Sol–gel preparation of low oxygen content, high surface area silicon nitride and imidonitride materials

Reactions of Si(NHMe)4 with ammonia are effectively catalysed by small ammonium triflate concentrations, and can be used to produce free-standing silicon imide gels. Firing at various temperatures produces amorphous or partially crystallised silicon imidonitride/nitride samples with high surface areas and low oxygen contents. The crystalline phase is entirely ?-Si3N4 and structural similarities are observed between the amorphous and crystallised materials

Sol–gel preparation of low oxygen content, high surface area silicon nitride and imidonitride materials

Reactions of Si(NHMe)4 with ammonia are effectively catalysed by small ammonium triflate concentrations, and can be used to produce free-standing silicon imide gels. Firing at various temperatures produces amorphous or partially crystallised silicon imidonitride/nitride samples with high surface areas and low oxygen contents. The crystalline phase is entirely α-Si3N4 and structural similarities are observed between the amorphous and crystallised materials

Rare Variant Analysis of Human and Rodent Obesity Genes in Individuals with Severe Childhood Obesity

A. Palotie on työryhmän UK10K Consortium jäsen.Obesity is a genetically heterogeneous disorder. Using targeted and whole-exome sequencing, we studied 32 human and 87 rodent obesity genes in 2,548 severely obese children and 1,117 controls. We identified 52 variants contributing to obesity in 2% of cases including multiple novel variants in GNAS, which were sometimes found with accelerated growth rather than short stature as described previously. Nominally significant associations were found for rare functional variants in BBS1, BBS9, GNAS, MKKS, CLOCK and ANGPTL6. The p.S284X variant in ANGPTL6 drives the association signal (rs201622589, MAF similar to 0.1%, odds ratio = 10.13, p-value = 0.042) and results in complete loss of secretion in cells. Further analysis including additional case-control studies and population controls (N = 260,642) did not support association of this variant with obesity (odds ratio = 2.34, p-value = 2.59 x 10(-3)), highlighting the challenges of testing rare variant associations and the need for very large sample sizes. Further validation in cohorts with severe obesity and engineering the variants in model organisms will be needed to explore whether human variants in ANGPTL6 and other genes that lead to obesity when deleted in mice, do contribute to obesity. Such studies may yield druggable targets for weight loss therapies.Peer reviewe

The dipolar endofullerene HF@C60

The cavity inside fullerenes provides a unique environment for the study of isolated atoms and molecules. We report encapsulation of hydrogen fluoride inside C60 using molecular surgery to give the endohedral fullerene HF@C60. The key synthetic step is the closure of the open fullerene cage while minimizing escape of HF. The encapsulated HF molecule moves freely inside the cage and exhibits quantization of its translational and rotational degrees of freedom, as revealed by inelastic neutron scattering and infrared spectroscopy. The rotational and vibrational constants of the encapsulated HF molecules were found to be redshifted relative to free HF. The NMR spectra display a large 1H-19F J coupling typical of an isolated species. The dipole moment of HF@C60 was estimated from the temperature-dependence of the dielectric constant at cryogenic temperatures and showed that the cage shields around 75% of the HF dipole

Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel

Imputing genotypes from reference panels created by whole-genome sequencing (WGS) provides a cost-effective strategy for augmenting the single-nucleotide polymorphism (SNP) content of genome-wide arrays. The UK10K Cohorts project has generated a data set of 3,781 whole genomes sequenced at low depth (average 7x), aiming to exhaustively characterize genetic variation down to 0.1% minor allele frequency in the British population. Here we demonstrate the value of this resource for improving imputation accuracy at rare and low-frequency variants in both a UK and an Italian population. We show that large increases in imputation accuracy can be achieved by re-phasing WGS reference panels after initial genotype calling. We also present a method for combining WGS panels to improve variant coverage and downstream imputation accuracy, which we illustrate by integrating 7,562 WGS haplotypes from the UK10K project with 2,184 haplotypes from the 1000 Genomes Project. Finally, we introduce a novel approximation that maintains speed without sacrificing imputation accuracy for rare variants

Recull de propostes per minimitzar l'impacte negatiu de gènere del sistema de teletreball a l'Ajuntament de Barcelona

Finançat amb el projecte "Impacto de GÉnero del TEletrabajo y rutinas de COnfinamiento: más allá de lo obvio" (Ref. SUPERACOVID19_2.2.IGETECO) i a través de l'Ajuntament de Barcelona pel Servei d'Estudi sobre propostes per minimitzar l'impacte negatiu de gènere del sistema de teletreball a l'Ajuntament de Barcelona (exp.20002682)El present document recull les propostes d'actuació contingues a l'estudi Propostes per minimitzar l'impacte negatiu de gènere del sistema de teletreball a l'Ajuntament de Barcelona realitzat pel Centre d'Estudis Sociològics sobre la Vida Quotidiana i el Treball (QUIT) de la Universitat Autònoma de Barcelona. L'emergència sanitària provocada per la Covid19 i el necessari confinament de la població per combatre la pandèmia ha significat, des del punt de vista de l'organització del treball, un canvi molt important cap a l'impuls de formes de treball a distància. Però aquest impuls del teletreball ha estat una resposta fruit de l'emergència, lògica davant la situació viscuda i, com a tal, no ha pogut ser planificada amb el temps i els mitjans necessaris

Whole-genome sequence-based analysis of thyroid function

Tiina Paunio on työryhmän UK10K Consortium jäsen.Normal thyroid function is essential for health, but its genetic architecture remains poorly understood. Here, for the heritable thyroid traits thyrotropin (TSH) and free thyroxine (FT4), we analyse whole-genome sequence data from the UK10K project (N = 2,287). Using additional whole-genome sequence and deeply imputed data sets, we report meta-analysis results for common variants (MAF >= 1%) associated with TSH and FT4 (N = 16,335). For TSH, we identify a novel variant in SYN2 (MAF = 23.5%, P = 6.15 x 10(-9)) and a new independent variant in PDE8B (MAF = 10.4%, P = 5.94 x 10(-14)). For FT4, we report a low-frequency variant near B4GALT6/ SLC25A52 (MAF = 3.2%, P = 1.27 x 10(-9)) tagging a rare TTR variant (MAF = 0.4%, P = 2.14 x 10(-11)). All common variants explain >= 20% of the variance in TSH and FT4. Analysis of rare variants (MAFPeer reviewe

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)

Nuclear magnetic resonance of novel type-II superconductors.

Nuclear magnetic resonance was crucial in the vindication of the theory of superconductivity in 1957, it still continues to provide vital information today in the ongoing challenge that is the determination of the mechanism for type-II superconductors.This forms the basis of this piece of work, which details the preparation, characterisation and cryogenic measurements of two new superconductors based on the cage like fullerides. In light of recent synthetic developments it has now become possible to encapsulate small molecules inside the fullerene cage, which may then be doped with alkali metals to form the superconducting materials. In this thesis the encapsulated molecules are water and hydrogen, and the topic is the study of normal and superconducting states from their response to the magnetic resonance technique.The materials are made using a vapour doping method, and their characterisation suggests high purity, with the superconducting transition temperatures modestly affected by the larger water molecule. The spectral lineshape suggests a unique window into the vortices in the superconducting state from both endohedral molecules, and the magnetic shift decays concomitant with s-wave symmetry of superconducting gap. The nuclear spin lattice relaxation rate is vastly different between molecules, highlighting the unique information available from these new probes.Magnesium diboride is also studied using a sample enriched with carbon-13, which allows a new window into this multiple-band superconductor. Measurements of the lineshape reveal the role of carbon as a flux pinning centre, and combined with Knight shift measurements suggest the doping procedure favours the chemical substitution scenario. Also ab-initio calculations yield results which match this scenario and agree well with experimental values