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

Decoding pooled RNAi screens by means of barcode tiling arrays

<p>Abstract</p> <p>Background</p> <p>RNAi screens via pooled short hairpin RNAs (shRNAs) have recently become a powerful tool for the identification of essential genes in mammalian cells. In the past years, several pooled large-scale shRNA screens have identified a variety of genes involved in cancer cell proliferation. All of those studies employed microarray analysis, utilizing either the shRNA's half hairpin sequence or an additional shRNA-associated 60 nt barcode sequence as a molecular tag. Here we describe a novel method to decode pooled RNAi screens, namely barcode tiling array analysis, and demonstrate how this approach can be used to precisely quantify the abundance of individual shRNAs from a pool.</p> <p>Results</p> <p>We synthesized DNA microarrays with six overlapping 25 nt long tiling probes complementary to each unique 60 nt molecular barcode sequence associated with every shRNA expression construct. By analyzing dilution series of expression constructs we show how our approach allows quantification of shRNA abundance from a pool and how it clearly outperforms the commonly used analysis via the shRNA's half hairpin sequences. We further demonstrate how barcode tiling arrays can be used to predict anti-proliferative effects of individual shRNAs from pooled negative selection screens. Out of a pool of 305 shRNAs, we identified 28 candidate shRNAs to fully or partially impair the viability of the breast carcinoma cell line MDA-MB-231. Individual validation of a subset of eleven shRNA expression constructs with potential inhibitory, as well as non-inhibitory, effects on the cell line proliferation provides further evidence for the accuracy of the barcode tiling approach.</p> <p>Conclusions</p> <p>In summary, we present an improved method for the rapid, quantitative and statistically robust analysis of pooled RNAi screens. Our experimental approach, coupled with commercially available lentiviral vector shRNA libraries, has the potential to greatly facilitate the discovery of putative targets for cancer therapy as well as sensitizers of drug toxicity.</p

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

Magnetic states at the surface of alpha Fe2O3 thin films doped with Ti, Zn, or Sn

The spin states at the surface of epitaxial thin films of hematite, both undoped and doped with 1% Ti, Sn or Zn, respectively, were probed with x-ray magnetic linear dichroism (XMLD) spectroscopy. Morin transitions were observed for the undoped (T_M~200 K) and Sn-doped (T_M~300 K) cases, while Zn and Ti-doped samples were always in the high and low temperature phases, respectively. In contrast to what has been reported for bulk hematite doped with the tetravalent ions Sn4+ and Ti4+, for which T_M dramatically decreases, these dopants substantially increase T_M in thin films, far exceeding the bulk values. The normalized Fe LII-edge dichroism for T<T_M does not strongly depend on doping or temperature, except for an apparent increase of the peak amplitudes for T<100 K. We observed magnetic field-induced inversions of the dichroism peaks. By applying a magnetic field of 6.5 T on the Ti-doped sample, a transition into the T>T_M state was achieved. The temperature dependence of the critical field for the Sn-doped sample was characterized in detail. It was demonstrated the sample-to-sample variations of the Fe LIII-edge spectra were, for the most part, determined solely by the spin orientation state. Calculations of the polarization-depedent spectra based on a spin-multiplet model were in reasonable agreement with the experiment and showed a mixed excitation character of the peak structures.Comment: 8 pages, 8 figure

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

Searching for Massive Outflows in Holmberg IX X-1 and NGC 1313 X-1: The Iron K Band

We have analysed all the good quality XMM-Newton data publicly available for the bright ULXs Holmberg IX X-1 and NGC 1313 X-1, with the aim of searching for discrete emission or absorption features in the Fe K band that could provide observational evidence for the massive outflows predicted if these sources are accreting at substantially super-Eddington rates. We do not find statistically compelling evidence for any atomic lines, and the limits that are obtained have interesting consequences. Any features in the immediate Fe K energy band (6-7 keV) must have equivalent widths weaker than ~30 eV for Holmberg IX X-1, and weaker than ~50 eV for NGC 1313 X-1 (at 99 per cent confidence). In comparison to the sub-Eddington outflows observed in GRS 1915+105, which imprint iron absorption features with equivalent widths of ~30 eV, the limits obtained here appear quite stringent, particularly when Holmberg IX X-1 and NGC 1313 X-1 must be expelling at least 5-10 times as much material if they host black holes of similar masses. The difficulty in reconciling these observational limits with the presence of strong line-of-sight outflows suggests that either these sources are not launching such outflows, or that they must be directed away from our viewing angle.Comment: 11 pages, 5 figures, accepted for publication in MNRA

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