Miracle-dz/UniFAR-FTUs huggingface dataset:
The Effect of Rilonacept versus Placebo on Health-Related Quality of Life in Patients with Poorly Controlled Familial Mediterranean Fever

Objective. To examine the effect of rilonacept on the health-related quality of life (HRQoL) in patients with poorly controlled familial Mediterranean fever (FMF). Methods. As part of a randomized, double-blinded trial comparing rilonacept and placebo for the treatment of FMF, patients/parents completed the modified Child Health Questionnaire (CHQ) at baseline, and at the start and end of each of 4 treatment courses, 2 each with rilonacept and placebo. Results. Fourteen subjects were randomized; mean age was 24.4 ± 11.8 years. At baseline the physical HRQoL score was significantly less (24.2 ± 49.5) but the psychosocial score was similar to the population norm (49.5 ± 10.0). There were significant improvements in most HRQoL concepts after rilonacept but not placebo. Significant differences between rilonacept and placebo were found in the physical (33.7 ± 16.4 versus 23.7 ± 14.5, P = 0.021) but not psychosocial scores (51.4 ± 10.3 versus 49.8 ± 12.4, P = 0.42). The physical HRQoL was significantly impacted by the treatment effect and patient global assessment. Conclusion. Treatment with rilonacept had a beneficial effect on the physical HRQoL in patients with poorly controlled FMF and was also significantly related to the patient global assessment. This trial is registered with ClinicalTrials.gov Identifier NCT00582907.
Modélisation bayésienne de la planification motrice des gestes de parole: Évaluation du rôle des différentes modalités sensorielles (Bayesian modeling of speech gesture motor planning: Evaluating the role of different sensory modalities )[In French]

La prise en compte des informations auditives et proprioceptives dans le contrôle de la parole est mise en évidence par un nombre croissant de résultats expérimentaux. Cependant, les modèles de production imposent le plus souvent l’une ou l’autre des modalités, ou n’offrent pas de cadre formel pour évaluer leurs contributions respectives. Nous proposons d’explorer le rôle de ces modalités sensorielles dans la planification des gestes de parole à partir d’un modèle bayésien représentant la structure des connaissances mises en jeu dans cette tâche. Le modèle permet d’envisager trois mécanismes de planification, reposant sur la modalité auditive, proprioceptive ou sur les deux conjointement. Nous comparons des simulations obtenues par les deux premiers mécanismes de planification. Les résultats indiquent des réalisations articulatoires différentes mais donnant néanmoins des réalisations auditives qualitativement similaires dans leur variabilité.
Getting to grips with the obesity epidemic in Europe

Obesity is a global epidemic. It is responsible for increased patient morbidity and mortality. Significant related pathologies including diabetes mellitus compound the overall risks. Obesity is a significant financial burden. This includes direct and indirect medical costs, amounting to millions of euros each year. Multiple European studies have outlined a steady incline in obesity prevalence rates. Tackling obesity is no easy task. Policy makers aiming to reduce obesity rates should adopt an evidence-based approach. This entails adopting both micro- and macro-interventions tweaked to each country’s individual requirements. The ideal way forward would be to tackle obesity from the individual, population-wide and food industry angles. The key towards a successful intervention is for each country to carry out well-planned health examination studies, in an attempt to pin point local risk factors. Having a correct individualized picture, each country can move forward and draw policies and interventional procedures. The aim should be to primarily improve the quality of life. Second, the country’s capital expenditure is also reduced.
Sparse Poisson coding for high dimensional document clustering

Document clustering plays an important role in large scale textual data analysis, which generally faces with great challenge of the high dimensional textual data. One remedy is to learn the high-level sparse representation by the sparse coding techniques. In contrast to traditional Gaussian noise-based sparse coding methods, in this paper, we employ a Poisson distribution model to represent the word-count frequency feature of a text for sparse coding. Moreover, a novel sparse-constrained Poisson regression algorithm is proposed to solve the induced optimization problem. Different from previous Poisson regression with the family of ℓ1-regularization to enhance the sparse solution, we introduce a sparsity ratio measure which make use of both ℓ1-norm and ℓ2-norm on the learned weight. An important advantage of the sparsity ratio is that it bounded in the range of 0 and 1. This makes it easy to set for practical applications. To further make the algorithm trackable for the high dimensional textual data, a projected gradient descent algorithm is proposed to solve the regression problem. Extensive experiments have been conducted to show that our proposed approach can achieve effective representation for document clustering compared with state-of-the-art regression methods.
Mass bounds in a model with a triplet Higgs

We perform an analysis of the Renormalization Group evolution of the couplings in an extension to the Standard Model which contains a real triplet in the Higgs sector. Insisting that the model remain valid up to 1 TeV allow us to map out the region of allowed mass for the Higgs bosons. We conclude that it is possible for there to be no light Higgs bosons without any otherwise dramatic deviation from the physics of the Standard Model.
The effect of a dual or a triple antithrombotic therapy with apixaban on thrombus formation in vivo and in an ex vivo perfusion chamber model

Background:There is a need to optimize pharmacological treatment in patients with acute coronary syndrome and concomitant atrial fibrillation, in particular with newer antithrombotic medicines. We have therefore studied if dual or triple combination of antithrombotic agents exert similar effects on coagulation activation in an in vivo model in the skin microvasculature and in an ex vivo perfusion chamber. Methods and Results:Shed blood platelet activation (&bgr;-thromboglobulin [&bgr;-TG]), thrombin generation (thrombin-antithrombin complex [TAT]) and volume as well as markers of thrombus size (D-dimer) and its platelet content (P-selectin) in a perfusion chamber were studied in a sequential, open-label, parallel group trial in 40 healthy male volunteers (n = 20 per group). Subjects received ticagrelor and apixaban without or with acetylsalicylic acid (ASA). Outcome parameters were assessed at 3 hours after therapy dosing, and at steady-state trough and peak conditions.A triple or dual therapy induced a comparable decrease in shed blood &bgr;-TG at 3 hours after therapy dosing but was more pronounced at steady-state conditions with the more intense treatment combination. During both antithrombotic regimens a similarly sustained inhibition in thrombin generation was observed which was accompanied by comparable increases in shed blood volume. In contrast, no treatment effect could be observed in the perfusion chamber experiment. Conclusion:Ticagrelor and apixaban with or without ASA inhibit platelet activation and thrombin formation in vivo in healthy subjects. Platelet inhibition was greater at steady-state conditions after triple therapy administration.
Conical expansion of the outer subventricular zone and the role of neocortical folding in evolution and development

There is a basic rule to mammalian neocortical expansion: as it expands, so does it fold. The degree to which it folds, however, cannot strictly be attributed to its expansion. Across species, cortical volume does not keep pace with cortical surface area, but rather folds appear more rapidly than expected. As a result, larger brains quickly become disproportionately more convoluted than smaller brains. Both the absence (lissencephaly) and presence (gyrencephaly) of cortical folds is observed in all mammalian orders and, while there is likely some phylogenetic signature to the evolutionary appearance of gyri and sulci, there are undoubtedly universal trends to the acquisition of folds in an expanding neocortex. Whether these trends are governed by conical expansion of neocortical germinal zones, the distribution of cortical connectivity, or a combination of growth- and connectivity-driven forces remains an open question. But the importance of cortical folding for evolution of the uniquely mammalian neocortex, as well as for the incidence of neuropathologies in humans, is undisputed. In this hypothesis and theory article, we will summarize the development of cortical folds in the neocortex, consider the relative influence of growth- vs. connectivity-driven forces for the acquisition of cortical folds between and within species, assess the genetic, cell-biological, and mechanistic implications for neocortical expansion, and discuss the significance of these implications for human evolution, development, and disease. We will argue that evolutionary increases in the density of neuron production, achieved via maintenance of a basal proliferative niche in the neocortical germinal zones, drive the conical migration of neurons toward the cortical surface and ultimately lead to the establishment of cortical folds in large-brained mammal species.
UMR 6070 First International Workshop on Composition : Objects , Aspects , Components , Services and Product Lines 15 March 2010 To be held in conjunction with The 9 th

Dynamic software product lines (DSPLs) are software product lines, which support late variability that is built into the system to address requirements that change at runtime. But it is difficult to ensure at runtime that all possible adaptations lead to a correct configuration. In this paper, we propose a novel approach for DSPLs that uses a dynamic feature model to describe the variability in the DSPLs and that uses a domain-specific language for declaratively implementing variations and their constraints. The approach combines several trends in aspect-oriented programming for DSPLs, namely dynamic aspects, runtime models of aspects, as well as detection and resolution of aspect interactions. The advantage is, that reconfigurations must not be specified for every feature combination, but only for interacting features. We have validated the approach in an example dynamic software product line from industry and preliminarily evaluated the approach.
A consistency theorem for regular conditional distributions

Let be a measurable space, a sub- -field and a random probability measure on , . In various frameworks, one looks for a probability P on such that is a regular conditional distribution for P given for all n. Conditions for such a P to exist are given. The conditions are quite simple when is a compact Hausdorff space equipped with the Borel or the Baire -field (as well as under similar assumptions). Applications to Gibbs measures and Bayesian statistics are given as well.
High-throughput assays for DNA gyrase and other topoisomerases

We have developed high-throughput microtitre plate-based assays for DNA gyrase and other DNA topoisomerases. These assays exploit the fact that negatively supercoiled plasmids form intermolecular triplexes more efficiently than when they are relaxed. Two assays are presented, one using capture of a plasmid containing a single triplex-forming sequence by an oligonucleotide tethered to the surface of a microtitre plate and subsequent detection by staining with a DNA-specific fluorescent dye. The other uses capture of a plasmid containing two triplex-forming sequences by an oligonucleotide tethered to the surface of a microtitre plate and subsequent detection by a second oligonucleotide that is radiolabelled. The assays are shown to be appropriate for assaying DNA supercoiling by Escherichia coli DNA gyrase and DNA relaxation by eukaryotic topoisomerases I and II, and E.coli topoisomerase IV. The assays are readily adaptable to other enzymes that change DNA supercoiling (e.g. restriction enzymes) and are suitable for use in a high-throughput format.
Specific Knockdown of OCT4 in Human Embryonic Stem Cells by Inducible Short Hairpin RNA Interference

Manipulation of gene function in embryonic stem cells by either over expression or downregulation is critical for understanding their subsequent cell fate. We have developed a tetracycline‐inducible short hairpin RNA interference (shRNAi) for human embryonic stem cells (hESCs) and demonstrated doxycycline dose‐dependent knockdown of the transcription factor OCT4 and the cell surface antigen β2‐microglobulin. The induced knockdown of OCT4 resulted in rapid differentiation of hESCs with a significant increase in transcription of genes associated with trophoblast and endoderm lineages, the extent of which was controlled by the degree of induction. Transgene toxicity, which may occur in conditional over‐expression strategies with hESCs, was not observed with wild‐type Tet repressor protein. The system allows efficient, reversible, and long‐term downregulation of target genes in hESCs and enables the generation of stable transfectants for the knockdown of genes essential for cell survival and self‐renewal, not necessarily possible by nonconditional shRNAi methods. STEM CELLS 2009;27:776–782
Prediction of Transcription Factor Binding Sites in Saccharomyces cerevisiae

Now that the complete genome sequences were determined for more than 500 species, it becomes possible to analyze the function at the genomic scale. One of the most vital functions in organisms is the regulation of gene expression achieved by a network of transcription factors and their target genes. In recent years, large amounts of sequence and structural information for transcription factors and the target genes have emerged from various ongoing genome projects. However, the mechanisms by which the transcription factors identify their target genes are not well understood yet. To achieve better understanding of the gene regulation mechanism, it is vital to elucidate which gene is controlled by which transcription factor by identifying binding sites of transcription factors. We have developed the methods to predict binding sites of transcription factors on the basis of structural information and computer simulations. In order to apply these methods to a genome-wide prediction, we conducted a pilot study for the yeast genome. For this purpose, we first constructed a database, to which we put together various kinds of data related to gene regulation in the yeast genome. We also integrate the predicted binding sites for each transcription factor into the database, and analyze the relationship with other annotation data in the database.
LOD human representations: a comparative study

Real-time crowd systems are increasing in popularity and importance. With this comes the need for accurate low level of detail (LOD) human model representations. Currently, the two most commonly used representations for large scale crowds are image based representations and low level geometric meshes. In this paper, we evaluate the effectiveness of the two representations in terms of their appearance and how accurately they convey motion. We show that low resolution geometry is not equivalent to image based representations at replicating the motion of high resolution geometry. We also report the distances from the camera at which impostors and different simplified meshes are perceptually equivalent to high resolution geometry.
Physiological and Technical-tactical Analysis in Brazilian Jiu-jitsu Competition

Purpose The present study aims at investigating the physiological response and technical-tactical parameters in Brazilian jiu-jitsu competition. Methods The study included 35 male Brazilian jiu-jitsu athletes (adult category, body mass: 80.2 ± 13.0 kg), graded from white to brown belt, during combats fought at regional level. Twenty-two fights were analyzed in terms of technique and time structure. Blood glucose, lactate and maximal isometric grip strength were determined before and after the fights. The rate of perceived exertion was also assessed after the fight, using the 6-20 Borg rating. The fights were recorded and the following variables were determined: the exertion/pause ratio and subjective intensity of actions, categorized between low and high intensity. Results The results indicated that during Brazilian jiu-jitsu fights, the glycolytic pathway is only moderately activated (lactate before: 4.4 (4.0 – 4.6) mmol/L, after: 10.1 (8.0 – 11.3) mmol/L; glucose before: 112.4 ± 22.3 mg/dL, after: 130.5 ± 31.0 mg/dL). The exertion during the fight resulted in significant reductions in handgrip strength (right hand grip before: 45.9 ± 10.3 kgf, after: 40.1 ± 9.5 kgf; left hand grip before: 44.2 ± 11.1 kgf, after: 37.0 ± 10.2 kgf). The athletes rated the fight as hard: 15 (13 – 15). Effort/pause ratio was 6:1, while high-intensity actions lasted approximately 4 s, resulting in a low/high intensity? ratio of 8:1. Conclusion It is recommended that coaches direct the training loads to simulate the energy demand imposed by the competitive matches, activating moderately the glycolytic pathway. Moreover, the time structure of combats can be used to prescribe both physical and technical-tactical training.
Use of the 5′ ‐flanking region of the mouse perforin gene to express human Fcγ receptor I in cytotoxic T lymphocytes

Expression of the gene encoding the cytolytic granule protein perforin is restricted to cytotoxic lymphocytes. To undertake a functional analysis of the immediate 5′‐promoter region of the mouse perforin gene, we transiently transfected mouse perforin promoter‐chloramphenicol acetyltransferase (CAT) reporter gene constructs into cytotoxic T, T lymphoid, B‐lymphoid, and nonlymphoid cell lines. The transcriptional activity of the perforin promoter was restricted to cytotoxic lymphocytes. The perforin promoter was controlled by several positive (in perforin‐positive cells) and negative (in perforin‐negative cells) cis‐acting regions, spread over at least 1.1 kilobases. The most specific expression of the CAT reporter gene in the interleukin‐2‐dependent cytotoxic T cell line CTLL‐R8 was obtained with the mouse perforin promoter encompassing positions ‐1104 to +1 in relation to the RNA cap site. This construct expressed 65‐ to 70‐fold higher CAT activity than the promoterless CAT construct in perforin‐expressing cells but only 1‐ to 5‐fold higher CAT activity than the promoterless construct in nonlymphoid cells. On the basis of these data, we used this most specifically active mouse perforin promoter, ‐1104 to +1, to express in CTLL‐R8, a chimeric human receptor comprising the extracellular domains of human FcγRI and the transmembrane and intracellular domains of TCR . Selection in G418‐containing medium produced CTLL‐R8 transfectant clones that (1) expressed high levels of human FcγRI mRNA; (2) expressed cell surface FcγRI as demonstrated by immunoprecipitation and their ability to bind the Fc portion of human and mouse monoclonal antibodies (mAbs) in an isotype‐specific manner, and (3) bound RBC expressing mucin‐1 (Muc‐1) peptide in the presence of a chimeric mouse‐human anti‐Muc‐1 mAb. Activation of CTLL‐R8 transfectants upon engagement of the human FcγRI was evidenced by their ability to lyse tumor target cells in an mAb isotype‐dependent manner. The successful expression of a functional chimeric gene in CTLL‐R8 suggests that the mouse perforin promoter represents a novel reagent for expressing exogenous genes in cytotoxic T lymphocytes. J. Leukoc. Biol. 55: 514–522; 1994.
Early response to immunosuppressive therapy predicts good renal outcome in lupus nephritis: lessons from long-term followup of patients in the Euro-Lupus Nephritis Trial.

OBJECTIVE In the Euro-Lupus Nephritis Trial (ELNT), 90 patients with lupus nephritis were randomly assigned to a high-dose intravenous cyclophosphamide (IV CYC) regimen (6 monthly pulses and 2 quarterly pulses with escalating doses) or a low-dose IV CYC regimen (6 pulses of 500 mg given at intervals of 2 weeks), each of which was followed by azathioprine (AZA). After a median followup of 41 months, a difference in efficacy between the 2 regimens was not observed. The present analysis was undertaken to extend the followup and to identify prognostic factors. METHODS Renal function was prospectively assessed quarterly in all 90 patients except 5 who were lost to followup. Survival curves were derived using the Kaplan-Meier method. RESULTS After a median followup of 73 months, there was no significant difference in the cumulative probability of end-stage renal disease or doubling of the serum creatinine level in patients who received the low-dose IV CYC regimen versus those who received the high-dose regimen. At long-term followup, 18 patients (8 receiving low-dose and 10 receiving high-dose treatment) had developed permanent renal impairment and were classified as having poor long-term renal outcome. We demonstrated by multivariate analysis that early response to therapy at 6 months (defined as a decrease in serum creatinine level and proteinuria <1 g/24 hours) was the best predictor of good long-term renal outcome. CONCLUSION Long-term followup of patients from the ELNT confirms that, in lupus nephritis, a remission-inducing regimen of low-dose IV CYC followed by AZA achieves clinical results comparable with those obtained with a high-dose regimen. Early response to therapy is predictive of good long-term renal outcome.
A Dynamic Analysis of Skill Formation and NEET status

This paper uses a dynamic Structural Equation Model to investigate the determinants of NEET (Not in Education, Employment or Training) status in adolescents. We model: the cumulative formation of cognitive ability over multiple periods through the life of the young person, up to completion of compulsory education; and the impact that cognitive ability has on NEET status at one and two years after compulsory education. Within this framework we address the issue of latent heterogeneity across individuals. The analysis finds that cognitive ability remains the key predictor of NEET status, and explains the persistence in NEET status. We also find evidence of significant indirect effects (of magnitudes similar to direct effects of ability) of aspirations of the young person and their parents in the prevention of NEET status. Health (general and mental) plays an important role in ability formation and in explaining NEET status; however, its impact differs between the sexes.
Barriers to Diffusion in Dendrites and Estimation of Calcium Spread Following Synaptic Inputs

The motion of ions, molecules or proteins in dendrites is restricted by cytoplasmic obstacles such as organelles, microtubules and actin network. To account for molecular crowding, we study the effect of diffusion barriers on local calcium spread in a dendrite. We first present a model based on a dimension reduction approach to approximate a three dimensional diffusion in a cylindrical dendrite by a one-dimensional effective diffusion process. By comparing uncaging experiments of an inert dye in a spiny dendrite and in a thin glass tube, we quantify the change in diffusion constants due to molecular crowding as Dcyto/Dwater = 1/20. We validate our approach by reconstructing the uncaging experiments using Brownian simulations in a realistic 3D model dendrite. Finally, we construct a reduced reaction-diffusion equation to model calcium spread in a dendrite under the presence of additional buffers, pumps and synaptic input. We find that for moderate crowding, calcium dynamics is mainly regulated by the buffer concentration, but not by the cytoplasmic crowding, dendritic spines or synaptic inputs. Following high frequency stimulations, we predict that calcium spread in dendrites is limited to small microdomains of the order of a few microns (<5 μm).