Synthesis and Biological Evaluation of Novobiocin Core Analogues as Hsp90 Inhibitors

Development of heat shock protein 90 (Hsp90) C‐terminal inhibitors has emerged as an exciting strategy for the treatment of cancer. Previous efforts have focused on modifications to the natural products novobiocin and coumermycin. Moreover, variations in both the sugar and amide moieties have been extensively studied, whereas replacements for the coumarin core have received less attention. Herein, 24 cores were synthesized with varying distances and angles between the sugar and amide moieties. Compounds that exhibited good anti‐proliferative activity against multiple cancer cell lines and Hsp90 inhibitory activity, were those that placed the sugar and amide moieties between 7.7 and 12.1 Å apart along with angles of 180°.     

Exhaustive search of the configurational space of heat-shock protein 90 with its inhibitor by multicanonical molecular dynamics based dynamic docking

Multicanonical molecular dynamics based dynamic docking was used to exhaustively search the configurational space of an inhibitor binding to the N-terminal domain of heat-shock protein 90 (Hsp90). The obtained structures at 300 K cover a wide structural ensemble, with the top two clusters ranked by their free energy coinciding with the native binding site. The representative structure of the most stable cluster reproduced the experimental binding configuration, but an interesting conformational change in Hsp90 could be observed. The combined effects of solvation and ligand binding shift the equilibrium from a preferred loop-in conformation in the unbound state to an α-helical one in the bound state for the flexible lid region of Hsp90. Thus, our dynamic docking method is effective at predicting the native binding site while exhaustively sampling a wide configurational space, modulating the protein structure upon binding.     

Comparative study of degree-based molecular descriptors of cyclodextrins through M-polynomial and NM-polynomial

Cyclodextrins are natural oligosaccharides used to increase the solubility of drugs. It has numerous applications in drug discovery, food storage and other fields. Loftsson et al. explained about applications of Cyclodextrins(CDs) in administrating the drugs through various ways. Jansook et al. has given insights into the structure, physicochemical properties and pharmaceutical applications of CDs. In the present work, cyclodextrin and its derivatives such as α, β, γ CDs are studied for which various degree and neighborhood degree-based topological indices are computed through M-polynomial and NM-polynomial respectively and the comparison of the indices for all three types of cyclodextrins are presented which are of great importance in QSPR/QSAR studies.     

Capturing C90 Isomers as CF3 Derivatives: C90(30)(CF3)14, C90(35)(CF3)16/18, and C90(45)(CF3)16/18

High‐temperature trifluoromethylation of a C₉₀ isomeric mixture with CF₃I followed by HPLC separation of C₉₀(CF₃)_n isomers resulted in the isolation of several individual C₉₀(CF₃)_14?18 compounds. Single crystal X‐ray diffraction with the use of synchrotron radiation resulted in the structure determination of C₉₀(30)(CF₃)₁₄, C₉₀(35)(CF₃)_16/18, and C₉₀(45)(CF₃)_16/18. Their addition patterns are discussed and compared with the known isomers C₉₀(30)(CF₃)₁₈ and C₉₀(35)(CF₃)₁₄, respectively. The presence of the most stable C₉₀ isomer, C₉₀(45), in the fullerene soot has been confirmed for the first time.     

Optimality conditions and duality results for nonsmooth vector optimization problems with the multiple interval-valued objective function

In this paper, both Fritz John and Karush-Kuhn-Tucker necessary optimality conditions are established for a (weakly) LU-efficient solution in the considered nonsmooth multiobjective programming problem with the multiple interval-objective function. Further, the sufficient optimality conditions for a (weakly) LU-efficient solution and several duality results in Mond-Weir sense are proved under assumptions that the functions constituting the considered nondifferentiable multiobjective programming problem with the multiple interval-objective function are convex.     

Hybrid projection methods for equilibrium problems with non‐Lipschitz type bifunctions

Based on the extended extragradient‐like method and the linesearch technique, we propose three projection methods for finding a common solution of a finite family of equilibrium problems. The linesearch used in the proposed algorithms has allowed to reduce some conditions imposed on equilibrium bifunctions. The strongly convergent theorems are established without the Lipschitz‐type condition of bifunctions. The paper also helps in the design and analysis of practical algorithms and gives us a generalization of some previously known problems. Copyright © 2017 John Wiley & Sons, Ltd.     

Low rank matrix recovery from rank one measurements

We study the recovery of Hermitian low rank matrices $X\in {\mathbb{C}}^{n\times n}$ from undersampled measurements via nuclear norm minimization. We consider the particular scenario where the measurements are Frobenius inner products with random rank-one matrices of the form $a_j{a}_j^{?}$ for some measurement vectors $a_1,\dots ,a_m$, i.e., the measurements are given by $b_j=\mathrm{tr}(X{a}_j{a}_j^{?})$. The case where the matrix $X=x{x}^{?}$ to be recovered is of rank one reduces to the problem of phaseless estimation (from measurements $b_j=|〈x,a_j〉{|}^2$) via the PhaseLift approach, which has been introduced recently. We derive bounds for the number m of measurements that guarantee successful uniform recovery of Hermitian rank r matrices, either for the vectors $a_j$, $j=1,\dots ,m$, being chosen independently at random according to a standard Gaussian distribution, or $a_j$ being sampled independently from an (approximate) complex projective t-design with $t=4$. In the Gaussian case, we require $m\ge Crn$ measurements, while in the case of 4-designs we need $m\ge \mathit{Cr}n\log ?(n)$. Our results are uniform in the sense that one random choice of the measurement vectors $a_j$ guarantees recovery of all rank r-matrices simultaneously with high probability. Moreover, we prove robustness of recovery under perturbation of the measurements by noise. The result for approximate 4-designs generalizes and improves a recent bound on phase retrieval due to Gross, Krahmer and Kueng. In addition, it has applications in quantum state tomography. Our proofs employ the so-called bowling scheme which is based on recent ideas by Mendelson and Koltchinskii.     

气相爆轰波在90矩形弯管中传播时胞格结构的演化

利用烟迹技术实验获得气相爆轰波在90矩形弯管中传播时留下的胞格图案，详细分析了胞格结构在矩形弯管中的演化规律。同时分析了90矩形弯管的曲率半径和预混气体初始压力对胞格结构演化的影响。实验所采用的预混气体初始压力为33.3、26.7、24.0、16.0、10.7 kPa，90矩形弯管的曲率半径分别为100、50 mm。研究爆轰波胞格结构在弯管中的演化过程有助于深入了解气相爆轰波绕射机理和石油天然气等管道设计。     

Optimal control of self-organized dynamics in cellular signal transduction

We demonstrate how model-based optimal control can be exploited in biological and biochemical modelling applications in several ways. In the first part, we apply optimal control to a detailed kinetic model of a glycolysis oscillator, which plays a central role in immune cells, in order to analyse potential regulatory mechanisms in the dynamics of associated signalling pathways. We demonstrate that the formulation of inverse problems with the aim to determine specific time-dependent input stimuli can provide important insight into dynamic regulations of self-organized cellular signal transduction. In the second part, we present an optimal control study aimed at target-oriented manipulation of a biological rhythm, an internal clock mechanism related to the circadian oscillator. This oscillator is responsible for the approximate endogenous 24 h (latin: circa dies) day-night rhythm in many organisms. On the basis of a kinetic model for the fruit fly Drosophila, we compute switching light stimuli via mixed-integer optimal control that annihilate the oscillations for a fixed time interval. Insight gained from such model-based specific manipulation may be promising in biomedical applications.