Effects of exoplanetary gravity on human locomotor ability

At some point in the future, if mankind hopes to settle planets outside the Solar System, it will be crucial to determine the range of planetary conditions under which human beings could survive and function. In this article, we apply physical considerations to future exoplanetary biology to determine the limitations which gravity imposes on several systems governing the human body. Initially, we examine the ultimate limits at which the human skeleton breaks and muscles become unable to lift the body from the ground. We also produce a new model for the energetic expenditure of walking, by modelling the leg as an inverted pendulum. Both approaches conclude that, with rigorous training, humans could perform normal locomotion at gravity no higher than 4 $g_{\textrm{Earth}}$.Comment: 12 pages, 4 figures, to be published in The Physics Teache

Dual channel rank-based intensity weighting for quantitative co-localization of microscopy images

BACKGROUND: Accurate quantitative co-localization is a key parameter in the context of understanding the spatial co-ordination of molecules and therefore their function in cells. Existing co-localization algorithms consider either the presence of co-occurring pixels or correlations of intensity in regions of interest. Depending on the image source, and the algorithm selected, the co-localization coefficients determined can be highly variable, and often inaccurate. Furthermore, this choice of whether co-occurrence or correlation is the best approach for quantifying co-localization remains controversial. RESULTS: We have developed a novel algorithm to quantify co-localization that improves on and addresses the major shortcomings of existing co-localization measures. This algorithm uses a non-parametric ranking of pixel intensities in each channel, and the difference in ranks of co-localizing pixel positions in the two channels is used to weight the coefficient. This weighting is applied to co-occurring pixels thereby efficiently combining both co-occurrence and correlation. Tests with synthetic data sets show that the algorithm is sensitive to both co-occurrence and correlation at varying levels of intensity. Analysis of biological data sets demonstrate that this new algorithm offers high sensitivity, and that it is capable of detecting subtle changes in co-localization, exemplified by studies on a well characterized cargo protein that moves through the secretory pathway of cells. CONCLUSIONS: This algorithm provides a novel way to efficiently combine co-occurrence and correlation components in biological images, thereby generating an accurate measure of co-localization. This approach of rank weighting of intensities also eliminates the need for manual thresholding of the image, which is often a cause of error in co-localization quantification. We envisage that this tool will facilitate the quantitative analysis of a wide range of biological data sets, including high resolution confocal images, live cell time-lapse recordings, and high-throughput screening data sets

Chemical Chaperones Improve Protein Secretion and Rescue Mutant Factor VIII in Mice with Hemophilia A.

nefficient intracellular protein trafficking is a critical issue in the pathogenesis of a variety of diseases and in recombinant protein production. Here we investigated the trafficking of factor VIII (FVIII), which is affected in the coagulation disorder hemophilia A. We hypothesized that chemical chaperones may be useful to enhance folding and processing of FVIII in recombinant protein production, and as a therapeutic approach in patients with impaired FVIII secretion. A tagged B-domain-deleted version of human FVIII was expressed in cultured Chinese Hamster Ovary cells to mimic the industrial production of this important protein. Of several chemical chaperones tested, the addition of betaine resulted in increased secretion of FVIII, by increasing solubility of intracellular FVIII aggregates and improving transport from endoplasmic reticulum to Golgi. Similar results were obtained in experiments monitoring recombinant full-length FVIII. Oral betaine administration also increased FVIII and factor IX (FIX) plasma levels in FVIII or FIX knockout mice following gene transfer. Moreover, in vitro and in vivo applications of betaine were also able to rescue a trafficking-defective FVIII mutant (FVIIIQ305P). We conclude that chemical chaperones such as betaine might represent a useful treatment concept for hemophilia and other diseases caused by deficient intracellular protein trafficking

Spectral Analysis for Matrix Hamiltonian Operators

In this work, we study the spectral properties of matrix Hamiltonians generated by linearizing the nonlinear Schr\"odinger equation about soliton solutions. By a numerically assisted proof, we show that there are no embedded eigenvalues for the three dimensional cubic equation. Though we focus on a proof of the 3d cubic problem, this work presents a new algorithm for verifying certain spectral properties needed to study soliton stability. Source code for verification of our comptuations, and for further experimentation, are available at http://www.math.toronto.edu/simpson/files/spec_prop_code.tgz.Comment: 57 pages, 22 figures, typos fixe

Time resolved study of cell death mechanisms induced by amine-modified polystyrene nanoparticles

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The systematic functional characterisation of Xq28 genes prioritises candidate disease genes

BACKGROUND: Well known for its gene density and the large number of mapped diseases, the human sub-chromosomal region Xq28 has long been a focus of genome research. Over 40 of approximately 300 X-linked diseases map to this region, and systematic mapping, transcript identification, and mutation analysis has led to the identification of causative genes for 26 of these diseases, leaving another 17 diseases mapped to Xq28, where the causative gene is still unknown. To expedite disease gene identification, we have initiated the functional characterisation of all known Xq28 genes. RESULTS: By using a systematic approach, we describe the Xq28 genes by RNA in situ hybridisation and Northern blotting of the mouse orthologs, as well as subcellular localisation and data mining of the human genes. We have developed a relational web-accessible database with comprehensive query options integrating all experimental data. Using this database, we matched gene expression patterns with affected tissues for 16 of the 17 remaining Xq28 linked diseases, where the causative gene is unknown. CONCLUSION: By using this systematic approach, we have prioritised genes in linkage regions of Xq28-mapped diseases to an amenable number for mutational screens. Our database can be queried by any researcher performing highly specified searches including diseases not listed in OMIM or diseases that might be linked to Xq28 in the future