Supernovae in Early-Type Galaxies: Directly Connecting Age and Metallicity with Type Ia Luminosity

We have obtained optical spectra of 29 early-type (E/S0) galaxies that hosted type Ia supernovae (SNe Ia). We have measured absorption-line strengths and compared them to a grid of models to extract the relations between the supernova properties and the luminosity-weighted age/composition of the host galaxies. The same analysis was applied to a large number of early-type field galaxies selected from the SDSS spectroscopic survey. We find no difference in the age and abundance distributions between the field galaxies and the SN Ia host galaxies. We do find a strong correlation suggesting that SNe Ia in galaxies whose populations have a characteristic age greater than 5 Gyr are ~ 1 mag fainter at V(max) than those found in galaxies with younger populations. However, the data cannot discriminate between a smooth relation connecting age and supernova luminosity or two populations of SN Ia progenitors. We find that SN Ia distance residuals in the Hubble diagram are correlated with host-galaxy metal abundance, consistent with the predictions of Timmes, Brown & Truran (2003). The data show that high iron abundance galaxies host less-luminous supernovae. We thus conclude that the time since progenitor formation primarily determines the radioactive Ni production while progenitor metal abundance has a weaker influence on peak luminosity, but one not fully corrected by light-curve shape and color fitters. Assuming no selection effects in discovering SNe Ia in local early-type galaxies, we find a higher specific SN Ia rate in E/S0 galaxies with ages below 3 Gyr than in older hosts. The higher rate and brighter luminosities seen in the youngest E/S0 hosts may be a result of recent star formation and represents a tail of the "prompt" SN Ia progenitors.Comment: 44 pages, 11 figures, 4 tables; ApJ Accepted (Sept. 20, 2008 issue

ACE inhibition attenuates radiation-induced cardiopulmonary damage

BACKGROUND AND PURPOSE: In thoracic irradiation, the maximum radiation dose is restricted by the risk of radiation-induced cardiopulmonary damage and dysfunction limiting tumor control. We showed that radiation-induced sub-clinical cardiac damage and lung damage in rats mutually interact and that combined irradiation intensifies cardiopulmonary toxicity. Unfortunately, current clinical practice does not include preventative measures to attenuate radiation-induced lung or cardiac toxicity. Here, we investigate the effects of the ACE inhibitor captopril on radiation-induced cardiopulmonary damage.MATERIAL AND METHODS: After local irradiation of rat heart and/or lungs captopril was administered orally. Cardiopulmonary performance was assessed using biweekly breathing rate measurements. At 8weeks post-irradiation, cardiac hemodynamics were measured, CT scans and histopathology were analyzed.RESULTS: Captopril significantly improved breathing rate and cardiopulmonary density/structure, but only when the heart was included in the radiation field. Consistently, captopril reduced radiation-induced pleural and pericardial effusion and cardiac fibrosis, resulting in an improved left ventricular end-diastolic pressure only in the heart-irradiated groups.CONCLUSION: Captopril improves cardiopulmonary morphology and function by reducing acute cardiac damage, a risk factor in the development of radiation-induced cardiopulmonary toxicity. ACE inhibition should be evaluated as a strategy to reduce cardiopulmonary complications induced by radiotherapy to the thoracic area.</p

Hedgehog Pathway as a Potential Intervention Target in Esophageal Cancer

Esophageal cancer (EC) is an aggressive disease with a poor prognosis. Treatment resistance is a major challenge in successful anti-cancer therapy. Pathological complete response after neoadjuvant chemoradiation (nCRT) is low, thus requiring therapy optimization. The Hedgehog (HH) pathway has been implicated in therapy resistance, as well as in cancer stemness. This article focusses on the HH pathway as a putative target in the treatment of EC. Immunohistochemistry on HH members was applied to EC patient material followed by modulation of 3D-EC cell cultures, fluorescence-activated cell sorting (FACS), and gene expression analysis after HH pathway modulation. Sonic Hedgehog (SHH) and its receptor Patched1 (PTCH1) were significantly enriched in EC resection material of patients with microresidual disease (mRD) after receiving nCRT, compared to the control group. Stimulation with SHH resulted in an up-regulation of cancer stemness in EC sphere cultures, as indicated by increased sphere formation after sorting for CD44+/CD24- EC cancer stem-like cell (CSC) population. On the contrary, inhibiting this pathway with vismodegib led to a decrease in cancer stemness and both radiation and carboplatin resistance. Our results strengthen the role of the HH pathway in chemoradiotherapy resistance. These findings suggest that targeting the HH pathway could be an attractive approach to control CSCs.</p

Type Ia Supernova Rate Measurements To Redshift 2.5 From CANDELS: Searching For Prompt Explosions In The Early Universe

dThe Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey (CANDELS) was a multi-cycle treasury program on the Hubble Space Telescope (HST) that surveyed a total area of -0.25 deg2 with -900 HST orbits spread across five fields over three years. Within these survey images we discovered 65 supernovae (SNe) of all types, out to z 2.5. We classify -24 of these as Type Ia SNe (SNe Ia) based on host galaxy redshifts and SN photometry (supplemented by grism spectroscopy of six SNe). Here we present a measurement of the volumetric SN Ia rate as a function of redshift, reaching for the first time beyond z =- 2 and putting new constraints on SN Ia progenitor models. Our highest redshift bin includes detections of SNe that exploded when the universe was only -3 Gyr old and near the peak of the cosmic star formation history. This gives the CANDELS high redshift sample unique leverage for evaluating the fraction of SNe Ia that explode promptly after formation ( 40 Myr. However, mild tension is apparent between ground-based low-z surveys and space-based high-z surveys. In both CANDELS and the sister HST program CLASH (Cluster Lensing And Supernova Survey with Hubble), we find a low rate of SNe Ia at z > 1. This could be a hint that prompt progenitors are in fact relatively rare, accounting for only 20% of all SN Ia explosions-though further analysis and larger samples will be needed to examine that suggestion. Key words: infrared: general - supernovae:Astronom

Type Ia Supernova Distances at z > 1.5 from the Hubble Space Telescope Multi-Cycle Treasury Programs: The Early Expansion Rate

We present an analysis of 15 Type Ia supernovae (SNe Ia) at redshift z > 1 (9 at 1.5 < z < 2.3) recently discovered in the CANDELS and CLASH Multi-Cycle Treasury programs using WFC3 on the Hubble Space Telescope. We combine these SNe Ia with a new compilation of 1050 SNe Ia, jointly calibrated and corrected for simulated survey biases to produce accurate distance measurements. We present unbiased constraints on the expansion rate at six redshifts in the range 0.07 < z < 1.5 based only on this combined SN Ia sample. The added leverage of our new sample at z > 1.5 leads to a factor of ~3 improvement in the determination of the expansion rate at z = 1.5, reducing its uncertainty to ~20%, a measurement of H(z=1.5)/H0=2.67 (+0.83,-0.52). We then demonstrate that these six measurements alone provide a nearly identical characterization of dark energy as the full SN sample, making them an efficient compression of the SN Ia data. The new sample of SNe Ia at z > 1 usefully distinguishes between alternative cosmological models and unmodeled evolution of the SN Ia distance indicators, placing empirical limits on the latter. Finally, employing a realistic simulation of a potential WFIRST SN survey observing strategy, we forecast optimistic future constraints on the expansion rate from SNe Ia.Comment: 14 pages, 5 figures, 7 tables; submitted to Ap

Generation and Differentiation of Adult Tissue-Derived Human Thyroid Organoids

Total thyroidectomy as part of thyroid cancer treatment results in hypothyroidism requiring lifelong daily thyroid hormone replacement. Unbalanced hormone levels result in persistent complaints such as fatigue, constipation, and weight increase. Therefore, we aimed to investigate a patient-derived thyroid organoid model with the potential to regenerate the thyroid gland. Murine and human thyroidderived cells were cultured as organoids capable of self-renewal and which expressed proliferation and putative stem cell and thyroid characteristics, without a change in the expression of thyroid tumor-related genes. These organoids formed thyroid-tissue-resembling structures in culture. (Xeno-)transplantation of 600,000 dispersed organoid cells underneath the kidney capsule of a hypothyroid mouse model resulted in the generation of hormone-producing thyroid-resembling follicles. This study provides evidence that thyroid-lineagespecific cells can form organoids that are able to self-renew and differentiate into functional thyroid tissue. Subsequent (xeno-)transplantation of these thyroid organoids demonstrates a proof of principle for functional miniature gland formation

High-throughput Proteomics Identifies THEMIS2 as Independent Biomarker of Treatment-free Survival in Untreated CLL

It remains challenging in chronic lymphocytic leukemia (CLL) to distinguish between patients with favorable and unfavorable time-to-first treatment (TTFT). Additionally, the downstream protein correlates of well-known molecular features of CLL are not always clear. To address this, we selected 40 CLL patients with TTFT ≤24 months and compared their B cell intracellular protein expression with 40 age- and sex-matched CLL patients with TTFT &gt;24 months using mass spectrometry. In total, 3268 proteins were quantified in the cohort. Immunoglobulin heavy-chain variable (IGHV) mutational status and trisomy 12 were most impactful on the CLL proteome. Comparing cases to controls, 5 proteins were significantly upregulated, whereas 3 proteins were significantly downregulated. Of these, only THEMIS2, a signaling protein acting downstream of the B cell receptor, was significantly associated with TTFT, independently of IGHV and TP53 mutational status (hazard ratio, 2.49 [95% confidence interval, 1.62-3.84]; P &lt; 0.001). This association was validated on the mRNA and protein level by quantitative polymerase chain reaction and ELISA, respectively. Analysis of 2 independently generated RNA sequencing and mass spectrometry datasets confirmed the association between THEMIS2 expression and clinical outcome. In conclusion, we present a comprehensive characterization of the proteome of untreated CLL and identify THEMIS2 expression as a putative biomarker of TTFT.</p

GALEX UV Color Relations for Nearby Early-Type Galaxies

We use GALEX/optical photometry to construct color-color relationships for early-type galaxies sorted by morphological type. We have matched objects in the GALEX GR1 public release and the first IR1.1 internal release, with the RC3 early-type galaxies having a morphological type -5.5<T<-1.5 with mean error in T<1.5, and mean error on (B-V)T<0.05. After visual inspection of each match, we are left with 130 galaxies with a reliable GALEX pipeline photometry in the far-UV and near-UV bands. This sample is divided into Ellipticals (-5.5<T<-3.5) and Lenticulars (-3.5<T<-1.5). After correction for the Galactic extinction, the color-color diagrams FUV-NUV vs. (B-V)_{Tc} are plotted for the two subsamples. We find a tight anti-correlation between the FUV-NUV and (B-V)_{Tc} colors for Ellipticals, the UV color getting bluer when the (B-V)_{Tc} get redder. This relationship very likely is an extension of the color-metallicity relationship into the GALEX NUV band. We suspect that the main source of the correlation is metal line blanketing in the NUV band. The FUV-NUV vs B-V correlation has larger scatter for lenticular galaxies; we speculate this reflects the presence of low level star formation. If the latter objects (i.e. those that are blue both in FUV-NUV and B-V) are interpreted as harboring recent star formation activity, this would be the case for a few percent (~4%) of Ellipticals and ~15% of Lenticulars; this would make about 10% of early-type galaxies with residual star formation in our full sample of 130 early-type galaxies. We also plot FUV-NUV vs. the Mg_2 index and central velocity dispersion. We find a tight anti-correlation between FUV-NUV and the Mg_2 index(...).Comment: 25 pages, 5 figures, accepted for publication in ApJS (abstract abridged), typos corrected in section 2.

The Look-back Time Evolution of Far-Ultraviolet Flux from the Brightest Cluster Elliptical Galaxies at z < 0.2

We present the GALEX UV photometry of the elliptical galaxies in Abell clusters at moderate redshifts (z < 0.2) for the study of the look-back time evolution of the UV upturn phenomenon. The brightest elliptical galaxies (M_r < -22) in 12 remote clusters are compared with the nearby giant elliptical galaxies of comparable optical luminosity in the Fornax and Virgo clusters. The sample galaxies presented here appear to be quiescent without signs of massive star formation or strong nuclear activity, and show smooth, extended profiles in their UV images indicating that the far-UV (FUV) light is mostly produced by hot stars in the underlying old stellar population. Compared to their counterparts in nearby clusters, the FUV flux of cluster giant elliptical galaxies at moderate redshifts fades rapidly with ~ 2 Gyrs of look-back time, and the observed pace in FUV - V color evolution agrees reasonably well with the prediction from the population synthesis models where the dominant FUV source is hot horizontal-branch stars and their progeny. A similar amount of color spread (~ 1 mag) in FUV - V exists among the brightest cluster elliptical galaxies at z ~ 0.1, as observed among the nearby giant elliptical galaxies of comparable optical luminosity.Comment: Accepted for publication in the Special GALEX ApJ Supplement, December 200

International Guillain-Barré Syndrome Outcome Study (IGOS): protocol of a prospective observational cohort study on clinical and biological predictors of disease course and outcome in Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy with a highly variable clinical presentation, course, and outcome. The factors that determine the clinical variation of GBS are poorly understood which complicates the care and treatment of individual patients. The protocol of the ongoing International GBS Outcome Study (IGOS), a prospective, observational, multi-centre cohort study that aims to identify the clinical and biological determinants and predictors of disease onset, subtype, course and outcome of GBS is presented here. Patients fulfilling the diagnostic criteria for GBS, regardless of age, disease severity, variant forms, or treatment, can participate if included within two weeks after onset of weakness. Information about demography, preceding infections, clinical features, diagnostic findings, treatment, course and outcome is collected. In addition, cerebrospinal fluid and serial blood samples for serum and DNA is collected at standard time points. The original aim was to include at least 1000 patients with a follow-up of 1-3 years. Data are collected via a web-based data entry system and stored anonymously. IGOS started in May 2012 and by January 2017 included more than 1400 participants from 143 active centres in 19 countries across 5 continents. The IGOS data/biobank is available for research projects conducted by expertise groups focusing on specific topics including epidemiology, diagnostic criteria, clinimetrics, electrophysiology, antecedent events, antibodies, genetics, prognostic modelling, treatment effects and long-term outcome of GBS. The IGOS will help to standardize the international collection of data and biosamples for future research of GBS. ClinicalTrials.gov Identifier: NCT01582763