Tailoring transient-amorphous states: towards fast and power-efficient phase-change memory and neuromorphic computing.

A new methodology for manipulating transient-amorphous states of phase-change memory (PCM) materials is reported as a viable means to boost the speed, yet reduce the power consumption of PC memories, and is applicable to new forms of PCM-based neuromorphic devices. Controlling multiple-pulse interactions with PC materials may provide an opportunity toward developing a new paradigm for ultra-fast neuromorphic computing.We acknowledge financial support from the Engineering and Physical Sciences Research Council (UK).This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/adma.20140269

Protective efficacy of commercial inactivated Newcastle disease virus vaccines in chickens against a recent Korean epizootic strain

Despite the intensive vaccination policy that has been put in place to control Newcastle disease virus (NDV), the recent emergence of NDV genotype VII strains in Korea has led to significant economic losses in the poultry industry. We assessed the ability of inactivated, oil-emulsion vaccines derived from La Sota or Ulster 2C NDV strains to protect chickens from challenge with Kr-005/00, which is a recently isolated Korean epizootic genotype VII strain. Six-week-old SPF chickens were vaccinated once and challenged three weeks later via the eye drop/intranasal route. All vaccinated birds were fully protected from disease, regardless of the vaccine strains used. All vaccinated and challenged groups showed significant sero-conversion 14 days after challenge. However, some vaccinated birds, despite being protected from disease, shed the challenge virus from their oro-pharynx and cloaca, albeit at significantly lower titers than the unvaccinated challenged control birds. The virological, serological, and epidemiological significance of our observations with regard to NDV disease eradication is discussed

Placental DNA methylation signatures of maternal smoking during pregnancy and potential impacts on fetal growth

Maternal smoking during pregnancy (MSDP) contributes to poor birth outcomes, in part through disrupted placental functions, which may be reflected in the placental epigenome. Here we present a meta-analysis of the associations between MSDP and placental DNA methylation (DNAm) and between DNAm and birth outcomes within the Pregnancy And Childhood Epigenetics (PACE) consortium (N = 1700, 344 with MSDP). We identify 443 CpGs that are associated with MSDP, of which 142 associated with birth outcomes, 40 associated with gene expression, and 13 CpGs are associated with all three. Only two CpGs have consistent associations from a prior meta-analysis of cord blood DNAm, demonstrating substantial tissue-specific responses to MSDP. The placental MSDP-associated CpGs are enriched for environmental response genes, growth-factor signaling, and inflammation, which play important roles in placental function. We demonstrate links between placental DNAm, MSDP and poor birth outcomes, which may better inform the mechanisms through which MSDP impacts placental function and fetal growth

Aging Studies for the Large Honeycomb Drift Tube System of the Outer Tracker of HERA-B

The HERA-B Outer Tracker consists of drift tubes folded from polycarbonate foil and is operated with Ar/CF4/CO2 as drift gas. The detector has to stand radiation levels which are similar to LHC conditions. The first prototypes exposed to radiation in HERA-B suffered severe radiation damage due to the development of self-sustaining currents (Malter effect). In a subsequent extended R&D program major changes to the original concept for the drift tubes (surface conductivity, drift gas, production materials) have been developed and validated for use in harsh radiation environments. In the test program various aging effects (like Malter currents, gain loss due to anode aging and etching of the anode gold surface) have been observed and cures by tuning of operation parameters have been developed.Comment: 14 pages, 6 figures, to be published in the Proceedings of the International Workshop On Aging Phenomena In Gaseous Detectors, 2-5 Oct 2001, Hamburg, German

The Outer Tracker Detector of the HERA-B Experiment. Part II: Front-End Electronics

The HERA-B Outer Tracker is a large detector with 112674 drift chamber channels. It is exposed to a particle flux of up to 2x10^5/cm^2/s thus coping with conditions similar to those expected for the LHC experiments. The front-end readout system, based on the ASD-8 chip and a customized TDC chip, is designed to fulfil the requirements on low noise, high sensitivity, rate tolerance, and high integration density. The TDC system is based on an ASIC which digitizes the time in bins of about 0.5 ns within a total of 256 bins. The chip also comprises a pipeline to store data from 128 events which is required for a deadtime-free trigger and data acquisition system. We report on the development, installation, and commissioning of the front-end electronics, including the grounding and noise suppression schemes, and discuss its performance in the HERA-B experiment

Risk of valvular heart disease associated with use of fenfluramine

BACKGROUND: Estimates of excess risk of valvular heart disease among prior users of fenfluramine and dexfenfluramine have varied widely. Two major forms of bias appear to contribute to this variability and also result in a systematic under-estimation of risk. The first, a form of nondifferential misclassification, is the result of including background, prevalent cases among both exposed and unexposed persons in calculations of risk. The second bias results from not considering the relatively short duration of exposure to drugs. METHODS: We examined data from all available echocardiographic studies reporting the prevalence of aortic regurgitation (AR) and mitral regurgitation (MR) among persons exposed to fenfluramine or dexfenfluramine and a suitable control group. We also included one study in which previously existing AR or MR had been excluded. We corrected for background prevalent cases, estimated incidence rates in unexposed persons, and performed a person-years analysis of apparent incidence rates based on exposure time to provide an unbiased estimate of relative risk. RESULTS: Appearance of new AR was strongly related to duration of exposure (R(2 )= 0.75, p < 0.0001). The summary relative risk for mild or greater AR was 19.6 (95% CI 16.3 – 23.5, p < 0.00001); for moderate or greater MR it was 5.9 (95% CI 4.0 – 8.6, p < 0.00001). CONCLUSION: These findings provide strong support for the view that fenfluramine and dexfenfluramine are potent causal factors in the development of both aortic and mitral valvular heart disease

Inclusive V0V^0 Production Cross Sections from 920 GeV Fixed Target Proton-Nucleus Collisions

Inclusive differential cross sections $d\sigma_{pA}/dx_F$ and $d\sigma_{pA}/dp_t^2$ for the production of \kzeros, \lambdazero, and \antilambda particles are measured at HERA in proton-induced reactions on C, Al, Ti, and W targets. The incident beam energy is 920 GeV, corresponding to $\sqrt {s} = 41.6$ GeV in the proton-nucleon system. The ratios of differential cross sections \rklpa and \rllpa are measured to be $6.2\pm 0.5$ and $0.66\pm 0.07$, respectively, for \xf $\approx-0.06$. No significant dependence upon the target material is observed. Within errors, the slopes of the transverse momentum distributions $d\sigma_{pA}/dp_t^2$ also show no significant dependence upon the target material. The dependence of the extrapolated total cross sections $\sigma_{pA}$ on the atomic mass $A$ of the target material is discussed, and the deduced cross sections per nucleon $\sigma_{pN}$ are compared with results obtained at other energies.Comment: 17 pages, 7 figures, 5 table

Valvular regurgitation and surgery associated with fenfluramine use: an analysis of 5743 individuals

<p>Abstract</p> <p>Background</p> <p>Use of fenfluramines for weight loss has been associated with the development of characteristic plaques on cardiac valves causing regurgitation. However, previously published studies of exposure to fenfluramines have been limited by relatively small sample size, short duration of follow-up, and the lack of any estimate of the frequency of subsequent valvular surgery. We performed an observational study of 5743 users of fenfluramines examined by echocardiography between July 1997 and February 2004 in a single large cardiology clinic.</p> <p>Results</p> <p>The prevalence of at least mild aortic regurgitation (AR) or moderate mitral regurgitation (MR) was 19.6% in women and 11.8% in men (<it>p </it>< 0.0001 for gender difference). Duration of use was strongly predictive of mild or greater AR (<it>p </it>< 0.0001 for trend), MR (<it>p </it>= 0.002), and tricuspid regurgitation (TR) (<it>p </it>< 0.0001), as was earlier scan date (<it>p </it>< 0.0001 for those scanned prior to 1 January 2000 versus later). Increasing age was also independently associated with increased risk of AR and MR (both <it>p </it>< 0.0001). With mean follow-up of 30.3 months, AR worsened in 15.2%, remained the same in 63.1%, and improved in 21.7%. Corresponding values for MR were 24.8%, 47.4% and 27.9%. Pulmonary hypertension was strongly associated with MR but not AR. Valve surgery was performed on 38 patients (0.66% of 5743), 25 (0.44%) with clear evidence of fenfluramine-related etiology.</p> <p>Conclusion</p> <p>Regurgitant valvulopathy was common in individuals exposed to fenfluramines, more frequent in females, and associated with duration of use in all valves assessed. Valve surgery was performed as frequently for aortic as mitral valves and some tricuspid valve surgeries were also performed. The incidence of surgery appeared to be substantially increased compared with limited general population data.</p

The QCD transition temperature: results with physical masses in the continuum limit II.

We extend our previous study [Phys. Lett. B643 (2006) 46] of the cross-over temperatures (T_c) of QCD. We improve our zero temperature analysis by using physical quark masses and finer lattices. In addition to the kaon decay constant used for scale setting we determine four quantities (masses of the \Omega baryon, K^*(892) and \phi(1020) mesons and the pion decay constant) which are found to agree with experiment. This implies that --independently of which of these quantities is used to set the overall scale-- the same results are obtained within a few percent. At finite temperature we use finer lattices down to a <= 0.1 fm (N_t=12 and N_t=16 at one point). Our new results confirm completely our previous findings. We compare the results with those of the 'hotQCD' collaboration.Comment: 19 pages, 8 figures, 3 table

Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a global epidemic that poses a major challenge to health-care systems. Improving metabolic control to approach normal glycaemia (where practical) greatly benefits long-term prognoses and justifies early, effective, sustained and safety-conscious intervention. Improvements in the understanding of the complex pathogenesis of T2DM have underpinned the development of glucose-lowering therapies with complementary mechanisms of action, which have expanded treatment options and facilitated individualized management strategies. Over the past decade, several new classes of glucose-lowering agents have been licensed, including glucagon-like peptide 1 receptor (GLP-1R) agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors and sodium/glucose cotransporter 2 (SGLT2) inhibitors. These agents can be used individually or in combination with well-established treatments such as biguanides, sulfonylureas and thiazolidinediones. Although novel agents have potential advantages including low risk of hypoglycaemia and help with weight control, long-term safety has yet to be established. In this Review, we assess the pharmacokinetics, pharmacodynamics and safety profiles, including cardiovascular safety, of currently available therapies for management of hyperglycaemia in patients with T2DM within the context of disease pathogenesis and natural history. In addition, we briefly describe treatment algorithms for patients with T2DM and lessons from present therapies to inform the development of future therapies