Heparin cofactor II in atherosclerotic lesions from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study

Heparin cofactor II (HCII) is a serine protease inhibitor (serpin) that has been shown to be a predictor of decreased atherosclerosis in the elderly and protective against atherosclerosis in mice. HCII inhibits thrombin in vitro and HCII-thrombin complexes have been detected in human plasma. Moreover, the mechanism of protection against atherosclerosis in mice was determined to be the inhibition of thrombin. Despite this evidence, the presence of HCII in human atherosclerotic tissue has not been reported. In this study, using samples of coronary arteries obtained from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study, we explore the local relationship between HCII and (pro)thrombin in atherosclerosis. We found that HCII and (pro)thrombin are co-localized in the lipid-rich necrotic core of atheromas. A significant positive correlation between each protein and the severity of the atherosclerotic lesion was present. These results suggest that HCII is in a position to inhibit thrombin in atherosclerotic lesions where thrombin can exert a proatherogenic inflammatory response. However, these results should be tempered by the additional findings from this, and other studies, that indicate the presence of other plasma proteins (antithrombin, albumin, and α1-protease inhibitor) in the same localized region of the atheroma

Large Synoptic Survey Telescope Galaxies Science Roadmap

The Large Synoptic Survey Telescope (LSST) will enable revolutionary studies of galaxies, dark matter, and black holes over cosmic time. The LSST Galaxies Science Collaboration has identified a host of preparatory research tasks required to leverage fully the LSST dataset for extragalactic science beyond the study of dark energy. This Galaxies Science Roadmap provides a brief introduction to critical extragalactic science to be conducted ahead of LSST operations, and a detailed list of preparatory science tasks including the motivation, activities, and deliverables associated with each. The Galaxies Science Roadmap will serve as a guiding document for researchers interested in conducting extragalactic science in anticipation of the forthcoming LSST era

Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer

Triple-negative (TN) breast cancer is an aggressive subtype of breast cancer associated with a unique set of epidemiologic and genetic risk factors. We conducted a two-stage genome-wide association study of TN breast cancer (stage 1: 1529 TN cases, 3399 controls; stage 2: 2148 cases, 1309 controls) to identify loci that influence TN breast cancer risk. Variants in the 19p13.1 and PTHLH loci showed genome-wide significant associations (P < 5 × 10− 8) in stage 1 and 2 combined. Results also suggested a substantial enrichment of significantly associated variants among the single nucleotide polymorphisms (SNPs) analyzed in stage 2. Variants from 25 of 74 known breast cancer susceptibility loci were also associated with risk of TN breast cancer (P < 0.05). Associations with TN breast cancer were confirmed for 10 loci (LGR6, MDM4, CASP8, 2q35, 2p24.1, TERT-rs10069690, ESR1, TOX3, 19p13.1, RALY), and we identified associations with TN breast cancer for 15 additional breast cancer loci (P < 0.05: PEX14, 2q24.1, 2q31.1, ADAM29, EBF1, TCF7L2, 11q13.1, 11q24.3, 12p13.1, PTHLH, NTN4, 12q24, BRCA2, RAD51L1-rs2588809, MKL1). Further, two SNPs independent of previously reported signals in ESR1 [rs12525163 odds ratio (OR) = 1.15, P = 4.9 × 10− 4] and 19p13.1 (rs1864112 OR = 0.84, P = 1.8 × 10− 9) were associated with TN breast cancer. A polygenic risk score (PRS) for TN breast cancer based on known breast cancer risk variants showed a 4-fold difference in risk between the highest and lowest PRS quintiles (OR = 4.03, 95% confidence interval 3.46–4.70, P = 4.8 × 10− 69). This translates to an absolute risk for TN breast cancer ranging from 0.8% to 3.4%, suggesting that genetic variation may be used for TN breast cancer risk prediction

How Many Varieties of Capitalism? Comparing the Comparative Institutional Analyses of Capitalist Diversity

This essay reviews the development of approaches within the comparative capitalisms (CC) literature and points to three theoretical innovations which, taken together, define and distinguish these approaches as a group. First, national economies are characterized by distinct institutional configurations that generate a particular systemic 'logic' of economic action. Second, the CC literature suggests a theory of comparative institutional advantage in which different institutional arrangements have distinct strengths and weaknesses for different kinds of economic activity. Third, the literature has been interpreted to imply a theory of institutional path dependence. Behind these unifying characteristics of the literature, however, lie a variety of analytical frameworks and typologies of capitalism. This paper reviews and compares these different frameworks by highlighting the fundamental distinctions among them and drawing out their respective contributions and limitations in explaining economic performance and institutional dynamics. The paper concludes that the way forward for this literature lies in developing a more dynamic view of individual institutions, the linkages between domains, and the role of politics and power.In diesem Discussion Paper werden Ansätze der Comparative-Capitalism-Diskussion vorgestellt. Sie haben drei theoretische Innovationen gemein. Erstens: Nationale Ökonomien werden durch institutionelle Konfigurationen geprägt, die auf jeweils eigene "systemische Logiken" wirtschaftlichen Handelns hinwirken. Zweitens: Die Comparative-Capitalism-Literatur beinhaltet eine Theorie der komparativen institutionellen Vorteile, der zufolge institutionellen Konfigurationen spezifische Wettbewerbsvorteile zugeordnet werden können. Zudem, drittens, beinhaltet die Comparative-Capitalism-Literatur auch eine implizite Theorie der Pfadabhängigkeit. Trotz dieser Gemeinsamkeiten unterscheiden sich die Ansätze hinsichtlich analytischer Zugriffe und Vorschläge zur Typologisierung nationaler Kapitalismen. Beim Vergleich dieser Ansätze werden besonders deren Stärken und Schwächen bei der Analyse wirtschaftlicher Performanz und institutioneller Entwicklungsdynamiken hervorgehoben. Der Aufsatz kommt zu dem Schluss, dass die Comparative-Capitalism-Literatur in dreierlei Hinsicht der Weiterentwicklung bedarf: hinsichtlich einer dynamischeren Modellierung von Institutionen, einem besseren Verständnis der Interaktion institutioneller Domänen und der Berücksichtigung von Macht und Politik in der Analyse von Produktionsregimen

The 4DGreenland project: Greenland hydrology assessment from remote sensing

The high latitudes of the Northern Hemisphere have experienced the largest regional warming over the last decades. On the Greenland ice sheet, rapid changes are observed in response to temperature increase, with the amount of liquid water at the surface particularly increasing. Understanding Greenland’s ice sheet hydrology is essential to assess its contribution to global sea-level rise in a future warming climate. With the objective of maximizing the use of Earth Observation (EO) data, the European Space Agency (ESA) has funded the 2-year project 4DGreenland (https://4dgreenland.eo4cryo.dk/) to assess and quantify the hydrology of the Greenland ice sheet. The project is focused on dynamic variations in the hydrological components of the ice sheet, and on quantifying the water fluxes between reservoirs including surface melt, supraglacial lakes and rivers, and subglacial melt and lakes. Efforts will focus on a thorough analysis of various components of the hydrological network in selected test regions and their impact on ice sheet flow. 4DGreenland started in September 2020. Here, we will present the project objectives, methods, and show initial results obtained within the project such as a comparison of supraglacial lake depths from optical imagery and ICESat-2 altimetry data, estimation of basal melt water production, and identification and mapping of surface meltwater presence and subglacial lakes from EO data