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SAFE Newsletter : 2017, Q1
(2017)
Hypoxia triggers several mechanisms to adapt cells to a low oxygen environment. Mitochondria are major consumers of oxygen and a potential source of reactive oxygen species (ROS). In response to hypoxia they exchange or modify distinct subunits of the respiratory chain and adjust their metabolism, especially lowering the citric acid cycle. Intermediates of the citric acid cycle participate in regulating hypoxia inducible factors (HIF), the key mediators of adaptation to hypoxia. Here we summarize how hypoxia conditions mitochondria with consequences for ROS-production and the HIF-pathway.
Der urheberrechtlich konnotierte Begriff des Plagiats zählt zu den anerkannten Grundtatbeständen wissenschaftlichen Fehlverhaltens. Der Beitrag zeigt indes, dass das Urheberrecht und das Wissenschaftsrecht keine konzentrischen Kreise bilden, sondern unterschiedliche Zwecke mit je anderen Regelungskonzepten verfolgen. Die Übernahme urheberrechtlicher Argumentationsmuster in die Wissenschaftsethik und das Wissenschaftsrecht erschwert die Herausbildung spezifisch wissenschaftsbezogener Kriterien zur Beurteilung wissenschaftlichen Fehlverhaltens. Als Alternative entwickelt der Beitrag ein Konzept wissenschaftlicher Redlichkeit, das sich am Recht gegen unlauteren Wettbewerb orientiert. Dazu werden weitreichende teleologische und strukturelle Gemeinsamkeiten des Lauterkeitsrechts und der Regeln zu wissenschaftlichem Fehlverhalten aufgedeckt. Insbesondere verfolgen beide Materien eine funktionale Teleologie. Das Lauterkeitsrecht gewährleistet die Funktionsbedingungen des wirtschaftlichen Wettbewerbs, das Verbot wissenschaftlichen Fehlverhaltens sichert die Funktionsbedingungen und damit zugleich den Zielerreichungsgrad des offenen Wissenschaftsprozesses und des Wettbewerbs um wissenschaftliche Reputation.
This paper reexamines the current legal landscape regarding the protection of trade marks and other industrial property rights in signs on the Internet. It is based on a comparative analysis of EU and national laws, in particular, German, U.S., and U.K. law. It starts with a short restatement of the principles governing trade mark conflicts that occur within a particular jurisdiction (part 2) and proceeds to the regulation of transnational disputes (part 3). This juxtaposition yields two basic approaches. Whereas trade mark conflicts within closed legal systems are generally adjudicated according to a binary either/or logic, transnational disputes are and should indeed be solved in a way that leads to a fair coexistence of conflicting trade mark laws and rights under multiple laws. This paper explains how geolocation technologies can alleviate the implementation of the principle of fair coexistence in concrete cases.
Die Geschichte des Urheberrechts ist die Geschichte seiner Expansion. In diesem Beitrag wird die Expansionsgeschichte des Urheberrechts, in der das Urheberrechtsgesetz 1965 letztlich nur eine, wenn auch wichtige Episode darstellt, in Anlehnung an Thesen des 1944 erschienenen, wirtschaftssoziologischen Klassikers „The Great Transformation. Politische und ökonomische Ursprünge von Gesellschaften und Wirtschaftssystemen“ von Karl Polanyi gedeutet. Im Zentrum steht dabei der Gedanke, dass in einer Informationsgesellschaft, deren Wirtschaft auf Märkten und Wettbewerb beruht, alle neuen Technologien und hiermit verknüpften immateriellen Leistungsergebnisse über Ausschließlichkeitsrechte zugeordnet werden müssen, damit gewährleistet ist, dass alle relevanten In- und Outputfaktoren handelbar sind, so dass ihre jeweiligen Erzeuger marktbasierte Einkünfte erzielen können. Der Aufsatz erläutert, dass sich diese Kommodifizierungslogik in der jüngeren deutschen Urheberrechtsgeschichte nachweisen lässt. Auf die soziologische und rechtliche Relevanz der entgegengesetzten Zugangsnorm wird im Schlussteil hingewiesen.
Genetic data in studies of systematics of Amazonian amphibians frequently reveal that purportedly widespread single species in reality comprise species complexes. This means that real species richness may be significantly higher than current estimates. Here we combine genetic, morphological, and bioacoustic data to assess the phylogenetic relationships and species boundaries of two Amazonian species of the Dendropsophus leucophyllatus species group: D. leucophyllatus and D. triangulum. Our results uncovered the existence of five confirmed and four unconfirmed candidate species. Among the confirmed candidate species, three have available names: Dendropsophus leucophyllatus, Dendropsophus triangulum, and Dendropsophus reticulatus, this last being removed from the synonymy of D. triangulum. A neotype of D. leucophyllatus is designated. We describe the remaining two confirmed candidate species, one from Bolivia and another from Peru. All confirmed candidate species are morphologically distinct and have much smaller geographic ranges than those previously reported for D. leucophyllatus and D. triangulum sensu lato. Dendropsophus leucophyllatus sensu stricto occurs in the Guianan region. Dendropsophus reticulatus comb. nov. corresponds to populations in the Amazon basin of Brazil, Ecuador, and Peru previously referred to as D. triangulum. Dendropsophus triangulum sensu stricto is the most widely distributed species; it occurs in Amazonian Ecuador, Peru and Brazil, reaching the state of Pará. We provide accounts for all described species including an assessment of their conservation status.
Natural killer (NK) cells play an important role following allogeneic hematopoietic stem cell transplantation (HSCT) exerting graft-versus-leukemia/tumor effect and mediating pathogen-specific immunity. Although NK cells are the first donor-derived lymphocytes reconstituting post-HSCT, their distribution of CD56++CD16− (CD56bright), CD56++CD16+ (CD56intermediate=int), and CD56+CD16++ (CD56dim) NK cells is explicitly divergent from healthy adults, but to some extent comparable to the NK cell development in early childhood. The proportion of CD56bright/CD56int/CD56dim changed from 15/8/78% in early childhood to 6/4/90% in adults, respectively. Within this study, we first compared the NK cell reconstitution post-HSCT to reference values of NK cell subpopulations of healthy children. Afterward, we investigated the reconstitution of NK cell subpopulations post-HSCT in correlation to acute graft versus host disease (aGvHD) and chronic graft versus host disease (cGvHD) as well as to viral infections. Interestingly, after a HSCT follow-up phase of 12 months, the distribution of NK cell subpopulations largely matched the 50th percentile of the reference range for healthy individuals. Patients suffering from aGvHD and cGvHD showed a delayed reconstitution of NK cells. Remarkably, within the first 2 months post-HSCT, patients suffering from aGvHD had significantly lower levels of CD56bright NK cells compared to patients without viral infection or without graft versus host disease (GvHD). Therefore, the amount of CD56bright NK cells might serve as an early prognostic factor for GvHD development. Furthermore, a prolonged and elevated peak in CD56int NK cells seemed to be characteristic for the chronification of GvHD. In context of viral infection, a slightly lower CD56 and CD16 receptor expression followed by a considerable reduction in the absolute CD56dim NK cell numbers combined with reoccurrence of CD56int NK cells was observed. Our results suggest that a precise analysis of the reconstitution of NK cell subpopulations post-HSCT might indicate the occurrence of undesired events post-HSCT such as severe aGvHD.values
BACKGROUND: Time-limited, early-life exposures to institutional deprivation are associated with disorders in childhood, but it is unknown whether effects persist into adulthood. We used data from the English and Romanian Adoptees study to assess whether deprivation-associated adverse neurodevelopmental and mental health outcomes persist into young adulthood.
METHODS: The English and Romanian Adoptees study is a longitudinal, natural experiment investigation into the long-term outcomes of individuals who spent from soon after birth to up to 43 months in severe deprivation in Romanian institutions before being adopted into the UK. We used developmentally appropriate standard questionnaires, interviews completed by parents and adoptees, and direct measures of IQ to measure symptoms of autism spectrum disorder, inattention and overactivity, disinhibited social engagement, conduct or emotional problems, and cognitive impairment (IQ score <80) during childhood (ages 6, 11, and 15 years) and in young adulthood (22-25 years). For analysis, Romanian adoptees were split into those who spent less than 6 months in an institution and those who spent more than 6 months in an institution. We used a comparison group of UK adoptees who did not experience deprivation. We used mixed-effects regression models for ordered-categorical outcome variables to compare symptom levels and trends between groups.
FINDINGS: Romanian adoptees who experienced less than 6 months in an institution (n=67 at ages 6 years; n=50 at young adulthood) and UK controls (n=52 at age 6 years; n=39 at young adulthood) had similarly low levels of symptoms across most ages and outcomes. By contrast, Romanian adoptees exposed to more than 6 months in an institution (n=98 at ages 6 years; n=72 at young adulthood) had persistently higher rates than UK controls of symptoms of autism spectrum disorder, disinhibited social engagement, and inattention and overactivity through to young adulthood (pooled p<0·0001 for all). Cognitive impairment in the group who spent more than 6 months in an institution remitted from markedly higher rates at ages 6 years (p=0·0001) and 11 years (p=0·0016) compared with UK controls, to normal rates at young adulthood (p=0·76). By contrast, self-rated emotional symptoms showed a late-onset pattern with minimal differences versus UK controls at ages 11 years (p=0·0449) and 15 years (p=0·17), and then marked increases by young adulthood (p=0·0005), with similar effects seen for parent ratings. The high deprivation group also had a higher proportion of people with low educational achievement (p=0·0195), unemployment (p=0·0124), and mental health service use (p=0·0120, p=0·0032, and p=0·0003 for use when aged <11 years, 11-14 years, and 15-23 years, respectively) than the UK control group. A fifth (n=15) of individuals who spent more than 6 months in an institution were problem-free at all assessments.
INTERPRETATION: Notwithstanding the resilience shown by some adoptees and the adult remission of cognitive impairment, extended early deprivation was associated with long-term deleterious effects on wellbeing that seem insusceptible to years of nurturance and support in adoptive families.
FUNDING: Economic and Social Research Council, Medical Research Council, Department of Health, Jacobs Foundation, Nuffield Foundation.
Peripheral tolerance is an important mechanism by which the immune system can guarantee a second line of defense against autoreactive T and B cells. One autoimmune disease that is related to a break of peripheral tolerance is diabetes mellitus type 1. Using the RIP-GP mouse model, we analyzed the role of the spleen and lymph nodes (LNs) in priming CD8+ T cells and breaking peripheral tolerance. We found that diabetes developed in splenectomized mice infected with the lymphocytic choriomeningitis virus (LCMV), a finding showing that the spleen was not necessary in generating autoimmunity. By contrast, the absence of LNs prevented the priming of LCMV-specific CD8+ T cells, and diabetes did not develop in these mice. Additionally, we found that dendritic cells are responsible for the distribution of virus in secondary lymphoid organs, when LCMV was administered intravenously. Preventing this distribution with the sphingosine-1-phosphate receptor antagonist FTY720 inhibits the transport of antigen to peripheral LNs and consequently prevented the onset of diabetes. However, in case of subcutaneous infection, administration of FTY720 could not inhibit the onset of diabetes because the viral antigen is already presented in the peripheral LNs. These findings demonstrate the importance of preventing the presence of antigen in LNs for maintaining tolerance.
Background. Colorectal cancers (CRC) shed DNA into blood circulation. There is growing evidence that the analysis of circulating tumor DNA can be effectively used for monitoring of disease, to track tumor heterogeneity and to evaluate response to treatment. Case Presentation. Here, we describe two cases of patients with advanced CRC. The first case is about a patient with no available tissue for analysis of RAS mutation status. Liquid biopsy revealed RAS-wild-type and the therapy with anti-EGFR (epidermal growth factor receptor) monoclonal antibody cetuximab could be initiated. In the second case, the mutational profile of a patient with initial wild-type RAS-status was continually tracked during the course of treatment. An acquired KRAS exon 3 mutation was detected. The number of KRAS mutated fragments decreased continuously after the discontinuation of the therapy with EGFR-specific antibodies. Conclusion. Liquid biopsy provides a rapid genotype result, which accurately reproduces the current mutation status of tumor tissue. Furthermore, liquid biopsy enables close monitoring of the onset of secondary resistance to anti-EGFR therapy.
Die vorliegende Ergänzung baut auf der 'Johannes-Bobrowski-Bibliographie von 2002' auf. Sie folgt dieser in Herangehensweise und Gliederung. Neben einigen dort nicht aufgeführten älteren Titeln enthält sie vor allem solche wissenschaftlichen Arbeiten zu und über Johannes Bobrowski, die zwischen 2002 und 2016 publiziert worden sind. Nicht systematisch erfasst wurden Neuausgaben und Übersetzungen seines Werkes sowie Miszellen, Zeitungsartikel und künstlerische Resonanzen.
Die Bibliographie ist in vier Abteilungen untergliedert:
A Das Werk Johannes Bobrowskis
B Literatur zu Leben und Werk Johannes Bobrowskis
C Resonanzen auf Johannes Bobrowski in Musik, bildender Kunst, Film, Literatur und Hörfunk
D Bobrowski-Medaille, Johannes-Bobrowski-Gesellschaft
We study platform design in online markets in which buying involves a (nonmonetary) cost for consumers caused by privacy and security concerns. Firms decide whether to require registration at their website before consumers learn relevant product information. We derive conditions under which a monopoly seller benefits from ex ante registration requirements and demonstrate that the profitability of registration requirements is increased when taking into account the prospect of future purchases or an informational value of consumer registration to the firm. Moreover, we consider the effectiveness of discounts (store credit) as a means to influence the consumers’ registration decision. Finally, we confirm the profitability of ex ante registration requirements in the presence of price competition.
Mean age of stratospheric air can be derived from observations of sufficiently long lived trace gases with approximately linear trends in the troposphere. Mean age can serve as a tracer to investigate stratospheric transport and long term changes in the strength of the overturning Brewer-Dobson circulation of the stratosphere. For this purpose, a low-cost method is required in order to allow for regular observations up to altitudes of about 30 km. Despite the desired low costs, high precision and accuracy are required in order to allow determination of mean age. We present balloon borne AirCore observations from two mid latitude sites: Timmins in Ontario/Canada and Lindenberg in Germany. During the Timmins campaign five AirCores sampled air in parallel from a large stratospheric balloon and were analysed for CO2, CH4 and partly CO. We show that there is good agreement between the different AirCores (better than 0.1 %) especially when vertical gradients are small. The measurements from Lindenberg were performed using small low-cost balloons and yielded very comparable results. We have used the observations to extend our long term data set of mean age observations at Northern Hemi-sphere mid latitudes. The time series now covers more than 40 years and shows a small, statis-tically not significant positive trend of 0.15 ± 0.18 years/decade. This trend is slightly smaller than the previous estimate of 0.24 ± 0.22 years/decade which was based on observations up to the year 2006. These observations are still in contrast to strong negative trends of mean age as derived from some model calculations.
We study exchangeable coalescent trees and the evolving genealogical trees in models for neutral haploid populations.
We show that every exchangeable infinite coalescent tree can be obtained as the genealogical tree of iid samples from a random marked metric measure space when the marks are added to the metric distances. We apply this representation to generalize the tree-valued Fleming-Viot process to include the case with dust in which the genealogical trees have isolated leaves.
Using the Donnelly-Kurtz lookdown approach, we describe all individuals ever alive in the population model by a random complete and separable metric space, the lookdown space, which we endow with a family of sampling measures. This yields a pathwise construction of tree-valued Fleming-Viot processes. In the case of coming down from infinity, we also read off a process whose state space is endowed with the Gromov-Hausdorff-Prohorov topology. This process has additional jumps at the extinction times of parts of the population.
In the case with only binary reproduction events, we construct the lookdown space also from the Aldous continuum random tree by removing the root and the highest leaf, and by deforming the metric in a way that corresponds to the time change that relates the Fleming-Viot process with a Dawson-Watanabe process. The sampling measures on the lookdown space are then image measures of the normalized local time measures.
We also show invariance principles for Markov chains that describe the evolving genealogy in Cannings models. For such Markov chains with values in the space of distance matrix distributions, we show convergence to tree-valued Fleming-Viot processes under the conditions of Möhle and Sagitov for the convergence of the genealogy at a fixed time to a coalescent with simultaneous multiple mergers. For the convergence of Markov chains with values in the space of marked metric measure spaces, an additional assumption is needed in the case with dust.
We document that natural disasters significantly weaken the stability of banks with business activities in affected regions, as reflected in lower z-scores, higher probabilities of default, higher non-performing assets ratios, higher foreclosure ratios, lower returns on assets and lower bank equity ratios. The effects are economically relevant and suggest that insurance payments and public aid programs do not sufficiently protect bank borrowers against financial difficulties. We also find that the adverse effects on bank stability dissolve after some years if no further disasters occur in the meantime.
This paper applies the theory of structured finance to the regulation of asset backed securities. We find the current regulation in Europe (Article 405 of the CRR) and the US (Section D of Dodd-Frank Act) to be severely flawed with respect to its key intention: the imposition of a strict loss retention requirement. While nominal retention is always 5%, the true level of loss retention varies across available retention options between zero loss retention and full loss retention at the extreme ends. Based on a standard model of structured finance transactions, we propose a new risk retention metric RM measuring the level of an issuer’s skin-in-the-game. The new metric could help to achieve a better implementation of CRR/CRD-IV and DFA, by making disclosure of the RM-number compulsory for all ABS transactions. There are also implications for the operation of rating agencies. On a general level, the RM metric will be instrumental in achieving simplicity and transparency in securitizations (STS).
Die erste Phase des im Dezember 2016 in Kraft getretenen Friedensabkommens zwischen der kolumbianischen Regierung und den FARC-Rebellen ist mit der Ankunft von ca. 6300 Kämpfern in den vereinbarten 26 Konzentrationszonen abgeschlossen. Dort wird nun der Prozess der Entwaffnung beginnen und die Vorbereitung auf die Eingliederung in das zivile Leben, ein Schritt, der der kolumbianischen Gesellschaft noch große Opfer abverlangen wird – sei es bezogen auf die Prozesse der justiziellen Aufarbeitung der Vergangenheit, sei es hinsichtlich der notwendigen Versöhnungsprozesse oder sei es bei der Suche nach neuen Formen des friedlichen Zusammenlebens. Sich in das zivile Leben einzufinden, dürfte insbesondere den ca. 7000 geschätzten Kindersoldaten Kolumbiens schwer fallen, die teilweise bereits im Alter von 12 Jahren von den illegalen bewaffneten Akteuren des Landes an Waffen ausgebildet wurden und ihre Kindheit bzw. Jugend in Guerilla-Verbänden verbracht haben. Die umfassende Betreuung der Kindersoldaten ist einer der zentralen Indikatoren für einen erfolgreichen Verlauf des Friedensprozesses in Kolumbien, wenn der Teufelskreis aus Gewalt, Vertreibung und Rekrutierung Minderjähriger durchbrochen werden soll. Sonst droht eine Verlängerung von Gewaltbiographien, die die Geschichte des Landes bereits in der Vergangenheit maßgeblich geprägt haben.