Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of interleukin‐1β and interleukin‐1 receptor antagonist in oxLDL‐treated human aortic smooth muscle cells and in the neointima of cholesterol‐fed endothelia‐denuded rabbits

The migration of vascular smooth muscle cells (VSMCs) from the media to the intima and the proliferation of intimal VSMCs are key events in restenotic lesion development. These events, which are preceded and accompanied by inflammation, are modulated by the proinflammatory cytokine, interleukin‐1β (IL‐1β), which induces vascular smooth muscle cells to express adhesion molecules and to proliferate. IL‐1β action is complex and regulated, in part, by its naturally occurring inhibitor, the IL‐1 receptor antagonist (IL‐1ra). Whether there was a temporal and spatial correlation between IL‐1β and IL‐1ra expression in, and release by, oxidized low density lipoproteins (oxLDL)‐stimulated human aortic smooth muscle cells (HASMCs) was determined by using ELISA and Western blot. In addition, IL‐1β and IL‐1ra expression was detected in the neointima of endothelia‐denuded cholesterol‐fed New Zealand white rabbits by immunohistochemistry and Western blot. In HASMCs, oxLDL induced IL‐β and IL‐1ra expression and release in a dose‐ and time‐dependent manner. Treatment with 20 μg/ml oxLDL resulted in increased IL‐1β release after 6 h, which peaked at 24 h, and in increased IL‐1ra release, first seen after 12 h, but continuing to increase for at least 48 h. In the cells, IL‐β expression showed a similar pattern to release, whereas IL‐1ra expression was seen in unstimulated cells and was not increased by oxLDL treatment. Confocal microscopy showed colocalization of IL‐β and IL‐1ra expression in oxLDL‐stimulated HASMCs. oxLDL caused significant induction of nuclear factor kappa B and activator protein‐1 DNA binding activity in HASMCs (6.6‐ and 3.3‐fold, respectively). In cholesterol‐fed endothelia‐denuded rabbits, the notably thickened intima showed significant IL‐1β and IL‐1ra expression. These results provide further support for the role of IL‐1 system in the pathogenesis of restenosis. This is the first demonstration of IL‐1β and IL‐1ra expression and secretion of oxLDL‐treated HASMCs and their expression in the rabbit neointima, suggesting that the smooth muscle cells of the intima are an important source of these factors. © 2003 Wiley‐Liss, Inc.
Neuro-Dynamic Programming : An Overview

Neuro-dynamic programming (NDP for short) is a relatively new class of dynamic programming methods for control and sequential decision making under uncertainty. These methods have the potential of dealing with problems that for a long time were thought to be intractable due to either a large state space or the lack of an accurate model. They combine ideas from the fields of neural networks, artificial intelligence, cognitive science, simulation, and approximation theory. We will delineate the major conceptual issues, survey a number of recent developments, describe some computational experience, and address a number of open questions. We consider systems where decisions are made in stages. The outcome of each decision is not fully predictable but can be anticipated to some extent before the next decision is made. Each decision results in some immediate cost but also affects the context in which future decisions are to be made and therefore affects the cost incurred in future stages. Dynamic programming (DP for short) provides a mathematical formalization of the tradeoff between immediate and future costs. Generally, in DP formulations there is a discrete-time dynamic system whose state evolves according to given transition probabilities that depend on a decision/control u. In particular, if we are in state i and we choose decision u, we move to state j with given probability pij(u). Simultaneously with this transition, we incur a cost g(i, u, j). In comparing, however, the available decisions u, it is not enough to look at the magnitude of the cost g(i, u, j); we must also take into account how desirable the next state j is. We thus need a way to rank or rate states j. This is done by using the optimal cost (over all remaining stages) starting from state j, which is denoted by J∗(j). These costs can be shown to
KIT Pathway Alterations in Mucosal Melanomas of the Vulva and Other Sites

Purpose: A significant proportion of mucosal melanomas contain alterations in KIT. The aim of this study was to characterize the pattern of KIT, NRAS, and BRAF mutations in mucosal melanomas at specific sites and to assess activation of the KIT downstream RAF/MEK/extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K)/AKT pathways in mucosal melanoma specimens. Experimental Design: Seventy-one primary mucosal melanomas from various sites were studied. Mutation analysis was done by DNA sequencing. Expression of KIT, phosphorylated (p)-ERK, and p-AKT was evaluated by immunohistochemistry. Results: KIT mutations were detected in 35% (8 of 23) of vulvar, 9% (2 of 22) of anorectal, 7% (1 of 14) of nasal cavity, and 20% (1 of 5) of penile melanomas. No KIT mutations were found in 7 vaginal melanomas. The difference in KIT mutation frequency between vulvar and nonvulvar cases was statistically significant (P = 0.014). The overall frequencies of NRAS and BRAF mutations were 10% and 6%, respectively. Notably, vaginal melanomas showed a NRAS mutation rate of 43%. KIT gene amplification (≥4 copies), as assessed by quantitative real-time PCR, was observed in 19% of cases. KIT expression was associated with KIT mutation status (P < 0.001) and was more common in vulvar than nonvulvar tumors (P = 0.016). Expression of p-ERK and p-AKT was observed in 42% and 59% of tumors, respectively, and occurred irrespective of KIT/NRAS/BRAF mutation status. NRAS mutation was associated with worse overall survival in univariate analysis. Conclusions: Results show that KIT mutations are more common in vulvar melanomas than other types of mucosal melanomas and that both the RAF/MEK/ERK and PI3K/AKT pathways are activated in mucosal melanoma specimens. Clin Cancer Res; 17(12); 3933–42. ©2011 AACR.
Direct, Dense, and Deformable: Template-Based Non-rigid 3D Reconstruction from RGB Video

In this paper we tackle the problem of capturing the dense, detailed 3D geometry of generic, complex non-rigid meshes using a single RGB-only commodity video camera and a direct approach. While robust and even real-time solutions exist to this problem if the observed scene is static, for non-rigid dense shape capture current systems are typically restricted to the use of complex multi-camera rigs, take advantage of the additional depth channel available in RGB-D cameras, or deal with specific shapes such as faces or planar surfaces. In contrast, our method makes use of a single RGB video as input, it can capture the deformations of generic shapes, and the depth estimation is dense, per-pixel and direct. We first compute a dense 3D template of the shape of the object, using a short rigid sequence, and subsequently perform online reconstruction of the non-rigid mesh as it evolves over time. Our energy optimization approach minimizes a robust photometric cost that simultaneously estimates the temporal correspondences and 3D deformations with respect to the template mesh. In our experimental evaluation we show a range of qualitative results on novel datasets, we compare against an existing method that requires multi-frame optical flow, and perform a quantitative evaluation against other template-based approaches on a ground truth dataset.
Aflatoxin M1 in raw milk from different regions of São Paulo state – Brazil

A total of 635 raw milk samples from 45 dairy farms, from three regions of São Paulo state – Brazil, were evaluated during 15 months for aflatoxin M1 (AFM1). AFM1 was determined by high performance liquid chromatograph with fluorescence detection. AFM1 was detected (>0.003 µg kg−1) in 72.9%, 56.3% and 27.5% of the samples from Bauru, Araçatuba and Vale do Paraíba regions, respectively. The mean AFM1 contamination considering all the samples was 0.021 µg kg−1. Furthermore, the concentration of AFM1 was quite different among Bauru (0.038 µg kg−1), Araçatuba (0.017 µg kg−1) and Vale do Paraíba (<0.01 µg kg−1) regions. Only three samples (0.5%) had higher contamination than the tolerated limit in Brazil (0.50 µg kg−1) and 64 samples (10.1%) had a higher contamination than the maximum limit as set by the European Union (0.050 µg kg−1). The estimated AFM1 daily intake was 0.358 and 0.120 ng kg−1 body weight per day for children and adults, respectively.
Sarcomere Protein Gene Mutations in Hypertrophic Cardiomyopathy of the Elderly

Background—Hypertrophic cardiomyopathy, a familial myocardial condition caused by sarcomere protein mutations, is usually recognized by early adulthood. Hypertrophic cardiomyopathy of the elderly has similar clinical features but, notably, a later age of onset and noncontributory family history. Causes of elderly-onset hypertrophic cardiomyopathy are unknown. Methods and Results—Eighteen women and 13 men diagnosed with late-onset hypertrophic cardiomyopathy were studied. Initial symptoms occurred at 59.3 (±12.3) years, and diagnosis was made at 62.8 (±10.8) years. None had family histories of cardiomyopathy. Echocardiography demonstrated maximal left ventricular wall thickness of 19.9±3.8 mm, systolic anterior motion of the mitral valve (58%), and, in 11 individuals, left ventricular outflow tract gradients (average, 63±42.8 mm). Sarcomere protein gene analyses revealed 8 sequence variants in cardiac myosin binding protein-C (1 nonsense, 1 splice acceptor site, and 3 missense), cardiac troponin I (2 missense), and &agr;-cardiac myosin heavy chain (1 missense). Seven variants were not found in over 170 normal chromosomes; 1 variant (cardiac myosin binding protein-C Arg326Gln) also occurred in a healthy adult. Conclusions—Hypertrophic cardiomyopathy of the elderly can be a genetic disorder caused by dominant sarcomere protein mutations. The distribution of mutations in elderly-onset disease is strikingly different (P <0.00001) from that of familial, early onset hypertrophic cardiomyopathy. Whereas defects in &bgr;-cardiac myosin heavy chain, cardiac troponin T, and &agr;-tropomyosin account for >45% of familial hypertrophic cardiomyopathy, none were found here. Rather, mutations in cardiac myosin binding protein-C, troponin I, and &agr;-cardiac myosin heavy chain caused elderly-onset hypertrophic cardiomyopathy.
Comparative Evaluation of Tactile Sensation by Electrical and Mechanical Stimulation

An electrotactile display is a tactile interface that provides tactile perception by passing electrical current through the surface of the skin. It is actively used instead of mechanical tactile displays for tactile feedback because of several advantages such as its small and thin size, light weight, and high responsiveness. However, the similarities and differences between these sensations is still not clear. This study directly compares the intensity sensation of electrotactile stimulation to that of mechanical stimulation, and investigates the characteristic sensation of anodic and cathodic stimulation. In the experiment, participants underwent a 30 pps electrotactile stimulus every one second to their middle finger, and were asked to match this intensity by adjusting the intensity of a mechanical tactile stimulus to an index finger. The results showed that anodic stimulation mainly produced vibration sensation, whereas cathodic sensation produced both vibration and pressure sensations. Relatively low pressure sensation was also observed for anodic stimulation but it remains low, regardless of the increasing of electrical intensity.
Large herbivores surf waves of green-up during spring

The green wave hypothesis (GWH) states that migrating animals should track or ‘surf’ high-quality forage at the leading edge of spring green-up. To index such high-quality forage, recent work proposed the instantaneous rate of green-up (IRG), i.e. rate of change in the normalized difference vegetation index over time. Despite this important advancement, no study has tested the assumption that herbivores select habitat patches at peak IRG. We evaluated this assumption using step selection functions parametrized with movement data during the green-up period from two populations each of bighorn sheep, mule deer, elk, moose and bison, totalling 463 individuals monitored 1–3 years from 2004 to 2014. Accounting for variables that typically influence habitat selection for each species, we found seven of 10 populations selected patches exhibiting high IRG—supporting the GWH. Nonetheless, large herbivores selected for the leading edge, trailing edge and crest of the IRG wave, indicating that other mechanisms (e.g. ruminant physiology) or measurement error inherent with satellite data affect selection for IRG. Our evaluation indicates that IRG is a useful tool for linking herbivore movement with plant phenology, paving the way for significant advancements in understanding how animals track resource quality that varies both spatially and temporally.
Coffee and cigarette use: association with suicidal acts in 352 Sardinian bipolar disorder patients.

OBJECTIVE Abuse of illicit drugs and alcohol is prevalent in bipolar disorder (BPD) patients, and is an adverse prognostic factor. Much less is known about correlates of nicotine and caffeine consumption, but tobacco smoking is tentatively associated with suicidal behavior. METHODS Retrospective analysis of demographic and clinical factors among 352 longitudinally assessed DSM-IV types I and II BPD patients contrasted patients with versus without consumption of nicotine or caffeine, based on univariate comparisons and multiple regression modeling. RESULTS Current smoking (46%) and coffee drinking (74% of cases) were common, and significantly and independently associated with suicidal acts [coffee: odds ratio (OR) = 2.42, 95% confidence interval (CI): 1.15-5.09; smoking: OR = 1.79, CI: 1.02-3.15; both p < 0.001]. Risk increased with more smoking (cigarettes/day; r(s) = 0.383; p < 0.0001) and greater coffee consumption (cups/day; r(s) = 0.312; p = 0.008). Neither intake was related to yearly rates of all episodes, depressions, or manias. CONCLUSIONS This is the first report to associate suicidal acts with coffee consumption in BPD patients, and it confirmed an association with smoking. Pending further evidence, the findings underscore the importance of monitoring use of even legal and mildly psychotropic substances by BPD patients.
Asthma: from childhood to adulthood

Asthma is one of the most common chronic and potentially disabling diseases in childhood and young adulthood. Parents of children with asthma frequently ask, “Will my child ‘outgrow’ his or her asthma? ” And often, the physician wants to comfort the parents with the assurance that most children do “outgrow” their asthma. But is this true? And, if so, there remains the question of what determines this favorable outcome of asthma. In spite of advances in our understanding of the pathophysiology of asthma, the natural history of the disease is still unclear. Moreover, it is not known whether early recognition and optimal treatment of asthma have any influence on its outcome later in life. In the last 50 years, several investigators have attempted to assess the prognosis of asthma from childhood to adulthood. There are, however, several problems with the results of these studies. First of all, the diagnosis of asthma has not been clearly defined in many studies, a fact which makes it difficult to interpret the conclusions. Various terms have been used such as “asthma”, “asthmatic bronchitis”. “wheezy bronchitis”, “allergic asthma”, “bacterial asthma”, and “wheezing”, further hampering clear interpretation of the results. In this review, we have defined asthma as a syndrome characterized by variable and often reversible airM. H. Grol’, J. Gerritsen’, D. S. Postma’
Activation of ATP‐sensitive potassium currents in guinea‐pig gall‐bladder smooth muscle by the neuropeptide CGRP.

1. The actions of a neuroactive peptide, calcitonin gene‐related peptide (CGRP), and the ATP‐sensitive potassium (K+ATP) channel activator lemakalim on guinea‐pig gall‐bladder smooth muscle cells were investigated using intracellular recording from intact preparations and whole‐cell patch clamp recording from acutely dissociated myocytes. 2. CGRP and lemakalim caused a glibenclamide‐sensitive hyperpolarization of the plasma membrane of intact cells with an associated suppression of spontaneous action potentials. 3. In isolated smooth muscle cells, CGRP (10 nM) and lemakalim (10 microM) activated currents that were glibenclamide sensitive, voltage independent and potassium selective. 4. External TEA+ at 1.0 and 10.0 mM inhibited glibenclamide‐sensitive, CGRP‐activated currents by 3.8 and 66.5%, respectively. 5. Increases in the intracellular ATP concentration from 0.1 to 5.0 mM reduced the glibenclamide‐sensitive potassium current in the presence of CGRP (10 nM) or lemakalim (10 microM) by > 60%. The increase in the intracellular ATP also reduced the steady‐state glibenclamide‐sensitive current by > 80%. 6. These findings indicate that CGRP activates K+ATP channels to hyperpolarize the membrane of gall‐bladder smooth muscle cells. This hyperpolarization may be an important mechanism underlying the relaxant effects of CGRP on the gall‐bladder.
Imaging , Diagnosis , Prognosis HLA and Killer Immunoglobulin-like Receptor Genes as Outcome Predictors of Hepatitis C Virus – Related Hepatocellular Carcinoma

Purpose: We evaluated the impact of the killer immunoglobulin-like receptors (KIR) of natural killer (NK) cells and of their HLA ligands over the clinical outcome of hepatitis C virus (HCV)–related hepatocellular carcinoma after curative treatment by either surgical resection or radiofrequency thermal
Recent advances in flexible sensors for wearable and implantable devices

Flexible devices are emerging as important applications for future display, robotics, in vitro diagnostics, advanced therapies, and energy harvesting. In this review, we provide an overview of recent achievements in flexible mechanical and electrical sensing devices, focusing on the properties and functions of polymeric layers. In the order of historical development, sensing platforms are classified into four types: electronic skins for robotics and medical applications, wearable devices for in vitro diagnostics, implantable devices for human organs or tissues for surgical applications, and advanced sensing devices with additional features such as transparency, self-power, and self-healing. In all of these examples, a polymer layer is used as a versatile component including a flexible structural support and a functional material to generate, transmit, and process mechanical and electrical inputs in various ways. We briefly discuss some outlooks and future challenges toward the next steps for flexible devices. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 1429–1441, 2013
ADAR2 affects mRNA coding sequence edits with only modest effects on gene expression or splicing in vivo

ABSTRACT Adenosine deaminases bind double stranded RNA and convert adenosine to inosine. Editing creates multiple isoforms of neurotransmitter receptors, such as with Gria2. Adar2 KO mice die of seizures shortly after birth, but if the Gria2 Q/R editing site is mutated to mimic the edited version then the animals are viable. We performed RNA-Seq on frontal cortices of Adar2-/- Gria2R/R mice and littermates. We found 56 editing sites with significantly diminished editing levels in Adar2 deficient animals with the majority in coding regions. Only two genes and 3 exons showed statistically significant differences in expression levels. This work illustrates that ADAR2 is important in site-specific changes of protein coding sequences but has relatively modest effects on gene expression and splicing in the adult mouse frontal cortex.
Cortical spreading ischaemia is a novel process involved in ischaemic damage in patients with aneurysmal subarachnoid haemorrhage

The term cortical spreading depolarization (CSD) describes a wave of mass neuronal depolarization associated with net influx of cations and water. Clusters of prolonged CSDs were measured time-locked to progressive ischaemic damage in human cortex. CSD induces tone alterations in resistance vessels, causing either transient hyperperfusion (physiological haemodynamic response) in healthy tissue; or hypoperfusion [inverse haemodynamic response = cortical spreading ischaemia (CSI)] in tissue at risk for progressive damage, which has so far only been shown experimentally. Here, we performed a prospective, multicentre study in 13 patients with aneurysmal subarachnoid haemorrhage, using novel subdural opto-electrode technology for simultaneous laser-Doppler flowmetry (LDF) and direct current-electrocorticography, combined with measurements of tissue partial pressure of oxygen (ptiO2). Regional cerebral blood flow and electrocorticography were simultaneously recorded in 417 CSDs. Isolated CSDs occurred in 12 patients and were associated with either physiological, absent or inverse haemodynamic responses. Whereas the physiological haemodynamic response caused tissue hyperoxia, the inverse response led to tissue hypoxia. Clusters of prolonged CSDs were measured in five patients in close proximity to structural brain damage as assessed by neuroimaging. Clusters were associated with CSD-induced spreading hypoperfusions, which were significantly longer in duration (up to 144 min) than those of isolated CSDs. Thus, oxygen depletion caused by the inverse haemodynamic response may contribute to the establishment of clusters of prolonged CSDs and lesion progression. Combined electrocorticography and perfusion monitoring also revealed a characteristic vascular signature that might be used for non-invasive detection of CSD. Low-frequency vascular fluctuations (LF-VF) (f < 0.1 Hz), detectable by functional imaging methods, are determined by the brain's resting neuronal activity. CSD provides a depolarization block of the resting activity, recorded electrophysiologically as spreading depression of high-frequency-electrocorticography activity. Accordingly, we observed a spreading suppression of LF-VF, which accompanied spreading depression of high-frequency-electrocorticography activity, independently of whether CSD was associated with a physiological, absent or inverse haemodynamic response. Spreading suppressions of LF-VF thus allow the differentiation of progressive ischaemia and repair phases in a fashion similar to that shown previously for spreading depressions of high-frequency-electrocorticography activity. In conclusion, it is suggested that (i) CSI is a novel human disease mechanism associated with lesion development and a potential target for therapeutic intervention in stroke; and that (ii) prolonged spreading suppressions of LF-VF are a novel ‘functional marker’ for progressive ischaemia.
[Detection, evaluation, and treatment of high blood cholesterol in adults].

This report is based on the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, which was recently issued by the National Institutes of Health of the United States of America. Also known as the Adult Treatment Panel (ATP) III, this new report updates two earlier such reports on high cholesterol. While continuing to concentrate on treating patients with coronary heart disease, the new report advocates more intensive treatment in order to reduce low-density lipoprotein (LDL) cholesterol in specific groups of individuals, pays special attention to primary prevention among patients with multiple risk factors, and recognizes as a secondary prevention concern a cluster of heart disease risk factors known as "the metabolic syndrome. " Other issues that the ATP III report covers include therapeutic lifestyle changes to reduce LDL, LDL-lowering drug therapy, and the management of specific dyslipidemias.