63 research outputs found
TRAPLINE: a standardized and automated pipeline for RNA sequencing data analysis, evaluation and annotation
Background: Technical advances in Next Generation Sequencing (NGS) provide a means to acquire deeper insights into cellular functions. The lack of standardized and automated methodologies poses a challenge for the analysis and interpretation of RNA sequencing data. We critically compare and evaluate state-of-the-art bioinformatics approaches and present a workflow that integrates the best performing data analysis, data evaluation and annotation methods in a Transparent, Reproducible and Automated PipeLINE (TRAPLINE) for RNA sequencing data processing (suitable for Illumina, SOLiD and Solexa). Results: Comparative transcriptomics analyses with TRAPLINE result in a set of differentially expressed genes, their corresponding protein-protein interactions, splice variants, promoter activity, predicted miRNA-target interactions and files for single nucleotide polymorphism (SNP) calling. The obtained results are combined into a single file for downstream analysis such as network construction. We demonstrate the value of the proposed pipeline by characterizing the transcriptome of our recently described stem cell derived antibiotic selected cardiac bodies ('aCaBs'). Conclusion: TRAPLINE supports NGS-based research by providing a workflow that requires no bioinformatics skills, decreases the processing time of the analysis and works in the cloud. The pipeline is implemented in the biomedical research platform Galaxy and is freely accessible via www.sbi.uni-rostock.de/RNAseqTRAPLINE or the specific Galaxy manual page (https://usegalaxy.org/u/mwolfien/p/trapline-manual)
Marked increase of final height by long-term aromatase inhibition in a boy with idiopathic short stature
Growth hormone (GH) is the most frequently used treatment in children with idiopathic short stature (ISS). Aromatase inhibitor (AI) therapy is still in an experimental state, and both final height (FH) and long-term efficacy data in ISS have not been published. We present a 14.5-year-old boy with ISS and a height of 142.7 cm [standard deviation score (SDS) -2.79]. Based on the baseline bone age (BA) of 13.5-14 years, his predicted adult height (PAH) by Bayley/Pinneau was 154 cm (SDS -3.77)-158.2 (SDS -3.15). After a 5-year letrozole monotherapy, FH was 169 cm (SDS -1.57) showing a height difference between PAH and FH from 10.8 to 15 cm. No permanent side effects of the medication have been observed. Both a transient occurrence and a spontaneous recovery of decreased bone mineral apparent density were seen, verified by dual-energy X-ray absorptiometry. Spinal magnetic resonance imaging revealed no vertebral abnormalities. AI therapy might be an effective and low-cost alternative to the use of GH. Further controlled trials should prove efficacy and safety of long-term AI therapy in boys with IS
High Precision Temperature Control of Normal-conducting RF GUN for a High Duty Cycle Free-Electron Laser
High precision temperature control of the RF GUN is necessary to optimally accelerate thousands of electrons within the injection part of the European X-ray free-electron laser XFEL and the Free Electron Laser FLASH. A difference of the RF GUN temperature from the reference value of only 0.01 K leads to detuning of the cavity and thus limits the performance of the whole facility. Especially in steady-state operation there are some undesired temperature oscillations when using classical standard control techniques like PID control. That is why a model based approach is applied here to design the RF GUN temperature controller for the free-electron lasers. A thermal model of the RF GUN and the cooling facility is derived based on heat balances, considering the heat dissipation of the Low-Level RF power. This results in a nonlinear model of the plant. The parameters are identified by fitting the model to data of temperature, pressure and control signal measurements of the FLASH facility, a pilot test facility for the European XFEL. The derived model is used for controller design. A linear model predictive controller was implemented in MATLAB/Simulink and tuned to stabilize the temperature of the RF GUN in steady-state operation. A test of the controller in simulation shows promising results
Optimizing topological cascade resilience based on the structure of terrorist networks
Complex socioeconomic networks such as information, finance and even
terrorist networks need resilience to cascades - to prevent the failure of a
single node from causing a far-reaching domino effect. We show that terrorist
and guerrilla networks are uniquely cascade-resilient while maintaining high
efficiency, but they become more vulnerable beyond a certain threshold. We also
introduce an optimization method for constructing networks with high passive
cascade resilience. The optimal networks are found to be based on cells, where
each cell has a star topology. Counterintuitively, we find that there are
conditions where networks should not be modified to stop cascades because doing
so would come at a disproportionate loss of efficiency. Implementation of these
findings can lead to more cascade-resilient networks in many diverse areas.Comment: 26 pages. v2: In review at Public Library of Science ON
Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism.
BACKGROUND: The use of levothyroxine to treat subclinical hypothyroidism is controversial. We aimed to determine whether levothyroxine provided clinical benefits in older persons with this condition. METHODS: We conducted a double-blind, randomized, placebo-controlled, parallel-group trial involving 737 adults who were at least 65 years of age and who had persisting subclinical hypothyroidism (thyrotropin level, 4.60 to 19.99 mIU per liter; free thyroxine level within the reference range). A total of 368 patients were assigned to receive levothyroxine (at a starting dose of 50 Όg daily, or 25 Όg if the body weight was <50 kg or the patient had coronary heart disease), with dose adjustment according to the thyrotropin level; 369 patients were assigned to receive placebo with mock dose adjustment. The two primary outcomes were the change in the Hypothyroid Symptoms score and Tiredness score on a thyroid-related quality-of-life questionnaire at 1 year (range of each scale is 0 to 100, with higher scores indicating more symptoms or tiredness, respectively; minimum clinically important difference, 9 points). RESULTS: The mean age of the patients was 74.4 years, and 396 patients (53.7%) were women. The mean (±SD) thyrotropin level was 6.40±2.01 mIU per liter at baseline; at 1 year, this level had decreased to 5.48 mIU per liter in the placebo group, as compared with 3.63 mIU per liter in the levothyroxine group (P<0.001), at a median dose of 50 Όg. We found no differences in the mean change at 1 year in the Hypothyroid Symptoms score (0.2±15.3 in the placebo group and 0.2±14.4 in the levothyroxine group; between-group difference, 0.0; 95% confidence interval [CI], -2.0 to 2.1) or the Tiredness score (3.2±17.7 and 3.8±18.4, respectively; between-group difference, 0.4; 95% CI, -2.1 to 2.9). No beneficial effects of levothyroxine were seen on secondary-outcome measures. There was no significant excess of serious adverse events prespecified as being of special interest. CONCLUSIONS: Levothyroxine provided no apparent benefits in older persons with subclinical hypothyroidism. (Funded by European Union FP7 and others; TRUST ClinicalTrials.gov number, NCT01660126 .)
Pharmacological prion protein silencing accelerates central nervous system autoimmune disease via T cell receptor signalling
The primary biological function of the endogenous cellular prion protein has remained unclear. We investigated its biological function in the generation of cellular immune responses using cellular prion protein gene-specific small interfering ribonucleic acid in vivo and in vitro. Our results were confirmed by blocking cellular prion protein with monovalent antibodies and by using cellular prion protein-deficient and -transgenic mice. In vivo prion protein gene-small interfering ribonucleic acid treatment effects were of limited duration, restricted to secondary lymphoid organs and resulted in a 70% reduction of cellular prion protein expression in leukocytes. Disruption of cellular prion protein signalling augmented antigen-specific activation and proliferation, and enhanced T cell receptor signalling, resulting in zeta-chain-associated protein-70 phosphorylation and nuclear factor of activated T cells/activator protein 1 transcriptional activity. In vivo prion protein gene-small interfering ribonucleic acid treatment promoted T cell differentiation towards pro-inflammatory phenotypes and increased survival of antigen-specific T cells. Cellular prion protein silencing with small interfering ribonucleic acid also resulted in the worsening of actively induced and adoptively transferred experimental autoimmune encephalomyelitis. Finally, treatment of myelin basic protein1â11 T cell receptor transgenic mice with prion protein gene-small interfering ribonucleic acid resulted in spontaneous experimental autoimmune encephalomyelitis. Thus, central nervous system autoimmune disease was modulated at all stages of disease: the generation of the T cell effector response, the elicitation of T effector function and the perpetuation of cellular immune responses. Our findings indicate that cellular prion protein regulates T cell receptor-mediated T cell activation, differentiation and survival. Defects in autoimmunity are restricted to the immune system and not the central nervous system. Our data identify cellular prion protein as a regulator of cellular immunological homoeostasis and suggest cellular prion protein as a novel potential target for therapeutic immunomodulation
Sicherung von DĂ€mmen, Deichen und Stauanlagen : Handbuch fĂŒr Theorie und Praxis ; Vol. V - 2015
Die UniversitĂ€t Siegen beschĂ€ftigt sich seit ĂŒber 15 Jahren wissenschaftlich und im Bereich der anwendungsorientierten Forschung mit diesem Thema und hat dazu mittlerweile fĂŒnf Symposien durchgefĂŒhrt.
Mit der Veröffentlichung soll die langjĂ€hrige Tradition als etablierte wissenschaftliche Plattform mit einem Wissensaustausch auf europĂ€ischer Ebene fortgesetzt werden. Die Bearbeitung dieser Thematik erfolgt auf der Basis der bewĂ€hrten Kooperation zwischen Geotechnik und Wasserbau an der UniversitĂ€t Siegen. Aktuelle Ereignisse, wie z.B. die aus England oder Australien im Februar des Jahres 2014, machen uns aber auch deutlich, dass ein absoluter Schutz gegen Extremereignisse nicht möglich ist. Sie zeigen aber auch, dass dort wo technischer Hochwasserschutz konsequent umgesetzt wurde SchĂ€den vermieden werden konnten. Wir sind nach den Ereignissen in den vergangenen Jahren aufgefordert wissenschaftlich noch leistungsfĂ€higere und duktilere Systeme zu entwickeln. Weiter ist die Wissenschaft in der Pflicht, die Zivile Sicherheit im Hochwasser-schutz permanent zu bewerten, zu bearbeiten und ganzheitliche-interdisziplinĂ€re und lĂ€nderĂŒbergreifende Lösungen fĂŒr die Zivilgesellschaft einzufordern
Global data on earthworm abundance, biomass, diversity and corresponding environmental properties
Publisher Copyright: © 2021, The Author(s).Earthworms are an important soil taxon as ecosystem engineers, providing a variety of crucial ecosystem functions and services. Little is known about their diversity and distribution at large spatial scales, despite the availability of considerable amounts of local-scale data. Earthworm diversity data, obtained from the primary literature or provided directly by authors, were collated with information on site locations, including coordinates, habitat cover, and soil properties. Datasets were required, at a minimum, to include abundance or biomass of earthworms at a site. Where possible, site-level species lists were included, as well as the abundance and biomass of individual species and ecological groups. This global dataset contains 10,840 sites, with 184 species, from 60 countries and all continents except Antarctica. The data were obtained from 182 published articles, published between 1973 and 2017, and 17 unpublished datasets. Amalgamating data into a single global database will assist researchers in investigating and answering a wide variety of pressing questions, for example, jointly assessing aboveground and belowground biodiversity distributions and drivers of biodiversity change.Peer reviewe
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