Miracle-dz/UniFAR-FTUs huggingface dataset:
A genome-wide association study of myasthenia gravis.

IMPORTANCE Myasthenia gravis is a chronic, autoimmune, neuromuscular disease characterized by fluctuating weakness of voluntary muscle groups. Although genetic factors are known to play a role in this neuroimmunological condition, the genetic etiology underlying myasthenia gravis is not well understood. OBJECTIVE To identify genetic variants that alter susceptibility to myasthenia gravis, we performed a genome-wide association study. DESIGN, SETTING, AND PARTICIPANTS DNA was obtained from 1032 white individuals from North America diagnosed as having acetylcholine receptor antibody-positive myasthenia gravis and 1998 race/ethnicity-matched control individuals from January 2010 to January 2011. These samples were genotyped on Illumina OmniExpress single-nucleotide polymorphism arrays. An independent cohort of 423 Italian cases and 467 Italian control individuals were used for replication. MAIN OUTCOMES AND MEASURES We calculated P values for association between 8,114,394 genotyped and imputed variants across the genome and risk for developing myasthenia gravis using logistic regression modeling. A threshold P value of 5.0×10(-8) was set for genome-wide significance after Bonferroni correction for multiple testing. RESULTS In the overall case-control cohort, we identified association signals at CTLA4 (rs231770; P=3.98×10(-8); odds ratio, 1.37; 95% CI, 1.25-1.49), HLA-DQA1 (rs9271871; P=1.08×10(-8); odds ratio, 2.31; 95% CI, 2.02-2.60), and TNFRSF11A (rs4263037; P=1.60×10(-9); odds ratio, 1.41; 95% CI, 1.29-1.53). These findings replicated for CTLA4 and HLA-DQA1 in an independent cohort of Italian cases and control individuals. Further analysis revealed distinct, but overlapping, disease-associated loci for early- and late-onset forms of myasthenia gravis. In the late-onset cases, we identified 2 association peaks: one was located in TNFRSF11A (rs4263037; P=1.32×10(-12); odds ratio, 1.56; 95% CI, 1.44-1.68) and the other was detected in the major histocompatibility complex on chromosome 6p21 (HLA-DQA1; rs9271871; P=7.02×10(-18); odds ratio, 4.27; 95% CI, 3.92-4.62). Association within the major histocompatibility complex region was also observed in early-onset cases (HLA-DQA1; rs601006; P=2.52×10(-11); odds ratio, 4.0; 95% CI, 3.57-4.43), although the set of single-nucleotide polymorphisms was different from that implicated among late-onset cases. CONCLUSIONS AND RELEVANCE Our genetic data provide insights into aberrant cellular mechanisms responsible for this prototypical autoimmune disorder. They also suggest that clinical trials of immunomodulatory drugs related to CTLA4 and that are already Food and Drug Administration approved as therapies for other autoimmune diseases could be considered for patients with refractory disease.
Sparsity oracle inequalities for the Lasso

This paper studies oracle properties of $\ell_1$-penalized least squares in nonparametric regression setting with random design. We show that the penalized least squares estimator satisfies sparsity oracle inequalities, i.e., bounds in terms of the number of non-zero components of the oracle vector. The results are valid even when the dimension of the model is (much) larger than the sample size and the regression matrix is not positive definite. They can be applied to high-dimensional linear regression, to nonparametric adaptive regression estimation and to the problem of aggregation of arbitrary estimators.
Motor Overflow in Nonretarded Children and Down Syndrome Adults

Two experiments are reported that examine motor overflow in Down syndrome and nonretarded persons. The two main purposes of the experiments were to determine the utility of motor overflow as a diagnostic tool and the relationship between motor overflow and transfer of training. In Experiment 1, nonretarded children and adults performed a unimanual finger-sequencing task. It was found that motor overflow follows a developmental course. As well, a positive relationship was found between motor overflow and intermanual transfer of training, and children were able to reduce their ipsilateral motor overflow with training. These results indicate that caution should be taken in diagnosing central nervous system dysfunction of a structural nature using motor overflow. In Experiment 2, similar procedures were used to examine younger children and Down syndrome adults. It was found that with conscious effort, even the children could reduce their motor overflow. A positive relationship between transfer of training and motor overflow was also evidenced in Down syndrome subjects. As well, there was greater transfer of training from the left hand to the right hand than the reverse, in both Down syndrome
Modeling task-genre relationships for IR in the workplace

Context influences the search process, but to date research has not definitively identified which aspects of context are the most influential for information retrieval, and thus are worthy of integration in today's retrieval systems. In this research, we isolated for examination two aspects of context: task and document genre and examined the relationship between them within a software engineering work domain. In this domain, the nature of the task has an impact on decisions of relevance and usefulness, and the document collection contains a distinctive set of genre. Our data set was a document repository created and used by our target population. The document surrogates were meta-tagged by purpose and document type. Correspondence analysis of this categorical data identified some specific relationships between genres and tasks, as well as four broad dimensions of variability underlying these relationships. These results have the potential to inform the design of a contextual retrieval system by refining search results for this domain.
Analysis of chopper controlled DC series motor

An analysis is presented of a chopper-controlled DC series motor. The analysis takes into consideration the various nonlinearities of the motor operation, like magnetic saturation, armature reaction and eddy currents, etc. In the proposed method the parameters used for numerical solutions are obtained from tests and design specifications. The time ratio control of the chopper voltage is mainly considered. A linear model is proposed for the steady-state analysis. The computed and experimental results show good agreement and prove the validity of the proposed technique. <<ETX>>
Loopfrog: A Static Analyzer for ANSI-C Programs

Practical software verification is dominated by two major classes of techniques. The first is model checking, which provides total precision, but suffers from the state space explosion problem. The second is abstract interpretation, which is usually much less demanding, but often returns a high number of false positives. We present Loopfrog, a static analyzer that combines the best of both worlds: the precision of model checking and the performance of abstract interpretation. In contrast to traditional static analyzers, it also provides `leaping' counterexamples to aid in the diagnosis of errors.
Choices and affective reactions to negative life events: An averaging/summation analysis

Three experiments investigated individuals’ preferences and affective reactions to negative life experiences. Participants had a more intense negative affective reaction when they were exposed to a highly negative life experience than when they were exposed to two negative events: a highly negative and a mildly negative life event. Participants also chose the situation containing two versus one negative event. Thus, “more negative events were better” when the events had different affective intensities. When participants were exposed to events having similar affective intensities, however, two negative events produced a more intense negative affective reaction. In addition, participants chose the situation having one versus two negative life experiences. Thus, “more negative events were worse” when the events had similar affective intensities. These results are consistent with an averaging/summation (A/S) model and delineate situations when “more” negative life events are “better” and when “more” negative life events are “worse. ” Results also ruled out several alternative interpretations including the peak-end rule and mental accounting interpretations.
The Conserved Dopaminergic Diencephalospinal Tract Mediates Vertebrate Locomotor Development in Zebrafish Larvae

The most conserved part of the vertebrate dopaminergic system is the orthopedia (otp)-expressing diencephalic neuronal population that constitutes the dopaminergic diencephalospinal tract (DDT). Although studies in the neonatal murine spinal cord in vitro suggest an early locomotor role of the DDT, the function of the DDT in developing vertebrates in vivo remains unknown. Here, we investigated the role of the DDT in the locomotor development of zebrafish larvae. To assess the development of the behavioral and neural locomotor pattern, we used high-throughput video tracking in combination with peripheral nerve recordings. We found a behavioral and neural correspondence in the developmental switch from an immature to mature locomotor pattern. Blocking endogenous dopamine receptor 4 (D4R) signaling in vivo either before or after the developmental switch prevented or reversed the switch, respectively. Spinal transections of post-switch larvae reestablished the immature locomotor pattern, which was rescued to a mature-like pattern via spinal D4R agonism. Selective chemogenetic ablation of otp b (otpb) neurons that contribute to the DDT perpetuated the immature locomotor pattern in vivo. This phenotype was recapitulated by diencephalic transections that removed the dopaminergic otpb population and was rescued to a mature-like locomotor pattern by D4R agonism. We conclude that the dopaminergic otpb population, via the DDT, is responsible for spinal D4R signaling to mediate the developmental switch to the mature locomotor pattern of zebrafish. These results, integrated with the mammalian literature, suggest that the DDT represents an evolutionarily conserved neuromodulatory system that is necessary for normal vertebrate locomotor development.
Athlete fear avoidance and pain interference are related to return to competition time following an acute injury in athletes

Context: Pain related fear and fear avoidance contribute to the development of chronic pain and longer rehabilitation times in the general population. Recent evidence suggests that fear avoidance might be associated with increased rehabilitation times in athletes with ACL reconstructions but there is little research on other injuries. Objective: The purpose of this study was to measure fear avoidance and return to competition times in athletes who have suffered an acute musculoskeletal injury. Participants: Thirty-five student-athletes (25 males, 10 females) participated in this study. Athletes competed in football, rugby, soccer, basketball, or hockey. Measures: Within 24 hours of suffering a musculoskeletal injury, participants completed a battery of questionnaires that assessed function, pain severity, interference and disability, depression, and psychosocial factors, which included (athlete) fear avoidance, catastrophizing and kinesiophobia. Return to competition was measured in days once the athlete returned to competition with no restrictions. Results: There was a significant improvement in pain and function from injury to return to competition. In addition, all participants experienced a decrease in pain disability, severity, and interference, as well as all psychosocial factors from injury onset to return to competition. Pearson correlations identified significant relationships between injury onset athlete fear avoidance, change in function, pain disability, pain interference, and depression, with return to competition. The regression analysis indicated a significant model, which accounted for 35.3% of the variance of return to competition times. Conclusion: It is possible that using injury onset measures of pain and athlete fear avoidance could predict rehabilitation times in athletes.
Effect of Moderate Swimming Exercise on Hyperglycaemia, Polyphagia, Polydipsia and Weight Loss in Streptozotocin-Induced Diabetic Rats

Purpose: The purpose of the current study is to evaluate the efficacy of regular exercise as a useful nonpharmacological strategy in attenuating the diabetes symptom such as hyperglycaemia, polyuria, polydipsia, polyphagia, and weight loss. Materials and Methods: Twenty male Wistar rats (200±20 gr) were divided to four groups (n = 5 per group): sedentary normal (N), trained normal (NE), sedentary diabetes (D) and trained diabetes (DE). Diabetes was induced by a single intraperitoneal injection of streptozotocin (50 mg/kg). The exercise protocol consisted of moderate intensity swimming of 30 min/day, 5 days/ week for eight weeks. Plasma glucose was evaluated at initiation and end of the experiment. Weekly weight change was calculated according to initial weight. Food conception and intake water were measured in certain day of week. Results: Induction of diabetes significantly raised plasma glucose (P = .001), increased food and water intake (P = .05) and decreased weight-gain (P = .05) in diabetic rats. Swimming exercise had small effect on plasma glucose, weight change, food intake and water intake of trained rats. Conclusion: According to the result of this study, it seems that exercise alone has small effect on management of diabetes symptoms and medical approach is necessaryfor this purpose.
Requirements for FGF3 and FGF10 during inner ear formation

Members of the fibroblast growth factor (FGF) gene family control formation of the body plan and organogenesis in vertebrates. FGF3 is expressed in the developing hindbrain and has been shown to be involved in inner ear development of different vertebrate species, including zebrafish, Xenopus, chick and mouse. In the mouse, insertion of a neomycin resistance gene into the Fgf3 gene via homologous recombination results in severe developmental defects during differentiation of the otic vesicle. We have addressed the precise roles of FGF3 and other FGF family members during formation of the murine inner ear using both loss- and gain-of-function experiments. We generated a new mutant allele lacking the entire FGF3-coding region but surprisingly found no evidence for severe defects either during inner ear development or in the mature sensory organ, suggesting the functional involvement of other FGF family members during its formation. Ectopic expression of FGF10 in the developing hindbrain of transgenic mice leads to the formation of ectopic vesicles, expressing some otic marker genes and thus indicating a role for FGF10 during otic vesicle formation. Expression analysis of FGF10 during mouse embryogenesis reveals a highly dynamic pattern of expression in the developing hindbrain, partially overlapping with FGF3 expression and coinciding with formation of the inner ear. However, FGF10 mutant mice have been reported to display only mild defects during inner ear differentiation. We thus created double mutant mice for FGF3 and FGF10, which form severely reduced otic vesicles, suggesting redundant roles of these FGFs, acting in combination as neural signals for otic vesicle formation.
Statistical properties of stock order books: empirical results and models

Abstract We investigate several statistical properties of the order book of three liquid stocks of the Paris Bourse. The results are to a large degree independent of the stock studied. The most interesting features concern (i) the statistics of incoming limit order prices, which follows a power-law around the current price with a diverging mean; and (ii) the shape of the average order book, which can be quantitatively reproduced using a ‘zero intelligence’ numerical model and qualitatively predicted using a simple approximation.
Dynamics of toxin and lectin receptors on a lymphoma cell line and its toxin-resistant variant using ferritin-conjugated, 125I-labeled ligand

The dynamics of the toxin Ricinus communis agglutinin II (RCAII or ricin) on cells of a murine lymphoma line (BW5147) and a toxin- resistant variant line (BW5147RicR.3) that is 200 times more resistant than the parent to direct RCAII cytotoxicity were examined using ferritin-conjugated, affinity purified, 125I-labeled RCAII (ferritin- 125I-RCAII). Ferritin-125I-RCAII was indistinguishable from native RCAII in quantitative binding and cytotoxicity experiments. When RCAII- sensitive BW5147 and -resistant BW5147RicR.3 cells were labeled with ferritin-125I-RCAII at various toxin concentrations (1--10 microgram/ml), no differences in toxin binding were observed. These same cells were examined by electron microscopy. At low ferritin-125I- RCAII concentrations (1-3 microgram/ml RCAII) where only the parental BW5147 cells were significantly more sensitive to RCAII, toxin receptors were internalized by ferritin-125I-RCAII-induced endocytosis. In parallel experiments, ferritin-125I-RCAII that bound to the resistant BW5147RicR.3 cells remained relatively dispersed or clustered, and there was little evidence of transport into cells via endocytosis. At higher ferritin-125I-RCAII concentrations (greater than 7 microgram/ml RCAII) where both parental and resistant variant cells are sensitive to the cytotoxic effects of RCAII, more ferritin- conjugated toxin was bound, and subsequent endocytosis occurred to a similar degree in both cell types. Endocytosis of ferritin-conjugated concanavalin A was indistinguishable on RCAII-sensitive parental and resistant variant cells at all concentrations tested. The results suggest that a specific defect on the selected BW5147RicR.3 cells prevents RCAII entry into these cells a low toxin concentrations, rendering them more resistant to the cytotoxic effects of RCAII.
The D-type cyclins and their role in tumorigenesis

SUMMARY The D-type cyclins are expressed during the progression from G0/G1 to S phase in the mammalian cell cycle. There is considerable evidence that they contribute to the development of specific cancers, both in humans and in mouse models. For example, cyclin D1 can be activated by chromosomal translocation, DNA amplification and retroviral integration. Cyclins D1, D2 and D3 preferentially associate with two closely related members of the cyclin-dependent kinase family, Cdk4 and Cdk6 and the various complexes are each capable of phosphorylating the retinoblastoma gene product (pRb), at least in vitro. This suggests that the growth promoting effects of the D-cyclins may be manifest via their interactions with tumour suppressor genes.
Algorithmic aspects of capacity in wireless networks

This paper considers two inter-related questions: (i) Given a wireless ad-hoc network and a collection of source-destination pairs {(si,ti)}, what is the maximum throughput capacity of the network, i.e. the rate at which data from the sources to their corresponding destinations can be transferred in the network? (ii) Can network protocols be designed that jointly route the packets and schedule transmissions at rates close to the maximum throughput capacity? Much of the earlier work focused on random instances and proved analytical lower and upper bounds on the maximum throughput capacity. Here, in contrast, we consider arbitrary wireless networks. Further, we study the algorithmic aspects of the above questions: the goal is to design provably good algorithms for arbitrary instances. We develop analytical performance evaluation models and distributed algorithms for routing and scheduling which incorporate fairness, energy and dilation (path-length) requirements and provide a unified framework for utilizing the network close to its maximum throughput capacity.Motivated by certain popular wireless protocols used in practice, we also explore "shortest-path like" path selection strategies which maximize the network throughput. The theoretical results naturally suggest an interesting class of congestion aware link metrics which can be directly plugged into several existing routing protocols such as AODV, DSR, etc. We complement the theoretical analysis with extensive simulations. The results indicate that routes obtained using our congestion aware link metrics consistently yield higher throughput than hop-count based shortest path metrics.
Cardiac Gap Junction Channels Show Quantitative Differences in Selectivity

Several proteins including connexin40 (Cx40) and connexin43 (Cx43) form gap junctions between cells of the heart; they may be found separately or may be coexpressed. These connexins form channels with differing conductance and permeability properties. Cx40 and Cx43 are each required for normal electrical conduction between cells in different regions of the heart. We hypothesized that the major difference between these connexins might be in their selective intercellular passage of small molecules such as second messengers, which can be assessed using biologically inert fluorescent probes. Therefore, we designed experimental paradigms to quantitate the permeability properties of these cardiac connexins using simultaneous measurement of junctional conductance (gj) by the double whole-cell patch-clamp technique and intercellular transfer of Lucifer Yellow (LY) by fluorescence microscopy. These studies were performed in HeLa cells stably transfected with Cx40 or Cx43 or cotransfected with both connexins. We found that homotypic Cx43 channels were about 5 times more permeable to LY than homotypic Cx40 channels (flux of ≈1560 versus ≈300 molecules/channel per second). Channels between heterotypic (Cx40-Cx43) cell pairs and between pairs of coexpressing cells exhibited intermediate LY permeability. The permeability ratio for LY relative to monovalent cation (K+) ranged from 0.0025 for Cx40 to 0.028 for Cx43. These permeability ratios suggest that the connexins are highly selective for solutes in the size and charge range of many second messengers. Moreover, the data indicate that coexpression of connexins does not generate unique permeability characteristics, but rather results in an intermediate permeability for solutes involved in metabolic/biochemical coupling.
STRENGTH IS IGNORANCE; SLAVERY IS FREEDOM: MANAGING CULTURE IN MODERN ORGANIZATIONS*

The article subjects the assumptions and prescriptions of the ‘Corporate Culture’literature to critical scrutiny. the body of the article is devoted to teasing out the distinctive basis of its appeal compared with earlier management theory. It is seen to build upon earlier efforts (e.g.‘theory Y’) to constitute a self-disciplining form of employee subjectivity by asserting that ‘practical autonomy’is conditional upon the development of a strong corporate culture. the paper illuminates the dark side of this project by drawing attention to the subjugating and totalitarian implications of its excellence/ quality prescriptions. to this end, parallels are drawn with the philosophy of control favoured by the Party in Orwell's Nineteen Eighty-Four. Specifically, the paper critiques the ‘doublethink’contention that autonomy can be realized in monocultural conditions that systematically constrain opportunities to wrestle with competing values standpoints and their associated life projects.