Preliminary Overview of Institutional Structures and Models: Information Systems for Energy/Environmental Planning and Management in GDR, Rhone-Alpes, and Wisconsin

This paper is one of a series describing a multidisciplinary IIASA research program on Integrated Energy System Modelling and Policy Analysis. The initial phase of this research program is focused on the energy systems of three regions: the State of Wisconsin in the U.S.A.; the German Democratic Republic; and the Rhone-Alpes Region in France. The primary purposes of the study are at least three-fold: (1) To identify existing patterns of regional energy use and supply at appropriate levels of disaggregation. (2) To compare alternative methodologies for regional energy forecasting, planning, and policy development. (3) To use the ,above methodologies to examine alternate energy policy strategies for each of the regions, to explore their implications from various perspectives using sets of indicators related to environmental impacts, energy use efficiency, etc., and to evaluate the adequacy of the alternative methodologies as policy tools. Out of these above three items should evolve improved methodologies for energy systems research and policy analysis. The comparative method, intersecting the different disciplines and nations which would be involved in this project, should serve as a powerful tool to the mutual benefit of the participating nations as well as to other countries facing similar energy problems. It could also serve as a prototype for similar studies on other resources such as materials, water, air, i.e. as a vehicle for development of an approach for improved resource management

Energy/Environment Models: Relationship to Planning in Wisconsin, GDR, Rhone Alps

This report is a description and cross-regional comparison of the institutional structures and modeling methodologies of the three regions participating in the IIASA Research Program on Management of Regional Energy/Environment Systems. Descriptions are presented for the state of Wisconsin (USA), the German Democratic Republic, and the Rhone-Alpes Region (France), by specialists and policy makers from the respective regions. These descriptions demonstrate quite vividly the relationships between the institutional structure of a region and its use of models and planning tools

Manipulation of Microenvironment with a Built-in Electrochemical Actuator in Proximity of a Dissolved Oxygen Microsensor

Biochemical sensors for continuous monitoring require dependable periodic self diagnosis with acceptable simplicity to check its functionality during operation. An in-situ self-diagnostic technique for a dissolved oxygen microsensor is proposed in an effort to devise an intelligent microsensor system with an integrated electrochemical actuation electrode. With a built-in platinum microelectrode that surrounds the microsensor, two kinds of microenvironments, called the oxygen-saturated or oxygen-depleted phases, can be created by water electrolysis, depending on the polarity. The functionality of the microsensor can be checked during these microenvironment phases. The polarographic oxygen microsensor is fabricated on a flexible polyimide substrate (Kapton) and the feasibility of the proposed concept is demonstrated in a physiological solution. The sensor responds properly during the oxygen-generating and oxygen-depleting phases. The use of these microenvironments for in-situ self-calibration is discussed to achieve functional integration, as well as structural integration, of the microsensor system

Entwicklung von Strukturmodellen für Hydroxy-Interkalierte Tonminerale zur quantitativen Rietveld-basierten Phasenanalyse von Böden

Chemische und physikalische Bodeneigenschaften werden entscheidend vom Tongehalt und der Zusammensetzung der Tonfraktion geprägt. Tonminerale pedogenen Ursprungs können dabei sehr komplex sein. Insbesondere unter sauren Bedingungen kann gelöstes Al in den Zwischenschichten quellfähiger 2:1 Tonminerale (Smectit, Vermiculit) durch die Bildung nicht austauschbarer Al-Polymere gebunden werden. So kann eine Reihe sogenannter Hydroxy-Interkalierter Minerale (HIM) entstehen. Gegenwärtig entziehen sich diese Phasen jedoch einer verlässlichen Quantifizierung mittels Röntgenbeugung und Rietveld-Analyse, da hierfür keine kristallografischen Strukturmodelle vorliegen. Ziel unseres Projektes ist daher die Entwicklung von Strukturmodellen für die quantitative Beschreibung pedogener HIM-Phasen, welche folgende Schritte umfasst: (1) Identifizierung wichtiger natürlich vorkommender HIM in Böden unterschiedlichen Verwitterungsgrades, (2) Abtrennung/Herstellung phasenreiner Proben zur Prüfung/Verbesserung des Strukturmodells, sowie (3) Überprüfung des Strukturmodells an natürlichen Proben (Phasengemischen). Die Identifizierung typischer HIM wurde anhand einer 120.000 Jahre alten Bodenchronosequenz (Franz-Josef Gletscher, Neuseeland) vorgenommen. Hierbei konnten diverse intermediäre Phasen wie z.B. Vermiculit, Chlorit und Chlorit-Hydroxy-Interkalierter Smectit identifiziert werden, weshalb Hydroxy-Interkalierter Smectit (HIS) als erstes zu erstellendes Strukturmodell ausgewählt wurde. Da sich HIM generell im gleichen Korngrößenbereich anderer Tonminerale befinden, bzw. mit diesen verwachsen sind, können sie nicht phasenrein abgetrennt werden, wie für den zweiten Schritt der Modellentwicklung notwendig. Aus diesem Grund wurde im Labor eine Probenserie von 7 HIS aus natürlichem Smectit (Bentonit von Milos, Griechenland) mit unterschiedlichem Grad der Al-Belegung (0-100%) hergestellt. Hierfür wurde zu 6 Teilproben 0,1 mol/L AlCl3 gegeben und mit 0,3 mol/L NaOH Lösung bis pH=5,5 titriert. Die Teilproben unterschieden sich anhand der Volumina 0,1 mol/L AlCl3 Lösung sowie den Reaktionszeiten. Eine siebte Teilprobe wurde nicht behandelt (0% Belegung). Alle Proben wurden mittels Multimethodeneinsatz charakterisiert. Der vorliegende Beitrag gibt einen Einblick in den Ablauf und die damit verbundenen Schwierigkeiten in der Entwicklung eines Strukturmodells für HIM, welche eine quantitative Beschreibung von Hydroxy-Interkalierten Tonmineralen in Böden zukünftig ermöglichen soll

Monoamine oxidase-A promotes protective autophagy in human SH-SY5Y neuroblastoma cells through Bcl-2 phosphorylation.

Monoamine oxidases (MAOs) are located on the outer mitochondrial membrane and are drug targets for the treatment of neurological disorders. MAOs control the levels of neurotransmitters in the brain via oxidative deamination and contribute to reactive oxygen species (ROS) generation through their catalytic by-product H2O2. Increased ROS levels may modulate mitochondrial function and mitochondrial dysfunction is implicated in a vast array of disorders. However, the downstream effects of MAO-A mediated ROS production in a neuronal model has not been previously investigated. In this study, using MAO-A overexpressing neuroblastoma cells, we demonstrate that higher levels of MAO-A protein/activity results in increased basal ROS levels with associated increase in protein oxidation. Increased MAO-A levels result in increased Lysine-63 linked ubiquitination of mitochondrial proteins and promotes autophagy through Bcl-2 phosphorylation. Furthermore, ROS generated locally on the mitochondrial outer membrane by MAO-A promotes phosphorylation of dynamin-1-like protein, leading to mitochondrial fragmentation and clearance without complete loss of mitochondrial membrane potential. Cellular ATP levels are maintained following MAO-A overexpression and complex IV activity/protein levels increased, revealing a close relationship between MAO-A levels and mitochondrial function. Finally, the downstream effects of increased MAO-A levels are dependent on the availability of amine substrates and in the presence of exogenous substrate, cell viability is dramatically reduced. This study shows for the first time that MAO-A generated ROS is involved in quality control signalling, and increase in MAO-A protein levels leads to a protective cellular response in order to mediate removal of damaged macromolecules/organelles, but substrate availability may ultimately determine cell fate. The latter is particularly important in conditions such as Parkinson's disease, where a dopamine precursor is used to treat disease symptoms and highlights that the fate of MAO-A containing dopaminergic neurons may depend on both MAO-A levels and catecholamine substrate availability

Aufträge zur Vorbereitung für den 2. Klausurtag

Aufträge für Lehrkräfte bis zum nächsten Klausurtag (Evaluation und Vorbereitung)

Primary care management for optimized antithrombotic treatment [PICANT]: study protocol for a cluster-randomized controlled trial

Background: Antithrombotic treatment is a continuous therapy that is often performed in general practice and requires careful safety management. The aim of this study is to investigate whether a best practice model that applies major elements of case management, including patient education, can improve antithrombotic management in primary health care in terms of reducing major thromboembolic and bleeding events. Methods: This 24-month cluster-randomized trial will be performed in 690 adult patients from 46 practices. The trial intervention will be a complex intervention involving general practitioners, health care assistants and patients with an indication for oral anticoagulation. To assess adherence to medication and symptoms in patients, as well as to detect complications early, health care assistants will be trained in case management and will use the Coagulation-Monitoring-List (Co-MoL) to regularly monitor patients. Patients will receive information (leaflets and a video), treatment monitoring via the Co-MoL and be motivated to perform self-management. Patients in the control group will continue to receive treatment-as-usual from their general practitioners. The primary endpoint is the combined endpoint of all thromboembolic events requiring hospitalization, and all major bleeding complications. Secondary endpoints are mortality, hospitalization, strokes, major bleeding and thromboembolic complications, severe treatment interactions, the number of adverse events, quality of anticoagulation, health-related quality of life and costs. Further secondary objectives will be investigated to explain the mechanism by which the intervention is effective: patients' assessment of chronic illness care, self-reported adherence to medication, general practitioners' and health care assistants' knowledge, patients' knowledge and satisfaction with shared decision making. Practice recruitment is expected to take place between July and December 2012. Recruitment of eligible patients will start in July 2012. Assessment will occur at three time points: baseline (T0), follow-up after 12 (T1) and after 24 months (T2). Discussion: The efficacy and effectiveness of individual elements of the intervention, such as antithrombotic interventions, self-management concepts in orally anticoagulated patients and the methodological tool, case-management, have already been extensively demonstrated. This project foresees the combination of several proven instruments, as a result of which we expect to profit from a reduction in the major complications associated with antithrombotic treatment

Drug metabolizing enzyme activities versus genetic variances for drug of clinical pharmacogenomic relevance

Enzymes are critically important in the transportation, metabolism, and clearance of most therapeutic drugs used in clinical practice today. Many of these enzymes have significant genetic polymorphisms that affect the enzyme's rate kinetics. Regarding drug metabolism, specific polymorphisms to the cytochrome (CYP) P450 enzyme family are linked to phenotypes that describe reaction rates as "ultra", "intermediate", and "poor," as referenced to "extensive" metabolizers that are assigned to wildtype individuals. Activity scores is an alternate designation that provides more genotype-to-phenotype resolution. Understanding the relative change in enzyme activities or rate of clearance of specific drugs relative to an individual's genotypes is an important component in the interpretation of pharmacogenomic data for personalized medicine. Currently, the most relevant drug metabolizing enzymes are CYP 2D6, CYP 2C9, CYP 2C19, thiopurine methyltransferase (TPMT) and UDP-glucuronosyltransferase (UGT). Each of these enzymes is reactive to a host of different drug substrates. Pharmacogenomic tests that are in routine clinical practice include CYP 2C19 for clopidogrel, TPMT for thiopurine drugs, and UDP-1A1 for irinotecan. Other tests where there is considerable data but have not been widely implemented includes CYP 2C9 for warfarin, CYP 2D6 for tamoxifen and codeine, and CYP 2C19 for the proton pump inhibitors

Stimulation programs for pediatric drug research – do children really benefit?

Most drugs that are currently prescribed in pediatrics have not been tested in children. Pediatric drug studies are stimulated in the USA by the pediatric exclusivity provision under the Food and Drug Administration Modernization Act (FDAMA) that grants patent extensions when pediatric labeling is provided. We investigated the effectiveness of these programs in stimulating drug research in children, thereby increasing the evidence for safe and effective drug use in the pediatric population. All drugs granted pediatric exclusivity under the FDAMA were analyzed by studying the relevant summaries of medical and clinical pharmacology reviews of the pediatric studies or, if these were unavailable, the labeling information as provided by the manufacturer. A systematic search of the literature was performed to identify drug utilization patterns in children. From July 1998 to August 2006, 135 drug entities were granted pediatric exclusivity. Most frequent drug groups were anti-depressants and mood stabilizers, ACE inhibitors, lipid-lowering preparations, HIV antivirals, and non-steroidal anti-inflammatory and anti-rheumatic drugs. The distribution of the different drugs closely matched the distribution of these drugs over the adult market, and not the drug utilization by children