Hubble Space Telescope and Ground-Based Observations of Type Ia Supernovae at Redshift 0.5: Cosmological Implications

We present observations of the Type Ia supernovae (SNe) 1999M, 1999N, 1999Q, 1999S, and 1999U, at redshift z~0.5. They were discovered in early 1999 with the 4.0~m Blanco telescope at Cerro Tololo Inter-American Observatory by the High-z Supernova Search Team (HZT) and subsequently followed with many ground-based telescopes. SNe 1999Q and 1999U were also observed with the Hubble Space Telescope. We computed luminosity distances to the new SNe using two methods, and added them to the high-z Hubble diagram that the HZT has been constructing since 1995. The new distance moduli confirm the results of previous work. At z~0.5, luminosity distances are larger than those expected for an empty universe, implying that a ``Cosmological Constant,'' or another form of ``dark energy,'' has been increasing the expansion rate of the Universe during the last few billion years.Comment: 68 pages, 22 figures. Scheduled for the 01 February 2006 issue of Ap.J. (v637

A comprehensive study of GRB 070125, a most energetic gamma ray burst

We present a comprehensive multiwavelength analysis of the bright, long duration gamma-ray burst GRB 070125, comprised of observations in $\gamma$-ray, X-ray, optical, millimeter and centimeter wavebands. Simultaneous fits to the optical and X-ray light curves favor a break on day 3.78, which we interpret as the jet break from a collimated outflow. Independent fits to optical and X-ray bands give similar results in the optical bands but shift the jet break to around day 10 in the X-ray light curve. We show that for the physical parameters derived for GRB 070125, inverse Compton scattering effects are important throughout the afterglow evolution. While inverse Compton scattering does not affect radio and optical bands, it may be a promising candidate to delay the jet break in the X-ray band. Radio light curves show rapid flux variations, which are interpreted as due to interstellar scintillation, and are used to derive an upper limit of $2.4 \times 10^{17}$ cm on the radius of the fireball in the lateral expansion phase of the jet. Radio light curves and spectra suggest a high synchrotron self absorption frequency indicative of the afterglow shock wave moving in a dense medium. Our broadband modeling favors a constant density profile for the circumburst medium over a wind-like profile ($R^{-2}$). However, keeping in mind the uncertainty of the parameters, it is difficult to unambiguously distinguish between the two density profiles. Our broadband fits suggest that \event is a burst with high radiative efficiency ($> 60$).Comment: 50 pages, 33 figures, sty file included, Appeared in 20 Aug 2008 edition of Astrophysical Journa

A Photometric Redshift of z ~ 9.4 for GRB 090429B

Gamma-ray bursts (GRBs) serve as powerful probes of the early universe, with their luminous afterglows revealing the locations and physical properties of star-forming galaxies at the highest redshifts, and potentially locating first-generation (Population III) stars. Since GRB afterglows have intrinsically very simple spectra, they allow robust redshifts from low signal-to-noise spectroscopy, or photometry. Here we present a photometric redshift of z ~ 9.4 for the Swift detected GRB 090429B based on deep observations with Gemini-North, the Very Large Telescope, and the GRB Optical and Near-infrared Detector. Assuming a Small Magellanic Cloud dust law (which has been found in a majority of GRB sight lines), the 90% likelihood range for the redshift is 9.06 7. The non-detection of the host galaxy to deep limits (Y(AB) ~ 28, which would correspond roughly to 0.001L* at z = 1) in our late-time optical and infrared observations with the Hubble Space Telescope strongly supports the extreme-redshift origin of GRB 090429B, since we would expect to have detected any low-z galaxy, even if it were highly dusty. Finally, the energetics of GRB 090429B are comparable to those of other GRBs and suggest that its progenitor is not greatly different from those of lower redshift bursts

Optical Spectra of Type Ia Supernovae at z=0.46 and z=1.2

We present optical spectra, obtained with the Keck 10-m telescope, of two high-redshift type Ia supernovae (SNe Ia) discovered by the High-z Supernova Search Team: SN 1999ff at z=0.455 and SN 1999fv at z~1.2, the highest-redshift published SN Ia spectrum. Both SNe were at maximum light when the spectra were taken. We compare our high-z spectra with low-z normal and peculiar SNe Ia as well as with SNe Ic, Ib, and II. There are no significant differences between SN 1999ff and normal SNe Ia at low redshift. SN 1999fv appears to be a SN Ia and does not resemble the most peculiar nearby SNe Ia.Comment: 6 pages including 2 figures; to appear in The Astrophysical Journal Letter

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Upper limits on the strength of periodic gravitational waves from PSR J1939+2134

The first science run of the LIGO and GEO gravitational wave detectors presented the opportunity to test methods of searching for gravitational waves from known pulsars. Here we present new direct upper limits on the strength of waves from the pulsar PSR J1939+2134 using two independent analysis methods, one in the frequency domain using frequentist statistics and one in the time domain using Bayesian inference. Both methods show that the strain amplitude at Earth from this pulsar is less than a few times $10^{-22}$.Comment: 7 pages, 1 figure, to appear in the Proceedings of the 5th Edoardo Amaldi Conference on Gravitational Waves, Tirrenia, Pisa, Italy, 6-11 July 200

Improving the sensitivity to gravitational-wave sources by modifying the input-output optics of advanced interferometers

We study frequency dependent (FD) input-output schemes for signal-recycling interferometers, the baseline design of Advanced LIGO and the current configuration of GEO 600. Complementary to a recent proposal by Harms et al. to use FD input squeezing and ordinary homodyne detection, we explore a scheme which uses ordinary squeezed vacuum, but FD readout. Both schemes, which are sub-optimal among all possible input-output schemes, provide a global noise suppression by the power squeeze factor, while being realizable by using detuned Fabry-Perot cavities as input/output filters. At high frequencies, the two schemes are shown to be equivalent, while at low frequencies our scheme gives better performance than that of Harms et al., and is nearly fully optimal. We then study the sensitivity improvement achievable by these schemes in Advanced LIGO era (with 30-m filter cavities and current estimates of filter-mirror losses and thermal noise), for neutron star binary inspirals, and for narrowband GW sources such as low-mass X-ray binaries and known radio pulsars. Optical losses are shown to be a major obstacle for the actual implementation of these techniques in Advanced LIGO. On time scales of third-generation interferometers, like EURO/LIGO-III (~2012), with kilometer-scale filter cavities, a signal-recycling interferometer with the FD readout scheme explored in this paper can have performances comparable to existing proposals. [abridged]Comment: Figs. 9 and 12 corrected; Appendix added for narrowband data analysi

A comparison of complementary measures of vitamin B6 status, function, and metabolism in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Background: Vitamin B6 insufficiency has been linked to increased risk of cancer and other chronic diseases. The circulating concentration of pyridoxal 5'-phosphate (PLP) is a commonly used measure of vitamin B6 status. Ratios of substrates indicating PLP coenzymatic function and metabolism may be useful complementary measures to further explore the role of vitamin B6 in health. Objectives: We explored the sensitivity of 5 outcomes, namely PLP concentration, homocysteine:cysteine (Hcy:Cys), cystathionine:cysteine (Cysta:Cys), the 3´-hydroxykynurenine ratio (HKr), and the 4-pyridoxic acid ratio (PAr) to vitamin B6 intake as well as personal and lifestyle characteristics. Medthods: Dietary intake and biomarker data were collected from participants from 3 nested case-control studies within the European Prospective Investigation into Cancer and Nutrition (EPIC). Bayesian regression models assessed the associations of the 5 biomarker outcomes with vitamin B6 intake and personal and lifestyle covariates. Analogous models examined the relations of Hcy:Cys, Cysta:Cys, and HKr with PLP. Results: In total, 4608 participants were included in the analyses. Vitamin B6 intake was most strongly associated with PLP, moderately associated with Hcy:Cys, Cysta:Cys, and HKr, and not associated with PAr (fold change in marker given a doubling of vitamin B6 intake: PLP 1.60 [95% credible interval (CrI): 1.50, 1.71]; Hcy:Cys 0.87 [95% CrI: 0.84, 0.90]; Cysta:Cys 0.89 [95% CrI: 0.84, 0.94]; HKr 0.88 [95% CrI: 0.85, 0.91]; PAr 1.00 [95% CrI: 0.95, 1.05]). PAr was most sensitive to age, and HKr was least sensitive to BMI and alcohol intake. Sex and menopause status were strongly associated with all 5 markers. Conclusions: We found that 5 different markers, capturing different aspects of vitamin B6-related biological processes, varied in their associations with vitamin B6 intake and personal and lifestyle predictors

Prognostic Value of Stromal Tumor-Infiltrating Lymphocytes in Young, Node-Negative, Triple-Negative Breast Cancer Patients Who Did Not Receive (neo)Adjuvant Systemic Therapy

PURPOSE: Triple-negative breast cancer (TNBC) is considered aggressive, and therefore, virtually all young patients with TNBC receive (neo)adjuvant chemotherapy. Increased stromal tumor-infiltrating lymphocytes (sTILs) have been associated with a favorable prognosis in TNBC. However, whether this association holds for patients who are node-negative (N0), young (< 40 years), and chemotherapy-naïve, and thus can be used for chemotherapy de-escalation strategies, is unknown. METHODS: We selected all patients with N0 TNBC diagnosed between 1989 and 2000 from a Dutch population-based registry. Patients were age < 40 years at diagnosis and had not received (neo)adjuvant systemic therapy, as was standard practice at the time. Formalin-fixed paraffin-embedded blocks were retrieved (PALGA: Dutch Pathology Registry), and a pathology review including sTILs was performed. Patients were categorized according to sTILs (< 30%, 30%-75%, and ≥ 75%). Multivariable Cox regression was performed for overall survival, with or without sTILs as a covariate. Cumulative incidence of distant metastasis or death was analyzed in a competing risk model, with second primary tumors as competing risk. RESULTS: sTILs were scored for 441 patients. High sTILs (≥ 75%; 21%) translated into an excellent prognosis with a 15-year cumulative incidence of a distant metastasis or death of only 2.1% (95% CI, 0 to 5.0), whereas low sTILs (< 30%; 52%) had an unfavorable prognosis with a 15-year cumulative incidence of a distant metastasis or death of 38.4% (32.1 to 44.6). In addition, every 10% increment of sTILs decreased the risk of death by 19% (adjusted hazard ratio: 0.81; 95% CI, 0.76 to 0.87), which are an independent predictor adding prognostic information to standard clinicopathologic variables (χ2 = 46.7, P < .001). CONCLUSION: Chemotherapy-naïve, young patients with N0 TNBC with high sTILs (≥ 75%) have an excellent long-term prognosis. Therefore, sTILs should be considered for prospective clinical trials investigating (neo)adjuvant chemotherapy de-escalation strategies

The North American tree-ring fire-scar network

Fire regimes in North American forests are diverse and modern fire records are often too short to capture important patterns, trends, feedbacks, and drivers of variability. Tree-ring fire scars provide valuable perspectives on fire regimes, including centuries-long records of fire year, season, frequency, severity, and size. Here, we introduce the newly compiled North American tree-ring fire-scar network (NAFSN), which contains 2562 sites, >37,000 fire-scarred trees, and covers large parts of North America. We investigate the NAFSN in terms of geography, sample depth, vegetation, topography, climate, and human land use. Fire scars are found in most ecoregions, from boreal forests in northern Alaska and Canada to subtropical forests in southern Florida and Mexico. The network includes 91 tree species, but is dominated by gymnosperms in the genus Pinus. Fire scars are found from sea level to >4000-m elevation and across a range of topographic settings that vary by ecoregion. Multiple regions are densely sampled (e.g., >1000 fire-scarred trees), enabling new spatial analyses such as reconstructions of area burned. To demonstrate the potential of the network, we compared the climate space of the NAFSN to those of modern fires and forests; the NAFSN spans a climate space largely representative of the forested areas in North America, with notable gaps in warmer tropical climates. Modern fires are burning in similar climate spaces as historical fires, but disproportionately in warmer regions compared to the historical record, possibly related to under-sampling of warm subtropical forests or supporting observations of changing fire regimes. The historical influence of Indigenous and non-Indigenous human land use on fire regimes varies in space and time. A 20th century fire deficit associated with human activities is evident in many regions, yet fire regimes characterized by frequent surface fires are still active in some areas (e.g., Mexico and the southeastern United States). These analyses provide a foundation and framework for future studies using the hundreds of thousands of annually- to sub-annually-resolved tree-ring records of fire spanning centuries, which will further advance our understanding of the interactions among fire, climate, topography, vegetation, and humans across North America