889 resultados para Parker, Wilder


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Several lines of evidence point strongly toward the importance of highly alpha-helical intermediates in the folding of all globular proteins, regardless of their native structure. However, experimental refolding studies demonstrate no observable alpha-helical intermediate during refolding of some beta-sheet proteins and have dampened enthusiasm for this model of protein folding. In this study, beta-sheet proteins were hypothesized to have potential to form amphiphilic helices at a period of <3.6 residues/turn that matches or exceeds the potential at 3.6 residues/turn. Hypothetically, such potential is the basis for an effective and unidirectional mechanism by which highly alpha-helical intermediates might be rapidly disassembled during folding and potentially accounts for the difficulty in detecting highly alpha-helical intermediates during the folding of some proteins. The presence of this potential was confirmed, indicating that a model entailing ubiquitous formation of alpha-helical intermediates during the folding of globular proteins predicts previously unrecognized features of primary structure. Further, the folding of fatty acid binding protein, a predominantly beta-sheet protein that exhibits no apparent highly alpha-helical intermediate during folding, was dramatically accelerated by 2,2,2-trifluoroethanol, a solvent that stabilizes alpha-helical structure. This observation suggests that formation of an alpha-helix can be a rate-limiting step during folding of a predominantly beta-sheet protein and further supports the role of highly alpha-helical intermediates in the folding of all globular proteins.

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The neurodegenerative disease Friedreich's ataxia (FRDA) is the most common autosomal-recessively inherited ataxia and is caused by a GAA triplet repeat expansion in the first intron of the frataxin gene. In this disease, transcription of frataxin, a mitochondrial protein involved in iron homeostasis, is impaired, resulting in a significant reduction in mRNA and protein levels. Global gene expression analysis was performed in peripheral blood samples from FRDA patients as compared to controls, which suggested altered expression patterns pertaining to genotoxic stress. We then confirmed the presence of genotoxic DNA damage by using a gene-specific quantitative PCR assay and discovered an increase in both mitochondrial and nuclear DNA damage in the blood of these patients (p<0.0001, respectively). Additionally, frataxin mRNA levels correlated with age of onset of disease and displayed unique sets of gene alterations involved in immune response, oxidative phosphorylation, and protein synthesis. Many of the key pathways observed by transcription profiling were downregulated, and we believe these data suggest that patients with prolonged frataxin deficiency undergo a systemic survival response to chronic genotoxic stress and consequent DNA damage detectable in blood. In conclusion, our results yield insight into the nature and progression of FRDA, as well as possible therapeutic approaches. Furthermore, the identification of potential biomarkers, including the DNA damage found in peripheral blood, may have predictive value in future clinical trials.

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Gemstone Team Saving Testudo

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This dissertation project identifies important works for solo saxophone by United States composers between 1975 and 2005. The quality, variety, expressiveness, and difficulty of the solo saxophone repertoire during these thirty years is remarkable and remedies, to some extent, the fact that the saxophone had been a largely neglected instrument in the realm of classical music. In twentieth-century music, including Jazz, the saxophone developed, nevertheless, a unique and significant voice as is evident in the saxophone repertoire that expands immensely in many instrumental settings, including the orchestra, solo works, and a wide variety of chamber ensembles. Historically, the saxophone in the United States first found its niche in Vaudeville, military bands, and jazz ensembles, while in Europe composers such as Debussy, D'Indy, Schmitt, Ibert, Glazounov, Heiden, and Desenclos recognized the potential of the instrument and wrote for it. The saxophone is well suited to the intimacy and unique timbral explorations of the solo literature, but only by the middle twentieth century did the repertoire allow the instrument to flourish into a virtuosic and expressive voice presented by successive generations of performers â Marcel Mule, Sigurd Rascher, Cecil Leeson, Jean-Marie Londeix, Fred Hemke, Eugene Rousseau, and Donald Sinta. The very high artistic level of theses soloists was inspiring and dozens of new compositions were commissioned. Through the 1960âs American composers such as Paul Creston, Leslie Bassett, Henry Cowell, Alec Wilder, and others produced eminent works for the saxophone, to be followed by an enormous output of quality compositions between 1975 and 2005. The works chosen for performance were selected from thousands of compositions between 1975 and 2005 researched for this project. The three recital dates were: April 6, 2005, in Gildenhorn Recital Hall, December 4, 2005, in Ulrich Recital Hall, and April 15, 2006, in Gildenhorn Recital Hall. Recordings of these recitals may be obtained in person or online from the Michelle Smith Performing Arts Library of the University of Maryland, College Park.

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A lateral on-chip electron-impact ion source utilizing a carbon nanotube field emission electron source was fabricated and characterized. The device consists of a cathode with aligned carbon nanotubes, a control grid, and an ion collector electrode. The electron-impact ionization of He, Ar, and Xe was studied as a function of field emission current and pressure. The ion current was linear with respect to gas pressure from 10-4 to 10-1 Torr. The device can operate as a vacuum ion gauge with a sensitivity of approximately 1 Torr-1. Ion currents in excess of 1 μA were generated. © 2007 American Institute of Physics.

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Data from a hilly forest study site at Batang Ule, Sumatra, are organized into 30 100-m à 10-m subplots lying perpendicular to the line of maximal topographic gradient, from the valley to the plateau/ridge. The following methodological question is addressed: what species diversity measures are best used in order to reveal the ecologically distinct regions in the site. The main tool used to answer this question is the α-diversity curve (Hα). Graphical examination of tree and species densities, and α-diversity curves identifies an anomalous species diversity behaviour of the â˜ridge above the slopeâ subplots which may have implications on land-facet class definitions. Factor analysis of the α-diversity curves indicates that the diversity space is two-dimensional: i.e. two diversity measures are sufficient to characterize the site; the species density (H0), and the Berger-Parker index (H[infty infinity]). In the two-dimensional diversity-space three distinct species diversity groups are found which relate to the topographic gradient at the Batang Ule site. The results are compared with those for a flat homogeneous site at Pasirmayang, Sumatra. The implications of the results on land-classifications in species-diversity mapping and conservation strategy are discussed.

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Separation of the proteins comprising the crystalline style of the mussel Choromytilus meridionalis (Krauss) by anion exchange chromatography shows that there are three fractions displaying α-amylase activity in both warm- and cold-acclimated mussels. These fractions correspond with one or more proteins which remain unbound to the resin (Peak I), a bound fraction which is eluted at 100â150 mM NaCl (Peak II) and a further fraction which is eluted at 200â250 mM NaCl (Peak III) but which may represent contamination carried over from Peak II. Cold-acclimation to 8°C results in the appearance of a fourth α-amylase fraction (Peak IV) which is eluted from the column between 300â400 mM NaCl. Thermal acclimation also results in changes in the activities of Fractions IâIV such that a specific activity of 0.47 mg glucose liberated per A280 unit of protein per 8 min incubation at 8°C in Fraction IV is increased nearly 10-fold to a specific rate of 4.10 in protein Fraction I following acclimation to 22°C. It is suggested that an increased of digestive activity may be of equal importance to a suppression of metabolic costs in the maintenance of energy flow into growth and reproduction in ectothermic organisms which experience an increase of environmental temperature, especially in bivalves such as C. meridionalis which do not show a compensatory increase in filtration rate.

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Aquaculture is currently the fastest expanding global animal food production sector and is a key future contributor to food security. An increase in food security will be dependent upon the development and improvement of sustainable practices. A prioritization exercise was undertaken, focusing on the future knowledge needs to underpin UK sustainable aquaculture (both domestic and imported products) using a â˜task forceâ group of 36 â˜practitionersâ and 12 â˜research scientistsâ who have an active interest in sustainable aquaculture. A long list of 264 knowledge needs related to sustainable aquaculture was developed in conjunction with the task force. The long list was further refined through a three stage process of voting and scoring, including discussions of each knowledge need. The top 25 knowledge needs are presented, as scored separately by â˜practitionersâ or â˜research scientistsâ. There was similar agreement in priorities identified by these two groups. The priority knowledge needs will provide guidance to structure ongoing work to make science accessible to practitioners and help to prioritize future science policy needs and funding. The process of knowledge exchange, and the mechanisms by which this can be achieved, effectively emerged as the top priority for sustainable aquaculture. Viable alternatives to wild fish-based aquaculture feeds, resource constraints that will potentially limit expansion of aquaculture, sustainable offshore aquaculture and the treatment of sea lice also emerged as strong priorities. Although the exercise was focused on UK needs for sustainable aquaculture, many of the emergent issues are considered to have global application.

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