Miracle-dz/UniFAR-FTUs huggingface dataset:
DNA-dependent protein kinase suppresses double-strand break-induced and spontaneous homologous recombination

DNA-dependent protein kinase (DNA-PK), composed of Ku70, Ku80, and the catalytic subunit (DNA-PKcs), is involved in repairing double-strand breaks (DSBs) by nonhomologous end-joining (NHEJ). Certain proteins involved in NHEJ are also involved in DSB repair by homologous recombination (HR). To test the effects of DNA-PKcs on DSB-induced HR, we integrated neo direct repeat HR substrates carrying the I-SceI recognition sequence into DNA-PKcs-defective Chinese hamster ovary (V3) cells. The DNA-PKcs defect was complemented with a human DNA-PKcs cDNA. DSB-induced HR frequencies were 1.5- to 3-fold lower with DNA-PKcs complementation. In complemented and uncomplemented strains, all products arose by gene conversion without associated crossover, and average conversion tract lengths were similar. Suppression of DSB-induced HR in complemented cells probably reflects restoration of NHEJ, consistent with competition between HR and NHEJ during DSB repair. Interestingly, spontaneous HR rates were 1.6- to >3.5-fold lower with DNA-PKcs complementation. DNA-PKcs may suppress spontaneous HR through NHEJ of spontaneous DSBs, perhaps at stalled or blocked replication forks. Because replication protein A (RPA) is involved in both replication and HR, and is phosphorylated by DNA-PKcs, it is possible that the suppression of spontaneous HR by DNA-PKcs reflects regulation of replication-dependent HR by DNA-PKcs, perhaps by means of phosphorylation of RPA.
Isokinetic Concentric Versus Eccentric Training of Shoulder Rotators with Functional Evaluation of Performance Enhancement in Elite Tennis Players

Thirty elite tennis players were randomly assigned to three groups to evaluate shoulder isokinetic internal and external rotation training: an isokinetic concentric group, an isokinetic eccentric group, and a control group with no training. Subjects were tested before and after training both concentrically and eccentrically using an isokinetic dynamometer. Functional output before and after training was assessed by the average and peak velocity of six maximal serves. The effect of training on serve velocity endurance was also assessed. Statisti cally significant concentric and eccentric strength gains (11 %) were obtained in both training groups when com pared with controls (decreased total average strain of 2%) (P < 0.0004). Serve velocity increased by greater than 11 % in both training groups, which was a signifi cant increase from the average of 1% in the control group (P < 0.0001). In the endurance study, training group subjects displayed a tendency to maintain their serve velocity (loss of approximately 2%) greater than controls (loss of 6.4%) (P< 0.05). Isokinetic training led to increases in objective and functional output in elite tennis players. This training regimen may have signifi cance in the final stages of the rehabilitation of injured shoulders as well as in improved performance and re duced injury risk.
Radial and non-radial decompositions of profit change: an application *

Grifell-Tatje and Lovell (1999) made a contribution to the literature by decomposing profit change in extended radial DEA framework into six mutually exclusive components. Their approach appears to suffer from two shortcomings. First, radial models do not achieve full efficiency when slacks are present, and therefore, the contributions of each of these components are grossly underestimated. Second, evaluations of these components, using base-period prices as weights, can be potentially misleading. To circumvent over these shortcomings, we, first, introduce non-radial DEA models, and second, provide strong theoretical argument in favor of either current-period prices/average price of both periods as weights to be used to value the contributions of each of these components. The Indian banking sector is taken as a case study to illustrate the radial and non-radial decompositions of profit change so as to empirically examine the role of competition on profit change as well as its six mutually exclusive components. Our broad empirical results are as follows: First, radial and non-radial models yield diametrical opposite sign on the contributions of various components. Second, the increasing efficiency change trend in all ownership groups after 2002 indicates an affirmative gesture about the effect of the reform process on the performance of the Indian banking sector. Third, despite the fact that nationalized banks are the oldest banks, they do not reflect their learning experience in their output-and resource allocation behaviors.
Ethnic Disparities in Ischemic Stroke, Intracerebral Hemorrhage, and Subarachnoid Hemorrhage Incidence in The Netherlands

Background and Purpose— Data on the incidence of stroke subtypes among ethnic minority groups are limited. We assessed ethnic differences in the incidence of stroke subtypes in the Netherlands. Methods— A Dutch nationwide register–based cohort study (n=7 423 174) was conducted between 1998 and 2010. We studied the following stroke subtypes: ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Cox proportional hazard models were used to estimate incidence differences between first-generation ethnic minorities and the Dutch majority population (ethnic Dutch). Results— Compared with ethnic Dutch, Surinamese men and women had higher incidence rates of all stroke subtypes combined (adjusted hazard ratios, 1.43; 95% confidence interval, 1.35–1.50 and 1.34; 1.28–1.41), ischemic stroke (1.68; 1.57–1.81 and 1.57; 1.46–1.68), intracerebral hemorrhage (2.08; 1.82–2.39 and 1.74; 1.50–2.00), and subarachnoid hemorrhage (1.25; 0.92–1.69 and 1.26; 1.04–1.54). By contrast, Moroccan men and women had lower incidence rates of all stroke subtypes combined (0.42; 0.36–0.48 and 0.37; 0.30–0.46), ischemic stroke (0.35; 0.27–0.45 and 0.34; 0.24–0.49), intracerebral hemorrhage (0.61; 0.41–0.92 and 0.32; 0.16–0.72), and subarachnoid hemorrhage (0.42; 0.20–0.88 and 0.34; 0.17–0.68) compared with ethnic Dutch counterparts. The results varied by stroke subtype and sex for the other minority groups. For example, Turkish women had a reduced incidence of subarachnoid hemorrhage, whereas Turkish men had an increased incidence of ischemic stroke and intracerebral hemorrhage compared with ethnic Dutch. Conclusions— Our findings suggest that Surinamese have an increased risk, whereas Moroccans have a reduced risk for all the various stroke subtypes. Among other ethnic minorities, the risk seems to depend on the stroke subtype and sex. These findings underscore the need to identify the root causes of these ethnic differences to assist primary and secondary prevention efforts.
Efficacy and toxicity of methotrexate (MTX) monotherapy versus MTX combination therapy with non-biological disease-modifying antirheumatic drugs in rheumatoid arthritis: a systematic review and meta-analysis

Objective: To evaluate the efficacy and toxicity of methotrexate (MTX) monotherapy compared with MTX combination with non-biological disease-modifying antirheumatic drugs (DMARDs) in adults with rheumatoid arthritis. Method: A systematic review of randomised trials comparing MTX alone and in combination with other non-biological DMARDs was carried out. Trials were identified in Medline, EMBASE, the Cochrane Library and ACR/EULAR meeting abstracts. Primary outcomes were withdrawals for adverse events or lack of efficacy. Results: A total of 19 trials (2025 patients) from 6938 citations were grouped by the type of patients randomised. Trials in DMARD naive patients showed no significant advantage of the MTX combination versus monotherapy; withdrawals for lack of efficacy or toxicity were similar in both groups (relative risk (RR) = 1.16; 95% CI 0.70 to 1.93). Trials in MTX or non-MTX DMARD inadequate responder patients also showed no difference in withdrawal rates between the MTX combo versus mono groups (RR = 0.86; 95% CI 0.49 to 1.51 and RR = 0.75; 95% CI 0.41 to 1.35), but in one study the specific combination of MTX with sulfasalazine and hydroxychloroquine showed a better efficacy/toxicity ratio than MTX alone with RR = 0.3 (95% CI 0.14 to 0.65). Adding leflunomide to MTX non-responders improved efficacy but increased the risk of gastrointestinal side effects and liver toxicity. Withdrawals for toxicity were most significant with ciclosporin and azathioprine combinations. Conclusion: In DMARD naive patients the balance of efficacy/toxicity favours MTX monotherapy. In DMARD inadequate responders the evidence is inconclusive. Trials are needed that compare currently used MTX doses and combination therapies.
Sprint starts and the minimum auditory reaction time

Abstract The simple auditory reaction time is one of the fastest reaction times and is thought to be rarely less than 100 ms. The current false start criterion in a sprint used by the International Association of Athletics Federations is based on this assumed auditory reaction time of 100 ms. However, there is evidence, both anecdotal and from reflex research, that simple auditory reaction times of less than 100 ms can be achieved. Reaction time in nine athletes performing sprint starts in four conditions was measured using starting blocks instrumented with piezoelectric force transducers in each footplate that were synchronized with the starting signal. Only three conditions were used to calculate reaction times. The pre-motor and pseudo-motor time for two athletes were also measured across 13 muscles using surface electromyography (EMG) synchronized with the rest of the system. Five of the athletes had mean reaction times of less than 100 ms in at least one condition and 20% of all starts in the first two conditions had a reaction time of less than 100 ms. The results demonstrate that the neuromuscular-physiological component of simple auditory reaction times can be under 85 ms and that EMG latencies can be under 60 ms.
Estimation and Prediction With HIV-Treatment Interruption Data

We consider longitudinal clinical data for HIV patients undergoing treatment interruptions. We use a nonlinear dynamical mathematical model in attempts to fit individual patient data. A statistically-based censored data method is combined with inverse problem techniques to estimate dynamic parameters. The predictive capabilities of this approach are demonstrated by comparing simulations based on estimation of parameters using only half of the longitudinal observations to the full longitudinal data sets.
Short Amplexus Duration in a Territorial Anuran: A Possible Adaptation in Response to Male-Male Competition

Mating duration is a reproductive behaviour that can impact fertilization efficiency and offspring number. Previous studies of factors influencing the evolution of mating duration have focused on the potential role of internal sperm competition as an underlying source of selection; most of these studies have been on invertebrates. For vertebrates with external fertilization, such as fishes and frogs, the sources of selection acting on mating duration remain largely unknown due, in part, to the difficulty of observing complete mating behaviours in natural conditions. In this field study, we monitored breeding activity in a population of the territorial olive frog, Rana adenopleura, to identify factors that affect the duration of amplexus. Compared with most other frogs, amplexus was short, lasting less than 11 min on average, which included about 8 min of pre-oviposition activity followed by 3 min of oviposition. We evaluated the relationship between amplexus duration and seven variables: male body size, male condition, operational sex ratio (OSR), population size, clutch size, territory size, and the coverage of submerged vegetation in a male’s territory. We also investigated the influence of these same variables, along with amplexus duration, on fertilization rate. Amplexus duration was positively related with clutch size and the degree of male-bias in the nightly OSR. Fertilization rate was directly related to male body size and inversely related to amplexus duration. Agonistic interactions between males in amplexus and intruding, unpaired males were frequent. These interactions often resulted in mating failure, prolonged amplexus duration, and reduced fertilization rates. Together, the pattern of our findings indicates short amplexus duration in this species may be an adaptive reproductive strategy whereby males attempt to reduce the risks of mating and fertilization failures and territory loss resulting from male-male competition.
Descriptors of breathlessness in cardiorespiratory diseases.

The purposes of this study were: to examine the decriptors of breathlessness chosen by a large sample of patients with cardiorespiratory disease; to determine test-retest reliability of a patient's selection of the descriptors; and to assess whether a patient's recall of the experience of breathlessness is the same as that provoked by physical activity. Questionnaire data were collected at an initial visit for patients who complained of breathlessness and at a second visit in a subgroup of patients. A total of 218 patients who sought medical care for difficulty breathing due to one of seven different conditions were recruited from an outpatient pulmonary disease clinic at a university medical center. Patients selected statements that described qualities of breathlessness from a 15-item questionnaire and completed pulmonary function tests. At a subsequent visit (4 to 15 d later) a subgroup of 16 patients with chronic obstructive pulmonary disease (COPD) repeated the questionnaire at rest (to assess reliability) and after walking in a hallway to provoke a moderate intensity of breathlessness (to compare recall with direct experiences). The relationship among descriptors was evaluated by cluster analysis. The "work/effort" cluster was common for all diagnoses. Each condition was characterized by more than one cluster except COPD. Each diagnosis was associated with a unique set of dusters (e.g., asthma with "work/effort" and "tight," interstitial lung disease with "work/effort" and "rapid" breathing). Percent agreement for all descriptors selected at Visits 1 and 2 (recall) was 79% (r = 0.82; p = 0.001). Percent agreement at Visit 2 between descriptors for recall and for breathlessness provoked by walking was 68% (r = 0.69; p = 0.004). We conclude that patients with different cardiorespiratory conditions experience distinct qualities of breathlessness. Patients' recall of their sensations of breathlessness is reliable and comparable to dyspnea with walking. Employing a questionnaire containing descriptors of breathlessness may help to establish a specific diagnosis and to identify mechanisms whereby a specific intervention relieves dyspnea.
GSK-3 as potential target for therapeutic intervention in cancer

The serine/threonine kinase glycogen synthase kinase-3 (GSK-3) was initially identified and studied in the regulation of glycogen synthesis. GSK-3 functions in a wide range of cellular processes. Aberrant activity of GSK-3 has been implicated in many human pathologies including: bipolar depression, Alzheimer's disease, Parkinson's disease, cancer, non-insulin-dependent diabetes mellitus (NIDDM) and others. In some cases, suppression of GSK-3 activity by phosphorylation by Akt and other kinases has been associated with cancer progression. In these cases, GSK-3 has tumor suppressor functions. In other cases, GSK-3 has been associated with tumor progression by stabilizing components of the beta-catenin complex. In these situations, GSK-3 has oncogenic properties. While many inhibitors to GSK-3 have been developed, their use remains controversial because of the ambiguous role of GSK-3 in cancer development. In this review, we will focus on the diverse roles that GSK-3 plays in various human cancers, in particular in solid tumors. Recently, GSK-3 has also been implicated in the generation of cancer stem cells in various cell types. We will also discuss how this pivotal kinase interacts with multiple signaling pathways such as: PI3K/PTEN/Akt/mTORC1, Ras/Raf/MEK/ERK, Wnt/beta-catenin, Hedgehog, Notch and others.
Local Anesthetics Depress the Calcium Current of Rat Sensory Neurons in Culture

BackgroundLocal anesthetics are known to inhibit the voltage-gated sodium current (INa) of the nerve membrane, but it has not been fully studied whether anesthetic concentrations of local anesthetics depress the voltage-gated calcium current (Ica) of mammalian neurons. The effects of local anesthetics on Ica, evoked in cultured rat dorsal root ganglion cells were studied. MethodsWhole cell patch clamp recordings were made from rat dorsal root ganglion cells cultured for 1–3 weeks. Ica, was recorded using patch electrodes filled with Cs-aspartate in Na+-free external solution containing 5 mM-Ba2+. All drugs, including local anesthetics, were applied by miniperfuslon from micropipettes by pressure ejection. ResultsTetracaine (300 μM) depressed the peak amplitudes of high voltage-activated (HVA)-Ica to 22.6 ± 8.8% of control values (n = 14) without affecting the current-voltage relation. A tetracaine dose-response curve for HVA-ICa Indicated an apparent dissociation constant of 79.5 μM. Tetracaine (30 μM) depressed nicardlpine-sensltive HVA-ICA (L-type) to 14.3 ± 6.7% (n = 6), β-conotoxin-sensitive HVA-Ica, (N-type) to 81.6 ± 9.6% (n = 7), and low voltage-activated (LVA)-Ica, (T-type) to 65.1 ± 11.1% (n = 6) of their respective controls. Local anesthetics other than tetracaine also depressed HVA-Ica but were of different potency; the rank sequence was dibucaine > tetracaine > bupivacaine > procaine = lidocaine. ConclusionsThese results suggest that both HVA-Ica and LVA-Ica, are depressed by tetracaine used at the concentrations required for spinal anesthesia and that the L-type Ca2+ channel among Ca2+ channel subtypes is the most susceptible to tetracaine. A good correlation between local anesthetic potencies to inhibit HVA-Ica, and their anesthetic potencies implies that the inhibition of calcium influx through voltage-gated channels may contribute to spinal anesthetic mechanisms.
The Ergogenic Effects of Transcranial Direct Current Stimulation on Exercise Performance

The physical limits of the human performance have been the object of study for a considerable time. Most of the research has focused on the locomotor muscles, lungs, and heart. As a consequence, much of the contemporary literature has ignored the importance of the brain in the regulation of exercise performance. With the introduction and development of new non-invasive devices, the knowledge regarding the behavior of the central nervous system during exercise has advanced. A first step has been provided from studies involving neuroimaging techniques where the role of specific brain areas have been identified during isolated muscle or whole-body exercise. Furthermore, a new interesting approach has been provided by studies involving non-invasive techniques to manipulate specific brain areas. These techniques most commonly involve the use of an electrical or magnetic field crossing the brain. In this regard, there has been emerging literature demonstrating the possibility to influence exercise outcomes in healthy people following stimulation of specific brain areas. Specifically, transcranial direct current stimulation (tDCS) has been recently used prior to exercise in order to improve exercise performance under a wide range of exercise types. In this review article, we discuss the evidence provided from experimental studies involving tDCS. The aim of this review is to provide a critical analysis of the experimental studies investigating the application of tDCS prior to exercise and how it influences brain function and performance. Finally, we provide a critical opinion of the usage of tDCS for exercise enhancement. This will consequently progress the current knowledge base regarding the effect of tDCS on exercise and provides both a methodological and theoretical foundation on which future research can be based.
Issues in the Classification of Multimodal Communication Signals

Communication involves complex behavior in multiple sensory channels, or “modalities. ” We provide an overview of multimodal communication and its costs and benefits, place examples of signals and displays from an array of taxa, sensory systems, and functions into our signal classification system, and consider issues surrounding the categorization of multimodal signals. The broadest level of classification is between signals with redundant and nonredundant components, with finer distinctions in each category. We recommend that researchers gather information on responses to each component of a multimodal signal as well as the response to the signal as a whole. We discuss the choice of categories, whether to categorize signals on the basis of the signal or the response, and how to classify signals if data are missing. The choice of behavioral assay may influence the outcome, as may the context of the communicative event. We also consider similarities and differences between multimodal and unimodal composite signals and signals that are sequentially, rather than simultaneously, multimodal.
Channel assignment and opportunistic spectrum access in two-tier cellular networks with cognitive small cells

Cognitive small cells using opportunistic spectrum access (OSA) are envisioned to be a key technology for future generation multi-tier cellular wireless networks. In a multi-tier cellular network with universal frequency reuse, macrocell users may suffer performance degradation due to inter-tier interference caused by closed-access small cells. On the other hand, when the traffic load served by the macro network tier is high, the OSA performance of the small cells will be poor. However, similar to that for the macrocell users, the quality-of-service (QoS) performance of the small cell users need to be guaranteed. Therefore, efficient channel sharing mechanisms need to be developed for macrocell and small cell users. In this paper, we investigate on two extremal channel assignment techniques, namely, the random channel assignment (RCA) and the sequential channel assignment (SCA) techniques in the macro tier in order to accommodate the overlaid cognitive small cells with an acceptable OSA performance. We show that, for downlink transmission, while the RCA scheme offers a low intra-tier interference for macro users, it results in a degraded OSA performance (in terms of probability of successful channel access) for the small cells. On the other hand, the SCA scheme enhances the OSA performance of the small cells at the expense of increased intra-tier interference for macro users. To quantify the performance gain achieved due to OSA by the small cells for these two channel assignment schemes, we compare the coverage probability of a generic macro user when the small cells are cognitive and when the small cells aggressively use the spectrum.