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Background There is lack of epidemiological data in regard to the accurate situation of Inflammatory Bowel Disease (IBD): Crohn’s disease (CD) and ulcerative colitis (UC) in Brazil. It is known that both diseases' progression is variable and the chronic iinflammation results in structural bowel damage. Comparative data between adult and pediatric patients in the IBD field, regarding different outcomes, is lacking globally. We aimed to analyze the proportion of use of biologicals, need for major abdominal surgery and hospitalizations in CD and UC , between adult and pediatric patients. Methods Cross-sectional and multicenter study. Data was collected from all consecutive IBD patients seen as outpatients or admitted to hospital, from 2015 – 2021, in two IBD tertiary centers from a capital from south Brazil. We included all patients with clinical, endoscopic, radiological or histological diagnosis of CD and UC. Patients with unclassified colitis or without available data in medical records for investigating variables of interest were excluded. Patients were classified in two main groups (CD and UC) and in two subgroups each, according to age range: adults and pediatrics. Analyses were made by frequency, proportion, Fisher’s exact test and Chi-squared test, through software IBM SPSS Statistics 28. Results Eight hundred and twenty-nine patients were included: 509 with CD (378 adults/131 pediatrics) and 320 with UC (225/95). There was significantly difference between diseases in the proportion of biological use 75.0% in CD and 31.6% in UC (p Conclusion There was a higher proportion of biological use, surgery and need for hospitalizations in CD as compared to UC. Comparing age ranges, pediatric patients with UC used more biologicals and required more hospitalizations than adults, but there was no difference in the need for abdominal surgery. In CD, there was no significant difference in the three main outcomes, between the age groups.

We examine general relativistic radiatively-driven spherical winds, using the basic equations for relativistic radiation hydrodynamics under the moment formalism. Moment equations are often closed, using the equilibrium diffusion approximation, which has an acausal problem, and furthermore, gives nodal-type critical points. Instead, we use the nonequilibrium diffusion approximation with a closure relation of a variable Eddington factor, $f(\tau,\beta)$, where $\tau$ is the optical depth and $\beta$ is the flow speed normalized by the speed of light. We then analyze the critical properties in detail for several parameters, and found that there appear saddle-type critical points as well as nodal type and spiral one. The most suitable type is the saddle one, which appears in a region close to a black hole. We also calculate transonic solutions with typical parameters, and show that the luminosity is almost comparable to the Eddington luminosity, the gas is quickly accelerated in the vicinity of the black hole, and wind terminal speeds are on the order of 0.1$-$0.3$~c$. These results of radiatively-driven black hole winds can be applied, e.g., to ultra-fast outflows (UFOs), which are supposed to be fast outflows from the vicinity of super massive black holes., Comment: 12 pages, 15 figures, published in MNRAS, some typos in equation (10) of the published article have been corrected

Unequivocal functional assessment of candidate genomic regulatory regions, such as transcriptional response elements, requires genetic alteration at their native chromosomal loci. Targeted DNA cleavage by Cas9 or other programmable nucleases enables analysis at virtually any genomic region, and diverse alleles generated by editing can be defined by deep sequencing for functional analysis. Interpretation of disrupted response elements, however, presents a special challenge, as these regions typically comprise clustered DNA binding motifs for multiple transcriptional regulatory factors (TFs); DNA sequence differences, natural or engineered, that affect binding by one TF can confer loss or gain of binding sites for other TFs. To address these and other analytical complexities, we created three computational tools that together integrate, in a single experiment, allele definition and TF binding motif evaluation for up to 9216 clones isolated, sequenced and propagated from Cas9-treated cell populations. We demonstrate 1) the capacity to functionally assess edited TF binding sites to query response element function, and 2) the efficacy and utility of these tools, by analyzing cell populations targeted by Cas9 for disruption of example glucocorticoid receptor (GR) binding motifs near FKBP5, a GR-regulated gene in the human adenocarcinoma cell line A549., Graphical Abstract Graphical AbstractWorkflow to evaluate (A) a genetically heterogeneous sample population includes (B) clonal isolation and PCR-barcoding of one or more target loci from diverse samples, followed by (C) computational resources to define alleles and altered transcription factor binding sites (TFBSs) that inform clone selection and regulatory analysis.

The glucocorticoid receptor (GR) regulates transcription through binding to specific DNA motifs, particularly at enhancers. While the motif to which it binds is constant across cell types, GR has cell type-specific binding at genomic loci, resulting in regulation of different genes. The presence of other bound transcription factors (TFs) is hypothesized to strongly influence where GR binds. Here, we addressed the roles of other TFs in the glucocorticoid response by comparing changes in GR binding and nascent transcription at promoters and distal candidate cis-regulatory elements (CCREs) in two distinct human cancer cell types. We found that after glucocorticoid treatment, GR binds to thousands of genomic loci that are primarily outside of promoter regions and are potentially enhancers. The majority of these GR binding sites are cell-type specific, and they are associated with pioneer factor binding. A small fraction of GR occupied regions (GORs) displayed increased bidirectional nascent transcription, which is a characteristic of many active enhancers, after glucocorticoid treatment. Non-promoter GORs with increased transcription were specifically enriched for AP-1 binding prior to glucocorticoid treatment. These results support a model of transcriptional regulation in which multiple classes of TFs are required. The pioneer factors increase chromatin accessibility, facilitating the binding of GR and additional factors. AP-1 binding poises a fraction of accessible sites to be rapidly transcribed upon glucocorticoid-induced GR binding. The coordinated activity of multiple TFs then results in cell type-specific changes in gene expression. We anticipate that many models of inducible gene expression also require multiple distinct TFs that act at multiple steps of transcriptional regulation.

To improve energy efficiency, flow control techniques for skin-friction drag and heat transfer with regard to wall turbulence are essential. This study performs direct numerical simulation of turbulent channel flows. The traveling-wave-like body force is employed as the flow control technique to break the similarity between momentum and heat transfer. The traveling wave control mimics the self-excited thin film in the corresponding experimental study. When the wave traveled slowly along the downstream direction, the skin-friction drag, heat transfer, and analogy factor were found to increase. Moreover, these parameters increased with an increase in the reference height of the traveling wave ( hw). Flow visualization shows turbulence enhancement owing to the increase in hw. Three-component decomposition elucidates the difference between the control effect on the Reynolds shear stress and the turbulent heat flux.

Background Hepatectomy with extrahepatic bile duct resection is associated with a high risk of posthepatectomy liver failure (PHLF). However, the utility of the remnant liver volume (RLV) in cholangiocarcinoma has not been studied intensively. Methods Patients who underwent major hepatectomy with extrahepatic bile duct resection between 2002 and 2018 were reviewed. The RLV was divided by body surface area (BSA) to normalize individual physical differences. Risk factors for clinically relevant PHLF were evaluated with special reference to the RLV/BSA. Results A total of 289 patients were included. The optimal cut-off value for RLV/BSA was determined to be 300 ml/m2. Thirty-two patients (11.1 per cent) developed PHLF. PHLF was more frequent in patients with an RLV/BSA below 300 ml/m2 than in those with a value of 300 ml/m2 or greater: 19 of 87 (22 per cent) versus 13 of 202 (6.4 per cent) (P, The present study showed the importance of considering the remnant liver volume (RLV) / body surface area (BSA) in addition to indocyanine green test for hepatectomy with extrahepatic bile duct resection. An RLV/BSA of 300 mL/m2 is a simple and useful cut-off value to predict posthepatectomy liver failure in patients who undergo major hepatectomy for cholangiocarcinoma. Remnant liver volume normalized using body surface area is a potential tool for predicting postoperative liver failure.

INTRODUCTION According to the anatomy-function-pathology classification, the recurrence rates of A2 and A3 hiatal hernia (HH) after laparoscopic fundoplication are higher than the rate of A1 HH. Therefore, we introduced mesh reinforcement for A2 and A3 cases. In addition, gastropexy was added to A3 cases. We present the strategy for HH repair. METHODS In all, 537 patients (mean age 55.4 ± 16.7 years, 219 women) who underwent primary laparoscopic fundoplication for HH from January 1995 to October 2019 were included. They were divided into three groups by A factor (A1:A2:A3 = 296:156:85). Their clinical data were collected in a prospective fashion and retrospectively reviewed. RESULTS The median age (years) of the patients in each group was A1:A2:A3 = 46:63:74 years, and age was directly proportional to the size of HH (P

Despite decades of clinical use, mechanisms of glucocorticoid resistance are poorly understood. We treated primary murine T lineage acute lymphoblastic leukemias (T-ALLs) with the glucocorticoid dexamethasone (DEX) alone and in combination with the pan-PI3 kinase inhibitor GDC-0941 and observed a robust response to DEX that was modestly enhanced by GDC-0941. Continuous in vivo treatment invariably resulted in outgrowth of drug-resistant clones, ~30% of which showed low glucocorticoid receptor (GR) protein expression. A similar proportion of relapsed human T-ALLs also exhibited markedly reduced GR protein levels. De novo or pre-existing mutations in the gene encoding GR (Nr3c1) occurred in relapsed clones derived from multiple independent parental leukemias. CRISPR/Cas9 gene editing confirmed that loss of GR expression confers DEX resistance. Exposing drug-sensitive T-ALLs to DEX in vivo altered transcript levels of multiple genes, and this response was attenuated in relapsed T-ALLs. These data implicate reduced GR protein expression as a frequent cause of glucocorticoid resistance in T-ALL.

Metazoan transcriptional regulatory factors (TFs) bind to genomic response elements and assemble with co-regulators into transcriptional regulatory complexes (TRCs) whose composition, structure and activities are gene-, cell- and physiological-context specific. Each TRC is a “regulatory logic module,” integrating incoming signaling information, which defines context and thereby recruits a distinct combination of co-regulators that together specify outgoing regulatory activity. Analyzing TRCs unique to every context is daunting, yet justified by their properties as self-contained regulatory modules. As proof-of-concept, we performed a forward genetic screen inC. eleganscarrying a synthetic simple response element for nuclear receptor NHR-25 upstream of a fluorescent reporter gene. We isolated independent mutations inuba-2, a component of the sumoylation signaling machinery, and inlir-2, which we demonstrated to be a novel co-regulator, interacting with NHR-25 through LxxLL motifs and modulating target gene expression. Our studies establish that an unbiased genetic screen readily identifies both afferent and efferent components that specify TRC function, and suggest that screening natural response elements of interest could illuminate molecular mechanisms of both context-specificity and transcriptional regulation.

In an antiferromagnetic zigzag chain, competition between the nearest and next-nearest neighbor interactions could give rise to magnetic frustration. Magnetic semiconductors RAgSe2 (R = Ho, Er, Tm, and Yb) crystallize in the ErAgSe2-type orthorhombic structure, where the R ions form a zigzag chain along the orthorhombic a-axis. The magnetic susceptibility data for all the samples follow the Curie-Weiss law between 40 and 300 K. The values of the effective magnetic moment μ βα are close to those expected for the free R 3+ ions. Negative values of the paramagnetic Curie temperature θρ indicate antiferromagnetic interactions. For R = Ho and Tm, the specific heat C(T) data exhibit no anomaly down to 0.4 K, which is ascribed to the nonmagnetic singlet ground states under the crystalline electric fields. On the other hand, for R = Er, C(T) shows peaks at T 1 = 1.3 K and T2 = 0.9 K, indicating successive antiferromagnetic transitions. For R = Yb, C(T) shows a lambda-type anomaly at T m = 1.8 K. The magnetic entropy at T m is only 30% of Rln2 expected for the ground state doublet, suggesting magnetic fluctuations above T m.

Powder neutron diffraction measurements were carried out to investigate the magnetic structure of the antiferromagnet NdRh2Zn20. The magnetic reflections observed for T ≤ 1.0 K are indexed by the propagation vector of k = (1/2, 1/2, 1/2). From the analysis of the intensity of magnetic reflections, a magnetic structure described by the Γ6 representation is proposed. The magnetic moments are parallel to the [ 11 2 ¯ ] or [ 1 ¯ 10 ] direction and stacked with a sequence of up-up-down-down along the [111] direction.

Controlling protein activity and localization is a key tool in modern biology. Mammalian steroid receptor ligand-binding domain (LBD) fusions have been used in a range of organisms and cell types to inactivate proteins of interest until the cognate steroid ligand is applied. Here, we demonstrate that the glucocorticoid receptor LBD confers ligand-gated control of a heterologous gene expression system (Q system) and the DAF-16 transcription factor in Caenorhabditis elegans. These experiments provide a powerful tool for temporal control of protein activity, and will bolster existing tools used to modulate gene expression and protein activity in this animal.

In order to clarify thermal fluctuation effects during ecodormancy on floral bud necrosis, 'Kousui' Japanese pear shoots were collected after 900 accumulated chilling hours (below 7.2°C) under natural conditions and exposed to three different conditions: constant 25°C (Treatment 1); fluctuating 25/15°C (12/12 h) temperatures (Treatment 2); and 25/15°C (12/12 h) with drastic reductions of temperature to 5°C (12 h) four sampling times (after exposure to accumulated temperatures of 2000, 4000, 6000, 8000 GDH) during the ecodormant phase (Treatment 3). Floral bud necrosis increased through dormancy release and heat accumulation, and buds exposed to extreme thermal fluctuation conditions (25/15°C+5°C) exhibited the highest amount of necrosis. Water content was lowest in buds exposed to 25/15°C+5°C. Sucrose concentration in buds undergoing extreme thermal fluctuation was highest at the end of heat accumulation period, suggesting low sucrose catabolism. Glucose content increased earlier shoots kept at a constant 25°C during the heat accumulation period, indicating higher availability of this carbohydrate for growth resumption. It is suggested that thermal fluctuations during ecodormancy lead to reductions of both water and glucose content, and a possible low catabolism of sucrose that increased both the occurrence and severity of floral bud necrosis.

A draft policy is generally supportive but should start mandating data sharing

XL-Calibur is a hard X-ray (15-80 keV) polarimetry mission operating from a stabilised balloon-borne platform in the stratosphere. It builds on heritage from the X-Calibur mission, which observed the accreting neutron star GX 301-2 from Antarctica, between December 29th 2018 and January 1st 2019. The XL-Calibur design incorporates an X-ray mirror, which focusses X-rays onto a polarimeter comprising a beryllium rod surrounded by Cadmium Zinc Telluride (CZT) detectors. The polarimeter is housed in an anticoincidence shield to mitigate background from particles present in the stratosphere. The mirror and polarimeter-shield assembly are mounted at opposite ends of a 12 m long lightweight truss, which is pointed with arcsecond precision by WASP - the Wallops Arc Second Pointer. The XL-Calibur mission will achieve a substantially improved sensitivity over X-Calibur by using a larger effective area X-ray mirror, reducing background through thinner CZT detectors, and improved anticoincidence shielding. When observing a 1 Crab source for $t_{\rm day}$ days, the Minimum Detectable Polarisation (at 99% confidence level) is $\sim$2$\%\cdot t_{\rm day}^{-1/2}$. The energy resolution at 40 keV is $\sim$5.9 keV. The aim of this paper is to describe the design and performance of the XL-Calibur mission, as well as the foreseen science programme., Comment: 19 pages, 17 figures. Accepted for publication in Astroparticle Physics

H. Sugai, et al., Recent developments of transition-edge sensors (TESs), based on extensive experience in ground-based experiments, have been making the sensor techniques mature enough for their application on future satellite cosmic microwave background (CMB) polarization experiments. LiteBIRD is in the most advanced phase among such future satellites, targeting its launch in Japanese Fiscal Year 2027 (2027FY) with JAXA’s H3 rocket. It will accommodate more than 4000 TESs in focal planes of reflective low-frequency and refractive medium-and-high-frequency telescopes in order to detect a signature imprinted on the CMB by the primordial gravitational waves predicted in cosmic inflation. The total wide frequency coverage between 34 and 448 GHz enables us to extract such weak spiral polarization patterns through the precise subtraction of our Galaxy’s foreground emission by using spectral differences among CMB and foreground signals. Telescopes are cooled down to 5 K for suppressing thermal noise and contain polarization modulators with transmissive half-wave plates at individual apertures for separating sky polarization signals from artificial polarization and for mitigating from instrumental 1/f noise. Passive cooling by using V-grooves supports active cooling with mechanical coolers as well as adiabatic demagnetization refrigerators. Sky observations from the second Sun–Earth Lagrangian point, L2, are planned for 3 years. An international collaboration between Japan, the USA, Canada, and Europe is sharing various roles. In May 2019, the Institute of Space and Astronautical Science, JAXA, selected LiteBIRD as the strategic large mission No. 2., This work was supported by World Premier International Research Center Initiative (WPI), MEXT, Japan, by JSPS Core-to-Core Program, A. Advanced Research Networks, and by JSPS KAKENHI Grant Numbers JP15H05891, JP17H01115, and JP17H01125. The Italian contribution to the LiteBIRD phase A is supported by the Italian Space Agency (ASI Grant No. 2016-24- H.1-2018) and the National Institute for Nuclear Physics (INFN). The French contribution to the LiteBIRD phase A is supported by the Centre National d’Etudes Spatiale (CNES), by the Centre National de la Recherche Scientifque (CNRS), and by the Commissariat à l’Energie Atomique (CEA). A Concurrent Design Facility study focused on the MHFT and Sub-Kelvin coolers has been led by the European Space Agency (ESA). The Canadian contribution to LiteBIRD is supported by the Canadian Space Agency. The US contribution is supported by NASA Grant no. 80NSSC18K0132

The University of California San Francisco (UCSF) Motivating INformed Decisions (MIND) Program, funded by an NIH Broadening Experiences in Scientific Training (BEST) award, was an experiment in career development and exploration. MIND activities were organized around three aims: provide coursework for students and postdocs to develop the skills and tools they need to explore a variety of career paths; connect these trainees with MIND Program partners who are biomedical Ph.D.s to take a closer look at different careers; and assess the types of support and information faculty need to mentor trainees with diverse career interests and build resources to support faculty in these endeavors. We discuss these aims in more detail, providing information about the programmatic structure, insights from our trainees, partners and faculty, and resources developed. We also share what worked and what didn't as we developed the program, and explain how MIND will be sustained at UCSF.