Abdominal functional electrical stimulation to improve respiratory function after spinal cord injury: a systematic review and meta-analysis

Objectives: Abdominal functional electrical stimulation (abdominal FES) is the application of a train of electrical pulses to the abdominal muscles, causing them to contract. Abdominal FES has been used as a neuroprosthesis to acutely augment respiratory function and as a rehabilitation tool to achieve a chronic increase in respiratory function after abdominal FES training, primarily focusing on patients with spinal cord injury (SCI). This study aimed to review the evidence surrounding the use of abdominal FES to improve respiratory function in both an acute and chronic manner after SCI. Settings: A systematic search was performed on PubMed, with studies included if they applied abdominal FES to improve respiratory function in patients with SCI. Methods: Fourteen studies met the inclusion criteria (10 acute and 4 chronic). Low participant numbers and heterogeneity across studies reduced the power of the meta-analysis. Despite this, abdominal FES was found to cause a significant acute improvement in cough peak flow, whereas forced exhaled volume in 1 s approached significance. A significant chronic increase in unassisted vital capacity, forced vital capacity and peak expiratory flow was found after abdominal FES training compared with baseline. Conclusions: This systematic review suggests that abdominal FES is an effective technique for improving respiratory function in both an acute and chronic manner after SCI. However, further randomised controlled trials, with larger participant numbers and standardised protocols, are needed to fully establish the clinical efficacy of this technique

RosettaScripts: A Scripting Language Interface to the Rosetta Macromolecular Modeling Suite

Macromolecular modeling and design are increasingly useful in basic research, biotechnology, and teaching. However, the absence of a user-friendly modeling framework that provides access to a wide range of modeling capabilities is hampering the wider adoption of computational methods by non-experts. RosettaScripts is an XML-like language for specifying modeling tasks in the Rosetta framework. RosettaScripts provides access to protocol-level functionalities, such as rigid-body docking and sequence redesign, and allows fast testing and deployment of complex protocols without need for modifying or recompiling the underlying C++ code. We illustrate these capabilities with RosettaScripts protocols for the stabilization of proteins, the generation of computationally constrained libraries for experimental selection of higher-affinity binding proteins, loop remodeling, small-molecule ligand docking, design of ligand-binding proteins, and specificity redesign in DNA-binding proteins

Protein Design Using Continuous Rotamers

Optimizing amino acid conformation and identity is a central problem in computational protein design. Protein design algorithms must allow realistic protein flexibility to occur during this optimization, or they may fail to find the best sequence with the lowest energy. Most design algorithms implement side-chain flexibility by allowing the side chains to move between a small set of discrete, low-energy states, which we call rigid rotamers. In this work we show that allowing continuous side-chain flexibility (which we call continuous rotamers) greatly improves protein flexibility modeling. We present a large-scale study that compares the sequences and best energy conformations in 69 protein-core redesigns using a rigid-rotamer model versus a continuous-rotamer model. We show that in nearly all of our redesigns the sequence found by the continuous-rotamer model is different and has a lower energy than the one found by the rigid-rotamer model. Moreover, the sequences found by the continuous-rotamer model are more similar to the native sequences. We then show that the seemingly easy solution of sampling more rigid rotamers within the continuous region is not a practical alternative to a continuous-rotamer model: at computationally feasible resolutions, using more rigid rotamers was never better than a continuous-rotamer model and almost always resulted in higher energies. Finally, we present a new protein design algorithm based on the dead-end elimination (DEE) algorithm, which we call iMinDEE, that makes the use of continuous rotamers feasible in larger systems. iMinDEE guarantees finding the optimal answer while pruning the search space with close to the same efficiency of DEE. Availability: Software is available under the Lesser GNU Public License v3. Contact the authors for source code

A Score of the Ability of a Three-Dimensional Protein Model to Retrieve Its Own Sequence as a Quantitative Measure of Its Quality and Appropriateness

BACKGROUND: Despite the remarkable progress of bioinformatics, how the primary structure of a protein leads to a three-dimensional fold, and in turn determines its function remains an elusive question. Alignments of sequences with known function can be used to identify proteins with the same or similar function with high success. However, identification of function-related and structure-related amino acid positions is only possible after a detailed study of every protein. Folding pattern diversity seems to be much narrower than sequence diversity, and the amino acid sequences of natural proteins have evolved under a selective pressure comprising structural and functional requirements acting in parallel. PRINCIPAL FINDINGS: The approach described in this work begins by generating a large number of amino acid sequences using ROSETTA [Dantas G et al. (2003) J Mol Biol 332:449-460], a program with notable robustness in the assignment of amino acids to a known three-dimensional structure. The resulting sequence-sets showed no conservation of amino acids at active sites, or protein-protein interfaces. Hidden Markov models built from the resulting sequence sets were used to search sequence databases. Surprisingly, the models retrieved from the database sequences belonged to proteins with the same or a very similar function. Given an appropriate cutoff, the rate of false positives was zero. According to our results, this protocol, here referred to as Rd.HMM, detects fine structural details on the folding patterns, that seem to be tightly linked to the fitness of a structural framework for a specific biological function. CONCLUSION: Because the sequence of the native protein used to create the Rd.HMM model was always amongst the top hits, the procedure is a reliable tool to score, very accurately, the quality and appropriateness of computer-modeled 3D-structures, without the need for spectroscopy data. However, Rd.HMM is very sensitive to the conformational features of the models' backbone

Modulation of spinal excitability following neuromuscular electrical stimulation superimposed to voluntary contraction

Purpose. Neuromuscular electrical stimulation (NMES) superimposed on voluntary muscle contraction has been recently shown as an innovative training modality within sport and rehabilitation, but its effects on the neuromuscular system are still unclear. The aim of this study was to investigate acute responses in spinal excitability, as measured by the Hoffmann (H) reflex, and in maximal voluntary contraction (MVIC) following NMES superimposed to voluntary isometric contractions (NMES+ISO) compared to passive NMES only and to voluntary isometric contractions only (ISO). Method. Fifteen young adults were required to maintain an ankle plantar-flexor torque of 20% MVC for 20 repetitions during each experimental condition (NMES+ISO, NMES and ISO). Surface electromyography was used to record peak-to-peak Hreflex and motor waves following percutaneous stimulation of the posterior tibial nerve in the dominant limb. An isokinetic dynamometer was used to assess maximal voluntary contraction output of the ankle plantar flexor muscles. Results. H-reflex amplitude was increased by 4.5% after the NMES+ISO condition (p < 0.05), while passive NMES and ISO conditions showed a decrease by 7.8% (p < 0.05) and no change in reflex responses, respectively. There was no change in amplitude of maximal motor wave and in MVIC torque during each experimental condition. Conclusion. The reported facilitation of spinal excitability following NMES+ISO could be due to a combination of greater motor neuronal and corticospinal excitability, thus suggesting that NMES superimposed onto isometric voluntary contractions may provide a more effective neuromuscular stimulus and, hence, training modality compared to NMES alone

Computational design of self-assembling cyclic protein homo-oligomers

Self-assembling cyclic protein homo-oligomers play important roles in biology, and the ability to generate custom homo-oligomeric structures could enable new approaches to probe biological function. Here we report a general approach to design cyclic homo-oligomers that employs a new residue-pair-transform method to assess the designability of a protein-protein interface. This method is sufficiently rapid to enable the systematic enumeration of cyclically docked arrangements of a monomer followed by sequence design of the newly formed interfaces. We use this method to design interfaces onto idealized repeat proteins that direct their assembly into complexes that possess cyclic symmetry. Of 96 designs that were characterized experimentally, 21 were found to form stable monodisperse homo-oligomers in solution, and 15 (four homodimers, six homotrimers, six homotetramers and one homopentamer) had solution small-angle X-ray scattering data consistent with the design models. X-ray crystal structures were obtained for five of the designs and each is very close to their corresponding computational model

The medicalization of current educational research and its effects on education policy and school reforms

Este artículo parte del supuesto de la aparición de una cultura pedagogizada durante los últimos 200 años, según la cual los problemas sociales percibidos se traducen en desafíos educativos. En consecuencia, tanto la investigación como las instituciones educativas crecieron, y una política educativa surgió como resultado de las negociaciones entre los profesionales, los investigadores y los responsables políticos. El documento mantiene que algunas experiencias específicas ocurridas durante la Segunda Guerra Mundial, provocaron un cambio fundamental en el papel social y cultural de los círculos académicos, que condujo a una cultura tecnocrática caracterizada por una mayor confianza mostrada hacia los expertos en lugar de a la práctica profesional (es decir, los maestros y administradores). Bajo este cambio tecnocrático, en primer lugar surgió un sistema tecnológico de razonamiento, que luego fue sustituido por un “paradigma” médico. El nuevo paradigma condujo a una medicalización de la investigación social, en el cual se da por sentado un particular entendimiento organicista de la realidad social, y su investigación se realiza bajo las más discutibles premisas. El resultado es que pese a la creciente importancia de la investigación en general, este cambio expertocrático y médico de la investigación social dio lugar a una reducción drástica de las oportunidades reformistas al privar a las partes interesadas de una amplia gama de investigación educativa, experiencia profesional, sentido común, y debate político.This paper starts from the assumption of the emergence of an educationalized culture over the last 200 years according to which perceived social problems are translated into educational challenges. As a result, both educational institutions and educational research grew, and educational policy resulted from negotiations between professionals, researchers, and policy makers. The paper argues that specific experiences in the Second World War triggered a fundamental shift in the social and cultural role of academia, leading up to a technocratic culture characterized by confidence in experts rather than in practicing professionals (i.e., teachers and administrators). In this technocratic shift, first a technological system of reasoning emerged, and it was then replaced by a medical “paradigm.” The new paradigm led to a medicalization of social research, in which a particular organistic understanding of the social reality is taken for granted and research is conducted under the mostly undiscussed premises of this particular understanding. The result is that despite the increased importance of research in general, this expertocratic and medical shift of social research led to a massive reduction in reform opportunities by depriving the reform stakeholders of abroad range of education research, professional experience, common sense, and political deliberation.Grupo FORCE (HUM-386). Departamento de Didáctica y Organización Escolar de la Universidad de Granad

The Effects of Reference-Command Preview on the Strategies that Humans Use in Command-Following Tasks

This thesis presents results from an experiment in which 22 human subjects each interact with a dynamic system 40 times over a one-week period. For each interaction, a subject performs a command-following task, where the reference command is the same for all 22 subjects but different on each trial. The subjects are divided into 2 groups of 11 subjects. One group performs the command-following task without reference-command preview. The other group is provided with 1-s preview of the reference command. The experimental results are used to examine the effects of reference-command preview. For the group with 1-s reference-command preview, the average identified feedforward time delay is approximately 26 ms over the last ten trials, whereas the average identified feedforward time delay is approximately 284 ms over the last ten trials for the group without preview. For the group with preview, the average identified feedforward controller approximates the inverse dynamics of the system with which the subjects interact better after 40 trials than on the first trial. In contrast, for the group without preview, the average identified feedforward controller does not approximate the inverse dynamics of the system better after 40 trials