Direct Rivaroxaban-Induced Factor Xa Inhibition Proves to be Cardioprotective in Rats

BACKGROUND: Acute myocardial infarction is a leading cause of death worldwide. Though highly beneficial, reperfusion of myocardium is associated with reperfusion injury. While indirect inhibition of Factor Xa has been shown to attenuate myocardial ischemia-reperfusion (I/R) injury, the underlying mechanism remains unclear. Our study sought to evaluate the effect of rivaroxaban (RIV), a direct inhibitor of Factor Xa, on myocardial I/R injury and determine its cellular targets. EXPERIMENTAL APPROACH: We used a rat model of 40-minutes coronary ligation followed by reperfusion. RIV (3 mg/Kg) was given per os 1 hour before reperfusion. Infarct size and myocardial proteic expression of survival pathways were assessed at 120 and 30 minutes of reperfusion, respectively. Plasmatic levels of P-selectin and von Willebrand factor were measured at 60 minutes of reperfusion. Cellular RIV effects were assessed using hypoxia-reoxygenation (H/R) models on human umbilical vein endothelial cells and on rat cardiomyoblasts (H9c2 cell line). KEY RESULTS: RIV decreased infarct size by 21% (42.9% vs. 54.2% in RIV-treated rats and controls respectively, p < 0.05) at blood concentrations similar to human therapeutic (387.7 ± 152.3 ng/mL) levels. RIV had no effect on H/R-induced modulation of endothelial phenotype, nor did it alter myocardial activation of RISK and SAFE pathways at 30 min after reperfusion. However, RIV exerted a cytoprotective effect on H9c2 cells submitted to H/R. CONCLUSION: RIV decreased myocardial I/R injury in rats at concentrations similar to human therapeutic ones. This protection was not associated with endothelial phenotype modulation but rather with potential direct cytoprotection on cardiomyocytes

Voltage controlled terahertz transmission through GaN quantum wells

We report measurements of radiation transmission in the 0.220--0.325 THz frequency domain through GaN quantum wells grown on sapphire substrates at room and low temperatures. A significant enhancement of the transmitted beam intensity with the applied voltage on the devices under test is found. For a deeper understanding of the physical phenomena involved, these results are compared with a phenomenological theory of light transmission under electric bias relating the transmission enhancement to changes in the differential mobility of the two-dimensional electron gas

The distribution of soil micro-nutrients and the effects on herbage micro-nutrient uptake and yield in three different pasture systems

Pasture micro-nutrient concentrations are often deficient for herbage productivity and the health of livestock. The aim of this study was to investigate soil and herbage micro-nutrient content and the effects on yield on the three pasture systems of the North Wyke Farm Platform (NWFP): high-sugar grass + legume mix minus nitrogen (N) fertilizer (blue/HSG + L); permanent pasture plus N fertilizer (green/P + N); high-sugar grass plus N fertilizer (red/HSG + N). The locations with high soil total micro-nutrient concentrations had a greater slope and higher soil organic matter (SOM) content. Herbage micro-nutrient concentrations were often greater at the locations with high soil total micro-nutrient concentrations. The concentration and uptake of nearly all mi-cro-nutrients was greatest in the herbage of the green/P + N system, which had the highest SOM content, whereas they were often lowest in the red/HSG + N system, which had the lowest SOM and the highest yield, indicating biomass dilution of micro-nutrients in the herbage. At the loca-tions with high soil micro-nutrient concentrations, yield was higher than at locations with low micro-nutrient concentrations, and was equal across the three pasture systems, regardless of fertilizer N treatment. Variation in micro-nutrient uptake/yield in the blue grass–legume system was predominantly explained by the soil molybdenum (Mo) concentration, possibly relating to the requirement for Mo in biological nitrogen fixation. There was, therefore, a trade-off in ploughing and re-seeding for higher yield, with the maintenance of SOM being important for herbage micro-nutrient content

Potential impacts of climate change on habitat suitability for the Queensland fruit fly

Anthropogenic climate change is a major factor driving shifts in the distributions of pests and invasive species. The Queensland fruit fly, Bactrocera tryoni Froggatt (Qfly), is the most economically damaging insect pest of Australia's horticultural industry, and its management is a key priority for plant protection and biosecurity. Identifying the extent to which climate change may alter the distribution of suitable habitat for Qfly is important for the development and continuation of effective monitoring programs, phytosanitary measures, and management strategies. We used Maxent, a species distribution model, to map suitable habitat for Qfly under current climate, and six climate scenarios for 2030, 2050 and 2070. Our results highlight that south-western Australia, northern regions of the Northern Territory, eastern Queensland, and much of south-eastern Australia are currently suitable for Qfly. This includes southern Victoria and eastern Tasmania, which are currently free of breeding populations. There is substantial agreement across future climate scenarios that most areas currently suitable will remain so until at least 2070. Our projections provide an initial estimate of the potential exposure of Australia's horticultural industry to Qfly as climate changes, highlighting the need for long-term vigilance across southern Australia to prevent further range expansion of this species

Hydrophilic polymer embolism identified in brain tumor specimens following Wada testing: A report of 2 cases

Hydrophilic polymers are commonly used as coatings on intravascular medical devices. As intravascular pro-cedures continue to increase in frequency, the risk of embolization of this material throughout the body has become evident. These emboli may be discovered incidentally but can result in serious complications includ-ing death. Here, we report the first two cases of hydrophilic polymer embolism (HPE) identified on brain tu-mor resection following Wada testing. One patient experienced multifocal vascular complications and diffuse cerebral edema, while the other had an uneventful postoperative course. Wada testing is frequently per-formed during preoperative planning prior to epilepsy surgery or the resection of tumors in eloquent brain regions. These cases demonstrate the need for increased recognition of this histologic finding to enable fur-ther correlation with clinical outcomes

Nonlinear electron transport in normally pinched-off quantum wire

Nonlinear electron transport in normally pinched-off quantum wires was studied. The wires were fabricated from AlGaAs/GaAs heterostructures with high-mobility two-dimensional electron gas by electron beam lithography and following wet etching. At certain critical source-drain voltage the samples exhibited a step rise of the conductance. The differential conductance of the open wires was noticeably lower than e^2/h as far as only part of the source-drain voltage dropped between source contact and saddle-point of the potential relief along the wire. The latter limited the electron flow injected to the wire. At high enough source-drain voltages the decrease of the differential conductance due to the real space transfer of electrons from the wire in GaAs to the doped AlGaAs layer was found. In this regime the sign of differential magnetoconductance was changed with reversing the direction of the current in the wire or the magnetic field, whet the magnetic field lies in the heterostructure plane and is directed perpendicular to the current. The dependence of the differential conductance on the magnetic field and its direction indicated that the real space transfer events were mainly mediated by the interface scattering.Comment: LaTeX 2e (epl.cls) 6 pages, 3 figure

Computational system identification of continuous-time nonlinear systems using approximate Bayesian computation

In this paper, we derive a system identification framework for continuous-time nonlinear systems, for the first time using a simulation-focused computational Bayesian approach. Simulation approaches to nonlinear system identification have been shown to outperform regression methods under certain conditions, such as non-persistently exciting inputs and fast-sampling. We use the approximate Bayesian computation (ABC) algorithm to perform simulation-based inference of model parameters. The framework has the following main advantages: (1) parameter distributions are intrinsically generated, giving the user a clear description of uncertainty, (2) the simulation approach avoids the difficult problem of estimating signal derivatives as is common with other continuous-time methods, and (3) as noted above, the simulation approach improves identification under conditions of non-persistently exciting inputs and fast-sampling. Term selection is performed by judging parameter significance using parameter distributions that are intrinsically generated as part of the ABC procedure. The results from a numerical example demonstrate that the method performs well in noisy scenarios, especially in comparison to competing techniques that rely on signal derivative estimation

The H3K27M mutation alters stem cell growth, epigenetic regulation, and differentiation potential

BACKGROUND: Neurodevelopmental disorders increase brain tumor risk, suggesting that normal brain development may have protective properties. Mutations in epigenetic regulators are common in pediatric brain tumors, highlighting a potentially central role for disrupted epigenetic regulation of normal brain development in tumorigenesis. For example, lysine 27 to methionine mutation (H3K27M) in the H3F3A gene occurs frequently in Diffuse Intrinsic Pontine Gliomas (DIPGs), the most aggressive pediatric glioma. As H3K27M mutation is necessary but insufficient to cause DIPGs, it is accompanied by additional mutations in tumors. However, how H3K27M alone increases vulnerability to DIPG tumorigenesis remains unclear. RESULTS: Here, we used human embryonic stem cell models with this mutation, in the absence of other DIPG contributory mutations, to investigate how H3K27M alters cellular proliferation and differentiation. We found that H3K27M increased stem cell proliferation and stem cell properties. It interfered with differentiation, promoting anomalous mesodermal and ectodermal gene expression during both multi-lineage and germ layer-specific cell specification, and blocking normal differentiation into neuroectoderm. H3K27M mutant clones exhibited transcriptomic diversity relative to the more homogeneous wildtype population, suggesting reduced fidelity of gene regulation, with aberrant expression of genes involved in stem cell regulation, differentiation, and tumorigenesis. These phenomena were associated with global loss of H3K27me3 and concordant loss of DNA methylation at specific genes in H3K27M-expressing cells. CONCLUSIONS: Together, these data suggest that H3K27M mutation disrupts normal differentiation, maintaining a partially differentiated state with elevated clonogenicity during early development. This disrupted response to early developmental cues could promote tissue properties that enable acquisition of additional mutations that cooperate with H3K27M mutation in genesis of DMG/DIPG. Therefore, this work demonstrates for the first time that H3K27M mutation confers vulnerability to gliomagenesis through persistent clonogenicity and aberrant differentiation and defines associated alterations of histone and DNA methylation

Collaboration between Science and Religious Education teachers in Scottish Secondary schools

The article reports on quantitative research that examines: (1) the current practice in collaboration; and (2) potential for collaboration between Science and Religious Education teachers in a large sample of Scottish secondary schools. The authors adopt and adapt three models (conflict; concordat and consonance) to interrogate the relationship between science and religion (and the perceived relation between these two subjects in schools) (Astley and Francis 2010). The findings indicate that there is evidence of limited collaboration and, in a few cases, a dismissive attitude towards collaboration (conflict and concordat and very weak consonance). There is, however, evidence of a genuine aspiration for greater collaboration among many teachers (moving towards a more robust consonance model). The article concludes by discussing a number of key factors that must be realised for this greater collaboration to be enacted

SoLid : Search for Oscillations with Lithium-6 Detector at the SCK-CEN BR2 reactor

Sterile neutrinos have been considered as a possible explanation for the recent reactor and Gallium anomalies arising from reanalysis of reactor flux and calibration data of previous neutrino experiments. A way to test this hypothesis is to look for distortions of the anti-neutrino energy caused by oscillation from active to sterile neutrino at close stand-off (similar to 6-8m) of a compact reactor core. Due to the low rate of anti-neutrino interactions the main challenge in such measurement is to control the high level of gamma rays and neutron background. The SoLid experiment is a proposal to search for active-to-sterile anti-neutrino oscillation at very short baseline of the SCK center dot CEN BR2 research reactor. This experiment uses a novel approach to detect anti-neutrino with a highly segmented detector based on Lithium-6. With the combination of high granularity, high neutron-gamma discrimination using 6LiF:ZnS(Ag) and precise localization of the Inverse Beta Decay products, a better experimental sensitivity can be achieved compared to other state-of-the-art technology. This compact system requires minimum passive shielding allowing for very close stand off to the reactor. The experimental set up of the SoLid experiment and the BR2 reactor will be presented. The new principle of neutrino detection and the detector design with expected performance will be described. The expected sensitivity to new oscillations of the SoLid detector as well as the first measurements made with the 8 kg prototype detector deployed at the BR2 reactor in 2013-2014 will be reported