Pluripotent stem cells can be isolated from embryos or derived by reprogramming. Pluripotency is stabilized by an interconnected network of pluripotency genes that cooperatively regulate gene ...expression. Here we describe the molecular principles of pluripotency gene function and highlight post-transcriptional controls, particularly those induced by RNA-binding proteins and alternative splicing, as an important regulatory layer of pluripotency. We also discuss heterogeneity in pluripotency regulation, alternative pluripotency states and future directions of pluripotent stem cell research.
Obesity increases the risk of clinical decompensation in cirrhosis, possibly by increasing portal pressure. Whether weight reduction can be safely achieved through lifestyle (LS) changes (diet and ...exercise) in overweight/obese patients with cirrhosis, and if weight loss reduces portal pressure in this setting, is unknown. This prospective, multicentric, uncontrolled pilot study enrolled patients with compensated cirrhosis, portal hypertension (hepatic venous pressure gradient HVPG ≥6 mm Hg), and body mass index (BMI) ≥26 kg/m2 in an intensive 16‐week LS intervention program (personalized hypocaloric normoproteic diet and 60 min/wk of supervised physical activity). We measured HVPG, body weight (BW) and composition, adipokines, health‐related quality of life, and safety data before and after the intervention. Changes in HVPG and BW were predefined as clinically relevant if ≥10% and ≥5%, respectively. Safety and BW were reassessed after 6 months. 60 patients were included and 50 completed the study (56 ± 8 years old; 62% male; nonalcoholic steatohepatitis etiology 24%; BMI 33.3 ± 3.2 kg/m2; Child A 92%; HVPG ≥10 mm Hg, 72%). LS intervention significantly decreased BW (average, –5.0 ± 4.0 kg; P < 0.0001), by ≥5% in 52% and ≥10% in 16%. HVPG also significantly decreased (from 13.9 ± 5.6 to 12.3 ± 5.2 mm Hg; P < 0.0001), by ≥10% in 42% and ≥20% in 24%. A ≥10% BW loss was associated with a greater decrease in HVPG (–23.7 ± 19.9% vs. –8.2 ± 16.6%; P = 0.024). No episodes of clinical decompensation occurred. Weight loss achieved at 16 weeks was maintained at 6 months; Child and Model for End‐Stage Liver Disease scores did not change. Conclusion: Sixteen weeks of diet and moderate exercise were safe and reduced BW and portal pressure in overweight/obese patients with cirrhosis and portal hypertension. (Hepatology 2017;65:1293‐1305).
Interest in stratospheric aerosol and its role in climate have increased over the last decade due to the observed increase in stratospheric aerosol since 2000 and the potential for changes in the ...sulfur cycle induced by climate change. This review provides an overview about the advances in stratospheric aerosol research since the last comprehensive assessment of stratospheric aerosol was published in 2006. A crucial development since 2006 is the substantial improvement in the agreement between in situ and space-based inferences of stratospheric aerosol properties during volcanically quiescent periods. Furthermore, new measurement systems and techniques, both in situ and space based, have been developed for measuring physical aerosol properties with greater accuracy and for characterizing aerosol composition. However, these changes induce challenges to constructing a long-term stratospheric aerosol climatology. Currently, changes in stratospheric aerosol levels less than 20% cannot be confidently quantified. The volcanic signals tend to mask any nonvolcanically driven change, making them difficult to understand. While the role of carbonyl sulfide as a substantial and relatively constant source of stratospheric sulfur has been confirmed by new observations and model simulations, large uncertainties remain with respect to the contribution from anthropogenic sulfur dioxide emissions. New evidence has been provided that stratospheric aerosol can also contain small amounts of nonsulfatematter such as black carbon and organics. Chemistry-climate models have substantially increased in quantity and sophistication. In many models the implementation of stratospheric aerosol processes is coupled to radiation and/or stratospheric chemistry modules to account for relevant feedback processes.
Kerr black holes with synchronised hair 1,2 are a counter example to the no hair conjecture, in General Relativity minimally coupled to simple matter fields (with mass μ) obeying all energy ...conditions. Since these solutions have, like Kerr, an ergoregion it has been a lingering possibility that they are afflicted by the superradiant instability, the same process that leads to their dynamical formation from Kerr. A recent breakthrough 3 confirmed this instability and computed the corresponding timescales for a sample of solutions. We discuss how these results and other observations support two conclusions: 1) starting from the Kerr limit, the increase of hair for fixed coupling μM (where M is the BH mass) increases the timescale of the instability; 2) there are hairy solutions for which this timescale, for astrophysical black hole masses, is larger than the age of the Universe. The latter conclusion introduces the limited, but physically relevant concept of effective stability. The former conclusion, allows us to identify an astrophysically viable domain of such effectively stable hairy black holes, occurring, conservatively, for Mμ≲0.25. These are hairy BHs that form dynamically, from the superradiant instability of Kerr, within an astrophysical timescale, but whose own superradiant instability occurs only in a cosmological timescale.
We investigate the reach at the LHC to probe light sterile neutrinos with displaced vertices. We focus on sterile neutrinos N with masses mN∼(5–30) GeV that are produced in rare decays of the ...standard model gauge bosons and decay inside the inner trackers of the LHC detectors. With a strategy that triggers on the prompt lepton accompanying the N displaced vertex and considers charged tracks associated with it, we show that the 13 TeV LHC with 3000/fb is able to probe active-sterile neutrino mixings down to |VlN|2≈10−9, with l=e, μ, which is an improvement of up to 4 orders of magnitude when comparing with current experimental limits from trileptons and proposed lepton-jets searches. In the case when τ mixing is present, mixing angles as low as |VτN|2≈10−8 can be accessed.
Background and Aims
Extrahepatic portal vein occlusion (EHPVO) from portal vein thrombosis is a rare condition associated with substantial morbidity and mortality. The purpose of this study is to ...investigate the efficacy of transjugular intrahepatic portosystemic shunts (TIPS) for the treatment of chronic EHPVO, cavernomatosis, and mesenteric venous thrombosis in adults without cirrhosis who are refractory to standard‐of‐care therapy.
Approach and Results
Thirty‐nine patients with chronic EHPVO received TIPS. Laboratory parameters and follow‐up were assessed at 1, 3, 6, 12, and 24 months, and every 6 months thereafter. Two hepatologists adjudicated symptom improvement attributable to mesenteric thrombosis and EHPVO before/after TIPS. Kaplan‐Meier was used to assess primary and overall TIPS patency, assessing procedural success. Adverse events, radiation exposure, hospital length‐of‐stay and patency were recorded. Cavernoma was present in 100%, with TIPS being successful in all cases using splenic, mesenteric, and transhepatic approaches. Symptom improvement was noted in 26 of 30 (87%) at 6‐month follow‐up. Twelve patients (31%) experienced TIPS thrombosis. There were no significant long‐term laboratory adverse events or deaths. At 36 months, freedom from primary TIPS thrombosis was 63%; following secondary interventions, overall patency was increased to 81%.
Conclusions
TIPS in chronic, noncirrhotic EHPVO with cavernomas and mesenteric venous thrombosis is technically feasible and does not adversely affect liver function. Most patients demonstrate subjective and objective benefit from TIPS. Improvement in patency rates are needed with proper timing of adjuvant anticoagulation.
This paper investigates the valuation of crowding in public transport trips and its implications in demand estimation and cost-benefit analysis. We use a choice-based stated preference survey where ...crowding levels are represented by means of specially designed pictures, and use these data to estimate flexible discrete choice models. We assume that the disutility associated with travelling under crowded conditions is proportional to travel time. Our results are consistent with and extend previous findings in the literature: passenger density has a significant effect on the utility of travelling by public transport; in fact, the marginal disutility of travel time in a crowded vehicle (6standing-passengers/m2) is 2.5 times higher than in a vehicle with available seats. We also compare the effects of different policies for improving bus operations, and the effect of adding crowding valuation in cost-benefit analysis. In doing that, we endogenise the crowding level as the result of the equilibrium between demand and supplied bus capacity. Our results indicate that important benefits may be accrued from policies designed to reduce crowding, and that ignoring crowding effects significantly overestimate the bus travel demand the benefits associated with pure travel time reductions.
We analyzed the coseismic and early postseismic deformation of the 2015, Mw 8.3 Illapel earthquake by inverting 13 continuous GPS time series. The seismic rupture concentrated in a shallow (<20 km ...depth) and 100 km long asperity, which slipped up to 8 m, releasing a seismic moment of 3.6 × 1021 Nm (Mw = 8.3). After 43 days, postseismic afterslip encompassed the coseismic rupture. Afterslip concentrated in two main patches of 0.50 m between 20 and 40 km depth along the northern and southern ends of the rupture, partially overlapping the coseismic slip. Afterslip and aftershocks confined to region of positive Coulomb stress change, promoted by the coseismic slip. The early postseismic afterslip was accommodated ~53% aseismically and ~47% seismically by aftershocks. The Illapel earthquake rupture is confined by two low interseismic coupling zones, which coincide with two major features of the subducting Nazca Plate, the Challenger Fault Zone and Juan Fernandez Ridge.
Key Points
Coseismic slip of the 2015 Illapel earthquake from cGPS data occurred in a highly locked interseismic region
Postseismic afterslip following the Illapel earthquake
The Challenger Fault Zone (CFZ) and the Juan Fernandez Ridge (JFR) played the role of barrier to seismic rupture
The thymus is an intricate primary lymphoid organ, wherein bone marrow-derived lymphoid progenitor cells are induced to develop into functionally competent T cells that express a diverse TCR ...repertoire, which is selected to allow for the recognition of foreign Ags while avoiding self-reactivity or autoimmunity. Thymus stromal cells, which can include all non-T lineage cells, such as thymic epithelial cells, endothelial cells, mesenchymal/fibroblast cells, dendritic cells, and B cells, provide signals that are essential for thymocyte development as well as for the homeostasis of the thymic stroma itself. In this brief review, we focus on the key roles played by thymic stromal cells during early stages of T cell development, such as promoting the homing of thymic-seeding progenitors, inducing T lineage differentiation, and supporting thymocyte survival and proliferation. We also discuss recent advances on the transcriptional regulation that govern thymic epithelial cell function as well as the cellular and molecular changes that are associated with thymic involution and regeneration.
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