A Bayesian method for evaluating and discovering disease loci associations

Background: A genome-wide association study (GWAS) typically involves examining representative SNPs in individuals from some population. A GWAS data set can concern a million SNPs and may soon concern billions. Researchers investigate the association of each SNP individually with a disease, and it is becoming increasingly commonplace to also analyze multi-SNP associations. Techniques for handling so many hypotheses include the Bonferroni correction and recently developed Bayesian methods. These methods can encounter problems. Most importantly, they are not applicable to a complex multi-locus hypothesis which has several competing hypotheses rather than only a null hypothesis. A method that computes the posterior probability of complex hypotheses is a pressing need. Methodology/Findings: We introduce the Bayesian network posterior probability (BNPP) method which addresses the difficulties. The method represents the relationship between a disease and SNPs using a directed acyclic graph (DAG) model, and computes the likelihood of such models using a Bayesian network scoring criterion. The posterior probability of a hypothesis is computed based on the likelihoods of all competing hypotheses. The BNPP can not only be used to evaluate a hypothesis that has previously been discovered or suspected, but also to discover new disease loci associations. The results of experiments using simulated and real data sets are presented. Our results concerning simulated data sets indicate that the BNPP exhibits both better evaluation and discovery performance than does a p-value based method. For the real data sets, previous findings in the literature are confirmed and additional findings are found. Conclusions/Significance: We conclude that the BNPP resolves a pressing problem by providing a way to compute the posterior probability of complex multi-locus hypotheses. A researcher can use the BNPP to determine the expected utility of investigating a hypothesis further. Furthermore, we conclude that the BNPP is a promising method for discovering disease loci associations. © 2011 Jiang et al

Wettability of amorphous and nanocrystalline Fe78B13Si9 substrates by molten Sn and Bi

The wettability of amorphous and annealing-induced nanocrystalline Fe78B13Si9 ribbons by molten Sn and Bi at 600 K was measured using an improved sessile drop method. The results demonstrate that the structural relaxation and crystallization in the amorphous substrates do not substantially change the wettability with molten Bi because of their invariable physical interaction, but remarkably deteriorate the wettability and interfacial bonding with molten Sn as a result of changing a chemical interaction to a physical one for the atoms at the interface

Realistic Standard Model Fermion Mass Relations in Generalized Minimal Supergravity (GmSUGRA)

Grand Unified Theories (GUTs) usually predict wrong Standard Model (SM) fermion mass relation m_e/m_{\mu} = m_d/m_s toward low energies. To solve this problem, we consider the Generalized Minimal Supergravity (GmSUGRA) models, which are GUTs with gravity mediated supersymmetry breaking and higher dimensional operators. Introducing non-renormalizable terms in the super- and K\"ahler potentials, we can obtain the correct SM fermion mass relations in the SU(5) model with GUT Higgs fields in the {\bf 24} and {\bf 75} representations, and in the SO(10) model. In the latter case the gauge symmetry is broken down to SU(3)_C X SU(2)_L X SU(2)_R X U(1)_{B-L}, to flipped SU(5)X U(1)_X, or to SU(3)_C X SU(2)_L X U(1)_1 X U(1)_2. Especially, for the first time we generate the realistic SM fermion mass relation in GUTs by considering the high-dimensional operators in the K\"ahler potential.Comment: JHEP style, 29 pages, no figure,references adde

Gamma (γ) tocopherol upregulates peroxisome proliferator activated receptor (PPAR) gamma (γ) expression in SW 480 human colon cancer cell lines

BACKGROUND: Tocopherols are lipid soluble antioxidants that exist as eight structurally different isoforms. The intake of γ-tocopherol is higher than α-tocopherol in the average US diet. The clinical results of the effects of vitamin E as a cancer preventive agent have been inconsistent. All published clinical trials with vitamin E have used α-tocopherol. Recent epidemiological, experimental and molecular studies suggest that γ-tocopherol may be a more potent chemopreventive form of vitamin E compared to the more-studied α-tocopherol. γ-Tocopherol exhibits differences in its ability to detoxify nitrogen dioxide, growth inhibitory effects on selected cancer cell lines, inhibition of neoplastic transformation in embryonic fibroblasts, and inhibition of cyclooxygenase-2 (COX-2) activity in macrophages and epithelial cells. Peroxisome proliferator activator receptor γ (PPARγ) is a promising molecular target for colon cancer prevention. Upregulation of PPARγ activity is anticarcinogenic through its effects on downstream genes that affect cellular proliferation and apoptosis. The thiazolidine class of drugs are powerful PPARγ ligands. Vitamin E has structural similarity to the thiazolidine, troglitazone. In this investigation, we tested the effects of both α and γ tocopherol on the expression of PPARγ mRNA and protein in SW 480 colon cancer cell lines. We also measured the intracellular concentrations of vitamin E in SW 480 colon cancer cell lines. RESULTS: We have discovered that the α and γ isoforms of vitamin E upregulate PPARγ mRNA and protein expression in the SW480 colon cancer cell lines. γ-Tocopherol is a better modulator of PPARγ expression than α-tocopherol at the concentrations tested. Intracellular concentrations increased as the vitamin E concentration added to the media was increased. Further, γ-tocopherol-treated cells have higher intracellular tocopherol concentrations than those treated with the same concentrations of α-tocopherol. CONCLUSION: Our data suggest that both α and γ tocopherol can upregulate the expression of PPARγ which is considered an important molecular target for colon cancer chemoprevention. We show that the expression of PPARγ mRNA and protein are increased and these effects are more pronounced with γ-tocopherol. γ-Tocopherol's ability to upregulate PPARγ expression and achieve higher intracellular concentrations in the colonic tissue may be relevant to colon cancer prevention. We also show that the intracellular concentrations of γ-tocopherol are several fold higher than α-tocopherol. Further work on other colon cancer cell lines are required to quantitate differences in the ability of these forms of vitamin E to induce apoptosis, suppress cell proliferation and act as PPAR ligands as well as determine their effects in conjunction with other chemopreventive agents. Upregulation of PPARγ by the tocopherols and in particular by γ-tocopherol may have relevance not only to cancer prevention but also to the management of inflammatory and cardiovascular disorders

General Gauge and Anomaly Mediated Supersymmetry Breaking in Grand Unified Theories with Vector-Like Particles

In Grand Unified Theories (GUTs) from orbifold and various string constructions the generic vector-like particles do not need to form complete SU(5) or SO(10) representations. To realize them concretely, we present orbifold SU(5) models, orbifold SO(10) models where the gauge symmetry can be broken down to flipped SU(5) X U(1)_X or Pati-Salam SU(4)_C X SU(2)_L X SU(2)_R gauge symmetries, and F-theory SU(5) models. Interestingly, these vector-like particles can be at the TeV-scale so that the lightest CP-even Higgs boson mass can be lifted, or play the messenger fields in the Gauge Mediated Supersymmetry Breaking (GMSB). Considering GMSB, ultraviolet insensitive Anomaly Mediated Supersymmetry Breaking (AMSB), and the deflected AMSB, we study the general gaugino mass relations and their indices, which are valid from the GUT scale to the electroweak scale at one loop, in the SU(5) models, the flipped SU(5) X U(1)_X models, and the Pati-Salam SU(4)_C X SU(2)_L X SU(2)_R models. In the deflected AMSB, we also define the new indices for the gaugino mass relations, and calculate them as well. Using these gaugino mass relations and their indices, we may probe the messenger fields at intermediate scale in the GMSB and deflected AMSB, determine the supersymmetry breaking mediation mechanisms, and distinguish the four-dimensional GUTs, orbifold GUTs, and F-theory GUTs.Comment: RevTex4, 45 pages, 15 tables, version to appear in JHE

Nosocomial Co-Transmission of Avian Influenza A(H7N9) and A(H1N1)pdm09 Viruses between 2 Patients with Hematologic Disorders

A nosocomial cluster induced by co-infections with avian influenza A(H7N9) and A(H1N1)pdm09 (pH1N1) viruses occurred in 2 patients at a hospital in Zhejiang Province, China, in January 2014. The index case-patient was a 57-year-old man with chronic lymphocytic leukemia who had been occupationally exposed to poultry. He had co-infection with H7N9 and pH1N1 viruses. A 71-year-old man with polycythemia vera who was in the same ward as the index case-patient for 6 days acquired infection with H7N9 and pH1N1 viruses. The incubation period for the second case-patient was estimated to be <4 days. Both case-patients died of multiple organ failure. Virus genetic sequences from the 2 case-patients were identical. Of 103 close contacts, none had acute respiratory symptoms; all were negative for H7N9 virus. Serum samples from both case-patients demonstrated strong proinflammatory cytokine secretion but incompetent protective immune responses. These findings strongly suggest limited nosocomial co-transmission of H7N9 and pH1N1 viruses from 1 immunocompromised patient to another.published_or_final_versio

Exogenous spatial precuing reliably modulates object processing but not object substitution masking

Object substitution masking (OSM) is used in behavioral and imaging studies to investigate processes associated with the formation of a conscious percept. Reportedly, OSM occurs only when visual attention is diffusely spread over a search display or focused away from the target location. Indeed, the presumed role of spatial attention is central to theoretical accounts of OSM and of visual processing more generally (Di Lollo, Enns, & Rensink, Journal of Experimental Psychology: General 129:481–507, 2000). We report a series of five experiments in which valid spatial precuing is shown to enhance the ability of participants to accurately report a target but, in most cases, without affecting OSM. In only one experiment (Experiment 5) was a significant effect of precuing observed on masking. This is in contrast to the reliable effect shown across all five experiments in which precuing improved overall performance. The results are convergent with recent findings from Argyropoulos, Gellatly, and Pilling (Journal of Experimental Psychology: Human Perception and Performance 39:646–661, 2013), which show that OSM is independent of the number of distractor items in a display. Our results demonstrate that OSM can operate independently of focal attention. Previous claims of the strong interrelationship between OSM and spatial attention are likely to have arisen from ceiling or floor artifacts that restricted measurable performance

Towards Quantum Repeaters with Solid-State Qubits: Spin-Photon Entanglement Generation using Self-Assembled Quantum Dots

In this chapter we review the use of spins in optically-active InAs quantum dots as the key physical building block for constructing a quantum repeater, with a particular focus on recent results demonstrating entanglement between a quantum memory (electron spin qubit) and a flying qubit (polarization- or frequency-encoded photonic qubit). This is a first step towards demonstrating entanglement between distant quantum memories (realized with quantum dots), which in turn is a milestone in the roadmap for building a functional quantum repeater. We also place this experimental work in context by providing an overview of quantum repeaters, their potential uses, and the challenges in implementing them.Comment: 51 pages. Expanded version of a chapter to appear in "Engineering the Atom-Photon Interaction" (Springer-Verlag, 2015; eds. A. Predojevic and M. W. Mitchell

Return to fertility after extended chemical castration with a GnRH antagonist

BACKGROUND: Antagonistic analogues of GnRH for the treatment of prostate cancer may be used clinically in persons for whom return to fertility after such treatment is important or desirable. The purpose of this study was, therefore, to evaluate the effects of a long term treatment with orntide, a GnRH antagonist, on testosterone levels and fertility in male rats. METHODS: Two groups of male rats received either 120-day orntide microspheres (8.8 mg orntide/kg/120 days) or vehicle alone (control group). Serum orntide and testosterone levels in both groups were monitored at certain intervals for 9 months from the initiation of treatment. After recovery of normal serum testosterone levels in the treated animals, each rat was housed with two proven breeder, but drug-naive, females. RESULTS: All mates of treated rats achieved pregnancy as rapidly as the mates of control rats although two of the control rats did not sire a litter with either female and one sired only one litter. The mean size of the litters of treated (12.3 offspring per litter) and control (10.6 offspring per litter) were similar. All offspring were grossly normal morphologically and behaviorally during the time to weaning. CONCLUSIONS: These results suggest that lack of fertility due to testosterone suppression is reversible after cessation of treatment with this GnRH antagonist