766 research outputs found

    Numerical analysis of nonlinear pneumatic structures

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    Numerical analysis of nonlinear behavior of inflatable structure

    Jameson\u27s Story: A Tale of the Human Condition Through Fiction

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    A work of fiction focusing on two characters living in the same world, but under much different circumstances. One must try and find out who he is while the other is attempting to uphold his way of life in a society threatening to take it away. The story delves into the ideas of a somewhat dystopian world; one in which our society could ultimately mirror in the near future. The work is unfinished, which is explained in the reflection paper at the beginning of the document

    Strukturelle Charakterisierung von Flavin-abhÀngigen Monooxygenasen aus Zonocerus variegatus und der humanen mitochondrialen Amidoxim-reduzierenden Komponente (mARC): Enzyme, welche an der Biotransformation beteiligt sind

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    Organisms are permanently exposed to foreign and harmful substances. These xenobiotics have to undergo metabolic processes in order to be eliminated from the organism. This process is called biotransformation. Therefore, it is of significant importance to increase our knowledge about enzymes involved in biotransformation processes and detoxification pathways, especially about their three-dimensional structures. This cumulative thesis focuses on structure determination of two biotransformation enzymes, the flavin-dependent monooxygenase from Zonocerus variegatus (ZvFMO) and the human mitochondrial amidoxime reducing component (mARC). FMOs are able to oxygenate heteroatom-containing substances, whereas the mARC enzyme system is very effectively reducing a broad range of heteroatom-hydroxylated xenobiotics. Different high-resolution ZvFMO structures provided insight into the coordination of cofactors and related conformational rearrangements of the enzyme. Furthermore, a hitherto unknown dimeric arrangement of subunits was observed for ZvFMO isoforms. To further investigate differences in the catalytic activity of ZvFMOs, a variety of ZvFMOa variants were generated. Thereby, significant impacts on enzyme activity were observed even for single exchanges within the substrate entry site. The elucidated mARC crystal structure was the first MOSC protein that clearly showed the coordination of its molybdenum cofactor and exhibited a topology, which contradicts in silico predictions of structural domains currently used for online databases. The large substrate spectrum could be correlated to a surface-exposed active site. Paralogue-specific amino acid residues were identified, which allow for the secure discrimination between mARC1 and mARC2 enzymes. Moreover, structural features indicate that mARC enzymes represent an evolutionary link between the two molybdoenzyme superfamilies of sulfite oxidases and xanthine oxidases.Organismen sind stĂ€ndig verschiedensten körperfremden und oft auch schĂ€dlichen Substanzen ausgesetzt. Solche Xenobiotika mĂŒssen metabolische Prozesse durchlaufen, um vom Organismus ausgeschieden werden zu können. Dieser Prozess wird als Biotransformation bezeichnet. Es ist daher wichtig, unser Wissen ĂŒber Biotransformationsenzyme und Detoxifizierungswege zu vertiefen, insbesondere ĂŒber deren dreidimensionale Strukturen. Diese kumulative Dissertation fokussiert sich auf die StrukturaufklĂ€rung zweier Biotransformationsenzyme, der flavinabhĂ€ngigen Monooxygenase aus Zonocerus variegatus (ZvFMO) und der menschlichen mitochondrialen Amidoxim-reduzierenden Komponente (mARC). FMOs katalysieren die Hydroxylierung von Heteroatom-haltigen Verbindungen, wĂ€hrend mARC-Enzyme die Reduktion Heteroatom-hydroxylierter Xenobiotika ausĂŒben. Verschiedene ZvFMO-Strukturen lieferten Erkenntnisse in die Koordination gebundener Kofaktoren und einhergehender KonformationsĂ€nderungen. Weiterhin wurde eine bisher unbekannte Dimerformation dieses Enzyms beobachtet. Um tiefere Einblicke in die katalytische AktivitĂ€t von ZvFMOs zu erhalten, wurden verschiedene Enzymvarianten untersucht. Dabei wurde festgestellt, dass vor allem im Substrateingangsbereich schon Einzelaustausche von AminosĂ€uren einen signifikanten Einfluss auf die EnzymaktivitĂ€t haben. Die gelöste mARC-Kristallstruktur war die erste MOSC-Proteinstruktur, die Einsicht in die Koordination des MolybdĂ€n-Kofaktors gab und eine Topologie aufwies, die bisherigen in silico -Vorhersagen widersprach. Das breite Substratspektrum dieses Enzyms konnte dem oberflĂ€chenexponierten aktiven Zentrum zugeschrieben werden. Weiterhin wurden Paralog-spezifische Seitenketten identifiziert, die eine sichere Unterscheidung zwischen mARC1 und mARC2-Proteinen erlauben. Zudem weisen einige strukturelle Merkmale darauf hin, dass mARC-Enzyme ein evolutionĂ€res Bindeglied zwischen zwei Molybdo-Enzymfamilien darstellen, den Sulfitoxidasen und den Xanthinoxidasen

    Structural complexity and social cohesion in gregarious animals: from conflict to cooperation

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    A social lifestyle is abundant in nature. The social interactions between animals form the basis for complex, highly dynamic structures and may determine group-level processes such as group cohesion. Social behavior is influenced by local environmental conditions, varies over time and has diverse, context-dependent functions. In my thesis I have investigated the spatial, temporal, contextual and structural aspects of social complexity in three model species. First, I explored effects of increasing population density on aggression and contact behavior within and between sexes in water striders (Aquarius paludum). The current, local density regime affected male mating behavior as males sought more frequent contacts to available mates in denser groups. Frequencies of male-to-male conflicts and the duration of male harassment behavior were unaffected by local density, however. Overall, males in high-density groups may experience intense scramble competition over reproductively active females. Current environmental conditions crucially affect the species’ mating system; yet, also the previously experienced environment should be considered. Second, in a flock of free-flying jackdaws (Corvus monedula) I studied seasonal variation in patterns of positive interactions between pair mates and linked the pair bond to group level dynamics. Jackdaw groups are dynamic social units into which mutualistic pair bonds are embedded. Both sexes invested into the bond with different social behaviors and at different times of the year; yet, these are likely the proximate mechanisms employed by males and females to perpetuate a successful bond and secure annual reproductive output. Third, I determined the factors regulating dyadic and polyadic conflict resolution in jackdaws and investigated patterns of social support between the sexes. Conflict aggressors receiving active, aggressive support had high chances of winning encounters and were probably at low risk of receiving counter-aggression. Females cooperated very closely with their mates during conflicts. In doing so, they likely secured male investment into offspring provisioning and care, whereas males might seek conflicts strategically to maintain or improve their social status. Conflicts and interventions hence constitute a vital aspect of jackdaws’ social system. Finally, I used a captive house sparrow (Passer domesticus) flock to determine the destabilizing effects of perturbations of group composition on social structure and behavior. The group’s dominance hierarchy destabilized after a second perturbation and did not re-establish itself quickly. Yet, irrespective of experimental treatment, birds fed regularly and interacted based on their initially determined dominance rank. Only females joined, rather than supplanted, feeding conspecifics more frequently following the second perturbation treatment, thereby shifting to a non-aggressive social foraging strategy. Thus, sparrows in this study might have tolerated and compensated for structural instability to some degree. In conclusion, environmental factors, like population density, may alter the social structure of animal groups, creating a potential for both conflict and cooperation. Cooperation is constantly threatened by the selfish interests of individuals, leading to intra-group conflicts, and group members must resolve these conflicts efficiently. Enduring social stability is likely required for maintaining higher-order structures, such as social alliances or linear hierarchies, but relatively simple mechanisms for mitigating conflicts may exist in fluctuating fission-fusion groups.Sosiaalinen elĂ€mĂ€ntapa on luonnossa yleinen. ElĂ€inyksilöiden vĂ€liset sosiaaliset vuorovaikutukset ovat perusta monimutkaisille ja hyvin dynaamisille sosiaalisille rakenteille. Sosiaalinen kĂ€yttĂ€ytyminen riippuu vallitsevista ympĂ€ristön olosuhteista. Esimerkiksi sosiaalista yhteenkuuluvuutta edistĂ€vĂ€ kĂ€yttĂ€ytyminen vahvistaa sosiaalisia siteitĂ€, kun taas vihamielinen kĂ€yttĂ€ytyminen liittyy ryhmĂ€nsisĂ€isiin ja ryhmien vĂ€lisiin ristiriitoihin. NĂ€mĂ€ sosiaalisen kĂ€yttĂ€ytymisen kaksi ÀÀripÀÀtĂ€ ovat sosiaalisten rakenteiden peruspilareita, ja vaikuttavat yhdessĂ€ ryhmĂ€n toimintaan ja tiiveyteen. Sosiaaliset jĂ€rjestelmĂ€t vaihtelevat tilassa ja ajallisesti sekĂ€ ovat rakenteellisesti hyvin monimutkaisia. VĂ€itöskirjatyössĂ€ni olen tutkinut kolmella mallilajilla nĂ€itĂ€ sosiaalisen kompleksisuuden eri ilmenemismuotoja. Tutkin vesimittareilla (Aquarius paludum) populaatiotiheyden kasvun vaikutuksia sukupuolten sisĂ€iseen ja sukupuolten vĂ€liseen aggressioon ja pariutumiskĂ€yttĂ€ytymiseen. Populaatiotiheys vaikutti koiraiden pariutumiskĂ€yttĂ€ytymiseen niiden etsiessĂ€ saatavilla olevia kumppaneita. Paikallinen populaatiotiheys ei kuitenkaan vaikuttanut koiraiden vĂ€listen hĂ€irintĂ€kĂ€yttĂ€ytymisten lukumÀÀrÀÀn tai kestoon. Kaiken kaikkiaan koiraat saattavat kuitenkin tiheissĂ€ populaatioissa kokea voimakasta kilpailua aktiivisesti lisÀÀntyvistĂ€ naaraista. SekĂ€ vallitsevat ettĂ€ aiemmissa elĂ€mĂ€nvaiheissa koetut ympĂ€ristön olosuhteet vaikuttavat merkittĂ€vĂ€sti pariutumisjĂ€rjestelmÀÀn. Tutkin vapaana elĂ€vĂ€ssĂ€ naakkaparvessa (Corvus monedula) parinsisĂ€isten positiivisten vuorovaikutusten esiintyvyyttĂ€ eri vuodenaikoina sekĂ€ parisiteen vaikutusta parven toimintaan. Naakkaparvessa kummallakin sukupuolella parisidettĂ€ yllĂ€pitĂ€vĂ€t sosiaalisen kĂ€yttĂ€ytymisen muodot vaihtelivat vuodenajoittain. KyseessĂ€ lienevĂ€t proksimaattiset mekanismit, joita naaraat ja koiraat kĂ€yttĂ€vĂ€t varmistaakseen lisÀÀntymisensĂ€ onnistumisen vuosittain. Tutkin naakoilla myös kahden- ja monenkeskisiin konfliktinratkaisutapoihin vaikuttavia tekijöitĂ€ sekĂ€ niitĂ€ tapoja, joilla naakkapuolisot tukivat toisiaan ristiriitaisissa tilanteissa. Ristiriitatilanteissa hyökkÀÀvĂ€t osapuolet, jotka saivat muilta yksilöiltĂ€ aktiivista sosiaalista tukea, voittivat useimmin ja yleensĂ€ vĂ€lttyivĂ€t uusilta ristiriidoilta. Naaraat tukivat puolisoitaan ristiriitatilanteissa. TĂ€mĂ€ todennĂ€köisesti auttoi niitĂ€ varmistamaan koiraan osallistumisen jĂ€lkelĂ€isten ruokintaan ja hoitoon. Koiraat puolestaan hakeutuivat ristiriitatilanteisiin joko yllĂ€pitÀÀkseen tai parantaakseen omaa sosiaalista asemaansa. Ristiriitatilanteet ja niiden ratkaiseminen ovat tĂ€rkeĂ€ osa naakkojen sosiaalista jĂ€rjestelmÀÀ. Lopuksi tutkin tarhaoloissa pidetyillĂ€ varpusilla (Passer domesticus) parvirakenteen hajoamisen ja yhdistymisen vaikutusta sen sosiaaliseen rakenteeseen ja yksilöiden kĂ€yttĂ€ytymiseen. Parven valtajĂ€rjestys hajosi hĂ€irinnĂ€n jĂ€lkeen, eikĂ€ enÀÀ palautunut ennalleen. TĂ€stĂ€ huolimatta parven jĂ€senet ruokailivat sÀÀnnöllisesti, ja yksilöiden vĂ€liset suhteet noudattivat kokeen alussa vakiintunutta valtajĂ€rjestystĂ€. Parven hĂ€irintĂ€kerran jĂ€lkeen naaraat olivat ruokaillessaan vĂ€hemmĂ€n aggressiivisia. Tutkimukseni siis osoitti, ettĂ€ varpuset pystyvĂ€t palauttamaan valtajĂ€rjestelmĂ€n sen hajottua ja uudelleen yhdistyessĂ€. Yhteenvetona voidaan todeta ympĂ€ristötekijöiden kuten populaatiotiheyden voivan vaikuttaa elĂ€inryhmien sosiaaliseen rakenteeseen, mikĂ€ luo paitsi ristiriitatilanteita myös yhteistyötĂ€. Yksilöiden itsekkÀÀt vaikuttimet vaarantavat jatkuvasti yhteistyön mahdollisuuksia, mikĂ€ johtaa ryhmĂ€nsisĂ€isiin ristiriitoihin, joita ryhmĂ€n jĂ€senten tulisi voida tehokkaasti ratkoa. Sosiaaliset rakenteet kuten yksilöiden yhteenliittymĂ€t tai lineaariset valtajĂ€rjestykset edellyttĂ€vĂ€t pitkĂ€kestoista sosiaalisten suhteiden vakautta. Alati koostumukseltaan muuttuvissa, toistuvasti hajoavissa ja uudelleen muodostuvissa elĂ€inryhmissĂ€ voivat kuitenkin toimia melko yksinkertaiset ristiriitoja lieventĂ€vĂ€t toimintamallit.Siirretty Doriast

    Rivaroxaban – an oral, direct Factor Xa inhibitor – lessons from a broad clinical study programme

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    Anticoagulants are recommended for the prevention and treatment of venous thromboembolism (VTE), prevention of stroke in patients with atrial fibrillation (AF) and secondary prevention in patients with acute coronary syndrome (ACS). There is a clinical need for novel anticoagulants offering improvements over current standard of care, such as fixed oral dosing and no need for routine monitoring. Rivaroxaban, an oral, once-daily, direct Factor Xa inhibitor, has recently completed the RECORD phase III programme for the prevention of VTE in patients undergoing total hip or knee replacement (THR or TKR), an indication for which it is approved in Europe and Canada. It is being investigated in large-scale phase III studies for VTE treatment and prevention of stroke in patients with AF, and phase III studies will soon commence for secondary prevention in patients with ACS. Phase I studies demonstrated that no routine anticoagulation monitoring was required, while phase II studies suggested that fixed daily doses had a wide therapeutic window. The four RECORD studies consistently showed that rivaroxaban was significantly more effective than enoxaparin in the prevention of VTE after THR and TKR, with a similar safety profile. This review describes the development of this novel anticoagulant, from bench to bedside

    Der Internet-Deckungsbeitragsrechner fĂŒr die „Öko-Milchkuhhaltung“ und fĂŒr ausgewĂ€hlte Futterbauverfahren des ökologischen Landbaus

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    Als UnterstĂŒtzung der landwirtschaftlichen Praxis wurde von der Bayerischen Landesanstalt fĂŒr Landwirtschaft (LfL) 2010 im Auftrag des Bayerischen Staatsministeriums fĂŒr Landwirtschaft und Forsten (StMELF) eine kostenfreie, internetgestĂŒtzte Anwendung „LfL DeckungsbeitrĂ€ge und Kalkulationsdaten“ zur Ermittlung der Produktionskosten ausgewĂ€hlter Produktionsverfahren der Landwirtschaft entwickelt (https://www.stmelf.bayern.de/idb/). In jĂŒngster Zeit wurden die bestehenden DeckungsbeitrĂ€ge (DB) um das Verfahren der ökologischen Milchviehhaltung und um eine Reihe ökologischer Futterbauverfahren ergĂ€nzt, weitere mehrjĂ€hrige Futterbauverfahren sind in Arbeit. Jeder DB ist fĂŒr die jeweiligen Leistungs- und Kostenpositionen mit bayerischen Durchschnittswerten vorbelegt. Die dabei ausgewiesenen Kosten, Preise und ErtrĂ€ge werden turnusmĂ€ĂŸig aktualisiert und sind ĂŒber eine eigene Datenbank hinterlegt. Eine FĂŒlle an Zusatzinformationen kann eingeblendet werden und hilft dabei, den DB an den eigenen Betrieb und die Region anzupassen. Mit einem weiterfĂŒhrenden Vollkostenansatz können die eigenen vollkostendeckenden Milch- oder Futterpreise ĂŒberschlĂ€gig kalkuliert werden. In der SensitivitĂ€tsanalyse im Zusatzmodul „DB PLUS“ werden die Auswirkungen von prozentualen Produkt- oder ProduktionsmittelpreisĂ€nderungen auf das ökonomische Ergebnis dargestellt
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