Thermal Frontal Polymerization with a Thermally Released Redox Catalyst

We studied thermal frontal polymerization using a redox systemin an attempt to lower the temperature of the frontally polymerizable system while increasing the front velocity so as to obtain a self-sustaining front in a thinner layer than without the redox components. A cobalt-containing polymer with a melting point of 63 C (Intelimer 6050X11) and cumene hydroperoxide were used with a triacrylate. The use of the Intelimer decreased the front velocity but allowed fronts to propagate in thinner layers and withmore filler while still having a pot life of days. Nonplanar modes of propagation occurred. Fronts propagated faster when 6-O-palmitoyl-L-ascorbic acid was used as a reductant. Interestingly, fronts were also faster with the reductant even without the Intelimer if kaolin clay was the filler; however, the pot life was significantly reduce

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

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

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∼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 × 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

Steroid receptor coactivator-1 modulates the function of Pomc neurons and energy homeostasis

Hypothalamic neurons expressing the anorectic peptide Pro-opiomelanocortin (Pomc) regulate food intake and body weight. Here, we show that Steroid Receptor Coactivator-1 (SRC-1) interacts with a target of leptin receptor activation, phosphorylated STAT3, to potentiate Pomc transcription. Deletion of SRC-1 in Pomc neurons in mice attenuates their depolarization by leptin, decreases Pomc expression and increases food intake leading to high-fat diet-induced obesity. In humans, fifteen rare heterozygous variants in SRC-1 found in severely obese individuals impair leptin-mediated Pomc reporter activity in cells, whilst four variants found in non-obese controls do not. In a knock-in mouse model of a loss of function human variant (SRC-1L1376P), leptin-induced depolarization of Pomc neurons and Pomc expression are significantly reduced, and food intake and body weight are increased. In summary, we demonstrate that SRC-1 modulates the function of hypothalamic Pomc neurons, and suggest that targeting SRC-1 may represent a useful therapeutic strategy for weight loss.Peer reviewe

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

Low-frequency variation in TP53 has large effects on head circumference and intracranial volume.

Cranial growth and development is a complex process which affects the closely related traits of head circumference (HC) and intracranial volume (ICV). The underlying genetic influences shaping these traits during the transition from childhood to adulthood are little understood, but might include both age-specific genetic factors and low-frequency genetic variation. Here, we model the developmental genetic architecture of HC, showing this is genetically stable and correlated with genetic determinants of ICV. Investigating up to 46,000 children and adults of European descent, we identify association with final HC and/or final ICV + HC at 9 novel common and low-frequency loci, illustrating that genetic variation from a wide allele frequency spectrum contributes to cranial growth. The largest effects are reported for low-frequency variants within TP53, with 0.5 cm wider heads in increaser-allele carriers versus non-carriers during mid-childhood, suggesting a previously unrecognized role of TP53 transcripts in human cranial development

The UK10K project identifies rare variants in health and disease

M. Kivimäki työryhmäjäsen.The contribution of rare and low-frequency variants to human traits is largely unexplored. Here we describe insights from sequencing whole genomes (low read depth, 7x) or exomes (high read depth, 80x) of nearly 10,000 individuals from population-based and disease collections. In extensively phenotyped cohorts we characterize over 24 million novel sequence variants, generate a highly accurate imputation reference panel and identify novel alleles associated with levels of triglycerides (APOB), adiponectin (ADIPOQ) and low-density lipoprotein cholesterol (LDLR and RGAG1) from single-marker and rare variant aggregation tests. We describe population structure and functional annotation of rare and low-frequency variants, use the data to estimate the benefits of sequencing for association studies, and summarize lessons from disease-specific collections. Finally, we make available an extensive resource, including individual-level genetic and phenotypic data and web-based tools to facilitate the exploration of association results.Peer reviewe

Plasma Wave Measurements from the Van Allen Probes

The twin Van Allen Probes spacecraft were launched on August 30, 2012 to study the Earth\u27s Van Allen radiation belts. The Electric and Magnetic Field Instrument Suite and Integrated Science (EMFISIS) investigation includes a plasma wave instrument (Waves) that simultaneously measures three orthogonal components of the wave magnetic field from ~10 Hz to 12 kHz and, with the support of the Electric Fields and Waves (EFW) instrument sensors, three components of the wave electric field from ~10 Hz to 12 kHz and a single electric component up to ~400 kHz. Since launch, a variety of plasma waves have been detected which are believed to play a role in the dynamics of the radiation belts, including whistler-mode chorus, plasmaspheric hiss, and magnetosonic equatorial noise. Lightning produced whistlers, electron cyclotron harmonic (ECH) emission, and the upper hybrid resonance (UHR) are also often detected. The UHR is used to determine the local electron plasma density (an important parameter of the plasma required for various modeling and simulation studies). Measuring all six components simultaneously allow the wave propagation parameters of these plasma wave emissions, including the Poynting flux, wave normal vector, and polarization, to be obtained. The Waves instrument is able to determine these parameters with both onboard and ground processing at very high time and frequency resolutions. We will summarize the EMFISIS plasma wave observations and discuss their role in the Van Allen Radiation Belt dynamics