The role of agonist and antagonist muscles in explaining isometric knee extension torque variation with hip joint angle.

PURPOSE: The biarticular rectus femoris (RF), operating on the ascending limb of the force-length curve, produces more force at longer lengths. However, experimental studies consistently report higher knee extension torque when supine (longer RF length) compared to seated (shorter RF length). Incomplete activation in the supine position has been proposed as the reason for this discrepancy, but differences in antagonistic co-activation could also be responsible due to altered hamstrings length. We examined the role of agonist and antagonist muscles in explaining the isometric knee extension torque variation with changes in hip joint angle. METHOD: Maximum voluntary isometric knee extension torque (joint MVC) was recorded in seated and supine positions from nine healthy males (30.2 ± 7.7 years). Antagonistic torque was estimated using EMG and added to the respective joint MVC (corrected MVC). Submaximal tetanic stimulation quadriceps torque was also recorded. RESULT: Joint MVC was not different between supine (245 ± 71.8 Nm) and seated (241 ± 69.8 Nm) positions and neither was corrected MVC (257 ± 77.7 and 267 ± 87.0 Nm, respectively). Antagonistic torque was higher when seated (26 ± 20.4 Nm) than when supine (12 ± 7.4 Nm). Tetanic torque was higher when supine (111 ± 31.9 Nm) than when seated (99 ± 27.5 Nm). CONCLUSION: Antagonistic co-activation differences between hip positions do not account for the reduced MVC in the supine position. Rather, reduced voluntary knee extensor muscle activation in that position is the major reason for the lower MVC torque when RF is lengthened (hip extended). These findings can assist standardising muscle function assessment and improving musculoskeletal modelling applications

Search for rare quark-annihilation decays, B --> Ds(*) Phi

We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context of the Standard Model, these decays are expected to be highly suppressed since they proceed through annihilation of the b and u-bar quarks in the B- meson. Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected with the BABAR detector at SLAC. We find no evidence for these decays, and we set Bayesian 90% confidence level upper limits on the branching fractions BF(B- --> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid Communications

An in vivo platform to select and evolve aggregation-resistant proteins

Protein biopharmaceuticals are highly successful, but their utility is compromised by their propensity to aggregate during manufacture and storage. As aggregation can be triggered by non-native states, whose population is not necessarily related to thermodynamic stability, prediction of poorly-behaving biologics is difficult, and searching for sequences with desired properties is labour-intensive and time-consuming. Here we show that an assay in the periplasm of E. coli linking aggregation directly to antibiotic resistance acts as a sensor for the innate (un-accelerated) aggregation of antibody fragments. Using this assay as a directed evolution screen, we demonstrate the generation of aggregation resistant scFv sequences when reformatted as IgGs. This powerful tool can thus screen and evolve ‘manufacturable’ biopharmaceuticals early in industrial development. By comparing the mutational profiles of three different immunoglobulin scaffolds, we show the applicability of this method to investigate protein aggregation mechanisms important to both industrial manufacture and amyloid disease

Measurement of the branching fraction for B−→D0K∗−B^- \to D^0 K^{*-}

We present a measurement of the branching fraction for the decay B- --> D0 K*- using a sample of approximately 86 million BBbar pairs collected by the BaBar detector from e+e- collisions near the Y(4S) resonance. The D0 is detected through its decays to K- pi+, K- pi+ pi0 and K- pi+ pi- pi+, and the K*- through its decay to K0S pi-. We measure the branching fraction to be B.F.(B- --> D0 K*-)= (6.3 +/- 0.7(stat.) +/- 0.5(syst.)) x 10^{-4}

Observation of a significant excess of π0π0\pi^{0}\pi^{0} events in B meson decays

We present an observation of the decay $B^{0} \to \pi^{0} \pi^{0}$ based on a sample of 124 million $B\bar{B}$ pairs recorded by the BABAR detector at the PEP-II asymmetric-energy $B$ Factory at SLAC. We observe $46 \pm 13 \pm 3$ events, where the first error is statistical and the second is systematic, corresponding to a significance of 4.2 standard deviations including systematic uncertainties. We measure the branching fraction \BR(B^{0} \to \pi^{0} \pi^{0}) = (2.1 \pm 0.6 \pm 0.3) \times 10^{-6}, averaged over $B^{0}$ and $\bar{B}^{0}$ decays

Analysis of motoneuron responses to composite synaptic volleys (computer simulation study)

This paper deals with the analysis of changes in motoneuron (MN) firing evoked by repetitively applied stimuli aimed toward extracting information about the underlying synaptic volleys. Spike trains were obtained from computer simulations based on a threshold-crossing model of tonically firing MN, subjected to stimulation producing postsynaptic potentials (PSPs) of various parameters. These trains were analyzed as experimental results, using the output measures that were previously shown to be most effective for this purpose: peristimulus time histogram, raster plot and peristimulus time intervalgram. The analysis started from the effects of single excitatory and inhibitory PSPs (EPSPs and IPSPs). The conclusions drawn from this analysis allowed the explanation of the results of more complex synaptic volleys, i.e., combinations of EPSPs and IPSPs, and the formulation of directions for decoding the results of human neurophysiological experiments in which the responses of tonically firing MNs to nerve stimulation are analyzed

Gene-Environment Interaction in Adults’ IQ Scores: Measures of Past and Present Environment

Gene-environment interaction was studied in a sample of young (mean age 26 years, N = 385) and older (mean age 49 years, N = 370) adult males and females. Full scale IQ scores (FSIQ) were analyzed using biometric models in which additive genetic (A), common environmental (C), and unique environmental (E) effects were allowed to depend on environmental measures. Moderators under study were parental and partner educational level, as well as urbanization level and mean real estate price of the participants’ residential area. Mean effects were observed for parental education, partner education and urbanization level. On average, FSIQ scores were roughly 5 points higher in participants with highly educated parents, compared to participants whose parents were less well educated. In older participants, IQ scores were about 2 points higher when their partners were highly educated. In younger males, higher urbanization levels were associated with slightly higher FSIQ scores. Our analyses also showed increased common environmental variation in older males whose parents were more highly educated, and increased unique environmental effects in older males living in more affluent areas. Contrary to studies in children, however, the variance attributable to additive genetic effects was stable across all levels of the moderators under study. Most results were replicated for VIQ and PIQ

Improving functional magnetic resonance imaging reproducibility

BACKGROUND: The ability to replicate an entire experiment is crucial to the scientific method. With the development of more and more complex paradigms, and the variety of analysis techniques available, fMRI studies are becoming harder to reproduce. RESULTS: In this article, we aim to provide practical advice to fMRI researchers not versed in computing, in order to make studies more reproducible. All of these steps require researchers to move towards a more open science, in which all aspects of the experimental method are documented and shared. CONCLUSION: Only by sharing experiments, data, metadata, derived data and analysis workflows will neuroimaging establish itself as a true data science

KneeTex: an ontology–driven system for information extraction from MRI reports

Background. In the realm of knee pathology, magnetic resonance imaging (MRI) has the advantage of visualising all structures within the knee joint, which makes it a valuable tool for increasing diagnostic accuracy and planning surgical treatments. Therefore, clinical narratives found in MRI reports convey valuable diagnostic information. A range of studies have proven the feasibility of natural language processing for information extraction from clinical narratives. However, no study focused specifically on MRI reports in relation to knee pathology, possibly due to the complexity of knee anatomy and a wide range of conditions that may be associated with different anatomical entities. In this paper we describe KneeTex, an information extraction system that operates in this domain. Methods. As an ontology–driven information extraction system, KneeTex makes active use of an ontology to strongly guide and constrain text analysis. We used automatic term recognition to facilitate the development of a domain–specific ontology with sufficient detail and coverage for text mining applications. In combination with the ontology, high regularity of the sublanguage used in knee MRI reports allowed us to model its processing by a set of sophisticated lexico–semantic rules with minimal syntactic analysis. The main processing steps involve named entity recognition combined with coordination, enumeration, ambiguity and co–reference resolution, followed by text segmentation. Ontology–based semantic typing is then used to drive the template filling process. Results. We adopted an existing ontology, TRAK (Taxonomy for RehAbilitation of Knee conditions), for use within KneeTex. The original TRAK ontology expanded from 1,292 concepts, 1,720 synonyms and 518 relationship instances to 1,621 concepts, 2,550 synonyms and 560 relationship instances. This provided KneeTex with a very fine–grained lexico–semantic knowledge base, which is highly attuned to the given sublanguage. Information extraction results were evaluated on a test set of 100 MRI reports. A gold standard consisted of 1,259 filled template records with the following slots: finding, finding qualifier, negation, certainty, anatomy and anatomy qualifier. KneeTex extracted information with precision of 98.00%, recall of 97.63% and F–measure of 97.81%, the values of which are in line with human–like performance. Conclusions. KneeTex is an open–source, stand–alone application for information extraction from narrative reports that describe an MRI scan of the knee. Given an MRI report as input, the system outputs the corresponding clinical findings in the form of JavaScript Object Notation objects. The extracted information is mapped onto TRAK, an ontology that formally models knowledge relevant for the rehabilitation of knee conditions. As a result, formally structured and coded information allows for complex searches to be conducted efficiently over the original MRI reports, thereby effectively supporting epidemiologic studies of knee conditions