Could chroman-4-one derivative be a better inhibitor of PTR1? – Reason for the identified disparity in its inhibitory potency in Trypanosoma brucei and Leishmania major

Most notable Kinetoplastids are of the genus Trypanosoma and Leishmania, affecting several millions of humans in Africa and Latin America. Current therapeutic options are limited by several drawbacks, hence the need to develop more efficacious inhibitors. An investigation to decipher the mechanism behind greater inhibitory potency of a chroman-4-one derivative (compound 1) in Trypanosoma brucei pteridine reductase 1 (TbPTR1) and Leishmania major pteridine reductase 1 (LmPTR1) was performed. Estimation of ΔG_bind revealed that compound 1 had a greater binding affinity in TbPTR1 with a ΔG_bind value of −49.0507 Kcal/mol than −29.2292 Kcal/mol in LmPTR1. The ΔGbind in TbPTR1 were predominantly contributed by “strong” electrostatic energy compared to the “weak” van der Waals in LmPTR1. In addition to this, the NADPH cofactor contributed significantly to the total energy of TbPTR1. A characteristic weak aromatic π interaction common in PTR1 was more prominent in TbPTR1 than LmPTR1. The consistent occurrence of high-affinity conventional hydrogen bond interactions as well as a steady interaction of crucial active site residues like Arg14/Arg17, Ser95/Ser111, Phe97/Phe113 in TbPTR1/LmPTR1 with chroman-4-one moiety equally revealed the important role the moiety played in the activity of compound 1. Overall, the structural and conformational analysis of the active site residues in TbPTR1 revealed them to be more rigid than LmPTR1. This could be the mechanism of interaction TbPTR1 employs in exerting a greater potency than LmPTR1. These findings will further give insight that will be assistive in modifying compound 1 for better potency and the design of novel inhibitors of PTR1.     

基于Kronecker型替换的黑盒多项式稀疏插值

本文基于新的Kronecker型替换,给出两个由黑盒表示的稀疏多项式的新确定性插值算法.令f∈R[x1,……,xn]是一个稀疏黑盒多项式,其次数上界为D.当R是C或者是有限域时,相对于已有算法,新算法具有更好的计算复杂度或者关于D的复杂度更低.特别地,对于一般黑盒模型,D是复杂度中的主要因素,而在所有的确定性算法中,本文的第二个算法的复杂度关于D是最低的.     

The Szegö kernel on a class of non-compact CR manifolds of high codimension

We generalize Nagel’s formula for the Szegö kernel and use it to compute the Szegö kernel on a class of non-compact CR manifolds whose tangent space decomposes into one complex direction and several totally real directions. We also discuss the control metric on these manifolds and relate it to the size of the Szegö kernel.     

An M/G/1 Retrial Queueing System with Two-Phase Service and Preemptive Resume

An M/G/1 retrial queueing system with additional phase of service and possible preemptive resume service discipline is considered. For an arbitrarily distributed retrial time distribution, the necessary and sufficient condition for the system stability is obtained, assuming that only the customer at the head of the orbit has priority access to the server. The steady-state distributions of the server state and the number of customers in the orbit are obtained along with other performance measures. The effects of various parameters on the system performance are analysed numerically. A general decomposition law for this retrial queueing system is established.     

Classification problems for shifts on modules over a principal ideal domain

In this paper we study symbolic dynamics over alphabets which are modules over a principal ideal domain, considering topological shifts which are also submodules. Our main result is the classification, up to algebraic and topological conjugacy, of the torsion-free, transitive, finite memory shifts.

     

一类非线性抛物型变分不等方程的全局吸引子及弱近似惯性流形

对由一类非线性抛物型变分不等方程所描述的无穷维动力系统，给出了存在全局吸引子及弱近似惯性流形的充分条件．