Information based clustering

In an age of increasingly large data sets, investigators in many different disciplines have turned to clustering as a tool for data analysis and exploration. Existing clustering methods, however, typically depend on several nontrivial assumptions about the structure of data. Here we reformulate the clustering problem from an information theoretic perspective which avoids many of these assumptions. In particular, our formulation obviates the need for defining a cluster "prototype", does not require an a priori similarity metric, is invariant to changes in the representation of the data, and naturally captures non-linear relations. We apply this approach to different domains and find that it consistently produces clusters that are more coherent than those extracted by existing algorithms. Finally, our approach provides a way of clustering based on collective notions of similarity rather than the traditional pairwise measures.Comment: To appear in Proceedings of the National Academy of Sciences USA, 11 pages, 9 figure

Thermal Testing of the Heatshield for Extreme Entry Environment Technology (HEEET) TPS

The testing of a thermal protection system (TPS) in multiple arc jets and laser facilities is critical not only to determine the ability of a material to withstand the harsh aerothermal environments but is also required to collect relevant data that allows construction of a thermal response model of the TPS for flight design. The present talk provides an overview of recent arcjet testing of the HEEET material, one of the families of materials from the 3D Woven TPS program, being developed under NASAs Heatshield for Extreme Entry Environment Technology (HEEET) project

Large Area Scene Selection Interface (LASSI). Methodology of Selecting Landsat Imagery for the Global Land Survey 2005

The Global Land Survey (GLS) 2005 is a cloud-free, orthorectified collection of Landsat imagery acquired during the 2004-2007 epoch intended to support global land-cover and ecological monitoring. Due to the numerous complexities in selecting imagery for the GLS2005, NASA and the U.S. Geological Survey (USGS) sponsored the development of an automated scene selection tool, the Large Area Scene Selection Interface (LASSI), to aid in the selection of imagery for this data set. This innovative approach to scene selection applied a user-defined weighting system to various scene parameters: image cloud cover, image vegetation greenness, choice of sensor, and the ability of the Landsat 7 Scan Line Corrector (SLC)-off pair to completely fill image gaps, among others. The parameters considered in scene selection were weighted according to their relative importance to the data set, along with the algorithm's sensitivity to that weight. This paper describes the methodology and analysis that established the parameter weighting strategy, as well as the post-screening processes used in selecting the optimal data set for GLS2005

Titin-Actin Interaction: PEVK-Actin-Based Viscosity in a Large Animal

Titin exhibits an interaction between its PEVK segment and the actin filament resulting in viscosity, a speed dependent resistive force, which significantly influences diastolic filling in mice. While diastolic disease is clinically pervasive, humans express a more compliant titin (N2BA:N2B ratio ~0.5–1.0) than mice (N2BA:N2B ratio ~0.2). To examine PEVK-actin based viscosity in compliant titin-tissues, we used pig cardiac tissue that expresses titin isoforms similar to that in humans. Stretch-hold experiments were performed at speeds from 0.1 to 10 lengths/s from slack sarcomere lengths (SL) to SL of 2.15 μm. Viscosity was calculated from the slope of stress-relaxation vs stretch speed. Recombinant PEVK was added to compete off native interactions and this found to reduce the slope by 35%, suggesting that PEVK-actin interactions are a strong contributor of viscosity. Frequency sweeps were performed at frequencies of 0.1–400 Hz and recombinant protein reduced viscous moduli by 40% at 2.15 μm and by 50% at 2.25 μm, suggesting a SL-dependent nature of viscosity that might prevent SL “overshoot” at long diastolic SLs. This study is the first to show that viscosity is present at physiologic speeds in the pig and supports the physiologic relevance of PEVK-actin interactions in humans in both health and disease

Information capacity of genetic regulatory elements

Changes in a cell's external or internal conditions are usually reflected in the concentrations of the relevant transcription factors. These proteins in turn modulate the expression levels of the genes under their control and sometimes need to perform non-trivial computations that integrate several inputs and affect multiple genes. At the same time, the activities of the regulated genes would fluctuate even if the inputs were held fixed, as a consequence of the intrinsic noise in the system, and such noise must fundamentally limit the reliability of any genetic computation. Here we use information theory to formalize the notion of information transmission in simple genetic regulatory elements in the presence of physically realistic noise sources. The dependence of this "channel capacity" on noise parameters, cooperativity and cost of making signaling molecules is explored systematically. We find that, at least in principle, capacities higher than one bit should be achievable and that consequently genetic regulation is not limited the use of binary, or "on-off", components.Comment: 17 pages, 9 figure

Perspectiva del estudiantado de Medicina sobre los contenidos LGBT en el curriculum del Grado de Medicina en España en 2019: un estudio observacional transversal

Introduction: Lesbian, gay, bisexual, and transgender (LGBT) individuals face significant barriers in accessing appropriate and comprehensive medical care. The objective of this study is to evaluate the degree of preparedness and comfort autoperceived by spanish medical students and the factors that most determine their learning. Method: An online questionnaire (2019) was distributed to students (n=349) at 41 spanish medical schools. Results: Of 349 survey respondents, 326 were included in the final analysis. Globally, LGBT-related curricular content is taught to 16% (45/282) of medical students. Students often felt prepared addressing human immunodeficiency virus (170/309; 55%) and sexual orientation (149/305; 49%). They felt least prepared discussing barriers to accesing medical care (53/307; 17%) and sex reassignment surgery (61/306; 20%). Medical education helped 26,5% (82/310) of students feel “more prepared” and 22,4% (66/295) of students feel “more comfortable” to care for LGBT patients. Conclusion: sample size doesn’t allow us to make generalizations. However, our results show a trend that generally, Spanish medical students feel as comfortable as students from other countries but less prepared to care for LGBT patients. Interaction with their peers has been shown as the most important source of formation.Introducción: Las personas lesbianas, gays, bisexuales y transexuales (LGBT) se enfrentan a barreras en el acceso a una asistencia médica adecuada. El objetivo de este estudio es evaluar el grado de preparación y comodidad autopercibido del estudiantado de Medicina y los factores que más han determinado su aprendizaje. Métodos: En 2019 se realizó una encuesta online a estudiantes de Medicina de las 43 Facultades de Medicina españolas (n=349). Resultados: De 349 respuestas, 326 fueron finalmente analizadas. Globalmente el contenido referente a la salud de las personas LGBT se enseña a un 16% (45 de 282) de estudiantes de Medicina. Los estudiantes se sienten más preparados para abordar VIH en personas LGBT (170/309; 55%) y orientación sexual (149/305; 49%). Se sintieron menos preparados para abordar las dificultades en el acceso a los servicios de salud por parte de personas LGBT (53/307; 17%) y cirugías de reafirmación de sexo (61/306; 20%). La educación médica ayudó a que el 26,5% (82/310) de los estudiantes se sintiesen más preparados y a que el 22,4% (66/295) se sintiesen más cómodos en el trato con pacientes LGBT. Discusión: el tamaño de nuestra muestra no permite considerar los resultados como generalizables, pero sí que muestra una tendencia de que en general el estudiantado de medicina español, se siente igual de cómodo, pero menos preparado para abordar temas de salud LGBT que los estudiantes de medicina de otros países y que lo que más ha fomentado su formación en este sentido ha sido su interacción con otros estudiantes

Network integration meets network dynamics

Molecular interaction networks provide a window on the workings of the cell. However, combining various types of networks into one coherent large-scale dynamic model remains a formidable challenge. A recent paper in BMC Systems Biology describes a promising step in this direction

Multi-membership gene regulation in pathway based microarray analysis

This article is available through the Brunel Open Access Publishing Fund. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Gene expression analysis has been intensively researched for more than a decade. Recently, there has been elevated interest in the integration of microarray data analysis with other types of biological knowledge in a holistic analytical approach. We propose a methodology that can be facilitated for pathway based microarray data analysis, based on the observation that a substantial proportion of genes present in biochemical pathway databases are members of a number of distinct pathways. Our methodology aims towards establishing the state of individual pathways, by identifying those truly affected by the experimental conditions based on the behaviour of such genes. For that purpose it considers all the pathways in which a gene participates and the general census of gene expression per pathway. Results: We utilise hill climbing, simulated annealing and a genetic algorithm to analyse the consistency of the produced results, through the application of fuzzy adjusted rand indexes and hamming distance. All algorithms produce highly consistent genes to pathways allocations, revealing the contribution of genes to pathway functionality, in agreement with current pathway state visualisation techniques, with the simulated annealing search proving slightly superior in terms of efficiency. Conclusions: We show that the expression values of genes, which are members of a number of biochemical pathways or modules, are the net effect of the contribution of each gene to these biochemical processes. We show that by manipulating the pathway and module contribution of such genes to follow underlying trends we can interpret microarray results centred on the behaviour of these genes.The work was sponsored by the studentship scheme of the School of Information Systems, Computing and Mathematics, Brunel Universit

Classes of fast and specific search mechanisms for proteins on DNA

Problems of search and recognition appear over different scales in biological systems. In this review we focus on the challenges posed by interactions between proteins, in particular transcription factors, and DNA and possible mechanisms which allow for a fast and selective target location. Initially we argue that DNA-binding proteins can be classified, broadly, into three distinct classes which we illustrate using experimental data. Each class calls for a different search process and we discuss the possible application of different search mechanisms proposed over the years to each class. The main thrust of this review is a new mechanism which is based on barrier discrimination. We introduce the model and analyze in detail its consequences. It is shown that this mechanism applies to all classes of transcription factors and can lead to a fast and specific search. Moreover, it is shown that the mechanism has interesting transient features which allow for stability at the target despite rapid binding and unbinding of the transcription factor from the target.Comment: 65 pages, 23 figure

Variations in Stress Sensitivity and Genomic Expression in Diverse S. cerevisiae Isolates

Interactions between an organism and its environment can significantly influence phenotypic evolution. A first step toward understanding this process is to characterize phenotypic diversity within and between populations. We explored the phenotypic variation in stress sensitivity and genomic expression in a large panel of Saccharomyces strains collected from diverse environments. We measured the sensitivity of 52 strains to 14 environmental conditions, compared genomic expression in 18 strains, and identified gene copy-number variations in six of these isolates. Our results demonstrate a large degree of phenotypic variation in stress sensitivity and gene expression. Analysis of these datasets reveals relationships between strains from similar niches, suggests common and unique features of yeast habitats, and implicates genes whose variable expression is linked to stress resistance. Using a simple metric to suggest cases of selection, we found that strains collected from oak exudates are phenotypically more similar than expected based on their genetic diversity, while sake and vineyard isolates display more diverse phenotypes than expected under a neutral model. We also show that the laboratory strain S288c is phenotypically distinct from all of the other strains studied here, in terms of stress sensitivity, gene expression, Ty copy number, mitochondrial content, and gene-dosage control. These results highlight the value of understanding the genetic basis of phenotypic variation and raise caution about using laboratory strains for comparative genomics