A lightweight, high strength dexterous manipulator for commercial applications

The concept, design, and features are described of a lightweight, high strength, modular robot manipulator being developed for space and commercial applications. The manipulator has seven fully active degrees of freedom and is fully operational in 1 G. Each of the seven joints incorporates a unique drivetrain design which provides zero backlash operation, is insensitive to wear, and is single fault tolerant to motor or servo amplifier failure. Feedback sensors provide position, velocity, torque, and motor winding temperature information at each joint. This sensing system is also designed to be single fault tolerant. The manipulator consists of five modules (not including gripper). These modules join via simple quick-disconnect couplings and self-mating connectors which allow rapid assembly and/or disassembly for reconfiguration, transport, or servicing. The manipulator is a completely enclosed assembly, with no exposed components or wires. Although the initial prototype will not be space qualified, the design is well suited to meeting space requirements. The control system provides dexterous motion by controlling the endpoint location and arm pose simultaneously. Potential applications are discussed

Genetic studies of IgA nephropathy: past, present, and future

Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide and an important cause of kidney disease in young adults. Highly variable clinical presentation and outcome of IgAN suggest that this diagnosis may encompass multiple subsets of disease that are not distinguishable by currently available clinical tools. Marked differences in disease prevalence between individuals of European, Asian, and African ancestry suggest the existence of susceptibility genes that are present at variable frequencies in these populations. Familial forms of IgAN have also been reported throughout the world but are probably underrecognized because associated urinary abnormalities are often intermittent in affected family members. Of the many pathogenic mechanisms reported, defects in IgA1 glycosylation that lead to formation of immune complexes have been consistently demonstrated. Recent data indicates that these IgA1 glycosylation defects are inherited and constitute a heritable risk factor for IgAN. Because of the complex genetic architecture of IgAN, the efforts to map disease susceptibility genes have been difficult, and no causative mutations have yet been identified. Linkage-based approaches have been hindered by disease heterogeneity and lack of a reliable noninvasive diagnostic test for screening family members at risk of IgAN. Many candidate-gene association studies have been published, but most suffer from small sample size and methodological problems, and none of the results have been convincingly validated. New genomic approaches, including genome-wide association studies currently under way, offer promising tools for elucidating the genetic basis of IgAN

The Oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility

Pathological classifications in current use for the assessment of glomerular disease have been typically opinion-based and built on the expert assumptions of renal pathologists about lesions historically thought to be relevant to prognosis. Here we develop a unique approach for the pathological classification of a glomerular disease, IgA nephropathy, in which renal pathologists first undertook extensive iterative work to define pathologic variables with acceptable inter-observer reproducibility. Where groups of such features closely correlated, variables were further selected on the basis of least susceptibility to sampling error and ease of scoring in routine practice. This process identified six pathologic variables that could then be used to interrogate prognostic significance independent of the clinical data in IgA nephropathy (described in the accompanying article). These variables were (1) mesangial cellularity score; percentage of glomeruli showing (2) segmental sclerosis, (3) endocapillary hypercellularity, or (4) cellular/ fibrocellular crescents; (5) percentage of interstitial fibrosis/ tubular atrophy; and finally (6) arteriosclerosis score. Results for interobserver reproducibility of individual pathological features are likely applicable to other glomerulonephritides, but it is not known if the correlations between variables depend on the specific type of glomerular pathobiology. Variables identified in this study withstood rigorous pathology review and statistical testing and we recommend that they become a necessary part of pathology reports for IgA nephropathy. Our methodology, translating a strong evidence-based dataset into a working format, is a model for developing classifications of other types of renal disease

Statistical assessment of functional categories of genes deregulated in pathological conditions by using microarray data

AbstractMotivation: A major challenge in current biomedical research is the identification of cellular processes deregulated in a given pathology through the analysis of gene expression profiles. To this end, predefined lists of genes, coding specific functions, are compared with a list of genes ordered according to their values of differential expression measured by suitable univariate statistics.Results: We propose a statistically well-founded method for measuring the relevance of predefined lists of genes and for assessing their statistical significance starting from their raw expression levels as recorded on the microarray. We use prediction accuracy as a measure of relevance of the list. The rationale is that a functional category, coded through a list of genes, is perturbed in a given pathology if it is possible to correctly predict the occurrence of the disease in new subjects on the basis of the expression levels of the genes belonging to the list only. The accuracy is estimated with multiple random validation strategy and its statistical significance is assessed against a couple of null hypothesis, by using two independent permutation tests. The utility of the proposed methodology is illustrated by analyzing the relevance of Gene Ontology terms belonging to biological process category in colon and prostate cancer, by using three different microarray data sets and by comparing it with current approaches.Availability: Source code for the algorithms is available from author upon request.Contact: [email protected] information: Colon cancer data set and a complete description of experimental results are available at: ftp://bioftp:[email protected]/supp-info.ht

A germline mutation in the androgen receptor gene in two brothers with breast cancer and Reifenstein syndrome

Breast cancer in men is rare--among the risk factors that have been identified are a family history of breast cancer and evidence of androgen insufficiency. We report a family in which two brothers who both developed breast cancer had clinical and endocrinological evidence of androgen resistance. Sequence analysis revealed a mutation in the androgen receptor gene on the X chromosome, within the region encoding the DNA binding domain. This is the first report of a germline mutation in a member of the steroid/thyroid hormone receptor superfamily associated with the development of cancer

Changes in gene expression in maize kernel in response to water and salt stress

Increasing pressure on limited water resources for agriculture, together with the global temperature increase, highlight the importance of breeding for drought-tolerant cultivars. A better understanding of the molecular nature of drought stress can be expected through the use of genomics approaches. Here, a macroarray of approximate to 2500 maize cDNAs was used for determining transcript changes during water- and salt-stress treatments of developing kernels at 15 days after pollination. Normalization of relative transcript abundances was carried out using a human nebulin control sequence. The proportions of transcripts that changed significantly in abundance upon treatment (> 2-fold compared to the control) were determined; 1.5% of the sequences examined were up-regulated by high salinity and 1% by water stress. Both stresses induced 0.8% of the sequences. These include genes involved in various stress responses: abiotic, wounding and pathogen attack (abscisic acid response binding factor, glycine and proline-rich proteins, pathogenesis-related proteins, etc.). The proportion of down-regulated genes was higher than that for up-regulated genes for water stress (3.2%) and lower for salt stress (0.7%), although only eight genes, predominantly involved in energy generation, were down-regulated in both stress conditions. Co-expression of genes of unknown function under defined conditions may help in elucidating their roles in coordinating stress responses