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The genetic integrity of each organism depends on the faithful segregation of its genome during mitosis. To meet this challenge, a cellular surveillance mechanism, termed the spindle assembly checkpoint (SAC), evolved that monitors the correct attachment of chromosomes and blocks progression through mitosis if corrections are needed. While the central role of the SAC for genome integrity is well established, its functional dissection has been hampered by the limited availability of appropriate small molecule inhibitors. Using a fluorescence polarization-based screen, we identify Mad2 inhibitor-1 (M2I-1), the first small molecule inhibitor targeting the binding of Mad2 to Cdc20, an essential protein-protein interaction (PPI) within the SAC. Based on computational and biochemical analyses, we propose that M2I-1 disturbs conformational dynamics of Mad2 critical for complex formation with Cdc20. Cellular studies revealed that M2I-1 weakens the SAC response, indicating that the compound might be active in cells. Thus, our study identifies the SAC specific complex formation between Mad2 and Cdc20 as a protein-protein interaction that can be targeted by small molecules.
Using the timing flexibility of modern automatic test equipment (ATE) test response data can be compacted without the need for additional X-masking logic. In this article the test response is compacted by several multiple input shift registers without feedback (NF-MISR). The shift registers are running on a k-times higher clock frequency than the test clock. For each test clock cycle only one out of the k outputs of each shift register is evaluated by the ATE. The impact of consecutive X values within the scan chains is reduced by a periodic permutation of the NF-MISR inputs. As a result, no additional external control signals or test set dependent control logic is required. The benefits of the proposed method are shown by the example of an implementation on a Verigy ATE. Experiments on three industrial circuits demonstrate the effectiveness of the proposed approach in comparison to a commercial DFT solution.
Similar to maternal care, paternal care is a source of neonatal sensory stimulation, which in primates and rodents has been shown to be essential for developing structure and function of sensory cortices. The aim of our study in the biparental rodent Octodon degus was to assess the impact of paternal deprivation on dendritic and synaptic development in the somatosensory cortex. We (i) quantified the amount of paternal care in relation to total parental investment and (ii) compared dendritic and synaptic development of pyramidal neurons in the somatosensory cortex of animals raised by a single mother or by both parents. On the behavioral level we show that paternal care comprises 37% of total parent-offspring interactions, and that the somatosensory stimulation provided by the fathers primarily consists of huddling, licking/grooming, and playing. On the morphological level we found that, compared with offspring raised by both parents (mother and father), the father-deprived animals displayed significantly reduced spine numbers on the basal dendrites of pyramidal neurons. Furthermore, paternal deprivation induces hemispheric asymmetry of the dendritic morphology of somatosensory pyramidal neurons. Father-deprived animals show shorter and less complex basal dendrites in the left somatosensory cortex compared with the right hemisphere. These findings indicate that paternal deprivation results in delayed or retarded dendritic and synaptic development of somatosensory circuits.
Previous research on open innovation (OI) has primarily focused on the organisational level of R&D intensive industries. With this paper, we contribute to research on the individual level of analysis by analysing specific perspectives in the context of creative industries. Our study is based on 36 interviews with Haute cuisine chefs in France, Germany, Great Britain, Italy, Spain, Sweden, and Switzerland listed in the 2012 Michelin Guide. Building on the OI capability concept, our results demonstrate that chefs use absorptive and desorptive capacity (AC, DC) as means to generate and market culinary innovations, respectively. Moreover, we found that chefs almost exclusively rely on their own inventive and innovative capabilities in the early stages of the culinary innovation process. In subsequent phases, however, chefs increasingly integrate other sources such as employees, suppliers, and guests. Our study contributes to the literature in two ways. First, we research the individual level within the OI process, and second, we provide insight into OI practices in the creative industries.
Das Werk analysiert umfassend das Verbrechen der Aggression im Sinne des Römischen Statuts. Ausgehend von der Rechtsgeschichte, werde die einschlägigen Artikel 8bis, 15bis und 15ter des Römischen Statuts, also die Definition des Verbrechens der Aggression, analysiert.
Ebenso behandelt das Buch weiterführende Entwicklungen des Verbrechens der Aggression über das Jahr 2017 hinaus – das Jahr, in dem es, wahrscheinlich, zu einer Entscheidung über die Aktivierung der Gerichtsbarkeit kommt
This paper presents an exploratory study investigating the influence of the factors (1) intermediary participation, (2) decision-making authority, (3) position in the enterprise, and (4) experience in open innovation on the perception and assessment of the benefits and risks expected from participating in open innovation projects. For this purpose, an online survey was conducted in Germany, Austria and Switzerland. The result of this paper is an empirical evidence showing whether and how these factors affect the perception of potential benefits and risks expected within the context of open innovation project participation. Furthermore, the identified effects are discussed against the theory. Existing theory regarding the benefits and risks of open innovation is expanded by (1) finding that they are perceived mostly independently of the factors, (2) confirming the practical relevance of benefits and risks, and (3) enabling a finer distinction between their degrees of relevance according to respective contextual specifics.
Article 15ter Exercise of jurisdiction over the crime of aggression (Security Council referral)
(2022)
Vorliegender Leitfaden ist eines der Ergebnisse des Forschungsprojekts „Open Innovation in Life Sciences“ (OIL), das von Mai 2008 bis April 2011 an der Universität Potsdam durchgeführt wurde. Er nimmt für sich in Anspruch, gerade Innovationsmanager in kleinen und mittleren Unternehmen (KMU) der Pharmaindustrie bei der Einführung des Open Innovation Managements zu unterstützen. Zielsetzung des Forschungsprojekts war es, (1) die Chancen und Risiken von Open Innovation unter besonderer Berücksichtigung der Anforderungen von Pharma-KMU zu analysieren und (2) daraus abgeleitet ein Konzept zur Implementierung von Open Innovation bei Pharma-KMU zu entwickeln. Der Ausgangspunkt des Projektes war die Erkenntnis, dass die Life Sciences-Branche im Allgemeinen und die Pharmaindustrie im Besonderen durch eine steigende Komplexität der Innovationsprozesse und eine zunehmende Tendenz zu Kooperationen gekennzeichnet ist. Vor diesem Hintergrund eröffnet gerade der Open Innovation-Ansatz für die Pharmabranche neue Gestaltungs- und damit Wachstumsmöglichkeiten. Open Innovation – definiert als die planvolle Öffnung der Innovationsprozesse und die strategische Einbindung des Unternehmensumfelds – wird dabei als zentraler Erfolgsfaktor für die Innovationsfähigkeit beschrieben.
Incorporating photochromic molecules into organic/inorganic hybrid materials may lead to photoresponsive systems. In such systems, the second-order nonlinear properties can be controlled via external stimulation with light at an appropriate wavelength. By creating photochromic molecular switches containing self-assembled monolayers on Si(111), we can demonstrate efficient reversible switching, which is accompanied by a pronounced modulation of the nonlinear optical (NLO) response of the system. The concept of utilizing functionalized photoswitchable Si surfaces could be a way for the generation of two-dimensional NLO switching materials, which are promising for applications in photonic and optoelectronic devices.
Plant proteins have become increasingly important for ecological reasons. Rapeseed is a novel source of plant proteins with high biological value, but its metabolic impact in humans is largely unknown. A randomized, controlled intervention study including 20 healthy subjects was conducted in a crossover design. All participants received a test meal without additional protein or with 28 g of rapeseed protein isolate or soy protein isolate (control). Venous blood samples were collected over a 360-min period to analyze metabolites; satiety was assessed using a visual analog scale. Postprandial levels of lipids, urea, and amino acids increased following the intake of both protein isolates. The postprandial insulin response was lower after consumption of the rapeseed protein than after intake of the soy protein (p< 0.05), whereas the postmeal responses of glucose, lipids, interleukin-6, minerals, and urea were comparable between the two protein isolates. Interestingly, the rapeseed protein exerted stronger effects on postprandial satiety than the soy protein (p< 0.05). The postmeal metabolism following rapeseed protein intake is comparable with that of soy protein. The favorable effect of rapeseed protein on postprandial insulin and satiety makes it a valuable plant protein for human nutrition.