Tracking Control for FES-Cycling based on Force Direction Efficiency with Antagonistic Bi-Articular Muscles

A functional electrical stimulation (FES)-based tracking controller is developed to enable cycling based on a strategy to yield force direction efficiency by exploiting antagonistic bi-articular muscles. Given the input redundancy naturally occurring among multiple muscle groups, the force direction at the pedal is explicitly determined as a means to improve the efficiency of cycling. A model of a stationary cycle and rider is developed as a closed-chain mechanism. A strategy is then developed to switch between muscle groups for improved efficiency based on the force direction of each muscle group. Stability of the developed controller is analyzed through Lyapunov-based methods.Comment: 8 pages, 4 figures, submitted to ACC201

Stationary Cycling Induced by Switched Functional Electrical Stimulation Control

Functional electrical stimulation (FES) is used to activate the dysfunctional lower limb muscles of individuals with neuromuscular disorders to produce cycling as a means of exercise and rehabilitation. However, FES-cycling is still metabolically inefficient and yields low power output at the cycle crank compared to able-bodied cycling. Previous literature suggests that these problems are symptomatic of poor muscle control and non-physiological muscle fiber recruitment. The latter is a known problem with FES in general, and the former motivates investigation of better control methods for FES-cycling.In this paper, a stimulation pattern for quadriceps femoris-only FES-cycling is derived based on the effectiveness of knee joint torque in producing forward pedaling. In addition, a switched sliding-mode controller is designed for the uncertain, nonlinear cycle-rider system with autonomous state-dependent switching. The switched controller yields ultimately bounded tracking of a desired trajectory in the presence of an unknown, time-varying, bounded disturbance, provided a reverse dwell-time condition is satisfied by appropriate choice of the control gains and a sufficient desired cadence. Stability is derived through Lyapunov methods for switched systems, and experimental results demonstrate the performance of the switched control system under typical cycling conditions.Comment: 8 pages, 3 figures, submitted to ACC 201

One-pot synthesis of (Z)-B-sulfonyl enoates from ethyl propiolate

B-Sulfonyl enoates may be synthesized through a one-pot two-step sequence from ethyl propiolate with good to excellent selectivity for the Z isomer. Trialkylamines catalyze thioconjugate additions of aryl thiols, and alkoxides catalyze the addition of aliphatic thiols. Addition of meta-chloroperbenzoic acid (mCPBA) and LiClO4 to the reaction mixture provides rapid access to the sulfonyl enoates. Yields of the pure Z isomer range from 51 – 90%

Cyclophilin D Regulates Antiviral CD8+ T Cell Survival in a Cell-Extrinsic Manner

CD8+ T cell–mediated immunity is critical for host defense against viruses and requires mitochondria-mediated type I IFN (IFN-I) signaling for optimal protection. Cyclophilin D (CypD) is a mitochondrial matrix protein that modulates the mitochondrial permeability transition pore, but its role in IFN-I signaling and CD8+ T cell responses to viral infection has not been previously explored. In this study, we demonstrate that CypD plays a critical extrinsic role in the survival of Ag-specific CD8+ T cell following acute viral infection with lymphocytic choriomeningitis virus in mice. CypD deficiency resulted in reduced IFN-I and increased CD8+ T cell death, resulting in a reduced antiviral CD8+ T cell response. In addition, CypD deficiency was associated with an increase in pathogen burden at an early time-point following infection. Furthermore, our data demonstrate that transfer of wild-type macrophages (expressing CypD) to CypD-deficient mice can partially restore CD8+ T cell responses. These results establish that CypD plays an extrinsic role in regulating optimal effector CD8+ T cell responses to viral infection. Furthermore, this suggests that, under certain circumstances, inhibition of CypD function may have a detrimental impact on the host’s ability to respond to viral infection

Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications.

Analysis of DNA methylation patterns relies increasingly on sequencing-based profiling methods. The four most frequently used sequencing-based technologies are the bisulfite-based methods MethylC-seq and reduced representation bisulfite sequencing (RRBS), and the enrichment-based techniques methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylated DNA binding domain sequencing (MBD-seq). We applied all four methods to biological replicates of human embryonic stem cells to assess their genome-wide CpG coverage, resolution, cost, concordance and the influence of CpG density and genomic context. The methylation levels assessed by the two bisulfite methods were concordant (their difference did not exceed a given threshold) for 82% for CpGs and 99% of the non-CpG cytosines. Using binary methylation calls, the two enrichment methods were 99% concordant and regions assessed by all four methods were 97% concordant. We combined MeDIP-seq with methylation-sensitive restriction enzyme (MRE-seq) sequencing for comprehensive methylome coverage at lower cost. This, along with RNA-seq and ChIP-seq of the ES cells enabled us to detect regions with allele-specific epigenetic states, identifying most known imprinted regions and new loci with monoallelic epigenetic marks and monoallelic expression

The Prevention of Delirium and Complications Associated with Surgical Treatments (PODCAST) study: protocol for an international multicentre randomised controlled trial

Introduction: Postoperative delirium is one of the most common complications of major surgery, affecting 10–70% of surgical patients 60 years and older. Delirium is an acute change in cognition that manifests as poor attention and illogical thinking and is associated with longer intensive care unit (ICU) and hospital stay, long-lasting cognitive deterioration and increased mortality. Ketamine has been used as an anaesthetic drug for over 50 years and has an established safety record. Recent research suggests that, in addition to preventing acute postoperative pain, a subanaesthetic dose of intraoperative ketamine could decrease the incidence of postoperative delirium as well as other neurological and psychiatric outcomes. However, these proposed benefits of ketamine have not been tested in a large clinical trial. Methods: The Prevention of Delirium and Complications Associated with Surgical Treatments (PODCAST) study is an international, multicentre, randomised controlled trial. 600 cardiac and major non-cardiac surgery patients will be randomised to receive ketamine (0.5 or 1 mg/kg) or placebo following anaesthetic induction and prior to surgical incision. For the primary outcome, blinded observers will assess delirium on the day of surgery (postoperative day 0) and twice daily from postoperative days 1–3 using the Confusion Assessment Method or the Confusion Assessment Method for the ICU. For the secondary outcomes, blinded observers will estimate pain using the Behavioral Pain Scale or the Behavioral Pain Scale for Non-Intubated Patients and patient self-report. Ethics and dissemination The PODCAST trial has been approved by the ethics boards of five participating institutions; approval is ongoing at other sites. Recruitment began in February 2014 and will continue until the end of 2016. Dissemination plans include presentations at scientific conferences, scientific publications, stakeholder engagement and popular media. Registration details The study is registered at clinicaltrials.gov, NCT01690988 (last updated March 2014). The PODCAST trial is being conducted under the auspices of the Neurological Outcomes Network for Surgery (NEURONS). Trial registration number NCT01690988 (last updated December 2013)

TbPIF5 Is a Trypanosoma brucei Mitochondrial DNA Helicase Involved in Processing of Minicircle Okazaki Fragments

Trypanosoma brucei's mitochondrial genome, kinetoplast DNA (kDNA), is a giant network of catenated DNA rings. The network consists of a few thousand 1 kb minicircles and several dozen 23 kb maxicircles. Here we report that TbPIF5, one of T. brucei's six mitochondrial proteins related to Saccharomyces cerevisiae mitochondrial DNA helicase ScPIF1, is involved in minicircle lagging strand synthesis. Like its yeast homolog, TbPIF5 is a 5′ to 3′ DNA helicase. Together with other enzymes thought to be involved in Okazaki fragment processing, TbPIF5 localizes in vivo to the antipodal sites flanking the kDNA. Minicircles in wild type cells replicate unidirectionally as theta-structures and are unusual in that Okazaki fragments are not joined until after the progeny minicircles have segregated. We now report that overexpression of TbPIF5 causes premature removal of RNA primers and joining of Okazaki fragments on theta structures. Further elongation of the lagging strand is blocked, but the leading strand is completed and the minicircle progeny, one with a truncated H strand (ranging from 0.1 to 1 kb), are segregated. The minicircles with a truncated H strand electrophorese on an agarose gel as a smear. This replication defect is associated with kinetoplast shrinkage and eventual slowing of cell growth. We propose that TbPIF5 unwinds RNA primers after lagging strand synthesis, thus facilitating processing of Okazaki fragments

Western men and Eastern arts: The significance of Eastern martial arts disciplines in British men's narratives of masculinity

Previous Western sociological research on Eastern martial arts has identified a tension between ‘traditional’ Eastern forms of practice and ‘modernized’ Western methods of training and competition. In particular, the ‘sportization’ of Eastern styles, where combat-centred arts based upon moral philosophies have transformed more or less into competitive activities following Western models of rationalized sport, has been an important theme. However, it is also suggested that Eastern martial arts hold special significance in the West for their seemingly esoteric nature. In this regard, such martial arts are considered significant because they are not ‘sports’, but rather disciplines, with fairly different connotations for practitioners. Drawing on interview data, this paper explores how Western practitioners of Eastern martial arts articulate this difference, principally by examining the place of martial artistry in British men's narratives of masculinity. Comparing themselves favourably to assumed, typical visions of Western sporting masculinity, such men draw upon the imagined uniqueness of their martial arts to construct a sense of moral superiority over other men. In so doing, they contribute to a rejection of what they believe to be ‘mainstream’ sporting Western masculinity, thus indicating the role that ‘alternative’ visions of physical culture can play in men's active constructions of gender