Neutrino-Mixing-Generated Lepton Asymmetry and the Primordial $^4$He Abundance

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莫西沙星与异烟肼治疗老年肺结核的效果对比

莫西沙星与异烟肼治疗老年肺结核的效果对比

and discomfort after cystoscopy: a single-center prospective randomized pilot study[J]. Medicina (Kaunas, Lithuania),2023,59(6):1165.[11]李和,邹筱萌,郑勤云,等.地佐辛复合丙泊酚在老年硬性膀胱镜检查中的麻醉剂量及效果探讨[J].浙江实用医学,2018,23(1):16-18.[12]俞欣欣,张磊,范皓.基于分子对接技术解析地佐辛与阿片受体相互作用[J].浙江中西医结合杂志,2020,30(3):250-252,268.[13] GU Z F,XIN L,WANG H X,et al. Doxapram alleviates lowSpO 2 induced by the combination of Propofol and Fentanyl during painless gastrointestinal endoscopy[J]. BMC Anesthesiology,2019,19(1):216.[14]李军.异丙酚在小儿麻醉中的应用[J].国外医学:麻醉学与复苏分册,1996(5):276-280.[15]徐峰,陈鑫,李金玉.成年患者麻醉诱导期低血压多因素回顾分析[J].中华急诊医学杂志,2015,24(3):332-334.[16]袁军.异丙酚配伍阿托品用于结肠镜检查的观察[J].长江大学学报(自然科学版)医学卷,2010,7(1):145-147.(收稿日期:2024-01-08)①徐州市传染病医院 江苏 徐州 221000通信作者:吴晓华莫西沙星与异烟肼治疗老年肺结核的效果对比沈琛琛① 吴晓华①【摘要】 目的:对比莫西沙星与异烟肼治疗老年肺结核的效果。

方法:选取2020年1月—2023年1月102例徐州市传染病医院收治102例老年肺结核患者作为研究对象,按照随机数表法将其分为A 组(n =51)和B 组(n =51)。

变时滞反馈控制的混合中立型随机延迟微分方程的指数稳定性

变时滞反馈控制的混合中立型随机延迟微分方程的指数稳定性

第50卷第6期2023年北京化工大学学报(自然科学版)Journal of Beijing University of Chemical Technology (Natural Science)Vol.50,No.62023引用格式:刘琪,兰光强.变时滞反馈控制的混合中立型随机延迟微分方程的指数稳定性[J].北京化工大学学报(自然科学版),2023,50(6):105-111.LIU Qi,LAN GuangQiang.Exponential stability of hybrid neutral stochastic differential delay equations with time⁃depend⁃ent delay feedback control[J].Journal of Beijing University of Chemical Technology (Natural Science),2023,50(6):105-111.变时滞反馈控制的混合中立型随机延迟微分方程的指数稳定性刘 琪 兰光强*(北京化工大学数理学院,北京 100029)摘 要:研究了变时滞反馈控制的混合中立型随机延迟微分方程(HNSDDEs)的指数稳定性㊂采用函数方法设置合适的变时滞反馈控制函数,得到了该系统的指数稳定性㊂对比已有的研究成果,本文的主要贡献是在变时滞反馈控制下对HNSDDEs 的指数稳定性作了进一步研究㊂最后,给出一个例子证明了结论的有效性㊂关键词:变时滞;混合中立型随机延迟微分方程(HNSDDEs);反馈控制;指数稳定性中图分类号:O211.6 DOI :10.13543/j.bhxbzr.2023.06.013收稿日期:2022-09-05基金项目:北京市自然科学基金(1192013)第一作者:女,1998年生,硕士生*通信联系人E⁃mail:langq@引 言带有变时滞反馈控制的混合中立型随机延迟微分方程(HNSDDEs)常被用于系统未来的建模,目前已经被广泛应用于种群生态㊁神经网络以及激光器动力学等领域㊂对于随机系统突然性的结构变化,常采用连续时间马氏链来描述,带有马氏链的随机延迟微分方程即为混合随机延迟微分方程㊂文献[1]具体研究了混合随机延迟微分方程,文献[2-4]则进一步考虑了其稳定性及有界性,文献[5-7]又扩展到了带中立项的混合随机延迟微分方程的稳定性研究㊂然而并非所有系统都是稳定的,因此设计一个合适的反馈控制使不稳定的系统变得稳定很有意义㊂相应地,文献[8-11]研究了系统稳定化问题㊂其中文献[8]研究了常时滞反馈控制的高阶非线性混合随机时滞微分方程的指数稳定性,文献[9]是在文献[10]的基础上进一步研究了变时滞反馈控制的HNSDDEs 的L p 渐进稳定性和H ∞稳定性㊂本文采用Lyapunov 函数方法,进一步研究了变时滞反馈控制下的HNSDDEs 的指数稳定性㊂文献[8]研究了常时滞反馈控制下的混合随机微分延迟方程的指数稳定性,其所涉及的时滞均为常量,本文进一步将常时滞推广到了函数时滞,并且将受控方程推广到了带有中立项的混合随机延迟微分方程,其难点在于找到时滞δ(t )的上界和利用引理2处理中立项㊂文献[9]研究了变时滞反馈控制的具有时变延迟的高度非线性HNSDDEs 的L p 渐近稳定性和H ∞稳定性,但缺少指数稳定性,本文则是通过进一步找到更合适的反馈函数确定了方程的收敛速度,即指数稳定性㊂1 基本假设与模型描述设(Ω,F ,{F t }t ≥0,P )是一个带有σ流(满足通常条件)的完备概率空间,{B (t )}t ≥0是定义在其上的m 维布朗运动,{r (t )}t ≥0是右连马氏链且独立于{B (t )}t ≥0,S ={1,2, ,N }是其状态空间,Γ=(γij )N ×N 是其生成算子㊂考虑变时滞反馈控制HNSDDEd ^x(t )=f (x (t ),x (t -τ(t )),t ,r (t ))d t +g (x (t ),x (t -τ(t )),t ,r (t ))d B (t ),t ≥0(1)其中^x(t )=x (t )-N (x (t -τ(t )),t ,r (t )),且初值满足{x(θ):-τ≤θ≤0}=φ∈C([-τ,0];n)r(0)=r0∈S(2)其中f,g,N均为Borel可测函数,并且满足f:n×n×+×S→ng:n×n×+×S→n×mN:n×+×S→n加上反馈控制函数u之后系统变为d^x(t)=[f(x(t),x(t-τ(t)),t,r(t))+u(x(t-δ(t)),t,r(t))]d t+g(x(t),x(t-τ(t)),t,r(t))㊃d B(t),t≥0(3)其中0≤δ(t)≤δ≤τ,0≤τ(t)≤τ㊂假设f(0,0,t,i)=N(0,t,i)≡0,g(0,0,t,i)≡0V(x,t,i)∈C2,1(n×+×S;+)为方便起见,简记^x=x-N(y,t,i)㊂对V(x,t,i)∈C2,1(n×+×S;+)定义如下算子LL V(x,y,t,i)=V t(^x,t,i)+V T x(^x,t,i)f(x,y,t, i)+12trace[g T(x,y,t,i)V xx(^x,t,i)g(x,y,t,i)]+∑j∈sγij V(^x,t,j)(4)为得到本文主要结论,提出以下假设㊂假设1 对任意l>0,存在K l>0,使得对任意i∈S,t∈+,且|x|∨|x|∨|y|∨|y|≤l,满足|f(x,y,t,i)-f(x,y,t,i)|∨|g(x,y,t,i)-g(x,y,t,i)|≤Kl(|x-x|+|y-y|)(5)假设2 存在K>0,m1>1,m2≥1,使得对∀x, y∈n,i∈S,t∈+,有|f(x,y,t,i)|≤K(|x|m1+|y|m1+1)|g(x,y,t,i)|≤K(|x|m2+|y|m2+1)(6)假设3 系统(3)中的时滞函数τ:+→[0,τ]满足τ′(t)=dτ(t)d t≤τ<1,t≥0(7)系统(3)反馈控制函数中的δ:+→[0,δ]满足δ′(t)=dδ(t)d t≤δ<1,t≥0(8)假设4 存在κ∈(0,1)使得对∀x,y∈n,i∈S,t∈+,有|N(x,t,i)-N(y,t,i)|≤κ(1-τ)|x-y|(9)并且N(0,t,i)≡0㊂假设5 存在常数c1,c2,c3,c4>0,c2>c3+c4和函数V∈C2,1(n×+×S;+),U1,U2∈C(×[-τ,+∞];+),使得对∀x,y∈n,i∈S,t∈+,有U1(x,t)≤V(x,t,i)≤U2(x,t)L V(x,y,t,i)+V x(x-N(y),t,i)u(z,t,i)≤c1-c2U2(x,t)+c3(1-τ)U2(y,t-τ(t))+c4(1-δ)U2(z,t-δ(t))(10)由文献[7]可得如下引理㊂引理1 设假设1~4成立,且假设5对于U1(x,t)=|x|w成立,那么系统(3)有唯一的全局解,并且满足sup-τ≤t<∞E|x(t)|w<∞,w≥2(m1∨m2)由文献[5]中引理2.2以及式(9)可得引理2 若p≥1,则[1-κ(1-τ)]p-1[|x|p-κ(1-τ)|y|p]≤|x-N(y,t,i)|p≤[1+κ(1-τ)]p-1[|x|p+κ(1-τ)|y|p](11) 2 主要结论与证明定义片段过程x(t)={x(t+s):-2τ≤s≤0,0≤t≤2τ}同理定义r(t),且令r(s)=r(0),s∈[-2τ,0)x(s)=φ(-τ),s∈[-2τ,-τ{)令U∈C2,1(n×+×S;+)且满足lim|x|→∞inf(t,i)∈+×SU(x,t,i[])=∞对于t∈+,定义V(x(t),t,r(t))=U(^x(t),t,r(t))+ρ∫0-δ∫t t+s J(v)㊃d v d s(12)其中ρ>0,且J(t):=δ|u(x(t-δ(t)),t,r(t))+f(x(t),x(t-τ(t)),t,r(t))|2+|g(x(t),x(t-τ(t)),t,r(t))|2对于x,y∈n,i∈S,s∈[-2τ,0),设f(x,y,s,i)≡f(x,y,0,i)g(x,y,s,i)≡g(x,y,0,i)u(z,s,i)≡u(z,0,i)由伊藤公式可得d U(^x(t),t,r(t))=[U t(^x(t),t,r(t))+ U T x(^x(t),t,r(t))(f(x(t),x(t-τ(t)),t,r(t))+ u(x(t-δ(t)),t,r(t)))+∑j∈Sγj,r(t)U(^x(t),t,j)+ 12trace[g T(x(t),x(t-τ(t)),t,r(t))U xx(^x(t),t,㊃601㊃北京化工大学学报(自然科学版) 2023年r(t))g(x(t),x(t-τ(t)),t,r(t))]d t+d B(t)(13)其中,B(t)是局部鞅,并且B(0)=0㊂整理式(13)得d U(^x(t),t,r(t))=l U(x(t),x(t-τ(t)),t, r(t))d t+U T x(^x(t),t,r(t))[u(x(t-δ(t)),t, r(t))-u(x(t),t,r(t))]d t+d B(t)其中,l U(x(t),x(t-τ(t)),t,r(t))=Ut(^x(t),t, r(t))+U T x(^x(t),t,r(t))[f(x(t),x(t-τ(t)),t, r(t))+u(x(t),t,r(t))]+∑j∈Sγj,r(t)U(^x(t),t,j)+ 12trace[g T(x(t),x(t-τ(t)),t,r(t))U xx(^x(t),t, r(t))g(x(t),x(t-τ(t)),t,r(t))]进而易得以下结论㊂引理3 V(x(t),t,r(t)),t≥0是伊藤过程,且有d V(x(t),t,r(t))=d B(t)+L V(x(t),t,r(t))㊃d t其中,L V(x(t),t,r(t))=l U(x(t),x(t-τ(t)),t, r(t))+ρδJ(t)-ρ∫t t-δJ(v)d v+U T x(^x(t),t,r(t))㊃[u(x(t-δ(t)),t,r(t))-u(x(t),t,r(t))](14)假设6 对于函数u:n×S×+→n,存在实数a i,a i,正数d i,d i和非负数b i,b i,e i,e i(i∈S),对于任意q1>1,p>2有x T[f(x,y,t,i)+u(x,t,i)]+12|g(x,y,t,i)|2≤a i|x|2+b i|y|2-d i|x|p+e i|y|px T[f(x,y,t,i)+u(x,t,i)]+q12|g(x,y,t,i)|2≤a i|x|2+b i|y|2-d i|x|p+e i|y|p且A1:=-2diag(a1,a2, ,a N)-ΓA2:=-(q1+1)diag(a1,a2, ,a N)-Γ是非奇异M矩阵(具体定义可参考文献[1]中的2.6部分),并有1>γ1,γ2>γ3,1>γ4,γ5>γ6(θ1,θ2, ,θN)T=A-11(1, ,1)T(θ1,θ2, ,θN)T=A-12(1, ,1)Tγ1=max i∈S2θi b i,γ2=min i∈S2θi d iγ3=max i∈S2θi e i,γ4=max i∈S(q1+1)θi b iγ5=min i∈S(q1+1)θi d i,γ6=max i∈S(q1+1)θi e i其中θi和θi是正数㊂需要注意的是,关于控制函数u的选取,考虑如下特殊情况x T f(x,y,t,i)+q-12|g(x,y,t,i)|2≤a(|x|2+ |y|2)-b|x|p+c|y|p其中a>0,b>c>0㊂由于|x|2,|y|2的系数均为正数,因此只能得到原方程的矩有界性,而得不到稳定性㊂此时可选取u(x,t,i)=Ax,其中矩阵A为实对称正定矩阵,且满足λmax(A)<-2a,从而x T[f(x,y,t,i)+u(x,t,i)]+q-12㊃|g(x,y,t,i)|2≤(λmax(A)+a)|x|2+a|y|2-b|x|p+c|y|p故加上控制项之后的系统指数稳定㊂假设7 存在U∈C2,1(n×+×S;+),H∈C(n;+),及常数0<α<1,0<β<λ,0<λ1,λ2,λ3,ρ1,ρ2,使得对任意的x,y∈n,i∈S,t∈+有l U(x,y,t,i)+λ1|U x(^x,t,i)|2+λ2㊃|f(x,y,t,i)|2+λ3|g(x,y,t,i)|2≤-λ|x|2+(1-τ)β|y|2-H(x)+(1-τ)αH(y)(15)其中,ρ1|x|p+q1-1≤H(x)≤ρ2(1+|x|p+q1-1)㊂假设8 存在λ4>0满足|u(x,t,i)-u(y,t,i)|≤λ4|x-y|(16)并且有u(0,t,i)=0㊂故有∀x∈n,u(x,t,i)≤λ4㊃|x|㊂定理1 令q∈[2,w),w≥2(m1∨m2)㊂若假设1~8成立,且常数满足κ(1-τ)<12δ≤λ1λ2(1-κ)(1-κ(1-τ))λ4∧2λ1λ3(1-κ)(1-κ(1-τ))λ24∧(λ-β)(1-δ)λ1(1-κ)(1-κ(1-τ))λ24则对任意初值,存在ε>0使得系统(3)的解满足lim t→∞sup1t ln(E|x(t)|q)≤-εw-q w-2(17)其中ε=ε1∧ε2∧ε3∧ε4,ε1,ε2,ε3,ε4分别是以下4个方程的根㊃701㊃第6期 刘 琪等:变时滞反馈控制的混合中立型随机延迟微分方程的指数稳定性εδ+2(1-κ)(1-κ(1-τ))=1[εh 3ρ-11(1+κ(1-τ))p +q 1-2](κe ετ+1)+e ετα=1ε(h 2+h 3)(1+κ(1-τ))(1+e ετκ)+βe ετ+2ρδ2λ24eεδ1-δ+λ4κ2(1-τ)e ετ(1-τ-δ+e εδ(1-τ ))λ1(1-δ-τ)=λ2e ετκ2(1-τ)2=1特别地,当q =2时有lim t →∞sup 1tln (E |x (t )|2)≤-ε(18)即满足均方指数稳定㊂证明:证明分为两步㊂1)第一步取k 0>0足够大使得‖φ‖:=sup -τ≤s ≤0φ(s )<k 0㊂定义σk =inf {t ≥0:|x (t )≥k |}(k ≥k 0),且inf ϕ=∞㊂由引理1和文献[7],当k →∞,则σk →∞,a.s.根据假设6再定义U (^x,i )=θi |^x |2+θi |^x |q 1+1(19)由伊藤公式有e εtEV (x (t ),t ,r (t ))=V (x (0),0,r (0))+∫te εs (εV (x (s ),s ,r (s ))+L V (x (s ),s ,r (s )))d s取h 1=min i ∈Sθi ,h 2=max i ∈S θi ,h 3=max i ∈Sθi ,结合式(12)可得h 1eε(t ∧σk )E |^x(t ∧σk )|2≤V (x (0),0,r (0))+∫t ∧σk0e εs E (L V (x (s ),s ,r (s )))d s +ερJ 1(t ∧σk )+∫t ∧σke εs (εh 2E |^x(s )|2+εh 3E |^x (s )|q 1+1)d s (20)其中,J 1(t ∧σk )=E ∫t ∧σke ε(s∫0-δ∫ss +uJ (v )d v d )u ㊃d s ㊂对于式(20)中的E |^x(t ∧σk )|2结合基本不等式可得到E |x (t ∧σk )|2≤2E |^x(t ∧σk )|2+2κ2(1-τ)2E |x (t ∧σk -τ(t ∧σk ))|2(21)对于式(20)中的L V (x (t ),t ,r (t ))结合式(14)和假设7有L V (x (t ),t ,r (t ))≤-λ|x (t )|2+(1-τ)β㊃|x (t -τ(t ))|2-H (x (t ))+(1-τ)αH (x (t -τ(t )))-λ1|U x (^x(t ),t ,r (t ))|2-λ2|f (x (t ),x (t -τ(t )),t ,r (t ))|2-λ3|g (x (t ),x (t -τ(t )),t ,r (t ))|2+ρδJ (t )-ρ∫tt-δJ (v )d v +U T x (^x (t ),t ,r (t ))㊃[u (x (t -δ(t )),t ,r (t ))-u (x (t ),t ,r (t ))]由假设8运用均值不等式可以得到U T x (^x (t ),t ,r (t ))[u (x (t -δ(t )),t ,r (t ))-u (x (t ),t ,r (t ))]≤λ1|U x (^x(t ),t ,r (t ))|2+λ244λ1㊃|x (t -δ(t ))-x (t )|2定义ρ=λ242λ1(1-κ)(1-κ(1-τ)),由定理1中δ满足的不等式知2ρδ2≤λ2,ρδ≤λ3㊂再由Hölder 不等式有E |x (t -δ(t ))-x (t )|2≤2E |^x(t )-^x (t -δ(t ))|2+2E |N (x (t -τ(t )),t ,r (t ))-N (x (t -τ(t )-δ(t ),t ,r (t ))|2≤4E∫tt-δ[δ|u (x (v -δ(v )),v ,r (v ))+f (x (v ),x (v -τ(v )),v ,r (v ))|2+|g (x (v ),x (v -τ(v )),v ,r (v ))|2]d v +2κ2(1-τ)2E |x (t -τ(t ))-x (t -τ(t )-δ(t ))|2所以有E L V (x (t ),t ,r (t ))≤-λE |x (t )|2+(1-τ)㊃βE |x (t -τ(t ))|2-EH (x (t ))+(1-τ)αEH (x (t -τ(t )))+2ρδ2λ24E |x (t -δ(t ))|2(+λ24λ1-)ρ㊃E∫t t -δJ (v )d v +λ4κ2(1-τ)22λ1E |x (t -τ(t ))-x (t -τ(t )-δ(t ))|2(22)对于式(20)中的E |^x(t )|q 1+1有以下关系式E |^x(t )|q 1+1≤E |^x (t )|2+E |^x (t )|p +q 1-1(23)又由假设7有|x (t )|p +q 1-1≤ρ-11H (x (t ))(24)所以结合式(20)~(23)有12h 1e ε(t ∧σk )E |x (t ∧σk )|2≤Π1+Π2+Π3+∫t ∧σke εs (εh 2E |^x(s )|2+εh 3E |^x (s )|2+εh 3㊃E |^x(s )|p +q 1-1)d s +∫t ∧σke εs E [-λ|x (s )|2+(1-τ)㊃β|x (s -τ(s ))|2-H (x (s ))+(1-τ)αH (x (s -τ(s )))+2ρδ2λ24|x (s -δ(s ))|2+λ4κ2(1-τ)22λ1㊃|x (s -τ(s ))-x (s -τ(s )-δ(s ))|2]d s(25)其中,Π1=h 1e ε(t ∧σk )κ2(1-τ)2E |x (t ∧σk -τ(t ∧σk ))|2Π2=V (x (0),0,r (0))㊃801㊃北京化工大学学报(自然科学版) 2023年Π3=ερJ 1(t ∧σk )(+λ24λ1-)ρJ 2(t ∧σk )J 2(t ∧σk )=E∫t ∧σke ε[s∫ss -δJ (v )d ]v d s易得J 1(t ∧σk )≤δJ 2(t ∧σk )㊂取ε1为ε1ρδ+λ24λ1-ρ=0的唯一解,则由ρ的定义知,对任意0<ε≤ε1,有Π3≤0㊂结合式(11),令k →∞,结合式(24),式(25)化为12h 1e εt E |x (t )|2≤Π1+Π2+Π4+Π5(26)其中,Π1=h 1e εt κ2(1-τ)2E |x (t -τ(t ))|2Π4=∫teεs{εh 3ρ-11[1+κ(1-τ)]p +q 1-2㊃[EH (x (s ))+κ(1-τ)EH (x (s -τ(s )))]-EH (x (s ))+(1-τ)αEH (x (s -τ(s )))}d sΠ5=∫te εs {ε(h 2+h 3)[1+κ(1-τ)]㊃[E |x (s )|2+κ(1-τ)E |x (s -τ(s ))|2]}d s +∫teε[s-λE |x (s )|2+(1-τ)βE |x (s -τ(s ))|2+2ρδ2λ24E |x (s -δ(s ))|2+λ4κ2(1-τ)22λ1E |x (s -τ(s ))-x (s -τ(s )-δ(s ))|]2d s对于Π2,由初值条件㊁假设2㊁假设8㊁引理2和式(12)得V (x (0),0,r (0))<∞,并且记为C 0,C 0为常数㊂对于Π4,根据假设3化简有Π4≤{[εh 3(1+κ(1-τ))p +q 1-2ρ-11](κe ετ+1)+e ετα-1}∫te εs E [H (x (s ))]d s +e ετ[εh 3(1+κ(1-τ))p +q 1-2ρ-11κ+α]∫-τe εs E [H (x (s ))]d s取ε2为[ε2h 3(1+κ(1-τ))p +q 1-2ρ-11](κe ε2τ+1)+e ε2τα-1=0的唯一解,则对任意0<ε≤ε2以及0<α<1即可满足Π4≤e ετ[εh 3(1+κ(1-τ))p +q 1-2ρ-11κ+α]㊃∫0-τe εs E [H (x (s ))]d s <∞(27)对于Π5,令ε3为ε3(h 2+h 3)(1+κ(1-τ))(1+e ε3τκ)+βe ε3τ+2ρδ2λ24eε3 δ1-δ+λ4κ2(1-τ)e ε3τ(1-τ-δ+e ε3δ(1-τ ))λ1(1-δ-τ)=λ的唯一解,对任意0<ε≤ε3,有Π5≤e [ετε(h 2+h 3)(1+κ(1-τ))κ+β+λ4κ2(1-τ)λ]1∫0-τe εs E |x (s )|2d s +2ρδ2λ24eεδ1-δ∫0-δe εs㊃E |x (s )|2d s +λ4κ2(1-τ)2e ε(τ+δ)λ1(1-δ-τ)∫-δ-τe εs E |x (s )|2d s [+ε(h 2+h 3)(1+κ-κτ)(1+e ετκ)+βe ετ+2ρδ2λ24eεδ1-δ+λ4κ2(1-τ)e ετ(1-τ-δ+e εδ(1-τ ))λ1(1-δ-τ)-]λ∫te εs E |x (s )|2d s ≤e [ετε(h 2+h 3)(1+κ(1-τ))κ+β+λ4κ2(1-τ)λ]1∫0-τe εs E |x (s )|2d s +2ρδ2λ24e εδ1-δ∫-δe εsE |x (s )|2d s +λ4κ2(1-τ)2e ε(τ+δ)λ1(1-δ-τ)㊃∫-δ-τe εs E |x (s )|2d s <∞(28)综上对任意0<ε≤ε1∧ε2∧ε3,可得12h 1e εt E |x (t )|2≤h 1e εt κ2(1-τ)2E |x (t -τ(t ))|2+C 1(29)其中C 1是一个常数㊂2)第二步式(29)经过整理可以得到e εt E |x (t )|2≤2e ετe ε(t -τ(t ))κ2(1-τ)2E |x (t -τ(t ))|2+2C 1h 1,故有sup 0≤s ≤t e εs E |x (s )|2≤2C 1h 1+2e ετκ2(1-τ)2sup 0≤s ≤t e εs ㊃E |x (s )|2+2κ2(1-τ)2e ετsup -τ≤s ≤0‖ϕ‖2由κ(1-τ)<12,令ε4为1-2e ε4τκ2(1-τ)2=0的唯一解,则对任意0<ε≤ε1∧ε2∧ε3∧ε4,有sup 0≤s ≤t e εs E |x (s )|2≤2C 1h 1+2κ2(1-τ)2e ετsup -τ≤s ≤0‖φ‖21-2κ2(1-τ)2e ετ:=C 2即当t ∈[0,∞)时,e εt E |x (t )|2≤C 2,即E |x (t )|2≤C 2e -εt ㊂对于任意的q ∈[2,w ),由Hölder 不等式得到㊃901㊃第6期 刘 琪等:变时滞反馈控制的混合中立型随机延迟微分方程的指数稳定性E |x (t )|q≤(E |x (t )|2)w - qw -2(E |x (t )|w)q -2w -2㊂由引理1知C 3:=E |x (t )|w <∞,故E |x (t )|q ≤C q -2w -23(C 2e -εt )w - qw -2≤C 4e -εt w - qw -2所以式(17)成立㊂特别地,当q =2时,有式(18)成立㊂3 例子考虑一维HNSDDEd[x (t )-N (x (t -τ(t )),t ,r (t ))]=f (x (t ),x (t -τ(t )),t ,r (t ))d t +g (x (t ),x (t -τ(t )),t ,r (t ))d B (t ),t ≥0(30)其中f (x ,y ,t ,1)=0.5x +y 3-6x 3f (x ,y ,t ,2)=x +y 3-4x3g (x ,y ,t ,1)=g (x ,y ,t ,2)=0.5y 2τ(t )=0.1(1-cos t ),N (y )=0.1y显然f ,g 不满足线性增长条件㊂令r (t )为一个连续的马氏链,状态空间S ={1,2},算子Γ=-22æèçöø÷1-1,B (t )为标准布朗运动且独立于r (t )㊂定义初值x (u )=0.2+cos u ,u ∈[-0.2,0],r (0)=2㊂由文献[10]可知系统(30)不稳定,以下将通过引入一个反馈控制函数使系统稳定㊂增加控制函数u (x ,t ,1)=-x ,u (x ,t ,2)=-2x ,增加控制函数后系统(3)的具体形式为 d[x (t )-0.1x (t -τ(t ))](=12x (t )+(x (t -τ(t )))3-6x (t )3-x (t - δ(t )))d t +12(x (t -τ(t )))2d B (t ),i (=1x (t )+(x (t -τ(t )))3-4x (t )3-2x (t - δ(t )))d t +12(x (t -τ(t )))2d B (t ),i ìîíïïïïïïïïïüþýïïïïïïïïï=2其中δ(t )=τ(t )㊂以下验证假设1~8㊂假设1显然成立㊂令m 1=3,m 2=2,可知假设2成立㊂令λ4=2,可知假设8成立㊂假设3对如下常数成立:δ=τ=0.2,δ=τ=0.1,且假设4对κ=19成立㊂取U 1(x ,t )=V (x ,i ,t )=|x |6,U 2(x ,t )=2.2x 6+x 8,由Young 不等式可得L V (x ,y ,t ,i )+V x (x -N (y ),t ,i )u (z ,t ,i )≤sup x ∈(43x 6-0.229x 8)-8×U 2(x ,t )+589×(1-τ)×U 2(y ,t -τ(t ))+109×(1-δ)×U 2(z ,t -δ(t ))故假设5对c 1=sup x ∈(43x 6-0.229x 8)<∞,c 2=8,c 3=589,c 4=109成立㊂取p =4,q 1=3,可知假设6成立㊂取U (x ,t ,i )=2x 2+x 4,i =1x 2+x 4,i ={2,再由Young 不等式,令λ1=0.05,λ2=0.1,λ3=4可得l U (x ,y ,t ,i )+λ1|U x (^x(t ),t ,i )|2+λ2㊃|f (x ,y ,t ,i )|2+λ3|g (x ,y ,t ,i )|2≤-1.845|x |2+0.369(1-τ)|y |2-6(x 4+x 6)+0.955×(1-τ)×6(y 4+y 6)若令H (x )=6(x 4+x 6),λ=1.845,β=0.369,α=0.955,则假设7成立㊂根据定理1条件发现κ,τ取值合理,进而可以得到δ≤0.0576时,定理1所有条件成立,故对∀w ≥6,∀q ∈[2,w ),存在ε>0使得lim t →∞sup1t ln (E |x (t )|q )≤-εw -qw -2特别地,q =2时有lim t →∞sup1tln (E |x (t )|2)≤-ε㊂4 结论本文采用函数方法,受文献[5]的启发在多项式增长的条件下讨论了变时滞反馈控制下的HNS⁃DDEs 的指数稳定性㊂最后,用一个例子证明了结论的有效性㊂参考文献:[1] MAO X R,YUAN C G.Stochastic differential equations with Markovian switching[M].London:Imperial CollegePress,2006.[2] FEI W Y,HU L J,MAO X R,et al.Delay dependentstability of highly nonlinear hybrid stochastic systems[J].Automatica,2017,82:165-170.[3] FEI C,SHEN M X,FEI W Y,et al.Stability of highlynonlinear hybrid stochastic integro⁃differential delay equa⁃tions[J].Nonlinear Analysis:Hybrid Systems,2019,31:180-199.㊃011㊃北京化工大学学报(自然科学版) 2023年[4] HU L J,MAO X R,SHEN Y.Stability and boundednessof nonlinear hybrid stochastic differential delay equations [J].Systems &Control Letters,2013,62:178-187.[5] WU A Q,YOU S R,MAO W,et al.On exponential sta⁃bility of hybrid neutral stochastic differential delay equa⁃tions with different structures [J].Nonlinear Analysis:Hybrid Systems,2021,39:100971.[6] SHEN M X,FEI W Y,MAO X R,et al.Stability ofhighly nonlinear neutral stochastic differential delay equa⁃tions[J].Systems &Control Letters,2018,115:1-8.[7] SHEN M X,FEI C,FEI W Y,et al.Boundedness andstability of highly nonlinear hybrid neutral stochastic sys⁃tems with multiple delays[J].Science China Information Sciences,2019,62:202205.[8] LI X Y,MAO X R.Stabilisation of highly nonlinear hy⁃brid stochastic differential delay equations by delay feed⁃back control[J].Automatica,2020,112:108657.[9] 周之薇,宋瑞丽.变时滞反馈控制的混合中立型随机延迟微分方程的稳定性[J].井冈山大学学报(自然科学版),2022,43(3):6-14.ZHOU Z W,SONG R L.Stabilization of the hybrid neu⁃tral stochastic differential equations controlled by thetime⁃varying delay feedback [J].Journal of Jinggangshan University (Natural Science),2022,43(3):6-14.(in Chinese)[10]SHEN M X,FEI C,FEI W Y,et al.Stabilisation by de⁃lay feedback control for highly nonlinear neutral stochasticdifferential equations [J ].Systems &Control Letters,2020,137:104645.[11]CHEN W M,XU S Y,ZOU Y.Stabilization of hybridneutral stochastic differential delay equations by delayfeedback control[J].Systems &Control Letters,2016,88:1-13.Exponential stability of hybrid neutral stochastic differential delay equations with time⁃dependent delay feedback controlLIU Qi LAN GuangQiang *(College of Mathematics and Physics,Beijing University of Chemical Technology,Beijing 100029,China)Abstract :The exponential stability of hybrid neutral stochastic differential delay equations (HNSDDEs)with time⁃dependent delay feedback control has been ing the Lyapunov function method,the exponential sta⁃bility of the system can be obtained by setting an appropriate feedback control function with a variable ⁃pared with the existing research results,the results of this work increase our understanding of the exponential stabil⁃ity of HNSDDEs under the influence of variable delay feedback.Finally,an example is given to prove the validity of the conclusions.Key words :time⁃dependent delay;hybrid neutral stochastic differential delay equations (HNSDDEs);feedbackcontrol;exponential stability(责任编辑:吴万玲)㊃111㊃第6期 刘 琪等:变时滞反馈控制的混合中立型随机延迟微分方程的指数稳定性。

作者姓名:卢滇楠

作者姓名:卢滇楠

附件6作者姓名:卢滇楠论文题目:温敏型高分子辅助蛋白质体外折叠的实验和分子模拟研究作者简介:卢滇楠,男,1978年4月出生, 2000年9月师从清华大学化工系生物化工研究所刘铮教授,从事蛋白质体外折叠的分子模拟和实验研究,于2006年1月获博士学位。

博士论文成果以系列论文形式集中发表在相关研究领域的权威刊物上。

截至2007年发表与博士论文相关学术论文21篇,其中第一作者SCI论文9篇(有4篇IF>3),累计他引20次(SCI检索),EI收录论文14篇(含双收),国内专利1项。

中文摘要引言蛋白质体外折叠是重组蛋白质药物生产的关键技术,也是现代生物化工学科的前沿领域之一,大肠杆菌是重要的重组蛋白质宿主体系,截止2005年FDA批准的64种重组蛋白药物中有26种采用大肠杆菌作为宿主体系,目前正在研发中的4000多种蛋白质药物中有90%采用大肠杆菌为宿主表达体系。

但由于大肠杆菌表达系统缺乏后修饰体系使得其生产的目标蛋白质多以无生物学活性的聚集体——包涵体的形式存在,在后续生产过程中需要对其进行溶解,此时蛋白质呈无规伸展链状结构,然后通过调整溶液组成诱导蛋白质发生折叠形成具有预期生物学活性的高级结构,这个过程就称之为蛋白质折叠或者复性,由于该过程是在细胞外进行的,又称之为蛋白质体外折叠技术。

蛋白质体外折叠技术要解决的关键问题是避免蛋白质的错误折叠以及形成蛋白质聚集体。

目前本领域的研究以具体技术和产品折叠工艺居多,折叠过程研究方面则多依赖宏观的结构和性质分析如各类光谱学和生物活性测定等,在研究方法上存在折叠理论、分子模拟与实验研究结合不够的问题,这些都不利于折叠技术的发展和应用。

本研究以发展蛋白质新型体外折叠技术为目标,借鉴蛋白质体内折叠的分子伴侣机制,提出以智能高分子作为人工分子伴侣促进蛋白质折叠的新思路,即通过调控高分子与蛋白质分子的相互作用,1)诱导伸展态的变性蛋白质塌缩形成疏水核心以抑制蛋白质分子间疏水作用所导致的聚集,2)与折叠中间态形成多种可逆解离复合物,丰富蛋白质折叠的途径以提高折叠收率。

雷公藤内酯醇对阿尔茨海默病模型大鼠海马突触素表达及突触超微结构的影响

雷公藤内酯醇对阿尔茨海默病模型大鼠海马突触素表达及突触超微结构的影响

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摘要 目的: 探讨雷公藤 内酯醇对 阿尔茨海默病模型大 鼠海马突触素表达及 突触超微 结构 的影 响。方法 : 鼠随机 分成对 大
照组、 模型组 、 治疗组 。模 型组给予 双侧海 马各一次性注射凝 聚态 A 。 0 , 1 g 治疗 组在海 马注射凝 聚态 A 。 , 日腹 后 每
腔注射雷公藤 内酯醇 0 4rg k ,1 . / g 5 a d后用免疫组织化学方法和蛋白免疫印迹技 术检 测海 马突触 素表 达情况 , 透射 电镜观 察 突触结构 的变化 。结果 : 与模 型组 相 比, 治疗 组海 马 区突触 素免疫 反应 阳性 产物 数量 ( 5 . 0 5 7 ) 1 28 士1 .6 及平 均光 密度 ( . 1 ±0 078 均增加 ; O38 O . 2 ) 突触素表达总量 ( 1 . 1 -1 0 ) 1 7 7 44 . 2及密度 比值 (. 7 . 3 亦增加 ; 9 O 8 ±0 0 ) 突触结构较清 晰 , 界面增 长, 突触后 电子致 密物增厚 。结论 : 雷公藤 内酯醇 可以增加 阿尔 茨海默病 模型大 鼠海马突触 素 的表 达 , 轻阿尔茨 海默病 减 模 型大 鼠海马突触损伤程度 。 关键词 雷公藤 内酯醇 ;阿尔茨海 默病 ; 突触素 ; 突触 ; 马 ; 鼠 海 大

二苯乙烯苷对多种老年性痴呆动物模型的影响及其作用机制

二苯乙烯苷对多种老年性痴呆动物模型的影响及其作用机制
乳 糖致 自由基增 高脑 老 化小 鼠模 型 、高胆 固醇 血症 致 Ap 增 高 大 鼠模 型 、慢性 脑缺 血 致 痴呆 模 型 大 鼠)上 发现 ,TS G灌 胃给药 能 够 明显 改 善 模 型 动物 的学 习 记忆 功能 ,其作 用 机 制 包 括 : ( 1 )
降低海马区神经元 A P P和 [ } _ 分泌酶表达 ,减少皮层和海马 A p 含量 ,减少颞 叶皮层淀粉样斑块
家药监局新药 临床研究批件 ,目前正在进行治疗轻中度 A D的 2 期临床试验 。 此外 ,我们还发现 T S G在体外试验和体 内试 验 中均具有抑制 a - s y n u c l e i n过表达和聚集 的 作用 ,而且在 自然衰老小 鼠中发现 T S G能够改善学 习记忆功能和运动功能 ,可作用在多个脑
2 0 1 3 年 第 三 十卷 第 二
二苯 乙烯苷对 多种 老年性痴呆动物模型 的影 响及 其作用机制
李林 张兰 张如意 王蓉 孙芳玲 张丽药物研 究 室 ,神经 变性 病教 育部 重点 实验 室
阿尔茨海默病 ( A D )是一种多因素相关的复杂性疾病 , 仅针对单靶点或单致病途径的药物 不易取得好的疗效 。而且通常干预时机太晚 ,当诊 断出痴呆 时患者脑 内已有 大量 神经元死亡 。 因此 ,应 当针对多靶点、多途径治疗 ,同时将治疗时机提前到痴呆发生前 ,才有可能在 A D的药
区 ,包括 抑 制 海 马 、大脑 皮 层 及 纹 状 体  ̄ - s y n u c l e i n过 表 达 和 聚 集 ,增 加 海 马 、纹 状 体 的 突 触
连接区域数量 ,并使线粒体超微结构维持正常 ;增强海马 、纹状体 的 C a MK I I 磷酸化活性 ,增
强突触素和 P S I ) - 9 5 表达 ,提高 s y n a p s i n I 磷 酸化活性 ,从而有效提 高突触 可塑性 。这些结果 提示 ,T S G除 了治疗 A D以外 ,还具有治疗帕金森病痴呆 、路易体痴呆 的前景 。

一种新的呫诺美林衍生物改善老年小鼠的记忆能力(英文)

一种新的呫诺美林衍生物改善老年小鼠的记忆能力(英文)

一种新的呫诺美林衍生物改善老年小鼠的记忆能力(英文)崔一卉;司文;殷亮;安述明;金晶;邓世宁;曹晓华【期刊名称】《神经科学通报:英文版》【年(卷),期】2008(24)4【摘要】目的为了分析EUK1001- 新的呫诺美林衍生物的功能性质,本实验以老年小鼠为实验材料,研究了该化合物的急性毒理以及对突触可塑性和识别记忆的影响。

方法通过口服及腹腔注射途径,对小鼠进行梯度剂量的毒理学实验,测定EUK1001的半致死剂量(median lethal dose, LD50); 采用新奇物体识别任务和离体脑片电生理学技术研究EUK1001对老年小鼠识别记忆和海马突触可塑性的影响。

结果EUK1001 比呫诺美林呈现出更小的毒副作用。

在新奇事物识别实验中,EUK1001能够显著改善老年小鼠在识别记忆任务中的表现。

此外,海马脑片灌流1 μmol/L的EUK1001,能直接诱导产生长时程突触增强(long-term potentiation)。

结论EUK1001能够改善正常老龄化过程中学习记忆能力的衰退。

【总页数】7页(P251-257)【关键词】呫诺美林;EUK1001;半致死剂量;海马;长时程增强;记忆【作者】崔一卉;司文;殷亮;安述明;金晶;邓世宁;曹晓华【作者单位】华东师范大学脑功能基因组学教育部重点实验室,上海市科学技术委员会重点实验室【正文语种】中文【中图分类】Q42【相关文献】1.米诺环素抑制星形胶质细胞活化改善老年小鼠70%肝切除手术后远期学习和记忆能力 [J], 金文杰;祁涛;封洲;陆顺梅;钱燕宁;黄亚辉2.一种新的呫诺美林衍生物促进小鼠神经元生成 [J], 张晓亮;董素珍3.参蓉补脑胶囊对老年痴呆模型小鼠学习记忆能力的改善作用及机制研究 [J], 屈相玲; 朴春梅; 熊成欢; 李平; 刘明; 周训蓉4.生巴戟天与盐巴戟天改善三氯化铝诱导的老年痴呆小鼠学习记忆能力的研究 [J], 阚海峰;肖凤霞;李宇邦;陈家兰;宋小欣;刘飞;叶凤英因版权原因,仅展示原文概要,查看原文内容请购买。

非等位基因

非等位基因

非等位基因概述非等位基因是指同一基因座上的不同等位基因。

等位基因是指在某个给定的基因座上,可以存在多种不同的变体。

每个个体继承了一对等位基因,一对等位基因可能会导致不同的表型表达。

非等位基因的存在使得遗传学研究更加复杂,因为不同的等位基因会对个体的表型产生不同的影响。

背景在生物学中,基因座是指染色体上一个特定的位置,该位置上的基因决定了某个特征的表达方式。

每个基因座上可以有多种不同的等位基因。

等位基因是指在某个特定基因座上的不同基因变体。

每个个体都会继承一对等位基因,通过这对等位基因的不同组合,决定了个体的表型。

然而,并非所有基因座上的等位基因都具有相同的表现型。

非等位基因的影响非等位基因的存在导致不同等位基因会对个体表型产生不同的影响。

有些非等位基因会表现出显性效应,也就是说,当个体继承了一个突变的等位基因时,即使同时继承了一个正常的等位基因,但显性效应会使得突变的等位基因的表型表达得到体现。

相反,有些非等位基因会表现出隐性效应,当个体继承了两个突变的等位基因时,才会表现出突变的表型。

除了显性和隐性效应之外,非等位基因还可能发生两种其他类型的表型效应。

一种是共显效应,当个体继承了两个不同的突变等位基因时,在表型表达上会表现出一种新的特征,这个特征并不是单个突变等位基因所能导致的。

另一种是部分显性效应,当个体继承了两个不同的突变等位基因时,表型表达将介于两个单独突变等位基因的表型之间。

重组和非等位基因重组是指两个不同的染色体交换部分基因序列的过程。

在重组的过程中,非等位基因可能会发生改变,导致新的等位基因组合形成。

这一过程使得非等位基因的表型效应更加复杂,因为新的等位基因可能将不同基因座的效应组合起来。

非等位基因的重要性非等位基因对生物的适应性和多样性起着重要作用。

通过对等位基因的各种组合的研究,人们可以更好地理解基因与表型之间的关系,并揭示遗传变异对物种适应环境的重要性。

总结非等位基因是指同一基因座上的不同等位基因。

【doc】吲哚里西啶和喹诺里西啶生物碱的来源及药理作用

【doc】吲哚里西啶和喹诺里西啶生物碱的来源及药理作用

吲哚里西啶和喹诺里西啶生物碱的来源及药理作用】52药学进展2001年第25卷第3期2~yanobiphenylcompound[P],EP0854i35,1998叭一28L7KageyamaH.Me~odforproductingallasymmetricbiary]derivative[p].EP571770.】99312一O1_[8]AsaiJ.KumaiSPreparationofbipheny[compounds[P:,.7P08109i43】996—04—30L9一HerrmannwA,BrossmerC,Oefe]eK,eta1.PaHadacycles RsStrumrallyDefinedCatalystsfortheHeckOlefinationof Chloro—andBromoarents[J].Clamd尉,1995,34134—1848[10]Toh~anCA.StericEffetsofPhosphorousLigandsin OvganometallicChemistryandHomogeneousCatays~[J].Clam脚,1997,77:313348.[1i]NormanDP,FllppinLA.StablerSR,etalNucleoph_¨c AromaticSubstitutionReactionsofNovel5(2一Methoxyphenyl/tetrazoleDerivativeswithOrgano]ltl1mReagents[J].JOr9,1999,64:93019306.吲哚里西啶和喹诺里西啶生物碱的来源及药理作用杨艳,郑志国,吉民,华维一(1_中国药科大学新药研究中心,江苏南京,210009;2海翔医药化工有限公司,浙江台州,318000)摘要:吲哚里西啶和喹诺里西啶类生物碱是从陆地和海洋动植物中提取得到的,具多种重要生物活性的化学成分.有些已进入临床试验阶段本文对这两类生物碱的来源,生物活性及药理作用进行了综述.关键词:目5l哚里西啶喹诺里西啶;生物碱;生物活性来源中图分类号:0692.3;R96文献标识码:A文章编号:10Ol一5094(2001)03--0152--04 SourcesandBioactivitiesofIndolizidineandQuinolizidlneAlkaloidsY ANGYan,ZHENGZhi—guo,JIMin.HUAWei—yi(1.Cev~rNewDrugRest,oh,Plwxmaceutu~lL;niver~dy,‰抑210009,China;2.p1wo,m&amp;CheraCo.LTD,TaLdv~u318000,China.)Al~tract:IndolizidineandQuinolizidinealkaloidswerefoundintheprogationofearthandoc ean.Theycxhibitedvariousbiologicalactivities.SomeofthemwereinthephaseIclinicaltrails.Thisarticl ereviewedtheresearchprogressesofthetwokindsofalkaloids,includingtheirbiologidalactivities,phar macologicaleffectsandSources.KeyWord:Indolizidine;QuinolizidineAlkaloids;Biologicalactivity;Sources植物产生生物碱是为了抵御食草性动物,微生物和竞争性植物的侵袭这些生物碱的生物作用主要包括细胞毒性,诱变性,致癌性,抗癌性,抗菌抗病毒活性以及对动植物靶细胞生化过程的影响等[.吲哚里西啶生物碱则不仅存在于植物也存在于动物,例如从植物中分离得到的Slaframine,Swainsonine,Castanospermine及其它含菲环,甾环吲哚里西啶;从蚂蚁及两栖动物中分离得到的Polycyclic,收稿B期:200103一】2;修回日期:2001—04一10Pu—miliotoxin等;从真菌代谢物中分离得到的StreptomycesMetabodites等.喹诺里西啶生物碱则存在于海洋生和植物中.l吲哚里西啶生物碱1.1Slaframine(SL)该化合物主要存在于丝菌豆果1.它可促进动物唾液分泌,加快胃液流速,因而可作为饲料添加吲哚里西啶和喹诺里西啶生物碱的来担及药理作用剂,特别是牛的饲料添加剂.它还可改变动物胰液的分泌而不影响其胰酶的分泌.如对动物定期给SL,可提高其激素水平和血液循环代谢速度.1.2羟基取代的吲哚里西啶羟基取代的吲哚里西啶包括单取代和多取代衍生物.它们具有多种生物活性,如Swainsonine和Cas—tancspermine为糖苷酶和糖蛋白酶抑制剂,在抗肿瘤和抗病毒研究中作为工具药使用,并有抑制昆虫体内消化酶的作用.一些吲哚里西啶氨基糖苷衍生物也具有糖苷酶抑制作用.1.2.1一羟基吲哚里西啶和1,2-二羟基吲哚里西啶生物碱一一取代和二取代的吲哚里西啶可作为Swainso-nine及Slaframine的合成中间体.Harrisis研究小组已经从疯草和紫云英中分离得到一取代和1,2-二取代及Swainsonine的乙酸酯,在真菌发酵培养中也提取到了二羟基化合物,结构亦经光谱鉴定.从紫云英叶中分离出新的生物碱被命名为Lentiginosine,其异构体被命名为2一异构一Lentiginosine,这两个二醇及其二乙酸酯的绝对构型已经氢谱和碳谱确证. Lentiginosine是一种良好的淀粉葡糖苷酶抑制剂,是迄今为止发现的第一个只含两个羟基的糖苷酶抑制剂,且只对葡糖淀粉酶起作用,对其它酶不起作用.其作用机制是结构中反式排列的羟基组与葡糖淀粉酶Arg54和Asp55残基之间的强氢键相互作用. 1.2.2Swainsonine(苦马豆素)及相关化合物_6该类物质从澳大利亚苦马豆属植物果实和根中提取得到北美疯草(黄芪属植物和棘豆属植物)及澳大利亚昆士兰南部番薯属植物中也含有苦马豆素.苦马豆素为水溶性吲哚类生物碱,长期来一直是研究糖蛋白Ⅳ一连接寡糖合成的工具药.其主要药理作用有(1)抗癌作用0]:苦马豆素能抑制恶性肿瘤细胞一连接的寡糖的合成,增加肿瘤细胞对天然免疫的敏感性.肿瘤细胞通常单个细胞或宿主循环细胞的凝集形式吸附于内皮而进入继发组织,然后外渗并侵入细胞外介质.体外体内试验表明苦马豆索能减步肿瘤细胞与内皮细胞的粘附.苦马豆素能阻止人肿瘤细胞浸润细胞外基质并阻止肿瘤细胞在体内的浸润转移,降低肿瘤细胞的侵袭能力.其作用机制可能是影响细胞外间质蛋白水解酶的基因编码蛋白表达,有效地减少了细胞外间质水解酶.(2)免疫作用0]:实验表明,苦马豆素具有免疫刺激作用,在抗肿瘤作用中具有重要意义肿瘤病人常表现为免疫功能低下,包括迟发性过敏反应,NK细胞活性低下,巨噬细胞移动及吞噬作用降低.苦马豆素能使环磷酰胺等药物造成的免疫抑制荷瘤鼠体内B细胞反应保持在正常水平.还可通过增加干细胞对内源性淋巴因子的反应来增强骨髓细胞的增殖作用, 并可能在肿瘤细胞和宿主免疫系统水平介导其抗肿瘤作用.苦马豆素能刺激淋巴细胞增殖,增强抗原刺激的T细胞的作用,激活自身抗肿瘤免疫.研究还表明,由于苦马豆素抑制了连接的寡糖的合成,导致肿瘤细胞内高甘露糖糖苷的积累,故能增强肿瘤细胞对NK和LAK细胞的敏感性苦马豆素作为一种新的抗癌药物已进入I期临床研.已发现的主要不良反应有水肿,轻度的肝功能障,血清淀粉酶增高,血清VitA降低.1.2.3Castanospermine(cA)和相关化合物CA类化合物最初从南美豆荚标本中得到CA对一些鳞翅类的昆虫具有很强的抑制其食性作用.这种作用可能与其能阻断昆虫味觉器官中的吡哺糖受体有关.CA具有双糖酶抑制作用Eta_",在大鼠小肠中能拮抗蔗糖酶,麦芽糖酶,茧密糖酶的活性,因而可作为潜在的抗糖尿病药物.并因其对人类生殖器中a一糖苷酶有抑制作用而可用来探测附睾的机能.CA具有极强的抗逆转录酶病毒作用,可用于抗病毒药物对抗Ranseher鼠白血病病毒的酶联免疫吸附测定(ELISA).并且由于可以抑制H1V病毒糖蛋白的形成,进而阻断HIV引导的多合体的形成,因而可作为抗AIDS药物,在体内可同拮抗HIV 的药物AZT协同作用.CA的6-0一丁酯衍生物的抗HIV和抗白血病病毒的作用更强.但这两种化合物毒性较大且无法穿过细胞膜屏障,因而限制了它们的临床应用.CA还具有抗肿瘤作用,能抑制黑色素瘤细胞中血小板的凝聚及其酪氨酸酶的活性其还能抑制人类肝细胞瘤细胞链HepG2抗胰蛋白酶的生物合成及转运.CA为有效的免疫抑制剂,能提高心脏及十二指肠移植的成活率.其免疫抑制作用具有剂量依赖性却无相关毒性,因而可与他克林(一种高教高毒副作用的免疫抑制剂)合用,降低他可林使用的剂量,具有良好的临床应用前景.1.3从蚂蚁和两栖动物["中分离得到的生物碱从埃及,莫纳岛,非洲等地的蚂蚁和加利佛尼亚的不确定工蚊,蚁后中都分离得到具有吲哚里西啶母核的生物碱从澳大利亚,哥伦比亚西北,巴拿马,巴拿马西部高原等地的毒蛙,螗赊和青蛙的皮肤提取物中也得到了此生物碱.这些生物碱是不定型的高效非竞争性钠离子阻断剂,主要作用于烟碱受体药学进展2001年第25卷第3期它们可同时作用于钠离子通道和钙离子通道从而增强并延长大鼠横膈膜组织的电生理活性,因而有潜在的抗心率失常作用.它们还有一定的神经毒性. 1.4其它吲哚里西啶类生物碱从灌木叶中提取得到的Ju~prosinene,海洋生物被膜中提取得到的Piclavines及药薯叶中得到的|pal bidine等具有杀菌,溶血作用并对心脑血管有影响. 对许多动物有毒并呈剂量依赖性,从肉汤培养的链霉菌中得到的代谢产物具有抑制血管紧张肽转化酶的作用,从我国和东南亚植物鳞茎中提取得的含吲哚里西啶母核的甾族生物碱则具镇咳作用.菲并吲哚里西啶生物碱主要从野生和培植的萝磨科植物及其地面部分提取得到.但从新苏格兰月桂科属,萝磨科属植物的根和茎的树皮中及相关属的地面部分以及从新几内亚巴布亚岛沿海省份的小榕树叶和日本的萝磨科植物中也提取得到了这类生物碱.该生物碱具有抗菌,抗阿米巴作用,可抑制哺乳动物细胞生长",并可通过与一些核苷的DNA键台或与细胞DNA的相互作用,抑制激素依赖性胸腺癌细胞MDA—MB231的生长,具有抗肿瘤活性2哇诺里西啶生物碱2.1白羽豆碱一金雀花碱一鹰爪豆碱一红豆碱组(Lupi nine—Cyffsine—sparteine—Matrine—OrmosiaGroup)喹诺里西啶类生物碱南非植物calpurniaaurea和Readeamem—branacea的地上部分有机提取物中的主要成分为喹诺里西啶类生物碱0.从南美洲的红豆属植物的根和茎,白羽豆属植物的根,美洲及亚洲豆科的地上部分可分离得到此类生物碱,从一些寄生植物中也能获得0.喹诺里西啶类生物碱会导致牲畜慢性中毒并产生成瘾性,除导致死亡外还引起母畜不孕,流产,眙儿畸形.该生物碱可改善安非他明诱发的神经运动障碍,减少氢化泼尼松引起的鼠爪水肿感染.金雀花碱能提高离体子宫平滑肌的收缩力,使几内亚猪的气管收缩加快.2.2其它由陆地生物中得到的喹诺里西啶类生物碱:Is,J93这类喹诺里西啶类生物碱主要有Myrtine, Epimyrffne,Furylqujn0lizidjne,Furylindolizidine, Nuphar,Lythraceae,和9b-Maphenalene.其中黄睡莲生物碱Nuphar是从水生黄睡莲的根茎中提取得到的.从加拿大海狸的味腺中也分离得到了类似物.在日本和我国,黄睡莲生物碱被用来治疗许多疾病,它具有很强的免疫抑制作用和对乙酰胆碱酯酶的抑制作用.对鼠脾细胞亦有很强的细胞毒性.黄睡莲生物碱强烈抑制莴苣根和种子胚轴的成长,并且可作为杀虫剂使用.Lythraceae从澳大利亚灌木花中得到,其具有明显的镇静,抗感染,抗痉挛和利尿作用,并可能有抗精神病作用.9bAzaphenalene生物碱从欧洲瓢虫分泌物中得到0.2.3从海洋生物中得到的喹诺里西啶类生物碱Saraines[22~2{]从地中海海绵体,印度尼西亚海绵体,日本海绵体,Okinawan海洋海绵体,海洋双壳类,百慕大群岛和委内瑞拉Clavelinapicta被膜中可分离得到Saraine.其为细胞毒素,具抗菌及杀微生物作用.还可作为灭虫剂和杀螨剂,对土豆蚜虫,蚊子和两点微蜘蛛幼虫有杀灭作用.3结语新的吲哚里西啶和喹诺里西啶类生物碱不断被发现,一些具有良好的生物活性的化台物也越来越得到重视,甚至被用作抗肿瘤,抗病毒药物研究的先导化台物.因而研究和开发这两类生物碱具有重要前景.参考文献[1]GrundonMF.IndolizidineandQuinotizidineAlkaloids[J]. Prod脚,l985,2235-238[23MichaelJP.IndolizidineandQuinollaldlneAlkaloids[J. ProdPep,l995,12535-552Ea3Kni~tDW,SibleyAW.T.眦synthesisof(一),slaframinefrom(2r,3s)一3-hydroxyproline.Jc8oo脑Trar~s1.1997:2l79—2l87.]Nove~iF,SIX~atoreA.Qulnolizidlnylderivativesof5,ll dihydro-6H—pyrido[2.3-hiE1,]benzndazepin一6一oFteaslig andsformuseariniereceptors[J].0w删(Ⅻ,l999.18.303l一3034.[5]ManabeS,ShJffloManab~.Enantieselective[2.3]Sigmatrop-icRearrangementofd—PropargyloxyaceOeAcidsMediatedby BuLl一(一)一S~teineCompMx[J].6确m乩,1998,6-335—336[6]JamesLTrat0】.g1calresearchattheUSDA—ARSpoi一$onollsplantr~earehlat~ratory[J].JT,l999,8】63—80.[7]WiekwireBM.WagnerC,BroquistHP,eta1.Pepecolic AcidBic~ythcsisinRNzoetonialeguminicolaEJ].J,l990,265:l748—14753.ES]刘炳亚,林言麓.尹浩然.苦马豆索抑制胃癌生长及转纤维素类脑溶包衣材料的应用15移的实验研究[J]中华肿瘤杂志,199920:198一l7O.]WongvithoonyapornP,BuckeCSvastiJ,eta1.Separation CharacterizationandSpecificityo£—Manesida~efromvigna umbeHata[J]BB/ocA~n,1998,62:613621[10]MetkleRK.ZhangY,RuestPJ,eta1.Cloning,express- ing,purificationandcharacterizationoftheroutinelysoso—malacidⅡmanosidase[J]Bu~Mm坷,1997,1336:132.[11]CarretroJC,GomezRA.StereoselecllveSythesisofPoly hydroxylatedIndolizidinesfromY_Hydroxy",口一Unsaturat edSulfones[J-.JmCLom1998,63:29933005[12]YuKL,RuedigerE,LuoG,et.a1.NovelquinoLizidlnesal—icylarrlideinfluenzafusioninhibitors[J].Bk~rgMe/Ckem厶,1999,9:2177—2180.[133DalyJw,MartinHThomasG,eta1.Alkaloidsfrom frogskin:thediscoveryofepibatidineandthepotentialfor developingnovelnon—opioidanMgasis[Jj.No/Prod脚, 2000.17:13I135.[143SlainJ,SeoY,ChoKW.StellettamB,Anc:windolizidine AIkaloidfromAspongeofthegenusstelletta[J]JNo/Prod.1997,50:611—613[】5]MmximoP,LourencoA.NewquintdizidineMkMoidsfrom CHexjussaei[J].JProd,2000,63:201—204.[16]孟协中,胡向群,张如明,等.黄花棘豆碱性生物碱的分离与鉴定[J].中草药,1994,25(1):5l[173BarbieriF,SparatoreF,CagnolJM.Antiproliferativeactiv—ityandinteractionswithcellcyderelatedproteinsofthe organotincompoundtriethylfin(IV)Lupinylsulfidehy—drochloride[J].C/~era丑缸2001,134£2739.[18]1wagawaT,KanekoM,OkamuraH.Anewquihzidine fromthepapuaNewGuineanSpongeXestospongiaealguarJ]JProd,2000,63:1310一l311.[1g]CombrinkKD,GulgezeHB,YuKL.Salicy/amidein hibitorsofinfluenzaVirusfusion[J]BMedkm".20O0,10:164952[203TadayaY;TasakaH,ChrbaJ,eta1.Newtypeoffebrifug ineandognes,bearingaquinolizialnemoietyShowpotent antimalarialactivityagainstPlasmodiummalariaparasite [J].JMedCl~em,1999,42:3163—3166.[21]Pi~telhL,BertoliA,GiachiII.Quinoiizidinealkaloids fromGenNtaephedroides[J]Bioehem掣Keel2001,29: 137—14】.[223QureshiA,PatrickLF—IAnⅡtUl1]or andAntifungalCyclePeptidesfromtheLithlstrdspongeMi—ercselerodermasp[J].T~rakedron,2000,55:3679—3685. [233CutignanoA,BffuleG.DragmacidinF:ANewAntiviral BromoindoleAlkaloidfromtheMediterraneanSpongeHal—icortexsp[J]Tetrm~edrozl,2000,5637433478[24]AbeY,Sea.tos,HoriM,eta1.Stellettamide—A,anovelinhibllorofcalmodulth.isolatedfromamarinesponge[JJPMvrmco/,1997,121:1309—13】4.纤维素类肠溶包衣材料的应用卞筱泓,黄文龙(中国药科大学新药研究中心,江苏南京210009)摘要;纤维索类聚合物是非常重要的药甩辅料.本文介绍了近年来纤维素类肠溶包衣材料的研究概况,包括其结构,理化性质,合成策略以及在包衣中的简单和特殊应用,并介绍了一种新的包衣方法——干法包衣.关键词:纤维素类聚合物;肠溶包衣;水性包衣;干法包衣中图分类号:R9442文献标识码:A文章编号:1001—5094(2001)03—0155—05 DevelopmentofCellulosicPolymersforEntericCoatingsBIANXiao-hong,HUANGWen—long(6'enLorofNewDragsP~search,6'lmzaplmrmace~icalUeiv~siQ,Nanjiag210009,)收稿日期;2001—03—21。

新插烯酸衍生物[发明专利]

新插烯酸衍生物[发明专利]

专利名称:新插烯酸衍生物
专利类型:发明专利
发明人:戴维·班纳,汉斯·希尔珀特,贝恩德·库恩,哈拉尔德·莫塞
申请号:CN200680044998.9
申请日:20061122
公开号:CN101321749A
公开日:
20081210
专利内容由知识产权出版社提供
摘要:本发明涉及新的式(I)的插烯酸衍生物及其生理上可接受的盐,其中A和R至R如说明书和权利要求中所定义。

这些化合物抑制糜蛋白酶和可以用作药物。

申请人:霍夫曼-拉罗奇有限公司
地址:瑞士巴塞尔
国籍:CH
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植酸-铪纳米酸性催化剂的制备及其立体选择性合成反式茴香脑的研究

植酸-铪纳米酸性催化剂的制备及其立体选择性合成反式茴香脑的研究

植酸-铪纳米酸性催化剂的制备及其立体选择性合成反式茴香脑的研究作者:赵灵雪刘怡璇陈嘉胜彭婉君陈露王宇航宋庆伟李虎杨松来源:《贵州大学学报(自然科学版)》2023年第06期摘要:生物质能源作为一种储量丰富、来源广泛、环境友好的绿色能源,可有效代替不可再生的化石能源。

以生物质基4-甲氧基苯丙酮(4-methoxyphenylacetone)为底物,在Lewis/Brnsted双功能酸催化剂的作用下,通过一锅级联氢化和脱水反应实现立体选择性多米诺催化合成反式茴香脑。

对PA-Hf(1 ∶2.5)催化剂进行X-射线衍射(XRD)、物理吸附(BET)、傅里叶变换红外光谱(FT-IR)、热重分析(TG)、扫描电镜(SEM)、透射电镜(TEM)等一系列表征,用于测量其物理及化学性质。

结果表明:PA-Hf(1 ∶2.5)催化剂具有良好的催化性能和化学稳定性,反式茴香脑的产率可达80.0%。

机理研究证明,Lewis酸位点对4-甲氧基苯丙酮的MPV还原反应至关重要,而Brnsted酸位点可以有效促进后续的脱水反应。

该催化剂经过5次循环使用后,仍能稳定高产率获得茴香脑。

PA-Hf(1 ∶2.5)良好的稳定性和重复使用性使其在多米诺级联生产茴香脑的新路线中表现出很好的应用前景。

关键词:生物质基材料;茴香脑;一锅级联转化;立体选择性;双功能催化剂中图分类号:O643.36文献标志码:A化石能源是一般燃料、化学品和材料的基础[1-3]。

然而,日益严重的能源危机和化石能源这种不可再生碳资源的大量消耗造成了一系列的环境问题[4-6]。

在对可再生能源进行探索的过程中,生物质能源作为储量丰富、来源广泛、环境友好的绿色能源,其开发利用被视为解决这些问题的途径之一,受到了世界各国研究人员的广泛关注[7-10]。

其中值得注意的是利用生物质资源作为原料,将其催化转化为高附加值的化学平台分子,如乳酸、茴香醇、山梨醇、二甲基呋喃和5-羟甲基糠醛等,一直是可持续化学研究领域的重点和热点[11]。

靶向赖氨酸探针分子的设计、合成及其应用研究

靶向赖氨酸探针分子的设计、合成及其应用研究

靶向赖氨酸探针分子的设计、合成及其应用研究下载提示:该文档是本店铺精心编制而成的,希望大家下载后,能够帮助大家解决实际问题。

文档下载后可定制修改,请根据实际需要进行调整和使用,谢谢!本店铺为大家提供各种类型的实用资料,如教育随笔、日记赏析、句子摘抄、古诗大全、经典美文、话题作文、工作总结、词语解析、文案摘录、其他资料等等,想了解不同资料格式和写法,敬请关注!Download tips: This document is carefully compiled by this editor. I hope that after you download it, it can help you solve practical problems. The document can be customized and modified after downloading, please adjust and use it according to actual needs, thank you! In addition, this shop provides you with various types of practical materials, such as educational essays, diary appreciation, sentence excerpts, ancient poems, classic articles, topic composition, work summary, word parsing, copy excerpts, other materials and so on, want to know different data formats and writing methods, please pay attention!基于您提出的题目"靶向赖氨酸探针分子的设计、合成及其应用研究",我撰写了一篇中文演示性文章。

光学纯丁苯那嗪的不对称合成尝试

光学纯丁苯那嗪的不对称合成尝试

光学纯丁苯那嗪的不对称合成尝试
姚彰彧;吴晓明;孙宏斌
【期刊名称】《中国药科大学学报》
【年(卷),期】2010()4
【摘要】参照文献方法,以3,4-二甲氧基苯乙胺为原料,首先合成重要中间体6,7-二甲氧基-1,2,3,4-四氢异喹啉-1-乙酸甲酯,经Mannich反应、Dieckmann缩合和水解脱羧合成外消旋丁苯那嗪,并对路线进行了优化,使合成工艺更经济、便捷。

并尝试通过拆分方法先确定11b位的构型,再诱导3位构型从而实现光学纯丁苯那嗪的手性合成。

但因光学纯丁苯那嗪在酸性条件下会发生消旋化,所以未能实现光学纯丁苯那嗪的手性合成。

【总页数】5页(P321-325)
【关键词】丁苯那嗪;不对称合成;拆分;消旋
【作者】姚彰彧;吴晓明;孙宏斌
【作者单位】中国药科大学新药研究中心
【正文语种】中文
【中图分类】TQ460.31
【相关文献】
1.非水电位滴定法测定丁苯那嗪原料药中丁苯那嗪含量 [J], 王颂佩;李晓敏;刘春仪;唐婕;陈正平
2.有机金属试剂与光学纯乙烯基亚砜的不对称合成 [J], 雍胜利;高俊芳;
3.含"点击"反应基团的苯并恶嗪类长波长光学探针的合成及其生物分析应用 [J], 李晓花;马会民
4.含“点击”反应基团的苯并恶嗪类长波长光学探针的合成及其生物分析应用 [J], 李晓花;马会民
5.有机金属试剂与光学纯乙烯基亚砜的不对称合成 [J], 雍胜利;高俊芳
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a rXiv:as tr o-ph/995259v221May1999Neutrino-Mixing-Generated Lepton Asymmetry and the Primordial 4He Abundance Xiangdong Shi,George M.Fuller and Kevork Abazajian Department of Physics,University of California,San Diego,La Jolla,California 92093-0319(January 23,1999)It has been proposed that an asymmetry in the electron neutrino sector may be generated by resonant active-sterile neutrino transformations during Big Bang Nucleosynthesis (BBN).We calculate the change in the primordial 4He yield Y resulting from this asymmetry,taking into account both the time evolution of the νe and ¯νe distribution function and the spectral distortions in these.We calculate this change in two schemes:(1)a lepton asymmetry directly generated by νe mixing with a lighter right-handed sterile neutrino νs ;and (2)a lepton asymmetry generated by a ντ↔νs or νµ↔νs trans-formation which is subsequently partially converted to an asymmetry in the νe ¯νe sector by a matter-enhanced active-active neutrino transformation.In the first scheme,we find that the percentage change in Y is between −1%and 9%(with the sign depending on the sign of the asymmetry),bounded by the Majorana mass limit m νe <∼1eV.In the second scheme,the max-imal percentage reduction in Y is 2%,if the lepton number asymmetry inneutrinos is positive;Otherwise,the percentage increase in Y is <∼5%form 2νµ,ντ−m 2νs <∼104eV.We conclude that the change in the primordial 4Heyield induced by a neutrino-mixing-generated lepton number asymmetry canbe substantial in the upward direction,but limited in the downward direction.PACS numbers:14.60.Pq;14.60.St;26.35.+c;95.30.-kI.INTRODUCTIONIt has been known that a resonant active-sterile neutrino transformation during the Big Bang Nucleosynthesis(BBN)epoch can generate lepton number asymmetries in the active neutrino sectors[1–4].The generated lepton number asymmetry Lνα(withναbeing any of the three active neutrino species)has an order of magnitudeLνα≡nνα−n¯να10(T/MeV)4for|Lνα|≪0.1.(1)In this equation,n is the particle proper number density,δm2≡m2νs −m2να,and T is thetemperature of the universe.The asymmetry may have an appreciable impact on the the primordial4He abundance Y if it is in theνe sector and if its magnitude at the weak freeze-out temperature T∼1MeV is|Lνe|>∼0.01.The resulting change of the primordial4He abundance,∆Y,however,is not easy to estimate.Not only is the generated asymmetry a function of time,but also theνe or ¯νe energy spectrum is distorted by mixing(in a time-dependent fashion as well).Therefore, previous attempts[5]to estimate∆Y in this lepton number generation scenario,employing BBN calculations based on a constant asymmetry and a thermal neutrino spectrum for electron-type neutrinos,is overly simplistic and may yield inaccurate results.In this paper,we discuss in detail the time evolution of Lνeand the distortion in theνe or ¯νe spectrum in this neutrino-mixing-driven lepton number asymmetry generating scenario. We then calculate∆Y taking into account these time-dependent and energy-dependent effects by modifying the standard BBN code accordingly.We consider two schemes:a direct one and an indirect one.The direct scheme involves a direct resonantνe↔νs transformation which generatesLνe[1,2].The indirect onefirst has a lepton asymmetry generated via a resonantνµ↔νsorντ↔νs transformation and then has the asymmetry partially transferred into Lνeby an active-activeνµ↔νe orντ↔νe transformation[5].In both cases,Eq.(1)indicates that theactive-sterile channel requires m2να−m2νs>∼0.1eV2to generate|Lνα|>∼0.01at a temperatureT∼1MeV.This implies mνα>∼0.3eV.In addition,the effective mixing angles associated with these neutrino oscillation channels have to be large enough to generate lepton numberasymmetries efficiently,but not so large as to produce too manyνs’s before or during the onset of the process.The excessνs’s may not only suppress the lepton number generation, but also yield a4He mass fraction that is too large[2,6].These conditions can be quantified as:|δm2/eV2|1/6sin22θ>∼10−11,(2) |δm2/eV2|sin42θ<∼10−9(10−7)forνα=νe(νµ,ντ).(3) whereθis the vacuum mixing angle.The change in the predicted primordial4He abundance can go either way,dependingon whether Lνeis positive(decreasing Y)or negative(increasing Y).Our detailed BBN calculations show that in the direct scheme,we have−0.002≤∆Y≤0.022,bounded by theνe Majorana mass limit mνe<∼1eV.This possible change in Y is significant compared to the uncertainty involved in the Y measurements.(The measured primordial4He abundance from Olive et al.is Y=0.234±0.002(stat.)±0.005(syst.)[7],while another group claims Y=0.244±0.002[8].)In fact,an increase in Y of magnitude>∼0.01due to a large negativeLνewould already be inconsistent with observations.In the indirect scheme,wefind that the maximal possible reduction in Y is0.005.The expected increase of Y goes up withm2νµ,ντ−m2νs,and can be as high as0.013for m2νµ,ντ−m2νs∼104eV2.In both schemes,∆Y is rather limited in the negative direction.The possible reduction in Y,resulting from a positive Lνe,may to some degree narrow the gap between the lower Y measurement[7] and the standard BBN prediction(Y=0.246±0.001[9]assuming a primordial deuterium abundance D/H≈3.4±0.3×10−5[10]).We note,however,that the maximal reduction of∆Y≈−0.005is achieved only in the indirect scheme when m2νµ,ντ−m2νs∼100to300eV2,implying an unstableνµorντwith mνµ,ντ>∼15eV[4].II.GENERATION OF LEPTON ASYMMETRY BY RESONANT ACTIVE-STERILE NEUTRINO TRANSFORMATIONThe formalism of active-sterile neutrino transformation and associated amplification oflepton asymmetry whenδm2≡m2νs −m2να<0has been discussed extensively elsewhere[1–3,6,11].Here we summarize the main conclusions of these papers,and then concentrateour discussion on thefinal stage of the amplification process,when T approaches the weak freeze-out temperature∼1MeV.Forνα↔νs transformation withδm2<0,a resonance occurs atT res≈T0 E1eV2 1/6,(4) where T0≈19(22)MeV forα=e(µ,τ),and E/T is the neutrino energy normalized by the ambient temperature.Below T res,lepton asymmetry may be amplified to asymptotically approach one of the two values in eq.(1).Before this asymptotic value is reached,however,there is a brief“chaotic”phase in which Lναoscillates around zero[2].As a result,thesign of Lναthat emerges from the chaotic phase is unpredictable.We should point out that the detailed numerical evolution of the generated lepton number remains controversial. For example,whether or not the evolution of the lepton number represents true chaos is not precisely known.However,our BBN arguments simply reply on the sensitivity of the generated lepton number to the neutrino oscillation parameters.This sensitivity leads to a causality consideration on the sign of the generated lepton number.A discussion of the causality consideration can be found in Ref.[12].It is not surprising that at these two asymptotic Lναvalues,eitherνα↔νs(if Lνα<0)or¯να↔¯νs(if Lνα>0)undergoes resonant transition due to matter effects.The systemmaintains the growth of Lναby converting one ofνα/¯ναresonantly but suppressing the transformation of the other.Of course,not allναor¯ναundergo the resonant transforma-tion,because neutrinos in the early universe have an energy distribution and the resonancecondition is energy dependent.When Lναis small,even the resonant conversion of a smallfraction of eitherναor¯ναwith energy E res will be enough to maintain the growth of Lνα. To quantify the above arguments,we note that the effective potential V=(V x,V y,V z)of theνα↔νs transformation channel isV x=−δm22Ecos2θ+V Lα+V Tα.(5)The contribution from matter-antimatter asymmetries(matter effect)is[13]V Lα≈±0.35G F T3 L0+2Lνα+ νβ=ναLνβ ,(6) where G F is the Fermi constant,and L0∼10−9represents the contributions from the baryonic asymmetry as well as the asymmetry in electron-positions.The“+”sign is for the neutrino oscillation channel,and the“−”sign is for the anti-neutrino oscillation channel. The contribution from the thermal neutrino background is V Tα,whose value is[13]V Tα≈−A nνα+n¯να(V2x+V2z)1/2,(8)which reduces to vacuum mixing when V Lαand V Tαare zero.Several physical processes with different times scales are involved in the resonantνα↔νs transformation process:(1)the local neutrino oscillation rate|V|;(2)the weak interaction rateΓ∼4G2F T5;(3)the Hubble expansion rate H=−˙T/T=5.5T2/m pl where m pl≈1.22×1028eV is the Planck mass;(4)the rate of change of|V|,|˙V|/|V|,caused by the change of lepton asymmetry and the Hubble expansion.If any one of the rates is much larger than the others,we may consider all the other processes as perturbations,which simplifies the picture greatly.For example,if|V|dominates we may consider the system as an ordinary neutrino transformation system with an effective mixing angle as in Eq.(8),and with all physical variables changing adiabatically.If the weak interaction dominates,each weakscattering acts as a“measurement”to the mixing system,effectively reducing the mixture toflavor eigenstatesναandνs.The neutrino transformation is hence suppressed,with a reduced sin2θeff=V x/(Γ/2).If the Hubble expansion dominates,the other processes are essentially“frozen out”.This is the case at T<∼1MeV when the two-body weak interaction freezes out and the neutron-to-proton ratio becomesfixed(other than from the free neutron decay process).If|˙V|dominates over|V|,neutrino amplitude evolution becomes non-adiabatic.The ratios of thefirst three rates are:V x eV2 TH ≈109 |δm2|MeV −3sin2θ;(10)ΓMeV 3.(11)In these ratios,an average E=3.15T is assumed.Since we are only concerned with |δm2|>∼0.1eV2,as long as sin2θ>∼10−6(the minimal mixing required to amplify Lνα,see Eq.(2)),the neutrino transformation rate easily dominates over the Hubble expansion and the weak interaction at T∼1MeV.We always have˙V x=HV x.At T<∼T res/2and away from resonances so that we canassume V Tα≪|δm2|/2E∼V Lα∼V z,we have|˙V z|∼|(H−˙Lνα/Lνα)V z|∼|HV z|.(Notethat Lναis limited to the T−4growth in Eq.(1).)Therefore at T<∼T res/2,the active-sterile neutrino transformation channels in our problem can be treated as ordinary oscillation channels with adiabatically varying mixing parameters except possibly at the resonances. We will discuss the question of adiabaticity at resonances later.At T<∼T res/2when we can neglect V Tα,the resonance condition V z=−δm2/2E cos2θ+V Lα=0gives the asymptotic values of Lναin Eq.(1).Note that for Lνα<0(Lνα>0)theνα(¯να)transformation channel is matter-enhanced.The fraction F of resonantly converted να(¯να)in the totalνα(¯να)distribution isF∼2 V x dǫ8F∼3˙V′z∼V x sin2θ′eV2Td V z ǫres f(ǫres)dǫres d V zǫres.(15)Thefirst condition simply implies that the timescale of completing the resonance has to be much longer than the neutrino oscillation period at resonance.This is satisfied if |δm2|sin22θ>∼10−9eV2.The second condition requires thatǫres move slowly through the spectrum.This amounts toLνα≤3Lνα(T)≈316(T/MeV)4Lνα.(18)In Eq.(17)βtakes account of the effect of collisions that redistribute energy among neutri-nos.We can identify two extreme cases.When the collisions are too inefficient to change the neutrino distribution atǫ>ǫres(such as when T<∼1MeV),β=1.In another limit,β≈1−8Lνα/3which obtains when the collisions are highly efficient(such as when T>∼1 MeV)and neutrinos are always distributed thermally.Eqs.(17)and(18)give a solution in fair agreement with the results obtained by solving Eq.(18)of Foot and Volkas[5].InFigure1we plot our results in terms of Lναvs.m2να−m2νsat various temperatures.FromFigure1we can deduce a power law relation applicable to|Lνα|<∼0.1,|Lνα|≈0.05|δm2/eV2|2/3(T/MeV)−8/3.(19) We note that this power law applies only in the stage when the resonance sweeps throughthe neutrino energy spectrum.When the resonance is stationary(Eq.(13)),the dependenceis|Lνα|∝|δm2|T−4instead.The asymmetry Lναis generated as the resonance conversion region moves up through the neutrino energy spectrum.This suggests a distortion of theνα(or¯να)energy spectrum(see also Ref.[14]).Indeed,when Lνα<∼0.1,most of the Lναis generated at the lowesttemperatures(Eq.[19]),when the neutrino scattering processes that tend to thermalize the neutrino spectrum are the most inefficient.The fact that the resonant transformation ofναtoνs(or¯να→¯νs)starts at lower neutrino energies only further deepens the inefficiency of neutrino re-thermalization,as neutrino interaction cross sections scale roughly linearly with neutrino energies.In Figure2,we plot a semi-analytical calculation of theναspectrum at T=1MeV for aνα→νs resonant transformation(which generates a negative Lνα)withm2να−m2νs=1eV2.In the calculation,the thermalization process is approximated as arelaxation process(with a rateΓ)driving the system toward a thermal distribution.As aresult of the inefficiency of this process,for cases with|δm2|<∼1eV2(so that Lνα<∼0.1at T∼1MeV),theναneutrino spectrum at and below its thermal decoupling temperature T∼1MeV can be well approximated by a thermal spectrum with a low energy cut-off.Theναdeficit below the cut-offenergy results in the Lναasymmetry.In the mean time,¯ναis not subject to resonant transformation.Its spectrum is therefore not significantly changed,due to the inefficiency of neutrino pair production.(The opposite is true if Lνα>0:the¯ναdistribution will have its lower energy region truncated but theναdistribution will remain intact.)III.DIRECT GENERATION OF ELECTRON-NEUTRINO ASYMMETRY BYRESONANTνE↔νS TRANSFORMATIONSIfα=e(the direct scheme to generate an asymmetry in theνe¯νe sector),theνe or¯νe spectral distortion will directly impact the neutron-to-proton ratio at the weak freeze-out temperature,and hence the4He yield.Figure3shows the changes in n↔p rates due to theneutrino spectral distortion in the case m2νe −m2νs=1eV2.When Lνe>0(i.e.,a deficit oflow energy¯νe),the major effect is an enhanced neutron decay rate at low temperatures due to the reduced Pauli-blocking of¯νe.For reaction p+¯νe→n+e+,the low energy deficit in¯νe is of little significance because only¯νe with E>1.9MeV can participate in the reaction. Conversely,its reverse reaction mostly generates¯νe at the higher end of the energy spectrum. Its rate is therefore insensitive to the spectral distortion at the lower end.When Lνe>0(a deficit of low energyνe),the rate for n+νe→p+e−is significantly reduced while the reverse rate is slightly increased.Figure4shows the resultant∆Y from the spectral distortion as afunction of m2νe −m2νsfor both Lνe>0and Lνe<0.The disparity between the two casesof opposite Lνeis transparent from Figure3:the change in n↔p rates is much larger whenLνe<0.Theνe Majorana mass limit(which is uncertain by a factor of2,ranging from mνe≤0.45eV to mνe <∼1eV[15–17])implies an upper limit m2νe−m2νs≤1eV2.1Figure4shows thatthe maximally allowed reduction in Y is only≈0.0021,about1%of the standard prediction. But the maximally allowed increase of Y can be as high as≈0.022,a9%effect.An increase this large in the predicted primordial4He abundance would have already been too large to accommodate observations[7,8].IV.INDIRECT GENERATION OF ELECTRON-NEUTRINO ASYMMETRY BYNEUTRINO TRANSFORMATIONSFor convenience in the indirect scheme,we assume that a Lντisfirst generated by aντ↔νs transformation process.This asymmetry may then be transferred to Lνeby a resonantντ↔νe oscillation[5].(Ordinary oscillations without resonance cannot transfer theasymmetry efficiently.)In fact we are likely to haveδm2(τs)≡m2νs−m2ντ≈δm2(τe)≡m2νe−m2ντif mντ≫mνe,mνs(which will be the case in order to have an appreciable impact on theprimordial4He abundance).Such a neutrino mass spectrum is consistent with a simultaneous solution of the solar neutrino problem[18]and the atmospheric neutrino problem[19].Forthe moment,we will simply assumeδm2(τs)≈δm2(τe).The matter asymmetry contributions to the effective potentials of the two neutrino trans-formation channels becomeV L(τs)≈±0.35G F T3(2Lντ−Lνe),V L(τe)≈±0.35G F T3(Lντ−Lνe).(20)Apparently,the¯ντ↔¯νs and¯ντ↔¯νe resonances when Lντ>0(or theντ↔νs andντ↔νeresonances when Lντ<0)do not simultaneously share the same part of the neutrino energy spectrum.Guaranteed adiabaticity(i.e.,satisfying Eq.[14]),the efficiency of resonant neutrino conversion is still determined by whether or not the neutrino collision time scale dominates over the timescale for a completeντtoνe(or¯ντto¯νe)transition at resonance(the resonance width).The collision timescale is important because the two resonances in Eq.(20)do not overlap,so for example,any deficit in¯ντcaused by the¯ντ↔¯νs resonant transition relies on neutrino scattering to redistribute neutrinos into the energy region where the¯ντ↔¯νe resonance occurs.In previous work[5]this redistribution has been assumed to be instant. However,this is not a good approximation at T<∼5MeV as we will show below.The ratio of the resonance timescale to the collision timescale isTV(τe)x H sin2θ(τe)∼Eq.(19),and tapers offat Lντ≈0.22when most ofντor¯ντhave undergone resonances.The transfer of Lντto Lνeis efficient at T>∼2MeV,but freezes out below∼2MeV.Itfreezes out at a higher temperature than Lντbecause theντ-νe(or¯ντ-¯νe)resonance occurs at a higher energy than theντ-νs(or¯ντ-¯νs)resonance(Eq.[20]).The resonance therefore sweeps through theνe(or¯νe)spectrum faster.Thefigure also shows that increase in the total neutrino energy density in this case(about2%,or∆Nν∼0.07)is moderate.The spectra ofνe and¯νe in the indirect scheme is only slightly distorted.Figure6showsthe modified¯νe spectrum when Lντ,Lνe>0for m2ντ−m2νe=m2ντ−m2νs=100eV2,comparedto an unperturbed active neutrino spectrum with zero chemical potential.The distortion issmall because the transfer of Lντinto Lνeoccurs in the entire energy distribution(albeit atdifferent temperatures),unlike in the direct scheme when the generation of Lνeoccurs onlyin low energies.The distortion inνe and¯νe spectra can be well approximated by an overallmultiplication factor1+δ±.The net asymmetry is therefore Lνe=3(δ+−δ−)/8,and the percentage increase in theνe¯νe number density due to pair production is(δ++δ−)/2.By modifying the standard BBN code with the newνe and¯νe spectra,and with theincreased total neutrino energy density,we obtain their effects on Y in Figure7.At m2ντ−m2νe =m2ντ−m2νs≪100eV2the effect on Y is dominated by the asymmetry in theνe¯νesector.But as m2ντ−m2νe=m2ντ−m2νsincreases,the increased total neutrino energydensity gradually becomes significant.The increased energy density causes Y to increase, regardless of the sign of the neutrino asymmetry.As a result of these two factors,a maximal reduction∆Y≈−0.005is achieved in cases of positive lepton number asymmetries whenm2ντ−m2νe=m2ντ−m2νs∼100to300eV2.This mass-squared-difference,however,impliesthat tau neutrinos are unstable,based on cosmological structure formation considerations [4].Figure7is very different from the previous estimates of Foot and Volkas[5].For example, Foot and Volkas have argued for a possible reduction∆Y≈−0.006across the mixingparameter range10<∼m2ντ−m2νe=m2ντ−m2νs<∼3000eV2.While our result clearly showsa concave feature of∆Y in this range,with a maximum at≈−0.005.Foot and Volkas’result also indicated that∆Y is smaller in the positive direction(when Lντ,Lνe<0)thanin the negative direction(when Lντ,Lνe>0).Our analysis indicates the opposite:whenLντ,Lνe<0,the changes in Y due to the spectral asymmetry and the extra neutrino energyadd constructively;while Lντ,Lνe<0,these two effects add destructively.∆Y,therefore,is larger in the positive direction than in the negative direction.These differences,we believe,stem from our detailed consideration of neutrino spectrum distortion and its time dependence.These factors are crucial to the neutron-to-proton freeze-out process,and in turn the primordial4He yield.V.SUMMARYWe have calculated the spectral distortions for neutrinos and the time dependence of the neutrino distribution function during the lepton asymmetry generation via resonant active-sterile neutrino transformation.We have included these crucial effects in our BBN calculation assessing the effect on the primordial4He abundance of the possible lepton num-ber asymmetry in theνe¯νe sector.We conclude that the possible increase in the primordial 4He yield,as a result of a negative lepton number asymmetry,can be substantial.The maximal increase can be as high as∼0.01to0.02(or5to9%)for mixing parameters that are consistent with neutrino mass constraints.The possible decrease due to a positive lepton number asymmetry,however,is limited to<∼0.002(or<∼1%)if the asymmetry is generated by a resonantνe↔νs mixing,or<∼0.005(or<∼2%)if the asymmetry is gener-ated by a three-family resonant mixing scheme.The magnitude of these possible changes in the primordial4He abundance induced by the neutrino-mixing-generated lepton num-ber asymmetry is comparable to or greater than the uncertainty of current primordial4He measurements.Therefore,the role of resonant active-sterile neutrino mixing in Big Bang Nucleosynthesis cannot be underestimated.X.S.,G.M.F.and K.A.are partially supported by NSF grant PHY98-00980at UCSD.[1]R.Foot,M.J.Thomson,and R.R.Volkas,Phys.Rev.D53,5349(1996).[2]X.Shi,Phys.Rev.D54,2753(1996).[3]R.Foot and R.R.Volkas,Phys.Rev.D55,5147(1997).[4]X.Shi and G.M.Fuller,Phys.Rev.D,in press.[5]R.Foot and R.R.Volkas,Phys.Rev.D56,6653(1997);N.F.Bell,R.Foot,R.R.Volkas,Phys.Rev.D5*******(1998).[6]X.Shi,D.N.Schramm,and B.D.Fields,Phys.Rev.D48,2568(1993);for an updatedversion,see Ref.[4].[7]K.A.Olive,E.Skillman,and G.Steigman,Astrophys.J.,483,788(1997).[8]Y.I.Izotov and T.X.Thuan,Astrophys.J.,500,188(1998).[9]R.E.Lopez and M.S.Turner,Phys.Rev.D,in press.[10]S.Burles and D.Tytler,to appear in the Proceedings of the Second Oak Ridge Symposiumon Atomic&Nuclear Astrophysics,ed.A.Mezzacappa(Institute of Physics,Bristol),and references therein.[11]K.Enqvist,K.Kainulainen,and M.Thomson,Nucl.Phys.B373,498(1992).[12]X.Shi and G.M.Fuller,Phys.Rev.Lett.,submitted.[13]D.N¨o tzold and G.Raffelt,Nucl.Phys.B307,924(1988).[14]D.P.Kirilova and M.V.Chizhov,Phys.Lett.B393,375(1997).[15]Y.Delais,et al.,Nucl.Phys.B434,503(1995).[16]M.G¨u nter,et al.,Phys.Rev.D55,54(1997).[17]L.Baudis,et al.,Phys.Lett.B407,219(1997).[18]See e.g.,N.Hata and ngacker,Phys.Rev.D56,6107(1997).[19]Y.Fukuda,et al.,Phys.Rev.Lett.,81,1562(1998).[20]Y.-Z.Qian,et al.,Phys.Rev.Lett.71,1965(1993);Y.-Z.Qian and G.M.Fuller,Phys.Rev.D52,656(1995);G.Sigl,Phys.Rev.D51,4035(1995).[21]B.Acker,et al.,Nucl.Phys.B434,503(1995).Figure Captions:Figure1.The magnitude of lepton asymmetry as a function ofδm2at various tempera-tures.The bands denote the range of the asymmetry enclosed by the two extreme cases: (1)collisions are completely inefficient(upper limits);(2)collisions are completely efficient (lower limits).Figure2.The solid curve:the calculatedνα(α=e,µ,τ)distribution function.The dashed curve:an unperturbed thermal neutrino distribution function with zero chemical potential.Figure3.The change in n↔p rates due to¯νe(if Lνe >0)orνe(if Lνe<0)spectral distortionfor m2νe −m2νs=1eV2.Figure4.The impact on the primordial4He abundance Y if an asymmetry inνe¯νe is generated by a resonantνe↔νs mixing in BBN.Baryon number density to photon number density ratio is set toη=5.1×10−10.Figure5.The solid curves:|Lντ|and|Lνe|as a function of temperature for m2ντ−m2νe=m2ντ−m2νs=100eV2.The dashed curve:the increase in the total neutrino energy densityas a function of temperature,normalized by the energy density of one thermalized active neutrinoflavor with zero chemical potential.Figure6.The solid curve:the calculatedνe distribution function in the indirect mixing scheme.The dashed curve:an unperturbed thermal neutrino distribution function with zero chemical potential.Inset:the ratio of the two distribution functions vs.neutrino energy.Figure7.The impact on the primordial4He abundance Y in the indirect neutrino mixingscheme,as a function of m2ντ−m2νe=m2ντ−m2νs.Baryon number density to photon numberdensity ratio is set toη=5.1×10−10.1010.00010.0010.010.110.00010.0010.010.1124680.940.960.981E/T。

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