Kevlar: A Mapping-Free Framework for Accurate Discovery of De Novo Variants.

De novo genetic variants are an important source of causative variation in complex genetic disorders. Many methods for variant discovery rely on mapping reads to a reference genome, detecting numerous inherited variants irrelevant to the phenotype of interest. To distinguish between inherited and de novo variation, sequencing of families (parents and siblings) is commonly pursued. However, standard mapping-based approaches tend to have a high false-discovery rate for de novo variant prediction. Kevlar is a mapping-free method for de novo variant discovery, based on direct comparison of sequences between related individuals. Kevlar identifies high-abundance k-mers unique to the individual of interest. Reads containing these k-mers are partitioned into disjoint sets by shared k-mer content for variant calling, and preliminary variant predictions are sorted using a probabilistic score. We evaluated Kevlar on simulated and real datasets, demonstrating its ability to detect both de novo single-nucleotide variants and indels with high accuracy

Predicting Students’ Physical Activity and Health-Related Well-Being: A Prospective Cross-Domain Investigation of Motivation Across School Physical Education and Exercise Settings \ud

A three-wave prospective design was used to assess a model of motivation guided by self-determination theory (Ryan & Deci, 2008) spanning the contexts of school physical education (PE) and exercise. The outcome variables examined were health-related quality of life (HRQoL), physical self-concept (PSC), and 4 days of objectively assessed estimates of activity. Secondary school students (n = 494) completed questionnaires at three separate time points and were familiarized with how to use a sealed pedometer. Results of structural equation modeling supported a model in which perceptions of autonomy support from a PE teacher positively predicted PE-related need satisfaction (autonomy, competence, and relatedness). Competence predicted PSC, whereas relatedness predicted HRQoL. Autonomy and competence positively predicted autonomous motivation toward PE, which in turn positively predicted autonomous motivation toward exercise (i.e., 4-day pedometer step count). Autonomous motivation toward exercise positively predicted step count, HRQoL, and PSC. Results of multisample structural equation modeling supported gender invariance. Suggestions for future work are discussed.\ud \u

Gain Modulation by an Urgency Signal Controls the Speed–Accuracy Trade-Off in a Network Model of a Cortical Decision Circuit

The speed–accuracy trade-off (SAT) is ubiquitous in decision tasks. While the neural mechanisms underlying decisions are generally well characterized, the application of decision-theoretic methods to the SAT has been difficult to reconcile with experimental data suggesting that decision thresholds are inflexible. Using a network model of a cortical decision circuit, we demonstrate the SAT in a manner consistent with neural and behavioral data and with mathematical models that optimize speed and accuracy with respect to one another. In simulations of a reaction time task, we modulate the gain of the network with a signal encoding the urgency to respond. As the urgency signal builds up, the network progresses through a series of processing stages supporting noise filtering, integration of evidence, amplification of integrated evidence, and choice selection. Analysis of the network's dynamics formally characterizes this progression. Slower buildup of urgency increases accuracy by slowing down the progression. Faster buildup has the opposite effect. Because the network always progresses through the same stages, decision-selective firing rates are stereotyped at decision time

PPARα contributes to protection against metabolic and inflammatory derangements associated with acute kidney injury in experimental sepsis

Abstract Sepsis‐associated acute kidney injury (AKI) is a significant problem in critically ill children and adults resulting in increased morbidity and mortality. Fundamental mechanisms contributing to sepsis‐associated AKI are poorly understood. Previous research has demonstrated that peroxisome proliferator‐activated receptor α (PPARα) expression is associated with reduced organ system failure in sepsis. Using an experimental model of polymicrobial sepsis, we demonstrate that mice deficient in PPARα have worse kidney function, which is likely related to reduced fatty acid oxidation and increased inflammation. Ultrastructural evaluation with electron microscopy reveals that the proximal convoluted tubule is specifically injured in septic PPARα deficient mice. In this experimental group, serum metabolomic analysis reveals unanticipated metabolic derangements in tryptophan‐kynurenine‐NAD+ and pantothenate pathways. We also show that a subgroup of children with sepsis whose genome‐wide expression profiles are characterized by repression of the PPARα signaling pathway has increased incidence of severe AKI. These findings point toward interesting associations between sepsis‐associated AKI and PPARα‐driven fatty acid metabolism that merit further investigation

Internal-quantum-state engineering using magnetic fields

We present a general, semi-classical theory describing the interaction of an atom with an internal state consisting of a number of degenerate energy levels with static and oscillating magnetic fields. This general theory is applied to the 3P2 metastable energy level of neon to determine the dynamics of the populations and coherences that are formed due to the interaction. Through these calculations we demonstrate how the interaction may be used for the internal state preparation of an atom

Comparison of Electron-Atom Collision Parameters for S to P Transitions under Reversal of Energy Transfer

Inelastic and superelastic electron scattering from the optically prepared 32P3/2 state of sodium has enabled atomic collision parameters to be deduced for the 4S-3P deexcitation and the 3S-3P excitation processes. These data are compared with convergent close coupling and second order distorted wave Born calculations. For excitation, both theories agree with experiment, whereas for deexcitation the close coupling theory is in better agreement. A long-standing proposal relating to the sign of the transferred angular momentum is not supported

Comparison of Electron-Atom Collision Parameters for S to P Transitions under Reversal of Energy Transfer

Inelastic and superelastic electron scattering from the optically prepared 32P3/2 state of sodium has enabled atomic collision parameters to be deduced for the 4S-3P deexcitation and the 3S-3P excitation processes. These data are compared with convergent close coupling and second order distorted wave Born calculations. For excitation, both theories agree with experiment, whereas for deexcitation the close coupling theory is in better agreement. A long-standing proposal relating to the sign of the transferred angular momentum is not supported

Winner-take-all selection in a neural system with delayed feedback

We consider the effects of temporal delay in a neural feedback system with excitation and inhibition. The topology of our model system reflects the anatomy of the avian isthmic circuitry, a feedback structure found in all classes of vertebrates. We show that the system is capable of performing a `winner-take-all' selection rule for certain combinations of excitatory and inhibitory feedback. In particular, we show that when the time delays are sufficiently large a system with local inhibition and global excitation can function as a `winner-take-all' network and exhibit oscillatory dynamics. We demonstrate how the origin of the oscillations can be attributed to the finite delays through a linear stability analysis.Comment: 8 pages, 6 figure

Sport injury prevention in-school and out-of-school?:A qualitative investigation of the trans-contextual model

OBJECTIVE:To investigate junior secondary school students' experiences and perspectives of in-school and out-of-school sport-safety, with a particular focus on the meaning and content that they applied to the motivational and social cognitive factors of sport injury prevention. DESIGN:Focus-group interview. METHOD:Participants were 128 junior secondary school students (Form 1 to Form 3) aged between 12 and 16 years from two secondary schools. We organised focus-group interviews by class (group size = six to nine students). Seventeen groups completed semi-structured interviews regarding their experience, beliefs, and motives for injury prevention in-school and out-of-school. We analysed data by thematic content analysis using a typological approach. RESULTS:Higher order themes (N = 7) including in-school and out-of-school motives and social cognitive factors and associated lower-order themes (N = 16), emerged from the analysis corresponding to constructs from trans-contextual model tenets. CONCLUSIONS:The current study is the first qualitative study to explore junior secondary school students' experience and perspectives on sport injury prevention, using trans-contextual model as a framework for investigation. The findings contribute to a better understanding on their motivational and social cognitive factors in adopting sport injury prevention. The content of the theme behavior also indicated the inadequacy of students' knowledge of effective sport injury prevention techniques, and underscored the importance of sport safety education