Miracle-dz/UniFAR-FTUs huggingface dataset:
Evidence for a Partially Folded Intermediate in α-Synuclein Fibril Formation*

Intracellular proteinaceous aggregates (Lewy bodies and Lewy neurites) of α-synuclein are hallmarks of neurodegenerative diseases such as Parkinson's disease, dementia with Lewy bodies, and multiple systemic atrophy. However, the molecular mechanisms underlying α-synuclein aggregation into such filamentous inclusions remain unknown. An intriguing aspect of this problem is that α-synuclein is a natively unfolded protein, with little or no ordered structure under physiological conditions. This raises the question of how an essentially disordered protein is transformed into highly organized fibrils. In the search for an answer to this question, we have investigated the effects of pH and temperature on the structural properties and fibrillation kinetics of human recombinant α-synuclein. Either a decrease in pH or an increase in temperature transformed α-synuclein into a partially folded conformation. The presence of this intermediate is strongly correlated with the enhanced formation of α-synuclein fibrils. We propose a model for the fibrillation of α-synuclein in which the first step is the conformational transformation of the natively unfolded protein into the aggregation-competent partially folded intermediate.
Gradient maintenance: A new algorithm for fast online replanning.

PURPOSE Clinical use of online adaptive replanning has been hampered by the unpractically long time required to delineate volumes based on the image of the day. The authors propose a new replanning algorithm, named gradient maintenance (GM), which does not require the delineation of organs at risk (OARs), and can enhance automation, drastically reducing planning time and improving consistency and throughput of online replanning. METHODS The proposed GM algorithm is based on the hypothesis that if the dose gradient toward each OAR in daily anatomy can be maintained the same as that in the original plan, the intended plan quality of the original plan would be preserved in the adaptive plan. The algorithm requires a series of partial concentric rings (PCRs) to be automatically generated around the target toward each OAR on the planning and the daily images. The PCRs are used in the daily optimization objective function. The PCR dose constraints are generated with dose-volume data extracted from the original plan. To demonstrate this idea, GM plans generated using daily images acquired using an in-room CT were compared to regular optimization and image guided radiation therapy repositioning plans for representative prostate and pancreatic cancer cases. RESULTS The adaptive replanning using the GM algorithm, requiring only the target contour from the CT of the day, can be completed within 5 min without using high-power hardware. The obtained adaptive plans were almost as good as the regular optimization plans and were better than the repositioning plans for the cases studied. CONCLUSIONS The newly proposed GM replanning algorithm, requiring only target delineation, not full delineation of OARs, substantially increased planning speed for online adaptive replanning. The preliminary results indicate that the GM algorithm may be a solution to improve the ability for automation and may be especially suitable for sites with small-to-medium size targets surrounded by several critical structures.
Genetic Polymorphism of CYP2D6 and CYP2C19 Metabolism Determined by Phenotyping Israeli Ethnic Groups

Genetic polymorphism of the cytochrome P450 isoenzymes CYP2D6 and CYP2C19 was determined by phenotyping four ethnic groups of the Israeli population. The groups consisted of Ethiopian subjects, Yemenite subjects, and Russian subjects representing first-generation new immigrants and an Israeli Arab group. Dextromethorphan was used as the probe for CYP2D6 activity and mephenytoin was used for CYP2C19 activity. The two drugs were administered simultaneously and urine samples were collected over a period of 8 hours. The CYP2D6 phenotype was determined from the ratio of dextromethorphan conversion to dextrorphan and the CYP2C19 phenotype from the ratio of S-mephenytoin and R-mephenytoin. The used liquid chromatographic method was able to completely separate dextrorphan and dextromethorphan. Fluorescence detection allowed dextromethorphan quantification at 1 ng/mL. Mephenytoin enantiomers were completely separated in high-performance liquid chromatography and the respective fractions were collected and analyzed using a gas chromatography/mass spectrometry system with selective ion monitoring. The prevalence of poor metabolizer phenotype of dextromethorphan (CYP2D6) in the Yemenite (0%) and Ethiopian groups (0%) was significantly different from the prevalence in the Russian (17%) and Israeli Arab (9%) groups. A significant difference was also found in the distribution of the metabolic ratio of the extensive metabolizer phenotype between the Ethiopian group and the Russian and Yemenite groups. No significant difference was found in the prevalence of poor mephenytoin metabolizer phenotype (CYP2C19) between the Yemenite (8%), Ethiopian (6%), Russian (9%), and Israeli Arab (8%) groups. No difference was observed in the distribution of metabolic ratio within the extensive metabolizer phenotype subgroups of the four ethnic groups.
Longitudinal Study of Hypertensive Subjects With Type 2 Diabetes Mellitus: Overall and Cardiovascular Risk

Despite adequate glycemic and blood pressure control, treated type 2 diabetic hypertensive subjects have a significantly elevated overall/cardiovascular risk. We studied 244 816 normotensive and 99 720 hypertensive subjects (including 7480 type 2 diabetics) attending medical checkups between 1992 and 2011. We sought to identify significant differences in overall/cardiovascular risk between hypertension with and without diabetes mellitus. Mean follow-up was 12.7 years; 14 050 all-cause deaths were reported. From normotensive to hypertensive populations, a significant progression in overall/cardiovascular mortality was observed. Mortality was significantly greater among diabetic than nondiabetic hypertensive subjects (all-cause mortality, 14.05% versus 7.43%; and cardiovascular mortality, 1.28% versus 0.7%). No interaction was observed between hemodynamic measurements and overall/cardiovascular risk, suggesting that blood pressure factors, even during drug therapy, could not explain the differences in mortality rates between diabetic and nondiabetic hypertensive patients. Using cross-sectional regression models, a significant association was observed between higher education levels, lower levels of anxiety and depression, and reduced overall mortality in diabetic hypertensive subjects, while impaired renal function, a history of stroke and myocardial infarction, and increased alcohol and tobacco consumption were significantly associated with increased mortality. Blood pressure and glycemic control alone cannot reverse overall/cardiovascular risk in diabetics with hypertension. Together with cardiovascular measures, overall prevention should include recommendations to reduce alcohol and tobacco consumption and improve stress, education levels, and physical activity.
Exercices et entraînement en co-contractions isométriques volontaires des muscles agonistes- antagonistes : facteurs d'influence

L’objectif general de la presente these etait d’etudier les effets et les facteurs d’influence des exercices et des programmes d’entrainement consistant en la co-contraction maximale isometrique volontaire (CCMIV) de l’articulation du coude : effet de l’entrainement en CCMIV sur la force explosive (Etude A), influence de l’heure habituelle d’entrainement (Etude B) et de charges additionnelles pendant les CCMIV (Etude C). Les resultats ont montre que 6 semaines d’entrainement en CCMIV peuvent ameliorer simultanement la force maximale volontaire des muscles sans alteration de la force explosive (Etude A et B) et independamment de l’heure habituelle d’entrainement (Etude B). Ces gains de force s’accompagnaient d’une augmentation de l’activite electromyographique des muscles agonistes (Etude A et B). Cependant, les resultats de l’etude B suggerent que l’entrainement le matin s’accompagne d’un meilleur gain de la force musculaire, masquant ainsi les differences de force entre le matin et le soir. Par ailleurs, l’etude C a montre qu’une charge additionnelle (50% FMV) associee a une CCMIV modifie le pattern d’activation des muscles agonistes-antagonistes : augmentation du niveau d’activation des muscles agonistes et diminution de celui des antagonistes. Par consequent, un programme d’entrainement en CCMIV avec charge additionnelle devrait comprendre des exercices avec charge pour les flechisseurs et les extenseurs. De plus, les resultats de l’etude C suggerent que le concept du flechisseur equivalent pourrait etre applique non seulement quand les flechisseurs agissent comme agonistes mais aussi quand ils agissent comme antagonistes.
Twenty years of ultrawideband: Opportunities and challenges

It has been 20 years since the word ultrawideband (UWB) has first been used in the open literature. In these 20 years, ideas have been transformed into real products. Yet, some might object that UWB has not yet lived upto the promises of gigabit wireless. This review shows that despite some drawbacks, UWB is not only needed because of the spectrum gridlock but it can still deliver its promises, including gigabit wireless. To do so, the gap between the potential, which is achievable, and the current performance must be closed. Thus, this review identifies some main issues of UWB (range, bit error rate performance, data rate, chip complexity and issues associated by strong narrowband interference). It shows that their reasons are well understood and addressed by erudite research, which includes low complexity chip design, alternative modulation schemes, multiple antenna systems, UWB radio-over-fibre, higher band UWB and interferer detection and suppression techniques. A specific feature of this review is the cross-layer approach. The latest findings from different system layers, for example, wave propagation, are linked to the system performance or complexity.
Long-Term Survival Outcomes and Causes of Late Death in Neonates, Infants, and Children Treated With Extracorporeal Life Support*

Objectives: Extracorporeal life support is a resource-intense treatment offered to the sickest patients. We aimed to investigate long-term survival rates and late deaths. Design: Retrospective cohort study. Setting: Tertiary referral center for extracorporeal life support. Patients: All patients who required extracorporeal life support from 1992 to 2010 at our center. The U.K. National Health Service number was used to trace survival status of all patients who received extracorporeal life support at our center, grouped by diagnosis. Death more than 90 days after extracorporeal life support was defined as late, and these medical records were reviewed. Interventions: None. Measurements and Main Results: A total of 741 children with 272 early deaths (36.7%) and 46 late deaths (6.2%) were included. Median follow-up time in survivors was 7.1 (interquartile range, 3.0–11.9) years. Five-year survival estimates were highest for meconium aspiration syndrome 88.0% (95% CI, 80.6–92.7%) and lowest for congenital heart disease 32.3% (95% CI, 25.1–39.8%). Five-year survival estimates conditional on being alive at 90 days were highest for meconium aspiration syndrome 97.9% (95% CI, 92.0–99.5%) and lowest for congenital diaphragmatic hernia 73.6% (52.3–86.5%). There was increased risk of late death in congenital diaphragmatic hernia, congenital heart disease, and acquired heart disease (p < 0.001, p < 0.01, p = 0.01) in comparison with the risk in meconium aspiration syndrome. For 46 late deaths, 17 had a cardiac cause, 16 had a respiratory cause, 10 had a comorbid cause, one died of sepsis, and in two, causation was unknown. Conclusions: Although the majority of deaths were early, late mortality was observed following extracorporeal life support. Late deaths were more prevalent in children with underlying complex long-term conditions, particularly heart disease and congenital diaphragmatic hernia. Evaluation of longer term survival is an important component of audit for extracorporeal life support outcomes.
Risk Factors for Development of Nontyphoid Salmonella Bacteremia

The objective of this paper was to identify risk factors for nontyphoid Salmonella bacteremia by making a retrospective chart review of 39 patients with nontyphoid Salmonella bacteremia. The control group included 30 patients with positive Salmonella stool culture (gastroenteritis group). Demographic factors, presenting signs and symptoms, antimicrobial treatment before admission, and microbiologic results were recorded. Nine patients (23%) were excluded owing to recognized risk factors for development of extraintestinal disease. Seventeen cases (57%) occurred during summer time, whereas the gastroenteritis group had a less seasonal tendency. Eighty percent of the patients with Salmonella bacteremia had a previous history of diarrhea. At admission more patients in the bacteremia group were febrile and had leukocytosis (73% vs 33% and 37% vs 20%, respectively). More patients in the bacteremia group had previous antibiotic treatment (57% vs 20%, p<0.01). The Salmonella types were mainly C and D in the bacteremia group (40% each), and B and C in the gastroenteritis group (26% and 52%, respectively). The risk factors for Salmonella bacteremia in previously healthy children include warm season, previous gastrointestinal illness, and preexposure to antibiotics.
In situ assessment of quality-related compounds in fruits by using fluorescence sensors

Fruit quality compounds, such as antioxidant phenolics and chlorophyll, were assessed in situ by using a fluorescence method applied by a portable sensor. Indices of anthocyanins (ANTH) and flavonols (FLAV) localized on the fruit surface were obtained based on their screening of chlorophyll fluorescence excitation. The chlorophyll content was estimated by the far red to red chlorophyll fluorescence ratio (CHL index), due to the partial reabsorption of red fluorescence by chlorophyll itself. In kiwifruits, the CHL index was found to be well linearly correlated to the chlorophyll content determined by wet chemistry on the same fruit samples. Full sunlight exposed kiwifruits possessed a higher content of chlorophyll than shaded kiwifruits. This is an important parameter to know for assessing fruit quality and storability. Based on the estimation of the red-pigmented anthocyanins, we defined a new rapid method to determine the maturity level of olives after harvest, giving the proportion of red and green olives, important for the quality of the olive oil produced. In plums, ANTH and FLAV were found to be linearly correlated to the actual content of compounds measured by HPLC analysis of skin extracts. These indices can be, therefore, used to predict the phenolic antioxidant potential of plums and to define their maturity stage.
Les rotavirus et leur prévention

Les rotavirus sont responsables d'un grand nombre de gastroenterites que les progres de l'hygiene n'ont pas reussi a reduire. Cependant, dans les pays developpes le probleme de ces episodes diarrheiques est surtout represente par leur cout financier, alors que dans les pays en voies de developpement c'est la mortalite infantile causee par ces infections qui pose un probleme de sante publique prioritaire. Une meilleure connaissance des mecanismes de la diarrhee a rotavirus peut deboucher sur l'elaboration d'une therapeutique symptomatique, mais l'espoir de voir reduire la mortalite infantile repose avant tout sur une vaccination efficace. Deux vaccins parfaitement toleres seront prochainement disponibles, RotaRix® et RotaTeq®. Les essais cliniques sur une grande echelle ont montre leur efficacite sur les gastroenterites severes. Cependant, les rotavirus presentent une tres grande diversite antigenique et la barriere d'espece s'est revelee fragile. Le phenomene d'emergence observe dans plusieurs pays developpes avec la souche G9 pourrait eventuellement se reproduire avec une souche non controlee par la vaccination. Ce risque necessite une vigilance epidemiologique et virologique durant la vaccination.
Do antioxidant vitamins have an anti-arrhythmic effect following cardiac surgery? A meta-analysis of randomised controlled trials

Background Postoperative atrial fibrillation (POAF) affects approximately 30% of patients undergoing elective cardiac surgery. While its pathogenesis is multifactorial, increasing evidence supports a role for oxidative stress in the electrophysiological remodelling associated with AF. Although prophylactic antioxidants appear to be a potentially attractive pharmacotherapy, there is still uncertainty regarding their efficacy. This study aims to provide a quantitative summary of the current evidence surrounding antioxidant vitamins and POAF prevention. Methods A systematic literature review identified five randomised controlled trials incorporating 567 patients (n=284 antioxidant, n=283 control). These were meta-analysed using random effects modelling. Heterogeneity, subgroup analysis, quality scoring and risk of bias were assessed. Primary endpoints were the incidence of POAF and all-cause arrhythmia. Secondary endpoints were length of stay in the intensive care unit (ITU) and length of hospital stay. Results Vitamins C and E significantly reduced the incidence of POAF (OR 0.43, 95% CI 0.21 to 0.89) and all-cause arrhythmia (OR 0.54, 95% CI 0.29 to 0.99) compared with controls. A significant reduction in both ITU stay (weighted mean difference (WMD) −0.44, 95% CI −0.70 to −0.17) and hospital stay (WMD −1.11, 95% CI −1.70 to −0.52) was also seen in the antioxidant group, without significant heterogeneity. Conclusions The prophylactic use of vitamins C and E may significantly reduce the incidence of POAF and all-cause arrhythmia following cardiac surgery. However, the overall quality of current studies is poor and further research should focus on adequately powered randomised controlled trials that standardise AF reporting, antioxidant protocol and the use of concomitant agents. Cost analysis should be considered to establish the potential economic benefit of antioxidant vitamin prophylaxis in POAF.
Gastrointestinal pathological changes in stem cell transplant patients

Purpose of reviewThe last 5 years have seen an expansion of knowledge about the gastrointestinal diseases that may present in haematopoietic stem cell transplant (HSCT) patients and also about new gastrointestinal diseases in this patient population. Recent findingsThis article summarizes the recent opinions and findings regarding gastrointestinal graft-versus-host disease, and viral and other opportunistic gastrointestinal infections that can develop in HSCT patients. This article also discusses the more newly described entities of mycophenolate-mofetil-related gastrointestinal injury and cord colitis syndrome. SummaryThis review emphasizes the need for comprehensive clinical information when assessing gastrointestinal endoscopic biopsies from HSCT patients. It is crucial that both clinicians and histopathologists are aware of several specific but rare gastrointestinal diseases that may develop in these patients, because several of these diseases have specific treatments.
ORIGINAL INVESTIGATIONS Pathogenesis and Treatment of Kidney Disease Effects of Atorvastatin on Kidney Outcomes and Cardiovascular Disease in Patients With Diabetes: An Analysis From the Collaborative Atorvastatin Diabetes Study (CARDS)

Background: We examined whether atorvastatin affects diabetic kidney disease and whether the effect of atorvastatin on cardiovascular disease (CVD) varies by kidney status in patients with diabetes. Study Design: The Collaborative Atorvastatin Diabetes Study (CARDS) randomized placebocontrolled trial. Setting & Participants: Patients with type 2 diabetes and no prior CVD (n 2,838). Intervention: Random allocation to atorvastatin, 10 mg/d, or placebo, with a median follow-up of 3.9 years. Outcomes: Estimated glomerular filtration rate (eGFR), albuminuria, CVD. Measurements: Baseline and follow-up GFRs were estimated by using the Modification of Diet in Renal Disease Study equation. Urinary albumin-creatinine ratio was measured on spot urine samples. Results: At baseline, 34% of patients had an eGFR of 30 to 60 mL/min/1.73 m 2 . Atorvastatin treatment was associated with a modest improvement in annual change in eGFR (net, 0.18 mL/min/1.73 m 2 /y; 95% confidence interval [CI], 0.04 to 0.32; P 0.01) that was most apparent in those with albuminuria (net improvement, 0.38 mL/min/1.73 m 2 /y; P 0.03). At baseline, 21.5% of patients had albuminuria and an additional 6.8% developed albuminuria during follow-up. Atorvastatin did not influence the incidence of albuminuria (hazard ratio, 1.49; 95% CI, 0.73 to 3.04; P 0.3) or regression to normoalbuminuria (hazard ratio, 1.19; 95% CI, 0.57 to 2.49; P 0.6). In 970 patients with a moderately decreased eGFR of 30 to 60 mL/min/1.73 m 2 , there was a 42% reduction in major CVD events with treatment, including a 61% reduction in stroke. This treatment effect was similar to the 37% (95% CI, 17 to 52; P 0.001) reduction in CVD observed in the study overall (P 0.4 for the eGFR-treatment interaction). Limitations: Low incidence rates of albuminuria and transition to more severe kidney status limit power to detect treatment effects. Conclusions: A modest beneficial effect of atorvastatin on eGFR, particularly in those with albuminuria, was observed. Atorvastatin did not influence albuminuria incidence. Atorvastatin was effective at decreasing CVD in those with and without a moderately decreased eGFR and achieved a high absolute benefit. Am J Kidney Dis 54:810-819. ©2009 by the National Kidney Foundation, Inc.
Collisions, rebounds and skimming

Repeated oblique impacts and rebounds of a solid body or bodies on horizontal shallow water are investigated through mathematical modelling. The inclinations from the horizontal are supposed small as the skimming evolves, for a thin typical body shape. The new formulation aimed at improved prediction as well as the background involved is presented together with nonlinear analysis and computation. Comparatively fast or slow collisions and rebounds are found to be of special interest over short time-scales.
Nonspecific DCT-block fingerprinting based on incomplete cryptography for DRM system

In the present digital world, Digital Rights Management (DRM) is essential to enforce persistent data protection right from the moment it is published. In spite of a need for DRM there are significant weaknesses in the current technology. Generally, DRM system is achieved with individual function modules of cryptography, fingerprinting and so on. In this typical system flow, all digital contents are temporarily disclosed with perfect condition via decryption process. This paper describes the elemental idea of a DRM method which is composed of an incomplete cryptography based on nonspecific DCT-block (Discrete Cosine Transform) and user fingerprinting mechanism to control the quality of digital contents. There are two fundamental steps in our proposed cryptography: incomplete encoding and incomplete decoding. These two steps will create the scrambled content using as trial content and fingerprinted content is used to prevent unauthorized duplication or business of digital contents, respectively. Experimental results on standard JPEG (Joint Photographic Experts Group) format show that the proposed method is suitable for DRM in the network distribution system.