Pressure induced anisotropy of electrical conductivity in polycrystalline molybdenum disulfide

Anisotropic specimens of MoS2 are obtained by pressing the microcrystalline powder into special die. This inelastic compression results in a rearrangement of the disulfide micro platelets observed by atomic force microscopy and reflected in the macroscopic anisotropy in electrical conductivity in these samples. The conductivity measured parallel and perpendicular to the direction of applied pressure exhibits an anisotropy factor of 10 at 1 GPa. This behaviour of the conductivity as a function of applied pressure is explained as the result of the simultaneous influence of a rearrangement of the micro platelets in the solid and the change of the inter-grain distances

Epitaxial growth of cubic MnSb on GaAs AND InGaAs(111)

The cubic polymorph of the binary transition metal pnictide (TMP) MnSb, c-MnSb, has been predicted to be a robust half-metallic ferromagnetic (HMF) material with minority spin gap ≳1 eV. Here, MnSb epilayers are grown by molecular beam epitaxy (MBE) on GaAs and In0.5Ga0.5As(111) substrates and analyzed using synchrotron radiation X-ray diffraction. We find polymorphic growth of MnSb on both substrates, where c-MnSb co-exists with the ordinary niccolite n-MnSb polymorph. The grain size of the c-MnSb is of the order of tens of nanometer on both substrates and its appearance during MBE growth is independent of the very different epitaxial strain from the GaAs (3.1%) and In0.5Ga0.5As (0.31%) substrates

Tolerance to highâ internalizing δ opioid receptor agonist is critically mediated by arrestin 2

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144602/1/bph14353.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144602/2/bph14353_am.pd

Cholesterol and oxysterol sulfates:Pathophysiological roles and analytical challenges

Cholesterol and oxysterol sulfates are important regulators of lipid metabolism, inflammation, cell apoptosis, and cell survival. Among the sulfate-based lipids, cholesterol sulfate (CS) is the most studied lipid both quantitatively and functionally. Despite the importance, very few studies have analysed and linked the actions of oxysterol sulfates to their physiological and pathophysiological roles. Overexpression of sulfotransferases confirmed the formation of a range of oxysterol sulfates and their antagonistic effects on liver X receptors (LXRs) prompting further investigations how are the changes to oxysterol/oxysterol sulfate homeostasis can contribute to LXR activity in the physiological milieu. Here, we aim to bring together for novel roles of oxysterol sulfates, the available techniques and the challenges associated with their analysis. Understanding the oxysterol/oxysterol sulfate levels and their pathophysiological mechanisms could lead to new therapeutic targets for metabolic diseases

Island and Mountain Ecosystems as Testbeds for Biological Control in the Anthropocene

For centuries, islands and mountains have incited the interest of naturalists, evolutionary biologists and ecologists. Islands have been the cradle for biogeography and speciation theories, while mountain ranges have informed how population adaptation to thermal floors shapes the distribution of species globally. Islands of varying size and mountains’ altitudinal ranges constitute unique “natural laboratories” where one can investigate the effects of species loss or global warming on ecosystem service delivery. Although invertebrate pollination or seed dispersal processes are steadily being examined, biological control research is lagging. While observations of a wider niche breadth among insect pollinators in small (i.e., species-poor) islands or at high (i.e., colder) altitudes likely also hold for biological control agents, such remains to be examined. In this Perspective piece, we draw on published datasets to show that island size alone does not explain biological control outcomes. Instead, one needs to account for species’ functional traits, habitat heterogeneity, host community make-up, phenology, site history or even anthropogenic forces. Meanwhile, data from mountain ranges show how parasitism rates of Noctuid moths and Tephritid fruit flies exhibit species- and context-dependent shifts with altitude. Nevertheless, future empirical work in mountain settings could clarify the thermal niche space of individual natural enemy taxa and overall thermal resilience of biological control. We further discuss how global databases can be screened, while ecological theories can be tested, and simulation models defined based upon observational or manipulative assays in either system. Doing so can yield unprecedented insights into the fate of biological control in the Anthropocene and inform ways to reinforce this vital ecosystem service under global environmental change scenarios.The development of this manuscript was funded by the Food and Agriculture Organization FAO through LOA/RAP/2021/57, executed by The University of Queensland. AS was supported by the "Ramon y Cajal" program (RYC2020029407-I), financed by the Spanish "Ministerio de Ciencia e Innovacion".info:eu-repo/semantics/publishedVersio

Epilepsy and neuropsychiatric comorbidities in mice carrying a recurrent Dravet syndrome SCN1A missense mutation

Dravet Syndrome (DS) is an encephalopathy with epilepsy associated with multiple neuropsychiatric comorbidities. In up to 90% of cases, it is caused by functional happloinsufficiency of the SCN1A gene, which encodes the alpha subunit of a voltage-dependent sodium channel (Nav1.1). Preclinical development of new targeted therapies requires accessible animal models which recapitulate the disease at the genetic and clinical levels. Here we describe that a C57BL/6 J knock-in mouse strain carrying a heterozygous, clinically relevant SCN1A mutation (A1783V) presents a full spectrum of DS manifestations. This includes 70% mortality rate during the first 8 weeks of age, reduced threshold for heat-induced seizures (4.7 °C lower compared with control littermates), cognitive impairment, motor disturbances, anxiety, hyperactive behavior and defects in the interaction with the environment. In contrast, sociability was relatively preserved. Electrophysiological studies showed spontaneous interictal epileptiform discharges, which increased in a temperature-dependent manner. Seizures were multifocal, with different origins within and across individuals. They showed intra/inter-hemispheric propagation and often resulted in generalized tonic-clonic seizures. 18F-labelled flourodeoxyglucose positron emission tomography (FDG-PET) revealed a global increase in glucose uptake in the brain of Scn1aWT/A1783V mice. We conclude that the Scn1aWT/A1783V model is a robust research platform for the evaluation of new therapies against DS

Growth of Pure Zinc-Blende GaAs(P) Core-Shell Nanowires with Highly Regular Morphology

The growth of self-catalyzed core–shell nanowires (NWs) is investigated systematically using GaAs(P) NWs. The defects in the core NW are found to be detrimental for the shell growth. These defects are effectively eliminated by introducing beryllium (Be) doping during the NW core growth and hence forming Be–Ga alloy droplets that can effectively suppress the WZ nucleation and facilitate the droplet consumption. Shells with pure zinc-blende crystal quality and highly regular morphology are successfully grown on the defect-free NW cores and demonstrated an enhancement of one order of magnitude for room-temperature emission compared to that of the defective shells. These results provide useful information on guiding the growth of high-quality shell, which can greatly enhance the NW device performance

Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Rucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma. Methods: In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries. Eligible patients were aged 18 years or older, had a platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma, had received at least two previous platinum-based chemotherapy regimens, had achieved complete or partial response to their last platinum-based regimen, had a cancer antigen 125 concentration of less than the upper limit of normal, had a performance status of 0–1, and had adequate organ function. Patients were ineligible if they had symptomatic or untreated central nervous system metastases, had received anticancer therapy 14 days or fewer before starting the study, or had received previous treatment with a poly(ADP-ribose) polymerase inhibitor. We randomly allocated patients 2:1 to receive oral rucaparib 600 mg twice daily or placebo in 28 day cycles using a computer-generated sequence (block size of six, stratified by homologous recombination repair gene mutation status, progression-free interval after the penultimate platinum-based regimen, and best response to the most recent platinum-based regimen). Patients, investigators, site staff, assessors, and the funder were masked to assignments. The primary outcome was investigator-assessed progression-free survival evaluated with use of an ordered step-down procedure for three nested cohorts: patients with BRCA mutations (carcinoma associated with deleterious germline or somatic BRCA mutations), patients with homologous recombination deficiencies (BRCA mutant or BRCA wild-type and high loss of heterozygosity), and the intention-to-treat population, assessed at screening and every 12 weeks thereafter. This trial is registered with ClinicalTrials.gov, number NCT01968213; enrolment is complete. Findings: Between April 7, 2014, and July 19, 2016, we randomly allocated 564 patients: 375 (66%) to rucaparib and 189 (34%) to placebo. Median progression-free survival in patients with a BRCA-mutant carcinoma was 16·6 months (95% CI 13·4–22·9; 130 [35%] patients) in the rucaparib group versus 5·4 months (3·4–6·7; 66 [35%] patients) in the placebo group (hazard ratio 0·23 [95% CI 0·16–0·34]; p<0·0001). In patients with a homologous recombination deficient carcinoma (236 [63%] vs 118 [62%]), it was 13·6 months (10·9–16·2) versus 5·4 months (5·1–5·6; 0·32 [0·24–0·42]; p<0·0001). In the intention-to-treat population, it was 10·8 months (8·3–11·4) versus 5·4 months (5·3–5·5; 0·36 [0·30–0·45]; p<0·0001). Treatment-emergent adverse events of grade 3 or higher in the safety population (372 [99%] patients in the rucaparib group vs 189 [100%] in the placebo group) were reported in 209 (56%) patients in the rucaparib group versus 28 (15%) in the placebo group, the most common of which were anaemia or decreased haemoglobin concentration (70 [19%] vs one [1%]) and increased alanine or aspartate aminotransferase concentration (39 [10%] vs none). Interpretation: Across all primary analysis groups, rucaparib significantly improved progression-free survival in patients with platinum-sensitive ovarian cancer who had achieved a response to platinum-based chemotherapy. ARIEL3 provides further evidence that use of a poly(ADP-ribose) polymerase inhibitor in the maintenance treatment setting versus placebo could be considered a new standard of care for women with platinum-sensitive ovarian cancer following a complete or partial response to second-line or later platinum-based chemotherapy. Funding: Clovis Oncology