RMD-QOSM - The Resource Management in Diffserv QoS model

This document describes an NSIS QoS Model for networks that use the Resource Management in Diffserv (RMD) concept. RMD is a technique for adding admission control and preemption function to Differentiated Services (Diffserv) networks. The RMD QoS Model allows devices external to the RMD network to signal reservation requests to edge nodes in the RMD network. The RMD Ingress edge nodes classify the incoming flows into traffic classes and signals resource requests for the corresponding traffic class along the data path to the Egress edge nodes for each flow. Egress nodes reconstitute the original requests and continue forwarding them along the data path towards the final destination. In addition, RMD defines notification functions to indicate overload situations within the domain to the edge nodes

QoS signaling across heterogeneous wired/wireless networks: resource management in diffserv using the NSIS protocol suite

Reservation-based Quality of Service (QoS) in a mixed wireless and wireline environment requires an end-to-end signaling protocol that is capable of adapting to the idiosyncrasies of the different networks. The QoS NSIS Signaling Protocol (QoSNSLP) has been created by the Next Steps In Signaling working group at the IETF to fulfill this need for an adaptive reservation protocol. It allows reservation requests to be interpreted by equipment implementing different QoS models along the path between a data sender and a data receiver. This paper describes the QoS-NSLP, and an example of a particular QoS model that is based on Resource Management in Diffserv (RMD). RMD provides a scalable dynamic resource management method for Diffserv networks. RMD has two basic functions to control the traffic load in a Diffserv domain: it provides admission control for flows entering the network and it has an algorithm that terminates the required amount of flows in case of congestion caused by failures (e.g. link or router) bandwidth and require per-flow reservations. On the other hand, the wireline networks tend to form the backbones and have relatively abundant bandwidth and carry a large number of flows, where aggregation is necessary since per-flow reservations suffer from scalability constraints

Thermal contact resistance for a CU/G-10CR interface in a cylindrical geometry

A major component of a high-T[sub c] superconductor current lead designed to provide current to low-T[sub c] superconductor magnets is the heat intercept connection, which is a cylindrical structure consisting of an inner Cu disk, a thin-walled G-10CR composite tube, and an outer Cu ring, assembled by a thermal interference fit. It was determined in a previous study that the thermal contact resistance (R[sub c]) between the composite tube and the two Cu pieces contributed a substantial portion of the total thermal resistance between the inner and outer Cu pieces. This report emphasizes the analysis of the data for the third and final design of the heat intercept connection. In particular, it is found that R[sub c] decreases dramatically with increasing heat flux, a result consistent with earlier studies of composite cylinders. However, for the present data, the thermal contact conductance [=1/R{sub c}]varies with the calculated contact pressure with a power-law exponent of approximately 10, as compared to a theoretical value near 1. In addition, the presence of He or N[sub 2] gas substantially reduces R [sub c] even though the contacting surfaces are coated with a thermal grease

Usage and uptake of virtual learning environments and technology assisted learning: Findings from a multi institutional, multi year comparative study

In early 2008 five Irish tertiary institutions conducted an online survey of their students’ usage of Virtual Learning Environments (VLEs) in their respective institutions. In 2009, the survey was run again with an expanded set of institutions and supplemented by a staff survey and detailed institutional case histories. The survey instruments used a common set of questions, and on condition of anonymity, the institutions pooled their results to allow us to compare and contrast the results. While many institutions routinely conduct in-house surveys or studies from time to time, this study is relatively unique in that it draws on data from multiple institutions, across multiple years, and diverse VLE platforms. The institutions who participated represented a diversity of organizational histories and VLE systems. The study identifies some of the key drivers and barriers to uptake and usage of an institutional VLE and identified that it is organizational factors, such as system maturity, rather than technical ones around system choice, that are the most significant factors in the uptake, usage and utility of the VLE systems. The paper also notes issues around the conduct of the survey, confidentiality and data sharing, and lessons from the experience

‘Pandemia’: a reckoning of UK universities’ corporate response to COVID-19 and its academic fallout:A reckoning of UK universities’ corporate response to COVID-19 and its academic fallout.

Universities in the UK, and in other countries like Australia and the USA, have responded to the operational and financial challenges presented by the COVID-19 pandemic by prioritising institutional solvency and enforcing changes to the work-practices and profiles of their staff. For academics, an adjustment to institutional life under COVID-19 has been dramatic and resulted in the overwhelming majority making a transition to prolonged remote-working. Many have endured significant work intensification; others have lost — or may soon lose — their jobs. The impact of the pandemic appears transformational and for the most part negative. This article reports the experiences of n=1,099 UK academics specific to the corporate response of institutional leadership to the COVID-19 crisis. We find articulated a story of universities in the grip of 'pandemia' and COVID-19 emboldening processes and protagonists of neoliberal governmentality and market-reform that pay little heed to considerations of human health and wellbeing

Snf2 family ATPases and DExx box helicases:differences and unifying concepts from high-resolution crystal structures

Proteins with sequence similarity to the yeast Snf2 protein form a large family of ATPases that act to alter the structure of a diverse range of DNA–protein structures including chromatin. Snf2 family enzymes are related in sequence to DExx box helicases, yet they do not possess helicase activity. Recent biochemical and structural studies suggest that the mechanism by which these enzymes act involves ATP-dependent translocation on DNA. Crystal structures suggest that these enzymes travel along the minor groove, a process that can generate the torque or energy in remodelling processes. We review the recent structural and biochemical findings which suggest a common mechanistic basis underlies the action of many of both Snf2 family and DExx box helicases

Nitric oxide and hypoxia stimulate erythropoietin receptor via MAPK kinase in endothelial cells

Erythropoietin receptor (EPOR) expression level determines the extent of erythropoietin (EPO) response. Previously we showed that EPOR expression in endothelial cells is increased at low oxygen tension and that EPO stimulation of endothelial cells during hypoxia can increase endothelial nitric oxide (NO) synthase (eNOS) expression and activation as well as NO production. We now observe that while EPO can stimulate NO production, NO in turn can regulate EPOR expression. Human umbilical vein endothelial cells (HUVEC) treated with 10-50 pM of NO donor diethylenetriamine NONOate (DETANO) for 24 h showed significant induction of EPOR gene expression at 5% and 2% of oxygen. Also human bone marrow microvascular endothelial cell line (TrHBMEC) cultured at 21 and 2% oxygen with 50 uM DETANO demonstrated a time and oxygen dependent induction of EPOR mRNA expression after 24 and 48 h, particularly at low oxygen tension. EPOR protein was also induced by DETANO at 2% oxygen in TrHBMEC and HUVEC. The activation of signaling pathways by NO donor stimulation appeared to be distinct from EPO stimulation. In reporter gene assays, DETANO treatment of HeLa cells at 2% oxygen increased EPOR promoter activity indicated by a 48% increase in luciferase activity with a 2 kb EPOR promoter fragment and a 71% increase in activity with a minimal EPOR promoter fragment containing 0.2 kb 5'. We found that DETANO activated MAPK kinase in TrHBMEC both in normoxia and hypoxia, while MAPK kinase inhibition showed significant reduction of EPOR mRNA gene expression at low oxygen tension, suggesting MAPK involvement in NO mediated induction of EPOR Furthermore, DETANO stimulated Ala anti-apoptotic activity after 30 min in normoxia, whereas it inhibited Akt phosphorylation in hypoxia. In contrast, EPO did not significantly increase MAPK activity while EPO stimulated Akt phosphorylation in TrHBMEC in normoxia and hypoxia. These observations provide a new effect of NO on EPOR expression to enhance EPO response in endothelial cells, particularly at low oxygen tensions

Genetic frontiers for conservation:An assessment of synthetic biology and biodiversity conservation

In recent years synthetic biology has emerged as a suite of techniques and technologies that enable humans to read, interpret, modify, design and manufacture DNA in order to rapidly influence the forms and functions of cells and organisms, with the potential to reach whole species and ecosystems. As synthetic biology continues to evolve, new tools emerge, novel applications are proposed, and basic research is applied. This assessment is one part of IUCN’s effort to provide recommendations and guidance regarding the potential positive and negative impacts of synthetic biology on biodiversity conservation; it comprises a full assessment and a short synthesis report

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Mosaic structural variation in children with developmental disorders

Delineating the genetic causes of developmental disorders is an area of active investigation. Mosaic structural abnormalities, defined as copy number or loss of heterozygosity events that are large and present in only a subset of cells, have been detected in 0.2–1.0% of children ascertained for clinical genetic testing. However, the frequency among healthy children in the community is not well characterized, which, if known, could inform better interpretation of the pathogenic burden of this mutational category in children with developmental disorders. In a case–control analysis, we compared the rate of large-scale mosaicism between 1303 children with developmental disorders and 5094 children lacking developmental disorders, using an analytical pipeline we developed, and identified a substantial enrichment in cases (odds ratio = 39.4, P-value 1.073e − 6). A meta-analysis that included frequency estimates among an additional 7000 children with congenital diseases yielded an even stronger statistical enrichment (P-value 1.784e − 11). In addition, to maximize the detection of low-clonality events in probands, we applied a trio-based mosaic detection algorithm, which detected two additional events in probands, including an individual with genome-wide suspected chimerism. In total, we detected 12 structural mosaic abnormalities among 1303 children (0.9%). Given the burden of mosaicism detected in cases, we suspected that many of the events detected in probands were pathogenic. Scrutiny of the genotypic–phenotypic relationship of each detected variant assessed that the majority of events are very likely pathogenic. This work quantifies the burden of structural mosaicism as a cause of developmental disorders