An RB-EZH2 Complex Mediates Silencing of Repetitive DNA Sequences

Repetitive genomic regions include tandem sequence repeats and interspersed repeats, such as endogenous retroviruses and LINE-1 elements. Repressive heterochromatin domains silence expression of these sequences through mechanisms that remain poorly understood. Here, we present evidence that the retinoblastoma protein (pRB) utilizes a cell-cycle-independent interaction with E2F1 to recruit enhancer of zeste homolog 2 (EZH2) to diverse repeat sequences. These include simple repeats, satellites, LINEs, and endogenous retroviruses as well as transposon fragments. We generated a mutant mouse strain carrying an F832A mutation in Rb1 that is defective for recruitment to repetitive sequences. Loss of pRB-EZH2 complexes from repeats disperses H3K27me3 from these genomic locations and permits repeat expression. Consistent with maintenance of H3K27me3 at the Hox clusters, these mice are developmentally normal. However, susceptibility to lymphoma suggests that pRB-EZH2 recruitment to repetitive elements may be cancer relevant

Outsourcing Governance: States and the Politics of a ‘Global Value Chain World’

Politics, and by extension states, are marginal in debates about the genesis, evolution and functioning of the GVC-based global economy. We contend here that the core complexity of state agency and state power needs to be much more carefully understood in GVC and related debates, as a basis on which the governance of the evolving GVC world can be properly theorised as revolving around the inseparability of economic and political power. We advance a framework for understanding the role of politics and states in the construction and maintenance of a GVC world, using a three-fold typology of facilitative, regulatory and distributive forms of governance, and propose a notion of ‘outsourcing governance’ as an attempt to capture the ways in which states purposefully, through active political agency, have engaged in a process of delegating a variety of governance functions and authority to private actors. Our overarching argument is normative: ‘outsourced governance’ of the form we currently observe is associated with regressive distributional outcomes, and is antithetical to an inclusive and sustainable global economy

Consensus recommendations for the use of automated insulin delivery technologies in clinical practice

The significant and growing global prevalence of diabetes continues to challenge people with diabetes (PwD), healthcare providers, and payers. While maintaining near-normal glucose levels has been shown to prevent or delay the progression of the long-term complications of diabetes, a significant proportion of PwD are not attaining their glycemic goals. During the past 6 years, we have seen tremendous advances in automated insulin delivery (AID) technologies. Numerous randomized controlled trials and real-world studies have shown that the use of AID systems is safe and effective in helping PwD achieve their long-term glycemic goals while reducing hypoglycemia risk. Thus, AID systems have recently become an integral part of diabetes management. However, recommendations for using AID systems in clinical settings have been lacking. Such guided recommendations are critical for AID success and acceptance. All clinicians working with PwD need to become familiar with the available systems in order to eliminate disparities in diabetes quality of care. This report provides much-needed guidance for clinicians who are interested in utilizing AIDs and presents a comprehensive listing of the evidence payers should consider when determining eligibility criteria for AID insurance coverage

Rovibrational structure and potential energy function of the X 0⁺ ground electronic state of ArXe

ISSN:0022-2852ISSN:1096-083

Testing Ethernet Networks for the ATLAS Data Collection System

This paper reports recent work on Ethernet traffic generation and analysis. We use Gigabit Ethernet NICs running customized embedded software and custom-built 32-port Fast Ethernet boards based on FPGAs to study the behavior of large Ethernet networks. The traffic generation software is able to accommodate many traffic distributions with the ultimate goal of generating traffic that resembles the data collection system of the ATLAS experiment at CERN. Each packet is time stamped with a global clock value and therefore we are able to compute an accurate measure of the network latency. Various other information collected from the boards is displayed in real time on a graphical interface. This work provides the tools to study a test bed representing a fraction of the 1600 ATLAS detector readout buffers and 600 Level 2 trigger CPUs using a combination of Fast Ethernet boards and the Gigabit Ethernet NICs