A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p <= 5 x 10(-7)). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1 x 10(-8)) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2 x 10(-8)) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 x 10(-8); rs1229984-ADH1B, p = 7 x 10(-9); and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.

Maternal diabetes affects cell proliferation in developing rat placenta

Placentation starts with the formation of a spheroidal trophoblastic shell surrounding the embryo, thus facilitating both implantation into the uterine stroma and contact with maternal blood. Although it is known that diabetes increases the placental size and weight, the mechanisms responsible for this alteration are still poorly understood. In mammals, cellular proliferation occurs in parallel to placental development and it is possible that diabetes induces abnormal uncontrolled cell proliferation in the placenta similar to that seen in other organs (e.g. retina). To test this hypothesis, the objective of this work was to determine cell proliferation in different regions of the placenta during its development in a diabetic rat model. Accordingly, diabetes was induced on day 2 of pregnancy in Wistar rats by a single injection of alloxan (40 mg/kg i.v.). Placentas were collected on days 14, 17, and 20 postcoitum. Immunoperoxidase was used to identify Ki67 nuclear antigen in placental sections. The number of proliferating cells was determined in the total placental area as well as in the labyrinth, spongiotrophoblast and giant trophoblast cell regions. During the course of pregnancy, the number of Ki67 positive cells decreased in both control and diabetic rat placentas. However, starting from day 17 of pregnancy, the number of Ki67 positive cells in the labyrinth and spongiotrophoblast regions was higher in diabetic rat placentas as compared to control. The present results demonstrate that placentas from the diabetic rat model have a significantly higher number of proliferating cells in specific regions of the placenta and at defined developmental stages. It is possible that this increased cell proliferation promotes thickness of the placental barrier consequently affecting the normal maternal-fetal exchanges.

An overview of the Amazonian Aerosol Characterization Experiment 2008 (AMAZE-08)

The Amazon Basin provides an excellent environment for studying the sources, transformations, and properties of natural aerosol particles and the resulting links between biological processes and climate. With this framework in mind, the Amazonian Aerosol Characterization Experiment (AMAZE-08), carried out from 7 February to 14 March 2008 during the wet season in the central Amazon Basin, sought to understand the formation, transformations, and cloud-forming properties of fine-and coarse-mode biogenic aerosol particles, especially as related to their effects on cloud activation and regional climate. Special foci included (1) the production mechanisms of secondary organic components at a pristine continental site, including the factors regulating their temporal variability, and (2) predicting and understanding the cloud-forming properties of biogenic particles at such a site. In this overview paper, the field site and the instrumentation employed during the campaign are introduced. Observations and findings are reported, including the large-scale context for the campaign, especially as provided by satellite observations. New findings presented include: (i) a particle number-diameter distribution from 10 nm to 10 mu m that is representative of the pristine tropical rain forest and recommended for model use; (ii) the absence of substantial quantities of primary biological particles in the submicron mode as evidenced by mass spectral characterization; (iii) the large-scale production of secondary organic material; (iv) insights into the chemical and physical properties of the particles as revealed by thermodenuder-induced changes in the particle number-diameter distributions and mass spectra; and (v) comparisons of ground-based predictions and satellite-based observations of hydrometeor phase in clouds. A main finding of AMAZE-08 is the dominance of secondary organic material as particle components. The results presented here provide mechanistic insight and quantitative parameters that can serve to increase the accuracy of models of the formation, transformations, and cloud-forming properties of biogenic natural aerosol particles, especially as related to their effects on cloud activation and regional climate.

Transport of North African dust from the Bod,l, depression to the Amazon Basin: a case study

Through long-range transport of dust, the North-African desert supplies essential minerals to the Amazon rain forest. Since North African dust reaches South America mostly during the Northern Hemisphere winter, the dust sources active during winter are the main contributors to the forest. Given that the Bod,l, depression area in southwestern Chad is the main winter dust source, a close link is expected between the Bod,l, emission patterns and volumes and the mineral supply flux to the Amazon. Until now, the particular link between the Bod,l, and the Amazon forest was based on sparse satellite measurements and modeling studies. In this study, we combine a detailed analysis of space-borne and ground data with reanalysis model data and surface measurements taken in the central Amazon during the Amazonian Aerosol Characterization Experiment (AMAZE-08) in order to explore the validity and the nature of the proposed link between the Bod,l, depression and the Amazon forest. This case study follows the dust events of 11-16 and 18-27 February 2008, from the emission in the Bod,l, over West Africa (most likely with contribution from other dust sources in the region) the crossing of the Atlantic Ocean, to the observed effects above the Amazon canopy about 10 days after the emission. The dust was lifted by surface winds stronger than 14 m s(-1), usually starting early in the morning. The lofted dust, mixed with biomass burning aerosols over Nigeria, was transported over the Atlantic Ocean, and arrived over the South American continent. The top of the aerosol layer reached above 3 km, and the bottom merged with the boundary layer. The arrival of the dusty air parcel over the Amazon forest increased the average concentration of aerosol crustal elements by an order of magnitude.

Cloud condensation nuclei in pristine tropical rainforest air of Amazonia: size-resolved measurements and modeling of atmospheric aerosol composition and CCN activity

Atmospheric aerosol particles serving as cloud condensation nuclei (CCN) are key elements of the hydrological cycle and climate. We have measured and characterized CCN at water vapor supersaturations in the range of S=0.10-0.82% in pristine tropical rainforest air during the AMAZE-08 campaign in central Amazonia. The effective hygroscopicity parameters describing the influence of chemical composition on the CCN activity of aerosol particles varied in the range of kappa approximate to 0.1-0.4 (0.16+/-0.06 arithmetic mean and standard deviation). The overall median value of kappa approximate to 0.15 was by a factor of two lower than the values typically observed for continental aerosols in other regions of the world. Aitken mode particles were less hygroscopic than accumulation mode particles (kappa approximate to 0.1 at D approximate to 50 nm; kappa approximate to 0.2 at D approximate to 200 nm), which is in agreement with earlier hygroscopicity tandem differential mobility analyzer (H-TDMA) studies. The CCN measurement results are consistent with aerosol mass spectrometry (AMS) data, showing that the organic mass fraction (f(org)) was on average as high as similar to 90% in the Aitken mode (D <= 100 nm) and decreased with increasing particle diameter in the accumulation mode (similar to 80% at D approximate to 200 nm). The kappa values exhibited a negative linear correlation with f(org) (R(2)=0.81), and extrapolation yielded the following effective hygroscopicity parameters for organic and inorganic particle components: kappa(org)approximate to 0.1 which can be regarded as the effective hygroscopicity of biogenic secondary organic aerosol (SOA) and kappa(inorg)approximate to 0.6 which is characteristic for ammonium sulfate and related salts. Both the size dependence and the temporal variability of effective particle hygroscopicity could be parameterized as a function of AMS-based organic and inorganic mass fractions (kappa(p)=kappa(org) x f(org)+kappa(inorg) x f(inorg)). The CCN number concentrations predicted with kappa(p) were in fair agreement with the measurement results (similar to 20% average deviation). The median CCN number concentrations at S=0.1-0.82% ranged from N(CCN,0.10)approximate to 35 cm(-3) to N(CCN,0.82)approximate to 160 cm(-3), the median concentration of aerosol particles larger than 30 nm was N(CN,30)approximate to 200 cm(-3), and the corresponding integral CCN efficiencies were in the range of N(CCN,0.10/NCN,30)approximate to 0.1 to N(CCN,0.82/NCN,30)approximate to 0.8. Although the number concentrations and hygroscopicity parameters were much lower in pristine rainforest air, the integral CCN efficiencies observed were similar to those in highly polluted megacity air. Moreover, model calculations of N(CCN,S) assuming an approximate global average value of kappa approximate to 0.3 for continental aerosols led to systematic overpredictions, but the average deviations exceeded similar to 50% only at low water vapor supersaturation (0.1%) and low particle number concentrations (<= 100 cm(-3)). Model calculations assuming aconstant aerosol size distribution led to higher average deviations at all investigated levels of supersaturation: similar to 60% for the campaign average distribution and similar to 1600% for a generic remote continental size distribution. These findings confirm earlier studies suggesting that aerosol particle number and size are the major predictors for the variability of the CCN concentration in continental boundary layer air, followed by particle composition and hygroscopicity as relatively minor modulators. Depending on the required and applicable level of detail, the information and parameterizations presented in this paper should enable efficient description of the CCN properties of pristine tropical rainforest aerosols of Amazonia in detailed process models as well as in large-scale atmospheric and climate models.

Rapid formation of isoprene photo-oxidation products observed in Amazonia

Isoprene represents the single most important reactive hydrocarbon for atmospheric chemistry in the tropical atmosphere. It plays a central role in global and regional atmospheric chemistry and possible climate feedbacks. Photo-oxidation of primary hydrocarbons (e. g. isoprene) leads to the formation of oxygenated VOCs (OVOCs). The evolution of these intermediates affects the oxidative capacity of the atmosphere (by reacting with OH) and can contribute to secondary aerosol formation, a poorly understood process. An accurate and quantitative understanding of VOC oxidation processes is needed for model simulations of regional air quality and global climate. Based on field measurements conducted during the Amazonian Aerosol Characterization Experiment (AMAZE-08) we show that the production of certain OVOCs (e. g. hydroxyacetone) from isoprene photo-oxidation in the lower atmosphere is significantly underpredicted by standard chemistry schemes. Recently reported fast secondary production could explain 50% of the observed discrepancy with the remaining part possibly produced via a novel primary production channel, which has been proposed theoretically. The observations of OVOCs are also used to test a recently proposed HO(x) recycling mechanism via degradation of isoprene peroxy radicals. If generalized our observations suggest that prompt photochemical formation of OVOCs and other uncertainties in VOC oxidation schemes could result in uncertainties of modelled OH reactivity, potentially explaining a fraction of the missing OH sink over forests which has previously been largely attributed to a missing source of primary biogenic VOCs.

On molecular chirality within naturally occurring secondary organic aerosol particles from the central Amazon Basin

In this perspectives article, we reflect upon the existence of chirality in atmospheric aerosol particles. We then show that organic particles collected at a field site in the central Amazon Basin under pristine background conditions during the wet and dry seasons consist of chiral secondary organic material. We show how the chiral response from the aerosol particles can be imaged directly without the need for sample dissolution, solvent extraction, or sample preconcentration. By comparing the chiral-response images with optical images, we show that chiral responses always originate from particles on the filter, but not all aerosol particles produce chiral signals. The intensity of the chiral signal produced by the size resolved particles strongly indicates the presence of chiral secondary organic material in the particle. Finally, we discuss the implications of our findings on chiral atmospheric aerosol particles in terms of climate-related properties and source apportionment.

Azimuthal correlations of electrons from heavy-flavor decay with hadrons in p plus p and Au plus Au collisions at root s(NN)=200 GeV

Measurements of electrons from the decay of open-heavy-flavor mesons have shown that the yields are suppressed in Au+Au collisions compared to expectations from binary-scaled p+p collisions. These measurements indicate that charm and bottom quarks interact with the hot dense matter produced in heavy-ion collisions much more than expected. Here we extend these studies to two-particle correlations where one particle is an electron from the decay of a heavy-flavor meson and the other is a charged hadron from either the decay of the heavy meson or from jet fragmentation. These measurements provide more detailed information about the interactions between heavy quarks and the matter, such as whether the modification of the away-side-jet shape seen in hadron-hadron correlations is present when the trigger particle is from heavy-meson decay and whether the overall level of away-side-jet suppression is consistent. We statistically subtract correlations of electrons arising from background sources from the inclusive electron-hadron correlations and obtain two-particle azimuthal correlations at root s(NN) = 200 GeV between electrons from heavy-flavor decay with charged hadrons in p+p and also first results in Au+Au collisions. We find the away-side-jet shape and yield to be modified in Au+Au collisions compared to p+p collisions.

Measurement of neutral mesons in p plus p collisions at root s=200 GeV and scaling properties of hadron production

The PHENIX experiment at the Relativistic Heavy Ion Collider has measured the invariant differential cross section for production of K(S)(0), omega, eta', and phi mesons in p + p collisions at root s 200 GeV. Measurements of omega and phi production in different decay channels give consistent results. New results for the omega are in agreement with previously published data and extend the measured p(T) coverage. The spectral shapes of all hadron transverse momentum distributions measured by PHENIX are well described by a Tsallis distribution functional form with only two parameters, n and T, determining the high-p(T) and characterizing the low-p(T) regions of the spectra, respectively. The values of these parameters are very similar for all analyzed meson spectra, but with a lower parameter T extracted for protons. The integrated invariant cross sections calculated from the fitted distributions are found to be consistent with existing measurements and with statistical model predictions.

Cross Section and Parity-Violating Spin Asymmetries of W(+/-) Boson Production in Polarized p plus p Collisions at root s=500 Gev

Large parity-violating longitudinal single-spin asymmetries A(L)(e+) = 0.86(-0.14)(+0.30) and Ae(L)(e-) = 0.88(-0.71)(+0.12) are observed for inclusive high transverse momentum electrons and positrons in polarized p + p collisions at a center-of-mass energy of root s = 500 GeV with the PHENIX detector at RHIC. These e(+/-) come mainly from the decay of W(+/-) and Z(0) bosons, and their asymmetries directly demonstrate parity violation in the couplings of the W(+/-) to the light quarks. The observed electron and positron yields were used to estimate W(+/-) boson production cross sections for the e(+/-) channels of sigma(pp -> W(+)X) X BR(W(+) -> e(+) nu(e)) = 144.1 +/- 21.2(stat)(-10.3)(+3.4)(syst) +/- 21.6(norm) pb, and sigma(pp -> W(-)X) X BR(W(-) -> e(-) (nu) over bar (e)) = 3.17 +/- 12.1(stat)(-8.2)(+10.1)(syst) +/- 4.8(norm) pb.

Cross section and double helicity asymmetry for eta mesons and their comparison to pi(0) production in p plus p collisions at root s=200 GeV

Measurements of double-helicity asymmetries in inclusive hadron production in polarized p + p collisions are sensitive to helicity-dependent parton distribution functions, in particular, to the gluon helicity distribution, Delta g. This study focuses on the extraction of the double-helicity asymmetry in eta production ((p) over right arrow + (p) over right arrow -> eta + X), the eta cross section, and the eta/pi(0) cross section ratio. The cross section and ratio measurements provide essential input for the extraction of fragmentation functions that are needed to access the helicity-dependent parton distribution functions.

Measurement of transverse single-spin asymmetries for J/psi production in polarized p plus p collisions at root s=200 GeV

We report the first measurement of transverse single-spin asymmetries in J/psi production from transversely polarized p + p collisions at root s = 200 GeV with data taken by the PHENIX experiment in 2006 and 2008. The measurement was performed over the rapidity ranges 1.2 < vertical bar y vertical bar < 2.2 and vertical bar y vertical bar < 0.35 for transverse momenta up to 6 GeV/c. J/psi production at the Relativistic Heavy Ion Collider is dominated by processes involving initial-state gluons, and transverse single-spin asymmetries of the J/psi can provide access to gluon dynamics within the nucleon. Such asymmetries may also shed light on the long-standing question in QCD of the J/psi production mechanism. Asymmetries were obtained as a function of J/psi transverse momentum and Feynman-x, with a value of -0.086 +/- 0.026(stat) +/- 0.003(syst) in the forward region. This result suggests possible nonzero trigluon correlation functions in transversely polarized protons and, if well defined in this reaction, a nonzero gluon Sivers distribution function.

High p(T) direct photon and pi(0) triggered azimuthal jet correlations and measurement of k(T) for isolated direct photons in p plus p collisions at root s=200 GeV

Correlations of charged hadrons of 1< p(T) < 10 Gev/c with high pT direct photons and pi(0) mesons in the range 5< p(T) < 15 Gev/c are used to study jet fragmentation in the gamma + jet and dijet channels, respectively. The magnitude of the partonic transverse momentum, k(T), is obtained by comparing to a model incorporating a Gaussian kT smearing. The sensitivity of the associated charged hadron spectra to the underlying fragmentation function is tested and the data are compared to calculations using recent global fit results. The shape of the direct photon-associated hadron spectrum as well as its charge asymmetry are found to be consistent with a sample dominated by quark-gluon Compton scattering. No significant evidence of fragmentation photon correlated production is observed within experimental uncertainties.

Transverse momentum dependence of J/psi polarization at midrapidity in p plus p collisions at root s=200 GeV

We report the measurement of the transverse momentum dependence of inclusive J/psi polarization in p + p collisions at root s = 200 GeV performed by the PHENIX Experiment at the Relativistic Heavy Ion Collider. The J/psi polarization is studied in the helicity, Gottfried-Jackson, and Collins-Soper frames for p(T) < 5 GeV/c and vertical bar y vertical bar < 0.35. The polarization in the helicity and Gottfried-Jackson frames is consistent with zero for all transverse momenta, with a slight (1.8 sigma) trend towards longitudinal polarization for transverse momenta above 2 GeV/c. No conclusion is allowed due to the limited acceptance in the Collins-Soper frame and the uncertainties of the current data. The results are compared to observations for other collision systems and center of mass energies and to different quarkonia production models.

Detailed measurement of the e(+)e(-) pair continuum in p plus p and Au plus Au collisions at root s(NN)=200 GeV and implications for direct photon production

PHENIX has measured the e(+)e(-) pair continuum in root s(NN) = 200 GeV Au+Au and p+p collisions over a wide range of mass and transverse momenta. The e(+)e(-) yield is compared to the expectations from hadronic sources, based on PHENIX measurements. In the intermediate-mass region, between the masses of the phi and the J/psi meson, the yield is consistent with expectations from correlated c (c) over bar production, although other mechanisms are not ruled out. In the low-mass region, below the phi, the p+p inclusive mass spectrum is well described by known contributions from light meson decays. In contrast, the Au+Au minimum bias inclusive mass spectrum in this region shows an enhancement by a factor of 4.7 +/- 0.4(stat) +/- 1.5(syst) +/- 0.9(model). At low mass (m(ee) < 0.3 GeV/c(2)) and high p(T) (1 < p(T) < 5 GeV/c) an enhanced e(+)e(-) pair yield is observed that is consistent with production of virtual direct photons. This excess is used to infer the yield of real direct photons. In central Au+Au collisions, the excess of the direct photon yield over the p+p is exponential in p(T), with inverse slope T = 221 +/- 19(stat) +/- 19(syst) MeV. Hydrodynamical models with initial temperatures ranging from T(init) similar or equal to 300-600 MeV at times of 0.6-0.15 fm/c after the collision are in qualitative agreement with the direct photon data in Au+Au. For low p(T) < 1 GeV/c the low-mass region shows a further significant enhancement that increases with centrality and has an inverse slope of T similar or equal to 100 MeV. Theoretical models underpredict the low-mass, low-p(T) enhancement.