市场需求信息不对称下的保兑仓融资风险控制策略

信息不对称风险广泛存在于保兑仓融资过程当中,本文运用Stackelberg博弈模型刻画融资系统成员关系,运用动态规划优化分析方法求解对应博弈均衡策略。总结出需求信息不对称的三种表现形式:信息造假,信息优势及信息隐匿,分析各类信息不对称情形对融资系统所造成影响,并相应提出实现信息显示功能的契约甄别机制。研究表明:零售商可从信息不对称中获取巨大信息优势,但对其他成员造成损害,其中信息隐匿对生产商损害程度更高;二部定价机制可实现信息甄别,但生产商须为之付出信息租金,造成效率损失;而合理参数设定下的二部定价加回购机制有助于进一步改进融资系统及各成员收益,甚至达到次协调状态,最终实现融资成员收益的帕累托改进。本研究对于控制供应链融资中的信息风险、改善融资效率提供了理论依据及决策参考。     

Identification of Flavonoids as Putative ROS-1 Kinase Inhibitors Using Pharmacophore Modeling for NSCLC Therapeutics

Non-small cell lung cancer (NSCLC) is a lethal non-immunogenic malignancy and proto-oncogene ROS-1 tyrosine kinase is one of its clinically relevant oncogenic markers. The ROS-1 inhibitor, crizotinib, demonstrated resistance due to the Gly2032Arg mutation. To curtail this resistance, researchers developed lorlatinib against the mutated kinase. In the present study, a receptor-ligand pharmacophore model exploiting the key features of lorlatinib binding with ROS-1 was exploited to identify inhibitors against the wild-type (WT) and the mutant (MT) kinase domain. The developed model was utilized to virtually screen the TimTec flavonoids database and the retrieved drug-like hits were subjected for docking with the WT and MT ROS-1 kinase. A total of 10 flavonoids displayed higher docking scores than lorlatinib. Subsequent molecular dynamics simulations of the acquired flavonoids with WT and MT ROS-1 revealed no steric clashes with the Arg2032 (MT ROS-1). The binding free energy calculations computed via molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) demonstrated one flavonoid (Hit) with better energy than lorlatinib in binding with WT and MT ROS-1. The Hit compound was observed to bind in the ROS-1 selectivity pocket comprised of residues from the β-3 sheet and DFG-motif. The identified Hit from this investigation could act as a potent WT and MT ROS-1 inhibitor.     

Weak Intermolecular Hydrogen Bonds with Fluorine: Detection and Implications for Enzymatic/Chemical Reactions,Chemical Properties,and Ligand/Protein Fluorine NMR Screening

It is known that strong hydrogen‐bonding interactions play an important role in many chemical and biological systems. However, weak or very weak hydrogen bonds, which are often difficult to detect and characterize, may also be relevant in many recognition and reaction processes. Fluorine serving as a hydrogen‐bond acceptor has been the subject of many controversial discussions and there are different opinions about it. It now appears that there is compelling experimental evidence for the involvement of fluorine in weak intramolecular or intermolecular hydrogen bonds. Using established NMR methods, we have previously characterized and measured the strengths of intermolecular hydrogen‐bond complexes involving the fluorine moieties CH₂F, CHF₂, and CF₃, and have compared them with the well‐known hydrogen‐bond complex formed between acetophenone and the strong hydrogen‐bond donor p‐fluorophenol. We now report evidence for the formation of hydrogen bonds involving fluorine with significantly weaker donors, namely 5‐fluoroindole and water. A simple NMR method is proposed for the simultaneous measurement of the strengths of hydrogen bonds between an acceptor and a donor or water. Important implications of these results for enzymatic/chemical reactions involving fluorine, for chemical and physical properties, and for ligand/protein ¹⁹F NMR screening are analyzed through experiments and theoretical simulations.     

Glutamine: fructose-6-phosphate amidotransferase (GFAT): homology modelling and designing of new inhibitors using pharmacophore and docking based hierarchical virtual screening protocol

Glutamine: fructose-6-phosphate amidotransferase (GFAT), also termed GFPT1 and GFAT1, catalyzes the first committed step of the hexosamine biosynthesis pathway in mammals and consequently plays an important role in type 2 diabetes. In the present study, a combination of pharmacophore modelling, homology modelling, and molecular docking analysis was performed to design new glutamine competitive inhibitors of human GFAT, and to investigate important interaction details of inhibitor molecules. A pharmacophore model of GFAT inhibitors was developed, subsequently validated, and utilized for the screening by the PHASE database to identify new molecules. Afterwards, homology modelling was performed to construct the glutamine-binding site of the GFAT protein. The modelled active site was utilized to dock the studied molecules to investigate important receptor-ligand interactions and to scrutinize database-screened molecules on the basis of essential interactions. This systematic in silico protocol helped us to identify new molecules that would be explored for the treatment of type 2 diabetes and its complications.     

Identification of Compounds that Selectively Stabilize Specific G‐Quadruplex Structures by Using a Thioflavin T‐Displacement Assay as a Tool

Small molecules are used in the G‐quadruplex (G4) research field in vivo and in vitro, and there are increasing demands for ligands that selectively stabilize different G4 structures. Thioflavin T (ThT) emits an enhanced fluorescence signal when binding to G4 structures. Herein, we show that ThT can be competitively displaced by the binding of small molecules to G4 structures and develop a ThT‐displacement high‐throughput screening assay to find novel and selective G4‐binding compounds. We screened approximately 28 000 compounds by using three different G4 structures and identified eight novel G4 binders. Analysis of the structural conformation and stability of the G4 structures in presence of these compounds demonstrated that the four compounds enhance the thermal stabilization of the structures without affecting their structural conformation. In addition, all four compounds also increased the G4‐structure block of DNA synthesis by Taq DNA polymerase. Also, two of these compounds showed selectivity between certain Schizosaccharomyces pombe G4 structures, thus suggesting that these compounds or their analogues can be used as selective tools for G4 DNA studies.     

Solvent‐free Synthesis of Water‐Soluble New Pyridinium Amines: Spectroscopic Characterization,Biological Screening,and Interaction Study with DNA

New water‐soluble pyridinium amines ( 2–8 ) were obtained by the solid‐state reactions of 4‐chloro‐1‐methylpyridin‐1‐ium triflate ( 1 ) and various primary aromatic amines. These compounds were characterized by ¹H , ¹³C NMR , FTIR , UV –vis, and fluorescence spectroscopic methods along with single‐crystal X‐ray structure determination. The interaction potentials of all newly synthesized compounds with calf thymus DNA (CT‐DNA ) were investigated by UV –vis and florescence spectroscopy accompanied by docking studies. UV –vis spectroscopy indicated that the binding of compounds with CT‐DNA takes place via the intercalative mode. The compounds were also screened for their potential as antioxidants and enzyme inhibition agents. Some compounds displayed excellent butyrylcholine and acetylcholine esterase inhibition activities and were effective in scavenging the 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH ) radical in a dose‐dependent manner comparable to a standard.     

ESR EVIDENCE OF AN ELECTRON TRANSFER BETWEEN ARYLPHOSPHINES AND ARYLNITROSO COMPOUNDS

Abstract

Electron transfer between arylphosphines and arylnitroso compounds gives rise to the formation of free radicals which have been characterized by esr     

Petra,Osiris, and Molinspiration Together as a Guide in Drug Design: Predictions and Correlation Structure/Antibacterial Activity Relationships of New N-Sulfonyl Monocyclic β-Lactams

We report in this article the design and calculated molecular properties of 18 new mono-cyclic β-lactams 4–21, on the basis of one hypothetical antibacterial pharmacophore structure designed to interact with both of Gram-positive bacteria and Gram-negative bacteria. The in vitro biological evaluation of these compounds allowed us to point out new potential non-nucleoside hits, with MIC values in the range of 2–8 μg/mL active against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa. A correlation structure/antibacterial activities relationship of these monocyclic β-lactams is described.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Microbial Screening of Copolymers of N‐Vinylimidazole with Phenacyl Methacrylate: Synthesis and Monomer Reactivity Ratios

N‐vinylimidazole (VIM), and phenacyl methacrylate (PAMA) copolymerized with different feed ratios using 1,4‐dioxane as a solvent and α,α'‐azobisisobutyronitrile (AIBN) as an initiator at 60°C. Structure and composition of copolymers for a wide range of monomer feed were determined by elemental analysis (content of N for VIM‐units) and by Fourier transform infrared spectroscopy through recorded analytical absorption bands for VIM (670 cm^?1 for C‐N of imidazole ring) and PAMA (1730 cm^?1 for C?O of ester group) units, respectively. Monomer reactivity ratios for VIM (M₁)‐PAMA (M₂) pair were determined by the application of conventional linearization methods such as Fineman‐Ross (F‐R) and Kelen‐Tüdös (KT) and a nonlinear error invariable model method using a computer program RREVM. The molecular weights (_w and _n) and polydispersity indices of the polymers were determined using gel permeation chromatography (GPC). Thermal behaviors of copolymers with various compositions were investigated by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Also, the apparent thermal decomposition activation energies (ΔE_d) were calculated by Ozawa method using the SETARAM Labsys TGA thermobalance. The antibacterial and antifungal effects of polymers were also tested on various bacteria, fungi and yeast.