Il ruolo delle idee e del loro cambiamento nei processi di policy making universitario nel mondo anglosassone dagli anni ottanta ad oggi. I casi di Inghilterra e Nuova Zelanda in prospettiva comparata

THE TITLE OF MY THESIS IS THE ROLE OF THE IDEAS AND THEIR CHANGE IN HIGHER EDUCATION POLICY-MAKING PROCESSES FROM THE EIGHTIES TO PRESENT-DAY: THE CASES OF ENGLAND AND NEW ZEALAND IN COMPARATIVE PERSPECTIVE UNDER A THEORETICAL POINT OF VIEW, THE AIM OF MY WORK IS TO CARRY OUT A RESEARCH MODELLED ON THE CONSTRUCTIVIST THEORY. IT FOCUSES ON THE ANALYSIS OF THE IMPACT OF IDEAS ON THE PROCESSES OF POLICY MAKING BY MEANS OF EPISTEMIC COMMUNITIES, THINK TANKS AND VARIOUS SOCIOECONOMIC CONTEXTS THAT MAY HAVE PLAYED A KEY ROLE IN THE CONSTRUCTION OF THE DIFFERENT PATHS. FROM MY POINT OF VIEW IDEAS CONSTITUTE A PRIORITY RESEARCH FIELD WHICH IS WORTH ANALYSING SINCE THEIR ROLE IN POLICY MAKING PROCESSES HAS BEEN TRADITIONALLY RATHER UNEXPLORED. IN THIS CONTEXT AND WITH THE AIM OF DEVELOPING A RESEARCH STRAND BASED ON THE ROLE OF IDEAS, I INTEND TO CARRY ON MY STUDY UNDER THE PERSPECTIVE OF CHANGE. DEPENDING ON THE DATA AND INFORMATION THAT I COLLECTED I EVALUATED THE WEIGHT OF EACH OF THESE VARIABLES AND MAYBE OTHERS SUCH AS THE INSTITUTIONS AND THE INDIVIDUAL INTERESTS, WHICH MAY HAVE INFLUENCED THE FORMATION OF THE POLICY MAKING PROCESSES. UNDER THIS LIGHT, I PLANNED TO ADOPT THE QUALITATIVE METHODOLOGY OF RESEARCH WHICH I BELIEVE TO BE VERY EFFECTIVE AGAINST THE MORE DIFFICULT AND POSSIBLY REDUCTIVE APPLICATION OF QUANTITIVE DATA SETS. I RECKON THEREFORE THAT THE MOST APPROPRIATE TOOLS FOR INFORMATION PROCESSING INCLUDE CONTENT ANALYSIS, AND IN-DEPTH INTERVIEWS TO PERSONALITIES OF THE POLITICAL PANORAMA (ÉLITE OR NOT) WHO HAVE PARTICIPATED IN THE PROCESS OF HIGHER EDUCATION REFORM FROM THE EIGHTIES TO PRESENT-DAY. THE TWO CASES TAKEN INTO CONSIDERATION SURELY SET AN EXAMPLE OF RADICAL REFORM PROCESSES WHICH HAVE OCCURRED IN QUITE DIFFERENT CONTEXTS DETERMINED BY THE SOCIOECONOMIC CHARACTERISTICS AND THE TRAITS OF THE ÉLITE. IN NEW ZEALAND THE DESCRIBED PROCESS HAS TAKEN PLACE WITH A STEADY PACE AND A GOOD GRADE OF CONSEQUANTIALITY, IN LINE WTH THE REFORMS IN OTHER STATE DIVISIONS DRIVEN BY THE IDEAS OF THE NEW PUBLIC MANAGEMENT. CONTRARILY IN ENGLAND THE REFORMATIVE ACTION OF MARGARET THATCHER HAS ACQUIRED A VERY RADICAL CONNOTATION AS IT HAS BROUGHT INTO THE AMBIT OF HIGHER EDUCATION POLICY CONCEPTS LIKE EFFICIENCY, EXCELLENCE, RATIONALIZATION THAT WOULD CONTRAST WITH THE GENERALISTIC AND MASS-ORIENTED IDEAS THAT WERE FASHIONABLE DURING THE SEVENTIES. THE MISSION I INTEND TO ACCOMPLISH THORUGHOUT MY RESEARCH IS TO INVESTIGATE AND ANALYSE INTO MORE DEPTH THE DIFFERENCES THAT SEEM TO EMERGE FROM TWO CONTEXTS WHICH MOST OF THE LITERATURE REGARDS AS A SINGLE MODEL: THE ANGLO-SAXON MODEL. UNDER THIS LIGHT, THE DENSE ANALYSIS OF POLICY PROCESSES ALLOWED TO BRING OUT BOTH THE CONTROVERSIAL AND CONTRASTING ASPECTS OF THE TWO REALITIES COMPARED, AND THE ROLE AND WEIGHT OF VARIABLES SUCH AS IDEAS (MAIN VARIABLE), INSTITUTIONAL SETTINGS AND INDIVIDUAL INTERESTS ACTING IN EACH CONTEXT. THE CASES I MEAN TO ATTEND PRESENT PECULIAR ASPECTS WORTH DEVELOPING AN IN-DEPTH ANALYSIS, AN OUTLINE OF WHICH WILL BE PROVIDED IN THIS ABSTRACT. ENGLAND THE CONSERVATIVE GOVERNMENT, SINCE 1981, INTRODUCED RADICAL CHANGES IN THE SECTOR OF HIGHER EDUCATION: FIRST CUTTING DOWN ON STATE FUNDINGS AND THEN WITH THE CREATION OF AN INSTITUTION FOR THE PLANNING AND LEADERSHIP OF THE POLYTECHNICS (NON-UNIVERSITY SECTOR). AFTERWARDS THE SCHOOL REFORM BY MARGARET THATCHER IN 1988 RAISED TO A GREAT STIR ALL OVER EUROPE DUE TO BOTH ITS CONSIDERABLE INNOVATIVE IMPRINT AND THE STRONG ATTACK AGAINST THE PEDAGOGY OF THE ‘ACTIVE’ SCHOOLING AND PROGRESSIVE EDUCATION, UNTIL THEN RECOGNIZED AS A MERIT OF THE BRITISH PUBLIC SCHOOL. IN THE AMBIT OF UNIVERSITY EDUCATION THIS REFORM, TOGETHER WITH SIMILAR MEASURES BROUGHT IN DURING 1992, PUT INTO PRACTICE THE CONSERVATIVE PRINCIPLES THROUGH A SERIES OF ACTIONS THAT INCLUDED: THE SUPPRESSION OF THE IRREMOVABILITY PRINCIPLE FOR UNIVERSITY TEACHERS; THE INTRODUCTION OF STUDENT LOANS FOR LOW-INCOME STUDENTS AND THE CANCELLATION OF THE CLEAR DISTINCTION BETWEEN UNIVERSITIES AND POLYTECHNICS. THE POLICIES OF THE LABOUR MAJORITY OF MR BLAIR DID NOT QUITE DIVERGE FROM THE CONSERVATIVES’ POSITION. IN 2003 BLAIR’S CABINET RISKED TO BECOME A MINORITY RIGHT ON THE OCCASION OF AN IMPORTANT UNIVERSITY REFORM PROPOSAL. THIS PROPOSAL WOULD FORESEE THE AUTONOMY FOR THE UNIVERSITIES TO RAISE UP TO 3.000 POUNDS THE ENROLMENT FEES FOR STUDENTS (WHILE FORMERLY THE CEILING WAS 1.125 POUNDS). BLAIR HAD TO FACE INTERNAL OPPOSITION WITHIN HIS OWN PARTY IN RELATION TO A MEASURE THAT, ACCORDING TO THE 150 MPS PROMOTERS OF AN ADVERSE MOTION, HAD NOT BEEN INCLUDED IN THE ELECTORAL PROGRAMME AND WOULD RISK CREATING INCOME-BASED DISCRIMINATION AMONG STUDENTS. AS A MATTER OF FACT THE BILL FOCUSED ON THE INTRODUCTION OF VERY LOW-INTEREST STUDENT LOANS TO BE SETTLED ONLY WHEN THE STUDENT WOULD HAVE FOUND A REMUNERATED OCCUPATION (A SYSTEM ALREADY PROVIDED FOR BY THE AUSTRALIAN LEGISLATION). NEW ZEALAND CONTRARILY TO MANY OTHER COUNTRIES, NEW ZEALAND HAS ADOPTED A VERY WIDE VISION OF THE TERTIARY EDUCATION. IT INCLUDES IN FACT THE FULL EDUCATIONAL PROGRAMME THAT IS INTERNATIONALLY RECOGNIZED AS THE POST-SECONDARY EDUCATION. SHOULD WE SPOTLIGHT A PECULIARITY OF THE NEW ZEALAND TERTIARY EDUCATION POLICY THEN IT WOULD BE ‘CHANGE’. LOOKING AT THE REFORM HISTORY RELATED TO THE TERTIARY EDUCATION SYSTEM, WE CAN CLEARLY IDENTIFY FOUR ‘SUB-PERIODS’ FROM THE EIGHTIES TO PRESENT-DAY: 1. BEFORE THE 80S’: AN ELITARIAN SYSTEM CHARACTERIZED BY LOW PARTICIPATION RATES. 2. BETWEEN MID AND LATE 80S’: A TREND TOWARDS THE ENLARGEMENT OF PARTICIPATION ASSOCIATED TO A GREATER COMPETITION. 3. 1990-1999: A FUTHER STEP TOWARDS A COMPETITIVE MODEL BASED ON THE MARKET-ORIENTED SYSTEM. 4. FROM 2000 TO TODAY: A CONTINUOUS EVOLUTION TOWARDS A MORE COMPETITIVE MODEL BASED ON THE MARKET-ORIENTED SYSTEM TOGETHER WITH A GROWING ATTENTION TO STATE CONTROL FOR SOCIAL AND ECONOMIC DEVELOPMENT OF THE NATION. AT PRESENT THE GOVERNMENT OF NEW ZEALAND OPERATES TO STRENGHTHEN THIS PROCESS, PRIMARILY IN RELATION TO THE ROLE OF TERTIARY EDUCATION AS A STEADY FACTOR OF NATIONAL WALFARE, WHERE PROFESSIONAL DEVELOPMENT CONTRIBUTES ACTIVELY TO THE GROWTH OF THE NATIONAL ECONOMIC SYSTEM5. THE CASES OF ENGLAND AND NEW ZEALAND ARE THE FOCUS OF AN IN-DEPTH INVESTIGATION THAT STARTS FROM AN ANALYSIS OF THE POLICIES OF EACH NATION AND DEVELOP INTO A COMPARATIVE STUDY. AT THIS POINT I ATTEMPT TO DRAW SOME PRELIMINARY IMPRESSIONS ON THE FACTS ESSENTIALLY DECRIBED ABOVE. THE UNIVERSITY POLICIES IN ENGLAND AND NEW ZEALAND HAVE BOTH UNDERGONE A SIGNIFICANT REFORMATORY PROCESS SINCE THE EARLY EIGHTIES; IN BOTH CONTEXTS THE IMPORTANCE OF IDEAS THAT CONSTITUTED THE BASE OF POLITICS UNTIL 1980 WAS QUITE RELEVANT. GENERALLY SPEAKING, IN BOTH CASES THE PRE-REFORM POLICIES WERE INSPIRED BY EGALITARIANISM AND EXPANSION OF THE STUDENT POPULATION WHILE THOSE BROUGHT IN BY THE REFORM WOULD PURSUE EFFICIENCY, QUALITY AND COMPETITIVENESS. UNDOUBTEDLY, IN LINE WITH THIS GENERAL TENDENCY THAT REFLECTS THE HYPOTHESIS PROPOSED, THE TWO UNIVERSITY SYSTEMS PRESENT SEVERAL DIFFERENCES. THE UNIVERSITY SYSTEM IN NEW ZEALAND PROCEEDED STEADILY TOWARDS THE IMPLEMENTATION OF A MANAGERIAL CONCEPTION OF TERTIARY EDUCATION, ESPECIALLY FROM 1996 ONWARDS, IN ACCORDANCE WITH THE REFORMATORY PROCESS OF THE WHOLE PUBLIC SECTOR. IN THE UNITED KINGDOM, AS IN THE REST OF EUROPE, THE NEW APPROACH TO UNIVERSITY POLICY-MAKING HAD TO CONFRONT A DEEP-ROOTED TRADITION OF PROGRESSIVE EDUCATION AND THE IDEA OF EDUCATION EXPANSION THAT IN FACT DOMINATED UNTIL THE EIGHTIES. FROM THIS VIEW POINT THE GOVERNING ACTION OF MARGARET THATCHER GAVE RISE TO A RADICAL CHANGE THAT REVOLUTIONIZED THE OBJECTIVES AND KEY VALUES OF THE WHOLE EDUCATIONAL SYSTEM, IN PARTICULAR IN THE HIGHER EDUCATION SECTOR. IDEAS AS EFFICIENCY, EXCELLENCE AND CONTROL OF THE PERFORMANCE BECAME DECISIVE. THE LABOUR CABINETS OF BLAIR DEVELOPED IN THE WAKE OF CONSERVATIVE REFORMS. THIS APPEARS TO BE A FOCAL POINT OF THIS STUDY THAT OBSERVES HOW ALSO IN NEW ZEALAND THE REFORMING PROCESS OCCURRED TRANSVERSELY DURING PROGRESSIVE AND CONSERVATIVE ADMINISTRATIONS. THE PRELIMINARY IMPRESSION IS THEREFORE THAT IDEAS DEEPLY MARK THE REFORMATIVE PROCESSES: THE AIM OF MY RESEARCH IS TO VERIFY TO WHICH EXTENT THIS STATEMENT IS TRUE. IN ORDER TO BUILD A COMPREHENSIVE ANALYLIS, FURTHER SIGNIFICANT FACTORS WILL HAVE TO BE INVESTIGATED: THE WAY IDEAS ARE PERCEIVED AND IMPLEMENTED BY THE DIFFERENT POLITICAL ELITES; HOW THE VARIOUS SOCIOECONOMIC CONTEXTS INFLUENCE THE REFORMATIVE PROCESS; HOW THE INSTITUTIONAL STRUCTURES CONDITION THE POLICY-MAKING PROCESSES; WHETHER INDIVIDUAL INTERESTS PLAY A ROLE AND, IF YES, TO WHICH EXTENT.

Synthese und Charakterisierung von Polymethylmethacrylat (PMMA)-Silika-Komposit-Partikeln und fluorierten Nanopartikeln unter Verwendung des Miniemulsionsprozesses

In der vorliegenden Dissertation wurden zwei verschiedene Fragestellungen bearbeitet. Zum einen wurde im Rahmen des Schwerpunktprojektes „Kolloidverfahrenstechnik“ und in Zusammenarbeit mit der Arbeitsgruppe von Prof. Dr. Heike Schuchmann vom KIT in Karlsruhe die Verkapselung von Silika-Nanopartikeln in eine PMMA-Hülle durch Miniemulsionspolymerisation entwickelt und der Aufskalierungsprozess unter Verwendung von Hochdruckhomogenisatoren vorangetrieben. Zum anderen wurden verschiedene fluorierte Nanopartikel durch den Miniemulsionsprozess generiert und ihr Verhalten in Zellen untersucht.rnSilika-Partikel konnten durch Miniemulsionspolymerisation in zwei unterschiedlichen Prozessen erfolgreich verkapselt werden. Bei der ersten Methode wurden zunächst modifizierte Silika-Partikel in einer MMA-Monomerphase dispergiert und anschließend durch den normalen Miniemulsionsprozess Silika-beladene Tröpfchen generiert. Diese konnten zu Komposit-Partikeln polymerisiert werden. Bei der Verkapselung durch den Fission/Fusion Prozess wurden die hydrophobisierten Silika-Partikel durch Fission und Fusion Prozesse in schon vorhandene Monomertröpfchen eingebracht, welche hinterher polymerisiert wurden. Um hydrophiles Silika in einem hydrophoben Monomer zu dispergieren, musste zunächst eine Modifizierung der Silika-Partikel stattfinden. Dies geschah unter anderem über eine chemische Anbindung von 3-Methacryloxypropyltri-methoxysilan an der Oberfläche der Silika-Partikel. Des Weiteren wurden die hydrophilen Silika-Partikel durch Adsorption von CTMA-Cl physikalisch modifiziert. Unter anderem durch die Variation des Verkapselungsprozesses, der Silika-Menge, der Tensidart und –menge und der Comonomere konnten Komposit-Partikel mit unterschiedlichen Morphologien, Größen, und Füllgraden erhalten werden.rnFluorierte Nanopartikel wurden erfolgreich über den Prozess der Miniemulsionspolymerisation synthetisiert. Als Monomere dienten dabei fluorierte Acrylate, fluorierte Methacrylate und fluoriertes Styrol. Es war möglich aus jeder dieser drei Gruppen an Monomeren fluorierte Nanopartikel herzustellen. Für genauere Untersuchungen wurden 2,3,4,5,6-Pentafluorstyrol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-Heptadecafluorodecyl-methacrylat und 1H,1H,2H,2H-Perfluorodecylacrylat als Monomere ausgewählt. Als Hydrophob zur Unterdrückung der Ostwaldreifung wurde Perfluromethyldecalin eingesetzt. Die stabilsten Miniemulsionen wurden wiederum mit den ionischen Tensid SDS generiert. Mit steigendem Gehalt an SDS gelöst in der kontinuierlichen Phase, wurde eine Verkleinerung der Partikelgröße festgestellt. Neben den Homopolymerpartikeln wurden auch Copolymerpartikel mit Acrylsäure erfolgreich synthetisiert. Zudem wurde noch das Verhalten der fluorierten Partikel in Zellen überprüft. Die fluorierten Partikel wiesen ein nicht toxisches Verhalten vor. Die Adsorption von Proteinen aus Humanem Serum wurde über ITC Messungen untersucht. rnSomit konnte gezeigt werden, dass die Technik der Miniemulsionspolymerisation eine abwechslungsreiche und effektive Methode ist, um Hybridnanopartikel mit verschiedenen Morphologien und oberflächenfunktionalisierte Nanopartikel erfolgreich zu generieren.rn

Molecular plating of thin lanthanide layers with improved material properties for nuclear applications

In der vorliegenden Arbeit werden Experimente beschrieben, die zu einem vertieften Verständnis fundamentaler Prozesse bei der elektrochemischen Herstellung von Dünnschichten, sog. Targets, für kernphysikalische und -chemische Studien führten. Targets wurden mittels 'Molecular Plating' (MP) hergestellt, indem eine Elektrodeposition aus organischem Medium in der Regel bei konstantem Strom in Zwei-Elektroden-Zellen. Die Resultate erlaubten, optimierte Herstellungs-bedingungen zu ermitteln, welche die Produktion deutlich verbesserter Targets erlaubten. MP bei konstantem Strom ist ein massentransportkontrollierter Prozess. Der angelegte Strom wird durch einen konstanten Fluss elektroaktiver Spezies zur Kathode – auf der die Schicht wächst – und Anode aufrechterhalten. Die Untersuchungen zeigten, dass das Zellenpotential des Elektrodepositionsystems immer durch den Ohm'schen Spannungsabfall auf Grund des Widerstandes der verwendeten Lösung dominiert wurde. Dies erlaubte die Herleitung einer Beziehung zwischen dem Zellenpotential und der Konzentration der elektroaktiven Spezies. Die Beziehung erlaubt die Erklärung des gemessenen zeitlichen Verlaufs des Zellenpotentials während der Abscheidung als Funktion der Elektrolytkonzentration. Dies dient als Basis, auf der nun ein umfassenderes Bild der Prozesse, die für die charakteristischen Minima im Potentialverlauf einer Abscheidung verantwortlich sind, gewonnen werden kann. Es konnte gezeigt werden, dass die Minima mit der fast vollständigen Entfernung (durch Abscheidung) der aus einem gelösten Salz erzeugten Nd-Ionen korrespondieren. Die abgeschiedene Spezies wurde als Nd3+ identifiziert, vermutlich als Carboxylat, Oxid oder Hydroxid, was auf Grund der hohen negative Werte des Standardredoxpotentials der Lanthanide verständlich erscheint. Von den vorliegenden elektroaktiven Spezies tragen die Nd3+ Ionen nur zu knapp 20% zum Gesamtstrom bei. Durch Elektrolyse tragen auch die Lösungsmittelkomponenten zu diese Strom bei. Die Gegenwart von elektrolysiertem Lösungsmittel wurde in Analysen der Dünnschichten bestätigt. Diese waren immer mit chemi- und physisorbierten Lösungsmittelmolekülen bedeckt. Die Analyse der Dünnschichten zeigte, dass die Oberflächen von einem furchenartiges Netz durchzogen waren, und dass diese während des Trocknen der Schichten nach dem MP entstanden. Ob die Schichten an Luft oder in inerter Atmosphäre trockneten, hatte keinen Einfluss. Es wurden Experimente mit mehreren Lösungsmitteln durchgeführt, die sich deutlich in ihren physikalischen Eigenschaften, v.a. dem Siedepunkt, unterschieden. Furchenfreie Dünnschichten konnten insbesondere bei MP in N,N-dimethylformamide (DMF) erzeugt werden. Die Verwendung von DMF in Kombination mit einer Abscheidung auf sehr glatten Substraten erlaubte die Produktion von sehr homogenen, glatten und defektfreien Schichten. Diese waren vermutlich geringeren inneren Spannungen während des Trocknens ausgesetzt, als Schichten auf raueren Substraten oder solche, die aus flüchtigeren Lösungsmitteln hergestellt wurden. Die Oberflächenrauigkeit des Substrats und das gewählte Lösungsmittel wurden so als Schlüsselfaktoren für die Produktion hochqualitativer Schichten identifiziert. Es konnte gezeigt werden, dass mit MP eine sehr effiziente Methode zur Herstellung homogener Schichten mit exzellenter Ausbeute ist. In weiteren Experimenten mit dem primordialen Alpha-Emitter 147Sm als Modellisotop wurde die Eignung solcher Schichten als Alpha-Quelle untersucht. Sowohl die Energieauflösung als auch der Anteil der Alpha-Teilchen, die den Detektor erreichten, waren von den Quelleneigenschaften abhängig. Die Effekte wurden verschiedenen Variablen der Dünnschicht zugeordnet, welche die Alpha-Spektren beeinflussten. Dominant war die Wahl des Lösungsmittels und die Rauigkeit des Substrats. Dies beeinflusste Schichtdicke und -morphologie sowie die Art des Schichtwachstums und veränderte die Detektionseffizienz in Alpha-Messungen bis zu 15%. Nur homogene, ebene Schichten, die aus DMF auf glatten Substraten abgeschieden wurden, eignen sich optimal als Alpha-Quelle. Die gewonnenen Ergebnisse erlauben die optimierte Herstellung nuklearer Targets durch MP. Künftige Anwendungen beinhalten insbesondere die Herstellung von Targets für neutroneninduzierte Spaltexperimente und untergrundarmeAlpha-Messungen sehr kleiner Aktivitäten.

From defined polymer architectures to structure-property relationships in vivo

Makromolekulare Wirkstoffträgersysteme sind von starkem Interesse bezüglich der klinischen Anwendung chemotherapeutischer Agenzien. Um ihr klinisches Potential zu untersuchen ist es von besonderer Bedeutung das pharmakokinetische Profil in vivo zu bestimmen. Jede Veränderung der Polymerstruktur beeinflusst die Körperverteilung des entsprechenden Makromoleküls. Aufgrund dessen benötigt man detailliertes Wissen über Struktur-Eigenschaftsbeziehungen im lebenden Organismus, um das Nanocarrier System für zukünftige Anwendungen einzustellen. In dieser Beziehung stellt das präklinische Screening mittels radioaktiver Markierung und Positronen-Emissions-Tomographie eine nützliche Methode für schnelle sowie quantitative Beobachtung von Wirkstoffträgerkandidaten dar. Insbesondere poly(HPMA) und PEG sind im Arbeitsgebiet Polymer-basierter Therapeutika stark verbreitet und von ihnen abgeleitete Strukturen könnten neue Generationen in diesem Forschungsbereich bieten.rnDie vorliegende Arbeit beschreibt die erfolgreiche Synthese verschiedener HPMA und PEG basierter Polymer-Architekturen – Homopolymere, Statistische und Block copolymere – die mittels RAFT und Reaktivesterchemie durchgeführt wurde. Des Weiteren wurden die genannten Polymere mit Fluor-18 und Iod-131 radioaktiv markiert und mit Hilfe von microPET und ex vivo Biodistributionsstudien in tumortragenden Ratten biologisch evaluiert. Die Variation in Polymer-Architektur und darauffolgende Analyse in vivo resultierte in wichtige Schlussfolgerungen. Das hydrophile / lipophile Gleichgewicht hatte einen bedeutenden Einfluss auf das pharmakokinetische Profil, mit besten in vivo Eigenschaften (geringe Aufnahme in Leber und Milz sowie verlängerte Blutzirkulationszeit) für statistische HPMA-LMA copolymere mit steigendem hydrophoben Anteil. Außerdem zeigten Langzeitstudien mit Iod-131 eine verstärkte Retention von hochmolekularen, HPMA basierten statistischen Copolymeren im Tumorgewebe. Diese Beobachtung bestätigte den bekannten EPR-Effekt. Hinzukommend stellen Überstrukturbildung und damit Polymergröße Schlüsselfaktoren für effizientes Tumor-Targeting dar, da Polymerstrukturen über 200 nm in Durchmesser schnell vom MPS erkannt und vom Blutkreislauf eliminiert werden. Aufgrund dessen wurden die hier synthetisierten HPMA Block copolymere mit PEG Seitengruppen chemisch modifiziert, um eine Verminderung in Größe sowie eine Reduktion in Blutausscheidung zu induzieren. Dieser Ansatz führte zu einer erhöhten Tumoranreicherung im Walker 256 Karzinom Modell. Generell wird die Körperverteilung von HPMA und PEG basierten Polymeren stark durch die Polymer-Architektur sowie das Molekulargewicht beeinflusst. Außerdem hängt ihre Effizienz hinsichtlich Tumorbehandlung deutlich von den individuellen Charakteristika des einzelnen Tumors ab. Aufgrund dieser Beobachtungen betont die hier vorgestellte Dissertation die Notwendigkeit einer detaillierten Polymer-Charakterisierung, kombiniert mit präklinischem Screening, um polymere Wirkstoffträgersysteme für individualisierte Patienten-Therapie in der Zukunft maßzuschneidern.rn

Microphysiological systems: Nuove piattaforme di coltura cellulare per applicazioni di interesse biomedico

In questo elaborato verranno presentati le finalità, gli sviluppi e le prospettive future di una tipologia di coltura cellulare, ovvero dei microphysiological systems - MPS (o organs-on-chips), nuovi microdispositivi atti a riprodorre il più fedelmente possibile le condizioni fisiologiche adatte per la crescita e il mantenimento di strutture cellulari complesse. Verranno quindi inizialmente descritte le specifiche di base di questi dispositivi, sottolineandone l'innovatività dal punto di vista tecnologico e funzionale. Grazie agli MPS è infatti stato possibile intraprendere studi per una migliore comprensione del comportamento in condizioni dinamiche di una vasta gamma di tessuti, e la risposta di questi a stimoli chimici e fisici, rappresentativi di condizioni fisiologiche o patologiche, aprendo così le porte a nuovi standard per la sperimentazione clinica. Verrà quindi proposto un caso di studio, che riguarda l'applicazione di quanto sopra all'ambito cardiocircolatorio, prendendo in esame un modello di heart-on-a-chip, descrivendolo in tutte le fasi della sua realizzazione e infine discutendo uno studio riguardante la risposta delle cellule del muscolo cardiaco a un trattamento farmacologico.

Angiographic geometric changes of the lumen arterial wall after bioresorbable vascular scaffolds and metallic platform stents at 1-year follow-up

The aim of this study was to compare the angiographic changes in coronary geometry of the bioresorbable vascular scaffolds (BVS) and metallic platform stent (MPS) between baseline and follow-up.

Classification of suppressor additives based on synergistic and antagonistic ensemble effects

Three fundamental types of suppressor additives for copper electroplating could be identified by means of potential Transient measurements. These suppressor additives differ in their synergistic and antagonistic interplay with anions that are chemisorbed on the metallic copper surface during electrodeposition. In addition these suppressor chemistries reveal different barrier properties with respect to cupric ions and plating additives (Cl, SPS). While the type-I suppressor selectively forms efficient barriers for copper inter-diffusion on chloride-terminated electrode surfaces we identified a type-II suppressor that interacts non-selectively with any kind of anions chemisorbed on copper (chloride, sulfate, sulfonate). Type-I suppressors are vital for the superconformal copper growth mode in Damascene processing and show an antagonistic interaction with SPS (Bis-Sodium-Sulfopropyl-Disulfide) which involves the deactivation of this suppressor chemistry. This suppressor deactivation is rationalized in terms of compositional changes in the layer of the chemisorbed anions due to the competition of chloride and MPS (Mercaptopropane Sulfonic Acid) for adsorption sites on the metallic copper surface. MPS is the product of the dissociative SPS adsorption within the preexisting chloride matrix on the copper surface. The non-selectivity in the adsorption behavior of the type-II suppressor is rationalized in terms of anion/cation pairing effects of the poly-cationic suppressor and the anion-modified copper substrate. Atomic-scale insights into the competitive Cl/MPS adsorption are gained from in situ STM (Scanning Tunneling Microscopy) using single crystalline copper surfaces as model substrates. Type-III suppressors are a third class of suppressors. In case of type-land type-II suppressor chemistries the resulting steady-state deposition conditions are completely independent on the particular succession of additive adsorption. In contrast to that a strong dependence of the suppressing capabilities on the sequence of additive adsorption ("first comes, first serves" principle) is observed for the type-IIIsuppressor. This behavior:is explained by a suppressor barrier that impedes not only the copper inter-diffusion but also the transport of other additives (e.g. SPS) to the copper surface. (C) 2011 Elsevier Ltd. All rights reserved.

Antinociceptive activity of pre- versus post-operative intra-articular bupivacaine in goats undergoing stifle arthrotomy

OBJECTIVE: To evaluate the peri-operative analgesic efficacy of intra-articular bupivacaine administered before or after stifle arthrotomy. STUDY DESIGN: Prospective, randomized, blind, placebo-controlled experimental trial. ANIMALS: Thirty-nine healthy goats. METHODS: The goats were allocated randomly to one of three intra-articular treatment groups: group PRE (bupivacaine before and saline after surgery), group POST (saline before and bupivacaine after surgery) and group CON (saline before and after surgery). Anaesthesia was maintained with a constant end-tidal sevoflurane of 2.5%. Intra-operatively heart rate (HR), respiratory rate and mean arterial blood pressure (MAP) after critical surgical events (CSE) were recorded and compared with pre-incision values. Propofol requirements to maintain surgical anaesthesia were recorded. Flunixin was administered for 5 days. Post-operative pain assessment at 20 minutes, 2 hours, 4 hours after recovery and on day 2 and 3 included a multidimensional pain score (MPS), a lameness score and mechanical nociceptive threshold (MNT) testing. Rescue analgesia consisted of systemic opioids. Data were analysed using Kruskal-Wallis, Mann-Whitney, Friedman or chi-square tests as appropriate. RESULTS: Intra-operatively, group PRE had lower HR and MAP at several CSEs than groups POST/CON and required less propofol [0 mg kg(-1) (0-0 mg kg(-1))] than group POST/CON [0.3 mg kg(-1) (0-0.6 mg kg(-1))]. Post-operatively, group POST had significantly higher peri-articular MNTs than groups PRE and CON up to 4 hours after recovery. No treatment effect was detected for MPS, lameness scores and rescue analgesic consumption at any time point. CONCLUSIONS AND CLINICAL RELEVANCE: Pre-operative intra-articular bupivacaine provided notable intra-operative analgesia in goats undergoing stifle arthrotomy but did not reduce post-operative pain. Post-operative intra-articular bupivacaine provided a short lasting reduction of peri-articular hyperalgesia without affecting the requirements for systemic analgesia. Multimodal perioperative pain therapy is recommended to provide adequate analgesia for stifle arthrotomy in goats.

Cause or effect of arteriogenesis: compositional alterations of microparticles from CAD patients undergoing external counterpulsation therapy

Recently, a clinical study on patients with stable coronary artery disease (CAD) showed that external counterpulsation therapy (ECP) at high (300 mmHg) but not at low inflation pressure (80 mmHg) promoted coronary collateral growth, most likely due to shear stress-induced arteriogenesis. The exact molecular mechanisms behind shear stress-induced arteriogenesis are still obscure. We therefore characterized plasma levels of circulating microparticles (MPs) from these CAD patients because of their ambivalent nature as a known cardiovascular risk factor and as a promoter of neovascularization in the case of platelet-derived MPs. MPs positive for Annexin V and CD31CD41 were increased, albeit statistically significant (P<0.05, vs. baseline) only in patients receiving high inflation pressure ECP as determined by flow cytometry. MPs positive for CD62E, CD146, and CD14 were unaffected. In high, but not in low, inflation pressure treatment, change of CD31CD41 was inversely correlated to the change in collateral flow index (CFI), a measure for collateral growth. MPs from the high inflation pressure group had a more sustained pro-angiogenic effect than the ones from the low inflation pressure group, with the exception of one patient showing also an increased CFI after treatment. A total of 1005 proteins were identified by a label-free proteomics approach from MPs of three patients of each group applying stringent acceptance criteria. Based on semi-quantitative protein abundance measurements, MPs after ECP therapy contained more cellular proteins and increased CD31, corroborating the increase in MPs. Furthermore, we show that MP-associated factors of the innate immune system were decreased, many membrane-associated signaling proteins, and the known arteriogenesis stimulating protein transforming growth factor beta-1 were increased after ECP therapy. In conclusion, our data show that ECP therapy increases platelet-derived MPs in patients with CAD and that the change in protein cargo of MPs is likely in favor of a pro angiogenic/arteriogenic property.

Attitudes and Social Factors as Predictors of Male Perpetration of Sexual Assault

Previous research has demonstrated a significant association between sexual assault perpetration and hooking up, male peer support for woman abuse, alcohol consumption, and rape myth acceptance (Burt, 1980; Flack, Daubman, Caron, Asadorian, D’Aureli, Gigliotti & Stine, 2007; Schwartz & DeKeseredy, 1997). In the present study, we tested these relationships on the collegiate level by asking male students to indicate levels of male peer support for woman abuse (MPS), acceptance of rape myths (RMA), alcohol consumption, and history of hooking up and sexual assault perpetration during their undergraduate experience. Participants in this study were 200 male Bucknell students (sophomores - seniors) who completed an online survey concerning these issues. The overall prevalence rate for some type of sexual assault perpetration was 10.5%. Specific prevalence rates for non-invasive contact, completed rape, and attempted rape were 5.5%, 2.0%, and 5.0%, respectively. Sexual assault perpetration was positively correlated with MPS and alcohol consumption but not with RMA. Sexual assault was perpetrated most frequently during acquaintance hook ups. These findings demonstrate direct, significant relationships between sexual assault perpetration, alcohol abuse, different types of hooking up, and rape-supportive attitudes, and an association between perpetration and MPS that requires further elaboration.

Dual in vitro perfusion of an isolated cotyledon as a model to study the implication of changes in the third trimester placenta on preeclampsia

In the current study perfusions of an isolated cotyledon of term placenta using standard medium were compared to medium containing xanthine plus xanthine oxidase (X+XO), which generates reactive oxygen species (ROS). A time-dependant increase in the levels of different cytokines (TNF-alpha, IL-1ss, IL-6, IL-8 and IL-10) was observed between 1 and 7h with more than 90% of the total recovered from the maternal compartment with no significant difference between the 2 groups. For 8-iso-PGF2alpha 90% of the total was found in the fetal compartment and a significantly higher total release was seen in the X+XO group. Microparticles (MPs) isolated from the maternal circuit were identified by flow cytometry as trophoblastic sheddings, whereas MPs from the fetal circuit were predominantly derived from endothelial cells. More than 90% of the total of MPs was found in the maternal circuit. The absolute amount of the total as well as the maternal fraction were significantly higher in the X+XO group. Immunohistochemistry (IHC) of the perfused tissue revealed staining for IL-1beta of villous stroma cells, which became clearly more pronounced in experiments with X+XO. Western blot of tissue homogenate revealed 2 isoforms of IL-1beta at 17 and 31kD. In X+XO experiments there was a tendency for increased expression of antioxidant enzymes in the tissue. Western blot of MPs from the maternal circuit showed increased expression of antioxidant enzymes in the X+XO group and for IL-1beta only the 17kD band was detected. In vitro reperfusion of human placental tissue results in mild tissue injury suggestive of oxidative stress. In view of the increased generation of ROS in perfused tissue with further increase under the influence of X+XO, the overall manifestation of oxidative stress remained rather mild. Preservation of antioxidant capacity of human placental tissue could be a sign of integrity of structure and function being maintained in vitro by dual perfusion of an isolated cotyledon. The observed changes resemble findings seen in placentae from preeclampsia.

Arc-flash analysis of utility power systems

The electric utility business is an inherently dangerous area to work in with employees exposed to many potential hazards daily. One such hazard is an arc flash. An arc flash is a rapid release of energy, referred to as incident energy, caused by an electric arc. Due to the random nature and occurrence of an arc flash, one can only prepare and minimize the extent of harm to themself, other employees and damage to equipment due to such a violent event. Effective January 1, 2009 the National Electric Safety Code (NESC) requires that an arc-flash assessment be performed by companies whose employees work on or near energized equipment to determine the potential exposure to an electric arc. To comply with the NESC requirement, Minnesota Power’s (MP’s) current short circuit and relay coordination software package, ASPEN OneLinerTM and one of the first software packages to implement an arc-flash module, is used to conduct an arc-flash hazard analysis. At the same time, the package is benchmarked against equations provided in the IEEE Std. 1584-2002 and ultimately used to determine the incident energy levels on the MP transmission system. This report goes into the depth of the history of arc-flash hazards, analysis methods, both software and empirical derived equations, issues of concern with calculation methods and the work conducted at MP. This work also produced two offline software products to conduct and verify an offline arc-flash hazard analysis.

CD39 is incorporated into plasma microparticles where it maintains functional properties and impacts endothelial activation

Plasma microparticles (MPs, <1.5 mum) originate from platelet and cell membrane lipid rafts and possibly regulate inflammatory responses and thrombogenesis. These actions are mediated through their phospholipid-rich surfaces and associated cell-derived surface molecules. The ectonucleotidase CD39/ecto-nucleoside triphosphate diphosphohydrolase1 (E-NTPDase1) modulates purinergic signalling through pericellular ATP and ADP phosphohydrolysis and is localized within lipid rafts in the membranes of endothelial- and immune cells. This study aimed to determine whether CD39 associates with circulating MPs and might further impact phenotype and function. Plasma MPs were found to express CD39 and exhibited classic E-NTPDase ecto-enzymatic activity. Entpd1 (Cd39) deletion in mice produced a pro-inflammatory phenotype associated with quantitative and qualitative differences in the MP populations, as determined by two dimensional-gel electrophoresis, western blot and flow cytometry. Entpd1-null MPs were also more abundant, had significantly higher proportions of platelet- and endothelial-derived elements and decreased levels of interleukin-10, tumour necrosis factor receptor 1 and matrix metalloproteinase 2. Consequently, Cd39-null MP augment endothelial activation, as determined by inflammatory cytokine release and upregulation of adhesion molecules in vitro. In conclusion, CD39 associates with circulating MP and may directly or indirectly confer functional properties. Our data also suggest a modulatory role for CD39 within MP in the exchange of regulatory signals between leucocytes and vascular cells.

Fuzzy Multi-Objective Linear Programming and Simulation Approach to the Development of Valid and Realistic Master Production Schedule

Master production schedule (MPS) plays an important role in an integrated production planning system. It converts the strategic planning defined in a production plan into the tactical operation execution. The MPS is also known as a tool for top management to control over manufacture resources and becomes input of the downstream planning levels such as material requirement planning (MRP) and capacity requirement planning (CRP). Hence, inappropriate decision on the MPS development may lead to infeasible execution, which ultimately causes poor delivery performance. One must ensure that the proposed MPS is valid and realistic for implementation before it is released to real manufacturing system. In practice, where production environment is stochastic in nature, the development of MPS is no longer simple task. The varying processing time, random event such as machine failure is just some of the underlying causes of uncertainty that may be hardly addressed at planning stage so that in the end the valid and realistic MPS is tough to be realized. The MPS creation problem becomes even more sophisticated as decision makers try to consider multi-objectives; minimizing inventory, maximizing customer satisfaction, and maximizing resource utilization. This study attempts to propose a methodology for MPS creation which is able to deal with those obstacles. This approach takes into account uncertainty and makes trade off among conflicting multi-objectives at the same time. It incorporates fuzzy multi-objective linear programming (FMOLP) and discrete event simulation (DES) for MPS development.

Combined Secondary Ion Mass Spectrometry Depth Profiling and Focused Ion Beam Analysis of Cu Films Electrodeposited under Oscillatory Conditions

The recrystallization behavior of Cu films electrodeposited under oscillatory conditions in the presence of plating additives was studied by means of secondary ion mass spectrometry (SIMS) and focused ion beam analysis. When combined with bis-(sodium-sulfopropyl)-disulfide (SPS), Imep levelers (polymerizates of imidazole and epichlorohydrin) show characteristic oscillations in the galvanostatic potential/time transient measurements. These are related to the periodic degradation and restoration of the active leveler ensemble at the interface. The leveler action relies on adduct formation between the Imep and MPS (mercaptopropane sulfonic acid)-stabilized CuI complexes that appear as intermediates of the copper deposition when SPS is present in the electrolyte. SIMS depth profiling proves that additives are incorporated into the growing film preferentially under transient conditions during the structural breakdown of the leveler ensemble and its subsequent restoration. In contrast, Cu films electrodeposited in the presence of a structurally intact Imep–CuI–MPS ensemble remain largely contamination free.