A transnational proposition: exploring cross-border cooperation among research institutes in foreign and security policy across wider Europe

The purpose of this research project is to analyse the opportunities and challenges that the foreign and security policy research institutes face in transnational cooperation across wider Europe. By specifically examining the capacities of non- and quasi-governmental actors to operate and cooperate at transnational level, the research informs the choices presented by the ongoing restructuring of the foreign and security policy sphere. The increasing deterritorialisation of foreign and security policy issues calls for transnational or multinational approaches to resolve them. As nation states fall short of the appropriate capacities, it is of interest to investigate how non- and quasi-governmental actors can contribute to transnational interaction. Therefore, their tools and capacities to operate and cooperate in the transnational sphere need to be established in the first place. In this context a broader geographical focus is chosen in order to study a more differentiated situation, instead of the already relatively integrated case of the European Union. The thesis first studies cooperation among research institutes in broader terms under consideration of their socio-political environment. It outlines differences in their organic development dependent on the geographic affiliation of the institutes, and identifies their tools as well as several defining characteristics. This is followed by an analysis of the fieldwork, discussing processes, opportunities and challenges in transnational cooperation as perceived by staff in research institutes. Subsequently, the thesis takes a more detailed look at applied cooperation among research institutes. Here it traces patterns and formats of interaction, and then delves into a case study on project- based cooperation that provides functional insights regarding research institutes cooperation across borders. In studying cooperation among research institutes from various perspectives, the research enables to investigate the integration among the different narratives. The study integrates a range of issues and concepts in an original manner, therefore it contributes to several significant debates. On the face of it, the thesis adds to the identification of a role for non- and quasi-governmental actors in an increasingly deterritorialised foreign and security policy sphere, using the example of research institutes. To address this aspect, the study considers both the broader implications of socio-political and economic interrelations for cooperation, as well as the detailed functional level of interaction. Moreover, based on the choice of geographical focus, the research project contributes to the literature on EU-Russia relations. Herein it adds to the extant literature by offering a perspective which acknowledges the implications of high politics but emphasises the role of non- and quasi-governmental actors. Beyond that, the thesis contributes to the theoretical debate on foreign and security policy in choosing a non-traditional approach to examine a non-traditional issue. Post-structuralism serves to facilitate a critical review of the construction of cooperation among Russian and EU-based public policy research institutes

Получение керамических мембран на основе оксида алюминия для очистки воды

We performed DNA microarray-based comparative genomic hybridization to identify somatic alterations specific to melanoma genome in 60 human cell lines from metastasized melanoma and from 44 corresponding peripheral blood mononuclear cells. Our data showed gross but nonrandom somatic changes specific to the tumor genome. Although the CDKN2A (78%) and PTEN (70%) loci were the major targets of mono-allelic and bi-allelic deletions, amplifications affected loci with BRAF (53%) and NRAS (12%) as well as EGFR (52%), MITF (40%), NOTCH2 (35%), CCND1 (18%), MDM2 (18%), CCNE1 (10%), and CDK4 (8%). The amplified loci carried additional genes, many of which could potentially play a role in melanoma. Distinct patterns of copy number changes showed that alterations in CDKN2A tended to be more clustered in cell lines with mutations in the BRAF and NRAS genes; the PTEN locus was targeted mainly in conjunction with BRAF mutations. Amplification of CCND1, CDK4, and other loci was signifi cantly increased in cell lines without BRAF-NRAS mutations and so was the loss of chromosome arms 13q and 16q. Our data suggest involvement of distinct genetic pathways that are driven either through oncogenic BRAF and NRAS mutations complemented by aberrations in the CDKN2A and PTEN genes or involve amplification of oncogenic genomic loci and loss of 13q and 16q. It also emerges that each tumor besides being affected by major and most common somatic genetic alterations also acquires additional genetic alterations that could be crucial in determining response to small molecular inhibitors that are being currently pursued

PAC-Bayesian Learning of Optimization Algorithms

We apply the PAC-Bayes theory to the setting of learning-to-optimize. To the best of our knowledge, we present the first framework to learn optimization algorithms with provable generalization guarantees (PAC-bounds) and explicit trade-off between a high probability of convergence and a high convergence speed. Even in the limit case, where convergence is guaranteed, our learned optimization algorithms provably outperform related algorithms based on a (deterministic) worst-case analysis. Our results rely on PAC-Bayes bounds for general, unbounded loss-functions based on exponential families. By generalizing existing ideas, we reformulate the learning procedure into a one-dimensional minimization problem and study the possibility to find a global minimum, which enables the algorithmic realization of the learning procedure. As a proof-of-concept, we learn hyperparameters of standard optimization algorithms to empirically underline our theory.Comment: Accepted to AISTATS 202

Inherited functional variants of the lymphocyte receptor CD5 influence melanoma survival

Despite the recent progress in treatment options, malignant melanoma remains a deadly disease. Besides therapy, inherited factors might modulate clinical outcome, explaining in part widely varying survival rates. T-cell effector function regulators on antitumor immune responses could also influence survival. CD5, a T-cell receptor inhibitory molecule, contributes to the modulation of antimelanoma immune responses as deduced from genetically modified mouse models. The CD5 SNPs rs2241002 (NM_014207.3:c.671C > T, p.Pro224Leu) and rs2229177 (NM_014207.3:c.1412C > T, p.Ala471Val) constitute an ancestral haplotype (Pro224-Ala471) that confers T-cell hyper-responsiveness and worsens clinical autoimmune outcome. The assessment of these SNPs on survival impact from two melanoma patient cohorts (Barcelona, N = 493 and Essen, N = 215) reveals that p.Ala471 correlates with a better outcome (OR= 0.57, 95% CI = 0.33-0.99, Adj. p = 0.043, in Barcelona OR = 0.63, 95% CI = 0.40-1.01, Adj. p = 0.051, in Essen). While, p.Leu224 was associated with increased melanoma-associated mortality in both cohorts (OR = 1.87, 95% CI = 1.07-3.24, Adj. p = 0.030 in Barcelona and OR = 1.84, 95% CI = 1.04-3.26, Adj. p = 0.037, in Essen). Furthermore survival analyses showed that the Pro224-Ala471 haplotype in homozygosis improved melanoma survival in the entire set of patients (HR = 0.27, 95% CI 0.11-0.67, Adj. p = 0.005). These findings highlight the relevance of genetic variability in immune-related genes for clinical outcome in melanoma

Dacarbazine (DTIC) versus vaccination with autologous peptide-pulsed dendritic cells (DC) in first-line treatment of patients with metastatic melanoma: a randomized phase III trial of the DC study group of the DeCOG

Background: This randomized phase III trial was designed to demonstrate the superiority of autologous peptide-loaded dendritic cell (DC) vaccination over standard dacarbazine (DTIC) chemotherapy in stage IV melanoma patients. Patients and methods: DTIC 850 mg/m2 intravenously was applied in 4-week intervals. DC vaccines loaded with MHC class I and II-restricted peptides were applied subcutaneously at 2-week intervals for the first five vaccinations and every 4 weeks thereafter. The primary study end point was objective response (OR); secondary end points were toxicity, overall (OS) and progression-free survival (PFS). Results: At the time of the first interim analysis 55 patients had been enrolled into the DTIC and 53 into the DC-arm (ITT). OR was low (DTIC: 5.5%, DC: 3.8%), but not significantly different in the two arms. The Data Safety & Monitoring Board recommended closure of the study. Unscheduled subset analyses revealed that patients with normal serum LDH and/or stage M1a/b survived longer in both arms than those with elevated serum LDH and/or stage M1c. Only in the DC-arm did those patients with (i) an initial unimpaired general health status (Karnofsky = 100) or (ii) an HLA-A2+/HLA-B44− haplotype survive significantly longer than patients with a Karnofsky index <100 (P = 0.007 versus P = 0.057 in the DTIC-arm) or other HLA haplotypes (P = 0.04 versus P = 0.57 in DTIC-treated patients). Conclusions: DC vaccination could not be demonstrated to be more effective than DTIC chemotherapy in stage IV melanoma patients. The observed association of overall performance status and HLA haplotype with overall survival for patients treated by DC vaccination should be tested in future trials employing DC vaccine

Differential influence of vemurafenib and dabrafenib on patients' lymphocytes despite similar clinical efficacy in melanoma

In this study, we demonstrate that vemurafenib but not dabrafenib reduces peripheral lymphocyte counts in melanoma patients while both agents show similar clinical efficacy. Within the lymphocyte compartment, vemurafenib selectively decreases circulating CD4+ T cells and changes their phenotype and function. This indicates that selective BRAFi need to be assessed individually for immunomodulatory effects, especially, when planning combinations with immunotherapie

Diskurse der Identität auf dem Immobilienmarkt. Eine Untersuchung anhand von Gated Communities in Istanbul.

This research projects deals with the discoursivity of spatial production. By looking at contemporary residential development in the city of Istanbul, I will examine the reciprocity of the material production of space on one hand, and social discourses on the other, in order to make a contribution to how physical space can be used as a source of research in urban studies. In real estate marketing social discourses are used as a source of reference for place branding or identity design. Branding concepts therefore relate to how social groups imagine their position or future position in society, imaginaries that are continuously influenced and changed by social dynamics within the city but also from the outside. How such urban identities are formed and it what way they relate to the urban environment is crucial to a wide spectrum of social and cultural science. The constitutive role urban space attains has been described and analysed in much detail. Such scrutiny however has yet to be applied to the visual and communicative forms of engagement, the build environment partakes in the formation and change of social discourses.Diese Dissertation setzt sich mit den Mechanismen diskursiver Stadtproduktion auseinander. Anhand einer Analyse aktueller Wohnbauprojekte in Istanbul wird untersucht, wie materielle Stadtproduktion auf der einen Seite und gesellschaftliche Diskurse auf der anderen ineinandergreifen, sich gegenseitig bedingen und beeinflussen. Gesellschaftsdiskurse tauchen im Stadtmarketing als Diskurse urbaner Identität auf. Sie stehen in engem Bezug zu einer idealisierten Vorstellung der eigenen gesellschaftlichen Position, werden aber auch durch Bewertungen von außen geprägt und verändert. Die Formation solcher Identitäten im Bereich des Stadtmarketing sowie ihre räumliche Umsetzung in Prozessen der Stadtproduktion ist von zentralem Interesse in der Stadtsoziologie. Die konstituierende Bedeutung des Raumes ist dabei weitestgehend erforscht worden, nicht jedoch die verändernde Wirkung, die städtischer Raum auf gesellschaftliche Diskurse hat - und umgekehrt. Dieser Komponente soll sich das vorliegende Forschungsvorhaben widmen

Diskurse der Identität auf dem Immobilienmarkt. Eine Untersuchung anhand von Gated Communities in Istanbul.

This research projects deals with the discoursivity of spatial production. By looking at contemporary residential development in the city of Istanbul, I will examine the reciprocity of the material production of space on one hand, and social discourses on the other, in order to make a contribution to how physical space can be used as a source of research in urban studies. In real estate marketing social discourses are used as a source of reference for place branding or identity design. Branding concepts therefore relate to how social groups imagine their position or future position in society, imaginaries that are continuously influenced and changed by social dynamics within the city but also from the outside. How such urban identities are formed and it what way they relate to the urban environment is crucial to a wide spectrum of social and cultural science. The constitutive role urban space attains has been described and analysed in much detail. Such scrutiny however has yet to be applied to the visual and communicative forms of engagement, the build environment partakes in the formation and change of social discourses.Diese Dissertation setzt sich mit den Mechanismen diskursiver Stadtproduktion auseinander. Anhand einer Analyse aktueller Wohnbauprojekte in Istanbul wird untersucht, wie materielle Stadtproduktion auf der einen Seite und gesellschaftliche Diskurse auf der anderen ineinandergreifen, sich gegenseitig bedingen und beeinflussen. Gesellschaftsdiskurse tauchen im Stadtmarketing als Diskurse urbaner Identität auf. Sie stehen in engem Bezug zu einer idealisierten Vorstellung der eigenen gesellschaftlichen Position, werden aber auch durch Bewertungen von außen geprägt und verändert. Die Formation solcher Identitäten im Bereich des Stadtmarketing sowie ihre räumliche Umsetzung in Prozessen der Stadtproduktion ist von zentralem Interesse in der Stadtsoziologie. Die konstituierende Bedeutung des Raumes ist dabei weitestgehend erforscht worden, nicht jedoch die verändernde Wirkung, die städtischer Raum auf gesellschaftliche Diskurse hat - und umgekehrt. Dieser Komponente soll sich das vorliegende Forschungsvorhaben widmen

Learning Optimal Algorithms for Parametric Optimization Problems

From an abstract point of view, the problem of optimally selecting a variable or arranging certain things in the best possible way occurs frequently and in a wide variety of situations. It is therefore not surprising that so-called optimization problems permanently have to be solved in science and industry. At the same time, however, nowadays these problems get increasingly complex and their solution more time- and energy-consuming. Thus, there is a constant need for ever more efficient optimization algorithms to solve such problems. "Learning-to-optimize" is a recent line of research that leverages machine learning techniques to automatically build and accelerated optimization algorithms. While the empirical results can be impressive, theoretical guarantees are mostly lacking, such that the application of learned optimization methods is still questionable and thus not widely adopted. This applies in particular to safety-critical applications with their need for guarantees, not least because there are already the conventional algorithms that can provably solve these problems. One of the reasons why the theoretical understanding of learned optimization algorithms lags so far behind is that the respective established mathematical language and the usual chains of reasoning in mathematical optimization and in machine learning are quite different: Mathematical optimization most often relies on geometric arguments and deductive reasoning, while machine learning models learn from observational data, that is, the results are data-dependent, such that the guarantees are of statistical nature. This results in the problem that most known proof-strategies fail sooner or later or, even worse, are not applicable at all. Therefore, this thesis provides a series of contributions towards new guarantees and a better theoretical understanding of learned optimization algorithms, aswell as away for bridging the gap between conventional optimization theory and learning-to-optimize. The first part considers a simplified model of an optimization algorithm and provides generalization guarantees for its performance based on the observations during training. Furthermore, it also introduces a corresponding learning procedure as well as several design choices for learning optimization algorithms. Since many limitations encountered in the first part are based on the inadequacy of the underlying model, the second part introduces a more faithful model of optimization algorithms and how practitioners use them. This construction is done in a bottom-up approach, which allows for minimal assumptions and wide applicability, and effectively solves the problems of the first part all at once. Even more so, this model offers the possibility for deriving generalization guarantees for most conceivable performance measures rather easily. Then, based on this new model, the third part provides a new proof-strategy with which the gap between conventional optimization theory and learning-to-optimize can be closed to a large extent. Here, the underlying idea is exemplified for the problem of proving convergence to stationary points of non-smooth and non-convex loss functions. This results in a generalization guarantee for the learned optimization algorithm which certifies that, roughly speaking, the probability that the learned algorithm will converge to a stationary point of the loss function is lower-bounded by corresponding quantities that are observable during training. Finally, the last part summarizes the contributions of this thesis and discusses its limitations. Further, it shows how the remaining problems can be explained based on the proposed model, which of these problems can potentially be solved based on statistical approaches and which will probably always have to be solved in the conventional way. Lastly, some potential directions for future research are discussed. Taken together, these results collectively contribute to a better understanding of learning-to-optimize and the overarching objective of obtaining more efficient optimization algorithms through the application of machine learning while keeping the needed theoretical guarantees