Seamless handover among heterogeneous mobile networks using stream control transmission protocol (SCTP)

Master'sMASTER OF ENGINEERIN

ProtQuant: a tool for the label-free quantification of MudPIT proteomics data

<p>Abstract</p> <p>Background</p> <p>Effective and economical methods for quantitative analysis of high throughput mass spectrometry data are essential to meet the goals of directly identifying, characterizing, and quantifying proteins from a particular cell state. Multidimensional Protein Identification Technology (MudPIT) is a common approach used in protein identification. Two types of methods are used to detect differential protein expression in MudPIT experiments: those involving stable isotope labelling and the so-called label-free methods. Label-free methods are based on the relationship between protein abundance and sampling statistics such as peptide count, spectral count, probabilistic peptide identification scores, and sum of peptide Sequest XCorr scores (ΣXCorr). Although a number of label-free methods for protein quantification have been described in the literature, there are few publicly available tools that implement these methods. We describe ProtQuant, a Java-based tool for label-free protein quantification that uses the previously published ΣXCorr method for quantification and includes an improved method for handling missing data.</p> <p>Results</p> <p><it>ProtQuant </it>was designed for ease of use and portability for the bench scientist. It implements the ΣXCorr method for label free protein quantification from MudPIT datasets. <it>ProtQuant </it>has a graphical user interface, accepts multiple file formats, is not limited by the size of the input files, and can process any number of replicates and any number of treatments. In addition,<it>ProtQuant </it>implements a new method for dealing with missing values for peptide scores used for quantification. The new algorithm, called ΣXCorr*, uses "below threshold" peptide scores to provide meaningful non-zero values for missing data points. We demonstrate that ΣXCorr* produces an average reduction in false positive identifications of differential expression of 25% compared to ΣXCorr.</p> <p>Conclusion</p> <p><it>ProtQuant </it>is a tool for protein quantification built for multi-platform use with an intuitive user interface. <it>ProtQuant </it>efficiently and uniquely performs label-free quantification of protein datasets produced with Sequest and provides the user with facilities for data management and analysis. Importantly, <it>ProtQuant </it>is available as a self-installing executable for the Windows environment used by many bench scientists.</p

Mapping gene associations in human mitochondria using clinical disease phenotypes

Nuclear genes encode most mitochondrial proteins, and their mutations cause diverse and debilitating clinical disorders. To date, 1,200 of these mitochondrial genes have been recorded, while no standardized catalog exists of the associated clinical phenotypes. Such a catalog would be useful to develop methods to analyze human phenotypic data, to determine genotype-phenotype relations among many genes and diseases, and to support the clinical diagnosis of mitochondrial disorders. Here we establish a clinical phenotype catalog of 174 mitochondrial disease genes and study associations of diseases and genes. Phenotypic features such as clinical signs and symptoms were manually annotated from full-text medical articles and classified based on the hierarchical MeSH ontology. This classification of phenotypic features of each gene allowed for the comparison of diseases between different genes. In turn, we were then able to measure the phenotypic associations of disease genes for which we calculated a quantitative value that is based on their shared phenotypic features. The results showed that genes sharing more similar phenotypes have a stronger tendency for functional interactions, proving the usefulness of phenotype similarity values in disease gene network analysis. We then constructed a functional network of mitochondrial genes and discovered a higher connectivity for non-disease than for disease genes, and a tendency of disease genes to interact with each other. Utilizing these differences, we propose 168 candidate genes that resemble the characteristic interaction patterns of mitochondrial disease genes. Through their network associations, the candidates are further prioritized for the study of specific disorders such as optic neuropathies and Parkinson disease. Most mitochondrial disease phenotypes involve several clinical categories including neurologic, metabolic, and gastrointestinal disorders, which might indicate the effects of gene defects within the mitochondrial system. The accompanying knowledgebase (http://www.mitophenome.org/) supports the study of clinical diseases and associated genes

Emergency department triage nurse initiated pain management

Objectives: 1) To determine the time difference to analgesia administration for patients with painful limb conditions using an emergency triage nurse initiated pain management protocol versus analgesia administration by emergency doctors after consultation. 2) To determine the frequency of adverse events following such a protocol implementation. Methods: For emergency department patients with isolated limb injury or inflammation, a triage nurse initiated pain management policy was implemented in 2004. The protocol did not require the triage nurse to consult a physician. The triage nurse would record the chief complaint, past medical history, allergy, medication, vital signs, and pain severity using a combination of 0 to 10 numerical and face pain scales. Unless contraindicated, the triage nurse would offer intramuscular ketorolac to patients with pain score ≥5. Medical charts of patients fulfilling the inclusion criteria were reviewed from 1 to 30 September 2004. Results: Two hundred seventy-three patients were reviewed, of whom 73.3% were men and the overall mean age was 40.1 years (standard deviation SD 19.5). Two hundred and nine patients (76.6%) had pain score recorded at triage, and the median was 6. One hundred and five patients (38.5%) received analgesia, of which 69 were given by triage nurses and 36 by physicians. The mean time interval for analgesia given by triage nurse was 2.5 minutes (SD 8.9) and that for physician was significantly longer (p&lt;0.0001) at 68.2 minutes (SD 59.5). There was no adverse drug reaction observed in patients who received intramuscular ketorolac given by triage nurses. Conclusion: The time interval for pain relief of emergency department patients with painful limb conditions was reduced when the triage nurse initiated pain management

Characterization of primary neurospheres generated from mouse ventral rostral hindbrain

Serotonergic (5-HT) neurons of the reticular formation play a key role in the modulation of behavior, and their dysfunction is associated with severe neurological and psychiatric disorders, such as depression and schizophrenia. However, the molecular mechanisms underlying the differentiation of the progenitor cells and the specification of the 5-HT phenotype are not fully understood. A primary neurosphere cell-culture system from mouse ventral rostral hindbrain at embryonic day 12 was therefore established. The generated primary neurospheres comprised progenitor cells and fully differentiated neurons. Bromodeoxyuridine incorporation experiments in combination with immunocytochemistry for neural markers revealed the proliferation capacity of the neural multipotent hindbrain progenitors within neurospheres and their ability to differentiate toward the neuronal lineage and serotonergic phenotype. Gene expression analysis by reverse transcription with the polymerase chain reaction showed that the neurospheres were regionally specified, as reflected by the expression of the transcription factors Gata2 and Pet1. Treatment of dissociated primary neurospheres with exogenous Shh significantly increased the number of 5-HT-immunopositive cells compared with controls, whereas neutralization of endogenous Shh significantly decreased the number of 5-HT neurons. Thus, the primary neurosphere culture system presented here allows the expansion of hindbrain progenitor cells and the experimental control of their differentiation toward the serotonergic phenotype. This culture system is therefore a useful model for in vitro studies dealing with the development of 5-HT neurons

Adjusting for BMI in analyses of volumetric mammographic density and breast cancer risk

Abstract Background Fully automated assessment of mammographic density (MD), a biomarker of breast cancer risk, is being increasingly performed in screening settings. However, data on body mass index (BMI), a confounder of the MD–risk association, are not routinely collected at screening. We investigated whether the amount of fat in the breast, as captured by the amount of mammographic non-dense tissue seen on the mammographic image, can be used as a proxy for BMI when data on the latter are unavailable. Methods Data from a UK case control study (numbers of cases/controls: 414/685) and a Norwegian cohort study (numbers of cases/non-cases: 657/61059), both with volumetric MD measurements (dense volume (DV), non-dense volume (NDV) and percent density (%MD)) from screening-age women, were analysed. BMI (self-reported) and NDV were taken as measures of adiposity. Correlations between BMI and NDV, %MD and DV were examined after log-transformation and adjustment for age, menopausal status and parity. Logistic regression models were fitted to the UK study, and Cox regression models to the Norwegian study, to assess associations between MD and breast cancer risk, expressed as odds/hazard ratios per adjusted standard deviation (OPERA). Adjustments were first made for standard risk factors except BMI (minimally adjusted models) and then also for BMI or NDV. OPERA pooled relative risks (RRs) were estimated by fixed-effect models, and between-study heterogeneity was assessed by the I 2 statistics. Results BMI was positively correlated with NDV (adjusted r = 0.74 in the UK study and r = 0.72 in the Norwegian study) and with DV (r = 0.33 and r = 0.25, respectively). Both %MD and DV were positively associated with breast cancer risk in minimally adjusted models (pooled OPERA RR (95% confidence interval): 1.34 (1.25, 1.43) and 1.46 (1.36, 1.56), respectively; I 2 = 0%, P >0.48 for both). Further adjustment for BMI or NDV strengthened the %MD–risk association (1.51 (1.41, 1.61); I 2 = 0%, P = 0.33 and 1.51 (1.41, 1.61); I 2 = 0%, P = 0.32, respectively). Adjusting for BMI or NDV marginally affected the magnitude of the DV–risk association (1.44 (1.34, 1.54); I 2 = 0%, P = 0.87 and 1.49 (1.40, 1.60); I 2 = 0%, P = 0.36, respectively). Conclusions When volumetric MD–breast cancer risk associations are investigated, NDV can be used as a measure of adiposity when BMI data are unavailable

Polymorphisms in genes of interleukin 12 and its receptors and their association with protection against severe malarial anaemia in children in western Kenya

Abstract Background: Malarial anaemia is characterized by destruction of malaria infected red blood cells and suppression of erythropoiesis. Interleukin 12 (IL12) significantly boosts erythropoietic responses in murine models of malarial anaemia and decreased IL12 levels are associated with severe malarial anaemia (SMA) in children. Based on the biological relevance of IL12 in malaria anaemia, the relationship between genetic polymorphisms of IL12 and its receptors and SMA was examined. Methods: Fifty-five tagging single nucleotide polymorphisms covering genes encoding two IL12 subunits, IL12A and IL12B, and its receptors, IL12RB1 and IL12RB2, were examined in a cohort of 913 children residing in Asembo Bay region of western Kenya. Results: An increasing copy number of minor variant (C) in IL12A (rs2243140) was significantly associated with a decreased risk of SMA (P = 0.006; risk ratio, 0.52 for carrying one copy of allele C and 0.28 for two copies). Individuals possessing two copies of a rare variant (C) in IL12RB1 (rs429774) also appeared to be strongly protective against SMA (P = 0.00005; risk ratio, 0.18). In addition, children homozygous for another rare allele (T) in IL12A (rs22431348) were associated with reduced risk of severe anaemia (SA) (P = 0.004; risk ratio, 0.69) and of severe anaemia with any parasitaemia (SAP) (P = 0.004; risk ratio, 0.66). In contrast, AG genotype for another variant in IL12RB1 (rs383483) was associated with susceptibility to high-density parasitaemia (HDP) (P = 0.003; risk ratio, 1.21). Conclusions: This study has shown strong associations between polymorphisms in the genes of IL12A and IL12RB1 and protection from SMA in Kenyan children, suggesting that human genetic variants of IL12 related genes may significantly contribute to the development of anaemia in malaria patients

Biallelic loss of function variants in PPP1R21 cause a neurodevelopmental syndrome with impaired endocytic function

Next‐generation sequencing (NGS) has been instrumental in solving the genetic basis of rare inherited diseases, especially neurodevelopmental syndromes. However, functional workup is essential for precise phenotype definition and to understand the underlying disease mechanisms. Using whole exome (WES) and whole genome sequencing (WGS) in four independent families with hypotonia, neurodevelopmental delay, facial dysmorphism, loss of white matter, and thinning of the corpus callosum, we identified four previously unreported homozygous truncating PPP1R21 alleles: c.347delT p.(Ile116Lysfs*25), c.2170_2171insGGTA p.(Ile724Argfs*8), c.1607dupT p.(Leu536Phefs*7), c.2063delA p.(Lys688Serfs*26) and found that PPP1R21 was absent in fibroblasts of an affected individual, supporting the allele's loss of function effect. PPP1R21 function had not been studied except that a large scale affinity proteomics approach suggested an interaction with PIBF1 defective in Joubert syndrome. Our co‐immunoprecipitation studies did not confirm this but in contrast defined the localization of PPP1R21 to the early endosome. Consistent with the subcellular expression pattern and the clinical phenotype exhibiting features of storage diseases, we found patient fibroblasts exhibited a delay in clearance of transferrin‐488 while uptake was normal. In summary, we delineate a novel neurodevelopmental syndrome caused by biallelic PPP1R21 loss of function variants, and suggest a role of PPP1R21 within the endosomal sorting process or endosome maturation pathway

The UK Biobank imaging enhancement of 100,000 participants: rationale, data collection, management and future directions

UK Biobank is a population-based cohort of half a million participants aged 40–69 years recruited between 2006 and 2010. In 2014, UK Biobank started the world’s largest multi-modal imaging study, with the aim of re-inviting 100,000 participants to undergo brain, cardiac and abdominal magnetic resonance imaging, dual-energy X-ray absorptiometry and carotid ultrasound. The combination of large-scale multi-modal imaging with extensive phenotypic and genetic data offers an unprecedented resource for scientists to conduct health-related research. This article provides an in-depth overview of the imaging enhancement, including the data collected, how it is managed and processed, and future direction