A new method for spike extraction using velocity selective recording demonstrated with physiological ENG in Rat

BACKGROUND: This paper describes a series of experiments designed to verify a new method of electroneurogram (ENG) recording that enables the rate of neural firing within prescribed bands of propagation velocity to be determined in real time. Velocity selective recording (VSR) has been proposed as a solution to the problem of increasing the information available from an implantable neural interface (typically with electrodes in circumferential nerve cuffs) and has been successful in transforming compound action potentials into the velocity domain. NEW METHOD: The new method extends VSR to naturally-evoked (physiological) ENG in which the rate of neural firing at particular velocities is required in addition to a knowledge of the velocities present in the recording. RESULTS: The experiments, carried out in rats required individual spikes to be distinct and non-overlapping, which could be achieved by a microchannel or small-bore cuff. In these experiments, strands of rat nerve were laid on ten hook electrodes in oil to demonstrate the principle. COMPARISON WITH EXISTING METHOD: The new method generates a detailed overview of the firing rates of neurons based on their conduction velocity and direction of propagation. In addition it allows real time working in contrast to existing spike sorting methods using statistical pattern processing techniques. CONCLUSIONS: Results show that by isolating neural activity based purely on conduction velocity it was possible to determine the onset of direct cutaneous stimulation of the L5 dermatome

Origin and diversity of an underutilized fruit tree crop, cempedak (Artocarpus integer, Moraceae)

PREMISE OF THE STUDY: Underutilized crops and their wild relatives are important resources for crop improvement and food security. Cempedak [Artocarpus integer (Thunb). Merr.] is a significant crop in Malaysia but underutilized elsewhere. Here we performed molecular characterization of cempedak and its putative wild relative bangkong (Artocarpus integer (Thunb). Merr. var. silvestris Corner) to address questions regarding the origin and diversity of cempedak. METHODS: Using data from 12 microsatellite loci, we assessed the genetic diversity and genetic/geographic structure for 353 cempedak and 175 bangkong accessions from Malaysia and neighboring countries and employed clonal analysis to characterize cempedak cultivars. We conducted haplotype network analyses on the trnH-psbA region in a subset of these samples. We also analyzed key vegetative characters that reportedly differentiate cempedak and bangkong. KEY RESULTS: We show that cempedak and bangkong are sister taxa and distinct genetically and morphologically, but the directionality of domestication origin is unclear. Genetic diversity was generally higher in bangkong than in cempedak. We found a distinct genetic cluster for cempedak from Borneo as compared to cempedak from Peninsular Malaysia. Finally, cempedak cultivars with the same names did not always share the same genetic fingerprint. CONCLUSIONS: Cempedak origins are complex, with likely admixture and hybridization with bangkong, warranting further investigation. We provide a baseline of genetic diversity of cempedak and bangkong in Malaysia and found that germplasm collections in Malaysia represent diverse coverage of the four cempedak genetic clusters detected

Quantitative principles of cis-translational control by general mRNA sequence features in eukaryotes.

BackgroundGeneral translational cis-elements are present in the mRNAs of all genes and affect the recruitment, assembly, and progress of preinitiation complexes and the ribosome under many physiological states. These elements include mRNA folding, upstream open reading frames, specific nucleotides flanking the initiating AUG codon, protein coding sequence length, and codon usage. The quantitative contributions of these sequence features and how and why they coordinate to control translation rates are not well understood.ResultsHere, we show that these sequence features specify 42-81% of the variance in translation rates in Saccharomyces cerevisiae, Schizosaccharomyces pombe, Arabidopsis thaliana, Mus musculus, and Homo sapiens. We establish that control by RNA secondary structure is chiefly mediated by highly folded 25-60 nucleotide segments within mRNA 5' regions, that changes in tri-nucleotide frequencies between highly and poorly translated 5' regions are correlated between all species, and that control by distinct biochemical processes is extensively correlated as is regulation by a single process acting in different parts of the same mRNA.ConclusionsOur work shows that general features control a much larger fraction of the variance in translation rates than previously realized. We provide a more detailed and accurate understanding of the aspects of RNA structure that directs translation in diverse eukaryotes. In addition, we note that the strongly correlated regulation between and within cis-control features will cause more even densities of translational complexes along each mRNA and therefore more efficient use of the translation machinery by the cell

A feasibility study for NOn-Traditional providers to support the management of Elderly People with Anxiety and Depression: the NOTEPAD study Protocol

BACKGROUND: Anxiety and depression are common among older people, with up to 20% reporting such symptoms, and the prevalence increases with co-morbid chronic physical health problems. Access to treatment for anxiety and depression in this population is poor due to a combination of factors at the level of patient, practitioner and healthcare system. There is evidence to suggest that older people with anxiety and/or depression may benefit both from one-to-one interventions and group social or educational activities, which reduce loneliness, are participatory and offer some activity. Non-traditional providers (support workers) working within third-sector (voluntary) organisations are a valuable source of expertise within the community but are under-utilised by primary care practitioners. Such a resource could increase access to care, and be less stigmatising and more acceptable for older people. METHODS: The study is in three phases and this paper describes the protocol for phase III, which will evaluate the feasibility of recruiting general practices and patients into the study, and determine whether support workers can deliver the intervention to older people with sufficient fidelity and whether this approach is acceptable to patients, general practitioners and the third-sector providers. Phase III of the NOTEPAD study is a randomised controlled trial (RCT) that is individually randomised. It recruited participants from approximately six general practices in the UK. In total, 100 participants aged 65 years and over who score 10 or more on PHQ9 or GAD7 for anxiety or depression will be recruited and randomised to the intervention or usual general practice care. A mixed methods approach will be used and follow-up will be conducted 12 weeks post-randomisation. DISCUSSION: This study will inform the design and methods of a future full-scale RCT. TRIAL REGISTRATION: ISRCTN, ID: ISRCTN16318986 . Registered 10 November 2016. The ISRCTN registration is in line with the World Health Organization Trial Registration Data Set. The present paper represents the original version of the protocol. Any changes to the protocol will be communicated to ISRCTN

Estimates of array and pool-construction variance for planning efficient DNA-pooling genome wide association studies

<p>Abstract</p> <p>Background</p> <p>Until recently, genome-wide association studies (GWAS) have been restricted to research groups with the budget necessary to genotype hundreds, if not thousands, of samples. Replacing individual genotyping with genotyping of DNA pools in Phase I of a GWAS has proven successful, and dramatically altered the financial feasibility of this approach. When conducting a pool-based GWAS, how well SNP allele frequency is estimated from a DNA pool will influence a study's power to detect associations. Here we address how to control the variance in allele frequency estimation when DNAs are pooled, and how to plan and conduct the most efficient well-powered pool-based GWAS.</p> <p>Methods</p> <p>By examining the variation in allele frequency estimation on SNP arrays between and within DNA pools we determine how array variance [var(e_array)] and pool-construction variance [var(e_construction)] contribute to the total variance of allele frequency estimation. This information is useful in deciding whether replicate arrays or replicate pools are most useful in reducing variance. Our analysis is based on 27 DNA pools ranging in size from 74 to 446 individual samples, genotyped on a collective total of 128 Illumina beadarrays: 24 1M-Single, 32 1M-Duo, and 72 660-Quad.</p> <p>Results</p> <p>For all three Illumina SNP array types our estimates of var(e_array) were similar, between 3-4 × 10^-4for normalized data. Var(e_construction) accounted for between 20-40% of pooling variance across 27 pools in normalized data.</p> <p>Conclusions</p> <p>We conclude that relative to var(e_array), var(e_construction) is of less importance in reducing the variance in allele frequency estimation from DNA pools; however, our data suggests that on average it may be more important than previously thought. We have prepared a simple online tool, PoolingPlanner (available at <url>http://www.kchew.ca/PoolingPlanner/</url>), which calculates the effective sample size (ESS) of a DNA pool given a range of replicate array values. ESS can be used in a power calculator to perform pool-adjusted calculations. This allows one to quickly calculate the loss of power associated with a pooling experiment to make an informed decision on whether a pool-based GWAS is worth pursuing.</p

Gliders2d: Source Code Base for RoboCup 2D Soccer Simulation League

We describe Gliders2d, a base code release for Gliders, a soccer simulation team which won the RoboCup Soccer 2D Simulation League in 2016. We trace six evolutionary steps, each of which is encapsulated in a sequential change of the released code, from v1.1 to v1.6, starting from agent2d-3.1.1 (set as the baseline v1.0). These changes improve performance by adjusting the agents' stamina management, their pressing behaviour and the action-selection mechanism, as well as their positional choice in both attack and defense, and enabling riskier passes. The resultant behaviour, which is sufficiently generic to be applicable to physical robot teams, increases the players' mobility and achieves a better control of the field. The last presented version, Gliders2d-v1.6, approaches the strength of Gliders2013, and outperforms agent2d-3.1.1 by four goals per game on average. The sequential improvements demonstrate how the methodology of human-based evolutionary computation can markedly boost the overall performance with even a small number of controlled steps.Comment: 12 pages, 1 figure, Gliders2d code releas

Dynamic in vitro measurement of patellar movement after total knee arthroplasty: an in vitro study

BACKGROUND: Changing the kinematic behaviour of patellar movement could be one of the reasons for anterior knee pain after implantation of a total knee arthroplasty (TKA). The aim of the current study was to measure the potential influence on patellar kinematics of patellar resurfacing during TKA. METHODS: Patellar movement before and after TKA with and without patellar resurfacing was measured under dynamic conditions in an in vitro cadaver simulation. Physiologic Musculus quadriceps forces were applied to five physiologic human knee specimens undergoing simulated isokinetic extension motions, patellar movement was measured using an ultrasonic measurement system. Thereafter, the Interax(® )I.S.A.-prosthesis system was implanted without and with resurfacing the patella, and patellar movement was again measured. RESULTS: The physiologic patella center moved on a semilunar path up to 6.4 mm (SD 6.4 mm) medially during extension. After TKA, the unresurfaced patella showed significantly less medial translation (p = 0.04) than the resurfaced patella. Subsequent resurfacing of the patella then resulted in a return to mediolateral positioning of the patella similar to the physiological case, whereas the resurfaced patella tilted up to twice as much as physiologic. CONCLUSION: The results of this study suggest that resurfacing of the patella during TKA can result in a restoration of the physiologic mediolateral shift of the patellofemoral joint while angulation of the patella remains unphysiologic

Inhibition of Hypoxia-Inducible Factor-1α (HIF-1α) Protein Synthesis by DNA damage inducing agents

10.1371/journal.pone.0010522PLoS ONE55