Lifshitz phase transitions in a one-dimensional Gamma model.

In this paper, we study quantum phase transitions and magnetic properties of a one-dimensional spin-1/2 Gamma model, which describes the off-diagonal exchange interactions between edge-shared octahedra with strong spin-orbit couplings along the sawtooth chain. The competing exchange interactions between the nearest neighbors and the second neighbors stabilize the semimetallic ground state in terms of spinless fermions, and give rise to a rich phase diagram, which consists of three gapless phases. We find distinct phases are characterized by the number of Weyl nodes in the momentum space, and such changes in the topology of the Fermi surface without symmetry breaking produce a variety of Lifshitz transitions, in which the Weyl nodes situating at k=π change from type I to type II.

Pyrolytic Kinetics of Polystyrene Particle in Nitrogen Atmosphere: Particle Size Effects and Application of Distributed Activation Energy Method.

This work was motivated by a study of particle size effects on pyrolysis kinetics and models of polystyrene particle. Micro-size polystyrene particles with four different diameters, 5, 10, 15, and 50 µm, were selected as experimental materials. Activation energies were obtained by isoconversional methods, and pyrolysis model of each particle size and heating rate was examined through different reaction models by the Coats-Redfern method.

Experimental study of the effect of typical halides on pyrolysis of ammonium nitrate using model reconstruction.

The energetic material ammonium nitrate (AN) is used as an industrial raw material; however, it presents a pyrolysis and explosion hazard during transportation and storage, especially when mixed with impurities. To study the effects of typical halides on the thermal decomposition kinetics of AN, a series of precision thermogravimetric analysis experiments at four heating rates were carried out in a nitrogen atmosphere. Based on derivative thermogravimetric analysis, the addition of sodium halides was found to change the kinetic reaction mechanism of AN pyrolysis.

An experimental and theoretical study of optimized selection and model reconstruction for ammonium nitrate pyrolysis.

Ammonium nitrate (AN) is a commonly-used industrial raw material in industrial explosives and fertilizers areas. However, as an energetic material, its danger exists during the production, transportation, and storage, resulting in a large number of accidents involving personal injury and property loss. To obtain the accurate kinetic triplet parameters of AN thermal decomposition, a series of thermogravimetry analysis (TGA) experiments was conducted with four different heating rates.

Sample width and thickness effects on upward flame spread over PMMA surface.

Upward flame spread has the same propagating direction with air flow and buoyancy, and features as the most hazardous fire case in all flame spread configurations. It has been a long time for fire researchers to find a simple and effective method to evaluate upward flame spread behaviors, especially for different materials and sample sizes. The aim of this work was motivated by the research of sample width and thickness effects on upward flame spread behavior, including flame spread rate during acceleration propagation for different sample thickness and width, theoretical global mass loss prediction based on Emmons's hypothesis, and dimensionless flame height scaling with dimensionless heat release rate for steady stage burning.

Experimental study on thermal hazard of tributyl phosphate-nitric acid mixtures using micro calorimeter technique.

During PUREX spent nuclear fuel reprocessing, mixture of tributyl phosphate (TBP) and hydrocarbon solvent are employed as organic solvent to extract uranium in consideration of radiation contaminated safety and resource recycling, meanwhile nitric acid is utilized to dissolve the spent fuel into small pieces. However, once TBP contacts with nitric acid or nitrates above 130°C, a heavy "red oil" layer would occur accompanied by thermal runaway reactions, even caused several nuclear safety accident. Considering nitric acid volatility and weak exothermic detection, C80micro calorimeter technique was used in this study to investigate thermal decomposition of TBP mixed with nitric acid.

Synergistic Activity of Combined NS5A Inhibitors.

Daclatasvir (DCV) is a first-in-class hepatitis C virus (HCV) nonstructural 5A replication complex inhibitor (NS5A RCI) that is clinically effective in interferon-free combinations with direct-acting antivirals (DAAs) targeting alternate HCV proteins. Recently, we reported NS5A RCI combinations that enhance HCV inhibitory potential in vitro, defining a new class of HCV inhibitors termed NS5A synergists (J. Sun, D.

Resensitizing daclatasvir-resistant hepatitis C variants by allosteric modulation of NS5A.

It is estimated that more than 170 million people are infected with hepatitis C virus (HCV) worldwide. Clinical trials have demonstrated that, for the first time in human history, the potential exists to eradicate a chronic viral disease using combination therapies that contain only direct-acting antiviral agents. HCV non-structural protein 5A (NS5A) is a multifunctional protein required for several stages of the virus replication cycle.

[Therapeutic Efficacy of Multigly-Cosidorum Tripterygium Combined with rhIL-11 for Immune Thrombocytopenia].

Objective: To study the therapeutic efficacy of multigly-cosidorum Tripterygium combined with rhIL-11 for treating patients with immune thrombocytopenia (ITP).

Methods: A total of 75 patients with ITP were divided into 2 group: experimental group and control group. The experimental group included 40 patients who had been treated with multigly-cosidorum Tripterygium combined with rhIL-11.

A new method to effectively and rapidly generate neurons from SH-SY5Y cells.

It is well known that neurons differentiated from SH-SY5Y cells can serve as cell models for neuroscience research; i.e., neurotoxicity and tolerance to morphine in vitro.

Comparison of daclatasvir resistance barriers on NS5A from hepatitis C virus genotypes 1 to 6: implications for cross-genotype activity.

A comparison of the daclatasvir (DCV [BMS-790052]) resistance barrier on authentic or hybrid replicons containing NS5A from hepatitis C virus (HCV) genotypes 1 to 6 (GT-1 to -6) was completed using a replicon elimination assay. The data indicated that genotype 1b (GT-1b) has the highest relative resistance barrier and genotype 2a (GT-2a M31) has the lowest. The rank order of resistance barriers to DCV was 1b>4a≥5a>6a≅1a>2a JFH>3a>2a M31.

Trait impulsivity and impaired prefrontal impulse inhibition function in adolescents with internet gaming addiction revealed by a Go/No-Go fMRI study.

Background: Recent studies suggest that Internet gaming addiction (IGA) is an impulse disorder, or is at least related to impulse control disorders. In the present study, we hypothesized that different facets of trait impulsivity may be specifically linked to the brain regions with impaired impulse inhibition function in IGA adolescents.

Methods: Seventeen adolescents with IGA and seventeen healthy controls were scanned during performance of a response-inhibition Go/No-Go task using a 3.

Discovery and development of hepatitis C virus NS5A replication complex inhibitors.

Lead inhibitors that target the function of the hepatitis C virus (HCV) nonstructural 5A (NS5A) protein have been identified by phenotypic screening campaigns using HCV subgenomic replicons. The demonstration of antiviral activity in HCV-infected subjects by the HCV NS5A replication complex inhibitor (RCI) daclatasvir (1) spawned considerable interest in this mechanistic approach. In this Perspective, we summarize the medicinal chemistry studies that led to the discovery of 1 and other chemotypes for which resistance maps to the NS5A protein and provide synopses of the profiles of many of the compounds currently in clinical trials.

Characterizations of HCV NS5A replication complex inhibitors.

The hepatitis C virus NS5A protein is an established and clinically validated target for antiviral intervention by small molecules. Characterizations are presented of compounds identified as potent inhibitors of HCV replication to provide insight into structural elements that interact with the NS5A protein. UV-activated cross linking and affinity isolation was performed with one series to probe the physical interaction between the inhibitors and the NS5A protein expressed in HCV replicon cells.

HCV NS5A replication complex inhibitors. Part 5: discovery of potent and pan-genotypic glycinamide cap derivatives.

The isoquinolinamide series of HCV NS5A inhibitors exemplified by compounds 2b and 2c provided the first dual genotype-1a/1b (GT-1a/1b) inhibitor class that demonstrated a significant improvement in potency toward GT-1a replicons compared to that of the initial program lead, stilbene 2a. Structure-activity relationship (SAR) studies that uncovered an alternate phenylglycine-based cap series that exhibit further improvements in virology profile, along with some insights into the pharmacophoric elements associated with the GT-1a potency, are described.

A 96-well based analysis of replicon elimination with the HCV NS5A replication complex inhibitor daclatasvir.

A 96-well based replicon elimination and colony formation assay is presented for comparing the resistance barrier of the hepatitis C virus (HCV) NS5A replication complex inhibitor daclatasvir (DCV, BMS-790052) on three HCV genotypes (gts) in a proof of concept experimental protocol. The 96-well assay format provides both individual colony as well as population characterization and is readily applicable to other HCV direct-acting antiviral agents (DAAs). The assay provides an assessment of HCV replication levels over a 5log10 range by measuring a luciferase reporter resident in the HCV replicons.

HCV NS5A replication complex inhibitors. Part 4. Optimization for genotype 1a replicon inhibitory activity.

A series of symmetrical E-stilbene prolinamides that originated from the library-synthesized lead 3 was studied with respect to HCV genotype 1a (G-1a) and genotype 1b (G-1b) replicon inhibition and selectivity against BVDV and cytotoxicity. SAR emerging from an examination of the prolinamide cap region revealed 11 to be a selective HCV NS5A inhibitor exhibiting submicromolar potency against both G-1a and G-1b replicons. Additional structural refinements resulted in the identification of 30 as a potent, dual G-1a/1b HCV NS5A inhibitor.

Altered default network resting-state functional connectivity in adolescents with Internet gaming addiction.

Purpose: Excessive use of the Internet has been linked to a variety of negative psychosocial consequences. This study used resting-state functional magnetic resonance imaging (fMRI) to investigate whether functional connectivity is altered in adolescents with Internet gaming addiction (IGA).

Methods: Seventeen adolescents with IGA and 24 normal control adolescents underwent a 7.

Persistence of resistant variants in hepatitis C virus-infected patients treated with the NS5A replication complex inhibitor daclatasvir.

Daclatasvir (DCV; BMS-790052) is a hepatitis C virus (HCV) NS5A replication complex inhibitor (RCI) with picomolar to low nanomolar potency and broad genotypic coverage in vitro. Viral RNA declines have been observed in the clinic for both alpha interferon-ribavirin (IFN-α-RBV) and IFN-RBV-free regimens that include DCV. Follow-up specimens (up to 6 months) from selected subjects treated with DCV in 14-day monotherapy studies were analyzed for genotype and phenotype.

HCV NS5A replication complex inhibitors. Part 3: discovery of potent analogs with distinct core topologies.

In a recent disclosure, we described the discovery of dimeric, prolinamide-based NS5A replication complex inhibitors exhibiting excellent potency towards an HCV genotype 1b replicon. That disclosure dealt with the SAR exploration of the peripheral region of our lead chemotype, and herein is described the SAR uncovered from a complementary effort that focused on the central core region. From this effort, the contribution of the core region to the overall topology of the pharmacophore, primarily vector orientation and planarity, was determined, with a set of analogs exhibiting <10 nM EC(50) in a genotype 1b replicon assay.

Neuropsychological study of patients with obsessive-compulsive disorder and their parents in China: searching for potential endophenotypes.

Objective: The existence of neuropsychological deficits has been implicated in obsessive-compulsive disorder (OCD), particularly memory, attention, and executive functions. However, few studies have focused on neuropsychological deficits in the relatives of OCD patients. The aim of this study was to investigate cognitive deficits in OCD patients and their parents.

HCV NS5A replication complex inhibitors. Part 2: investigation of stilbene prolinamides.

In a previous disclosure,(1) we reported the dimerization of an iminothiazolidinone to form 1, a contributor to the observed inhibition of HCV genotype 1b replicon activity. The dimer was isolated via bioassay-guided fractionation experiments and shown to be a potent inhibitor of genotype 1b HCV replication for which resistance mapped to the NS5A protein. The elements responsible for governing HCV inhibitory activity were successfully captured in the structurally simplified stilbene prolinamide 2.

Aquaporin 4 knockdown exacerbates streptozotocin-induced diabetic retinopathy through aggravating inflammatory response.

Diabetic retinopathy is a leading cause of reduced visual acuity and acquired blindness. Diabetes is known to alter the amount of retinal expression of the water-selective channels aquaporin 4 (AQP4). However, the function and impact of AQP4 in diabetic retinopathy is not well understood.

Impact of a baseline polymorphism on the emergence of resistance to the hepatitis C virus nonstructural protein 5A replication complex inhibitor, BMS-790052.

Unlabelled: The influence of naturally occurring polymorphisms on the potency of the HCV nonstructural protein 5A (NS5A) replication complex inhibitor, BMS-790052, was investigated by evaluating hybrid replicons in which the entire NS5A coding region of genotype (GT) la and 1b laboratory (lab) strains (H77c and Con1) were replaced with the corresponding regions of specimens collected from 10 GT-1a- and 6 GT-1b-infected subjects. For baseline (BL) specimens, with no previously observed resistance variants identified by population sequencing, the median 50% effective concentration (EC(50) ) values for BMS-790052 were similar for the clinically derived and lab strains. A Q30R variant was observed at viral breakthrough (VBT) in one of the GT-1a-infected subjects.