Hot-spot formation in stacks of intrinsic Josephson junctions in Bi2Sr2CaCu2O8

We have studied experimentally and numerically temperature profiles and the formation of hot spots in intrinsic Josephson junction stacks in Bi2Sr2CaCu2O8 (BSCCO). The superconducting stacks are biased in a state where all junctions are resistive. The formation of hot spots in this system is shown to arise mainly from the strongly negative temperature coefficient of the c-axis resistivity of BSCCO at low temperatures. This leads to situations where the maximum temperature in the hot spot can be below or above the superconducting transition temperature Tc. The numerical simulations are in good agreement with the experimental observations

Short-term Wind Power Forecasting Using Advanced Statistical Methods

Disponible sur : http://anemos.cma.fr/download/publications/pub_2006_paper_EWEC06_WP3statistical.pdfInternational audienceThis paper describes some of the statistical methods considered in the ANEMOS project for short-termforecasting of wind power. The total procedure typically involves various steps, and all these steps are described in the paper. These steps include downscaling from reference MET forecasts to the actual wind farm, wind farm power curve models, dynamical models for prediction of wind power or wind speed, estimating the uncertainty of the wind power forecast, and finally, methods for upscaling are considered. The upscaling part considers how a total regional production can be estimated using a small number of reference wind farms. Keywords: Forecasting, power curve, wind farmpower curve, upscaling, uncertainty estimation, probabilistic forecasts, adaptation

CircRNAs are here to stay: A perspective on the MLL recombinome

Chromosomal translocations harbored by cancer genomes are important oncogenic drivers. In MLL rearranged acute leukemia (MLLre) MLL/KMT2A fuses with over 90 partner genes. Mechanistic studies provided clues of MLL fusion protein leukemogenic potential, but models failed to fully recapitulate the disease. Recently, expression of oncogenic fusion circular RNAs (f-circ) by MLL-AF9 fusion was proven. This discovery, together with emerging data on the importance and diversity of circRNAs formed the incentive to study the circRNAs of the MLL recombinome. Through interactions with other RNAs, such as microRNAs, and with proteins, circRNAs regulate cellular processes also related to cancer development. CircRNAs can translate into functional peptides too. MLL and most of the 90 MLL translocation partners do express circRNAs and exploration of our RNA-seq dataset of sorted blood cell populations provided new data on alternative circular isoform generation and expression variability of circRNAs of the MLL recombinome. Further, we provided evidence that rearrangements of MLL and three of the main translocation partner genes can impact circRNA expression, supported also by preliminary observations in leukemic cells. The emerging picture underpins the view that circRNAs are worthwhile to be considered when studying MLLre leukemias and provides a new perspective on the impact of chromosomal translocations in cancer cells at large

Impact of Renal Impairment on Beta-Blocker Efficacy in Patients With Heart Failure.

BACKGROUND: Moderate and moderately severe renal impairment are common in patients with heart failure and reduced ejection fraction, but whether beta-blockers are effective is unclear, leading to underuse of life-saving therapy. OBJECTIVES: This study sought to investigate patient prognosis and the efficacy of beta-blockers according to renal function using estimated glomerular filtration rate (eGFR). METHODS: Analysis of 16,740 individual patients with left ventricular ejection fraction <50% from 10 double-blind, placebo-controlled trials was performed. The authors report all-cause mortality on an intention-to-treat basis, adjusted for baseline covariates and stratified by heart rhythm. RESULTS: Median eGFR at baseline was 63 (interquartile range: 50 to 77) ml/min/1.73 m2; 4,584 patients (27.4%) had eGFR 45 to 59 ml/min/1.73 m2, and 2,286 (13.7%) 30 to 44 ml/min/1.73 m2. Over a median follow-up of 1.3 years, eGFR was independently associated with mortality, with a 12% higher risk of death for every 10 ml/min/1.73 m2 lower eGFR (95% confidence interval [CI]: 10% to 15%; p < 0.001). In 13,861 patients in sinus rhythm, beta-blockers reduced mortality versus placebo; adjusted hazard ratio (HR): 0.73 for eGFR 45 to 59 ml/min/1.73 m2 (95% CI: 0.62 to 0.86; p < 0.001) and 0.71 for eGFR 30 to 44 ml/min/1.73 m2 (95% CI: 0.58 to 0.87; p = 0.001). The authors observed no deterioration in renal function over time in patients with moderate or moderately severe renal impairment, no difference in adverse events comparing beta-blockers with placebo, and higher mortality in patients with worsening renal function on follow-up. Due to exclusion criteria, there were insufficient patients with severe renal dysfunction (eGFR <30 ml/min/1.73 m2) to draw conclusions. In 2,879 patients with atrial fibrillation, there was no reduction in mortality with beta-blockers at any level of eGFR. CONCLUSIONS: Patients with heart failure, left ventricular ejection fraction <50% and sinus rhythm should receive beta-blocker therapy even with moderate or moderately severe renal dysfunction

Goltz syndrome (focal dermal hypoplasia) with unilateral ocular, cutaneous and skeletal features: case report

<p>Abstract</p> <p>Background</p> <p>Goltz syndrome or focal dermal hypoplasia (FDH) is an uncommon multisystem disorder. Herein, we report a typical case of FDH with unilateral ocular, cutaneous and skeletal features.</p> <p>Case Presentation</p> <p>a 4-year-old girl presented with microphthalmos and iris coloboma of the left eye, facial asymmetry, and a low-set protruding ear. Cutaneous changes included hypopigmented atrophic macules on the left side of the face, chest, abdomen and limbs. Characteristic lobster claw deformity of left hand and oligodactyly and syndactyly of left foot were present.</p> <p>Conclusions</p> <p>FDH usually affects both sides of the body. This case represents the unusual unilateral manifestation of the syndrome.</p

Spatial correlation structures of wind speed and irradiance in Europe as modelled in regional climate models and the ERA5 reanalysis

Objective & Background For comprehensive energy systems analysis considering high shares of weather-dependent renewables, the spatiotemporal characteristics of meteorological input data (in particular, wind speed and irradiance) are of considerable interest. Studies aiming to evaluate the potential effects of future climate change rely on model-based projections of these variables. In order to reach as high a spatiotemporal resolution as possible, global climate models (GCM) can be used as drivers for regional climate models (RCM). In doing so, global climate effects are considered on large scales, while the higher resolution computations are limited to the domain of interest. Here, we analyse such regional climate model outputs as well as reanalysis data with regards to their suitability in energy systems analysis, using spatial correlation structures of the wind and solar resource anomalies. Method Based on 10 years of historical experiments of EURO-CORDEX regional climate model output and ERA5 reanalyses, we compute climate anomalies of both wind speed and irradiance for each point in space and time by subtracting the multi-year mean of each point from the instantaneous values at that point. In doing so, we largely remove effects of seasonal and diurnal cycles, especially in the case of irradiance. From each of these wind speed and irradiance anomaly fields, we sample distinct two-dimensional correlation structures (i.e., maps of the correlation coefficient between each pixel’s time series and a reference pixel’s series). Increasing the number of reference pixels hence increases the number of spatial correlation structures available in the analysis. We finally estimate the degree of similarity between the spatial correlation structures of each EURO-CORDEX member and its corresponding ERA5 counterpart using the coefficient of pattern correlation (i.e., the correlation coefficient of the mapped spatial correlation structures in vector form). Principal Findings Kernel density estimates and box-plot statistics of all available pattern correlations show that the wind speed anomaly spatial correlation structures tend to be better represented than their irradiance counterparts. Between different driving global models, the performance is relatively similar for wind speed anomaly correlation structures, while solar irradiance anomaly structures can be associated with a few unusually low pattern correlations for some global models. In terms of regional climate models, these cases of low pattern correlation values are largely associated with the SMHI-RCA4 regional model during the summer. Discussion This initial comparison of CORDEX model output and ERA5 reanalysis based on correlation structures in wind speed and solar irradiance anomalies allows to help in the selection of global and regional models when compiling an ensemble for use in energy systems analysis. In this context, the spatial correlation structures of wind speed need less attention when selecting model outputs, while the irradiance anomaly projections of the regional climate model SMHI-RCA4 should be handled with caution. Increasing the number of reference points used in the spatial correlation structure calculations may lead to further insights regarding potential regional differences in CORDEX model performances

Functional relevance of circRNA aberrant expression in pediatric acute leukemia with KMT2A::AFF1 fusion

: Circular RNAs (circRNAs) are emerging molecular players in leukemogenesis and promising therapeutic targets. In KMT2A::AFF1 (MLL::AF4)-rearranged leukemia, an aggressive disease compared with other pediatric B-cell precursor (BCP) acute lymphoblastic leukemia (ALL), data about circRNAs are limited. Here, we disclose the circRNA landscape of infant patients with KMT2A::AFF1 translocated BCP-ALL showing dysregulated, mostly ectopically expressed, circRNAs in leukemia cells. Most of these circRNAs, apart from circHIPK3 and circZNF609, previously associated with oncogenic behavior in ALL, are still uncharacterized. An in&nbsp;vitro loss-of-function screening identified an oncogenic role of circFKBP5, circKLHL2, circNR3C1, and circPAN3 in KMT2A::AFF1 ALL, whose silencing affected cell proliferation and apoptosis. Further study in an extended cohort disclosed a significantly correlated expression of these oncogenic circRNAs and their putative involvement in common regulatory networks. Moreover, it showed that circAFF1 upregulation occurs in a subset of cases with HOXA KMT2A::AFF1 ALL. Collectively, functional analyses and patient data reveal oncogenic circRNA upregulation as a relevant mechanism that sustains the malignant cell phenotype in KMT2A::AFF1 ALL

A Novel Fluorescent Imaging Agent for Diffuse Optical Tomography of the Breast: First Clinical Experience in Patients

Purpose: This is the first clinical evaluation of a novel fluorescent imaging agent (Omocianine) for breast cancer detection with diffuse optical tomography (DOT). Procedures: Eleven women suspected of breast cancer were imaged with DOT at multiple time points (up to 24 h) after receiving an intravenous injection of Omocianine (doses 0.01 to 0.1 mg/kg bodyweight). Breast MRI was obtained for comparison. Results: Histopathology showed invasive cancer in ten patients and fibroadenoma in one patient. With the lowest dose of Omocianine, two of three lesions were detected; with the second dose, three of three lesions were detected; with the two highest doses, none of five lesions were detected. Lesion location on DOT showed excellent agreement with MRI. Optimal lesion-tobackground signals were obtained after 8 h. No adverse events occurred. Conclusions: Lowest doses of Omocianine performed best in lesion detection; DOT using a lowdose fluorescent agent is feasible and safe for breast cancer visualization in patients

Increased Levels of Inflammatory Cytokines and Endothelin-1 in Alveolar Macrophages from Patients with Chronic Heart Failure

BACKGROUND: Pathophysiological interactions between heart and lungs in heart failure (HF) are well recognized. We investigated whether expression of different factors known to be increased in the myocardium and/or the circulation in HF is also increased in alveolar macrophages in HF. METHODOLOGY/PRINCIPAL FINDINGS: Lung function, hemodynamic parameters, gene expression in alveolar macrophages, and plasma levels in the pulmonary and femoral arteries of HF patients (n = 20) were compared to control subjects (n = 16). Our principal findings were: (1) Lung function was significantly lower in HF patients compared to controls (P<0.05). (2) mRNA levels of ET-1, tumor necrosis factor (TNF)-α and interleukin-6 (IL-6) were increased in alveolar macrophages from HF patients. (3) Plasma levels of ET-1, TNFα, IL-6 and MCP-1 were significantly increased in HF patients, whereas our data indicate a net pulmonary release of MCP-1 into the circulation in HF. CONCLUSIONS/SIGNIFICANCE: Several important cytokines and ET-1 are induced in alveolar macrophages in human HF. Further studies should clarify whether increased synthesis of these factors affects pulmonary remodeling and, directly or indirectly, adversely affects the failing myocardium