Serendipitous Identification of a Covalent Activator of Liver Pyruvate Kinase

Enzymes are effective biological catalysts that accelerate almost all metabolic reactions in living organisms. Synthetic modulators of enzymes are useful tools for the study of enzymatic reactions and can provide starting points for the design of new drugs. Here, we report on the discovery of a class of biologically active compounds that covalently modifies lysine residues in human liver pyruvate kinase (PKL), leading to allosteric activation of the enzyme (EC₅₀=0.29 μM). Surprisingly, the allosteric activation control point resides on the lysine residue K282 present in the catalytic site of PKL. These findings were confirmed by structural data, MS/MS experiments, and molecular modelling studies. Altogether, our study provides a molecular basis for the activation mechanism and establishes a framework for further development of human liver pyruvate kinase covalent activators.     

Densification and properties of bulk nanocrystalline functional ceramics with grain size below 50 nm

The synthesis and functional characterization of dense bulk nanometric oxides are reviewed, with particular emphasis on the modifications that a grain size in the low nanometric range (10–50 nm) introduces in their physical properties. The preparation of ceramics with low porosity and extremely small grain size is particularly challenging and mostly relies on the sintering of extremely fine nanopowder. The most popular methods for the preparation of the starting nanopowders are introduced and briefly discussed as well as the most widely employed densification techniques. The role of nanostructure in controlling phase stability, electrical and thermal transport, optical and magnetic properties of nano-oxides is discussed in details. Several examples are given where bulk materials prepared with grain size equal or below 50 nm show characteristics that are either enhanced or, in some cases, completely different from those possessed by the same materials, but with larger grain sizes.     

用三带和全带模型蒙特卡罗方法模拟纤锌矿相GaN体材料输运特性结果的比较

报道了分别用三带和全带模型蒙特卡罗方法模拟纤锌矿相GaN体材料输运特性的结果,并对基于两种模型的模拟结果进行了比较.在低场区,基于两种模型获得的输运特性基本相同,但在高场区却表现出明显的差别.这是因为在高场区,电子平均能量较高,多数电子处于能带图中的高能态位置,电子能量与波矢量的关系表现出明显的非椭圆特性.由于三带模型假定了能量与波矢量简单关系,故算得的平均能量,高于由全带蒙特卡罗模拟算得的能量.从而导致其它特性的差别.全带模型包含了基于能带理论算得的能带结构的所有特性,故模拟结果更加精确.     

A Mixed Ligand Approach for the Asymmetric Hydrogenation of 2‐Substituted Pyridinium Salts

Herein we describe a new methodology for the asymmetric hydrogenation (AH) of 2‐substituted pyridinium salts. An iridium catalyst based on a mixture of a chiral monodentate phosphoramidite and an achiral phosphine was shown to hydrogenate N‐benzyl‐2‐arylpyiridinium bromides to the corresponding N‐benzyl‐2‐arylpiperidines with full conversion and good enantioselectivity. The mechanism of the reaction under optimized conditions was investigated via kinetic measurements and isotopic labeling experiments. Our study suggests that the hydrogenation starts with a 1,4‐hydride addition and that the enantiodiscriminating step involves the reduction of an iminium intermediate.

     

Toward the first nonpeptidic molecular tong inhibitor of wild-type and mutated HIV-1 protease dimerization

Herein we describe the synthesis and HIV-1 protease (PR) inhibitory activity of 16 new peptidomimetic molecular tongs with a naphthalene scaffold. Their peptidic character was progressively decreased. Two of these molecules exhibited the best dimerization inhibition activity toward HIV-1 wild-type and multimutated ANAM-11 proteases obtained to date for this class of molecules (～40?nM for wild-type PR and 100?nM for ANAM-11 PR). Although the peptidic character of one molecular tong was completely suppressed, the mechanism of inhibition and inhibitory potency toward both proteases were maintained.     

Fire Performance Assessment of a Fiber Reinforced Polymer Wall Panel Used in a Single Family Dwelling

This paper describes a fire performance assessment of a sandwich panel selected as the primary material in a high-performance house developed for the 2013 China Solar Decathlon competition. The sandwich panel has fiber reinforced polymer skins and a foam plastic core. Evaluation of fire performance showed that the selected panel would not comply with U.S. building code requirements for a single-family dwelling without additional protection. However, the use of an intumescent fire protective coating, coupled with the installation of a residential fire sprinkler system, is shown to be effective in meeting the intent of the fire and life safety requirements of the International Residential Code. Fire testing shows that the application of an intumescent fire protective coating to the panels significantly decreases the heat release rate, the smoke production characteristics, and the extent of flame spread on the panels.