The Positive Feedback of Pop III Objects on Galaxy Formation

We study the formation of molecular hydrogen in cooling gas behind shocks produced during the blow-away process thought to occur in the first collapsed, luminous (Pop III) objects in the early universe. We find that for a wide range of physical parameters the $H_2$ fraction is $f \approx 6 \times 10^{-3}$. The $H_2$ mass produced in such explosions can exceed the amount of relic $H_2$ destroyed inside the photodissociation region surrounding a given Pop III. We conclude that these first objects, differently from the suggestion of Haiman et al 1997, might have a net positive feedback on subsequent galactic formation. We discuss the effects of radiation and the implications of our results for the soft-UV background.Comment: 16 pages, aasms4.sty, LaTeX, 2 figures. submitted to ApJ Letter

Infrared Spectroscopy of Molecular Supernova Remnants

We present Infrared Space Observatory spectroscopy of sites in the supernova remnants W28, W44, and 3C391, where blast waves are impacting molecular clouds. Atomic fine-structure lines were detected from C, N, O, Si, P, and Fe. The S(3) and S(9) lines of H2 were detected for all three remnants. The observations require both shocks into gas with moderate (~ 100 /cm3) and high (~10,000 /cm3) pre-shock densities, with the moderate density shocks producing the ionic lines and the high density shock producing the molecular lines. No single shock model can account for all of the observed lines, even at the order of magnitude level. We find that the principal coolants of radiative supernova shocks in moderate-density gas are the far-infrared continuum from dust grains surviving the shock, followed by collisionally-excited [O I] 63.2 and [Si II] 34.8 micron lines. The principal coolant of the high-density shocks is collisionally-excited H2 rotational and ro-vibrational line emission. We systematically examine the ground-state fine structure of all cosmically abundant elements, to explain the presence or lack of all atomic fine lines in our spectra in terms of the atomic structure, interstellar abundances, and a moderate-density, partially-ionized plasma. The [P II] line at 60.6 microns is the first known astronomical detection. There is one bright unidentified line in our spectra, at 74.26 microns. The presence of bright [Si II] and [Fe II] lines requires partial destruction of the dust. The required gas-phase abundance of Fe suggests 15-30% of the Fe-bearing grains were destroyed. The infrared continuum brightness requires ~1 Msun of dust survives the shock, suggesting about 1/3 of the dust mass was destroyed, in agreement with the depletion estimate and with theoretical models for dust destruction.Comment: 40 pages; 10 figures; accepted by ApJ July 11, 200

The Heavy Element Enrichment of Lyman alpha Clouds in the Virgo Supercluster

Using high S/N STIS echelle spectra (FWHM=7 km/s) of 3C 273, we constrain the metallicities of two Lya clouds in the vicinity of the Virgo cluster. We detect C II, Si II, and Si III absorption lines in the Lya absorber at z = 0.00530. Previous observations with FUSE have revealed Ly beta - Ly theta lines at this redshift, thereby accurately constraining N(H I). We model the ionization of the gas and derive [C/H] = -1.2^{+0.3}_{-0.2}, [Si/C] = 0.2+/-0.1, and log n_{H} = -2.8+/-0.3. The model implies a small absorber thickness, ~70 pc, and thermal pressure p/k ~ 40 cm^{-3} K. It is most likely that the absorber is pressure confined by an external medium because gravitational confinement would require a very high ratio of dark matter to baryonic matter. Based on Milky Way sight lines in which carbon and silicon abundances have been reliably measured in the same interstellar cloud (including new measurements presented herein), we argue that the overabundance of Si relative to C is not due to dust depletion. Instead, this probably indicates that the gas has been predominately enriched by Type II supernovae. Such enrichment is most plausibly provided by an unbound galactic wind, given the absence of galaxies within a projected distance of 100 kpc and the presence of galaxies capable of driving a wind at larger distances. We also constrain the metallicity and physical conditions of the Virgo absorber at z = 0.00337 based on detections of O VI and H I and an upper limit on C IV. If this absorber is collisionally ionized, the O VI/C IV limit requires T > 10^{5.3} K. For either collisional ionization or photoionization, we find that [O/H] > -2.0 at z = 0.00337.Comment: Final Ap.J. versio

Time-Dependent Ionization in Radiatively Cooling Gas

We present new computations of the equilibrium and non-equilibrium cooling efficiencies and ionization states for low-density radiatively cooling gas containing cosmic abundances of the elements H, He, C, N, O, Ne, Mg, Si, S, and Fe. We present results for gas temperatures between 1e4 and 1e8 K, assuming dust-free and optically thin conditions, and no external radiation. For non-equilibrium cooling we solve the coupled time-dependent ionization and energy loss equations for a radiating gas cooling from an initially hot, >5e6K equilibrium state, down to 1e4K. We present results for heavy element compositions ranging from 1e-3 to 2 times the elemental abundances in the Sun. We consider gas cooling at constant density (isochoric) and at constant pressure (isobaric). We calculate the critical column densities and temperatures at which radiatively cooling clouds make the dynamical transition from isobaric to isochoric evolution. We construct ion ratio diagnostics for the temperature and metallicity in radiatively cooling gas. We provide numerical estimates for the maximal cloud column densities for which the gas remains optically thin to the cooling radiation. We present our computational results in convenient on-line figures and tables (see http://wise-obs.tau.ac.il/~orlyg/cooling/).Comment: 20 pages, 12 figures. ApJS in press. Electronic data available at http://wise-obs.tau.ac.il/~orlyg/cooling

Polar body array CGH for prediction of the status of the corresponding oocyte. Part II: technical aspects

The purpose of this study was to assess the technical aspects related to polar body (PB) biopsy, which might have an influence on the results of the microarray comparative genomic hybridization analysis. Furthermore, a comparison was made between two biopsy methods (mechanical and laser). Biopsy of the first and second PB (PB1 and PB2) was performed by mechanical- or laser-assisted biopsy in two different IVF centres. PBs were separately amplified by whole genome amplification. The method of biopsy, mechanical or laser had no influence on the proportion of successfully biopsied oocytes. Especially, for the PB2, the timing of biopsy after ICSI was directly correlated to amplification efficiency. Special care has to be taken with respect to the timing of biopsy of the PB2. Mechanical- and laser-assisted biopsy give the same performance in terms of diagnostic efficienc

Evaluation of a candidate breast cancer associated SNP in ERCC4 as a risk modifier in BRCA1 and BRCA2 mutation carriers. Results from the Consortium of Investigators of Modifiers of BRCA1/BRCA2 (CIMBA)

Background: In this study we aimed to evaluate the role of a SNP in intron 1 of the ERCC4 gene (rs744154), previously reported to be associated with a reduced risk of breast cancer in the general population, as a breast cancer risk modifier in BRCA1 and BRCA2 mutation carriers. Methods: We have genotyped rs744154 in 9408 BRCA1 and 5632 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and assessed its association with breast cancer risk using a retrospective weighted cohort approach. Results: We found no evidence of association with breast cancer risk for BRCA1 (per-allele HR: 0.98, 95% CI: 0.93–1.04, P=0.5) or BRCA2 (per-allele HR: 0.97, 95% CI: 0.89–1.06, P=0.5) mutation carriers. Conclusion: This SNP is not a significant modifier of breast cancer risk for mutation carriers, though weak associations cannot be ruled out. A Osorio1, R L Milne2, G Pita3, P Peterlongo4,5, T Heikkinen6, J Simard7, G Chenevix-Trench8, A B Spurdle8, J Beesley8, X Chen8, S Healey8, KConFab9, S L Neuhausen10, Y C Ding10, F J Couch11,12, X Wang11, N Lindor13, S Manoukian4, M Barile14, A Viel15, L Tizzoni5,16, C I Szabo17, L Foretova18, M Zikan19, K Claes20, M H Greene21, P Mai21, G Rennert22, F Lejbkowicz22, O Barnett-Griness22, I L Andrulis23,24, H Ozcelik24, N Weerasooriya23, OCGN23, A-M Gerdes25, M Thomassen25, D G Cruger26, M A Caligo27, E Friedman28,29, B Kaufman28,29, Y Laitman28, S Cohen28, T Kontorovich28, R Gershoni-Baruch30, E Dagan31,32, H Jernström33, M S Askmalm34, B Arver35, B Malmer36, SWE-BRCA37, S M Domchek38, K L Nathanson38, J Brunet39, T Ramón y Cajal40, D Yannoukakos41, U Hamann42, HEBON37, F B L Hogervorst43, S Verhoef43, EB Gómez García44,45, J T Wijnen46,47, A van den Ouweland48, EMBRACE37, D F Easton49, S Peock49, M Cook49, C T Oliver49, D Frost49, C Luccarini50, D G Evans51, F Lalloo51, R Eeles52, G Pichert53, J Cook54, S Hodgson55, P J Morrison56, F Douglas57, A K Godwin58, GEMO59,60,61, O M Sinilnikova59,60, L Barjhoux59,60, D Stoppa-Lyonnet61, V Moncoutier61, S Giraud59, C Cassini62,63, L Olivier-Faivre62,63, F Révillion64, J-P Peyrat64, D Muller65, J-P Fricker65, H T Lynch66, E M John67, S Buys68, M Daly69, J L Hopper70, M B Terry71, A Miron72, Y Yassin72, D Goldgar73, Breast Cancer Family Registry37, C F Singer74, D Gschwantler-Kaulich74, G Pfeiler74, A-C Spiess74, Thomas v O Hansen75, O T Johannsson76, T Kirchhoff77, K Offit77, K Kosarin77, M Piedmonte78, G C Rodriguez79, K Wakeley80, J F Boggess81, J Basil82, P E Schwartz83, S V Blank84, A E Toland85, M Montagna86, C Casella87, E N Imyanitov88, A Allavena89, R K Schmutzler90, B Versmold90, C Engel91, A Meindl92, N Ditsch93, N Arnold94, D Niederacher95, H Deißler96, B Fiebig97, R Varon-Mateeva98, D Schaefer99, U G Froster100, T Caldes101, M de la Hoya101, L McGuffog49, A C Antoniou49, H Nevanlinna6, P Radice4,5 and J Benítez1,3 on behalf of CIMB

Polar body array CGH for prediction of the status of the corresponding oocyte. Part I: clinical results

Several randomized controlled trials have not shown a benefit from preimplantation genetic screening (PGS) biopsy of cleavage-stage embryos and assessment of up to 10 chromosomes for aneuploidy. Therefore, a proof-of-principle study was planned to determine the reliability of alternative form of PGS, i.e. PGS by polar body (PB) biopsy, with whole genome amplification and microarray-based comparative genomic hybridization (array CGH) analysis. In two centres, all mature metaphase II oocytes from patients who consented to the study were fertilized by ICSI. The first and second PBs (PB1and PB2) were biopsied and analysed separately for chromosome copy number by array CGH. If either or both of the PBs were found to be aneuploid, the corresponding zygote was then also processed by array CGH for concordance analysis. Both PBs were biopsied from a total of 226 zygotes from 42 cycles (average 5.5 per cycle; range 1-15) in 41 couples with an average maternal age of 40.0 years. Of these, the ploidy status of the zygote could be predicted in 195 (86%): 55 were euploid (28%) and 140 were aneuploid (72%). With only one exception, there was at least one predicted aneuploid zygote in each cycle and in 19 out of 42 cycles (45%), all zygotes were predicted to be aneuploid. Fresh embryos were transferred in the remaining 23 cycles (55%), and one frozen transfer was done. Eight patients had a clinical pregnancy of which seven were evolutive (ongoing pregnancy rates: 17% per cycle and 30% per transfer). The ploidy status of 156 zygotes was successfully analysed by array CGH: 38 (24%) were euploid and 118 (76%) were aneuploid. In 138 cases complete information was available on both PBs and the corresponding zygotes. In 130 (94%), the ploidy status of the zygote was concordant with the ploidy status of the PBs and in 8 (6%), the results were discordant. This proof-of-principle study indicates that the ploidy of the zygote can be predicted with acceptable accuracy by array CGH analysis of both PB

Induction of sodium iodide symporter gene and molecular characterisation of HNF3β/FoxA2, TTF-1 and C/EBPβ in thyroid carcinoma cells

Thyroid carcinoma cells often do not express thyroid-specific genes including sodium iodide symporter (NIS), thyroperoxidase (TPO), thyroglobulin (TG), and thyrotropin-stimulating hormone receptor (TSHR). Treatment of thyroid carcinoma cells (four papillary and two anaplastic cell lines) with histone deacetylase inhibitors (SAHA or VPA) modestly induced the expression of the NIS gene. The promoter regions of the thyroid-specific genes contained binding sites for hepatocyte nuclear factor 3 β (HNF3β)/forkhead box A2 (FoxA2), thyroid transcription factor 1 (TTF-1), and CCAAT/enhancer binding protein β (C/EBPβ). Quantitative reverse transcription-polymerase chain reaction (RT–PCR) showed decreased expression of HNF3β/FoxA2 and TTF-1 mRNA in papillary thyroid carcinoma cell lines, when compared with normal thyroid cells. Forced expression of these genes in papillary thyroid carcinoma cells inhibited their growth. Furthermore, the CpG island in the promoter region of HNF3β/FoxA2 was aberrantly methylated; and treatment with 5-aza-2-deoxycytidine (5-Az) induced its expression. Immunohistochemical staining showed that C/EBPβ was localised in the nucleus in normal thyroid cells but was detected in the cytoplasm in papillary thyroid carcinoma cells. Subcellular fractionation of papillary thyroid carcinoma cell lines also demonstrated high levels of expression of C/EBPβ in the cytoplasm, suggesting that a large proportion of C/EBPβ protein is inappropriately localised in the cytoplasm. In summary, these findings reveal novel abnormalities in thyroid carcinoma cell