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Der Autor versucht mit dieser kurzen Einführung eine Übersicht über den Stand der Forschung zu einem Thema zu geben, das in der Forschung bisher noch nicht ausreichend berücksichtigt wurde: der außerschulischen, privatwirtschaftlich organisierten Zusatzbildung, der sogenannten Shadow Education. Der Fokus der Arbeit richtet sich dabei auf die Länder Japan, welches bereits seit den 1970er Jahren ein System außerschulischer Bildungsinstitutionen besitzt, dessen Einfluss auf den Bildungserwerb junger Menschen so stark ist wie in kaum einem anderen Land, und Deutschland, dessen Schattenbildungs- oder Nachhilfesystem noch keinen derartig starken Einfluss ausübt, jedoch in den vergangenen Jahren steten Zuwachs verzeichnen konnte. Interessierten soll dieser Einblick durch die umfangreiche Bibliographie eine Hilfe bei der Recherche zu diesem Thema bieten.
We are interested in modeling some two-level population dynamics, resulting from the interplay of ecological interactions and phenotypic variation of individuals (or hosts) and the evolution of cells (or parasites) of two types living in these individuals. The ecological parameters of the individual dynamics depend on the number of cells of each type contained by the individual and the cell dynamics depends on the trait of the invaded individual. Our models are rooted in the microscopic description of a random (discrete) population of individuals characterized by one or several adaptive traits and cells characterized by their type. The population is modeled as a stochastic point process whose generator captures the probabilistic dynamics over continuous time of birth, mutation and death for individuals and birth and death for cells. The interaction between individuals (resp. between cells) is described by a competition between individual traits (resp. between cell types). We look for tractable large population approximations. By combining various scalings on population size, birth and death rates and mutation step, the single microscopic model is shown to lead to contrasting nonlinear macroscopic limits of different nature: deterministic approximations, in the form of ordinary, integro- or partial differential equations, or probabilistic ones, like stochastic partial differential equations or superprocesses. The study of the long time behavior of these processes seems very hard and we only develop some simple cases enlightening the difficulties involved.
A phagocyte-specific Irf8 gene enhancer establishes early conventional dendritic cell commitment
(2011)
Haematopoietic development is a complex process that is strictly hierarchically organized. Here, the phagocyte lineages are a very heterogeneous cell compartment with specialized functions in innate immunity and induction of adaptive immune responses. Their generation from a common precursor must be tightly controlled. Interference within lineage formation programs for example by mutation or change in expression levels of transcription factors (TF) is causative to leukaemia. However, the molecular mechanisms driving specification into distinct phagocytes remain poorly understood. In the present study I identify the transcription factor Interferon Regulatory Factor 8 (IRF8) as the specification factor of dendritic cell (DC) commitment in early phagocyte precursors. Employing an IRF8 reporter mouse, I showed the distinct Irf8 expression in haematopoietic lineage diversification and isolated a novel bone marrow resident progenitor which selectively differentiates into CD8α+ conventional dendritic cells (cDCs) in vivo. This progenitor strictly depends on Irf8 expression to properly establish its transcriptional DC program while suppressing a lineage-inappropriate neutrophile program. Moreover, I demonstrated that Irf8 expression during this cDC commitment-step depends on a newly discovered myeloid-specific cis-enhancer which is controlled by the haematopoietic transcription factors PU.1 and RUNX1. Interference with their binding leads to abrogation of Irf8 expression, subsequently to disturbed cell fate decisions, demonstrating the importance of these factors for proper phagocyte cell development. Collectively, these data delineate a transcriptional program establishing cDC fate choice with IRF8 in its center.
A systems biological approach towards the molecular basis of heterosis in Arabidopsis thaliana
(2011)
Heterosis is defined as the superiority in performance of heterozygous genotypes compared to their corresponding genetically different homozygous parents. This phenomenon is already known since the beginning of the last century and it has been widely used in plant breeding, but the underlying genetic and molecular mechanisms are not well understood. In this work, a systems biological approach based on molecular network structures is proposed to contribute to the understanding of heterosis. Hybrids are likely to contain additional regulatory possibilities compared to their homozygous parents and, therefore, they may be able to correctly respond to a higher number of environmental challenges, which leads to a higher adaptability and, thus, the heterosis phenomenon. In the network hypothesis for heterosis, presented in this work, more regulatory interactions are expected in the molecular networks of the hybrids compared to the homozygous parents. Partial correlations were used to assess this difference in the global interaction structure of regulatory networks between the hybrids and the homozygous genotypes. This network hypothesis for heterosis was tested on metabolite profiles as well as gene expression data of the two parental Arabidopsis thaliana accessions C24 and Col-0 and their reciprocal crosses. These plants are known to show a heterosis effect in their biomass phenotype. The hypothesis was confirmed for mid-parent and best-parent heterosis for either hybrid of our experimental metabolite as well as gene expression data. It was shown that this result is influenced by the used cutoffs during the analyses. Too strict filtering resulted in sets of metabolites and genes for which the network hypothesis for heterosis does not hold true for either hybrid regarding mid-parent as well as best-parent heterosis. In an over-representation analysis, the genes that show the largest heterosis effects according to our network hypothesis were compared to genes of heterotic quantitative trait loci (QTL) regions. Separately for either hybrid regarding mid-parent as well as best-parent heterosis, a significantly larger overlap between the resulting gene lists of the two different approaches towards biomass heterosis was detected than expected by chance. This suggests that each heterotic QTL region contains many genes influencing biomass heterosis in the early development of Arabidopsis thaliana. Furthermore, this integrative analysis led to a confinement and an increased confidence in the group of candidate genes for biomass heterosis in Arabidopsis thaliana identified by both approaches.
We present XMM-Newton and Chandra observations of the born-again planetary nebula A 30. These X-ray observations reveal a bright unresolved source at the position of the central star whose X-ray luminosity exceeds by far the model expectations for photospheric emission and for shocks within the stellar wind. We suggest that a “born-again hot bubble” may be responsible for this X-ray emission. Diffuse X-ray emission associated with the petal-like features and one of the H-poor knots seen in the optical is also found. The weakened emission of carbon lines in the spectrum of the diffuse emission can be interpreted as the dilution of stellar wind by mass-loading or as the detection of material ejected during a very late thermal pulse.
This Thesis puts its focus on the physics of neutron stars and its description with methods of numerical relativity. In the first step, a new numerical framework the Whisky2D code will be developed, which solves the relativistic equations of hydrodynamics in axisymmetry. Therefore we consider an improved formulation of the conserved form of these equations. The second part will use the new code to investigate the critical behaviour of two colliding neutron stars. Considering the analogy to phase transitions in statistical physics, we will investigate the evolution of the entropy of the neutron stars during the whole process. A better understanding of the evolution of thermodynamical quantities, like the entropy in critical process, should provide deeper understanding of thermodynamics in relativity. More specifically, we have written the Whisky2D code, which solves the general-relativistic hydrodynamics equations in a flux-conservative form and in cylindrical coordinates. This of course brings in 1/r singular terms, where r is the radial cylindrical coordinate, which must be dealt with appropriately. In the above-referenced works, the flux operator is expanded and the 1/r terms, not containing derivatives, are moved to the right-hand-side of the equation (the source term), so that the left hand side assumes a form identical to the one of the three-dimensional (3D) Cartesian formulation. We call this the standard formulation. Another possibility is not to split the flux operator and to redefine the conserved variables, via a multiplication by r. We call this the new formulation. The new equations are solved with the same methods as in the Cartesian case. From a mathematical point of view, one would not expect differences between the two ways of writing the differential operator, but, of course, a difference is present at the numerical level. Our tests show that the new formulation yields results with a global truncation error which is one or more orders of magnitude smaller than those of alternative and commonly used formulations. The second part of the Thesis uses the new code for investigations of critical phenomena in general relativity. In particular, we consider the head-on-collision of two neutron stars in a region of the parameter space where two final states a new stable neutron star or a black hole, lay close to each other. In 1993, Choptuik considered one-parameter families of solutions, S[P], of the Einstein-Klein-Gordon equations for a massless scalar field in spherical symmetry, such that for every P > P⋆, S[P] contains a black hole and for every P < P⋆, S[P] is a solution not containing singularities. He studied numerically the behavior of S[P] as P → P⋆ and found that the critical solution, S[P⋆], is universal, in the sense that it is approached by all nearly-critical solutions regardless of the particular family of initial data considered. All these phenomena have the common property that, as P approaches P⋆, S[P] approaches a universal solution S[P⋆] and that all the physical quantities of S[P] depend only on |P − P⋆|. The first study of critical phenomena concerning the head-on collision of NSs was carried out by Jin and Suen in 2007. In particular, they considered a series of families of equal-mass NSs, modeled with an ideal-gas EOS, boosted towards each other and varied the mass of the stars, their separation, velocity and the polytropic index in the EOS. In this way they could observe a critical phenomenon of type I near the threshold of black-hole formation, with the putative solution being a nonlinearly oscillating star. In a successive work, they performed similar simulations but considering the head-on collision of Gaussian distributions of matter. Also in this case they found the appearance of type-I critical behaviour, but also performed a perturbative analysis of the initial distributions of matter and of the merged object. Because of the considerable difference found in the eigenfrequencies in the two cases, they concluded that the critical solution does not represent a system near equilibrium and in particular not a perturbed Tolmann-Oppenheimer-Volkoff (TOV) solution. In this Thesis we study the dynamics of the head-on collision of two equal-mass NSs using a setup which is as similar as possible to the one considered above. While we confirm that the merged object exhibits a type-I critical behaviour, we also argue against the conclusion that the critical solution cannot be described in terms of equilibrium solution. Indeed, we show that, in analogy with what is found in, the critical solution is effectively a perturbed unstable solution of the TOV equations. Our analysis also considers fine-structure of the scaling relation of type-I critical phenomena and we show that it exhibits oscillations in a similar way to the one studied in the context of scalar-field critical collapse.
Background
Riociguat is the first of a new class of drugs, the soluble guanylate cyclase (sGC) stimulators. Riociguat has a dual mode of action: it sensitizes sGC to the body’s own NO and can also increase sGC activity in the absence of NO. The NO-sGC-pathway is impaired in many cardiovascular diseases such as heart failure, pulmonary hypertension and diabetic nephropathy (DN). DN leads to high cardiovascular morbidity and mortality. There is still a high unmet medical need. The urinary albumin excretion rate is a predictive biomarker for these clinical events. Therefore, we investigated the effect of riociguat, alone and in combination with the angiotensin II receptor antagonist (ARB) telmisartan on the progression of DN in diabetic eNOS knock out mice, a new model closely resembling human pathology.
Methods
Seventy-six male eNOS knockout C57BL/6J mice were divided into 4 groups after receiving intraperitoneal high-dose streptozotocin: telmisartan (1 mg/kg), riociguat (3 mg/kg), riociguat+telmisartan (3 and 1 mg/kg), and vehicle. Fourteen mice were used as non-diabetic controls. After 12 weeks, urine and blood were obtained and blood pressure measured. Glucose concentrations were highly increased and similar in all diabetic groups.
Results
Riociguat, alone (105.2 ± 2.5 mmHg; mean±SEM; n = 14) and in combination with telmisartan (105.0 ± 3.2 mmHg; n = 12), significantly reduced blood pressure versus diabetic controls (117.1 ± 2.2 mmHg; n = 14; p = 0.002 and p = 0.004, respectively), whereas telmisartan alone (111.2 ± 2.6 mmHg) showed a modest blood pressure lowering trend (p = 0.071; n = 14). The effects of single treatment with either riociguat (97.1 ± 15.7 µg/d; n = 13) or telmisartan (97.8 ± 26.4 µg/d; n = 14) did not significantly lower albumin excretion on its own (p = 0.067 and p = 0.101, respectively). However, the combined treatment led to significantly lower urinary albumin excretion (47.3 ± 9.6 µg/d; n = 12) compared to diabetic controls (170.8 ± 34.2 µg/d; n = 13; p = 0.004), and reached levels similar to non-diabetic controls (31.4 ± 10.1 µg/d, n = 12).
Conclusion
Riociguat significantly reduced urinary albumin excretion in diabetic eNOS knock out mice that were refractory to treatment with ARB’s alone. Patients with diabetic nephropathy refractory to treatment with ARB’s have the worst prognosis among all patients with diabetic nephropathy. Our data indicate that additional stimulation of sGC on top of standard treatment with ARB`s may offer a new therapeutic approach for patients with diabetic nephropathy resistant to ARB treatment.
Unique column combinations of a relational database table are sets of columns that contain only unique values. Discovering such combinations is a fundamental research problem and has many different data management and knowledge discovery applications. Existing discovery algorithms are either brute force or have a high memory load and can thus be applied only to small datasets or samples. In this paper, the wellknown GORDIAN algorithm and "Apriori-based" algorithms are compared and analyzed for further optimization. We greatly improve the Apriori algorithms through efficient candidate generation and statistics-based pruning methods. A hybrid solution HCAGORDIAN combines the advantages of GORDIAN and our new algorithm HCA, and it significantly outperforms all previous work in many situations.
"Kinderwelt ist Bewegungswelt" (Schmidt, 1997, S. 156, zitiert nach Schmidt, Hartmann-Tews & Brettschneider, 2003, S. 31). Das kindliche Bewegungsverhalten hat sich bereits im Grundschulalter verändert, so dass sich Bewegungsaktivitäten von Kindern erheblich unterscheiden und keineswegs mehr verallgemeinert werden können. Richtet man den Fokus auf die Frage „Wie bewegt sind unsere Kinder?“ so scheint diese von den Medien bereits beantwortet zu sein, da dort von ansteigendem Bewegungsmangel der heutigen Kinder gegenüber früheren Generationen berichtet wird. Wenn es in den Diskussionen um den Gesundheitszustand unserer Kinder geht, nimmt die körperlich-sportliche Aktivität eine entscheidende Rolle ein. Bewegungsmangel ist hierbei ein zentraler Begriff der in der Öffentlichkeit diskutiert wird. Bei der Betrachtung der einzelnen Studien fällt auf, dass deutliche Defizite in der Messung der körperlich-sportlichen Aktivität bestehen. Zentraler Kritikpunkt in den meisten Studien ist die subjektive Erfassung der körperlich-sportlichen Aktivität. Ein Großteil bisheriger Untersuchungen zum Bewegungsverhalten basiert auf Beobachtungen, Befragungen oder Bewegungstagebüchern. Diese liefern ausschließlich zum Teil subjektive Einschätzungen der Kinder oder Eltern über die tatsächliche Bewegungszeit und -intensität. Das objektive Erfassen der Aktivität bzw. Inaktivität ist zwar seit einigen Jahren zentraler Gegenstand vieler Studien, dennoch gilt es, dieses noch sachkundiger zu lösen, um subjektive und objektive Daten zu vergleichen. Um dem Bewegungsmangel der heutigen Kinder entgegenzuwirken, sind empirisch abgesicherte Erkenntnisse über die Bedingungsfaktoren und die Folgen des veränderten Bewegungsverhaltens dringend nötig. Die Quer- und Längsschnittuntersuchung umfasst die Bereiche Anthropometrie, die Erfassung der körperlich-sportlichen Aktivität und die Herzfrequenzmessung über 24h. Für die Studie konnten 106 Jungen und Mädchen im Zeitraum von Januar 2007 bis April 2009 rekrutiert und überprüft werden. Die physiologischen Parameter wurden mit Hilfe des ACTIHEART-Messsytems aufgezeichnet und berechnet. Die Ergebnisse zur körperlich-sportlichen Aktivität wurden in die Untersuchungsabschnitte Schulzeit gesamt, Pause, Sportunterricht, Nachmittag und 24h unterteilt. Durch das Messsystem werden die Bewegungsaktivität und die Herzfrequenz synchron aufgezeichnet. Das System nimmt die Beschleunigungswerte des Körpers auf und speichert sie im frei wählbaren Zeitintervall, Short oder Long Term, in Form von „activity counts“ ab. Das Messsytem berechnet weiterhin die Intensität körperlicher Aktivität.
Alexander von Humboldt verstand sich zwar sicher nicht als Direktor eines Museums, war aber sehr wohl der Welt der Museen, Bibliotheken und Archive nicht nur als Besucher und Leser, sondern auch als Sammler und Forscher verpflichtet. Durch seine Forschungsreisen nach Amerika und Asien vermehrte er im Verlauf eines langen Gelehrtenlebens viele Sammlungen durch eigene Sammeltätigkeit vor Ort. Seine Feldforschung blieb dabei nicht auf naturwissenschaftliche Aspekte begrenzt, sondern bezog ganz selbstverständlich auch die verschiedenartigsten kulturwissenschaftlichen Forschungsgegenstände mitein. Diese transdisziplinär agierende Praxis im Feld lässt sich zugleich als eine transareale, einzelne Areas übergreifende und damit im Sinne von TransArea Studies aus den Beziehungen, Zirkulationen und Wechselwirkungen jenseits des bloß Territorialen sich speisende Wissenschaftskonzeption begreifen. So lässt sich in seiner Auseinandersetzung mit der amerikanischen Tropenwelt eine doppelte transareale Relationalität erkennen, die einerseits intern die Tropenwelt unterschiedlicher Kontinente miteinander verbindet, andererseits aber extern die Tropen insbesondere mit den gemäßigten Zonen in Relation setzt, um dadurch erst globale Zusammenhänge - einschließlich der sich verändernden Schneegrenzen oder der Wanderungsbewegungen der Pflanzenformen, für die sich die mobile Wissenschaft Humboldts in besonderem Maße interessierte - skizzieren und erläutern zu können. Die Tropen sind für ihn die Zone höchster Mannigfaltigkeit und Vielverbundenheit - oder um es mit heutigen Begriffen zum Ausdruck zu bringen: die TransArea par excellence.