Genetic Variation and Antioxidant Response Gene Expression in the Bronchial Airway Epithelium of Smokers at Risk for Lung Cancer

Prior microarray studies of smokers at high risk for lung cancer have demonstrated that heterogeneity in bronchial airway epithelial cell gene expression response to smoking can serve as an early diagnostic biomarker for lung cancer. As a first step in applying functional genomic analysis to population studies, we have examined the relationship between gene expression variation and genetic variation in a central molecular pathway (NRF2-mediated antioxidant response) associated with smoking exposure and lung cancer. We assessed global gene expression in histologically normal airway epithelial cells obtained at bronchoscopy from smokers who developed lung cancer (SC, n=20), smokers without lung cancer (SNC, n=24), and never smokers (NS, n=8). Functional enrichment analysis showed that the NRF2-mediated, antioxidant response element (ARE)-regulated genes, were significantly lower in SC, when compared with expression levels in SNC. Importantly, we found that the expression of MAFG (a binding partner of NRF2) was correlated with the expression of ARE genes, suggesting MAFG levels may limit target gene induction. Bioinformatically we identified single nucleotide polymorphisms (SNPs) in putative ARE genes and to test the impact of genetic variation, we genotyped these putative regulatory SNPs and other tag SNPs in selected NRF2 pathway genes. Sequencing MAFG locus, we identified 30 novel SNPs and two were associated with either gene expression or lung cancer status among smokers. This work demonstrates an analysis approach that integrates bioinformatics pathway and transcription factor binding site analysis with genotype, gene expression and disease status to identify SNPs that may be associated with individual differences in gene expression and/or cancer status in smokers. These polymorphisms might ultimately contribute to lung cancer risk via their effect on the airway gene expression response to tobacco-smoke exposure.Intramural Research Program of the National Institute of Environmental Health Sciences; National Institutes of Health (Z01 ES100475, U01ES016035, R01CA124640

Heralded generation of entangled photon pairs

Entangled photons are a crucial resource for quantum communication and linear optical quantum computation. Unfortunately, the applicability of many photon-based schemes is limited due to the stochastic character of the photon sources. Therefore, a worldwide effort has focused in overcoming the limitation of probabilistic emission by generating two-photon entangled states conditioned on the detection of auxiliary photons. Here we present the first heralded generation of photon states that are maximally entangled in polarization with linear optics and standard photon detection from spontaneous parametric down-conversion. We utilize the down-conversion state corresponding to the generation of three photon pairs, where the coincident detection of four auxiliary photons unambiguously heralds the successful preparation of the entangled state. This controlled generation of entangled photon states is a significant step towards the applicability of a linear optics quantum network, in particular for entanglement swapping, quantum teleportation, quantum cryptography and scalable approaches towards photonics-based quantum computing

The Plasmodium berghei Ca(2+)/H(+) exchanger, PbCAX, is essential for tolerance to environmental Ca(2+) during sexual development.

Ca(2+) contributes to a myriad of important cellular processes in all organisms, including the apicomplexans, Plasmodium and Toxoplasma. Due to its varied and essential roles, free Ca(2+) is tightly regulated by complex mechanisms. These mechanisms are therefore of interest as putative drug targets. One pathway in Ca(2+) homeostatic control in apicomplexans uses a Ca(2+)/H(+) exchanger (a member of the cation exchanger family, CAX). The P. falciparum CAX (PfCAX) has recently been characterised in asexual blood stage parasites. To determine the physiological importance of apicomplexan CAXs, tagging and knock-out strategies were undertaken in the genetically tractable T. gondii and P. berghei parasites. In addition, a yeast heterologous expression system was used to study the function of apicomplexan CAXs. Tagging of T. gondii and P. berghei CAXs (TgCAX and PbCAX) under control of their endogenous promoters could not demonstrate measureable expression of either CAX in tachyzoites and asexual blood stages, respectively. These results were consistent with the ability of parasites to tolerate knock-outs of the genes for TgCAX and PbCAX at these developmental stages. In contrast, PbCAX expression was detectable during sexual stages of development in female gametocytes/gametes, zygotes and ookinetes, where it was dispersed in membranous networks within the cytosol (with minimal mitochondrial localisation). Furthermore, genetically disrupted parasites failed to develop further from "round" form zygotes, suggesting that PbCAX is essential for ookinete development and differentiation. This impeded phenotype could be rescued by removal of extracellular Ca(2+). Therefore, PbCAX provides a mechanism for free living parasites to multiply within the ionic microenvironment of the mosquito midgut. Ca(2+) homeostasis mediated by PbCAX is critical and suggests plasmodial CAXs may be targeted in approaches designed to block parasite transmission

All-Optical Switching Demonstration using Two-Photon Absorption and the Classical Zeno Effect

Low-contrast all-optical Zeno switching has been demonstrated in a silicon nitride microdisk resonator coupled to a hot atomic vapor. The device is based on the suppression of the field build-up within a microcavity due to non-degenerate two-photon absorption. This experiment used one beam in a resonator and one in free-space due to limitations related to device physics. These results suggest that a similar scheme with both beams resonant in the cavity would correspond to input power levels near 20 nW.Comment: 4 pages, 5 figure

Imperfect Detectors in Linear Optical Quantum Computers

We discuss the effects of imperfect photon detectors suffering from loss and noise on the reliability of linear optical quantum computers. We show that for a given detector efficiency, there is a maximum achievable success probability, and that increasing the number of ancillary photons and detectors used for one controlled sign flip gate beyond a critical point will decrease the probability that the computer will function correctly. We have also performed simulations of some small logic gates and estimate the efficiency and noise levels required for the linear optical quantum computer to function properly.Comment: 13 pages, 5 figure

Validation of the Harvard Lyman-α in situ water vapor instrument: Implications for the mechanisms that control stratospheric water vapor

Building on previously published details of the laboratory calibrations of the Harvard Lyman-α photofragment fluorescence hygrometer (HWV) on the NASA ER-2 and WB-57 aircraft, we describe here the validation process for HWV, which includes laboratory calibrations and intercomparisons with other Harvard water vapor instruments at water vapor mixing ratios from 0 to 10 ppmv, followed by in-flight intercomparisons with the same Harvard hygrometers. The observed agreement exhibited in the laboratory and during intercomparisons helps corroborate the accuracy of HWV. In light of the validated accuracy of HWV, we present and evaluate a series of intercomparisons with satellite and balloon borne water vapor instruments made from the upper troposphere to the lower stratosphere in the tropics and midlatitudes. Whether on the NASA ER-2 or WB-57 aircraft, HWV has consistently measured about 1–1.5 ppmv higher than the balloon-borne NOAA/ESRL/GMD frost point hygrometer (CMDL), the NOAA Cryogenic Frost point Hygrometer (CFH), and the Microwave Limb Sounder (MLS) on the Aura satellite in regions of the atmosphere where water vapor is <10 ppmv. Comparisons in the tropics with the Halogen Occultation Experiment (HALOE) on the Upper Atmosphere Research Satellite show large variable differences near the tropopause that converge to ~10% above 460 K, with HWV higher. Results we show from the Aqua Validation and Intercomparison Experiment (AquaVIT) at the AIDA chamber in Karlsruhe do not reflect the observed in-flight differences. We illustrate that the interpretation of the results of comparisons between modeled and measured representations of the seasonal cycle of water entering the lower tropical stratosphere is dictated by which data set is used

An assessment of the readiness of ablative materials for preflight application to the shuttle orbiter

The shuttle orbiter relies primarily on a reusable surface insulation (RSI) thermal protection system (TPS). The RSI is very efficient in its thermal performance; however, the RSI tile system has shown poor mechanical integrity. The state-of-the-art of the ablative TPS is reviewed, and an assessment made of the ablator's readiness for use on the shuttle orbiter. Unresolved technical issues with regard to the ablative TPS are identified. Short time, highly focused analytical and experimental programs were initiated to: (1) identify candidate ablation materials; (2) assess the data base for these materials; (3) evaluate the need and kind of waterproof coating; (4) calculate thermal and other stresses in an ablator tile; (5) identify an acceptable ablator/RSI tile joint filler; and (6) assess the sensitivity of the ablator to sequential heat pulses. Results from some of these programs are discussed

24^{24}Mg(pp, α\alpha)21^{21}Na reaction study for spectroscopy of 21^{21}Na

The $^{24}$Mg($p$, $\alpha$)$^{21}$Na reaction was measured at the Holifield Radioactive Ion Beam Facility at Oak Ridge National Laboratory in order to better constrain spins and parities of energy levels in $^{21}$Na for the astrophysically important $^{17}$F($\alpha, p$)$^{20}$Ne reaction rate calculation. 31 MeV proton beams from the 25-MV tandem accelerator and enriched $^{24}$Mg solid targets were used. Recoiling $^{4}$He particles from the $^{24}$Mg($p$, $\alpha$)$^{21}$Na reaction were detected by a highly segmented silicon detector array which measured the yields of $^{4}$He particles over a range of angles simultaneously. A new level at 6661 $\pm$ 5 keV was observed in the present work. The extracted angular distributions for the first four levels of $^{21}$Na and Distorted Wave Born Approximation (DWBA) calculations were compared to verify and extract angular momentum transfer.Comment: 11 pages, 6 figures, proceedings of the 18th International Conference on Accelerators and Beam Utilization (ICABU2014

Recent direct reaction experimental studies with radioactive tin beams

Direct reaction techniques are powerful tools to study the single-particle nature of nuclei. Performing direct reactions on short-lived nuclei requires radioactive ion beams produced either via fragmentation or the Isotope Separation OnLine (ISOL) method. Some of the most interesting regions to study with direct reactions are close to the magic numbers where changes in shell structure can be tracked. These changes can impact the final abundances of explosive nucleosynthesis. The structure of the chain of tin isotopes is strongly influenced by the Z=50 proton shell closure, as well as the neutron shell closures lying in the neutron-rich, N=82, and neutron-deficient, N=50, regions. Here we present two examples of direct reactions on exotic tin isotopes. The first uses a one-neutron transfer reaction and a low-energy reaccelerated ISOL beam to study states in 131Sn from across the N=82 shell closure. The second example utilizes a one-neutron knockout reaction on fragmentation beams of neutron-deficient 106,108Sn. In both cases, measurements of gamma rays in coincidence with charged particles proved to be invaluable.Comment: 11 pages, 5 figures, Zakopane Conference on Nuclear Physics "Extremes of the Nuclear Landscape", Zakopane, Poland, August 31 - September 7, 201