Проповеди и конфессиональная культура в Германии раннемодерного периода. Католические проповеди в 1650–1800 гг.

With the Council of Trent, Catholicism defined itself for the first time as a confession with distinct identifying features. In order not only to create but also to maintain such a Catholic Confessionalised identity, Catholic preachers needed to react to contemporary settings and currents as well as to fixed points of reference, as represented by the decrees of Trent. The scope provided by the Trent decree on preaching, “super lectione et praedicatione,” was so wide that, based upon it, individual ideas could be constructed about what constituted a “good” sermon. This can be seen in the various hermeneutics of the Council that developed up to the 18th century, and the associated post-Tridentine practices of piety, which are commonly grouped under the terms “Baroque” and “Enlightenment.” This article, which analyses sermons from the perspective of aesthetics of production and reception, is nonetheless able to show that along with Baroque and Enlightened piety, Jansenist influences also coexisted, something which has hardly been appreciated so far in research. At the same time, the preachers and the audiences do not seem to have understood the complex network of variously coded elements of Catholic confessional culture as a contradiction: the pastoral strategies of Catholics from the years 1650 to 1800 seem rather not to have been characterised by wave-like motion, with specific extensions on the ritual-sensual or rational-iconoclastic levels, as has been assumed in research. Such asynchrony can also be recognised in textual samples drawn from the Russian Orthodox history of preaching.Тридентский собор способствовал самоопределению католицизма как конфессии с особыми отличительными признаками. Для того, чтобы не только создать, но и поддерживать такую католическую идентичность, католические проповедники должны были реагировать на современное им окружение и тенденции развития, равно как и на отправные позиции, зафиксированные в Тридентских постановлениях. Область, охваченная декретом Тридентского собора о проповедях “super praedicatione”, была настолько широка, что, опираясь на нее, можно было выстроить индивидуальные представления о том, что именно составляло “хорошую” проповедь. Это можно видеть по различной интерпретации Собора вплоть до XVIII в. и связанным с ней посттридентским практикам благочестия, объединяемых обычно под названием “барочных” и “просвещенческих”. В настоящей статье, где проповеди исследуются с точки зрения их создания и рецепции, тем не менее можно показать, что с барочными и просвещенческими практиками соседствовали и янсенистские влияния, — чему предыдущие исследования практически не уделяли внимания. В то же время проповедники и их аудитория, очевидно, не видели в комплексе разнонаправленных элементов католической конфессиональной культуры противоречий. Пастырские стратегии католиков 1650–1800 гг., в частности, не характеризует, как принято считать в историографии, волнообразный ритм, с соответствующими ответвлениями в ритуально-сенсуалистскую или рационально-иконоборческую сферу. Подобную асинхронность можно также обнаружить по образцам текстов, представляющих историю проповедничества в русском православии

Abstract Natural Scenario Language Version 1.0

The development of modern driving assistant systems (assisted as well as automated) requires extensive testing and exact specification to ensure the quality of the developed systems. Therefore, scenarios are used throughout the whole process to act as accompanying artifact to assist within the design, implementation and testing procedures. Depending on the respective use case, different levels of abstraction, used natural languages and degrees of completeness are used for the scenarios. Due to the lack of an appropriate method for the specification of abstract scenarios that satisfies those needs for efficient usage, the language stiEF (acronym for “scenario-accompanied, text-based, iterative Evaluation of automated driving Functions”) was designed. This paper provides all details about the syntax and semantics of stiEF for the freeway domain. This enables the reader to read, understand, write and use stiEF for scenario descriptions

When cell death goes wrong:inflammatory outcomes of failed apoptosis and mitotic cell death

Apoptosis is a regulated cellular pathway that ensures that a cell dies in a structured fashion to prevent negative consequences for the tissue or the organism. Dysfunctional apoptosis is a hallmark of numerous pathologies, and treatments for various diseases are successful based on the induction of apoptosis. Under homeostatic conditions, apoptosis is a non-inflammatory event, as the activation of caspases ensures that inflammatory pathways are disabled. However, there is an increasing understanding that under specific conditions, such as caspase inhibition, apoptosis and the apoptotic machinery can be re-wired into a process which is inflammatory. In this review we discuss how the death receptor and mitochondrial pathways of apoptosis can activate inflammation. Furthermore, we will highlight how cell death due to mitotic stress might be a special case when it comes to cell death and the induction of inflammation

Mitochondria as multifaceted regulators of cell death

Through their many and varied metabolic functions, mitochondria power life. Paradoxically, mitochondria also have a central role in apoptotic cell death. Upon induction of mitochondrial apoptosis, mitochondrial outer membrane permeabilization (MOMP) usually commits a cell to die. Apoptotic signalling downstream of MOMP involves cytochrome c release from mitochondria and subsequent caspase activation. As such, targeting MOMP in order to manipulate cell death holds tremendous therapeutic potential across different diseases, including neurodegenerative diseases, autoimmune disorders and cancer. In this Review, we discuss new insights into how mitochondria regulate apoptotic cell death. Surprisingly, recent data demonstrate that besides eliciting caspase activation, MOMP engages various pro-inflammatory signalling functions. As we highlight, together with new findings demonstrating cell survival following MOMP, this pro-inflammatory role suggests that mitochondria-derived signalling downstream of pro-apoptotic cues may also have non-lethal functions. Finally, we discuss the importance and roles of mitochondria in other forms of regulated cell death, including necroptosis, ferroptosis and pyroptosis. Collectively, these new findings offer exciting, unexplored opportunities to target mitochondrial regulation of cell death for clinical benefit

PARP13 regulates cellular mRNA post-transcriptionally and functions as a pro-apoptotic factor by destabilizing TRAILR4 transcript

Poly(ADP-ribose) polymerase-13 (​PARP13/​ZAP/​ZC3HAV1) is an antiviral factor, active against specific RNA viruses such as murine leukaemia virus, Sindbis virus and human immunodeficiency virus. During infection, ​PARP13 binds viral RNA via its four CCCH-type zinc-finger domains and targets it for degradation by recruiting cellular messenger RNA (mRNA) decay factors such as the exosome complex and ​XRN1. Here we show that ​PARP13 binds to and regulates cellular mRNAs in the absence of viral infection. Knockdown of ​PARP13 results in the misregulation of hundreds of transcripts. Among the most upregulated transcripts is ​TRAILR4 that encodes a decoy receptor for ​TRAIL—a pro-apoptotic cytokine that is a promising target for the therapeutic inhibition of cancers. ​PARP13 destabilizes ​TRAILR4 mRNA post-transcriptionally in an exosome-dependent manner by binding to a region in its 3′ untranslated region. As a consequence, ​PARP13 represses ​TRAILR4 expression and increases cell sensitivity to ​TRAIL-mediated apoptosis, acting as a key regulator of the cellular response to ​TRAIL.National Cancer Institute (U.S.) (Cancer Center Support (Core) Grant P30-CA14051)National Institutes of Health (U.S.) (RO1GM087465)Kathy and Curt Marble Cancer Research Fund (Frontier Research Programme Grant)Massachusetts Institute of Technology. Ludwig Center for Molecular Oncology (Postdoctoral Fellowship)MIT School of Science (Fellowship in Cancer Research

Beiträge zur szenarienbegleiteten Entwicklung von automatisierten Fahrfunktionen

The complexity of the development of modern automobiles is steadily increasing, especially due to the topic of automated driving functions. Unlike former driver assistance systems, which only support the driving tasks, modern systems have to take full control over the car. This imposes high demands on the quality and robustness of the systems and their development processes. However, the information exchange between the development phases is still conducted manually by using text-based data (e.g., the specification). Previous attempts to optimize this process by using model-based approaches failed because of the insufficient willingness of the developers to adapt them, mainly due to the initial learning curve or the conversion expense. Because the testing of modern driving functions is more and more based on simulations, the importance of the corresponding traffic scenario descriptions is rising. Those descriptions are currently created manually, either as plain text or directly as simulation model. Additionally, a reliable estimation of the required test effort for multi-sensor systems already during early development phases is crucial for a sound project planning. Such a project planning also includes a selection of the software development processed, methods and tools that should be applied. Available approaches do not offer a quick graphic overview or the possibility to compare quite different approaches. The taxonomy proposed in this work provides such an option, based on the V-Model and further annotations. Neither the customer expectations regarding automated driving systems, nor the rating of the development methods by the developers remain stable. Hence, in this work, the results from three conducted surveys are given to get a review of the current state of the domain. To optimize the transitions between the development phases and to lower the adaptation effort for the developers, two iterative, text-based concepts for the formulation of requirements and scenario descriptions are proposed, each of them combined with a corresponding domain-specific language in the framework JetBrains Meta Programming System (MPS). Although existing approaches are also using textual formats, they do not support multilingual representations, data at different abstraction levels or the automatic generation of the handover artifacts (e.g., models) required for the development. Even though methods to estimate the test effort for multisensor systems are available, they rely either on the physical sensor models or implementation details. In this work, an approach is given, that can determine this effort to be conducted for a defined confidence level already during the specification phase and solely based on the sensor characteristics. These five concepts contribute to the scenario-accompanied development process of automated driving functions.Die Komplexität der Entwicklung moderner Fahrzeuge steigt kontinuierlich, besonders auch durch das aktuelle Thema der automatisierten Fahrfunktionen. Im Gegensatz zu früheren Fahrerassistenzsystemen, die nur unterstützend auf das Fahrzeug einwirken, müssen zukünftige Systeme die vollständige Kontrolle über das Fahrzeug übernehmen können. Das stellt hohe Anforderungen an die Qualität und die Robustheit der Systeme und folglich auch deren Entwicklungsprozesse. Dennoch werden Informationen zwischen den einzelnen Entwicklungsphasen immer noch manuell und in textbasierter Form (z.B. als Lastenheft) ausgetauscht. Bisherige Versuche, dies durch modellbasierte Ansätze zu optimieren, scheiterten meist an dem mangelnden Adaptionswillen der Entwickler aufgrund des initialen Lern- und Umstellungsaufwands. Da zur Erprobung moderner Fahrfunktionen immer stärker auf Simulationen gesetzt wird, steigt auch die Bedeutung der dafür notwendigen Szenarienbeschreibungen. Diese werden bisher manuell, entweder als Text oder direkt als Simulationsmodell, erstellt. Zusätzlich ist eine belastbare Abschätzung des notwendigen Testaufwands gerade für Multisensorsysteme bereits in einer frühen Phase für eine solide Projektplanung unumgänglich. Solch eine Projektplanung umfasst auch eine Auswahl der einzusetzenden Softwareentwicklungsprozesse, -methoden und -werkzeuge. Die dafür verfügbaren Ansätze bieten aber weder einen schnellen graphischen Überblick, noch können sie sehr unterschiedliche Ansätze vergleichen. Die in dieser Arbeit vorgestellte Taxonomie bietet diese Möglichkeit auf Basis des V-Modells und zusätzlicher Annotationen. Da weder die Kundenerwartungen an automatisierte Fahrsysteme, noch die Bewertungen der Entwicklungsmethoden durch die Entwickler konstant bleiben, werden für eine aktuelle Bestandsaufnahme im Rahmen dieser Arbeit die Ergebnisse von drei Umfragen zu diesen Themen vorgestellt. Um einerseits die Übergänge zwischen den Entwicklungsphasen zu optimieren, andererseits aber den Adaptionsaufwand für die Nutzer gering zu halten, werden weiterhin zwei iterative textbasierte Konzepte zur Erstellung von Anforderungen und Szenarienbeschreibungen, jeweils mit einer passenden domänenspezifischen Sprache im Framework JetBrains Meta Programming System (MPS) vorgestellt. Bereits verfügbare Ansätze arbeiten zwar auch textbasiert, sind aber weder multilingual, noch verwenden sie verschieden abstrakte Daten oder können die für die Entwicklung notwendigen Übergabeartefakte (z.B. Modelle) automatisch generieren. Auch wenn es bereits Lösungen zur Testaufwandsschätzung für Multisensorsysteme gibt, benötigen diese entweder die physikalischen Sensormodelle oder Implementierungsdetails. In dieser Arbeit wird deshalb ein Ansatz vorgestellt, der schon in der Spezifikationsphase, allein auf Basis der Sensorcharakteristika, den zu leistenden Testaufwand für ein definiertes Konfidenzniveau ermitteln kann. Diese fünf Konzepte tragen zur szenarienbegleiteten Entwicklung automatisierter Fahrfunktionen bei