Maßstäbe gesetzt und praktiziert. Zum Ende der "Ära Foley"

Mit der Ernennung des Präsidenten des Päpstlichen Rates für die Sozialen Kommunikationsmittel, Erzbischof John P. Foley, zum Pro-Grassmeister des Ritterordens vom Hl. Grab und damit zum Nachfolger des italienischen Kardinals Carlo Furno, der ebenfalls im Alter von 72 Jahren in dieses Amt berufen worden war, ist nunmehr die "Ära Foley" in der Leitung dieses Rates zu Ende gegangen.Eine umfassende Darstellung der Präsidentschaft von Erzbischof Foley kann hier nicht vorgelegt werden, zumal seine mehr als 23-jährige unermüdliche Tätigkeit, vor allem außerhalb der Kurie und des Vatikans, längere Recherchen für eine sorgfältige Darstellung und Analyse notwendig macht und ein langjähriger Mitarbeiter sicher nicht die einzige Stimme in der Würdigung einer "Ära" sein sollte. Daher sollen an dieser Stelle ein kurzer Rückblick und einige Schlaglichter aus der täglichen Erfahrung und Beobachtung genügen. (...

Regulating the mobility of Cd, Cu and Pb in an acid soil with amendments of phosphogypsum, sugar foam, and phosphoric rock

11 pages, figures, and tables statistics.When acid soil has been contaminated by metals as a result of industrial discharges, accidental spills, or acid mine drainage it may be desirable to retain the metals in the soil rather than allow them to leach away. We have investigated the potential of phosphogypsum (PG), sugar foam (SF), and phosphoric rock (PR) to regulate the availability and mobility of Pb, Cd and Cu. We have also identified changes in attenuation during incubation for 1 year and the effect of aging on metal speciation in amended soils. We studied miscible displacement in columns of undisturbed soil previously treated with solutions of the amendments and soluble metals and, subsequently, single and sequential chemical metal extractions. All amendments increased the soil’s metal retention capacity. This, in turn, increased the amount of metal extractable by diethylenetriaminepentaacetic acid (DTPA). However, over time the amounts of DTPAextractable metal decreased, particularly for Cu and Pb. Both Cu and Cd were held preferentially within the acetic acid-extractable fraction (operationally defined exchangeable fraction – EX fraction), whereas Pb was associated mainly with the hydroxylammonium-extractable fraction (operationally defined bound to Fe and Al hydroxides – OX fraction). Both Pb and Cu in the oxide and organic fractions increased in the PG- and SF-treated soils. In general, the distribution of metal did not change in the PR-treated columns after the incubation. Finally, scanning electron microscopy in back-scattered electron mode (SEM–BSE) showed the formation of Al-hydroxy polymers which provides the soils with additional cation sorption capacity. In the PG- and PR-treated columns, P and S were associated with these formations. The three metals were associated with the Al polymers, probably through direct coordination or the formation of ternary complexes with the inorganic ligands phosphate and sulphate.This research was supported by the Spanish Ministry of Science and Technology within the framework of the research project AGL2002-04545-C03-01. We are especially grateful to Laura Barrios for her assistance in the statistical treatment of the data, to Fertiberia, S.A. and Azucarera Ebro, S.L. for supplying us with samples of phosphogypsum and sugar foam, respectively, and to Guoping Lu, anonymous referees and the Editors for their review and comments.Peer reviewe

Stimulated Transitions of Directed Nonequilibrium Self-Assemblies

Near-equilibrium stimulus-responsive polymers have been used extensively to introduce morphological variations in dependence of adaptable conditions. Far-less-well studied are triggered transformations at constant conditions. These require the involvement of metastable states, which are either able to approach the equilibrium state after deviation from metastability or can be frozen on returning from nonequilibrium to equilibrium. Such functional nonequilibrium macromolecular systems hold great promise for on-demand transformations, which result in substantial changes in their material properties, as seen for triggered gelations. Herein, a diblock copolymer system consisting of a hydrophilic block and a block that is responsive to both pressure and temperature, is introduced. This species demonstrates various micellar transformations upon leaving equilibrium/nonequilibrium states, which are triggered by a temperature deflection or a temporary application of hydrostatic pressure

Envelhecimento (in)ativo e desenvolvimento emocional em reclusos

Este projeto pretende apresentar o contributo do programa de Exercício Físico e do Desenvolvimento Emocional nos reclusos. Para isso optamos por desenvolver um estudo de carácter Quantitativo, Exploratório, Quasi - Experimental, Longitudinal e Descritivo. A amostra é constituída por 20 reclusos do Estabelecimento Prisional de Izeda, com idade média de 41,10±10,19 anos, distribuída entre os 24 e os 67 anos. Dos 20 reclusos, 9 foram designados para integrarem o Grupo de Investigação e os restantes o Grupo de Controlo. A seleção foi feita de forma aleatória. O Grupo de Investigação foi submetido a um programa de atividades de duas a três sessões semanais, durante 8 semanas, tendo cada sessão a duração de 1:15 Horas. Foi aplicada a escala EVCE e o questionário SF-36v2, com a complementaridade das avaliações do estado funcional dos reclusos. As características psicométrica obtidas na escala EVCE e no questionário SF-36v2 permitem-nos verificar que neste estudo se obtem uma boa consistência interna. Após a realização das sessões de intervenção, verificamos que não houve alterações estatisticamente significativas entre os parâmetros do Grupo de Controlo e o Grupo de Investigação. Desta forma, podemos concluir que o programa de intervenção teria melhores resultados se tivesse uma duração maior ao longo do tempo.This project aims to present the contribution of an Exercise Program and of an Emotional Development Program in prison. For this study we chose to develop a Quantitative Explorational, Quasi - Experimental, Descriptive and Longitudinal. The sample consists of 20 inmates of the Izeda Prison, with a mean age of 41.10± 10.19 years, distributed between 24 and 67 years. Of the 20 inmates, nine were appointed to serve on the Research Group and the remaining To the Control Group. The selection was done randomly. The Research Group has undergone program of activities two to three times per week for 8 weeks, with each session lasting 1h15m. EVCE scale and SF-36v2 were applied, the functional status of the inmates was assessed. The psychometric characteristics obtained in EVCE scale and SF-36v2 allow us to verify that this study gives a good internal consistency. After completion of intervention sessions, we found that there were no statistically significant changes between the parameters of the Control Group and Research Group. Thus, we can conclude that the intervention program would have better results if it had a longer duration over tim

The Cyclophilin-Binding Agent Sanglifehrin A Is a Dendritic Cell Chemokine and Migration Inhibitor

Sanglifehrin A (SFA) is a cyclophilin-binding immunosuppressant but the immunobiology of action is poorly understood. We and others have reported that SFA inhibits IL-12 production and antigen uptake in dendritic cells (DC) and exhibits lower activity against lymphocytes. Here we show that SFA suppresses DC chemokine production and migration. Gene expression analysis and subsequent protein level confirmation revealed that SFA suppressed CCL5, CCL17, CCL19, CXCL9 and CXCL10 expression in human monocyte-derived DC (moDC). A systems biology analysis, Onto Express, confirmed that SFA interferes with chemokine-chemokine receptor gene expression with the highest impact. Direct comparison with the related agent cyclosporine A (CsA) and dexamethasone indicated that SFA uniquely suppresses moDC chemokine expression. Competitive experiments with a 100-fold molar excess of CsA and with N-Methyl-Val-4-cyclosporin, representing a nonimmunosuppressive derivative of CsA indicated chemokine suppression through a cyclophilin-A independent pathway. Functional assays confirmed reduced migration of CD4+ Tcells and moDCs to supernatant of SFA-exposed moDCs. Vice versa, SFA-exposed moDC exhibited reduced migration against CCL19. Moreover, SFA suppressed expression of the ectoenzyme CD38 that was reported to regulate DC migration and cytokine production. These results identify SFA as a DC chemokine and migration inhibitor and provide novel insight into the immunobiology of SFA

Der Deutsche Fassweinmarkt – Eine Warenstromanalyse der Fassweintransporte in Rheinland-Pfalz

In der deutschen Weinwirtschaft deckt der Fassweinhandel eine große Menge des Weinmarktes ab und nimmt somit eine herausragende Stellung ein. Für ein besseres Verständnis des komplexen deutschen Fassweinmarktes und seiner Entwicklung in den Jahren 2000 bis 2012, wurde eine explorative Datenanalyse der Fasswein-Warenströme erstellt. Die Datengrundlage bildet eine neue Datenbank der Fassweintransporte im Bundesland Rheinland-Pfalz, die zusammen mit den offiziellen Statistiken die Struktur und Entwicklung des Marktes darstellen. Die Bildung eines Zwei-Stufen-Handelsmodells zeigt deutlich die intensive Vernetzung und Arbeitsteilung sowie einen Konzentrationsprozess in der Weinbranche, zusammen mit einer Verbesserung des Qualitätsmanagements. Dagegen haben jahrgangsbedingte Ernteschwankungen keinen erkennbaren Einfluss auf die Warenströme der deutschen Fassweine

Der Weinmarkt in Rheinland-Pfalz - Eine Zeitreihenanalyse der Fassweinwarenströme

In der deutschen Weinwirtschaft deckt der Fassweinhandel eine große Menge des Weinmarktes ab und nimmt somit eine herausragende Stellung ein. Für ein besseres Verständnis des komplexen deutschen Weinwirtschaft in dem Spannungsfeld eines liberalen Marktes und einer regulierten heimischen Produktion wurde die Entwicklung in den Jahren 2000 bis 2012 in einer explorativen Datenanalyse der Fasswein-Warenströme analysiert. Die Datengrundlage bildet eine neue Datenbank der Fassweintransporte im Bundesland Rheinland-Pfalz, die zusammen mit den offiziellen Statistiken die Struktur und Entwicklung des Marktes darstellen. Die Bildung eines Zwei-Stufen-Handelsmodells zeigt deutlich die intensive Vernetzung und Arbeitsteilung sowie einen Konzentrationsprozess in der Weinbranche

Pharmakologische Manipulation Dendritischer Zellen in vitro und in vivo

Dendritische Zellen gehören zum angeborenen Immunsystem und präsentieren professionelle Antigen-präsentierende Zellen, die immunologische Antworten initiieren und anregen. In den bestimmten Fällen wie einer Transplantation ist es erwünscht, dass die körpereigene Abwehr selektiv reduziert wird, so dass der Körper das körperfremde Organ nicht abstößt, jedoch gleichzeitig eine ausreichende Immunität gegen Bakterien, Viren und Krebs erhalten bleibt.Ein therapeutischer Ansatz wäre die selektive Hemmung dendritischer Zellen. Sie spielen eine zentrale Rolle im Immmunsystem und präsentieren interessante Ziele für die pharmakologische Manipulation. Eine Hemmung dendritischer Zellen führt zu einer verringerten endozytotischen Antigenaufnahme, -präsentation und Produktion proinflammatorischer Zytokine und könnte folglich die chronsiche Organabstoßung verzögern oder verhindern. In dieser Arbeit wurde untersucht, ob man Sanglifehrin A (SFA), eine neue immunophilin bindende Substanz, zur pharmakologischen Programmierung tolerogener Dendritischer Zellen nutzen kann, um einen Effekt in Alloimmunitätsmodellen und Organtransplantationsmodellen zu zeigen. Die pharmakologischen Effekte von SFA auf dendritische Zellen wurden in vitro und in vivo untersucht. In ersten Versuchen zeigten wir, dass SFA keinen Effekt auf Differenzierung oder phänotypische Reifung von Dendriten hat. Als nächstes untersuchten wir eine Reihe von Zytokinen, unter anderem IL-12p70, das eine wichtige Rolle bei der Pathogenese von Entzündungen und Autoimmunerkrankungen spielt. Wir fanden heraus, das SFA die Produktion von bioaktivem IL-12p70 in dendritschen Zellen reduziert, die Hauptquelle für bioaktives IL-12. Im direkten Vergleich zu dem verwandten Calcineurin-Inhibitor Cyclosporin A und dem mammalian Target of Rapamycin (mToR) Hemmer Rapamycin, hemmt nur SFA schon innerhalb einer Stunde 80 95 % der IL-12p70 Produktion von differenzierten Dendriten. Um zu zeigen, das es sich um einen stimulusunabhängigen Mechanismus handelt, wurden die Versuche sowohl mit Toll-like Rezepor 3 als auch 4 Liganden durchgeführt. Es wurden Rezeptorverdrängungsexperimente durchgeführt, bei denen molare Überschüsse von Cyclosporin A vor der Zugabe von SFA zur Zellkultur gegeben wurden. Die Ergebnisse zeigen eine äqipotente Hemmung der IL-12p70 Produktion mit oder ohne Cyclopsorin A: Daraus lässt sich eine Cyclophilin- unabhängige Blockade der IL-12p70 Produktion durch SFA vermuten.Die starke Hemmung der IL-12p70 Produktion wurde in einer Versuchsreihe mit gereinigten peripheren Blut-Dendriten bestätigt. Echtzeit-PCRs ergaben eine 84-95% Hemmung der IL-12p40-, IL-12p35- und der IL-23-spezifischen p19 Transkription.In einem nächsten Schritt sollte untersucht werden, ob diese in vitro Ergebnisse im in vivo Mausmodell reproduzierbar sind, um die klinische Relevanz dieser Ergebnisse zu klären. Die in vivo Untersuchungen zeigten, das dreitägige Injektionen von SFA in Mäuse (Kontrolltiere erhielten eine wirkstofffreie Trägerlösungen injiziert) und die darauffolgende in vivo Stimulation mit LPS/IL-4 70% der Produktion von bioaktivem IL-12 hemmten. Mit weiteren unabhängigen Modellen zeigten wir, das SFA mehr als 90% der IL-12p70 Produktion hemmt, während es keinen Effekt auf IL-10 und TNF-a hat. Die in vivo Behandlung mit SFA zeigte keine Einfluß auf die in vivo Expansion oder die phänotypische Reifung von DC Subtypen und hatte keinen Effekt auf die DC Population.Außerdem hemmte SFA die rezeptorvermittelte Endozytose und Makropinozytose und die indirekte Antigenpräsentation von CD11c+ dendritschen Zellen in vivo. Unsere Ergebnisse zeigten zum ersten Mal den Effekt von Sanglifehrin A in vivo. Die Ergebnisse lassen vermuten, insbesondere die Bestätigung durch die in vivo Experimente, das es sich bei Sanglifehrin A um eine Subanz mit einem einzigartigen Wirkprofil gegenüber dendritschen Zellen handelt: starke Hemmung sowohl der Antigen-Aufnahme als als auch der IL-12p70 Produktion, aber keinen signifikanten Einfluß auf Differenzierung, Expansion oder Expression von Oberflächenmarkern dendritischer Zellen. Unserem Wissen nach gab es bisher keine immunosuppressive Substanz, die zwei Schlüsselfunktionen, IL-12 Produktion und Antigenaufnahme hemmt, aber keine Effekte auf Differenzierung oder Expansion hat.Wir vermuten, das SFA eine neue Klasse immunophilinbindender Immunsuppressiva darstellt, die eine hohe Aktivität auf dendritische Zellen zeigt und in der Kombination mit anderen Immunsuppressiva synergistische Wirkungen entfaltet. Somit könnte die Kombination von immunsuppressiven Substanzen mit Sanglifehrin A ein wirkungsvoller Ansatz sein, um chronische Tranplantatabstoßung zu verhindern.Dendritic Cells (DC) belong to the innate immunity and present professional Antigen (AG) presenting cells that initiate and regulate immune responses. Acute organ rejection is very well controllable with the available immunosuppressive drugs, but new drugs still have to be developed for chronic allograft rejection.A selective inhibition of dendritic cells desirably leads to less endocytotic capacity, Ag uptake and presentation and production of proinflammatory cytokines and is assumed delaying allograph rejection. With respect to the central role of DC in immunity, they are interesting therapeutic targets for pharmacological manipulation of immune responses. The impact of Sangliferin A (SFA) as a novel means for pharmacological programming of tolerogenic DC in models of alloimmunity and solid organ transplantation is to be evaluated. Therefore the pharmacological effects of the novel immunophilin-binding agent SFA on DC were investigated in vitro and in vivo.This work shows that SFA does not affect DC differentiation and phenotypical maturation. IL-12p70 plays a critical role in the pathogenesis of inflammation and autoimmune diseases. We discovered that SFA abrogates bioactive IL-12p70 production by human DC, the major producers of this cytokine. In direct comparison to the related calcineurin inhibitor Cyclosporin A and the mammalian target of Rapamycin inhibitor Rapamycin, SFA acts uniquely within 1h to inhibit (80-95%) IL-12p70 production by differentiated DC. To show that the inhibition is stimulus independent further experiments with Toll-like receptor 3 and 4 ligands were performed. Competitive experiments with a molar excess of Cyclosporin A indicate a cyclophilin A independent blockade of IL-12p70 production. We confirm potent inhibition of IL12p70 production by SFA using purified human blood DC.Real-time RT-PCR reveals 84-94% suppression of IL-12p40, IL-12p35 and IL-23-specific p19 transcription.Another major aim of this work was to reproduce the in vitro findings in an in vivo mouse model in order to clarify the clinical relevance of these findings. Within these in vivo investigations it could be shown, that three day in vivo injections of SFA into mice and stimulation of the animals with LPS/IL-4 blocked 70% of bioactive IL-12 production compared to vehicle injected control animals. By using independent models, we provide evidence that SFA abrogates that SFA abrogates >90% IL-12p70 production in vivo while having no effect on IL-10 AND TNF-a. SFA treatment in vivo showed no influence on in vivo expansion or phenotypic maturation of DC subsets and had nor effects on DC subpopulations.Furthermore, SFA profoundly decreases DC receptor-mediated endocytosis and macropinocytosis and inhibits indirect antigen presentation of CD11c+ DC in vivo. Our results are the first to reveal the immunosuppressive activity of SFA in vivo. Taken together, our in vivo experiments suggest that SFA displays a unique mode of action with respect to DC: strong inhibition of both antigen uptake and bioactive IL-12 production but no significant effects on DC differentiation, expansion and surface costimulatory expression. To our knowledge, no immunosuppressive agent has been reported to date that allows potent suppression on the two key DC functions antigen uptake and IL-12 production without interfering with DC differentiation or DC expansion.We propose that SFA represents a novel class of immunophilin-binding immunosuppressants with high activity against DC and in addition has synergetic effects if combined with other immunopilins like CsA. For an effective prevention of chronic allograft rejection the combination of immunosuppressive drugs with SFA might be a powerful approach

Inter- and intramolecular complexation of copolymers : On the way to non-equilibrium micelles

Macromolecular non-equilibrium self-assemblies hold great promise for on-demand transformations, which result in substantial changes in their physico-chemical properties. For these non-equilibrium self-assemblies, the pathway for the self-assembly determines the final metastable morphology. In contrast to equilibrium structures, it is therefore possible to create different well-defined morphologies at the same conditions. At the moment, stimuli-sensitive polymers are used extensively to introduce structural variations in dependence of adaptable conditions, like temperature or pressure. Triggered structural transformations at constant conditions have been much less investigated. They require the involvement of metastable states, which are able to occupy another local energetic minimum after small deviations from metastability. Hereby changes in the morphology of self-assembled structures are of high interest. A change from e.g. spherical structures to worm-like structures will also induce a change in macroscopic properties. Here, we are interested in systems which allow a switch between different defined self-assembled structures via a small trigger, or in systems where we are able to generate different defined self-assembled structures depending on the used pathway. To achieve this, we use a ternary star-shaped polymeric system. This system is based on a polymer which is water-soluble under all investigated conditions and which stabilizes the self-assembled structures in water. It further consists of several polycationic arms, which form an interpolyelectrolyte complex (IPEC) in presence of an anionic polymer. The complex phase-separates from water and, therefore, causes aggregation and self-assembly upon complexation. Due to the nature of this complex, the possibility for structural rearrangements can be adjusted. Finally, the star-shaped polymer has a temperature-sensitive arm. We observe that the temperature response of this arm is hindered due to weak complex between the temperature-responsive arm and the polycationic arm. Hence, we further investigate ways to regain the temperature response. While placing the polymers at an oil/water interface even enhances the complexation, we find via experiments and simulation a dependence of the amount of formed weak complex on the topology and composition of the star-shaped polymer. This enables the synthesis of a star with the same chemical constituents, but still showing a temperature response, possibly suitable for the generation of non-equilibrium structures. Further, a less capricious diblock copolymer system is studied. By tuning the synthesis concentration and/or relative block lengths, the copolymer can be designed to form self-assembled spherical micelles, spherical crew-cut micelles, worm-like micelles or vesicles. Within certain parameters, it is anticipated that the equilibrium nanostructures are produced, while other parameters lead to kinetically trapped structures. Despite their non-equilibrated nature, these dispersions are kinetically stable for months, as long as certain triggers are avoided. Then, the kinetically trapped structures undergo a morphological transition resulting in a pronounced change in the macroscopic properties

Hydrophobically controlled self-association of pH- and thermo-sensitive triblock copolymers based on poly(acrylic acid- co -tert-butyl acrylate) and poly(propylene oxide)

International audienc