Untersuchung genomischer Alterationen bei myelodysplastischen Syndromen (MDS) und juveniler myelomonozytärer Leukämie (JMML) im Kindesalter mittels hochauflösender array-CGH

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Digital Sovereignty Strategies for Every Nation

Digital Sovereignty must be on the agenda of every modern nation. Digital technology is becoming part of our life details, from the vital essentials, like food and water management, to transcendence in the Metaverse and Space. Protecting these digital assets will, therefore, be inevitable for a modern country to live, excel and lead. Digital Sovereignty is a strategic necessity to protect these digital assets from the monopoly of friendly rational states, and the threats of unfriendly Malicious states and behaviors. In this work, we revisit the definition and scope of digital sovereignty through extending it to cover the entire value chain of using, owning, and producing digital assets. We emphasize the importance of protecting the operational resources, both raw materials and human expertise, in addition to research and innovation necessary to achieve sustainable sovereignty. We also show that digital sovereignty by autonomy is often impossible, and by mutual cooperation is not always sustainable. To this end, we propose implementing digital sovereignty using Nash Equilibrium, often studied in Game Theory, to govern the relation with Rational states. Finally, we propose a digital sovereignty agenda for different country's digital profiles, based on their status quo, priorities, and capabilities. We survey state-of-the-art digital technology that is useful to make the current digital assets sovereign. Additionally, we propose a roadmap that aims to develop a sovereign digital nation, as close as possible to autonomy. Finally, we draw attention to the need of more research to better understand and implement digital sovereignty from different perspectives: technological, economic, and geopolitical

Mid-

This thesis explores a personal and cultural tension between rootedness and restlessness, set against the backdrop of my native Midwest. The large-format portrait and landscape photographs reflect a paradoxical longing to pull up stakes and put down roots, and the liminal state we often dwell in as a result. Playing on the conception of the Midwest as a transient zone to be passed through en route to somewhere else, the work refers to the pervasive belief that our greatest hopes and potentials can only be realized in some other place, at some future or past time. It’s a syndrome I grapple with myself, centrifugally lapping the country in perpetual search for an impossible landing pad. As American society drifts increasingly towards untethered mobility and develops a homogenized temporary landscape in its wake, our identifications with distinct regional home places are more likely to reach mythical proportions. As such, the Midwest becomes not just my centripetal anchor, but also my stage — a metaphorical intersection between movement and stasis drawing from observation, experience, memory and fantasy. Here, my personal myth of place unfolds

SO LONG AS WE STILL LIVE: POLISH EFFORTS IN ESTABLISHING A MILITARY RECRUITMENT CENTER IN NORTH AMERICA DURING THE SECOND WORLD WAR.

Following their retreat to Great Britain in 1940, the Polish government and its military sought out fresh reserves to reinforce their depleted armed forces. With mainland Europe being overrun by the enemy, the Poles turned to the prospect of recruiting from the Polish émigré community on the American continent (Polonia). A generation earlier, over 20,000 Polish-Americans had enlisted to fight for the liberation of their homeland in the Blue Army. Seeking to recreate this success, the Poles established a recruitment center in Windsor, Ontario and a training camp in Owen Sound, Ontario. Despite their efforts, by 1942, the Poles only managed to attract just over 800 recruits to their military. The lack of recruits can be linked to several factors such as the Polish government’s mistreatment of Polish-American veterans from the First World War, a changing and more North Americanized youth within the Polonia, and a lack of cultural awareness on the part of the Polish government in terms of what North American Poles prioritized

Discovering Jewish Studies Collections in Academic Libraries: A Practical Guide

The U.S. colleges and universities offering non-sectarian educational programs in Jewish Studies rely on the support of their academic libraries for research materials and library services. For college libraries which use Library of Congress Classification scheme, it is a common practice to integrate studies resources into their general library collections. Since Jewish Studies sources span a vast number of subjects within all major disciplines, shelving integration leads to the dispersion of all relevant sources and such dispersion in turn leads to a variety of problems for library professionals and library users. For collection development librarians the problems range from lack of information about collection\u27s size, strengths or weaknesses, and for library users interested in browsing the collection, dispersion of subjects creates a major roadblock. This practical guide aims at providing a solution to such problems. By identifying all relevant Library of Congress call numbers and the corresponding Library of Congress subject headings, the guide offers a simplified access to Jewish Studies sources in general library collections. It is arranged by four major discipline: Arts & Humanities, Social Sciences, Sciences, and General Works & Bibliographies. Within each discipline, specific LC call number ranges and corresponding subjects are listed. The subjects are further subdivided and precisely identified. The guide will assist collection development librarians, library liaisons, grants and fundraising professionals and especially the Jewish Studies faculty and students, in identifying and locating relevant sources

Structural basis of cooperative DNA recognition by the plasmid conjugation factor, TraM

The conjugative transfer of F-like plasmids such as F, R1, R100 and pED208, between bacterial cells requires TraM, a plasmid-encoded DNA-binding protein. TraM tetramers bridge the origin of transfer (oriT) to a key component of the conjugative pore, the coupling protein TraD. Here we show that TraM recognizes a high-affinity DNA-binding site, sbmA, as a cooperative dimer of tetramers. The crystal structure of the TraM–sbmA complex from the plasmid pED208 shows that binding cooperativity is mediated by DNA kinking and unwinding, without any direct contact between tetramers. Sequence-specific DNA recognition is carried out by TraM’s N-terminal ribbon–helix–helix (RHH) domains, which bind DNA in a staggered arrangement. We demonstrate that both DNA-binding specificity, as well as selective interactions between TraM and the C-terminal tail of its cognate TraD mediate conjugation specificity within the F-like family of plasmids. The ability of TraM to cooperatively bind DNA without interaction between tetramers leaves the C-terminal TraM tetramerization domains free to make multiple interactions with TraD, driving recruitment of the plasmid to the conjugative pore

Identifying corruption through latent class models: evidence from transition economies

Evaluation of corrupt activities is incrementally based on administration of questionnaires to firms in business, and generally involves a large number of items. Data collected by questionnaires of this type can be analyzed by Latent Class (LC) models in order to classify firms into homogeneous groups according to the perception of corruption. In this paper, we propose a multidimensional framework, based on an LC model, to identify various types of corruption. By using a dataset for transition economies, we identify four classes of corrupt activities, which go beyond the usual classification into administrative and political types of corruption; we then validate our estimates by using a direct administrative corruption index from the same dataset and by comparing, at country level, corruption perception rankings published by Transparency International. The potential of the proposed approach is illustrated through an application to the relationship between firms' competitiveness and the identified latent corruption classes, with evident heterogeneity in the interpretation of results regarding policy implications

Structural characterization and interaction studies of ubiquitin-like proteins

Ubiquitin is a highly conserved protein involved in several cellular processes like protein degradation, endocytosis, signal transduction and DNA repair. The discovery of ubiquitin-like proteins (UBL) and ubiquitin-like domains (ULD) increases the number of regulation pathways where the property of the ubiquitin-fold is profitable. Autophagy is the catabolic pathway used in cells to deliver cytosolic components and dysfunctional organelles to the lysosome for degradation. MAP1LC3 proteins are ubiquitin-like proteins involved in one hand for the expansion of the autophagosome, which sequesters cytosolic substrates. In the other hand, these proteins (LC3- and GABARAP- subfamilies) bind to autophagic receptors linked to polyubiquitinated proteins aggregates. For this project, the 3D structure of the GABARAPL-1/NBR1-LIR complex was determined and confirmed that GABARAPL-1 belongs to the MAP1LC3 proteins family, structurally characterized by an ubiquitin-fold, consisting of a central beta-sheet formed by four beta-strands and two alpha-helices on one side of the beta-sheet, preceded N terminally by two alpha-helices, resulting in the formation of two hydrophobic pockets, hp1 and hp2. The autophagic receptor NBR1 interacts with GABARAPL-1 through the hp1 and hp2 with its LIR motif taking an extended beta conformation upon binding, forming an intermolecular beta-sheet with the second beta-strand of GABARAPL 1. This LC3- interacting region (LIR) consists of an Theta XX Gamma sequence preceded by acidic amino acids, with Theta and Gamma represented by any aromatic and hydrophobic residues, respectively. Interaction studies of the LIR domains of p62, Nix and NBR1 with different members of the MAP1LC3 proteins family indicate that the presence of a tryptophan in the LIR motif increases the binding affinity. Substitution to other aromatic amino acids or increasing the number of negatively charged residues at the N-terminus of the LIR motif, however, has little effect on the binding affinity due to enthalpy-entropy compensation, suggesting that effector proteins can interact with a wide variety of different sequences with similar and moderate binding affinities. Additionally to be present in proteins dealing with protein folding and degradation, ubiquitin-like domain were found protein involved in the regulation of signal transduction like TBK1, a serine/threonine kinase responsible for induction of immune response. In this second project, based on the NMR chemical shifts of the TBK1 domain contained between amino acids 302 and 383, secondary structure prediction programs (TALOS and CSI) confirmed the presence of an Ubiquitin-like domain in TBK1 by identifying one alpha-helix and four beta-strands sequentially aligned like following beta-beta-alpha-beta-beta. This alignment corresponds perfectly with the secondary structure elements of Ubiquitin and proved that TBK1_ULD belongs to the UBL protein superfamily. The similarity to ubiquitin was even bigger by the presence in addition of a small beta-strand and a short helix, which are observed as the beta 5-strand and a 310-helix in Ubiquitin, respectively. The first attempts on the 3D structure determination confirmed the Ub-fold but due to the lack of assignment in TBK1_ULD, only a structure based on ubiquitin as a model was determined. Interaction studies of TBK1_ULD with the IAD-SRR domain of IRF3 showed that both side of the molecule seems involved and that the TBK1/IRF3 interaction is more complex than a one to one binding process. Unfortunately, the instability of TBK1_ULD associated to the difficulty in the purification of IAD-SRR did not allow to further study this interaction more precisely. Finally, to overcome the difficulty encountered in NMR experiments because of low expression and/or poor solubility, an expression vector using the intrinsic property of ubiquitin was designed. Fused to proteins or peptides targets, this construct produced proteins and peptides in a larger amount than with traditional expression vectors and also with a less cost than chemical synthesis for pure labeled peptides for NMR structural studies. The presence of a hexa histidine tag was useful for the isolation and the purification of the constructs. The existence of a TEV cleavage site was created to keep the possibility of releasing the ubiquitin moiety from the expressed protein or peptide. Moreover, the ubiquitin-tag could also still be attached to the protein/peptide of interest when biophysical methods like NMR, ITC or CD spectroscopy are applied, providing the same results than for the protein/peptide moiety alone