We combine new high sensitivity ultraviolet (UV) imaging from the Wide Field Camera 3 (WFC3) on the Hubble Space Telescope (HST) with existing deep HST/Advanced Camera for Surveys optical images from ...the Great Observatories Origins Deep Survey (GOODS) program to identify UV-dropouts, which are Lyman break galaxy (LBG) candidates at z {approx_equal} 1-3. These new HST/WFC3 observations were taken over 50 arcmin{sup 2} in the GOODS-South field as a part of the Early Release Science program. The uniqueness of these new UV data is that they are observed in three UV/optical (WFC3 UVIS) channel filters (F225W, F275W, and F336W), which allows us to identify three different sets of UV-dropout samples. We apply Lyman break dropout selection criteria to identify F225W-, F275W-, and F336W-dropouts, which are z {approx_equal} 1.7, 2.1, and 2.7 LBG candidates, respectively. We use multi-wavelength imaging combined with available spectroscopic and photometric redshifts to carefully access the validity of our UV-dropout candidates. Our results are as follows: (1) these WFC3 UVIS filters are very reliable in selecting LBGs with z {approx_equal} 2.0, which helps to reduce the gap between the well-studied z {approx}> 3 and z {approx} 0 regimes; (2) the combined number counts with average redshift z {approx_equal} 2.2 agree very well with the observed change in the surface densities as a function of redshift when compared with the higher redshift LBG samples; and (3) the best-fit Schechter function parameters from the rest-frame UV luminosity functions at three different redshifts fit very well with the evolutionary trend of the characteristic absolute magnitude, M*, and the faint-end slope, {alpha}, as a function of redshift. This is the first study to illustrate the usefulness of the WFC3 UVIS channel observations to select z {approx}< 3 LBGs. The addition of the new WFC3 on the HST has made it possible to uniformly select LBGs from z {approx_equal} 1 to z {approx_equal} 9 and significantly enhance our understanding of these galaxies using HST sensitivity and resolution.
This major extension of existing scholarship on the fragmentation of international law utilises the concept of 'regimes' from international law and international relations literature to define ...functional areas such as human rights or trade law. Responding to existing approaches, which focus on the resolution of conflicting norms between regimes, it contains a variety of critical, sociological and doctrinal perspectives on regime interaction. Leading international law scholars and practitioners reflect on how, in situations of diversity and concurrent activity, such interaction shapes and controls knowledge and norms in often hegemonic ways. The contributors draw on topical examples of interacting regimes, including climate, trade and investment regimes, to argue for new methods of regime interaction. Together, the essays combine approaches from international, transnational and comparative constitutional law to provide important insights into an issue that continues to challenge international legal theory and practice.
The MYC oncoproteins are thought to stimulate tumor cell growth and proliferation through amplification of gene transcription, a mechanism that has thwarted most efforts to inhibit MYC function as ...potential cancer therapy. Using a covalent inhibitor of cyclin-dependent kinase 7 (CDK7) to disrupt the transcription of amplified MYCN in neuroblastoma cells, we demonstrate downregulation of the oncoprotein with consequent massive suppression of MYCN-driven global transcriptional amplification. This response translated to significant tumor regression in a mouse model of high-risk neuroblastoma, without the introduction of systemic toxicity. The striking treatment selectivity of MYCN-overexpressing cells correlated with preferential downregulation of super-enhancer-associated genes, including MYCN and other known oncogenic drivers in neuroblastoma. These results indicate that CDK7 inhibition, by selectively targeting the mechanisms that promote global transcriptional amplification in tumor cells, may be useful therapy for cancers that are driven by MYC family oncoproteins.
Display omitted
•THZ1, a covalent CDK7 inhibitor, is highly potent against MYC-driven cancer cells•THZ1 causes MYCN-amplified neuroblastoma regression without toxicity•THZ1 acts by suppressing MYCN-induced global transcriptional amplification•THZ1 selectivity correlates with downregulation of super-enhancer-associated genes
CDK7 inhibition induces cytotoxic effects in neuroblastoma cells through massive downregulation of MYC-induced transcriptional amplification and preferential disruption of super-enhancer-associated oncogenic drivers.
Epithelial regeneration is critical for barrier maintenance and organ function after intestinal injury. The intestinal stem cell (ISC) niche provides Wnt, Notch and epidermal growth factor (EGF) ...signals supporting Lgr5(+) crypt base columnar ISCs for normal epithelial maintenance. However, little is known about the regulation of the ISC compartment after tissue damage. Using ex vivo organoid cultures, here we show that innate lymphoid cells (ILCs), potent producers of interleukin-22 (IL-22) after intestinal injury, increase the growth of mouse small intestine organoids in an IL-22-dependent fashion. Recombinant IL-22 directly targeted ISCs, augmenting the growth of both mouse and human intestinal organoids, increasing proliferation and promoting ISC expansion. IL-22 induced STAT3 phosphorylation in Lgr5(+) ISCs, and STAT3 was crucial for both organoid formation and IL-22-mediated regeneration. Treatment with IL-22 in vivo after mouse allogeneic bone marrow transplantation enhanced the recovery of ISCs, increased epithelial regeneration and reduced intestinal pathology and mortality from graft-versus-host disease. ATOH1-deficient organoid culture demonstrated that IL-22 induced epithelial regeneration independently of the Paneth cell niche. Our findings reveal a fundamental mechanism by which the immune system is able to support the intestinal epithelium, activating ISCs to promote regeneration.
We report the discovery of a powerful molecular wind from the nucleus of the non-interacting nearby S0 field galaxy NGC 1266. The single-dish CO profile exhibits emission to ?400 km s--1 and requires ...a nested Gaussian fit to be properly described. Interferometric observations reveal a massive, centrally concentrated molecular component with a mass of 1.1 X 109 M and a molecular outflow with a molecular mass of 2.4 X 107 M . The molecular gas close to the systemic velocity consists of a rotating, compact nucleus with a mass of about 4.1 X 108 M within a radius of 60 pc. This compact molecular nucleus has a surface density of 2.7 X 104 M pc--2, more than two orders of magnitude larger than that of giant molecular clouds in the disk of the Milky Way, and it appears to sit on the Kennicutt-Schmidt relation despite its extreme kinematics and energetic activity. We interpret this nucleus as a disk that confines the outflowing wind. A mass outflow rate of 13 M yr--1 leads to a depletion timescale of 85 Myr. The star formation in NGC 1266 is insufficient to drive the outflow, and thus it is likely driven by the active galactic nucleus. The concentration of the majority of the molecular gas in the central 100 pc requires an extraordinary loss of angular momentum, but no obvious companion or interacting galaxy is present to enable the transfer. NGC 1266 is the first known outflowing molecular system that does not show any evidence of a recent interaction.
Science Cafés, informal venues to promote bidirectional dialog, inquiry and learning about science between community members, scientists, healthcare and service providers, hold promise as an ...innovative tool for healthcare researchers and community members to improve health outcomes, especially among populations with health disparities. However, the process of optimizing science cafés is under-studied. We describe the pilot evaluation of a series of Science Cafés, called Garden Cafés (n = 9), conducted from September 2015 through April 2016 in Olmsted County, MN and Duval County, FL to connect Mayo Clinic researchers and local service providers with the community. Selection of discussion topics was guided by a county health needs assessment, which identified community priorities. Before leaving the events, community participants completed a brief anonymous survey assessing sociodemographics and their knowledge of research benefits, readiness to participate as a partner in health research, and health and science literacy confidence. Of the 112 attendees who responded, 51% were female and 51% were Black. Respondents reported that participating in the event significantly improved (all at p<0.001) their understanding on all three measures. Preliminary findings suggest that Garden Cafés are an effective forum to increase community understanding and disposition to collaborate in health research, especially in members from diverse backgrounds.
PDF
