Statistical analysis of magnetic divertor configuration influence on H-mode transitions

DIII-D plasmas are compared for two upper divertor configurations: with the outer strike point on the small angle slot (SAS) divertor target and with the outer strike point on the horizontal divertor target (HT). Scanning the vertical distance between the magnetic null point and the divertor target over a range 0.10–0.16 m is shown to increase the threshold power, Pth , and edge plasma power, PLoss , for the low-to-high confinement (L–H) and H–L transitions respectively, by up to a factor of 1.4. The X-point height scans were performed at three L-mode core plasma line average electron densities, n¯e= 1.2, 2.2 and 3.6 ×1019m−3 , to investigate the density dependence of divertor magnetic configuration influence on Pth . The X-point height, Zx-pt , was further extended across the range 0.16–0.22 m with the more open HT divertor configuration, for which a clear decrease in Pth with increasing Zx-pt is observed. The dependence of Pth on divertor magnetic geometry is further investigated using a time-dependent probability density function (PDF) model and information geometry to elucidate the roles played by pedestal plasma turbulence and perpendicular velocity flows. The degree of stochasticity of the plasma turbulence is observed to be sensitive to the plasma heating rate. The calculated square of the information rate shows changes in the relative density fluctuations and perpendicular velocity PDFs begin 2–5 ms prior to the L–H transition for three plasmas; providing a crucial measurement of the dynamic timescale of external transport barrier formation. Additionally, both information length and rate provide potential predictors of the L–H transition for these plasmas

IMAGINE-IMpact Assessment of Guidelines Implementation and Education : The Next Frontier for Harmonising Urological Practice Across Europe by Improving Adherence to Guidelines

Funding support: The IMAGINE ADT audit is supported by a seeding grant from the EAU Research Foundation.Peer reviewedPostprin

Arm bone loading index predicts DXA musculoskeletal outcomes in two samples of post-menarcheal girls

Abstract Objective: A site-specific bone loading index was developed to predict post-menarcheal arm bone mass, geometry, areal density and non-bone lean mass using organized activity records. Methods: Two cohorts of post-menarcheal girls (A= 55, B= 48) met analysis inclusion criteria: 1) Whole body and non-dominant radius DXA scans +1.0 to +2.6 years post-menarche; 2) detailed, organized activity records available for 36 months prior to the focal DXA scan; 3) accompanying anthropometric data. DXA non-dominant arm and radius regions of interest (1/3, Ultradistal (UD)) were evaluated. An arm bone loading index (arm totBLI) was developed and refined to describe >50 activities. Separate regression analyses for Cohorts A&B tested explanatory value of arm totBLI for DXA outcomes, accounting for gynecological age, height and whole body non-bone lean mass. Results: In both cohorts, arm totBLI reflecting 3 years of peri-menarcheal activity exposure exhibited strong explanatory value for post-menarcheal radius and arm outcomes (squared semi-partial r =0.07-0.34, p<0.05), except Arm Area. For both cohorts and most outcomes, arm totBLI explained significant variance, even after adjusting for local muscle mass. Conclusions: In two independent cohorts, arm totBLI may consistently indicate osteogenic and sarcogenic properties of represented activities; additional research is necessary for further refinement and validation

Unpacking overuse of androgen deprivation therapy for prostate cancer to inform de-implementation strategies

Peer reviewe

A Water-Bridged Cysteine-Cysteine Redox Regulation Mechanism in Bacterial Protein Tyrosine Phosphatases

The emergence of multidrug-resistant Mycobacterium tuberculosis (Mtb) strains highlights the need to develop more efficacious and potent drugs. However, this goal is dependent on a comprehensive understanding of Mtb virulence protein effectors at the molecular level. Here, we used a post-expression cysteine (Cys)-to-dehydrolanine (Dha) chemical editing strategy to identify a water-mediated motif that modulates accessibility of the protein tyrosine phosphatase A (PtpA) catalytic pocket. Importantly, this water-mediated Cys-Cys non-covalent motif is also present in the phosphatase SptpA from Staphylococcus aureus, which suggests a potentially preserved structural feature among bacterial tyrosine phosphatases. The identification of this structural water provides insight into the known resistance of Mtb PtpA to the oxidative conditions that prevail within an infected host macrophage. This strategy could be applied to extend the understanding of the dynamics and function(s) of proteins in their native state and ultimately aid in the design of small-molecule modulators.e thank CNPq Brazil (fellowship 200456/2015-6 to J.B.B. and grants 454507/2014-3 and 300606/2010-9 to H.T.), the Fundação para a Ciência e a Tecnologia (FCT Investigator award IF/00624/2015 to G.J.L.B.), the European Union (Marie-Sklodowska Curie Innovative Training Network Protein Conjugates; Marie Skłodowska-Curie Individual Fellowship 743640 to T.R.; Marie-Curie Intra-European Fellowship 626890 to O.B.), the Ministerio de Economía, Industria, y Competitividad (project CTQ2015-67727-R to F.C.), and the Biotechnology and Biological Sciences Research Council (PhD studentship to L.D.) for funding. G.J.L.B. is a Royal Society University Research Fellow and the recipient of a European Research Council Starting Grant (TagIt, 676832 ). We also acknowledge funding by LISBOA-01-0145-FEDER-007391, co-financed by FEDER through the Programa Operacional Regional de Lisboa (Lisboa 2020) of PORTUGAL 2020 and by FCT Portugal

PRC2 loss induces chemoresistance by repressing apoptosis in T cell acute lymphoblastic leukemia

The tendency of mitochondria to undergo or resist BCL2-controlled apoptosis (so-called mitochondrial priming) is a powerful predictor of response to cytotoxic chemotherapy. Fully exploiting this finding will require unraveling the molecular genetics underlying phenotypic variability in mitochondrial priming. Here, we report that mitochondria) apoptosis resistance in T cell acute lymphoblastic leukemia (T-ALL) is mediated by inactivation of polycomb repressive complex 2 (PRC2). In T-ALL clinical specimens, loss-of-function mutations of PRC2 core components (EZH2, FED, or SUZ12) were associated with mitochondrial apoptosis resistance. In T-ALL cells, PRC2 depletion induced resistance to apoptosis induction by multiple chemotherapeutics with distinct mechanisms of action. PRC2 loss induced apoptosis resistance via transcriptional up-regulation of the LIM domain transcription factor CRIP2 and downstream up-regulation of the mitochondrial chaperone TRAP1. These findings demonstrate the importance of mitochondrial apoptotic priming as a prognostic factor in T-ALL and implicate mitochondrial chaperone function as a molecular determinant of chemotherapy response

Matrix metalloproteinases in lung biology

Despite much information on their catalytic properties and gene regulation, we actually know very little of what matrix metalloproteinases (MMPs) do in tissues. The catalytic activity of these enzymes has been implicated to function in normal lung biology by participating in branching morphogenesis, homeostasis, and repair, among other events. Overexpression of MMPs, however, has also been blamed for much of the tissue destruction associated with lung inflammation and disease. Beyond their role in the turnover and degradation of extracellular matrix proteins, MMPs also process, activate, and deactivate a variety of soluble factors, and seldom is it readily apparent by presence alone if a specific proteinase in an inflammatory setting is contributing to a reparative or disease process. An important goal of MMP research will be to identify the actual substrates upon which specific enzymes act. This information, in turn, will lead to a clearer understanding of how these extracellular proteinases function in lung development, repair, and disease

Laminin γ2 fragments are increased in the circulation of patients with early phase acute lung injury

Katayama, M., Ishizaka, A., Sakamoto, M. et al. Intensive Care Med (2010) 36: 479. https://doi.org/10.1007/s00134-009-1719-