Search for K isomers in 252,254 No and 260 Sg and investigation of their nuclear structure

Study of K isomerism in the transfermium region around the deformed shells at N=152, Z=102, and N=162, Z=108 provides important information on the structure of heavy nuclei. Recent calculations suggest that the K-isomerism can enhance the stability of such nuclei against alpha emission and spontaneous fission. Nuclei showing K isomerism have neutron and proton orbitals with large spin projections on the symmetry axis which is due to multi quasiparticle states with aligned spins K. Quasi-particle states are formed by breaking pairs of nucleons and raising one or two nucleons in orbitals near the Fermi surface above the gap, forming high K (multi)quasi-particle states mainly at low excitation energies. Experimental examples are the recently studied two quasi-particle K isomers in 250,256-Fm, 254-No, and 270-Ds. Nuclei in this region, are produced with cross sections ranging from several nb up to µb, which are high enough for a detailed decay study. In this work, K isomerism in Sg and No isotopes was studied at the velocity filter SHIP of GSI, Darmstadt. The data were obtained by using a new data acquisition system which was developed and installed during this work. 252,254-No and 260-Sg were produced in fusion evaporation reactions of 48-Ca and 54-Cr projectiles with 206,208-Pb targets at beam energies close to the Coulomb barrier. A new K isomer was discovered in 252-No at excitation energy of 1.25 MeV, which decays to the ground state rotational band via gamma emission. It has a half-life of about 100 ms. The population of the isomeric state was about 20% of the ground state population. Detailed investigations were performed on 254-No in which two isomeric states (275 ms and 198 µs) were already discovered by R.-D. Herzberg, but due to the higher number of observed gamma decays more detailed information about the decay path of the isomers was obtained in the present work. In 260-Sg, we observed no statistically significant component with a half life different from that of the ground state. A comparison between experimental results and theoretical calculations of the single particle energies shows a fair agreement. The structure of the here studied nuclei is in particular important as single particle levels are involved which are relevant for the next shell closure expected to form the region of the shell stabilized superheavy elements at proton numbers 114, 120, or 126 and neutron number 184. K isomers, in particular, could be an ideal tool for the synthesis and study of these isotopes due to enhanced spontaneous fission life times which could result in higher alpha to spontaneous fission branching ratios and longer half lifes.

Nanodiamanten in primitiven Meteoriten: Strukturuntersuchungen und Einfluss des Rückstoßes bei beta-Zerfällen

Im Rahmen dieser Arbeit wurden Untersuchungen zur Rückstoßeffekten, sowie Ausheizversuche zur Erforschung struktureller Veränderungen und Änderung der Edelgaskonzentrationen und Ausgasungsmuster in meteoritischen Nanodiamanten durchgeführt. In der ersten Versuchsserie wurden die durch prompte "?"-Strahlung bei Neutronenaktivierung von Brom in terrestrische Detonationsdiamanten und durch den "?"-Zerfall von 22Na in synthetischen und meteoritischen Diamanten verursachten Rückstoßverluste bestimmt. Diese wurden mit theoretischen Verlustwerten, berechnet mit Hilfe der SRIM-Software und der Korngrößenverteilung, verglichen. Im Fall der prompten "?"-Strahlung war der Unterschied signifikant. Hierzu können allerdings systematische Unsicherheiten in den gemessenen Verlusten, wie z.B. unbekannte Br-Verteilung innerhalb der Diamanten beigetragen haben. Die Ergebnisse des zweiten Versuchs bei kleineren Rückstoß-Energien, wie sie auch in der Natur vorkommen würden, zeigten dagegen keinen signifikanten Unterschied. Dies führt zu der Schlussfolgerung, dass weder das „Fehlen“ einiger in Supernovae Typ II gebildeter Radionuklide, wie 26Al, 44Ti, in den Diamanten noch die in einem für die Erklärung des Xe-H vorgeschlagenen Modell benötigte frühzeitige Trennung der Vorläuferkerne stabiler Xe-Isotope von den stabilen Xe-Isotopen durch Rückstoßverluste erklärt werden kann. In der zweiten Versuchsreihe wurden meteoritische Nanodiamantproben bei unterschiedlichen Temperaturen im Vakuum vorgeheizt und danach, um die Heizprodukte zu entfernen, chemisch behandelt. Bei allen Vorheiztemperaturen wurden zwiebelähnliche Strukturen registriert und auch in den nachbehandelten Proben wurden, bedingt durch die wegen Verklumpung der Proben eingeschränkte chemische Behandlung, neben Diamanten unveränderte, oder teilweise zerstörte Umwandlungsprodukte gefunden. Weiterhin wurden Edelgaskonzentrationen und Ausgasungsmuster gemessen, um die durch Vorheizen und chemische Behandlung bedingten Veränderungen im Vergleich zu den Original-Diamanten zu untersuchen. Ein unerwartetes Ergebnis dieser Untersuchungen war, dass die vorgeheizten und chemisch nachbehandelten Proben deutlich niedrigere Ausbeuten im Vergleich zu den nur vorgeheizten zeigten, was darauf hindeutete, dass die während des Vorheizens entstandenen Umwandlungsprodukte, wie z.B. zwiebelähnliche Strukturen, Edelgase zurückhalten konnten, die später (teilweise) durch chemische Behandlung entfernt wurden.

Gen knockdown der Metalloproteasen Meprin alpha 1, alpha 2 und beta im Zebrabärbling Danio rerio

Die Metalloproteasen Meprin α und β übernehmen Schlüsselfunktionen in vielen (patho-) physiologischenrnProzessen. So sind sie beteiligt an der Umstrukturierung der extrazellulären Matrix, an immunologischenrnReaktionen oder an entzündlichen Gewebserkrankungen. Die beiden Enzyme kommenrnhauptsächlich in den Bürstensaummembranen von Niere und Darm sowie in der Haut von Vertebratenrnvor. Für die Erforschung der biologischen Aktivität der Meprine wurde in dieser Arbeit der ModellorganismusrnDanio rerio verwendet, der vor allem durch die Möglichkeit der gentechnischen Manipulationrnprädestiniert ist. Im Fisch konnten drei homologe Enzyme (Meprin α1, α2 und β) nachgewiesenrnwerden. Während mRNA-Analysen eine nahezu ubiquitäre Verteilung der Meprine offenbarten,rnkonnte ich mittels spezifischer Antikörper die Expression auf Proteinebene nachweisen. WährendrnMeprin α1 und β verstärkt im Darmepithel und in der Epidermis lokalisiert sind, konnte Meprinrnα2 ausschließlich in der Lamina propria des Darms identifiziert werden.rnDer Hauptteil der vorliegenden Arbeit zielt auf die spezifische Reduzierung des Expressionslevels derrnMeprine in Embryonen des Zebrabärblings. Dies wurde durch die Mikroinjektion von sogenanntenrnMorpholinos in die Zygote erzielt. Morpholinos sind RNA-Moleküle, die spezifisch an die mRNA desrnZielproteins binden können und die Translation verhindern. Die auftretenden Effekte durch das Fehlenrnder Meprine lassen so Rückschlüsse auf ihre physiologische Funktion zu. Nach der Injektion vonrnMorpholinos gegen Meprin α1 zeigten sich lediglich leichte epidermale Deformationen. Bei Meprin βrnhingegen kam es zu einer massiven Fehlbildung von Organen im Rumpf- und Schwanzbereich. Diesesrnführte zu erheblichen Defekten; die Embryonen starben innerhalb der ersten 24 Stunden nach derrnBefruchtung. Demzufolge müssen Meprin α1 und Meprin β insbesondere an der Gewebsdifferenzierungrnbeteiligt sein. Dies korreliert mit verschiedenen Experimenten, u.a. an knockout Mäusen, ausrndenen hervorgeht, dass die Prozessierung und Aktivierung der Cytokine Interleukin-1β oder Interleukin-rn18 durch Meprin β erfolgen kann.rnDie Injektion von Meprin α2-Morpholinos erbrachte ein weiteres, eindrucksvolles Ergebnis: Das Blutgefäßsystemrnvon injizierten Embryonen war vollständig unterbrochen und es sammelten sich Erythrozytenrnim Bereich der Caudalvene an. Diese Phänotypen gleichen den knockdown-Experimenten mitrndem vascular endothelial growth factor VEGF-A, dem entscheidenden Wachstumsfaktor in der Angiogenesern(Blutgefäßbildung). Eine Inkubation des humanen VEGF-A mit (humanem) rekombinantemrnMeprin α bzw. β führte zu einer differenzierten Prozessierung des Moleküls. Diese Ergebnisse legenrnnahe, dass Meprin α pro-angiogenetisch wirkt, indem es VEGF-A prozessiert und damit die Gefäßbildungrnaktiviert. Aus den Daten dieser Arbeit wird die hohe Signifikanz der Meprine für die Proliferationrnund Differenzierung spezieller Gewebe deutlich, welche somit eine wichtige Grundlage für Studienrnan höheren Vertebraten darstellt.

Funktionelle Charakterisierung der Metalloendopeptidasen Meprin alpha und Meprin beta unter besonderer Berücksichtigung pathologischer Umstände in der menschlichen Dermis

Im Rahmen dieser Arbeit wurden zwei neuentdeckte Astacin-ähnliche-Proteasen LAST undrnLAST_MAM aus dem Pfeilschwanzkrebs Limulus polyphemus funktionell charakterisiert.rnInsbesondere LAST_MAM, eignet sich zur phylogenetischen Untersuchung, hinsichtlich derrnEvolution von Astacin-ähnlichen-Proteasen mit MAM-Domäne, zu denen auch die Meprinernzählen. Es wurde deutlich, dass LAST_MAM nicht unmittelbar mit anderen Astacinen, diernüber eine MAM-Domäne verfügen, verwandt ist, und dass von einer divergenten Entwicklungrndieser Proteasen und der MAM-Domäne selbst ausgegangen werden muss.rnMeprin Metalloendopeptidasen werden in membrangebundener und sezernierter Form,rnvorwiegend in Epithelien aber auch in intestinalen Leukozyten und bestimmten Krebszellenrnexprimiert. Meprin

Molecular interaction of the human metalloprotease meprin beta with the amyloid precursor protein, ADAM10, and ADAM17 based on proteomics

Die Zinkendopeptidasen Meprin α und β sind Schlüsselkomponenten in patho(physiologischen) Prozessen wie Entzündung, Kollagenassemblierung und Angiogenese. Nach ihrer Entdeckung in murinen Bürstensaummembranen und humanen Darmepithelien, wurden weitere Expressionsorte identifiziert, z.B. Leukozyten, Krebszellen und die humane Haut. Tiermodelle, Zellkulturen und biochemische Analysen weisen auf Funktionen der Meprine in der Epithelialdifferenzierung, Zellmigration, Matrixmodellierung, Angiogenese, Bindegewebsausbildung und immunologische Prozesse hin. Dennoch sind ihre physiologischen Substrate weitgehend noch unbekannt. Massenspektrometrisch basierte Proteomics-Analysen enthüllten eine einzigartige Spaltspezifität für saure Aminosäurereste in der P1´ Position und identifizierten neue biologische Substratkandidaten. Unter den 269 extrazellulären Proteinen, die in einem Substratscreen identifiziert wurden, stellten sich das amyloid precursor protein (APP) and ADAM10 (a disintegrin and metalloprotease 10) als sehr vielversprechende Kandidaten heraus. Mehrere Schnittstellen innerhalb des APP Proteins, hervorgerufen durch verschiedenen Proteasen, haben unterschiedlichen Auswirkungen zur Folge. Die β-Sekretase BACE (β-site APP cleaving enzyme) prozessiert APP an einer Schnittstelle, welche als initialer Schritt in der Entwicklung der Alzheimer Erkrankung gilt. Toxische Aβ (Amyloid β)-Peptide werden in den extrazellulären Raum freigesetzt und aggregieren dort zu senilen Plaques. Membran verankertes Meprin β hat eine β-Sekretase Aktivität, die in einem Zellkultur-basierten System bestätigt werden konnte. Die proteolytische Effizienz von Meprin β wurde in FRET (Fluorescence Resonance Energy Transfer)-Analysen bestimmt und war um den Faktor 104 höher als die von BACE1. Weiterhin konnte gezeigt werden, dass Meprin β die ersten zwei Aminosäuren prozessiert und somit aminoterminal einen Glutamatrest freisetzt, welcher nachfolgend durch die Glutaminylzyklase in ein Pyroglutamat zykliert werden kann. Trunkierte Aβ-Peptide werden nur in Alzheimer Patienten generiert. Aufgrund einer erhöhten Hydrophobie weisen diese Peptide eine höhere Tendenz zur Aggregation auf und somit eine erhöhte Toxizität. Bis heute wurde keine Protease identifiziert, welche diese Schnittstelle prozessiert. Die Bildung der Meprin vermittelten N-terminalen APP Fragmenten wurde in vitro und in vivo detektiert. Diese N-APP Peptide hatten keine cytotoxischen Auswirkungen auf murine und humane Gehirnzellen, obwohl zuvor N-APP als Ligand für den death receptor (DR) 6 identifiziert wurde, der für axonale Degenerationsprozesse verantwortlich ist. rnIm nicht-amyloidogenen Weg prozessiert ADAM10 APP und entlässt die Ektodomäne von der Zellmembran. Wir konnten das ADAM10 Propeptid als Substrat von Meprin β identifizieren und in FRET Analysen, in vitro und in vivo zeigen, dass die Meprin vermittelte Prozessierung zu einer erhöhten ADAM10 Aktivität führt. Darüber hinaus wurde ADAM10 als Sheddase für Meprin β identifiziert. Shedding konnte durch Phorbol 12-myristate 13-acetate (PMA) oder durch das Ionophor A23187 hervorgerufen werden, sowie durch ADAM10 Inhibitoren blockiert werden. rnDiese Arbeit konnte somit ein komplexes proteolytisches Netwerk innerhalb der Neurophysiologie aufdecken, welches für die Entwicklung der Alzheimer Demenz wichtig sein kann.rn

Messung des elektrischen Neutron-Formfaktors in der Reaktion 3 He(e,e'n)pp bei Q 2 = 1.58 (GeV/c) 2

Die elektromagnetischen Nukleon-Formfaktoren sind fundamentale Größen, welche eng mit der elektromagnetischen Struktur der Nukleonen zusammenhängen. Der Verlauf der elektrischen und magnetischen Sachs-Formfaktoren G_E und G_M gegen Q^2, das negative Quadrat des Viererimpulsübertrags im elektromagnetischen Streuprozess, steht über die Fouriertransformation in direkter Beziehung zu der räumlichen Ladungs- und Strom-Verteilung in den Nukleonen. Präzise Messungen der Formfaktoren über einen weiten Q^2-Bereich werden daher für ein quantitatives Verständnis der Nukleonstruktur benötigt.rnrnDa es keine freien Neutrontargets gibt, gestaltet sich die Messung der Neutron-Formfaktoren schwierig im Vergleich zu der Messung am Proton. Konsequenz daraus ist, dass die Genauigkeit der vorhandenen Daten von Neutron-Formfaktoren deutlich geringer ist als die von Formfaktoren des Protons; auch der vermessene Q^2-Bereich ist kleiner. Insbesondere der elektrische Sachs-Formfaktor des Neutrons G_E^n ist schwierig zu messen, da er aufgrund der verschwindenden Nettoladung des Neutrons im Verhältnis zu den übrigen Nukleon-Formfaktoren sehr klein ist. G_E^n charakterisiert die Ladungsverteilung des elektrisch neutralen Neutrons und ist damit besonders sensitiv auf die innere Struktur des Neutrons.rnrnIn der hier vorgestellten Arbeit wurde G_E^n aus Strahlhelizitätsasymmetrien in der quasielastischen Streuung vec{3He}(vec{e}, e'n)pp bei einem Impulsübertrag von Q^2 = 1.58 (GeV/c)^2 bestimmt. Die Messung fand in Mainz an der Elektronbeschleunigeranlage Mainzer Mikrotron innerhalb der A1-Kollaboration im Sommer 2008 statt. rnrnLongitudinal polarisierte Elektronen mit einer Energie von 1.508 GeV wurden an einem polarisierten ^3He-Gastarget, das als effektives, polarisiertes Neutrontarget diente, gestreut. Die gestreuten Elektronen wurden in Koinzidenz mit den herausgeschlagenen Neutronen detektiert; die Elektronen wurden in einem magnetischen Spektrometer nachgewiesen, durch den Nachweis der Neutronen in einer Matrix aus Plastikszintillatoren wurde der Beitrag der quasielastischen Streuung am Proton unterdrückt.rnrnAsymmetrien des Wirkungsquerschnitts bezüglich der Elektronhelizität sind bei Orientierung der Targetpolarisation in der Streuebene und senkrecht zum Impulsübertrag sensitiv auf G_E^n / G_M^n; mittels deren Messung kann G_E^n bestimmt werden, da der magnetische Formfaktor G_M^n mit vergleichsweise hoher Präzision bekannt ist. Zusätzliche Messungen der Asymmetrie bei einer Polarisationsorientierung parallel zum Impulsübertrag wurden genutzt, um systematische Fehler zu reduzieren.rnrnFür die Messung inklusive statistischem (stat) und systematischem (sys) Fehler ergab sich G_E^n = 0.0244 +/- 0.0057_stat +/- 0.0016_sys.

The low-energy β− and electron emitter 161Tb as an alternative to 177Lu for targeted radionuclide therapy

The low-energy β− emitter 161Tb is very similar to 177Lu with respect to half-life, beta energy and chemical properties. However, 161Tb also emits a significant amount of conversion and Auger electrons. Greater therapeutic effect can therefore be expected in comparison to 177Lu. It also emits low-energy photons that are useful for gamma camera imaging. The 160Gd(n,γ)161Gd→161Tb production route was used to produce 161Tb by neutron irradiation of massive 160Gd targets (up to 40 mg) in nuclear reactors. A semiautomated procedure based on cation exchange chromatography was developed and applied to isolate no carrier added (n.c.a.) 161Tb from the bulk of the 160Gd target and from its stable decay product 161Dy. 161Tb was used for radiolabeling DOTA-Tyr3-octreotate; the radiolabeling profile was compared to the commercially available n.c.a. 177Lu. A 161Tb Derenzo phantom was imaged using a small-animal single-photon emission computed tomography camera. Up to 15 GBq of 161Tb was produced by long-term irradiation of Gd targets. Using a cation exchange resin, we obtained 80%–90% of the available 161Tb with high specific activity, radionuclide and chemical purity and in quantities sufficient for therapeutic applications. The 161Tb obtained was of the quality required to prepare 161Tb–DOTA-Tyr3-octreotate. We were able to produce 161Tb in n.c.a. form by irradiating highly enriched 160Gd targets; it can be obtained in the quantity and quality required for the preparation of 161Tb-labeled therapeutic agents.

Matrix metalloproteinases contribute to brain damage in experimental pneumococcal meningitis

The present study was performed to evaluate the role of matrix metalloproteinases (MMP) in the pathogenesis of the inflammatory reaction and the development of neuronal injury in a rat model of bacterial meningitis. mRNA encoding specific MMPs (MMP-3, MMP-7, MMP-8, and MMP-9) and the inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) were significantly (P < 0.04) upregulated, compared to the beta-actin housekeeping gene, in cortical homogenates at 20 h after infection. In parallel, concentrations of MMP-9 and TNF-alpha in cerebrospinal fluid (CSF) were significantly increased in rats with bacterial meningitis compared to uninfected animals (P = 0.002) and showed a close correlation (r = 0.76; P < 0. 001). Treatment with a hydroxamic acid-type MMP inhibitor (GM6001; 65 mg/kg intraperitoneally every 12 h) beginning at the time of infection significantly lowered the MMP-9 (P < 0.02) and TNF-alpha (P < 0.02) levels in CSF. Histopathology at 25.5 +/- 5.7 h after infection showed neuronal injury (median [range], 3.5% [0 to 17.5%] of the cortex), which was significantly (P < 0.01) reduced to 0% (0 to 10.8%) by GM6001. This is the first report to demonstrate that MMPs contribute to the development of neuronal injury in bacterial meningitis and that inhibition of MMPs may be an effective approach to prevent brain damage as a consequence of the disease.

Study of the effect of biodiesel fuel on passive oxidation in a catalyzed particulate filter

A 2007 Cummins ISL 8.9L direct-injection common rail diesel engine rated at 272 kW (365 hp) and 317 kW (425 hp) was used to load the filter to 2.2 g/L and passively oxidize particulate matter (PM) within an aftertreatment system consisting of a diesel oxidation catalyst (DOC) and catalyzed particulate filter (CPF). The tests conducted with the engine rated at 365 hp used a 2007 DOC and CPF. The tests conducted with the engine rated at 425 hp used a 2010 DOC and 2007 CPF. Understanding the passive NO2 oxidation kinetics of PM within the CPF allows for reducing the frequency of active regenerations (hydrocarbon injection) and the associated fuel penalties. Modeling the passive oxidation of accumulated PM in the CPF will lead to creating accurate state estimation strategies. The MTU 1-D CPF model will be used to simulate data collected from this study to examine differences in the PM oxidation kinetics when soy methyl ester (SME) biodiesel is used as the source of fuel for the engine, and when the engine is operated at a higher power rating. A test procedure developed by Hutton et al. [1, 2] was modified to improve the ability to model the experimental data and provide additional insight into passively oxidized PM in a partially regenerated CPF. A test procedure was developed to allow PM oxidation rates by NO2 to be determined from engine test cell data. An experimental matrix consisting of CPF inlet temperatures from 250 to 450 °C with varying NOX/PM from 25 to 583and NO2/PM ratios from 5 to 240 was used. SME biodiesel was volumetrically blended with ULSD in 10% (B10) and 20% (B20) portions. This blended fuel was then used to evaluate the effect of biodiesel on passive oxidation rates. Four tests were performed with B10 and four tests with B20. Gathering data to determine the effect of fuel type (ULSD and biodiesel blends) on PM oxidation is the primary goal. The engine used for this testing was then configured to a higher power rating and one of the tests planned was performed. Additional testing is scheduled to take place with ULSD fuel to determine the affect the engine rating has on the PM oxidation. The experimental reaction rates during passive oxidation varied based upon the average CPF temperature, NO2 concentrations, and the NOX/PM ratios for each engine rating and with all fuels. The data analysis requires a high fidelity model that includes NO2 and thermal oxidation mechanisms and back diffusion to determine the details of the PM oxidation process.

Extracts of Lindera obtusiloba induce antifibrotic effects in hepatic stellate cells via suppression of a TGF-beta-mediated profibrotic gene expression pattern

Liver fibrosis is characterized by high expression of the key profibrogenic cytokine transforming growth factor (TGF)-beta and the natural tissue inhibitor of metalloproteinases (TIMP)-1, leading to substantial accumulation of extracellular matrix. Liver fibrosis originates from various chronic liver diseases, such as chronic viral hepatitis that, to date, cannot be treated sufficiently. Thus, novel therapeutics, for example, those derived from Oriental medicine, have gained growing attention. In Korea, extracts prepared from Lindera obtusiloba are used for centuries for treatment of inflammation, improvement of blood circulation and prevention of liver damage, but experimental evidence of their efficacy is lacking. We studied direct antifibrotic effects in activated hepatic stellate cells (HSCs), the main target cell in the fibrotic liver. L. obtusiloba extract (135 mug/ml) reduced the de novo DNA synthesis of activated rat and human HSCs by about 90%, which was not accompanied by cytotoxicity of HSC, primary hepatocytes and HepG2 cells, pointing to induction of cellular quiescence. As determined by quantitative polymerase chain reaction, simultaneous treatment of HSCs with TGF-beta and L. obtusiloba extract resulted in reduction of TIMP-1 expression to baseline level, disruption of the autocrine loop of TGF-beta autoinduction and increased expression of fibrolytic matrix metalloproteinase (MMP)-3. In addition, L. obtusiloba reduced gelatinolytic activity of HSC by interfering with profibrogenic MMP-2 activity. Since L. obtusiloba extract prevented intracellular oxidative stress experimentally induced by tert-butylhydroperoxide, we concluded that the direct antifibrotic effect of L. obtusiloba extract might be mediated by antioxidant activity. Thus, L. obtusiloba, traditionally used in Oriental medicine, may complement treatment of chronic liver disease.

Creating a public tool to assess and promote transparency in global land deals: the experience of the Land Matrix

The Beta version of the Land Matrix (Land Matrix 2012) was launched in April 2012 as a tool to promote public participation in building a constantly evolving database on large-scale land deals, and making the data visible and understandable. The aim of the Land Matrix partnership is to promote transparency and open data in decisionmaking over land and investment, as a step towards greater accountability. Since its launch, the Land Matrix has attracted a high degree of attention, and stirred some controversy. It provides valuable lessons on the challenges and benefits of promoting open data on practices that are often shrouded in secrecy. This paper critically examines the ongoing efforts by the Land Matrix partnership to build a public tool to promote greater transparency in decision-making over land and investment at a global level. It intends to provoke discussion of the extent to which such a tool can ultimately promote greater transparency and be a step towards greater accountability and improved decision-making. It will present the Land Matrix and its value addition, before detailing the challenges it encountered related to the measurement of the largescale land acquisition phenomenon. It will then specify how it intends to address these issues in order to establish a dynamic and participatory tool for open development.

Beta 1-integrins are required for hippocampal AMPA receptor-dependent synaptic transmission, synaptic plasticity, and working memory.

Integrins comprise a large family of cell adhesion receptors that mediate diverse biological events through cell-cell and cell-extracellular matrix interactions. Recent studies have shown that several integrins are localized to synapses with suggested roles in synaptic plasticity and memory formation. We generated a postnatal forebrain and excitatory neuron-specific knock-out of beta1-integrin in the mouse. Electrophysiological studies demonstrated that these mutants have impaired synaptic transmission through AMPA receptors and diminished NMDA receptor-dependent long-term potentiation. Despite the impairment in hippocampal synaptic transmission, the mutants displayed normal hippocampal-dependent spatial and contextual memory but were impaired in a hippocampal-dependent, nonmatching-to-place working memory task. These phenotypes parallel those observed in animals carrying knock-outs of the GluR1 (glutamate receptor subunit 1) subunit of the AMPA receptor. These observations suggest a new function of beta1-integrins as regulators of synaptic glutamate receptor function and working memory.

Transport of 234U in the Opalinus Clay on centimetre to decimetre scales

The Opalinus Clay formation in North Switzerland is a potential host rock for a deep underground radioactive waste repository. The distribution of U-238, U-234 and Th-230 was studied in rock samples of the Opalinus Clay from an exploratory borehole at Benken (Canton of Zurich) using MC-ICP-MS. The aim of U-234 was to assess the in situ, long-term migration behaviour in this rock. Very low hydraulic conductivities of the Opalinus Clay, reducing potential of the pore water and its chemical equilibrium with the host rock are expected to render both U-238 and Th-230 immobile. If U is heterogeneously distributed in the Opalinus Clay, gradients in the supply of U-234 from the rock matrix to the pore water by the decay of U-238 will be established. Diffusive redistribution separates U-234 from its immobile parent U-238 resulting in bulk rock U-234/U-238 activity disequilibria. These may provide a means of estimating the mobility of U-234 in the rock if the diffusion rate of U-234 is significant compared to its decay rate. Sampling was carried out on two scales. Drilling of cm-spaced samples from the drill-core was done to study mobility over short distances and elucidate possible small-scale lithological control. Homogenized 25-cm-long portions of a 2-m-long drill-core section were prepared to provide information on transport over a longer distance. Variations in U and/or Th content on the cm-scale between clays and carbonate-sandy layers are revealed by beta-scanning, which shows that the (dominant) clay is richer in both elements. Samples were digested using aqua regia followed by total HF dissolution, yielding two fractions. in all studied samples U was found to be concentrated in the HF digestion fraction. It has a high U/Th ratio and a study by SEM-EDS points to sub-mu m up to several mu m in size zircon grains as the main U-rich phase. This fraction consistently has U-234/U-238 activity ratios below unity. The minute zircon grains constitute the major reservoir of U in the rock and act as constant rate suppliers of U-234 into the rock matrix and the pore water. The aqua regia leach fraction was found to be enriched in Th, and complementary to the HF fraction, having U-234/U-238 activity ratios above unity. It is believed that these U activity ratios reflect the surplus of having U-234 delivered from the zircon grains. Some cm-spaced samples show bulk rock U-234/U-238 activity ratios that are markedly out of equilibrium. In most of them a striking negative correlation between the total U content and the bulk rock U-234/U-238 activity ratios is observed. This is interpreted to indicate net U-234 transfer from regions of higher supply of U-234 towards those of lower supply which is, in most cases, equivalent to transfer from clayey towards carbonate/sandy portions of the rock. In contrast, the 25 cm averaged samples all have uniform bulk rock U-234/U-238 activity ratios in equilibrium, indicating U immobility in the last 1-1.5 Ma on this spatial scale. It is concluded that the small-scale lithological variations which govern U spatial distribution in the Opalinus Clay are the major factor determining U-234 in situ supply rates, regulating its diffusive fluxes and controlling the observed bulk rock U-234/U-238 activity ratios. A simple box-model is presented to simulate the measured bulk rock U-234/U-238 activity ratios and to give an additional insight into the studied system. (C) 2008 Elsevier Ltd. All rights reserved.

Proteomic identification of in vivo substrates for matrix metalloproteinases 2 and 9 reveals a mechanism for resolution of inflammation.

Clearance of allergic inflammatory cells from the lung through matrix metalloproteinases (MMPs) is necessary to prevent lethal asphyxiation, but mechanistic insight into this essential homeostatic process is lacking. In this study, we have used a proteomics approach to determine how MMPs promote egression of lung inflammatory cells through the airway. MMP2- and MMP9-dependent cleavage of individual Th2 chemokines modulated their chemotactic activity; however, the net effect of complementing bronchoalveolar lavage fluid of allergen-challenged MMP2(-/-)/MMP9(-/-) mice with active MMP2 and MMP9 was to markedly enhance its overall chemotactic activity. In the bronchoalveolar fluid of MMP2(-/-)/MMP9(-/-) allergic mice, we identified several chemotactic molecules that possessed putative MMP2 and MMP9 cleavage sites and were present as higher molecular mass species. In vitro cleavage assays and mass spectroscopy confirmed that three of the identified proteins, Ym1, S100A8, and S100A9, were substrates of MMP2, MMP9, or both. Function-blocking Abs to S100 proteins significantly altered allergic inflammatory cell migration into the alveolar space. Thus, an important effect of MMPs is to differentially modify chemotactic bioactivity through proteolytic processing of proteins present in the airway. These findings provide a molecular mechanism to explain the enhanced clearance of lung inflammatory cells through the airway and reveal a novel approach to target new therapies for asthma.

Function and formation of $\beta$1,4-galactosyltransferase-specific adhesions during growth and differentiation of F9 embryonal carcinoma cells

Galactosyltransferase (GalTase) is localized in the Golgi, where it functions in oligosaccharide synthesis, as well as on the cell surface where it serves as a cell adhesion molecule. GalTase-specific adhesions are functional in a number of important biological events, including F9 embryonal carcinoma (EC) cell adhesions. GalTase-based adhesions are formed by recognition and binding to terminal N-acetylglucosamine (GlcNAc) residues on its glycoprotein counterpart on adjacent cell surfaces. The object of this work has been to investigate the formation and function of GalTase-specific adhesions during F9 cell growth and differentiation. We initially investigated GalTase synthesis during differentiation and found that the increase in GalTase activity was specific for the Golgi compartment; surface GalTase levels remained constant during differentiation. These data indicated that the increase in cell adhesions expected with increased cell-matrix interaction in differentiated F9 cells is not the consequence of increased surface GalTase expression and, more interestingly, that the two pools of GalTase are under differential regulation. Synthesis and recognition of the consociate glycoprotein component was next investigated. Surface GalTase recognized several surface glycoproteins in a pattern that changes with differentiation. Uvomorulin, lysosome-associated membrane protein-1 (LAMP-1), and laminin were recognized by surface GalTase and are, therefore, potential components in GalTase-specific adhesions. Furthermore, these interactions were aberrant in an adhesion-defective F9 cell line that results, at least in part, from abnormal oligosaccharide synthesis. The function played by surface GalTase in growth and induction of differentiation was examined. Inhibition of surface GalTase function by a panel of reagents inhibited F9 cell growth. GalTase expression at both the transcription and protein levels were differentially regulated during the cell cycle, with surface expression greatest in the G1 phase. Disruption of GalTase adhesion by exposure to anti-GalTase antibodies during this period resulted in extension of the G2 phase, a result similar to that seen with agents known to inhibit growth and induce differentiation. Finally, other studies have suggested that a subset of cell adhesion molecules have the capability to induce differentiation in EC cells systems. We have determined in F9 cells that dissociating GalTase adhesion by galactosylation of and release of the consociate glycoproteins induces differentiation, as defined by increased laminin synthesis. The ability to induce differentiation by surface galactosylation was greatest in cells grown in cultures promoting cell-cell adhesions, relative to cultures with minimal cell-cell interactions. ^