Miracle-dz/UniFAR-FTUs huggingface dataset:
Brief Periods of Nitric Oxide Inhalation Protect against Myocardial Ischemia–Reperfusion Injury

Background:Prolonged breathing of nitric oxide reduces myocardial ischemia–reperfusion injury, but the precise mechanisms responsible for the cardioprotective effects of inhaled nitric oxide are incompletely understood. Methods:The authors investigated the fate of inhaled nitric oxide (80 parts per million) in mice and quantified the formation of nitric oxide metabolites in blood and tissues. The authors tested whether the accumulation of nitric oxide metabolites correlated with the ability of inhaled nitric oxide to protect against cardiac ischemia–reperfusion injury. Results:Mice absorbed nitric oxide in a nearly linear fashion (0.19 ± 0.02 &mgr;mol/g · h). Breathing nitric oxide rapidly increased a broad spectrum of nitric oxide metabolites. Levels of erythrocytic S-nitrosothiols, N-nitrosamines, and nitrosyl-hemes increased dramatically within 30 s of commencing nitric oxide inhalation. Marked increases of lung S-nitrosothiol and liver N-nitrosamine levels were measured, as well as elevated cardiac and brain nitric oxide metabolite levels. Breathing low oxygen concentrations potentiated the ability of inhaled nitric oxide to increase cardiac nitric oxide metabolite levels. Concentrations of each nitric oxide metabolite, except nitrate, rapidly reached a plateau and were similar after 5 and 60 min. In a murine cardiac ischemia–reperfusion injury model, breathing nitric oxide for either 5 or 60 min before reperfusion decreased myocardial infarction size as a fraction of myocardial area at risk by 31% or 32%, respectively. Conclusions:Breathing nitric oxide leads to the rapid accumulation of a variety of nitric oxide metabolites in blood and tissues, contributing to the ability of brief periods of nitric oxide inhalation to provide cardioprotection against ischemia–reperfusion injury. The nitric oxide metabolite concentrations achieved in a target tissue may be more important than the absolute amounts of nitric oxide absorbed.
Rearchitecting the music business: Mitigating music piracy by cutting out the record companies

Disintermediation - the process of removing superfluous agents in a transaction chain - has been a major promise of e-commerce. Disintermediation offers the benefits of lowering prices to consumers and a better information-feedback loop between producers and consumers. In this paper, I propose a systematic model of disintermediation in the recorded-music business. Were such a model successful and tied to digital distribution, prices to consumers would fall considerably, artist compensation would rise, online piracy would drop, and the information-feedback loops necessary for signaling consumer tastes back to artists would become far more efficient as information asymmetries were mitigated. Such a model would leverage recommender systems as a way to determine consumer choices beyond the use of simple sales figures.
Peroxisomal Proteostasis Involves a Lon Family Protein That Functions as Protease and Chaperone*

Background: A putative Lon protease has been identified in peroxisomes of various species (Pln). Results: Pln is an ATP-dependent protease that digests unfolded substrates e.g. oxidatively damaged catalase-peroxidase, and displays chaperone-like activity, circumventing accumulation of protein aggregates in peroxisomes that compromise organelle function. Conclusion: Pln is a bifunctional protein with chaperone and protease activities. Significance: Pln is crucial for peroxisome proteostasis. Proteins are subject to continuous quality control for optimal proteostasis. The knowledge of peroxisome quality control systems is still in its infancy. Here we show that peroxisomes contain a member of the Lon family of proteases (Pln). We show that Pln is a heptameric protein and acts as an ATP-fueled protease and chaperone. Hence, Pln is the first chaperone identified in fungal peroxisomes. In cells of a PLN deletion strain peroxisomes contain protein aggregates, a major component of which is catalase-peroxidase. We show that this enzyme is sensitive to oxidative damage. The oxidatively damaged, but not the native protein, is a substrate of the Pln protease. Cells of the pln strain contain enhanced levels of catalase-peroxidase protein but reduced catalase-peroxidase enzyme activities. Together with the observation that Pln has chaperone activity in vitro, our data suggest that catalase-peroxidase aggregates accumulate in peroxisomes of pln cells due to the combined absence of Pln protease and chaperone activities.
[The short version of the Japanese version of the Zarit Caregiver Burden Interview (J-ZBI_8): its reliability and validity].

The Zarit Burden Interview (ZBI) is the instrument most widely used in North America and Europe for assessing the burden experienced by family caregivers who look after the community-residing impaired elderly. The Japanese version of the ZBI (J-ZBI) is the most widely used in Japan for the same purpose. We used data from 691 caregivers in relation to their caregiver burden with the 22-item J-ZBI. Following a factor analysis, the 8-item short version of the J-ZBI, the J-ZBI_8, was proposed with the following two factors: Personal strain (5 items) and Role strain (3 items). Cronbach's alpha of the J-ZBI_8 was 0.89, indicating the high reliability of this instrument. Pearson's correlation coefficient between J-ZBI and J-ZBI_8 was 0.93, and the same coefficient between J-ZBI_8 and item 22 (a single global burden) was 0.68. These data indicated that J-ZBI_8 had a high concurrent validity. In addition, caregivers who declared that they did not encounter any difficulties in looking after the impaired elderly had a significantly lower J-ZBI_8 score (3.45; SD = 4.57) than those who claimed that they had such difficulties (9.31; SD = 7.19) by the t-test; this indicated that J-ZBI_8 had a high construct validity. These results indicated that the short version, the J-ZBI_8, had a high reliability and validity. Therefore, the J-ZBI_8 produced results comparable to those of the full version, i.e. the J-ZBI. The shorter yet no less reliable and valid 8 item version will thus lead to easier administration of the instrument for assessing family caregiver burden in clinical settings.
Morphological and functional aspects of two different types of hair cells in the goldfish sacculus.

1. With the use of whole-cell mode of the patch-clamp method, we examined the electrical responses of hair cells enzymatically isolated from the goldfish sacculus. 2. Hair cells from the rostral saccule had a short cell body and were ovoidal or eggplantlike in shape, whereas hair cells from the caudal saccule had a variable shape. Many had a longer cell body and were cylindrical or gourd-like in shape, but some short hair cells were also present in the caudal saccule. 3. The short hair cells had a resting potential of about -75 mV. In current-clamp experiments, these hair cells elicited damped oscillatory-potential changes of a relatively small amplitude in response to a depolarizing current. A current in the opposite direction produced a slow hyperpolarization, much larger in amplitude. 4. Resonant frequency of the short, or the oscillatory, type of hair cells ranged from 40 to 200 Hz or higher. However, resonance was generally of a poor quality as compared with that noted for hair cells in the turtle cochlea or frog sacculus. 5. The long hair cells had a resting potential of -90 to -100 mV. In current-clamp experiments, these hair cells elicited an all-or-none spike approximately 50 mV in amplitude in response to a depolarizing current. The spike was usually followed by a plateau, which was maintained for the duration of the depolarizing pulse. In some hair cells, damped slow oscillatory waves were evoked at a rate of 5-15 Hz. On the other hand, a hyperpolarizing current produced potential changes much smaller in amplitude. 6. Voltage-clamp experiments showed that Ca2+-activated K+ channel and A-current, especially its high-threshold subclass, were involved in the generation of outward rectification in the oscillatory-type hair cells. On the other hand, Na+, in addition to Ca2+, was involved in the generation of spike in the spike-type hair cells. Spike potentials were elicited even in the presence of tetrodotoxin (TTX), but the rate of rise was slower as compared with the intact spikes. 7. The spike-type hair cells had an inwardly rectifying K+ channel similar to that noted in the tunicate egg and chick vestibular hair cell. However, the oscillatory-type hair cells had an inwardly rectifying channel similar to the hyperpolarization-activated current, Ih, of the rod inner segment, or sinoatrial nodal cell, or lacked the inwardly rectifying channel. Differences in the resting membrane potential between the oscillatory- and spike-type hair cells are probably related to differences in the inwardly rectifying channels. 8. Effects of sound stimulation were simulated by injecting a half-wave rectified sinusoidal current of various frequencies. (ABSTRACT TRUNCATED AT 400 WORDS)
Nanometric ionic-liquid films on silica: a joint experimental and computational study

Atomic force microscopy images for [bmim][Tf2N] films deposited at ambient conditions by drop-casting show a population of terraced islands of mesoscopic area (1–100 μ2) and ∼50 nm height. The regularity of terraces and steps, stiff mechanical properties and a fragile fracture mode all suggest that the islands are solid-like, even though bulk [bmim][Tf2N] is liquid at the temperature of the experiment. Molecular dynamics simulations for a homogeneous [bmim][Tf2N] film 4 nm thick on silica also display marked layering in proximity to silica of periodicity closely matching the experimental estimate of the step height. The density modulation of the simulated sample, however, decays into an approximatively homogeneous and fluid-like density distribution ∼2 nm from the solid surface. The detailed comparison of experiments and simulations is contained in the closing section of the paper.
Combination of citrus polymethoxyflavones, green tea polyphenols, and Lychee extracts suppresses obesity and hepatic steatosis in high-fat diet induced obese mice.

SCOPE SlimTrym® is a formulated product composed of citrus polymethoxyflavones (PMFs), green tea extract, and lychee extract. We investigated the effect of dietary SlimTrym® on diet-induced obesity and associated non-alcoholic fatty liver disease (NAFLD) in mice. METHODS AND RESULTS Male C57BL/6 mice were fed a normal diet (ND), high fat diet (HFD) or HFD containing 0.1% or 0.5% SlimTrym® for 16 weeks. Dietary SlimTrym® significantly reduced weight gain and relative perigonadal, retroperitoneal, mesenteric fat weight as well as the size of adipocyte in HFD-fed mice. SlimTrym® supplementation also effectively diminished hepatic steatosis and the serum levels of glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), triacylglycerol (TG), and total cholesterol (TCHO). Down-regulation of peroxisome proliferator-activated receptor (PPAR)γ, sterol regulatory element-binding protein (SREBP)-1, and the activation of AMP-activated protein kinase (AMPK) signaling by SlimTrym® in both adipose tissue and liver may be responsible for the observed anti-obesity effects. CONCLUSION SlimTrym® supplementation potentially diminished diet-induced obesity and hepatic steatosis via regulating AMPK signaling and molecules involved in lipid metabolism.
Endovascular treatment of thoracic aortic aneurysms.

UNLABELLED Descending thoracic aortic aneurysms (TAA) and chronic dissections have high morbidity and mortality rates. For 10 years, the evolution of both imaging techniques and aortic stent-graft design has brought a new therapeutic hope for patients at high risk for surgery presenting non-ruptured or emergency cases of TAA. Our goal is to describe the endovascular technique, review its state of the art and compare its mid-term results to those of conventional surgery. We also describe surgical ways to manage complex TAA, involving the aortic arch and/or the celiac aorta, as therapeutic solutions for high risk patients for surgery with unfitted anatomy for endovascular repair. After a review of the literature dealing with the natural history, the etiology, and the surgical treatment, we describe the endovascular devices, the conventional stent-grafting technique and we detail the adjunctive procedures we used to manage complex cases. We then retrospectively report our personal 38-patient experience from October 1999 to February 2003. Thirty-three patients presented with TAA and the average age was 70 years old (35-88), while the male/female ratio was 5.3. All of them were at high risk for surgery, of which 27% required adjunctive procedures to achieve proximal and/or distal neck management. The in-hospital death rate was 9%. We reported no case of paraplegia and only 1 patient with post-operative regressive stroke (3%). All the aneurysmal sacs were successfully excluded without early endoleak. During follow-up period (mean: 2 years; 1-40 months), we observed a late death rate of 10%. All aneurysmal sac remained excluded by the endografts and no stent-graft migration was observed. No late endoleak appeared during the follow-up course, but 1 patient presented a proximal aortic enlargement, which required total transposition of the supra-aortic vessels and stent-graft extension. The endovascular repair of TAA and chronic dissections proved to be feasible and offers hopeful mid-term RESULTS With a very low morbidity-mortality rate, compared to surgery, the endovascular technique may represent an unquestionable therapeutic options, especially for patients at high risk for surgery. However, long-term results are needed to point out the durability of descending thoracic aortic stent-grafting. Neck management must be encouraged in order to avoid type 1 endoleaks in cases with short landing zones.
Cognitive development prior to onset of psychosis

Schizophrenia patients commonly exhibit substantial and diffuse cognitive impairment. Evidence suggests that subtle cognitive deficits are already apparent in childhood and adolescence, many years prior to onset of psychosis. While there is almost unequivocal evidence of some degree of cognitive impairment in individuals who later develop schizophrenia, the literature remains inconclusive regarding the exact nature of this impairment and warrants careful review and interpretation. Meta-analytic findings suggest that individuals who later develop schizophrenia, but not related disorders, such as bipolar disorder, exhibit a premorbid IQ deficit of around 8 points. Several studies have also found evidence for premorbid deficits across most cognitive domains, such as language, processing speed and executive functions. Longitudinal studies, although rare, suggest that individuals who go on to develop schizophrenia may show a course of increasing cognitive impairment prior to onset of psychosis. While evidence regarding the etiology of premorbid deficits is scarce, common and rare genetic variants, as well as environmental factors such as obstetric complications and cannabis use may play an important role and warrant further examination. In this selected review, we give an overview of population-based studies on premorbid cognitive deficits in schizophrenia, with a special focus on evidence regarding the specificity, profile and course of these deficits.
Investigating the role of FGF‐2 in stem cell maintenance by global phosphoproteomics profiling

Human embryonic stem cells (hESCs) are of immense interest for regenerative medicine as a source of tissue replacement. Expansion of hESCs as a pluripotent population requires a balance between survival, proliferation and self‐renewal signals. One of the key growth factors that maintains this balance is fibroblast growth factor‐2 (FGF‐2). However, the underlying molecular mechanisms are poorly understood. We recently profiled specifically tyrosine phosphorylation events that occur during FGF‐2 stimulation of hESCs (Ding et al., J. Cell. Physiol. 2010, 225, 417–428). Here, we complement this phosphoproteome profiling by analyzing temporal dynamics of mostly serine and threonine protein phosphorylation events. Our multi‐dimensional strategy combines strong cation exchange chromatography to reduce the sample complexity followed by titanium dioxide off‐line for the enrichment of phosphopeptides and dimethylation‐based stable isotope labeling for quantification. This approach allowed us to identify and quantify 3261 unique proteins from which 1064 proteins were found to be phosphorylated in one or more residues (representing 1653 unique phosphopeptides). Approximately 40% of the proteins (553 unique phosphopeptides) showed differential phosphorylation upon FGF‐2 treatment. Among those are several members of the canonical pathways involved in pluripotency and self‐renewal (e.g. Wnt and PI3K/AKT), hESC‐associated proteins such as SOX2, RIF1, SALL4, DPPA4, DNMT3B and 53 proteins that are target genes of the pluripotency transcription factors SOX2, OCT4 and NANOG. These findings complement existing pluripotency analyses and provide new insights into how FGF‐2 assists in maintaining the undifferentiated state of hESCs.
Cost-effectiveness analysis of treatment with epoietin-α for patients with anaemia due to renal failure: The case of Sweden

Objective. Anaemia is a common complication of renal failure. It can be treated with erythropoietin (EPO) administration, red blood cell transfusion (RBCT), or a combination of both. EPO has been registered for the treatment of renal anaemia in Sweden since the beginning of the 1990s, and is the primary treatment regimen for anaemia related to renal failure. The objective of this study was to carry out a cost-effectiveness analysis from a provider perspective of a treatment strategy comprising EPO and complementary RBCT compared to the traditional treatment of RBCT alone for patients with anaemia associated with renal failure in Sweden. Material and methods. Incremental costs and quality-adjusted life-years (QALYs) associated with EPO (epoietin-α) treatment compared to the traditional therapy of RBCT were estimated. The QALY gains were estimated using a modified version of a Markov model, which is used by the UK National Institute of Clinical Excellence in their evaluations of EPO treatment in the UK. Swedish treatment practice (i.e. EPO doses and iron supplementation), patient characteristics and unit costs were used throughout the study. Results. The estimated cost per QALY gained from administration of EPO to renal patients falls within the range acceptable in Sweden for both haemodialysis and peritoneal dialysis patients. Conclusions. EPO administration to renal patients is much more costly in Sweden than in the UK, primarily due to the higher dosage of EPO and iron supplementation used in Sweden. However, Swedish patients reach higher haemoglobin levels, and thereby achieve higher QALY gains, compared to patients in the UK.
Community-based FitSTEPS for life exercise program for persons with cancer: 5-year evaluation.

PURPOSE To determine the effects of a community-based program of exercise on quality of life (QOL) of persons with cancer over time. METHODS Participants were referred by their physician to participate in an individualized program of exercise at one of 14 community centers. The Medical Outcomes Survey, Short Form, version 2.0 (SF-36) was used to assess QOL. Individual participants were monitored for 2 years. Data collection took place at baseline, every 3 months months during year 1, and every 6 months during year 2. RESULTS Enrolled participants (n = 701) had been diagnosed with different cancers and were at all stages; 177 completed data collection for 2 years. One-way analysis of variance (n = 177) supported the positive impact of exercise on QOL over time. Significant subscale scores of the SF-36, including Physical Function (F = 2.13, P ≤ .047), Role Physical (F = 3.78, P ≤ .001), Vitality (F = 5.97, P ≤ .001), Social Function (F = 4.46, P ≤ .001), Role Emotional (F = 2.56, P ≤ .01), Mental Health (F = 2.16, P ≤ .05), and General Health (F = 3.42, P ≤ .01), were sustainable over time. CONCLUSION This research introduces the concept of a long-term community-based program of individualized exercise as a feasible and effective intervention to improve QOL for persons with all stages of cancer. Improvements, noted at the 3-month time point, appear to be sustainable for extended time (24 months). Attrition is problematic and needs to be addressed. Results from this study have significance for practice recommendations and health policy reimbursement issues.
Implementation and evaluation of adaptive video streaming based on Markov decision process

In HTTP-based adaptive streaming systems, media server simply stores video content segmented into a series of small chunks coded in different qualities and sizes. The decision for next chunk's quality level to achieve a high quality viewing experience is left to the client which is a challenging task, especially in mobile environment due to unexpected changes in network bandwidth. Using computer simulations, previous work has demonstrated that Markov decision process (MDP) is very effective for such decision making and that it can reduce video freezing or re-buffering events drastically compared to other methods of adaptation. However, to date there has been no practical implementation and evaluation of MDP-based DASH players. In this work, we extend a publicly available DASH player recently released by DASH industry forum to realise a real DASH player that implements MDP-based video adaptation. We implement two alternative MDP optimisation algorithms, value iteration and Q learning and evaluate their performances in real driving conditions under 300 minutes of video streaming. Our results show that value iteration and Q learning reduce video freezing by a factor of 8 and 11, respectively, compared to the default decision making algorithm implemented in the public DASH player.