Encounters, Interactions, and Connectivities from an Art Historical Perspective

Transcultural encounters, interactions, and connectivities have been among the core interests of the discipline of art history in recent years. Focusing on the premodern period, this image series addresses these issues through a number of case studies ranging from the Caucasus to the Mediterranean, the Indian Ocean world, Sub-Saharan Africa, Latin America and the Pacific. By no means exhaustive, the following case studies are analyzed paying equal attention to diverse materials, media, and their intersections from architecture and objects of material culture to maps and paintings. Approached from an empirico-historical perspective and addressing some methodological problems, this image series thus aims to introduce readers to and sharpen our understanding of the current reflections within the field of research

Safety and efficacy of nonacog alfa for the treatment of haemophilia B in children younger than 6 years of age in a routine clinical care setting: the EUREKIX registry study.

INTRODUCTION European regulatory authorities request postmarketing safety and efficacy data for factor IX (FIX) products. AIM Collect additional clinical data from routine nonacog alfa use in children aged <6 years with haemophilia B. METHODS The EUREKIX registry included retrospective and prospective data collection phases. Safety was assessed via adverse drug reactions (ADRs)/adverse events (AEs) and events of special interest (ESIs) as the primary objective; efficacy was evaluated via annualised bleeding rates (ABRs). RESULTS The retrospective phase comprised 37 subjects. Of these, 25 had severe haemophilia B. One subject experienced 2 ADRs; another experienced 4 ESIs of hypersensitivity. Median ABR in subjects receiving a predominantly on-demand regimen (prophylaxis <50% of time; n = 11) was 2.0; median ABR was 3.8 in those receiving predominantly prophylactic treatment (prophylaxis ≥50% of time; n = 24). Joint bleeding was infrequent (median ABR, 0.4; n = 35). The prospective phase included 26 subjects, with 17 continuing from the retrospective phase. A total of 20 subjects had severe haemophilia B. Three subjects experienced 7 treatment-related AEs; 3 experienced 4 ESIs. Median ABR was 4.5 and 1.1 in subjects who received predominantly on-demand (n = 5) or prophylactic treatment (n = 19), respectively; the overall median ABR for joint bleeding events was 0.0. CONCLUSIONS Overall, nonacog alfa treatment effectively controlled bleeding events, with no new safety signals identified. These data support the safety and efficacy of nonacog alfa in routine clinical settings in children aged <6 years

Early Paleozoic accretionary orogens along the Western Gondwana margin

Early Paleozoic accretionary orogens dominated the Western Gondwana margin and were characterized by nearly continuous subduction associated with crustal extension and back-arc basin development. The southwestern margin is represented by Famatinian and Pampean basement realms exposed in South America, both related to the protracted Paleozoic evolution of the Terra Australis Orogen, whereas the northwestern margin is mainly recorded in Cadomian domains of Europe and adjacent regions. However, no clear relationships between these regions were so far established. Based on a compilation and reevaluation of geological, paleomagnetic, petrological, geochronological and isotopic evidence, this contribution focuses on crustal-scale tectonic and geodynamic processes occurring in Western Gondwana accretionary orogens, aiming at disentangling their common Early Paleozoic evolution. Data show that accretionary orogens were dominated by high-temperature/low-pressure metamorphism and relatively high geothermal gradients, resulting from the development of extended/hyperextended margins and bulk transtensional deformation. In this sense, retreating-mode accretionary orogens characterized the Early Paleozoic Gondwana margin, though short-lived pulses of compression/transpression also occurred. The existence of retreating subduction zones favoured mantle-derived magmatism and mixing with relatively young (meta)sedimentary sources in a thin continental crust. Crustal reworking of previous forearc sequences due to trenchward arc migration thus took place through assimilation and anatexis in the arc/back-arc regions. Therefore, retreating-mode accretionary orogens were the locus of Early Paleozoic crustal growth in Western Gondwana, intimately associated with major flare-up events, such as those related to the Cadomian and Famatian arcs. Slab roll back, probably resulting from decreasing convergence rates and plate velocities after Gondwana assembly, was a key factor for orogen-scale geodynamic processes. Coupled with synchronous oblique subduction and crustal-scale dextral deformation, slab roll back might trigger toroidal mantle flow, thus accounting for bulk dextral transtension, back-arc extension/transtension and a large-scale anticlockwise rotation of Gondwana mainland.Fil: Oriolo, Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires; ArgentinaFil: Schulz, Bernhard. Technische Universität Bergakademie Freiberg; AlemaniaFil: Geuna, Silvana Evangelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires; ArgentinaFil: Gonzalez, Pablo Diego. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Río Negro. Sede Alto Valle. Instituto de Investigaciones en Paleobiología y Geología; ArgentinaFil: Otamendi, Juan Enrique. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente; ArgentinaFil: Sláma, Jiří. The Czech Academy of Sciences. Institute of Geology; República ChecaFil: Druguet, Elena. Universitat Autònoma de Barcelona; EspañaFil: Siegesmund, Siegfried. Universität Göttingen; Alemani

Functional interdependence of the actin regulators CAP1 and cofilin1 in control of dendritic spine morphology

The vast majority of excitatory synapses are formed on small dendritic protrusions termed dendritic spines. Dendritic spines vary in size and density that are crucial determinants of excitatory synaptic transmission. Aberrations in spine morphogenesis can compromise brain function and have been associated with neuropsychiatric disorders. Actin filaments (F-actin) are the major structural component of dendritic spines, and therefore, actin-binding proteins (ABP) that control F-actin dis-/assembly moved into the focus as critical regulators of brain function. Studies of the past decade identified the ABP cofilin1 as a key regulator of spine morphology, synaptic transmission, and behavior, and they emphasized the necessity for a tight control of cofilin1 to ensure proper brain function. Here, we report spine enrichment of cyclase-associated protein 1 (CAP1), a conserved multidomain protein with largely unknown physiological functions. Super-resolution microscopy and live cell imaging of CAP1-deficient hippocampal neurons revealed impaired synaptic F-actin organization and dynamics associated with alterations in spine morphology. Mechanistically, we found that CAP1 cooperates with cofilin1 in spines and that its helical folded domain is relevant for this interaction. Moreover, our data proved functional interdependence of CAP1 and cofilin1 in control of spine morphology. In summary, we identified CAP1 as a novel regulator of the postsynaptic actin cytoskeleton that is essential for synaptic cofilin1 activity

Fluc-EGFP reporter mice reveal differential alterations of neuronal proteostasis in aging and disease

The cellular protein quality control machinery is important for preventing protein misfolding and aggregation. Declining protein homeostasis (proteostasis) is believed to play a crucial role in age‐related neurodegenerative disorders. However, how neuronal proteostasis capacity changes in different diseases is not yet sufficiently understood, and progress in this area has been hampered by the lack of tools to monitor proteostasis in mammalian models. Here, we have developed reporter mice for in vivo analysis of neuronal proteostasis. The mice express EGFP‐fused firefly luciferase (Fluc‐EGFP), a conformationally unstable protein that requires chaperones for proper folding, and that reacts to proteotoxic stress by formation of intracellular Fluc‐EGFP foci and by reduced luciferase activity. Using these mice, we provide evidence for proteostasis decline in the aging brain. Moreover, we find a marked reaction of the Fluc‐EGFP sensor in a mouse model of tauopathy, but not in mouse models of Huntington’s disease. Mechanistic investigations in primary neuronal cultures demonstrate that different types of protein aggregates have distinct effects on the cellular protein quality control. Thus, Fluc‐EGFP reporter mice enable new insights into proteostasis alterations in different diseases

Migration, Mobility and Human Rights at the Eastern Border of the European Union - Space of Freedom and Security

This edited collection of migration papers would like to emphasise the acute need for migration related study and research in Romania. At this time, migration and mobility are studied as minor subjects in Economics, Sociology, Political Sciences and European Studies only (mostly at post-graduate level). We consider that Romanian universities need more ‘migration studies’, while research should cover migration as a whole, migration and mobility being analysed from different points of view – social, economical, legal etc. Romania is part of the European Migration Space not only as a source of labourers for the European labour market, but also as source of quality research for the European scientific arena. Even a country located at the eastern border of the European Union, we consider Romania as part of the European area of freedom, security and justice, and therefore interested in solving correctly all challenges incurred by the complex phenomena of migration and workers’ mobility at the European level. The waves of illegal immigrants arriving continuously on the Spanish, Italian and Maltese shores, and the workers’ flows from the new Member States from Central and Eastern Europe following the 2004 accession, forced the EU officials and the whole Europe to open the debate on the economical and mostly social consequences of labour mobility. This study volume is our contribution to this important scientific debate. Starting with the spring of 2005, the Jean Monnet European Centre of Excellence and the School of High Comparative European Studies (SISEC), both within the West University of Timisoara, have proposed a series of events in order to raise the awareness of the Romanian scientific environment on this very sensitive issues: migration and mobility in the widen European Space. An annual international event to celebrate 9 May - The Europe Day was already a tradition for SISEC (an academic formula launched back in 1995 in order to prepare national experts in European affairs, offering academic post-graduate degrees in High European Studies). With the financial support from the Jean Monnet Programme (DG Education and Culture, European Commission), a first migration panel was organised in the framework of the international colloquium ‘Romania and the European Union in 2007’ held in Timisoara between 6 and 7 of May 2005 (panel Migration, Asylum and Human Rights at the Eastern Border of the European Union). Having in mind the positive welcoming of the migration related subjects during the 2005 colloquium, a second event was organised on 5 May 2006 in the framework of the European Year of Workers’ Mobility: the international colloquium Migration and Mobility: Assets and Challenges for the Enlargement of the European Union. In the same period, the Jean Monnet European Centre of Excellence, SISEC and The British Council in Bucharest have jointly edited two special issues of The Romanian Journal of European Studies, no.4/2005 and 5-6/2006, both dedicated to migration and mobility. Preliminary versions of many of the chapters of this volume were presented at the above mentioned international events. The papers were chosen according to their scientific quality, after an anonymously peer-review selection. The authors debate both theoretical issues and practical results of their research. They are renowned experts at international level, members of the academia, PhD students or experienced practitioners involved in the management of the migration flows at the governmental level. This volume was financed by the Jean Monnet Programme of the Directorate General Education and Culture, European Commission, throughout the Jean Monnet European Centre of Excellence (C03/0110) within the West University of Timisoara, Romania, and is dedicated to the European Year of Workers’ Mobility 2006. Timisoara, December 200

Guideline for Trustworthy Artificial Intelligence -- AI Assessment Catalog

Artificial Intelligence (AI) has made impressive progress in recent years and represents a key technology that has a crucial impact on the economy and society. However, it is clear that AI and business models based on it can only reach their full potential if AI applications are developed according to high quality standards and are effectively protected against new AI risks. For instance, AI bears the risk of unfair treatment of individuals when processing personal data e.g., to support credit lending or staff recruitment decisions. The emergence of these new risks is closely linked to the fact that the behavior of AI applications, particularly those based on Machine Learning (ML), is essentially learned from large volumes of data and is not predetermined by fixed programmed rules. Thus, the issue of the trustworthiness of AI applications is crucial and is the subject of numerous major publications by stakeholders in politics, business and society. In addition, there is mutual agreement that the requirements for trustworthy AI, which are often described in an abstract way, must now be made clear and tangible. One challenge to overcome here relates to the fact that the specific quality criteria for an AI application depend heavily on the application context and possible measures to fulfill them in turn depend heavily on the AI technology used. Lastly, practical assessment procedures are needed to evaluate whether specific AI applications have been developed according to adequate quality standards. This AI assessment catalog addresses exactly this point and is intended for two target groups: Firstly, it provides developers with a guideline for systematically making their AI applications trustworthy. Secondly, it guides assessors and auditors on how to examine AI applications for trustworthiness in a structured way