Incompressible Fluids of the de Sitter Horizon and Beyond

There are (at least) two surfaces of particular interest in eternal de Sitter space. One is the timelike hypersurface constituting the lab wall of a static patch observer and the other is the future boundary of global de Sitter space. We study both linear and non-linear deformations of four-dimensional de Sitter space which obey the Einstein equation. Our deformations leave the induced conformal metric and trace of the extrinsic curvature unchanged for a fixed hypersurface. This hypersurface is either timelike within the static patch or spacelike in the future diamond. We require the deformations to be regular at the future horizon of the static patch observer. For linearized perturbations in the future diamond, this corresponds to imposing incoming flux solely from the future horizon of a single static patch observer. When the slices are arbitrarily close to the cosmological horizon, the finite deformations are characterized by solutions to the incompressible Navier-Stokes equation for both spacelike and timelike hypersurfaces. We then study, at the level of linearized gravity, the change in the discrete dispersion relation as we push the timelike hypersurface toward the worldline of the static patch. Finally, we study the spectrum of linearized solutions as the spacelike slices are pushed to future infinity and relate our calculations to analogous ones in the context of massless topological black holes in AdS$_4$.Comment: 27 pages, 8 figure

Pediatric hospital discharge interventions to reduce subsequent utilization: A systematic review

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106901/1/jhm2134.pd

Processing-Induced Disorder in Pharmaceutical Materials

This chapter focuses on the major types of pharmaceutical processing methods that have been widely reported to produce disordered material either intentionally or unintentionally. Milling is one of the most frequently used unit operations used by the pharmaceutical industry for reducing the particle size of solids. Thermal processing techniques are mainly used for controlling or improving the release and the subsequent bioavailability of an active pharmaceutical ingredient (API). Techniques such as melt-mixing, spray-congealing, sintering, melt-granulation, and hot-melt extrusion (HME) have developed and evolved rapidly for large-scale pharmaceutical production. Solvent-evaporation-based methods are important processing techniques for both raw materials, such as crystallization of the raw drug, and formulation manufacturing in the pharmaceutical industry. The chapter discusses the processing that can potentially induce the formation of the disordered state during the manufacture of formulations. The widely used solvent-evaporation-based processing techniques in pharmaceutical formulation production include spray-drying, freeze-drying, film casting, and film coating

Public awareness and healthcare professional advice for obesity as a risk factor for cancer in the UK:a cross-sectional survey

BACKGROUND: Overweight and obesity is the second biggest preventable cause of cancer after smoking, causing ~3.4 million deaths worldwide. This study provides current UK data on awareness of the link between obesity and cancer by socio-demographic factors, including BMI, and explores to what degree healthcare professionals provide weight management advice to patients. METHODS: Cross-sectional survey of 3293 adults completed an online survey in February/March 2016, weighted to be representative of the UK population aged 18+. RESULTS: Public awareness of the link between obesity and cancer is low (25.4% unprompted and 57.5% prompted). Higher levels of awareness existed for least deprived groups (P < 0.001), compared to more deprived groups. Most respondents had seen a healthcare practitioner in the past 12 months (91.6%) and 17.4% had received advice about their weight, although 48.4% of the sample were overweight/obese. CONCLUSION: Cancer is not at the forefront of people’s minds when considering health conditions associated with overweight or obesity. Socio-economic disparities exist in health knowledge across the UK population, with adults from more affluent groups being most aware. Healthcare professionals are uniquely positioned to provide advice about weight, but opportunities for intervention are currently under-utilized in healthcare settings

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV

Local induction of lymphangiogenesis with engineered fibrin-binding VEGF-C promotes wound healing by increasing immune cell trafficking and matrix remodeling

Lymphangiogenesis occurs in inflammation and wound healing, yet its functional roles in these processes are not fully understood. Consequently, clinically relevant strategies for therapeutic lymphangiogenesis remain underdeveloped, particularly using growth factors. To achieve controlled, local capillary lymphangiogenesis with protein engineering and determine its effects on fluid clearance, leukocyte trafficking, and wound healing, we developed a fibrin-binding variant of vascular endothelial growth factor C (FB-VEGF-C) that is slowly released upon demand from infiltrating cells. Using a novel wound healing model, we show that implanted fibrin containing FB-VEGF-C, but not free VEGF-C, could stimulate local lymphangiogenesis in a dose-dependent manner. Importantly, the effects of FB-VEGF-C were restricted to lymphatic capillaries, with no apparent changes to blood vessels and downstream collecting vessels. Leukocyte intravasation and trafficking to lymph nodes were increased in hyperplastic lymphatics, while fluid clearance was maintained at physiological levels. In diabetic wounds, FB-VEGF-C-induced lymphangiogenesis increased extracellular matrix deposition and granulation tissue thickening, indicators of improved wound healing. Together, these results indicate that FB-VEGF-C is a promising strategy for inducing lymphangiogenesis locally, and that such lymphangiogenesis can promote wound healing by enhancing leukocyte trafficking without affecting downstream lymphatic collecting vessels. (C) 2017 The Authors. Published by Elsevier Ltd

Association of melanocortin 1 receptor gene (MC1R) polymorphisms with skin reflectance and freckles in Japanese.

Most studies on the genetic basis of human skin pigmentation have focused on people of European ancestry and only a few studies have focused on Asian populations. We investigated the association of skin reflectance and freckling with genetic variants of melanocortin 1 receptor (MC1R) gene in Japanese. DNA samples were obtained from a total of 653 Japanese individuals (ages 19-40 years) residing in Okinawa; skin reflectance was measured using a spectrophotometer and freckling status was determined for each individual. Lightness index (L*) and freckling status were not correlated with age, body mass index or ancestry (Ryukyuan or Main Islanders of Japan). Among the 10 nonsynonymous variants that were identified by direct sequencing of the coding region of MC1R, two variants--R163Q and V92M--with the derived allele frequencies of 78.6 and 5.5%, respectively, were most common. Multiple regression analysis showed that the 163Q allele and the presence of nonsynonymous rare variants (allele frequencies <5%) were significantly associated with an increase in sex-standardized skin lightness (L* of CIELAB (CIE 1976 (L*a*b*) color space)) of the inner upper arm. Relative to the 92V allele, the 92M allele was significantly associated with increased odds of freckling. This is the first study to show an association between the 163Q allele and skin reflectance values; this association indicated that light-toned skin may have been subjected to positive selection in East Asian people

Prepatterning in the Stem Cell Compartment

The mechanism by which an apparently uniform population of cells can generate a heterogeneous population of differentiated derivatives is a fundamental aspect of pluripotent and multipotent stem cell behaviour. One possibility is that the environment and the differentiation cues to which the cells are exposed are not uniform. An alternative, but not mutually exclusive possibility is that the observed heterogeneity arises from the stem cells themselves through the existence of different interconvertible substates that pre-exist before the cells commit to differentiate. We have tested this hypothesis in the case of apparently homogeneous pluripotent human embryonal carcinoma (EC) stem cells, which do not follow a uniform pattern of differentiation when exposed to retinoic acid. Instead, they produce differentiated progeny that include both neuronal and non-neural phenotypes. Our results suggest that pluripotent NTERA2 stem cells oscillate between functionally distinct substates that are primed to select distinct lineages when differentiation is induced

Revisiting the B-cell compartment in mouse and humans: more than one B-cell subset exists in the marginal zone and beyond.

International audienceABSTRACT: The immunological roles of B-cells are being revealed as increasingly complex by functions that are largely beyond their commitment to differentiate into plasma cells and produce antibodies, the key molecular protagonists of innate immunity, and also by their compartmentalisation, a more recently acknowledged property of this immune cell category. For decades, B-cells have been recognised by their expression of an immunoglobulin that serves the function of an antigen receptor, which mediates intracellular signalling assisted by companion molecules. As such, B-cells were considered simple in their functioning compared to the other major type of immune cell, the T-lymphocytes, which comprise conventional T-lymphocyte subsets with seminal roles in homeostasis and pathology, and non-conventional T-lymphocyte subsets for which increasing knowledge is accumulating. Since the discovery that the B-cell family included two distinct categories - the non-conventional, or extrafollicular, B1 cells, that have mainly been characterised in the mouse; and the conventional, or lymph node type, B2 cells - plus the detailed description of the main B-cell regulator, FcγRIIb, and the function of CD40+ antigen presenting cells as committed/memory B-cells, progress in B-cell physiology has been slower than in other areas of immunology. Cellular and molecular tools have enabled the revival of innate immunity by allowing almost all aspects of cellular immunology to be re-visited. As such, B-cells were found to express "Pathogen Recognition Receptors" such as TLRs, and use them in concert with B-cell signalling during innate and adaptive immunity. An era of B-cell phenotypic and functional analysis thus began that encompassed the study of B-cell microanatomy principally in the lymph nodes, spleen and mucosae. The novel discovery of the differential localisation of B-cells with distinct phenotypes and functions revealed the compartmentalisation of B-cells. This review thus aims to describe novel findings regarding the B-cell compartments found in the mouse as a model organism, and in human physiology and pathology. It must be emphasised that some differences are noticeable between the mouse and human systems, thus increasing the complexity of B-cell compartmentalisation. Special attention will be given to the (lymph node and spleen) marginal zones, which represent major crossroads for B-cell types and functions and a challenge for understanding better the role of B-cell specificities in innate and adaptive immunology