CANDELS: The progenitors of compact quiescent galaxies at z~2

We combine high-resolution HST/WFC3 images with multi-wavelength photometry to track the evolution of structure and activity of massive (log(M*) > 10) galaxies at redshifts z = 1.4 - 3 in two fields of the Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey (CANDELS). We detect compact, star-forming galaxies (cSFGs) whose number densities, masses, sizes, and star formation rates qualify them as likely progenitors of compact, quiescent, massive galaxies (cQGs) at z = 1.5 - 3. At z > 2 most cSFGs have specific star-formation rates (sSFR = 10^-9 yr^-1) half that of typical, massive SFGs at the same epoch, and host X-ray luminous AGN 30 times (~30%) more frequently. These properties suggest that cSFGs are formed by gas-rich processes (mergers or disk-instabilities) that induce a compact starburst and feed an AGN, which, in turn, quench the star formation on dynamical timescales (few 10^8 yr). The cSFGs are continuously being formed at z = 2 - 3 and fade to cQGs by z = 1.5. After this epoch, cSFGs are rare, thereby truncating the formation of new cQGs. Meanwhile, down to z = 1, existing cQGs continue to enlarge to match local QGs in size, while less-gas-rich mergers and other secular mechanisms shepherd (larger) SFGs as later arrivals to the red sequence. In summary, we propose two evolutionary scenarios of QG formation: an early (z > 2), fast-formation path of rapidly-quenched cSFGs that evolve into cQGs that later enlarge within the quiescent phase, and a slow, late-arrival (z < 2) path for SFGs to form QGs without passing through a compact state.Comment: Submitted to the Astrophysical Journal Letters, 6 pages, 4 figure

Genomic organisation of the Mal d 1 gene cluster on linkage group 16 in apple

European populations exhibit progressive sensitisation to food allergens, and apples are one of the foods for which sensitisation is observed most frequently. Apple cultivars vary greatly in their allergenic characteristics, and a better understanding of the genetic basis of low allergenicity may therefore allow allergic individuals to increase their fruit intake. Mal d 1 is considered to be a major apple allergen, and this protein is encoded by the most complex allergen gene family. Not all Mal d 1 members are likely to be involved in allergenicity. Therefore, additional knowledge about the existence and characteristics of the different Mal d 1 genes is required. In the present study, we investigated the genomic organisation of the Mal d 1 gene cluster in linkage group 16 of apple through the sequencing of two bacterial artificial chromosome clones. The results provided new information on the composition of this family with respect to the number and orientation of functional and pseudogenes and their physical distances. The results were compared with the apple and peach genome sequences that have recently been made available. A broad analysis of the whole apple genome revealed the presence of new genes in this family, and a complete list of the observed Mal d 1 genes is supplied. Thus, this study provides an important contribution towards a better understanding of the genetics of the Mal d 1 family and establishes the basis for further research on allelic diversity among cultivars in relation to variation in allergenicity

The SAURON project - III. Integral-field absorption-line kinematics of 48 elliptical and lenticular galaxies

We present the stellar kinematics of 48 representative elliptical and lenticular galaxies obtained with our custom-built integral-field spectrograph SAURON operating on the William Herschel Telescope. The data were homogeneously processed through a dedicated reduction and analysis pipeline. All resulting SAURON datacubes were spatially binned to a constant minimum signal-to-noise. We have measured the stellar kinematics with an optimized (penalized pixel-fitting) routine which fits the spectra in pixel space, via the use of optimal templates, and prevents the presence of emission lines to affect the measurements. We have thus generated maps of the mean stellar velocity, the velocity dispersion, and the Gauss-Hermite moments h3 and h4 of the line-of-sight velocity distributions. The maps extend to approximately one effective radius. Many objects display kinematic twists, kinematically decoupled components, central stellar disks, and other peculiarities, the nature of which will be discussed in future papers of this series.Comment: 23 pages, 18 figures. Accepted for publication in MNRAS. Version with full resolution images available at http://www.strw.leidenuniv.nl/sauron/papers/emsellem2004_sauron3.pd

Admixture Mapping of 15,280 African Americans Identifies Obesity Susceptibility Loci on Chromosomes 5 and X

The prevalence of obesity (body mass index (BMI) ≥30 kg/m2) is higher in African Americans than in European Americans, even after adjustment for socioeconomic factors, suggesting that genetic factors may explain some of the difference. To identify genetic loci influencing BMI, we carried out a pooled analysis of genome-wide admixture mapping scans in 15,280 African Americans from 14 epidemiologic studies. Samples were genotyped at a median of 1,411 ancestry-informative markers. After adjusting for age, sex, and study, BMI was analyzed both as a dichotomized (top 20% versus bottom 20%) and a continuous trait. We found that a higher percentage of European ancestry was significantly correlated with lower BMI (ρ = −0.042, P = 1.6×10−7). In the dichotomized analysis, we detected two loci on chromosome X as associated with increased African ancestry: the first at Xq25 (locus-specific LOD = 5.94; genome-wide score = 3.22; case-control Z = −3.94); and the second at Xq13.1 (locus-specific LOD = 2.22; case-control Z = −4.62). Quantitative analysis identified a third locus at 5q13.3 where higher BMI was highly significantly associated with greater European ancestry (locus-specific LOD = 6.27; genome-wide score = 3.46). Further mapping studies with dense sets of markers will be necessary to identify the alleles in these regions of chromosomes X and 5 that may be associated with variation in BMI

CHD1 Remodels Chromatin and Influences Transient DNA Methylation at the Clock Gene frequency

Circadian-regulated gene expression is predominantly controlled by a transcriptional negative feedback loop, and it is evident that chromatin modifications and chromatin remodeling are integral to this process in eukaryotes. We previously determined that multiple ATP–dependent chromatin-remodeling enzymes function at frequency (frq). In this report, we demonstrate that the Neurospora homologue of chd1 is required for normal remodeling of chromatin at frq and is required for normal frq expression and sustained rhythmicity. Surprisingly, our studies of CHD1 also revealed that DNA sequences within the frq promoter are methylated, and deletion of chd1 results in expansion of this methylated domain. DNA methylation of the frq locus is altered in strains bearing mutations in a variety of circadian clock genes, including frq, frh, wc-1, and the gene encoding the frq antisense transcript (qrf). Furthermore, frq methylation depends on the DNA methyltransferase, DIM-2. Phenotypic characterization of Δdim-2 strains revealed an approximate WT period length and a phase advance of approximately 2 hours, indicating that methylation plays only an ancillary role in clock-regulated gene expression. This suggests that DNA methylation, like the antisense transcript, is necessary to establish proper clock phasing but does not control overt rhythmicity. These data demonstrate that the epigenetic state of clock genes is dependent on normal regulation of clock components

The JWST Early Release Science Program for Direct Observations of Exoplanetary Systems II: A 1 to 20 Micron Spectrum of the Planetary-Mass Companion VHS 1256-1257 b

We present the highest fidelity spectrum to date of a planetary-mass object. VHS 1256 b is a $<$20 M$_\mathrm{Jup}$ widely separated ($\sim$8\arcsec, a = 150 au), young, planetary-mass companion that shares photometric colors and spectroscopic features with the directly imaged exoplanets HR 8799 c, d, and e. As an L-to-T transition object, VHS 1256 b exists along the region of the color-magnitude diagram where substellar atmospheres transition from cloudy to clear. We observed VHS 1256~b with \textit{JWST}'s NIRSpec IFU and MIRI MRS modes for coverage from 1 $\mu$m to 20 $\mu$m at resolutions of $\sim$1,000 - 3,700. Water, methane, carbon monoxide, carbon dioxide, sodium, and potassium are observed in several portions of the \textit{JWST} spectrum based on comparisons from template brown dwarf spectra, molecular opacities, and atmospheric models. The spectral shape of VHS 1256 b is influenced by disequilibrium chemistry and clouds. We directly detect silicate clouds, the first such detection reported for a planetary-mass companion.Comment: Accepted ApJL Iterations of spectra reduced by the ERS team are hosted at this link: https://github.com/bemiles/JWST_VHS1256b_Reduction/tree/main/reduced_spectr

The JWST Early Release Science Program for Direct Observations of Exoplanetary Systems IV: NIRISS Aperture Masking Interferometry Performance and Lessons Learned

We present a performance analysis for the aperture masking interferometry (AMI) mode on board the James Webb Space Telescope Near Infrared Imager and Slitless Spectrograph (JWST/NIRISS). Thanks to self-calibrating observables, AMI accesses inner working angles down to and even within the classical diffraction limit. The scientific potential of this mode has recently been demonstrated by the Early Release Science (ERS) 1386 program with a deep search for close-in companions in the HIP 65426 exoplanetary system. As part of ERS 1386, we use the same dataset to explore the random, static, and calibration errors of NIRISS AMI observables. We compare the observed noise properties and achievable contrast to theoretical predictions. We explore possible sources of calibration errors, and show that differences in charge migration between the observations of HIP 65426 and point-spread function calibration stars can account for the achieved contrast curves. Lastly, we use self-calibration tests to demonstrate that with adequate calibration, NIRISS AMI can reach contrast levels of $\sim9-10$ mag. These tests lead us to observation planning recommendations and strongly motivate future studies aimed at producing sophisticated calibration strategies taking these systematic effects into account. This will unlock the unprecedented capabilities of JWST/NIRISS AMI, with sensitivity to significantly colder, lower mass exoplanets than ground-based setups at orbital separations inaccessible to JWST coronagraphy.Comment: 20 pages, 12 figures, submitted to AAS Journal

The \textit{JWST} Early Release Science Program for Direct Observations of Exoplanetary Systems III: Aperture Masking Interferometric Observations of the star HIP\,65426 at 3.8 μm\boldsymbol{3.8\,\rm{\mu m}}

We present aperture masking interferometry (AMI) observations of the star HIP 65426 at $3.8\,\rm{\mu m}$ as a part of the \textit{JWST} Direct Imaging Early Release Science (ERS) program obtained using the Near Infrared Imager and Slitless Spectrograph (NIRISS) instrument. This mode provides access to very small inner working angles (even separations slightly below the Michelson limit of ${}0.5\lambda/D$ for an interferometer), which are inaccessible with the classical inner working angles of the \textit{JWST} coronagraphs. When combined with \textit{JWST}'s unprecedented infrared sensitivity, this mode has the potential to probe a new portion of parameter space across a wide array of astronomical observations. Using this mode, we are able to achieve a contrast of $\Delta m_{F380M}{\sim }7.8$\,mag relative to the host star at a separation of {\sim}0.07\arcsec but detect no additional companions interior to the known companion HIP\,65426\,b. Our observations thus rule out companions more massive than 10{-}12\,\rm{M\textsubscript{Jup}} at separations ${\sim}10{-}20\,\rm{au}$ from HIP\,65426, a region out of reach of ground or space-based coronagraphic imaging. These observations confirm that the AMI mode on \textit{JWST} is sensitive to planetary mass companions orbiting at the water frost line, even for more distant stars at $\sim$100\,pc. This result will allow the planning and successful execution of future observations to probe the inner regions of nearby stellar systems, opening essentially unexplored parameter space.Comment: 15 pages, 9 figures, submitted to ApJ Letter

Treatment in advanced colorectal cancer: what, when and how?

Treatment of advanced colorectal cancer (CRC) increasingly requires a multidisciplinary approach and multiple treatment options add to the complexity of clinical decision-making. Recently novel targeted therapy against angiogenesis and epidermal growth factor receptor completed a plethora of phase III studies. The addition of bevacizumab to chemotherapy improved the efficacy over chemotherapy alone in both first and second line settings, although the magnitude of benefit may not be as great when a more optimal chemotherapy platform is used. Studies performed thus far did not address conclusively whether bevacizumab should be continued in subsequent lines of treatment. Anti-angiogenesis tyrosine kinase inhibitors have not shown any additional benefit over chemotherapy alone so far. Although some benefits were seen with cetuximab in all settings of treating advanced CRC, K-ras mutation status provides an important determinant of who would not benefit from such a treatment. Caution should be exercised in combining anti-angiogenesis with anti-EGFR strategy until further randomised data become available. In this review, we have focused on the implications of these trial results on the everyday management decisions of treating advanced CRC