The Ground Sloth, Megalonyx, from Pleistocene Deposits of the Old Crow Basin, Yukon, Canada

The bear-sized ground sloth Megalonyx, endemic to North America, was widespread during the Pleistocene, reaching as far north as Alaska, Yukon, and Northwest Territories. Twenty-two specimens collected from 10 localities in the Old Crow Basin, northern Yukon, include several bones that can be referred to Jefferson's ground sloth (Megalonyx jeffersonii) on the basis of the distinctive morphology of the upper and lower caniniform teeth. All of the Yukon specimens are relatively small, suggesting a geological age earlier than Wisconsinan - probably Sangamonian. The Alaskan, Yukon, and Northwest Territories records imply that the species occupied a broad east-west range in northwestern North America during a warm phase of the late Pleistocene. Le paresseux marcheur Megalonyx, de la taille d'un ours, qui était endémique à l'Amérique du Nord, occupait au pléistocène une vaste aire s'étendant au Nord jusqu'en Alaska, au Yukon et aux Territoires du Nord-Ouest. Vingt-deux spécimens recueillis à 10 emplacements dans le bassin de Old Crow (partie nord du Yukon), comprennent plusieurs os que l'on peut attribuer au paresseux marcheur de Jefferson (Megalonyx jeffersonii) si l'on se fie à la morphologie particulière des dents supérieures et inférieures en forme de canines. Tous les spécimens du Yukon ont une taille relativement petite, ce qui suggère qu'ils datent d'un âge géologique antérieur au wisconsinien - probablement le sangamonien. Les relevés faits en Alaska, au Yukon et dans les Territoires du Nord-Ouest laissent entendre que l'espèce occupait une vaste aire s'étendant d'est en ouest dans la partie nord-occidentale de l'Amérique du Nord durant une phase de réchauffement du pléistocène tardif.

Fire Emergency Evacuation from a School Building Using an Evolutionary Virtual Reality Platform

In the last few years, modern technologies such as numerical simulations, virtual and augmented reality, and agent-based models represented effective tools to study phenomena, which may not be experimentally reproduced due to costs, inherent hazards, or other constraints (e.g., fire or earthquake emergencies and evacuation from buildings). This paper shows how to integrate a virtual reality platform with numerical simulation tools to reproduce an evolutionary fire emergency scenario. It is computed in real time based on the building information model and a fluid dynamic software. A specific software was also used to simulate in real time the crowd dynamic in the virtual environment during the emergency evacuation process. To demonstrate the applicability of the proposed methodology, the emergency fire evacuation process for an existing school building is presented. The results show that the proposed virtual reality-based system can be employed for reproducing fire emergency scenarios. It can be used to help decision-makers to determine emergency plans and to help firefighters as a training tool to simulate emergency evacuation actions

Deuterium retention and erosion in liquid Sn samples exposed to D2 and Ar plasmas in GyM device

The use of tin (Sn) as a liquid metal for plasma facing components has been recently proposed as a solution to the high heat load issue on the divertor target plates in nuclear fusion reactors. Due to its low vapor pressure, low reactivity with hydrogen and good resilience to neutron impact, tin is a good candidate as plasma facing component. However its high atomic number poses concerns about plasma contamination.In this paper two fundamental aspects have been investigated: deuterium retention and erosion fluxes from the Sn surface towards the plasma. The samples were exposed to plasma inside the linear machine GyM in magnetic cusp configuration. This setup permits to expose free liquid specimens without the need for the Capillary Porous System. Moreover it permits to lower the magnetic field in order to increase Sn Larmor radius and consequently limit Sn re-deposition in erosion experiments.Ex-situ analyses by ion beam diagnostics on solid samples exposed to deuterium plasma have proved that the amount of retained atomic deuterium is very low, approximately 0.18 at% estimated by Nuclear Reaction Analysis and 0.25 at% estimated by Elastic Recoil Detection Analysis.In the framework of erosion studies, the spectroscopic parameter S/XB was evaluated in Ar plasma for the SnI line at 380.1 nm by Optical Emission Spectroscopy and mass loss measurements in the 5–11 eV Te range, at a density ne ∼ 1.5 × 1011 cm−3. An average value of 150 ± 23 was obtained. Keywords: Liquid metals, Deuterium retention, Erosion, Double-cusp magnetic configuration, Ion beam diagnostics, S/XB spectroscopic paramete

Shwachman-Bodian-Diamond syndrome (SBDS) protein is a direct inhibitor of protein phosphatase 2A (PP2A) activity and overexpressed in acute myeloid leukaemia.

Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase inactivated in many cancers including acute myeloid leukaemia (AML). Activation of PP2A is emerging as a therapeutic strategy, however the mechanisms underpinning PP2A inhibition are not well understood. Using myeloid progenitor cells harbouring oncogenic mutant c-KIT and characterised by PP2A inhibition, we have identified the ribosome biogenesis protein SBDS, as a target of the PP2A activating drugs FTY720 and AAL(S). We show SBDS binds to PP2A complexes comprised of the B55α regulatory subunit of PP2A. shRNA mediated knockdown of SBDS increased PP2A activity and induced apoptosis. At diagnosis, AML patients expressed significantly more SBDS mRNA than healthy controls, with relapsed patients expressing significantly more SBDS mRNA than both healthy controls and patients at diagnosis. Together, our data presents a role for SBDS in the dysregulation of PP2A in AML

The relationship between seminal leukocytes, oxidative status in the ejaculate, and apoptotic markers in human spermatozoa

The aim of this study was to investigate the relationship between seminal leukocytes, reactive oxygen species (ROS) production in the ejaculate, and markers of apoptosis in human spermatozoa. Semen samples were collected from 60 patients attending fertility clinics at the Reproductive Biology Unit at Tygerberg Academic Hospital and Vincent Pallotti Hospital, Cape Town, South Africa. The concentration of seminal leukocytes was determined and was correlated with ROS production in the ejaculate, the percentage of superoxide (·O2 )- and hydrogen peroxide (H2O2)-positive spermatozoa, glutathione activation in the ejaculate, and with markers of apoptosis in spermatozoa, namely cysteine-dependent aspartate-directed proteases (caspase)-3/7 activation, mitochondrial membrane potential (ΔΨm), and the percentage of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive sperm. Significant correlations with the concentration of seminal leukocytes were found for ROS production in the ejaculate, the percentage of ·O2 -positive spermatozoa, and caspase-3/7 activation in the ejaculate. Leukocytospermic samples showed significantly higher ROS production, percentage of ·O2 -positive sperm, GSH activation, and caspase-3/7 activation compared to non-leukocytospermic samples. The percentage of ·O2 -positive sperm was significantly correlated with sperm ΔΨm and caspase-3/7 activation in the ejaculate. Sperm ΔΨm and TUNEL-positive sperm did not correlate with seminal leukocyte concentration. Data demonstrate that high seminal leukocyte concentrations that leads to increased seminal ROS production, and is also associated with caspase activation in the male germ cell and increased mitochondrial ROS production. The latter could possibly be a result of disturbed ΔΨm. The activation of caspase-3/7 could then follow the increased intrinsic superoxide levels due to depleted intrinsic glutathione (GSH). These cellular events might not directly and immediately lead to DNA fragmentation as an endpoint of apoptosis because of topological hindrances.Web of Scienc

Dissection of DLBCL Microenvironment Provides a Gene Expression-Based Predictor of Survival Applicable to Formalin-Fixed Paraffin-Embedded Tissue

Background Gene expression profiling (GEP) studies recognized a prognostic role for tumor microenvironment (TME) in diffuse large B-cell lymphoma (DLBCL), but the routinely adoption of prognostic stromal signatures remains limited. Patients and methods Here, we applied the computational method CIBERSORT to generate a 1028-gene matrix incorporating signatures of 17 immune and stromal cytotypes. Then, we carried out a deconvolution on publicly available GEP data of 482 untreated DLBCLs to reveal associations between clinical outcomes and proportions of putative tumor-infiltrating cell types. Forty-five genes related to peculiar prognostic cytotypes were selected and their expression digitally quantified by NanoString technology on a validation set of 175 formalin-fixed, paraffin-embedded DLBCLs from two randomized trials. Data from an unsupervised clustering analysis were used to build a model of clustering assignment, whose prognostic value was also assessed on an independent cohort of 40 cases. All tissue samples consisted of pretreatment biopsies of advanced-stage DLBCLs treated by comparable R-CHOP/R-CHOP-like regimens. Results In silico analysis demonstrated that higher proportion of myofibroblasts (MFs), dendritic cells, and CD4+ T cells correlated with better outcomes and the expression of genes in our panel is associated with a risk of overall and progression-free survival. In a multivariate Cox model, the microenvironment genes retained high prognostic performance independently of the cell-of-origin (COO), and integration of the two prognosticators (COO\u2009+\u2009TME) improved survival prediction in both validation set and independent cohort. Moreover, the major contribution of MF-related genes to the panel and Gene Set Enrichment Analysis suggested a strong influence of extracellular matrix determinants in DLBCL biology. Conclusions Our study identified new prognostic categories of DLBCL, providing an easy-to-apply gene panel that powerfully predicts patients\u2019 survival. Moreover, owing to its relationship with specific stromal and immune components, the panel may acquire a predictive relevance in clinical trials exploring new drugs with known impact on TME