2,068 research outputs found

    An Updated Classification of Meditation Methods Using Principles of Taxonomy and Systematics

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    This paper revisits the proposal for the classification of meditation methods which we introduced in our initial 2013 publication, “Toward a Universal Taxonomy and Definition of Meditation”. At that time, we advanced the thesis that meditation methods could be effectively segregated into three orthogonal categories by integrating the taxonomic principle of functional essentialism and the paradigm of Affect and Cognition; and we presented relevant research findings which supported that assertion. This iteration expands upon those theoretical and methodological elements by articulating a more comprehensive Three Tier Classification System which accounts for the full range of meditation methods; and demonstrates how recent neuroscience research continues to validate and support our thesis. This paper also introduces a novel criterion-based protocol for formulating classification systems of meditation methods, and demonstrates how this model can be used to compare and evaluate various other taxonomy proposals that have been published over the past 15 years

    Characteristics of HIV-Infected Children at Enrollment into Care and at Antiretroviral Therapy Initiation in Central Africa

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    Background Despite the World Health Organization (WHO) regularly updating guidelines to recommend earlier initiation of antiretroviral therapy (ART) in children, timely enrollment into care and initiation of ART in sub-Saharan Africa in children lags behind that of adults. The impact of implementing increasingly less restrictive ART guidelines on ART initiation in Central Africa has not been described. Materials and Methods Data are from the Central Africa International Epidemiologic Databases to Evaluate AIDS (IeDEA) pediatric cohort of 3,426 children (0±15 years) entering HIV care at 15 sites in Burundi, DRC, and Rwanda. Measures include CD4 count, WHO clinical stage, age, and weight-for-age Z score (WAZ), each at enrollment into HIV care and at ART initiation. Changes in the medians or proportions of each measure by year of enrollment and year of ART initiation were assessed to capture potential impacts of changing ART guidelines. Results Median age at care enrollment decreased from 77.2 months in 2004±05 to 30.3 months in 2012±13. The median age at ART initiation (n = 2058) decreased from 83.0 months in 2004±05 to 66.9 months in 2012±13. The proportion of children 24 months of age at enrollment increased from 12.7% in 2004±05 to 46.7% in 2012±13, and from 9.6% in 2004±05 to 24.2% in 2012±13 for ART initiation. The median CD4 count at enrollment into care increased from 563 (IQR: 275, 901) in 2004±05 to 660 (IQR: 339, 1071) cells/μl in 2012±13, and the median CD4 count at ART initiation increased from 310 (IQR:167, 600) in 2004±05 to 589 (IQR: 315, 1113) cells/μl in 2012±13. From 2004±05 to 2012±13, median WAZ improved from -2 (IQR: -3.4, -1.1) to -1 (IQR: -2.5, -0.2) at enrollment in care and from -2 (IQR: -3.8, -1.6) to -1 (IQR: -2.6, -0.4) at ART initiation. Discussion and Conclusion Although HIV-infected children 24 months of age accounted for half of all children enrolling in care in our cohort during 2012±13, they represented less than a quarter of all those who were initiated on ART during the same period. Further research is needed to identify barriers to timely diagnosis, linkage to care, and initiation of ART among children with HIV infection

    Coalitions in the quantum Minority game: classical cheats and quantum bullies

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    In a one-off Minority game, when a group of players agree to collaborate they gain an advantage over the remaining players. We consider the advantage obtained in a quantum Minority game by a coalition sharing an initially entangled state versus that obtained by a coalition that uses classical communication to arrive at an optimal group strategy. In a model of the quantum Minority game where the final measurement basis is randomized, quantum coalitions outperform classical ones when carried out by up to four players, but an unrestricted amount of classical communication is better for larger coalition sizes.Comment: 12 pages, 1 figur

    Antischistosomal Properties of Sclareol and Its Heck-Coupled Derivatives:Design, Synthesis, Biological Evaluation and Untargeted Metabolomics

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    Sclareol, a plant-derived diterpenoid widely used as a fragrance and flavoring substance, is well-known for its promising antimicrobial and anticancer properties. However, its activity on helminth parasites has not been previously reported. Here, we show that sclareol is active against larval (IC50 ≈ 13 μM), juvenile (IC50 = 5.0 μM), and adult (IC50 = 19.3 μM) stages of Schistosoma mansoni, a parasitic trematode responsible for the neglected tropical disease schistosomiasis. Microwave-assisted synthesis of Heck-coupled derivatives improved activity, with the substituents choice guided by the Matsy decision tree. The most active derivative 12 showed improved potency and selectivity on larval (IC50 ≈ 2.2 μM, selectivity index (SI) ≈ 22 in comparison to HepG2 cells), juvenile (IC50 = 1.7 μM, SI = 28.8), and adult schistosomes (IC50 = 9.4 μM, SI = 5.2). Scanning electron microscopy studies revealed that compound 12 induced blebbing of the adult worm surface at sublethal concentration (12.5 μM); moreover, the compound inhibited egg production at the lowest concentration tested (3.13 μM). The observed phenotype and data obtained by untargeted metabolomics suggested that compound 12 affects membrane lipid homeostasis by interfering with arachidonic acid metabolism. The same methodology applied to praziquantel (PZQ)-treated worms revealed sugar metabolism alterations that could be ascribed to the previously reported action of PZQ on serotonin signaling and/or effects on glycolysis. Importantly, our data suggest that compound 12 and PZQ exert different antischistosomal activities. More studies will be necessary to confirm the generated hypothesis and to progress the development of more potent antischistosomal sclareol derivatives

    Submesoscale processes at shallow salinity fronts in the Bay of Bengal : observations during the winter monsoon

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    Author Posting. © American Meteorological Society, 2018. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 48 (2018): 479-509, doi:10.1175/JPO-D-16-0283.1.Lateral submesoscale processes and their influence on vertical stratification at shallow salinity fronts in the central Bay of Bengal during the winter monsoon are explored using high-resolution data from a cruise in November 2013. The observations are from a radiator survey centered at a salinity-controlled density front, embedded in a zone of moderate mesoscale strain (0.15 times the Coriolis parameter) and forced by winds with a downfront orientation. Below a thin mixed layer, often ≤10 m, the analysis shows several dynamical signatures indicative of submesoscale processes: (i) negative Ertel potential vorticity (PV); (ii) low-PV anomalies with O(1–10) km lateral extent, where the vorticity estimated on isopycnals and the isopycnal thickness are tightly coupled, varying in lockstep to yield low PV; (iii) flow conditions susceptible to forced symmetric instability (FSI) or bearing the imprint of earlier FSI events; (iv) negative lateral gradients in the absolute momentum field (inertial instability); and (v) strong contribution from differential sheared advection at O(1) km scales to the growth rate of the depth-averaged stratification. The findings here show one-dimensional vertical processes alone cannot explain the vertical stratification and its lateral variability over O(1–10) km scales at the radiator survey.S. Ramachandran acknowledges support from the National Science Foundation through award OCE 1558849 and the U.S. Office of Naval Research, Grants N00014-13-1-0456 and N00014-17- 1-2355. A. Tandon acknowledges support from the U.S. Office of Naval Research, Grants N00014-13-1-0456 and N00014-17-1-2355. J. T. Farrar and R. A. Weller were supported by the U.S. Office of Naval Research, Grant N00014-13-1-0453, to collect the UCTD data and process theUCTD and shipboard meteorological data. J. Nash, J. Mackinnon, and A. F. Waterhouse acknowledge support from the U. S. Office of Naval Research, Grants N00014-13-1-0503 and N00014-14-1-0455. E. Shroyer acknowledges support from the U. S. Office of Naval Research, Grants N00014-14-10236 and N00014-15- 12634. A. Mahadevan acknowledges support fromthe U. S. Office of Naval Research, Grant N00014-13-10451. A. J. Lucas and R. Pinkel acknowledge support from the U. S. Office of Naval Research, Grant N00014-13-1-0489.2018-08-2

    On Random Bubble Lattices

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    We study random bubble lattices which can be produced by processes such as first order phase transitions, and derive characteristics that are important for understanding the percolation of distinct varieties of bubbles. The results are relevant to the formation of topological defects as they show that infinite domain walls and strings will be produced during appropriate first order transitions, and that the most suitable regular lattice to study defect formation in three dimensions is a face centered cubic lattice. Another application of our work is to the distribution of voids in the large-scale structure of the universe. We argue that the present universe is more akin to a system undergoing a first-order phase transition than to one that is crystallizing, as is implicit in the Voronoi foam description. Based on the picture of a bubbly universe, we predict a mean coordination number for the voids of 13.4. The mean coordination number may also be used as a tool to distinguish between different scenarios for structure formation.Comment: several modifications including new abstract, comparison with froth models, asymptotics of coordination number distribution, further discussion of biased defects, and relevance to large-scale structur

    Natural history of murine gamma-herpesvirus infection

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    Murine gamma-herpesvirus 68 (MHV-68) is a natural pathogen of small rodents and insectivores (mice, voles and shrews). The primary infection is characterized by virus replication in lung epithelial cells and the establishment of a latent infection in B lymphocytes. The virus is also observed to persist in lung epithelial cells, dendritic cells and macrophages. Splenomegaly is observed two weeks after infection, in which there is a CD4+ T-cell-mediated expansion of B and T cells in the spleen. At three weeks post-infection an infectious mononucleosis-like syndrome is observed involving a major expansion of Vbeta4+CD8+ T cells. Later in the course of persistent infection, ca. 10% of mice develop lymphoproliferative disease characterized as lymphomas of B-cell origin. The genome from MHV-68 strain g2.4 has been sequenced and contains ca. 73 genes, the majority of which are collinear and homologous to other gamma-herpesviruses. The genome includes cellular homologues for a complement-regulatory protein, Bcl-2, cyclin D and interleukin-8 receptor and a set of novel genes M1 to M4. The function of these genes in the context of latent infections, evasion of immune responses and virus-mediated pathologies is discussed. Both innate and adaptive immune responses play an active role in limiting virus infection. The absence of type I interferon (IFN) results in a lethal MHV-68 infection, emphasizing the central role of these cytokines at the initial stages of infection. In contrast, type II IFN is not essential for the recovery from infection in the lung, but a failure of type II IFN receptor signalling results in the atrophy of lymphoid tissue associated with virus persistence. Splenic atrophy appears to be the result of immunopathology, since in the absence of CD8+ T cells no pathology occurs. CD8+ T cells play a major role in recovery from the primary infection, and also in regulating latently infected cells expressing the M2 gene product. CD4+ T cells have a key role in surveillance against virus recurrences in the lung, in part mediated through 'help' in the genesis of neutralizing antibodies. In the absence of CD4+ T cells, virus-specific CD8+ T cells are able to control the primary infection in the respiratory tract, yet surprisingly the memory CD8+ T cells generated are unable to inhibit virus recurrences in the lung. This could be explained in part by the observations that this virus can downregulate major histocompatibility complex class I expression and also restrict inflammatory cell responses by producing a chemokine-binding protein (M3 gene product). MHV-68 provides an excellent model to explore methods for controlling gamma-herpesvirus infection through vaccination and chemotherapy. Vaccination with gp150 (a homologue of gp350 of Epstein-Barr virus) results in a reduction in splenomegaly and virus latency but does not block replication in the lung, nor the establishment of a latent infection. Even when lung virus infection is greatly reduced following the action of CD8+ T cells, induced via a prime-boost vaccination strategy, a latent infection is established. Potent antiviral compounds such as the nucleoside analogue 2'deoxy-5-ethyl-beta-4'-thiouridine, which disrupts virus replication in vivo, cannot inhibit the establishment of a latent infection. Clearly, devising strategies to interrupt the establishment of latent virus infections may well prove impossible with existing methods

    Genomics of Ocular Chlamydia trachomatis After 5 Years of SAFE Interventions for Trachoma in Amhara, Ethiopia.

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    BACKGROUND: To eliminate trachoma as a public health problem, the World Health Organization recommends the SAFE (surgery, antibiotics, facial cleanliness, and environmental improvement) strategy. As part of the SAFE strategy in the Amhara Region, Ethiopia, the Trachoma Control Program distributed >124 million doses of antibiotics between 2007 and 2015. Despite this, trachoma remained hyperendemic in many districts and a considerable level of Chlamydia trachomatis (Ct) infection was evident. METHODS: We utilized residual material from Abbott m2000 Ct diagnostic tests to sequence 99 ocular Ct samples from Amhara and investigated the role of Ct genomic variation in continued transmission of Ct. RESULTS: Sequences were typical of ocular Ct at the whole-genome level and in tissue tropism-associated genes. There was no evidence of macrolide resistance in this population. Polymorphism around the ompA gene was associated with village-level trachomatous inflammation-follicular prevalence. Greater ompA diversity at the district level was associated with increased Ct infection prevalence. CONCLUSIONS: We found no evidence for Ct genomic variation contributing to continued transmission of Ct after treatment, adding to evidence that azithromycin does not drive acquisition of macrolide resistance in Ct. Increased Ct infection in areas with more ompA variants requires longitudinal investigation to understand what impact this may have on treatment success and host immunity

    A new family of giardial cysteine-rich non-VSP protein genes and a novel cyst protein

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    © 2006 Davids et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The definitive version was published in PLoS ONE 1 (2006): e44, doi:10.1371/journal.pone.0000044.Since the Giardia lamblia cyst wall is necessary for survival in the environment and host infection, we tested the hypothesis that it contains proteins other than the three known cyst wall proteins. Serial analysis of gene expression during growth and encystation revealed a gene, “HCNCp” (High Cysteine Non-variant Cyst protein), that was upregulated late in encystation, and that resembled the classic Giardia variable surface proteins (VSPs) that cover the trophozoite plasmalemma. HCNCp is 13.9% cysteine, with many “CxxC” tetrapeptide motifs and a transmembrane sequence near the C-terminus. However, HCNCp has multiple “CxC” motifs rarely found in VSPs, and does not localize to the trophozoite plasmalemma. Moreover, the HCNCp C-terminus differed from the canonical VSP signature. Full-length epitope-tagged HCNCp expressed under its own promoter was upregulated during encystation with highest expression in cysts, including 42 and 21 kDa C-terminal fragments. Tagged HCNCp targeted to the nuclear envelope in trophozoites, and co-localized with cyst proteins to encystation-specific secretory vesicles during encystation. HCNCp defined a novel trafficking pathway as it localized to the wall and body of cysts, while the cyst proteins were exclusively in the wall. Unlike VSPs, HCNCp is expressed in at least five giardial strains and four WB subclones expressing different VSPs. Bioinformatics identified 60 additional large high cysteine membrane proteins (HCMp) containing ≥20 CxxC/CxC's lacking the VSP-specific C-terminal CRGKA. HCMp were absent or rare in other model or parasite genomes, except for Tetrahymena thermophila with 30. MEME analysis classified the 61 gHCMp genes into nine groups with similar internal motifs. Our data suggest that HCNCp is a novel invariant cyst protein belonging to a new HCMp family that is abundant in the Giardia genome. HCNCp and the other HCMp provide a rich source for developing parasite-specific diagnostic reagents, vaccine candidates, and subjects for further research into Giardia biology

    Weak Lensing with SDSS Commissioning Data: The Galaxy-Mass Correlation Function To 1/h Mpc

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    (abridged) We present measurements of galaxy-galaxy lensing from early commissioning imaging data from the Sloan Digital Sky Survey (SDSS). We measure a mean tangential shear around a stacked sample of foreground galaxies in three bandpasses out to angular radii of 600'', detecting the shear signal at very high statistical significance. The shear profile is well described by a power-law. A variety of rigorous tests demonstrate the reality of the gravitational lensing signal and confirm the uncertainty estimates. We interpret our results by modeling the mass distributions of the foreground galaxies as approximately isothermal spheres characterized by a velocity dispersion and a truncation radius. The velocity dispersion is constrained to be 150-190 km/s at 95% confidence (145-195 km/s including systematic uncertainties), consistent with previous determinations but with smaller error bars. Our detection of shear at large angular radii sets a 95% confidence lower limit s>140s>140^{\prime\prime}, corresponding to a physical radius of 260h1260h^{-1} kpc, implying that galaxy halos extend to very large radii. However, it is likely that this is being biased high by diffuse matter in the halos of groups and clusters. We also present a preliminary determination of the galaxy-mass correlation function finding a correlation length similar to the galaxy autocorrelation function and consistency with a low matter density universe with modest bias. The full SDSS will cover an area 44 times larger and provide spectroscopic redshifts for the foreground galaxies, making it possible to greatly improve the precision of these constraints, measure additional parameters such as halo shape, and measure the properties of dark matter halos separately for many different classes of galaxies.Comment: 28 pages, 11 figures, submitted to A
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