Miracle-dz/UniFAR-FTUs huggingface dataset:
Physiological responses to caffeine during endurance running in habitual caffeine users.

Several studies have found that caffeine improved endurance exercise performance, but the factors which are responsible for this are not fully understood. Possibilities include an increased free fatty acid (FFA) oxidation and a resultant sparing of muscle glycogen as well as an enhancement of neuromuscular function during exercise. In order to further examine these factors, six varsity level runners (VO2max = 63.3 ml.kg-1.min-1) were studied over 90 min of treadmill running (70% VO2max) in a thermoneutral environment in order to determine the metabolic and neuromuscular effects of caffeine (6 mg.kg-1) administered in a randomized, crossover, double-blind manner. Subjects were habitual caffeine consumers (200 mg.d-1) and were given identical diets during each 3-d testing period. Caffeine administration, 60 min prior to exercise, significantly (P less than 0.05) increased plasma FFA levels both prior to and during exercise. Caffeine administration did not alter any of the other variables examined: VO2, HR, RER, rating of perceived exertion; plasma levels of glucose, lactate, epinephrine, and norepinephrine; or neuromuscular function (maximal voluntary strength, peak twitch torque, and motor unit activation). We conclude that caffeine administration (6 mg.kg-1) in athletic, habitual caffeine consumers increased plasma FFA levels but had neither metabolic nor neuromuscular effects that would be of potential ergogenic benefit in endurance running.
Assessing the Clinical Significance of Botanical Supplementation on Human Cytochrome P450 3A Activity: Comparison of a Milk Thistle and Black Cohosh Product to Rifampin and Clarithromycin

Phytochemical‐mediated modulation of cytochrome P450 enzymes (CYPs) may underlie many herb‐drug interactions. This study's purpose was to assess the effects of milk thistle and black cohosh supplementation on CYP3A activity and compare them to a clinically recognized inducer, rifampin, and inhibitor, clarithromycin. Healthy volunteers were randomly assigned to receive a standardized milk thistle (900 mg) or black cohosh (80 mg) supplement for 14 days. Subjects also received rifampin (600 mg) and clarithromycin (1000 mg) for 7 days as positive controls for CYP3A induction and inhibition, respectively. Midazolam was administered orally before and after each supplementation and control period. The effects of milk thistle, black cohosh, rifampin, and clarithromycin on midazolam pharmacokinetics were determined using noncompartmental techniques. Unlike those observed for rifampin and clarithromycin, midazolam pharmacokinetics was unaffected by milk thistle or black cohosh. Milk thistle and black cohosh appear to have no clinically relevant effect on CYP3A activity in vivo.
Pharmacokinetic evaluation of pemetrexed

Introduction: Pemetrexed is a multi-targeted antifolate cytotoxic agent that has demonstrated activity in a number of very common cancer types including NSCLC in both first- and second-line settings and in the treatment of malignant mesothelioma. Areas covered: This article focuses on all of the currently published pharmacokinetic data of pemetrexed reviewing a number of different scenarios and patient populations. All the articles reviewed in this manuscript are from peer-reviewed English-spoken literature without any limitations to the time of publication. Expert opinion: Pemetrexed's clearance correlates with renal function and it may be safely used with vitamin supplementation in patients with creatinine clearance ≥ 45 ml/min. The pharmacokinetics of pemetrexed is also largely unchanged in third-space fluids and can be feasibly and safely administered in combination with several other cytotoxic or targeted agents. It is the author's opinion that pemetrexed is already a valuable cytotoxic agent which has proved useful in several malignancies. However, future trials might expand on the combined use of pemetrexed with other targeted agents that could be beneficial to other selected patients harboring relevant mutations or other biological features.
Spectral patterns and frequency response characteristics of arterial pressure in heart paced dogs

The role of heart rate in buffering and/or generating aortic pressure (AP) oscillations that occur at rest and in response to oscillatory blood volume shifts was studied. Six supine dogs with chronic AV blockade were used to examine: 1) resting HR and AP spectra when the ventricular rate was controlled by atrial depolarization (natural sinus rhythm); 2) resting AP and stroke volume (SV) spectra when the heart was AV sequentially paced at 60, 120, and 180 bpm before and after ganglionic blockade; and 3) the frequency response characteristics of AP and SV to whole-body sinusoidal acceleration (/spl plusmn/2g/sub 2/, 0.008-0.23 Hz) at each heart rate before and after ganglionic blockade. During atrial regulation of HR, the spectra of both AP and HR had dominant peaks located at the breathing frequency (0.2-0.4 Hz) and relatively smaller peaks centered at /spl sim/0.05 Hz. During constant heart rate pacing, the spectra of AP had a dominant component at /spl sim/0.05 Hz. The power of this component was: 1) larger than during atrial regulation, 2) increased with increasing pacing rate, and 3) abolished by ganglionic blockade. There was no effect of pacing rate or ganglionic blockade on SV spectra. During oscillatory acceleration, AP regulation in the heart paced dogs was frequency dependent. Regions of good regulation occurred below 0.016 Hz and above 0.1 Hz, and poor regulation between 0.035 and 0.075 Hz centered at /spl sim/0.05 Hz. The oscillations in the poor regulation region were enhanced by increased pacing rate. After ganglionic blockade, the frequency response of AP was primarily hydraulic (low-pass). The frequency response of SV had a neural component. It is concluded that: 1) resting AP fluctuations at respiratory frequencies resulted from respiration-linked HR variation; 2) the 0.05-Hz fluctuations in AP during rest and the poor regulation of AP at 0.05 Hz during acceleration resulted from a peripheral vascular response that lagged disturbances by /spl sim/10 s; 3) HR regulation was important in minimizing AP variation in the 0.05-Hz region both at rest and during oscillatory acceleration; and 4) inotropic control of SV was an important component of AP regulation during low-frequency acceleration. <<ETX>>
Three Different Routes of Inoculation for Experimental Infection with Schmallenberg Virus in Sheep

&NA; Schmallenberg virus (SBV) is an emerging Orthobunyavirus affecting European domestic ruminants. In this study, three groups of ewes (n = 3) were inoculated with 1 ml of an SBV infectious serum, via the subcutaneous (SC), intradermal (ID) or intranasal (IN) route. The ewes were monitored for 10 days and no clinical signs were reported. IN inoculation failed to generate any detectable RNAemia. SC and ID inoculation induced typical SBV RNAemia and seroconversion upon day 6 post‐inoculation in 3/3 and 2/3 sheep, respectively. In all the animals that showed RNAemia, the viral genome could be detected in spleen and mesenteric lymph nodes. Both the SC and ID routes seem suitable to properly reproduce field conditions, as comparable observations were reported regarding RNAemia, seroconversion and viral genome detection in organs.
Contribution of foods consumed away from home to energy intake in Brazilian urban areas: the 2008–9 Nationwide Dietary Survey

The objectives of the present study were to estimate the dietary contribution of away-from-home food consumption, to describe the contribution of away-from-home foods to energy intake, and to investigate the association between eating away from home and total energy intake in Brazilian urban areas. In the first Brazilian Nationwide Dietary Survey, conducted in 2008–9, food records were collected from 25 753 individuals aged 10 years or older, living in urban areas of Brazil. Foods were grouped into thirty-three food groups, and the mean energy intake provided by away-from-home food consumption was estimated. Linear regression models were used to evaluate the association between away-from-home food consumption and total energy intake. All analyses considered the sample design effect. Of the total population, 43 % consumed at least one food item away from home. The mean energy intake from foods consumed away from home was 1408 kJ (337 kcal), averaging 18 % of total energy intake. Eating away from home was associated with increased total energy intake, except for men in the highest income level. The highest percentage of away-from-home energy sources was for food with a high content of energy, such as alcoholic beverages (59 %), baked and deep-fried snacks (54 %), pizza (42 %), soft drinks (40 %), sandwiches (40 %), and sweets and desserts (30 %). The consumption of foods away from home was related to a greater energy intake. The characterisation of away-from-home food habits is necessary in order to properly design strategies to promote healthy food consumption in the away-from-home environment.
Multiregional Oligopoly with Capacity Constraints

We develop a model of Cournot competition between capacity-constrained firms that sell a single good to multiple regions. We provide a novel characterization for the unique equilibrium allocation of the good across regions and design an algorithm to compute it. We show that a reduction in transportation costs by a firm may negatively impact the profit of all firms and reduce aggregate consumer surplus if such a firm is capacity constrained. Our results imply that policies promoting free trade may have unintended consequences and reduce aggregate welfare in capacity-constrained industries. This paper was accepted by David Simchi-Levi, revenue management and market analytics.
Band‐Like Electron Transport with Record‐High Mobility in the TCNQ Family

The occurrence of extremely pronounced band-like transport with very high electron mobility in fluorinated tetracyanoquinodimethane (F2 -TCNQ) single-crystal field-effect transistors is discovered. This finding identifies the Fx -TCNQ family as a paradigm to investigate the fundamental aspects of electronic transport in organic crystals.
Receptive field organization of bipolar and amacrine cells in the goldfish retina

1. Intracellular recordings were made from bipolar and amacrine cells in the isolated goldfish retina. Cells were identified mainly from their response patterns to a spot and an annulus in reference to the knowledge obtained from the previous work of intracellular Procion Yellow injection. Using white light and monochromatic lights receptive field organization of recorded cells were analysed.
Mechanistic Studies on the Inactivation of the Proteasome by Lactacystin

Lactacystin is a Streptomyces metabolite that inhibits cell cycle progression and induces differentiation in a murine neuroblastoma cell line. The cellular target of lactacystin is the 20 S proteasome, also known as the multicatalytic proteinase complex, an essential component of the ubiquitin-proteasome pathway for intracellular protein degradation. In aqueous solution at pH 8, lactacystin undergoes spontaneous hydrolysis to yield N-acetyl-L-cysteine and the inactive lactacystin analog, clasto-lactacystin dihydroxy acid. We have studied the mechanism of lactacystin hydrolysis under these conditions and found that it proceeds exclusively through the intermediacy of the active lactacystin analog, clasto-lactacystin β-lactone. Conditions that stabilize lactacystin (and thus prevent the transient accumulation of the intermediate β-lactone) negate the ability of lactacystin to inactivate the proteasome. Together these findings suggest that lactacystin acts as a precursor for clasto-lactacystin β-lactone and that the latter is the sole species that interacts with the proteasome.
Climatic Drivers of Diarrheagenic Escherichia coli Incidence: A Systematic Review and Meta-analysis.

BACKGROUND Positive associations have been noted between temperature and diarrhea incidence, but considerable uncertainty surrounds quantitative estimates of this relationship because of pathogen-specific factors and a scarcity of data on the influence of meteorological factors on the risk of disease. Quantifying these relationships is important for disease prevention and climate change adaptation. METHODS To address these issues, we performed a systematic literature review of studies in which at least 1 full year of data on the monthly incidence of diarrheagenic Escherichia coli were reported. We characterized seasonal patterns of disease incidence from 28 studies. In addition, using monthly time- and location-specific weather data for 18 studies, we performed univariate Poisson models on individual studies and a meta-analysis, using a generalized estimating equation, on the entire data set. RESULTS We found an 8% increase in the incidence of diarrheagenic E. coli (95% confidence interval, 5%-11%; P < .0001) for each 1°C increase in mean monthly temperature. We found a modest positive association between 1-month-lagged mean rainfall and incidence of diarrheagenic E. coli, which was not statistically significant when we controlled for temperature. CONCLUSIONS These results suggest that increases in ambient temperature correspond to an elevated incidence of diarrheagenic E. coli and underscore the need to redouble efforts to prevent the transmission of these pathogens in the face of increasing global temperatures.
Neurourology and Urodynamics 34 : 513 – 518 ( 2015 ) Diagnostic Accuracy of Tc-99 m DMSA Scintigraphy and Renal Ultrasonography for Detecting Renal Scarring and Relative Function in Patients With Spinal Dysraphism

Paul W. Veenboer, Monique G. G. Hobbelink, J. L. H. Ruud Bosch, Pieter Dik, Floris W. A. van Asbeck, Frederik J. A. Beek, and Laetitia M. O. de Kort Department of Urology, University Medical Center Utrecht, Utrecht, The Netherlands Division of Image, Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands Department of Pediatric Urology, University Medical Center Utrecht, Utrecht, The Netherlands Department of Rehabilitation Medicine, University Medical Center Utrecht, Utrecht, The Netherlands Department of Pediatric Radiology, University Medical Center Utrecht, Utrecht, The Netherlands
IL-10-Secreting Regulatory T Cells Do Not Express Foxp3 but Have Comparable Regulatory Function to Naturally Occurring CD4+CD25+ Regulatory T Cells 1

Regulatory T cells (TReg) control immune responses to self and nonself Ags. The relationship between Ag-driven IL-10-secreting TReg (IL-10-TReg) and naturally occurring CD4+CD25+ TReg is as yet unclear. We show that mouse IL-10-TReg obtained using either in vitro or in vivo regimens of antigenic stimulation did not express the CD4+CD25+ TReg-associated transcription factor Foxp3. However, despite the absence of Foxp3 expression, homogeneous populations of IL-10-TReg inhibited the in vitro proliferation of CD4+CD25− T cells with a similar efficiency to that of CD4+CD25+ TReg. This inhibition of T cell proliferation by IL-10-TReg was achieved through an IL-10-independent mechanism as seen for CD4+CD25+ TReg and was overcome by exogenous IL-2. Both IL-10-TReg and CD4+CD25+ TReg were similar in that they produced little to no IL-2. These data show that Foxp3 expression is not a prerequisite for IL-10-TReg activity in vitro or in vivo, and suggest that IL-10-TReg and naturally occurring CD4+CD25+ TReg may have distinct origins.
The optimum density of sodium channels in an unmyelinated nerve.

In introducing this meeting I wish to refer to a theoretical development which may be relevant to some of our discussion. Present estimates suggest that the density of sodium channels varies between 2.5/(xm2 in the 0.2 pirn diameter axons of the olfactory nerve of the garfish (Colquhoun, Henderson & Ritchie 1972) to about 500/pim2 in the giant nerve fibres of the squid (Keynes & Rojas 1974). Since giant nerve fibres are considered to be an adaptation to rapid movement it is of interest to consider whether there is an optimum density of sodium channels at which conduction velocity is maximal. If this can be established it is then important to develop methods for calculating the optimum density on different sets of assumptions.
Formalization of the Operation Recorder based on Graph Transformation Theory

Software engineering has come a long way in its short history. With the recent advent of modeldriven development, which places models at the center of all development efforts, some of the existing deficiencies of traditional, code-centric software development approaches have been addressed. However, at the same time new problems arose, which require, for example, techniques to describe, control and verify the evolution of models. Drawing from past experiences and findings in the field of code-centric software evolution is only partly feasible due to the inherent graph-based nature of models, which renders the adoption and porting of previously developed solutions for text-based software development impractical. The graph-based nature of models suggests the application of graph transformation-theoretic concepts to models, in order to formally describe their manipulation by means of graph-rewriting rules. Though the concepts and techniques provided by the theory of graph transformation may seem intuitive, the specification of accurate rewriting rules is a non-trivial and time-consuming task, which requires adequate tool support and thorough knowledge of the underlying theory. Unfortunately, due to the heterogeneity of the employed approaches, a tool’s capability to specify graph rewriting rules and the degree of assistance offered for this task is hard to determine without prior investigation. Thus, a survey of existing tools was conducted, which revealed the Operation Recorder as a suitable tooling environment. In contrast to all other surveyed tools, it offers a by-demonstration environment, which allows to showcase the intended transformation instead of requiring its manual construction by means of dedicated transformation languages. The Operation Recorder, however, lacks a concise, formal basis which prevents the verification of its transformations. Therefore, a framework to describe attributed graphs with inheritance, composition and multiplicities is presented with the aim to embed the Operation Recorder into this framework. For this purpose, a conceptual alignment is pursued which demonstrates the equivalence and interchangeability of the concepts provided by the Operation Recorder and those provided by the theory of graph transformation.
Inducers of oxidative stress block ciliary neurotrophic factor activation of Jak/STAT signaling in neurons

Generation of reactive oxygen species (ROS) with the accumulation of oxidative damage has been implicated in neurodegenerative disease and in the degradation of nervous system function with age. Here we report that ROS inhibit the activity of ciliary neurotrophic factor (CNTF) in nerve cells. Treatment with hydrogen peroxide (H2O2) as a generator of ROS inhibited CNTF‐mediated Jak/STAT signaling in all cultured nerve cells tested, including chick ciliary ganglion neurons, chick neural retina, HMN‐1 motor neuron hybrid cells, and SH‐SY5Y and BE(2)‐C human neuroblastoma cells. H2O2 treatment of non‐neuronal cells, chick skeletal muscle and HepG2 hepatoma cells, did not inhibit Jak/STAT signaling. The H2O2 block of CNTF activity was seen at concentrations as low as 0.1 mm and within 15 min, and was reversible upon removal of H2O2 from the medium. Also, two other mediators of oxidative stress, nitric oxide and rotenone, inhibited CNTF signaling. Treatment of neurons with H2O2 and rotenone also inhibited interferon‐γ‐mediated activation of Jak/STAT1. Depleting the intracellular stores of reduced glutathione by treatment of BE(2)‐C cells with nitrofurantoin inhibited CNTF activity, whereas addition of reduced glutathione protected cells from the effects of H2O2. These results suggest that disruption of neurotrophic factor signaling by mediators of oxidative stress may contribute to the neuronal damage observed in neurodegenerative diseases and significantly affect the utility of CNTF‐like factors as therapeutic agents in preventing nerve cell death.
Effect of inflammatory bowel disease classification changes on NOD2 genotype–phenotype associations in a population‐based cohort

Background: NOD2 mutations are associated with Crohn's disease (CD) in Caucasian clinic‐based cohorts. Data from population‐based cohorts are limited. Clinic‐based studies may overestimate this association. Genotype–phenotype relationships are yet to be assessed using the Montreal classification. We hypothesized that the NOD2–CD association would be weaker in a population‐based cohort, and that the Montreal classification would strengthen genotype–phenotype associations. Methods: A population‐based case‐control study was performed including 91% of all people in Canterbury, New Zealand, with inflammatory bowel disease (IBD); NOD2 genotyping was performed and patients were phenotyped according to the Vienna and Montreal classification systems. Results: The NOD2 genotype was available on 684 CD, 643 ulcerative colitis (UC), 36 indeterminate colitis/IBDU (IBD unclassified) patients, and 201 controls. Control frequencies for the 702W, 908R, and 1007fs alleles were 0.030, 0.012, and 0.010, respectively, compared with 0.074, 0.027, and 0.040 for CD. The 702W (P = 0.001) and 1007fs (P = 0.002) alleles were significantly associated with CD. Younger age of diagnosis (<17 years) was associated with 1 (odds ratio (OR) 1.9 [95% confidence intervals 0.98–3.6]) or 2 (OR 6.5 [2.3–18.6]) NOD2 mutations compared with diagnosis >40 years. Ileal disease was most strongly associated with NOD2 mutations (1 mutation OR 3.9 [2.4–6.3], 2 mutations OR 6.7 [2.4–18.5]). Penetrating disease was associated with NOD2 mutations using the Montreal but not the Vienna classification. Conclusions: The association between NOD2 mutations and CD was found to be weaker in our population‐based cohort than in previous studies that used referral‐based cohorts. Application of the Montreal classification led to a strengthening of the NOD2 genotype–phenotype association. (Inflamm Bowel Dis 2007)
Incorporating Individual Error Rate into Association Test of Unmatched Case-Control Design

Objectives: Genotyping error commonly occurs and could reduce the power and bias statistical inference in genetics studies. In addition to genotypes, some automated biotechnologies also provide quality measurement of each individual genotype. We studied the relationship between the quality measurement and genotyping error rate. Furthermore, we propose two association tests incorporating the genotyping quality information with the goal to improve statistical power and inference. Methods: 50 pairs of DNA sample duplicates were typed for 232 SNPs by BeadArray technology. We used scatter plot, smoothing function and generalized additive models to investigate the relationship between genotype quality score (q) and inconsistency rate (ĩ) among duplicates. We constructed two association tests: (1) weighted contingency table test (WCT) and (2) likelihood ratio test (LRT) to incorporate individual genotype error rate (Εi), in unmatched case-control setting. Results: In the 50 duplicates, we found q and ĩ were in strong negative association, suggesting the genotypes with low quality score were more likely to be mistyped. The WCT improved the statistical power and partially corrects the bias in point estimation. The LRT offered moderate power gain, but was able to correct the bias in odds ratio estimation. The two new methods also performed favorably in some scenarios when Εi was mis-specified. Conclusions: With increasing number of genetic studies and application of automated genotyping technology, there is a growing need to adequately account for individual genotype error rate in statistical analysis. Our study represents an initial step to address this need and points out a promising direction for further research.