Design criteria for bottom-withdrawal (lake-cleaning) spillway

"A pond or lake equipped with a bottom-withdrawal spillway will store the highest quality water possible for a reservoir in a given location. This is desirable when the reservoir will provide water for municipalities, livestock, households, fish production, recreation, field or orchard spraying, trickle irrigation, or other uses requiring high quality water."--First page.David Rausch (USDA-ARS, Watershed Research Unit), Don Pfost (Department of Agricultural Engineering, College of Agriculture), and Larry W. Caldwell (USDA, Soil Conservation Service, Columbia, Missouri)New 4/85/10

Prediction modeling for Board of Certification exam success for a professional master’s athletic training program

Introduction: The Commission on Accreditation of Athletic Training Education mandates accredited athletic training programs have a minimum, three-year aggregate, first-attempt pass rate on the Board of Certification (BOC) examination of 70%. No studies have examined first-attempt BOC exam success for students enrolled in a professional master’s athletic training program (PMATP). Purpose: The purpose of this study was to identify factors associated with first-attempt success on the BOC examination for PMATP students. Methods: This cohort designed study used common application data from subjects’ university and PMATP applications to create prediction models to identify those factors that predict first-attempt success on the BOC exam. Results: A four-factor model was produced to predict first-attempt BOC exam success. Both models demonstrated a student with two, three or more predictors had an odds ratio of 16.0 or greater, a relative frequency of success of 1.45 or greater, and correctly predicted first-attempt success on the BOC exam over 92% of the time. Conclusions: It is possible to predict success on the BOC exam for students from a PMATP based on common application data. Recommendations: Although this project involved predicting success on the athletic training certification exam, the procedures and methods used could be adapted to any academic program

An Overview of the Characterization of the Space Launch Vehicle Aerodynamic Environments

Aerodynamic environments are some of the rst engineering data products that are needed to design a space launch vehicle. These products are used in performance predic- tions, vehicle control algorithm design, as well as determing loads on primary and secondary structures in multiple discipline areas. When the National Aeronautics and Space Admin- istration (NASA) Space Launch System (SLS) Program was established with the goal of designing a new, heavy-lift launch vehicle rst capable of lifting the Orion Program Multi- Purpose Crew Vehicle (MPCV) to low-earth orbit and preserving the potential to evolve the design to a 200 metric ton cargo launcher, the data needs were no di erent. Upon commencement of the new program, a characterization of aerodynamic environments were immediately initiated. In the time since, the SLS Aerodynamics Team has produced data describing the majority of the aerodynamic environment de nitions needed for structural design and vehicle control under nominal ight conditions. This paper provides an overview of select SLS aerodynamic environments completed to date

Aeroelastic Response and Protection of Space Shuttle External Tank Cable Trays

Sections of the Space Shuttle External Tank Liquid Oxygen (LO2) and Liquid Hydrogen (LH2) cable trays are shielded from potentially damaging airloads with foam Protuberance Aerodynamic Load (PAL) Ramps. Flight standard design LO2 and LH2 cable tray sections were tested with and without PAL Ramp models in the United States Air Force Arnold Engineering Development Center s (AEDC) 16T transonic wind tunnel to obtain experimental data on the aeroelastic stability and response characteristics of the trays and as part of the larger effort to determine whether the PAL ramps can be safely modified or removed. Computational Fluid Dynamic simulations of the full-stack shuttle launch configuration were used to investigate the flow characeristics around and under the cable trays without the protective PAL ramps and to define maximum crossflow Mach numbers and dynamic pressures experienced during launch. These crossflow conditions were used to establish wind tunnel test conditions which also included conservative margins. For all of the conditions and configurations tested, no aeroelastic instabilities or unacceptable dynamic response levels were encountered and no visible structural damage was experienced by any of the tested cable tray sections. Based upon this aeroelastic characterization test, three potentially acceptable alternatives are available for the LO2 cable tray PAL Ramps: Mini-Ramps, Tray Fences, or No Ramps. All configurations were tested to maximum conditions, except the LH2 trays at -15 deg. crossflow angle. This exception is the only caveat preventing the proposal of acceptable alternative configurations for the LH2 trays as well. Structural assessment of all tray loads and tray response measurements from launches following the Shuttle Return To Flight with the existing PAL Ramps will determine the acceptability of these PAL Ramp alternatives

Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription

AbstractBackground: Glycogen synthase kinase-3 (GSK-3) is a serine/threonine protein kinase, the activity of which is inhibited by a variety of extracellular stimuli including insulin, growth factors, cell specification factors and cell adhesion. Consequently, inhibition of GSK-3 activity has been proposed to play a role in the regulation of numerous signalling pathways that elicit pleiotropic cellular responses. This report describes the identification and characterisation of potent and selective small molecule inhibitors of GSK-3.Results: SB-216763 and SB-415286 are structurally distinct maleimides that inhibit GSK-3α in vitro, with Kis of 9 nM and 31 nM respectively, in an ATP competitive manner. These compounds inhibited GSK-3β with similar potency. However, neither compound significantly inhibited any member of a panel of 24 other protein kinases. Furthermore, treatment of cells with either compound stimulated responses characteristic of extracellular stimuli that are known to inhibit GSK-3 activity. Thus, SB-216763 and SB-415286 stimulated glycogen synthesis in human liver cells and induced expression of a β-catenin-LEF/TCF regulated reporter gene in HEK293 cells. In both cases, compound treatment was demonstrated to inhibit cellular GSK-3 activity as assessed by activation of glycogen synthase, which is a direct target of this kinase.Conclusions: SB-216763 and SB-415286 are novel, potent and selective cell permeable inhibitors of GSK-3. Therefore, these compounds represent valuable pharmacological tools with which the role of GSK-3 in cellular signalling can be further elucidated. Furthermore, development of similar compounds may be of use therapeutically in disease states associated with elevated GSK-3 activity such as non-insulin dependent diabetes mellitus and neurodegenerative disease

Resource-oriented music therapy for psychiatric patients with low therapy motivation: Protocol for a randomised controlled trial [NCT00137189]

BACKGROUND: Previous research has shown positive effects of music therapy for people with schizophrenia and other mental disorders. In clinical practice, music therapy is often offered to psychiatric patients with low therapy motivation, but little research exists about this population. The aim of this study is to examine whether resource-oriented music therapy helps psychiatric patients with low therapy motivation to improve negative symptoms and other health-related outcomes. An additional aim of the study is to examine the mechanisms of change through music therapy. METHODS: 144 adults with a non-organic mental disorder (ICD-10: F1 to F6) who have low therapy motivation and a willingness to work with music will be randomly assigned to an experimental or a control condition. All participants will receive standard care, and the experimental group will in addition be offered biweekly sessions of music therapy over a period of three months. Outcomes will be measured by a blind assessor before and 1, 3, and 9 months after randomisation. DISCUSSION: The findings to be expected from this study will fill an important gap in the knowledge of treatment effects for a patient group that does not easily benefit from treatment. The study's close link to clinical practice, as well as its size and comprehensiveness, will make its results well generalisable to clinical practice

Impact on Malaria Parasite Multiplication Rates in Infected Volunteers of the Protein-in-Adjuvant Vaccine AMA1-C1/Alhydrogel+CPG 7909

BACKGROUND: Inhibition of parasite growth is a major objective of blood-stage malaria vaccines. The in vitro assay of parasite growth inhibitory activity (GIA) is widely used as a surrogate marker for malaria vaccine efficacy in the down-selection of candidate blood-stage vaccines. Here we report the first study to examine the relationship between in vivo Plasmodium falciparum growth rates and in vitro GIA in humans experimentally infected with blood-stage malaria. METHODS: In this phase I/IIa open-label clinical trial five healthy malaria-naive volunteers were immunised with AMA1/C1-Alhydrogel+CPG 7909, and together with three unvaccinated controls were challenged by intravenous inoculation of P. falciparum infected erythrocytes. RESULTS: A significant correlation was observed between parasite multiplication rate in 48 hours (PMR) and both vaccine-induced growth-inhibitory activity (Pearson r = -0.93 [95% CI: -1.0, -0.27] P = 0.02) and AMA1 antibody titres in the vaccine group (Pearson r = -0.93 [95% CI: -0.99, -0.25] P = 0.02). However immunisation failed to reduce overall mean PMR in the vaccine group in comparison to the controls (vaccinee 16 fold [95% CI: 12, 22], control 17 fold [CI: 0, 65] P = 0.70). Therefore no impact on pre-patent period was observed (vaccine group median 8.5 days [range 7.5-9], control group median 9 days [range 7-9]). CONCLUSIONS: Despite the first observation in human experimental malaria infection of a significant association between vaccine-induced in vitro growth inhibitory activity and in vivo parasite multiplication rate, this did not translate into any observable clinically relevant vaccine effect in this small group of volunteers. TRIAL REGISTRATION: ClinicalTrials.gov [NCT00984763]

Fusion transcripts and their genomic breakpoints in polyadenylated and ribosomal RNA-minus RNA sequencing data

BACKGROUND: Fusion genes are typically identified by RNA sequencing (RNA-seq) without elucidating the causal genomic breakpoints. However, non–poly(A)-enriched RNA-seq contains large proportions of intronic reads that also span genomic breakpoints. RESULTS: We have developed an algorithm, Dr. Disco, that searches for fusion transcripts by taking an entire reference genome into account as search space. This includes exons but also introns, intergenic regions, and sequences that do not meet splice junction motifs. Using 1,275 RNA-seq samples, we investigated to what extent genomic breakpoints can be extracted from RNA-seq data and their implications regarding poly(A)-enriched and ribosomal RNA–minus RNA-seq data. Comparison with whole-genome sequencing data revealed that most genomic breakpoints are not, or minimally, transcribed while, in contrast, the genomic breakpoints of all 32 TMPRSS2-ERG–positive tumours were present at RNA level. We also revealed tumours in which the ERG breakpoint was located before ERG, which co-existed with additional deletions and messenger RNA that incorporated intergenic cryptic exons. In breast cancer we identified rearrangement hot spots near CCND1 and in glioma near CDK4 and MDM2 and could directly associate this with increased expression. Furthermore, in all datasets we find fusions to intergenic regions, often spanning multiple cryptic exons that potentially encode neo-antigens. Thus, fusion transcripts other than classical gene-to-gene fusions are prominently present and can be identified using RNA-seq. CONCLUSION: By using the full potential of non–poly(A)-enriched RNA-seq data, sophisticated analysis can reliably identify expressed genomic breakpoints and their transcriptional effects

Molecular subgroups of medulloblastoma: an international meta-analysis of transcriptome, genetic aberrations, and clinical data of WNT, SHH, Group 3, and Group 4 medulloblastomas

Medulloblastoma is the most common malignant brain tumor in childhood. Molecular studies from several groups around the world demonstrated that medulloblastoma is not one disease but comprises a collection of distinct molecular subgroups. However, all these studies reported on different numbers of subgroups. The current consensus is that there are only four core subgroups, which should be termed WNT, SHH, Group 3 and Group 4. Based on this, we performed a meta-analysis of all molecular and clinical data of 550 medulloblastomas brought together from seven independent studies. All cases were analyzed by gene expression profiling and for most cases SNP or array-CGH data were available. Data are presented for all medulloblastomas together and for each subgroup separately. For validation purposes, we compared the results of this meta-analysis with another large medulloblastoma cohort (n = 402) for which subgroup information was obtained by immunohistochemistry. Results from both cohorts are highly similar and show how distinct the molecular subtypes are with respect to their transcriptome, DNA copy-number aberrations, demographics, and survival. Results from these analyses will form the basis for prospective multi-center studies and will have an impact on how the different subgroups of medulloblastoma will be treated in the future

SeqAn An efficient, generic C++ library for sequence analysis

<p>Abstract</p> <p>Background</p> <p>The use of novel algorithmic techniques is pivotal to many important problems in life science. For example the sequencing of the human genome <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> would not have been possible without advanced assembly algorithms. However, owing to the high speed of technological progress and the urgent need for bioinformatics tools, there is a widening gap between state-of-the-art algorithmic techniques and the actual algorithmic components of tools that are in widespread use.</p> <p>Results</p> <p>To remedy this trend we propose the use of SeqAn, a library of efficient data types and algorithms for sequence analysis in computational biology. SeqAn comprises implementations of existing, practical state-of-the-art algorithmic components to provide a sound basis for algorithm testing and development. In this paper we describe the design and content of SeqAn and demonstrate its use by giving two examples. In the first example we show an application of SeqAn as an experimental platform by comparing different exact string matching algorithms. The second example is a simple version of the well-known MUMmer tool rewritten in SeqAn. Results indicate that our implementation is very efficient and versatile to use.</p> <p>Conclusion</p> <p>We anticipate that SeqAn greatly simplifies the rapid development of new bioinformatics tools by providing a collection of readily usable, well-designed algorithmic components which are fundamental for the field of sequence analysis. This leverages not only the implementation of new algorithms, but also enables a sound analysis and comparison of existing algorithms.</p