The Color-Magnitude Effect in Early-Type Cluster Galaxies

We present the analysis of the color-magnitude relation (CMR) for a sample of 57 X-ray detected Abell clusters within the redshift interval 0.02 <= z <= 0.18. We use the B-R vs R color-magnitude plane to establish that the CMR is present in all our low-redshift clusters and can be parameterized by a single straight line.We find that the CMRs for this large cluster sample of different richness and cluster types are consistent with having universal properties. The k-corrected color of the individual CMRs in the sample at a fixed absolute magnitude have a small intrinsic dispersion of ~0.05 mag. The slope of the CMR is consistent with being the same for all clusters, with the variations entirely accountable by filter band shifting effects. We determine the mean of the dispersion of the 57 CMRs to be 0.074 mag, with a small rms scatter of 0.026 mag. However, a modest amount of the dispersion arises from photometric measurement errors and possible background cluster superpositions; and the derived mean dispersion is an upper limit. Models which explain the CMR in terms of metallicity and passive evolution can naturally reproduce the observed behavior of the CMR in this paper. The observed properties of the CMR are consistent with models in which the last episode of significant star formation in cluster early-type galaxies occurred significantly more than ~3 Gyr ago, and that the core set of early-type galaxies in clusters were formed more than 7 Gyr ago. (abridged)Comment: Accepted ApJ, 17 pages, 4 figures (high-res fig 1 available in ApJ version

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year

The contribution of X-linked coding variation to severe developmental disorders

Abstract: Over 130 X-linked genes have been robustly associated with developmental disorders, and X-linked causes have been hypothesised to underlie the higher developmental disorder rates in males. Here, we evaluate the burden of X-linked coding variation in 11,044 developmental disorder patients, and find a similar rate of X-linked causes in males and females (6.0% and 6.9%, respectively), indicating that such variants do not account for the 1.4-fold male bias. We develop an improved strategy to detect X-linked developmental disorders and identify 23 significant genes, all of which were previously known, consistent with our inference that the vast majority of the X-linked burden is in known developmental disorder-associated genes. Importantly, we estimate that, in male probands, only 13% of inherited rare missense variants in known developmental disorder-associated genes are likely to be pathogenic. Our results demonstrate that statistical analysis of large datasets can refine our understanding of modes of inheritance for individual X-linked disorders

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

A detailed chemical kinetic modeling, ignition delay time and jet-stirred reactor study of methanol oxidation

A shock tube (ST) and a rapid compression machine (RCM) have been used to measure new ignition delay times for methanol oxidation over a wide range of pressures (2-50 atm) and equivalence ratios (0.5, 1.0, and 2.0). These measurements include dilute and fuel/'air' conditions (1.5-21.9% methanol), over a temperature range of 820-1650 K. The new data has been compared to previously published studies and provides insight into internal combustion engine relevant conditions which are previously un-studied at pressures of 10, 30, 40 and 50 atm. In addition to these ignition delay times, species concentrations have also been measured using a jet-stirred reactor (JSR). In these experiments methanol concentrations of 2000 and 4000 ppm were used at equivalence ratios of 0.2-2.0, at pressures of 1-20 atm, and in the temperature range of 800-1200 K with residence times varying from 0.05-2.00 s. The newly measured experimental data was used to develop a new detailed chemical kinetic model (Mech15.34). This model was also validated using available literature data. The new model is capable of predicting all of the validation data with reasonable accuracy, with some discrepancy in predicting formaldehyde in the JSR data. All of this, results in a robustly validated and accurate, new detailed chemical kinetic model. (C) 2015 The Combustion Institute. Published by Elsevier Inc. All rights reserved.Ultan Burke and Alexander Heufer would like to acknowledge the financial support from the Irish Research Council (IRC). Wayne Metcalfe and Sinead Burke would like to acknowledge the financial support of Saudi Aramco.peer-reviewed2018-01-2

The pyrolysis of 2-methylfuran: a quantum chemical, statistical rate theory and kinetic modelling study

Due to the rapidly growing interest in the use of biomass derived furanic compounds as potential platform chemicals and fossil fuel replacements, there is a simultaneous need to understand the pyrolysis and combustion properties of such molecules. To this end, the potential energy surfaces for the pyrolysis relevant reactions of the biofuel candidate 2-methylfuran have been characterized using quantum chemical methods (CBS-QB3, CBS-APNO and G3). Canonical transition state theory is employed to determine the high-pressure limiting kinetics, k(T), of elementary reactions. Rice-Ramsperger-Kassel-Marcus theory with an energy grained master equation is used to compute pressure-dependent rate constants, k(T, p), and product branching fractions for the multiple-well, multiple-channel reaction pathways which typify the pyrolysis reactions of the title species. The unimolecular decomposition of 2-methylfuran is shown to proceed via hydrogen atom transfer reactions through singlet carbene intermediates which readily undergo ring opening to form collisionally stabilised acyclic C5H6O isomers before further decomposition to C-1-C-4 species. Rate constants for abstraction by the hydrogen atom and methyl radical are reported, with abstraction from the alkyl side chain calculated to dominate. The fate of the primary abstraction product, 2-furanylmethyl radical, is shown to be thermal decomposition to the n-butadienyl radical and carbon monoxide through a series of ring opening and hydrogen atom transfer reactions. The dominant bimolecular products of hydrogen atom addition reactions are found to be furan and methyl radical, 1-butene-1-yl radical and carbon monoxide and vinyl ketene and methyl radical. A kinetic mechanism is assembled with computer simulations in good agreement with shock tube speciation profiles taken from the literature. The kinetic mechanism developed herein can be used in future chemical kinetic modelling studies on the pyrolysis and oxidation of 2-methylfuran, or the larger molecular structures for which it is a known pyrolysis/combustion intermediate (e.g. cellulose, coals, 2,5-dimethylfuran).We would like to acknowledge the support of Science Foundation Ireland under grant number [08/IN1./I2055] as part of their Principal Investigator Awards

Autoignition of ethanol in a rapid compression machine

Ethanol is a renewable source of energy and significant attention has been directed to the development of a validated chemical kinetic mechanism for this fuel. The experimental data for the autoignition of ethanol in the low temperature range at elevated pressures are meager. In order to provide experimental data sets for mechanism validation at such conditions, the autoignition of homogeneous ethanol/oxidizer mixtures has been investigated in a rapid compression machine. Experiments cover a range of pressures (10-50 bar), temperatures (825-985 K) and equivalence ratios of 0.3-1.0. Ignition delay data are deduced from the experimental pressure traces. Under current experimental conditions of elevated pressures and low temperatures, chemistry pertaining to hydroperoxyl radicals assumes importance. A chemical kinetic mechanism that can accurately predict the autoignition characteristics of ethanol at low temperatures and elevated pressures has been developed and this mechanism is compared with other models available in the literature. (C) 2013 The Combustion Institute. Published by Elsevier Inc. All rights reserved