Miracle-dz/UniFAR-FTUs huggingface dataset:
Rate of disease progression: a prognostic biomarker in ALS

Objective To assess the utility of rate of disease progression (ΔFS) as a prognostic biomarker in amyotrophic laterals sclerosis (ALS). Methods A total of 203 patients with ALS were prospectively recruited over a 10-year period. At initial visit, the following variables were collected: demographic details, symptom duration, site of onset, phenotype, riluzole use and Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) scores. The ΔFS score at initial visit was calculated by dividing the ALSFRS-R total score by symptom duration (months). The primary end point was survival. Kaplan-Meier survival curves were used to illustrate the distribution of survival from a specified point, while multiple Cox proportional hazards modelling with backward stepwise variable selection was used to identify the independent predictors of survival at initial visit. Results The ΔFS score at initial visit was a significant predictor of survival in ALS (p<0.001), and remained significant when adjusted for age and site of onset (p<0.001). 3 prognostic subgroups emerged, with a ΔFS score of <0.47 associated with a median survival of 2.4 years, which was significantly greater when compared with an initial ΔFS score of between 0.47 and 1.11 (1.6 years, p<0.05) and a score >1.11 (0.7 years, p<0.001). Importantly, multiple Cox proportional hazards modelling identified ΔFS as a highly significant independent predictor of survival in ALS (p<0.001) along with site of disease onset (p<0.01). Conclusions Rate of disease progression appears to be a simple and sensitive clinical prognostic biomarker in ALS that could be potentially utilised in clinical practice and future therapeutic trials.
RNA Secondary Structure Prediction

In this unit, protocols are provided for predicting RNA secondary structure with the user‐friendly RNAstructure desktop computer program and the RNAstructure Web server. The minimum free energy structure and a set of suboptimal structures with similar free energies are predicted. Prediction of high‐affinity oligonucleotide binding sites to a structured RNA target is also presented. © 2016 by John Wiley & Sons, Inc.
Aperiodic multiprocessor scheduling for real-time stream processing applications

This thesis presents an algorithm that uses a new dataflow model, variable- rate phased dataflow, to compute buffer capacities that guarantee satisfaction of timing and resource constraints for task graphs that have inter-task synchro- nisation behaviour that is dependent on the processed data stream and that have tasks that are scheduled by run-time schedulers that guarantee resource budgets. This is an important extension of data ow analysis techniques, which allows to model a larger class of applications and allows to include the effects of a larger class of run-time schedulers. This is exemplified by the case study with an MP3 playback application, for which we are not aware of alternative approaches to compute buffer capacities that are sufficient to satisfy the timing constraints. Furthermore, we improved the accuracy with which the effects of run-time schedulers that guarantee tasks a minimum resource budget are mod- elled in data ow graphs. Instead of capturing the effects of run-time scheduling using response times, we capture these effects with a model that has a latency and a rate parameter. Response times do not capture that multiple task exe- cutions can occur subsequently in the same allocated budget. This is captured with the model with a latency and a rate parameter, which results in improved accuracy of the derived bounds on the temporal behaviour. Further, our algo- rithm has an attractive computational complexity. Every cyclo-static dataflow graph that is an intuitive model of a task graph is a variable-rate phased dataflow graph, i.e. every cyclo-static data ow graph in which no actor has any auto- concurrency. The algorithm that computes buffer capacities has a polynomial complexity in the size of the cyclo-static dataflow graph. The validity of our analysis is confirmed by simulation in both a data ow simulator as well as in a cycle-accurate simulator.
Light-Enhanced Microbial Organic Carbon Yield

Molecular evidence for proteorhodopsin- and bacteriochlorophyll-based photoheterotrophy is widespread in oligotrophic marine microbial community metagenomes, and has been implicated in light-enhanced growth rates, substrate uptake rates, and anapleurotic carbon fixation, thus complicating the web of interactions within the ‘microbial loop. ’ We quantified photoheterotrophic metabolism of the oxidized organic acid glycolate, a fast-turnover and exclusively phytoplankton-derived substrate at an oligotrophic site in the subtropical North Pacific Ocean. As expected, concentration-dependent changes in uptake rates were observed over the diel cycle, with maxima occurring at midday. Although no light-enhanced substrate uptake rates were observed, samples exposed to light altered the balance between assimilation and respiration, resulting in an approximately four-fold increase in glycolate-specific assimilation efficiency. Energy demand for such a metabolic adjustment was linearly related to light, consistent with photoheterotrophy.
Effectiveness of a lifestyle intervention in promoting the well-being of independently living older people: results of the Well Elderly 2 Randomised Controlled Trial

Background Older people are at risk for health decline and loss of independence. Lifestyle interventions offer potential for reducing such negative outcomes. The aim of this study was to determine the effectiveness and cost-effectiveness of a preventive lifestyle-based occupational therapy intervention, administered in a variety of community-based sites, in improving mental and physical well-being and cognitive functioning in ethnically diverse older people. Methods A randomised controlled trial was conducted comparing an occupational therapy intervention and a no-treatment control condition over a 6-month experimental phase. Participants included 460 men and women aged 60–95 years (mean age 74.9±7.7 years; 53% <$12 000 annual income) recruited from 21 sites in the greater Los Angeles metropolitan area. Results Intervention participants, relative to untreated controls, showed more favourable change scores on indices of bodily pain, vitality, social functioning, mental health, composite mental functioning, life satisfaction and depressive symptomatology (ps<0.05). The intervention group had a significantly greater increment in quality-adjusted life years (p<0.02), which was achieved cost-effectively (US $41 218/UK £24 868 per unit). No intervention effect was found for cognitive functioning outcome measures. Conclusions A lifestyle-oriented occupational therapy intervention has beneficial effects for ethnically diverse older people recruited from a wide array of community settings. Because the intervention is cost-effective and is applicable on a wide-scale basis, it has the potential to help reduce health decline and promote well-being in older people. Trial Registration clinicaltrials.gov identifier: NCT0078634.
Analysis of Surface Crack Propagation in Lubricated Rolling Contact

Growth behavior of surface cracks formed on lubricated rolling-sliding contact surfaces is studied by calculating three-dimensional mixed-mode stress intensity factors KI, KII, and KIII. It is shown from the viewpoint of the fatigue crack propagation that the hydraulic pressure effect pointed out by Way may be accepted as a possible mechanism of surface crack growth. Some of the experimental facts on pitting are also confirmed qualitatively.
Modelling Tensile Strain Response in Asphalt Pavements

ABSTRACT Traditionally, HMA pavement designs and modeling methods have historically been based on the fundamental assumption that fatigue cracking generally initiates at the bottom of the HMA layer due to excessive tensile stresses/strains, and then propagates upwards to the surface. However, fatigue cracking can either be bottom-up or top-down initiated depending on the location of the maximum horizontal tensile stresses and strains in the HMA layer. Various factors such as the pavement structure and wheel/tire loading configurations influence both the location and magnitude of the fatigue crack-related tensile strains that are induced in the HMA layer. In this study, the influence of these factors on the tensile strains responses and potential location of fatigue crack initiation in HMA pavements was investigated. To address the non-uniformity distribution of the tire-pavement contact pressure (TPCP), including the vertical tire-pavement contact pressure and horizontal tire-pavement stress, a three-dimensional finite element program was utilized for the computational simulations and numerical analyses. Specifically, the actual TPCP of different tire types and tread patterns measured under variable load levels and tire inflation pressures were utilized to evaluate and analyze the potential locations of maximum tensile strains in terms of fatigue crack initiation. The results showed that the longitudinal and low latitudinal tire-pavement stress hardly influence the maximum tensile strains in the HMA layer; and that the maximum tensile strains can occur either at the top or bottom (or both) of the HMA layer, thus inducing top-down and/or bottom-up fatigue crack initiation. Just like heavy-truck tire loading, the study also demonstrated that light-truck tire loading can induce excessive fatigue crack-related tensile strains in the pavement.
Influence of cooling rate on pVT-data of semicrystalline polymers

For numerical simulations of the injection-molding process, an accurate description of the specific volume is needed to predict differential shrinkage during and after molding, which causes thermally induced stresses and controls the dimensional accuracy and long-term dimensional stability. For amorphous polymers, for which it can often be assumed that cooling-rate dependence can be ignored, standard techniques enable measurements of the specific volume as a function of temperature and pressure. For semicrystalline polymers, the situation is more complicated since the specific volume depends strongly on the degree of crystallinity, which itself depends on the thermomechanical history, that is, temperature and pressure (for quiescent crystallization). This requires the use of a combined experimental–numerical technique to interpret the data and to determine the specific volume. Standard equipment can only be used at relatively low cooling rates. Since high cooling rates are present during injection molding, improved experimental techniques must be designed. A setup based on the confining fluid technique is built, which can reach cooling rates to 60 Ks−1 and pressures to 20 × 106 Pa. During an experiment, the specific volume is measured together with the temperature history and pressure. Using an accurate model to calculate the crystalline structure, together with a specific-volume model which depends on this structure, enables the determination of model parameters. Comparing both the measurements and the model predictions, leads to the conclusion that modeling of the crystallization kinetics results in accurate predictions of the specific volume. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 82: 1170–1186, 2001
Association between sleep quality and quality of life in nursing professionals working rotating shifts

OBJECTIVE To analyze the association between sleep quality and quality of life of nursing professionals according to their work schedules. METHODS A prospective, cross-sectional, observational study was conducted between January and December 2010, with 264 nursing professionals, drawn from 989 subjects at Botucatu General Hospital and stratified by professional category. The Pittsburg Sleep Quality Index and the WHOQOL-bref were administered to evaluate sleep quality and quality of life, respectively. Self-reported demographic data were collected with a standard form. Continuous variables were reported as means and standard deviations, and categorical variables were expressed as proportions. Associations were evaluated using Spearman’s correlation coefficient. The association of night-shift work and gender with sleep disturbance was evaluated by logistic regression analysis using a model adjusted for age and considering sleep disturbance the dependent variable. The level of significance was p < 0.05. RESULTS Night-shift work was associated with severe worsening of at least one component of sleep quality in the model adjusted for age (OR = 1.91; 95%CI 1.04;3.50; p = 0.036). Female gender was associated with sleep disturbance (OR = 3.40; 95%CI 1.37;8.40; p = 0.008). Quality of life and quality of sleep were closely correlated (R = -0.56; p < 0.001). CONCLUSIONS Characteristics of the nursing profession affect sleep quality and quality of life, and these two variables are associated.
Population pharmacokinetics of ritonavir-boosted atazanavir in HIV-infected patients and healthy volunteers

Objectives The aim of this study was to develop and validate a population pharmacokinetic model to: (i) describe ritonavir-boosted atazanavir concentrations (300/100 mg once daily) and identify important covariates; and (ii) evaluate the predictive performance of the model for lower, unlicensed atazanavir doses (150 and 200 mg once daily) boosted with ritonavir (100 mg once daily). Methods Non-linear mixed effects modelling was applied to determine atazanavir pharmacokinetic parameters, inter-individual variability (IIV) and residual error. Covariates potentially related to atazanavir pharmacokinetics were explored. The final model was assessed by means of a visual predictive check for 300/100, 200/100 and 150/100 mg once daily. Results Forty-six individuals were included (30 HIV-infected). A one-compartment model with first-order absorption and lag-time best described the data. Final estimates of apparent oral clearance (CL/F), volume of distribution (V/F) and absorption rate constant [relative standard error (%) and IIV (%)] were 7.7 L/h (5, 29), 103 L (13, 48) and 3.4 h−1 (34, 154); a lag-time of 0.96 h (1) was determined. Ritonavir area under the curve (AUC0–24) was the only significant covariate. Overall, 94%–97% of observed concentrations were within the 95% prediction intervals for all three regimens. Conclusions A population pharmacokinetic model for ritonavir-boosted atazanavir has been developed and validated. Ritonavir AUC0–24 was significantly associated with atazanavir CL/F. The model was used to investigate other, particularly lower, ritonavir-boosted atazanavir dosing strategies.
Does Facial Processing Prioritize Change Detection?

There is broad consensus among researchers both that faces are processed more holistically than other objects and that this type of processing is beneficial. We predicted that holistic processing of faces also involves a cost, namely, a diminished ability to localize change. This study (N = 150) utilized a modified change-blindness paradigm in which some trials involved a change in one feature of an image (nose, chin, mouth, hair, or eyes for faces; chimney, porch, window, roof, or door for houses), whereas other trials involved no change. People were better able to detect the occurrence of a change for faces than for houses, but were better able to localize which feature had changed for houses than for faces. Half the trials used inverted images, a manipulation that disrupts holistic processing. With inverted images, the critical interaction between image type (faces vs. houses) and task (change detection vs. change localization) disappeared. The results suggest that holistic processing reduces change-localization abilities.
ESTIMATION OF THE NUMBER OF INDIVIDUALS FOUNDING COLONIZED POPULATIONS

Abstract A method for estimating the number of founding chromosomes in an isolated population is introduced. The method assumes that n/2 diploid individuals are sampled from a population and that alleles are identified at L unlinked loci. The population is assumed to have been founded T generations in the past by individuals carrying c chromosomes drawn randomly from a known source population, which has also been sampled. If c is small and the population grew rapidly after it was founded, accurate estimates of c can be obtained and those estimates are not sensitive to details of the history of population sizes. If c is larger or the population remained small after it was founded, then estimates of c depend on the history of population sizes. We test the performance of our method on simulated data and demonstrate its use on data from a rainbow trout (Oncorhynchus mykiss) population.
Distinct Inhibitory Effects of Tacrolimus and Cyclosporin A on Calcineurin Phosphatase Activity

We have compared the pharmacodynamic properties of calcineurin inhibitors tacrolimus and cyclosporin A in rats to clarify the different therapeutic drug monitoring strategy of both drugs in a clinical situation. In various tissue extracts, the inhibition of calcineurin activity by cyclosporin A was significantly greater than that by tacrolimus at the same drug concentration (1 μM) in the thymus, heart, liver, spleen, kidney, and testis (p < 0.05). The time profiles of blood concentrations and calcineurin activity in whole blood were examined after single or repeated administration of each drug in rats. A substantial time delay in the inhibition was observed following the single administration of tacrolimus or cyclosporin A, resulting in an anticlockwise hysteresis in the relationship between blood concentrations and calcineurin inhibition in whole blood. In contrast, such a hysteresis loop diminished after the repeated administration of each drug, and the recovery rate of calcineurin activity was greater for the inhibition induced by cyclosporin A than by tacrolimus. Furthermore, tacrolimus produced a comparable inhibition of calcineurin activity in whole blood at lower blood concentrations than cyclosporin A. Overall, the effect compartment model well described the time profiles of calcineurin activity in whole blood after the single and repeated administrations of each drug. These findings suggest that the properties of calcineurin inhibition differ between tacrolimus and cyclosporin A. Distinct pharmacodynamics may partly contribute to the therapeutic drug monitoring strategy in transplant patients receiving calcineurin inhibitors.
cAMP signaling microdomains and their observation by optical methods

The second messenger cyclic AMP (cAMP) is a major intracellular mediator of many hormones and neurotransmitters and regulates a myriad of cell functions, including synaptic plasticity in neurons. Whereas cAMP can freely diffuse in the cytosol, a growing body of evidence suggests the formation of cAMP gradients and microdomains near the sites of cAMP production, where cAMP signals remain apparently confined. The mechanisms responsible for the formation of such microdomains are subject of intensive investigation. The development of optical methods based on fluorescence resonance energy transfer (FRET), which allow a direct observation of cAMP signaling with high temporal and spatial resolution, is playing a fundamental role in elucidating the nature of such microdomains. Here, we will review the optical methods used for monitoring cAMP and protein kinase A (PKA) signaling in living cells, providing some examples of their application in neurons, and will discuss the major hypotheses on the formation of cAMP/PKA microdomains.
Endopeptidase-Mediated Beta Lactam Tolerance

In many bacteria, inhibition of cell wall synthesis leads to cell death and lysis. The pathways and enzymes that mediate cell lysis after exposure to cell wall-acting antibiotics (e.g. beta lactams) are incompletely understood, but the activities of enzymes that degrade the cell wall (‘autolysins’) are thought to be critical. Here, we report that Vibrio cholerae, the cholera pathogen, is tolerant to antibiotics targeting cell wall synthesis. In response to a wide variety of cell wall- acting antibiotics, this pathogen loses its rod shape, indicative of cell wall degradation, and becomes spherical. Genetic analyses revealed that paradoxically, V. cholerae survival via sphere formation required the activity of D,D endopeptidases, enzymes that cleave the cell wall. Other autolysins proved dispensable for this process. Our findings suggest the enzymes that mediate cell wall degradation are critical for determining bacterial cell fate - sphere formation vs. lysis – after treatment with antibiotics that target cell wall synthesis.
Non-invasive assessment of inspiratory muscle performance during exercise in patients with chronic heart failure.

AIMS The aim of this study was to assess inspiratory performance at rest and during exercise in patients with chronic heart failure in comparison with healthy controls using a non-invasive index: the tension-time index of inspiratory muscles (TTMUS). METHODS We studied 13 patients with chronic heart failure (57 +/- 7 years) and 10 control subjects (58 +/- 6 years) at rest and during an incremental maximal exercise test. Measurements included breathing pattern (inspiratory time, total time of respiratory cycle, minute ventilation, tidal volume and respiratory frequency), mouth occlusion pressure and mean inspiratory pressure (calculated as follows: 5 x mouth occlusion pressure x inspiratory time). The maximal inspiratory pressure was measured at rest. TTMUS was calculated from the equation: TTMUS = PI/PIMAX x TI/TTOT, where PI/PIMAX is the ratio of mean inspiratory pressure to maximal inspiratory pressure and TI/TTOT is the ratio of mean inspiratory time to total time of the respiratory cycle. RESULTS At rest, the results in patients showed non-significantly higher mouth occlusion pressure, lower maximal inspiratory pressure (P < 0.001), and a higher ratio of mean inspiratory pressure to maximal inspiratory pressure (P < 0.01). There was no difference in the breathing pattern. TTMUS was thus significantly higher in the patients with chronic heart failure (P < 0.001). At maximal exercise (77 +/- 16 W for patients with chronic heart failure vs 142 +/- 27 W for controls, P < 0.001), the ratio of mean inspiratory time to total time of respiratory cycle, the mouth occlusion pressure and the ratio of mean inspiratory pressure to maximal inspiratory pressure were not different. TTMUS was thus comparable in the two groups. During exercise, at comparable workloads (20, 40 and 60 W), the patients showed higher mouth occlusion pressure (P < 0.01) and a higher ratio of mean inspiratory pressure to maximal inspiratory pressure (P < 0.001), whereas the ratio of mean inspiratory time to total time of the respiratory cycle was similar. TTMUS was thus higher in the patients at each workload (P < 0.05). CONCLUSION This study shows that the determination of TTMUS at rest and during exercise allows the observation of alterations in inspiratory muscle performance as a result of both reduced inspiratory strength, as measured by the maximal inspiratory pressure, and increased ventilatory drive, as reflected by the mouth occlusion pressure in patients with chronic heart failure. The non-invasiveness of this new index is an additional argument for its use in a clinical setting.
Story telling: A preferred strategy in oral health education

Methods: This intervention study was conducted on 117 female elementary school students in 1391-92. Random and clustered sampling was done from 4 groups of grade 3 in elementary school data selection was through a questionnaire, so that knowledge, attitude and practice of students were evaluated and compared before and after administration of methods. Data were analyzed using SPSS17 software through T-test and ANOVA.