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Die hier zu besprechende Publikation umfasst die Akten einer internationalen Tagung zum Gymnasion in der Kaiserzeit, die vom 23. bis 24. November 2007 an der Johann Wolfgang Goethe-Universität in Frankfurt veranstaltet wurde. Sie ergänzt somit zeitlich und thematisch den bereits 2004 publizierte Band zum hellenistischen Gymnasion, der aus den Beiträgen einer gleichnamigen Tagung im Jahre 2001 hervorging und von Daniel Kah und Peter Scholz herausgegeben wurde. Ziel des Frankfurter Forschungsprogramms war die Untersuchung der antiken Wissenskultur, ihrer Rolle bei der Gestaltung der hellenistischen Kultur und deren Wirkung auf die römische Welt. Die Institution des Gymnasions war als repräsentative Fallstudie für beide Tagungen ausgewählt worden. Der vorliegende Band, der 2015 von Peter Scholz und Dirk Wiegandt herausgegeben wurde, umfasst eine Einleitung und elf Einzelstudien, neun davon von Verfassern mit einem althistorischen und/oder epigraphischen Hintergrund, und zwei von Archäologen. Folglich betrifft der größte Teil des Bandes Fragestellungen, die sich aus den Zeugnissen der schriftlichen Überlieferung ergeben. ...
Günter Grass'ın 'Yengeç Yürüyüşü" Romanında 'Konrad' Karakterini Dijital Kuşak Olarak Çözümleme
(2021)
"Yengeç Yürüyüşü" romanında, 1945 yılında Nasyonal Sosyalist dönemde torpillenen "Wilhelm Gustloff" gemisinin batırılış öyküsüyle birlikte Pokriefke ailesinin üç kuşak üyelerinin de aile öyküsüne yer verilmiştir."Y kuşağı" teknolojiye olan yatkınlığı ile bilinirken, günümüzde "Z kuşağı", iletişim araçları olarak internet ve akıllı telefonları daha etkin bir şekilde kullanmaktadır. Bu durumda her iki dijital kuşak da iletişim teknolojilerini iyi derecede kullanan teknoloji gurusu olarak kabul edilmektedir. Dijital temelli teknolojik gelişmelerin yaşamı değiştirmeye başladığı iki binli yıllar bu bağlamda dönüm noktası olarak ele alınabilir. Romanın olay örgüsünde 1995'lere gelindiğinde genç Konrad'ın dijital iletişim aracı olarak bilgisayar kullanması sonucunda internetten beslenen antisemitizmle yollarının kesişmesinin de öyküsü anlatılır. Romanda, ben-anlatıcı Paul'un başarısız gazetecilik kariyeri, ironik bir şekilde, yetenekli bir bilgisayar kullanıcısı olan oğlu Konrad'ın Neo-Nazilerin www.blutzeuge.de sayfasını düzenli olarak ziyaret etmesi gerçeği ile bir paradox oluşturur. Baba Paul'un başarısızlığının aksine Konrad, büyükanne Tulla'nın yardımıyla bir bilgisayar edinerek ihtiyacı olan bilgiyi elde etmekte başarılı olacaktır. Ancak, istediği bilgiye kavuşan Konrad, internet aracılığıyla bir yandan başarılı araştırmalara imza atarken öte yandan da internet üzerinden tanıştığı bir genci öldürme eylemine karışır. Bu olayla Nasyonal Sosyalist döneminin ideolojik propaganda çalışmalarının Neonazizm aracılığıyla yürütülmeye devam edildiğine bir göndermede bulunulduğu söylenebilir. Bu çalışmada üçüncü kuşak aile üyesi olan Konrad'ın dijital ortamı kullanarak kendisinden önceki kuşakların hatalarını yinelediği kesitler, metin odaklı bir yaklaşımla irdelenerek örnek ve alıntılarla çözümlenmeye çalışılacaktır.
Die Anzahl der Werke zum Thema Antikriegsliteratur, vor allem im Zusammenhang mit dem Ersten Weltkrieg, ist im literarischen Bereich reichlich vorhanden. Die deutsche Literatur bietet durch ihre umfangreiche Anzahl Möglichkeiten diese Werke zu untersuchen. Die Darstellung des Krieges in dem Roman "Im Westen nichts Neues" ist deshalb bemerkenswert, weil es viele Beispiele zum Thema Kriegstrauma enthält. Wie wird Kriegstrauma im Roman "Im Westen nichts Neues" in der Gegenwartsliteratur geschildert bzw. thematisiert? Um diese Frage zu beantworten, soll das Motiv, "Kriegstrauma" und dessen Darstellungen, die im Roman vorkommen, gelöst werden. Der Ausdruck auf der ersten Seite der Einführung des Romans "Die Schrecken des Ersten Weltkrieges sind die Schrecken aller Kriege", deutet auf das Hauptthema im Roman. Dieser Roman wird auch heute 100 Jahre nach dem Ersten Weltkrieg als ein Zeitzeugen-Dokument angesehen. Der Roman schildert die Erfahrungen eines einfachen Frontsoldaten im Ersten Weltkrieg, den Erich Maria Remarque im Jahre 1927 als er an der Westfront Dienst war geschrieben hat. Im Roman "Im Westen nichts Neues" wird die Geschichte des deutschen Soldaten Paul Bäumer und seiner Kameraden im Ersten Weltkrieg erzählt. Traumata / Kriegstraumata / Kriegserlebnisse der Soldaten an der Front sind ein zentrales Thema des Romans.
Ukrainische Bricolage : wie die Kulturszene der Ukraine dazu beiträgt, ihr Land zu verteidigen
(2023)
Der im Februar 2022 begonnene völkerrechtswidrige Angriffskrieg der Russischen Föderation gegen die benachbarte Ukraine führte neben flächendeckender Zerstörung in manchen Gebieten zur Vertreibung zahlloser Menschen und zum Tod einer Vielzahl von Zivilist:innen und Soldat:innen. Außenpolitisch markiert der Ukrainekrieg damit das Ende der postsowjetischen Transformationsphase und bildet den Beginn einer wohl länger währenden Konfrontation zwischen dem Aggressor und den NATO-Staaten. Die westeuropäische Berichterstattung behandelt den Krieg umfangreich, jedoch kommen nur selten Stimmen aus der Ukraine zu Wort. Die hiesige Diskussion wird somit von westlichen Expert:innen bestimmt, die meist aus einer gewissen Distanz heraus über das Land und seine Bewohner:innen sprechen. Im Fokus der Diskussion bleiben vorwiegend die militärisch-politische Entwicklung sowie die überregionalen und globalen Auswirkungen des Konflikts. Sichtweisen und Positionen einzelner und vor allem 'kleinerer' Akteur:innen, die abseits staatlicher Organisationen und Institutionen agieren, geraten auf diese Weise aus dem Blick oder werden einem breiteren Publikum gar nicht erst bekannt. Es verwundert somit nicht, dass bisher Formen ästhetischer Kommunikation und künstlerische Projekte im Kontext des Krieges in der Ukraine zu wenig behandelt werden. [...] Ziel der von Herwig Höller und Peter Deutschmann konzipierten hybriden Diskussionsrunde "Von der Kunst im Krieg. Künstlerische Strategien im ukrainischen Kommunikationsdesign" und der ebenfalls hybriden Tagung "Ukrainische Bricolage", die vom 1.-2. Dezember 2022 stattfanden, war es, die nicht zu unterschätzende Rolle der ukrainischen kreativen Szene im derzeitigen Krieg hervorzuheben. So beeinflussen und prägen seit Beginn der Kampfhandlungen diese Akteur:innen u.a. über soziale Medien oder mittels Crowdfunding finanzierte Design-Kampagnen den Widerstand im Land sowie die öffentliche Diskussion im Westen. Statt aus distanzierter Sicht über die ukrainische Kunst und ihre Produzent:innen zu sprechen, kamen im Rahmen der von Peter Deutschmann und Herwig Höller organisierten Veranstaltungen verschiedene Kunstschaffende zu Wort, deren Projekte im Weiteren kurz skizziert werden. Bevor jedoch die Beiträge der Tagung "Ukrainische Bricolage" im Einzelnen betrachtet werden, soll zuvor auf die Diskussionsrunde am Abend eingegangen werden.
The main aim of this thesis work was to elucidate the catalytic mechanism of several enzyme complexes on the basis of their three-dimensional structure. All investigated enzyme complexes occur in the anaerobic energy metabolism and have an essential function by the challenging degradation of aromatic compounds and the flavin-based electron bifurcation (FBEB)/confurcation, an energy-coupling mechanism. More specifically, I studied the phthaloyl-CoA decarboxylase of Thauera chlorobenzoica (Pcd) involved in phthalate ester decomposition, the FBEB protein complexes lactate dehydrogenase/electron-transfer flavoprotein (Ldh/EtfAB) of Acetobacterium woodii, the heterodisulfide-related subunit HdrA of the sulfur- oxidizing bacteria Hyphomicrobium denitrificans (sHdrA). In addition, I contributed to the structure determination of the caffeyl-CoA reductase- EtfAB complex of A. woodii and the naphthoyl-CoA reductase of the sulfate-respiring enrichment culture N47 (mentioned in the Appendix E and F).
Ekphrasis is a tool used with the purpose opening different levels of meaning in a literary text, which can be seen in Patricia Görg’s tale “Glücksspagat”. In the tale, parallel to the representation of the daily life of the museums keeper Maat, the reader is faced with fragments of ekphrasises of paintings and TV-simulations. The richness of this tale is achieved particularly due to the alternations between the ekphrasises. This article discusses the various functions of the use of Ekphrasis and simulations in the tale and focuses on the way they contribute to the creation of meaning.
Her yeni edebî metnin kendinden öncekilerden ya ilham aldığı ya da yeniden üretilerek ortaya çıktığı gerçeği bugün edebiyat çevreleri tarafından kabul edilen bir görüştür. Sinema sanatı edebiyat ile her zaman yakın ilişki içerisinde olmuştur. Senaryolar ise edebî metinlerden beslenerek onlardan ilham almıştır ya da özgün senaryo ile edebî metin benzeşmiştir. Edebiyattan beslenen sinema böylece kendi türünü de oluşturmaya başlamıştır. Özellikle melodram türü sinema filmleri 1960 - 1975 yılları arasında Yeşilçam sinemasına hâkim olmuştur. Hamdi Değirmencioğlu'nun 1973 yılında 10. Antalya Altın Portakal Film Festivalinde kendisine ödül kazandıran "Hayat mı Bu?" adlı melodram türündeki senaryosu Grimm Kardeşlerin Halk efsanesi olan "Die zwei gleichen Söhne" ile benzerlikler taşımaktadır. Grimm Kardeşlerin 1816–1818 yılları arasında yayınlanmış olan "Deutsche Sagen" (Alman Efsaneleri) eserinde toplam 585 halk efsanesi yer almaktadır. Halk efsanesine konu olan Genç Kral Pepin / III. Pepin (714-768) tarihsel gerçek bir kişidir ve hikâyesi Alman efsaneleri arasında 441. sırada yer almaktadır. Onun hayatından yola çıkarak anne kompleksinin negatif özellikli arketipi olan üvey anne figürüne farklı bir yorum katan bu Alman halk efsanesi, Değirmencioğlu'nun senaryosunu yazdığı 1972 yapımlı Yeşilçam Sinema filmindeki üvey anne figürü ile benzeşmektedir. Bu çalışmada, Grimm Kardeşlerin "Die zwei gleichen Söhne" adlı efsanesi ile Hamdi Değirmencioğlu'nun "Hayat mı Bu?" adlı film senaryosu metinlerarasılık kuramı ile incelenmeye çalışılmıştır.
Dr. Z. Ece Kaya, 1978 in Istanbul geboren, ist u. a. Diplom-Politologin und promovierte Erziehungswissenschaftlerin. Ihre Arbeitsschwerpunkte sind Erziehungswissenschaften in der NS-Zeit sowie pädagogische Antworten auf Rassismus und Nationalismus. Sie arbeitet auch als Übersetzerin, Sprachlehrerin und als Theaterpädagogin. Für ihre Dissertation »Kolonialpädagogische Schriften in der NS-Zeit: ,Eine spezifisch deutsche Theorie der Kolonisation‘ – Zur Geschichte des Kolonialrassismus in der deutschen Erziehungswissenschaft « wurde sie 2017 mit dem Werner-Pünder-Preis ausgezeichnet.
This paper empirically tests the role of bank lending tightening on non-financial corporate (NFC) bond issuance in the eurozone. By utilizing a unique data set provided by the ECB Bank Lending Survey, we capture the "pure" credit supply effect on corporate external financing. We find that tightened credit standards positively affect the NFC bond issuance: A 1pp increase in banks reporting considerable tightening on loans leads to around a 7% increase in firms' bond issuance in the eurozone. Focusing on a spectrum of aspects contributing to bank credit tightening, we document that banks' balance sheet constraints, as well as the perception of risk lead to significantly higher NFC bond issuance. In addition, we show that stricter lending conditions, such as wider margins, higher collateral requirements and covenants significantly increase NFC bond issuance volumes too. Furthermore, the impact of bank credit tightening on firms' bond issuance is particularly observable in core eurozone countries and not in peripheral countries. This is partially due to the underdeveloped of debt capital markets in the peripheral countries.
Gegenstand dieser Arbeit war die Untersuchung der optischen und elektronischen Eigenschaften von metallorganischen Materialien, die mit dem Verfahren der Elektronenstrahlinduzierten Deposition hergestellt wurden. Da es sich bei diesen noch relativ unerforschten Endprodukten um Materialmengen von wenigen Nanogramm Gewicht und geometrische Abmessungen im Sub-µm-Bereich handelt, wurden hierzu neue Verfahren der Herstellung, Strukturierung und Charakterisierung entwickelt. Sowohl die optischen als auch die elektronischen Eigenschaften dieser Deponate besitzen einen gemeinsamen physikalischen Nenner in ihrer inneren Morphologie: ein nanokristallines dielektrisches Verbundmaterial, das aus metallischen Kristalliten und organischen Polymeren gebildet wird. Im Hinblick auf die Durchführung der Untersuchungen war das Augenmerk auf zwei potentielle industrielle Anwendungen gerichtet: den Photonischen Kristallen und den Einzelelektronen-Phänomenen bei Raumtemperatur. Mit Hilfe von Beugungsexperimenten im Fernfeld wird ein Verfahren gezeigt, das eine der periodischen Struktur von Photonischen Kristallen angepaßte Charakterisierung von Materialstrukturen mit optischer Bandlücke ermöglicht. Das mathematische Grundgerüst bildet dabei eine rigorose Streutheorie, die als Lösung der Helmholtz-Gleichung an dielektrischen Zylindern mit wenigen hundert nm Durchmesser den Experimenten zugrunde gelegt wird und sowohl für die praktische Dimensionierung des Versuchsaufbaus als auch für die theoretische Auswertung der Meßdaten, z.B. für die Brechungsindexbestimmung, dient. Die Herstellung und Kontrolle der Eigenschaften von Einzelelektronen-Tunnelelementen (SETs, Single Electron Tunneling Devices), welche bei hohen Temperaturen mit einer abzählbar kleinen Anzahl von Elektronen noch arbeiten, dürfte wohl eine der größten Herausforderungen in der heutigen Festkörperelektronik sein. Obwohl die Idee dazu, auf Basis der "Orthodoxen Theorie", bis auf die 80er Jahre des vergangenen Jahrhunderts zurückgeht, konnten nennenswerte Ergebnisse nur unter "Laborbedingungen" mit entsprechend hohem experimentellem Aufwand erzielt werden. In der vorliegenden Arbeit wird ein neuer Weg gegangen, um die beiden wesentlichen Bedingungen der orthodoxen Theorie, nämlich die Kleinheit der Kapazitäten und hohe Tunnelwiderstände, durch das ungeordnete nanokristalline Netzwerk der metallorganischen Deponate zu erfüllen. Die Motivation hierzu liegt in der hochohmigen organischen Matrix der Deponate, die mit darin eingebetteten elektrisch isolierten Nanokristalliten (die mit Durchmessern zwischen 1 nm und 2.5 nm ausgezeichnete Quantenpunkte bilden) eine ideale Umgebung für den Betrieb von Einzelelektronen-Tunnelelementen bereitstellen. Ein stabiles Verhalten unter hohen Temperaturen und eine ausgeprägte Resistenz gegen quantenmechanische Fluktuationen (z. B. dem Co-Tunneln oder Hintergrundladungen) wird durch den Aufbau von nanokristallinen Netzwerken, die in der Arbeit als "Über-SET" bezeichnet werden, erreicht. Mit Hilfe der entwickelten speziellen Technik lassen sich Nanokristallite elektrisch bis zur quantenmechanischen Tunnelgrenze voneinander isolieren und als Quantenpunkte betreiben. Die dabei beobachtbaren Phänomene sind diskretisierte I/U-Kennlinien und das Blockade-Verhalten der Spannung bei Raumtemperatur, deren Entstehung in Monte-Carlo-Simulationen auf zwei physikalische Grundprinzipien zurückgeführt wird: der Ausbildung von Einfangzuständen (Traps) für Elektronen an Grenzstellen und dem Mechanismus des negativen differentiellen Widerstandes (NDR, Negative Differential Resistance). Beide Effekte fungieren in einer gegenseitigen Kombination zueinander durch Coulomb-Wechselwirkungen zu einem mikroskopischen Schalter für den gesamten Strom.
In a 1949 letter, Cesare Pavese describes with great zeal the genesis of a new work - one he compares, albeit with a certain amount of irony, to Dante's Commedia. [...] This embryonic project would quickly become the novel "La luna e i falò", completed in less than two months and published shortly before Pavese's suicide in 1950. On the surface, there would seem little reason to take seriously the analogy drawn by the author between "La luna" and the "Commedia", for the novel in question contains no explicit references to the medieval poet. Tristan Kay argues in this essay, however, that the presence of Dante in "La luna" is both more pervasive and more significant than has previously been suggested. While critics have noted in passing several narrative and structural parallels between the two texts, which Kay details in Section II, no attempt has been made to consider their wider significance in our understanding of Pavese's novel. What follows is a reading of "La luna" which shows that the "Commedia" functions not simply as a formal model for Pavese, but, more importantly, as an ideological anti-model, in dialogue with which the author articulates his deeply pessimistic understanding of the human condition.
Objective: We sought to evaluate the efficacy and tolerability of intranasal midazolam (in‐MDZ) as first‐line inhospital therapy in patients with status epilepticus (SE) during continuous EEG recording.
Methods: Data on medical history, etiology and semiology of SE, anticonvulsive medication usage, efficacy and safety of in‐MDZ were retrospectively reviewed between 2015 and 2018. Time to end of SE regarding the administration of in‐MDZ and ß‐band effects were analyzed on EEG and with frequency analysis.
Results: In total, 42 patients (mean age: 52.7 ± 22.7 years; 23 females) were treated with a median dose of 5 mg of in‐MDZ (range: 2.5–15 mg, mean: 6.4 mg, SD: 2.6) for SE. The majority of the patients suffered from nonconvulsive SE (n = 24; 55.8%). In total, 24 (57.1%) patients were responders, as SE stopped following the administration of in‐MDZ without any other drugs being given. On average, SE ceased on EEG at 05:05 (minutes:seconds) after the application of in‐MDZ (median: 04:56; range: 00:29–14:53; SD:03:13). Frequency analysis showed an increased ß‐band on EEG after the application of in‐MDZ at 04:07 on average (median: 03:50; range: 02:20–05:40; SD: 01:09). Adverse events were recorded in six patients (14.3%), with nasal irritations present in five (11.9%) and prolonged sedation occurring in one (2.6%) patient.
Conclusions: This pharmaco‐EEG–based study showed that in‐MDZ is effective and well‐tolerated for the acute treatment of SE. EEG and clinical effects of in‐MDZ administration occurred within 04:07 and 5:05 on average. Intranasal midazolam appears to be an easily applicable and rapidly effective alternative to buccal or intramuscular application as first‐line treatment if an intravenous route is not available.
In this paper, I argue that this apparent problem is accounted for by the interaction of constraints. For the fixed segment [ɛ] in Cɛ-reduplication, I argue that [ɛ] is the second least marked vowel in Palauan, which appears when the default vowel [ǝ] cannot appear. I show that the Palauan facts are not only consistent with the proposals of Urbanczyk (1999) and Alderete et. al (1999), but they actually provide support of their claims. In the following section, I discuss Urbanczyk's (1999) arguments concerning ROOT faithfulness in reduplication and possible asymmetries between affix reduplicants and root reduplicants. In Section 3, I introduce Palauan reduplication and discuss Finer's (1986) observations on the resulting state verb (RSV) form. I show that the RSV forms support the classification that Cɛ-reduplicants are affixes, and CVCV -reduplicants are roots. In Section 4, I discuss the shape and vowel quality of the two reduplicants. The CVCV-reduplicant has three variants: CǝCǝ, CǝC and CV. I explain this variation, illustrating why [ǝ] appears in the first two variations. Then, I discuss the shape and vowel quality of the Cɛ-reduplicant, arguing that the fixed segment [ɛ] in Cɛ-reduplication is a special case of TETU. I show that root faithfulness constraints are crucial in determining the shape and vowel quality of the reduplicants. Section 5 is the conclusion.
In order to elucidate what species among so many kind of marine organisms are likely to be consmed Iargely by the balaenopterid whales, the existing evidence on the food habits of baleen whales is reviewed. To meet with this primary purpose the report was mainly focussed on to describe qualitative aspects of food species having been known to date from the notable whaling grounds over the world rather than documenting quantitative subjects. One of interesting facts noticed throughout the contribution was that there exists fairly intense diversity in the assembly of food species composition by regions such as; northern hemisphere vs. southern hemisphere, Pacific region vs. Atlantic region, inshore waters vs. offshore waters, embayed waters vs. open waters, where the former usually shows more diversed complexity than the latter. The fact however suggests that although the composition of food species locally varies over the various whaling grounds, the food organisms as taxonomical groups are very similar one another even in locally isolated whaIing grounds when the food organisms and their assemblies are considered by the family or genus basis. In this connection many evidences given in the text may suggest that the balaenopterid whales as a whole may substantially live on quite simply compositioned forage assembly in comparison with tremendous variety of organisms existing in the marine ecosystems. One of important aspects of the baleen whales food must be found in their characteristics of forming dense swarms, schools, and/or aggregations in the shallower enough layers to be fed by the whales. The present and past status of larger baleen whales as the mighty monarch through their evolutional pathways may entirely depend upon the spatial distribution pattern of possible food organisms, i.e. the animal aggregations.
In Christian history spiritual awakenings are a recurring and important phenomenon. The Blantyre Spiritual Awakening was characterized by an overt evangelistic fervour among bands of people that belonged to an ever growing Born Again Movement in the city, from 1974 into the 1980s. This history covers The Blantyre Awakening which revived Evangelical Christianity in Malawi and prepared the way for the emerging Charismatic Movement.
Liebe als Lebenswerk : Phyllis und ihre Verlobung mit Narciß im 6. Buch von Goethes "Lehrjahren"
(2014)
Die 'Schöne Seele' ist die Erzählerfigur des VI. Buchs von Goethes Roman "Wilhelm Meisters Lehrjahre". Ihr Leben erscheint dem Leser als eine Hinführung zu frei gewählter Ehelosigkeit und religiöser Askese; sie kündigt nämlich ihre Verlobung mit Narciß auf, dem Anschein nach wegen der damit verbundenen, vom wahren Verhältnis zu Gott ablenkenden Formen gesellschaftlicher Unterhaltung, wird Stiftsdame und Anhängerin des zeitgenössisch verbreiteten Pietismus in seiner Hallenser wie dann schließlich auch seiner Zinzendorfischen Form. Der Name "Schöne Seele" ist ihr von ihren jungen Verwandten zugedacht, weil sie ihren Verzicht angeblich nicht als Verlust erleidet, sondern als Moment glücklicher Selbstvervollkommnung.
Kawa zeigt, daß diese bislang vorherrschende Lesart den Chakakter der 'Bekenntnisse' als Dokument der (fiktiven) Romanempirie übersieht. Damit stehe dieser Text nämlich in einem vielseitigen Konfliktfeld, in dessen Kontext es seine spezifische Gestalt erst erhalte; er sei sowohl von der Verfasserin selbst wie von den Propagatoren des Manuskripts, also den Mitgliedern der 'Turmgesellschaft', entsprechend gekürzt und geschönt worden. Die schließlich an den Lesrer tradierte Fassung sei hinsichtlich ihres Wahrheitsgehalts fragwürdig und gebe nur bei gründlicher philologischer Bemühung den Blick darauf frei, daß Phyllis, wie sich die ansonsten namenlose Hauptgestalt gelegentlich nennt, sich der maitressenhaften Beziehung mit ihrem fürstlichen 'Mentor' und 'Oheim' zu entziehen versucht, dabei aber nicht die Unterstützung ihres Verlobten und nur teilweise die ihrer Familie erhält. Ihrem Verlobten sei nämlich für die Zweckehe und damit für die äußerliche Legitimation des Oheims, der auf diese Weise ungestört sein Verhältnis zu seiner Nichte fortsetzen wolle, eine außergewöhnliche Karriere als Kompensation versprochen worden.
Nach dem Zerwürfnis mit Narciß führt Phyllis aber noch ein langes, mit zahlreichen erotischen Affairen durchsetztes Leben, das bei entsprechend scharfsinnig ausgerichteter Lektüre auch in allen anderen Büchern des Romans und selbst noch in "Wilhelm Meisters Lehrjahre" auf wie immer versteckte Weise in unterschiedlichsten Auftritten faßbar wird. Der Leser muß zum Zwecke der Einsicht in diese Handlungs-Stationen verborgene genalogische Zusammenhänge beim Figurenensemble auflösen und eine Person identifizieren, die im Roman unter mehreren Namen und Bezeichnungen auftritt.
Hingewiesen wird am Ende auf den Umstand, daß die Schreiberin sich dabei zunehmend von der Nicht-Existenz der Erbsünde und von einem künftigen Sündenerlaß überzeuge, wie er mit dem Theologem der "Herwiederbringung der Dinge" in der Gnosis (z.B. bei Origenes) verbunden ist und im radikalen Pietismus (z.B. bei Klopstock) wiederbelebt wird. Dieser Aspekt der prognostizierten 'Rettung', der erst noch bearbeitet werden muß, verknüpft das Schicksal der "Schönen Seele" eng mit dem Schluß von 'Faust II'.
Die Geschichte "Nicht zu weit" wird – abweichend von der Forschungstradition – im Nachfolgenden nicht unter dem Thema 'Liebes- und Eheverhältnisse im ausgehenden Feudalabsolutismus' begriffen, sondern als Rätseltext, der unter anderem Gestalten und Ereignisse aus den 'Lehrjahren' spiegelt und dem in den 'Wanderjahren' die Funktion zugewiesen ist, das Projekt Odoards in Mißkredit zu bringen. Überdies stelle ich – über die Analyse der Geschichte "Nicht zu weit" hinausgehend – eine neue These zu der Identität des 'Redakteurs' der 'Wanderjahre' auf. – Alle Thesen werden weitestgehend eng am Text entlang plausibilisiert, wenigstens ist das die Absicht. Insofern ist der Charakter des Vorliegenden im Kern ein philologischer. Allerdings können hier nicht alle Voraussetzungen, die ich in aus meinen diversen Studien (gedruckt und ungedruckt) – insbesondere zu den 'Lehrjahren' – einbringe, in voller Breite belegt werden.
Previous investigation of seismic anisotropy indicates the presence of a simple mantle flow regime beneath the Turkish-Anatolian Plateau and Arabian Plate. Numerical modeling suggests that this simple flow is a component of a large-scale global mantle flow associated with the African superplume, which plays a key role in the geodynamic framework of the Arabia-Eurasia continental collision zone. However, the extent and impact of the flow pattern farther east beneath the Iranian Plateau and Zagros remains unclear. While the relatively smoothly varying lithospheric thickness beneath the Anatolian Plateau and Arabian Plate allows progress of the simple mantle flow, the variable lithospheric thickness across the Iranian Plateau is expected to impose additional boundary conditions on the mantle flow field. In this study, for the first time, we use an unprecedented data set of seismic waveforms from a network of 245 seismic stations to examine the mantle flow pattern and lithospheric deformation over the entire region of the Iranian Plateau and Zagros by investigation of seismic anisotropy. We also examine the correlation between the pattern of seismic anisotropy, plate motion using GPS velocities and surface strain fields. Our study reveals a complex pattern of seismic anisotropy that implies a similarly complex mantle flow field. The pattern of seismic anisotropy suggests that the regional simple mantle flow beneath the Arabian Platform and eastern Turkey deflects as a circular flow around the thick Zagros lithosphere. This circular flow merges into a toroidal component beneath the NW Zagros that is likely an indicator of a lateral discontinuity in the lithosphere. Our examination also suggests that the main lithospheric deformation in the Zagros occurs as an axial shortening across the belt, whereas in the eastern Alborz and Kopeh-Dagh a belt-parallel horizontal lithospheric deformation plays a major role.
This work addresses the investigation of the biosynthesis mechanisms of type II polyketide synthase (PKS) and fatty acid synthase (FAS) derived specialized metabolites (SMs) from Photorhabdus laumondii.
The elucidation of the biosynthetic pathway of the bacterial 3,5-dihydroxy-4-isopropyl-trans-stilbene (IPS) was one of the major topics of this thesis. IPS exhibits several bioactive characteristics as it inhibits the phenoloxidase of insects, acts antibacterial, but also influences the soluble epoxide hydrolase which is involved in inflammatory reactions. It was recently approved as a treatment against psoriasis by the FDA and is the first Photorhabdus derived drug.
The stilbene generation in Photorhabdus requires the formation of the two acyl-carrier-protein (ACP) bound 5-phenyl-2,4-pentadienoyl- and isovaleryl-β-ketoacyl-moieties. The ketosynthase (KS)/cyclase StlD catalyzes a ring formation via a Michael-addition between the two intermediates which is then further processed by an aromatase. The formation of 5-phenyl-2,4-pentadienoyl-ACP was shown via in vitro assays with purified proteins by proving the influence of the KS FabH, ketoreductase FabG and dehydratase FabA or FabZ of the fatty acid metabolism. While E. coli was able to complement most of these enzymes in attempts to produce IPS in the heterologous host, the Photorhabdus derived FabH was not replaceable despite 73 % sequence identity with the E. coli based isoenzyme, acting as a gatekeeper enzyme for cinnamic acid (CA) moieties. Furthermore, the ability to incorporate meta-substituted halogenated CA-derivatives was shown in order to produce 3-chloro- and 3-bromo-IPS. While studying the stilbene biosynthesis, the ability of Photorhabdus and Xenorhabdus to produce hydrazines was also discovered.
The second investigated biosynthesis was the formation of benzylideneacetone (BZA). BZA is produced by Photorhabdus and Xenorhabdus strains acting as a suppressor for the immune cascade of insects and has also antibiotic activities towards Gram-negative bacteria. Due to its structural similarity towards CA and the intermediates during the stilbene formation, a shared mechanism for Photorhabdus and Xenorhabdus budapestensis was proposed due to their ability to produce CA. The production of BZA was also dependent on the stilbene related CoA-ligase, the ACP and FabH. It was verified in vitro and in vivo in E. coli yielding a 150-fold increase of the BZA production compared to the Photorhabdus and Xenorhabdus wildtype (WT) strains.
The second part of this work deals with the optimization of P. laumondii strains regarding the production titers of IPS. Therefore, several deletions of other SM related genes as well as promoter exchanges in front of stilbene related genes were carried out. These approaches were combined with the upregulation of the phenylalanine by heterologous plasmid expression, since it is the precursor of CA. Another approach applied in parallel was the optimization of the cultivation conditions with different media and supplementation with XAD-resins. It was proved that media rich on fatty acids or peptides led to higher optical densities of the cultures and thus to higher titers of stilbenes. Since IPS is inhibiting the phenoloxidase, an enzyme important for the insect immunity, it was hypothesized that cultivation in media containing insects might enhance the output of this SM. Starting from 23 mg/l of IPS in the P. laumondii WT strain, it was possible to increase the production levels to more than 860 mg/l by utilizing the mentioned approaches.
The last topic of this thesis focuses on the production of epoxidated IPS (EPS) and its derivatives. Under laboratory conditions, only a low titer of EPS was observed for the wildtype strain. However, the optimized IPS strains and IPS-production conditions could also be applied for EPS which led to higher productions and also to the detection of many new derivatives. Most of the EPS derivatives were amino acid or peptide derived acting as nucleophiles to open the epoxide ring and yielding β-amino-alcohols. However, purification and chemical synthesis attempts to obtain EPS failed due to its poor stability. Epoxides were utilized in in vitro assays with amino acids, peptides and proteins to get insights whether epoxidations might act as posttranslational modification in Photorhabdus. The reactions were performed with styrene oxide and stilbene oxide replacing EPS based on their structural similarity. The modifications were executed successfully although proteomics approaches with in vivo data are required to confirm these findings. During the purification attempts of EPS, further derivatives were detected. The structures of dimerized stilbenes, a cis-isomer of IPS and another derivative that might incorporate an amino-group in the resveratrol ring were proposed on the basis of the HPLC-MS data.
Die deutsche Illustration
(1904)
Protective ant-plant mutualisms that are exploited by non-defending parasitic ants represent prominent model systems for ecology and evolutionary biology. The mutualist Pseudomyrmex ferrugineus is an obligate plant-ant and fully depends on acacias for nesting space and food. The parasite Pseudomyrmex gracilis facultatively nests on acacias and uses host-derived food rewards but also external food sources. Integrative analyses of genetic microsatellite data, cuticular hydrocarbons and behavioral assays showed that an individual acacia might be inhabited by the workers of several P. gracilis queens, whereas one P. ferrugineus colony monopolizes one or more host trees. Despite these differences in social organization, neither of the species exhibited aggressive behavior among conspecific workers sharing a tree regardless of their relatedness. This lack of aggression corresponds to the high similarity of cuticular hydrocarbon profiles among ants living on the same tree. Host sharing by unrelated colonies, or the presence of several queens in a single colony are discussed as strategies by which parasite colonies could achieve the observed social organization. We argue that in ecological terms, the non-aggressive behavior of non-sibling P. gracilis workers — regardless of the route to achieve this social structure — enables this species to efficiently occupy and exploit a host plant. By contrast, single large and long-lived colonies of the mutualist P. ferrugineus monopolize individual host plants and defend them aggressively against invaders from other trees. Our findings highlight the necessity for using several methods in combination to fully understand how differing life history strategies affect social organization in ants.
Chemokines play a key role in the cellular infiltration of inflamed tissue. They are released by a wide variety of cell types during the initial phase of host response to injury, allergens, antigens, or invading microorganisms, and selectively attract leukocytes to inflammatory foci, inducing both migration and activation. Monocyte chemoattractant protein-1 (MCP-1), a member of the CC chemokine superfamily, functions in attracting monocytes, T lymphocytes, and basophils to sites of inflammation. MCP-1 is produced by monocytes, fibroblasts, vascular endothelial cells and smooth muscle cells in response to various stimuli such as tumour necrosis factor-a (TNF-a), interferon-g (IFN-g), and interleukin-1b (IL-1b). It also plays an important role in the pathogenesis of chronic inflammation, and overexpression of MCP-1 has been implicated in diseases including glomerulonephritis and rheumatoid arthritis. Oligonucleotide-directed triple helix formation offers a means to target specific sequences in DNA and interfere with gene expression at the transcriptional level. Triple helix-forming oligonucleotides (TFOs) bind to homopurine/homopyrimidine sequences, forming a stable, sequence-specific complex with the duplex DNA. Purine-rich sequences are frequent in gene regulatory regions and TFOs directed to promoter sequences have been shown to prevent binding of transcription factors and inhibit transcription initiation and elongation. Exogenous TFOs that bind homopurine/ homopyrimidine DNA sequences and form triple-helices can be rationally designed, while the intracellular delivery of single-stranded RNA TFOs has not been studied in detail before. In this study, expression vectors were constructed which directed transcription of either a 19 nt triplex-forming pyrimidine CU-TFO sequence targeting the human MCP-1 or two different 19 nt GU- or CA-control sequences, respectively, together with the vector encoded hygromycin resistance mRNA as one fusion transcript. HEK 293 cells were stable transfected with these vectors and several TFO and control cell lines were generated. Functional relevant triplex formation of a TFO with a corresponding 19 bp GC-rich AP-1/SP-1 site of the human MCP-1 promoter was shown. Binding of synthetic 19 nt CUTFO to the MCP-1 promoter duplex was verified by triplex blotting at pH 6.7. Underlining binding specificity, control sequences, including the GU- and CA-sequence, a TFO containing one single mismatch and a MCP-1 promoter duplex containing two mismatches, did not participate in triplex formation. Establishing a magnetic capture technique with streptavidin microbeads it was verified that at pH 7.0 the 19 nt TFO embedded in a 1.1 kb fusion transcript binds to a plasmid encoded MCP-1 promoter target duplex three times stronger than the controls. Finally, cell culture experiments revealed 76 ± 10.2% inhibition of MCP-1 protein secretion in TNF-a stimulated CU-TFO harboring cell lines and up to 88% after TNF-a and IFN-g costimulation in comparison to controls. Expression of interleukin-8 (IL-8) as one TNF-a inducible control gene was not affected by CU-TFO, demonstrating both highly specific and effective chemokine gene repression. Furthermore, another chemokine target, regulated upon activation normal T cell expressed and secreted (RANTES), which plays an essential role in inflammation by recruiting T lymphocytes, macrophages and eosinophils to inflammatory sites, was analysed using the triplex approach. A 28 nt TFO was designed targeting the murine RANTES gene promoter, and gel mobility shift assays demonstrated that the phosphodiester TFO formed a sequencespecific triplex with the double-stranded target DNA with a Kd of 2.5 x 10-7 M. It was analysed whether RANTES expression could be inhibited at the transcriptional level testing the TFO in two different cell lines, T helper-1 lymphocytes and brain microvascular endothelial cells (bend3 cells). Although there was a sequence-specific binding of the TFO detectable in the gel shift assays, there was no inhibitory effect of the exogenously added and phosphorothioate stabilised TFO on endogenous RANTES gene expression visible. Additionally, the small interfering RNA (siRNA) approach was tested as another strategy to inhibit expression of the pro-inflammatory chemokines MCP-1 and RANTES. Two different methods were pursuit, describing transient transfection with vector derived and synthetic siRNA. The vector pSUPER containing the siRNA coding sequence was used to suppress endogenous MCP-1 in HEK 293 cells. An empty vector without RNA sequence served as a control. Inhibition due to the siRNA was measured in stimulated and unstimulated cells. In TNF-a stimulated cells MCP-1 protein synthesis was decreased by 35 ± 11% after siRNA transfection. Using a synthetic double-stranded siRNA, the TNF-a induced MCP-1 protein secretion could be successfully inhibited about 62.3 ± 10.3% in HEK 293 cells, indicating that the siRNA is functional in these cells to suppress chemokine expression. The siRNA approach targeting murine RANTES in Th1 cells and b-end3 cells revealed no inhibition of endogenous gene expression. Gene therapy approaches rely on efficient transfer of genes to the desired target cells. A wide variety of viral and nonviral vectors have been developed and evaluated for their efficiency of transduction, sustained expression of the transgene, and safety. Among them, lentiviruses have been widely used for gene therapy applications. In order to improve the delivery of TFOs or siRNAs into the target cells, cloning of the lentiviral transfer vector SEW, the production of lentiviral particles by transient transfection were performed with the aim to generate lentiviral vector-derived TFOs in further experiments. Here, Th1 cells were transduced with infectious lentiviral particles and transduction efficacy was measured. Transduction efficacy higher than 82% could be achieved using the lentiviral vector SEW, opening optimal possibilities for the TFO or siRNA approach.
Der 28. April 1789
(1889)
Volk und Proletariat
(1889)
We test whether investor mood affects trading with data on all stock market transactions in Finland, utilizing variation in daylight and local weather. We find some evidence that environmental mood variables (local weather, length of day, daylight saving and lunar phase) affect investors’ direction of trade and volume. The effect magnitudes are roughly comparable to those of classical seasonals, such as the Monday effect. The statistical significance of the mood variables is weak in many cases, however. Only very little of the day-to-day variation in trading is collectively explained by all mood variables and calendar effects, but lower frequency variation seems connected to holiday seasons.
We use unique data from financial advisers’ professional exam scores and combine it with other variables to create an index of financial sophistication. Using this index to explain long-term stock return expectations, we find that more sophisticated financial advisers tend to have lower return expectations. A one standard deviation increase in the sophistication index reduces expected returns by 1.1 percentage points. The effect is stronger for emerging market stocks (2.3 percentage points). The sophistication effect contributes 60% to the model fit, while employer fixed effects combined contribute less than 30%. These results help understand the formation of potentially excessively optimistic expectations.
A natural experiment in which customer-owned mutual companies converted to publicly listed firms created a plausibly exogenous shock to the stock market participation status of tens of thousands of people. We find the shock changed the way people vote in the affected areas, with a 10% increase in share-ownership rate being followed by a 1.3%–3.1% increase in right-of-center vote share. The institutional details and additional tests suggest that wealth, liquidity, and tax-related incentives cannot fully explain the results. A plausible explanation is that the associated increase in the salience of stock ownership causes a shift in voters’ attention.
It’s intuitively plausible to suppose that there are many things that we can be rationally certain of, at least in many contexts. The present paper argues that, given this principle of Abundancy, there is a Preface Paradox for (rational) credence. Section 1 gives a statement of the paradox, discusses its relation to its familiar counterpart for (rational) belief, and points out the congeniality between Abundancy and broadly contextualist trends in epistemology. This leads to the question whether considerations of context-sensitivity might lend themselves to solving the Preface for credence. Sections 2 and 3 scrutinize two approaches in this spirit—one mimicking Hawthorne’s (2002) Semantic Contextualist approach to an epistemic version of the Preface, the other one analogous to Clarke’s (2015) Sensitivist approach to the doxastic version—arguing that neither approach succeeds as it stands.
We investigate complexes of two paramagnetic metal ions Gd3+ and Mn2+ to serve as polarizing agents for solid-state dynamic nuclear polarization (DNP) of 1H, 13C, and 15N at magnetic fields of 5, 9.4, and 14.1 T. Both ions are half-integer high-spin systems with a zero-field splitting and therefore exhibit a broadening of the mS = −1/2 ↔ +1/2 central transition which scales inversely with the external field strength. We investigate experimentally the influence of the chelator molecule, strong hyperfine coupling to the metal nucleus, and deuteration of the bulk matrix on DNP properties. At small Gd-DOTA concentrations the narrow central transition allows us to polarize nuclei with small gyromagnetic ratio such as 13C and even 15N via the solid effect. We demonstrate that enhancements observed are limited by the available microwave power and that large enhancement factors of >100 (for 1H) and on the order of 1000 (for 13C) can be achieved in the saturation limit even at 80 K. At larger Gd(III) concentrations (≥10 mM) where dipolar couplings between two neighboring Gd3+ complexes become substantial a transition towards cross effect as dominating DNP mechanism is observed. Furthermore, the slow spin-diffusion between 13C and 15N, respectively, allows for temporally resolved observation of enhanced polarization spreading from nuclei close to the paramagnetic ion towards nuclei further removed. Subsequently, we present preliminary DNP experiments on ubiquitin by site-directed spin-labeling with Gd3+ chelator tags. The results hold promise towards applications of such paramagnetically labeled proteins for DNP applications in biophysical chemistry and/or structural biology.
Metal ions as novel polarizing agents for dynamic nuclear polarization enhanced NMR spectroscopy
(2017)
High-spin complexes of Gd(III) and Mn(II) were introduced as polarizing agents (PAs) for solid-state dynamic nuclear polarization (DNP) in 2011. This dissertation was undertaken in 2013, with the intention of exploring these PAs further. Major goals of this work were to understand their DNP mechanism(s) and explore their application in biomolecular research. This cumulative thesis details the methods, advantages, and practical implications of using high-spin PAs for MAS DNP. Data from electron paramagnetic resonance (EPR) and NMR spectroscopy are discussed for a complete understanding of DNP mechanisms.
Out of the two main mechanisms − solid effect (SE) and cross effect (CE − active under experimental conditions of solid-state DNP, commonly used nitroxide PAs evoke CE owing to their broad EPR spectra. On the other hand, DNP mechanisms evoked by high-spin metal ions seem non-trivial due to additional features (originating from spin-orbit coupling or zero field splitting) in their EPR spectra. The features of the EPR signal generally influence the shape of enhancement profiles. Therefore, the metal ion with a simpler EPR signal i.e., Gd(III) , is chosen as the starting point for the investigation of DNP mechanisms. Varying concentrations (2, 10, 20 mM) of a water-soluble and stable complex Gd-DOTA was dissolved as the PA in a glycerol-water solution of 13C,15N - urea. Field profiles of DNP enhancement on each nuclear type (1H, 13C, and 15N) establishes SE as the active DNP mechanism at the smallest PA concentration (2 mM). This confirms the theoretical predictions that narrow line width of the Gd(III) EPR signal arising from the central transition (CT, ms = -1/2 +1/2) allows for resolved SE DNP. However, that is no longer the case at higher PA concentrations of 10 and 20 mM. At higher Gd(III) concentrations, the CE mechanism contributes significantly and varies with nuclear Larmor frequency (ωn) of the concerned nuclei. The enhancement maxima shifts towards the EPR resonance as the contribution from CE increases. This shift is evident in the field profiles of 15N and 13C, whereas that of 1H is least influenced. This observation can be explained by combining theoretical estimates with the experimental data; the CE is evoked by increased dipolar coupling (Dee) – a prerequisite for CE – between neighboring Gd(III) spins as the statistical inter-spin distance shortens at elevated concentrations. This finding is important because the knowledge of active DNP mechanisms is essential for accurate interpretation of results from DNP experiments.
From the experiments on Gd-DOTA it becomes clear that concentration, inter-spin distances, and hence induced Dee are intertwined. In order to explicitly address the influence of inter-spin distances on DNP mechanisms we started a collaboration with the group of Adelheid Godt (Bielefeld). In this collaborative project, bis-complexes of the type Gd(III)-spacer-Gd(III) with variable spacer lengths were investigated. These PAs provided an excellent model system where the influence of only inter-spin distances can be determined for a fixed Gd(III) concentration. A small PA concentration of 4 mM is used to ensure absence of significant inter-molecular dipolar interactions. A mono-Gd complex of similar geometry and chemistry is taken as a reference for SE DNP.
The mono-Gd complex yields enhancements arising from SE as expected from negligible inter-molecular Dee. The contribution of CE increases as the inter-spin distances between Gd(III) ions become shorter going from 3.4 nm 2.1 nm 1.4 nm 1.2 nm due to corresponding increase in Dee. The extent of CE on ωn follows the same trend as for Gd-DOTA. Highest CE contribution is observed on nuclei with the smallest ωn 15N because smaller ωn approaches the width of the EPR signal, this is an additional requirement for CE DNP.
The field position for maximum DNP enhancement corresponding to Gd-DOTA, is used for DNP experiments on Ubiquitin with an attached Gd-tag as PA. The success of DNP on this sample illustrates the possibility of site-directed DNP with metal ions tags as PAs. As a perspective Gd-tags can be used to examine change in conformation of a protein that would give higher enhancements due to CE if two Gd(III) labeled domains are closer in space. In a separate project, Mn(II) (s=5/2) bound to the divalent site of a hammerhead ribozyme was used as a PA which resulted in the first demonstration of intra-complex DNP using an intrinsically bound metal ion PA.
Der Drömling ist mit einer Fläche von ca. 320 km2 das größte Feucht- und Niedermoorgebiet im deutschen Altpleistozän, das noch große geschlossene Niedermoorkomplexe aufweist. Das Gebiet ist Lebensraum zahlreicher seltener und vom Aussterben bedrohter Tier- und Pflanzenarten. Mit dem im Zuge der Kultivierung entstandenen umfangreichen Graben- und Stauanlagensystem und den historisch bedeutsamen Rimpau’schen Moordammkulturen ist die Drömlingsniederung zugleich eine einmalige Kulturlandschaft.
The title compound, C22H18N2O2, was derived from 1-(2-hydroxyphenyl)-3-(4-methoxyphenyl)propane-1,3-dione. The central pyrazole ring forms dihedral angles of 16.83 (5), 48.97 (4) and 51.68 (4)°, respectively, with the methoxyphenyl, phenyl and hydroxyphenyl rings. The crystal packing is stabilized by O-H...N hydrogen bonding. Key indicators: single-crystal X-ray study; T = 173 K; mean σ(C–C) = 0.002 Å; R factor = 0.037; wR factor = 0.096; data-to-parameter ratio = 17.0.
ATP-binding cassette (ABC) transporters, a superfamily of integral membrane proteins, catalyse the translocation of substrates across the cellular membrane by ATP hydrolysis. Here we demonstrate by nucleotide turnover and binding studies based on 31P solid-state NMR spectroscopy that the ABC exporter and lipid A flippase MsbA can couple ATP hydrolysis to an adenylate kinase activity, where ADP is converted into AMP and ATP. Single-point mutations reveal that both ATPase and adenylate kinase mechanisms are associated with the same conserved motifs of the nucleotide-binding domain. Based on these results, we propose a model for the coupled ATPase-adenylate kinase mechanism, involving the canonical and an additional nucleotide-binding site. We extend these findings to other prokaryotic ABC exporters, namely LmrA and TmrAB, suggesting that the coupled activities are a general feature of ABC exporters.
G-protein-coupled receptor (GPCR) expression is extensively studied in bulk cDNA, but heterogeneity and functional patterning of GPCR expression in individual vascular cells is poorly understood. Here, we perform a microfluidic-based single-cell GPCR expression analysis in primary smooth muscle cells (SMC) and endothelial cells (EC). GPCR expression is highly heterogeneous in all cell types, which is confirmed in reporter mice, on the protein level and in human cells. Inflammatory activation in murine models of sepsis or atherosclerosis results in characteristic changes in the GPCR repertoire, and we identify functionally relevant subgroups of cells that are characterized by specific GPCR patterns. We further show that dedifferentiating SMC upregulate GPCRs such as Gpr39, Gprc5b, Gprc5c or Gpr124, and that selective targeting of Gprc5b modulates their differentiation state. Taken together, single-cell profiling identifies receptors expressed on pathologically relevant subpopulations and provides a basis for the development of new therapeutic strategies in vascular diseases.
The re-emergence of tuberculosis in its present-day manifestations - single, multiple and extensive drug-resistant forms and as HIV-TB coinfections - has resulted in renewed research on fundamental questions such as the nature of the organism itself, Mycobacterium tuberculosis, the molecular basis of its pathogenesis, definition of the immunological response in animal models and humans, and development of new intervention strategies such as vaccines and drugs. Foremost among these developments has been the precise chemical definition of the complex and distinctive cell wall of M. tuberculosis, elucidation of the relevant pathways and underlying genetics responsible for the synthesis of the hallmark moieties of the tubercle bacillus such as the mycolic acid-arabinogalactan-peptidoglycan complex, the phthiocerol- and trehalose-containing effector lipids, the phosphatidylinositol-containing mannosides, lipomannosides and lipoarabinomannosides, major immunomodulators, and others. In this review, the laboratory personnel who have been the focal point of some to these developments review recent progress towards a comprehensive understanding of the basic physiology and functions of the cell wall of M. tuberculosis.
Seit 2000 ist die promovierte Geoökologin als Referatsleiterin in der Berliner Senatsverwaltung u.a. für die atomrechtliche Aufsichts- und Genehmigungsbehörde, die Katastrophenschutzbehörde, die Strahlenmessstelle Berlin und das Berliner Luftgütemessnetz zuständig. Seit 2010 ist Heike Kaupp stellvertretende Abteilungsleiterin der Abteilung Integrativer Umweltschutz. Sie ist Fellow des Mercator Science-Policy Fellowship-Programms an den Rhein-Main-Universitäten.
Background: Computed tomography (CT) low-dose (LD) imaging is used to lower radiation exposure, especially in vascular imaging; in current literature, this is mostly on latest generation high-end CT systems.
Purpose: To evaluate the effects of reduced tube current on objective and subjective image quality of a 15-year-old 16-slice CT system for pulmonary angiography (CTPA).
Material and Methods: CTPA scans from 60 prospectively randomized patients (28 men, 32 women) were examined in this study on a 15-year-old 16-slice CT scanner system. Standard CT (SD) settings were 100 kV and 150 mAs, LD settings were 100 kV and 50 mAs. Attenuation of the pulmonary trunk, various anatomic landmarks, and image noise were quantitatively measured; contrast-to-noise ratios (CNR) and signal-to-noise ratios (SNR) were calculated. Three independent blinded radiologists subjectively rated each image series using a 5-point grading scale.
Results: CT dose index (CTDI) in the LD series was 66.46% lower compared to the SD settings (2.49 ± 0.55 mGy versus 7.42 ± 1.17 mGy). Attenuation of the pulmonary trunk showed similar results for both series (SD 409.55 ± 91.04 HU; LD 380.43 HU ± 93.11 HU; P = 0.768). Subjective image analysis showed no significant differences between SD and LD settings regarding the suitability for detection of central and peripheral PE (central SD/LD, 4.88; intra-class correlation coefficients [ICC], 0.894/4.83; ICC, 0.745; peripheral SD/LD, 4.70; ICC, 0.943/4.57; ICC, 0.919; all P > 0.4).
Conclusion: The LD protocol, on a 15-year-old CT scanner system without current high-end hardware or post-processing tools, led to a dose reduction of approximately 67% with similar subjective image quality and delineation of central and peripheral pulmonary arteries.