49 research outputs found
Bildungsplanung
Bildungsplanung ist ein spezieller Bereich der Planung der sozialen Infrastruktur. Insofern bestehen Querverbindungen zu der kommunalen und regionalen Planung, der Sicherung der Daseinsvorsorge und zu dem Zentrale-Orte-Konzept. Einen besonderen Fokus legt der Beitrag auf das Themenfeld der Schulentwicklungsplanung
Nova Geminorum 1912 and the Origin of the Idea of Gravitational Lensing
Einstein's early calculations of gravitational lensing, contained in a
scratch notebook and dated to the spring of 1912, are reexamined. A hitherto
unknown letter by Einstein suggests that he entertained the idea of explaining
the phenomenon of new stars by gravitational lensing in the fall of 1915 much
more seriously than was previously assumed. A reexamination of the relevant
calculations by Einstein shows that, indeed, at least some of them most likely
date from early October 1915. But in support of earlier historical
interpretation of Einstein's notes, it is argued that the appearance of Nova
Geminorum 1912 (DN Gem) in March 1912 may, in fact, provide a relevant context
and motivation for Einstein's lensing calculations on the occasion of his first
meeting with Erwin Freundlich during a visit in Berlin in April 1912. We also
comment on the significance of Einstein's consideration of gravitational
lensing in the fall of 1915 for the reconstruction of Einstein's final steps in
his path towards general relativity.Comment: 31 p
Conversion from calcineurin inhibitor to belatacept-based maintenance immunosuppression in renal transplant recipients:A randomized phase 3b Trial
Significance Statement This randomized trial demonstrates the safety and efficacy of conversion from calcineurin inhibitor (CNI)? to belatacept-based maintenance immunosuppression in renal transplant recipients 6?60 months post-transplant. Patients converted to belatacept showed sustained improvement in renal function associated with an acceptable safety profile consistent with prior experience and a smaller treatment difference in acute rejection postconversion compared with that observed in earlier studies in de novo renal allograft recipients. These results favor the use of belatacept as an alternative to continued long-term CNI-based maintenance immunosuppression, which is particularly relevant for CNI-intolerant patients, including those who experience nephrotoxicity. These data help inform clinical practice guidelines regarding the conversion of such patients to an alternative immunosuppressive drug regimen.Background Calcineurin inhibitors (CNIs) are standard of care after kidney transplantation, but they are associated with nephrotoxicity and reduced long-term graft survival. Belatacept, a selective T cell costimulation blocker, is approved for the prophylaxis of kidney transplant rejection. This phase 3 trial evaluated the efficacy and safety of conversion from CNI-based to belatacept-based maintenance immunosuppression in kidney transplant recipients.Methods Stable adult kidney transplant recipients 6?60 months post-transplantation under CNI-based immunosuppression were randomized (1:1) to switch to belatacept or continue treatment with their established CNI. The primary end point was the percentage of patients surviving with a functioning graft at 24 months.Results Overall, 446 renal transplant recipients were randomized to belatacept conversion (n=223) or CNI continuation (n=223). The 24-month rates of survival with graft function were 98% and 97% in the belatacept and CNI groups, respectively (adjusted difference, 0.8; 95.1% CI, ?2.1 to 3.7). In the belatacept conversion versus CNI continuation groups, 8% versus 4% of patients experienced biopsy-proven acute rejection (BPAR), respectively, and 1% versus 7% developed de novo donor-specific antibodies (dnDSAs), respectively. The 24-month eGFR was higher with belatacept (55.5 versus 48.5 ml/min per 1.73 m(2) with CNI). Both groups had similar rates of serious adverse events, infections, and discontinuations, with no unexpected adverse events. One patient in the belatacept group had post-transplant lymphoproliferative disorder.Conclusions Switching stable renal transplant recipients from CNI-based to belatacept-based immunosuppression was associated with a similar rate of death or graft loss, improved renal function, and a numerically higher BPAR rate but a lower incidence of dnDSA. Clinical Trial registry name and registration number: A Study in Maintenance Kidney Transplant Recipients Following Conversion to Nulojix? (Belatacept)-Based, NCT01820572Nephrolog
Novel structural arrangement of nematode cystathionine β-synthases: characterization of Caenorhabditis elegans CBS-1
CBSs (cystathionine β-synthases) are eukaryotic PLP (pyridoxal 5 *-phosphate)-dependent proteins that maintain cellular homocysteine homoeostasis and produce cystathionine and hydrogen sulfide. In the present study, we describe a novel structural arrangement of the CBS enzyme encoded by the cbs-1 gene of the nematode Caenorhabditis elegans. The CBS-1 protein contains a unique tandem repeat of two evolutionarily conserved catalytic regions in a single polypeptide chain. These repeats include a catalytically active C-terminal module containing a PLP-binding site and a less conserved N-terminal module that is unable to bind the PLP cofactor and cannot catalyse CBS reactions, as demonstrated by analysis of truncated variants and active-site mutant proteins. In contrast with other metazoan enzymes, CBS-1 lacks the haem and regulatory Bateman domain essential for activation by AdoMet (S-adenosylmethionine) and only forms monomers. We determined the tissue and subcellular distribution of CBS-1 and showed that cbs-1 knockdown by RNA interference leads to delayed development and to an approximately 10-fold elevation of homocysteine concentrations in nematode extracts. The present study provides the first insight into the metabolism of sulfur amino acids and hydrogen sulfide in C. elegans and shows that nematode CBSs possess a structural feature that is unique among CBS proteins
Die Entwicklung regionaler Schulstrukturen in peripheren ländlichen Räumen unter dem Paradigma demografischer Schrumpfung. Das Beispiel zweier Landkreise des Landes Brandenburg
In großen zusammenhängenden Regionen der ostdeutschen Länder gewinnt die Frage des Erhalts regionaler Bildungssysteme in peripheren Räumen mit geringer Bevölkerungsdichte und großer Zentrenferne eine neue Dimension. Verschärft wird die Lage durch den dramatischen Einbruch der Schülerzahlen. Szenarien der Bevölkerungsentwicklung deuten darauf hin, dass in einigen Jahren auch Regionen in den westdeutschen Bundesländern mit diesem Problem konfrontiert sein werden. Die Zielkonkurrenz zwischen Schrumpfungsszenarien und annähernd ausgewogenen gleichwertigen schulischen Versorgungsstrukturen erfordert neue Entwicklungsstrategien auf der Ebene regionaler Planung ebenso wie auf der Ebene einzelschulischer Entwicklung. Rechtlich garantierte Wahloptionen für Bildungslaufbahnen treten zurück hinter das Ziel der Garantie einer schulischen Mindestversorgung. In diesem Beitrag werden die quantitativen Rahmendaten und planerischen Prozesse für zwei periphere ländliche Regionen des Landes Brandenburg dargestellt und in ihren vorläufigen Ergebnissen bewertet. (DIPF/Orig.)In larger interconnected regions in the East German Laender the question of the preservation of regional educational systems in peripheral areas with a low population density and in great distance to urban centers has gained a new dimension. The situation is aggravated by the dramatic decline in the number of students. Scenarios concerning population development indicate that, within a few years, rural areas in the West German Laender will be confronted with the same problem. The conflicting targets of serving a shrinking population and of providing a nearly balanced, equally matched structure of educational provision demands new strategies of development on the level of regional planning as well as on the level of the development of the individual schools. Options concerning the choice of an educational career guaranteed by law recede behind the need to guarantee a minimal supply of education. The author presents the quantitative framework data and planning processes for two peripheral rural areas in Brandenburg and evaluates the preliminary results. (DIPF/Orig.
Safe cosmetics without animal testing? Contributions of the EU Project Sens-it-iv
The 7th Ammendment to the Cosmetics Directive of the European Commission (Directive 76/768/EEC2) bans the marketing of cosmetics containing animal-tested ingredients since March 2009. Excepted are only tests for repeated dose toxicity, for which the animal ban will come into effect by 2013. One major concern for cosmetics, i.e. the risk of containing skin (contact) sensitizers, has in the past been addressed almost exclusively by animal testing. It is this problem attracting the central interest of the integrated research project Sens-it-iv (Novel Testing Strategies for in vitro Assessment of Allergens, http://www.sens-it-iv.eu ), funded by the EC within framework 6 since October 2005. Here, the 28 Sens-it-iv partners from 10 European States present the 5 most promising types of in vitro assays selected for further refinement. These are: (1) a human epidermal equivalent (EE) model to rank contact allergens according to their sensitizing potency, (2) identification of contact sensitizers, including pro-haptens, through intracellular production of IL-18 by the human keratinocyte cell line NCTC 2544, (3) determination of activation markers such as CD86, CD54 and most prominently CXCL8 (IL-8) on/in dendritic cell lines, (4) contact sensitizer-specific migration of MUTZ Langerhans cells towards the chemokine CXCL12, and (5) the allergen-specific activation and proliferation of na < ve human T cells. Ongoing genomic and proteomic experiments are in the process of identifying larger sensitizer-specific biological marker signatures to be integrated into the above assays. We hope to supply the European control agencies with a basis for further validation of in vitro assays by the end of 2010