Discovery of structurally diverse natural product antagonists of chemokine receptor CXCR3

The chemokines (CXCL9, CXCL10 and CXCL11) and associated CXCR3 receptor are expressed during the inflammatory process from multiple sclerosis, atherosclerosis or organ transplantation resulting in the recruitment of lymphocytes leading to tissue damage. It is hypothesized that blocking of the ligand/CXCR3 receptor interaction has potential to provide opportunity for development of agents that would block tissue rejection. In this paper, four classes of natural product inhibitors (IC₅₀ ranging 0.1–41 M) have been described that block the CXCR3 receptor interaction of IP-10 ligand. These include a cyclic thiopeptide (duramycin), polyketide glycosides (roselipins), steroidal glycosides (hypoglausin A and dioscin) and a novel alkyl pyridinium alkaloid that were isolated by bioassay-guided fractionation of the organic extracts derived from actinomycete, fungal, plant and marine sources and discovered using ¹²⁵ I IP-10/CXCR3 binding assay. Duramycin was the most potent with an IC₅₀ of 0.1 M. Roselipins 2A, 2B and 1A showed IC₅₀ values of 14.6, 23.5, and 41 M, respectively. Diosgenin glycosides dioscin, hypoglaucin A and kallstroemin D exhibited IC₅₀ values of 2.1, 0.47 and 3 M, respectively. A novel cyclic 3-alkyl pyridinium salt isolated from a sponge displayed a binding IC₅₀ of 0.67 M.     

Freeze-out volume in multifragmentation --Dynamical simulations

Stochastic mean-field simulations for multifragmenting sources at the same excitation energy per nucleon have been performed. The freeze-out volume, a concept which needs to be precisely defined in this dynamical approach, was shown to increase as a function of three parameters: freeze-out instant, fragment multiplicity and system size.     

Bounds on the Unstable Eigenvalue for the Asymmetric Renormalization Operator for Period Doubling

We establish rigorous bounds for the unstable eigenvalue of the period-doubling renormalization operator for asymmetric unimodal maps. Herglotz-function techniques and cone invariance ideas are used. Our result generalizes an established result for conventional period doubling.This research is supported by The Leverhulme Trust (grant number F/00144/W).     

MODIFIED APPROXIMATE PROXIMAL POINT ALGORITHMS FOR FINDING ROOTS OF MAXIMAL MONOTONE OPERATORS

§1　Introduction and preliminariesA set T Rn×Rnis called a monotone operator on Rn,if T has the property(x,y) ,(x′,y′)∈T 〈x -x′,y -y′〉≥0 ,where〈·,·〉denotes the inner product on Rn.T is maximal if(considered as a graph) itis not strictly contained in any other monotone operator on Rn.It is well known that thetheory of maximal monotone operators plays an important role in the study of convexprogramming and variational inequalities since itcan provide a powerful general framework…     

一类二阶泛函微分方程周期解存在性问题

利用重合度理论研究一类二阶泛函微分方程x″(t)+f(t,x_t)x′~n+β(t)g(x(t-τ(t)))=p(t)的周期解问题,本文得到了周期解存在的新的结果。     

265Bh(Z=107)同位素的首次观测

在兰州的重离子加速器上用²⁶Mg离子束轰击²⁴³Am靶,产生了新同位素²⁶⁵Bh.通过观测新同位素²⁶⁵Bh和它的已知子核²⁶¹Db和²⁵⁷Lr之间的α衰变的关联,实现了对新核素的鉴别.实验中使用了一套新建立的具有数个探测器对的转轮收集探测系统.将该系统用于特殊的母–子核搜索模式,从而大大减少了本底.共测得了8个²⁶⁵Bh的α衰变关联事件;同时4个已知核²⁶⁴Bh的衰变关联事件也被鉴别出来.实验测得²⁶⁵Bh的α衰变能量为(9.24±0.05)MeV,半衰期为0.94+0.70–0.31s.     

激光大气等离子体时间演化特性的光谱研究

采用延时光谱法和谱线演化法 ,对YAG脉冲激光器 1 0 6 μm光束击穿一个大气压的空气所产生的等离子体进行了时间分辨光谱研究。对激光大气等离子体连续光谱的短波带与长波带分别进行了时间分辨测量 ,结果表明两者的衰变速率均在等离子体激发约 0 5微秒以后明显变慢。分析认为这种衰变速率的变慢可能与空气中氧对自由电子的吸附与去吸附有关。对激光大气等离子体线状光谱所作的时间分辨测量则表明 ,大部分线状光谱的演化寿命大于其标称寿命 ,部分线状光谱还呈现“衰变—增涨—衰变”的复杂形式。分析认为线状光谱的这些演化特征可能与等离子体在衰变期间的各种复合过程和能量转移过程有关。