De Novo Truncating Mutations in WASF1 Cause Intellectual Disability with Seizures.

Next-generation sequencing has been invaluable in the elucidation of the genetic etiology of many subtypes of intellectual disability in recent years. Here, using exome sequencing and whole-genome sequencing, we identified three de novo truncating mutations in WAS protein family member 1 (WASF1) in five unrelated individuals with moderate to profound intellectual disability with autistic features and seizures. WASF1, also known as WAVE1, is part of the WAVE complex and acts as a mediator between Rac-GTPase and actin to induce actin polymerization. The three mutations connected by Matchmaker Exchange were c.1516C>T (p.Arg506Ter), which occurs in three unrelated individuals, c.1558C>T (p.Gln520Ter), and c.1482delinsGCCAGG (p.Ile494MetfsTer23). All three variants are predicted to partially or fully disrupt the C-terminal actin-binding WCA domain. Functional studies using fibroblast cells from two affected individuals with the c.1516C>T mutation showed a truncated WASF1 and a defect in actin remodeling. This study provides evidence that de novo heterozygous mutations in WASF1 cause a rare form of intellectual disability

Tackling Africa's digital divide

Innovations in ‘sustainable’ photonics technologies such as free-space optical links and solar-powered equipment provide developing countries with new cost-effective opportunities for deploying future-proof telecommunication networks

Cardiac output in idiopathic normal pressure hydrocephalus: association with arterial blood pressure and intracranial pressure wave amplitudes and outcome of shunt surgery

<p>Abstract</p> <p>Background</p> <p>In patients with idiopathic normal pressure hydrocephalus (iNPH) responding to shunt surgery, we have consistently found elevated intracranial pressure (ICP) wave amplitudes during diagnostic ICP monitoring prior to surgery. It remains unknown why ICP wave amplitudes are increased in these patients. Since iNPH is accompanied by a high incidence of vascular co-morbidity, a possible explanation is that there is reduced vascular compliance accompanied by elevated arterial blood pressure (ABP) wave amplitudes and even altered cardiac output (CO). To investigate this possibility, the present study was undertaken to continuously monitor CO to determine if it is correlated to ABP and ICP wave amplitudes and the outcome of shunting in iNPH patients. It was specifically addressed whether the increased ICP wave amplitudes seen in iNPH shunt responders were accompanied by elevated CO and/or ABP wave amplitude levels.</p> <p>Methods</p> <p>Prospective iNPH patients (29) were clinically graded using an NPH grading scale. Continuous overnight minimally-invasive monitoring of CO and ABP was done simultaneously with ICP monitoring; the CO, ABP, and ICP parameters were parsed into 6-second time windows. Patients were assessed for shunt surgery on clinical grade, Evan's index, and ICP wave amplitude. Follow-up clinical grading was performed 12 months after surgery.</p> <p>Results</p> <p>ICP wave amplitudes but not CO or ABP wave amplitude, showed good correlation with the response to shunt treatment. The patients with high ICP wave amplitude did not have accompanying high levels of CO or ABP wave amplitude. Correlation analysis between CO and ICP wave amplitudes in individual patients showed different profiles [significantly positive in 10 (35%) and significantly negative in 16 (55%) of 29 recordings]. This depended on whether there was also a correlation between ABP and ICP wave amplitudes and on the average level of ICP wave amplitude.</p> <p>Conclusions</p> <p>These results gave no evidence that the increased levels of ICP wave amplitudes seen in iNPH shunt responders prior to surgery were accompanied by elevated levels of ABP wave amplitudes or elevated CO. In the individual patients the correlation between CO and ICP wave amplitude was partly related to an association between ABP and ICP wave amplitudes which can be indicative of the state of cerebrovascular pressure regulation, and partly related to the ICP wave amplitude which can be indicative of the intracranial compliance.</p

Measurement of inclusive very forward jet cross sections in proton-lead collisions at \sqrt{sNN} = 5:02 TeV

Measurements of differential cross sections for inclusive very forward jet production in proton-lead collisions as a function of jet energy are presented. The data were collected with the CMS experiment at the LHC in the laboratory pseudorapidity range −6.6 < η < −5.2. Asymmetric beam energies of 4 TeV for protons and 1.58 TeV per nucleon for Pb nuclei were used, corresponding to a center-of-mass energy per nucleon pair of \sqrt{sNN} = 5:02 TeV. Collisions with either the proton (p+Pb) or the ion (Pb+p) traveling towards the negative η hemisphere are studied. The jet cross sections are unfolded to stable-particle level cross sections with p_{T} ≳ 3 GeV, and compared to predictions from various Monte Carlo event generators. In addition, the cross section ratio of p+Pb and Pb+p data is presented. The results are discussed in terms of the saturation of gluon densities at low fractional parton momenta. None of the models under consideration describes all the data over the full jet-energy range and for all beam configurations. Discrepancies between the differential cross sections in data and model predictions of more than two orders of magnitude are observed

A Deep Neural Network for Simultaneous Estimation of b Jet Energy and Resolution

We describe a method to obtain point and dispersion estimates for the energies of jets arising from b quarks produced in proton-proton collisions at an energy of s = 13 TeV at the CERN LHC. The algorithm is trained on a large sample of simulated b jets and validated on data recorded by the CMS detector in 2017 corresponding to an integrated luminosity of 41 fb - 1 . A multivariate regression algorithm based on a deep feed-forward neural network employs jet composition and shape information, and the properties of reconstructed secondary vertices associated with the jet. The results of the algorithm are used to improve the sensitivity of analyses that make use of b jets in the final state, such as the observation of Higgs boson decay to b b ¯

Evidence for Top Quark Production in Nucleus-Nucleus Collisions

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Search for an exotic decay of the Higgs boson to a pair of light pseudoscalars in the final state with two bquarks and two tau leptons in proton-proton collisions at root s=13 TeV The CMS Collaboration

A search for an exotic decay of the Higgs boson to a pair of light pseudoscalar bosons is performed for the first time in the final state with two b quarks and two tau leptons. The search is motivated in the context of models of physics beyond the standard model (SM), such as two Higgs doublet models extended with a complex scalar singlet (2HDM + S), which include the next-to-minimal supersymmetric SM (NMSSM). The results are based on a data set of proton-proton collisions corresponding to an integrated luminosity of 35.9 fb(-1), accumulated by the CMS experiment at the LHC in 2016 at a center-of-mass energy of 13 TeV. Masses of the pseudoscalar boson between 15 and 60 GeVare probed, and no excess of events above the SM expectation is observed. Upper limits between 3 and 12% are set on the branching fraction B(h -> aa -> 2 tau 2b) assuming the SM production of the Higgs boson. Upper limits are also set on the branching fraction of the Higgs boson to two light pseudoscalar bosons in different 2HDM + S scenarios. Assuming the SM production cross section for the Higgs boson, the upper limit on this quantity is as low as 20% for a mass of the pseudoscalar of 40 GeV in the NMSSM. (C) 2018 The Author(s). Published by Elsevier B.V.Peer reviewe