2,328 research outputs found

    Collaborative virtual 3D environment for internet-accessible physics experiments

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    Immersive 3D worlds have increasingly raised the interest of researchers and practitioners for various learning and training settings over the last decade. These virtual worlds can provide multiple communication channels betweeen users and improve presence and awareness in the learning process. Consequently virtual 3D environments facilitate collaborative learning and training scenarios. In this paper we focus on the integration of internet-accessible physics experiments (iLabs) combined with the TEALsim 3D simulation toolkit in project Wonderland, Sun's toolkit for creating collaborative 3D virtual worlds. Within such a collaborative environment these tools provide the opportunity for teachers and students to work together as avatars as they control actual equipment, visualize physical phenomenon generated by the experiment, and discuss the results. In particular we will outline the steps of integration, future goals, as well as the value of a collaboration space in Wonderland's virtual world

    Community-linked maternal death review (CLMDR) to measure and prevent maternal mortality: a pilot study in rural Malawi.

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    In Malawi, maternal mortality remains high. Existing maternal death reviews fail to adequately review most deaths, or capture those that occur outside the health system. We assessed the value of community involvement to improve capture and response to community maternal deaths

    Routine activities and proactive police activity: a macro-scale analysis of police searches in London and New York City

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    This paper explored how city-level changes in routine activities were associated with changes in frequencies of police searches using six years of police records from the London Metropolitan Police Service and the New York City Police Department. Routine activities were operationalised through selecting events that potentially impacted on (a) the street population, (b) the frequency of crime or (c) the level of police activity. OLS regression results indicated that routine activity variables (e.g. day of the week, periods of high demand for police service) can explain a large proportion of the variance in search frequency throughout the year. A complex set of results emerged, revealing cross-national dissimilarities and the differential impact of certain activities (e.g. public holidays). Importantly, temporal frequencies in searches are not reducible to associations between searches and recorded street crime, nor changes in on-street population. Based on the routine activity approach, a theoretical police-action model is proposed

    Recent advances in the genetics of SDH-related paraganglioma and pheochromocytoma

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    The last 10 years have seen enormous progress in the field of paraganglioma and pheochromocytoma genetics. The identification of the first gene related to paraganglioma, SDHD, encoding a subunit of mitochondrial succinate dehydrogenase (SDH), was quickly followed by the identification of mutations in SDHC and SDHB. Very recently several new SDH-related genes have been discovered. The SDHAF2 gene encodes an SDH co-factor related to the function of the SDHA subunit, and is currently exclusively associated with head and neck paragangliomas. SDHA itself has now also been identified as a paraganglioma gene, with the recent identification of the first mutation in a patient with extra-adrenal paraganglioma. Another SDH-related co-factor, SDHAF1, is not currently known to be a tumor suppressor, but may shed some light on the mechanisms of tumorigenesis. An entirely novel gene associated with adrenal pheochromocytoma, TMEM127, suggests that other new paraganglioma susceptibility genes may await discovery. In addition to these recent discoveries, new techniques related to mutation analysis, including genetic analysis algorithms, SDHB immunohistochemistry, and deletion analysis by MLPA have improved the efficiency and accuracy of genetic analysis. However, many intriguing questions remain, such as the striking differences in the clinical phenotype of genes that encode proteins with an apparently very close functional relationship, and the lack of expression of SDHD and SDHAF2 mutations when inherited via the maternal line. Little is still known of the origins and causes of truly sporadic tumors, and the role of oxygen in the relationships between high-altitude, familial and truly sporadic paragangliomas remains to be elucidated

    The first Dutch SDHB founder deletion in paraganglioma – pheochromocytoma patients

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    Contains fulltext : 81280.pdf (publisher's version ) (Open Access)BACKGROUND: Germline mutations of the tumor suppressor genes SDHB, SDHC and SDHD play a major role in hereditary paraganglioma and pheochromocytoma. These three genes encode subunits of succinate dehydrogenase (SDH), the mitochondrial tricarboxylic acid cycle enzyme and complex II component of the electron transport chain. The majority of variants of the SDH genes are missense and nonsense mutations. To date few large deletions of the SDH genes have been described. METHODS: We carried out gene deletion scanning using MLPA in 126 patients negative for point mutations in the SDH genes. We then proceeded to the molecular characterization of deletions, mapping breakpoints in each patient and used haplotype analysis to determine whether the deletions are due to a mutation hotspot or if a common haplotype indicated a single founder mutation. RESULTS: A novel deletion of exon 3 of the SDHB gene was identified in nine apparently unrelated Dutch patients. An identical 7905 bp deletion, c.201-4429_287-933del, was found in all patients, resulting in a frameshift and a predicted truncated protein, p.Cys68HisfsX21. Haplotype analysis demonstrated a common haplotype at the SDHB locus. Index patients presented with pheochromocytoma, extra-adrenal PGL and HN-PGL. A lack of family history was seen in seven of the nine cases. CONCLUSION: The identical exon 3 deletions and common haplotype in nine patients indicates that this mutation is the first Dutch SDHB founder mutation. The predominantly non-familial presentation of these patients strongly suggests reduced penetrance. In this small series HN-PGL occurs as frequently as pheochromocytoma and extra-adrenal PGL

    Conformational effects on the Circular Dichroism of Human Carbonic Anhydrase II: a multilevel computational study

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    Circular Dichroism (CD) spectroscopy is a powerful method for investigating conformational changes in proteins and therefore has numerous applications in structural and molecular biology. Here a computational investigation of the CD spectrum of the Human Carbonic Anhydrase II (HCAII), with main focus on the near-UV CD spectra of the wild-type enzyme and it seven tryptophan mutant forms, is presented and compared to experimental studies. Multilevel computational methods (Molecular Dynamics, Semiempirical Quantum Mechanics, Time-Dependent Density Functional Theory) were applied in order to gain insight into the mechanisms of interaction between the aromatic chromophores within the protein environment and understand how the conformational flexibility of the protein influences these mechanisms. The analysis suggests that combining CD semi empirical calculations, crystal structures and molecular dynamics (MD) could help in achieving a better agreement between the computed and experimental protein spectra and provide some unique insight into the dynamic nature of the mechanisms of chromophore interactions
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