Interventionsradiologische Behandlung akuter Blutungen

Seit vielen Jahren stellt die kathetergestützte Embolisation eine wertvolle Alternative zur offenen chirurgischen Behandlung bei Patienten mit bedrohlichen, arteriellen Blutungen dar. Die Embolisation soll vor allem den Vorteil einer geringeren perioperativen Morbidität und Mortalität im Vergleich zu den alternativen Behandlungsformen bieten. Histoacryl als flüssiges Embolisationsmaterial, ist vom Handling her schwieriger, als partikuläre Embolisationsmaterialien, bietet aber den Vorteil des sicheren und sofortigen Gefäßverschlusses unabhängig von der Gerinnungssituation. Die hier vorliegende Studie soll den Stellenwert von Histoacryl als Embolisat beleuchten und hervorheben. Bei der Studie handelt es sich um eine Untersuchung des Behandlungserfolges von akuten inneren arteriellen Blutungen mittels Embolisation von Patienten des Marburger Universitätsklinikums

Genes and pathways for CO2 fixation in the obligate, chemolithoautotrophic acidophile, Acidithiobacillus ferrooxidans, Carbon fixation in A. ferrooxidans

<p>Abstract</p> <p>Background</p> <p><it>Acidithiobacillus ferrooxidans </it>is chemolithoautotrophic γ-proteobacterium that thrives at extremely low pH (pH 1-2). Although a substantial amount of information is available regarding CO₂uptake and fixation in a variety of facultative autotrophs, less is known about the processes in obligate autotrophs, especially those living in extremely acidic conditions, prompting the present study.</p> <p>Results</p> <p>Four gene clusters (termed <it>cbb1-4</it>) in the <it>A. ferrooxidans </it>genome are predicted to encode enzymes and structural proteins involved in carbon assimilation via the Calvin-Benson-Bassham (CBB) cycle including form I of ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO, EC 4.1.1.39) and the CO₂-concentrating carboxysomes. RT-PCR experiments demonstrated that each gene cluster is a single transcriptional unit and thus is an operon. Operon <it>cbb1 </it>is divergently transcribed from a gene, <it>cbbR</it>, encoding the LysR-type transcriptional regulator CbbR that has been shown in many organisms to regulate the expression of RubisCO genes. Sigma⁷⁰-like -10 and -35 promoter boxes and potential CbbR-binding sites (T-N₁₁-A/TNA-N₇TNA) were predicted in the upstream regions of the four operons. Electrophoretic mobility shift assays (EMSAs) confirmed that purified CbbR is able to bind to the upstream regions of the <it>cbb1</it>, <it>cbb2 </it>and <it>cbb3 </it>operons, demonstrating that the predicted CbbR-binding sites are functional <it>in vitro</it>. However, CbbR failed to bind the upstream region of the <it>cbb4 </it>operon that contains <it>cbbP</it>, encoding phosphoribulokinase (EC 2.7.1.19). Thus, other factors not present in the assay may be required for binding or the region lacks a functional CbbR-binding site. The <it>cbb3 </it>operon contains genes predicted to encode anthranilate synthase components I and II, catalyzing the formation of anthranilate and pyruvate from chorismate. This suggests a novel regulatory connection between CO₂fixation and tryptophan biosynthesis. The presence of a form II RubisCO could promote the ability of <it>A. ferrooxidans </it>to fix CO₂at different concentrations of CO₂.</p> <p>Conclusions</p> <p><it>A. ferrooxidans </it>has features of <it>cbb </it>gene organization for CO₂-assimilating functions that are characteristic of obligate chemolithoautotrophs and distinguish this group from facultative autotrophs. The most conspicuous difference is a separate operon for the <it>cbbP </it>gene. It is hypothesized that this organization may provide greater flexibility in the regulation of expression of genes involved in inorganic carbon assimilation.</p

The Dynamics of Business Model Transformation: Innovation and Internationalization

Els darrers anys, els models de negoci han experimentat un impuls notable en la recerca acadèmica. Com a resposta a les demandes recents de la literatura en matèria de direcció estratègica, aquesta tesi amplia l’estudi dels models de negoci mitjançant l’anàlisi d‘una dimensió que rarament s‘estudia a la literatura: la transformació del model de negoci i les seves dinàmiques internes. Malgrat el paper destacat dels models de negoci en la recerca recent, se sap poc sobre com es transformen els models de negoci en el temps i com s’adapten a ecosistemes canviants. A través de tres assaigs, aquesta tesi explora la transformació dels models de negoci centrant-se en la dinàmica de la innovació dels models de negoci i la transformació d’aquests models amb la internacionalització. Avançant en les conclusions empíriques dels tres assaigs i les idees integradores que impulsen l’agenda de la recerca sobre els models de negoci, proposo un nou model conceptual i presento la transformació del model de negoci com un constructe multidimensional, que es basa en les eleccions estratègiques de l’empresa. Aquestes eleccions, a seu torn, es reflecteixen en les limitacions que determinen l’espai d‘oportunitat de l‘empresa focal, que s‘ha de realitzar amb l‘objectiu d‘incrementar la creació de valor de l‘empresa focal i el seu potencial de captació de valor. Aquesta tesi té com a fonaments la recerca en direcció estratègica i la teoria de l’organització, i també es basa en la teoria institucional i la internacionalització, cosa que contribueix als debats actuals en els camps de l’estratègia, la innovació i la direcció internacional. Alhora que se centra en el desenvolupament de la teoria i adopta un enfocament semiconstructivista, la tesi utilitza diversos mètodes de recerca, com l’anàlisi teòrica, la grounded theory, i recorre a diversos casos per desenvolupar i demostrar diverses proposicions, i també el concepte de transformació dels models de negoci en la literatura. La tesi conclou proposant potencials vies per al desenvolupament d’investigacions futures.En los últimos años, los modelos de negocio han cobrado sustancial impulso en la investigación académica. Como respuesta a las recientes peticiones de la literatura en dirección estratégica, esta tesis extiende el estudio de modelos de negocio mediante la exploración de una dimensión raramente considerada en la literatura: la transformación del modelo de negocio y sus dinámicas subyacentes. A pesar del papel destacado de los modelos de negocio en la investigación reciente, poco se sabe acerca de cómo los modelos de negocio se transforman en el tiempo y cómo se adaptan a ecosistemas cambiantes. A través de tres ensayos, esta tesis explora la transformación de modelos de negocio enfocándose en la dinámica de la innovación de los modelos de negocio y la transformación de los modelos de negocio en la internacionalización. Avanzando en los hallazgos empíricos de los tres ensayos y las ideas integradoras que impulsan la agenda de investigación modelo de negocio, propongo un nuevo modelo conceptual y presento la transformación del modelo de negocio como un constructo multidimensional, que reside en las elecciones estratégicas de la empresa. Estos, a su vez, se reflejan por las restricciones que determinan espacio de oportunidades de la empresa focal, que ha de ser realizado con el objetivo de aumentar la creación y captura de valor potencial de la misma. Esta tesis tiene como pilares la investigación en dirección estratégica así como la teoría de organización, basándose en la teoría institucional y la internacionalización, lo que contribuye a los debates actuales dentro de los campos de estrategia, innovación y dirección internacional. Mientras se mantiene el foco en el desarrollo de la teoría, en un enfoque semi-constructivista, la tesis emplea diversos métodos de investigación, como el análisis teórico, grounded theory, y varios estudios de caso para desarrollar y testear diversas proposiciones, así como establecer el concepto de transformación de modelos de negocio en literatura. La tesis concluye con potenciales vías para el desarrollo de futuras investigaciones.In recent years, business models have gained substantial momentum in academic research. As a response to recent calls in strategic management literature for novel research, this dissertation extends the study of business models by exploring a dimension rarely considered in literature: business model transformation and its underlying dynamics. Despite the prominent role of business models in recent research, little is known about how business models transform over time and adapt to evolving ecosystems. In three essays, I address this gap by exploring the notion of business model transformation enabled through its dynamics of business model innovation and business model growth through internationalization. Advancing on the empirical findings from the three essays and the integrative insights that move the business model research agenda forward, I propose a conceptual model and introduce business model transformation as a multi-dimensional construct, which resides in the focal firm’s strategic choices. These choices, in turn, are reflected by the constraints that determine the focal firm’s opportunity space, which is to be realized with the objective to increase the focal firm’s value creation and value capture potential. I theoretically build on strategic management research as well as on organization, institutional and internationalization theory as the three pillars of this thesis, contributing to the current debates within the strategy, innovation and international management fields. While maintaining the focus on theory development, in a semi-constructivist approach, I employ diverse research methods, such as theoretical analysis, grounded theory, and multiple case studies to develop and test various propositions, as well as establish the concept of business model transformation in literature. The thesis concludes with fruitful avenues for future research

Potenziale Finanzieller Grundbildung für die Verbraucherbildung

Ausgelotet werden Schnittstellen zwischen Finanzieller Grundbildung als Teilbereich einer umfassenderen ökonomischen Grundbildung und der Verbraucherbildung Erwachsener. Der kompetente Umgang mit Geld in alltäglichen Angelegenheiten als notwendige Bedingung einer sozialen Teilhabe zeichnet sich durch eine große Komplexität an Handlungsanforderungen aus und erfordert neue Ansätze der Ansprache. Hier eröffnet die Sensibilisierung von Multiplikatoren aus unterschiedlichen Disziplinen neue Zugänge

Immersive Learning for Low-Literate People: Opportunities of Augmented Reality in Basic Financial Literacy

Vorliegende Befunde zeigen, dass die Versprechungen der Digitalisierung des Lernens (noch) nicht eingelöst werden konnten. Der Zugang zur Bildung ist trotz digitaler Angebote in den verschiedenen Bildungssektoren hoch selektiv, die Nutzung von Bildungsangeboten hängt (nach wie vor) von der individuellen Bildungssozialisation, vom Alter und Wohnort ab. Gerade für die Erwachsenenbildung, die in hohem Masse auf die freiwillige Beteiligung an ihren Bildungsangeboten setzt, sind diese Befunde alles andere als ermutigend. Der Beitrag zeigt auf, mit welchen Ansätzen immersive Angebote der Erwachsenenbildung – und hier insbesondere im Bereich der Alphabetisierung/Grundbildung – eine hohe Teilnehmendenbindung sowie günstige Lernprognosen realisieren können. Der Fokus liegt insbesondere darauf, wie immersive Lerngelegenheiten inhaltlich und didaktisch gestaltet sein müssen, um vielfältige Herausforderungen in Grundbildungskursen (u. a. lebensweltrelevante Themen, Lernortunabhängigkeit, Kollaborationsfähigkeit) zu adressieren. Das hier vorgestellte Konzept stellt auch auf die sich zunehmend wandelnde Rolle von Kursangeboten in der Grundbildung (von sozialen Räumen hin zu Lernräumen) ab und lotet hierfür die Potenziale immersiver und spielerischer Kursgestaltung mittels Augmented Reality aus.The present findings show that the promises of the digitalisation of learning have not (yet) been fulfilled. Despite digital offerings, access to education is highly selective in the various educational sectors, and the use of educational offerings (still) depends on individual educational socialisation, age and place of residence. These findings are anything but encouraging, especially for adult education, which relies heavily on voluntary participation in its educational offerings. The article shows which approaches immersive adult education offers – and here especially in the area of literacy/basic education – can use to realise a high level of participant loyalty as well as favourable learning prognoses. The focus is particularly on how immersive learning opportunities must be designed in terms of content and instruction in order to address a variety of challenges in basic education courses (e.g. topics relevant to life, independence of learning location, ability to collaborate). The concept presented here also focuses on the increasingly changing role of course offerings in basic education (from social spaces to learning spaces) and explores the potential of immersive and game-based course design with augmented reality

Genome sequence of the bioplastic-producing ‘‘Knallgas’’ bacterium Ralstonia eutropha H16

The H2-oxidizing lithoautotrophic bacterium Ralstonia eutropha H16 is a metabolically versatile organism capable of subsisting, in the absence of organic growth substrates, on H2 and CO2 as its sole sources of energy and carbon. R. eutropha H16 first attracted biotechnological interest nearly 50 years ago with the realization that the organism’s ability to produce and store large amounts of poly[R-(–)-3-hydroxybutyrate] and other polyesters could be harnessed to make biodegradable plastics. Here we report the complete genome sequence of the two chromosomes of R. eutropha H16. Together, chromosome 1 (4,052,032 base pairs (bp)) and chromosome 2 (2,912,490 bp) encode 6,116 putative genes. Analysis of the genome sequence offers the genetic basis for exploiting the biotechnological potential of this organism and provides insights into its remarkable metabolic versatility

13C-assisted metabolic flux analysis to investigate heterotrophic and mixotrophic metabolism in Cupriavidus necator H16

Introduction. Cupriavidus necator H16 is a gram-negative bacterium, capable of lithoautotrophic growth by utilizing hydrogen as an energy source and fixing carbon dioxide (CO2) through Calvin-Benson-Bassham (CBB) cycle. The potential to utilize synthesis gas (Syngas) and the prospects of rerouting carbon from polyhydroxybutyrate synthesis to value-added compounds makes C. necator an excellent chassis for industrial application. Objectives. In the context of lack of sufficient quantitative information of the metabolic pathways and to advance in rational metabolic engineering for optimized product synthesis in C. necator H16, we carried out a metabolic flux analysis based on steady-state 13C-labelling. Methods. In this study, steady-state carbon labelling experiments, using either D-[1-13C]fructose or [1,2-13C]glycerol, were undertaken to investigate the carbon flux through the central carbon metabolism in C. necator H16 under heterotrophic and mixotrophic growth conditions, respectively. Results. We found that the CBB cycle is active even under heterotrophic condition, and growth is indeed mixotrophic. While Entner-Doudoroff (ED) pathway is shown to be the major route for sugar degradation, tricarboxylic acid (TCA) cycle is highly active in mixotrophic condition. Enhanced flux is observed in reductive pentose phosphate pathway (redPPP) under the mixotrophic condition to supplement the precursor requirement for CBB cycle. The flux distribution was compared to the mRNA abundance of genes encoding enzymes involved in key enzymatic reactions of the central carbon metabolism. Conclusion. This study leads the way to establishing 13C-based quantitative fluxomics for rational pathway engineering in C. necator H16

Studies on the production of branched-chain alcohols in engineered Ralstonia eutropha

Wild-type Ralstonia eutropha H16 produces polyhydroxybutyrate (PHB) as an intracellular carbon storage material during nutrient stress in the presence of excess carbon. In this study, the excess carbon was redirected in engineered strains from PHB storage to the production of isobutanol and 3-methyl-1-butanol (branched-chain higher alcohols). These branched-chain higher alcohols can directly substitute for fossil-based fuels and be employed within the current infrastructure. Various mutant strains of R. eutropha with isobutyraldehyde dehydrogenase activity, in combination with the overexpression of plasmid-borne, native branched-chain amino acid biosynthesis pathway genes and the overexpression of heterologous ketoisovalerate decarboxylase gene, were employed for the biosynthesis of isobutanol and 3-methyl-1-butanol. Production of these branched-chain alcohols was initiated during nitrogen or phosphorus limitation in the engineered R. eutropha. One mutant strain not only produced over 180 mg/L branched-chain alcohols in flask culture, but also was significantly more tolerant of isobutanol toxicity than wild-type R. eutropha. After the elimination of genes encoding three potential carbon sinks (ilvE, bkdAB, and aceE), the production titer improved to 270 mg/L isobutanol and 40 mg/L 3-methyl-1-butanol. Semicontinuous flask cultivation was utilized to minimize the toxicity caused by isobutanol while supplying cells with sufficient nutrients. Under this semicontinuous flask cultivation, the R. eutropha mutant grew and produced more than 14 g/L branched-chain alcohols over the duration of 50 days. These results demonstrate that R. eutropha carbon flux can be redirected from PHB to branched-chain alcohols and that engineered R. eutropha can be cultivated over prolonged periods of time for product biosynthesis.United States. Dept. of EnergyUnited States. Advanced Research Projects Agency-Energ

Revealing the Functions of the Transketolase Enzyme Isoforms in Rhodopseudomonas palustris Using a Systems Biology Approach

BACKGROUND: Rhodopseudomonas palustris (R. palustris) is a purple non-sulfur anoxygenic phototrophic bacterium that belongs to the class of proteobacteria. It is capable of absorbing atmospheric carbon dioxide and converting it to biomass via the process of photosynthesis and the Calvin-Benson-Bassham (CBB) cycle. Transketolase is a key enzyme involved in the CBB cycle. Here, we reveal the functions of transketolase isoforms I and II in R. palustris using a systems biology approach. METHODOLOGY/PRINCIPAL FINDINGS: By measuring growth ability, we found that transketolase could enhance the autotrophic growth and biomass production of R. palustris. Microarray and real-time quantitative PCR revealed that transketolase isoforms I and II were involved in different carbon metabolic pathways. In addition, immunogold staining demonstrated that the two transketolase isoforms had different spatial localizations: transketolase I was primarily associated with the intracytoplasmic membrane (ICM) but transketolase II was mostly distributed in the cytoplasm. Comparative proteomic analysis and network construction of transketolase over-expression and negative control (NC) strains revealed that protein folding, transcriptional regulation, amino acid transport and CBB cycle-associated carbon metabolism were enriched in the transketolase I over-expressed strain. In contrast, ATP synthesis, carbohydrate transport, glycolysis-associated carbon metabolism and CBB cycle-associated carbon metabolism were enriched in the transketolase II over-expressed strain. Furthermore, ATP synthesis assays showed a significant increase in ATP synthesis in the transketolase II over-expressed strain. A PEPCK activity assay showed that PEPCK activity was higher in transketolase over-expressed strains than in the negative control strain. CONCLUSIONS/SIGNIFICANCE: Taken together, our results indicate that the two isoforms of transketolase in R. palustris could affect photoautotrophic growth through both common and divergent metabolic mechanisms