Climate-friendly technologies in the mobile air-conditioning sector: A patent citation analysis

The development of climate-friendly technologies and its diffusion across countries is of key importance to slow climate change. This paper considers technologies in the mobile air-conditioning (MAC) sector which is a major contributor of fluorinatedgreenhouse gas emissions. Using patents as an indicator of innovations and patent citations as a proxy for knowledge flows the inducement of new environmental and non-environmental technologies and its diffusion within and across countries and withinand across patent applicant- and firm-types is analyzed. We find that most environmental patents originate from Germany and the US and are filed by individuals rather than firms. Most knowledge flows take place within countries. Regarding cross-countryflows most environmental knowledge diffuses from French and German patents, which is likely to be a result of regulatory activities in Europe and intensified research on environmentally benign MAC systems. Yet, this exchange of knowledge is not very intensive and stable, so that the impact of EU regulations on US and Japanese patenting behaviour remains fairly weak.Environmental innovation, patent, count data models

The Determinants of Environmental Innovations and Patenting: Germany Reconsidered

This paper provides new evidence on the objectives and determinants of different typesof innovations and patents, environmental as opposed to other innovations and patents,and different variants of environmental innovations and patents. We investigate howfirm-specific and sector-specific driving forces differ by innovation type. Moreover, weoutline the functions that different innovation types have for environmental and innovationpolicies. We find that eco-innovators put relatively more attention to cost reduction, inparticular the reduction of energy and resource costs, compared to other innovators.Cost pressure and reliable, predictable and strict framework conditions of environmentalpolicy turns out to be an important driver for more incremental, firm-level eco-innovationscontributing to the diffusion of principally known technologies among firms. By contrast,more far-reaching patented eco-innovations are driven by the opportunity to create newmarkets and by government subsidies.Environmental innovation, patent, discrete choice models

Die Bedeutung des Low Molecular Weight Protein 7 (LMP7)- spezifischen Inhibitors ONX 0914 bei der viralen Infektion der Maus

Herzinsuffizienz ist eine der häufigsten Todesursachen. Ein Auslöser hierfür kann eine entzündliche Herzerkrankung sein, die durch virale Infektionen beispielsweise mit CoxsackievirusB3 ausgelöst werden können. Dabei ist der Schaden im Herzmuskel sowohl durch direkte Viruszytotoxizität vermittelt als auch auf eine Aktivierung von immunologischen Prozessen zurückzuführen. Ein mögliches therapeutisches Ziel sind daher Modulatoren einer überschießend aktivierten Immunantwort. Diesbezüglich ist die zelluläre Proteolyse durch das Immunproteasom von Bedeutung. Das Immunproteasom wird anlagebedingt in Immunzellen exprimiert und während viraler Infektionen im Herzmuskel durch Interferonstimulus hochreguliert. Das Immunproteasom ist für die Aufrechterhaltung der Proteinhomöostase und Major Histocompatibility Complex-Klasse-I-Antigenprozessierung verantwortlich und moduliert zelluläre Signalkaskaden. Ziel dieser Studie war es, den immunmodulatorischen Effekt des Immunproteasominhibitors ONX 0914 während einer CoxsackievirusB3-Infektion zu untersuchen. Dazu benutzten wir ein Mausmodel mit genetisch-bedingt geringer (C57BL/6) oder hoher Suszeptibilität (A/J) gegenüber einer CoxsackievirusB3-Infektion. Die Mäuse wurden mit dem für die Immunproteasomuntereinheit LMP7 spezifischen Inhibitor ONX 0914 beginnend einen Tag vor CoxsackievirusB3-Infektion behandelt. Über 8 Tage wurden die Versuchsgruppen auf Anzeichen von Sepsis und Herzinsuffizienz untersucht. Ebenso wurde der Einfluss des Immunproteasoms auf die Zelldifferenzierung von Immunzellen in vivo sowie die Modulation pro-inflammatorischer Signalwege nach Aktivierung von Toll-Like Rezeptoren in Abhängigkeit von ONX 0914 in Makrophagen in vitro untersucht. Die ONX 0914-Behandlung bei niedrig-suszeptiblen C57BL/6-Mäusen resultierte in einer erhöhten Viruslast im Herzmuskel und einer gering verstärkten kardialen Pathologie. Es zeigte sich jedoch weder eine erhöhte Mortalität noch wurden andere Zeichen einer Herzinsuffizienz beobachtet. Insofern wiesen diese Mäuse unter Immunproteasom-inhibition weiterhin einen milden Phänotyp auf und bildeten eine adäquate antivirale Immunantwort aus. Im Gegensatz dazu wurde in dem hoch-suszeptiblen A/J-Stamm die kardiale Pathologie durch die ONX 0914 Behandlung aufgehoben. Der fulminante Krankheitsverlauf, der sich in der Kontrollgruppe zeigte, wurde durch eine Immunproteasominhibition verhindert. Dies zeigte sich anhand der reduzierten kardialen Inflammation und der verminderten Organschädigung. Außerdem konnte die an septische Verläufe erinnernde überschießende Aktivierung der Immunantwort deutlich reduziert werden. In dem hoch-empfindlichen A/J Stamm steigerte eine Behandlung mit ONX 0914 das bei Myokarditis reduzierte Herzzeitvolumen und bewahrte die Mäuse vor einem schweren Krankheitsverlauf mit hoher Mortalität. In vitro Untersuchungen bestätigten, dass ONX 0914 die proinflammatorische Zytokin- und Chemokinantwort auf virusgenetische molekulare Muster reduziert, was sich zumindest teilweise auf eine verringerte Mitogen-activated Proteinkinase-Aktivierung zurückführen lässt. Dies könnte die in vivo reduzierte proinflammatorische Immunantwort, die den septischen Phänotyp verhinderte, erklären. Die Ergebnisse dieser Studie zeigen, dass das Immunproteasom eine vielversprechende pharmakologische Zielstruktur bei Infektionen mit ausgeprägter Virus-induzierter Immunpathologie darstellen kann.Heart failure ranks among the leading causes for mortality. It can be caused by inflammatory heart diseases due to an infection with CoxsackievirusB3. Because the heart pathology upon virus infection is closely linked to direct viral pathology and immunopathology, it is crucial to identify targets modulating pre-disposing immune factors. A putative factor is the immunoproteasome, which is expressed by immune cells and is upregulated during viral infection by interferon signaling in cardiac tissue. The immunoproteasome is responsible for maintaining protein homeostasis and major histocompatibility complex class I processing, and modulates cell signaling. The aim of this study was to investigate the immunomodulatory effect of the immunoproteasome inhibitor ONX 0914 during CoxsackievirusB3 infection. Therefore, we utilized a murine model with genetically anchored low (C57BL/6) or high susceptibility (A/J) for CoxsackievirusB3 infection and the LMP7 immunoproteasome subunit selective inhibitor ONX 0914. An immunoproteasome inhibitor treatment was initiated prior to infection of mice with a CoxsackievirusB3 Nancy strain. Mice were analyzed for sepsis and heart failure parameters. Effects of immunoproteasome-proteolysis on immune cell differentiation were analyzed in vivo. Immunoproteasome-dependent modulation of pro-inflammatory signaling was investigated in vitro using bone marrow-derived macrophages. These cells and their progenitors represent key effector cells during CoxsackievirusB3-induced myocarditis. During viral infection in the low-grade susceptible C57BL/6-strain, ONX 0914-treatment resulted in an increased viral load of the heart with consequently slightly aggravated cardiac pathologies. However, neither increased mortality nor other signs for heart failure were detected. Conversely, in the highly susceptible A/J-strain heart pathology was reversed upon immunoproteasome inhibition. The fulminant pathology was prevented by ONX 0914-treatment as indicated by reduced heart inflammation and diminished organ damage. Furthermore, activation of a sepsis-like immune response found in vehicle-treated mice was prevented by ONX 0914. Whilst in C57BL/6 mice the immune-proteasome ameliorated viral replication in the heart, inhibitor-treated mice still showed low susceptibility to CoxsackievirusB3 infection and induced a potent antiviral immune response. However, with hereditary high susceptibility ONX 0914-treatment improved cardiac output during acute myocarditis, and saved animals from severe illness and high mortality. In vitro studies confirmed that ONX 0914-treatment reduced pro-inflammatory cytokine and chemokine production upon stimulation with viral genomic patterns partially attributed to reduced mitogen-activated protein kinase-activation. This could explain the attenuated pro-inflammatory response that prevented the septic phenotype. The results of this study suggest that the immunoproteasome might be a promising new drug target to overcome the consequences of overwhelming immune response activation during infection

Value-Driven Design of non-commercial systems through bargain modeling

The design and development of large scale complex engineered systems requires dependence and coordination of thousands of individuals. In practice, this has shown to span industries, encompassing multiple companies and organizations, and force decisions to be driven mainly by customer requirements. One issue in this development process is related to the stakeholders\u27 desires and their ability to effectively communicate their preferences to the design teams. Value-Driven Design is an approach stemming from systems engineering that addresses this issue by directly incorporating the operational context of the system in this communication of preference. Value-Driven Design is formed on the premise that a design can be created that maximizes the design organization\u27s preference. It is recognized that other preferences, possibly competing, exist as well and will have an influence on the design. This thesis explores how the negotiation of value preferences can be captured in bargaining models to determine the optimal design for the set of negotiators, taking into account conflicting preferences and player impatience. A notional strategic strike aircraft system is used as an example to illustrate the importance of design perspectives in the emerging practice of Value-Driven Design

Correcting Sample Selection in FARS Data to Estimate Seatbelt Use

In this paper, we use 2006 FARS data to estimate seatbelt use in the United States. We apply a method to correct the FARS data for sample selection bias introduced by Levitt and Porter (2001), as well as discuss the advantages of using FARS data for seatbelt analysis. Furthermore, based on assumptions of independence for seatbelt choice, we establish a lower and upper bound for seatbelt usage rates, and that once we correct for sample selection bias, the seatbelt usage estimates from the corrected FARS emerge at least as a comparable alternative to NOPUS estimates. This implies that researchers can use corrected FARS to complement NOPUS, thus being able to utilize the rich cross-sectional details available in FARS data to analyze various relevant research questions

Determinants of Seat Belt Use: Regression Analysis with FARS Data Corrected for Self-Selection

We develop a methodology to use FARS data as an alternative to NOPUS in estimating seat belt usage. The advantages of using FARS over NOPUS are that (i) FARS is broader because it contains more variables relevant for policy analysis, (ii) FARS allows for easy multivariate regression analysis, and, finally, (iii) FARS data is more cost-effective. Methodology: We apply a binary logit model in our analysis to determine the likelihood of seat belt usage given various occupant, vehicle, and built environment characteristics. Using FARS data, we derive coefficient estimates for categories such as vehicle occupants\u27 age and night time seat belt use that observational surveys like NOPUS cannot easily provide. Results: Our results indicate that policies should focus on passengers (as opposed to drivers), male and young vehicle occupants, and that law enforcement should focus on pick-up trucks, rural roads, and nights. We find evidence that primary seat belt laws are effective. Conclusions: Although this is primarily a methodological paper, we present and discuss our results in the context of public policy so that our findings are relevant for road safety practitioners, researchers, and policymakers

Einstein's Hole Argument and its Legacy

In 1915 not being able to find field equations for a generally covariant theory of gravitation Einstein came up with a fundamental argument against general covariance – the hole argument. This essay discusses the hole argument and focusses on its consequences for substantivalism and determinism. Two different definitions of determinism are introduced and their compatibility with general covariance from a substantivalist's point of view is discussed

Role of Proteasomes in Inflammation

The ubiquitin–proteasome system (UPS) is involved in multiple cellular functions including the regulation of protein homeostasis, major histocompatibility (MHC) class I antigen processing, cell cycle proliferation and signaling. In humans, proteasome loss-of-function mutations result in autoinflammation dominated by a prominent type I interferon (IFN) gene signature. These genomic alterations typically cause the development of proteasome-associated autoinflammatory syndromes (PRAAS) by impairing proteasome activity and perturbing protein homeostasis. However, an abnormal increased proteasomal activity can also be found in other human inflammatory diseases. In this review, we cast a light on the different clinical aspects of proteasomal activity in human disease and summarize the currently studied therapeutic approaches

Auf dem Weg zu einer an den Klimawandel angepassten Siedlungsentwicklung?

Während sich die Siedlungs- und Verkehrsfläche in Deutschland weiterhin ausdehnt, ergeben sich neue Anforderungen an den Raum, die in gesteigerten Flächenkonkurrenzen und in der Verschärfung bestehender Umweltrisiken resultieren. Neben einer stärkeren Berücksichtigung von Klimaschutz und Energiewende bei der Entwicklung der Siedlungsstruktur wird ihre Anpassung an den Klimawandel gefordert, um negative Auswirkungen auf Bevölkerung, Wirtschaft und Infrastruktur abzuwenden. Im Rahmen des Forschungsprojektes CC-LandStraD („Climate Change – Land Use Strategies“) werden Wechselwirkungen zwischen der Landnutzung und dem Klimawandel für alle relevanten Landnutzungssektoren untersucht. Hierfür werden Landnutzungsänderungen in Deutschland bis zum Jahr 2030 simuliert und dabei ausgehend von einem Referenzszenario unterschiedliche Maßnahmen zum Klimaschutz und zur Anpassung an den Klimawandel implementiert. Die Wirksamkeit der Maßnahmen kann mithilfe von Indikatoren abgeschätzt werden. Es zeigt sich, dass sich die Flächenkonkurrenzen in einigen Regionen aufgrund der stärkeren Berücksichtigung von Klimaschutz und Klimaanpassung in der Siedlungsflächenentwicklung verschärfen werden. Betroffen sind vor allem die Regionen, die bereits heute entweder eine hohe Siedlungsdynamik aufweisen oder unter einem gewissen Anpassungsdruck (z. B. hinsichtlich Maßnahmen zum Hochwasserschutz) stehen