The humankind genome: from genetic diversity to the origin of human diseases

Genome-wide association studies have failed to establish common variant risk for the majority of common human diseases. The underlying reasons for this failure are explained by recent studies of resequencing and comparison of over 1200 human genomes and 10 000 exomes, together with the delineation of DNA methylation patterns (epigenome) and full characterization of coding and noncoding RNAs (transcriptome) being transcribed. These studies have provided the most comprehensive catalogues of functional elements and genetic variants that are now available for global integrative analysis and experimental validation in prospective cohort studies. With these datasets, researchers will have unparalleled opportunities for the alignment, mining, and testing of hypotheses for the roles of specific genetic variants, including copy number variations, single nucleotide polymorphisms, and indels as the cause of specific phenotypes and diseases. Through the use of next-generation sequencing technologies for genotyping and standardized ontological annotation to systematically analyze the effects of genomic variation on humans and model organism phenotypes, we will be able to find candidate genes and new clues for disease’s etiology and treatment. This article describes essential concepts in genetics and genomic technologies as well as the emerging computational framework to comprehensively search websites and platforms available for the analysis and interpretation of genomic data.

High Prevalence of Skin Disorders among HTLV-1 Infected Individuals Independent of Clinical Status

Background Human T-cell lymphotropic virus type 1 (HTLV-1) infection can increase the risk of developing skin disorders. This study evaluated the correlation between HTLV-1 proviral load and CD4+ and CD8+ T cells count among HTLV-1 infected individuals, with or without skin disorders (SD) associated with HTLV-1 infection [SD-HTLV-1: xerosis/ichthyosis, seborrheic dermatitis or infective dermatitis associated to HTLV-1 (IDH)]. Methods A total of 193 HTLV-1-infected subjects underwent an interview, dermatological examination, initial HTLV-1 proviral load assay, CD4+ and CD8+ T cells count, and lymphproliferation assay (LPA). Results A total of 147 patients had an abnormal skin condition; 116 (79%) of them also had SD-HTLV-1 and 21% had other dermatological diagnoses. The most prevalent SD-HTLV-1 was xerosis/acquired ichthyosis (48%), followed by seborrheic dermatitis (28%). Patients with SD-HTLV-1 were older (51 vs. 47 years), had a higher prevalence of myelopathy/tropical spastic paraparesis (HAM/TSP) (75%), and had an increased first HTLV-1 proviral load and basal LPA compared with patients without SD-HTLV-1. When excluding HAM/TSP patients, the first HTLV-1 proviral load of SD-HTLV-1 individuals remains higher than no SD-HTLV-1 patients. Conclusions There was a high prevalence of skin disorders (76%) among HTLV-1-infected individuals, regardless of clinical status, and 60% of these diseases are considered skin disease associated with HTLV-1 infection.

Comparison of flow cytometry and indirect immunofluorescence assay in the diagnosis and cure criterion after therapy of American tegumentary leishmaniasis by anti-live Leishmania (Viannia) braziliensis immunoglobulin G

The aim of this study was to compare the techniques of indirect immunofluorescence assay (IFA) and flow cytometry to clinical and laboratorial evaluation of patients before and after clinical cure and to evaluate the applicability of flow cytometry in post-therapeutic monitoring of patients with American tegumentary leishmaniasis (ATL). Sera from 14 patients before treatment (BT), 13 patients 1 year after treatment (AT), 10 patients 2 and 5 years AT were evaluated. The results from flow cytometry were expressed as levels of IgG reactivity, based on the percentage of positive fluorescent parasites (PPFP). The 1:256 sample dilution allowed us to differentiate individuals BT and AT. Comparative analysis of IFA and flow cytometry by ROC (receiver operating characteristic curve) showed, respectively, AUC (area under curve) = 0.8 (95% CI = 0.64–0.89) and AUC = 0.90 (95% CI = 0.75–0.95), demonstrating that the flow cytometry had equivalent accuracy. Our data demonstrated that 20% was the best cut-off point identified by the ROC curve for the flow cytometry assay. This test showed a sensitivity of 86% and specificity of 77% while the IFA had a sensitivity of 78% and specificity of 85%. The after-treatment screening, through comparative analysis of the technique performance indexes, 1, 2 and 5 years AT, showed an equal performance of the flow cytometry compared with the IFA. However, flow cytometry shows to be a better diagnostic alternative when applied to the study of ATL in the cure criterion. The information obtained in this work opens perspectives to monitor cure after treatment of ATL.

Inclusive J/psi production in pp collisions at root s=2.76 TeV

The ALICE Collaboration has measured inclusive J/psi production in pp collisions at a center-of-mass energy root s = 2.76 TeV at the LHC. The results presented in this Letter refer to the rapidity ranges vertical bar y vertical bar < 0.9 and 2.5 < y <4 and have been obtained by measuring the electron and muon pair decay channels, respectively. The integrated luminosities for the two channels are L-int(e) = 1.1 nb(-1) and L-int(mu) = 19.9 nb(-1), and the corresponding signal statistics are N-J/psi(e+e-) = 59 +/- 14 and N-J/psi(mu+mu-) = 1364 +/- 53. We present d sigma(J/psi)/dy for the two rapidity regions under study and, for the forward-y range, d(2)sigma(J/psi)/dydp(t) in the transverse momentum domain 0 < p(t) < 8 GeV/c. The results are compared with previously published results at root s = 7 TeV and with theoretical calculations. (C) 2012 CERN. Published by Elsevier B.V. All rights reserved.

A search for anisotropy in the arrival directions of ultra high energy cosmic rays recorded at the Pierre Auger Observatory

Observations of cosmic rays arrival directions made with the Pierre Auger Observatory have previously provided evidence of anisotropy at the 99% CL using the correlation of ultra high energy cosmic rays (UHECRs) with objects drawn from the Veron-Cetty Veron catalog. In this paper we report on the use of three catalog independent methods to search for anisotropy. The 2pt-L, 2pt+ and 3pt methods, each giving a different measure of self-clustering in arrival directions, were tested on mock cosmic ray data sets to study the impacts of sample size and magnetic smearing on their results, accounting for both angular and energy resolutions. If the sources of UHECRs follow the same large scale structure as ordinary galaxies in the local Universe and if UHECRs are deflected no more than a few degrees, a study of mock maps suggests that these three method can efficiently respond to the resulting anisotropy with a P-value = 1.0% or smaller with data sets as few as 100 events. using data taken from January 1, 2004 to July 31, 2010 we examined the 20, 30, ... , 110 highest energy events with a corresponding minimum energy threshold of about 49.3 EeV. The minimum P-values found were 13.5% using the 2pt-L method, 1.0% using the 2pt+ method and 1.1% using the 3pt method for the highest 100 energy events. In view of the multiple (correlated) scans performed on the data set, these catalog-independent methods do not yield strong evidence of anisotropy in the highest energy cosmic rays.

J/psi Polarization in pp Collisions at root s=7 TeV

The ALICE Collaboration has studied J/psi production in pp collisions at root s = 7 TeV at the LHC through its muon pair decay. The polar and azimuthal angle distributions of the decay muons were measured, and results on the J/psi polarization parameters lambda(theta) and lambda(phi) were obtained. The study was performed in the kinematic region 2: 5 < y < 4, 2 < p(t) < 8 GeV/c, in the helicity and Collins-Soper reference frames. In both frames, the polarization parameters are compatible with zero, within uncertainties.

Nuclear-modification factor for open-heavy-flavor production at forward rapidity in Cu plus Cu collisions at root s(NN)=200 GeV

Background: Heavy-flavor production in p + p collisions is a good test of perturbative-quantum-chromodynamics (pQCD) calculations. Modification of heavy-flavor production in heavy-ion collisions relative to binary-collision scaling from p + p results, quantified with the nuclear-modification factor (R-AA), provides information on both cold-and hot-nuclear-matter effects. Midrapidity heavy-flavor R-AA measurements at the Relativistic Heavy Ion Collider have challenged parton-energy-loss models and resulted in upper limits on the viscosity-entropy ratio that are near the quantum lower bound. Such measurements have not been made in the forward-rapidity region. Purpose: Determine transverse-momentum (p(T)) spectra and the corresponding R-AA for muons from heavy-flavor meson decay in p + p and Cu + Cu collisions at root s(NN) = 200 GeV and y = 1.65. Method: Results are obtained using the semileptonic decay of heavy-flavor mesons into negative muons. The PHENIX muon-arm spectrometers measure the p(T) spectra of inclusive muon candidates. Backgrounds, primarily due to light hadrons, are determined with a Monte Carlo calculation using a set of input hadron distributions tuned to match measured-hadron distributions in the same detector and statistically subtracted. Results: The charm-production cross section in p + p collisions at root s = 200 GeV, integrated over p(T) and in the rapidity range 1.4 < y < 1.9, is found to be d(sigma e (e) over bar)/dy = 0.139 +/- 0.029 (stat)(-0.058)(+0.051) (syst) mb. This result is consistent with a perturbative fixed-order-plus-next-to-leading-log calculation within scale uncertainties and is also consistent with expectations based on the corresponding midrapidity charm-production cross section measured by PHENIX. The R-AA for heavy-flavor muons in Cu + Cu collisions is measured in three centrality bins for 1 < p(T) < 4 GeV/c. Suppression relative to binary-collision scaling (R-AA < 1) increases with centrality. Conclusions: Within experimental and theoretical uncertainties, the measured charm yield in p + p collisions is consistent with state-of-the-art pQCD calculations. Suppression in central Cu + Cu collisions suggests the presence of significant cold-nuclear-matter effects and final-state energy loss.

Geochronological constraints on the age of a Permo-Triassic impact event: U-Pb and Ar-40/Ar-39 results for the 40 km Araguainha structure of central Brazil

Impact cratering has been a fundamental geological process in Earth history with major ramifications for the biosphere. The complexity of shocked and melted rocks within impact structures presents difficulties for accurate and precise radiogenic isotope age determination, hampering the assessment of the effects of an individual event in the geological record. We demonstrate the utility of a multi-chronometer approach in our study of samples from the 40 km diameter Araguainha impact structure of central Brazil. Samples of uplifted basement granite display abundant evidence of shock deformation, but U/Pb ages of shocked zircons and the Ar-40/Ar-39 ages of feldspar from the granite largely preserve the igneous crystallization and cooling history. Mixed results are obtained from in situ Ar-40/Ar-39 spot analyses of shocked igneous biotites in the granite, with deformation along kink-bands resulting in highly localized, partial resetting in these grains. Likewise, spot analyses of perlitic glass from pseudotachylitic breccia samples reflect a combination of argon inheritance from wall rock material, the age of the glass itself, and post-impact devitrification. The timing of crater formation is better assessed using samples of impact-generated melt rock where isotopic resetting is associated with textural evidence of melting and in situ crystallization. Granular aggregates of neocrystallized zircon form a cluster of ten U-Pb ages that yield a "Concordia" age of 247.8 +/- 3.8 Ma. The possibility of Pb loss from this population suggests that this is a minimum age for the impact event. The best evidence for the age of the impact comes from the U-Th-Pb dating of neocrystallized monazite and Ar-40/Ar-39 step heating of three separate populations of post-impact, inclusion-rich quartz grains that are derived from the infill of miarolitic cavities. The Pb-206/U-238 age of 254.5 +/- 3.2 Ma (2 sigma error) and Pb-208/Th-232 age of 255.2 +/- 4.8 Ma (2 sigma error) of monazite, together with the inverse, 18 point isochron age of 254 +/- 10 Ma (MSWD = 0.52) for the inclusion-rich quartz grains yield a weighted mean age of 254.7 +/- 2.5 Ma (0.99%, 2 sigma error) for the impact event. The age of the Araguainha crater overlaps with the timing of the Permo-Triassic boundary, within error, but the calculated energy released by the Araguainha impact is insufficient to be a direct cause of the global mass extinction. However, the regional effects of the Araguainha impact event in the Parana-Karoo Basin may have been substantial. (C) 2012 Elsevier Ltd. All rights reserved.

Cross-national differences in questionnaires do not necessarily reflect comparable differences in disorder prevalence

To examine whether the widely used Strengths and Difficulties Questionnaire (SDQ) can validly be used to compare the prevalence of child mental health problems cross nationally. We used data on 29,225 5- to 16-year olds in eight population-based studies from seven countries: Bangladesh, Brazil, Britain, India, Norway, Russia and Yemen. Parents completed the SDQ in all eight studies, teachers in seven studies and youth in five studies. We used these SDQ data to calculate three different sorts of "caseness indicators" based on (1) SDQ symptoms, (2) SDQ symptoms plus impact and (3) an overall respondent judgement of 'definite' or 'severe' difficulties. Respondents also completed structured diagnostic interviews including extensive open-ended questions (the Development and Well-Being Assessment, DAWBA). Diagnostic ratings were all carried out or supervised by the DAWBA's creator, working in conjunction with experienced local professionals. As judged by the DAWBA, the prevalence of any mental disorder ranged from 2.2% in India to 17.1% in Russia. The nine SDQ caseness indicators (three indicators times three informants) explained 8-56% of the cross-national variation in disorder prevalence. This was insufficient to make meaningful prevalence estimates since populations with a similar measured prevalence of disorder on the DAWBA showed large variations across the various SDQ caseness indicators. The relationship between SDQ caseness indicators and disorder rates varies substantially between populations: cross-national differences in SDQ indicators do not necessarily reflect comparable differences in disorder rates. More generally, considerable caution is required when interpreting cross-cultural comparisons of mental health, particularly when these rely on brief questionnaires.

Description of atmospheric conditions at the Pierre Auger Observatory using the Global Data Assimilation System (GDAS)

Atmospheric conditions at the site of a cosmic ray observatory must be known for reconstructing observed extensive air showers. The Global Data Assimilation System (GDAS) is a global atmospheric model predicated on meteorological measurements and numerical weather predictions. GDAS provides altitude-dependent profiles of the main state variables of the atmosphere like temperature, pressure, and humidity. The original data and their application to the air shower reconstruction of the Pierre Auger Observatory are described. By comparisons with radiosonde and weather station measurements obtained on-site in Malargue and averaged monthly models, the utility of the GDAS data is shown. (C) 2012 Elsevier B.V. All rights reserved.

Tracing latitudinal gradient, river discharge and water masses along the Subtropical South American Coast using benthic Foraminifera assemblages

More than 30% of Buccella peruviana (D'Orbigny), Globocassidulina crassa porrecta (Earland & Heron-Allen), Cibicides mackannai (Galloway & Wissler) and C. refulgens (Montfort) indicate the presence of cold Sub Antarctic Shelf Water in winter, from 33.5 to 38.3 degrees S, deeper than 100 m, in the southern part of the study area. In summer, the abundance of this association decreases to less than 15% around 37.5-38.9 degrees S where two species (Globocassidulina subglobosa (Brady), Uvigerina peregrina (Cushman) take over. G. subglobosa, U. peregrina, and Hanzawaia boueana (D'Orbigny) are found at 27-33 degrees S in both seasons in less than 55 m deep in the northern part, and are linked with warm Subtropical Shelf Water and Tropical Water. Freshwater influence was signalized by high silicate concentration and by the presence of Pseudononion atlanticum (Cushman), Bolivina striatula (Cushman), Buliminella elegantissima (D'Orbigny), Bulimina elongata (D'Orbigny), Elphidium excavatum (Terquem), E. poeyanum (D'Orbigny), Ammobaculites exiguus (Cushman & Bronnimann), Arenoparrella mexicana (Kornfeld), Gaudryina exillis (Cushman & Bronnimann), Textularia earlandi (Parker) and thecamoebians in four sectors of the shelf. The presence of Bulimina marginata (D'Orbigny) between 34.1-32.8 degrees S in the winter and 34.2-32.7 degrees S in the summer indicates that the influence of the Subtropical Shelf Front on the sediment does not change seasonally, otherwise, the presence of Angulogerina angulosa (Williamson) in the winter, only in Mar del Plata (38.9 degrees S), show that Malvinas currents are not influencing the sediment in the summer.

Behaviour of displacement piles in sand under cyclic axial loading

Field experiments have demonstrated that piles driven into sand can respond to axial cyclic loading in Stable, Unstable or Meta-Stable ways, depending on the combinations of mean and cyclic loads and the number of cycles. An understanding of the three styles of responses is provided by experiments involving a highly instrumented model displacement pile and an array of soil stress sensors installed in fine sand in a pressurised calibration chamber. The different patterns of effective stress developing on and around the shaft are reported, along with the results of static load tests that track the effects on shaft capacity. The interpretation links these observations to the sand's stress strain behaviour. The interface-shear characteristics, the kinematic yielding, the local densification, the growth of a fractured interface-shear zone and the restrained dilatancy at the pile soil interface are all found to be important. The model tests are shown to be compatible with the full-scale behaviour and to provide key information for improving the modelling and the design rules. (C) 2012 The Japanese Geotechnical Society. Production and hosting by Elsevier B.V. All rights reserved.

Measurement of electrons from semileptonic heavy-flavor hadron decays in pp collisions at root s=7 TeV

The differential production cross section of electrons from semileptonic heavy-flavor hadron decays has been measured at midrapidity (\y\ < 0.5) in proton-proton collisions at root s = 7 TeV with ALICE at the LHC. Electrons were measured in the transverse momentum range 0.5 < p(t) < 8 GeV/c. Predictions from a fixed-order perturbative QCD calculation with next-to-leading-log resummation agree with the data within the theoretical and experimental uncertainties. DOI: 10.1103/PhysRevD.86.112007

The rapid atmospheric monitoring system of the Pierre Auger Observatory

The Pierre Auger Observatory is a facility built to detect air showers produced by cosmic rays above 10(17) eV. During clear nights with a low illuminated moon fraction, the UV fluorescence light produced by air showers is recorded by optical telescopes at the Observatory. To correct the observations for variations in atmospheric conditions, atmospheric monitoring is performed at regular intervals ranging from several minutes (for cloud identification) to several hours (for aerosol conditions) to several days (for vertical profiles of temperature, pressure, and humidity). In 2009, the monitoring program was upgraded to allow for additional targeted measurements of atmospheric conditions shortly after the detection of air showers of special interest, e. g., showers produced by very high-energy cosmic rays or showers with atypical longitudinal profiles. The former events are of particular importance for the determination of the energy scale of the Observatory, and the latter are characteristic of unusual air shower physics or exotic primary particle types. The purpose of targeted (or "rapid") monitoring is to improve the resolution of the atmospheric measurements for such events. In this paper, we report on the implementation of the rapid monitoring program and its current status. The rapid monitoring data have been analyzed and applied to the reconstruction of air showers of high interest, and indicate that the air fluorescence measurements affected by clouds and aerosols are effectively corrected using measurements from the regular atmospheric monitoring program. We find that the rapid monitoring program has potential for supporting dedicated physics analyses beyond the standard event reconstruction.

Giant magnetofossils and hyperthermal events

Magnetotactic bacteria biomineralize magnetic minerals with precisely controlled size, morphology, and stoichiometry. These cosmopolitan bacteria are widely observed in aquatic environments. If preserved after burial, the inorganic remains of magnetotactic bacteria act as magnetofossils that record ancient geomagnetic field variations. They also have potential to provide paleoenvironmental information. In contrast to conventional magnetofossils, giant magnetofossils (most likely produced by eukaryotic organisms) have only been reported once before from Paleocene-Eocene Thermal Maximum (PETM; 55.8 Ma) sediments on the New Jersey coastal plain. Here, using transmission electron microscopic observations, we present evidence for abundant giant magnetofossils, including previously reported elongated prisms and spindles, and new giant bullet-shaped magnetite crystals, in the Southern Ocean near Antarctica, not only during the PETM, but also shortly before and after the PETM. Moreover, we have discovered giant bullet-shaped magnetite crystals from the equatorial Indian Ocean during the Mid-Eocene Climatic Optimum (similar to 40 Ma). Our results indicate a more widespread geographic, environmental, and temporal distribution of giant magnetofossils in the geological record with a link to "hyperthermal" events. Enhanced global weathering during hyperthermals, and expanded suboxic diagenetic environments, probably provided more bioavailable iron that enabled biomineralization of giant magnetofossils. Our micromagnetic modelling indicates the presence of magnetic multi-domain (i.e., not ideal for navigation) and single domain (i.e., ideal for navigation) structures in the giant magnetite particles depending on their size, morphology and spatial arrangement. Different giant magnetite crystal morphologies appear to have had different biological functions, including magnetotaxis and other non-navigational purposes. Our observations suggest that hyperthermals provided ideal conditions for giant magnetofossils, and that these organisms were globally distributed. Much more work is needed to understand the interplay between magnetofossil morphology, climate, nutrient availability, and environmental variability.