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The protein known as PI3K-interacting protein (PIK3IP1), or transmembrane inhibitor of PI3K (TrIP), is highly expressed by T cells and can modulate PI3K activity in these cells. Several studies have also revealed that TrIP is rapidly downregulated following T cell activation. However, it is unclear how this downregulation is controlled. Using a novel monoclonal antibody that robustly stains cell-surface TrIP, we demonstrate that TrIP is lost from the surface of activated T cells in a manner dependent on the strength of signaling through the T cell receptor and specific downstream signaling pathways, in particular classical PKC isoforms. TrIP expression returns by 24 h after stimulation, suggesting that it may play a role in resetting T cell receptor signaling at later time points. We also provide evidence that ADAM family proteases are required for both constitutive and stimulation-induced downregulation of TrIP in T cells. Finally, by expressing truncated forms of TrIP in cells, we identify the region in the extracellular stalk domain of TrIP that is targeted for proteolytic cleavage., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The protein known as PI3K-interacting protein (PIK3IP1), or transmembrane inhibitor of PI3K (TrIP), is highly expressed by T cells and can modulate PI3K activity in these cells. Several studies have also revealed that TrIP is rapidly downregulated following T cell activation. However, it is unclear as to how this downregulation is controlled. Using a novel monoclonal antibody that robustly stains cell-surface TrIP, we demonstrate that TrIP is lost from the surface of activated T cells in a manner dependent on the strength of signaling through the T cell receptor (TCR) and specific downstream signaling pathways, in particular classical PKC isoforms. TrIP expression returns by 24 hours after stimulation, suggesting that it may play a role in resetting TCR signaling at later time points. We also provide evidence that ADAM family proteases are required for both constitutive and stimulation-induced downregulation of TrIP in T cells. Finally, by expressing truncated forms of TrIP in cells, we identify the region in the extracellular stalk domain of TrIP that is targeted for proteolytic cleavage., Competing Interests: Conflict of Interest The authors declare that they have no conflicts of interest relevant to the contents of this article.

Background: Falls due to stumbling are prevalent for transfemoral prosthesis users and may lead to increased injury risk. This preliminary case series analyzes the transfemoral prosthesis user stumble recovery response to highlight key deficits in current commercially-available prostheses and proposes potential interventions to improve recovery outcomes., Methods: Six transfemoral prosthesis users were perturbed on their prosthetic limb at least three times while walking on a treadmill using obstacle perturbations in early, mid and late swing. Kinematic data were collected to characterize the response, while fall rate and key kinematic recovery metrics were used to assess the quality of recovery and highlight functional deficits in current commercially-available prostheses., Results: Across all participants, 13 (54%) of the 24 trials resulted in a fall (defined as > 50% body-weight support) with all but one participant (83%) falling at least once and two participants (33%) falling every time. In contrast, in a previous study of seven young, unimpaired, non-prosthesis users using the same experimental apparatus, no falls occurred across 190 trials. For the transfemoral prosthesis users, early swing had the highest rate of falling at 64%, followed by mid-swing at 57%, and then late swing at 33%. The trend in falls was mirrored by the kinematic recovery metrics (peak trunk angle, peak trunk angular velocity, forward reach of the perturbed limb, and knee angle at ground contact). In early swing all four metrics were deficient compared to non-prosthesis user controls. In mid swing, all but trunk angular velocity were deficient. In late swing only forward reach was deficient., Conclusion: Based on the stumble recovery responses, four potential deficiencies were identified in the response of the knee prostheses: (1) insufficient resistance to stance knee flexion upon ground contact; (2) insufficient swing extension after a perturbation; (3) difficulty initiating swing flexion following a perturbation; and (4) excessive impedance against swing flexion in early swing preventing the potential utilization of the elevating strategy. Each of these issues can potentially be addressed by mechanical or mechatronic changes to prosthetic design to improve quality of recovery and reduce the likelihood a fall., (© 2024. The Author(s).)

The ride-sharing trend is booming because of modern technologies and plays a significant role in transitioning to sustainable transportation methods. This study utilizes a comprehensive dataset collected from an online survey administered to over 1300 individuals in Bangladesh in 2023. Its specific focus is to examine the usage patterns of ride-sharing applications, such as Pathao and Uber. It builds upon previous research to analyze the factors influencing the use of these services and current trends in shared transportation. Additionally, it investigates the challenges associated with utilizing shared transportation amenities and proposes potential improvements to make ride-sharing or pooling more attractive. The study diligently worked to establish an inclusive framework and terminology to enhance policies and gain a more detailed understanding of the transportation choices and requirements of communities. To bridge the gap between theory and practice, we adopted an implementation-oriented research approach and conducted a comprehensive quantitative and inferential analysis of the survey data. The inclination of an individual to opt for or perceive collective or merged services depends on several demographic, geographical, and built-environment factors. The findings highlight the necessity of enhanced security measures, increased public awareness of ride-sharing benefits, and the formulation of legislative measures to promote sustainable mobility. Two examples of potential measures we have found to improve and encourage the use of ride-sharing services include reducing uncertainty about shared rides and minimizing passenger discomfort. These measures can be implemented through operational adjustments, government regulations, and employer programs. An essential conclusion was reached regarding the importance of prioritizing improvements in ride-sharing operations, rather than relying solely on cash incentives to promote behavioral change. Furthermore, it was determined that regardless of the changes, policies, or programs implemented, it is imperative to enhance public awareness and education., Competing Interests: The authors declare that they have no competing interests.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Trips and falls are a major concern for older adults. The resulting injury and loss of mobility can have a significant impact on quality of life. An emerging field of study, known as Perturbation Training, has been shown to reduce injury rates associated with trips and falls in older adults. Treadmills traditionally used for Perturbation Training are large, expensive, and immobile, forcing users to travel long distances to receive care. A portable treadmill would serve a larger portion of the at-risk population than current methods. We developed a portable, low-cost, twin-belt perturbation treadmill capable of high-intensity Perturbation Training. Belt speeds are controlled by a custom mechanical and software interface, allowing operators with no programming experience to control the device. The treadmill can accommodate users up to 118 kg and provides a maximum acceleration and speed of 12 m/s 2 and 3.3 m/s, respectively, under full load. The total weight is 180 kg, and the treadmill can be moved like a wheelbarrow, with handles in the back and wheels in the front. The prototype was validated with mechanical and human participant testing, showing it as a viable device for Perturbation Training. In this paper, we will go over the design, fabrication, and validation processes used to create the Portable Perturbation Treadmill., (Copyright © 2024 by ASME.)

Understanding why falls during pregnancy occur at over 25% rate over gestation has clinical impacts on the health of pregnant individuals. Attention, proprioception, and perception of the environment are required to prevent trips and falls. This research aimed to understand how the changes to these neurocognitive processes control obstacle avoidance through gestation. Seventeen pregnant participants were tested five times in 6-week intervals. Participants walked an obstacle course (OC), and we analyzed the crossings over obstacles that were set to 10% of participants' body height. Participants also performed an attentional network test (ANT: performance of specific components of attention), an obstacle perception task (OP: ability to visually define an obstacle and translate that to a body posture), and a joint position sense task (JPS: ability to recognize and recreate a joint position from somatosensation). In the OC task, average leading and trailing foot crossing heights significantly reduced by 13% and 23% respectively, with no change in variation, between weeks 13 and 31 of pregnancy, indicating an increased risk of obstacle contact during this time. The variability in minimum leading foot distances from the obstacle was correlated with all three neurocognition tasks (ANT, OP, and JPS). Increased fall rates in the second and third trimesters of pregnancy may be driven by changes in attention, with additional contributions of joint position sense and environmental perception at various stages of gestation. The results imply that a holistic examination on an individual basis may be required to determine individual trip risk and appropriate safety modifications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Malaria is caused by Plasmodium parasites that multiply inside host cells and can be lethal when P. falciparum is involved. We identified tRip as a membrane protein that facilitates the import of exogenous transfer RNA (tRNA) into the parasite. tRip encompasses a tRNA binding domain exposed on the parasite surface. We used the SELEX approach to isolate high-affinity and specific tRip-binding RNA motifs from a library of random 25 nucleotide-long sequences. In five rounds of combined negative and positive selections, an enriched pool of aptamers was obtained; sequencing revealed that they were all different in their primary sequence; only by comparing their structure predictions did most of the selected aptamers reveal a conserved 5-nucleotide motif sequence. We showed that the integral motif is essential for tRip-binding while the rest of the molecule can be significantly reduced or mutated as long as the motif is presented in a single-stranded region. Such RNA aptamers bind in place of the original tRNA substrate and act as an efficient competitor, suggesting that they can block tRip function and slow parasite development., Competing Interests: Declaration of competing interest Authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Competing Interests: All authors declare no relevant financial relationships.

Background: Successful recovery following a perturbation during walking depends on a quick well-coordinated response from the body. As such, lower limb joint power and work provide critical information characterizing the success of the recovery after a perturbation. Therefore, this study aimed to investigate lower-limb joint power and the relative contribution of each joint to the total leg work during the recovery following a trip-induced perturbation., Methods: Twenty-four young male volunteers walked at 1.1 m/s for 2 min, followed by two unexpected perturbations induced by rapidly decelerating the right belt of the split-belt treadmill. Joint moments and powers were calculated using an inverse dynamic approach. Joint work was found as the integral of joint power with respect to time. Statistical parametric mapping (SPM) and paired-sample t-tests were used to compare joint power and work between recovery and unperturbed steps., Results: Compared to normal walking, recovery from the trip required a significant increase in both positive (+27 %, p < 0.05) and negative(+28 %,p < 0.05) leg work. During unperturbed walking, the ankle was the key contributor to both positive (ankle=50 %, hip=34 %, and knee=15 %) and negative (ankle=62 %, knee=32 %, and hip=6 %) leg work. During recovery, the knee eccentric work significantly increased (+83 %,p < 0.05) making it the main contributor to the negative leg work (knee=46 %, ankle=45 %, and hip=9 %). The hip positive work also increased during recovery (+62.7 %, p < 0.05), while ankle and the knee positive work remained unchanged., Significance: These findings highlight the importance of eccentric work of the knee, and concentric work of the hip joint during recovery from trip-induced perturbations. The additional mechanical demand of producing and absorbing more power during recovery is primarily imposed on the knee and hip, rather than the ankle. This new insight into the specific functions of lower-limb joints during recovery from trip-induced perturbations has important implications for the design of targeted fall prevention interventions., Competing Interests: Declaration of Competing Interest None of the authors has any financial or personal relationship with other people or organizations that could inappropriately influence this work, including employment, consultancies, stock ownership, honoraria, paid expert testimony, patent applications/registrations, and grants or other funding., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

CHO cells are most commonly used for the synthesis of recombinant proteins in biopharmaceutical production. When stable producer cell lines are obtained, the locus of transgene integration into the genome has a great influence on the level of its expression. Therefore, the identification of genomic loci ensuring a high level of protein production is very important. Here, we used the TRIP assay to study the influence of the local chromatin environment on the activity of transgenes in CHO cells. For this purpose, reporter constructs encoding eGFP under the control of four promoters were stably integrated into the genome of CHO cells using the piggyBac transposon. Each individual transgene contained a unique tag, a DNA barcode, and the resulting polyclonal cell population was cultured for almost a month without any selection. Next, using the high-throughput sequencing, genomic localizations of barcodes, as well as their abundances in the population and transcriptional activities were identified. In total, ~640 transgenes more or less evenly distributed across all chromosomes of CHO cells were characterized. More than half of the transgenes were completely silent. The most active transgenes were identified to be inserted in gene promoters and 5' UTRs. Transgenes carrying Chinese hamster full-length promoter of the EF-1α gene showed the highest activity. Transgenes with a truncated version of the same promoter and with the mouse PGK gene promoter were on average 10 and 19 times less active, respectively. In total, combinations of genomic loci of CHO cells and transgene promoters that together provide different levels of transcriptional activity of the model reporter construct were described., Competing Interests: The authors declare no conflict of interest., (Copyright © AUTHORS.)

Dilatometric experiments were conducted with the main purpose of measuring the transformation-induced coefficients of 13% chromium and 4% nickel, which are martensitic stainless steel base and filler materials used for hydraulic turbine manufacturing. To this end, a set of experiments was conducted in a quenching dilatometer equipped with loading capabilities. The measurement system was further improved by means of modified pushrods to allow for the use of specimens with geometries that are compliant with tensile test standards. This improvement allowed for the measurement of the materials' phases and respective yield strengths. The dataset was further used to determine the relationship between the applied external stress and the martensitic start temperature (Ms) upon cooling. The TRIP coefficient's K values for both the S41500 steel and E410NiMo filler material were measured at 8.12×10-5 and 7.11×10-5, respectively. Additionally, the solid phase transformation model parameters for both the austenitic and martensitic transformation of the filler material were measured. These parameters were then used to model austenitic-phase-transformation kinetics and martensite transformation, including transformation-induced plasticity effects. Good agreement was achieved between the calculation and the experiments.

Safety shoes are known to challenge dynamic balance, but the interaction between footwear and trips has not been thoroughly explored. This study investigated the biomechanical differences on dynamic balance during unexpected trip perturbations between safety shoes and everyday shoes. The vertical position of the whole-body center of mass (CoM) and the linear momentum of the swing leg from seven females and sixteen males were analyzed in five subsequent gait cycles. Additionally, the recovery strategies (i.e., the displacement of the foot after tripping) were classified. Wearing safety shoes, the linear momentum of the foot and whole leg increased, and the vertical position of the whole-body CoM was lower after the perturbation. Additionally, the recovery strategy when wearing safety shoes demonstrated a lower displacement of the foot. In conclusion, wearing safety shoes was found to have negative biomechanical effects when having to circumvent a trip, and this potentially increased the risk of falling., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The use of targeted integration for industrial CHO cell line development currently requires significant upfront effort to identify genomic loci capable of supporting multigram per liter therapeutic protein production from a limited number of transgene copies. To address this barrier to widespread adoption, we characterized transgene expression from thousands of stable hotspots in the CHO genome using the Thousands of Reporters Integrated in Parallel high-throughput screening method. This genome-scale data set was used to define a limited set of epigenetic properties of hotspot regions with sizes on the order of 10 kb. Cell lines with landing pad integrations at eight retargeted hotspot candidates consistently exhibited higher transgene mRNA expression than a commercially viable hotspot in equivalent culture conditions. Initial benchmarking of NISTmAb and trastuzumab productivity from one of these hotspots yielded mAb productivities of approximately 0.7-2 g/L (qP range: 2.9-8.2 pg/cell/day) in small-scale fed-batches. These findings indicate the list of hotspot candidates identified here will be a valuable resource for targeted integration platform development within the CHO community., (© 2023 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals LLC.)

Trip perturbations are proposed to be a leading cause of falls in older adults. To prevent trip-falls, trip-related fall risk should be assessed and subsequent task-specific interventions improving recovery skills from forward balance loss should be provided to the individuals at risk of trip-fall. Therefore, this study aimed to develop trip-related fall risk prediction models from one's regular gait pattern using machine-learning approaches. A total of 298 older adults (≥60 years) who experienced a novel obstacle-induced trip perturbation in the laboratory were included in this study. Their trip outcomes were classified into three classes: no-falls ( n = 192), falls with lowering strategy (L-fall, n = 84), and falls with elevating strategy (E-fall, n = 22). A total of 40 gait characteristics, which could potentially affect trip outcomes, were calculated in the regular walking trial before the trip trial. The top 50% of features ( n = 20) were selected to train the prediction models using a relief-based feature selection algorithm, and an ensemble classification model was selected and trained with different numbers of features (1-20). A ten-times five-fold stratified method was utilized for cross-validation. Our results suggested that the trained models with different feature numbers showed an overall accuracy between 67% and 89% at the default cutoff and between 70% and 94% at the optimal cutoff. The prediction accuracy roughly increased along with the number of features. Among all the models, the one with 17 features could be considered the best model with the highest AUC of 0.96, and the model with 8 features could be considered the optimal model, which had a comparable AUC of 0.93 and fewer features. This study revealed that gait characteristics in regular walking could accurately predict the trip-related fall risk for healthy older adults, and the developed models could be a helpful assessment tool to identify the individuals at risk of trip-falls.

Occupational exoskeletons have become more prevalent as an ergonomic control to reduce the physical demands of workers. While beneficial effects have been reported, there is relatively little evidence regarding potential adverse effects of exoskeletons on fall risk. The purpose of this study was to investigate the effects of a leg-support exoskeleton on reactive balance after simulated slips and trips. Six participants (three females) used a passive, leg-support exoskeleton that provided chair-like support in three experimental conditions (no exoskeleton, low-seat setting, high-seat setting). In each of these conditions, participants were exposed to 28 treadmill perturbations from an upright standing posture simulating a backward slip (0.4-1.6 m/s) or a forward trip (0.75-2.25 m/s). The exoskeleton increased the probability of a failed recovery, and adversely affected reactive balance kinematics, after simulated slips and trips. After simulated slips, the exoskeleton decreased initial step length 0.039 m, decreased mean step speed 0.12 m/s, anteriorly displaced touchdown position of the initial recovery step by 0.045 m, and decreased PSIS height at initial step touchdown by 1.7 % sof its standing height. After simulated trips, the exoskeleton increased trunk angle at step 2.4 degrees, and decreased initial step length 0.033 m. These effects appeared to result from the exoskeleton inhibiting regular stepping motion due to its posterior placement on the lower limbs, added mass, and mechanical constraints on participant movement. Our results suggest care may be needed among leg-support exoskeleton users when at risk of slips or trips and motivate potential exoskeleton design modifications to reduce fall risk., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

tRip is a tRNA import protein specific to Plasmodium, the causative agent of malaria. In addition to its membrane localization and tRNA trafficking properties, tRip has the capacity to associate with three aminoacyl-tRNA synthetases (aaRS), the glutamyl- (ERS), glutaminyl- (QRS), and methionyl- (MRS) tRNA synthetases. In eukaryotes, such multi-aaRSs complexes (MSC) regulate the moonlighting activities of aaRSs. In Plasmodium, tRip and the three aaRSs all contain an N-terminal GST-like domain involved in the assembly of two independent complexes: the Q-complex (tRip:ERS:QRS) and the M-complex (tRip:ERS:MRS) with a 2:2:2 stoichiometry and in which the association of the GST-like domains of tRip and ERS (tRip-N:ERS-N) is central. In this study, the crystal structure of the N-terminal GST-like domain of ERS was solved and made possible further investigation of the solution architecture of the Q- and M-complexes by small-angle x-ray scattering (SAXS). This strategy relied on the engineering of a tRip-N-ERS-N chimeric protein to study the structural scaffold of both Plasmodium MSCs and confirm the unique homodimerization pattern of tRip in solution. The biological impact of these structural arrangements is discussed., (© 2023 The Authors. Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.)

Background: Transfemoral prosthesis users' high fall rate is related to increased injury risk, medical costs, and fear of falling. Better understanding how stumble conditions (e.g., participant age, prosthesis type, side tripped, and swing phase of perturbation) affect transfemoral prosthesis users could provide insight into response deficiencies and inform fall prevention interventions., Methods: Six unilateral transfemoral prosthesis users experienced obstacle perturbations to their sound limb in early, mid, and late swing phase. Fall outcome, recovery strategy, and kinematics of each response were recorded to characterize (1) recoveries versus falls for transfemoral prosthesis users and (2) prosthesis user recoveries versus healthy adult recoveries., Results: Out of 26 stumbles, 15 resulted in falls with five of six transfemoral prosthesis users falling at least once. By contrast, in a previously published study of seven healthy adults comprising 214 stumbles using the same experimental apparatus, no participants fell. The two oldest prosthesis users fell after every stumble, stumbles in mid swing resulted in the most falls, and prosthesis type was not related to strategy/fall outcomes. Prosthesis users who recovered used the elevating strategy in early swing, lowering strategy in late swing, and elevating or lowering/delayed lowering with hopping in mid swing, but exhibited increased contralateral (prosthetic-side) thigh abduction and trunk flexion relative to healthy controls. Falls occurred if the tripped (sound) limb did not reach ample thigh/knee flexion to sufficiently clear the obstacle in the elevating step, or if the prosthetic limb did not facilitate a successful step response after the initial sound-side elevating or lowering step. Such responses generally led to smaller step lengths, less anterior foot positioning, and more forward trunk flexion/flexion velocity in the resulting foot-strikes., Conclusions: Introducing training (e.g., muscle strength or task-specific motor skill) and/or modifying assistive devices (e.g., lower-limb prostheses or exoskeletons) may improve responses for transfemoral prosthesis users. Specifically, training or exoskeleton assistance could help facilitate sufficient thigh/knee flexion for elevating; training or prosthesis assistance could provide support-limb counteracting torques to aid in elevating; and training or prosthesis assistance could help initiate and safely complete prosthetic swing., (© 2022. The Author(s).)

Genetically encoded biosensors are powerful tools to monitor cellular behavior, but the difficulty in generating appropriate reporters for chromatin factors hampers our ability to dissect epigenetic pathways. Here, we present TRACE (transgene reporters across chromatin environments), a high-throughput, genome-wide technique to generate fluorescent human reporter cell lines responsive to manipulation of epigenetic factors. By profiling GFP expression from a large pool of individually barcoded lentiviral integrants in the presence and absence of a perturbation, we identify reporters responsive to pharmacological inhibition of the histone lysine demethylase LSD1 and genetic ablation of the PRC2 subunit SUZ12. Furthermore, by manipulating the HIV-1 host factor LEDGF through targeted deletion or fusion to chromatin reader domains, we alter lentiviral integration site preferences, thus broadening the types of chromatin examined by TRACE. The phenotypic reporters generated through TRACE will allow the genetic interrogation of a broad range of epigenetic pathways, furthering our mechanistic understanding of chromatin biology., Competing Interests: Declaration of interests R.E.K. is a member of Molecular Cell’s Advisory Board., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Slips, trips, and falls (STFs) are the second leading cause of non-fatal injuries and can lead to fatal incidents in the mining industry. Hazard identification is an essential first step in remediating STF hazards and creating a safer work environment. Previous research has identified industry-specific risk factors for STFs, evaluated exposures to those risk factors, and developed taxonomies of the hazards for the construction and farming sectors. In comparison, ErgoMine-a mobile device application-based ergonomics audit tool-is the only systematic evaluation tool that covers STF hazards in the mining industry. However, ErgoMine was not specifically developed to address STF hazards. This paper describes the development of a taxonomy that helps identify STF hazards at surface mining sites and provides recommendations to address these hazards to inform future evaluation tools. The objective was to develop a taxonomy that was self-explanatory, observable, repeatable, and solution oriented. In addition to current regulations, standards and guidelines were used to develop the taxonomy to ensure the focus was beyond basic compliance. A detailed description of how the STF hazard taxonomy was created for walkways, stairways, and fixed ladders is provided, along with two specific applications of its use. The STF hazard taxonomy can be used to develop tools like checklists and ergonomics audits to identify and remediate slip, trip, and fall hazards at surface mining facilities, thereby improving worker safety., (Published by Elsevier Ltd.)

The present study analyzes the cyclic crack propagation behavior in an austenitic steel processed by electron beam powder bed fusion (PBF-EB). The threshold value of crack growth as well as the crack growth behavior in the Paris regime were studied. In contrast to other austenitic steels, the building direction during PBF-EB did not affect the crack propagation rate, i.e., the crack growth rates perpendicular and parallel to the building direction were similar due to the isotropic microstructure characterized by equiaxed grains. Furthermore, the influence of significantly different building parameters was studied and, thereby, different energy inputs causing locally varying manganese content. Crack growth behavior was not affected by these changes. Even a compositional gradation within the same specimen, i.e., crack growth through an interface of areas with high and areas with low manganese content, did not lead to a significant change of the crack growth rate. Thus, the steel studied is characterized by a quite robust cyclic crack growth behavior independent from building direction and hardly affected by typical parameter deviations in the PBF-EB process.

Background: Differences in reactive stepping strategy to recover balance have been investigated as a function of age and sex, but to date have been measured using discrete step or joint specific measures. It is unknown how whole-body strategy or underlying motor control objectives differ between age and sex groups in forward reactive stepping., Research Question: Does whole-body movement and/or motor control strategy differ as a function of age or sex in a forward reactive step to maintain balance?, Methods: Forty young and older adults (45 females, 35 males) participated in this study. All participants performed five reactive stepping trials in response to a forward balance perturbation while whole-body kinematics and ground reaction forces were collected. Features of whole-body movement strategy were determined using a principal component analysis model. Average principal component (PC) scores were compared between groups as a measure of whole-body movement strategy and within participant relative standard deviation of PC scores were compared to determine if motor control objectives differed across groups., Results: Significant differences in reactive stepping strategy were observed both as a function of age and sex. Older adults had a greater step length and width, greater anterior trunk and pelvis translation, greater knee flexion angles and anterior translation of the hip joint on the stepping leg compared to young participants. Males had lesser step length and width, as well as greater trunk flexion compared to females. No differences in relative standard deviation of PC scores were observed between age or sex-based groups suggesting that motor control objectives were similar between groups., Significance: This study demonstrates how whole-body movement strategy differs as a function of age and sex, which explains why previously reported discrete outcomes occur. Additionally, it does not seem that motor control strategy objectives differ between age or sex groups in forward reactive stepping., (Crown Copyright © 2021. Published by Elsevier B.V. All rights reserved.)

High strength and ductility, often mutually exclusive properties of a structural material, are also responsible for damage tolerance. At low temperatures, due to high surface energy, single element metallic nanowires such as Ag usually transform into a more preferred phase via nucleation and propagation of partial dislocation through the nanowire, enabling superplasticity. In high entropy alloy (HEA) CoNiCrFeMn nanowires, the motion of the partial dislocation is hindered by the friction due to difference in the lattice parameter of the constituent atoms which is responsible for the hardening and lowering the ductility. In this study, we have examined the temperature-dependent superplasticity of single component Ag and multicomponent CoNiCrFeMn HEA nanowires using molecular dynamics simulations. The results demonstrate that Ag nanowires exhibit apparent temperature-dependent superplasticity at cryogenic temperature due to (110) to (100) cross-section reorientation behavior. Interestingly, HEA nanowires can perform exceptional strength-ductility trade-offs at cryogenic temperatures. Even at high temperatures, HEA nanowires can still maintain good flow stress and ductility prior to failure. Mechanical properties of HEA nanowires are better than Ag nanowires due to synergistic interactions of deformation twinning, FCC-HCP phase transformation, and the special reorientation of the cross-section. Further examination reveals that simultaneous activation of twining induced plasticity and transformation induced plasticity are responsible for the plasticity at different stages and temperatures. These findings could be very useful for designing nanowires at different temperatures with high stability and superior mechanical properties in the semiconductor industry.

This study examined the effects of perturbation training on the contextual interference and generalization of encountering a novel opposing perturbation. One hundred and sixty-nine community-dwelling healthy older adults (69.6 ± 6.4 years) were randomly assigned to one of the three groups: slip-perturbation training (St, n = 67) group received 24 slips, trip-perturbation training (Tt, n = 67) group received 24 trips, and control (Ctrl: n = 31) group received only non-perturbed walking trials (ClinicalTrials.gov NCT03199729; https://clinicaltrials.gov/ct2/show/NCT03199729). After training, all groups had 30 min of rest and three post-training non-perturbed walking trials, followed by a reslip and a novel trip trial for St, a retrip and a novel slip trial for Tt, and randomized novel slip and trip trials for Ctrl. The margin of stability (MOS), step length, and toe clearance of post-training walking trials were compared among three groups to examine interferences in proactive adjustment. Falls, MOS at the instant of recovery foot touchdown, and hip height of post-training perturbation trials were investigated to detect interferences and generalization in reactive responses. Results indicated that prior adaptation to slip perturbation training, resulting in walking with a greater MOS (more anterior) and a shorter step length ( p < 0.01) than that of the Ctrl group, would be associated with a greater likelihood to forward balance loss if encountered with a trip. The trip adaptation training mainly induced a higher toe clearance during walking ( p < 0.01) than the Ctrl group, which could lead to reduced effectiveness of the reactive response when encountered with a novel slip. However, there was no difference in the reactive MOS, limb support, and falls between the control group and the slip and trip training groups on their respective opposing novel perturbation post-training (MOS, limb support, and falls for novel slip: Tt = Ctrl; for the novel trip: St = Ctrl, both p > 0.05). Current findings suggested that, although perturbation training results in proactive adjustments that could worsen the reactive response (interference) when exposed to an unexpected opposing perturbation, older adults demonstrated the ability to immediately generalize the training-induced adaptive reactive control to maintain MOS, to preserve limb support control, and to reduce fall risk., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bhatt, Wang, Wang and Kannan.)

Medium manganese steels can exhibit both high strength and ductility due to transformation-induced plasticity (TRIP), caused by metastable retained austenite, which in turn can be adjusted by intercritical annealing. This study addresses the laser additive processability and mechanical properties of the third-generation advanced high strength steels (AHSS) on the basis of medium manganese steel using Laser Powder Bed Fusion (LPBF). For the investigations, an alloy with a manganese concentration of 5 wt.% was gas atomized and processed by LPBF. Intercritical annealing was subsequently performed at different temperatures (630 and 770 °C) and three annealing times (3, 10 and 60 min) to adjust the stability of the retained austenite. Higher annealing temperatures lead to lower yield strength but an increase in tensile strength due to a stronger work-hardening. The maximum elongation at fracture was approximately in the middle of the examined temperature field. The microstructure and properties of the alloy were further investigated by scanning electron microscopy (SEM), hardness measurements, X-ray diffraction (XRD), electron backscatter diffraction (EBSD) and element mapping.

During mRNA transcription, diverse RNA-binding proteins (RBPs) are recruited to RNA polymerase II (RNAP II) transcription machinery. These RBPs bind to distinct sites of nascent RNA to co-transcriptionally operate mRNA processing. Recent studies have revealed a close relationship between transcription and co-transcriptional RNA processing, where one affects the other's activity, indicating an essential role of protein-RNA interactions for the fine-tuning of mRNA production. Owing to their limited amount in cells, the detection of protein-RNA interactions specifically assembled on the transcribing RNAP II machinery still remains challenging. Currently, cross-linking and immunoprecipitation (CLIP) has become a standard method to detect in vivo protein-RNA interactions, although it requires a large amount of input materials. Several improved methods, such as infrared-CLIP (irCLIP), enhanced CLIP (eCLIP), and target RNA immunoprecipitation (tRIP), have shown remarkable enhancements in the detection efficiency. Furthermore, the utilization of an RNA editing mechanism or proximity labeling strategy has achieved the detection of faint protein-RNA interactions in cells without depending on crosslinking. This review aims to explore various methods being developed to detect endogenous protein-RNA interaction sites and discusses how they may be applied to the analysis of co-transcriptional RNA processing.

Poor bone status is associated with increased complications following orthopedic surgery. Therefore, assessing site-specific skeletal status prior to or after orthopedic surgery to optimize outcomes is appealing. The trabecular bone score (TBS) approach, a surrogate for microarchitecture, was adapted to the Texture Research Investigational Platform (TRIP), which allows assessment of many skeletal sites imaged by various modalities. TRIP generates a bone texture score (TBS ORTHO), which could potentially guide surgical decision-making and offer insight into postsurgical fracture risk. As distal femur bone loss occurs following total knee arthroplasty (TKA), we hypothesized that TBS ORTHO after TKA would identify poorer texture in the operated femur compared to the nonoperated. We evaluated 30 subjects (15 M/15 F) with unilateral TKA 2-5 yr previously, mean age 67.9 yr and body mass index 30 kg/m 2 . Using a Lunar iDXA, lumbar spine and entire femur scans were obtained, the latter using the atypical femur fracture feature. Distal femur bone mineral density (BMD) and TBS ORTHO were obtained using manual regions of interest (ROI) at 15% and 25% of leg length from the intercondylar notch. TBS ORTHO was determined using distal femur DICOM images and TRIP v1.0 (Medimaps, France). Differences in operated vs nonoperated femur were evaluated by paired t test. As previously reported, operated leg BMD was approx 10% lower at 15% and 25% ROIs. Similarly, TBS ORTHO values in the operated leg were approx 5% lower (p < 0.05) at these same ROIs. Distal femur TBS ORTHO and BMD were largely unrelated. TBS ORTHO reproducibility at these ROIs was approx 3.5%. In conclusion, this pilot study documents the feasibility of reproducibly obtaining distal femur TBS ORTHO values. Lower values were observed in the surgical leg, consistent with the bone loss that follows TKA. Further work is indicated to refine TRIP use and evaluate whether such data provides guidance for surgical decision-making and improves periprosthetic fracture prediction., (Copyright © 2019 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

Background: Women have an increased likelihood of sustaining a fall-related injury compared to men; however, little is known about fall prevention strategies between genders. The purpose of this study was to compare the gender differences in lower limb reactions and three-dimensional recovery patterns following a treadmill-induced trip perturbation., Methods: Seventy-six participants who are right limb dominant enrolled in the study, which included 41 females (26.15 [9.92] years old) and 35 males (27.11 [9.15] years old). The outcome measures included a three-dimensional (3D) range of motion (ROM) analysis on the bilateral hip, knee, and ankle joints following the trip perturbation at a 0.89 m/s velocity for 0.12 m. This induced trip caused subjects to walk forward for a 0.26 s duration., Findings: The female group demonstrated significantly increased frontal plane ROM in the right hip (t = 2.71, p = 0.01) and left ankle (t = 2.16, p = 0.03) as well as increased sagittal plane ROM in the right (t = 2.07, p = 0.04) and left (t = 2.36, p = 0.02) ankles. There was a significant gender interaction on 3D body region (F = 6.84, p = 0.01) following the perturbation., Interpretation: There was a 3D gender difference on the lower limbs for balance control. The female group demonstrated increased sagittal motion in both ankles following a trip perturbation. In addition, their ROM increased on the dominant hip and non-dominant ankle in the frontal plane, which was compensated by step width for standing stability. Clinicians might want to consider the implications of gender differences on lower limb reaction patterns to help patients avoid potential injuries/falls., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Worn shoes are known to contribute to slip-and-fall risk, a common cause of workplace injuries. However, guidelines for replacing shoes are not well developed. Recent experiments and lubrication theory suggest that the size of the worn region is an important contributor to the shoe tread's ability to drain fluid and therefore the under-shoe friction. This study evaluated a simple test for comparing the size of the worn region relative to a common object (AAA and AA battery) as a means of determining shoe replacement. This study consisted of three components involving slip-resistant shoes: Experiment #1: a longitudinal, mechanical, accelerated wear experiment; Experiment #2: a longitudinal experiment where the same shoes were tested after each month of worker use; and Experiment #3: a cross-sectional experiment that exposed participants to a slippery condition, while donning their own worn shoes. The COF (Experiments #1 and #2); under-shoe fluid pressure (all experiments); and slip severity (Experiment #3) were compared across outcomes (fail/pass) of the battery tests. Larger fluid pressures, lower coefficient of friction, and more severe slips were observed for shoes that failed the battery tests compared with those passing the tests. This method offers promise for assessing loss in friction and an increase in slip risk for slip-resistant shoes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Choroidal melanoma (CM) remains the most prevalent form of intraocular malignancy, and the prognosis of affected patients is poor. While the E3 ubiquitin ligase TRAF-interacting protein (TRIP) is known to play key regulatory roles in multiple diseases, its relevance in CM remains uncertain. In the present study, we found that TRIP overexpression is sufficient to inhibit the proliferation, invasion, and epithelial-mesenchymal transition (EMT) of CM cells in vitro, whereas the opposite phenotypes are observed following TRIP knockdown. We further determined that TRIP is able to promote the K48-polyubiquitination of EMT-associated transcription factor Twist-related protein 1, thereby suppressing EMT progression. Together, our results suggest that TRIP plays an important role in regulating the progression of CM and that it may therefore be an important therapeutic target for the treatment of this disease., (© 2020 Federation of European Biochemical Societies.)

This study determined the effect of mixed (slip- and trip-like stance perturbation) training on reactive responses in people with chronic stroke (PwCS) and examined modulation of their reactive responses on higher intensity perturbations posttraining (scaling). Twelve PwCS were exposed to consecutive blocks of treadmill-based slip-like and trip-like perturbations and mixed-stance perturbations. A higher intensity trial was provided postblock and postmixed training. Postural stability [center-of-mass position (CoMP) and velocity (CoMV)], compensatory step length, step count, and trunk angle were examined. PwCS demonstrated an anterior positioning of the CoM, increased step length, and reduced compensatory step count with slip-like block training ( P < 0.05). Trip-like block training resulted in reductions in step count, step length, and trunk angle ( P < 0.05); however, CoMP remained unchanged ( P > 0.05). With mixed training, there was a decrease rather than an increase in step length for slip-like perturbations but a continued decrease in step length and trunk angle was seen on trip-like perturbations ( P < 0.05); however, CoMP and step count remained unchanged for both. For both perturbations, the higher intensity trials demonstrated no change from the last block trial. Postmixed block, the higher intensity trial demonstrated an increase only in step count on trip-like perturbation. Between postblock and postmixed higher intensity trials, an increase in step count and decrease in step length was noted only for slip-like perturbations. Block training with slip- and trip-like stance perturbations can enhance reactive responses among PwCS. Although mixed perturbation training continued to improve trip-induced adaptation, prior slip-induced adaptive changes were not maintained and further slip-adaptation was not seen. PwCS demonstrated partial scaling of reactive responses postblock and postmixed training. NEW & NOTEWORTHY Block perturbation training led to development of favorable reactive responses to counteract treadmill-based, slip-like and trip-like stance perturbations among people with chronic stroke. During mixed block, previously acquired adaptive changes in reactive responses from slip-block training were not maintained, probably due to interference offered by trip block. Instead, on trip-like perturbations, trip block-induced adaptation was maintained and continued to show further improvement. Our findings might provide future direction for designing effective mixed perturbation training paradigms to counteract both opposing perturbation types.

RNA processing occurs co-transcriptionally through the dynamic recruitment of RNA processing factors to RNA polymerase II (RNAPII). However, transcriptome-wide identification of protein-RNA interactions specifically assembled on transcribing RNAPII is challenging. Here, we develop the targeted RNA immunoprecipitation sequencing (tRIP-seq) method that detects protein-RNA interaction sites in thousands of cells. The high sensitivity of tRIP-seq enables identification of protein-RNA interactions at functional subcellular levels. Application of tRIP-seq to the FUS-RNA complex in the RNAPII machinery reveals that FUS binds upstream of alternative polyadenylation (APA) sites of nascent RNA bound to RNAPII, which retards RNAPII and suppresses the recognition of the polyadenylation signal by CPSF. Further tRIP-seq analyses demonstrate that the repression of APA is achieved by a complex composed of FUS and U1 snRNP on RNAPII, but not by either one alone. Moreover, our analysis reveals that FUS mutations in familial amyotrophic lateral sclerosis (ALS) that impair the FUS-U1 snRNP interaction aberrantly activate the APA sites. tRIP-seq provides new insights into the regulatory mechanism of co-transcriptional RNA processing by RNA processing factors., (© 2020 The Authors.)

Background: Trips account for over half of outdoor falls among community-dwelling older adults., Aims: To investigate to what extent obstacle-induced trip-perturbation training could reduce fall-risk among older adults and to see whether training effects could be retained short term., Methods: Forty community-dwelling older adults were exposed to 24 repeated trip-perturbations given in a "blocked-and-mixed" manner during over-ground gait. Another trip was given 30 min post-training. For each trip, recovery strategies and outcomes (fall versus no fall) were analyzed. Within-trial changes to proactive and reactive dynamic center of mass stability, pre-trip toe clearance and trunk angle, trunk angle at recovery completion, and recovery step length were analyzed., Results: 48% of participants fell on their novel trip. The fall rate decreased significantly for subsequent trips, with no falls on the last trip. The decreased fall incidence resulted from improved feedforward and feedback adjustments for controlling center of mass stability and body kinematics. Proactive adaptations included reduced forward center of mass velocity, which lessened forward instability, and larger toe clearance, which increased the likelihood of obstacle avoidance. Reactive adjustments included reduced forward instability and improved trunk control (reduced forward rotation) at recovery step completion. Post-training, training effects were retained in terms of fall incidence, with slight decay in toe clearance and reactive stability., Conclusions: Older adults demonstrated appropriate locomotor-based proactive and reactive adaptations to repeated obstacle-induced trips with short-term retention similar to young adults, and thus could reduce their fall-risk through such training.

Objectives/hypothesis: Optimizing value of medical service trips (MSTs) requires alignment of the services provided with the needs and desires of hosts. Our aim was to understand which MST services Vietnamese otolaryngologists find most beneficial and contrast to those believed most important by volunteers., Study Design: Cross-sectional survey., Methods: Otolaryngologists from a tertiary care institution travel to Vietnam yearly. In March 2018, surveys were distributed to Vietnamese otolaryngology faculty, residents, and US otolaryngology volunteers. The value of 11 MST-provided services were graded on a five-point Likert scale. Services included observing US otolaryngology volunteers perform surgery, US otolaryngology volunteer lectures, paper/electronic lecture material, instrument donation, minifellowships in the United States, among others. Respondents also voted for the single most important service. Responses were analyzed via Kruskal-Wallis analysis of variance and Wilcoxon rank sum test., Results: A total of 153 survey responses were recorded. There were 52% respondents who identified as male and 39% as female. The highest-valued services by Vietnamese otolaryngologists were didactic lectures given by US otolaryngology volunteers (4.6/5 ± 0.6), and reviewing cases with US otolaryngology volunteers in the clinic (4.4/5 ± 0.9). The least important services were instrument donation and seeing US otolaryngology volunteers assist with surgery (≤4.1/5). The highest-value services perceived by US otolaryngology volunteers were reviewing cases in the clinic and sponsoring minifellowships (4.9 ± 0.4). Vietnamese faculty perceived the single most important service to be US volunteer lectures (20/74 votes), whereas Vietnamese residents perceived minifellowships to be most important (13/34 votes) CONCLUSIONS: Vietnamese otolaryngologists desire an education-focused relationship with US otolaryngology volunteers, with didactic lectures and sponsored US fellowships having the highest value and performance of surgeries having less value., Level of Evidence: 4 Laryngoscope, 130:E305-E310, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

The transformation induced plasticity (TRIP) effect is investigated during a load path change using a cruciform sample. The transformation properties are followed by in-situ neutron diffraction derived from the central area of the cruciform sample. Additionally, the spatial distribution of the TRIP effect triggered by stress concentrations is visualized using neutron Bragg edge imaging including, e.g., weak positions of the cruciform geometry. The results demonstrate that neutron diffraction contrast imaging offers the possibility to capture the TRIP effect in objects with complex geometries under complex stress states.

Background: Appropriately responding to unexpected perturbations, such as a trip, is critical to sustain balance and avoid falling during walking., Research Question: How do arm motion and walking asymmetry affect postural stability when recovering from a trip perturbation?, Methods: Fifteen healthy young individuals, who had no experience with treadmill induced perturbations, participated in this study. The Computer-Assisted Rehabilitation Environment system (CAREN-Extended) was used to simulate unexpected perturbations while walking symmetrically and asymmetrically with various arm swings (normal, bound, released). Whole-body angular momentum (WBAM), peak trunk angular velocities, Center of Mass (COM), step width and stance time were analyzed before and when recovering from trip perturbations., Results: Participants were able to recover their postural stability within three strides following the sudden anterior-posterior trip perturbation. The perturbation increased peak trunk angular velocity, the COM excursion and WBAM but did not affect stance time and step width. The arm conditions had significant effects on peak trunk angular velocity, WBAM and step width during pre-perturbation. Walking conditions had a significant effect on all variables during pre-perturbation; however, post-perturbation showed significant effects only for peak trunk angular velocity, WBAM, and COM., Significance: Unexpected perturbation had effects on most of gait variables; nevertheless, participants fully recovered and adapted their gait pattern to sudden perturbations even without using their arms while walking symmetrically and asymmetrically. Arm movements could help young individuals recover after a perturbation but are not essential for perturbations of moderate magnitude. The effect of medial-lateral perturbations on gait still need to be investigated., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest. This funding source had no involvement in: study design; data collection, analysis and interpretation of data; the writing of the report; or in the decision to submit the article for publication., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The ballistic performance of armour steel welds using austenitic filler materials is poor on account of the disparity in the mechanical properties of the weld and base metals. Consequently, a novel Keyhole Gas Tungsten Arc Welding process with a trapezoidal AISI309 austenitic stainless steel interlayer was developed to tailor chemical composition and microstructure by controlling the solidification sequence. Results show that the dilution rate in the weld metal region can reach up to 43.5% by placing a specially designed interlayer in between the base metal, providing a major scope for microstructure modification. Detailed weld analysis was undertaken by X-ray diffraction, optical and secondary and transmission electron microscopy, energy dispersive spectroscopy and electron back-scattering diffraction. The results from Vickers hardness indents and Charpy impact toughness testing at -40 °C show that the properties of the weld metal region are comparable to that of the base metal. This is ascribed to the weld metal comprising a two phase microstructure of martensite and retained austenite, which contribute to improvements in strength and toughness, respectively. Furthermore, the tailored chemical composition, microstructure and low temperature phase transformation in the weld metal may reduce the tendency toward both solidification cracking and hydrogen assisted cold cracking.

In balance perturbations that elicit backwards reactive steps, body configuration at stepping contact is related to likelihood of balance recovery. However, less is known about the relationship between body configuration (at stepping contact) and underlying centre of mass (COM) dynamics during dynamic perturbations requiring a forward reactive step. Accordingly, the primary objective of this study was to characterize the potential relationships between body configuration and COM displacement during simulated trips. Towards determining the robustness of these relationships, trips were simulated in both baseline and increased passive joint stiffness conditions. Sixteen healthy adults participated in this study. Trips were simulated using a tether release paradigm where participants were suddenly released, necessitating a forward step (onto a force plate) to recover their balance. Trials were performed in a baseline unconstrained condition, and in a 'corset' condition to increase passive stiffness of the trunk and hips. In all trials, whole body kinematics and kinetics were collected. Multiple linear regression models were run to assess the relationship of body angles to COM displacement in both the anteroposterior (AP) and mediolateral (ML) planes. Regression models showed a significant association of sagittal plane body configuration to both COM displacement at stepping contact and maximum COM displacement in the AP plane. Across models, the strongest predictor was the trail leg angle. Associations were stronger in the increased passive stiffness condition (average R 2  = 0.366) compared to the baseline condition (average R 2  = 0.266). Poor association of body configuration to COM displacement was found in the ML plane. The significant associations observed between body configuration and COM dynamics in simulated trips supports the potential downstream application of these models in identifying individuals with impaired balance control and increased fall risk., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019. Published by Elsevier B.V.)

Background: The experimental study of stumble recovery is essential to better understanding the reflexive mechanisms that help prevent falls as well as the deficiencies in fall-prone populations. This study would benefit from a system that can introduce perturbations that: 1) are realistic (e.g., obstacle disrupting the foot in swing phase), 2) are unanticipated by subjects, 3) are controllable in their timing, and 4) allow for kinematic and kinetic evaluation., Methods: A stumble perturbation system was designed that consists of an obstacle delivery apparatus that releases an obstacle onto a force-instrumented treadmill and a predictive targeting algorithm which controls the timing of the perturbation to the foot during swing phase. Seven healthy subjects were recruited to take part in an experimental protocol for system validation, which consisted of two sub-experiments. First, a perception experiment determined whether subjects could perceive the obstacle as it slid onto the treadmill belt. Second, a perturbation experiment assessed the timing accuracy of perturbations relative to a target percent swing input by the experimenter. Data from this experiment were then used to demonstrate that joint kinematics and kinetics could be computed before and after the perturbation., Results: Out of 168 perception trials (24 per subject), not a single obstacle was perceived entering the treadmill by the subjects. Out of 196 perturbation trials, 190 trials successfully induced a stumble event, with a mean targeting accuracy, relative to the desired percent swing, of 25 ms (6.2% of swing phase). Joint kinematic and kinetic results were then computed for three common stumble recovery strategies and shown to be qualitatively consistent with results from prior stumble studies conducted overground., Conclusions: The stumble perturbation system successfully introduced realistic obstacle perturbations that were unanticipated by subjects. The targeting accuracy substantially reduced mistrials (i.e., trials that did not elicit a stumble) compared to previous studies. This accuracy enables stumble recovery to be studied more systematically as a function of when the perturbation occurs during swing phase. Lastly, joint kinematic and kinetic estimates allow for a comprehensive analysis of stumble recovery biomechanics.

Background: Trips and slips, the two most common gait perturbations, often cause falls. Multiple studies have focused mainly on the kinematics of multiple body segments in response to an unexpected trip or slip induced by mechanical obstacles, cables, treadmills, and slippery agents or contaminants on a floor. Few studies have examined the joint moments of the compensatory limb following an unexpected trip on an obstacle., Research Question: This proof-of-concept study sought to assess the ankle, knee, and hip moments of the compensatory limb during normal walking and the first stepping response following the two most common gait perturbations., Methods: Eighteen healthy young adults completed 4 trials (2 trials with a random trip perturbation and 2 trials with a random slip perturbation) while walking on a split-belt treadmill. In each trial, the motorized treadmill induced either an unexpected trip or slip perturbation to the left foot between the 31 st and 40th step randomly. A motion capture system recorded the positions of body segments, the joint moments (i.e., ankle, knee, and hip moments) of the compensatory limb were quantified, and the maximum joint moments were assessed during normal walking and the first stepping response., Results: Compensatory limb's ankle plantarflexion, knee flexion, hip flexion, and hip extension moments were significantly higher for a slip perturbation than for a trip perturbation during the first stepping response. Compensatory limb's knee flexion, hip flexion, and hip extension moments were also significantly higher during the first stepping response to a slip perturbation compared to normal walking., Significance: This proof-of-concept study is the first to investigate the ankle, knee, and hip moments of the compensatory limb during the first stepping response following unexpected gait perturbations induced by a split-belt treadmill. The findings are expected to improve the gait perturbation paradigms developed for training balance-impaired individuals., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

The implementation of hollow S60HS glass microspheres and Fillite 106 cenospheres in a martensitically transformable AISI 304L stainless steel matrix was realized by means of metal injection molding of feedstock with varying fractions of the filler material. The so-called TRIP-steel syntactic foams were studied with respect to their behavior under quasi-static compression and dynamic impact loading. The interplay between matrix material behavior and foam structure was discussed in relation to the findings of micro-structural investigations, electron back scatter diffraction EBSD phase analyses and magnetic measurements. During processing, the cenospheres remained relatively stable retaining their shape while the glass microspheres underwent disintegration associated with the formation of pre-cracked irregular inclusions. Consequently, the AISI 304L/Fillite 106 syntactic foams exhibited a higher compression stress level and energy absorption capability as compared to the S60HS-containing variants. The &alpha; &prime; -martensite kinetic of the steel matrix was significantly influenced by material composition, strain rate and arising deformation temperature. The highest ferromagnetic &alpha; &prime; -martensite phase fraction was detected for the AISI 304L/S60HS batches and the lowest for the TRIP-steel bulk material. Quasi-adiabatic sample heating, a gradual decrease in strain rate and an enhanced degree of damage controlled the mechanical deformation response of the studied syntactic foams under dynamic impact loading.

Background: TRIP (Transmission Reduction Intervention Project) was a network-based, contact tracing approach to locate and link to care, mostly people who inject drugs (PWID) with recent HIV infection., Objective: We investigated whether sequences from HIV-infected participants with high viral load cluster together more frequently than what is expected by chance., Methods: Paired end reads were generated for 104 samples using Illumina MiSeq next-generation sequencing., Results: 63 sequences belonged to previously identified local transmission networks of PWID (LTNs) of an HIV outbreak in Athens, Greece. For two HIV-RNA cut-offs (105 and 106 IU/mL), HIV transmissions were more likely between PWID with similar levels of HIV-RNA (p<0.001). 10 of the 14 sequences (71.4%) from PWID with HIV-RNA >106 IU/mL were clustered in 5 pairs. For 4 of these clusters (80%), there was in each one of them at least one sequence from a recently HIVinfected PWID., Conclusion: We showed that transmissions are more likely among PWID with high viremia., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Trip Database is a freely available search engine based in the United Kingdom. Trip directs users to journal articles, practice guidelines, and other research to support evidence-based medical practice. This column includes sample searches in both the free version and in the subscription Pro version.

Background/aim: Walking requires the integration of the sensory and motor systems. Cognitive distractions have been shown to interfere with negotiation of complex walking environments, especially in populations at greater risk for falls (e.g. the elderly). With the pervasiveness of mobile messaging and the recent introduction of augmented reality mobile gaming, it is increasingly important to understand how distraction associated with the simultaneous use of a mobile device impacts navigation of the complex walking environments experienced in daily life. In this study, we investigated how gait kinematics were altered when participants performed a texting task during step negotiation., Methods: Twenty participants (13 female, 7 males) performed a series of walking trials involving a step-deck obstacle, consisting of at least 3 texting trials and 3 non-texting trials., Results: When texting, participants ascended more slowly and demonstrated reduced dual-step foot toe clearance. Participants similarly descended more slowly when texting and demonstrated reduced single-step foot heel clearance as well as reduced dual-step foot fore-aft heel clearance., Conclusion: These data support the conclusion that texting during stair negotiation results in changes to gait kinematics that may increase the potential for gait disruptions, falls, and injury. Further research should examine the effect texting has on performing other common complex locomotor tasks, actual fall risk, and the patterns of resulting injury rate and severity when negotiating complex environments., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Metal additive manufacturing has strongly gained scientific and industrial importance during the last decades due to the geometrical flexibility and increased reliability of parts, as well as reduced equipment costs. Within the field of metal additive manufacturing methods, selective laser melting (SLM) is an eligible technique for the production of fully dense bulk material with complex geometry. In the current study, we addressed the application of SLM for processing a high-manganese TRansformation-/TWinning-Induced Plasticity (TRIP/TWIP) steel. The solidification behavior was analyzed by careful characterization of the as-built microstructure and element distribution using optical and scanning electron microscopy (SEM). In addition, the deformation behavior was studied using uniaxial tensile testing and SEM. Comparison with conventionally produced TRIP/TWIP steel revealed that elemental segregation, which is normally very pronounced in high-manganese steels and requires energy-intensive post processing, is reduced due to the high cooling rates during SLM. Also, the very fast cooling promoted ε- and α'-martensite formation prior to deformation. The superior strength and pronounced anisotropy of the SLM-produced material was correlated with the microstructure based on the process-specific characteristics.

Understanding travel behavior is critical for an effective urban planning as well as for enabling various context-aware service provisions to support mobility as a service (MaaS). Both applications rely on the sensor traces generated by travellers' smartphones. These traces can be used to interpret travel modes, both for generating automated travel diaries as well as for real-time travel mode detection. Current approaches segment a trajectory by certain criteria, e.g., drop in speed. However, these criteria are heuristic, and, thus, existing approaches are subjective and involve significant vagueness and uncertainty in activity transitions in space and time. Also, segmentation approaches are not suited for real time interpretation of open-ended segments, and cannot cope with the frequent gaps in the location traces. In order to address all these challenges a novel, state based bottom-up approach is proposed. This approach assumes a fixed atomic segment of a homogeneous state, instead of an event-based segment, and a progressive iteration until a new state is found. The research investigates how an atomic state-based approach can be developed in such a way that can work in real time, near-real time and offline mode and in different environmental conditions with their varying quality of sensor traces. The results show the proposed bottom-up model outperforms the existing event-based segmentation models in terms of adaptivity, flexibility, accuracy and richness in information delivery pertinent to automated travel behavior interpretation., Competing Interests: The authors declare no conflict of interest.

RNAi technologies enable the testing of gene function in a cell-type- and stage-specific manner in Drosophila. The development of genome-wide RNAi libraries has allowed expansion of this approach to the genome scale and supports identification of most genes required for a given process in a cell type of choice. However, a large-scale RNAi approach also harbors many potential pitfalls that can complicate interpretation of the results. Here, we summarize published screens and provide a guide on how to optimally plan and perform a large-scale, in vivo RNAi screen. We highlight the importance of assay design and give suggestions on how to optimize the assay conditions by testing positive and negative control genes. These genes are used to estimate false-negative and false-positive rates of the screen data. We discuss the planning and logistics of a large-scale screen in detail and suggest bioinformatics platforms to identify and select gene groups of interest for secondary assays. Finally, we review various options to confirm RNAi knock-down specificity and thus identify high confidence genes for more detailed case-by-case studies in the future.

Background: Walkway codes and standards are created through consensus by committees based on a number of factors, including historical precedence, common practice, cost, and, sometimes, empirical data. The authors maintain that codes and standards that can have an impact on human safety and welfare should give consideration in their formulation to the results of pertinent scientific research., Purpose: This article extends a companion one in examining many elements of common walkway codes and standards related specifically to lighting, warnings and markings. It indicates which elements are based on or supported by empirical data; and which elements could benefit from additional scientific research., Practical Applications: This article identifies areas in which additional research leading toward scientific based codes and standards may be beneficial in enhancing the safety of pedestrian walkway surfaces., (Copyright © 2015 Elsevier Ltd and The Ergonomics Society. All rights reserved.)

Background: Altered gait mechanics are common following stroke and may increase the risk of falls. Paretic gait impairments have been previously compared to the non-paretic limb or control participants. Unfortunately, the biomechanical parameters underlying instances of naturally occurring unsuccessful foot clearance (trips) have yet to be examined in individuals with chronic stroke., Methods: Gait data from 26 participants with chronic stroke were obtained on a dual-belt instrumented treadmill. Instances of successful and unsuccessful foot swing were identified. Temporal, kinematic, and kinetic measures of the paretic limb occurring during late stance, toe-off, and swing were compared between trip and non-trip steps using paired samples t-tests. An α = 0.004 was used to adjust for multiple comparisons., Findings: In the paretic limb, the ankle angle at toe off (P = 0.003; d = 0.64), knee flexion velocity at toe off (P < 0.001; d = 0.73), and peak knee extension moment during terminal stance (P < 0.001; d = 0.74) were significantly different between trips and non-trip steps. During trip steps, ankle plantarflexion at toe-off was 1.0° greater, knee flexion velocity was reduced by 17.6°/sec, and peak knee extension moment was increased by 0.011 Nm/kg · m compared to non-trip steps., Interpretation: It appears to take only minor changes in the movement of the paretic limb to result in a trip in individuals with chronic stroke. Although small, the multi-joint biomechanical changes occurring in the paretic limb during unsuccessful foot clearance result in a functionally longer limb. Thus, interventions targeting multiple joints in the paretic limb may be needed to reduce the risk of trips following stroke., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

In this special edition of Genomics, we present reviews of the current state of the field in identifying and functionally understanding transcriptional enhancers in cells and developing tissues. Typically several enhancers coordinate the expression of an individual target gene, each controlling that gene's expression in specific cell types at specific times. Until recently, identifying each gene's enhancers had been challenging because enhancers do not occupy prescribed locations relative to their target genes. Recently there have been powerful advances in DNA sequencing and other technologies that make it possible to identify the majority of enhancers in virtually any cell type of interest. The reviews in this edition of Genomics highlight some of these new and powerful approaches., (Copyright © 2015 Elsevier Inc. All rights reserved.)