State of the art: Reproduction and pregnancy in rheumatic diseases

Throughout the last decade, increasing awareness has been raised on issues related to reproduction in rheumatic diseases including basic research to clarify the important role of estrogens in the etiology and pathophysiology of immune/inflammatory diseases. Sub- or infertility is a heterogeneous condition that can be related to immunological mechanisms, to pregnancy loss, to disease burden, to therapy, and to choices in regard to family size. Progress in reproductive medicine has made it possible for more patients with rheumatic disease to have children. Active disease in women with rheumatoid arthritis (RA) affects their children's birth weight and may have long-term effects on their future health status. Pregnancy complications as preeclampsia and intrauterine growth restriction are still increased in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS), however, biomarkers can monitor adverse events, and several new therapies may improve outcomes. Pregnancies in women with APS remain a challenge, and better therapies for the obstetric APS are needed. New prospective studies indicate improved outcomes for pregnancies in women with rare diseases like systemic sclerosis and vasculitis. TNF inhibitors hold promise for maintaining remission in rheumatological patients and may be continued at least in the first half of pregnancy. Pre-conceptional counseling and interdisciplinary management of pregnancies are essential for ensuring optimal pregnancy outcomes.

Markers of endothelial cell activation and immune activation are increased in patients with severe leptospirosis and associated with disease severity

OBJECTIVES Previous studies concluded that haemorrhage is one of the most accurate prognostic factors of mortality in leptospirosis. Therefore, endothelial cell activation was investigated in relation to disease severity in severe leptospirosis. METHODS Prospective cohort study of severe leptospirosis patients. Plasma levels of sE-selectin and Von Willebrand factor (VWF) were determined. Consequently, an in vitro endothelial cell model was used to assess endothelial activation after exposure to virulent Leptospira. Finally, immune activation, as a potential contributing factor to endothelial cell activation, was determined by soluble IL2-receptor (sIL-2r) and soluble Fas-ligand (sFasL) levels. RESULTS Plasma levels of sE-selectin and VWF strongly increased in patients compared to healthy controls. Furthermore, sE-selectin was significantly elevated (203 ng/ml vs. 157 ng/ml, p < 0.05) in survivors compared to non-survivors. Endothelial cells exposed to virulent Leptospira showed increased VWF expression. E-selectin and ICAM-1 expression did not change. Immunohistochemistry revealed the presence of intracellular Leptospira and qPCR suggested replication. In vivo analysis showed that increased levels of sFasL and sIL-2r were both strongly associated with mortality. Furthermore sIL-2r levels were increased in patients that developed bleeding and significantly correlated to duration of hospital stay. DISCUSSION Markers of endothelial activation and immune activation were associated with disease severity in leptospirosis patients.

Modelo de computación conexionista inspirado en las redes de procesadores evolutivos y su aprendizaje

La informática teórica es una disciplina básica ya que la mayoría de los avances en informática se sustentan en un sólido resultado de esa materia. En los últimos a~nos debido tanto al incremento de la potencia de los ordenadores, como a la cercanía del límite físico en la miniaturización de los componentes electrónicos, resurge el interés por modelos formales de computación alternativos a la arquitectura clásica de von Neumann. Muchos de estos modelos se inspiran en la forma en la que la naturaleza resuelve eficientemente problemas muy complejos. La mayoría son computacionalmente completos e intrínsecamente paralelos. Por este motivo se les está llegando a considerar como nuevos paradigmas de computación (computación natural). Se dispone, por tanto, de un abanico de arquitecturas abstractas tan potentes como los computadores convencionales y, a veces, más eficientes: alguna de ellas mejora el rendimiento, al menos temporal, de problemas NPcompletos proporcionando costes no exponenciales. La representación formal de las redes de procesadores evolutivos requiere de construcciones, tanto independientes, como dependientes del contexto, dicho de otro modo, en general una representación formal completa de un NEP implica restricciones, tanto sintácticas, como semánticas, es decir, que muchas representaciones aparentemente (sintácticamente) correctas de casos particulares de estos dispositivos no tendrían sentido porque podrían no cumplir otras restricciones semánticas. La aplicación de evolución gramatical semántica a los NEPs pasa por la elección de un subconjunto de ellos entre los que buscar los que solucionen un problema concreto. En este trabajo se ha realizado un estudio sobre un modelo inspirado en la biología celular denominado redes de procesadores evolutivos [55, 53], esto es, redes cuyos nodos son procesadores muy simples capaces de realizar únicamente un tipo de mutación puntual (inserción, borrado o sustitución de un símbolo). Estos nodos están asociados con un filtro que está definido por alguna condición de contexto aleatorio o de pertenencia. Las redes están formadas a lo sumo de seis nodos y, teniendo los filtros definidos por una pertenencia a lenguajes regulares, son capaces de generar todos los lenguajes enumerables recursivos independientemente del grafo subyacente. Este resultado no es sorprendente ya que semejantes resultados han sido documentados en la literatura. Si se consideran redes con nodos y filtros definidos por contextos aleatorios {que parecen estar más cerca a las implementaciones biológicas{ entonces se pueden generar lenguajes más complejos como los lenguajes no independientes del contexto. Sin embargo, estos mecanismos tan simples son capaces de resolver problemas complejos en tiempo polinomial. Se ha presentado una solución lineal para un problema NP-completo, el problema de los 3-colores. Como primer aporte significativo se ha propuesto una nueva dinámica de las redes de procesadores evolutivos con un comportamiento no determinista y masivamente paralelo [55], y por tanto todo el trabajo de investigación en el área de la redes de procesadores se puede trasladar a las redes masivamente paralelas. Por ejemplo, las redes masivamente paralelas se pueden modificar de acuerdo a determinadas reglas para mover los filtros hacia las conexiones. Cada conexión se ve como un canal bidireccional de manera que los filtros de entrada y salida coinciden. A pesar de esto, estas redes son computacionalmente completas. Se pueden también implementar otro tipo de reglas para extender este modelo computacional. Se reemplazan las mutaciones puntuales asociadas a cada nodo por la operación de splicing. Este nuevo tipo de procesador se denomina procesador splicing. Este modelo computacional de Red de procesadores con splicing ANSP es semejante en cierto modo a los sistemas distribuidos en tubos de ensayo basados en splicing. Además, se ha definido un nuevo modelo [56] {Redes de procesadores evolutivos con filtros en las conexiones{ , en el cual los procesadores tan solo tienen reglas y los filtros se han trasladado a las conexiones. Dicho modelo es equivalente, bajo determinadas circunstancias, a las redes de procesadores evolutivos clásicas. Sin dichas restricciones el modelo propuesto es un superconjunto de los NEPs clásicos. La principal ventaja de mover los filtros a las conexiones radica en la simplicidad de la modelización. Otras aportaciones de este trabajo ha sido el dise~no de un simulador en Java [54, 52] para las redes de procesadores evolutivos propuestas en esta Tesis. Sobre el término "procesador evolutivo" empleado en esta Tesis, el proceso computacional descrito aquí no es exactamente un proceso evolutivo en el sentido Darwiniano. Pero las operaciones de reescritura que se han considerado pueden interpretarse como mutaciones y los procesos de filtrado se podrían ver como procesos de selección. Además, este trabajo no abarca la posible implementación biológica de estas redes, a pesar de ser de gran importancia. A lo largo de esta tesis se ha tomado como definición de la medida de complejidad para los ANSP, una que denotaremos como tama~no (considerando tama~no como el número de nodos del grafo subyacente). Se ha mostrado que cualquier lenguaje enumerable recursivo L puede ser aceptado por un ANSP en el cual el número de procesadores está linealmente acotado por la cardinalidad del alfabeto de la cinta de una máquina de Turing que reconoce dicho lenguaje L. Siguiendo el concepto de ANSP universales introducido por Manea [65], se ha demostrado que un ANSP con una estructura de grafo fija puede aceptar cualquier lenguaje enumerable recursivo. Un ANSP se puede considerar como un ente capaz de resolver problemas, además de tener otra propiedad relevante desde el punto de vista práctico: Se puede definir un ANSP universal como una subred, donde solo una cantidad limitada de parámetros es dependiente del lenguaje. La anterior característica se puede interpretar como un método para resolver cualquier problema NP en tiempo polinomial empleando un ANSP de tama~no constante, concretamente treinta y uno. Esto significa que la solución de cualquier problema NP es uniforme en el sentido de que la red, exceptuando la subred universal, se puede ver como un programa; adaptándolo a la instancia del problema a resolver, se escogerín los filtros y las reglas que no pertenecen a la subred universal. Un problema interesante desde nuestro punto de vista es el que hace referencia a como elegir el tama~no optimo de esta red.---ABSTRACT---This thesis deals with the recent research works in the area of Natural Computing {bio-inspired models{, more precisely Networks of Evolutionary Processors first developed by Victor Mitrana and they are based on P Systems whose father is Georghe Paun. In these models, they are a set of processors connected in an underlying undirected graph, such processors have an object multiset (strings) and a set of rules, named evolution rules, that transform objects inside processors[55, 53],. These objects can be sent/received using graph connections provided they accomplish constraints defined at input and output filters processors have. This symbolic model, non deterministic one (processors are not synchronized) and massive parallel one[55] (all rules can be applied in one computational step) has some important properties regarding solution of NP-problems in lineal time and of course, lineal resources. There are a great number of variants such as hybrid networks, splicing processors, etc. that provide the model a computational power equivalent to Turing machines. The origin of networks of evolutionary processors (NEP for short) is a basic architecture for parallel and distributed symbolic processing, related to the Connection Machine as well as the Logic Flow paradigm, which consists of several processors, each of them being placed in a node of a virtual complete graph, which are able to handle data associated with the respective node. All the nodes send simultaneously their data and the receiving nodes handle also simultaneously all the arriving messages, according to some strategies. In a series of papers one considers that each node may be viewed as a cell having genetic information encoded in DNA sequences which may evolve by local evolutionary events, that is point mutations. Each node is specialized just for one of these evolutionary operations. Furthermore, the data in each node is organized in the form of multisets of words (each word appears in an arbitrarily large number of copies), and all the copies are processed in parallel such that all the possible events that can take place do actually take place. Obviously, the computational process just described is not exactly an evolutionary process in the Darwinian sense. But the rewriting operations we have considered might be interpreted as mutations and the filtering process might be viewed as a selection process. Recombination is missing but it was asserted that evolutionary and functional relationships between genes can be captured by taking only local mutations into consideration. It is clear that filters associated with each node allow a strong control of the computation. Indeed, every node has an input and output filter; two nodes can exchange data if it passes the output filter of the sender and the input filter of the receiver. Moreover, if some data is sent out by some node and not able to enter any node, then it is lost. In this paper we simplify the ANSP model considered in by moving the filters from the nodes to the edges. Each edge is viewed as a two-way channel such that the input and output filters coincide. Clearly, the possibility of controlling the computation in such networks seems to be diminished. For instance, there is no possibility to loose data during the communication steps. In spite of this and of the fact that splicing is not a powerful operation (remember that splicing systems generates only regular languages) we prove here that these devices are computationally complete. As a consequence, we propose characterizations of two complexity classes, namely NP and PSPACE, in terms of accepting networks of restricted splicing processors with filtered connections. We proposed a uniform linear time solution to SAT based on ANSPFCs with linearly bounded resources. This solution should be understood correctly: we do not solve SAT in linear time and space. Since any word and auxiliary word appears in an arbitrarily large number of copies, one can generate in linear time, by parallelism and communication, an exponential number of words each of them having an exponential number of copies. However, this does not seem to be a major drawback since by PCR (Polymerase Chain Reaction) one can generate an exponential number of identical DNA molecules in a linear number of reactions. It is worth mentioning that the ANSPFC constructed above remains unchanged for any instance with the same number of variables. Therefore, the solution is uniform in the sense that the network, excepting the input and output nodes, may be viewed as a program according to the number of variables, we choose the filters, the splicing words and the rules, then we assign all possible values to the variables, and compute the formula.We proved that ANSP are computationally complete. Do the ANSPFC remain still computationally complete? If this is not the case, what other problems can be eficiently solved by these ANSPFCs? Moreover, the complexity class NP is exactly the class of all languages decided by ANSP in polynomial time. Can NP be characterized in a similar way with ANSPFCs?

Orientation in operator algebras

A concept of orientation is relevant for the passage from Jordan structure to associative structure in operator algebras. The research reported in this paper bridges the approach of Connes for von Neumann algebras and ourselves for C*-algebras in a general theory of orientation that is of geometric nature and is related to dynamics.

Defect in regulated secretion of P-selectin affects leukocyte recruitment in von Willebrand factor-deficient mice

Stimulation of endothelial cells by various inflammatory mediators leads to release of Weibel–Palade bodies and therefore to exocytosis of both P-selectin (adhesion receptor for leukocytes) and von Willebrand factor (vWf) (platelet ligand). The potential role of vWf in leukocyte recruitment was investigated with the use of vWf-deficient mice. We report a strong reduction of leukocyte rolling in venules of vWf-deficient mice. Similarly, vWf deficiency led to a decrease in neutrophil recruitment in a cytokine-induced meningitis model as well as in early skin wounds. In all instances with an antibody that preferentially recognizes plasma membrane P-selectin, we observed a dramatic reduction in P-selectin expression at the cell surface of vWf-deficient endothelium. With confocal microscopy, we found that the typical rodlike shape of the Weibel–Palade body is missing in vWf −/− endothelial cells and that part of the P-selectin content in the vWf −/− cells colocalized with LAMP-1, a lysosomal marker. However, intracellular P-selectin levels were similar in tumor necrosis factor α- and lipopolysaccharide-activated cells of both genotypes. We conclude that the absence of vWf, as found in severe von Willebrand disease, leads to a defect in Weibel–Palade body formation. This defect results in decreased P-selectin translocation to the cell surface and reduced leukocyte recruitment in early phases of inflammation.

Critical behavior of su(1|1) supersymmetric spin chains with long-range interactions

We introduce a general class of su(1|1) supersymmetric spin chains with long-range interactions which includes as particular cases the su(1|1) Inozemtsev (elliptic) and Haldane-Shastry chains, as well as the XX model. We show that this class of models can be fermionized with the help of the algebraic properties of the su(1|1) permutation operator and take advantage of this fact to analyze their quantum criticality when a chemical potential term is present in the Hamiltonian. We first study the low-energy excitations and the low-temperature behavior of the free energy, which coincides with that of a (1+1)-dimensional conformal field theory (CFT) with central charge c=1 when the chemical potential lies in the critical interval (0,E(π)), E(p) being the dispersion relation. We also analyze the von Neumann and Rényi ground state entanglement entropies, showing that they exhibit the logarithmic scaling with the size of the block of spins characteristic of a one-boson (1+1)-dimensional CFT. Our results thus show that the models under study are quantum critical when the chemical potential belongs to the critical interval, with central charge c=1. From the analysis of the fermion density at zero temperature, we also conclude that there is a quantum phase transition at both ends of the critical interval. This is further confirmed by the behavior of the fermion density at finite temperature, which is studied analytically (at low temperature), as well as numerically for the su(1|1) elliptic chain.

Measuring ageing and the need for longer working lives in the EU. CEPS Working Document No. 417/February 2016 Wednesday, 24 February 2016

This study considers different ways of measuring the ageing of societies and their implications for public policy. The first part characterises the ongoing ageing of the population in the EU28 by relating it to past and future longer-term demographic trends for broad groups of countries. It goes beyond traditional chronological measures to include recently suggested prospective measures of ageing. The second part of the study is concerned with economic dependency ratios; a more relevant measure for summarising the economic challenges related to ageing. Three main findings emerge: first, prospective indicators of ageing reveal the challenge of population ageing to be less onerous than traditional chronological measures would suggest. Their relevance, however, will depend on the degree to which policy changes can respond to the changing age structure of the population. Second, substantial increases in the length of working lives are necessary to maintain current economic dependency ratios. Taking a year-2000 perspective view of the economic challenges of ageing shows that substantial progress has been made. Third, looking towards 2050, education will have limited direct impact on the scale of the ageing challenge.

Sedimentological, geochemical, micropaleontological and rock magnetic proxies of sediment core GeoB6211-2

Surface currents and sediment distribution of the SE South American upper continental margin are under influence of the South American Monsoon System (SAMS) and the Southern Westerly Wind Belt (SWWB). Both climatic systems determine the meridional position of the Subtropical Shelf Front (STSF) and probably also of the Brazil-Malvinas Confluence (BMC). We reconstruct the changing impact of the SAMS and the SWWB on sediment composition at the upper Rio Grande Cone off southern Brazil during the last 14 cal kyr combining sedimentological, geochemical, micropaleontological and rock magnetic proxies of marine sediment core GeoB 6211-2. Sharp reciprocal changes in ferri- and paramagnetic mineral content and prominent grain-size shifts give strong clues to systematic source changes and transport modes of these mostly terrigenous sediments. Our interpretations support the assumption that the SAMS over SE South America was weaker than today during most of the Late Glacial and entire Early Holocene, while the SWWB was contracted to more southern latitudes, resembling modern austral summer-like conditions. In consequence, the STSF and the BMC were driven to more southern positions than today's, favoring the deposition of Fe-rich but weakly magnetic La Plata River silts at the Rio Grande Cone. During the Mid Holocene, the northern boundary of the SWWB migrated northward, while the STSF reached its northernmost position of the last 14 cal kyr and the BMC most likely arrived at its modern position. This shift enabled the transport of Antarctic diatoms and more strongly magnetic Argentinean shelf sands to the Rio Grande Cone, while sediment contributions from the La Plata River became less important. During the Late Holocene, the modern El Niño Southern Oscillation set in and the SAMS and the austral tradewinds intensified, causing a southward shift of the STSF to its modern position. This reinforced a significant deposition of La Plata River silts at the Rio Grande Cone. These higher magnetic silts with intermediate Fe contents mirror the modern more humid terrestrial climatic conditions over SE South America.

A simple proof of the strong subadditivity inequality

Arguably the deepest fact known about the von Neumann entropy, the strong subadditivity inequality is a potent hammer in the quantum information theorist's toolkit. This short tutorial describes a simple proof of strong subadditivity due to Petz [Rep. on Math. Phys. 23 (1), 57-65 (1986)]. It assumes only knowledge of elementary linear algebra and quantum mechanics.

Migration und Utopie im deutschen Gegenwartskino am Beispiel von Achim von Borries’ "England!" und Hans-Christian Schmids "Lichter"

Achim von Borries’ England! and Hans-Christian Schmid’s Distant Lights [Lichter] are two key examples of how the current issue of (economic) migration from eastern to western Europe is explored in contemporary German cinema. Set in two locations that act as places of transit for migrants from the east - the capital Berlin and the economically depressed border region along the river Oder - the films show their characters’ utopian strive for a better future. Even though they deal with it in very different ways, both films emphasise the heightened role of the imagination in a globalised world and highlight its problematic consequences.