938 research outputs found
Genome Majority Vote Improves Gene Predictions
No full textMichael E. Wall is with Los Alamos National Laboratory, Sindhu Raghavan is with UT Austin and Los Alamos National Laboratory, Judith D. Cohn is with Los Alamos National Laboratory, John Dunbar is with Los Alamos National Laboratory.Recent studies have noted extensive inconsistencies in gene start sites among orthologous genes in related microbial genomes. Here we provide the first documented evidence that imposing gene start consistency improves the accuracy of gene start-site prediction. We applied an algorithm using a genome majority vote (GMV) scheme to increase the consistency of gene starts among orthologs. We used a set of validated Escherichia coli genes as a standard to quantify accuracy. Results showed that the GMV algorithm can correct hundreds of gene prediction errors in sets of five or ten genomes while introducing few errors. Using a conservative calculation, we project that GMV would resolve many inconsistencies and errors in publicly available microbial gene maps. Our simple and logical solution provides a notable advance toward accurate gene maps.This work was primarily funded by Los Alamos National Laboratory Directed Research and Development program (LDRD) grant 20080138DR. MEW and JDC received additional support from NIH/National Library of Medicine grant R01LM010120, and MEW received additional support from LDRD grant 20110435DR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Computer Scienc
Michel Foucault and Judith Butler: troubling Butler's appropriation of Foucault's work
No full textOne of the main influences on Judith Butler‘s thinking has been the work of Michel Foucault. Although this relationship is often commented on, it is rarely discussed in any detail. My thesis makes a contribution in this area. It presents an analysis of Foucault‘s work with the aim of countering Butler‘s representation of his thinking. In the first part of the thesis, I show how Butler initially interprets Foucault‘s project through Nietzschean genealogy, psychoanalysis and Derridean discourse, and how she later develops this interpretation in line with the progress of her own project. In the main part of the thesis, I present an analysis of Foucault‘s thinking in the period from The Archaeology of Knowledge (1969) to The History of Sexuality volume 1 (1976). This analysis focuses on the aspect of his work which has most influenced Butler‘s thinking: namely the notion of a relationship between knowledge, discourse and power. The other issues in his work which Butler addresses—genealogy, the subject, the body, abnormality, and sexuality—are discussed within this framework. I show how, in the early 1970s, Foucault develops the notion of power-knowledge, and sets out a relationship between power-knowledge and discourse which is overlooked by Butler. I argue that Butler interprets Foucaultian power through the notions of repression and social norms, and ignores the concepts of technology and strategy which form a key part of Foucault‘s thinking. I show how, from The Archaeology of Knowledge on, Foucault develops a socio-historical ontology and a genealogy of the subject, both of which are at variance with Butler‘s interpretation of his thinking
International year of older persons: Mentoring research project
No full textA report, by Judith MacCallum and Susan Beltman, Murdoch University, that identifies models of good practice of mentoring in school settings. The report looks at issues associated with the implementation of mentoring programs in school settings and key recommendations for consideration by Australian schools and education systems
Hydrothermal growth and characterization of titanium dioxide nanostructures for use in dye sensitized solar cells
No full textAs the world's energy needs continue to grow, next generation photovoltaic cells are in high demand because they offer the possibility of an inexpensive alternative to current energy production techniques. Dye sensitized solar cells (DSSC's), utilize common materials and low cost commercialization techniques, which make them a compelling choice for research in this area. This research focuses on the titanium dioxide coating, which transfers electrons from the photoactive dye to the electrode. 3-4% efficient DSSC's using doctor bladed titanium dioxide coatings with a specific surface area of 55-60m2/g have been demonstrated in our laboratory. To enhance the efficiency of these cells, both the surface area and the electron conduction of the titania layer must be optimized. This has been done by utilizing high aspect ratio nanoparticles of titania instead of mesoporous layers formed with spherical particles. Anodization of titanium metal or anodic alumina membrane templating are common ways to produce nanorods, but involve complex processes leading toward expensive commercialization. This research instead focuses on the hydrothermal growth of nanofibrous titania on a titanium metal substrate, removing the need for dispersion and deposition procedures as well as using a low temperature processing method. Depending upon the formulation utilized, a variety of structures can be produced, from thick carpets of nanofiber strands to large platelets. The composition and morphology of the products have been characterized with respect to the growth conditions using electron microscopy, energy dispersive spectroscopy and x-ray diffraction. The compositional analysis is used to investigate the complicated reaction mechanisms in the system. Coatings of titania nanotubes were then tested in the DSSC's, as were those with the titanium metal substrate acting as the photo anode. Modeling the geometric parameters of the different pore structures of the coatings helps us to understand the advantages afforded by these new cells.Ph.D.Includes bibliographical references (p. 164-172)by Judith D. Sorg
Between the waves: currents in contemporary feminist thought
No full textWith a continuing focus on liberal feminism, Marxist feminism and essentialism, one would be forgiven for
thinking that feminist theory is unable to break free from the ‘second wave’. This is not the case. This article reviews three books which take on these feminist issues and offer new readings on the questions at the heart of feminism. Each provides clear links to feminism of the past but also connects to present debate and makes
suggestions for future directions for feminism. There is plenty of literature which bemoans the end of feminism and some which triumphantly hails our era as post-feminist: no longer in need of feminist theory. Contrary to such claims, each book tackles the problem of women’s oppression from a different perspective, each presents different solutions and in so doing they demonstrate that feminism is alive and well
XLBlocks: a Block-based Formula Editor for Spreadsheet Formulas
No full textSpreadsheets are frequently used in industry to support critical business decisions. Unfortunately, they also suffer from error-proneness, which sometimes results in costly consequences. Experiments in the field of program education have shown that programmers tend to make fewer errors and can better focus on the logic of a program if they use a block-based language instead of a textual one. We hypothesize that a block-based formula editor could support spreadsheet users in a similar way. Therefore, we develop XLBlocks and conduct a think-aloud study with 13 experienced spreadsheet users from industry. Participants are asked to create and edit several formulas, using our block-based language. We then ask them to evaluate this editor using the Cognitive Dimensions of Notations framework. We found that for all dimensions the block-based formula editor received a better evaluation than the default text-based formula editor.Accepted author manuscriptSoftware Engineerin
Prediction of Functional Sites in SCOP Domains using Dynamics Perturbation Analysis
No full textDynamics perturbation analysis (DPA) finds regions in a protein structure where proteins are "ticklish", i.e., where interactions cause a large change in protein dynamics. Previously, such regions were shown to predict the location of native binding sites in a docking test set, but the more general applicability of DPA to the prediction of functional sites in proteins was not shown. Here we describe the results of applying an accelerated algorithm, called Fast DPA, to predict functional sites in over 50,000 SCOP domains
Modulation of ion channels by natural products - identification of hERG channel inhibitors and GABAA receptor ligands from plant extracts
No full textIon channels are expressed in virtually all cell types in the human body and are involved in various physiological processes. Hence, it is not surprising that ion channels play an important role in modern drug discovery. Lead compounds are nowadays routinely tested against a panel of ion channels to evaluate selectivity and potential off-target activities.
The human ether-à-go-go-related gene (hERG) channel, a voltage-gated potassium channel, is the currently most critical antitarget with respect to cardiac safety. Inhibition of the hERG channel can prolong the QT interval on the electrocardiogram (ECG) and, as a consequence, lead to life-threatening arrhythmia. Considering the daily intake of plant-derived foods and herbal products, surprisingly few natural products have been tested for hERG blocking properties. In the course of an interdisciplinary hERG project, a selection of widely used herbal drugs and dietary plants was screened by means of a two-microelectrode voltage-clamp assay with Xenopus oocytes. Moderate hERG block was observed for the traditional Chinese herbal drug Coptidis rhizoma and black pepper fruits, and successfully tracked by HPLC-based activity profiling to dihydroberberine and piperine, respectively. The hERG blocking activity of cinnamon, guarana, and nutmeg, in contrast, was attributed to tannins. Our screening data suggest that major European medicinal plants and frequently consumed food plants are associated with a low risk for hERG inhibition. However, the case of Coptidis rhizoma pointed towards a need for a more thorough assessment of herbal drugs of the traditional Chinese medicine (TCM). Subsequent screening of a plant-derived alkaloid library led to the identification of several potent hERG blockers. Further investigations are certainly warranted to assess the cardiac safety profile of these alkaloids.
Dehydroevodiamine (DHE), a major bioactive constituent of the traditional Chinese herbal drug Evodiae fructus, has been previously shown to inhibit several cardiac ion currents in vitro. For further evaluation of its in vivo pharmacological and toxicological properties, gram amounts of DHE were needed. Since DHE is not commercially available, we developed an efficient method for its gram-scale isolation from a crude Evodia extract. Our approach is based on a combination of cation-exchange chromatography and preparative RP-HPLC. Moreover, the DHE content in commercially available Evodia products was assessed by HPLC-PDA analysis. A daily intake of up to mg amounts of DHE was calculated from recommended doses of these products. We also devised a procedure for the production of DHE-depleted Evodia products, should DHE indeed turn out to be toxicologically relevant.
The gamma-aminobutyric acid type A (GABAA) receptor, a ligand-gated chloride channel, mediates fast inhibitory neurotransmission in the central nervous system (CNS), and is thus a clinically important drug target. In the search for positive α1β2γ2S GABAA receptor modulators of plant origin, we investigated an extract of Curcuma kwangsiensis rhizomes. HPLC-based activity profiling was used in combination with a two-microelectrode voltage-clamp assay on Xenopus oocytes to identify the active constituents. Targeted isolation afforded a series of 11 structurally related labdane diterpenoids, including four new natural products. Structure elucidation was achieved by comprehensive analysis of HR-ESI-TOF-MS and NMR data. The absolute configuration of the compounds was assigned by electronic circular dichroism (ECD). The highest GABAA receptor modulating activity was observed for zerumin A.
From a more general perspective, this study demonstrates that HPLC-based activity profiling is an effective strategy to characterize bioactive compounds in crude natural extracts
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