Interindividueller Vergleich der PSMA-Radioliganden 617, I&T und 11 in der PET/CT-Diagnostik beim biochemischen Rezidiv des Prostatakarzinoms

Der biochemische Rückfall von Prostatakrebs ist diagnostisch herausfordernd, aber von großer klinischer Bedeutung für die nachfolgende Patientenbehandlung. Die PET/CT mit radioaktiv markierten PSMA-Liganden übertrifft herkömmliche diagnostische Methoden beim Nachweis eines Tumorrezidivs. Mehrere Radiopharmaka standen und stehen zur Verfügung. Ziel dieser Studie war es zu untersuchen, ob sich die routinemäßig angewandten 68Ga-PSMA-Liganden PSMA-617, -I&T und -11 (HBED-CC) in der physiologischen und pathologischen Verteilung oder in der Tumorerkennungsrate unterscheiden. Eine retrospektive Auswertung von 190 Patienten (39 Patienten erhielten PSMA-617, 68 Patienten PSMA-I&T und 83 Patienten PSMA-11) zeigte signifikante Unterschiede in der Tracer-Akkumulation in allen untersuchten Organen. Die geringe Retention in den Kompartimenten Blutpool, Knochen und Muskelgewebe ist ein theoretischer Vorteil von PSMA-11. Die Bewertung der Aufnahme von Tumorläsionen und der Erkennungsrate ergab keine Überlegenheit eines der drei Radiopharmaka, weder in der Gesamtpopulation noch in besonders herausfordernden Untergruppen wie Patienten mit sehr niedrigen PSA-Werten. Wir schließen daraus, dass alle drei 68Ga-PSMA-Liganden in diesem klinisch wichtigen Szenario gleichermaßen geeignet sind und sich im Falle von Nichtverfügbarkeit oder Produktionseinschränkungen gegenseitig ersetzen können

Apelin Controls Angiogenesis-Dependent Glioblastoma Growth

Glioblastoma (GBM) present with an abundant and aberrant tumor neo-vasculature. While rapid growth of solid tumors depends on the initiation of tumor angiogenesis, GBM also progress by infiltrative growth and vascular co-option. The angiogenic factor apelin (APLN) and its receptor (APLNR) are upregulated in GBM patient samples as compared to normal brain tissue. Here, we studied the role of apelin/APLNR signaling in GBM angiogenesis and growth. By functional analysis of apelin in orthotopic GBM mouse models, we found that apelin/APLNR signaling is required for in vivo tumor angiogenesis. Knockdown of tumor cell-derived APLN massively reduced the tumor vasculature. Additional loss of the apelin signal in endothelial tip cells using the APLN-knockout (KO) mouse led to a further reduction of GBM angiogenesis. Direct infusion of the bioactive peptide apelin-13 rescued the vascular loss-of-function phenotype specifically. In addition, APLN depletion massively reduced angiogenesis-dependent tumor growth. Consequently, survival of GBM-bearing mice was significantly increased when APLN expression was missing in the brain tumor microenvironment. Thus, we suggest that targeting vascular apelin may serve as an alternative strategy for anti-angiogenesis in GBM

Middle East - North Africa and the millennium development goals : implications for German development cooperation

          Closed-loop controlled combustion is a promising technique to improve the overall performance of internal combustion engines and Diesel engines in particular. In order for this technique to be implemented some form of feedback from the combustion process is required. The feedback signal is processed and from it combustionrelated parameters are computed. These parameters are then fed to a control process which drives a series of outputs (e.g. injection timing in Diesel engines) to control their values. This paper’s focus lies on the processing and computation that is needed on the feedback signal before this is ready to be fed to the control process as well as on the electronics necessary to support it. A number of feedback alternatives are briefly discussed and for one of them, the in-cylinder pressure sensor, the CA50 (crank angle in which the integrated heat release curve reaches its 50% value) and the IMEP (Indicated Mean Effective Pressure) are identified as two potential control variables. The hardware architecture of a system capable of calculating both of them on-line is proposed and necessary feasibility size and speed considerations are made by implementing critical blocks in VHDL targeting a flash-based Actel ProASIC3 automotive-grade FPGA

A method for characterizing the chemical heterogeneity of comb-copolymers and its dependence on synthesis routes

The heterogeneity in chemical structure of polymers is difficult to characterize and consequently remains an often-overlooked factor in mechanistic studies of functional polymers, as well as in their industrial scale optimization. In this study, we present a method to characterize chemical heterogeneity and apply it to illustrate how it can be affected differently in different synthesis routes. The polymers used are comb-copolymer dispersants used in particulate suspensions which are composed of a polycarboxylate backbone onto which PEG side chains are grafted. The largest use of these polymers concerns concrete, where they are referred to as poly(carboxylate ether) (PCE) superplasticizers and produced at a very large industrial scale. Apart from their practical relevance, PCEs provide a good test case for studying the means and benefits of characterizing chemical heterogeneity. Indeed, the simple addition of a UV detector to a traditional SEC setup with RI detection allowed us to monitor variations in the grafting ratio in dependence on the molecular size. We show that the synthesis pathway significantly impacts the chemical heterogeneity. The suggested method is versatile and can be adapted for a wide range of hydrophilic copolymers. Thus, we present a tool to comprehensively analyze the molecular heterogeneity of dispersants and give a deep insight into their chemical dispersity.ISSN:2073-436

Stable carbon and oxygen isotope composition of benthic foraminifera

Seventeen surface sediment samples from the North Atlantic Ocean off NE-Greenland between 76° and 81°N, and nine samples from the South Atlantic Ocean close to Bouvet Island between 48° and 55°S were taken with the aid of a Multiple Corer and investigated for their live (Rose Bengal stained) benthic foraminiferal content within the upper 15 cm of sediment. Preferentially endobenthic Melonis barleeanum, Melonis zaandami, and Bulimina aculeata as well as preferentially epibenthic Lobatula lobatula were counted from 1-cm-thick sediment slices each and analyzed for stable carbon and oxygen isotopic compositions of their calcareous tests. Live and dead specimens were counted and measured separately. The carbon isotopic composition of the foraminifera was compared to that of the dissolved inorganic carbon (DIC) of simultaneously sampled bottom water. During a period of one month, one station off NE-Greenland was replicately sampled once every week and samples were processed as above. Live specimens of Lobatula lobatula are confined to the uppermost two centimeters of sediment. Live specimens of Melonis spp. are found down to 8 cm within the sediment but with a distinct sub-surface maximum between 2 and 5 cm. The down-core distribution of live Bulimina aculeata shows a distinct surface maximum in the top centimeter and constant but low numbers down to 11-cm subbottom depth. The average stable carbon isotopic composition (d13C versus per mil PDB) of live Lobatula lobatula off NE-Greenland is by 0.4±0.1 per mil higher than the d13CDIC of the ambient bottom water at the time of sampling. There is evidence that this species calcify before the ice-free season, when bottom water d13CDIC is supposed to be higher. This would reconfirm the one-to-one relationship between d13C of ambient water DIC and cibicids, widely used by paleoceanographers. Live Melonis barleeanum show a negative offset from bottom water DIC of -1.7±0.6 per mil in the uppermost sediment and of -2.2±0.5 per mil in 3-4-cm subbottom depth. All d13C values of live Melonis spp. decrease within the upper four centimeters, regardless of the time of sampling and site investigated. The offset of live Bulimina aculeata from bottom water d13CDIC values of 8 stations rather constantly amounts to -0.6±0.1 per mil, no matter what subbottom depth the specimens are from. At one station however, where is strong indication of elevated organic carbon flux, the negative offset averaged over all sub-bottom depths increases to -1.5±0.2 per mil. Buliminids actively move within the sediment and by this either record an average isotope signal of the pore water or the signal of one specific calcification depth. The recorded signal, however, depends on the organic carbon flux and reflects general but site-specific pore water d13CDIC values. If compared with epibenthic d13C values from the same site, not influenced by pore water and related phytodetritus layer effects, Buliminad13C values bear some potential as a paleoproductivity proxy. Specimens of Melonis spp. seem to prefer a more static way of life and calcify at different but individually fix depths within the sediment. Although live specimens thus record a stratified pore water d13C signal, there is no means yet to correct for bioturbational and early diagenetic effects in fossil faunas

Microhabitat preferences and stable carbon isotopes of endobenthic foraminifera: clue to quantitative reconstruction of oceanic new production?

Seventeen surface sediment samples from the North Atlantic Ocean off NE-Greenland between 76° and 81°N, and nine samples from the South Atlantic Ocean close to Bouvet Island between 48° and 55°S were taken with the aid of a Multiple Corer and investigated for their live (Rose Bengal stained) benthic foraminiferal content within the upper 15 cm of sediment. Preferentially endobenthic Melonis barleeanum, M. zaandami, and Bulimina aculeata as well as preferentially epibenthic Lobatula lobatula were counted from 1-cm-thick sediment slices each and analyzed for stable carbon and oxygen isotopic compositions of their calcareous tests. Live and dead specimens were counted and measured separately. The carbon isotopic composition of the foraminifera was compared to that of the dissolved inorganic carbon (DIC) of simultaneously sampled bottom water. During a period of one month one station off NE-Greenland was replicately sampled once every week and samples were processed as above.Live specimens of Lobatula lobatula are confined to the uppermost two centimeters of sediment. Live specimens of Melonis spp. are found down to eight centimeters within the sediment but with a distinct sub-surface maximum between two and five centimeters. The down-core distribution of live Bulimina aculeata shows a distinct surface maximum in the top centimeter and constant but low numbers down to 11 cm subbottom depth.The average stable carbon isotopic composition (d13C per mil VPDB) of live L. lobatula off NE-Greenland is by 0.4 ± 0.1 per mil higher than the d13CDIC of the ambient bottom water at the time of sampling. There is evidence that this species calcify before the ice-free season, when bottom water d13CDIC is supposed to be higher. This would reconfirm the one-to-one relationship between d13C of ambient water DIC and cibicids, widely used by paleoceanographers. Live M. barleeanum show a negative offset from bottom water DIC of -1.7 ± 0.6 per mil in the uppermost sediment and of -2.2 ± 0.5 per mil in three to four centimeters subbottom depth. All d13C values of live Melonis spp. decrease within the upper four centimeters, regardless of the time of sampling and site investigated. The offset of live B. aculeata from bottom water d13CDIC values of eight stations rather constantly amounts -0.6 ± 0.1 per mil, no matter what subbottom depth the specimens are from. At one station however, where is strong indication of elevated organic carbon flux, the negative offset averaged over all sub-bottom depths increases to -1.5 ± 0.2 per mil. Buliminids actively move within the sediment and by this either record an average isotope signal of the pore water or the signal of one specific calcification depth. The recorded signal, however, depends on the organic carbon flux and reflects general but site specific pore water d13CDIC values. If compared with epibenthic d13C values from the same site, not influenced by pore water and related phytodetritus layer effects, Bulimina d13C values bear some potential as a paleoproductivity proxy. Specimens of Melonis spp. seem to prefer a more static way of life and calcify at different but individually fix depths within the sediment. Although live specimens thus record a stratified pore water d13C signal, there is no means yet to correct for bioturbational and early diagenetic effects in fossil faunas