Neuromuscular control: from a biomechanist's perspective

Understanding neural control of movement necessitates a collaborative approach between many disciplines, including biomechanics, neuroscience, and motor control. Biomechanics grounds us to the laws of physics that our musculoskeletal system must obey. Neuroscience reveals the inner workings of our nervous system that functions to control our body. Motor control investigates the coordinated motor behaviours we display when interacting with our environment. The combined efforts across the many disciplines aimed at understanding human movement has resulted in a rich and rapidly growing body of literature overflowing with theories, models, and experimental paradigms. As a result, gathering knowledge and drawing connections between the overlapping but seemingly disparate fields can be an overwhelming endeavour. This review paper evolved as a need for us to learn of the diverse perspectives underlying current understanding of neuromuscular control. The purpose of our review paper is to integrate ideas from biomechanics, neuroscience, and motor control to better understand how we voluntarily control our muscles. As biomechanists, we approach this paper starting from a biomechanical modelling framework. We first define the theoretical solutions (i.e., muscle activity patterns) that an individual could feasibly use to complete a motor task. The theoretical solutions will be compared to experimental findings and reveal that individuals display structured muscle activity patterns that do not span the entire theoretical solution space. Prevalent neuromuscular control theories will be discussed in length, highlighting optimality, probabilistic principles, and neuromechanical constraints, that may guide individuals to families of muscle activity solutions within what is theoretically possible. Our intention is for this paper to serve as a primer for the neuromuscular control scientific community by introducing and integrating many of the ideas common across disciplines today, as well as inspire future work to improve the representation of neural control in biomechanical models

Computer simulations of domain growth and phase separation in two-dimensional binary immiscible fluids using dissipative particle dynamics

We investigate the dynamical behavior of binary fluid systems in two dimensions using dissipative particle dynamics. We find that following a symmetric quench the domain size R(t) grows with time t according to two distinct algebraic laws R(t) = t^n: at early times n = 1/2, while for later times n = 2/3. Following an asymmetric quench we observe only n = 1/2, and if momentum conservation is violated we see n = 1/3 at early times. Bubble simulations confirm the existence of a finite surface tension and the validity of Laplace's law. Our results are compared with similar simulations which have been performed previously using molecular dynamics, lattice-gas and lattice-Boltzmann automata, and Langevin dynamics. We conclude that dissipative particle dynamics is a promising method for simulating fluid properties in such systems.Comment: RevTeX; 22 pages, 5 low-resolution figures. For full-resolution figures, connect to http://www.tcm.phy.cam.ac.uk/~ken21/tension/tension.htm

VEGF regulates local inhibitory complement proteins in the eye and kidney

10.1172/JCI86418Journal of Clinical Investigation1271199-21

αEβ7 Integrin Identifies Subsets of Pro-Inflammatory Colonic CD4+ T Lymphocytes in Ulcerative Colitis.

Background and Aims The αEβ7 integrin is crucial for retention of T lymphocytes at mucosal surfaces through its interaction with E-cadherin. Pathogenic or protective functions of these cells during human intestinal inflammation, such as ulcerative colitis [UC], have not previously been defined, with understanding largely derived from animal model data. Defining this phenotype in human samples is important for understanding UC pathogenesis and is of translational importance for therapeutic targeting of αEβ7-E-cadherin interactions. Methods αEβ7+ and αEβ7- colonic T cell localization, inflammatory cytokine production and expression of regulatory T cell-associated markers were evaluated in cohorts of control subjects and patients with active UC by immunohistochemistry, flow cytometry and real-time PCR of FACS-purified cell populations. Results CD4+αEβ7+ T lymphocytes from both healthy controls and UC patients had lower expression of regulatory T cell-associated genes, including FOXP3, IL-10, CTLA-4 and ICOS in comparison with CD4+αEβ7- T lymphocytes. In UC, CD4+αEβ7+ lymphocytes expressed higher levels of IFNγ and TNFα in comparison with CD4+αEβ7- lymphocytes. Additionally the CD4+αEβ7+ subset was enriched for Th17 cells and the recently described Th17/Th1 subset co-expressing both IL-17A and IFNγ, both of which were found at higher frequencies in UC compared to control. Conclusion αEβ7 integrin expression on human colonic CD4+ T cells was associated with increased production of pro-inflammatory Th1, Th17 and Th17/Th1 cytokines, with reduced expression of regulatory T cell-associated markers. These data suggest colonic CD4+αEβ7+ T cells are pro-inflammatory and may play a role in UC pathobiology

Spinodal decomposition of off-critical quenches with a viscous phase using dissipative particle dynamics in two and three spatial dimensions

We investigate the domain growth and phase separation of hydrodynamically-correct binary immiscible fluids of differing viscosity as a function of minority phase concentration in both two and three spatial dimensions using dissipative particle dynamics. We also examine the behavior of equal-viscosity fluids and compare our results to similar lattice-gas simulations in two dimensions.Comment: 34 pages (11 figures); accepted for publication in Phys. Rev.

Costa Rica Rift hole deepened and logged

During Leg 111 of the Ocean Drilling Program, scientists on the drilling vessel JOIDES Resolution studied crustal structure and hydrothermal processes in the eastern equatorial Pacific. Leg 111 spent 43 days on its primary objective, deepening and logging Hole 5048, a deep reference hole in 5.9-million-year-old crust 200 km south of the spreading axis of the Costa Rica Rift. Even before Leg 111 , Hole 5048 was the deepest hole drilled into the oceanic crust, penetrating 274.5 m of sediments and 1,075.5 m of pillow lavas and sheeted dikes to a total depth of 1,350 m below sea floor (mbsf). Leg 111 deepened the hole by 212.3 m to a total depth of 1,562.3 mbsf (1,287.8 m into basement), and completed a highly successful suite of geophysical logs and experiments, including sampling of borehole waters

Association Between Response to Etrolizumab and Expression of Integrin αE and Granzyme A in Colon Biopsies of Patients With Ulcerative Colitis

Background & AimsEtrolizumab is a humanized monoclonal antibody against the β7 integrin subunit that has shown efficacy vs placebo in patients with moderate to severely active ulcerative colitis (UC). Patients with colon tissues that expressed high levels of the integrin αE gene (ITGAE) appeared to have the best response. We compared differences in colonic expression of ITGAE and other genes between patients who achieved clinical remission with etrolizumab vs those who did.MethodsWe performed a retrospective analysis of data collected from 110 patients with UC who participated in a phase 2 placebo-controlled trial of etrolizumab, as well as from 21 patients with UC or without inflammatory bowel disease (controls) enrolled in an observational study at a separate site. Colon biopsies were collected from patients in both studies and analyzed by immunohistochemistry and gene expression profiling. Mononuclear cells were isolated and analyzed by flow cytometry. We identified biomarkers associated with response to etrolizumab. In the placebo-controlled trial, clinical remission was defined as total Mayo Clinic Score ≤2, with no individual subscore >1, and mucosal healing was defined as endoscopic score ≤1.ResultsColon tissues collected at baseline from patients who had a clinical response to etrolizumab expressed higher levels of T-cell−associated genes than patients who did not respond (P < .05). Colonic CD4+ integrin αE+ cells from patients with UC expressed higher levels of granzyme A messenger RNA (GZMA mRNA) than CD4+ αE− cells (P < .0001); granzyme A and integrin αE protein were detected in the same cells. Of patients receiving 100 mg etrolizumab, a higher proportion of those with high levels of GZMA mRNA (41%) or ITGAE mRNA (38%) than those with low levels of GZMA (6%) or ITGAE mRNA (13%) achieved clinical remission (P < .05) and mucosal healing (41% GZMAhigh vs 19% GZMAlow and 44% ITGAEhigh vs 19% ITGAElow). Compared with ITGAElow and GZMAlow patients, patients with ITGAEhigh and GZMAhigh had higher baseline numbers of epithelial crypt-associated integrin αE+ cells (P < .01 for both), but a smaller number of crypt-associated integrin αE+ cells after etrolizumab treatment (P < .05 for both). After 10 weeks of etrolizumab treatment, expression of genes associated with T-cell activation and genes encoding inflammatory cytokines decreased by 40%−80% from baseline (P < .05) in patients with colon tissues expressing high levels of GZMA at baseline.ConclusionsLevels of GZMA and ITGAE mRNAs in colon tissues can identify patients with UC who are most likely to benefit from etrolizumab; expression levels decrease with etrolizumab administration in biomarkerhigh patients. Larger, prospective studies of markers are needed to assess their clinical value

Identifying predictors of translocation success in rare plant species

The fundamental goal of a rare plant translocation is to create self-sustaining populations with the evolutionary resilience to persist in the long term. Yet, most plant translocation syntheses focus on a few factors influencing short-term benchmarks of success (e.g., survival and reproduction). Short-term benchmarks can be misleading when trying to infer future growth and viability because the factors that promote establishment may differ from those required for long-term persistence. We assembled a large (n = 275) and broadly representative data set of well-documented and monitored (7.9 years on average) at-risk plant translocations to identify the most important site attributes, management techniques, and species' traits for six life-cycle benchmarks and population metrics of translocation success. We used the random forest algorithm to quantify the relative importance of 29 predictor variables for each metric of success. Drivers of translocation outcomes varied across time frames and success metrics. Management techniques had the greatest relative influence on the attainment of life-cycle benchmarks and short-term population trends, whereas site attributes and species' traits were more important for population persistence and long-term trends. Specifically, large founder sizes increased the potential for reproduction and recruitment into the next generation, whereas declining habitat quality and the outplanting of species with low seed production led to increased extinction risks and a reduction in potential reproductive output in the long-term, respectively. We also detected novel interactions between some of the most important drivers, such as an increased probability of next-generation recruitment in species with greater seed production rates, but only when coupled with large founder sizes. Because most significant barriers to plant translocation success can be overcome by improving techniques or resolving site-level issues through early intervention and management, we suggest that by combining long-term monitoring with adaptive management, translocation programs can enhance the prospects of achieving long-term success

LibrettOS: A Dynamically Adaptable Multiserver-Library OS

We present LibrettOS, an OS design that fuses two paradigms to simultaneously address issues of isolation, performance, compatibility, failure recoverability, and run-time upgrades. LibrettOS acts as a microkernel OS that runs servers in an isolated manner. LibrettOS can also act as a library OS when, for better performance, selected applications are granted exclusive access to virtual hardware resources such as storage and networking. Furthermore, applications can switch between the two OS modes with no interruption at run-time. LibrettOS has a uniquely distinguishing advantage in that, the two paradigms seamlessly coexist in the same OS, enabling users to simultaneously exploit their respective strengths (i.e., greater isolation, high performance). Systems code, such as device drivers, network stacks, and file systems remain identical in the two modes, enabling dynamic mode switching and reducing development and maintenance costs. To illustrate these design principles, we implemented a prototype of LibrettOS using rump kernels, allowing us to reuse existent, hardened NetBSD device drivers and a large ecosystem of POSIX/BSD-compatible applications. We use hardware (VM) virtualization to strongly isolate different rump kernel instances from each other. Because the original rumprun unikernel targeted a much simpler model for uniprocessor systems, we redesigned it to support multicore systems. Unlike kernel-bypass libraries such as DPDK, applications need not be modified to benefit from direct hardware access. LibrettOS also supports indirect access through a network server that we have developed. Applications remain uninterrupted even when network components fail or need to be upgraded. Finally, to efficiently use hardware resources, applications can dynamically switch between the indirect and direct modes based on their I/O load at run-time. [full abstract is in the paper]Comment: 16th ACM SIGPLAN/SIGOPS International Conference on Virtual Execution Environments (VEE '20), March 17, 2020, Lausanne, Switzerlan

<i>Neisseria</i> species as pathobionts in bronchiectasis

Neisseria species are frequently identified in the bronchiectasis microbiome, but they are regarded as respiratory commensals. Using a combination of human cohorts, next-generation sequencing, systems biology, and animal models, we show that bronchiectasis bacteriomes defined by the presence of Neisseria spp. associate with poor clinical outcomes, including exacerbations. Neisseria subflava cultivated from bronchiectasis patients promotes the loss of epithelial integrity and inflammation in primary epithelial cells. In vivo animal models of Neisseria subflava infection and metabolipidome analysis highlight immunoinflammatory functional gene clusters and provide evidence for pulmonary inflammation. The murine metabolipidomic data were validated with human Neisseria-dominant bronchiectasis samples and compared with disease in which Pseudomonas-, an established bronchiectasis pathogen, is dominant. Metagenomic surveillance of Neisseria across various respiratory disorders reveals broader importance, and the assessment of the home environment in bronchiectasis implies potential environmental sources of exposure. Thus, we identify Neisseria species as pathobionts in bronchiectasis, allowing for improved risk stratification in this high-risk group.Published versio