Alien Registration- Wentworth, Mercina J. (Pittsfield, Somerset County)

https://digitalmaine.com/alien_docs/6472/thumbnail.jp

Hamstrings force-length relationships and their implications for angle-specific joint torques: a narrative review

Temporal biomechanical and physiological responses to physical activity vary between individual hamstrings components as well as between exercises, suggesting that hamstring muscles operate differently, and over different lengths, between tasks. Nevertheless, the force-length properties of these muscles have not been thoroughly investigated. The present review examines the factors influencing the hamstrings’ force-length properties and relates them to in vivo function. A search in four databases was performed for studies that examined relations between muscle length and force, torque, activation, or moment arm of hamstring muscles. Evidence was collated in relation to force-length relationships at a sarcomere/fiber level and then moment arm-length, activation-length, and torque-joint angle relations. Five forward simulation models were also used to predict force-length and torque-length relations of hamstring muscles. The results show that, due to architectural differences alone, semitendinosus (ST) produces less peak force and has a flatter active (contractile) fiber force-length relation than both biceps femoris long head (BFlh) and semimembranosus (SM), however BFlh and SM contribute greater forces through much of the hip and knee joint ranges of motion. The hamstrings’ maximum moment arms are greater at the hip than knee, so the muscles tend to act more as force producers at the hip but generate greater joint rotation and angular velocity at the knee for a given muscle shortening length and speed. However, SM moment arm is longer than SM and BFlh, partially alleviating its reduced force capacity but also reducing its otherwise substantial excursion potential. The current evidence, bound by the limitations of electromyography techniques, suggests that joint angle-dependent activation variations have minimal impact on force-length or torque-angle relations. During daily activities such as walking or sitting down, the hamstrings appear to operate on the ascending limbs of their force-length relations while knee flexion exercises performed with hip angles 45 – 90° promote more optimal force generation. Exercises requiring hip flexion at 45 – 120° and knee extension 45 – 0° (e.g. sprint running) may therefore evoke greater muscle forces and, speculatively, provide a more optimum adaptive stimulus. Finally, increases in resistance to stretch during hip flexion beyond 45° result mainly from SM and BFlh muscles

Defining functional DNA elements in the human genome

With the completion of the human genome sequence, attention turned to identifying and annotating its functional DNA elements. As a complement to genetic and comparative genomics approaches, the Encyclopedia of DNA Elements Project was launched to contribute maps of RNA transcripts, transcriptional regulator binding sites, and chromatin states in many cell types. The resulting genome-wide data reveal sites of biochemical activity with high positional resolution and cell type specificity that facilitate studies of gene regulation and interpretation of noncoding variants associated with human disease. However, the biochemically active regions cover a much larger fraction of the genome than do evolutionarily conserved regions, raising the question of whether nonconserved but biochemically active regions are truly functional. Here, we review the strengths and limitations of biochemical, evolutionary, and genetic approaches for defining functional DNA segments, potential sources for the observed differences in estimated genomic coverage, and the biological implications of these discrepancies. We also analyze the relationship between signal intensity, genomic coverage, and evolutionary conservation. Our results reinforce the principle that each approach provides complementary information and that we need to use combinations of all three to elucidate genome function in human biology and disease

Error and Error Mitigation in Low-Coverage Genome Assemblies

The recent release of twenty-two new genome sequences has dramatically increased the data available for mammalian comparative genomics, but twenty of these new sequences are currently limited to ~2× coverage. Here we examine the extent of sequencing error in these 2× assemblies, and its potential impact in downstream analyses. By comparing 2× assemblies with high-quality sequences from the ENCODE regions, we estimate the rate of sequencing error to be 1–4 errors per kilobase. While this error rate is fairly modest, sequencing error can still have surprising effects. For example, an apparent lineage-specific insertion in a coding region is more likely to reflect sequencing error than a true biological event, and the length distribution of coding indels is strongly distorted by error. We find that most errors are contributed by a small fraction of bases with low quality scores, in particular, by the ends of reads in regions of single-read coverage in the assembly. We explore several approaches for automatic sequencing error mitigation (SEM), making use of the localized nature of sequencing error, the fact that it is well predicted by quality scores, and information about errors that comes from comparisons across species. Our automatic methods for error mitigation cannot replace the need for additional sequencing, but they do allow substantial fractions of errors to be masked or eliminated at the cost of modest amounts of over-correction, and they can reduce the impact of error in downstream phylogenomic analyses. Our error-mitigated alignments are available for download.National Science Foundation (U.S.) (Faculty Early Career Development grant DBI-0644111)National Science Foundation (U.S.) (Faculty Early Career Development grant DBI-0644282)National Science Foundation (U.S.) (Faculty Early Career Development grant U54 HG004555-01)David & Lucile Packard FoundationDavid & Lucile Packard Foundation (Fellowship for Science and Engineering

Non ictal onset zone: A window to ictal dynamics

The focal and network concepts of epilepsy present different aspects of electroclinical phenomenon of seizures. Here, we present a 23-year-old man undergoing surgical evaluation with left fronto-temporal electrocorticography (ECoG) and microelectrode-array (MEA) in the middle temporal gyrus (MTG). We compare action-potential (AP) and local field potentials (LFP) recorded from MEA with ECoG. Seizure onset in the mesial-temporal lobe was characterized by changes in the pattern of AP-firing without clear changes in LFP or ECoG in MTG. This suggests simultaneous analysis of neuronal activity in differing spatial scales and frequency ranges provide complementary insights into how focal and network neurophysiological activity contribute to ictal activity

EFFECTS OF A 10 WEEK TRAINING PROGRAM ON PHYSICAL CONDITIONING AND INSTEP KICK KINEMATICS IN SOCCER

The instep kick is the kick of choice in soccer scoring and passing over medium to long distances. Its success depends on many factors including the strength of the muscles responsible for the actions of the (kicking lower) extremity, the rate of muscle force production, the synchronization and energy transfer between lower extremity segments (Plagenhoef, 1971), the linear approach velocity (Opavsky, 1988) and approach angle (Isokawa and Less, 1988), and the ability of muscle to utilize effectively the stretch/shorten cycle (BOhrle, 1985). Ultimately, on a given kick, the velocity of the kicking foot and the point of (foot) force application on the ball determine the trajectory characteristics of the ball. Other factors such as flexibility and aerobic/anaerobic capacities also determine the ability of players to successfully perform in a game. The purpose of this study was to study the effects of a 10 week training program on selected physical conditioning and instep kick kinematic parameters in soccer

Why highly expressed proteins evolve slowly

Much recent work has explored molecular and population-genetic constraints on the rate of protein sequence evolution. The best predictor of evolutionary rate is expression level, for reasons which have remained unexplained. Here, we hypothesize that selection to reduce the burden of protein misfolding will favor protein sequences with increased robustness to translational missense errors. Pressure for translational robustness increases with expression level and constrains sequence evolution. Using several sequenced yeast genomes, global expression and protein abundance data, and sets of paralogs traceable to an ancient whole-genome duplication in yeast, we rule out several confounding effects and show that expression level explains roughly half the variation in Saccharomyces cerevisiae protein evolutionary rates. We examine causes for expression's dominant role and find that genome-wide tests favor the translational robustness explanation over existing hypotheses that invoke constraints on function or translational efficiency. Our results suggest that proteins evolve at rates largely unrelated to their functions, and can explain why highly expressed proteins evolve slowly across the tree of life.Comment: 40 pages, 3 figures, with supporting informatio

LLMs Understand Glass-Box Models, Discover Surprises, and Suggest Repairs

We show that large language models (LLMs) are remarkably good at working with interpretable models that decompose complex outcomes into univariate graph-represented components. By adopting a hierarchical approach to reasoning, LLMs can provide comprehensive model-level summaries without ever requiring the entire model to fit in context. This approach enables LLMs to apply their extensive background knowledge to automate common tasks in data science such as detecting anomalies that contradict prior knowledge, describing potential reasons for the anomalies, and suggesting repairs that would remove the anomalies. We use multiple examples in healthcare to demonstrate the utility of these new capabilities of LLMs, with particular emphasis on Generalized Additive Models (GAMs). Finally, we present the package $\texttt{TalkToEBM}$ as an open-source LLM-GAM interface

Aubergene - a sensitive genome alignment tool.

Motivation: The accumulation of genome sequences will only accelerate in the coming years. We aim to use this abundance of data to improve the quality of genomic alignments and devise a method which is capable of detecting regions evolving under weak or no evolutionary constraints. Results: We describe a genome alignment program AuberGene, which explores the idea of transitivity of local alignments. Assessment of the program was done based on a 2 Mbp genomic region containing the CFTR gene of 13 species. In this region, we can identify 53% of human sequence sharing common ancestry with mouse, as compared with 44% found using the usual pairwise alignment. Between human and tetraodon 93 orthologous exons are found, as compared with 77 detected by the pairwise human-tetraodon comparison. AuberGene allows the user to (1) identify distant, previously undetected, conserved orthogonal regions such as ORFs or regulatory regions; (2) identify neutrally evolving regions in related species which are often overlooked by other alignment programs; (3) recognize false orthologous genomic regions. The increased sensitivity of the method is not obtained at the cost of reduced specificity. Our results suggest that, over the CFTR region, human shares 10% more sequence with mouse than previously thought (∼50%, instead of 40% found with the pairwise alignment). © 2006 Oxford University Press

Survey of variation in human transcription factors reveals prevalent DNA binding changes

Published in final edited form as: Science. 2016 Mar 25; 351(6280): 1450–1454. Published online 2016 Mar 24. doi: 10.1126/science.aad2257Sequencing of exomes and genomes has revealed abundant genetic variation affecting the coding sequences of human transcription factors (TFs), but the consequences of such variation remain largely unexplored. We developed a computational, structure-based approach to evaluate TF variants for their impact on DNA binding activity and used universal protein-binding microarrays to assay sequence-specific DNA binding activity across 41 reference and 117 variant alleles found in individuals of diverse ancestries and families with Mendelian diseases. We found 77 variants in 28 genes that affect DNA binding affinity or specificity and identified thousands of rare alleles likely to alter the DNA binding activity of human sequence-specific TFs. Our results suggest that most individuals have unique repertoires of TF DNA binding activities, which may contribute to phenotypic variation.National Institutes of Health; NHGRI R01 HG003985; P50 HG004233; A*STAR National Science Scholarship; National Science Foundatio