Detection of brown dwarf-like objects in the core of NGC3603

We use near-infrared data obtained with the Wide Field Camera 3 (WFC3) on the Hubble Space Telescope to identify objects having the colors of brown dwarfs (BDs) in the field of the massive galactic cluster NGC 3603. These are identified through use of a combination of narrow and medium band filters spanning the J and H bands, and which are particularly sensitive to the presence of the 1.3-1.5{\mu}m H2O molecular band - unique to BDs. We provide a calibration of the relationship between effective temperature and color for both field stars and for BDs. This photometric method provides effective temperatures for BDs to an accuracy of {\pm}350K relative to spectroscopic techniques. This accuracy is shown to be not significantly affected by either stellar surface gravity or uncertainties in the interstellar extinction. We identify nine objects having effective temperature between 1700 and 2200 K, typical of BDs, observed J-band magnitudes in the range 19.5-21.5, and that are strongly clustered towards the luminous core of NGC 3603. However, if these are located at the distance of the cluster, they are far too luminous to be normal BDs. We argue that it is unlikely that these objects are either artifacts of our dataset, normal field BDs/M-type giants or extra-galactic contaminants and, therefore, might represent a new class of stars having the effective temperatures of BDs but with luminosities of more massive stars. We explore the interesting scenario in which these objects would be normal stars that have recently tidally ingested a Hot Jupiter, the remnants of which are providing a short-lived extended photosphere to the central star. In this case, we would expect them to show the signature of fast rotation.Comment: 26 Pages, 8 Figures, Accepted for publication on Ap

GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment

Imagining union: European cultural identity in the pre-federal future perfect

Water masers are found in dense molecular clouds closely associated with supermassive black holes at the centres of active galaxies. On the basis of the understanding of the local water-maser luminosity function, it was expected that masers at intermediate and high redshifts would be extremely rare. However, galaxies at redshifts z>2 might be quite different from those found locally, not least because of more frequent mergers and interaction events. Here we use gravitational lensing to search for masers at higher redshifts than would otherwise be possible, and find a water maser at redshift 2.64 in the dust- and gas-rich, gravitationally lensed type-1 quasar MGJ0414+0534 (refs 6-13). The isotropic luminosity is 10,000 (, solar luminosity), which is twice that of the most powerful local water maser and half that of the most distant maser previously known. Using the locally determined luminosity function, the probability of finding a maser this luminous associated with any single active galaxy is 10-6. The fact that we see such a maser in the first galaxy we observe must mean that the volume densities and luminosities of masers are higher at redshift 2.64

On-demand manufacturing of clinical-quality biopharmaceuticals

© 2018, Nature Publishing Group. All rights reserved. Conventional manufacturing of protein biopharmaceuticals in centralized, large-scale, single-product facilities is not well-suited to the agile production of drugs for small patient populations or individuals. Previous solutions for small-scale manufacturing are limited in both process reproducibility and product quality, owing to their complicated means of protein expression and purification1–4. We describe an automated, benchtop, multiproduct manufacturing system, called Integrated Scalable Cyto-Technology (InSCyT), for the end-to-end production of hundreds to thousands of doses of clinical-quality protein biologics in about 3 d. Unlike previous systems, InSCyT includes fully integrated modules for sustained production, efficient purification without the use of affinity tags, and formulation to a final dosage form of recombinant biopharmaceuticals. We demonstrate that InSCyT can accelerate process development from sequence to purified drug in 12 weeks. We used integrated design to produce human growth hormone, interferon a-2b and granulocyte colony-stimulating factor with highly similar processes on this system and show that their purity and potency are comparable to those of marketed reference products

On-demand manufacturing of clinical-quality biopharmaceuticals

© 2018, Nature Publishing Group. All rights reserved. Conventional manufacturing of protein biopharmaceuticals in centralized, large-scale, single-product facilities is not well-suited to the agile production of drugs for small patient populations or individuals. Previous solutions for small-scale manufacturing are limited in both process reproducibility and product quality, owing to their complicated means of protein expression and purification1–4. We describe an automated, benchtop, multiproduct manufacturing system, called Integrated Scalable Cyto-Technology (InSCyT), for the end-to-end production of hundreds to thousands of doses of clinical-quality protein biologics in about 3 d. Unlike previous systems, InSCyT includes fully integrated modules for sustained production, efficient purification without the use of affinity tags, and formulation to a final dosage form of recombinant biopharmaceuticals. We demonstrate that InSCyT can accelerate process development from sequence to purified drug in 12 weeks. We used integrated design to produce human growth hormone, interferon a-2b and granulocyte colony-stimulating factor with highly similar processes on this system and show that their purity and potency are comparable to those of marketed reference products

Modification of Crystal Shape through Deep Temperature Cycling

The evolution of particle shape is an important consideration in many industrial crystallizations. This article 12 describes the design of temperature-cycling experiments (between alternating positive and negative supersaturations) to 13 substantially change crystal shape with only a small number of cycles. The growth and dissolution of monosodium glutamate 14 crystals of varying shapes were monitored using in-process attenuated total reflection−Fourier transform infrared spectroscopy 15 (ATR-FTIR), focused beam reflectance measurement (FBRM), particle vision and measurement (PVM), and off-line optical 16 microscopy. The growth and dissolution kinetics were estimated in a multidimensional population balance model based on solute 17 concentration and crystal dimension measurements. This model fitted the experimental data with a limited number of parameters 18 of small uncertainty. In addition, with the estimated kinetic parameters, the model predicted the crystal size and shape 19 distribution in a different temperature-cycling experiment reasonably well. In contrast to previous studies that have estimated 20 kinetics along multiple crystal axes in mixed-tank crystallizers, this study implements dissolution terms in the multidimensional 21 population balance model along multiple axes

Assessment of recent process analytical technology (PAT) trends : a multiauthor review

This multiauthor review article aims to bring readers up to date with some of the current trends in the field of process analytical technology (PAT) by summarizing each aspect of the subject (sensor development, PAT based process monitoring and control methods) and presenting applications both in industrial laboratories and in manufacture e.g. at GSK, AstraZeneca and Roche. Furthermore, the paper discusses the PAT paradigm from the regulatory science perspective. Given the multidisciplinary nature of PAT, such an endeavour would be almost impossible for a single author, so the concept of a multiauthor review was born. Each section of the multiauthor review has been written by a single expert or group of experts with the aim to report on its own research results. This paper also serves as a comprehensive source of information on PAT topics for the novice reader

Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes

Identifying genetic risk factors for highly heterogeneous disorders such as epilepsy remains challenging. Here we present, to our knowledge, the largest whole-exome sequencing study of epilepsy to date, with more than 54,000 human exomes, comprising 20,979 deeply phenotyped patients from multiple genetic ancestry groups with diverse epilepsy subtypes and 33,444 controls, to investigate rare variants that confer disease risk. These analyses implicate seven individual genes, three gene sets and four copy number variants at exome-wide significance. Genes encoding ion channels show strong association with multiple epilepsy subtypes, including epileptic encephalopathies and generalized and focal epilepsies, whereas most other gene discoveries are subtype specific, highlighting distinct genetic contributions to different epilepsies. Combining results from rare single-nucleotide/short insertion and deletion variants, copy number variants and common variants, we offer an expanded view of the genetic architecture of epilepsy, with growing evidence of convergence among different genetic risk loci on the same genes. Top candidate genes are enriched for roles in synaptic transmission and neuronal excitability, particularly postnatally and in the neocortex. We also identify shared rare variant risk between epilepsy and other neurodevelopmental disorders. Our data can be accessed via an interactive browser, hopefully facilitating diagnostic efforts and accelerating the development of follow-up studies