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Eingehende Analyse der Aarhus-Konvention, Espoo-Konvention und UVP-Richtlinie Das Buch untersucht eingehend die Vorgaben des europaischen Atomrechts der Aarhus-Konvention, der Espoo-Konvention sowie der UVP-Richtlinie im Hinblick auf Laufzeit- und Betriebsgenehmigungsverlangerungen. Als Beispiele werden dabei Betriebs- und Laufzeitverlangerungen der tschechischen Kernkraftwerke Temelin und Dukovany herangezogen. Die Laufzeitverlangerung bestehender Atomkraftwerke durch Regierungsakte, Gesetze und Erlasse bietet keine Losung, die dem Grundsatz der Nachhaltigkeit entspricht. Sie ist sogar volker-, europa- und grundrechtswidrig. Um Rechtskonformitat herzustellen, bedarf es einer Umweltvertraglichkeitsprufung, die auch grenzuberschreitend durchgefuhrt werden muss.

During the processing of the helical surfaces on CNC machines, independent of the number of axes of the machine, there will certainly appear geometric deviations from the theoretical profile. Errors of form, which appear in this situation, can be detected through successive measurements. In order to diminish them, it is possible to use a method of compensation the deviations previously measured, which consists in adapting the CNC code used to obtain the helical profiles to the conditions required by the imprecision generated by the geometry of the machine.

In the case of complex surfaces, the processing on 5 axes CNC machines may be approached by taking into consideration the fact that the axis of the cutting tool must stand in a normal direction towards the plan of the surface that needs processing. In this case, a data file will be used, which will be transferred to an application which is capable of generating the CNC code that can be recognized by the programming language of the machine. At the same time, in order to optimize this procedure, the processing of the 3D solid surfaces may be approached. In this case, the piece which is considered a solid, may be decomposed into successive sections that will optimally be processed on the 5 axes CNC machine using the facilities of the 5 axes CNC machine. One viable solution that can be applied in the case of the processing of the 3D surfaces is the decomposition of a solid into successive sections, according to the processing plan. If we use the procedure above described for the processing of the 3D complex surfaces, essential benefits will occur, related to the conditions of the processing, using a cutting tool on a 5 axes CNC machine, especially as compared to the 3 axes CNC machine. In the case of the processing procedure of a 3D complex surface held on a 3 axes CNC machine, risks may appear, such as obtaining a surface with form errors caused by inappropriate position of the cutting tool towards the generated outline. This inconvenient may be eliminated when using a 5 axes CNC machine. This procedure is the subject of the study presented in this article.

Problem Translational research aims to move scientific discoveries across the biomedical spectrum from the laboratory to humans, and to ultimately transform clinical practice and public health policies. Despite efforts to accelerate translational research through national initiatives, several major hurdles remain. Approach The authors created the Pitt Innovation Challenge (PInCh) as an incentive-based, problem-focused approach to solving identified clinical or public health problems at the University of Pittsburgh Clinical and Translational Science Institute in spring 2014. With input from a broad range of stakeholders, PInCh leadership arrived at the challenge question: How do we empower individuals to take control of their own health outcomes? The authors developed the PInCh's three-round proposal submission and review process as well as an online contest management tool to support the process. Outcomes Ninety-two teams submitted video proposals in round one. Proposals included mobile applications (29; 32%), other information technology (19; 21%), and community program (22; 24%) solutions. Ten teams advanced to the final round, where three were awarded $100,000 to implement their solution over 12 months. In a 6-month follow-up survey, 6/11 (55%) team leaders stated the PInCh helped to facilitate connections outside their normal sphere of collaborators. Next steps Additional educational training sessions related to problem-focused research will be developed. The PInCh will be expanded to engage investment and industry communities to facilitate the translation of solutions to clinical practice via commercialization pathways. External organizations and other universities will be engaged to use the PInCh as a mechanism to fuel innovation in their spaces.

tives can lead to innovations that can change the world. The amount of money available for prizes has more than tripled over the last decade to an estimated $1$2 billion, and the sector continues to grow rapidly. Famous prizes, such as the Longitude Prize, the Orteig Prize, and Napoleon’s food preservation prize (see text box on next page), provide powerful evidence of the enormous benefits that be achieved by people competing for prizes. Although hugely popular a century ago, interest in prizes declined during the 1900s, replaced in large part with grant funding. Grants have been credited with establishing the research centers and institutes of excellence that have been behind much of the rapid rise in innovation over the last 100 years. However, after a century of grant-funding cycles that have become ever more deeply entrenched in the complex relationship between funders and recipients, the connection between grant funding and innovation leaves room for improvement While grant funding regroups, the awarding of prizes is again proliferating, not only in terms of numbers but in ambition and aims. The rapid growth of information technology and social media are helping to fuel this proliferation. Most observers see 2004 as the start of this upward trend, as that is the year that Scaled Composites launched a reusable manned spacecraft twice within two weeks—a feat that won the company the $10 million Ansari X PRIZE. From 2004 to 2009, the number of prizes offering large incentives more than tripled across the globe.

Nur ein Verhalten des Verpfl, welches eindeutig gegen das im Exekutionstitel ausgesprochene Unterlassungsgebot verstost, rechtfertigt die Exekutionsschritte gem § 355 EO. Die Auslegung eines Exekutionstitels, wonach die Wendung "jegliche Inbestandgabe von Betriebsflachen ist zu unterlassen" nicht blos den Abschluss von Bestandvertragen sondern auch deren Aufrechterhaltung beinhaltet, ist abzulehnen.

Aim. Molecular imaging studies with benzamide radioligands can reveal competition from endogenous binding at D2/3-receptors in living brain. However, single photon emission computed tomography (SPECT) methods suffer from limited spatial resolution, and ( 11 C)-labeled ligands are only available at positron emission to- mography (PET) research sites with cyclotron-radiochemistry facilities, whereas ( 18 F) can be transported, due to its longer physical half-life. Therefore, we endeavored to characterize the vulnerabilities of the benzamide antagonist ( 18 F)desmethoxyfallypride (DMFP) and its high-affinity congener ( 18 F)fallypride (FP) to competition from endoge- nous dopamine in living mouse brain. Methods. Groups of awake mice were pre- treated with saline, amphetamine (10 mg/kg), or reserpine (5 mg/kg), followed by i.v. tracer injections. Mice were killed at 2.5-90 min (DMFP) or 2.5-180 min (FP) circula- tion times. Brains were dissected and regional radioactivity concentration measured by gamma counting. Other groups of mice were anesthetized for dynamic microPET recordings with DMFP or FP. Binding potentials (BPND) were calculated using cerebel- lum as reference region. Results. With 90-min circulation, DMFP BPND in striatum was 2.4 by dissection and 2.2 by microPET, which showed a 62% decrease in response to amphetamine-evoked dopamine release and a 33% increase after reserpine-evoked dopamine depletion. With 120-min circulation, FP BPND in striatum was 24.1 by dis- section and 9.2 by microPET, which showed a 31% decrease in the amphetamine group, but no effect of reserpine. Dissection showed similar sensitivities for FP bind- ing, but only a 29% amphetamine-evoked reduction for DMFP. Conclusions. Relative to gold standard ex vivo results, microPET estimates of DMFP BPND were unbiased, whereas FP BPND in striatum was substantially underestimated. Both tracers proved suitable for revealing pharmacologically evoked changes in competition at D2/3-recep- tors in striatum of living mice. Synapse 64:313-322, 2010. V

In malignant gliomas, the integrin adhesion receptors seem to play a key role for invasive growth and angiogenesis. However, there is still a controversy about the expression and the distribution of alpha(v)beta(3) integrin caused by malignancy. The aim of our study was to assess the extent and pattern of alpha(v)beta(3) integrin expression within primary glioblastomas (GBMs) compared with low-grade gliomas (LGGs). Tumor samples were immunostained for the detection of alpha(v)beta(3) integrin and quantified by an imaging software. The expression of alpha(v)beta(3) was found to be significantly higher in GBMs than in LGGs, whereby focal strong reactivity was restricted to GBMs only. Subsequent analysis revealed that not only endothelial cells but also, to a large extent, glial tumor cells contribute to the overall amount of alpha(v)beta(3) integrin in the tumors. To further analyze the integrin subunits, Western blots from histologic sections were performed, which demonstrated a significant difference in the expression of the beta(3) integrin subunit between GBMs and LGGs. The presented data lead to new insights in the pattern of alpha(v)beta(3) integrin in gliomas and are of relevance for the inhibition of alpha(v)beta(3) integrin with specific RGD peptides and interfering drugs to reduce angiogenesis and tumor growth.

Sustainability—a term compromising a group of themes and being of immense importance for today’s and all future generations. It has developed in last decades to one of the most central concepts in environmental law and poses an important component of political and juridical aims. The Treaty of Amsterdam implemented sustainability in primary law as a basic objective of the European Union. As a consequence, the EU established the Sustainable Development Strategy (EU SDS) with the aim to improve the living situation of all generations. Also on a national level, many measures have been taken to enhance the “sustainable development” approach. But one has to ask the question: does the concept of sustainability work? Do the measures taken, inter alia, in the fields of transport, energy, climate change and waste management lead to the desired success or is it just a sublime goal, a program without (sufficient) implementation? Or is it even just a tokenism?

The cell cycle regulator p27 Kip1 (p27) is controlled by 26S proteasome-mediated proteolysis by two different pathways. From the S till the G2 phase of the cell cycle, degradation of p27 takes place in the nucleus and is initiated by CDK2-dependent phosphorylation of threonine 187 with subsequent ubiquitination by the SCF Skp2 ubiquitin ligase. During the Gl cell cycle phase (G1), p27 breakdown is cytosolic and is initiated by nuclear export with subsequent ubiquitination by a RING finger ligase called kipl ubiquitination complex. Here we show that the COP9 signalosome (CSN) is a regulator of p27 proteolysis during Gl. The CSN interacts with p27 and the CSN-associated kinase CK2 phosphorylates p27 at two regions. One is central to the protein (amino acids 101-113), and the other was mapped near to the C-terminus (amino acids 170-189). Elimination of the putative C-terminal phosphorylation sites stabilizes ectopic p27 towards proteasomal degradation and abolishes CSN-p27 binding. Inhibition of CSN-associated kinase activity by curcumin attenuates loss of p27 upon cell cycle re-entry. Similar but not additive effects of the phosphoinositol-3-kinase blocker LY 290042 may point to a common pathway of CSN-associated CK2 and protein kinase B/Akt (Akt) in regulating p27 abundance. Akt is found in Flag pulldowns of lysates obtained from cells permanently expressing Flag-tagged CSN2, indicating that Akt is a novel kinase associated with the CSN. Thus, the CSN seems to regulate p27 proteolysis at Gl downstream of Ras-mediated signal pathways.

As directed by the Council of the Aerospace Medical Association, the Commercial Spaceflight Working Group has developed the following position paper concerning medical issues for commercial suborbital spaceflight crewmembers. This position paper has been approved by the AsMA Council to become a policy of the AsMA.

This study investigates the effects of (111)In-oxine incorporation on human mesenchymal stem cells' (hMSC) biology and viability, and the applicability of (111)In-oxine for single-photon emission computed tomography/X-ray computed tomography (SPECT/CT) monitoring of hMSC in vivo.HMSC were labelled with 10 Bq/cell. Cellular retention of radioactivity, cell survival, and migration were evaluated over 48 h. Metabolic activity was assessed over 14 days and the hMSC's stem cell character was evaluated. Serial SPECT/CT was performed after intra-osseous injection to athymic rats over 48 h.Labelling efficiency was 25%, with 61% of incorporated (111)In remaining in the hMSC at 48 h. The radiolabelling was without effect on cell viability, stem cell character, and plasticity, whereas metabolic activity and migration were significantly reduced. Grafted cells could be imaged in situ with SPECT/CT.(111)In-oxine labelling moderately impaired hMSC's functional integrity while preserving their stem cell character. Combined SPECT/CT imaging of (111)In-oxine-labelled hMSC opens the possibility for non-invasive sequential monitoring of therapeutic stem cells.

We used microPET to map the dose–response to the novel P-glycoprotein (P-gp) inhibitor tariquidar (TQD) of the initial influx of the P-gp substrate [ 18 F]-MPPF in rat brain, and to test for effects of P-gp inhibition on the subsequent binding of [ 18 F]-MPPF to serotonin 5-HT 1A receptors. Summation maps of [ 18 F]-MPPF uptake during the first 100 seconds after intravenous injection were calculated in groups of rats with vehicle (glucose 5%) pretreatment, or following pretreatment with TQD at doses of 5, 15, or 30 mg/kg. The early summation image ( K 1 -weighted), were validated as a surrogate marker for the physiological blood–brain clearance ( K 1 ; ml g − 1 min − 1 ) by linear graphic analysis of the unidirectional blood–brain clearance relative to an image-based arterial input measured in the left ventricle of the heart. In the same animals, parametric maps of the [ 18 F]-MPPF binding potential (BP ND ) were calculated from the entire 60-minute emission recordings using conventional reference tissue methods. All [ 18 F]-MPPF recordings were followed by an [ 18 F]-FDG emission recording, the summation of which was used for spatial normalization to a rat brain atlas. Test–retest variability of K 1 -weighted uptake and BP ND was 25%. TQD treatment evoked a global dose-dependent increase in K 1 -weighted summation, which increased 2.5-fold with TQD (30 mg/kg), suggesting an IC 50 of 5 mg/kg TQD. All TQD doses increased the apparent [ 18 F]-MPPF BP ND calculated by the Logan method by 30%–40%, a bias likely arising due to increased free [ 18 F]-MPPF concentrations in brain. TQD (15 mg/kg) evoked a 45% global increase in [ 18 F]-FDG uptake, suggesting perturbation of brain energy metabolism due to P-gp blockade.

Background A Paramecium tetraurelia pilot genome project, the subsequent sequencing of a Megabase chromosome as well as the Paramecium genome project aimed at gaining insight into the genome of Paramecium. These cells display a most elaborate membrane trafficking system, with distinct, predictable pathways in which actin could participate. Previously we had localized actin in Paramecium; however, none of the efforts so far could proof the occurrence of actin in the cleavage furrow of a dividing cell, despite the fact that actin is unequivocally involved in cell division. This gave a first hint that Paramecium may possess actin isoforms with unusual characteristics. The genome project gave us the chance to search the whole Paramecium genome, and, thus, to identify and characterize probably all actin isoforms in Paramecium. Results The ciliated protozoan, P. tetraurelia, contains an actin multigene family with at least 30 members encoding actin, actin-related and actin-like proteins. They group into twelve subfamilies; a large subfamily with 10 genes, seven pairs and one trio with > 82% amino acid identity, as well as three single genes. The different subfamilies are very distinct from each other. In comparison to actins in other organisms, P. tetraurelia actins are highly divergent, with identities topping 80% and falling to 30%. We analyzed their structure on nucleotide level regarding the number and position of introns. On amino acid level, we scanned the sequences for the presence of actin consensus regions, for amino acids of the intermonomer interface in filaments, for residues contributing to ATP binding, and for known binding sites for myosin and actin-specific drugs. Several of those characteristics are lacking in several subfamilies. The divergence of P. tetraurelia actins and actin-related proteins between different P. tetraurelia subfamilies as well as with sequences of other organisms is well represented in a phylogenetic tree, where P. tetraurelia sequences only partially cluster. Conclusion Analysis of different features on nucleotide and amino acid level revealed striking differences in isoforms of actin and actin-related proteins in P. tetraurelia, both within the organism and in comparison to other organisms. This diversification suggests unprecedented specification in localization and function within a unicellular eukaryote.

We have selected a conserved immunogenic region from several actin genes of Paramecium, recently cloned in our laboratory, to prepare antibodies for Western blots and immunolocalization. According to cell fractionation analysis, most actin is structure-bound. Immunofluorescence shows signal enriched in the cell cortex, notably around ciliary basal bodies (identified by anti-centrin antibodies), as well as around the oral cavity, at the cytoproct and in association with vacuoles (phagosomes) up to several μm in size. Subtle strands run throughout the cell body. Postembedding immunogold labeling/EM analysis shows that actin in the cell cortex emanates, together with the infraciliary lattice, from basal bodies to around trichocyst tips. Label was also enriched around vacuoles and vesicles of different size including “discoidal” vesicles that serve the formation of new phagosomes. By all methods used, we show actin in cilia. Although none of the structurally well-defined filament systems in Paramecium are exclusively formed by actin, actin does display some ordered, though not very conspicuous, arrays throughout the cell. F-actin may somehow serve vesicle trafficking and as a cytoplasmic scaffold. This is particularly supported by the postembedding/EM labeling analysis we used, which would hardly allow for any large-scale redistribution during preparation.

All bacterial strains classified into the family Rhizobiaceae can be induced to undergo a fundamental genome rearrangement. The special structure of their genome allows the formation of five distinctive phenotypes, each one adapted to a different habitat (Fig. 1). This genome rearrangement can be induced by DNA-damaging agents, UV irridiation or chemical mutagenesis. For expression, cells have to be protected against photorepair and their replication has to be reduced by stress treatment. The rearrangement process is, with special exceptions, reversible. Classes I and II comprise Agrobacteria and Rhizobia, class III nitrogen-fixing strains and classes IV and V two different carotenoid-pigmented types. One of the class V strains has been shown to be an effective legume-symbiont. DNA characteristics and inter-class hybridization results show not only that the genomes are completely reconstructed during each step of rearrangement, but also that the bacteria of all five classes are genetically correlated. In many cases the genetic label has been maintained during rearrangement into the different classes. The identity of each class is protected by a class-specific restriction and modification system, which was analyzed by phage typing experiments and by functional analysis of class-specific restriction endonucleases. We propose to designate the classes as different species of Rhizobiaceae. The unidirectional rearrangement between nodulating Rhizobia and tumorgenic Agrobacteria has been interpreted as a sequence of decreasing complexity of genomic regions coding for the plant interactions of these bacteria.

This paper describes and compares the newly established archeological Lagunillas phase for the Lake Maracaibo Basin in northwestern Venezuela. Lagunillas is characterized by subsistence based on corn, by pile dwellings, and by complex pottery emphasizing plastic decorative techniques. A set of radiocarbon dates places Lagunillas into Period II (1000 B.C.-300 A.C.) of the regional chronology. Although it shares some traits with other western Venezuelan pottery traditions, Lagunillas also shows northern Colombian, Ecuadorian, and, indirectly, Amazonian influences.

Excavations of a workshop and cemetery in the high Venezuelan Andes yielded winged artifacts made of serpentinite at various stages of finish. Serpentinites are unknown in the Venezuelan Andes, and the raw material was obtained from natural sources located in northern South American or possibly the Antilles, or by trade.