A Prolific Solvate Former, Galunisertib, under the Pressure of Crystal Structure Prediction, Produces Ten Diverse Polymorphs

The solid form screening of galunisertib produced many solvates, prompting an extensive investigation into possible risks to the development of the favored monohydrate form. Inspired by crystal structure prediction, the search for neat polymorphs was expanded to an unusual range of experiments, including melt crystallization under pressure, to work around solvate formation and the thermal instability of the molecule. Ten polymorphs of galunisertib were found; however, the structure predicted to be the most stable has yet to be obtained. We present the crystal structures of all ten unsolvated polymorphs of galunisertib, showing how state-of-the-art characterization methods can be combined with emerging computational modeling techniques to produce a complete structure landscape and assess the risk of late-appearing, more stable polymorphs. The exceptional conformational polymorphism of this prolific solvate former invites further development of methods, computational and experimental, that are applicable to larger, flexible molecules with complex solid form landscapes

Light hadron, Charmonium(-like) and Bottomonium(-like) states

Hadron physics represents the study of strongly interacting matter in all its manifestations and the understanding of its properties and interactions. The interest on this field has been revitalized by the discovery of new light hadrons, charmonium- and bottomonium-like states. I review the most recent experimental results from different experiments.Comment: Presented at Lepton-Photon 2011, Mumbai, India; 21 pages, 18 figures; add more references; some correctio

Lumps of plasma in arbitrary dimensions

We use the AdS/CFT correspondence in a regime in which the field theory reduces to fluid dynamics to construct an infinite class of new black objects in Scherk-Schwarz compactified AdS(d+2) space. Our configurations are dual to black objects that generalize black rings and have horizon topology S^(d-n) x T^n, for n less than or equal to (d-1)/2. Locally our fluid configurations are plasma sheets that curve around into tori whose radii are large compared to the thickness of the sheets (the ratio of these radii constitutes a small parameter that permits the perturbative construction of these configurations). These toroidal configurations are stabilized by angular momentum. We study solutions whose dual horizon topologies are S^3 x S^1, S^4 x S^1 and S^3 x T^2 in detail; in particular we investigate the thermodynamic properties of these objects. We also present a formal general construction of the most general stationary configuration of fluids with boundaries that solve the d-dimensional relativistic Navier-Stokes equation.Comment: 32 pages, 10 figures; v2: Some figures are modified and a few references added

Transposing tirtha: Understanding religious reforms and locative piety in early modern Hinduism

The paper deals with a historical and hitherto obscure case of de-commercialisation of sacred geography of India. Sahajanand Swami, an eighteenth century religious leader from Gujarat who became popular as Bhagwan Swaminarayan took an initiative to eliminate corruption in Dwarka, one of the most sacred destination in Hindu imagination. He also attempted to transpose the piety of Dwarka and recreate a parallel religious experience at Vadtal, an important site in Swaminarayan Hinduism. This process of making sacred sites more egalitarian is classified here as a 'religious reform'. The paper assesses this bivalent pursuit as an institutional reform within religion as well as a religious process in the context of piety, authority and orthodoxy. Through the example of Sahajanand Swami, it is argued to calibrate the colonial paradigm of reform that was largely contextual to social issues and western thought and failed to appreciate the religious reforms of that era. By constructing a nuanced typology of 'religious reform' distinct from 'social reforms', the paper eventually calls for a reassessment of religious figures who have significantly contributed in reforming the Hindu tradition in the medieval and modern era

Compressed representation of a partially defined integer function over multiple arguments

In OLAP (OnLine Analitical Processing) data are analysed in an n-dimensional cube. The cube may be represented as a partially defined function over n arguments. Considering that often the function is not defined everywhere, we ask: is there a known way of representing the function or the points in which it is defined, in a more compact manner than the trivial one

Search for new physics with same-sign isolated dilepton events with jets and missing transverse energy

A search for new physics is performed in events with two same-sign isolated leptons, hadronic jets, and missing transverse energy in the final state. The analysis is based on a data sample corresponding to an integrated luminosity of 4.98 inverse femtobarns produced in pp collisions at a center-of-mass energy of 7 TeV collected by the CMS experiment at the LHC. This constitutes a factor of 140 increase in integrated luminosity over previously published results. The observed yields agree with the standard model predictions and thus no evidence for new physics is found. The observations are used to set upper limits on possible new physics contributions and to constrain supersymmetric models. To facilitate the interpretation of the data in a broader range of new physics scenarios, information on the event selection, detector response, and efficiencies is provided.Comment: Published in Physical Review Letter

A distinct bacterial dysbiosis associated skin inflammation in ovine footrot

Ovine footrot is a highly prevalent bacterial disease caused by Dichelobacter nodosus and characterised by the separation of the hoof horn from the underlying skin. The role of innate immune molecules and other bacterial communities in the development of footrot lesions remains unclear. This study shows a significant association between the high expression of IL1β and high D. nodosus load in footrot samples. Investigation of the microbial population identified distinct bacterial populations in the different disease stages and also depending on the level of inflammation. Treponema (34%), Mycoplasma (29%) and Porphyromonas (15%) were the most abundant genera associated with high levels of inflammation in footrot. In contrast, Acinetobacter (25%), Corynebacteria (17%) and Flavobacterium (17%) were the most abundant genera associated with high levels of inflammation in healthy feet. This demonstrates for the first time there is a distinct microbial community associated with footrot and high cytokine expression

Measurement of jet fragmentation into charged particles in pp and PbPb collisions at sqrt(s[NN]) = 2.76 TeV

Jet fragmentation in pp and PbPb collisions at a centre-of-mass energy of 2.76 TeV per nucleon pair was studied using data collected with the CMS detector at the LHC. Fragmentation functions are constructed using charged-particle tracks with transverse momenta pt > 4 GeV for dijet events with a leading jet of pt > 100 GeV. The fragmentation functions in PbPb events are compared to those in pp data as a function of collision centrality, as well as dijet-pt imbalance. Special emphasis is placed on the most central PbPb events including dijets with unbalanced momentum, indicative of energy loss of the hard scattered parent partons. The fragmentation patterns for both the leading and subleading jets in PbPb collisions agree with those seen in pp data at 2.76 TeV. The results provide evidence that, despite the large parton energy loss observed in PbPb collisions, the partition of the remaining momentum within the jet cone into high-pt particles is not strongly modified in comparison to that observed for jets in vacuum.Comment: Submitted to the Journal of High Energy Physic

A review of data needed to parameterize a dynamic model of measles in developing countries

<p>Abstract</p> <p>Background</p> <p>Dynamic models of infection transmission can project future disease burden within a population. Few dynamic measles models have been developed for low-income countries, where measles disease burden is highest. Our objective was to review the literature on measles epidemiology in low-income countries, with a particular focus on data that are needed to parameterize dynamic models.</p> <p>Methods</p> <p>We included age-stratified case reporting and seroprevalence studies with fair to good sample sizes for mostly urban African and Indian populations. We emphasized studies conducted before widespread immunization. We summarized age-stratified attack rates and seroprevalence profiles across these populations. Using the study data, we fitted a "representative" seroprevalence profile for African and Indian settings. We also used a catalytic model to estimate the age-dependent force of infection for individual African and Indian studies where seroprevalence was surveyed. We used these data to quantify the effects of population density on the basic reproductive number <it>R</it>₀.</p> <p>Results</p> <p>The peak attack rate usually occurred at age 1 year in Africa, and 1 to 2 years in India, which is earlier than in developed countries before mass vaccination. Approximately 60% of children were seropositive for measles antibody by age 2 in Africa and India, according to the representative seroprevalence profiles. A statistically significant decline in the force of infection with age was found in 4 of 6 Indian seroprevalence studies, but not in 2 African studies. This implies that the classic threshold result describing the critical proportion immune (<it>p</it>_c) required to eradicate an infectious disease, <it>p</it>_c= 1-1/<it>R</it>₀, may overestimate the required proportion immune to eradicate measles in some developing country populations. A possible, though not statistically significant, positive relation between population density and <it>R</it>₀for various Indian and African populations was also found. These populations also showed a similar pattern of waning of maternal antibodies. Attack rates in rural Indian populations show little dependence on vaccine coverage or population density compared to urban Indian populations. Estimated <it>R</it>₀values varied widely across populations which has further implications for measles elimination.</p> <p>Conclusions</p> <p>It is possible to develop a broadly informative dynamic model of measles transmission in low-income country settings based on existing literature, though it may be difficult to develop a model that is closely tailored to any given country. Greater efforts to collect data specific to low-income countries would aid in control efforts by allowing highly population-specific models to be developed.</p