C-band superconductor/semiconductor hybrid field-effect transistor amplifier on a LaAlO3 substrate

A single-stage C-band superconductor/semiconductor hybrid field-effect transistor amplifier was designed, fabricated, and tested at 77 K. The large area (1 inch x 0.5 inches) high temperature superconducting Tl-Ba-Ca-Cu-O (TBCCO) thin film was rf magnetron sputtered onto a LaAlO3 substrate. The film had a transition temperature of about 92 K after it was patterned and etched. The amplifier showed a gain of 6 dB and a 3 dB bandwidth of 100 MHz centered at 7.9 GHz. An identical gold amplifier circuit was tested at 77 K, and these results are compared with those from the hybrid amplifier

Discovery of Novel Nonactive Site Inhibitors of the Prothrombinase Enzyme Complex

© 2016 American Chemical Society. The risk of serious bleeding is a major liability of anticoagulant drugs that are active-site competitive inhibitors targeting the Factor Xa (FXa) prothrombin (PT) binding site. The present work identifies several new classes of small molecule anticoagulants that can act as nonactive site inhibitors of the prothrombinase (PTase) complex composed of FXa and Factor Va (FVa). These new classes of anticoagulants were identified, using a novel agnostic computational approach to identify previously unrecognized binding pockets at the FXa-FVa interface. From about three million docking calculations of 281 128 compounds in a conformational ensemble of FXa heavy chains identified by molecular dynamics (MD) simulations, 97 compounds and their structural analogues were selected for experimental validation, through a series of inhibition assays. The compound selection was based on their predicted binding affinities to FXa and their ability to successfully bind to multiple protein conformations while showing selectivity for particular binding sites at the FXa/FVa interface. From these, thirty-one (31) compounds were experimentally identified as nonactive site inhibitors. Concentration-based assays further identified 10 compounds represented by four small-molecule families of inhibitors that achieve dose-independent partial inhibition of PTase activity in a nonactive site-dependent and self-limiting mechanism. Several compounds were identified for their ability to bind to protein conformations only seen during MD, highlighting the importance of accounting for protein flexibility in structure-based drug discovery approaches

Some aspects of heavy ion fusion-fission dynamics

Study of heavy ion induced fusion-fission reactions at near and below barrier energies has attracted a great deal of attention in recent years, due to the observations of anomalous features in the fragment angular distributions for many target-projectile systems. Additionally there are also measurements of the fragment spin distributions and time-scales of the fusion-fission reactions, which have provided important information on the dynamics of these processes. In the present paper, the emphasis would be to highlight some of the recent experimental findings and their implications on the dynamics of the fusion-fission reactions in heavy ion collisions at near and above barrier energies

Bonding mechanism from the impact of thermally sprayed solid particles

Power particles are mainly in solid state prior to impact on substrates from high velocity oxy-fuel (HVOF) thermal spraying. The bonding between particles and substrates is critical to ensure the quality of coating. Finite element analysis (FEA) models are developed to simulate the impingement process of solid particle impact on substrates. This numerical study examines the bonding mechanism between particles and substrates and establishes the critical particle impact parameters for bonding. Considering the morphology of particles, the shear-instability–based method is applied to all the particles, and the energy-based method is employed only for spherical particles. The particles are given the properties of widely used WC-Co powder for HVOF thermally sprayed coatings. The numerical results confirm that in the HVOF process, the kinetic energy of the particle prior to impact plays the most dominant role in particle stress localization and melting of the interfacial contact region. The critical impact parameters, such as particle velocity and temperature, are shown to be affected by the shape of particles, while higher impact velocity is required for highly nonspherical powder

A Combination of Two Human Monoclonal Antibodies Limits Fetal Damage by Zika Virus in Macaques

Human infection by Zika virus (ZIKV) during pregnancy can lead to vertical transmission and fetal aberrations, including microcephaly. Prophylactic administration of antibodies can diminish or prevent ZIKV infection in animal models, but whether passive immunization can protect nonhuman primates and their fetuses during pregnancy has not been determined. Z004 and Z021 are neutralizing monoclonal antibodies to domain III of the envelope (EDIII) of ZIKV. Together the two antibodies protect nonpregnant macaques against infection even after Fc modifications to prevent antibody-dependent enhancement in vitro (ADE) and extend their half-lives. Here we report on prophylactic co-administration of the Fc-modified antibodies to pregnant rhesus macaques challenged 3 times with ZIKV during first and second trimester. The two antibodies did not entirely eliminate maternal viremia but limited vertical transmission protecting the fetus from neurologic damage. Thus, maternal passive immunization with two antibodies to EDIII can shield primate fetuses from the harmful effects of ZIKV

Venetoclax induces deep hematologic remissions in t(11;14) relapsed/refractory AL amyloidosis

Venetoclax is efficacious in relapsed/refractory t(11;14) multiple myeloma, thus warranting investigation in light-chain amyloidosis (AL). This retrospective cohort includes 43 patients with previously treated AL, from 14 centers in the US and Europe. Thirty-one patients harbored t(11;14), 11 did not, and one t(11;14) status was unknown. Patients received a venetoclax-containing regimen for at least one 21- or 28-day cycle; the median prior treatments was three. The hematologic response rate for all patients was 68%; 63% achieved VGPR/CR. t(11;14) patients had higher hematologic response (81% vs. 40%) and higher VGPR/CR rate (78% vs. 30%, odds ratio: 0.12, 95% CI 0.02-0.62) than non-t(11;14) patients. For the unsegregated cohort, median progression-free survival (PFS) was 31.0 months and median OS was not reached (NR). For t(11;14), median PFS was NR and for non-t(11;14) median PFS was 6.7 months (HR: 0.14, 95% CI 0.04-0.53). Multivariate analysis incorporating age, sex, prior lines of therapy, and disease stage suggested a risk reduction for progression or death in t(11;14) patients. Median OS was NR for either subgroup. The organ response rate was 38%; most responders harbored t(11;14). Grade 3 or higher adverse events occurred in 19% with 7% due to infections. These promising results require confirmation in a randomized clinical trial