Torque-onset determination: Unintended consequences of the threshold method.

BACKGROUND: Compared with visual torque-onset-detection (TOD), threshold-based TOD produces onset bias, which increases with lower torques or rates of torque development (RTD). PURPOSE: To compare the effects of differential TOD-bias on common contractile parameters in two torque-disparate groups. METHODS: Fifteen boys and 12 men performed maximal, explosive, isometric knee-extensions. Torque and EMG were recorded for each contraction. Best contractions were selected by peak torque (MVC) and peak RTD. Visual-TOD-based torque-time traces, electromechanical delays (EMD), and times to peak RTD (tRTD) were compared with corresponding data derived from fixed 4-Nm- and relative 5%MVC-thresholds. RESULTS: The 5%MVC TOD-biases were similar for boys and men, but the corresponding 4-Nm-based biases were markedly different (40.3±14.1 vs. 18.4±7.1ms, respectively; p<0.001). Boys-men EMD differences were most affected, increasing from 5.0ms (visual) to 26.9ms (4Nm; p<0.01). Men's visually-based torque kinetics tended to be faster than the boys' (NS), but the 4-Nm-based kinetics erroneously depicted the boys as being much faster to any given %MVC (p<0.001). CONCLUSIONS: When comparing contractile properties of dissimilar groups, e.g., children vs. adults, threshold-based TOD methods can misrepresent reality and lead to erroneous conclusions. Relative-thresholds (e.g., 5% MVC) still introduce error, but group-comparisons are not confounded

The Electromyographic Threshold in Girls and Women.

BACKGROUND: The electromyographic threshold (EMGTh) is thought to reflect increased high-threshold/type-II motor-unit (MU) recruitment and was shown higher in boys than in men. Women differ from men in muscular function. PURPOSE: Establish whether females' EMGTh and girls‒women differences are different than males'. METHODS: Nineteen women (22.9±3.3yrs) and 20 girls (10.3±1.1yrs) had surface EMG recorded from the right and left vastus lateralis muscles during ramped cycle-ergometry to exhaustion. EMG root-mean-squares were averaged per pedal revolution. EMGTh was determined as the least residual sum of squares for any two regression-line data divisions, if the trace rose ≥3SD above its regression line. EMGTh was expressed as % final power-output (%Pmax) and %VO2pk power (%PVO2pk). RESULTS: EMGTh was detected in 13 (68%) of women, but only 9 (45%) of girls (p<0.005) and tended to be higher in the girls (%Pmax= 88.6±7.0 vs. 83.0±6.9%, p=0.080; %PVO2pk= (101.6±17.6 vs. 90.6±7.8%, p=0.063). When EMGTh was undetected it was assumed to occur at 100%Pmax or beyond. Consequently, EMGTh values turned significantly higher in girls than in women (94.8±7.4 vs. 88.4±9.9 %Pmax, p=0.026; and 103.2±11.7 vs. 95.2±9.9 %PVO2pk, p=0.028). CONCLUSIONS: During progressive exercise, girls appear to rely less on higher-threshold/type-II MUs than do women, suggesting differential muscle activation strategy

The Magnetic Electron Ion Spectrometer (MagEIS) Instruments Aboard the Radiation Belt Storm Probes (RBSP) Spacecraft

This paper describes the Magnetic Electron Ion Spectrometer (MagEIS) instruments aboard the RBSP spacecraft from an instrumentation and engineering point of view. There are four magnetic spectrometers aboard each of the two spacecraft, one low-energy unit (20–240 keV), two medium-energy units (80–1200 keV), and a high-energy unit (800–4800 keV). The high unit also contains a proton telescope (55 keV–20 MeV). The magnetic spectrometers focus electrons within a selected energy pass band upon a focal plane of several silicon detectors where pulse-height analysis is used to determine if the energy of the incident electron is appropriate for the electron momentum selected by the magnet. Thus each event is a two-parameter analysis, an approach leading to a greatly reduced background. The physics of these instruments are described in detail followed by the engineering implementation. The data outputs are described, and examples of the calibration results and early flight data presented

Generative technologies for model animation in the TopCased platform

International audienceDomain Specific Modeling Languages (DSML) are more and more used to handle high level concepts, and thus bring complex software development under control. The increasingly recurring definition of new languages raises the problem of the definition of support tools such as editor, simulator, compiler, etc. In this paper we propose generative technologies that have been designed to ease the development of model animation tools inside the TopCased platform. These tools rely on the automatically generated graphical editors of TopCased and provide additional generators for building model animator graphical interface. We also rely on an architecture for executable metamodel (i.e., the TopCased model execution metamodeling pattern) to bind the behavioral semantics of the modeling language. These tools were designed in a pragmatic manner by abstracting the various model animators that had been hand-coded in the TopCased project, and then validated by refactoring these animators

Characterization of Changes in Serum Anti-Glycan Antibodies in Crohn's Disease – a Longitudinal Analysis

INTRODUCTION: Anti-glycan antibodies are a promising tool for differential diagnosis and disease stratification of patients with Crohn's disease (CD). We longitudinally assessed level and status changes of anti-glycan antibodies over time in individual CD patients as well as determinants of this phenomenon. METHODS: 859 serum samples derived from a cohort of 253 inflammatory bowel disease (IBD) patients (207 CD, 46 ulcerative colitis (UC)) were tested for the presence of anti-laminarin (Anti-L), anti-chitin (Anti-C), anti-chitobioside (ACCA), anti-laminaribioside (ALCA), anti-mannobioside (AMCA) and anti-Saccharomyces cerevisiae (gASCA) antibodies by ELISA. All patients had at least two and up to eleven serum samples taken during the disease course. RESULTS: Median follow-up time for CD was 17.4 months (Interquartile range (IQR) 8.0, 31.6 months) and for UC 10.9 months (IQR 4.9, 21.0 months). In a subgroup of CD subjects marked changes in the overall immune response (quartile sum score) and levels of individual markers were observed over time. The marker status (positive versus negative) remained widely stable. Neither clinical phenotype nor NOD2 genotype was associated with the observed fluctuations. In a longitudinal analysis neither changes in disease activity nor CD behavior led to alterations in the levels of the glycan markers. The ability of the panel to discriminate CD from UC or its association with CD phenotypes remained stable during follow-up. In the serum of UC patients neither significant level nor status changes were observed. CONCLUSIONS: While the levels of anti-glycan antibodies fluctuate in a subgroup of CD patients the antibody status is widely stable over time

Development of SYK NanoBRET cellular target engagement assays for gain–of–function variants

Spleen tyrosine kinase (SYK) is a non-receptor tyrosine kinase that is activated by phosphorylation events downstream of FcR, B-cell and T-cell receptors, integrins, and C-type lectin receptors. When the tandem Src homology 2 (SH2) domains of SYK bind to phosphorylated immunoreceptor tyrosine-based activation motifs (pITAMs) contained within these immunoreceptors, or when SYK is phosphorylated in interdomain regions A and B, SYK is activated. SYK gain-of-function (GoF) variants were previously identified in six patients that had higher levels of phosphorylated SYK and phosphorylated downstream proteins JNK and ERK. Furthermore, the increased SYK activation resulted in the clinical manifestation of immune dysregulation, organ inflammation, and a predisposition for lymphoma. The knowledge that the SYK GoF variants have enhanced activity was leveraged to develop a SYK NanoBRET cellular target engagement assay in intact live cells with constructs for the SYK GoF variants. Herein, we developed a potent SYK-targeted NanoBRET tracer using a SYK donated chemical probe, MRL-SYKi, that enabled a NanoBRET cellular target engagement assay for SYK GoF variants, SYK(S550Y), SYK(S550F), and SYK(P342T). We determined that ATP-competitive SYK inhibitors bind potently to these SYK variants in intact live cells. Additionally, we demonstrated that MRL-SYKi can effectively reduce the catalytic activity of SYK variants, and the phosphorylation levels of SYK(S550Y) in an epithelial cell line (SW480) stably expressing SYK(S550Y)

Age-related changes in global motion coherence: conflicting haemodynamic and perceptual responses

Our aim was to use both behavioural and neuroimaging data to identify indicators of perceptual decline in motion processing. We employed a global motion coherence task and functional Near Infrared Spectroscopy (fNIRS). Healthy adults (n = 72, 18-85) were recruited into the following groups: young (n = 28, mean age = 28), middle-aged (n = 22, mean age = 50), and older adults (n = 23, mean age = 70). Participants were assessed on their motion coherence thresholds at 3 different speeds using a psychophysical design. As expected, we report age group differences in motion processing as demonstrated by higher motion coherence thresholds in older adults. Crucially, we add correlational data showing that global motion perception declines linearly as a function of age. The associated fNIRS recordings provide a clear physiological correlate of global motion perception. The crux of this study lies in the robust linear correlation between age and haemodynamic response for both measures of oxygenation. We hypothesise that there is an increase in neural recruitment, necessitating an increase in metabolic need and blood flow, which presents as a higher oxygenated haemoglobin response. We report age-related changes in motion perception with poorer behavioural performance (high motion coherence thresholds) associated with an increased haemodynamic response

HAGE (DDX43) is a biomarker for poor prognosis and a predictor of chemotherapy response in breast cancer

Background: HAGE protein is a known immunogenic cancer-specific antigen. Methods: The biological, prognostic and predictive values of HAGE expression was studied using immunohistochemistry in three cohorts of patients with BC (n=2147): early primary (EP-BC; n=1676); primary oestrogen receptor-negative (PER-BC; n=275) treated with adjuvant anthracycline-combination therapies (Adjuvant-ACT); and primary locally advanced disease (PLA-BC) who received neo-adjuvant anthracycline-combination therapies (Neo-adjuvant-ACT; n=196). The relationship between HAGE expression and the tumour-infiltrating lymphocytes (TILs) in matched prechemotherapy and postchemotherapy samples were investigated. Results: Eight percent of patients with EP-BC exhibited high HAGE expression (HAGEþ) and was associated with aggressive clinico-pathological features (Ps<0.01). Furthermore, HAGEþexpression was associated with poor prognosis in both univariate and multivariate analysis (Ps<0.001). Patients with HAGE+ did not benefit from hormonal therapy in high-risk ER-positive disease. HAGE+ and TILs were found to be independent predictors for pathological complete response to neoadjuvant-ACT; P<0.001. A statistically significant loss of HAGE expression following neoadjuvant-ACT was found (P=0.000001), and progression-free survival was worse in those patients who had HAGE+ residual disease (P=0.0003). Conclusions: This is the first report to show HAGE to be a potential prognostic marker and a predictor of response to ACT in patients with BC

Do Neuro-Muscular Adaptations Occur in Endurance-Trained Boys and Men?

Most research on the effects of endurance training has focused on endurance training's health-related benefits and metabolic effects in both children and adults. The purpose of this study was to examine the neuromuscular effects of endurance training and to investigate whether they differ in children (9.0-12.9 years) and adults (18.4-35.6 years). Maximal isometric torque, rate of torque development (RTD), rate of muscle activation (Q30), electromechanical delay (EMD), and time to peak torque and peak RTD were determined by isokinetic dynamometry and surface electromyography (EMG) in elbow and knee flexion and extension. The subjects were 12 endurance-trained and 16 untrained boys, and 15 endurance-trained and 20 untrained men. The adults displayed consistently higher peak torque, RTD, and Q30, in both absolute and normalized values, whereas the boys had longer EMD (64.7+/-17.1 vs. 56.6+/-15.4 ms) and time to peak RTD (98.5+/-32.1 vs. 80.4+/-15.0 ms for boys and men, respectively). Q30, normalized for peak EMG amplitude, was the only observed training effect (1.95+/-1.16 vs. 1.10+/-0.67 ms for trained and untrained men, respectively). This effect could not be shown in the boys. The findings show normalized muscle strength and rate of activation to be lower in children compared with adults, regardless of training status. Because the observed higher Q30 values were not matched by corresponding higher performance measures in the trained men, the functional and discriminatory significance of Q30 remains unclear. Endurance training does not appear to affect muscle strength or rate of force development in either men or boys