Contact processing within walking robots' design

Magdeburg, Univ., Fak. für Elektrotechnik und Informationstechnik, Diss., 2011

Validation of a Brazilian Portuguese Version of the Walking Estimated-Limitation Calculated by History (WELCH)

Abstract Background: The Walking Estimated-Limitation Calculated by History (WELCH) questionnaire has been proposed to evaluate walking impairment in patients with intermittent claudication (IC), presenting satisfactory psychometric properties. However, a Brazilian Portuguese version of the questionnaire is unavailable, limiting its application in Brazilian patients. Objective: To analyze the psychometric properties of a translated Brazilian Portuguese version of the WELCH in Brazilian patients with IC. Methods: Eighty-four patients with IC participated in the study. After translation and back-translation, carried out by two independent translators, the concurrent validity of the WELCH was analyzed by correlating the questionnaire scores with the walking capacity assessed with the Gardner treadmill test. To determine the reliability of the WELCH, internal consistency and test–retest reliability with a seven-day interval between the two questionnaire applications were calculated. Results: There were significant correlations between the WELCH score and the claudication onset distance (r = 0.64, p = 0.01) and total walking distance (r = 0.61, p = 0.01). The internal consistency was 0.84 and the intraclass correlation coefficient between questionnaire evaluations was 0.84. There were no differences in WELCH scores between the two questionnaire applications. Conclusion: The Brazilian Portuguese version of the WELCH presents adequate validity and reliability indicators, which support its application to Brazilian patients with IC.

Design of biped robot walking based on non-linear periodical oscillations

Magdeburg, Univ., Fak. für Elektrotechnik und Informationstechnik, Diss., 2012

Design of biped robot walking with double-support phase

Otto-von-Guericke-Universität Magdeburg, Fakultät für Maschinenbau, Univ., Dissertation, 2015

MB-MDR: Model-Based Multifactor Dimensionality Reduction for detecting interactions in high-dimensional genomic data

L’anàlisi de l’efecte dels gens i els factors ambientals en el desenvolupament de malalties complexes és un gran repte estadístic i computacional. Entre les diverses metodologies de mineria de dades que s’han proposat per a l’anàlisi d’interaccions una de les més populars és el mètode Multifactor Dimensionality Reduction, MDR, (Ritchie i al. 2001). L’estratègia d’aquest mètode és reduir la dimensió multifactorial a u mitjançant l’agrupació dels diferents genotips en dos grups de risc: alt i baix. Tot i la seva utilitat demostrada, el mètode MDR té alguns inconvenients entre els quals l’agrupació excessiva de genotips pot fer que algunes interaccions importants no siguin detectades i que no permet ajustar per efectes principals ni per variables confusores. En aquest article il•lustrem les limitacions de l’estratègia MDR i d’altres aproximacions no paramètriques i demostrem la conveniència d’utilitzar metodologies parametriques per analitzar interaccions en estudis cas-control on es requereix l’ajust per variables confusores i per efectes principals. Proposem una nova metodologia, una versió paramètrica del mètode MDR, que anomenem Model-Based Multifactor Dimensionality Reduction (MB-MDR). La metodologia proposada té com a objectiu la identificació de genotips específics que estiguin associats a la malaltia i permet ajustar per efectes marginals i variables confusores. La nova metodologia s’il•lustra amb dades de l’Estudi Espanyol de Cancer de Bufeta.

Rare genomic structural variants in complex disease: lessons from the replication of associations with obesity.

The limited ability of common variants to account for the genetic contribution to complex disease has prompted searches for rare variants of large effect, to partly explain the 'missing heritability'. Analyses of genome-wide genotyping data have identified genomic structural variants (GSVs) as a source of such rare causal variants. Recent studies have reported multiple GSV loci associated with risk of obesity. We attempted to replicate these associations by similar analysis of two familial-obesity case-control cohorts and a population cohort, and detected GSVs at 11 out of 18 loci, at frequencies similar to those previously reported. Based on their reported frequencies and effect sizes (OR≥25), we had sufficient statistical power to detect the large majority (80%) of genuine associations at these loci. However, only one obesity association was replicated. Deletion of a 220 kb region on chromosome 16p11.2 has a carrier population frequency of 2×10(-4) (95% confidence interval [9.6×10(-5)-3.1×10(-4)]); accounts overall for 0.5% [0.19%-0.82%] of severe childhood obesity cases (P = 3.8×10(-10); odds ratio = 25.0 [9.9-60.6]); and results in a mean body mass index (BMI) increase of 5.8 kg.m(-2) [1.8-10.3] in adults from the general population. We also attempted replication using BMI as a quantitative trait in our population cohort; associations with BMI at or near nominal significance were detected at two further loci near KIF2B and within FOXP2, but these did not survive correction for multiple testing. These findings emphasise several issues of importance when conducting rare GSV association, including the need for careful cohort selection and replication strategy, accurate GSV identification, and appropriate correction for multiple testing and/or control of false discovery rate. Moreover, they highlight the potential difficulty in replicating rare CNV associations across different populations. Nevertheless, we show that such studies are potentially valuable for the identification of variants making an appreciable contribution to complex disease.

Soft tissue sarcomas with complex genomic profiles.

Soft tissue sarcomas (STS) with complex genomic profiles (50% of all STS) are predominantly composed of spindle cell/pleomorphic sarcomas, including leiomyosarcoma, myxofibrosarcoma, pleomorphic liposarcoma, pleomorphic rhabdomyosarcoma, malignant peripheral nerve sheath tumor, angiosarcoma, extraskeletal osteosarcoma, and spindle cell/pleomorphic unclassified sarcoma (previously called spindle cell/pleomorphic malignant fibrous histiocytoma). These neoplasms show, characteristically, gains and losses of numerous chromosomes or chromosome regions, as well as amplifications. Many of them share recurrent aberrations (e.g., gain of 5p13-p15) that seem to play a significant role in tumor progression and/or metastatic dissemination. In this paper, we review the cytogenetic, molecular genetic, and clinicopathologic characteristics of the most common STS displaying complex genomic profiles. Features of diagnostic or prognostic relevance will be discussed when needed.

Genomic, Epigenomic and Transcriptomic Molecular Characterization of Splenic Marginal Zone Lymphoma Reveals Recurrent Abnormalities in miR-182

Splenic marginal zone lymphoma (SMZL) is a low grade B-cell non-Hodgkin's lymphoma. The molecular pathology of this entity remains poorly understood. To characterise this lymphoma at the molecular level, we performed an integrated analysis of 1) genome wide genetic copy number alterations 2) gene expression profiles and 3) epigenetic DNA methylation profiles.We have previously shown that SMZL is characterised by recurrent alterations of chromosomes 7q, 6q, 3q, 9q and 18; however, gene resolution oligonucleotide array comparative genomic hybridisation did not reveal evidence of cryptic amplification or deletion in these regions. The most frequently lost 7q32 region contains a cluster of miRNAs. qRT-PCR revealed that three of these (miR-182/96/183) show underexpression in SMZL, and miR-182 is somatically mutated in >20% of cases of SMZL, as well as in >20% of cases of follicular lymphoma, and between 5-15% of cases of chronic lymphocytic leukaemia, MALT-lymphoma and hairy cell leukaemia. We conclude that miR-182 is a strong candidate novel tumour suppressor miRNA in lymphoma.The overall gene expression signature of SMZL was found to be strongly distinct fromthose of other lymphomas. Functional analysis of gene expression data revealed SMZL to be characterised by abnormalities in B-cell receptor signalling (especially through the CD19/21-PI3K/AKT pathway) and apoptotic pathways. In addition, genes involved in the response to viral infection appeared upregulated. SMZL shows a unique epigenetic profile, but analysis of differentially methylated genes showed few with methylation related transcriptional deregulation, suggesting that DNA methylation abnormalities are not a critical component of the SMZL malignant phenotype.

Systematic identification of genomic markers of drug sensitivity in cancer cells.

Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers for responses to targeted agents. Here, to uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we screened a panel of several hundred cancer cell lines--which represent much of the tissue-type and genetic diversity of human cancers--with 130 drugs under clinical and preclinical investigation. In aggregate, we found that mutated cancer genes were associated with cellular response to most currently available cancer drugs. Classic oncogene addiction paradigms were modified by additional tissue-specific or expression biomarkers, and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. Unexpected relationships were revealed, including the marked sensitivity of Ewing's sarcoma cells harbouring the EWS (also known as EWSR1)-FLI1 gene translocation to poly(ADP-ribose) polymerase (PARP) inhibitors. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies.

Characterization of a Trypanosoma cruzi genomic fragment complementary to several species-specific mRNAs but different from the spliced leader sequence

We have isolated a clone of Trypanosoma cruzi genimic DNA, lambda 3b2-5, which contains sequences that are reiterated in the genome. Northtern blot analysis showed that clone 3b2-5 hybridizes to 1,200-5,000 bases different mRNA species. The number of mRNAs species hybridized to clone 3b2-5 exceeds its coding capacity showing that this clone carries sequences that are common to several mRNAs species and conserved in the poly A(+) RNA. These sequences are not homologous to the T. cruzi spliced leader sequence, since clone 3b2-5 hybridize to a synthetic 20 nucleotice complementary to the spliced leader sequence. Clone 3b2-5 does not hybridize to DNA and RNA from several genera of Trypanosomatidae and other Trypanosoma species indicating that it carries T. cruzi species-specific sequences.

Effectiveness of three different walking prescription durations on total physical activity in normal- and overweight women.

OBJECTIVE: While there is a dose-response relationship between physical activity (PA) and health benefit, little is known about the effectiveness of different PA prescriptions on total daily PA. AIM: To test, under real-life conditions and using an objective, non-invasive measurement technique (accelerometry), the effect of prescribing additional physical activity (walking only) of different durations (30, 60 and 90 min/day) on compliance (to the activity prescribed) and compensation (to total daily PA). Participants in each group were prescribed 5 sessions of walking per week over 4 weeks. METHODS: 55 normal-weight and overweight women (mean BMI 25 ± 5 kg/m(2), height 165 ± 1 cm, weight 68 ± 2 kg and mean age 27 ± 1 years) were randomly assigned to 3 prescription groups: 30, 60 or 90 min/day PA. RESULTS: Walking duration resulted in an almost linear increase in the number of steps per day during the prescription period from an average of about 10,000 steps per day for the 30-min prescription to about 14,000 for the 90-min prescription. Compliance was excellent for the 30-min prescription but decreased significantly with 60-min and 90-min prescriptions. In parallel, degree of compensation subsequent to exercise increased progressively as length of prescription increased. CONCLUSION: A 30-min prescription of extra walking 5 times per week was well tolerated. However, in order to increase total PA further, much more than 60 min of walking may need to be prescribed in the majority of individuals. While total exercise 'volume' increased with prescriptions longer than 30 min, compliance to the prescription decreased and greater compensation was evident. © 2014 S. Karger GmbH, Freiburg.

Molecular characterization of a Streptococcus gallolyticus genomic island encoding a pilus involved in endocarditis.

Background. Streptococcus gallolyticus is a causative agent of infective endocarditis associated with colon cancer. Genome sequence of strain UCN34 revealed the existence of 3 pilus loci (pil1, pil2, and pil3). Pili are long filamentous structures playing a key role as adhesive organelles in many pathogens. The pil1 locus encodes 2 LPXTG proteins (Gallo2178 and Gallo2179) and 1 sortase C (Gallo2177). Gallo2179 displaying a functional collagen-binding domain was referred to as the adhesin, whereas Gallo2178 was designated as the major pilin. Methods. S. gallolyticus UCN34, Pil1(+) and Pil1(-), expressing various levels of pil1, and recombinant Lactococcus lactis strains, constitutively expressing pil1, were studied. Polyclonal antibodies raised against the putative pilin subunits Gallo2178 and Gallo2179 were used in immunoblotting and immunogold electron microscopy. The role of pil1 was tested in a rat model of endocarditis. Results. We showed that the pil1 locus (gallo2179-78-77) forms an operon differentially expressed among S. gallolyticus strains. Short pilus appendages were identified both on the surface of S. gallolyticus UCN34 and recombinant L. lactis-expressing pil1. We demonstrated that Pil1 pilus is involved in binding to collagen, biofilm formation, and virulence in experimental endocarditis. Conclusions. This study identifies Pil1 as the first virulence factor characterized in S. gallolyticus.

Effect of training-sample size and classification difficulty on the accuracy of genomic predictors.

Introduction: As part of the MicroArray Quality Control (MAQC)-II project, this analysis examines how the choice of univariate feature-selection methods and classification algorithms may influence the performance of genomic predictors under varying degrees of prediction difficulty represented by three clinically relevant endpoints. Methods: We used gene-expression data from 230 breast cancers (grouped into training and independent validation sets), and we examined 40 predictors (five univariate feature-selection methods combined with eight different classifiers) for each of the three endpoints. Their classification performance was estimated on the training set by using two different resampling methods and compared with the accuracy observed in the independent validation set. Results: A ranking of the three classification problems was obtained, and the performance of 120 models was estimated and assessed on an independent validation set. The bootstrapping estimates were closer to the validation performance than were the cross-validation estimates. The required sample size for each endpoint was estimated, and both gene-level and pathway-level analyses were performed on the obtained models. Conclusions: We showed that genomic predictor accuracy is determined largely by an interplay between sample size and classification difficulty. Variations on univariate feature-selection methods and choice of classification algorithm have only a modest impact on predictor performance, and several statistically equally good predictors can be developed for any given classification problem.