Mechanisms of Na+-Ca2+ Exchange Inhibition by Amphiphiles in CardiacMyocytes: Importance of Transbilayer Movement

The membrane lipid environment and lipid signaling pathways are potentially involved in the modulation of the activity of the cardiac Na+-Ca2+ exchanger (NCX). In the present study biophysical mechanisms of interactions of amphiphiles with the NCX and the functional consequences were examined. For this purpose, intracellular Ca2+ concentration jumps were generated by laser-flash photolysis of caged Ca2+ in guinea-pig ventricular myocytes and Na+-Ca2+ exchange currents (INa/Ca) were recorded in the whole-cell configuration of the patch-clamp technique. The inhibitory effect of amphiphiles increased with the length of the aliphatic chain between C7 and C10 and was more potent with cationic or anionic head groups than with uncharged head groups. Long-chain cationic amines (C12) exhibited a cut-off in their efficacy in INa/Ca inhibition. Analysis of the time-course, comparison with the Ni2+-induced INa/Ca block and confocal laser scanning microscopy experiments with fluorescent lipid analogs (C6- and C12-NBD-labeled analogs) suggested that amphiphiles need to be incorporated into the membrane. Furthermore, NCX block appears to require transbilayer movement of the amphiphile to the inner leaflet ("flip”). We conclude that both, hydrophobic and electrostatic interactions between the lipids and the NCX may be important factors for the modulation by lipids and could be relevant in cardiac diseases where the lipid metabolism is altere

Long-term follow-up and residual sequelae after treatment for intracerebral germ-cell tumour in children and adolescents

Background: Information on long-term follow-up of children and adolescents treated for intracerebral germ-cell tumour is scant. We report on the results of a small series of patients treated at a single institution. Patients and methods: Hospital records from 15 patients treated between 1980 and 1998 were reviewed. An attempt was made to correlate sequelae to tumour location and treatment modalities. Results: This cohort constitutes 5.5% of all brain tumours diagnosed at our institution. Histology: 10 germinomas, 2 benign teratomas, 2 malignant teratomas, and one mixed germ-cell tumour. Overall survival was 87%, with a mean follow-up time of 7 years and 8 months. The majority of patients have long-term sequelae involving one or several organ systems. In 66% endocrine, in 47% ophthalmologic, in 60% neuropsycho-logical defects were observed. Endocrine and ophthalmologic sequelae show a correlation to tumour location. Neuropsycho-logical long-term abnormalities are frequent and are associated with cranial irradiation in particular at young age, but less with tumour location, irradiation dose or surgery. Conclusions: Our preliminary data suggest that today intracerebral germinomas and mature teratomas have a good prognosis even when a relapse occurs. The outcome for mixed germ-cell tumours and malignant teratomas is less favourable. Although long-term sequelae are present in the majority of patients, there is some evidence that patients treated after 1990 suffer fewer severe long-term defects, thereby indicating that recent treatment protocols may result in a reduction of sequela

Gesellschaftliche Leistungen der biologischen Landwirtschaft

Zusammenfassuung: In diesem Bericht werden die wissenschaftlichen Ergebnisse nationaler und internationaler Studien zu den gesellschaftlichen Leistungen des Biolandbaus zusammengefasst. Als Referenzen werden dabei sowohl die konventionelle wie auch die integrierte Landwirtschaft herangezogen. Es ist den Autoren bewusst, dass alle Landwirtschaftsmethoden in der Schweiz und im Ausland eine grosse Streubreite aufweisen, da der Einfluss der regionalen sozioökonomischen Rahmenbedingungen, der Standortfaktoren, der Betriebsleiter und der unterschiedlichen staatlichen und privaten Regulierungen gross ist. Trotzdem ergeben sich für die verschiedenen Landwirtschaftsmethoden klare Unterschiede, die bei den agrarpolitischen Massnahmen berücksichtigt werden müssen. Bezüglich der positiven Externalitäten weist der Biolandbau klare Mehrleistungen in der Biodiversität auf. Dies sowohl auf der Ebene der Genetik, der Arten und besonders auch der Habitate. Deutlich sind die Mehrleistungen des Biolandbaus auch im Bereich des Humusaufbaus, was eine höhere CO2-Sequestrierung zur Folge hat. Obwohl eine dauerhafte Honorierung der Vermeidung negativer Externalitäten im bisherigen Konzept der Weiterentwicklung des Direktzahlungssystems (WDZ) nicht vorgesehen ist, sind hier die Vorteile der biologischen Landwirtschaft beträchtlich. Dies betrifft die Nährstoff- und Pflanzenschutzmittelverluste in Grund- und Oberflächengewässer sowie in andere Umweltkompartimente, der Verbrauch von nicht erneuerbarer Energie, die Emissionen von Klimagasen und die Belastungen mit Tiermedikamenten. Die nationalen und internationalen Studien zeigen auf, dass der Biolandbau sich besonders durch Systemwirkungen auszeichnet: erhöhte Biodiversität, verbesserter Schutz des Bodens, wirksame Vermeidung von Umweltbelastungen, effiziente Nutzung von natürlichen Ressourcen, geringer Verbrauch nicht erneuerbarer Energie und verbessertes Tierwohl. Dies sind die Effekte von komplexen Response-Massnahmen der Betriebsleiter auf einfach zu kontrollierende Einschränkungen und Verbote. Dadurch entstehen nicht zu unterschätzende Zusatzleistungen und Synergien bei der Erreichung der vom Bund definierten Ziele. Um den Mehrleistungen des Biolandbaus gerecht zu werden, schlagen die Autoren zwei neue Massnahmen vor: 1) Biodiversitätsbeitrag für Acker, Sonderkulturen und intensive Wiesen und 2) CO2-Sequestrationsbeiträge. Damit sind aber die gesellschaftlich wichtigen Mehrleistungen des Biolandbaus noch nicht abgegolten. Bei der Vermeidung negativer Externalitäten werden höhere umweltschutzrelevante Effekte erzielt. Diese können i) durch die Einführung eines negativen Anreizsystems nach dem Polluter-Pays-Principle (z.B. Stickstoffsteuer, CO2 - Abgabe), ii) durch ein höheres Einstiegsniveau bei den Cross-Compliance-Massnahmen für alle Betriebe (ÖLNplus) oder iii) durch einen finanziellen Ausgleich für die Mehrleistungen des Biolandbaus abgegolten werden. Die „Förderung des Biolandbaus“ als systemorientierte Massnahme macht auch nach dem Grundsatz des effizienten Einsatzes von Steuermitteln Sinn und stellt eine kosteneffektive Massnahme dar. Einerseits können damit die deutlich höheren positiven Externalitäten abgegolten werden, andererseits wird die stärkere Vermeidung von negativen Externalitäten genügend berücksichtigt

Remote Construction of N-Heterocycles via 1,4-Palladium Shift-Mediated Double C-H Activation

In the past years, Pd0-catalyzed C(sp3)-H activation provided efficient and step-economical methods to synthesize carbo- and heterocycles via direct C(sp2)-C(sp3) bond formation. We report herein that a 1,4-Pd shift allows access to N-heterocycles which are difficult to build via a direct reaction. It is shown that o-bromo-N-methylanilines undergo a 1,4-Pd shift at the N-methyl group, followed by intramolecular trapping by C(sp2)-H or C(sp3)-H activation at another nitrogen substituent and remote C-C bond formation to generate biologically relevant isoindolines and β-lactams. The product selectivity is influenced by the employed ligand, with NHCs favoring the product of remote C-C coupling against products arising from direct C-C coupling and N-demethylation

Differential (2+1) Jet Event Rates and Determination of alpha_s in Deep Inelastic Scattering at HERA

Events with a (2+1) jet topology in deep-inelastic scattering at HERA are studied in the kinematic range 200 < Q^2< 10,000 GeV^2. The rate of (2+1) jet events has been determined with the modified JADE jet algorithm as a function of the jet resolution parameter and is compared with the predictions of Monte Carlo models. In addition, the event rate is corrected for both hadronization and detector effects and is compared with next-to-leading order QCD calculations. A value of the strong coupling constant of alpha_s(M_Z^2)= 0.118+- 0.002 (stat.)^(+0.007)_(-0.008) (syst.)^(+0.007)_(-0.006) (theory) is extracted. The systematic error includes uncertainties in the calorimeter energy calibration, in the description of the data by current Monte Carlo models, and in the knowledge of the parton densities. The theoretical error is dominated by the renormalization scale ambiguity.Comment: 25 pages, 6 figures, 3 tables, submitted to Eur. Phys.

Multiplicity Structure of the Hadronic Final State in Diffractive Deep-Inelastic Scattering at HERA

The multiplicity structure of the hadronic system X produced in deep-inelastic processes at HERA of the type ep -> eXY, where Y is a hadronic system with mass M_Y< 1.6 GeV and where the squared momentum transfer at the pY vertex, t, is limited to |t|<1 GeV^2, is studied as a function of the invariant mass M_X of the system X. Results are presented on multiplicity distributions and multiplicity moments, rapidity spectra and forward-backward correlations in the centre-of-mass system of X. The data are compared to results in e+e- annihilation, fixed-target lepton-nucleon collisions, hadro-produced diffractive final states and to non-diffractive hadron-hadron collisions. The comparison suggests a production mechanism of virtual photon dissociation which involves a mixture of partonic states and a significant gluon content. The data are well described by a model, based on a QCD-Regge analysis of the diffractive structure function, which assumes a large hard gluonic component of the colourless exchange at low Q^2. A model with soft colour interactions is also successful.Comment: 22 pages, 4 figures, submitted to Eur. Phys. J., error in first submission - omitted bibliograph

Multi-Jet Event Rates in Deep Inelastic Scattering and Determination of the Strong Coupling Constant

Jet event rates in deep inelastic ep scattering at HERA are investigated applying the modified JADE jet algorithm. The analysis uses data taken with the H1 detector in 1994 and 1995. The data are corrected for detector and hadronization effects and then compared with perturbative QCD predictions using next-to-leading order calculations. The strong coupling constant alpha_S(M_Z^2) is determined evaluating the jet event rates. Values of alpha_S(Q^2) are extracted in four different bins of the negative squared momentum transfer~\qq in the range from 40 GeV2 to 4000 GeV2. A combined fit of the renormalization group equation to these several alpha_S(Q^2) values results in alpha_S(M_Z^2) = 0.117+-0.003(stat)+0.009-0.013(syst)+0.006(jet algorithm).Comment: 17 pages, 4 figures, 3 tables, this version to appear in Eur. Phys. J.; it replaces first posted hep-ex/9807019 which had incorrect figure 4

A Search for Selectrons and Squarks at HERA

Data from electron-proton collisions at a center-of-mass energy of 300 GeV are used for a search for selectrons and squarks within the framework of the minimal supersymmetric model. The decays of selectrons and squarks into the lightest supersymmetric particle lead to final states with an electron and hadrons accompanied by large missing energy and transverse momentum. No signal is found and new bounds on the existence of these particles are derived. At 95% confidence level the excluded region extends to 65 GeV for selectron and squark masses, and to 40 GeV for the mass of the lightest supersymmetric particle.Comment: 13 pages, latex, 6 Figure