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The number of sequenced bacteriophage genomes is growing at an exponential rate. The majority of sequenced bacteriophage genomes are annotated by one or more of several freely available gene identification programs (Glimmer, GeneMark, RAST, Prodigal, etc.). No program has been shown to consistently outperform the others; thus, the choice of which program to use is not obvious. We present the Phage Commander application for rapid identification of bacteriophage genes using multiple gene identification programs. Phage Commander runs a bacteriophage genome sequence through nine gene identification programs (and an additional program for identification of tRNAs) and integrates the results within a single output table. Phage Commander also generates formatted output files for direct export to National Center for Biotechnology Information GenBank or genome visualization programs such as DNA Master. Users can select the threshold for which genes to export (genes identified by at least one program, genes identified by at least two programs, etc.). Phage Commander was benchmarked using eight high-quality bacteriophage genomes whose genes are backed by experimental data. Our results show that the most accurate annotations are obtained by exporting genes identified by at least two or three programs. Many groups opt to manually curate the annotations obtained from gene identification programs, and Phage Commander was designed to facilitate manual curation of genome annotations. Our benchmarking results show that manual curation does indeed produce more accurate annotations than any individual gene identification program. The authors thus recommend manually curating the output of Phage Commander to generate maximally accurate annotations. Phage Commander is currently being used in the corresponding author's bacteriophage genome annotation class and has reduced the labor cost and improved the quality of genome annotations.

Background Individuals born very low birthweight (VLBW) are at increased risk of impaired cardiovascular and respiratory function in adulthood. To identify markers to predict future risk for VLBW individuals, we analyzed DNA methylation at birth and at 28 years in the New Zealand (NZ) VLBW cohort (all infants born Results Genomic DNA from archived newborn heel-prick blood (n = 109 VLBW, 51 controls) and from peripheral blood at ~ 28 years (n = 215 VLBW, 96 controls) was analyzed on Illumina Infinium MethylationEPIC 850 K arrays. Following quality assurance and normalization, methylation levels were compared between VLBW cases and controls at both ages by linear regression, with genome-wide significance set to p p = 3.44E−11). The top 20 CpGs that differed most between VLBW cases and controls featured clusters in ARID3A, SPATA33, and PLCH1 and these 3 genes, along with MCF2L, TRBJ2-1 and SRC, led the list of 15,000 differentially methylated regions (DMRs) reaching FDR-adj significance. Fifteen of the 20 top CpGs in the neonate EWAS showed associations between methylation at birth and adult cardiovascular traits (particularly LnRHI). In 28-year-old adults, twelve CpGs differed between VLBW cases and controls at FDR-adjusted significance, including hypermethylation in EBF4 (four CpGs), CFI and UNC119B and hypomethylation at three CpGs in HIF3A and one in KCNQ1. DNA methylation GrimAge scores at 28 years were significantly greater in VLBW cases versus controls and weakly associated with cardiovascular traits. Four CpGs were identified where methylation differed between VLBW cases and controls in both neonates and adults, three reversing directions with age (two CpGs in EBF4, one in SNAI1 were hypomethylated in neonates, hypermethylated in adults). Of these, cg16426670 in EBF4 at birth showed associations with several cardiovascular traits in adults. Conclusions These findings suggest that methylation patterns in VLBW neonates may be informative about future adult cardiovascular and respiratory outcomes and have value in guiding early preventative care to improve adult health.

Executive function difficulties are common among children born very preterm and/or very low birthweight (1500 g; VLBW), but little is known about whether they persist into adulthood.Examine the nature and pattern of self-reported executive functioning at 23 and 28 years of age using data from a national cohort study of adults born VLBW and a comparison group of same-age full-term (FT) born adults. Also examined were associations between executive function difficulties and socio-economic outcomes.All infants born VLBW in New Zealand during 1986 were prospectively included in an audit of retinopathy of prematurity (n = 413), with 250 (77% of survivors) followed to median age 28 years. A comparison group of FT adults was also recruited at age 23 and followed to 28 years (n = 100). Across both adult assessments, executive functioning was assessed using the Behaviour Rating Inventory of Executive Function-Adult Version (BRIEF-A) and analysed with semi-parametric models to examine the effects of age and group on executive function.At 23 and 28 years, VLBW adults had increased risk of executive function impairment compared with FT adults in behaviour regulation (relative risk [CI] 2.37, 95% confidence interval (CI)1.27, 4.45), meta-cognition (RR 6.03, 95% CI 2.18, 16.78) and global functioning (RR 3.20, 95% CI 1.40, 7.28). Impaired global executive functioning was associated with lower socio-economic status (regression estimate [b] = -0.43, 95% CI -0.59, -0.27) and a reduced likelihood of home ownership by age 28 years (RR 0.98, 95% CI 0.96, 1.00), even after controlling for sex, ethnicity and parental socio-economic backgrounds for both groups.VLBW-born adults continue to experience more executive function difficulties in their everyday life relative to term controls at age 28 years. These difficulties were negatively associated with their socio-economic opportunities as young adults.

Antenatal corticosteroids (ACS) given to mothers with anticipated very preterm delivery are widely used and improve infant outcomes. Follow-up studies of the first trials of ACS have shown no adverse effects, but recently there have been concerns about possible longer-term harms.We aimed to assess the relationship of ACS therapy to a range of physical health and welfare measures in a cohort of very low birthweight (VLBW;1500 g) young adults.Population-based cohort follow-up study. All VLBW infants born in New Zealand in 1986 were included in a prospective audit of retinopathy of prematurity. Perinatal data collection included information on ACS. At 26-30 years, 250 of 323 (77%) survivors participated, 58% having received ACS, with 229 assessed in one centre, including cardiovascular, metabolic, respiratory and neurocognitive measures. Differences in outcome between those receiving/not receiving ACS were summarised by the mean difference for continuous outcomes supplemented by Cohen's d as a standardised measure of effect size (ES), and risk ratios (RRI) for dichotomous outcomes, adjusted for relevant covariates using generalised linear regression methods.There were no or minimal adverse effects of receipt of ACS versus no receipt across a range of health and welfare outcomes, both for the full cohort (adjusted ES range d = 0.01-0.23; adjusted RR range 0.78-2.03) and for individuals with gestation28 weeks (extremely preterm; EP), except for a small increase in rates of major depression. In EP adults, receipt of ACS was associated with a higher incidence of hypertension, but might have a small benefit for IQ.In this population-based VLBW cohort, we detected minimal adverse outcomes associated with exposure to ACS by the third decade of life, a similar result to the 30-year follow-up of participants in the first ACS trial. However, further follow-up is warranted.

BACKGROUND There is individual variation in physiological ageing. Former very low birthweight (VLBW; birthweight

This paper describes our implementation of several neural networks built on a field programmable gate array (FPGA) and used to recognize a handwritten digit dataset—the Modified National Institute of Standards and Technology (MNIST) database. We also propose a novel hardware-friendly activation function called the dynamic Rectifid Linear Unit (ReLU)—D-ReLU function that achieves higher performance than traditional activation functions at no cost to accuracy. We built a 2-layer online training multilayer perceptron (MLP) neural network on an FPGA with varying data width. Reducing the data width from 8 to 4 bits only reduces prediction accuracy by 11%, but the FPGA area decreases by 41%. Compared to networks that use the sigmoid functions, our proposed D-ReLU function uses 24% - 41% less area with no loss to prediction accuracy. Further reducing the data width of the 3-layer networks from 8 to 4 bits, the prediction accuracies only decrease by 3% - 5%, with area being reduced by 9% - 28%. Moreover, FPGA solutions have 29 times faster execution time, even despite running at a 60× lower clock rate. Thus, FPGA implementations of neural networks offer a high-performance, low power alternative to traditional software methods, and our novel D-ReLU activation function offers additional improvements to performance and power saving.

Being born preterm (PT, &lt, 37 weeks gestation) or at very low birth weight (VLBW, &lt, 1500 g) is associated with increased rates of cardiopulmonary disorders in childhood. As survivors age, late cardiac effects, including right ventricular (RV) remodelling and occult pulmonary hypertension are emerging. In this population-based study, we aimed to investigate right heart structure and function in young adults born PT at VLBW compared to normal-weight term-born controls. The New Zealand VLBW Study has followed all infants born in 1986 with birth weight &lt, 1500 g. All were born preterm from 24 to 37 weeks. A total of 229 (71% of survivors) had echocardiograms aged 26–30 years which were compared to age-matched, term-born, normal-weight controls (n = 100). Young adults born preterm at very low birth weight exhibited smaller RV dimensions compared to term-born peers. Standard echocardiographic measures of RV function did not differ, but mildly reduced function was detected by RV longitudinal strain. This difference was related to birth weight and gestational age but not lung function or left ventricular function. Echocardiographic strain imaging may be an important tool to detect differences in RV function preterm and VLBW.

The number of sequenced phage genomes is growing at an exponential rate. The majority of newly sequenced phage genomes are annotated by one or more of several freely-available auto-annotation programs. No program has been shown to consistently outperform the others; thus the choice of which program to use is not obvious. We present the software Phage Commander for rapid annotation of phage genomes using multiple auto-annotation programs. Phage Commander runs a phage genome sequence through nine auto-annotation programs and integrates the results within a single output. Phage Commander generates properly formatted output files for direct export to NCBI GenBank. Users can select the threshold for determining which genes should be exported. Phage Commander was benchmarked using eight high-quality phage genomes whose genes have been identified through experiments. Results show that the best results are obtained by exporting genes identified by at least two or three of the nine auto-annotation programs.

Introduction Being born at very low birth weight (VLBW, Purpose To assess differences in right heart function using strain in young adults born at VLBW, compared to normal weight term born controls. Methods The New Zealand Very Low Birth Weight Study has followed all infants born in 1986 with birth weight Results VLBW subjects were smaller than their peers as young adults (Table 1). Strain measurement showed reduced myocardial deformation among VLBW subjects (RV myocardial GLS: −22.4% vs −23.5%, p=0.008; RV endocardial GLS: −23.6% vs −24.9%, p=0.005; free wall myocardial GLS −25.2% vs −26.1%, p=0.039; free wall endocardial GLS −26.7% vs −27.9%, p=0.009). TR velocity was higher in VLBW: 224 cm/s v 210 cm/s (p=0.002). RV S', and FAC were not different. Conclusion Young adults born at VLBW have impaired myocardial strain despite preserved RV function as assessed by standard techniques. Echocardiographic strain imaging may be an important tool to detect subclinical RV dysfunction. Graph 1 Funding Acknowledgement Type of funding source: None

In this study, the authors introduce MIPSfpga and its accompanying set of learning materials. MIPSfpga is a teaching infrastructure that offers access to the non-obfuscated Register-Transfer Level (RTL) source code of the MIPS microAptiv UP processor. The core is made available by Imagination Technologies for academic use and is targeted to a field-programmable gate array (FPGA), making it ideal for both the classroom and research. The supporting materials and labs focus on hands-on learning that emphasises computer architecture, system on chip (SoC) design and hardware–software codesign. Among other things, students learn to set up the MIPS soft-core processor on an FPGA, run and debug programs on the core in simulation and in hardware, add new peripherals to the system, understand the microarchitecture and extend it to support new features, experiment with different cache sizes and content management policies, add new instructions using the CorExtend interface available in MIPS processors, and understand SoCs in embedded systems and how they are designed and built up in layers to run complex software such as Linux.

Background B-type natriuretic peptide (BNP) is a cardiac hormone released with an N-terminal fragment (NTproBNP) under conditions of ventricular pressure or volume overload. BNP has been proposed for use as a biomarker of cardiac dysfunction in premature infants in the setting of hemodynamically significant patent ductus arteriosus (HsPDA) and bronchopulmonary dysplasia (BPD). In adult settings the presence of proBNP and glycosylated isoforms may affect assay interpretation. However, there are limited data on how immature preterm physiology may affect BNP or NTproBNP levels and no published data on post-translational BNP processing in premature infants. Methods Pooled serial plasma samples from preterm infants born at less than 30 weeks gestation were analyzed for BNP congeners using Luminex® assay and high performance liquid chromatography. Samples were grouped according to clinical status: Group 1, no HsPDA and no BPD, Group 2 HsPDA and no/mild BPD, Group 3 HsPDA and moderate/severe BPD. Results Plasma from 15 infants was analyzed, and across all three groups NTproBNP predominated with minimal amounts of other isoforms; no glycosylation was detected. Conclusions NTproBNP appears to be the predominant isoform across each of our clinical groups in our pooled sample analysis with no evidence of significant glycosylation. This suggests NTproBNP is likely to be a robust marker in this clinical setting.

For millenia, legged locomotion has been of central importance to humans for hunting, agriculture, transportation, sport, and warfare. Today, the same principal considerations of locomotor performance and economy apply to legged systems designed to serve, assist, or be worn by humans in urban and natural environments. Energy comes at a premium not only for animals, wherein suitably fast and economical gaits are selected through organic evolution, but also for legged robots that must carry sufficient energy in their batteries. Although a robot's energy is spent at many levels, from control systems to actuators, we suggest that the mechanical cost of transport is an integral energy expenditure for any legged system-and measuring this cost permits the most direct comparison between gaits of legged animals and robots. Although legged robots have matched or even improved upon total cost of transport of animals, this is typically achieved by choosing extremely slow speeds or by using regenerative mechanisms. Legged robots have not yet reached the low mechanical cost of transport achieved at speeds used by bipedal and quadrupedal animals. Here we consider approaches used to analyze gaits and discuss a framework, termed mechanical cost analysis, that can be used to evaluate the economy of legged systems. This method uses a point mass perspective to evaluate the entire stride as well as to identify individual events that accrue mechanical cost. The analysis of gait began at the turn of the last century with spatiotemporal analysis facilitated by the advent of cine film. These advances gave rise to the "gait diagram," which plots duty factors and phase separations between footfalls. This approach was supplanted in the following decades by methods using force platforms to determine forces and motions of the center of mass (CoM)-and analytical models that characterize gait according to fluctuations in potential and kinetic energy. Mechanical cost analysis draws from these approaches and provides a unified framework that interprets the spatiotemporal sequencing of leg contacts within the context of CoM dynamics to determine mechanical cost in every instance of the stride. Diverse gaits can be evaluated and compared in biological and engineered systems using mechanical cost analysis.

Este paper se basa en un artículo anterior titulado ”Practical experiences based on MIPSfpga”, publicado en el Workshop on Computer Architecture Education (celebrado en la conferencia ISCA-2017). Incluye algunas modificaciones: (1) Hemos ampliado la Sección II-D (que en este paper corresponde a la Sección 2.4) y la Sección III-A (que corresponde a la Sección 3); (2) Hemos eliminado las Secciones III-B y III-C; (3)., En este artículo se describe el uso de la infraestructura docente MIPSfpga v2.0 en las prácticas de la asignatura Arquitectura de Sistemas Integrados, una asignatura obligatoria en el Grado en Ingeniería Electrónica de Comunicaciones que se imparte en la Universidad Complutense de Madrid., In this paper we describe the use of the MIPSfpga v2.0 teaching infrastructure for the labs included in the course Integrated Systems Architecture, a compulsory subject in the fourth year of the Electronic Engineering of Communications degree offered at University Complutense of Madrid., Universidad de Granada: Departamento de Arquitectura y Tecnología de Computadores; Vicerrectorado para la Garantía de la Calidad., Los autores agradecen la contribución de Imagination University Program, University of Nevada, Las Vegas, Imperial College London (UK), Grupo ArTeCS de la Universidad Complutense de Madrid y contratos TIN2015-65277-R, TIN2015- 65316-P y Artículo-83 (no 411-2016), Munir Hasan (IMG UK), Prashant Deokar (IMG India), Mahesh Firke (IMG India) Parimal Patel (Xilinx), Kent Brinkley (IMG USA), Rick Leatherman (IMG USA), Chuck Swartley (IMG USA), Sean Raby (IMG UK), Michio Abe (IMG Japan), Bingli Wang (IMG China), Sachin Sundar (IMG USA), Alex Wong (Digilent Inc.), Matthew Fortune (IMG UK), Jeffrey Deans (IMG UK), Laurence Keung (IMG UK), Roy Kravitz (Portland State University), Dennis Pinto (UCM), Tejaswini Angel (Portland State University), Christian White, Gibson Fahnestock, Jason Wong, Cathal McCabe (Xilinx), Larissa Swanland (Digilent).

We evaluated the effect of antenatal sildenafil on neonatal cardiovascular function in a subgroup of 27 infants of mothers participating in the STRIDER-NZAus randomized controlled trial. In this small study, we found no association between antenatal sildenafil and neonatal cardiac dysfunction including no pulmonary hypertension in exposed or unexposed infants.

To describe the survival, in-hospital morbidity, brain metrics and two-year neurodevelopmental outcomes of two extremely preterm cohorts and discuss the contribution of changes in clinical practice to these outcomes.Retrospective comparative cohort study, of two cohorts of neonates born28 weeks gestation: 47 infants born 1998-2000 and 39 infants 2006-2009.Comparing historical to the contemporary cohort respectively, admission temperature (35.9 degrees C, 36.5) and CRIB (Clinical Risk Index in Babies) score (5.4, 3.1) improved. Inotrope support fell significantly (55.3%, 28.2%). High frequency ventilation days fell (8.0, 2.7). CPAP days increased significantly (32.2, 47.9). Chronic lung disease at 36 weeks corrected age fell significantly (61.7%, 38.5%). Red cell transfusions decreased in number (7.1, 4.8) and volume (96.2ml/kg, 70.4ml/kg). Retinopathy of prematurity (ROP) rates dropped significantly (66.0%, 28.2%). Survival was not significantly different. Nutritional improvements included shorter days to first enteral feed (3.4, 2.0), target protein (5.4, 4.3) and lipid levels (7.1, 4.1) with better breastfeeding rates at discharge (19.2%, 38.5%). By 36 weeks z scores for weight (-0.90, -0.39) were improved but not length (-1.94, -1.26) or head circumference (-0.72, -0.69). MRI brain metrics showed a significant improvement in bifrontal (59.2, 65.9), biparietal (73.7, 79.3) and transcerebellar diameter (50.6, 52.6) with improved neurodevelopmental outcome at two years.The contemporary cohort had better initial physiological stability, less chronic lung disease and retinopathy, improved body growth at 36 weeks and brain metrics at term equivalent. Improvement in neurodevelopment at two years has been seen and further analysis will be important to understand the impact of the changes in clinical care.

We present nine polymorphic di- and tri-nucleotide repeat nuclear microsatellite markers selected specifically for their use in high throughput studies concerning the dioecious allotetraploid Salix alba-Salix fragilis willow complex. These taxa and their hybrids are difficult to discriminate using morphological characters. Thus, multiplex reactions were developed for these microsatellite loci and their effectiveness to distinguish individuals, especially hybrids, and their inheritance patterns in controlled crosses were determined. All loci displayed disomic-monogenic inheritance which allowed for the genotype data to be analysed as for a diploid organism. The nine loci produced a total of 67 alleles (mean, 7.4 alleles per locus; range, 3-11 alleles) in a reference panel of 57 individuals from two germplasm collections and natural populations. Gene diversity values (as measured by the expected heterozygosity) ranged from 0.000-0.820. A total of 53 distinct multilocus genotypes were observed, and ordination analysis revealed three separate clusters corresponding to S. alba, S. fragilis and hybrids. The microsatellite loci described here will be used in population genetic studies to investigate genetic variation, gene flow, levels of hybridisation and the extent of introgression in natural populations of the S. alba-S. fragilis complex. They are also useful for clonal identification, conservation and sustainable management of germplasm collections, genetic mapping and the selection of individuals and/or certification of controlled crosses for breeding programmes.

This paper has described the philosophy and content of a textbook on Digital Design and Computer Architecture. The text fills a niche in programs that appreciate the elegance of Patterson & Hennessy's Computer Organization and Design but wish to integrate digital logic with architecture in a single course or cohesive sequence.

The analysis of terrestrial locomotion over the past half century has focused largely on strategies of mechanical energy recovery used during walking and running. In contrast, we describe the underlying mechanics of legged locomotion as a collision-like interaction that redirects the centre of mass (CoM). We introduce the collision angle, determined by the angle between the CoM force and velocity vectors, and show by computing the collision fraction, a ratio of actual to potential collision, that the quadrupedal walk and gallop employ collision-reduction strategies while the trot permits greater collisions. We provide the first experimental evidence that a collision-based approach can differentiate quadrupedal gaits and quantify interspecific differences. Furthermore, we show that this approach explains the physical basis of a commonly used locomotion metric, the mechanical cost of transport. Collision angle and collision fraction provide a unifying analysis of legged locomotion which can be applied broadly across animal size, leg number and gait.

The genus Salix (willow) contains a number of species of great value as biomass crops. Efforts to breed varieties with improved biomass yields and resistances to pests and diseases are limited by the lack of knowledge on the genetic basis of the traits. We have used AFLP and microsatellite markers to construct a genetic map of willow from a full-sib cross of the diploid species Salix viminalis (2n = 38). In accordance with a double pseudo-testcross approach, separate parental maps were constructed and merged to produce a consensus map comprising 291 AFLP and 39 willow microsatellite markers. Nineteen poplar microsatellites were also tested in willow. Five of these amplified loci, of which two were mapped. Linkage groups of the consensus map that could be identified in the parental maps are presented here and spanned 1,256.5 cM with an average interval between markers of 4.4 cM.