Magnetar giant flare high-energy emission

High energy ($> 250$ keV) emission has been detected persisting for several tens of seconds after the initial spike of magnetar giant flares. It has been conjectured that this emission might arise via inverse Compton scattering in a highly extended corona generated by super-Eddington outflows high up in the magnetosphere. In this paper we undertake a detailed examination of this model. We investigate the properties of the required scatterers, and whether the mechanism is consistent with the degree of pulsed emission observed in the tail of the giant flare. We conclude that the mechanism is consistent with current data, although the origin of the scattering population remains an open question. We propose an alternative picture in which the emission is closer to that star and is dominated by synchrotron radiation. The $RHESSI$ observations of the December 2004 flare modestly favor this latter picture. We assess the prospects for the Fermi Gamma-Ray Space Telescope to detect and characterize a similar high energy component in a future giant flare. Such a detection should help to resolve some of the outstanding issues.Comment: 20 pages, 14 figure

Ectonucleoside triphosphate diphosphohydrolase-1/CD39 affects the response to ADP of female rat platelets

There is evidence that an imbalance of extracellular purine levels may be associated with increased cardiovascular risk. Platelets play a pivotal role in vascular homeostasis and thrombosis and are important source of purine nucleotides and nucleosides. Hydrolysis of nucleotides ATP and ADP is regulated by two ectonucleotidases, triphosphate diphosphohydrolase-1 (NTPDase-1/CD39) and ecto-5’-nucleotidase (ecto-5’-NT/CD73). CD39 enzyme is expressed on the endothelium, circulating blood cells, and smooth muscle cells; there is evidence that changes in CD39 expression and activity affects the potential thrombogenic of a tissue. Gender difference in the cardiovascular risk has been extensively observed; however, while the age-dependent difference in the prevalence of cardiovascular events between men and women has been attributed to the loss of the protective effect of estrogens in the postmenopausal period, the physiological mechanism behind gender disparity is still unclear. Here, we evaluated comparatively male and female rat platelet reactivity and considered the possible role of CD39 at the basis of difference observed. We found a reduced in vitro response to ADP (1–30 µM) of female compared to male platelets, associated to increased platelet CD39 expression and activity. Platelet response to ADP was strongly increased by incubation (10 min) with the CD39 inhibitor, ARL67156 (100 µM), while male platelet response was unaffected. Rat treatment with clopidogrel (30 mg/kg, per os) inhibited ex vivo platelet aggregation. Bleeding time was prolonged in female compared to male. Taken together, our results suggest that platelet ATPase and ADPase activity might be a reliable predictor of platelet reactivity

Why do some asthma patients respond poorly to glucocorticoid therapy?

Glucocorticosteroids are the first-line therapy for controlling airway inflammation in asthma. They bind intracellular glucocorticoid receptors to trigger increased expression of anti-inflammatory genes and suppression of pro-inflammatory gene activation in asthmatic airways. In the majority of asthma patients, inhaled glucocorticoids are clinically efficacious, improving lung function and preventing exacerbations. However, 5–10 % of the asthmatic population respond poorly to high dose inhaled and then systemic glucocorticoids. These patients form a category of severe asthma associated with poor quality of life, increased morbidity and mortality, and constitutes a major societal and health care burden. Inadequate therapeutic responses to glucocorticoid treatment is also reported in other inflammatory conditions such as rheumatoid arthritis and inflammatory bowel disease; however, asthma represents the most studied steroid-refractory disease. Several cellular and molecular events underlying glucocorticoid resistance in asthma have been identified involving abnormalities of glucocorticoid receptor signaling pathways. These events have been strongly related to immunological dysregulation, genetic, and environmental factors such as cigarette smoking or respiratory infections. A better understanding of the multiple mechanisms associated with glucocorticoid insensitivity in asthma phenotypes could improve quality of life for people with asthma but would also provide transferrable knowledge for other inflammatory diseases. In this review, we provide an update on the molecular mechanisms behind steroid-refractory asthma. Additionally, we discuss some therapeutic options for treating those asthmatic patients who respond poorly to glucocorticoid therapy

MicroRNA Roles in Cell Reprogramming Mechanisms

Cell reprogramming is a groundbreaking technology that, in few decades, generated a new paradigm in biomedical science. To date we can use cell reprogramming to potentially generate every cell type by converting somatic cells and suitably modulating the expression of key transcription factors. This approach can be used to convert skin fibroblasts into pluripotent stem cells as well as into a variety of differentiated and medically relevant cell types, including cardiomyocytes and neural cells. The molecular mechanisms underlying such striking cell phenotypes are still largely unknown, but in the last decade it has been proven that cell reprogramming approaches are significantly influenced by non-coding RNAs. Specifically, this review will focus on the role of microRNAs in the reprogramming processes that lead to the generation of pluripotent stem cells, neurons, and cardiomyocytes. As highlighted here, non-coding RNA-forced expression can be sufficient to support some cell reprogramming processes, and, therefore, we will also discuss how these molecular determinants could be used in the future for biomedical purposes

Keck and Gemini spectral characterization of Lucy mission fly-by target (152830) Dinkinesh

Recently, the inner main belt asteroid (152830) Dinkinesh was identified as an additional fly-by target for the Lucy mission. The heliocentric orbit and approximate absolute magnitude of Dinkinesh are known, but little additional information was available prior to its selection as a target. In particular, the lack of color spectrophotometry or spectra made it impossible to assign a spectral type to Dinkinesh from which its albedo could be estimated. We set out to remedy this knowledge gap by obtaining visible wavelength spectra with the Keck telescope on 2022 November 23 and with Gemini-South on 2022 December 27. The spectra measured with the Keck I/Low Resolution Imaging Spectrometer (LRIS) and the Gemini South/Gemini Multi-Object Spectrograph South (GMOS-S) are most similar to the average spectrum of S- and Sq-type asteroids. The most diagnostic feature is the $\approx$15$\pm$1$\%$ silicate absorption feature at $\approx$0.9-1.0~micron. Small S- and Sq-type asteroids have moderately high albedos ranging from 0.17-0.35. Using this albedo range for Dinkinesh in combination with measured absolute magnitude, it is possible to derive an effective diameter and surface brightness for this body. The albedo, size and surface brightness are important inputs required for planning a successful encounter by the Lucy spacecraft.Comment: 7 pages, 1 figure. Under review in Icaru

Fatigue assessment of Ti-6Al-4V titanium alloy laser welded joints in absence of filler material by means of full-field techniques

The aim of this research activity was to study the fatigue behavior of laser welded joints of titanium alloy, in which the welding was performed using a laser source and in the absence of filler material, by means of unconventional full field techniques: Digital Image Correlation (DIC), and Infrared Thermography (IRT). The DIC technique allowed evaluating the strain gradients around the welded zone. The IRT technique allowed analyzing the thermal evolution of the welded surface during all the fatigue tests. The fatigue limit estimated using the Thermographic Method corresponds with good approximation to the value obtained from the experimental fatigue tests. The obtained results provided useful information for the development of methods and models to predict the fatigue behavior of welded T-joints in titanium alloy

Computational simulation methodologies for mechanobiological modelling: a cell-centred approach to neointima development in stents

The design of medical devices could be very much improved if robust tools were available for computational simulation of tissue response to the presence of the implant. Such tools require algorithms to simulate the response of tissues to mechanical and chemical stimuli. Available methodologies include those based on the principle of mechanical homeostasis, those which use continuum models to simulate biological constituents, and the cell-centred approach, which models cells as autonomous agents. In the latter approach, cell behaviour is governed by rules based on the state of the local environment around the cell; and informed by experiment. Tissue growth and differentiation requires simulating many of these cells together. In this paper, the methodology and applications of cell-centred techniques—with particular application to mechanobiology—are reviewed, and a cell-centred model of tissue formation in the lumen of an artery in response to the deployment of a stent is presented. The method is capable of capturing some of the most important aspects of restenosis, including nonlinear lesion growth with time. The approach taken in this paper provides a framework for simulating restenosis; the next step will be to couple it with more patient-specific geometries and quantitative parameter data

Identification of Faba bean genetic loci associated with quantitative resistance to the fungus Botrytis fabae, causal agent of chocolate spot

Introduction: Chocolate spot, caused by the ascomycete fungus Botrytis fabae, is a devastating foliar disease and a major constraint on the quality and yield of faba beans (Vicia faba). The use of fungicides is the primary strategy for controlling the disease. However, high levels of partial genetic resistance have been identified and can be exploited to mitigate the disease. Methods: The partially resistant V. faba cultivar Maris Bead and susceptible Egyptian accession ig70726 were crossed, and a genetic mapping population of 184 individuals was genotyped in the F2 generation and screened for resistance to B. fabae infection in the F3, F5, and F6 generations in a series of field experiments. A high-density linkage map of V. faba containing 3897 DArT markers spanning 1713.7 cM was constructed. Results: Multiple candidate quantitative trait loci (QTLs) in 11 separate regions of the V. faba genome were identified; some on chromosomes 2, 3, and 6 overlapped with loci previously linked to resistance to Ascochyta leaf and pod blight caused by the necrotrophic fungus Ascochyta fabae. A transcriptomics experiment was conducted at 18 h post-inoculation in seedlings of both parents of the mapping population, identifying several differentially expressed transcripts potentially involved in early stage defence against B. fabae, including cell-wall associated protein kinases, NLR genes, and genes involved in metabolism and response to reactive oxygen species. Discussion: This study identified several novel candidate QTLs in the V. faba genome that contribute to partial resistance to chocolate spot, but differences between growing seasons highlighted the importance of multi-year phenotyping experiments when searching for candidate QTLs for partial resistance

Coronary covered stents

Covered stents offer an effective bail-out strategy in vessel perforations, are an alternative to surgery for the exclusion of coronary aneurysms, and have a potential role in the treatment of friable embolisation-prone plaques. The aim of this manuscript is to offer an overview of currently available platforms and to report results obtained in prior studies