Differential dynamics of the serotonin(1A) receptor in membrane bilayers of varying cholesterol content revealed by all atom molecular dynamics simulation

The serotonin(1A) receptor belongs to the superfamily of G protein-coupled receptors (GPCRs) and is a potential drug target in neuropsychiatric disorders. The receptor has been shown to require membrane cholesterol for its organization, dynamics and function. Although recent work suggests a close interaction of cholesterol with the receptor, the structural integrity of the serotonin(1A) receptor in the presence of cholesterol has not been explored. In this work, we have carried out all atom molecular dynamics simulations, totaling to 3s, to analyze the effect of cholesterol on the structure and dynamics of the serotonin(1A) receptor. Our results show that the presence of physiologically relevant concentration of membrane cholesterol alters conformational dynamics of the serotonin(1A) receptor and, on an average lowers conformational fluctuations. Our results show that, in general, transmembrane helix VII is most affected by the absence of membrane cholesterol. These results are in overall agreement with experimental data showing enhancement of GPCR stability in the presence of membrane cholesterol. Our results constitute a molecular level understanding of GPCR-cholesterol interaction, and represent an important step in our overall understanding of GPCR function in health and disease.

Stimuli-responsive colorimetric and NIR fluorescence combination probe for selective reporting of cellular hydrogen peroxide

Hydrogen peroxide (H2O2) is a key reactive oxygen species and a messenger in cellular signal transduction apart from playing a vital role in many biological processes in living organisms. In this article, we present phenyl boronic acid-functionalized quinone-cyanine (QCy-BA) in combination with AT-rich DNA (exogenous or endogenous cellular DNA), i.e., QCy-BA subset of DNA as a stimuli-responsive NIR fluorescence probe for measuring in vitro levels of H2O2. In response to cellular H2O2 stimulus, QCy-BA converts into QCy-DT, a one-donor-two-acceptor (D2A) system that exhibits switch-on NIR fluorescence upon binding to the DNA minor groove. Fluorescence studies on the combination probe QCy-BA subset of DNA showed strong NIR fluorescence selectively in the presence of H2O2. Furthermore, glucose oxidase (GOx) assay confirmed the high efficiency of the combination probe QCy-BA subset of DNA for probing H2O2 generated in situ through GOx-mediated glucose oxidation. Quantitative analysis through fluorescence plate reader, flow cytometry and live imaging approaches showed that QCy-BA is a promising probe to detect the normal as well as elevated levels of H2O2 produced by EGF/Nox pathways and post-genotoxic stress in both primary and senescent cells. Overall, QCy-BA, in combination with exogenous or cellular DNA, is a versatile probe to quantify and image H2O2 in normal and disease-associated cells.

Hydrogen Bonds Computing Server (HBCS): an online web server to compute hydrogen-bond interactions and their precision

Hydrogen bonds in biological macromolecules play significant structural and functional roles. They are the key contributors to most of the interactions without which no living system exists. In view of this, a web-based computing server, the Hydrogen Bonds Computing Server (HBCS), has been developed to compute hydrogen-bond interactions and their standard deviations for any given macromolecular structure. The computing server is connected to a locally maintained Protein Data Bank (PDB) archive. Thus, the user can calculate the above parameters for any deposited structure, and options have also been provided for the user to upload a structure in PDB format from the client machine. In addition, the server has been interfaced with the molecular viewers Jmol and JSmol to visualize the hydrogen-bond interactions. The proposed server is freely available and accessible via the World Wide Web at http://bioserver1.physics.iisc.ernet.in/hbcs/.

Dynamic Characteristics of Spherically Converging Detonation Waves

The spherically converging detonation wave was numerically investigated by solving the one-dimensional multi-component Euler equations in spherical coordinates with a dispersion-controlled dissipative scheme. Finite rate and detailed chemical reaction models were used and numerical solutions were obtained for both a spherical by converging detonation in a stoichiometric hydrogen-oxygen mixture and a spherically focusing shock in air. The results showed that the post-shock pressure approximately arises to the same amplitude in vicinity of the focal point for the two cases, but the post-shock temperature level mainly depends on chemical reactions and molecular dissociations of a gas mixture. While the chemical reaction heat plays an important role in the early stage of detonation wave propagation, gas dissociations dramatically affect the post-shock flow states near the focal point. The maximum pressure and temperature, non-dimensionalized by their initial value, are approximately scaled to the propagation radius over the initial detonation diameter. The post-shock pressure is proportional to the initial pressure of the detonable mixture, and the post-shock temperature is also increased with the initial pressure, but in a much lower rate than that of the post-shock pressure.

Investigation of kerosene combustion characteristics with pilot hydrogen in model supersonic combustors

Experimental investigations on the ignition and combustion stabilization of kerosene with pilot hydrogen in Mach 2.5 airflows were conducted using two test combustors, with cross sections of 30.5 x 30 and 51 x 70 mm, respectively. Various integrated modules, including the combinations of different pilot injection schemes and recessed cavity flameholders with different geometries, were designed and tested. The stagnation pressure of vitiated air varied within the range of 1.1-1.8 NiPa, while the stagnation temperature varied from 1500 to 1900 K. Specifically, effects of the pilot hydrogen injection scheme, cavity geometry, and combustor scaling on the minimally required pilot hydrogen equivalence ratio were systematically examined. Results indicated that the cavity depth and length had significant effects on the ignition and flameholding, whereas the slanted angle of the aft wall was relatively less important. Two cavities in tandem were shown to be a more effective flameholding mechanism than that with a single cavity. The minimally required pilot hydrogen equivalence ratio for kerosene ignition and stable combustion was found to be as low as 0.02. Furthermore, combustion efficiency of 80% was demonstrated to be achievable for kerosene with the simultaneous use of pilot hydrogen and a recessed cavity to promote the ignition and global burning.

The Complete Proof of the Virial Theorem in the Refined TFD Theory for all Electrons of an Atom in a Solid

The complete proof of the virial theorem in refined Thomas-Fermi-Dirac theory for all electrons of an atom in a solid is given.

经典轨道的封闭性和径向Schrodinger方程的因式分解

研究表明，保证经典轨道具有封闭性的Bertrand定理可以进一步推广，在适当的角动量睛，仍存在着非椭圆的闭合轨道。对于屏蔽Coulomb场，可获得广义Runge-Lenz矢量。这种轨道封闭性与径向Schrodinger方程因式分解相对应。

Spherical nanometer-sized diamond obtained from detonation

Ultrafine diamond (UFD) was synthesized under high pressure and high temperatures generated by explosive detonation. The structure, composition, surface and thermal stability of UFD were studied by use of XRD, TEM, Raman Spectroscopy, FTIR, etc. The influences of the synthesis conditions and purification conditions on the properties of UFD were analyzed. The UFD had an average size of 4-6 nm, commonly exhibiting a spherical shape. The highest yield was of up to 10 mass% of the explosive. Attempts were made to use UFD as an additive to metal-diamond sintering and as crystallite seeds of CVD diamond films. The results show that UFD can decrease the coefficient of friction of the composite by 30%, and raise the nucleation density in CVD diamond films by 2-3 times.