The molecular gas content of z > 6.5 Lyman-alpha emitters

We present results from a sensitive search for CO J=1-0 line emission in two z> 6.5 Lyman-alpha emitters (LAEs) with the Green Bank Telescope. CO J=1-0 emission was not detected from either object. For HCM 6A, at z ~ 6.56, the lensing magnification factor of ~4.5 implies that the CO non-detection yields stringent constraints on the CO J=1-0 line luminosity and molecular gas mass of the LAE, L'(CO) < 6.1x10^9 x (dV/300)^(1/2) K km/s pc^2 and M(H_2) < 4.9x10^9 x (dV/300)^(1/2) x (X(CO)/0.8) Msun. These are the strongest limits obtained so far for a z >~ 6 galaxy. For IOK-1, the constraints are somewhat less sensitive, L'(CO) < 2.3x10^10 x (dV/300)^(1/2) K km/s pc^2 and M(H_2) < 1.9x10^10 x (dV/300)^(1/2) x (X(CO)/0.8) Msun. The non-detection of CO J=1-0 emission in HCM~6A, whose high estimated star formation rate, dust extinction, and lensing magnification make it one of the best high-z LAEs for such a search, implies that typical z >~ 6 LAEs are likely to have significantly lower CO line luminosities than massive sub-mm galaxies and hyperluminous infrared quasars at similar redshifts, due to either a significantly lower molecular gas content or a higher CO-to-H_2 conversion factor.Comment: Accepted for publication in ApJ Letter

Interethnic differences in pancreatic cancer incidence and risk factors: The Multiethnic Cohort.

While disparity in pancreatic cancer incidence between blacks and whites has been observed, few studies have examined disparity in other ethnic minorities. We evaluated variations in pancreatic cancer incidence and assessed the extent to which known risk factors account for differences in pancreatic cancer risk among African Americans, Native Hawaiians, Japanese Americans, Latino Americans, and European Americans in the Multiethnic Cohort Study. Risk factor data were obtained from the baseline questionnaire. Cox regression was used to estimate the relative risks (RRs) and 95% confidence intervals (CIs) for pancreatic cancer associated with risk factors and ethnicity. During an average 16.9-year follow-up, 1,532 incident pancreatic cancer cases were identified among 184,559 at-risk participants. Family history of pancreatic cancer (RR 1.97, 95% CI 1.50-2.58), diabetes (RR 1.32, 95% CI 1.14-1.54), body mass index ≥30&nbsp;kg/m2 (RR 1.25, 95% CI 1.08-1.46), current smoking (&lt;20 pack-years RR 1.43, 95% CI 1.19-1.73; ≥20 pack-years RR 1.76, 95% CI 1.46-2.12), and red meat intake (RR 1.17, 95% CI 1.00-1.36) were associated with pancreatic cancer. After adjustment for these risk factors, Native Hawaiians (RR 1.60, 95% CI 1.30-1.98), Japanese Americans (RR 1.33, 95% CI 1.15-1.54), and African Americans (RR 1.20, 95% CI 1.01-1.42), but not Latino Americans (RR 0.90, 95% CI 0.76-1.07), had a higher risk of pancreatic cancer compared to European Americans. Interethnic differences in pancreatic cancer risk are not fully explained by differences in the distribution of known risk factors. The greater risks in Native Hawaiians and Japanese Americans are new findings and elucidating the causes of these high rates may improve our understanding and prevention of pancreatic cancer

Self-regulation of black hole accretion via jets in early protogalaxies

The early growth of black holes (BHs) in high-redshift galaxies is likely regulated by their feedback on the surrounding gas. While radiative feedback has been extensively studied, the role of mechanical feedback has received comparatively less scrutiny to date. Here we use high-resolution parsec-scale hydrodynamical simulations to study jet propagation and its effect on BH accretion onto 100 ${\rm M_\odot}$ BHs in the dense, low-metallicity gas expected in early protogalaxies. As the jet propagates, it shocks the surrounding gas and forms a jet cocoon. The cocoon consists of a rapidly-cooling cold phase at the interface with the background gas and an over-pressured subsonic phase of reverse shock-heated gas filling the cocoon interior. We systematically vary the background gas density and temperature, BH feedback efficiency, and the jet model. We found that the jet cocoon width roughly follows a scaling derived by assuming momentum conservation in the jet propagation direction, and energy conservation in the lateral directions. Depending on the assumed gas and jet properties, the cocoon either stays elongated out to a large radius or isotropizes before reaching the Bondi radius, forming a nearly spherical bubble. Lower jet velocities and higher background gas densities result in self-regulation to higher momentum fluxes and elongated cocoons. In all cases, the outward momentum flux of the cocoon balances the inward momentum flux of the inflowing gas near the Bondi radius, which ultimately regulates BH accretion. The larger the distance the jet cocoon reaches, the longer the variability timescale of the BH accretion rate. Overall, the average accretion rate always remains below the Bondi rate, and exceeds the Eddington rate only if the ambient medium is dense and cold, and/or the jet is weak. We derive the combination of jet and ambient gas parameters yielding super-Eddington growth.Comment: 16 pages, 11 figure

Variation in genetic admixture and population structure among Latinos: the Los Angeles Latino eye study (LALES)

<p>Abstract</p> <p>Background</p> <p>Population structure and admixture have strong confounding effects on genetic association studies. Discordant frequencies for age-related macular degeneration (AMD) risk alleles and for AMD incidence and prevalence rates are reported across different ethnic groups. We examined the genomic ancestry characterizing 538 Latinos drawn from the Los Angeles Latino Eye Study [LALES] as part of an ongoing AMD-association study. To help assess the degree of Native American ancestry inherited by Latino populations we sampled 25 Mayans and 5 Mexican Indians collected through Coriell's Institute. Levels of European, Asian, and African descent in Latinos were inferred through the USC Multiethnic Panel (USC MEP), formed from a sample from the Multiethnic Cohort (MEC) study, the Yoruba African samples from HapMap II, the Singapore Chinese Health Study, and a prospective cohort from Shanghai, China. A total of 233 ancestry informative markers were genotyped for 538 LALES Latinos, 30 Native Americans, and 355 USC MEP individuals (African Americans, Japanese, Chinese, European Americans, Latinos, and Native Hawaiians). Sensitivity of ancestry estimates to relative sample size was considered.</p> <p>Results</p> <p>We detected strong evidence for recent population admixture in LALES Latinos. Gradients of increasing Native American background and of correspondingly decreasing European ancestry were observed as a function of birth origin from North to South. The strongest excess of homozygosity, a reflection of recent population admixture, was observed in non-US born Latinos that recently populated the US. A set of 42 SNPs especially informative for distinguishing between Native Americans and Europeans were identified.</p> <p>Conclusion</p> <p>These findings reflect the historic migration patterns of Native Americans and suggest that while the 'Latino' label is used to categorize the entire population, there exists a strong degree of heterogeneity within that population, and that it will be important to assess this heterogeneity within future association studies on Latino populations. Our study raises awareness of the diversity within "Latinos" and the necessity to assess appropriate risk and treatment management.</p

Suppression and Spatial Variation of Early Galaxies and Minihalos

We study the effect of the relative velocity of dark matter and baryonic fluids after the epoch of recombination on the evolution of the first bound objects in the early universe. Recent work has shown that, although relative motion of the two fluids is formally a second order effect in density, it has a dramatic impact on the formation and distribution of the first cosmic structures. Focusing on the gas content, we analyze the effect of relative velocity on the properties of halos over a wide range of halo masses and redshifts. We calculate accurately the linear evolution of the baryon and dark matter fluctuations, and quantify the resulting effect on halos based on an analytical formalism that has been carefully checked with simulations in the case with no relative velocity. We estimate the effect on the abundance of and gas fraction in early halos. We find that the relative velocity effect causes several changes: (i) the characteristic mass that divides gas-rich and gas-poor halos is increased by roughly an order of magnitude, from 2 10^4 Msun to about 2 10^5 Msun; (ii) this characteristic mass has a large scatter (full width at half maximum is ~ 1.5 10^5 Msun at z=20); (iii) the fraction of baryons in star-less gas minihalos is suppressed by a factor of 4 at z=20; (iv) the fraction of baryons in halos that can cool and form stars is suppressed by a factor of 1.5 at z=20; and (v) there are enhanced spatial variations of these various fractions.Comment: 10 pages, 10 figure

Polymorphic repeat in AIB1 does not alter breast cancer risk

INTRODUCTION: A causal association between endogenous and exogenous estrogens and breast cancer has been established. Steroid hormones regulate the expression of proteins that are involved in breast cell proliferation and development after binding to their respective steroid hormone receptors. Coactivator and corepressor proteins have recently been identified that interact with steroid hormone receptors and modulate transcriptional activation [1]. AIB1 (amplified in breast 1) is a member of the steroid receptor coactivator (SRC) family that interacts with estrogen receptor (ER)α in a ligand-dependent manner, and increases estrogen-dependent transcription [2]. Amplification and overexpression of AIB1 has been observed in breast and ovarian cancer cell lines and in breast tumors [2,3]. A polymorphic stretch of glutamine amino acids, with unknown biologic function, has recently been described in the carboxyl-terminal region of AIB1 [4]. Among women with germline BRCA1 mutations, significant positive associations were observed between AIB1 alleles with 26 or fewer glutamine repeats and breast cancer risk [5] AIM: To establish whether AIB1 repeat alleles are associated with breast cancer risk and specific tumor characteristics among Caucasian women. PATIENTS AND METHODS: We evaluated associations prospectively between AIB1 alleles and breast cancer risk in the Nurses' Health Study using a nested case-control design. The Nurses' Health Study was initiated in 1976, when 121 700 US-registered nurses between the ages of 30 and 55 years returned an initial questionnaire reporting medical histories and baseline health-related exposures. Between 1989 and 1990 blood samples were collected from 32 826 women. Eligible cases in this study consisted of women with pathologically confirmed incident breast cancer from the subcohort who gave a blood specimen. Cases with a diagnosis anytime after blood collection up to June 1, 1994, with no previously diagnosed cancer except for nonmelanoma skin cancer were included. Controls were randomly selected participants who gave a blood sample and were free of diagnosed cancer (except nonmelanoma skin cancer) up to and including the interval in which the cases were diagnosed, and were matched to cases on year of birth, menopausal status, postmenopausal hormone use, and time of day, month and fasting status at blood sampling. The nested case-control study consisted of 464 incident breast cancer cases and 624 matched controls. The protocol was approved by the Committee on Human Subjects, Brigham and Womens' Hospital, Boston, Massachusetts USA. Information regarding breast cancer risk factors was obtained from the 1976 baseline questionnaire, subsequent biennial questionnaires, and a questionnaire that was completed at the time of blood sampling. Histopathologic characteristics, such as stage, tumor size and ER and progesterone receptor (PR) status, were ascertained from medical records when available and used in case subgroup analyses. AIB1 repeat alleles were determined by automated fluorescence-based fragment detection from polymerase chain reaction (PCR)-amplified DNA extracted from peripheral blood lymphocytes. Fluorescent 5' -labeled primers were utilized for PCR amplification, and glutamine repeat number discrimination was performed using the ABI Prism 377 DNA Sequencer (Perkin-Elmer, Foster City, CA, USA). Genotyping was performed by laboratory personnel who were blinded to case-control status, and blinded quality control samples were inserted to validate genotyping identification procedures (n = 110); concordance for the blinded samples was 100%. Methods regarding plasma hormone assays have previously been reported [6]. Conditional and unconditional logistic regression models, including terms for the matching variables and other potential confounders, were used to assess the association of AIB1 alleles and breast cancer characterized by histologic subtype, stage of disease, and ER and PR status. We also evaluated whether breast cancer risk associated with AIB1 genotype differed within strata of established breast cancer risk factors, and whether repeat length in AIB1 indirectly influenced plasma hormone levels. RESULTS: The case-control comparisons of established breast cancer risk factors among these women have previously been reported [7], and are generally consistent with expectation. The mean age of the women was 58.3 (standard deviation [SD] 7.1) years, ranging from 43 to 69 years at blood sampling. There were 188 premenopausal and 810 postmenopausal women, with mean ages of 48.1 (SD 2.8) years and 61.4 (SD 5.0) years, respectively, at blood sampling. Women in this study were primarily white; Asians, African-Americans and Hispanics comprised less than 1% of cases or controls. The distribution of AIB1 glutamine repeat alleles and AIB1 genotypes for cases and controls are presented in Table 1. Women with AIB1 alleles of 26 glutamine repeats or fewer were not at increased risk for breast cancer (odds ratio [OR] 1.01, 95% confidence interval [CI] 0.75-1.36; Table 2). Results were also similar by menopausal status and in analyses additionally adjusting for established breast cancer risk factors. Among premenopausal women, the OR for women with at least one allele with 26 glutamine repeats or fewer was 0.82 (95% Cl 0.37-1.81), and among postmenopausal women the OR was 1.09 (95% Cl 0.78-1.52; Table 2). We did not observe evidence of a positive association between shorter repeat length and advanced breast cancer, defined as women with breast cancer having one or more involved nodes (OR 1.07, 95% Cl 0.64-1.78), or with cancers with a hormone-dependent phenotype (ER-positive: OR 1.16, 95% Cl 0.81-1.65; Table 3). No associations were observed among women who had one or more alleles with 26 glutamine repeats or fewer, with or without a family history of breast cancer (family history: OR 1.09; 95% Cl 0.46-2.58; no family history: OR 0.94; 95% Cl 0.68-1.31; test for interaction P = 0.65). We also did not observe associations with breast cancer risk to be modified by other established breast cancer risk factors. Among postmenopausal controls not using postmenopausal hormones, geometric least-squared mean plasma levels of estrone sulfate and estrone were similar among carriers and noncarriers of AIB1 alleles with 26 glutamine repeats or fewer (both differences: ≤ +3.5%; P >0.50). Mean levels of estradiol were slightly, but nonsignificantly elevated among carriers of alleles with 26 glutamine repeats or fewer (+11.6%; P = 0.08). DISCUSSION: In this population-based nested case-control study, women with at most 26 repeating glutamine codons (CAG/CAA) within the carboxyl terminus of AIB1 were not at increased risk for breast cancer. We did not observe shorter repeat alleles to be positively associated with breast cancer grouped by histologic subtype, stage of disease, or by ER and PR status. These data suggest that AIB1 repeat length is not a strong independent risk factor for postmenopausal breast cancer, and does not modify the clinical presentation of the tumor among Caucasian women in the general population

Polymorphic repeat in AIB1 does not alter breast cancer risk

We assessed the association between a glutamine repeat polymorphism in AIB1 and breast cancer risk in a case-control study (464 cases, 624 controls) nested within the Nurses' Health Study cohort. We observed no association between AIB1 genotype and breast cancer incidence, or specific tumor characteristics. These findings suggest that AIB1 repeat genotype does not influence postmenopausal breast cancer risk among Caucasian women in the general population