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In cases in which there is the possibility of massive human losses, the threshold likelihood of their occurrence, and the non-excessive costs of their prevention, we ought to act now. This is all the more definitely the case because it may well be that this is the time-of-last-opportunity to head off one or more potential disasters, all of which may still be preventable by sufficiently rapid reductions in carbon emissions from the combustion of fossil fuel. It is unfair that the present generation should incur as heavy a burden as it does of seizing the last opportunity for prevention of disasters like large sea-level rises, but the unfairness is not sufficient to make the burden unreasonable to bear, especially since it is not in fact as heavy as often believed.
Sparse coding is a popular approach to model natural images but has faced two main challenges: modelling low-level image components (such as edge-like structures and their occlusions) and modelling varying pixel intensities. Traditionally, images are modelled as a sparse linear superposition of dictionary elements, where the probabilistic view of this problem is that the coefficients follow a Laplace or Cauchy prior distribution. We propose a novel model that instead uses a spike-and-slab prior and nonlinear combination of components. With the prior, our model can easily represent exact zeros for e.g. the absence of an image component, such as an edge, and a distribution over non-zero pixel intensities. With the nonlinearity (the nonlinear max combination rule), the idea is to target occlusions; dictionary elements correspond to image components that can occlude each other. There are major consequences of the model assumptions made by both (non)linear approaches, thus the main goal of this paper is to isolate and highlight differences between them. Parameter optimization is analytically and computationally intractable in our model, thus as a main contribution we design an exact Gibbs sampler for efficient inference which we can apply to higher dimensional data using latent variable preselection. Results on natural and artificial occlusion-rich data with controlled forms of sparse structure show that our model can extract a sparse set of edge-like components that closely match the generating process, which we refer to as interpretable components. Furthermore, the sparseness of the solution closely follows the ground-truth number of components/edges in the images. The linear model did not learn such edge-like components with any level of sparsity. This suggests that our model can adaptively well-approximate and characterize the meaningful generation process.
Ceraceosorus bombacis is an early-diverging lineage of smut fungi and a pathogen of cotton trees (Bombax ceiba). To study the evolutionary genomics of smut fungi in comparison with other fungal and oomycete pathogens, the genome of C. bombacis was sequenced and comparative genomic analyses were performed. The genome of 26.09 Mb encodes for 8,024 proteins, of which 576 are putative-secreted effector proteins (PSEPs). Orthology analysis revealed 30 ortholog PSEPs among six Ustilaginomycotina genomes, the largest groups of which are lytic enzymes, such as aspartic peptidase and glycoside hydrolase. Positive selection analyses revealed the highest percentage of positively selected PSEPs in C. bombacis compared with other Ustilaginomycotina genomes. Metabolic pathway analyses revealed the absence of genes encoding for nitrite and nitrate reductase in the genome of the human skin pathogen Malassezia globosa, but these enzymes are present in the sequenced plant pathogens in smut fungi. Interestingly, these genes are also absent in cultivable oomycete animal pathogens, while nitrate reductase has been lost in cultivable oomycete plant pathogens. Similar patterns were also observed for obligate biotrophic and hemi-biotrophic fungal and oomycete pathogens. Furthermore, it was found that both fungal and oomycete animal pathogen genomes are lacking cutinases and pectinesterases. Overall, these findings highlight the parallel evolution of certain genomic traits, revealing potential common evolutionary trajectories among fungal and oomycete pathogens, shaping the pathogen genomes according to their lifestyle.
Background: Xanthophyllomyces dendrorhous is a basal agaricomycete with uncertain taxonomic placement, known for its unique ability to produce astaxanthin, a carotenoid with antioxidant properties. It was the aim of this study to elucidate the organization of its CoA-derived pathways and to use the genomic information of X. dendrorhous for a phylogenomic investigation of the Basidiomycota.
Results: The genome assembly of a haploid strain of Xanthophyllomyces dendrorhous revealed a genome of 19.50 Megabases with 6385 protein coding genes. Phylogenetic analyses were conducted including 48 fungal genomes. These revealed Ustilaginomycotina and Agaricomycotina as sister groups. In the latter a well-supported sister-group relationship of two major orders, Polyporales and Russulales, was inferred. Wallemia occupies a basal position within the Agaricomycotina and X. dendrorhous represents the basal lineage of the Tremellomycetes, highlighting that the typical tremelloid parenthesomes have either convergently evolved in Wallemia and the Tremellomycetes, or were lost in the Cystofilobasidiales lineage. A detailed characterization of the CoA-related pathways was done and all genes for fatty acid, sterol and carotenoid synthesis have been assigned.
Conclusions: The current study ascertains that Wallemia with tremelloid parenthesomes is the most basal agaricomycotinous lineage and that Cystofilobasidiales without tremelloid parenthesomes are deeply rooted within Tremellomycetes, suggesting that parenthesomes at septal pores might be the core synapomorphy for the Agaricomycotina. Apart from evolutionary insights the genome sequence of X. dendrorhous will facilitate genetic pathway engineering for optimized astaxanthin or oxidative alcohol production.
Background: Astrocytomas are the most common primary brain tumors distinguished into four histological grades. Molecular analyses of individual astrocytoma grades have revealed detailed insights into genetic, transcriptomic andepigenetic alterations. This provides an excellent basis to identify similarities and differences between astrocytoma grades. Methods: We utilized public omics data of all four astrocytoma grades focusing on pilocytic astrocytomas (PA I), diffuse astrocytomas (AS II), anaplastic astrocytomas (AS III) and glioblastomas (GBM IV) to identify similarities and differences using well-established bioinformatics and systems biology approaches. We further validated the expression and localization of Ang2 involved in angiogenesis using immunohistochemistry. Results: Our analyses show similarities and differences between astrocytoma grades at the level of individual genes, signaling pathways and regulatory networks. We identified many differentially expressed genes that were either exclusively observed in a specific astrocytoma grade or commonly affected in specific subsets of astrocytoma grades in comparison to normal brain. Further, the number of differentially expressed genes generally increased with the astrocytoma grade with one major exception. The cytokine receptor pathway showed nearly the same number of differentially expressed genes in PA I and GBM IV and was further characterized by a significant overlap of commonly altered genes and an exclusive enrichment of overexpressed cancer genes in GBM IV. Additional analyses revealed a strong exclusive overexpression of CX3CL1 (fractalkine) and its receptor CX3CR1 in PA I possibly contributing to the absence of invasive growth. We further found that PA I was significantly associated with the mesenchymal subtype typically observed for very aggressive GBM IV. Expression of endothelial and mesenchymal markers (ANGPT2, CHI3L1) indicated a stronger contribution of the micro-environment to the manifestation of the mesenchymal subtype than the tumor biology itself. We further inferred a transcriptional regulatory network associated with specific expression differences distinguishing PA I from AS II, AS III and GBM IV. Major central transcriptional regulators were involved in brain development, cell cycle control, proliferation, apoptosis, chromatin remodeling or DNA methylation. Many of these regulators showed directly underlying DNA methylation changes in PA I or gene copy number mutations in AS II, AS III and GBM IV. Conclusions: This computational study characterizes similarities and differences between all four astrocytoma grades confirming known and revealing novel insights into astrocytoma biology. Our findings represent a valuable resource for future computational and experimental studies.
During CNS development and adult neurogenesis, immature neurons travel from the germinal zones towards their final destination using cellular substrates for their migration. Classically, radial glia and neuronal axons have been shown to act as physical scaffolds to support neuroblast locomotion in processes known as gliophilic and neurophilic migration, respectively (Hatten, 1999; Marin and Rubenstein, 2003; Rakic, 2003). In adulthood, long distance neuronal migration occurs in a glial-independent manner since radial glia cells differentiate into astrocytes after birth. A series of studies highlight a novel mode of neuronal migration that uses blood vessels as scaffolds, the so-called vasophilic migration. This migration mode allows neuroblast navigation in physiological and also pathological conditions, such as neuronal precursor migration after ischemic stroke or cerebral invasion of glioma tumor cells. Here we review the current knowledge about how vessels pave the path for migrating neurons and how trophic factors derived by glio-vascular structures guide neuronal migration both during physiological as well as pathological processes
‘Being with oneself in the other’ is a well-known formula that Hegel uses to characterize the basic relation of subjective freedom. This phrase points to the fact that subjects can only come to themselves if they remain capable of going beyond themselves. This motif also plays a significant role in Hegel’s philosophy of art. The article further develops this motif by exploring the extent to which this polarity of selfhood and otherhood is also characteristic of states of aesthetic freedom. It does not offer an exegesis of Hegel’s writings, but attempts to remain as close as possible to the spirit of Hegel’s philosophy – with some help from Kant and Adorno. The argument begins with some key terms on the general state of subjective freedom in order to distinguish it from the particular role of aesthetic freedom and then, finally, drawing again on Hegel, works out the sense in which aesthetic freedom represents an important variant of freedom.
Diffusion tensor imaging (DTI) is amongst the simplest mathematical models available for diffusion magnetic resonance imaging, yet still by far the most used one. Despite the success of DTI as an imaging tool for white matter fibers, its anatomical underpinnings on a microstructural basis remain unclear. In this study, we used 65 myelin-stained sections of human premotor cortex to validate modeled fiber orientations and oft used microstructure-sensitive scalar measures of DTI on the level of individual voxels. We performed this validation on high spatial resolution diffusion MRI acquisitions investigating both white and gray matter. We found a very good agreement between DTI and myelin orientations with the majority of voxels showing angular differences less than 10°. The agreement was strongest in white matter, particularly in unidirectional fiber pathways. In gray matter, the agreement was good in the deeper layers highlighting radial fiber directions even at lower fractional anisotropy (FA) compared to white matter. This result has potentially important implications for tractography algorithms applied to high resolution diffusion MRI data if the aim is to move across the gray/white matter boundary. We found strong relationships between myelin microstructure and DTI-based microstructure-sensitive measures. High FA values were linked to high myelin density and a sharply tuned histological orientation profile. Conversely, high values of mean diffusivity (MD) were linked to bimodal or diffuse orientation distributions and low myelin density. At high spatial resolution, DTI-based measures can be highly sensitive to white and gray matter microstructure despite being relatively unspecific to concrete microarchitectural aspects.
Background: Hundreds of West African healthcare workers (HCW) have become ill with Ebola virus disease (EVD) and died during the recent outbreak. The occurrence of occupational infections in laboratories could be due to the lack of use of personal protective equipment, the failure to implement specific regulations about the use of equipment and how to work with hazardous materials. Our study attempted to assess the information as well as training level of HCW of a German high level isolation unit and their concern over an occupationally acquired EVD.
Methods: During the recent Ebola virus outbreak a survey was conducted among HCWs, using an anonymous questionnaire.
Results: Although 70% of our total study population stated that they have all the information needed to care for Ebola patients, only 18.2% of laboratory workers and 29.4% of the HCW of the virology department felt sufficiently trained. The HCW rated the Internet (64.3%) and the daily press (54.3%) as the most important sources of information. Medical literature (45.7%) and official institutions (40.4%) were rated less often.
Conclusions: Formulated pointedly, the HCW turned to popular science to get the information they need to feel safe. Further in house training regarding practical skills and reference to scientific literature would be a better solution to ensure workplace safety.
Background: The pathomechanisms of atherosclerosis and vascular remodelling are under intense research. Only a few in vivo tools to study these processes longitudinally in animal experiments are available. Here, we evaluated the potential of micro-CT technology.
Methods: Lumen areas of the common carotid arteries (CCA) in the ApoE-/- partial carotid artery ligation mouse model were compared between in vivo and ex vivo micro-CT technique and serial histology in a total of 28 animals. AuroVist-15 nm nanoparticles were used as in vivo blood pool contrast agent in a Skyscan 1176 micro-CT at resolution of 18 μmeter voxel size and a mean x-ray dose of 0.5 Gy. For ex vivo imaging, animals were perfused with MicroFil and imaged at 9 μmeter voxel size. Lumen area was evaluated at postoperative days 7, 14, and 28 first by micro-CT followed by histology.
Results: In vivo micro-CT and histology revealed lumen loss starting at day 14. The lumen profile highly correlated (r = 0.79, P<0.0001) between this two methods but absolute lumen values obtained by histology were lower than those obtained by micro-CT. Comparison of in vivo and ex vivo micro-CT imaging revealed excellent correlation (r = 0.83, P<0.01). Post mortem micro-CT yielded a higher resolution than in vivo micro-CT but there was no statistical difference of lumen measurements in the partial carotid artery ligation model.
Conclusion: These data demonstrate that in vivo micro-CT is a feasible and accurate technique with low animal stress to image remodeling processes in the murine carotid artery.
Cardiac arrhythmias are often associated with mutations in ion channels or other proteins. To enable drug development for distinct arrhythmias, model systems are required that allow implementing patient-specific mutations. We assessed a muscular pump in Caenorhabditis elegans. The pharynx utilizes homologues of most of the ion channels, pumps and transporters defining human cardiac physiology. To yield precise rhythmicity, we optically paced the pharynx using channelrhodopsin-2. We assessed pharynx pumping by extracellular recordings (electropharyngeograms--EPGs), and by a novel video-microscopy based method we developed, which allows analyzing multiple animals simultaneously. Mutations in the L-type VGCC (voltage-gated Ca(2+)-channel) EGL-19 caused prolonged pump duration, as found for analogous mutations in the Cav1.2 channel, associated with long QT syndrome. egl-19 mutations affected ability to pump at high frequency and induced arrhythmicity. The pharyngeal neurons did not influence these effects. We tested whether drugs could ameliorate arrhythmia in the optogenetically paced pharynx. The dihydropyridine analog Nemadipine A prolonged pump duration in wild type, and reduced or prolonged pump duration of distinct egl-19 alleles, thus indicating allele-specific effects. In sum, our model may allow screening of drug candidates affecting specific VGCCs mutations, and permit to better understand the effects of distinct mutations on a macroscopic level.
The implementation of pump-probe experiments with ultrashort laser pulses enables the study of dynamical processes in atoms or molecules, which may provide a deeper inside in their physical origin. The application of this method to systems as nitrous oxide, which is not only a simple example for polyatomic molecules but which also plays a crucial role in the greenhouse effect, promises interesting and beneficial findings. This thesis presents, on the one hand, the technical extension of an existing experimental setup for high-harmonic generation (HHG) and ultra-fast laser physics by an extreme ultraviolet (XUV) spectrometer for the in-situ observation of the harmonic spectrum during ongoing measurements. The present setup enables the production of short laser pulse trains in the XUV spectral range with durations of a few hundred attoseconds (1 as = 10^−18 s) via HHG and supports to perform XUV-IR pump-probe experiments using the infrared (IR) driving field with durations of a few femtoseconds. Moreover, a reaction microscope is implemented, which enables the coincident detection of several charged particles emerging from an ionization or dissociation process and to reconstruct their full 3-D-momentum vectors. With this technique it is possible to perform time-resolved momentum spectroscopy of few-particle quantum systems. Here, the design and the calibration of the XUV spectrometer is presented as well as a first application to the analysis of experimental data by providing information on the produced photon energies. On the other hand, the results of an XUV-pump IR-probe measurement on nitrous oxide (N2O) are discussed. With the broad harmonic spectrum (∼ 17 − 45 eV) it is possible to address several states of the singly and doubly ionized cation. One reaction channel is the single ionization into a stable state of N2O+. Here, the coincidently measured photoelectron energies allow the observation of sidebands, which served to estimate the pulse durations of the involved XUV pulse trains as well as of the fundamental IR pulses. Additionally, single ionization of nitrous oxide can lead to a dissociation into a charged and a neutral fragment. The four respective dissociation channels are compared by presenting their branching ratios, kinetic energy release (KER) distributions and their dependencies on the time delay between pump and probe pulse. In the production of the dication, there are two competitive processes: direct double ionization considering photon energies above the double-ionization threshold, and autoionization of singly ionized and excited molecules in the case of photon energies near the double-ionization threshold. In both cases, the ionization leads to a Coulomb explosion into two charged fragments, where the N − N bond or the N − O bond may dissociate. The influence of the IR-probe field on the ionization yield and the KER was investigated for both dissociation channels and compared. In addition, the corresponding photoelectron energy spectra are presented, which show indications for autoionizing states being involved, and their dependence on the delay and the KER of the respective ions is analyzed.
Im Rahmen dieser Arbeit werden verschiedene Modellsysteme untersucht, die Metriken der klassischen Allgemeinen Relativitätstheorie mit Erweiterungen vergleichen, in denen Ereignishorizonte nicht existieren müssen. Die untersuchten Korrekturterme sind durch Schwachfeldmessungen, wie sie zum Beispiel in unserem Sonnensystem durchgeführt werden, nicht überprüfbar. Es ist deshalb nötig solche Systeme zu betrachten, in denen die vollständigen Gleichungen berücksichtigt werden müssen und keine Entwicklungen für schwache Felder gemacht werden können. Es gibt eine Reihe von astrophysikalischen Systemen, die diese Bedingungen erfüllen, wie das Galaktische Zentrum oder Doppelsternsysteme.
Im zweiten Kapitel der Arbeit werden Testteilchenorbits in einem Zentralpotential beschrieben und Unterschiede zwischen der klassischen und einer modifizierten Kerr-Metrik herausgearbeitet. Drei neue Phänomene der modifizierten Metrik gegenüber der Klassischen treten hier in Erscheinung. Zum einen haben Teilchen, die sich auf prograden Bahnen um den Zentralkörper drehen, ein Maximum in ihrer Winkelgeschwindigkeit. Zum anderen ist das Phänomen des frame-draggings deutlich schwächer ausgeprägt. Schließlich tritt ein letzter stabiler Orbit für entsprechend schnell rotierende Zentralkörper nicht mehr auf. Gleichzeitig sind die Unterschiede in den beiden Metriken für große Abstände (r > 10m) nahezu vernachlässigbar. In Kapitel 3 werden diese Ergebnisse auf zwei unterschiedliche Modelle zur Beschreibung von Akkretionsscheiben angewendet. Untersucht wird zum einen das Verhalten der Eisen-Kα-Emissionslinie und zum anderen der Energiefluss aus einer Akkretionsscheibe.
In der Form der Eisen-Kα-Emissionslinie gibt es eine deutliche Zunahme des rotverschobenen Anteils der Strahlung in der modifizierten Kerr-Metrik gegenüber der klassischen Kerr-Metrik. Die Akkretionsscheibe nach Page und Thorne zeigt unter Verwendung der modifizierten Kerr-Metrik eine signifikante Erhöhung der abgestrahlten Energie, wenn der Zentralkörper so schnell rotiert, dass kein letzter stabiler Orbit mehr auftritt. Zusätzlich gibt es hier in der Scheibe einen dunklen Ring im Vergleich zu den Bildern höherer Ordnung, die in der klassischen Kerr-Metrik auftreten. Erklärbar sind diese Phänomene dadurch, dass sich Teilchen auf stabilen Bahnen in der modifizierten Kerr-Metrik näher an den Zentralkörper heran bewegen können, als es in der klassischen Kerr-Metrik der Fall ist. Die Rotverschiebung ist für beide Fälle annäherend gleich.
Kapitel 4 gibt eine kurze Einführung in die Beschreibung von Gravitationswellen im Rahmen der linearisierten Allgemeinen Relativitätstheorie. Hier wird als Modell ein Binärsystem, wie etwa der Hulse-Taylor-Pulsar, betrachtet. Die Unterschiede zwischen der klassischen Theorie und einer Beschreibung unter Hinzunahme von Zusatztermen sind hier erwartungsgemäß sehr gering, da die Linearisierung der Gleichungen dazu führt, dass Starkfeldeffekte vernachlässigt werden. Für große Abstände, was in diesem Fall auch schwache Felder impliziert, sind die Erweiterungen der Gleichungen vernachlässigbar. Hier werden zum Teil auch Effekte in der klassischen ART vernachlässigt.
In Kapitel 5 befindet sich ein kurzer Ausblick in die 3+1-Formulierung der Einsteingleichungen für die numerische Beschreibung von Gravitationsphänomenen. Diese Beschreibung ermöglicht es auch komplexe Systeme ohne viele nähernde Annahmen genau beschreiben zu können. Diese Systeme können zum einen Akkretionsscheiben um kompakte Objekte sein, aber auch die Verschmelzung von zwei massiven Objekten und die damit verbundenen Gravitationswellensignale. Dadurch lassen sich die Vorhersagen der ART oder etwaiger Erweiterungen präziser modellieren.
Die vorgestellten Ergebnisse liegen innerhalb der Einschränkungen durch aktuelle Messungen. Zukünftige Messungen wie genauere Beobachtungen des Galaktischen Zentrums durch das Event Horizon Telescope sind aber voraussichtlich dazu in der Lage zwischen den untersuchten Metriken zu unterscheiden.
In der Region Rhein-Main steht mit dem Rhein-Main-Mobilitätspanel (RMP) seit dem Jahr 2008 ein Datensatz zur Verfügung, der im Vergleich zu früheren Datensätzen eine verbesserte Beschreibung der regionalen Mobilitätsentwicklung ermöglicht. In dieser Methodenstudie wird überprüft, inwieweit Anschlussmöglichkeiten dieses Datensatzes mit anderen regionalen Datensätzen bestehen. Das Ziel dieser Studie ist somit die Prüfung, inwiefern in der Region Rhein-Main vorliegende Mobilitäts- und andere (insbesondere raumbezogene) Daten mit dem RMP kombiniert werden können, um daraus neue Erkenntnisse und Handlungsoptionen für die Entscheidungsträger vor Ort zu entwickeln. Im Rahmen der Studie werden sowohl ein Vergleich der Stichprobenzusammensetzung und der Erhebungsmethodik als auch der erfassten Kennziffern durchgeführt und Möglichkeiten zur Kombination mit Raumstrukturdaten überprüft. Weiterhin werden zentrale Mobilitätskennziffern der betrachteten Erhebungen (MiD 2002, 2008; SrV 2008; Deutsches Mobilitätspanel 2002-2008) gegenübergestellt und die Anwendbarkeit des harmonisierten und kombinierten Datensatzes hinsichtlich einer inhaltlichen Fragestellung überprüft.
In dieser Arbeit werden Verfahren vorgestellt, mit dem sich hochaufgelöste wissenschaftliche Illustrationen in einem interaktiven Vorgang erstellen lassen. Die Basis dafür bildet die neu eingeführte GPU-basierte Illustrations-Pipeline, in der auf Grundlage eines 3D-Modells Bildebenen frei angelegt und miteinander kombiniert werden können. In einer Ebene wird ein bestimmter Aspekt der Illustration mit einer auswählbaren Technik gezeigt. Die Parameter der Technik sind interaktiv editierbar. Um Effizienz zu gewährleisten ist das gesamte Verfahren so konzipiert, dass es soweit wie möglich die Berechnungen auf der GPU durchführt. So ist es möglich, dass die Illustrationen mit interaktiven Frameraten gerendert werden.
Im Rahmen des FRANZ-Projektes wurde nach einer Ionenquelle verlangt welche in der Lage ist einen intensiven hochbrillanten Protonenstrahl von 200 mA bei 120 keV im Dauerstrichbetrieb zur Verfügung zu stellen, bei gleichzeitig niedriger Strahlemittanz. Der recht hohe Protonenstrom von 200 mA stellt dabei eine Herausforderung an den Experimentator dar.
Die grundsätzliche Problematik bei der Entwicklung einer solchen Ionenquelle besteht im Wesentlichen darin, ein geeignetes Extraktionssystem zu designen, welches in der Lage ist den geforderten hohen Protonenstrom zu extrahieren und transportieren. In diesem Zusammenhang wurden Abschätzungen bezüglich des notwendigen Emissionsradius, der elektrischen Feldstärke im Extraktionsspalt sowie des Protonenanteils für den verlangten Protonenstrom von 200 mA durchgeführt. Für die praktische Umsetzung wurden Lösungsstrategien erarbeitet. Ziel war es die elektrische Feldstärke im Gap so hoch wie möglich und den Radius der Emissionsöffnung so klein wie möglich zu wählen, bei gleichzeitig möglichst hohem Protonenanteil. Basierend auf diesen Erkenntnissen wurde ein Prototyp der Bogenentladungs-Volumenionenquelle entwickelt und erfolgreich in Betrieb genommen.
Zur Steigerung des Protonenanteils im Wasserstoffplasma wurden diverse Parameter der Ionenquelle optimiert wie bspw. Bogenleistung, Gasdruck sowie insbesondere die Feldverteilung und die magnetische Flussdichte des magnetischen Filters. Diese Ergebnisse wurden mit dem verbesserten theoretischen Modell zur Erzeugung von atomaren Wasserstoffionenstrahlen verglichen. Um die elektrische Feldstärke im Extraktionsspalt zu steigern wurden die Elektroden aus einem thermisch belastbaren Material hergestellt und einer speziellen Oberflächenbehandlung unterzogen. Des Weiteren wurden theoretische und experimentelle Untersuchungen bezüglich der Emissionsstromdichte und der Strahlqualität durchgeführt. Weiterhin wurde die Emittanz des Ionenstrahls berechnet sowie mit einer eigens am Institut für Angewandte Physik entwickelten Pepperpot-Emittanzmessanlage experimentell bestimmt. Die vorliegende Dissertation präsentiert die Ergebnisse der Entwicklung dieser hocheffizienten Bogenentladungs-Volumenionenquelle.
A premise of the capabilities perspective in strategy is that firm-specific capabilities allow some firms to be unusually adept at exploiting growth opportunities. Since few firms have the capacity to internally generate the quantity or variety of strategic resources needed to exploit growth opportunities, the ability to externally acquire complementary resources is critical to the acquisition of competitive advantage. However, the external sourcing of resources exposes the firm’s strategic resources to risks of expropriation. We argue this threat gives capable firms incentive to use internally generated strategic resources to pursue growth opportunities before turning to external sources. A pecking order theory of strategic resource deployment is implied. Data from a 22-year sample of cross-border investment partnership decisions made by U.S.-based venture capital firms lend support to our theory.
Background & aims: Current guidelines recommend immunosuppressive treatment (IT) in patients with primary sclerosing cholangitis (PSC) and elevated aminotransferase levels more than five times the upper limit of normal and elevated serum IgG-levels above twice the upper limit of normal. Since there is no evidence to support this recommendation, we aimed to assess the criteria that guided clinicians in clinical practice to initiate IT in patients with previously diagnosed PSC.
Methods: This is a retrospective analysis of 196 PSC patients from seven German hepatology centers, of whom 36 patients had received IT solely for their liver disease during the course of PSC. Analyses were carried out using methods for competing risks.
Results: A simplified autoimmune hepatitis (AIH) score >5 (HR of 36, p<0.0001) and a modified histological activity index (mHAI) greater than 3/18 points (HR 3.6, p = 0.0274) were associated with the initiation of IT during the course of PSC. Of note, PSC patients who subsequently received IT differed already at the time of PSC diagnosis from those patients, who did not receive IT during follow-up: they presented with increased levels of IgG (p = 0.004) and more frequently had clinical signs of cirrhosis (p = 0.0002).
Conclusions: This is the first study which investigates the parameters associated with IT in patients with PSC in clinical practice. A simplified AIH score >5 and a mHAI score >3, suggesting concomitant features of AIH, influenced the decision to introduce IT during the course of PSC. In German clinical practice, the cutoffs used to guide IT may be lower than recommended by current guidelines.