1,522 research outputs found

    Singing synthesis with an evolved physical model

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    A two-dimensional physical model of the human vocal tract is described. Such a system promises increased realism and control in the synthesis. of both speech and singing. However, the parameters describing the shape of the vocal tract while in use are not easily obtained, even using medical imaging techniques, so instead a genetic algorithm (GA) is applied to the model to find an appropriate configuration. Realistic sounds are produced by this method. Analysis of these, and the reliability of the technique (convergence properties) is provided

    Harnessing post-translational modifications for next-generation HIV immunogens

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    The extensive post-translational modifications of the envelope spikes of the human immunodeficiency virus (HIV) present considerable challenges and opportunities for HIV vaccine design. These oligomeric glycoproteins typically have over 30 disulfide bonds and around a 100 N-linked glycosylation sites, and are functionally dependent on protease cleavage within the secretory system. The resulting mature structure adopts a compact fold with the vast majority of its surface obscured by a protective shield of glycans which can be targeted by broadly neutralizing antibodies (bnAbs). Despite the notorious heterogeneity of glycosylation, rare B-cell lineages can evolve to utilize and cope with viral glycan diversity, and these structures therefore present promising targets for vaccine design. The latest generation of recombinant envelope spike mimetics contains re-engineered post-translational modifications to present stable antigens to guide the development of bnAbs by vaccination

    Changing Patterns of lung, liver, and head and neck non-AIDS-defining cancers relative to HIV status in Tanzania between 2002-2014

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    Abstract Background Tanzania, like other low-income countries, has an increasing cancer burden that remains underestimated. Infection-associated malignancies, particularly HIV-infection, represent a great proportion of cancer burden in Tanzania and throughout Africa. Availability of HIV treatment and improved survival of HIV patients are suggested factors related to increasing prevalence of non-AIDS-defining cancers (NADCs). This study examined patterns of NADCs and proportions of HIV-positivity at the Ocean Road Cancer Institute (ORCI). Methods We reviewed logbooks of all ORCI patients diagnosed and/or treated for lung, liver, and head and neck cancers during 2002–2014. The number of total cancers diagnosed at ORCI during this period was used to calculate proportions of NADCs. We abstracted medical records to obtain demographic and clinical profiles and HIV status information for 1127 patients diagnosed or treated during 2010–2014. Trends in numbers and proportions of NADCs were analyzed using Joinpoint regression. Characteristics of NADC patients were analyzed using multinomial logistic regression. Results NADCs diagnosed at ORCI increased by 33.8% from 2002 to 2014 while the proportion of NADCs relative to all cancers significantly decreased from 6.8% in 2002 to 5.6% in 2014 (APC = -2.74%). Numbers and proportions of lung and liver cancers increased compared to all cancer diagnoses from 2002 to 2014. The number of head and neck cancers increased while decreasing proportionally compared to all cancer diagnoses from 2002 to 2014. Among patients with pathologically confirmed NADCs between 2010 and 2014, HIV prevalence showed a non-statistically significant decrease from 8.1 to 7.1% (APC = -3.77%). Conclusions Absolute numbers of lung, liver, and head and neck cancers increased at ORCI by 1/3 since 2002. Improving survivorship of HIV patients and varying immunodeficiency status may have contributed to the increasing number of NADCs. Total cancer diagnoses nearly doubled during this period, leading to a smaller relative proportion of NADCs diagnosed in 2014 compared to 2002. Late- stage diagnosis and short survival of NADCs included this study may explain possible underestimation and smaller increase in proportion of these particular NADCs compared to other NADCs studied in Tanzania. The slight decrease in proportion of HIV-positive NADC patients during 2010–2014 may suggest increasing patient longevity and more effective HIV management in Tanzania.http://deepblue.lib.umich.edu/bitstream/2027.42/134744/1/13027_2016_Article_106.pd

    The structure of epitaxial V2O3 films and their surfaces : a medium energy ion scattering study

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    Medium energy ion scattering, using 100 keV H+ incident ions, has been used to investigate the growth of epitaxial films, up to thicknesses of ~200 Å, of V2O3 on both Pd(111) and Au(111). Scattered-ion energy spectra provide a measure of the average film thickness and the variations in this thickness, and show that, with suitable annealing, the crystalline quality is good. Plots of the scattering yield as a function of scattering angle, so-called blocking curves, have been measured for two different incidence directions and have been used to determine the surface structure. Specifically, scattering simulations for a range of different model structures show poor agreement with experiment for half-metal (….V’O3V) and vanadyl (….V’O3V=O) terminations, with and without surface interlayer relaxations. However, good agreement with experiment is found for the modified oxygen-termination structure, first proposed by Kresse et al., in which a subsurface V half-metal layer is moved up into the outermost V buckled metal layer to produce a VO2 overlayer on the underlying V2O3, with an associated layer structure of ….O3VV’’V’O3

    The changing pattern of ano-rectal cancer, squamous cell carcinoma of the eye, and Hodgkin’s lymphoma as non-AIDS-defining cancers, by HIV status, in Tanzania over 11 years (2002-2012): a retrospective case-report study

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    Abstract Background In Tanzania, 5.1% of adults aged 15-49 are infected with HIV. While rates of HIV-related malignancies have declined globally with antiretroviral therapy (ART), including Tanzania, rates of non-AIDS-defining cancers (NADCs) are believed to have increased. Therefore, we determined trends of three NADCs in Tanzania: ano-rectal cancer, squamous cell carcinoma of the eye, and Hodgkin’s lymphoma. Methods This study was conducted at the Ocean Road Cancer Institute (ORCI) in Dar es Salaam. All medical records of patients diagnosed with ano-rectal cancer, squamous cell carcinoma of the eye, and Hodgkin’s lymphoma between 2002 and 2012 were reviewed regarding HIV status, cancer clinical characteristics and management. Analysis was conducted to determine trends and proportions in these three NADCs and patient characteristics. Results We identified 980 NADCs. The relative proportion of these three NADCs at ORCI out of all cancers treated increased from 2.37% in 2002 to a peak of 4.34% in 2009. The prevalence of HIV in patients diagnosed with these NADCs also increased—from 6.67% in 2002 to 20.87% in 2010—and 85% of squamous cell carcinoma of the eye cancer patients with a reported HIV status were HIV-positive. Conclusions The frequency and proportions of these three NADCs in Tanzania have increased over the past 11 years, as has the prevalence of HIV positivity amongst these NADC patients. The current and possibly increasing burden of NADCs in Tanzania and other low- and middle-income countries with high HIV rates should be a focus for future cancer prevention and control and HIV therapy programs.http://deepblue.lib.umich.edu/bitstream/2027.42/111050/1/13027_2014_Article_524.pd

    Four-Hundred-and-Ninety-Million-Year Record of Bacteriogenic Iron Oxide Precipitation at Sea-Floor Hydrothermal Vents

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    Fe oxide deposits are commonly found at hydrothermal vent sites at mid-ocean ridge and back-arc sea floor spreading centers, seamounts associated with these spreading centers, and intra-plate seamounts, and can cover extensive areas of the seafloor. These deposits can be attributed to several abiogenic processes and commonly contain micron-scale filamentous textures. Some filaments are cylindrical casts of Fe oxyhydroxides formed around bacterial cells and are thus unquestionably biogenic. The filaments have distinctive morphologies very like structures formed by neutrophilic Fe oxidizing bacteria. It is becoming increasingly apparent that Fe oxidizing bacteria have a significant role in the formation of Fe oxide deposits at marine hydrothermal vents. The presence of Fe oxide filaments in Fe oxides is thus of great potential as a biomarker for Fe oxidizing bacteria in modern and ancient marine hydrothermal vent deposits. The ancient analogues of modern deep-sea hydrothermal Fe oxide deposits are jaspers. A number of jaspers, ranging in age from the early Ordovician to late Eocene, contain abundant Fe oxide filamentous textures with a wide variety of morphologies. Some of these filaments are like structures formed by modern Fe oxidizing bacteria. Together with new data from the modern TAG site, we show that there is direct evidence for bacteriogenic Fe oxide precipitation at marine hydrothermal vent sites for at least the last 490 Ma of the Phanerozoic

    A comparison of massively parallel nucleotide sequencing with oligonucleotide microarrays for global transcription profiling

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    <p>Abstract</p> <p>Background</p> <p>RNA-Seq exploits the rapid generation of gigabases of sequence data by Massively Parallel Nucleotide Sequencing, allowing for the mapping and digital quantification of whole transcriptomes. Whilst previous comparisons between RNA-Seq and microarrays have been performed at the level of gene expression, in this study we adopt a more fine-grained approach. Using RNA samples from a normal human breast epithelial cell line (MCF-10a) and a breast cancer cell line (MCF-7), we present a comprehensive comparison between RNA-Seq data generated on the Applied Biosystems SOLiD platform and data from Affymetrix Exon 1.0ST arrays. The use of Exon arrays makes it possible to assess the performance of RNA-Seq in two key areas: detection of expression at the granularity of individual exons, and discovery of transcription outside annotated loci.</p> <p>Results</p> <p>We found a high degree of correspondence between the two platforms in terms of exon-level fold changes and detection. For example, over 80% of exons detected as expressed in RNA-Seq were also detected on the Exon array, and 91% of exons flagged as changing from Absent to Present on at least one platform had fold-changes in the same direction. The greatest detection correspondence was seen when the read count threshold at which to flag exons Absent in the SOLiD data was set to <it>t</it><1 suggesting that the background error rate is extremely low in RNA-Seq. We also found RNA-Seq more sensitive to detecting differentially expressed exons than the Exon array, reflecting the wider dynamic range achievable on the SOLiD platform. In addition, we find significant evidence of novel protein coding regions outside known exons, 93% of which map to Exon array probesets, and are able to infer the presence of thousands of novel transcripts through the detection of previously unreported exon-exon junctions.</p> <p>Conclusions</p> <p>By focusing on exon-level expression, we present the most fine-grained comparison between RNA-Seq and microarrays to date. Overall, our study demonstrates that data from a SOLiD RNA-Seq experiment are sufficient to generate results comparable to those produced from Affymetrix Exon arrays, even using only a single replicate from each platform, and when presented with a large genome.</p

    An automatic corpus based method for a building Multiple Fuzzy Word Dataset

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    Fuzzy sentence semantic similarity measures are designed to be applied to real world problems where a computer system is required to assess the similarity between human natural language and words or prototype sentences stored within a knowledge base. Such measures are often developed for a specific corpus/domain where a limited set of words and sentences are evaluated. As new “fuzzy” measures are developed the research challenge is on how to evaluate them. Traditional approaches have involved rigorous and complex human involvement in compiling benchmark datasets and obtaining human similarity measures. Existing datasets often contain limited fuzzy words and do allow the fuzzy measures to be exhaustively tested. This paper presents an automatic method for the generation of a Multiple Fuzzy Word Dataset (MFWD) from a corpus. A Fuzzy Sentence Pairing Algorithm is used to extract and augment high, medium and low similarity sentence pairs with multiple fuzzy words. Human ratings are collected through crowdsourcing and the MFWD is evaluated using both fuzzy and traditional sentence similarity measures. The results indicated that fuzzy measures returned a higher correlation with human ratings compared with traditional measures

    The utility of MAS5 expression summary and detection call algorithms

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    <p>Abstract</p> <p>Background</p> <p>Used alone, the MAS5.0 algorithm for generating expression summaries has been criticized for high False Positive rates resulting from exaggerated variance at low intensities.</p> <p>Results</p> <p>Here we show, with replicated cell line data, that, when used alongside detection calls, MAS5 can be both selective and sensitive. A set of differentially expressed transcripts were identified that were found to be changing by MAS5, but unchanging by RMA and GCRMA. Subsequent analysis by real time PCR confirmed these changes. In addition, with the Latin square datasets often used to assess expression summary algorithms, filtered MAS5.0 was found to have performance approaching that of its peers.</p> <p>Conclusion</p> <p>When used alongside detection calls, MAS5 is a sensitive and selective algorithm for identifying differentially expressed genes.</p
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