Neue Wege zu enantiomerenreinen Alkaloidbausteinen

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The scope and patterns of mobilization and conflict in EU interest group politics

The literature on interest group mobilization in EU legislative politics is heavily focused on organizations as much attention is concentrated on groups’ organizational characteristics, their activities towards different institutional venues, and their attempts to influence policies in one or a small set of policy cases. Yet, despite our growing knowledge about interest group politics, we know little about the pervasiveness of lobbying or the patterns of conflict and mobilization in EU interest group politics. How are conflict and mobilization in EU interest group politics structured? Can we speak of structural patterns of interest group conflict and mobilization or is the EU rather a balkanized lobbying arena? In order to analyze these questions we adopt a policy-centered account, instead of an organization-centered perspective, of interest group politics. More precisely, for a sample of 116 pieces of legislation we analyze the scope of interest group mobilization, the divisiveness of mobilization processes and the nature of conflict that is mobilized through the activities of lobbyists. For our empirical analyses, we triangulate evidence from different sources including media-analyses, interviews with 80 experts in the European Commission, interviews with 143 lobbyists and consultations. We conclude with a discussion of how our understanding of conflict structures complements policy field- and organization-based explanations of interest group politics

Patterns of Conflict and Mobilization: Mapping Interest Group Activity in EU Legislative Policymaking

Contemporary studies on interest group politics have mainly used single interest organizations as their central objects of study. This has led to a rich body of knowledge on the motivations of interest group mobilization, strategy development and even policy access and influence. The focus on single interest groups, however, has resulted in limited knowledge on aggregate patterns of interest groups’ activity. This article seeks to address this lacuna, by examining patterns of mobilization and conflict of interest groups’ activity in EU legislative policymaking. To do so, it adopts a unique policy-centred research design and an empirical assessment of policy mobilization for a sample of 125 EU legislative proposals based on extensive media coding as well as structured elite interviews. We find that levels of policy mobilization vary substantively across different legislative proposals and that political conflict between interest groups is remarkably low. This suggests that interest group conflict and mobilization contribute little to EU politicization and that in cases where interest groups voice opposing positions, conflicts do not occur between business and non-business groups. Our findings have important implications for our understanding of interest groups in EU legislative policymaking

Endophilin-A coordinates priming and fusion of neurosecretory vesicles via intersectin

Endophilins-A are conserved endocytic adaptors with membrane curvature-sensing and -inducing properties. We show here that, independently of their role in endocytosis, endophilin-A1 and endophilin-A2 regulate exocytosis of neurosecretory vesicles. The number and distribution of neurosecretory vesicles were not changed in chromaffin cells lacking endophilin-A, yet fast capacitance and amperometry measurements revealed reduced exocytosis, smaller vesicle pools and altered fusion kinetics. The levels and distributions of the main exocytic and endocytic factors were unchanged, and slow compensatory endocytosis was not robustly affected. Endophilin-A’s role in exocytosis is mediated through its SH3-domain, specifically via a direct interaction with intersectin-1, a coordinator of exocytic and endocytic traffic. Endophilin-A not able to bind intersectin-1, and intersectin-1 not able to bind endophilin-A, resulted in similar exocytic defects in chromaffin cells. Altogether, we report that two endocytic proteins, endophilin-A and intersectin-1, are enriched on neurosecretory vesicles and regulate exocytosis by coordinating neurosecretory vesicle priming and fusion

Global Tipping Points Report 2023: Ch1.2: Cryosphere tipping points.

Drastic changes in our planet’s frozen landscapes have occurred over recent decades, from Arctic sea ice decline and thawing of permafrost soils to polar amplification, the retreat of glaciers and ice loss from the ice sheets. In this chapter, we assess multiple lines of evidence for tipping points in the cryosphere – encompassing the ice sheets on Greenland and Antarctica, sea ice, mountain glaciers and permafrost – based on recent observations, palaeorecords, numerical modelling and theoretical understanding. With about 1.2°C of global warming compared to pre-industrial levels, we are getting dangerously close to the temperature thresholds of some major tipping points for the ice sheets of Greenland and West Antarctica. Crossing these would lock in unavoidable long-term global sea level rise of up to 10 metres. There is evidence for localised and regional tipping points for glaciers and permafrost and, while evidence for global-scale tipping dynamics in sea ice, glaciers and permafrost is limited, their decline will continue with unabated global warming. Because of the long response times of these systems, some impacts of crossing potential tipping points will unfold over centuries to millennia. However, with the current trajectory of greenhouse gas (GHG) emissions and subsequent anthropogenic climate change, such largely irreversible changes might already have been triggered. These will cause far-reaching impacts for ecosystems and humans alike, threatening the livelihoods of millions of people, and will become more severe the further global warming progresses

Cabozantinib in Advanced Hepatocellular Carcinoma: Efficacy and Safety Data from an International Multicenter Real-Life Cohort

Background and Aims: The multikinase inhibitor cabozantinib has been approved for hepatocellular carcinoma (HCC) previously treated with sorafenib. We report safety and efficacy data of an international, multicenter, real-life cohort of patients with advanced HCC treated with cabozantinib. Methods: Patients with HCC who were treated with cabozantinib were retrospectively identified across 11 centers in Austria, Switzerland, and Germany. Patients’ characteristics, adverse events, duration of treatment and overall survival (OS) data were analyzed until April 1, 2020. Results: Eighty-eight patients from 11 centers were included. The predominant underlying liver diseases were NAFLD/NASH in 26 (30%) and hepatitis C infection in 21 (24%) patients. Seventy-eight patients (89%) were classified as Barcelona clinic liver cancer (BCLC) stage C. Sixty patients (68%) were Child-Pugh A, whereas 22 (25%) were Child-Pugh B, respectively. Cabozantinib was used as systemic second- and third-line or later treatment in 41 (47%) and 46 (52%) patients, respectively. The following best responses under cabozantinib were documented: partial response in 6 (7%), stable disease in 28 (32%), and progressive disease in 28 (32%) patients, respectively. Fifty-two patients (59%) died during follow-up. The median OS from start of cabozantinib treatment was 7.0 months in the entire cohort and 9.7 months in Child-Pugh A patients, while Child-Pugh B patients had a median OS of 3.4 months, respectively. Thirty-seven (42%) patients fulfilled the CELESTIAL inclusion and exclusion criteria, showing a median OS of 11.1 months. Most common adverse events were fatigue (15.6%) and diarrhea (15.6%). Conclusion: Cabozantinib treatment was effective, safe, and feasible in patients with advanced HCC in patients with compensated cirrhosis. Patients in the real-life setting had more advanced liver disease – in which 25% of patients were Child-Pugh B. However, OS in patients with Child-Pugh A cirrhosis was similar to that reported in the phase 3 trial (CELESTIAL)

Reception Test of Petals for the End Cap TEC+ of the CMS Silicon Strip Tracker

The silicon strip tracker of the CMS experiment has been completed and was inserted into the CMS detector in late 2007. The largest sub system of the tracker are its end caps, comprising two large end caps (TEC) each containing 3200 silicon strip modules. To ease construction, the end caps feature a modular design: groups of about 20 silicon modules are placed on sub-assemblies called petals and these self-contained elements are then mounted onto the TEC support structures. Each end cap consists of 144 such petals, which were built and fully qualified by several institutes across Europe. Fro

Integration of the End Cap TEC+ of the CMS Silicon Strip Tracker

The silicon strip tracker of the CMS experiment has been completed and inserted into the CMS detector in late 2007. The largest sub-system of the tracker is its end cap system, comprising two large end caps (TEC) each containing 3200 silicon strip modules. To ease construction, the end caps feature a modular design: groups of about 20 silicon modules are placed on sub-assemblies called petals and these self-contained elements are then mounted into the TEC support structures. Each end cap consists of 144 petals, and the insertion of these petals into the end cap structure is referred to as TEC integration. The two end caps were integrated independently in Aachen (TEC+) and at CERN (TEC--). This note deals with the integration of TEC+, describing procedures for end cap integration and for quality control during testing of integrated sections of the end cap and presenting results from the testing

A time-resolved proteomic and prognostic map of COVID-19

COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease

Clinical and virological characteristics of hospitalised COVID-19 patients in a German tertiary care centre during the first wave of the SARS-CoV-2 pandemic: a prospective observational study

Purpose: Adequate patient allocation is pivotal for optimal resource management in strained healthcare systems, and requires detailed knowledge of clinical and virological disease trajectories. The purpose of this work was to identify risk factors associated with need for invasive mechanical ventilation (IMV), to analyse viral kinetics in patients with and without IMV and to provide a comprehensive description of clinical course. Methods: A cohort of 168 hospitalised adult COVID-19 patients enrolled in a prospective observational study at a large European tertiary care centre was analysed. Results: Forty-four per cent (71/161) of patients required invasive mechanical ventilation (IMV). Shorter duration of symptoms before admission (aOR 1.22 per day less, 95% CI 1.10-1.37, p < 0.01) and history of hypertension (aOR 5.55, 95% CI 2.00-16.82, p < 0.01) were associated with need for IMV. Patients on IMV had higher maximal concentrations, slower decline rates, and longer shedding of SARS-CoV-2 than non-IMV patients (33 days, IQR 26-46.75, vs 18 days, IQR 16-46.75, respectively, p < 0.01). Median duration of hospitalisation was 9 days (IQR 6-15.5) for non-IMV and 49.5 days (IQR 36.8-82.5) for IMV patients. Conclusions: Our results indicate a short duration of symptoms before admission as a risk factor for severe disease that merits further investigation and different viral load kinetics in severely affected patients. Median duration of hospitalisation of IMV patients was longer than described for acute respiratory distress syndrome unrelated to COVID-19