Transposable elements: structure and dynamic of the autonomous retrotransposon R2 in Arthropoda with non-canonical reproduction

Eukaryotic ribosomal DNA constitutes a multi gene family organized in a cluster called nucleolar organizer region (NOR); this region is composed usually by hundreds to thousands of tandemly repeated units. Ribosomal genes, being repeated sequences, evolve following the typical pattern of concerted evolution. The autonomous retroelement R2 inserts in the ribosomal gene 28S, leading to defective 28S rDNA genes. R2 element, being a retrotransposon, performs its activity in the genome multiplying its copy number through a “copy and paste” mechanism called target primed reverse transcription. It consists in the retrotranscription of the element’s mRNA into DNA, then the DNA is integrated in the target site. Since the retrotranscription can be interrupted, but the integration will be carried out anyway, truncated copies of the element will also be present in the genome. The study of these truncated variants is a tool to examine the activity of the element. R2 phylogeny appears, in general, not consistent with that of its hosts, except some cases (e.g. Drosophila spp. and Reticulitermes spp.); moreover R2 is absent in some species (Fugu rubripes, human, mouse, etc.), while other species have more R2 lineages in their genome (the turtle Mauremys reevesii, the Japanese beetle Popilia japonica, etc). R2 elements here presented are isolated in 4 species of notostracan branchiopods and in two species of stick insects, whose reproductive strategies range from strict gonochorism to unisexuality. From sequencing data emerges that in Triops cancriformis (Spanish gonochoric population), in Lepidurus arcticus (two putatively unisexual populations from Iceland) and in Bacillus rossius (gonochoric population from Capalbio) the R2 elements are complete and encode functional proteins, reflecting the general features of this family of transposable elements. On the other hand, R2 from Italian and Austrian populations of T. cancriformis (respectively unisexual and hermaphroditic), Lepidurus lubbocki (two elements within the same Italian population, gonochoric but with unfunctional males) and Bacillus grandii grandii (gonochoric population from Ponte Manghisi) have sequences that encode incomplete or non-functional proteins in which it is possible to recognize only part of the characteristic domains. In Lepidurus couesii (Italian gonochoric populations) different elements were found as in L. lubbocki, and the sequencing is still in progress. Two hypothesis are given to explain the inconsistency of R2/host phylogeny: vertical inheritance of the element followed by extinction/diversification or horizontal transmission. My data support previous study that state the vertical transmission as the most likely explanation; nevertheless horizontal transfer events can’t be excluded. I also studied the element’s activity in Spanish populations of T. cancriformis, in L. lubbocki, in L. arcticus and in gonochoric and parthenogenetic populations of B. rossius. In gonochoric populations of T. cancriformis and B. rossius I found that each individual has its own private set of truncated variants. The situation is the opposite for the remaining hermaphroditic/parthenogenetic species and populations, all individuals sharing – in the so far analyzed samples - the majority of variants. This situation is very interesting, because it isn’t concordant with the Muller’s ratchet theory that hypothesizes the parthenogenetic populations being either devoided of transposable elements or TEs overloaded. My data suggest a possible epigenetic mechanism that can block the retrotransposon activity, and in this way deleterious mutations don’t accumulate.

Reverse genetic studies of Benyvirus - Polymyxa betae molecular interaction: Role of the RNA4-encoded protein in virus transmission

Beet necrotic yellow vein virus (BNYVV), the leading infectious agent that affects sugar beet, is included within viruses transmitted through the soil from plasmodiophorid as Polymyxa betae. BNYVV is the causal agent of Rhizomania, which induces abnormal rootlet proliferation and is widespread in the sugar beet growing areas in Europe, Asia and America; for review see (Peltier et al., 2008). In this latter continent, Beet soil-borne mosaic virus (BSBMV) has been identified (Lee et al., 2001) and belongs to the benyvirus genus together with BNYVV, both vectored by P. betae. BSBMV is widely distributed only in the United States and it has not been reported yet in others countries. It was first identified in Texas as a sugar beet virus morphologically similar but serologically distinct to BNYVV. Subsequent sequence analysis of BSBMV RNAs evidenced similar genomic organization to that of BNYVV but sufficient molecular differences to distinct BSBMV and BNYVV in two different species (Rush et al., 2003). Benyviruses field isolates usually consist of four RNA species but some BNYVV isolates contain a fifth RNA. RNAs -1 contains a single long ORF encoding polypeptide that shares amino acid homology with known viral RNA-dependent RNA polymerases (RdRp) and helicases. RNAs -2 contains six ORFs: capsid protein (CP), one readthrough protein, triple gene block proteins (TGB) that are required for cell-to-cell virus movement and the sixth 14 kDa ORF is a post-translation gene silencing suppressor. RNAs -3 is involved on disease symptoms and is essential for virus systemic movement. BSBMV RNA-3 can be trans-replicated, trans-encapsidated by the BNYVV helper strain (RNA-1 and -2) (Ratti et al., 2009). BNYVV RNA-4 encoded one 31 kDa protein and is essential for vector interactions and virus transmission by P. betae (Rahim et al., 2007). BNYVV RNA-5 encoded 26 kDa protein that improve virus infections and accumulation in the hosts. We are interest on BSBMV effect on Rhizomania studies using powerful tools as full-length infectious cDNA clones. B-type full-length infectious cDNA clones are available (Quillet et al., 1989) as well as A/P-type RNA-3, -4 and -5 from BNYVV (unpublished). A-type BNYVV full-length clones are also available, but RNA-1 cDNA clone still need to be modified. During the PhD program, we start production of BSBMV full-length cDNA clones and we investigate molecular interactions between plant and Benyviruses exploiting biological, epidemiological and molecular similarities/divergences between BSBMV and BNYVV. During my PhD researchrs we obtained full length infectious cDNA clones of BSBMV RNA-1 and -2 and we demonstrate that they transcripts are replicated and packaged in planta and able to substitute BNYVV RNA-1 or RNA-2 in a chimeric viral progeny (BSBMV RNA-1 + BNYVV RNA-2 or BNYVV RNA-1 + BSBMV RNA-2). During BSBMV full-length cDNA clones production, unexpected 1,730 nts long form of BSBMV RNA-4 has been detected from sugar beet roots grown on BSBMV infected soil. Sequence analysis of the new BSBMV RNA-4 form revealed high identity (~100%) with published version of BSBMV RNA-4 sequence (NC_003508) between nucleotides 1-608 and 1,138-1,730, however the new form shows 528 additionally nucleotides between positions 608-1,138 (FJ424610). Two putative ORFs has been identified, the first one (nucleotides 383 to 1,234), encode a protein with predicted mass of 32 kDa (p32) and the second one (nucleotides 885 to 1,244) express an expected product of 13 kDa (p13). As for BSBMV RNA-3 (Ratti et al., 2009), full-length BSBMV RNA-4 cDNA clone permitted to obtain infectious transcripts that BNYVV viral machinery (Stras12) is able to replicate and to encapsidate in planta. Moreover, we demonstrated that BSBMV RNA-4 can substitute BNYVV RNA-4 for an efficient transmission through the vector P. betae in Beta vulgaris plants, demonstrating a very high correlation between BNYVV and BSBMV. At the same time, using BNYVV helper strain, we studied BSBMV RNA-4’s protein expression in planta. We associated a local necrotic lesions phenotype to the p32 protein expression onto mechanically inoculated C. quinoa. Flag or GFP-tagged sequences of p32 and p13 have been expressed in viral context, using Rep3 replicons, based on BNYVV RNA-3. Western blot analyses of local lesions contents, using FLAG-specific antibody, revealed a high molecular weight protein, which suggest either a strong interaction of BSBMV RNA4’s protein with host protein(s) or post translational modifications. GFP-fusion sequences permitted the subcellular localization of BSBMV RNA4’s proteins. Moreover we demonstrated the absence of self-activation domains on p32 by yeast two hybrid system approaches. We also confirmed that p32 protein is essential for virus transmission by P. betae using BNYVV helper strain and BNYVV RNA-3 and we investigated its role by the use of different deleted forms of p32 protein. Serial mechanical inoculation of wild-type BSBMV on C. quinoa plants were performed every 7 days. Deleted form of BSBMV RNA-4 (1298 bp) appeared after 14 passages and its sequence analysis shows deletion of 433 nucleotides between positions 611 and 1044 of RNA-4 new form. We demonstrated that this deleted form can’t support transmission by P. betae using BNYVV helper strain and BNYVV RNA-3, moreover we confirmed our hypothesis that BSBMV RNA-4 described by Lee et al. (2001) is a deleted form. Interesting after 21 passages we identifed one chimeric form of BSBMV RNA-4 and BSBMV RNA-3 (1146 bp). Two putative ORFs has been identified on its sequence, the first one (nucleotides 383 to 562), encode a protein with predicted mass of 7 kDa (p7), corresponding to the N-terminal of p32 protein encoded by BSBMV RNA-4; the second one (nucleotides 562 to 789) express an expected product of 9 kDa (p9) corresponding to the C-terminal of p29 encoded by BSBMV RNA-3. Results obtained by our research in this topic opened new research lines that our laboratories will develop in a closely future. In particular BSBMV p32 and its mutated forms will be used to identify factors, as host or vector protein(s), involved in the virus transmission through P. betae. The new results could allow selection or production of sugar beet plants able to prevent virus transmission then able to reduce viral inoculum in the soil.

Messung der B s-Oszillation mit dem semileptonischen Zerfall B 0 s D - s (phi pi -) my + ny my mit dem D0-Detektor

Das Standardmodell (SM) der Teilchenphysik beschreibt sehr präzise die fundamentalen Bausteine und deren Wechselwirkungen (WW). Trotz des Erfolges gibt es noch offene Fragen, die vom SM nicht beantwortet werden können. Ein noch noch nicht abgeschlossener Test besteht aus der Messung der Stärke der schwachen Kopplung zwischen Quarks. Neutrale B- bzw. $bar{B}$-Mesonen können sich innerhalb ihrer Lebensdauer über einen Prozeß der schwachen WW in ihr Antiteilchen transformieren. Durch die Messung der Bs-Oszillation kann die Kopplung Vtd zwischen den Quarksorten Top (t) und Down (d) bestimmt werden. Alle bis Ende 2005 durchgeführten Experimente lieferten lediglich eine untere Grenze für die Oszillationsfrequenz von ms>14,4ps-1. Die vorliegenden Arbeit beschreibt die Messung der Bs-Oszillationsfrequenz ms mit dem semileptonischen Kanal BsD(-)+. Die verwendeten Daten stammen aus Proton-Antiproton-Kollisionen, die im Zeitraum von April 2002 bis März 2006 mit dem DØ-Detektor am Tevatron-Beschleuniger des Fermi National Accelerator Laboratory bei einer Schwerpunktsenergie von $sqrt{s}$=1,96TeV aufgezeichnet wurden. Die verwendeten Datensätze entsprechen einer integrierten Luminosität von 1,3fb-1 (620 millionen Ereignisse). Für diese Oszillationsmessung wurde der Quarkinhalt des Bs-Mesons zur Zeit der Produktion sowie des Zerfalls bestimmt und die Zerfallszeit wurde gemessen. Nach der Rekonstruktion und Selektion der Signalereignisse legt die Ladung des Myons den Quarkinhalt des Bs-Mesons zur Zeit des Zerfalls fest. Zusätzlich wurde der Quarkinhalt des Bs-Mesons zur Zeit der Produktion markiert. b-Quarks werden in $pbar{p}$-Kollisionen paarweise produziert. Die Zerfallsprodukte des zweiten b-Hadrons legen den Quarkinhalt des Bs-Mesons zur Zeit der Produktion fest. Bei einer Sensitivität von msenss=14,5ps-1 wurde eine untere Grenze für die Oszillationsfrequenz ms>15,5ps-1 bestimmt. Die Maximum-Likelihood-Methode lieferte eine Oszillationsfrequenz ms>(20+2,5-3,0(stat+syst)0,8(syst,k))ps-1 bei einem Vertrauensniveau von 90%. Der nicht nachgewiesene Neutrinoimpuls führt zu dem systematischen Fehler (sys,k). Dieses Resultat ergibt zusammen mit der entsprechenden Oszillation des Bd-Mesons eine signifikante Messung der Kopplung Vtd, in Übereinstimmung mit weiteren Experimenten über die schwachen Quarkkopplungen.

Multicelled Behaviour in E. coli: Design and experimental characterization of an engineered library of hybrid promoters.

Synthetic biology has recently had a great development, many papers have been published and many applications have been presented, spanning from the production of biopharmacheuticals to the synthesis of bioenergetic substrates or industrial catalysts. But, despite these advances, most of the applications are quite simple and don’t fully exploit the potential of this discipline. This limitation in complexity has many causes, like the incomplete characterization of some components, or the intrinsic variability of the biological systems, but one of the most important reasons is the incapability of the cell to sustain the additional metabolic burden introduced by a complex circuit. The objective of the project, of which this work is part, is trying to solve this problem through the engineering of a multicellular behaviour in prokaryotic cells. This system will introduce a cooperative behaviour that will allow to implement complex functionalities, that can’t be obtained with a single cell. In particular the goal is to implement the Leader Election, this procedure has been firstly devised in the field of distributed computing, to identify the process that allow to identify a single process as organizer and coordinator of a series of tasks assigned to the whole population. The election of the Leader greatly simplifies the computation providing a centralized control. Further- more this system may even be useful to evolutionary studies that aims to explain how complex organisms evolved from unicellular systems. The work presented here describes, in particular, the design and the experimental characterization of a component of the circuit that solves the Leader Election problem. This module, composed of an hybrid promoter and a gene, is activated in the non-leader cells after receiving the signal that a leader is present in the colony. The most important element, in this case, is the hybrid promoter, it has been realized in different versions, applying the heuristic rules stated in [22], and their activity has been experimentally tested. The objective of the experimental characterization was to test the response of the genetic circuit to the introduction, in the cellular environment, of particular molecules, inducers, that can be considered inputs of the system. The desired behaviour is similar to the one of a logic AND gate in which the exit, represented by the luminous signal produced by a fluorescent protein, is one only in presence of both inducers. The robustness and the stability of this behaviour have been tested by changing the concentration of the input signals and building dose response curves. From these data it is possible to conclude that the analysed constructs have an AND-like behaviour over a wide range of inducers’ concentrations, even if it is possible to identify many differences in the expression profiles of the different constructs. This variability accounts for the fact that the input and the output signals are continuous, and so their binary representation isn’t able to capture the complexity of the behaviour. The module of the circuit that has been considered in this analysis has a fundamental role in the realization of the intercellular communication system that is necessary for the cooperative behaviour to take place. For this reason, the second phase of the characterization has been focused on the analysis of the signal transmission. In particular, the interaction between this element and the one that is responsible for emitting the chemical signal has been tested. The desired behaviour is still similar to a logic AND, since, even in this case, the exit signal is determined by the hybrid promoter activity. The experimental results have demonstrated that the systems behave correctly, even if there is still a substantial variability between them. The dose response curves highlighted that stricter constrains on the inducers concentrations need to be imposed in order to obtain a clear separation between the two levels of expression. In the conclusive chapter the DNA sequences of the hybrid promoters are analysed, trying to identify the regulatory elements that are most important for the determination of the gene expression. Given the available data it wasn’t possible to draw definitive conclusions. In the end, few considerations on promoter engineering and complex circuits realization are presented. This section aims to briefly recall some of the problems outlined in the introduction and provide a few possible solutions.

I materiali dell'assenza nella poesia della fine secolo portoghese

Il presente studio ha come obiettivo quello di chiarire le dinamiche culturali iscritte nella fine secolo portoghese a partire dall’analisi di alcune opere letterarie -in particolar modo poetiche - tra cui spicca il Só di António Nobre. L’Ultimatum inglese del 1890 mandando in frantumi il progetto imperiale in Africa, scatena un conflitto che si manifesta non solo a livello di un confronto con l’Altro, ma soprattutto, per le sue implicazioni simboliche, nei termini di un confronto interno proprio con l’immaginario nazionale. L’Ultimatum mette in crisi l’iperidentità descritta da Eduardo Lourenço come il frutto di una storia marcata da una deriva atlantica rispetto al resto d’Europa ed elaborata durante secoli di letteratura come il volto più autentico del Portogallo. Contemporaneamente segna inesorabilmente la distanza da quell’immaginario europeo e moderno che in stretto legame con il progetto imperiale ne costituiva le fondamenta. La poesia dell’epoca segue il paradigma apocalittico che associa al pianto e all’invettiva gli elementi di un’aspettativa messianica di riscatto: alla rabbia segue l’invito di riporre l’attenzione nelle glorie di un tempo in modo da rafforzare il Portogallo decaduto. La rivisitazione in chiave rigeneratrice del passato e dello spazio nazionale è una costante della letterautra neoromantica, l’opera di Antonio Nobre tuttavia non può essere affrontata secondo questa lettura: non si tratta qui di nessun recupero dell’età dell’oro, al contrario, la modernità dell’autore sta nel dichiarare l’impraticabilità di un immaginario che più che perduto non è mai esistito e si rivela dunque nella sua natura di feticcio.

Pretrattamenti termo-meccanici ed enzimatici su scarti dell'industria enologica per la produzione di Biogas

A fundamental assumption for by-product from winery industy waste-management is their economic and commercial increase in value. High energetic value recovery from winery industry is an attractive economic solution to stimulate new sustainable process. Approach of this work is based about physic and biological treatment with grape stalks and grape marc to increase polysaccharides components of cell wall and energetic availability of this by-products. Grape stalks for example have a high percentage of lignin and cellulose and can’t be used, whitout pretreatment, for an anaerobic digestion process. Our findings show enzymatic and thermo-mechanical pre-treatments in combined application for optimise hydrolytic mechanism on winemaking wastes which represents 0,9 milion ton/year in Italy and on straw, cereal by-products with high lignin content. A screening of specifically industrial enzymatic complex for the hydrolysis lignocellulosic biomass were tested using the principal polysaccharides component of the vegetal cells. Combined thermo-mechanical and enzymatic pretreatment improve substrates conversion in batch test fermentation experiment. The conservation of the grape stalks, at temperature above 0°C, allow the growth of spontaneus fermentation that reduce their polysaccharides content so had investigated anarobic condition of conservation. The other objective of this study was to investigate the capability of a proprietary strain of L.buchneri LN 40177 to enhance the accessibility of fermentable forage constituents during the anaerobic conservation process by releasing the enzyme ferulate esterase. The time sequence study by batch tests showed that the L. buchneri LN-40177 inoculated grape stalk substrate was more readily available in the fermenter. In batch tests with grape stalk, after mechanical treatment, the L. buchneri LN41077 treated substrate yielded on average 70% more biogas per kg/DM. Thermo-mechanical, enzymatic and biological treatment with L. buchneri LN-40177 can increase the biogas production from low fermented biomasses and the consequent their useful in anaerobic biodigesters for agro-bioenergy production.

I limiti al diritto di proprietà derivanti dagli strumenti di pianificazione urbanistica. I vincoli urbanistici.

Nella prima parte viene ricostruito il concetto di vincolo espropriativo alla luce dell’elaborazione della giurisprudenza della Corte costituzionale e della Corte EDU, giungendo alla conclusione che rientrano in tale concetto le limitazioni al diritto di proprietà che: - derivano da scelte discrezionali dell’Amministrazione non correlate alle caratteristiche oggettive del bene; - superano la normale tollerabilità nel senso che impediscono al proprietario la prosecuzione dell’uso in essere o incidono sul valore di mercato del bene in modo sproporzionato rispetto alle oggettive caratteristiche del bene e all’interesse pubblico perseguito. Ragione di fondo della teoria dei vincoli è censurare l’eccessiva discrezionalità del potere urbanistico, imponendo una maggiore obiettività e controllabilità delle scelte urbanistiche. Dalla teoria dei vincoli consegue altresì che nell’esercizio del potere urbanistico l’Amministrazione, pur potendo differenziare il territorio, deve perseguire l’obiettivo del riequilibrio economico degli interessi incisi dalle sue determinazioni. L’obbligo della corresponsione dell’indennizzo costituisce la prima forma di perequazione urbanistica. Nel terzo e nel quarto capitolo viene analizzata la giurisprudenza civile e amministrativa in tema di vincoli urbanistici, rilevandone la non corrispondenza rispetto all’elaborazione della Corte costituzionale e l’incongruità dei risultati applicativi. Si evidenzia in particolare la necessità del superamento del criterio basato sulla distinzione zonizzazioni-localizzazioni e di considerare conformative unicamente quelle destinazioni realizzabili ad iniziativa privata che in concreto consentano al proprietario di conseguire un’utilità economica proporzionata al valore di mercato del bene. Nel quinto capitolo viene analizzato il rapporto tra teoria dei vincoli e perequazione urbanistica, individuandosi il discrimine tra i due diversi istituti non solo nel consenso, ma anche nella proporzionalità delle reciproche prestazioni negoziali. Attraverso la perequazione non può essere attribuito al proprietario un’utilità inferiore a quella che gli deriverebbe dall’indennità di esproprio.

Nanomechanical and phononic properties of structured soft materials

Significant interest in nanotechnology, is stimulated by the fact that materials exhibit qualitative changes of properties when their dimensions approach ”finite-sizes”. Quantization of electronic, optical and acoustic energies at the nanoscale provides novel functions, with interests spanning from electronics and photonics to biology. The present dissertation involves the application of Brillouin light scattering (BLS) to quantify and utilize material displacementsrnfor probing phononics and elastic properties of structured systems with dimensions comparable to the wavelength of visible light. The interplay of wave propagation with materials exhibiting spatial inhomogeneities at sub-micron length scales provides information not only about elastic properties but also about structural organization at those length scales. In addition the vector nature of q allows, for addressing the directional dependence of thermomechanical properties. To meet this goal, one-dimensional confined nanostructures and a biological system possessing high hierarchical organization were investigated. These applications extend the capabilities of BLS from a characterization tool for thin films to a method for unravelingrnintriguing phononic properties in more complex systems.

Der enzymatische und anti-oxidative Mechanismus des anti-atherogenen Enzyms Paraoxonase-2

Das humane Enzym PON2 ist in eine Vielzahl pathophysiologischer Prozesse involviert und ist durch zwei Funktionen gekennzeichnet - eine enzymatische Laktonase-Aktivität und eine anti-oxidative Aktivität. Durch die Laktonase-Aktivität hydrolysiert PON2 vorwiegend das bakterielle Signalmolekül 3oxoC12. PON2 ist als Bestandteil des angeborenen Immunsystems anzusehen und trägt wahrscheinlich zur Immunabwehr gegen Infektionen mit den human-pathogenen Pseudomonas aeruginosa Bakterien bei. Durch die anti-oxidative Aktivität vermindert PON2 oxidative Schäden und verringert redox-abhängige pro-apoptotische Stimulation. Diese einzigartige Funktion von PON2 ist jedoch ambivalent zu betrachten, da hohe PON2-Spiegel zwar Arteriosklerose reduzieren können, aber im Verdacht stehen Tumorzellen zu stabilisieren.rnIn dieser Arbeit wurden die noch unbekannten Mechanismen und der Zusammenhang der enzymatischen und der anti-oxidativen Aktivität analysiert. In diesem Rahmen wurde gezeigt, dass PON2 spezifisch die Superoxidfreisetzung an Komplex I und III der Atmungskette in der inneren Mitochondrienmembran reduzieren kann. PON2 veränderte dabei weder die Aktivitäten der Superoxiddismutasen noch die Cytochrom C-Expression. Weiterhin konnte in dieser Arbeit erstmals gezeigt werden, dass PON2 O2- nicht direkt abbaut, sondern vielmehr dessen Bildung verhindert. Diese Erkenntnisse implizieren, dass PON2 die anti-oxidative Aktivität über eine Beeinflussung des Quinon-Pools vermittelt. Anhand von verschiedenen Punktmutationen konnte gezeigt werden, dass die Histidinreste-114 und -133 für die Laktonase-Aktivität essentiell sind. Weiterhin wurden die Glykosylierungsstellen von PON2 identifiziert und gezeigt, dass die Glykosylierung, nicht aber der natürliche Polymorphismus Ser/Cys311 für die Laktonase-Aktivität von Bedeutung ist. Von besonderer Bedeutung ist, dass keine dieser Mutationen die anti-oxidative Aktivität beeinflusste, wodurch erstmals die Unabhängigkeit der beiden Funktionen von PON2 gezeigt werden konnte. rnEs war bekannt, dass PON2 gegen intrinsische und ER-Stress-induzierte Apoptose schützt. Die Spezifität der anti-oxidativen / anti-apoptotischen Wirkung wurde hier an einem weiteren pathophysiologischen Modell untersucht. 7-Ketocholesterol (7-KC) ist der Hauptbestandteil des pro-arteriosklerotischen oxLDL und verursacht in Zellen des Gefäßsystems ER-Stress, oxidativen Stress und Apoptose. Unerwarteterweise konnte PON2 Endothelzellen nicht gegen den 7-KC-induzierten Zelltod schützen. Mehrere unabhängige experimentelle Ansätze belegen, dass 7-KC in Endothelzellen im Gegensatz zu Gefäßmuskelzellen den Zelltod über Autophagie und nicht über ER-Stress oder intrinsische Apoptose bewirkt. Weiterhin führt 7-KC, wie auch 3oxoC12 und Thapsigargin zu einem Abbau der PON2-mRNA, die über die 5’UTR der PON2-mRNA vermittelt wird. Diese Arbeit vermittelt detaillierte mechanistische Einsichten in die Funktionen von PON2, die für ihre Rolle bei Arteriosklerose, in der körpereigenen Immunabwehr und bei Krebs entscheidend sind.rn

La valutazione della ricerca scientifica: Uno studio empirico nelle Scienze umane

Nel corso degli ultimi anni si è assistito ad un ampio dibattito sull’uso della valutazione della ricerca nelle università e nelle strutture di ricerca. Nell’ambito di tale dibattito, nella presente tesi, vengono analizzate le più importanti metodologie per la valutazione della ricerca presenti a livello internazionale, i principali strumenti qualitativi di valutazione della ricerca (in particolare la peer review), gli strumenti quantitativi, quali la bibliometria, e le caratteristiche dei più importanti archivi bibliografici citazionali (es. Scopus, Web of Science), approfondendo i principali indicatori citazionali utilizzati nelle scienze umane e sociali (es. Indice H). Inoltre la tesi affronta il tema dell’impatto socio-economico della ricerca e le principali criticità di questo innovativo strumento, attraverso uno studio di caso realizzato nel Regno Unito. Una successiva analisi empirica riguarda le principali liste di riviste realizzate a livello internazionale e nazionale, nel settore scientifico di Storia e Filosofia della scienza. I risultati degli studi mostrano che le liste internazionali di riviste possono rappresentare, un punto di partenza a cui devono necessariamente essere affiancati altri strumenti di valutazione (peer review, analisi citazionali, etc); mentre le liste nazionali rischiano, invece, di essere uno strumento poco utile ed in alcuni casi inadeguato al fine di una corretta valutazione della ricerca, a causa della scarsa internazionalizzazione dei repertori e dei giudizi generalmente troppo elevati attribuiti alle riviste. Un ulteriore risultato raggiunto nella presente tesi riguarda la valutazione della ricerca nelle diverse discipline scientifiche: nelle Scienze umane e sociali risulta esserci uno scarso grado di presenza di pubblicazioni scientifiche nei principali archivi bibliografici e citazionali internazionali. Questa situazione limita fortemente l’attendibilità delle analisi statistiche basate su indici e indicatori quantitativi, per valutare la produttività scientifica di un ricercatore, oppure di una istituzione di ricerca.

"All'opera ha fatto seguito il ballo": Danza e stampa nell'Italia fascista

Basata sul reperimento di un’ampia mole di testi giornalistici (come cronache, interviste, elzeviri e articoli di “Terza”) dedicati alle pratiche coreiche e pubblicati in Italia nel corso del ventennio fascista, la tesi ricostruisce i lineamenti di quello che, seppure ancora embrionale e certo non specialistico, si può comunque ritenere una sorta di “pensiero italiano” sulla danza del Primo Novecento. A partire dalla ricognizione sistematica di numerose testate quotidiane e periodiche e, pertanto, dalla costruzione di un nutrito corpus di fonti primarie, si è proceduto all’analisi dei testi reperiti attraverso un approccio metodologico che, fondamentalmente storiografico, accoglie tuttavia alcuni rudimenti interpretativi elaborati in ambito semiotico (con particolare riferimento alle teorizzazioni di Jurij Lotman e Umberto Eco), il tutto al fine di cogliere, pur nell’estrema varietà formale e contenutistica offerta dal materiale documentario, alcune dinamiche culturali di fondo attraverso le quali disegnare, da un lato, il panorama delle tipologie di danza effettivamente praticate sulle scene italiane del Ventennio,e, dall’altro, quello dell’insieme di pensieri, opinioni e gusti orbitanti attorno ad esse Ne è scaturita una trattazione fondamentalmente tripartita in cui, dopo la messa in campo delle questioni metodologiche, si passa dapprima attraverso l’indagine dei tre principali generi di danza che, nella stampa del periodo fascista, si ritenevano caratteristici della scena coreica internazionale – qui definiti nei termini di “ballo teatrale”, “ballo russo” e “danze libere” – e, successivamente, si presenta un approfondimento su tre singolari figure di intellettuali che, ognuno con un’attitudine estremamente personale, hanno dedicato alla danza un’attenzione speciale: Anton Giulio Bragaglia, Paolo Fabbri e Marco Ramperti. Un’ampia antologia critica completa il lavoro ripercorrendone gli snodi principali.

Search for high mass resonances decaying into electron-positron pairs in proton-proton collisions at sqrt(s) = 7 TeV with the ATLAS detector

The Standard Model of particle physics was developed to describe the fundamental particles, which form matter, and their interactions via the strong, electromagnetic and weak force. Although most measurements are described with high accuracy, some observations indicate that the Standard Model is incomplete. Numerous extensions were developed to solve these limitations. Several of these extensions predict heavy resonances, so-called Z' bosons, that can decay into an electron positron pair. The particle accelerator Large Hadron Collider (LHC) at CERN in Switzerland was built to collide protons at unprecedented center-of-mass energies, namely 7 TeV in 2011. With the data set recorded in 2011 by the ATLAS detector, a large multi-purpose detector located at the LHC, the electron positron pair mass spectrum was measured up to high masses in the TeV range. The properties of electrons and the probability that other particles are mis-identified as electrons were studied in detail. Using the obtained information, a sophisticated Standard Model expectation was derived with data-driven methods and Monte Carlo simulations. In the comparison of the measurement with the expectation, no significant deviations from the Standard Model expectations were observed. Therefore exclusion limits for several Standard Model extensions were calculated. For example, Sequential Standard Model (SSM) Z' bosons with masses below 2.10 TeV were excluded with 95% Confidence Level (C.L.).

Chemical interaction between ocean and atmosphere

The exchange of chemical constituents between ocean and atmosphere provides potentially important feedback mechanisms in the climate system. The aim of this study is to develop and evaluate a chemically coupled global atmosphere-ocean model. For this, an atmosphere-ocean general circulation model with atmospheric chemistry has been expanded to include oceanic biogeochemistry and the process of air-sea gas exchange. The calculation of seawater concentrations in the oceanic biogeochemistry submodel has been expanded from DMS, CO₂

Ringier (Familie)

Famille de pasteurs, politiciens et entrepreneurs de Zofingue, attestée pour la première fois en 1527, lorsque leur aïeul Jean, tonnelier originaire de Nîmes, obtint la bourgeoisie de Zofingue. Michael (1521-1605), avoyer, l'un de ses cinq fils, est l'ancêtre de la branche des imprimeurs et éditeurs. Après lui, de nombreux R. consolidèrent durablement l'influence de la famille. A partir du XVIIIe s., divers membres firent des carrières politiques, tels Samuel (1706-1786), avoyer, et Rudolf Friedrich (1805-1886), président de la ville. Les R. furent aussi très liés à l'Eglise. Le fils de Michael, Moritz (1557-1615), fut pasteur et doyen à Zofingue. Jusqu'au XIXe s., la famille compta une trentaine d'ecclésiastiques, essentiellement des pasteurs officiant sur le territoire bernois, tels Johann Heinrich ( -> 3) et Michael ( -> 8). Les conseillers Beat (1712-1778) et Niklaus (1734-1766) furent les premiers R. actifs dans la production protoindustrielle de drap. D'autres négociants suivirent jusqu'au milieu du XIXe s. L'architecte Niklaus Emanuel (1744-1815) construisit l'hôtel de ville de Zofingue (1792-1795) de style baroque tardif. Johann Rudolf ( -> 4) se distingua sous la République helvétique (1798-1803). Samuel (1767-1826), conseiller municipal de Zofingue, créa les armoiries du canton d'Argovie en 1803. Les R. s'affirmèrent sur le plan cantonal avec Karl Ludwig ( -> 6), chancelier, et Arnold ( -> 1), conseiller d'Etat et plusieurs fois landamman, et sur le plan fédéral avec Johann Rudolf ( -> 5), conseiller national, et Gottlieb ( -> 2), conseiller aux Etats et chancelier de la Confédération. Johann Rudolf (1803-1874) fonda, en 1833, l'imprimerie Ringier à Zofingue, reprise par son fils Franz Emil (1837-1898). A partir de 1898, Paul August ( -> 9), représentant de la troisième génération d'imprimeurs, agrandit l'entreprise dont il fit la principale imprimerie et maison d'édition de Suisse. Cette expansion se poursuivit après 1960 sous son fils Hans (1906-2003). Avec les fils de celui-ci, Christoph (naissance1941, dans la firme jusqu'en 1991) et Michael (naissance1949), Ringier devint, à partir de 1985, une entreprise multinationale et multimédia. Bibliographie – F. Schoder, Ortsbürger von Zofingen, 1962 – P. Meier, T. Häussler, Zwischen Masse, Markt und Macht, 2009

Magnetic Flip Flops for Space Applications

The radiation environment of space presents a significant threat to the reliability of nonvolatile memory technologies. Ionizing radiation disturbs the charge stored on floating gates, and cosmic rays can permanently damage thin oxides. A new memory technology based on the magnetic tunneling junction (MTJ) appears to offer superior resistance to radiation effects and virtually unlimited write endurance. A magnetic flip flop has a number of potential applications, such as the configuration memory in field-programmable logic devices. However, using MTJs in a flip flop requires radically different circuitry for storing and retrieving data. New techniques are needed to insure that magnetic flip flops are reliable in the radiation environment of space. We propose a new radiation-tolerant magnetic flip flop that uses the inherent resistance of the MTJ to increase its immunity to single event upset and employs a robust “Pac-man” magnetic element.