458 research outputs found

    Integrating Communication Skills and Planning Techniques

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    Practitioners have long stressed the need to teach professional commumcations skills to planning students. This paper describes ten years of experience in teaching a course in which communications skills and techniques of gathering and analyzing information are taught concurrently while investigating a problem of importance in the community. The course involves an ongoing collaboration, a "marriage of convenience," between an academic and a planner, casting city/county planning staff as clients for students This has proven useful for pedagogy and has had some positive impact on the community.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69149/2/10.1177_0739456X9201100206.pd

    Global organization of metabolic fluxes in the bacterium, Escherichia coli

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    Cellular metabolism, the integrated interconversion of thousands of metabolic substrates through enzyme-catalyzed biochemical reactions, is the most investigated complex intercellular web of molecular interactions. While the topological organization of individual reactions into metabolic networks is increasingly well understood, the principles governing their global functional utilization under different growth conditions pose many open questions. We implement a flux balance analysis of the E. coli MG1655 metabolism, finding that the network utilization is highly uneven: while most metabolic reactions have small fluxes, the metabolism's activity is dominated by several reactions with very high fluxes. E. coli responds to changes in growth conditions by reorganizing the rates of selected fluxes predominantly within this high flux backbone. The identified behavior likely represents a universal feature of metabolic activity in all cells, with potential implications to metabolic engineering.Comment: 15 pages 4 figure

    Functional characterization of a melon alcohol acyl-transferase gene family involved in the biosynthesis of ester volatiles. Identification of the crucial role of a threonine residue for enzyme activity

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    Volatile esters, a major class of compounds contributing to the aroma of many fruit, are synthesized by alcohol acyl-transferases (AAT). We demonstrate here that, in Charentais melon (Cucumis melo var. cantalupensis), AAT are encoded by a gene family of at least four members with amino acid identity ranging from 84% (Cm-AAT1/Cm-AAT2) and 58% (Cm-AAT1/Cm-AAT3) to only 22% (Cm-AAT1/Cm-AAT4). All encoded proteins, except Cm-AAT2, were enzymatically active upon expression in yeast and show differential substrate preferences. Cm-AAT1 protein produces a wide range of short and long-chain acyl esters but has strong preference for the formation of E-2-hexenyl acetate and hexyl hexanoate. Cm-AAT3 also accepts a wide range of substrates but with very strong preference for producing benzyl acetate. Cm-AAT4 is almost exclusively devoted to the formation of acetates, with strong preference for cinnamoyl acetate. Site directed mutagenesis demonstrated that the failure of Cm-AAT2 to produce volatile esters is related to the presence of a 268-alanine residue instead of threonine as in all active AAT proteins. Mutating 268-A into 268-T of Cm-AAT2 restored enzyme activity, while mutating 268-T into 268-A abolished activity of Cm-AAT1. Activities of all three proteins measured with the prefered substrates sharply increase during fruit ripening. The expression of all Cm-AAT genes is up-regulated during ripening and inhibited in antisense ACC oxidase melons and in fruit treated with the ethylene antagonist 1-methylcyclopropene (1-MCP), indicating a positive regulation by ethylene. The data presented in this work suggest that the multiplicity of AAT genes accounts for the great diversity of esters formed in melon

    High and low density patches in simulated liquid water

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    We present insights into the nature of structural heterogeneities in liquid water by characterizing the empty space within the hydrogen bond network. Using molecular dynamics simulations, we show that density fluctuations create regions of empty space characterized by a diverse morphology – from spherical to fractal-like voids. These voids allow for the identification of low and high density patches of the liquid, encompassing short (0.3-0.5 nm) as well as long (1-2 nm) length-scales. In addition, we show that the formation of these patches is coupled to collective fluctuations involving the topology of hydrogen-bonded rings of water molecules. In particular, water molecules in the high density patches tend to be slightly more tetrahedral – which is consistent with the predictions of the hydrophobic effect

    Opinion dynamics: models, extensions and external effects

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    Recently, social phenomena have received a lot of attention not only from social scientists, but also from physicists, mathematicians and computer scientists, in the emerging interdisciplinary field of complex system science. Opinion dynamics is one of the processes studied, since opinions are the drivers of human behaviour, and play a crucial role in many global challenges that our complex world and societies are facing: global financial crises, global pandemics, growth of cities, urbanisation and migration patterns, and last but not least important, climate change and environmental sustainability and protection. Opinion formation is a complex process affected by the interplay of different elements, including the individual predisposition, the influence of positive and negative peer interaction (social networks playing a crucial role in this respect), the information each individual is exposed to, and many others. Several models inspired from those in use in physics have been developed to encompass many of these elements, and to allow for the identification of the mechanisms involved in the opinion formation process and the understanding of their role, with the practical aim of simulating opinion formation and spreading under various conditions. These modelling schemes range from binary simple models such as the voter model, to multi-dimensional continuous approaches. Here, we provide a review of recent methods, focusing on models employing both peer interaction and external information, and emphasising the role that less studied mechanisms, such as disagreement, has in driving the opinion dynamics. [...]Comment: 42 pages, 6 figure

    A proteogenomic update to Yersinia: enhancing genome annotation

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    <p>Abstract</p> <p>Background</p> <p>Modern biomedical research depends on a complete and accurate proteome. With the widespread adoption of new sequencing technologies, genome sequences are generated at a near exponential rate, diminishing the time and effort that can be invested in genome annotation. The resulting gene set contains numerous errors in even the most basic form of annotation: the primary structure of the proteins.</p> <p>Results</p> <p>The application of experimental proteomics data to genome annotation, called proteogenomics, can quickly and efficiently discover misannotations, yielding a more accurate and complete genome annotation. We present a comprehensive proteogenomic analysis of the plague bacterium, <it>Yersinia pestis KIM</it>. We discover non-annotated genes, correct protein boundaries, remove spuriously annotated ORFs, and make major advances towards accurate identification of signal peptides. Finally, we apply our data to 21 other <it>Yersinia </it>genomes, correcting and enhancing their annotations.</p> <p>Conclusions</p> <p>In total, 141 gene models were altered and have been updated in RefSeq and Genbank, which can be accessed seamlessly through any NCBI tool (e.g. blast) or downloaded directly. Along with the improved gene models we discover new, more accurate means of identifying signal peptides in proteomics data.</p

    inGeno – an integrated genome and ortholog viewer for improved genome to genome comparisons

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    BACKGROUND: Systematic genome comparisons are an important tool to reveal gene functions, pathogenic features, metabolic pathways and genome evolution in the era of post-genomics. Furthermore, such comparisons provide important clues for vaccines and drug development. Existing genome comparison software often lacks accurate information on orthologs, the function of similar genes identified and genome-wide reports and lists on specific functions. All these features and further analyses are provided here in the context of a modular software tool "inGeno" written in Java with Biojava subroutines. RESULTS: InGeno provides a user-friendly interactive visualization platform for sequence comparisons (comprehensive reciprocal protein – protein comparisons) between complete genome sequences and all associated annotations and features. The comparison data can be acquired from several different sequence analysis programs in flexible formats. Automatic dot-plot analysis includes output reduction, filtering, ortholog testing and linear regression, followed by smart clustering (local collinear blocks; LCBs) to reveal similar genome regions. Further, the system provides genome alignment and visualization editor, collinear relationships and strain-specific islands. Specific annotations and functions are parsed, recognized, clustered, logically concatenated and visualized and summarized in reports. CONCLUSION: As shown in this study, inGeno can be applied to study and compare in particular prokaryotic genomes against each other (gram positive and negative as well as close and more distantly related species) and has been proven to be sensitive and accurate. This modular software is user-friendly and easily accommodates new routines to meet specific user-defined requirements

    Functional diversity of chemokines and chemokine receptors in response to viral infection of the central nervous system.

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    Encounters with neurotropic viruses result in varied outcomes ranging from encephalitis, paralytic poliomyelitis or other serious consequences to relatively benign infection. One of the principal factors that control the outcome of infection is the localized tissue response and subsequent immune response directed against the invading toxic agent. It is the role of the immune system to contain and control the spread of virus infection in the central nervous system (CNS), and paradoxically, this response may also be pathologic. Chemokines are potent proinflammatory molecules whose expression within virally infected tissues is often associated with protection and/or pathology which correlates with migration and accumulation of immune cells. Indeed, studies with a neurotropic murine coronavirus, mouse hepatitis virus (MHV), have provided important insight into the functional roles of chemokines and chemokine receptors in participating in various aspects of host defense as well as disease development within the CNS. This chapter will highlight recent discoveries that have provided insight into the diverse biologic roles of chemokines and their receptors in coordinating immune responses following viral infection of the CNS

    Decreased DGCR8 expression and miRNA dysregulation in individuals with 22q11.2 deletion syndrome

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    Deletion of the 1.5-3 Mb region of chromosome 22 at locus 11.2 gives rise to the chromosome 22q11.2 deletion syndrome (22q11DS), also known as DiGeorge and Velocardiofacial Syndromes. It is the most common micro-deletion disorder in humans and one of the most common multiple malformation syndromes. The syndrome is characterized by a broad phenotype, whose characterization has expanded considerably within the last decade and includes many associated findings such as craniofacial anomalies (40%), conotruncal defects of the heart (CHD; 70-80%), hypocalcemia (20-60%), and a range of neurocognitive anomalies with high risk of schizophrenia, all with a broad phenotypic variability. These phenotypic features are believed to be the result of a change in the copy number or dosage of the genes located in the deleted region. Despite this relatively clear genetic etiology, very little is known about which genes modulate phenotypic variations in humans or if they are due to combinatorial effects of reduced dosage of multiple genes acting in concert. Here, we report on decreased expression levels of genes within the deletion region of chromosome 22, including DGCR8, in peripheral leukocytes derived from individuals with 22q11DS compared to healthy controls. Furthermore, we found dysregulated miRNA expression in individuals with 22q11DS, including miR-150, miR-194 and miR-185. We postulate this to be related to DGCR8 haploinsufficiency as DGCR8 regulates miRNA biogenesis. Importantly we demonstrate that the level of some miRNAs correlates with brain measures, CHD and thyroid abnormalities, suggesting that the dysregulated miRNAs may contribute to these phenotypes and/or represent relevant blood biomarkers of the disease in individuals with 22q11DS
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