Suchergebnisse

The treatment of Parkinson's disease (PD), the second most common neurodegenerative human disorder, continues to be symptomatic. Development of drugs able to stop or at least slowdown PD progression would benefit several million people worldwide. SynuClean-D is a low molecular weight 2-pyridone-based promising drug candidate that inhibits the aggregation of α-synuclein in human cultured cells and prevents degeneration of dopaminergic neurons in a Caenorhabditis elegans model of PD. Improving SynuClean-D pharmacokinetic/pharmacodynamic properties, performing structure/activity studies and testing its efficacy in mammalian models of PD requires the use of gr-amounts of the compound. However, not enough compound is on sale, and no synthetic route has been reported until now, which hampers the molecule progress towards clinical trials. To circumvent those problems, we describe here an efficient and economical route that enables the synthesis of SynuClean-D with good yields as well as the synthesis of SynuClean-D derivatives. Structure-activity comparison of the new compounds with SynuClean-D reveals the functional groups of the molecule that can be disposed of without activity loss and those that are crucial to interfere with α-synuclein aggregation. Several of the derivatives obtained retain the parent's compound excellent in vitro anti-aggregative activity, without compromising its low toxicity. Computational predictions and preliminary testing indicate that the blood brain barrier (BBB) permeability of SynuClean-D is low. Importantly, several of the newly designed and obtained active derivatives are predicted to display good BBB permeability. The synthetic route developed here will facilitate their synthesis for BBB permeability determination and for efficacy testing in mammalian models of PD. ; This research was funded by Spanish Ministry of Science and Innovation (grants PID2019-107293GB-I00 to JS and PID2019-105017RB-I00 to SV), by Gobierno de Aragón, Spain (grants LMP30_18 and E45_20R to JS), by ICREA (ICREA-Academia 2015 to SV) and by "la Caixa" Banking Foundation, Spain (grant CaixaImpulse CI18-00019, to SV). AM was a recipient of a predoctoral FPU fellowship from the Spanish Government. ; Peer reviewed

Sandiaga Uno, Indonesia's vice-presidential candidate paired with Prabowo Subianto, has framed the coming presidential election as a referendum on the Indonesian economy, and considers the main priorities to be: 1. job creation; 2. keeping prices stable; 3. maintaining strong and firm leadership in order to create a clean government; and 4. developing infrastructure through public-private partnerships.

Die Europäische Union hat eine wichtige Rolle in der aktuellen Politikarena für Umweltschutz in den Mitgliedsstaaten. Eine freiwillige Maßnahme ist das Eco Management and Audit Scheme (= EMAS), das Organisationen bei der Verbesserung ihrer Umweltleistungen unterstützt. In der zweiten Überarbeitung von EMAS, bietet Artikel 45 Mitgliedsstaaten die Möglichkeit einen Anerkennungsantrag für nicht-formelle Umweltmanagementsysteme einzureichen, um zu zeigen, dass diese teilweise die Anforderungen der EMAS III Verordnung abdecken und damit eine offizielle Anerkennung als Vorstufe zu EMAS III erreicht wird. Wegen fehlender Entscheidungen über diese Anträge und fehlender wissenschaftlicher Untersuchung bietet diese Forschungsarbeit Empfehlungen für folgende Antragsteller um Anwendbarkeit und Erfolg der Implementierung von Artikel 45 zu verbessern.Deshalb wird eine Evaluierung der Implementierungsprozesse durchgeführt, durch erstens: Einblicke in die Implementierunsgprozesse von Österreich, Spanien, Belgien und Schweden; und zweitens: Analyse der Perspektiven von der zuständigen Stelle in der Europäischen Kommission und einem Repräsentanten von Adelphi Consult, die eine wichtige Potenzialanalyse von Artikel 45 durchgeführt haben. Verwendete Methoden sind partizipative Aktionsforschung und halbstrukturierte Interviews.Die Ergebnisse zeigen, dass fehlendes Wissen über die Verfahren, Unsicherheiten wegen der weiteren Schritte und fehlende Kommunikation mit den Politik-Verantwortlichen zu Problemen für die Antragsteller führen. Fehlende Humanressourcen und Unsicherheiten über die Bearbeitung der Anträge führen zu Verzögerungen auf der Politik-Seite.Für folgende Antragsteller werden drei chronologische Stufen von Empfehlungen zur Verfügung gestellt. Diese betreffen Förderung der Teilnahme von allen involvierten Akteuren, baldige Kommunikation mit den Entscheidungsträgern in der Europäischen Kommission und Einsatz für Erfahrungsaustausch mit vormaligen Antragstellern. ; The European Union plays a big role nowadays in policy-making for environmental conservation in the European Member States. One voluntary tool is the Eco Management and Audit Scheme (= EMAS) which aims to support organizations to enhance their environmental performance. Within the second EMAS revision, Article 45 intends Member States to hand in a recognition request for their non-formal environmental management systems to show that these cover partially the requirements of the EMAS III regulation and therefore are officially recognized as pre-step to EMAS III. The result of the implementation process of Article 45 is the submission of a written recognition request to the European Commission. Due to lacking decisions on these requests and the missing scientific examination, this research provides recommendations to following candidates to improve the applicability and success of the implementation of Article 45. Consequently, an evaluation of the implementation processes is accomplished by firstly, providing insights into the implementation processes in Austria, Spain, Belgium and Sweden and secondly, by analyzing the perspectives of the person in charge in the European Commission and of a representative of Adelphi Consult that provided an important study on the potentials of Article 45. The main methods used are participatory action research and semi-structured interviews.The results show that missing knowledge on procedures, uncertainties about further progresses and missing communication with the policy-makers lead to challenges for the applicants. Missing human resources and uncertainties on the processing of the requests lead to laggings on the decisions from policy-side. To future petitioners three subsequent sets of recommendations are provided. These concern encouragement of participation of all involved parties, early communication with decision-makers in the European Commission and investigation for experience exchange with former applicants. ; by Elisabeth Ritt ; Abweichender Titel laut Übersetzung der Verfasserin/des Verfassers ; Zsfassungen in dt. und engl. Sprache ; Graz, Univ., Masterarb., 2013 ; (VLID)234360

Explores how attention to TV news impacted affective evaluations of US presidential candidates during the last two months of the 1992 campaign, using National Election Study data (N = 1,703 respondents). Analyses indicate that attentiveness to campaign news significantly influenced evaluations in a manner consistent with the tone of news coverage for each candidate. By disaggregating the data by party & ideology, however, this effect was found to be conditional, depending critically on the character & intensity of political predispositions. The interplay between political predispositions & the valence of network coverage is emphasized, underscoring the contingent effect of media messages. The importance of partisan reinforcement as a major consequence of news media reception during the campaign is discussed. 4 Tables, 2 Figures, 1 Appendix, 70 References. Adapted from the source document.

The National Annenberg Election Survey of 2000 offers a fresh perspective on central issues in the long-standing debate about impact of campaign spending by congressional challengers & incumbents. Examination of changes over time & across panel waves in knowledge & evaluations of Senate candidates & in consequent voting intentions strongly confirms the efficacy of challengers' expenditures. Challengers gained support over time in direct proportion to their level of spending. Incumbents adjusted their level of spending to that of their challengers, & their levels of familiarity & favorability increased over time, but to a degree unrelated to how much they spent. Their expenditures did not appear to offset the effects produced by challengers' spending. Tables, Figures, Appendixes, References. [Copyright 2005 Elsevier Ltd.]

SURVEY RESEARCH ON THE 1980 PRESIDENTIAL ELECTION DOES NOT SUPPORT THE CONTENTION THAT SOPHISTICATED VOTING IS EMPLOYED BY VOTERS TO AVOID THEIR LEAST PREFERRED ALTERNATIVE. COMPLETE PREFERENCE ORDERINGS FOR ANDERSON, CARTER, AND REAGAN ARE INFERRED FROM SURVEY RESPONSES FOR A SAMPLE OF VOTERS. DATA ANALYSIS FOCUSES ON REPORTED VOTE FOR PREFERENCE GROUPS WHICH RANK ANDERSON FIRST, COMPARING THOSE WHO VOTED FOR ANDERSON TO THOSE WHO VOTED FOR THEIR SECOND CHOICE. RESULTS SHOW THAT SOPHISTICATED VOTERS APPEAR TO HAVE VOTED ON THE BASIS OF POSITIVE ASPECTS OF THEIR SECOND MOST PREFERRED CANDIDATE RATHER THAN IN AVOIDANCE OF NEGATIVE ASPECTS OF THEIR LEAST PREFERRED CANDIDATE.

Incomplete understanding of the connection between campaign spending and election outcomes has hindered evaluation of enacted and proposed congressional campaign finance reforms. Reanalysis of the 1972 and 1974 House and Senate campaign spending data using both OLS and 2SLS regression models shows that spending by challengers has a much greater impact on the outcome than does spending by incumbents. A similar analysis of the effects of spending on voters' recall of candidates in the 1972 and 1974 SRC surveys supports the explanation that campaign expenditures buy nonincumbents the necessary voter recognition already enjoyed by incumbents prior to the campaign. The 1974 survey questions on Senate candidates indicate that, although the inability to remember candidates' names does not preclude having opinions about them, voters recalling candidates are much more likely to offer evaluative comments, and these more frequently refer to candidates personally. Aware voters offer more negative as well as positive evaluations (though positive outnumber negative); familiarity is not automatically advantageous. And voters' evaluations of candidates strongly influence how they vote. The implications of these findings for congressional campaign finance policy are readily apparent.

The thermal behavior of a commercial paraffin with a melting temperature of 58 ºC is analyzed as a phase change material (PCM) candidate for industrial waste heat recovery and domestic hot water applications. A full and complete characterization of this PCM is performed based on two different approaches: a laboratory characterization (mass range of milligrams) and an analysis in a pilot plant (mass range of kilograms). In the laboratory characterization, its thermal and cycling stability, its health hazard as well as its phase change thermal range, enthalpy and specific heat are analyzed using a differential scanning calorimeter, thermogravimetric analysis, thermocycling and infrared spectroscopy. Laboratory analyses showed its suitability up to 80 ºC and for 1200 cycles. In the pilot plant analysis, its thermal behavior was analyzed in a shell-and-tube heat exchanger under different heat transfer fluid mass flow rates in terms of temperature, power and energy rates. Results from the pilot plant analysis allowed understanding the different methods of heat transfer in real charging and discharging processes as well as the influence of the geometry of the tank on the energy transferred and required time for charging and discharging processes. ; The work is partially funded by the Spanish government (ULLE10-4E-1305, ENE2015- 64117-C5-1-R and ENE2015-64117-C5-3-R). This project has received funding from the European Commission Seventh Framework Programme (FP/2007–2013) under Grant agreement N PIRSES-GA-2013-610692 (INNOSTORAGE) and No ENER/FP7/295983 (MERITS), and from the European Union's Horizon 2020 Research and Innovation Programme under Grant agreement No 657466 (INPATH-TES). The authors would like to thank the Catalan Government for the quality accreditation given to their research groups GREA (2014 SGR 123) and DIOPMA (2014 SGR 1543). Jaume Gasia would like to thank the Departament d'Universitats, Recerca i Societat de la Informació de la Generalitat de Catalunya for his research fellowship (2016FI_B 00047). Laia Miró would like to thank the Spanish Government for her research fellowship (BES-2012-051861). Alvaro de Gracia and Camila Barreneche would like to thank the Ministerio de Economia y Competitividad de España for Grant Juan de la Cierva, FJCI-2014-19940 and FJCI-2014-22886, respectively.

The relationship between voters' perceptions of party leaders' personality traits & their subsequent party identification & voting behavior was examined in the Nov 1981 Belgian national elections based on evaluations made by 201 voters of 4 well-known leaders of the main Flemish political parties. Factor analysis reveals 3 main dimensions of personality traits -- reliability, expertness, & self-control -- & 4 types of voters -- convinced, policy-oriented, routine, & indifferent. Party leaders' personality traits variably affected voting behavior depending on voter type. Overall, the personality profiles of each leader were quite similar; however, Rs identified with a certain party tended to rate politicians from that party more favorably, particularly on reliability & attractiveness dimensions. 6 Tables, 1 Figure. Modified HA

THIS ARTICLE FINDS THAT SPECIAL ELECTIONS ARE A SUBSET OF OPEN-SEAT ELECTIONS, WITH BOTH TYPES OF CONTEST STRONGLY IMPACTED BY CANDIDATE AND CONSTITUENCY INFLUENCES. IT FINDS NO EVIDENCE OF A SUBSTANTIAL PRESIDENTIAL-APPROVED EFFECT IN SPECIAL ELECTIONS. THE ABSENCE OF SUCH A RELATIONSHIP UNDERSCORES THE IMPORTANCE OF CANDIDATES AND CONSTITUENT PREFERENCES IN STRUCTURING ELECTIONS AND INDICATES THE INAPPROPRIATENESS OF DRAWING NATIONAL IMPLICATIONS FROM SPECIAL HOUSE CONTESTS.