Optimizing Spatiotemporal Analysis Using Multidimensional Indexing with GeoWave

The open source software GeoWave bridges the gap between geographic information systems and distributed computing. This is done by preserving locality of multidimensional data when indexing it into a single-dimensional key-value store, using space filling curves. This means that like values in each dimension are stored physically close together in the datastore. We demonstrate the efficiencies and benefits of the GeoWave indexing algorithm to store and query billions of spatiotemporal data points. We show how this indexing strategy can be used to reduce query and processing times by multiple orders of magnitude using publicly available taxi trip data published by the New York City Taxi & Limousine Commission. Furthermore, we demonstrate how this efficiency lends itself to analysis that would otherwise be unfeasible

Hydropower plans in eastern and southern Africa increase risk of concurrent climate-related electricity supply disruption

Hydropower comprises a significant and rapidly expanding proportion of electricity production in eastern and southern Africa. In both regions, hydropower is exposed to high levels of climate variability and regional climate linkages are strong, yet an understanding of spatial interdependences is lacking. Here we consider river basin configuration and define regions of coherent rainfall variability using cluster analysis to illustrate exposure to the risk of hydropower supply disruption of current (2015) and planned (2030) hydropower sites. Assuming completion of the dams planned, hydropower will become increasingly concentrated in the Nile (from 62% to 82% of total regional capacity) and Zambezi (from 73% to 85%) basins. By 2030, 70% and 59% of total hydropower capacity will be located in one cluster of rainfall variability in eastern and southern Africa, respectively, increasing the risk of concurrent climate-related electricity supply disruption in each region. Linking of nascent regional electricity sharing mechanisms could mitigate intraregional risk, although these mechanisms face considerable political and infrastructural challenges

Intra- and Inter-Tumor Heterogeneity of BRAFV600EMutations in Primary and Metastatic Melanoma

The rationale for using small molecule inhibitors of oncogenic proteins as cancer therapies depends, at least in part, on the assumption that metastatic tumors are primarily clonal with respect to mutant oncogene. With the emergence of BRAFV600E as a therapeutic target, we investigated intra- and inter-tumor heterogeneity in melanoma using detection of the BRAFV600E mutation as a marker of clonality. BRAF mutant-specific PCR (MS-PCR) and conventional sequencing were performed on 112 tumors from 73 patients, including patients with matched primary and metastatic specimens (n = 18). Nineteen patients had tissues available from multiple metastatic sites. Mutations were detected in 36/112 (32%) melanomas using conventional sequencing, and 85/112 (76%) using MS-PCR. The better sensitivity of the MS-PCR to detect the mutant BRAFV600E allele was not due to the presence of contaminating normal tissue, suggesting that the tumor was comprised of subclones of differing BRAF genotypes. To determine if tumor subclones were present in individual primary melanomas, we performed laser microdissection and mutation detection via sequencing and BRAFV600E-specific SNaPshot analysis in 9 cases. Six of these cases demonstrated differing proportions of BRAFV600Eand BRAFwild-type cells in distinct microdissected regions within individual tumors. Additional analyses of multiple metastatic samples from individual patients using the highly sensitive MS-PCR without microdissection revealed that 5/19 (26%) patients had metastases that were discordant for the BRAFV600E mutation. In conclusion, we used highly sensitive BRAF mutation detection methods and observed substantial evidence for heterogeneity of the BRAFV600E mutation within individual melanoma tumor specimens, and among multiple specimens from individual patients. Given the varied clinical responses of patients to BRAF inhibitor therapy, these data suggest that additional studies to determine possible associations between clinical outcomes and intra- and inter-tumor heterogeneity could prove fruitful

B Cells and B Cell Blasts Withstand Cryopreservation While Retaining Their Functionality for Producing Antibody

In individuals who have once developed humoral immunity to an infectious/foreign antigen, the antibodies present in their body can mediate instant protection when the antigen re-enters. Such antigen-specific antibodies can be readily detected in the serum. Long term humoral immunity is, however, also critically dependent on the ability of memory B cells to engage in a secondary antibody response upon re-exposure to the antigen. Antibody molecules in the body are short lived, having a half-life of weeks, while memory B cells have a life span of decades. Therefore, the presence of serum antibodies is not always a reliable indicator of B cell memory and comprehensive monitoring of humoral immunity requires that both serum antibodies and memory B cells be assessed. The prevailing view is that resting memory B cells and B cell blasts in peripheral blood mononuclear cells (PBMC) cannot be cryopreserved without losing their antibody secreting function, and regulated high throughput immune monitoring of B cell immunity is therefore confined to—and largely limited by—the need to test freshly isolated PBMC. Using optimized protocols for freezing and thawing of PBMC, and four color ImmunoSpot® analysis for the simultaneous detection of all immunoglobulin classes/subclasses we show here that both resting memory B cells and B cell blasts retain their ability to secrete antibody after thawing, and thus demonstrate the feasibility of B cell immune monitoring using cryopreserved PBMC

Photoemission from Pt(111)-(hex)-Rb and Pt(111)-(4x1)-RbO using polarised synchrotron radiation

BMBF - BUNDESMINISTERIUM FÜR BILDUNG UND FORSCHUNGDAAD - DEUTSCHER AKADEMISCHER AUSTAUSCHDIENSTCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORFAPERGS - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DO RIO GRANDE DO SULIn various experiments it has been demonstrated that the circular dichroism in the angular distribution of photoelectrons (CDAD) is not only observed from oriented initial states (aligned adsorbed molecules or magnetized samples), but also arises as a consequence of the scattering of photoelectrons from the surrounding atoms in a solid or an adsorbate. In this work we will show first measurements performed at the SGM beamline of the Brazilian Synchrotron Light Source (LNLS) on a (4×1) superstructure of 1 ML RbO adsorbed on Pt(111). Measurements from the 4s core levels of Rb adsorbed at Pt(111) were also performed at the PM-III beamline at BESSY. The measured variations of the intensity and the CDAD with respect to the photon energy are interpreted in terms of photoelectron diffraction. The results will be used to discuss the possibility of photoelectron holography using circularly polarized light.In various experiments it has been demonstrated that the circular dichroism in the angular distribution of photoelectrons (CDAD) is not only observed from oriented initial states (aligned adsorbed molecules or magnetised samples), but also arises as a consequence of the scattering of photoelectrons from the surrounding atoms in a solid or an adsorbate. In this work we will show first measurements performed at the SGM beamline of the Brazilian Synchrotron Light Source (LNLS) on a (4x1) superstructure of 1 ML RbO adsorbed on Pt(111). Measurements from the 4s core levels of Rb adsorbed at Pt(111) were also performed at the PM-III beamline at BESSY. The measured variations of the intensity and the CDAD with respect to the photon energy are interpreted in terms of photoelectron diffraction. The results will be used to discuss the possibility of photoelectron holography using circularly polarised light.8. International Conference on Electronic Spectroscopy and Structure114-116345350BMBF - BUNDESMINISTERIUM FÜR BILDUNG UND FORSCHUNGDAAD - DEUTSCHER AKADEMISCHER AUSTAUSCHDIENSTCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORFAPERGS - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DO RIO GRANDE DO SULBMBF - BUNDESMINISTERIUM FÜR BILDUNG UND FORSCHUNGDAAD - DEUTSCHER AKADEMISCHER AUSTAUSCHDIENSTCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORFAPERGS - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DO RIO GRANDE DO SUL05 SC8 UMA 0PROBALFeder, R., (1977) Solid State Commun., 21, p. 109Ritchie, B., (1975) Phys. Rev. a, 12, p. 567Fecher, G.H., Oelsner, A., Ostertag, Ch., Schönhense, G., (1995) J. Electron Spectrosc. Relat. Phenom., 76, p. 97Gabor, D., (1948) Nature (Lond.), 161, p. 777Szöke, A., Short wavelength coherent radiation (1986) AIP Conference Proceedings, 147, p. 361Schönhense, G., Hormes, J., (1996) VUV and Soft X-Ray Photoionization, , New York: PlenumOelsner, A., Fecher, G.H., (1999) J. Electron Spectrosc. Relat. Phenom., 101-103, p. 455Oelsner, A., (1998) Experimente Zur Entwicklung der Grundlagen für Die Polarisationsabhängige Photoelektronenholographie, , Aachen: Shaker Verlag. Ph.D. ThesisLiebsch, A., (1974) Phys. Rev. Lett., 21, p. 1203Fadley, C.S., (1994) J. Electron Spectrosc. Relat. Phenom., 68, p. 1908 a 12 de Agosto de 2000Berkeley, CA, Estados UnidosClark Kerr Campus, University of Californi

Early auto‐immune targeting of photoreceptor ribbon synapses in mouse models of multiple sclerosis

Abstract Optic neuritis is one of the first manifestations of multiple sclerosis. Its pathogenesis is incompletely understood, but considered to be initiated by an auto‐immune response directed against myelin sheaths of the optic nerve. Here, we demonstrate in two frequently used and well‐validated mouse models of optic neuritis that ribbon synapses in the myelin‐free retina are targeted by an auto‐reactive immune system even before alterations in the optic nerve have developed. The auto‐immune response is directed against two adhesion proteins (CASPR1/CNTN1) that are present both in the paranodal region of myelinated nerves as well as at retinal ribbon synapses. This occurs in parallel with altered synaptic vesicle cycling in retinal ribbon synapses and altered visual behavior before the onset of optic nerve demyelination. These findings indicate that early synaptic dysfunctions in the retina contribute to the pathology of optic neuritis in multiple sclerosis