Adaptations to isolated shoulder fatigue during simulated repetitive work. Part I: Fatigue

Upper extremity muscle fatigue is challenging to identify during industrial tasks and places changing demands on the shoulder complex that are not fully understood. The purpose of this investigation was to examine adaptation strategies in response to isolated anterior deltoid muscle fatigue while performing simulated repetitive work. Participants completed two blocks of simulated repetitive work separated by an anterior deltoid fatigue protocol; the first block had 20 work cycles and the post-fatigue block had 60 cycles. Each work cycle was 60 s in duration and included 4 tasks: handle pull, cap rotation, drill press and handle push. Surface EMG of 14 muscles and upper body kinematics were recorded. Immediately following fatigue, glenohumeral flexion strength was reduced, rating of perceived exertion scores increased and signs of muscle fatigue (increased EMG amplitude, decreased EMG frequency) were present in anterior and posterior deltoids, latissimus dorsi and serratus anterior. Along with other kinematic and muscle activity changes, scapular reorientation occurred in all of the simulated tasks and generally served to increase the width of the subacromial space. These findings suggest that immediately following fatigue people adapt by repositioning joints to maintain task performance and may also prioritize maintaining subacromial space width.     

Process analytical technologies to monitor the liquid phase of anaerobic cultures

Recent advances in sensor development and miniaturization offer new possibilities to monitor and control bioprocesses. Specific requirements for anaerobic processes in terms of low costs and high robustness against insoluble fractions and impurities in media led to a decelerated penetration of new technology in this field. Since no regulatory framework demands for process monitoring and documentation like in the pharmaceutical industry, the implementation of new sensors beyond long-established methods is not conducted as intensively.Nevertheless, many attempts have been made in recent years to adopt sensors and show their applicability in anaerobic fermentation processes. New possibilities arise for improved monitoring, control and faster process development through digitalization. This review aims to provide an overview over these recent attempts with the focus on the liquid phase in the upstream part of pure culture bioprocesses for anaerobic bulk compound, food, and beverage production. In particular, methods that monitor the viability, metabolic activity or related parameters are discussed, like electrochemical, impedance and spectroscopy probes, and methods related to fluid flow and gradient formation, like acoustic and mobile sensors.     

New insights into the binding mode of pyridine-3-carboxamide inhibitors of E. coli DNA gyrase

Previously we have reported on a series of pyridine-3-carboxamide inhibitors of DNA gyrase and DNA topoisomerase IV that were designed using a computational de novo design approach and which showed promising antibacterial properties. Herein we describe the synthesis of additional examples from this series aimed specifically at DNA gyrase, along with crystal structures confirming the predicted mode of binding and in vitro ADME data which describe the drug-likeness of these compounds.     

Structural and functional characterization of galactooligosaccharides in Nostoc commune: beta-D-galactofuranosyl-(1-->6)-[beta-D-galactofuranosyl-(1-->6)]2-beta-D-1,4-anhydrogalactitol and beta-(1-->6)-galactofuranosylated homologues

A new class of galactooligosaccharides has been identified from the terrestrial cyanobacterium Nostoc commune by MS and NMR techniques. These consist of beta-D-galactofuranosyl-(1-->6)-[beta-D-galactofuranosyl-(1-->6)]n-beta-d-1,4-anhydrogalactitols with n ranging from 2 to 8, corresponding to compounds designated 1 through 7. In total these saccharides amounted to approximately 0.35% of the dry thallus of N. commune, while in several other cyanobacteria they were not detected. Possibly they play some role in protection from damage by heat and desiccation as suggested by experiments with heterologous systems. For example, phosphoglucomutase (EC 2.7.5.1) from rabbit muscle was protected against heat inactivation by these oligosaccharides, and alpha-amylase (EC 3.2.1.1) from porcine pancreas by the oligosaccharides 6 and 7. The homologues of lower molecular mass, however, enhanced heat sensitivity of alpha-amylase. The viability of Escherichia coli was completely abolished by desiccation, whereas in the presence of 4 survival rates were approximately 50% of controls not subjected to desiccation. The newly identified saccharides are compared with known galactofuranose-based oligo- and polysaccharides and possible biological functions of them are discussed.     

Modifying dipalmitoylphosphatidylcholine monolayers by n-hexadecanol and dipalmitoylglycerol

The monolayer structure of pure dipalmitoylphosphatidylcholine (DPPC) and equimolar mixtures of DPPC/n-hexadecanol (C(16)OH) and DPPC/dipalmitoylglycerol (DPG) are studied by the film balance technique and grazing incidence X-ray diffraction measurements. At 20 degrees C, the binary systems exhibit complete miscibility. In contrast to pure DPPC monolayers, a condensing effect is observed in the presence of both non-phospholipid additives; but the phase transition behavior differs. The tilt angle of the hydrocarbon chains in the DPPC/C(16)OH mixture is significantly smaller than in pure DPPC monolayers. The tilt of the chains is even further reduced in the mixed monolayer of DPPC/DPG. A comparison of the three systems reveals distinct structural features such as phase state, chain tilt, and molecular area over a wide range of surface pressures. Therefore, these monolayers provide a highly suitable model to investigate the influence of structural parameters on biological processes occurring at the membrane surface, e.g. enzymatic reactions and adsorption events.     

Analogues containing the paramagnetic amino acid TOAC as substrates for angiotensin I-converting enzyme

The angiotensin I-converting enzyme (ACE) converts the decapeptide angiotensin I (Ang I) into angiotensin II by releasing the C-terminal dipeptide. A novel approach combining enzymatic and electron paramagnetic resonance (EPR) studies was developed to determine the enzyme effect on Ang I containing the paramagnetic 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid (TOAC) at positions 1, 3, 8, and 9. Biological assays indicated that TOAC(1)-Ang I maintained partly the Ang I activity, and that only this derivative and the TOAC(3)-Ang I were cleaved by ACE. Quenching of Tyr(4) fluorescence by TOAC decreased with increasing distance between both residues, suggesting an overall partially extended structure. However, the local bend known to be imposed by the substituted diglycine TOAC is probably responsible for steric hindrance, not allowing the analogues containing TOAC at positions 8 and 9 to act as substrates. In some cases, although substrates and products differ by only two residues, the difference between their EPR spectral lineshapes allows monitoring the enzymatic reaction as a function of time.     

Correlations of pelvis state to foot placement do not imply within-step active control

Experimental studies of human walking have shown that within an individual step, variations in the center of mass (CoM) state can predict corresponding variations in the next foot placement. This has been interpreted by some to indicate the existence of active control in which the nervous system uses the CoM state at or near mid-stance to regulate subsequent foot placement. However, the passive dynamics of the moving body and/or moving limbs also contribute (perhaps strongly) to foot placement, and thus to its variation. The extent to which correlations of CoM state to foot placement reflect the effects of within-step active control, those of passive dynamics, or some combination of both, remains an important and still open question. Here, we used an open-loop-stable 2D walking model to show that this predictive ability cannot by itself be taken as evidence of within-step active control. In our simulations, we too find high correlations between the CoM state and subsequent foot placement, but these correlations are entirely due to passive dynamics as our system has no active control, either within a step or between steps. This demonstrates that any inferences made from such correlations about within-step active control require additional supporting evidence beyond the correlations themselves. Thus, these within-step predictive correlations leave unresolved the relative importance of within-step active control as compared to passive dynamics, meaning that such methods should be used to characterize control in human walking only with caution.     

An application of scissored-pair control moment gyroscopes in a design of wearable balance assistance device for the elderly

Impaired balance control ability and degraded functional mobility increases the risk of falling in elderly people. The elderly show more postural sway when standing compared with young people. A sway fall occurs when the center of gravity moves outside the limit of stability. In order to reduce the fall risk from the excessive sway, this study presents the design of wearable balance assistance device for the elderly. Scissored-pair control moment gyroscopes were selected as a torque actuator. A two-axis inclination sensor was used to detect the inclined angle of the wearer’s body. The direction of sway was calculated from the detected inclined angle. The designed device weighs 8.2 kg with a height of 32 cm × width of 40 cm × depth of 22 cm. A multi-segment model of a standing human was used to investigate the device’s performance for balance recovery. According to the simulations, balance recovery in any direction was successfully accomplished with the appropriate initial angle. The relationship between the effective initial angle and detected inclined angle was subsequently established. The stability provided by activation of the device was able to limit the unstable user’s sway boundary. The designed device shows promise for use as a balance assistance device for the elderly.     

Comparison of the human-exosuit interaction using ankle moment and ankle positive power inspired walking assistance

Previous ankle exoskeleton assistance techniques that were able to demonstrate metabolic reductions can be categorized into those that delivered moment profiles similar to the biological ankle moment throughout the stance phase, and others that delivered positive power only during push off. Both assistance techniques and a powered-off condition were compared in treadmill walking (1.5 m s⁻¹) with a soft exosuit. We hypothesized that both techniques can result in a similar metabolic reduction when providing a similar level of average positive exosuit power at each ankle (0.12 W kg⁻¹) and hip (0.02 W kg⁻¹) while the underlying global center-of-mass and local joint biomechanics would be different. We found a similar net metabolic rate reduction of 15% relative to walking with the suit powered-off for both techniques. The ankle moment inspired technique showed larger magnitudes of reductions for biological moment and power at the hip and the ankle. The ankle power inspired technique might benefit from higher biological efficiency, when reducing positive instead of negative power at the knee and when almost keeping the isometric function of the plantarflexors before push-off. Changes at the ankle caused energetic reductions at the knee, hip and the center-of-mass. A major contribution to metabolic reduction might be based on them. As the lower limb biomechanics that led to these reductions were different, we believe that humans alter their gait to maximize their energetic benefit based on the exosuit assistance. For further insights on mechanisms that lead to metabolic reduction, joint mechanics and muscle-tendon dynamics must be analyzed in combination.     

Quality control and integration of genotypes from two calling pipelines for whole genome sequence data in the Alzheimer's disease sequencing project

The Alzheimer's Disease Sequencing Project (ADSP) performed whole genome sequencing (WGS) of 584 subjects from 111 multiplex families at three sequencing centers. Genotype calling of single nucleotide variants (SNVs) and insertion-deletion variants (indels) was performed centrally using GATK-HaplotypeCaller and Atlas V2. The ADSP Quality Control (QC) Working Group applied QC protocols to project-level variant call format files (VCFs) from each pipeline, and developed and implemented a novel protocol, termed “consensus calling,” to combine genotype calls from both pipelines into a single high-quality set. QC was applied to autosomal bi-allelic SNVs and indels, and included pipeline-recommended QC filters, variant-level QC, and sample-level QC. Low-quality variants or genotypes were excluded, and sample outliers were noted. Quality was assessed by examining Mendelian inconsistencies (MIs) among 67 parent-offspring pairs, and MIs were used to establish additional genotype-specific filters for GATK calls. After QC, 578 subjects remained. Pipeline-specific QC excluded ~12.0% of GATK and 14.5% of Atlas SNVs. Between pipelines, ~91% of SNV genotypes across all QCed variants were concordant; 4.23% and 4.56% of genotypes were exclusive to Atlas or GATK, respectively; the remaining ~0.01% of discordant genotypes were excluded. For indels, variant-level QC excluded ~36.8% of GATK and 35.3% of Atlas indels. Between pipelines, ~55.6% of indel genotypes were concordant; while 10.3% and 28.3% were exclusive to Atlas or GATK, respectively; and ~0.29% of discordant genotypes were. The final WGS consensus dataset contains 27,896,774 SNVs and 3,133,926 indels and is publicly available.