First Look at z > 1 Bars in the Rest-Frame Near-Infrared with JWST Early CEERS Imaging

Stellar bars are key drivers of secular evolution in galaxies and can be effectively studied using rest-frame near-infrared (NIR) images, which trace the underlying stellar mass and are less impacted by dust and star formation than rest-frame UV or optical images. We leverage the power of {\it{JWST}} CEERS NIRCam images to present the first quantitative identification and characterization of stellar bars at $z>1$ based on rest-frame NIR F444W images of high resolution (~1.3 kpc at z ~ 1-3). We identify stellar bars in these images using quantitative criteria based on ellipse fits. For this pilot study, we present six examples of robustly identified bars at $z>1$ with spectroscopic redshifts, including the two highest redshift bars at ~2.136 and 2.312 quantitatively identified and characterized to date. The stellar bars at $z$ ~ 1.1-2.3 presented in our study have projected semi-major axes of ~2.9-4.3 kpc and projected ellipticities of ~0.41-0.53 in the rest-frame NIR. The barred host galaxies have stellar masses ~ $1 \times 10^{10}$ to $2 \times 10^{11}$ $M_{\odot}$, star formation rates of ~ 21-295 $M_{\odot}$ yr$^{-1}$, and several have potential nearby companions. Our finding of bars at $z$ ~1.1-2.3 demonstrates the early onset of such instabilities and supports simulations where bars form early in massive dynamically cold disks. It also suggests that if these bars at lookback times of 8-10 Gyr survive out to present epochs, bar-driven secular processes may operate over a long time and have a significant impact on some galaxies by z ~ 0.Comment: 16 pages, 5 figures. Accepted for Publication in Astrophysical Journal Letter

First Look at z > 1 Bars in the Rest-frame Near-infrared with JWST Early CEERS Imaging

Stellar bars are key drivers of secular evolution in galaxies and can be effectively studied using rest-frame near-infrared (NIR) images, which trace the underlying stellar mass and are less impacted by dust and star formation than rest-frame UV or optical images. We leverage the power of JWST CEERS NIRCam images to present the first quantitative identification and characterization of stellar bars at z &gt; 1 based on rest-frame NIR F444W images of high resolution (∼1.3 kpc at z ∼ 1-3). We identify stellar bars in these images using quantitative criteria based on ellipse fits. For this pilot study, we present six examples of robustly identified bars at z &gt; 1 with spectroscopic redshifts, including the two highest-redshift bars at z ∼ 2.136 and 2.312 quantitatively identified and characterized to date. The stellar bars at z ∼ 1.1-2.3 presented in our study have projected semimajor axes of ∼2.9-4.3 kpc and projected ellipticities of ∼0.41-0.53 in the rest-frame NIR. The barred host galaxies have stellar masses ∼1 × 10 10 to 2 × 10 11 M ⊙ and star formation rates of ∼21-295 M ⊙ yr −1, and several have potential nearby companions. Our finding of bars at z ∼ 1.1-2.3 demonstrates the early onset of such instabilities and supports simulations where bars form early in massive dynamically cold disks. It also suggests that if these bars at lookback times of 8-11 Gyr survive out to present epochs, bar-driven secular processes may operate over a long time and have a significant impact on some galaxies by z ∼ 0.</p

CANDELS: The Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey - The Hubble Space Telescope Observations, Imaging Data Products and Mosaics

This paper describes the Hubble Space Telescope imaging data products and data reduction procedures for the Cosmic Assembly Near-IR Deep Extragalactic Legacy Survey (CANDELS). This survey is designed to document the evolution of galaxies and black holes at $z\sim1.5-8$, and to study Type Ia SNe beyond $z>1.5$. Five premier multi-wavelength sky regions are selected, each with extensive multiwavelength observations. The primary CANDELS data consist of imaging obtained in the Wide Field Camera 3 / infrared channel (WFC3/IR) and UVIS channel, along with the Advanced Camera for Surveys (ACS). The CANDELS/Deep survey covers \sim125 square arcminutes within GOODS-N and GOODS-S, while the remainder consists of the CANDELS/Wide survey, achieving a total of \sim800 square arcminutes across GOODS and three additional fields (EGS, COSMOS, and UDS). We summarize the observational aspects of the survey as motivated by the scientific goals and present a detailed description of the data reduction procedures and products from the survey. Our data reduction methods utilize the most up to date calibration files and image combination procedures. We have paid special attention to correcting a range of instrumental effects, including CTE degradation for ACS, removal of electronic bias-striping present in ACS data after SM4, and persistence effects and other artifacts in WFC3/IR. For each field, we release mosaics for individual epochs and eventual mosaics containing data from all epochs combined, to facilitate photometric variability studies and the deepest possible photometry. A more detailed overview of the science goals and observational design of the survey are presented in a companion paper.Comment: 39 pages, 25 figure

Development and Validation of the Gene Expression Predictor of High-grade Serous Ovarian Carcinoma Molecular SubTYPE (PrOTYPE).

PURPOSE: Gene expression-based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation of clinical utility has been hindered by nonstandardized methods, which are not applicable in a clinical setting. We sought to generate a clinical grade minimal gene set assay for classification of individual tumor specimens into HGSOC subtypes and confirm previously reported subtype-associated features. EXPERIMENTAL DESIGN: Adopting two independent approaches, we derived and internally validated algorithms for subtype prediction using published gene expression data from 1,650 tumors. We applied resulting models to NanoString data on 3,829 HGSOCs from the Ovarian Tumor Tissue Analysis consortium. We further developed, confirmed, and validated a reduced, minimal gene set predictor, with methods suitable for a single-patient setting. RESULTS: Gene expression data were used to derive the predictor of high-grade serous ovarian carcinoma molecular subtype (PrOTYPE) assay. We established a de facto standard as a consensus of two parallel approaches. PrOTYPE subtypes are significantly associated with age, stage, residual disease, tumor-infiltrating lymphocytes, and outcome. The locked-down clinical grade PrOTYPE test includes a model with 55 genes that predicted gene expression subtype with >95% accuracy that was maintained in all analytic and biological validations. CONCLUSIONS: We validated the PrOTYPE assay following the Institute of Medicine guidelines for the development of omics-based tests. This fully defined and locked-down clinical grade assay will enable trial design with molecular subtype stratification and allow for objective assessment of the predictive value of HGSOC molecular subtypes in precision medicine applications.See related commentary by McMullen et al., p. 5271.Core funding for this project was provided by the National Institutes of Health (R01-CA172404, PI: S.J. Ramus; and R01-CA168758, PIs: J.A. Doherty and M.A.Rossing), the Canadian Institutes for Health Research (Proof-of-Principle I program, PIs: D.G.Huntsman and M.S. Anglesio), the United States Department of Defense Ovarian Cancer Research Program (OC110433, PI: D.D. Bowtell). A. Talhouk is funded through a Michael Smith Foundation for Health Research Scholar Award. M.S. Anglesio is funded through a Michael Smith Foundation for Health Research Scholar Award and the Janet D. Cottrelle Foundation Scholars program managed by the BC Cancer Foundation. J. George was partially supported by the NIH/National Cancer Institute award number P30CA034196. C. Wang was a Career Enhancement Awardee of the Mayo Clinic SPORE in Ovarian Cancer (P50 CA136393). D.G. Huntsman receives support from the Dr. Chew Wei Memorial Professorship in Gynecologic Oncology, and the Canada Research Chairs program (Research Chair in Molecular and Genomic Pathology). M. Widschwendter receives funding from the European Union’s Horizon 2020 European Research Council Programme, H2020 BRCA-ERC under Grant Agreement No. 742432 as well as the charity, The Eve Appeal (https://eveappeal.org.uk/), and support of the National Institute for Health Research (NIHR) and the University College London Hospitals (UCLH) Biomedical Research Centre. G.E. Konecny is supported by the Miriam and Sheldon Adelson Medical Research Foundation. B.Y. Karlan is funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124. H.R. Harris is 20 supported by the NIH/National Cancer Institute award number K22 CA193860. OVCARE (including the VAN study) receives support through the BC Cancer Foundation and The VGH+UBC Hospital Foundation (authors AT, BG, DGH, and MSA). The AOV study is supported by the Canadian Institutes of Health Research (MOP86727). The Gynaecological Oncology Biobank at Westmead, a member of the Australasian Biospecimen Network-Oncology group, was funded by the National Health and Medical Research Council Enabling Grants ID 310670 & ID 628903 and the Cancer Institute NSW Grants ID 12/RIG/1-17 & 15/RIG/1-16. The Australian Ovarian Cancer Study Group was supported by the U.S. Army Medical Research and Materiel Command under DAMD17-01-1-0729, The Cancer Council Victoria, Queensland Cancer Fund, The Cancer Council New South Wales, The Cancer Council South Australia, The Cancer Council Tasmania and The Cancer Foundation of Western Australia (Multi-State Applications 191, 211 and 182) and the National Health and Medical Research Council of Australia (NHMRC; ID199600; ID400413 and ID400281). BriTROC-1 was funded by Ovarian Cancer Action (to IAM and JDB, grant number 006) and supported by Cancer Research UK (grant numbers A15973, A15601, A18072, A17197, A19274 and A19694) and the National Institute for Health Research Cambridge and Imperial Biomedical Research Centres. Samples from the Mayo Clinic were collected and provided with support of P50 CA136393 (E.L.G., G.L.K, S.H.K, M.E.S.)

CANDELS: The Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey

The Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey (CANDELS) is designed to document the first third of galactic evolution, over the approximate redshift (z) range 8--1.5. It will image >250,000 distant galaxies using three separate cameras on the Hubble Space Telescope, from the mid-ultraviolet to the near-infrared, and will find and measure Type Ia supernovae at z>1.5 to test their accuracy as standardizable candles for cosmology. Five premier multi-wavelength sky regions are selected, each with extensive ancillary data. The use of five widely separated fields mitigates cosmic variance and yields statistically robust and complete samples of galaxies down to a stellar mass of 10^9 M_\odot to z \approx 2, reaching the knee of the ultraviolet luminosity function (UVLF) of galaxies to z \approx 8. The survey covers approximately 800 arcmin^2 and is divided into two parts. The CANDELS/Deep survey (5\sigma\ point-source limit H=27.7 mag) covers \sim 125 arcmin^2 within GOODS-N and GOODS-S. The CANDELS/Wide survey includes GOODS and three additional fields (EGS, COSMOS, and UDS) and covers the full area to a 5\sigma\ point-source limit of H \gtrsim 27.0 mag. Together with the Hubble Ultra Deep Fields, the strategy creates a three-tiered "wedding cake" approach that has proven efficient for extragalactic surveys. Data from the survey are nonproprietary and are useful for a wide variety of science investigations. In this paper, we describe the basic motivations for the survey, the CANDELS team science goals and the resulting observational requirements, the field selection and geometry, and the observing design. The Hubble data processing and products are described in a companion paper.Comment: Submitted to Astrophysical Journal Supplement Series; Revised version, subsequent to referee repor

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant