231 research outputs found

    Precise and multifunctional conjugates for targeted siRNA delivery

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    Malignant infarction in cats following prolonged middle cerebral artery occlusion : volumes of severe blood flow reduction predict fatal outcome

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    Severity and duration of cerebral blood flow (CBF) reduction are main determinants of injury in core and penumbra zones of focal brain ischemia. To study the putative role and predictive significance of the volume of these zones for induction of a malignant course due to edema formation in large hemispheric stroke, we examined reduction of CBF and oxygen metabolism (CMRO2) by sequential positron emission tomography (PET) in a transient ischemia model in cats that is susceptible to secondary deterioration after reperfusion.peer-reviewe

    Glutamate and purine catabolites in relation to free radical production during focal ischemia-reperfusion : an in vivo study in cats

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    The in-vivo interrelation between excitotoxicity and oxidative stress following cerebral ischemia in cats was investigated. To elucidate the role of this mechanism in cerebral ischemia, the study presented herein sought to investigate the spatial and temporal features of the free radical response to elevations of glutamate and purine catabolites in a reproducible model of in vivo focal ischemia/reperfusion. The time course of neurochemical and Reactive Oxygen Species (ROS) were simultaneously conducted in ischemic focus and perifocal region of the brain.peer-reviewe

    Extracellular glutamate accumulates only in final, ischemic stage of progressive epidural mass lesion in cats

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    Epidural mass lesions may cause ischemia due to progressive intracranial hypertension. In order to 1) investigate the impact of intracranial pressure (ICP) on accumulation of neuroactive substances, and 2) test the significance of neurochemical monitoring for early prediction of fatal outcome, we gradually raised ICP in cats by inflation of an epidural balloon: We assessed extracellular substrate alterations in the contralateral cortex in relation to changes of ICP, cerebral perfusion pressure (CPP) and mean arterial blood pressure (MABP). In a complementary experiment, regional cerebral blood flow was assessed by sequential positron emission tomography (PET).peer-reviewe

    Junge Mütter auf dem Weg in eine Teilzeitberufsausbildung : Eine empirisch-rekonstruktive Untersuchung erwerbsbezogener Haushaltsentscheidungen

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    Unter welchen Voraussetzungen und wie gelingt erfolgreichen Müttern trotz erschwerter Lebensumstände die berufliche Eingliederung? Dieser Frage geht die vorliegende – auf empirisches Datenmaterial bezugnehmende – Arbeit auf den Grund. Bekannt ist, dass vielen Frauen, die in einem jungen Lebensalter ein Kind zur Welt gebracht haben, der berufliche Einstieg nach der familienintensiven Phase erschwert wird. Mangelhafte Betreuungsmöglichkeiten und fehlende Qualifikationen sind hierfür die zentralen Ursachen. Ohne einen Berufsabschluss verschlechtern sich die Erwerbschancen junger Mütter oft dauerhaft. Dies wirkt sich höchst negativ auf ihre Wohlstandsposition und das familiäre Wohlbefinden aus. Besonders von diesen Problemen betroffen sind Alleinerziehende. Bei ihnen liegt der Anteil von Frauen, die ohne Berufsabschluss geblieben sind, und die Leistungen der Grundsicherung nach dem SGB II beziehen bei rund 70 Prozent. Andererseits gelten insbesondere diese jungen Mütter als verantwortungsbewusst, hoch engagiert, sozial kompetent und besonders belastbar. Um jungen Müttern den Weg in eine Berufsausbildung zu erleichtern und ihnen dadurch den Weg in die Erwerbsarbeit und in eine bessere Lebenslage zu eröffnen, besteht seit mittlerweile rund zehn Jahren die Möglichkeit zur Berufsausbildung in Teilzeit (§ 8 Berufsbildungsgesetz und § 27 Handwerksordnung). Um dieses Angebot bekannt zu machen und möglichst viele junge Mütter zur Ausübung einer qualifizierten Beschäftigung zu befähigen, gibt es Förderprogramme wie das NRW-Programm „Teilzeitberufsausbildung – Einstieg begleiten – Perspektiven öffnen“ (TEP). Bis zum Jahr 2015 wurden rund 3.000 junge Mütter im Rahmen dieses Programms beruflich gefördert. Die angestrebten Übergangsquoten in die Ausbildung wurden dabei bislang allerdings nicht erreicht. Vor diesem Hintergrund wird in der vorliegenden Arbeit untersucht, wie junge Mütter auf dem Weg in die Ausbildung noch wirkungsvoller unterstützt werden können. Das Ergebnis dieser Arbeit ist eine lebenslagenbezogene Erklärung ihrer beruflichen Eingliederungserfolge in Abhängigkeit zu ihrem Entscheidungsverhalten und unter erschwerten Lebensbedingungen. Rekonstruiert wird darin, wie erfolgreiche Mütter den Weg in die Ausbildung meistern. Dies geschieht auf der Grundlage eines theoriegestützten Vergleichs von unterschiedlichen Untersuchungsfällen. Haushaltsökonomische, entscheidungstheoretische, verhaltensökonomische sowie institutionenökonomische Modelle bilden die Grundlagen einer solchen lebenslagenbezogenen Erklärung. Dabei zeichnen sich vier relevante Schlüsselkategorien des beruflichen Eingliederungserfolgs junger Mütter ab. Die Untersuchungsergebnisse zeigen, dass ihr Entscheidungsverhalten – erstens – durch eine sehr verantwortungsbewusste Haushaltsführung gekennzeichnet. Erfolgreiche Mütter bekunden ihre Erwerbsbereitschaft erst unter genau bestimmten Voraussetzungen, denn sie wollen das Wohlergehen ihrer Kinder durch die Ausübung einer Erwerbstätigkeit nicht zusätzlich gefährden. Gleichwohl wollen sie sozialen Verhaltensanforderungen in bestmöglicher Weise gerecht werden, zum Beispiel indem sie ihren Kindern ein (berufliches) Vorbild sein und ihnen gute Zukunftschancen eröffnen wollen. Aus diesen Gründen nehmen sie arbeitsmarktrelevante Unterstützungsangebote wie TEP bereitwillig in Anspruch, da sie sich durch diese Angebote größere berufliche Eingliederungschancen erhoffen. Wichtig für den Eingliederungserfolg ist zudem die Verfügbarkeit von persönlichen Unterstützungsnetzwerken, die junge Mütter bei der Aufnahme einer Berufsausbildung beziehungsweise Beschäftigung entlasten, da sie diese aktiv nutzen. Zweitens haben junge Mütter realistische Vorstellungen im Hinblick auf die Konsequenzen möglicher beruflicher Handlungsalternativen. Sie informieren sich gründlich über verschiedene Optionen und wägen deren Vor- und Nachteile anhand von mehreren Entscheidungskriterien genau gegeneinander ab. Aufgrund der Rückmeldungen, die sie zum Beispiel während eines betrieblichen Praktikums erhalten, gelangen erfolgreiche Mütter außerdem zu einer realistischeren Selbsteinschätzung im Hinblick auf ihre Kompetenzen, die erforderlich sind, um den beruflichen Anforderungen vonseiten potenzieller Arbeitgeber gerecht zu werden. Unter objektiven Beschränkungen wie zum Beispiel bestimmten Zulassungsvoraussetzungen oder Angebotsknappheit sind sie bereit, sich gegenüber weiteren Alternativen zu öffnen. Drittens sind junge Mütter, denen im Rahmen der Ausbildungsvorbereitung der Berufseinstieg gelingt, höchst optimistisch im Hinblick darauf, dass sie ihre beruflichen Handlungspläne eigenverantwortlich verwirklichen werden. Sie nutzen ihre Einflussmöglichkeiten auf das angestrebte Handlungsergebnis, achten dabei umgekehrt aber auch auf ihre Belastungsgrenzen. Sie überwinden Zweifel und Widerstände und gehen dabei äußerst planvoll vor. Viertens verbinden erfolgreiche Mütter mit dem gelingenden Berufsabschluss die Erwartung einer verstärkten Befriedigung ihrer familiären und individuellen Bedürfnisse. Der konkrete Nutzen besteht aus ihrer subjektiven Sicht in größerem materiellen Wohlstand und mehr Wohlbefinden. Junge Mütter, denen mithilfe von Unterstützungsangeboten wie TEP der berufliche Einstieg gelingt, streben eine größtmögliche wirtschaftliche Unabhängigkeit von anderen an und sie orientieren sich dabei an einem glücklichen und stabilen Familienleben. Diese vier Faktoren beeinflussen maßgeblich den beruflichen Eingliederungserfolg von jungen Müttern. Auf der Grundlage dieser Einsichten unterbreitet die Arbeit Vorschläge, wie diesen Faktoren bei der künftigen beruflichen Förderung von jungen Müttern noch stärker Rechnung getragen werden kann.Young mothers on their road to part-time vocational training – An empirical-reconstructive study in household decision-making How and under which circumstances do young mothers succeed with their vocational integration despite of adverse personal living conditions? Based on empirical data, the present dissertation scrutinizes this question. It has been proven that, many women, who have given birth at a young age, do face difficulties during their job entry after staying at home for a long time. The main causes for these circumstances are lacking qualifications and childcare services. Without vocational qualification young mothers’ employment chances deteriorate permanently which has a negative impact on their economic vitality and their family wellbeing. Single mothers are particularly affected by these problems. Within the group of single mothers the percentage of women without professional qualification receiving jobseeker’s allowance takes up to 70 percent. At the same time, young women are said to be responsible, extremely dedicated, socially competent and very resilient. In order to facilitate young mothers’ entry into vocational training and therefore to help them find their way into successful employment, there is the possibility of attending a part-time vocational training since approximately 10 years (§ 8 Vocational Training Act and § 27 Trade and Crafts Code). For the purpose of increasing awareness of this offer public and to enable as many young mothers as possible to participate in qualified employment, support programs like “Teilzeitberufsausbildung – Einstieg begleiten – Perspektiven öffnen” (TEP) in North Rhine-Westphalia have been established. Until 2015 approximately 3,000 young mothers have been supported in the context of this program. Nevertheless, the envisaged transitional quota has not been reached yet. Against this background, the present study investigates how young mothers can be supported more efficiently on their way into vocational training. Taking all circumstances and living conditions into account, the result of the present thesis is an explanation for their professional integration success depending on their decision behavior and their aggravated living conditions. The explanation reconstructs how successful mothers manage their way into vocational training. It rests on evidence which is on a theory-based comparison of various examination cases. Based on household-, decision-theoretical-, behavior-economic, and institutional-economic models, this dissertation comprises all significant living conditions. Consequently, four relevant key categories for a successful labor market integration of young mothers emerged. First of all, the research results illustrate that their decision behavior is characterized by a very responsible household management. Successful mothers express their willingness to attend gainful employment only under certain conditions, because they do not want to endanger their children’s well-being. Nevertheless, they intend to fulfill socially demanded behavioral requirements at the best, for example by wanting to be a (professional) role model for their children. For these reasons they willingly make use of labor-market relevant support programs like TEP. By doing so, they hope to gain better opportunities for professional integration. Furthermore, the availability of personal support networks, which relieve young mothers when starting an apprenticeship or being employed, is of crucial importance, as they make active use of them. Secondly, young mothers have realistic ideas about the consequences of possible action alternatives. They familiarize themselves thoroughly with different options and weigh the respective advantages and disadvantages based on several decision criteria. Due to the feedback they receive, for example during a professional internship, successful young mothers obtain a more realistic self-image with regard to the professional competencies that are needed to meet the requirements of potential employers. With objective limitations they are prepared to open up to alternatives – for example concerning admission requirements or a structural shortage of supply. Thirdly, young women who successfully enter the job market in the context of their preparation for vocational training are highly optimistic regarding the fact that they will autonomously realize their professional action plans. They seize their potential influence on the envisaged action outcomes, but are also aware of their personal limits. They overcome doubts and resistance and proceed systematically. Fourthly, young mothers associate a successful professional qualification with their expectation of better meeting their family and individual needs. From their subjective point of view, the concrete advantages to be gained are a higher importance of material prosperity and well-being. Young mothers, who successfully enter the job market by means of support programs like TEP, strive for the greatest possible economic independence from others and orient themselves towards a happy and stable family life

    Li–Na interdiffusion and diffusion-driven lithium isotope fractionation in pegmatitic melts

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    In this study, we investigate the diffusion of Li and its stable isotopes (6Li and 7Li) in flux-rich (1.8 % Li2O, 2.6 % B2O3, 2.3 % P2O5 and 3 % F) pegmatitic melts in order to contribute to the understanding of Li enrichment in such systems. Two glasses were synthesized with a model pegmatitic composition, one of which is highly enriched in Li (> 1 wt %, PEG2-blue) and the other one essentially Li-free (PEG2-Li-free). Diffusion couple experiments were performed to determine the chemical diffusivity of Li in dry pegmatitic melts. Experiments were conducted using rapid-heat and rapid-quench cold-seal pressure vessels in a temperature range of 650–940 ∘C at 100 MPa with Ar as the pressure medium. We observed rapidly formed diffusion profiles, driven by an interdiffusive exchange of the monovalent alkalis Li and Na, while the other elements are immobile on the timescale of experiments (1–30 min). From these experiments, activation energies for Li–Na interdiffusion were determined as 99 ± 7 kJ mol−1 with a pre-exponential factor of log D0 = −5.05 ± 0.33 (D0 in m2 s−1). Li and Na partitioning between the stronger depolymerized PEG2-blue and the less depolymerized PEG2-Li-free leads to a concentration jump at the interface; i.e. Na is enriched in the more depolymerized PEG2-blue. Li–Na interdiffusion coefficients in the studied melt composition are in a similar range as Li and Na tracer diffusivities in other dry aluminosilicate melts, confirming little to no effect of aluminosilicate melt composition on Li diffusivity. Thus, added fluxes do not enhance the Li diffusivity in the same way as observed for H2O (Holycross et al., 2018; Spallanzani et al., 2022). Using melt viscosity as a proxy for the polymerization of the melt shows that water has a stronger potential to depolymerize a melt compared to other fluxing elements. Faster diffusion of 6Li compared to 7Li leads to a strong Li isotope fractionation along the diffusion profile, resulting in δ7Li as low as −80 ‰ relative to the diffusion-unaffected regions. This diffusive isotope fractionation can be quantified with an empirical isotope fractionation factor (β) of 0.20 ± 0.04, similar to previously observed β values for Li diffusion in melts. This suggests in accordance with previously published data that a β value of ca. 0.2 seems to be universally applicable to diffusive Li isotope fractionation in aluminosilicate melts

    Nanosized Multifunctional Polyplexes for Receptor-Mediated SiRNA Delivery

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    Although our understanding of RNAi and our knowledge on designing and synthesizing active and safe siRNAs significantly increased during the past decade, targeted delivery remains the major limitation in the development of siRNA therapeutics. On one hand, practical considerations dictate robust chemistry reproducibly providing precise carrier molecules. On the other hand, the multistep delivery process requires dynamic multifunctional carriers of substantial complexity. We present a monodisperse and multifunctional carrier system, synthesized by solid phase supported chemistry, for siRNA delivery in vitro and in vivo. The sequence-defined assembly includes a precise cationic (oligoethanamino)amide core, terminated at the ends by two cysteines for bioreversible polyplex stabilization, at a defined central position attached to a monodisperse polyethylene glycol chain coupled to a terminal folic acid as cell targeting ligand. Complexation with an endosomolytic influenza peptide-siRNA conjugate results in nanosized functional polyplexes of 6 nm hydrodynamic diameter. The necessity of each functional substructure of the carrier system for a specific and efficient gene silencing was confirmed. The nanosized polyplexes showed stability in vivo, receptor-specific cell targeting, and silencing of the EG5 gene in receptor-positive tumors. The nanosized appearance of these particles can be precisely controlled by the oligomer design (from 5.8 to 8.8 nm diameter). A complete surface charge shielding together with the high stability result in good tolerability in vivo and the absence of accumulation in nontargeted tissues such as liver, lung, or spleen. Due to their small size, siRNA polyplexes are efficiently cleared by the kidney

    Climate-Smart Agriculture in Cocoa: A Training Manual for Field Officers

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    This training manual has been developed to raise awareness among cocoa farmers in Ghana on the effects of climate change on their cocoa production and to give them tools (in the form of recommendations) to mitigate these (negative) effects. The topics can be used by field/extension officers in addition to topics on good agricultural practices

    Climate-Smart Agriculture in Cocoa: A Training Manual for Field Officers

    Get PDF
    This training manual has been developed to raise awareness among cocoa farmers in Ghana on the effects of climate change on their cocoa production and to give them tools (in the form of recommendations) to mitigate these (negative) effects. The topics can be used by field/extension officers in addition to topics on good agricultural practices
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