Structure and superconductivity of LiFeAs

The lithium ions in Lithium iron arsenide phases with compositions close to LiFeAs have been located using powder neutron diffraction. These phases exhibit superconductivity at temperatures at least as high as 16 K demonstrating that superconductivity in compounds with [FeAs]- anti-PbO-type anionic layers occurs in compounds with at least three different structure types and occurs for a wide range of As-Fe-As bond angles.Comment: 3 pages, 3 figures, 3 table

Discovery and functional characterization of cardiovascular long noncoding RNAs

Recent advances in sequencing and genomic technologies have resulted in the discovery of thousands of previously unannotated long noncoding RNAs (lncRNAs). However, their function in the cardiovascular system remains elusive. Here we review and discuss considerations for cardiovascular lncRNA discovery, annotation and functional characterization. Although we primarily focus on the heart, the proposed pipeline should foster functional and mechanistic exploration of these transcripts in various cardiovascular pathologies. Moreover, these insights could ultimately lead to novel therapeutic approaches targeting lncRNAs for the amelioration of cardiovascular diseases including heart failure

Biological Characterization of Gene Response to Insulin-Induced Hypoglycemia in Mouse Retina.

Glucose is the most important metabolic substrate of the retina and maintenance of normoglycemia is an essential challenge for diabetic patients. Chronic, exaggerated, glycemic excursions could lead to cardiovascular diseases, nephropathy, neuropathy and retinopathy. We recently showed that hypoglycemia induced retinal cell death in mouse via caspase 3 activation and glutathione (GSH) decrease. Ex vivo experiments in 661W photoreceptor cells confirmed the low-glucose induction of death via superoxide production and activation of caspase 3, which was concomitant with a decrease of GSH content. We evaluate herein retinal gene expression 4 h and 48 h after insulin-induced hypoglycemia. Microarray analysis demonstrated clusters of genes whose expression was modified by hypoglycemia and we discuss the potential implication of those genes in retinal cell death. In addition, we identify by gene set enrichment analysis, three important pathways, including lysosomal function, GSH metabolism and apoptotic pathways. Then we tested the effect of recurrent hypoglycemia (three successive 4h periods of hypoglycemia spaced by 48 h recovery) on retinal cell death. Interestingly, exposure to multiple hypoglycemic events prevented GSH decrease and retinal cell death, or adapted the retina to external stress by restoring GSH level comparable to control situation. We hypothesize that scavenger GSH is a key compound in this apoptotic process, and maintaining "normal" GSH level, as well as a strict glycemic control, represents a therapeutic challenge in order to avoid side effects of diabetes, especially diabetic retinopathy

Polymorphism in cyclohexanol

The crystal structures and phase behaviour of phase II and the metastable phases III0 and III of cyclohexanol, C6H11OH, have been determined using high-resolution neutron powder, synchrotron X-ray powder and single-crystal X-ray diffraction techniques. Cyclohexanol-II is formed by a transition from the plastic phase I cubic structure at 265 K and crystallizes in a tetragonal structure, space group P�4421c (Z0 = 1), in which the molecules are arranged in a hydrogen-bonded tetrameric ring motif. The structures of phases III0 and III are monoclinic, space groups P21/c (Z0 = 3) and Pc (Z0 = 2), respectively, and are characterized by the formation of hydrogen-bonded molecular chains with a threefold-helical and wave-like nature, respectively. Phase III crystallizes at 195 K from a sample of phase I that is supercooled to ca 100 K. Alternatively, phase III may be grown via phase III0, the latter transforming from supercooled phase I at ca 200 K. Phase III0 is particularly unstable and is metastable with respect to both I and II. Its growth is realised only under very restricted conditions, thus making its characterization especially challenging. The cyclohexanol molecules adopt a chair conformation in all three phases with the hydroxyl groups in an equatorial orientation. No evidence was found indicating hydroxyl groups adopting an axial orientation, contrary to the majority of spectroscopic literature on solid-state cyclohexanol; however, the H atom of the equatorial OH groups is found to adopt both in-plane and out-of-plane orientations

Electric-field tuning of the valley splitting in silicon corner dots

We perform an excited state spectroscopy analysis of a silicon corner dot in a nanowire field-effect transistor to assess the electric field tunability of the valley splitting. First, we demonstrate a back-gate-controlled transition between a single quantum dot and a double quantum dot in parallel that allows tuning the device in to corner dot formation. We find a linear dependence of the valley splitting on back-gate voltage, from $880~\mu \text{eV}$ to $610~\mu \text{eV}$ with a slope of $-45\pm 3~\mu \text{eV/V}$ (or equivalently a slope of $-48\pm 3~\mu \text{eV/(MV/m)}$ with respect to the effective field). The experimental results are backed up by tight-binding simulations that include the effect of surface roughness, remote charges in the gate stack and discrete dopants in the channel. Our results demonstrate a way to electrically tune the valley splitting in silicon-on-insulator-based quantum dots, a requirement to achieve all-electrical manipulation of silicon spin qubits.Comment: 5 pages, 3 figures. In this version: Discussion of model expanded; Fig. 3 updated; Refs. added (15, 22, 32, 34, 35, 36, 37

Reducing the burden of hypoglycaemia in people with diabetes through increased understanding:design of the Hypoglycaemia Redefining Solutions for Better Lives (Hypo-RESOLVE) project

Background Hypoglycaemia is the most frequent complication of treatment with insulin or insulin secretagogues in people with diabetes. Severe hypoglycaemia, i.e. an event requiring external help because of cognitive dysfunction, is associated with a higher risk of adverse cardiovascular outcomes and all‐cause mortality, but underlying mechanism(s) are poorly understood. There is also a gap in the understanding of the clinical, psychological and health economic impact of ‘non‐severe’ hypoglycaemia and the glucose level below which hypoglycaemia causes harm. Aim To increase understanding of hypoglycaemia by addressing the above issues over a 4‐year period. Methods Hypo‐RESOLVE is structured across eight work packages, each with a distinct focus. We will construct a large, sustainable database including hypoglycaemia data from >100 clinical trials to examine predictors of hypoglycaemia and establish glucose threshold(s) below which hypoglycaemia constitutes a risk for adverse biomedical and psychological outcomes, and increases healthcare costs. We will also investigate the mechanism(s) underlying the antecedents and consequences of hypoglycaemia, the significance of glucose sensor‐detected hypoglycaemia, the impact of hypoglycaemia in families, and the costs of hypoglycaemia for healthcare systems. Results The outcomes of Hypo‐RESOLVE will inform evidence‐based definitions regarding the classification of hypoglycaemia in diabetes for use in daily clinical practice, future clinical trials and as a benchmark for comparing glucose‐lowering interventions and strategies across trials. Stakeholders will be engaged to achieve broadly adopted agreement. Conclusion Hypo‐RESOLVE will advance our understanding and refine the classification of hypoglycaemia, with the ultimate aim being to alleviate the burden and consequences of hypoglycaemia in people with diabetes

Oxidative phosphorylation flexibility in the liver of mice resistant to high-fat diet-induced hepatic steatosis.

OBJECTIVE To identify metabolic pathways that may underlie susceptibility or resistance to high-fat diet-induced hepatic steatosis. RESEARCH DESIGN AND METHODS We performed comparative transcriptomic analysis of the livers of A/J and C57Bl/6 mice, which are, respectively, resistant and susceptible to high-fat diet-induced hepatosteatosis and obesity. Mice from both strains were fed a normal chow or a high-fat diet for 2, 10, and 30 days, and transcriptomic data were analyzed by time-dependent gene set enrichment analysis. Biochemical analysis of mitochondrial respiration was performed to confirm the transcriptomic analysis. RESULTS Time-dependent gene set enrichment analysis revealed a rapid, transient, and coordinate upregulation of 13 oxidative phosphorylation genes after initiation of high-fat diet feeding in the A/J, but not in the C57Bl/6, mouse livers. Biochemical analysis using liver mitochondria from both strains of mice confirmed a rapid increase by high-fat diet feeding of the respiration rate in A/J but not C57Bl/6 mice. Importantly, ATP production was the same in both types of mitochondria, indicating increased uncoupling of the A/J mitochondria. CONCLUSIONS Together with previous data showing increased expression of mitochondrial β-oxidation genes in C57Bl/6 but not A/J mouse livers, our present study suggests that an important aspect of the adaptation of livers to high-fat diet feeding is to increase the activity of the oxidative phosphorylation chain and its uncoupling to dissipate the excess of incoming metabolic energy and to reduce the production of reactive oxygen species. The flexibility in oxidative phosphorylation activity may thus participate in the protection of A/J mouse livers against the initial damages induced by high-fat diet feeding that may lead to hepatosteatosis

Gluco-incretins regulate beta-cell glucose competence by epigenetic silencing of Fxyd3 expression.

BACKGROUND/AIMS: Gluco-incretin hormones increase the glucose competence of pancreatic beta-cells by incompletely characterized mechanisms. METHODS: We searched for genes that were differentially expressed in islets from control and Glp1r-/-; Gipr-/- (dKO) mice, which show reduced glucose competence. Overexpression and knockdown studies; insulin secretion analysis; analysis of gene expression in islets from control and diabetic mice and humans as well as gene methylation and transcriptional analysis were performed. RESULTS: Fxyd3 was the most up-regulated gene in glucose incompetent islets from dKO mice. When overexpressed in beta-cells Fxyd3 reduced glucose-induced insulin secretion by acting downstream of plasma membrane depolarization and Ca++ influx. Fxyd3 expression was not acutely regulated by cAMP raising agents in either control or dKO adult islets. Instead, expression of Fxyd3 was controlled by methylation of CpGs present in its proximal promoter region. Increased promoter methylation reduced Fxyd3 transcription as assessed by lower abundance of H3K4me3 at the transcriptional start site and in transcription reporter assays. This epigenetic imprinting was initiated perinatally and fully established in adult islets. Glucose incompetent islets from diabetic mice and humans showed increased expression of Fxyd3 and reduced promoter methylation. CONCLUSIONS/INTERPRETATION: Because gluco-incretin secretion depends on feeding the epigenetic regulation of Fxyd3 expression may link nutrition in early life to establishment of adult beta-cell glucose competence; this epigenetic control is, however, lost in diabetes possibly as a result of gluco-incretin resistance and/or de-differentiation of beta-cells that are associated with the development of type 2 diabetes

Low-temperature tunable radio-frequency resonator for sensitive dispersive readout of nanoelectronic devices

We present a sensitive, tunable radio-frequency resonator designed to detect reactive changes in nanoelectronic devices down to dilution refrigerator temperatures. The resonator incorporates GaAs varicap diodes to allow electrical tuning of the resonant frequency and the coupling to the input line. We find a resonant frequency tuning range of 8.4 MHz at 55 mK that increases to 29 MHz at 1.5 K. To assess the impact on performance of different tuning conditions, we connect a quantum dot in a silicon nanowire field-effect transistor to the resonator, and measure changes in the device capacitance caused by cyclic electron tunneling. At 250 mK, we obtain an equivalent charge sensitivity of $43~\mu e / \sqrt{\text{Hz}}$ when the resonator and the line are impedance-matched and show that this sensitivity can be further improved to $31~\mu e / \sqrt{\text{Hz}}$ by re-tuning the resonator. We understand this improvement by using an equivalent circuit model and demonstrate that for maximum sensitivity to capacitance changes, in addition to impedance matching, a high-quality resonator with low parasitic capacitance is desired.Comment: Includes supplementary informatio

Large dispersive interaction between a CMOS double quantum dot and microwave photons

We report a large coupling rate, $g_0/(2\pi)=183$ MHz, between the charge state of a double quantum dot in a CMOS split-gate silicon nanowire transistor and microwave photons in a lumped-element resonator formed by hybrid integration with a superconducting inductor. We enhance the coupling by exploiting the large interdot lever arm of an asymmetric split-gate device, $\alpha=0.72$, and by inductively coupling to the resonator to increase its impedance, $Z_\text{r}=560$ $\Omega$. In the dispersive regime, the large coupling strength at the DQD hybridisation point produces a frequency shift comparable to the resonator linewidth, the optimal setting for maximum state visibility. We exploit this regime to demonstrate rapid gate-based readout of the charge degree of freedom, with an SNR of 3.3 in 50 ns. In the resonant regime, the fast charge decoherence rate precludes reaching the strong coupling regime, but we show a clear route to spin-photon circuit quantum electrodynamics using hybrid CMOS systems.Comment: 9 pages, 7 figure