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Bis zum Ende des dritten Bewirtschaftungszyklusses von 2021 bis 2027 müssen alle Oberflächengewässer den guten Zustand erreichen, den die Europäische Wasserrahmenrichtlinie (WRRL) definiert. Nach 20-jährigem Bestehen der WRRL ist eine Zielerreichung für Deutschland in weiter Ferne, wobei die Gründe neben der Flächenverfügbarkeit zumeist in den finanziellen und personellen Ressourcen liegen. Während Bewertungsmethoden vorliegen, die den volkswirtschaftlichen Nutzen zu erfassen im Stande sind, verbleibt die Entscheidung, ab welchen Grenzen und welchen Vergleichsmaßstäben unverhältnismäßige Kosten vorliegen, letztendlich eine politische. Die Dissertation zeigt aus einer umweltökonomischen Perspektive auf, in welchen Fällen auf aufwändige (kleinräumige) Nutzenbewertungen verzichtet werden kann. Zudem wird ein Top-Down-Ansatz empfohlen, um die Verhältnismäßigkeit der Umsetzung der WRRL selbst pragmatisch und transaktionskostenarm zu überprüfen.

Thrombin is the pivotal enzyme in the biochemistry of secondary hemostasis crucial to maintaining homeostasis of hemostasis. In contrast to routine coagulation tests (PT or aPTT) or procoagulant or anticoagulant factor assays (e.g. fibrinogen, factor VIII, antithrombin or protein C), the thrombin generation assay (TGA), also named thrombin generation test (TGT) is a so-called "global assay" that provides a picture of the hemostasis balance though a continuous and simultaneous measurement of thrombin formation and inhibition. First described in the early 1950s, as a manual assay, efforts have been made in order to standardize and automate the assay to offer researchers, clinical laboratories and the pharmaceutical industry a versatile tool covering a wide range of clinical and non-clinical applications. This review describes technical options offered to properly run TGA, including a review of preanalytical and analytical items, performance, interpretation, and applications in physiology research and pharmacy.

Determining patient's coagulation profile, i.e. detecting a bleeding tendency or the opposite, a thrombotic risk, is crucial for clinicians in many situations. Routine coagulation assays and even more specialized tests may not allow a relevant characterization of the hemostatic balance. In contrast, thrombin generation assay (TGA) is a global assay allowing the dynamic continuous and simultaneous recording of the combined effects of both thrombin generation and thrombin inactivation. TGA thus reflects the result of procoagulant and anticoagulant activities in blood and plasma. Because of this unique feature, TGA has been widely used in a wide array of settings from both research, clinical and pharmaceutical perspectives. This includes diagnosis, prognosis, prophylaxis, and treatment of inherited and acquired bleeding and thrombotic disorders. In addition, TGA has been shown to provide relevant information for the diagnosis of coagulopathies induced by infectious diseases, comprising also disturbance of the coagulation system in COVID-19, or for the assessment of early recurrence in breast cancer. This review article aims to document most clinical applications of TGA.

Friedreich's ataxia (FA) is a hereditary system degeneration, which progressively affects sensory functions such as proprioceptive feedback, which causes progressive ataxia in FA patients. While major clinical features of movement disorders in FA patients have been identified, the underlying impaired neural control is not sufficiently understood. To elucidate the underlying control mechanism, we investigated single-joint movements of the upper limb in FA patients. Small, tolerable force perturbations were induced during voluntary single-joint arm movements to examine the compensatory reaction of the FA patient's motor system. Movement kinematics were measured, and muscle torques were quantified. We first found that as in healthy subjects, unperturbed single-joint movements in FA patients preserved similar temporal profiles of hand velocity and muscle torques, however, scaled in duration and amplitude. In addition, the small perturbations were compensated for efficiently in both groups, with the endpoint error

An oak tree trunk was found in July 2013, deep in a Rhondda valley peat bog, Wales. The artefact has been found to have a calibrated carbon date of about 4300 BC. Knife cut markings on the wood surface are interpreted as evidence of dual Sun and Moon calendars; the first comprehensible writing and reading in human history, a statement of five day weeks, four weeks a month, sixteen months a year, the Sun calendar year of 365 days, the Moon calendar of five day weeks, six weeks a month, twelve months a year.

Wie jede öffentlichkeitssuchende Institution oder Person legen auch die katholische Kirche und ihre Päpste großen Wert auf das eigene Image. Dabei weicht die intendierte Selbstdarstellung oftmals von der medialen Wahrnehmung ab oder steht ihr sogar diametral entgegen. Ganz gleich ob Pius XII. als „Hitlers Papst“, Johannes XXIII. als „Revoluzzer“ oder Paul VI. als „Antipillenpapst“ – es existieren eine Fülle von außen zugetragener printmedialer Papst-Images, deren Entstehung, Verlauf und Brüche es in diesem Buch mithilfe einer mediensemiotischen, textbasierten Methodik auszumachen und nachzuzeichnen gilt.

A common culture existed across Britain, Ireland and western Europe six thousand years ago. Writing came into being in Wales 4,270 BC, Irish symbols portrayed Sun and Moon calendars 3,500 BC. Arithmetic and geometry developed in Denmark 3,100 BC, Scandinavians navigated the oceans using a sixty-four point compass. France’s Carnac stone rows exhibit Sun and Moon calendars counts, linear measures. Brython’s [Wales] and Cornwall’s Bronze Age 2,000 BC inaugurated mining, widespread copper and tin industries and commerce in Britain and across Europe. Five day weeks Sun and Moon calendars endured for four thousand years in the western Isles and Europe until the beginning of the Roman Empire two thousand years ago. This book is about how they came to be and how it was done in prehistoric times.

Botrytis cinerea is a major plant pathogen infecting more than 1400 plant species. During invasion, the fungus rapidly kills host cells, which is believed to be supported by induction of programmed plant cell death. To comprehensively evaluate the contributions of most of the currently known plant cell death inducing proteins (CDIPs) and metabolites for necrotrophic infection, an optimized CRISPR/Cas9 protocol was established which allowed to perform serial marker-free mutagenesis to generate multiple deletion mutants lacking up to 12 CDIPs. Whole genome sequencing of a 6x and 12x deletion mutant revealed a low number of off-target mutations which were unrelated to Cas9-mediated cleavage. Secretome analyses confirmed the loss of secreted proteins encoded by the deleted genes. Infection tests with the mutants revealed a successive decrease in virulence with increasing numbers of mutated genes, and varying effects of the knockouts on different host plants. Comparative analysis of mutants confirmed significant roles of two polygalacturonases (PG1, PG2) and the phytotoxic metabolites botrydial and botcinins for infection, but revealed no or only weak effects of deletion of the other CDIPs. Nicotiana benthamiana plants with mutated or silenced coreceptors of pattern recognition receptors, SOBIR1 and BAK1, showed similar susceptibility as control plants to infection by B. cinerea wild type and a 12x deletion mutant. These results raise doubts about a major role of manipulation of these plant defence regulators for B. cinerea infection. Despite the loss of most of the known phytotoxic compounds, the on planta secretomes of the multiple mutants retained substantial phytotoxic activity, proving that further, as yet unknown CDIPs contribute to necrosis and virulence. Our study has addressed for the first time systematically the functional redundancy of fungal virulence factors, and demonstrates that B. cinerea releases a highly redundant cocktail of proteins to achieve necrotrophic infection of a wide variety of host plants.

A common culture existed across Britain, Ireland and western Europe six thousand years ago. Writing came into being in Wales 4,270 BC, Irish symbols portrayed Sun and Moon calendars 3,500 BC. Arithmetic and geometry developed in Denmark 3,100 BC, Scandinavians navigated the oceans using a sixty-four point compass. France’s Carnac stone rows exhibit Sun and Moon calendars counts, linear measures. The Bronze Age 2,000 BC inaugurated mining, widespread copper and tin industries and commerce in Britain and across Europe. Five day weeks Sun and Moon calendars endured for four thousand years in the western Isles and Europe until the beginning of the Roman Empire two thousand years ago. This book is about how they came to be and how it was done in prehistoric times.

A common culture existed across Britain, Ireland and western Europe six thousand years ago. Writing came into being in Wales 4,270 BC, Irish symbols portrayed Sun and Moon calendars 3,500 BC. Arithmetic and geometry developed in Denmark 3,100 BC, Scandinavians navigated the oceans using a sixty-four point compass. France’s Carnac stone rows exhibit Sun and Moon calendars and linear measures. The Bronze Age 2,000 BC inaugurated mining, widespread copper and tin industries and commerce in Britain and across Europe. Five day weeks Sun and Moon calendars endured for four thousand years in the western Isles and Europe until the beginning of the Roman Empire two thousand years ago.

On the occasion of the 10th openHPI anniversary, this technical report provides information about the HPI MOOC platform, including its core features, technology, and architecture. In an introduction, the platform family with all partner platforms is presented; these now amount to nine platforms, including openHPI. This section introduces openHPI as an advisor and research partner in various projects. In the second chapter, the functionalities and common course formats of the platform are presented. The functionalities are divided into learner and admin features. The learner features section provides detailed information about performance records, courses, and the learning materials of which a course is composed: videos, texts, and quizzes. In addition, the learning materials can be enriched by adding external exercise tools that communicate with the HPI MOOC platform via the Learning Tools Interoperability (LTI) standard. Furthermore, the concept of peer assessments completed the possible learning materials. The section then proceeds with further information on the discussion forum, a fundamental concept of MOOCs compared to traditional e-learning offers. The section is concluded with a description of the quiz recap, learning objectives, mobile applications, gameful learning, and the help desk. The next part of this chapter deals with the admin features. The described functionality is restricted to describing the news and announcements, dashboards and statistics, reporting capabilities, research options with A/B testing, the course feed, and the TransPipe tool to support the process of creating automated or manual subtitles. The platform supports a large variety of additional features, but a detailed description of these features goes beyond the scope of this report. The chapter then elaborates on common course formats and openHPI teaching activities at the HPI. The chapter concludes with some best practices for course design and delivery. The third chapter provides insights into the technology and architecture behind openHPI. A special characteristic of the openHPI project is the conscious decision to operate the complete application from bare metal to platform development. Hence, the chapter starts with a section about the openHPI Cloud, including detailed information about the data center and devices, the used cloud software OpenStack and Ceph, as well as the openHPI Cloud Service provided for the HPI. Afterward, a section on the application technology stack and development tooling describes the application infrastructure components, the used automation, the deployment pipeline, and the tools used for monitoring and alerting. The chapter is concluded with detailed information about the technology stack and concrete platform implementation details. The section describes the service-oriented Ruby on Rails application, inter-service communication, and public APIs. It also provides more information on the design system and components used in the application. The section concludes with a discussion of the original microservice architecture, where we share our insights and reasoning for migrating back to a monolithic application. The last chapter provides a summary and an outlook on the future of digital education. Anlässlich des 10-jährigen Jubiläums von openHPI informiert dieser technische Bericht über die HPI-MOOC-Plattform einschließlich ihrer Kernfunktionen, Technologie und Architektur. In einer Einleitung wird die Plattformfamilie mit allen Partnerplattformen vorgestellt; diese belaufen sich inklusive openHPI aktuell auf neun Plattformen. In diesem Abschnitt wird außerdem gezeigt, wie openHPI als Berater und Forschungspartner in verschiedenen Projekten fungiert. Im zweiten Kapitel werden die Funktionalitäten und gängigen Kursformate der Plattform präsentiert. Die Funktionalitäten sind in Lerner- und Admin-Funktionen unterteilt. Der Bereich Lernerfunktionen bietet detaillierte Informationen zu Leistungsnachweisen, Kursen und den Lernmaterialien, aus denen sich ein Kurs zusammensetzt: Videos, Texte und Quiz. Darüber hinaus können die Lernmaterialien durch externe Übungstools angereichert werden, die über den Standard Learning Tools Interoperability (LTI) mit der HPI MOOC-Plattform kommunizieren. Das Konzept der Peer-Assessments rundet die möglichen Lernmaterialien ab. Der Abschnitt geht dann weiter auf das Diskussionsforum ein, das einen grundlegenden Unterschied von MOOCs im Vergleich zu traditionellen E-Learning-Angeboten darstellt. Zum Abschluss des Abschnitts folgen eine Beschreibung von Quiz-Recap, Lernzielen, mobilen Anwendungen, spielerischen Lernens und dem Helpdesk. Der nächste Teil dieses Kapitels beschäftigt sich mit den Admin-Funktionen. Die Funktionalitätsbeschreibung beschränkt sich Neuigkeiten und Ankündigungen, Dashboards und Statistiken, Berichtsfunktionen, Forschungsoptionen mit A/B-Tests, den Kurs-Feed und das TransPipe-Tool zur Unterstützung beim Erstellen von automatischen oder manuellen Untertiteln. Die Plattform unterstützt außerdem eine Vielzahl zusätzlicher Funktionen, doch eine detaillierte Beschreibung dieser Funktionen würde den Rahmen des Berichts sprengen. Das Kapitel geht dann auf gängige Kursformate und openHPI-Lehrveranstaltungen am HPI ein, bevor es mit einigen Best Practices für die Gestaltung und Durchführung von Kursen schließt. Zum Abschluss des technischen Berichts gibt das letzte Kapitel eine Zusammenfassung und einen Ausblick auf die Zukunft der digitalen Bildung. Ein besonderes Merkmal des openHPI-Projekts ist die bewusste Entscheidung, die komplette Anwendung von den physischen Netzwerkkomponenten bis zur Plattformentwicklung eigenständig zu betreiben. Bei der vorliegenden deutschen Variante handelt es sich um eine gekürzte Übersetzung des technischen Berichts 148, bei der kein Einblick in die Technologien und Architektur von openHPI gegeben wird. Interessierte Leser:innen können im technischen Bericht 148 (vollständige englische Version) detaillierte Informationen zum Rechenzentrum und den Geräten, der Cloud-Software und dem openHPI Cloud Service aber auch zu Infrastruktur-Anwendungskomponenten wie Entwicklungstools, Automatisierung, Deployment-Pipeline und Monitoring erhalten. Außerdem finden sich dort weitere Informationen über den Technologiestack und konkrete Implementierungsdetails der Plattform inklusive der serviceorientierten Ruby on Rails-Anwendung, die Kommunikation zwischen den Diensten, öffentliche APIs, sowie Designsystem und -komponenten. Der Abschnitt schließt mit einer Diskussion über die ursprüngliche Microservice-Architektur und die Migration zu einer monolithischen Anwendung.

The miscellaneous information about so-called Roman Roads mentioned in my books Stonehenge Sacred Symbolism 2011, Stonehenge Complete 2015 required consolidation; this is an account of three straight tracks in Britain’s Bronze Age, the bat and ball game cricket and the soccer/football game. With a title ‘Three Country Tracks’ I chronicle a tale of four thousand years ago, a research paper based upon and derived directly from prehistory and Britain’s Stonehenge ancient monument in particular.