :图像去噪 ;RO F模型 ;泊松噪声 ;分 裂 B r e g ma n算 法;全 变分 中 图法分类 号 : T P 3 9 1 . 7 2 文献标识号 : A 文章编号 :1 0 0 0 — 7 0 2 4( 2 0 1 3 )0 7 - 2 4 5 5 — 0 5
e n c e a n d u n i q u e n e s s re a p r o v d e f o r t h e s o l u t i o n o f t h e mo d i f i d e ROF mo d e l ,a nd s t r o n g n o n l i n e ri a t y i n t h e f i d e l i t y t e m r i s p r o c e s s d e b y t h e o n e s t e p - l a g t e c h n i q u e Th e n,s p l i t Br e g ma n a l g o r i t h m i s e mp l o y e d t o ol s v e t h e mo d i f i e d R OF mo de l e f f i c i e n t l y .Nu me r i c a l e x er p i me n t s re a p r o v i d d e t o v li a d a t e t h e e f f e c t i v e n e s s nd a e f f i c i e n c y o f t h e p r o p o s d e a p p r o a c h .F or r e a l C T d a t a ,t h e p r o p o s e d a p p oa r c h ou c l d p r e s e r v e
The macronucleus of Vorticella convallaria(Linn.)during conjugation
188
B. R. SESHACHAR A Nቤተ መጻሕፍቲ ባይዱD C. M. S. DASS
is amitotic. The micronucleus, however, always divides by mitosis. 4 What is the nature and significance of the differential . staining of macro- and micronucleus 1 The micronucleus often gives an extremely poor reaction with Feulgen or methyl green, while the macronucleus is brilliantly positive. 5. What is the significance of the breaking up and absorption of the marconucleus at the time of conjugation? 6. What is the origin of the DNA of the new macronucleus after conjugation? Conclusive answers for these questions have not yet been provided but an attempt has been made in previous papers for an approach towar,ds them (Seshachar, '47, '50a and '50b ; Seshachar and Srinath, '47). The purpose of this paper is t o attempt answers to some of the others, particularly t o questions 5 and 6, above.
Voronoi Diagrams - A Survey of a Fundamental Geometric Data Structure
convex hull, crystal structure, divide-and-conquer,
geometric data structure, growth
model, higher dimensional embedding, hyperplane arrangement,
k-set, motion
@ 1991 ACM 0360-0300/91/0900-0345
$01.50
ACM Computing Surveys, Vol. 23, No. 3, September 1991
346
q
Franz A urenhammer
CONTENTS
INTRODUCTION
1. HISTORICAL PERSPECTIVE
unified exposition of its mathematical
and algorithmic properties. Finally, the paper
provides the first comprehensive bibliography
on Voronoi diagrams and related
Relatlon to Higher Dimensional ObJects.
3.2 The Topology of Planar Diagrams:
Divide-and-Conquer
ConstructIon
and its Variants.
33 A Deformation of the Voronoi Diagram:
structures.
Categories and Subject Descriptors: F.2.2 [Analysis of Algorithms
python bonferroni方法
python bonferroni方法
Bonferroni 方法是一种用于多重比较校正的统计方法,常用于控制多重假设检验的整体错误率。
在统计学中,多重假设检验指的是同时检验多个关于总体参数的假设。
由于同时进行多个假设检验,会增加发生错误的概率。
因此,为了控制整体错误率,需要对每个单独的检验进行校正。
Bonferroni 方法的基本思想是将显著性水平(通常是0.05或0.01)除以进行的比较的数量,得到每个检验的校正显著性水平。
如果某个检验的p值低于校正显著性水平,则可以拒绝相应的零假设。
假设有k个不相关的假设检验,那么Bonferroni 校正的校正显著性水平为α/k。
例如,如果进行10个独立的假设检验,希望保持整体错误率在0.05水平下控制,那么每个检验的校正显著性水平就是0.05/10=0.005。
使用Bonferroni 方法进行多重比较校正的优点是简单易用,并且保守性较高,但其缺点是可能导致Type II 错误(即误拒真)。
在比较数量较多的情况下,Bonferroni 方法的校正显著性水平较为保守,可能会导致较多的假阳性结果。
其他的多重比较校正方法还包括Holm-Bonferroni 方法、False Discovery
Rate(FDR)等。
不同的多重比较校正方法适用于不同的情况,研究者在选择使用何种方法时需要综合考虑相关因素。
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Reproduction numbers and sub-threshold endemic equilibria for compartmental models of disease trans
Reproduction numbers and sub-threshold endemicequilibria for compartmental models of disease transmissionP.van den Driesschea,1,James Watmough b,*,2aDepartment of Mathematics and Statistics,University of Victoria,Victoria,BC,Canada V8W 3P4b Department of Mathematics and Statistics,University of New Brunswick,Fredericton,NB,Canada E3B 5A3Received 26April 2001;received in revised form 27June 2001;accepted 27June 2001Dedicated to the memory of John JacquezAbstractA precise definition of the basic reproduction number,R 0,is presented for a general compartmental disease transmission model based on a system of ordinary differential equations.It is shown that,if R 0<1,then the disease free equilibrium is locally asymptotically stable;whereas if R 0>1,then it is unstable.Thus,R 0is a threshold parameter for the model.An analysis of the local centre manifold yields a simple criterion for the existence and stability of super-and sub-threshold endemic equilibria for R 0near one.This criterion,together with the definition of R 0,is illustrated by treatment,multigroup,staged progression,multistrain and vector–host models and can be applied to more complex models.The results are significant for disease control.Ó2002Elsevier Science Inc.All rights reserved.Keywords:Basic reproduction number;Sub-threshold equilibrium;Disease transmission model;Disease control1.IntroductionOne of the most important concerns about any infectious disease is its ability to invade a population.Many epidemiological models have a disease free equilibrium (DFE)at whichtheMathematical Biosciences 180(2002)29–48/locate/mbs*Corresponding author.Tel.:+1-5064587323;fax:+1-5064534705.E-mail addresses:pvdd@math.uvic.ca (P.van den Driessche),watmough@unb.ca (J.Watmough).URL:http://www.math.unb.ca/$watmough.1Research supported in part by an NSERC Research Grant,the University of Victoria Committee on faculty research and travel and MITACS.2Research supported by an NSERC Postdoctoral Fellowship tenured at the University of Victoria.0025-5564/02/$-see front matter Ó2002Elsevier Science Inc.All rights reserved.PII:S0025-5564(02)00108-630P.van den Driessche,J.Watmough/Mathematical Biosciences180(2002)29–48population remains in the absence of disease.These models usually have a threshold parameter, known as the basic reproduction number,R0,such that if R0<1,then the DFE is locally as-ymptotically stable,and the disease cannot invade the population,but if R0>1,then the DFE is unstable and invasion is always possible(see the survey paper by Hethcote[1]).Diekmann et al.[2]define R0as the spectral radius of the next generation matrix.We write down in detail a general compartmental disease transmission model suited to heterogeneous populations that can be modelled by a system of ordinary differential equations.We derive an expression for the next generation matrix for this model and examine the threshold R0¼1in detail.The model is suited to a heterogeneous population in which the vital and epidemiological parameters for an individual may depend on such factors as the stage of the disease,spatial position,age or behaviour.However,we assume that the population can be broken into homo-geneous subpopulations,or compartments,such that individuals in a given compartment are indistinguishable from one another.That is,the parameters may vary from compartment to compartment,but are identical for all individuals within a given compartment.We also assume that the parameters do not depend on the length of time an individual has spent in a compart-ment.The model is based on a system of ordinary equations describing the evolution of the number of individuals in each compartment.In addition to showing that R0is a threshold parameter for the local stability of the DFE, we apply centre manifold theory to determine the existence and stability of endemic equilib-ria near the threshold.We show that some models may have unstable endemic equilibria near the DFE for R0<1.This suggests that even though the DFE is locally stable,the disease may persist.The model is developed in Section2.The basic reproduction number is defined and shown to bea threshold parameter in Section3,and the definition is illustrated by several examples in Section4.The analysis of the centre manifold is presented in Section5.The epidemiological ramifications of the results are presented in Section6.2.A general compartmental epidemic model for a heterogeneous populationConsider a heterogeneous population whose individuals are distinguishable by age,behaviour, spatial position and/or stage of disease,but can be grouped into n homogeneous compartments.A general epidemic model for such a population is developed in this section.Let x¼ðx1;...;x nÞt, with each x i P0,be the number of individuals in each compartment.For clarity we sort the compartments so that thefirst m compartments correspond to infected individuals.The distinc-tion between infected and uninfected compartments must be determined from the epidemiological interpretation of the model and cannot be deduced from the structure of the equations alone,as we shall discuss below.It is plausible that more than one interpretation is possible for some models.A simple epidemic model illustrating this is given in Section4.1.The basic reproduction number can not be determined from the structure of the mathematical model alone,but depends on the definition of infected and uninfected compartments.We define X s to be the set of all disease free states.That isX s¼f x P0j x i¼0;i¼1;...;m g:In order to compute R0,it is important to distinguish new infections from all other changes inpopulation.Let F iðxÞbe the rate of appearance of new infections in compartment i,Vþi ðxÞbe therate of transfer of individuals into compartment i by all other means,and VÀi ðxÞbe the rate oftransfer of individuals out of compartment i.It is assumed that each function is continuously differentiable at least twice in each variable.The disease transmission model consists of non-negative initial conditions together with the following system of equations:_x i¼f iðxÞ¼F iðxÞÀV iðxÞ;i¼1;...;n;ð1Þwhere V i¼VÀi ÀVþiand the functions satisfy assumptions(A1)–(A5)described below.Sinceeach function represents a directed transfer of individuals,they are all non-negative.Thus,(A1)if x P0,then F i;Vþi ;VÀiP0for i¼1;...;n.If a compartment is empty,then there can be no transfer of individuals out of the compartment by death,infection,nor any other means.Thus,(A2)if x i¼0then VÀi ¼0.In particular,if x2X s then VÀi¼0for i¼1;...;m.Consider the disease transmission model given by(1)with f iðxÞ,i¼1;...;n,satisfying con-ditions(A1)and(A2).If x i¼0,then f iðxÞP0and hence,the non-negative cone(x i P0, i¼1;...;n)is forward invariant.By Theorems1.1.8and1.1.9of Wiggins[3,p.37]for each non-negative initial condition there is a unique,non-negative solution.The next condition arises from the simple fact that the incidence of infection for uninfected compartments is zero.(A3)F i¼0if i>m.To ensure that the disease free subspace is invariant,we assume that if the population is free of disease then the population will remain free of disease.That is,there is no(density independent) immigration of infectives.This condition is stated as follows:(A4)if x2X s then F iðxÞ¼0and VþiðxÞ¼0for i¼1;...;m.The remaining condition is based on the derivatives of f near a DFE.For our purposes,we define a DFE of(1)to be a(locally asymptotically)stable equilibrium solution of the disease free model,i.e.,(1)restricted to X s.Note that we need not assume that the model has a unique DFE. Consider a population near the DFE x0.If the population remains near the DFE(i.e.,if the introduction of a few infective individuals does not result in an epidemic)then the population will return to the DFE according to the linearized system_x¼Dfðx0ÞðxÀx0Þ;ð2Þwhere Dfðx0Þis the derivative½o f i=o x j evaluated at the DFE,x0(i.e.,the Jacobian matrix).Here, and in what follows,some derivatives are one sided,since x0is on the domain boundary.We restrict our attention to systems in which the DFE is stable in the absence of new infection.That is, (A5)If FðxÞis set to zero,then all eigenvalues of Dfðx0Þhave negative real parts.P.van den Driessche,J.Watmough/Mathematical Biosciences180(2002)29–4831The conditions listed above allow us to partition the matrix Df ðx 0Þas shown by the following lemma.Lemma 1.If x 0is a DFE of (1)and f i ðx Þsatisfies (A1)–(A5),then the derivatives D F ðx 0Þand D V ðx 0Þare partitioned asD F ðx 0Þ¼F 000 ;D V ðx 0Þ¼V 0J 3J 4;where F and V are the m Âm matrices defined byF ¼o F i o x j ðx 0Þ !and V ¼o V i o x jðx 0Þ !with 16i ;j 6m :Further ,F is non-negative ,V is a non-singular M-matrix and all eigenvalues of J 4have positive real part .Proof.Let x 02X s be a DFE.By (A3)and (A4),ðo F i =o x j Þðx 0Þ¼0if either i >m or j >m .Similarly,by (A2)and (A4),if x 2X s then V i ðx Þ¼0for i 6m .Hence,ðo V i =o x j Þðx 0Þ¼0for i 6m and j >m .This shows the stated partition and zero blocks.The non-negativity of F follows from (A1)and (A4).Let f e j g be the Euclidean basis vectors.That is,e j is the j th column of the n Ân identity matrix.Then,for j ¼1;...;m ,o V i o x jðx 0Þ¼lim h !0þV i ðx 0þhe j ÞÀV i ðx 0Þh :To show that V is a non-singular M-matrix,note that if x 0is a DFE,then by (A2)and (A4),V i ðx 0Þ¼0for i ¼1;...;m ,and if i ¼j ,then the i th component of x 0þhe j ¼0and V i ðx 0þhe j Þ60,by (A1)and (A2).Hence,o V i =o x j 0for i m and j ¼i and V has the Z sign pattern (see Appendix A).Additionally,by (A5),all eigenvalues of V have positive real parts.These two conditions imply that V is a non-singular M-matrix [4,p.135(G 20)].Condition (A5)also implies that the eigenvalues of J 4have positive real part.Ã3.The basic reproduction numberThe basic reproduction number,denoted R 0,is ‘the expected number of secondary cases produced,in a completely susceptible population,by a typical infective individual’[2];see also [5,p.17].If R 0<1,then on average an infected individual produces less than one new infected individual over the course of its infectious period,and the infection cannot grow.Conversely,if R 0>1,then each infected individual produces,on average,more than one new infection,and the disease can invade the population.For the case of a single infected compartment,R 0is simply the product of the infection rate and the mean duration of the infection.However,for more complicated models with several infected compartments this simple heuristic definition of R 0is32P.van den Driessche,J.Watmough /Mathematical Biosciences 180(2002)29–48insufficient.A more general basic reproduction number can be defined as the number of new infections produced by a typical infective individual in a population at a DFE.To determine the fate of a‘typical’infective individual introduced into the population,we consider the dynamics of the linearized system(2)with reinfection turned off.That is,the system _x¼ÀD Vðx0ÞðxÀx0Þ:ð3ÞBy(A5),the DFE is locally asymptotically stable in this system.Thus,(3)can be used to de-termine the fate of a small number of infected individuals introduced to a disease free population.Let wi ð0Þbe the number of infected individuals initially in compartment i and letwðtÞ¼w1ðtÞ;...;w mðtÞðÞt be the number of these initially infected individuals remaining in the infected compartments after t time units.That is the vector w is thefirst m components of x.The partitioning of D Vðx0Þimplies that wðtÞsatisfies w0ðtÞ¼ÀV wðtÞ,which has the unique solution wðtÞ¼eÀVt wð0Þ.By Lemma1,V is a non-singular M-matrix and is,therefore,invertible and all of its eigenvalues have positive real parts.Thus,integrating F wðtÞfrom zero to infinity gives the expected number of new infections produced by the initially infected individuals as the vector FVÀ1wð0Þ.Since F is non-negative and V is a non-singular M-matrix,VÀ1is non-negative[4,p.137 (N38)],as is FVÀ1.To interpret the entries of FVÀ1and develop a meaningful definition of R0,consider the fate of an infected individual introduced into compartment k of a disease free population.The(j;k)entry of VÀ1is the average length of time this individual spends in compartment j during its lifetime, assuming that the population remains near the DFE and barring reinfection.The(i;j)entry of F is the rate at which infected individuals in compartment j produce new infections in compartment i. Hence,the(i;k)entry of the product FVÀ1is the expected number of new infections in com-partment i produced by the infected individual originally introduced into compartment k.Fol-lowing Diekmann et al.[2],we call FVÀ1the next generation matrix for the model and set R0¼qðFVÀ1Þ;ð4Þwhere qðAÞdenotes the spectral radius of a matrix A.The DFE,x0,is locally asymptotically stable if all the eigenvalues of the matrix Dfðx0Þhave negative real parts and unstable if any eigenvalue of Dfðx0Þhas a positive real part.By Lemma1, the eigenvalues of Dfðx0Þcan be partitioned into two sets corresponding to the infected and uninfected compartments.These two sets are the eigenvalues of FÀV and those ofÀJ4.Again by Lemma1,the eigenvalues ofÀJ4all have negative real part,thus the stability of the DFE is determined by the eigenvalues of FÀV.The following theorem states that R0is a threshold parameter for the stability of the DFE.Theorem2.Consider the disease transmission model given by(1)with fðxÞsatisfying conditions (A1)–(A5).If x0is a DFE of the model,then x0is locally asymptotically stable if R0<1,but un-stable if R0>1,where R0is defined by(4).Proof.Let J1¼FÀV.Since V is a non-singular M-matrix and F is non-negative,ÀJ1¼VÀF has the Z sign pattern(see Appendix A).Thus,sðJ1Þ<0()ÀJ1is a non-singular M-matrix;P.van den Driessche,J.Watmough/Mathematical Biosciences180(2002)29–483334P.van den Driessche,J.Watmough/Mathematical Biosciences180(2002)29–48where sðJ1Þdenotes the maximum real part of all the eigenvalues of the matrix J1(the spectral abscissa of J1).Since FVÀ1is non-negative,ÀJ1VÀ1¼IÀFVÀ1also has the Z sign pattern.Ap-plying Lemma5of Appendix A,with H¼V and B¼ÀJ1¼VÀF,we have ÀJ1is a non-singular M-matrix()IÀFVÀ1is a non-singular M-matrix:Finally,since FVÀ1is non-negative,all eigenvalues of FVÀ1have magnitude less than or equal to qðFVÀ1Þ.Thus,IÀFVÀ1is a non-singular M-matrix;()qðFVÀ1Þ<1:Hence,sðJ1Þ<0if and only if R0<1.Similarly,it follows thatsðJ1Þ¼0()ÀJ1is a singular M-matrix;()IÀFVÀ1is a singular M-matrix;()qðFVÀ1Þ¼1:The second equivalence follows from Lemma6of Appendix A,with H¼V and K¼F.The remainder of the equivalences follow as with the non-singular case.Hence,sðJ1Þ¼0if and only if R0¼1.It follows that sðJ1Þ>0if and only if R0>1.ÃA similar result can be found in the recent book by Diekmann and Heesterbeek[6,Theorem6.13].This result is known for the special case in which J1is irreducible and V is a positive di-agonal matrix[7–10].The special case in which V has positive diagonal and negative subdiagonal elements is proven in Hyman et al.[11,Appendix B];however,our approach is much simpler(see Section4.3).4.Examples4.1.Treatment modelThe decomposition of fðxÞinto the components F and V is illustrated using a simple treat-ment model.The model is based on the tuberculosis model of Castillo-Chavez and Feng[12,Eq.(1.1)],but also includes treatment failure used in their more elaborate two-strain model[12,Eq.(2.1)].A similar tuberculosis model with two treated compartments is proposed by Blower et al.[13].The population is divided into four compartments,namely,individuals susceptible to tu-berculosis(S),exposed individuals(E),infectious individuals(I)and treated individuals(T).The dynamics are illustrated in Fig.1.Susceptible and treated individuals enter the exposed com-partment at rates b1I=N and b2I=N,respectively,where N¼EþIþSþT.Exposed individuals progress to the infectious compartment at the rate m.All newborns are susceptible,and all indi-viduals die at the rate d>0.Thus,the core of the model is an SEI model using standard inci-dence.The treatment rates are r1for exposed individuals and r2for infectious individuals. However,only a fraction q of the treatments of infectious individuals are successful.Unsuc-cessfully treated infectious individuals re-enter the exposed compartment(p¼1Àq).The diseasetransmission model consists of the following differential equations together with non-negative initial conditions:_E¼b1SI=Nþb2TI=NÀðdþmþr1ÞEþpr2I;ð5aÞ_I¼m EÀðdþr2ÞI;ð5bÞ_S¼bðNÞÀdSÀb1SI=N;ð5cÞ_T¼ÀdTþr1Eþqr2IÀb2TI=N:ð5dÞProgression from E to I and failure of treatment are not considered to be new infections,but rather the progression of an infected individual through the various compartments.Hence,F¼b1SI=Nþb2TI=NB B@1C CA and V¼ðdþmþr1ÞEÀpr2IÀm Eþðdþr2ÞIÀbðNÞþdSþb1SI=NdTÀr1EÀqr2Iþb2TI=NB B@1C CA:ð6ÞThe infected compartments are E and I,giving m¼2.An equilibrium solution with E¼I¼0has the form x0¼ð0;0;S0;0Þt,where S0is any positive solution of bðS0Þ¼dS0.This will be a DFE if and only if b0ðS0Þ<d.Without loss of generality,assume S0¼1is a DFE.Then,F¼0b100;V¼dþmþr1Àpr2Àm dþr2;givingVÀ1¼1ðdþmþr1Þðdþr2ÞÀm pr2dþr2pr2m dþmþr1and R0¼b1m=ððdþmþr1Þðdþr2ÞÀm pr2Þ.A heuristic derivation of the(2;1)entry of VÀ1and R0are as follows:a fraction h1¼m=ðdþmþr1Þof exposed individuals progress to compartment I,a fraction h2¼pr2=ðdþr2Þof infectious individuals re-enter compartment E.Hence,a fractionh1of exposed individuals pass through compartment I at least once,a fraction h21h2passthroughat least twice,and a fraction h k 1h k À12pass through at least k times,spending an average of s ¼1=ðd þr 2Þtime units in compartment I on each pass.Thus,an individual introduced into com-partment E spends,on average,s ðh 1þh 21h 2þÁÁÁÞ¼s h 1=ð1Àh 1h 2Þ¼m =ððd þm þr 1Þðd þr 2ÞÀm pr 2Þtime units in compartment I over its expected lifetime.Multiplying this by b 1gives R 0.The model without treatment (r 1¼r 2¼0)is an SEI model with R 0¼b 1m =ðd ðd þm ÞÞ.The interpretation of R 0for this case is simpler.Only a fraction m =ðd þm Þof exposed individuals progress from compartment E to compartment I ,and individuals entering compartment I spend,on average,1=d time units there.Although conditions (A1)–(A5)do not restrict the decomposition of f i ðx Þto a single choice for F i ,only one such choice is epidemiologically correct.Different choices for the function F lead to different values for the spectral radius of FV À1,as shown in Table 1.In column (a),treatment failure is considered to be a new infection and in column (b),both treatment failure and pro-gression to infectiousness are considered new infections.In each case the condition q ðFV À1Þ<1yields the same portion of parameter space.Thus,q ðFV À1Þis a threshold parameter in both cases.The difference between the numbers lies in the epidemiological interpretation rather than the mathematical analysis.For example,in column (a),the infection rate is b 1þpr 2and an exposed individual is expected to spend m =ððd þm þr 1Þðd þr 2ÞÞtime units in compartment I .However,this reasoning is biologically flawed since treatment failure does not give rise to a newly infected individual.Table 1Decomposition of f leading to alternative thresholds(a)(b)Fb 1SI =N þb 2TI =N þpr 2I 0000B B @1C C A b 1SI =N þb 2TI =N þpr 2I m E 000B B @1C C A Vðd þm þr 1ÞE Àm E þðd þr 2ÞI Àb ðN ÞþdS þb 1SI =N dT Àr 1E Àqr 2I þb 2TI =N 0B B @1C C A ðd þm þr 1ÞE ðd þr 2ÞI Àb ðN ÞþdS þb 1SI =N dT Àr 1E Àqr 2I þb 2TI =N 0B B @1C C A F0b 1þpr 200 0b 1þpr 2m 0 V d þm þr 10Àm d þr 2d þm þr 100d þr 2 q (FV À1)b 1m þpr 2mðd þm þr 1Þðd þr 2Þffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffib 1m þpr 2mðd þm þr 1Þðd þr 2Þs 36P.van den Driessche,J.Watmough /Mathematical Biosciences 180(2002)29–484.2.Multigroup modelIn the epidemiological literature,the term‘multigroup’usually refers to the division of a het-erogeneous population into several homogeneous groups based on individual behaviour(e.g., [14]).Each group is then subdivided into epidemiological compartments.The majority of mul-tigroup models in the literature are used for sexually transmitted diseases,such as HIV/AIDS or gonorrhea,where behaviour is an important factor in the probability of contracting the disease [7,8,14,15].As an example,we use an m-group SIRS-vaccination model of Hethcote[7,14]with a generalized incidence term.The sample model includes several SI multigroup models of HIV/ AIDS as special cases[8,15].The model equations are as follows:_I i ¼X mj¼1b ijðxÞS i I jÀðd iþc iþ iÞI i;ð7aÞ_S i ¼ð1Àp iÞb iÀðd iþh iÞS iþr i R iÀX mj¼1b ijðxÞS i I j;ð7bÞ_Ri¼p i b iþc i I iþh i S iÀðd iþr iÞR i;ð7cÞfor i¼1;...;m,where x¼ðI1;...;I m;S1;...;S m;R1;...;R mÞt.Susceptible and removed individu-als die at the rate d i>0,whereas infected individuals die at the faster rate d iþ i.Infected in-dividuals recover with temporary immunity from re-infection at the rate c i,and immunity lasts an expected1=r i time units.All newborns are susceptible,and a constant fraction b i are born into each group.A fraction p i of newborns are vaccinated at birth.Thereafter,susceptible individuals are vaccinated at the rate h i.The incidence,b ijðxÞdepends on individual behaviour,which determines the amount of mixing between the different groups(see,e.g.,Jacquez et al.[16]). The DFE for this model isx0¼ð0;...;0;S01;...;S0m;R01;...;R0mÞt;whereS0 i ¼b i d ið1Àp iÞþr iðÞd iðd iþh iþr iÞ;R0 i ¼b iðh iþd i p iÞd iðd iþh iþr iÞ:Linearizing(7a)about x¼x0givesF¼S0i b ijðx0ÞÂÃandV¼½ðd iþc iþ iÞd ij ;where d ij is one if i¼j,but zero otherwise.Thus,FVÀ1¼S0i b ijðx0Þ=ðd iÂþc iþ iÞÃ:P.van den Driessche,J.Watmough/Mathematical Biosciences180(2002)29–4837For the special case with b ij separable,that is,b ijðxÞ¼a iðxÞk jðxÞ,F has rank one,and the basic reproduction number isR0¼X mi¼1S0ia iðx0Þk iðx0Þd iþc iþ i:ð8ÞThat is,the basic reproduction number of the disease is the sum of the‘reproduction numbers’for each group.4.3.Staged progression modelThe staged progression model[11,Section3and Appendix B]has a single uninfected com-partment,and infected individuals progress through several stages of the disease with changing infectivity.The model is applicable to many diseases,particularly HIV/AIDS,where transmission probabilities vary as the viral load in an infected individual changes.The model equations are as follows(see Fig.2):_I 1¼X mÀ1k¼1b k SI k=NÀðm1þd1ÞI1;ð9aÞ_Ii¼m iÀ1I iÀ1Àðm iþd iÞI i;i¼2;...;mÀ1;ð9bÞ_Im¼m mÀ1I mÀ1Àd m I m;ð9cÞ_S¼bÀbSÀX mÀ1k¼1b k SI k=N:ð9dÞThe model assumes standard incidence,death rates d i>0in each infectious stage,and thefinal stage has a zero infectivity due to morbidity.Infected individuals spend,on average,1=m i time units in stage i.The unique DFE has I i¼0,i¼1;...;m and S¼1.For simplicity,define m m¼0. Then F¼½F ij and V¼½V ij ,whereF ij¼b j i¼1;j6mÀ1;0otherwise;&ð10ÞV ij¼m iþd i j¼i;Àm j i¼1þj;0otherwise:8<:ð11ÞLet a ij be the(i;j)entry of VÀ1.Thena ij¼0i<j;1=ðm iþd iÞi¼j;Q iÀ1k¼jm kQ ik¼jðm kþd kÞj<i:8>>><>>>:ð12ÞThus,R0¼b1m1þd1þb2m1ðm1þd1Þðm2þd2Þþb3m1m2ðm1þd1Þðm2þd2Þðm3þd3ÞþÁÁÁþb mÀ1m1...m mÀ2ðm1þd1Þ...ðm mÀ1þd mÀ1Þ:ð13ÞThe i th term in R0represents the number of new infections produced by a typical individual during the time it spends in the i th infectious stage.More specifically,m iÀ1=ðm iÀ1þd iÀ1Þis the fraction of individuals reaching stage iÀ1that progress to stage i,and1=ðm iþd iÞis the average time an individual entering stage i spends in stage i.Hence,the i th term in R0is the product of the infectivity of individuals in stage i,the fraction of initially infected individuals surviving at least to stage i,and the average infectious period of an individual in stage i.4.4.Multistrain modelThe recent emergence of resistant viral and bacterial strains,and the effect of treatment on their proliferation is becoming increasingly important[12,13].One framework for studying such sys-tems is the multistrain model shown in Fig.3,which is a caricature of the more detailed treatment model of Castillo-Chavez and Feng[12,Section2]for tuberculosis and the coupled two-strain vector–host model of Feng and Velasco-Hern a ndez[17]for Dengue fever.The model has only a single susceptible compartment,but has two infectious compartments corresponding to the two infectious agents.Each strain is modelled as a simple SIS system.However,strain one may ‘super-infect’an individual infected with strain two,giving rise to a new infection incompartment。
内蒙古道虎沟中侏罗世小蝎蛉科(昆虫纲,长翅目)昆虫化石
Acta Zootaxonomica Sinica ,32(2):405-411(Apr .,2007)动物分类学报ISSN 100020739国家自然科学基金项目(30025006,30370184,30430100),北京市自然科学基金项目(5032003),北京市教育委员会科技发展计划重点项目(KZ 200410028013),北京市市属市管高等学校拔尖创新人才项目共同资助.3通讯作者,E 2mail :rendong @mail .cnu .edu .cn 收稿日期:2006Ο10Ο26,修订日期:2007Ο01Ο15.405内蒙古道虎沟中侏罗世小蝎蛉科(昆虫纲,长翅目)昆虫化石孙建海 任 东3 史宗冈首都师范大学生命科学学院 北京 100037摘 要 描述小蝎蛉科化石1新属2新种:多脉原始小蝎蛉Proto choristella po lyneura gen .et sp .nov .,美丽原始小蝎蛉P .form o sa gen .et sp .nov .。
简要讨论了小蝎蛉科的起源与演化。
所有化石标本均采于内蒙古宁城道虎沟中侏罗世九龙山组地层,模式标本现保存于首都师范大学生命科学学院。
关键词 长翅目,小蝎蛉科,新属,新种.中图分类号 Q 915181917 小蝎蛉科Nannochoristidae Tillyard ,1917是现生长翅目中的一个小科,目前已知现生种类2属8种(Penny ,1975),其中Nanno chorista 分布在澳大利亚东部和南美,Micro chorista 仅在新西兰发现;化石种类6属10余种,产于澳大利亚晚二叠世的Neo choristella 和Nanno choristella (Riek ,1953);产于东亚外贝加尔侏罗系下部地层的Dahuro chorista ,Dahuro larva 和Itaphlebia (Sukatcheva ,1985),以及产于中国北京早白垩世卢尚坟组的J ichoristella (Ren ,1995),Sukatcheva (1985)最初将Itaphlebia属归入中生蝎蛉科Mesopanorpodidae ,随后Novkoshonov (1997)将其转移到小蝎蛉科中。
小鼠淋巴结位置
Research paperAnatomy and nomenclature of murine lymph nodes:Descriptive study and nomenclatory standardization in BALB/cAnNCrl miceWim Van den Broeck a,⁎,Annie Derore b,c ,Paul Simoens aaDepartment of Morphology,Faculty of Veterinary Medicine,Ghent University,Salisburylaan 133,B-9820Merelbeke,BelgiumbInnogenetics NV ,Industriepark Zwijnaarde 7,B-9052Ghent,BelgiumcFlanders Interuniversity Institute for Biotechnology (VIB),Technologiepark 927,B-9052Ghent,BelgiumReceived 21November 2005;received in revised form 10January 2006;accepted 26January 2006Available online 6March 2006AbstractMurine lymph nodes are intensively studied but often assigned incorrectly in scientific papers.In BALB/cAnNCrl mice,we characterized a total of 22different lymph nodes.Peripheral nodes were situated in the head and neck region (mandibular,accessory mandibular,superficial parotid,cranial deep cervical nodes),and at the forelimb (proper axillary,accessory axillary nodes)and hindlimb (subiliac,sciatic,popliteal nodes).Intrathoracic lymph nodes included the cranial mediastinal,tracheobronchal and caudal mediastinal nodes.Abdominal lymph nodes were associated with the gastrointestinal tract (gastric,pancreaticoduodenal,jejunal,colic,caudal mesenteric nodes)or were located along the major intra-abdominal blood vessels (renal,lumbar aortic,lateral iliac,medial iliac and external iliac nodes).Comparative and nomenclative aspects of murine lymph nodes are discussed.The position of the lymph nodes of BALB/cAnNCrl mice is summarized and illustrated in an anatomical chart containing proposals for both an official nomenclature according to the Nomina Anatomica Veterinaria and English terms.©2006Elsevier B.V .All rights reserved.Keywords:Mouse;Lymph node;Nomenclature1.IntroductionRodents,and mice in particular,have long been used as laboratory animals in various scientific experiments.The possibility to produce different murine strains and a variety of knock-out mice,the high reproductive rate of these animals,and the ease of their handling have made them the preferential laboratory animal.In immunolog-ical sciences,murine lymph nodes (lnn.)are often used to isolate lymphocytes in order to study fundamentalaspects of immunology and immunopathology.The methodology to recognize and dissect these lymph nodes requires at least a basic anatomical knowledge.In numerous studies,however,inaccurate,misleading or even enigmatic terms such as genital nodes (Cain and Rank,1995)or tonsillar nodes (Deaglio et al.,1996)have sometimes been assigned to murine lymph nodes.The ambiguity of murine lymph node (ln.)nomenclature is illustrated by the lymph node at the ear base of mice which has been variably designated by various terms such as parotid ln.(Cuq,1966;Grassé,1972;Popesko et al.,1992),lateral mandibular ln.(Cuq,1966),and facial ln.(Wolvers et al.,1999),while numerous recent studies refer to an allegedly auricular ln.(Anjuère et al.,1999;Dearman et al.,1996;Sailstad et al.,1995)or pre-Journal of Immunological Methods 312(2006)12–19/locate/jim⁎Corresponding author.Tel.:+3292747716;fax:+3292647790.E-mail address:wim.vandenbroeck@UGent.be (W.Van den Broeck).0022-1759/$-see front matter ©2006Elsevier B.V .All rights reserved.doi:10.1016/j.jim.2006.01.022auricular ln.(Hendrickx et al.,1992)in this region.Given this confusion,it becomes very difficult to reproduce the experimental reports or compare different scientific results.Nevertheless,the localization of the different lymph nodes with their respective names in mice has been thoroughly described in a number of anatomical publications (Barone et al.,1950;Cuq,1966;Kawashima et al.,1964),but these papers are seldom referred to.A sample bibliographic (Medline)search from 1989to 1999demonstrated that of 293randomly chosen papers in which the words “mouse lymph node(s)”are used,89citations (i.e.30%)used only vague terms such as “lymph node ”,“peripheral lymph node ”,“draining lymph node ”,“local lymph node ”,or “regional lymph node ”instead of the precise anatomical names.In the remaining 204publications,at least 42different specific names were given to the lymph nodes that were studied.Only 1article,however,contained some figures illustrating the anatomical position and identification of the lymph nodes in question (Wolvers et al.,1999).In contrast,in the remaining 203studies the exact scientific identification of the node was lacking:59of these investigations referred to previous publica-tions in which the nomenclature used was not based on asufficiently scientific anatomical support,while in the remaining 144articles no anatomical reference was given at all.In an attempt to rectify this situation,we first characterized the lymph nodes in BALB/cAnNCrl mice and then summarized our findings in an anatomical chart.2.Materials and methods 2.1.AnimalsSeventy female BALB/cAnNCrl mice (Iffa Credo N.V .,Brussels,Belgium)aged 8to 32weeks were housed in groups of 3to 6animals in conventional type II cages containing nesting material as environmental enrich-ment (Brain et al.,1994)along with water and food supply ad libitum.At the end of the experiments,all animals were euthanized by intraperitoneal (IP)injec-tion of 30μl T61(Hoechst Roussel Vet,Brussels,Belgium).All experimental studies described in this paper were approved by the Institutional Animal Welfare Committee of Innogenetics (September 15,1999).Table 1Protocols used for demonstrating murine lymph nodes Protocol Route of administrationSedation/anaesthesia Product Quantity (μl)Incubation (days)Number of animals I Intravenous (lateral caudal vein)–Ink+RAS a 200b 103II Subcutaneous,mental region –Ink+CFA c 60b 286III Subcutaneous,mental region –Ink+RAS 10b 214IV Subcutaneous,frontal region –Ink+CFA 60b 286V Subcutaneous,auricular base–Ink+RAS 10b 216VI Subcutaneous,palmar metacarpal region –Ink+CFA 40b 183426VII Subcutaneous,plantar metatarsal region –Ink+CFA 40b 183426VIII Intranasal instillation Sedation Ink+RAS 2×30b,d 10e 317e 3IX Intraperitoneal –Ink+tR f2000g 143X PeroralSedation Ink+RAS or CFA 500b 216XI Intrahepatic h Anaesthesia Ink+RAS 30b 216XIIIntralienal iAnaesthesiaInk+RAS50b216a RAS:Ribi Adjuvant System®,RIBI Immuno Chem Research,Inc.,Hamilton,USA.bEqual quantities ink/RAS or CFA.cCFA:Complete Freunds Adjuvant®,Difco Laboratories,Detroit,Michigan,USA.dTwo administrations of 30μl with 21-day interval.eDays after the last administration.ftR:Thioglycollate+Resazurin®,Sanofi Diagnostics Pasteur,Marnes-la-Coquette,France.g50μl ink+1950μl Thioglycollate +Resazurin®.hAfter anaesthesia,the abdominal wall was incised 5mm caudal to the xiphoid process under surgical conditions;after the injection of the solution into the left and right hepatic lobes,the abdominal incision was closed.iAfter anaesthesia,the left abdominal wall was incised under surgical conditions;after the injection of the solution into the spleen,the abdominal incision was closed.13W.Van den Broeck et al./Journal of Immunological Methods 312(2006)12–19Table 2List of lymph nodes observed in the present study of BALB/cAnNCrl mice #English name Official name Protocol Occurrencea Topography2Accessory mandibular ln.Ln.mandibularis accessorius I,II,IV ,V Constant (21/21)Dorsolateral to the mandibular lymph nodeSuperficial parotid ln.Ln.parotideus superficialisI,II,IV ,VConstant (21/21)Ventral to the external acoustic pore,caudal to the extraorbital lacrimal gland,cranioventral to the parotid salivary gland,dorsal to the junction between the superficial temporal vein (v.)and the maxillary v.4Cranial deep cervical ln.Ln.cervicalisprofundus cranialis I,II,IV ,VIConstant (24/24)Medial to the external jugular vein and sternocephalic muscle (m.),lateral to sternohyoid m.,caudal to digastric m.,dorsal to the trachea5Proper axillary ln.Ln.axillaris propriusI,VIConstant (12/12)Medial to the shoulder,dorsolateral to ascending pectoral m.,at the junction between the lateral thoracic vein and the axillary vein6Accessory axillary ln.Ln.axillaris accessorius I,VI Constant (12/12)Caudal to triceps brachii m.,lateral to cutaneous trunci m.,in subcutaneous adipose tissue7Subiliac ln.Ln.subiliacusI,VIIConstant (12/12)In the fold of the flank (plica lateralis)cranial to thigh musculature,near the deep circumflex iliac artery (a.)and v.8Sciatic ln.Ln.ischiadicus I,VIIConstant (12/12)Medial to gluteus superficialis m.,caudal to gluteus medius m.and sciatic nerve9Popliteal ln.Ln.popliteus I,VII Constant(12/12)In the popliteal fossa between biceps femoris m.and semitendinosus m.10Cranial mediastinal lnn.Lnn.mediastinales craniales I Constant(3/3)Bilaterally 2lymph nodes located lateral to the thoracic thymus and along the internal thoracic a.and v.11Tracheobronchal ln.Ln.tracheobronchalis VIII Constant(6/6)Single (unpaired)lymph node at the tracheal bifurcation 12Caudal mediastinal ln.Ln.mediastinalis caudalis I Constant(3/3)Single (unpaired)lymph node in the caudal mediastinum,ventral to the esophagus,along the ventral vagal trunk 13Gastric ln.Ln.gastricus I,IX,X,XI,XII Constant(24/24)Single (unpaired)lymph node in the lesser omentum at the minor curvature of the stomach14Pancreaticoduodenal ln.Ln.pancreaticoduodenalis I,IX,X,XI,XII Constant(24/24)Single (unpaired)lymph node in the mesoduodenum,dorsal to the portal vein,surrounded by pancreatic tissue 15Jejunal lnn.Lnn.jejunales I,IX,X,XI,XII Constant(24/24)Large cluster of lymph nodes in the mesojejunum along the cranial mesenteric a.16Colic ln.Ln.colicus I,IX,X,XI,XII Constant(24/24)In the mesocolon at the transition between ascending colon and transverse colon17Caudal mesenteric ln.Ln.mesentericus caudalis I,IX,X,XI,XII Constant(24/24)Single (unpaired)lymph node in the caudal mesentery at the origin of the caudal mesenteric a.18Renal ln.Ln.renalis I,VII,IX,X,XI,XII Constant(33/33)Dorsal to the ipsilateral kidney nearby the renal blood vessels,caudal to the adrenal gland19Lumbar aortic ln.Ln.lumbalis aorticus VII bInconstant(4/6bilateral,2/6only left)Lateral to (and adjacent with)the abdominal aorta,halfway between the origin of the renal and common iliac arteries20Lateral iliac ln.Ln.iliacus lateralis I Inconstant(2/3only right,1/3absent)In adipose tissue caudolateral to the kidney along the deep circumflex iliac a.21Medial iliac ln.Ln.iliacus medialis I,VII,IX,X Constant(21/21)Major bilateral lymph node at the terminal segment of the abdominal aorta and the origin of the common iliac a.22External iliac ln.Ln.iliacus externus I Constant(3/3)Small lymph node along the initial (intra-abdominal)segment of the external iliac a.,before the latter enters the femoral canalEnglish and official Latin names of each node are given together with their frequency and a short description of their topography.aF :number of animals in which lymph nodes were found,E :number of animals in which these particular lymph nodes were examined.bProtocol VII with 42incubation days.14W.Van den Broeck et al./Journal of Immunological Methods 312(2006)12–192.2.Stimulation of lymph nodesAs murine lymph nodes are hardly distinguishable from the surrounding fat and connective tissue(Cuq, 1966),they were stimulated and colored in vivo by an injection of Indian ink in combination with an adjuvant prior to euthanasia and subsequent dissection of the animals.Intravenous injections were performed in three mice to obtain a general overview(protocol I),whereas different additional stimulation protocols were used to demonstrate the presence of particular nodes in various body regions(protocols II–XII).In some protocols,a previous sedation of the mice by intramuscular injection of1μl/g body weight of a solution of200μl ketamine (Ketalar,Parke Davis,Dublin,Ireland)and30μl xylazine(Rompun2%,Bayer,Brussels,Belgium)was required.In a few cases,anaesthesia was induced by injecting the mice intraperitoneally with220μl of a solution containing200μl ketamine,100μl xylazine and 700μl physiological salt solution.The different protocol details are listed in Table1.The specific protocols that have been used to identify the particular nodes are listed in Table2.2.3.Histological examinationThe lymphoid architecture of the in vivo colored structures was verified by histological examination. Dissected lymph nodes were fixed in3.5%phosphate-buffered formaldehyde immediately after necropsy. Paraffin sections were made and stained with eosin–haematoxylin.3.ResultsBased on their topography,the murine lymph nodes were divided into peripheral(head and neck region, forelimb,hindlimb),intrathoracic,and intra-abdominal lymph nodes.A precise nomenclature based on the Nomina Anatomica Veterinaria(2005),equivalent English terms,and the topography of the lymph nodes are described in Table2.The anatomical position ofthe Fig.1.Peripheral lymph nodes in the mouse.(1a)Ventro-lateral view of the head and throat region with sublingual(a),mandibular(b)and parotid (c)salivary gland and the extraorbital lacrimal gland(d),(1b)ventral view of the axillary region,(1c)lateral view of the thorax and forelimb,(1d) dorsal view of the sacral region with the sciatic nerve(a),and(1e)ventral view of the spread hindlimbs;numbers(1–9)according to the description in Table2.15 W.Van den Broeck et al./Journal of Immunological Methods312(2006)12–19exposed lymph nodes is illustrated in 14photographs (Figs.1–3)and 2drawings (Fig.4).Nine peripheral lymph nodes are constant and bilaterally present,namely the mandibular,accessory mandibular,superficial parotid,and cranial deep cervical ln.in the head and neck regions,the axillary and accessory axillary ln.in the forelimb,and the subiliac,sciatic and popliteal ln.in the hindlimb region.Intrathoracic nodes are few in number and consist of the cranial mediastinal lnn.,tracheobronchal ln.and the caudal mediastinal ln.Intra-abdominal lymph nodes are either associated with the gastroin-testinal tract or lie along the major abdominal arteries.The former group consists of the gastric and pancrea-ticoduodenal ln.,the jejunal lnn.and colic ln.which together represent the cranial mesenteric lnn.,and the caudal mesenteric ln.The other intra-abdominal lymph nodes include the bilateral renal,medial iliac and external iliac ln.,as well as the inconstant lumbar aortic and lateral iliac ln.The latter lymph node was observed in 2out of 3mice that were stimulated by intravenous injection.Other lymph nodes such as the facial (Wolvers et al.,1999),auricular or pre-auricular (Anjuère et al.,1999;Dearman et al.,1996;Hendrickx et al.,1992;Sailstad et al.,1995),superficial cervical (Barone et al.,1950;Cuq,1966),caudal deep cervical (Barone et al.,1950),pulmonary (Teitelbaum et al.,1999),hepatic and lienal (Barone et al.,1950),(ileo)cecal (Barone et al.,1950;Cuq,1966),sacral (Popesko et al.,1992),and femoral (Björkdahl et al.,1999;Mishell et al.,1980)lymph nodes were not observed in any of the BALB/cAnNCrl mice that were examined in the present study.Furthermore,there was no evidence of the presence of a submental lymph node (Cook,1983;Jacoby and Fox,1984),but a number of subcutaneous submental lymph nodules were demonstrated just caudal to the inter-mandibular synchondrosis by histological examination.4.DiscussionWe sought to definitely localize lymph nodes in mice and to provide an up-to-date anatomical determination chart to identify the different nodes.Most oftheseFig.2.Intrathoracic and intra-abdominal lymph nodes in the mouse.(2a)Ventral view of the thoracic cavity with the right lung (a)and thymus (b),both turned over to the left side,(2b)ventral view of the thoracic cavity with oesophagus (a),heart (b)and thymus (c),(2c)ventral view of the abdominal cavity with stomach (a),liver (b)and spleen (c),(2d)exposed mesentery,and (2e)ventral view of the abdominal cavity with the left uterine horn (a)and the caudal mesenteric artery (b);numbers (10–17)according to the description in Table 2.16W.Van den Broeck et al./Journal of Immunological Methods 312(2006)12–19lymph nodes have already been described in anatomical papers (Barone et al.,1950;Cuq,1966;Kawashima et al.,1964),but bibliometric analysis indicates that contemporary investigators are often not familiar with these publications.As a consequence,the nomenclature of murine lymph nodes used in recent literature lacks uniformity and is sometimes inadequate or even incorrect.By using different conventional in vivo staining techniques,22lymph nodes could be demonstrated in BALB/cAnNCrl mice.They were named by analogy to the terms listed in Nomina Anatomica Veterinaria (2005).This terminology is based on precise nomen-clatory principles leading to short and simple terms with instructive and descriptive value.Several lymph nodes that were observed in BALB/cAnNCrl mice could be identified because of their comparative and topographic similarities with analogous lymph nodes in domestic carnivores,pigs,and herbivores,and they were named accordingly.However mice lack several lymph nodes that are present in other mammals,such as the deep parotid or proper lumbar lymph nodes.Despite the absence of these complementary structures in mice,the terms superficial parotid and lumbar aortic lymph nodes were retained because the pertaining adjectives have useful descriptive value.This was also the case for the term cranial deep cervical lymph node,although the superficial cervical and caudal deep cervical lymph nodes were not observed in BALB/cAnNCrl mice.No additional topographic adjective was used for the single tracheobronchal lymph node because a precise homol-ogy with either the right,left,or middle tracheobronchal lymph node of domestic animals could not be ascertained in the present study or by data from the literature (Cuq,1966;Kawashima et al.,1964).A number of lymph nodes that has been described in murine species by other authors were not found in the present study.The facial lymph node as mentioned by Wolvers et al.(1999),and the auricular (Anjuère et al.,1999;Dearman et al.,1996;Sailstad et al.,1995)and pre-auricular lymph node (Hendrickx et al.,1992)probably correspond with the superficial parotid ln.described in our study.The submental ln.,illustrated as bilateral lymph nodes in two papers (Cook,1983;Jacoby and Fox,1984),were not observed as nodes as such,but subcutaneous median lymph noduleswereFig.3.Intra-abdominal lymph nodes in the mouse (ventral view).(3a,3b,3c,3d)Ventral views of the abdominal cavity with the right kidney (a)(turned over to the left side in 3a),the right adrenal gland (b),the descending colon (c)(displaced in 3c)and the deep circumflex iliac artery (d);numbers (7,17–22)according to the description in Table 2.17W.Van den Broeck et al./Journal of Immunological Methods 312(2006)12–19present just caudal to the intermandibular synchondro-sis.Furthermore,there was no evidence of the caudal deep cervical ln.which has been described ventral to the trachea and dorsal to the sternum at the level of the first two ribs (Barone et al.,1950).Similarly,the existence of the superficial cervical ln.which has inconstantly be seen medial to the cervical part of the trapezius muscle and cranial to the supraspinatus muscle (Barone et al.,1950;Cuq,1966),and the presence of the femoral ln.which has been described in the inguinal region (Björkdahl et al.,1999;Mishell et al.,1980)could not be demonstrated.An intrathoracic pulmonary lymph node (Teitelbaum et al.,1999)was also absent in all mice examined in the present study.The (ileo)cecal lnn.,described in the ileocecal mesentery as accessory nodes (Barone et al.,1950;Cuq,1966),were not observed inour study,whereas the sacral ln.which has been illustrated by Popesko et al.(1992)most likely refers to the caudal mesenteric ln.as defined by Kawashima et al.(1964).Despite the minute dissections and the use of specific intrahepatic and intralienal stimulation techni-ques,our study failed to demonstrate the existence of hepatic and lienal lymph nodes in BALB/cAnNCrl mice.The presence of these nodes in mice has been discussed by Barone et al.(1950).According to these authors,murine lienal nodes are absent,which corre-sponds with the present findings in BALB/cAnNCrl mice.On the other hand,they observed a (retro)hepatic or portal lymph node which could hardly be discerned from the lymph nodes adjacent to the stomach and the pancreas.This lymph node corresponds most likely with the pancreaticoduodenal lymph node described in the present study.A novel finding in our study was the presence of a small and inconstant lateral iliac lymph node in BALB/cAnNCrl mice.The presence and lymphoid nature of the latter lymph node were verified by histological examination.It is not unlikely that this structure,along with other lymph nodes,might also be demonstrated in other murine species and breeds.To date,no precise nor conclusive data are available concerning the presence of hemal lymph nodes in mice.The exact function of these nodes,which are very obvious in some domestic animal species such as oxen and sheep,has still to be elucidated,but probably they perform a spleen-like function,as suggested by their morphology (Bassan et al.,1999).In the present study,the presence of hemal lymph nodes could not be demonstrated neither by macroscopic nor by micro-scopic examination in any of the stimulated or unstimulated regions in BALB/cAnNCrl mice.In summary,we recommend that scientific papers on laboratory animals,and on mice in particular,should carefully observe universally accepted rules of nomen-clature for the identification of all lymphatic organs that are described and investigated.ReferencesAnjuère,F.,Martin,P.,Ferrero,I.,López Fraga,M.,Martinez delHoyo,G.,Wright,N.,Ardavin,C.,1999.Definition of dendritic cell subpopulations present in the spleen,Peyer's patches,lymph nodes and skin of the mouse.Blood 93,590.Barone,R.,Bertrand,M.,Desenclos,R.,1950.Recherches anatomi-ques sur les ganglions lymphatiques des petits rongeurs de laboratoire.Rev.Méd.Vét.101,423.Bassan,N.,Vasquez,F.,Vinuesa,M.,Cerrutti,P.,Bernardi,S.,1999.Morphological alterations in hemal nodes in splenectomized cattle.Arq.Bras.Med.Vet.Zootec.51,445.Björkdahl,O.,Akerblad,P.,Gjörloff-Wingren,A.,Leanderson,T.,Dohlsten,M.,1999.Lymphoid hyperplasia in transgenicmiceFig.4.Schematic drawing of the localization of the lymph nodes in the mouse.(4a)Ventral and (4b)lateral view;numbers (1–22)according to the description in Table 2;superficial or exposed lymph nodes are in black,the deeply located lymph nodes are dotted.18W.Van den Broeck et al./Journal of Immunological Methods 312(2006)12–19over-expressing a secreted form of the human interleukin-1βgene product.Immunology96,128.Brain,P.F.,Büttner, D.,Costa,P.,Gregory,J.A.,Heine,W.O.P., Koolhaas,J.,Militzer,K.,Ödberg, F.O.,Scharmann,W., Stauffacher,M.,1994.Rodents.In:O'Donoghue,P.N.(Ed.),The Accommodation of Laboratory Animals in Accordance with Animal Welfare Requirements.Proceedings of an International Workshop held at the Bundesgesundheitsamt.Bonn,Germany, p.1.Cain,T.K.,Rank,R.G.,1995.Local Th1-like responses are induced by intravaginal infection of mice with the mouse pneumonitis biovar of Chlamidia trachomatis.Infect.Immun.63,1784.Cook,M.J.,1983.Anatomy.In:Foster,H.L.,Small,J.D.,Fox,J.G.(Eds.),The Mouse in Biomedical Research:V olume III.Normative 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Grassé,P.P.,1972.In:Grassé,P.P.(Ed.),Traitéde Zoölogie.Tome XVI,Fascicule IV.Masson,Paris,p.848.Hendrickx,R.L.,Tumpey,T.M.,Finnegan,A.,1992.IFN-γand IL-2 are protective in the skin but pathologic in the corneas of HSV-1-infected mice.J.Immunol.149,3023.Jacoby,R.O.,Fox,J.G.,1984.Biology and diseases of mice.In:Fox,J.G.,Cohen,B.J.,Loew,F.M.(Eds.),Laboratory Animal Medicine.Academic Press Inc,New York,p.140.Kawashima,Y.,Sugimura,M.,Hwang,Y.,Kudo,N.,1964.The lymph system in mice.Jpn.J.Vet.Res.12,69.Mishell,B.B.,Shiigi,S.M.,Henry,C.,Chan,E.L.,North,J.,Gallily, R.,Slomich,M.,Miller,K.,Marbrook,J.,Parks,D.,Good,A.H., 1980.Preparation of mouse cell suspensions.In:Meshell,B.B., Shiig,S.M.(Eds.),Selected Methods in Cellular Immunology.W.F.Freeman and Company,San Francisco,p.13.Nomina Anatomica Veterinaria(NA V),2005.In:Waibl,H.,Gasse,H.,Constantinescu,G.,Hashimoto,Y.,Simoens,P.(Eds.),World Association of Veterinary Anatomists,5th edition, pp.120–122(Hannover,Columbia,Sapporo,Ghent),http://www./.Popesko,P.,Rajtová,V.,Horák,J.,1992.In:Popesko,P.(Ed.),A Colour Atlas of the Anatomy of Small Laboratory Animals.Rat, Mouse,Golden Hamster,vol.2.Wolfe Publishing Ltd,London, p.105.Sailstad,D.M.,Krishnan,S.D.,Tepper,J.S.,Doerfler,D.L.,Selgrade, M.K.,1995.Dietary vitamin A enhances sensitivity of the local lymph node assay.Toxicology96,157.Teitelbaum,R.,Schubert,W.,Gunther,L.,Kress,Y.,Macaluso,F., Pollard,J.W.,McMurray,D.N.,Bloom,B.R.,1999.The M cell asa portal of entry to the lung for the bacterial pathogenMycobacterium tuberculosis.Immunity10,641.Wolvers,D.A.W.,Coenen-de Roo,C.J.J.,Mebius,R.E.,Van der Cammen,M.J.F.,Tirion,F.,Miltenburg,A.M.M.,Kraal,G.,1999.Intranasally induced immunological tolerance is determined by characteristics of the draining lymph nodes:studies with OV A and human cartilage gp-39.J.Immunol.162,1994.19W.Van den Broeck et al./Journal of Immunological Methods312(2006)12–19。
ipilimumab结构式 -回复
ipilimumab结构式-回复Ipilimumab, also known as Yervoy, is a monoclonal antibody drug used in the treatment of certain types of cancer. It was approved by the US Food and Drug Administration (FDA) in 2011 and has since become an important option for patients with advanced melanoma and other cancers.The structure of ipilimumab can be represented as follows:[C=O][R][CH2][R][CH2][R][CH2][R][CH][CH]/ \[H] [CH3]Ipilimumab works by targeting a protein called cytotoxicT-lymphocyte-associated antigen 4 (CTLA-4). This protein is found on the surface of certain immune cells and helps regulate the immune response. By blocking CTLA-4, ipilimumab allows the immune system to better recognize and fight cancer cells.The development of ipilimumab was a result of extensive research into cancer immunotherapy. Immunotherapy is a type of treatment that harnesses the power of the immune system to fight cancer. It has revolutionized the field of oncology and has shown promising results in improving patient outcomes.Ipilimumab is typically administered intravenously, meaning that itis given directly into a vein. The drug is usually given in combination with other cancer treatments, such as chemotherapy or radiation therapy. The specific treatment regimen and dosage will vary depending on the type and stage of cancer being treated.One of the unique aspects of ipilimumab is its potential to induce long-term remission in some patients. Clinical trials have shown that a significant number of patients treated with ipilimumab experience prolonged survival, even after discontinuing treatment. This phenomenon, known as "durable response," has provided hope to many patients and healthcare professionals alike.However, ipilimumab is not without its side effects. The most common side effects include fatigue, diarrhea, rash, and itching. More serious, though less common, side effects can occur, such as inflammation in the liver, colon, or other organs. Regular monitoring and close collaboration between patients and healthcare providers are crucial to managing any potential side effects.In conclusion, ipilimumab is a monoclonal antibody drug used in the treatment of certain types of cancer, particularly advancedmelanoma. Its unique mechanism of action, targeting CTLA-4, allows the immune system to better recognize and fight cancer cells. While it has shown promising results in improving patient outcomes, it is important to understand and manage its potential side effects. With ongoing research and advancements in cancer immunotherapy, ipilimumab represents a significant step forward in the fight against cancer.。
关于因为相信所以看见的分论点
关于因为相信所以看见的分论点引言人们常常说“眼见为实”,即只有亲眼目睹才能真正相信。
然而,相信也可以导致我们看到事物。
在这篇文章中,我将探讨“因为相信所以看见”这一观点,并提出一些支持和反驳这一观点的分论点。
支持观点1. 信念能够影响我们的感知我们的信念和态度可以影响我们对事物的看法。
当我们相信某个观点或理论时,我们会更容易注意到和接受与之相关的证据,而忽略或排除不符合的信息。
这种选择性注意的现象被称为“认知偏差”,它说明了我们的信念如何影响我们的感知。
2. 信念可以改变我们的解释和理解我们的信念和预期也会影响我们对事物的解释和理解。
当我们相信某个事情是真实的时,我们会更有可能找到支持这一观点的解释,并将其视为正确的。
这种解释的倾向被称为“确认偏差”,它表明我们的信念如何影响我们对事物的理解。
3. 信念可以引发错觉信念还可以导致我们产生错觉和幻觉。
当我们强烈相信某个事情存在时,我们的大脑会产生对应的感知体验,即使这个事情实际上并不存在。
这种现象被称为“信念引导的错觉”,它说明了我们的信念如何影响我们的感知体验。
4. 信念可以激发我们的观察力和洞察力相信某个事情存在或某个观点正确可以激发我们对这个事情的观察和洞察。
当我们相信某个事情是真实的时,我们会更加关注和观察与之相关的细节和特征,以确认或证明我们的信念。
这种注意力的集中和观察的深入可以帮助我们发现事物的更多细节和特点。
反驳观点1. 眼见为实,信则有据尽管信念可以影响我们的感知和理解,但真实的事实和证据仍然是我们判断事物的基础。
我们不能仅仅依靠信念而忽视或排除与之相悖的真实证据。
相信某个事情并不意味着它一定存在,我们仍然需要通过眼见和实证来验证和确认。
2. 人类感官的局限性人类的感官存在局限性,我们无法完全准确地感知和理解事物。
即使我们相信某个事情存在,我们的感知也可能受到感官的限制和偏差。
因此,我们不能完全依赖于信念来决定事物的真实性,而应该结合实证和科学方法来进行判断。
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Bregman Voronoi Diagrams:Properties,Algorithms andApplications ∗Frank Nielsen †Jean-Daniel Boissonnat ‡Richard Nock §Abstract The Voronoi diagram of a finite set of objects is a fundamental geometric structure that subdivides the embedding space into regions,each region consisting of the points that are closer to a given object than to the others.We may define many variants of Voronoi diagrams depending on the class of objects,the distance functions and the embedding space.In this paper,we investigate a framework for defining and building Voronoi diagrams for a broad class of distance functions called Bregman divergences.Bregman divergences include not only the traditional (squared)Euclidean distance but also various divergence measures based on entropic functions.Accordingly,Bregman Voronoi diagrams allow to define information-theoretic Voronoi diagrams in statistical parametric spaces based on the relative entropy of distributions.We define several types of Bregman diagrams,establish correspondences between those diagrams (using the Legendre transformation),and show how to compute them efficiently.We also introduce extensions of these diagrams,e.g.k -order and k -bag Bregman Voronoi dia-grams,and introduce Bregman triangulations of a set of points and their connexion with Bregman Voronoi diagrams.We show that these triangulations capture many of the properties of the celebrated Delaunay triangulation.Finally,we give some applications of Bregman Voronoi diagrams which are of interest in the context of computational geometry and machine learning.Categories and Subject Descriptors :I.3.5[Computer Graphics ]Computational Ge-ometry and Object Modeling —Geometric algorithms,languages,and systems;F.2.2[Anal-ysis of Algorithms and Problem Complexity ]:Nonnumerical Algorithms and Problems —Geometrical problems and computations;G.2.1[Discrete Mathematics ]:Combina-torics.∗A preliminary version appeared in the 18th ACM-SIAM Symposium on Discrete Algorithms (SODA),pp.746-755,2007.Related materials are available online at http://www.csl.sony.co.jp/person/nielsen/BregmanVoronoi/—Version for arXiv (small resolution jpg/png files).†Sony Computer Science Laboratories Inc.,Fundamental Research Laboratory,Japan.‡INRIA Sophia-Antipolis,GEOMETRICA,France.§Universit´e Antilles-Guyane,CEREGMIA,France.1a r X i v :0709.2196v 1 [c s .C G ] 14 S e p 2007General Terms:Algorithms,TheoryKeywords:Computational Information Geometry,Voronoi diagram,Delaunay triangula-tion,Bregman divergence,Bregman ball,Legendre transformation,Quantification,Sam-pling,Clustering1Introduction and prior workThe Voronoi diagram vor(S )of a set of n points S ={p 1,...,p n }of the d -dimensional Euclidean space R d is defined as the cell complex whose d -cells are the Voronoi regions {vor(p i )}i ∈{1,..,n }where vor(p i )is the set of points of R d closer to p i than to any other point of S with respect to a distance function δ:vor(p i )def={x ∈R d |δ(p i ,x )≤δ(p j ,x )∀p j ∈S}.Points {p i }i are called the Voronoi sites or Voronoi generators .Since its inception in disguise by Descartes in the 17th century [5],Voronoi diagrams have found a broad spectrum of applications in putational geometers have focused at first on Euclidean Voronoi diagrams [5]by considering the case where δ(x ,y )is the Euclidean distance ||x −y ||= d i =1(x i −y i )2.Voronoi diagrams have been later on defined and studied for other distance functions,most notably the L 1distance ||x −y ||1= d i =1|x i −y i |(Manhattan distance)and the L ∞distance ||x −y ||∞=max i ∈{1,...,d }|x i −y i |[10,5].Klein further presented an abstract framework for describing and computing the fundamental structures of abstract Voronoi diagrams [26,11].In artificial intelligence,machine learning techniques also rely on geometric concepts for building classifiers in supervised problems (e.g.,linear separators,oblique decision trees,etc.)or clustering data in unsupervised settings (e.g.,k -means,support vector clustering [2],etc.).However,the considered data sets S and their underlying spaces X are usually not metric spaces.The notion of distance between two elements of X needs to be replaced by a pseudo-distance that is not necessarily symmetric and may not satisfy the triangle inequality .Such a pseudo-distance is also referred to as distortion ,(dis)similarity or divergence in the literature.For example,in parametric statistical spaces X ,a vector point represent a distri-bution and its coordinates store the parameters of the associated distribution.A notion of “distance”between two such points is then needed to represent the divergence between the corresponding distributions.Very few works have tackled an in-depth study of Voronoi diagrams and their applications for such a kind of statistical spaces.This is all the more important even for ordinary Voronoi diagrams as Euclidean point location of sites are usually observed in noisy environments (e.g.,imprecise point measures in computer vision experiments),and “noise”is often modeled by means of Normal distributions (so-called “Gaussian noise”).To the best of our knowledge,statistical Voronoi diagrams have only been considered in a 4-page short paper of Onishi and2Figure1:Ordinary Euclidean Voronoi diagram of a given set S of seven sites.In the bounded Voronoi cell vor(p6),every point p∈vor(p6)is closer to p6than to any other site of S(with respect to the Euclidean distance).Dashed segments denote infinite edges delimiting unbounded cells.Imai[34]which relies on Kullback-Leibler divergence of d D multivariate normal distributions to study combinatorics of their Voronoi diagrams,and subsequently in a2-page video paper of Sadakane et al.[40]which defines the divergence implied by a convex function and its conjugate,and present the Voronoi diagram withflavors of information geometry[1](see also[35]and related short communications[25,24]).Our study of Bregman Voronoi diagrams generalizes and subsumes these preliminary studies using an easier concept of divergence: Bregman divergences[12,6]that do not rely explicitly on convex conjugates.Bregman divergences encapsulate the squared Euclidean distance and many widely used divergences, e.g.the Kullback-Leibler divergence.It should be noticed however that other divergences have been defined and studied in the context of Riemannian geometry[1].Sacrifying for some generality,while not very restrictive in practice,allows a much simpler treatment and our study of Bregman divergences is elementary and does not rely on Riemannian geometry. In this paper,we give a thorough treatment of Bregman Voronoi diagrams which elegantly unifies the ordinary Euclidean Voronoi diagram and statistical Voronoi diagrams.Our con-tributions are summarized as follows:•Since Bregman divergences are not symmetric,we define two types of Bregman Voronoi diagrams.One is an affine diagram with convex polyhedral cells while the other one is curved.The cells of those two diagrams are in1-1correspondence through the Legendre transformation.We also introduce a third-type symmetrized Bregman Voronoi diagram.3•We present a simple way to compute the Bregman Voronoi diagram of a set of points by lifting the points in a higher dimensional space using an extra dimension.This mapping leads also to combinatorial bounds on the size of these diagrams.We also define weighted Bregman Voronoi diagrams and show that the class of these diagrams is identical to the class of affine(or power)diagrams.Special cases of weighted Bregman Voronoi diagrams are the k-order and k-bag Bregman Voronoi diagrams.•We define two triangulations of a set of points.Thefirst one captures some of the most important properties of the well-known Delaunay triangulation.The second triangulation is called a geodesic Bregman triangulation since its edges are geodesic arcs.Differently from thefirst triangulation,this triangulation is the geometric dual of thefirst-type Bregman Voronoi diagram of its vertices.•We give a few applications of Bregman Voronoi diagrams which are of interest in the context of computational geometry and machine learning.The outline of the paper is as follows:In Section2,we define Bregman divergences and recall some of their basic properties.In Section3,we study the geometry of Bregman spaces and characterize bisectors,balls and geodesics.Section4is devoted to Bregman Voronoi diagrams and Section5to Bregman triangulations.In Section6,we select of few applications of interest in computational geometry and machine learning.Finally,Section7concludes the paper and mention further ongoing investigations.Notations.In the whole paper,X denotes an open convex domain of R d and F:X→R a strictly convex and differentiable function.F denotes the graph of F,i.e.the set of points (x,z)∈X×R where z=F(x).We writeˆx for the point(x,F(x))∈F.∇F,∇2F and ∇−1F denote respectively the gradient,the Hessian and the inverse gradient of F.2Bregman divergencesIn this section,we recall the definition of Bregman1divergences and some of their main properties(§2.1).We show that the notion of Bregman divergence encapsulates the squared Euclidean distance as well as several well-known information-theoretic divergences.We intro-duce the notion of dual divergences(§2.2)and show how this comes in handy for symmetriz-ing Bregman divergences(§2.3).Finally,we prove that the Kullback-Leibler divergence of distributions that belong to the exponential family of distributions can be viewed as a Bregman divergence(§2.4).1Lev M.Bregman historically pioneered this notion in the seminal work[12]on minimization of a convex objective function under linear constraints.See http://www.math.bgu.ac.il/serv/segel/bregman.html. We gratefully acknowledge him for sending us this historical paper.4Figure2:Visualizing the Bregman divergence.D F(.||q)is the vertical distance between F and the hyperplane tangent to F atˆq.2.1Definition and basic propertiesFor any two points p and q of X⊆R d,the Bregman divergence2D F(·||·):X→R of p to q associated to a strictly convex and differentiable function F(called the generator function of the divergence)is defined asD F(p||q)def=F(p)−F(q)− ∇F(q),p−q ,(1)where∇F=[∂F∂x1...∂F∂x d]T denotes the gradient operator,and p,q the inner(or dot)product: di=1p i q i.Informally speaking,Bregman divergence D F is the tail of the Taylor expansion of F.See[16] for an axiomatic characterization of Bregman divergences as“permissible”divergences.Lemma1The Bregman divergence D F(p||q)is geometrically measured as the vertical dis-tance betweenˆp and the hyperplane H q tangent to F at pointˆq:D F(p||q)=F(p)−H q(p).Proof:The tangent hyperplane to hypersurface F:z=F(x)at pointˆq is H q:z= F(q)+ ∇F(q),x−q .It follows that D F(p||q)=F(p)−H q(p)(see Figure2).We now give some basic properties of Bregman divergences.Thefirst property seems to be new.The others are well known.First,observe that,for most functions F,the associated Bregman divergence is not symmetric,i.e.D F(p||q)=D F(q||p)(the symbol||is put to emphasize this point,as is standard in information theory).The following lemma proves this claim.2See Java TM applet at http://www.csl.sony.co.jp/person/nielsen/BregmanDivergence/5Lemma 2Let F be properly defined for D F to exist.Then D F is symmetric if and only if the Hessian ∇2F is constant on X .Proof:(⇒)From Eq.1,the symmetry D F (p ||q )=D F (q ||p )yields:F (p )=F (q )+12 p −q ,∇F (q )+∇F (p ) .(2)A Taylor expansion of F around q using the Lagrange form of the remainder also yields:F (p )=F (q )+ p −q ,∇F (q ) +12(p −q )T ∇2F (q )(p −q )+16p −q ,∇F 3(r pq ),(3)with r pq on the line segment pq .Equations (2)and (3)yield the following constraint:p −q ,∇F (p ) = p −q ,∇F (q ) +(p −q )T ∇2F (q )(p −q )+13p −q ,∇F 3(r pq ).(4)On the other hand,if we make the Taylor expansion of ∇F around q and then multiply both sides by p −q ,we separately obtain:p −q ,∇F (p ) = p −q ,∇F (q ) +(p −q )T ∇2F (q )(p −q )+12p −q ,∇F 3(s pq ),with s pq on the line segment pq .However,for this to equal Eq.(4),we must have p −q ,∇F 3(r pq )=(3/2) p −q ,∇F 3(s pq )for each p and q in X .If we pick p and q very close to each other,this equality cannot be true,except when the third differentials are all zero on r pq and s pq .Repeating this argument over each subset of X having non zero measure,we obtain that the third differentials of F must be zero everywhere but on subsets of X with zero measure,which implies that the second differentials (the Hessian of F ,∇2F )are constant everywhere on X .(⇐)Assume the hessian ∇2F is constant on X .In this case,because F is strictly convex,the Hessian ∇2F is positive definite,and we can factor it as ∇2F =P −1DP where D is a diagonal matrix and P a unitary rotation matrix.Reasoning in thebasis of X formed by P ,each element x is mapped to Px ,and we have F (x )= i d i x 2i ,where the d i ’s are the diagonal coefficients of D .The symmetry of D F is then immediate (i.e.,D F is a generalized quadratic distance).Property 1(Non-negativity)The strict convexity of generator function F implies that,for any p and q in X ,D F (p ||q )≥0,with D F (p ||q )=0if and only if p =q .Property 2(Convexity)Function D F (p ||q )is convex in its first argument p but not nec-essarily in its second argument q .6Bregman divergences can easily be constructed from simpler ones.For instance,multivariate Bregman divergences D F can be created from univariate generator functions coordinate-wise as F (x )= d i =1f i (x i )with ∇F =[d f 1d x 1...d f d d x d]T .Because positive linear combinations of strictly convex and differentiable functions are strictly convex and differentiable functions,new generator functions (and corresponding Bregman divergences)can also be built as positive linear combinations of elementary gen-erator functions.This is an important property as it allows to handle mixed data sets of heterogenous types in a unified framework.Property 3(Linearity)Bregman divergence is a linear operator,i.e.,for any two strictly convex and differentiable functions F 1and F 2defined on X and for any λ≥0:D F 1+λF 2(p ||q )=D F 1(p ||q )+λD F 2(p ||q ).Property 4(Invariance under linear transforms)G (x )=F (x )+ a ,x +b ,with a ∈R d and b ∈R ,is a strictly convex and differentiable function on X ,and D G (p ||q )=D F (p ||q ).Examples of Bregman divergences are the squared Euclidean distance (obtained for F (x )= x 2and the generalized quadratic distance function F (x )=x T Qx where Q is a positive definite matrix.When Q is taken to be the inverse of the variance-covariance matrix,D F is the Mahalanobis distance,extensively used in computer vision.More importantly,the notion of Bregman divergence encapsulates various information measures based on entropic functions such as the Kullback-Leibler divergence based on the (unnormalized)Shannon entropy,or the Itakura-Saito divergence based on Burg entropy (commonly used in sound processing).Table 1lists the main univariate Bregman divergences.2.2Legendre dualityWe now turn to an essential notion of convex analysis:Legendre transform that will allow us to associate to any Bregman divergence a dual Bregman divergence.Let F be a strictly convex and differentiable real-valued function on X .The Legendre transformation makes use of the duality relationship between points and lines to associate to F a convex conjugate function F ∗:R d →R given by [38]:F ∗(y )=sup x ∈X{ y ,x −F (x )}.The supremum is reached at the unique point where the gradient of G (x )= y ,x −F (x )vanishes or,equivalently,when y =∇F (x ).7Dom.XFunction F Gradient Inv.grad.Divergence D F (p ||q )RSquared function Squared loss (norm)x 22x x 2(p −q )2R +,α∈NNorm-like Norm-like α>1x ααx α−1(x α)1α−1p α+(α−1)q α−αpq α−1R +Unnorm.Shannon entropy Kullback-Leibler div.(I-div.)x log x −x log x exp(x )p log p q −p +q Exponential Exponential loss Rexp x exp x log x exp(p )−(p −q +1)exp(q )R +∗Burg entropy Itakura-Saito divergence −log x −1x −1x p q −log p q −1[0,1]Bit entropyLogistic loss x log x +(1−x )log(1−x )log x 1−x exp x 1+exp x p log p q +(1−p )log 1−p 1−q Dual bit entropyDual logistic loss R log(1+exp x )exp x 1+exp x log x 1−x log 1+exp p 1+exp q −(p −q )exp q 1+exp q [−1,1]Hellinger-like Hellinger-like −√1−x 2x√1−x 2x√1+x 21−pq √1−q 2− 1−p 2Table 1:Some common univariate Bregman divergences D F .As is well-known,F ∗is strictly convex.To see this,consider the epigraph epi(F ∗),i.e.the set of points (y ,z )such that F ∗(y )≤z .Clearly,(y ,z )∈epi(F ∗)iffG x (y )= y ,x −F (x )≤z for all x ∈X .Therefore,epi(F ∗)=∩x ∈X epi(G x ).Since G x (y )is an affine function,epi(G x )is a half-space and epi(F ∗)being the intersection of half-spaces is a convex set,which proves that F ∗is convex.The strict convexity follows from the fact that otherwise,F would not be differentiable in at least one point z ∈X :at this point, y α,z −F (z )≥ y α,x −F (x ),∀x ∈X ,and y α=αy 1+(1−α)y 2,∀α∈[0,1],y 1y 2being a segment on which F ∗is not strictly convex.Thus,y 1y 2would be a subdifferential of F in z contradicting the fact that F is differentiable.For convenience,we write x =∇F (x )(omitting the F in the x notation as it should be clear from the context).Figure 3gives a geometric interpretation of the Legendre ing this notation,Eq.1can be rewritten asD F (p ||q )=F (p )−F (q )− q ,p −q .(5)Since F is a strictly convex and differentiable real-valued function on X ,its gradient ∇F is well defined as well as its inverse ∇−1F .Writing X for the gradient space {∇F (x )=x |x ∈X },the convex conjugate F ∗of F is the function:X ⊂R d →R defined byF ∗(x )= x ,x −F (x ).(6)8Figure3:Legendre transformation of a strictly convex function F:The z-intercept (0,−F∗(y ))of the tangent hyperplane H y:z= y ,x −F∗(y )of F atˆy defines the value of the Legendre transform F∗for the dual coordinate y =∇F(y).Any hyperplane passing through an other point of F and parallel to H y necessarily intersects the z-axis above −F∗(y ).Deriving this expression,we get∇F∗(x ),d x = x,d x + x ,d x − ∇F(x),d x = x,d x = ∇−1F(x ),d x , from which we deduce that∇F∗=∇−1F.From Eq.6,we also deduce(F∗)∗=F.From the above discussion,it follows that D F∗is a Bregman divergence,which we call the Legendre dual divergence of D F.We have:Lemma3D F(p||q)=F(p)+F∗(q )− p,q =D F∗(q ||p )Proof:By Eq.5,D F(p||q)=F(p)−F(q)− p−q,q ,and,according to Eq.6,we have F(p)= p ,p −F∗(p )and F(q)= q ,q −F∗(q ).Hence,D F(p||q)= p ,p −F∗(p )− p,q +F∗(q )=D F∗(q ||p )since p=∇F−1∇F(p)=∇F∗(p ).Observe that,when D F is symmetric,D F∗is also symmetric.The Legendre transform of the quadratic form F(x)=12x T Qx,where Q is a symmetricinvertible matrix,is F∗(y)=12y T Q−1y(corresponding divergences D F and D F∗are bothgeneralized quadratic distances).To compute F∗,we use the fact that∇F∗=∇−1F and obtain F∗as F∗=∇−1F.Forexample,the Hellinger-like measure is obtained by setting F(x)=−√1−x2(see Table1).The inverse gradient is x√1+x2and the dual convex conjugate isx d x√1+x2=√1+x2.Inte-grating functions symbolically may be difficult or even not possible,and,in some cases,it will be required to approximate numerically the inverse gradient∇−1F(x).9Let us consider the univariate generator functions defining the divergences of Table1.Both the squared function F(x)=x2and Burg entropy F(x)=−log x are self-dual,i.e.F=F∗. This is easily seen by noticing that the gradient and inverse gradient are identical(up to some constant factor).For the exponential function F(x)=exp x,we have F∗(y)=y log y−y(the unnormalized Shannon entropy)and for the dual bit entropy F(x)=log(1+exp x),we have F∗(y)= y log y+log(1−y),the bit entropy.Note that the bit entropy function is a particular Bregman generator satisfying F(x)=F(1−x).2.3Symmetrized Bregman divergencesFor non-symmetric d-variate Bregman divergences D F,we define the symmetrized divergenceS F(p,q)=S F(q,p)=12(D F(p||q)+D F(q||p))=12p−q,p −q .An example of such a symmetrized divergence is the symmetric Kullback-Leibler divergence (SKL)widely used in computer vision and sound processing(see for example[29]).A key observation is to note that the divergence S F between two points of X can be measured as a divergence in X×X ⊂R2d.More precisely,let˜x=[x x ]T be the2d-dimensional vector obtained by stacking the coordinates of x on top of those of x ,the gradient of F at x.We have:Theorem1S F(p,q)=12D˜F(˜p||˜q)where˜F(˜x)=F(x)+F∗(x )and D˜Fis the Bregmandivergence defined over X×X ⊂R2d for the generator function˜F. Proof:Using Lemma3,we haveS F(p,q)=12(D F(p||q)+D F(q||p))=12(D F(p||q)+D F∗(p ||q ))=12D˜F(˜p||˜q)It should be noted that˜x lies on the d-manifold˜X={[x x ]T|x∈R d}of R2d.Note also that S F(p,q)is symmetric but not a Bregman divergence in general since˜X may not be convex,while D˜Fis a non symmetric Bregman divergence in X×X .2.4Exponential families2.4.1Parametric statistical spaces and exponential familiesA statistical space X is an abstract space where coordinates of vector pointsθ∈X encode the parameters of statistical distributions.The dimension d=dim X of the statistical space10coincides with the finite number of free parameters of the distribution laws.For example,the space X ={[µσ]T |(µ,σ)∈R ×R +∗}of univariate normal distributions N (µ,σ)is a 2D parametric statistical space,extensively studied in information geometry [1]under the auspices of differential geometry.A prominent class of distribution families called the exponential families E F [1]admits the same canonical probability distribution functionp (x |θ)def =exp { θ,f (x ) −F (θ)+C (x )},(7)where f (x )denotes the sufficient statistics and θ∈X represents the natural parameters .Space X is thus called the natural parameter space and,since log x p (x |θ)d x =log 1=0,we have F (θ)=log x exp { θ,f (x ) +C (x )}d x .F is called the cumulant function or the log-partition function.F fully characterizes the exponential family E F while term C (x )ensures density normalization.(That is,p (x |θ)is indeed a probability density function satisfying xp (x |θ)d x =1.)When the components of the sufficient statistics are affinely independent,this canonical rep-resentation is said to be minimal ,and the family E F is called a full exponential family of order d =dim X .Moreover,we consider regular exponential families E F that have their support domains topologically open.Regular exponential families include many famous distribution laws such as Bernoulli (multinomial),Normal (univariate,multivariate and rectified),Pois-son,Laplacian,negative binomial,Rayleigh,Wishart,Dirichlet,and Gamma distributions.Table 2summarizes the various relevant parts of the canonical decompositions of some of these usual statistical distributions.Observe that the product of any two distributions of the same exponential family is another exponential family distribution that may not have any-more a nice parametric form (except for products of normal distribution pdfs that yield again normal distribution pdfs).Thus exponential families provide a unified treatment framework of common distributions.Note,however,that the uniform distribution does not belong to the exponential families.2.4.2Kullback-Leibler divergence of exponential familiesIn such statistical spaces X ,a basic primitive is to measure the distortion between any two distributions.The Kullback-Leibler divergence (also called relative entropy or information divergence,I -divergence)is a standard information-theoretic measure between two statisticaldistributions d 1and d 2defined as KL(d 1||d 2)def = x d 1(x )log d 1(x )2d x .This statistical measure is not symmetric nor does the triangle inequality holds.The link with Bregman divergences comes from the remarkable property that the Kullback-Leibler divergence of any two distributions of the same exponential family with respective natural parameters θp and θq is obtained from the Bregman divergence induced by the cumu-lant function of that family by swapping arguments.By a slight abuse of notations,we denote by KL(θp ||θq )the oriented Kullback-Leibler divergence between the probability density func-tions defined by the respective natural parameters,i.e.KL(θp ||θq )def = x p (x |θp )log p (x |θp )p (x |θq )d x .11Exponential familyCanonical probability density function:exp { θ,f (x ) −F (θ)+C (x )}NaturalSufficient Cumulant function F (θ)Dens.Norm.parameters θstatistics f (x )C (x )Bernouilli B (q )(Tossing coin with Pr(heads)=q and Pr(tails)=1−q )log q 1−q x log(1+exp θ)0Multinomial M (q 1,...,q d +1)(Extend Bernouilli with Pr(x i )=q i andi q i =1)θi =log q i 1−P d j =1q i f i (x )=x i log(1+ d i =1exp θi )0Beta β(θ1,θ2)(Bernouilli conjugate prior)[θ1θ2]T [log x log(1−x )]T log B (θ1+1,θ2+1)F (θ)=log Γ(θ1+1)Γ(θ2+1)Γ(θ1+θ2−2)(with Γ(x )= ∞0t x −1exp(−t )d t )=(x −1)Γ(x −1))Univariate Normal N (µ,σ2)[µσ2−12σ2]T [x x 2]T −θ214θ2+12log(−πθ2)0Multivariate Normal N (µ,Σ)[Σ−1µ−12Σ−1][x xx T ]12µT Σ−1µ+12log det(2πΣ)0Rayleigh R (σ2)(used in ultrasound imageries)−12σ2x 2log −12θlog xLaplacian L (θ)(used in radioactivity decay)θ−x −log θPoisson P (λ)(counting process)log λx exp θ−log x !Gamma γ(θ1,θ2)(waiting times in Poisson processes)[θ1θ2]T [log x x ]T log Γ(θ1+1)+(θ2+1)log(−θ2)0Dirichlet D (α)(varying proportion model ||x ||=1,conjugate prior of Multinomial)θi =αi −1f i (x )=log x i log Γ( i θi +d )− i Γ(θi +1)0Table 2:Canonical decompositions of usual exponential families.12The following theorem is the extension to the continuous case of a result mentioned in [6].Theorem 2The Kullback-Leibler divergence of any two distributions of the same expo-nential family with natural parameters θp and θq is obtained from the Bregman divergence induced by the cumulant function F as:KL(θp ||θq )=D F (θq ||θp ).Before proving the theorem,we note that∇F (θ)= x f (x )exp { θ,f (x ) −F (θ)+C (x )}d x .(8)The coordinates of µdef =∇F (θ)=[ x f (x )p (x |θ)d x ]=E θ(f (x ))are called the expecta-tion parameters .As an example,consider the univariate normal distribution N (µ,σ)with sufficient statistics [x x 2]T (see Table 2).The expectation parameters are µ=∇F (θ)=[µµ2+σ2]T ,where µ= x x p (x |θ)d x and µ2+σ2= x x 2p (x |θ)d x .We now prove the theorem.Proof:KL(θp ||θq )=x p (x |θp )log p (x |θp )p (x |θq )d x =x p (x |θp )(F (θq )−F (θp )+ θp −θq ,f (x ) )d x =x p (x |θp )(D F (θq ||θp )+ θq −θp ,∇F (θp ) + θp −θq ,f (x ) )d x =D F (θq ||θp )+ x p (x |θp ) θq −θp ,∇F (θp )−f (x ) )d x =D F (θq ||θp )− x p (x |θp ) θq −θp ,f (x ) d x + θq −θp ,∇F (θp ) (Eq .8)=D F (θq ||θp )2.4.3Dual parameterizations and dual divergencesThe notion of dual Bregman divergences introduced earlier and dual parameterizations ex-tend naturally to statistical spaces.Since,µ=∇F (θ)(Eq.8),the convex conjugate of F (θ)is F ∗(µ)= θ,µ −F (θ)(Eq.6).From Lemma 3,we then deduce the following theorem.Theorem 3D F (θp ||θq )=D F ∗(µq ||µp )where F ∗denote the convex conjugate of F .13Bernouilli dual divergences:Logistic loss/binary relative entropyF(θ)=log(1+expθ)D F(θ||θ )=log1+expθ1+expθ −(θ−θ )expθ1+expθf(θ)=expθ1+expθ=µF∗(µ)=µlogµ+(1−µ)log(1−µ)D F∗(µ ||µ)=µ logµµ+(1−µ)log1−µ1−µf∗(µ)=logµ1−µ=θPoisson dual divergences:Exponential loss/Unnormalized Shannon entropyF(θ)=expθD F(θ||θ )=expθ−expθ −(θ−θ )expθ f(θ)=expθ=µF∗(µ)=µlogµ−µD F∗(µ ||µ)=µ logµµ+µ−µ f∗(µ)=logµ=θTable3:Examples of dual parameterizations of exponential families and their corresponding Kullback-Leibler(Bregman)divergences for the Bernoulli and Poisson distributions.Table3presents some examples of dual parameterizations of exponential families(i.e.,the naturalθ-parameters and expectationµ-parameters and dual Legendre cumulant functions), and describe the corresponding Bregman divergences induced by the Kullback-Leibler diver-gences.Finally,we would like to point out that Banerjee et al.[6]have shown that there is a bijection between the regular exponential families and a subset of the Bregman divergences called regular Bregman divergences.3Elements of Bregman geometryIn this section,we discuss several basic geometric properties that will be useful when studying Bregman Voronoi diagrams.Specifically,we characterize Bregman bisectors,Bregman balls and Bregman geodesics.Since Bregman divergences are not symmetric,we describe several types of Bregman bisectors in§3.1.We subsequently characterize Bregman balls by using a lifting transform that extends a construction well-known in the Euclidean case(§3.2). Finally,we characterize geodesics and show an orthogonality property between bisectors and geodesics in§3.3.3.1Bregman bisectorsSince Bregman divergences are not symmetric,we can define several types of bisectors.The Bregman bisector of thefirst type is defined asH F(p,q)={x∈X|D F(x||p)=D F(x||q)}.Similarly,we define the Bregman bisector of the second type asHF(p,q)={x∈X|D F(p||x)=D F(q||x)}.14。