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Der dokumentarische Blick. Bild- und Geschichtsproduktion bei Omer Fast, Walid Raad und Sven Johne
(2014)
Der dokumentarische Blick. Bild- und Geschichtsproduktion bei Omer Fast, Walid Raad und Sven Johne Eine staubige Straße in einer kargen Landschaft irgendwo im nirgendwo. Zwei Fahrzeuge. Ein blutüberströmter junger Mann auf der Rückbank in den Armen einer Frau. Die Frontscheibe ist zersplittert. Eine Szenerie, die sich in Gedanken leicht ausmalen lässt. Es spielt noch keine Rolle ob sie wahr ist oder Fiktion. Das Bild taucht vor dem inneren Auge auf, konstruiert aus ein paar Schlagworten. Die beschriebene Szene stammt aus der Videoarbeit The Casting von Omer Fast.
Unternehmen sind heutzutage nicht mehr nur Hersteller von Gebrauchsgegenständen. Ihr Firmenname und ihr Logo bedeuten für die Kunden mehr als die Kennzeichnung der hergestellten Produkte und ihre Bedeutung scheint über das bloße Verständnis von Markenprodukten als Statussymbole und Prestigeobjekte hinaus zu gehen. Wie sonst ist zu erklären, dass Menschen vor den Geschäften der Bekleidungskette „Abercrombie & Fitch“ Schlange stehen und lange Wartezeiten in Kauf nehmen, um sich Kleidung zu kaufen? Und warum sonst, musste dem Ansturm auf den Apple-Store in Peking beim Verkaufsstart des iPhone 4GS mit der Polizei entgegengewirkt werden?
"Tank man and Ai Weiwei" : die Stilisierung zu
Heldenfiguren durch massenmediale Echtzeitübertragung
(2014)
Heute herrscht ein Drang zur exzessiven Rationalität. Unterstrichen wird diese durch die unhaltbare Dokumentation des banalen Alltags. Bei Facebook, Twitter und anderen Netzwerken darf jeder mitverfolgen, was sein nebenan zum Beispiel im Urlaub auf Bali zum Frühstück gegessen hat. Erzählungen reichen nicht mehr aus, um zu beweisen, dass ein Ereignis geschehen ist. Erst durch Fotos werden Erlebnisse authentisch oder zumindest fühlt es sich für viele noch echter an. Videos werden bei Youtube hochgeladen und ganze Fotoalben auf Facebook für die “Freunde” bereit gestellt. Diverse Massenmedien werden genutzt, um Tatsachen aufzuzeigen, wie man es auch aus dem Fernsehen kennt. Es geht um die Wiedergabe tatsächlicher Geschehnisse. Das gilt sowohl für den Alltag als auch beispielsweise für politische Angelegenheiten. Zwischen nüchternen Nachrichten und Berichterstattungen ergibt sich ein Raum für die Sehnsüchte nach eher irrationalen Geschichten, Verschwörungstheorien und modernen Mythen. Kein Wunder, dass scheinbar unauffällige Alltagsfiguren durch Presse und Fernsehen manchmal zu Heldentypen stilisiert werden. Auf der Bühne politischer Ereignisse kommt es zu einer Zusammenarbeit von Journalismus und „Übermenschfiktionen“...
Der Werther-Effekt
(2014)
Die vorliegende Untersuchung spezialisiert sich auf das Thema des Suizids und listet dabei auserwählte prominente Persönlichkeiten auf, die ihrem Leben selbst ein Ende setzen wollten. Dabei soll besonders auf ein Phänomen eingegangen werden, das in der Wissenschaft allgemein unter dem „Werther-Effekt“ bekannt ist; eine seit Jahrhunderten beobachtete Häufung von Selbstmorden, denen immer der Suizid einer bekannten Persönlichkeit voran gegangen ist. Basierend auf den empirischen Untersuchungen von David Phillips, der einen kausalen Zusammenhang zwischen prominenten Suizidenten und Selbstmördern aus der Gesellschaft bestätigt hat, soll zunächst dargelegt werden, was genau unter dem „Werther-Effekt“ zu verstehen ist. In die Diskussion immer mit eingebunden ist die Rolle der Medien. Vorangestellt wird eine Erläuterung, die erklärt, warum diese Art Selbstmord „Werther-Effekt“ genannt wird. Anhand von vier berühmten Persönlichkeiten werden unterschiedliche Beispiele für den „Werther-Effekt“ dargestellt. Mit Marilyn Monroe als berühmteste und beliebteste Schauspielerin ihrer Zeit, zeigt sich inwieweit die Berichterstattung über ihren Tod durch die Medien zum Selbstmordantrieb für die normale Bevölkerung werden kann...
Migrant Mother
(2014)
Als die Photographin Dorothea Lange im März 1936 auf dem Weg zu ihrer Familie in San Francisco den Highway entlang fuhr, hätte sie wohl nicht damit gerechnet, gleich ein Jahrhundertfoto aufzunehmen. (Abb. 1) Sie hatte soeben einen einmonatigen Aufenthalt in Süd Kalifornien hinter sich und ihre Arbeit für die Resettlement Administration waren abgeschlossen. Sie war auf dem Weg nach Hause, als sie am Rande der Straße im Vorbeifahren ein Schild mit der Aufschrift „Pea-Pickers Camp“ sah erschien ihr dies nicht ungewöhnlich. Es war die Zeit der großen Depression, in der viele Menschen arbeitslos waren und auf der Suche nach Arbeit umher zogen. Daher waren solche Camps, in denen die Wanderarbeiter ihre Zelte und Baracken errichteten, nicht selten.
Schlagen wir an einem beliebigen Tag die Fernsehzeitung auf, begegnet uns auf mindestens einem Fernsehsender eine kriminalpathologische Serie. Die Faszination des Menschen am Tod lässt dieses Format wie Pilze aus dem Boden schießen. Doch woher kommt die Lust am Morbiden? Einen emotionalen Zusammenhang kann es nicht geben, da es sich nur um fiktive Personen handelt. Doch wenn die persönliche Trauer keine Rolle spielt, warum schauen sich dann so viele Menschen Leichen in Film und Fernsehen an? Vielleicht ist es die Angst vor dem Unbekannten, vor dem Tod, die uns dazu treibt. Der Mensch strebt auf diese Weise danach, Erfahrungen mit dem Tod zu sammeln, in dem er versucht den Objekten des Todes, also den Toten, nahe zu kommen. Es ist ein Versuch mit dem Unausweichlichen umzugehen. Doch finden wir den inszenierten Tod nicht nur im Abendprogramm des Privatfernsehens. Häufig begegnet er uns auch in den Nachrichten besonders detailreich, wenn es sich dabei um den Tod eines Machthabers handelt. Der inszenierte Tod begegnet uns zum Beispiel in den verschiedenen Aufnahmen von der Hinrichtung Sadam Husseins. Die Präsentation dieser Bilder in den Medien hat noch eine weitere Dimension und um die soll es in der vorliegenden Arbeit gehen...
Zwischen Perspektiven und Disziplinen: Ist das denn noch Kunstgeschichte? Alle reden von Bilderflut. Von einem täglichen stoßwellenartigen Einbrechen von Medienbildern aus Zeitung, Fernsehen, von Werbetafeln und aus dem Internet. In Fachkreisen hat sich der Begriff Iconic Turn durchgesetzt, die ikonische Wende der Bildnutzung und Untersuchung analog zum sprachwissenschaftlichen Modell des Linguistic Turn. Das Gefühl einer Überwältigung durch die Bilder der Massenmedien zeigt sich vor allem in der Überforderung, die unüberschaubare Bildmasse, die täglich auf den Betrachter einwirkt, zu erfassen und zu erschließen. Schuld ist aber nicht nur die große Menge an Bildmaterial, durch die das persönliche und das kollektive Bildgedächtnis stets erweitert werden - und das zum Großteil unbemerkt. Die Überforderung ergibt sich vor allem aus der Unfähigkeit, die Flut der hoch komplexen, teilweise wenig greifbaren Informationsgehalte des Gesehen zu filtern und zu verarbeiten...
Beim Durchblättern einer alten SPIEGEL-Ausgabe, die irgendwo herumlag, erregte ein Pressebild meine Aufmerksamkeit. Unter Mitteilungen war ein Photo zu sehen, das eine Person zeigte, die zum Sprung von einer Balkonbrüstung angesetzt hatte. Dieses Bild fesselte deshalb meinen Blick, weil dieser sich im Sprung befindende Mensch so gar nicht hineinpassen wollte in das mondäne, distinguierte Ambiente der Innenarchitektur. Als Fremdkörper störte er die klassizistische Fassade auf eine erhebliche, jedoch sehr leise Weise...
Die folgenden wissenschaftlichen Untersuchungen basieren auf dieser Fragestellung: Lassen sich die mit dem neuzeitlichen Medium der Videokamera dokumentierten Tsunamivideos mit den kunsthistorischen Abbildungen der biblischen Sintflut vergleichen? Und wenn ja, gibt es einen ikonographischen Zusammenhang zwischen den Bildern dieser augenscheinlich so konträren „Bildträgern“? Es ergeben sich somit zwei Themenschwerpunkte: Zum einen die Übertragung der beiden Tsunamis in Südasien und Japan durch das Kommunikationsmedium Handy und der Videokamera und die mit sich bringende Überlegung bezüglich der evozierten Emotionen durch diese neue Art der Dokumentation. Denn der Betrachter steht hilflos einer „Flut“ von Bildern gegenüber, die aus seinen eigenen Reihen kommen. Er sieht nicht mehr die für politische Zwecke oder von den Medien manipulierten Bilder, sondern Echtzeitzeugnisse menschlicher Schicksalsschläge und Ängste...
"The falling man"
(2014)
Der 11. September 2001 ist einer der meist dokumentierten Tage in der Geschichte. Auch über 10 Jahre danach gibt es noch zahlreiche Reportagen zu den Terroranschlägen im Fernsehen, Gedenkfeiern werden live und weltweit übertragen, Videos, Aufnahmen und dokumentierte Einzelschicksale in Endlosschleife gezeigt und wiederholt. Die Aufnahmen der Menschen, die in den besagten Stunden aus den obersten Stockwerken des World Trade Centers stürzten, fielen oder sprangen, blieben besonders in Erinnerung und stießen auf unterschiedlichste Reaktionen. Insgesamt wurde in den Medien von etwa 200 „Jumpers“ gesprochen. Ein Foto rückte dabei besonders in den Fokus des öffentlichen Interesses „The falling man“ (Abb.1) Eine Aufnahme aus einer Serie von 12 Fotografien (Abb.2)...
Am klaren sonnigen Tag des 11. Septembers 2001 entführen neunzehn Al-Quaida Terroristen vier Flugzeuge im amerikanischen Luftraum. Um 8:46 Uhr Ortszeit kracht der American Airlines Flug AA 11 in den Nordturm des World Trade Centers. An Bord des Flugzeuges befinden sich 81 Passagiere und elf Besatzungsmitglieder. Nur 18 Minuten später, um 09:03 Uhr, fliegt Flug UA 175 mit 65 Passagieren und 9 Besatzungsmitgliedern in den Südturm.1 Um 9:30 Uhr wird der Flug AA 77 mit 58 Passagieren und sechs Besatzungsmitgliedern in die Nordwestseite des Pentagons geleitet. Um 10:03 Uhr stürzt Flug UA 93 auf ein Feld in Pennsylvania. Letzteres geschah auf Grund eines Kampfes zwischen den Flugzeugentführern und mutigen Passagieren. Spekulationen zufolge sollte das Flugzeug ins Weiße Haus fliegen. In der Zwischenzeit, um 9:59 Uhr, beginnt bereits der Südturm des World Trade Centers einzustürzen, um 10:28 Uhr folgt der Nordturm...
Die Geschichte des Mondes und seiner wissenschaftliche Erschließung ist in einem wechselseitigen Verhältnis eng an die Entdeckung neuer Technologien sowie die Geschichte der Medien geknüpft. Ausgehend von der Entwicklung des Teleskops über die Entdeckung der Fotografie Mitte des 19. Jahrhunderts, bis hin zu den Sonden ab Mitte der 1950er Jahre kulminiert diese Entwicklung in der ersten bemannten Raumfahrt. Als Höhepunkt dieser Entwicklung setzen die Astronauten Neil Armstrong und Buzz Aldrin als erste Menschen am 20. Juli 19692 selbst den Fuß auf den Mond und dokumentieren dieses Ereignis fotografisch. Doch was kommt danach? Am 8. Juli 2011 wurde das Raumfahrtprogramm der NASA eingestellt. Weitere Reisen zum Mond wurden seit dem Apollo-Programm nicht mehr unternommen...
Betrachtet man das Phänomen des „embedded journalism“ kommt einem zwangsläufig die Frage nach der Nutzbarkeit des Kriegsjournalismus auf. Anfänglich muss zunächst der Grundgedanke des embedding aus gesellschaftlicher und politischer Sicht nachvollzogen werden. Das Konzept dieser Medienberichterstattung wurde von der USRegierung für den Irakkrieg beziehungsweise den dritten Golfkrieg 2003 vorgestellt mit dem anscheinend notwendigen Grund, eine objektive und transparente Kriegsberichterstattung für die Weltöffentlichkeit zu ermöglichen und somit das Einmarschieren einer Weltmacht in ein islamisches Land rechtfertigen zu können. Der damalige US-Präsident George W. Bush rechtfertigte den Krieg mit der Aussage, dass der irakische Diktator Saddam Hussein Massenvernichtungswaffen herstellen würde und mit der Terrororganisation Al Quaida in Verbindung stünde.2 Somit erklärte er nicht nur das irakische Oberhaupt zum Feind der USA, sondern ein ganzes Land zum Feind der freien und kapitalistischen Welt...
Walter Benjamin sah die Vergangenheit nicht in Geschichten, sondern „in Bildern zerfallen.“1 Wie kaum ein anderes Ereignis in der Moderne drückte sich der Vietnamkrieg in einer Vielzahl von Bildern aus und kann in diesem Zusammenhang als erster und in seiner Konsequenz vielleicht als einziger TV-Krieg in der Geschichte bezeichnet werden2. Im Gegensatz zu “klassischen Ikonen“ verankerten die elektronisch generierten Bilder des Krieges ihren Staus als Medienikone durch ihre Zirkulation im Medienapparat...
In einer fast unüberschaubaren Vielzahl von Quellen, allen voran das Internet, stehen uns heute Bildmaterialien zu allen gesellschaftspolitischen Ereignissen zur Verfügung. Hier entsteht die grundlegende Problematik der Bildquellennachweise, vor denen auch die Redaktion dieser Publikation stand. Immer und überall zugänglich, ist jedoch nicht immer klar: was ist zu belegen, wie sind sie zu belegen und wie ist zu verfahren, wenn es keinen Urheber/Quelle gibt oder dieser nicht (mehr) nachzuweisen ist? Die Autorinnen wollen an dieser Stelle jenes Dilemma nicht in Form von Gesetzestexten wiedergeben, sondern primär ein Bewusstsein dafür schaffen, wie man sich mit der freien Verfügbarkeit von Bildmaterialien auseinandersetzt und ihr begegnet. Es sollen vielmehr Fragen aufgeworfen werden die den Sachverhalt der Materie verdeutlichen. Im Einzelnen können hier nur einige Denkanstöße gegeben werden um auf die Problematik innerhalb des Bildurheberrechtsgesetzes aufmerksam zu machen...
„Alles, was wir über unsere Gesellschaft, ja über die Welt, in der wir leben, wissen, wissen wir durch die Massenmedien“ behauptet der Soziologe Niklas Luhmann. Die Medien fungieren demzufolge als Vermittler und Träger von Informationen.2 Die Abbilder unserer Umwelt erreichen uns täglich in den verschiedensten medialen Ausprägungen. Während vor rund 100 Jahren noch die Gazette oder das Radio diese Funktionen erfüllten und nach der Etablierung des Fernsehens ein relatives Gleichgewicht der Massenmedien hergestellt war, ersetzen heute überwiegend Nachrichtensendungen im Fernsehen, Online-Informationsangebote und sogar Applikationen auf Smartphones diese Art der Vermittlung. Ein erneuter Umbruch in der Nutzung der Medien ist seit der Etablierung des World Wide Web evident...
Als Anfang der 50er Jahre eine globale Krisensituation mit dem Aufkommen neuer Kommunikationstechnologien und der Entstehung einer konsumorientierten Massenkultur korrelierte, veranlasste die Bilderflut von Atomtests und Reklameaufnahmen den Soziologen Lewis Mumford zur Auseinandersetzung mit einem Diskurs, der erst in der jüngsten Zeit seinen vorläufigen Höhepunkt finden sollte...
This thesis is structured into 7 chapters:
• Chapter 2 gives an overview of the ultrashort high intensity laser interaction with matter. The laser interaction with an induced plasma is described, starting from the kinematics of single electron motion, followed by collective electron effects and the ponderamotive motion in the laser focus and the plasma transparency for the laser beam. The three different mechanisms prepared to accelerate and propagate electrons through matter are discussed. The following indirect acceleration of protons is explained by the Target Normal Sheath Acceleration (TNSA) mechanism. Finally some possible applications of laser accelerated protons are explained briefly.
• Chapter 3 deals with the modeling of geometry and field mapping of magnetic lens. Initial proton and electron distributions, fitted to PHELIX measured data are generated, a brief description of employed codes and used techniques in simulation is given, and the aberrations at the solenoid focal spot is studied.
• Chapter 4 presents a simulation study for suggested corrections to optimize the proton beam as a later beam source. Two tools have been employed in these suggested corrections, an aperture placed at the solenoid focal spot as energy selection tool, and a scattering foil placed in the proton beam to smooth the radial energy beam profile correlation at the focal spot due to chromatic aberrations. Another suggested correction has been investigated, to optimize the beam radius at the focal spot by lens geometry controlling.
• Chapter 5 presents a simulation study for the de-neutralization problem in TNSA caused by the fringing fields of pulsed magnetic solenoid and quadrupole. In this simulation, we followed an electrostatic model, wherethe evolution of both, self and mutual fields through the pulsed magnetic solenoid could be found, which is not the case in the quadrupole and only the growth of self fields could be found. The field mapping of magnetic elements is generated by the Matlab program, while the TraceWin code is employed to study the tracking through magnetic elements.
• Chapter 6 describes the PHELIX laser parameters at GSI with chirp pulse amplification technique (CPA), and Gafchromic Radiochromic film RCF) as a spatial energy resolver film detector. The results of experiments with laser proton acceleration, which were performed in two experimental areas at GSI (Z6 area and PHELIX Laser Hall (PLH)), are presented in section 6.3.
• Chapter 7 includes the main results of this work, conclusions and gives a perspective for future experimental activities.
Background: With increasing life expectancy the number of people affected by multimorbidity rises. Knowledge of factors associated with health-related quality of life in multimorbid people is scarce. We aimed to identify the factors that are associated with self-rated health (SRH) in aged multimorbid primary care patients.
Methods: Cross-sectional study with 3,189 multimorbid primary care patients aged from 65 to 85 years recruited in 158 general practices in 8 study centers in Germany. Information about morbidity, risk factors, resources, functional status and socio-economic data were collected in face-to-face interviews. Factors associated with SRH were identified by multivariable regression analyses.
Results: Depression, somatization, pain, limitations of instrumental activities (iADL), age, distress and Body Mass Index (BMI) were inversely related with SRH. Higher levels of physical activity, income and self-efficacy expectation had a positive association with SRH. The only chronic diseases remaining in the final model were Parkinson's disease and neuropathies. The final model accounted for 35% variance of SRH. Separate analyses for men and women detected some similarities; however, gender specific variation existed for several factors.
Conclusion: In multimorbid patients symptoms and consequences of diseases such as pain and activity limitations, as well as depression, seem to be far stronger associated with SRH than the diseases themselves. High income and self-efficacy expectation are independently associated with better SRH and high BMI and age with low SRH.
A 48 year old patient with dilated cardiomyopathy and chronic acne inversa underwent implantation of a LVAD system (Heartmate II, Thoratec, USA) March 2011. During 2011 and 2012 the patient was repeatedly readmitted for treatment of driveline infection with MRSA. Colonization was controlled with Linezolid and Rifampicin however reoccurred after discontinuation. In August 2012 the LVAD-system was exchanged due to pump dysfunction (HVAD, HeartWare Inc., USA). Postoperatively, the patient presented with ascites which secreted through the driveline exit. Consequently, the abdominal wall was surgically corrected to prevent exit of peritoneal fluid through the driveline, and the patient was discharged with sterile wound swabs. However 6 weeks after discharge the driveline exit wound started secreting pus showing abundant growth of multi resistant staphylococcus aureus (MRSA). With clinical signs of increasing liver failure with regular need for paracentesis, and clinical signs of local infection, a CT scan of the abdomen was performed revealing an enrichment of contrast medium along the driveline and an abscess-like formation on the abdominal wall. Patient was admitted receiving regular dose Daptomycin and Rifampicin. The latter was discontinued after ten days. The abscess, surrounding driveline exit and abdominal wall cavity was excised and vacuum treatment initiated. Total duration of Daptomycin therapy was 3 weeks. While first week skin and wound swabs were still positive for MRSA, all samples were sterile after the second week. Inflammation was monitored by leucocyte count and IL6. The secretion of pus along the driveline ceased, the wound cavity was closed subsequently. After discharge and stop of antibiotics skin and driveline swabs remained negative for MRSA (10 weeks).
Mechanics has an important role during morphogenesis, both in the generation of forces driving cell shape changes and in determining the effective material properties of cells and tissues. Drosophila dorsal closure has emerged as a reference model system for investigating the interplay between tissue mechanics and cellular activity. During dorsal closure, the amnioserosa generates one of the major forces that drive closure through the apical contraction of its constituent cells. We combined quantitation of live data, genetic and mechanical perturbation and cell biology, to investigate how mechanical properties and contraction rate emerge from cytoskeletal activity. We found that a decrease in Myosin phosphorylation induces a fluidization of amnioserosa cells which become more compliant. Conversely, an increase in Myosin phosphorylation and an increase in actin linear polymerization induce a solidification of cells. Contrary to expectation, these two perturbations have an opposite effect on the strain rate of cells during DC. While an increase in actin polymerization increases the contraction rate of amnioserosa cells, an increase in Myosin phosphorylation gives rise to cells that contract very slowly. The quantification of how the perturbation induced by laser ablation decays throughout the tissue revealed that the tissue in these two mutant backgrounds reacts very differently. We suggest that the differences in the strain rate of cells in situations where Myosin activity or actin polymerization is increased arise from changes in how the contractile forces are transmitted and coordinated across the tissue through ECadherin-mediated adhesion. Altogether, our results show that there is an optimal level of Myosin activity to generate efficient contraction and suggest that the architecture of the actin cytoskeleton and the dynamics of adhesion complexes are important parameters for the emergence of coordinated activity throughout the tissue.
The mitochondrial kinase PINK1 and the ubiquitin ligase Parkin are participating in quality control after CCCP- or ROSinduced mitochondrial damage, and their dysfunction is associated with the development and progression of Parkinson’s disease. Furthermore, PINK1 expression is also induced by starvation indicating an additional role for PINK1 in stress response. Therefore, the effects of PINK1 deficiency on the autophago-lysosomal pathway during stress were investigated. Under trophic deprivation SH-SY5Y cells with stable PINK1 knockdown showed downregulation of key autophagic genes, including Beclin, LC3 and LAMP-2. In good agreement, protein levels of LC3-II and LAMP-2 but not of LAMP-1 were reduced in different cell model systems with PINK1 knockdown or knockout after addition of different stressors. This downregulation of autophagic factors caused increased apoptosis, which could be rescued by overexpression of LC3 or PINK1. Taken together, the PINK1-mediated reduction of autophagic key factors during stress resulted in increased cell death, thus defining an additional pathway that could contribute to the progression of Parkinson’s disease in patients with PINK1 mutations.
Consequences of a human TRPA1 genetic variant on the perception of nociceptive and olfactory stimuli
(2014)
Background: TRPA1 ion channels are involved in nociception and are also excited by pungent odorous substances. Based on reported associations of TRPA1 genetics with increased sensitivity to thermal pain stimuli, we therefore hypothesized that this association also exists for increased olfactory sensitivity.
Methods: Olfactory function and nociception was compared between carriers (n = 38) and non-carriers (n = 43) of TRPA1 variant rs11988795 G.A, a variant known to enhance cold pain perception. Olfactory function was quantified by assessing the odor threshold, odor discrimination and odor identification, and by applying 200-ms pulses of H2S intranasal. Nociception was assessed by measuring pain thresholds to experimental nociceptive stimuli (blunt pressure, electrical stimuli, cold and heat stimuli, and 200-ms intranasal pulses of CO2).
Results: Among the 11 subjects with moderate hyposmia, carriers of the minor A allele (n = 2) were underrepresented (34 carriers among the 70 normosmic subjects; p = 0.049). Moreover, carriers of the A allele discriminated odors significantly better than non-carriers (13.161.5 versus 12.361.6 correct discriminations) and indicated a higher intensity of the H2S stimuli (29.2613.2 versus 21612.8 mm VAS, p = 0.006), which, however, could not be excluded to have involved a trigeminal component during stimulation. Finally, the increased sensitivity to thermal pain could be reproduced.
Conclusions: The findings are in line with a previous association of a human TRPA1 variant with nociceptive parameters and extend the association to the perception of odorants. However, this addresses mainly those stimulants that involve a trigeminal component whereas a pure olfactory effect may remain disputable. Nevertheless, findings suggest that future TRPA1 modulating drugs may modify the perception of odorants.
Background: Ribavirin (RBV) remains part of several interferon-free treatment strategies even though its mechanisms of action are still not fully understood. One hypothesis is that RBV increases responsiveness to type I interferons. Pegylated Interferon alpha (PEG-IFNa) has recently been shown to alter natural killer (NK) cell function possibly contributing to control of hepatitis C virus (HCV) infection. However, the effects of ribavirin alone or in combination with IFNa on NK cells are unknown.
Methods: Extensive ex vivo phenotyping and functional analysis of NK cells from hepatitis C patients was performed during antiviral therapy. Patients were treated for 6 weeks with RBV monotherapy (n = 11), placebo (n = 13) or PEG-IFNa-2a alone (n = 6) followed by PEG-IFNa/RBV combination therapy. The effects of RBV and PEG-IFNa-2a on NK cells were also studied in vitro after co-culture with K562 or Huh7.5 cells.
Results: Ribavirin monotherapy had no obvious effects on NK cell phenotype or function, neither ex vivo in patients nor in vitro. In contrast, PEG-IFNa-2a therapy was associated with an increase of CD56bright cells and distinct changes in expression profiles leading to an activated NK cell phenotype, increased functionality and decline of terminally differentiated NK cells. Ribavirin combination therapy reduced some of the IFN effects. An activated NK cell phenotype during therapy was inversely correlated with HCV viral load.
Conclusions: PEG-IFNa activates NK cells possibly contributing to virological responses independently of RBV. The role of NK cells during future IFN-free combination therapies including RBV remains to be determined.
It was long assumed that translation initiation in prokaryotes generally occurs via the so-called Shine Dalgarno (SD) mechanism. Recently, it became clear that translation initiation in prokaryotes is more heterogeneous. In the haloarchaeon Haloferax volcanii, the majority of transcripts is leaderless and most transcripts with a 5′-UTR lack a SD motif. Nevertheless, a bioinformatic analysis predicted that 20–30% of all genes are preceded by a SD motif in haloarchaea. To analyze the importance of the SD mechanism for translation initiation in haloarchaea experimentally the monocistronic sod gene was chosen, which contains a 5′-UTR with an extensive SD motif of seven nucleotides and a length of 19 nt, the average length of 5′UTRs in this organism. A translational fusion of part of the sod gene with the dhfr reporter gene was constructed. A mutant series was generated that matched the SD motif from zero to eight positions, respectively. Surprisingly, there was no correlation between the base pairing ability between transcripts and 16S rRNA and translational efficiency in vivo under several different growth conditions. Furthermore, complete replacement of the SD motif by three unrelated sequences did not reduce translational efficiency. The results indicate that H. volcanii does not make use of the SD mechanism for translation initiation in 5′-UTRs. A genome analysis revealed that while the number of SD motifs in 5′-UTRs is rare, their fraction within open reading frames is high. Possible biological functions for intragenic SD motifs are discussed, including re-initiation of translation at distal genes in operons.
Haloferax volcanii uses extracellular DNA as a source for carbon, nitrogen, and phosphorous. However, it can also grow to a limited extend in the absence of added phosphorous, indicating that it contains an intracellular phosphate storage molecule. As Hfx. volcanii is polyploid, it was investigated whether DNA might be used as storage polymer, in addition to its role as genetic material. It could be verified that during phosphate starvation cells multiply by distributing as well as by degrading their chromosomes. In contrast, the number of ribosomes stayed constant, revealing that ribosomes are distributed to descendant cells, but not degraded. These results suggest that the phosphate of phosphate-containing biomolecules (other than DNA and RNA) originates from that stored in DNA, not in rRNA. Adding phosphate to chromosome depleted cells rapidly restores polyploidy. Quantification of desiccation survival of cells with different ploidy levels showed that under phosphate starvation Hfx. volcanii diminishes genetic advantages of polyploidy in favor of cell multiplication. The consequences of the usage of genomic DNA as phosphate storage polymer are discussed as well as the hypothesis that DNA might have initially evolved in evolution as a storage polymer, and the various genetic benefits evolved later.
Background: It is not well established how psychosocial factors like social support and depression affect health-related quality of life in multimorbid and elderly patients. We investigated whether depressive mood mediates the influence of social support on health-related quality of life.
Methods: Cross-sectional data of 3,189 multimorbid patients from the baseline assessment of the German MultiCare cohort study were used. Mediation was tested using the approach described by Baron and Kenny based on multiple linear regression, and controlling for socioeconomic variables and burden of multimorbidity.
Results: Mediation analyses confirmed that depressive mood mediates the influence of social support on health-related quality of life (Sobel's p < 0.001). Multiple linear regression showed that the influence of depressive mood (beta = -0.341, p < 0.01) on health-related quality of life is greater than the influence of multimorbidity (beta = -0.234, p < 0.01).
Conclusion: Social support influences health-related quality of life, but this association is strongly mediated by depressive mood. Depression should be taken into consideration in research on multimorbidity, and clinicians should be aware of its importance when caring for multimorbid patients.
Ultraviolet-B (UVB)-induced inflammation produces a dose-dependent mechanical and thermal hyperalgesia in both humans and rats, most likely via inflammatory mediators acting at the site of injury. Previous work has shown that the gene expression of cytokines and chemokines is positively correlated between species and that these factors can contribute to UVB-induced pain. In order to investigate other potential pain mediators in this model we used RNA-seq to perform genome-wide transcriptional profiling in both human and rat skin at the peak of hyperalgesia. In addition we have also measured transcriptional changes in the L4 and L5 DRG of the rat model. Our data show that UVB irradiation produces a large number of transcriptional changes in the skin: 2186 and 3888 genes are significantly dysregulated in human and rat skin, respectively. The most highly up-regulated genes in human skin feature those encoding cytokines (IL6 and IL24), chemokines (CCL3, CCL20, CXCL1, CXCL2, CXCL3 and CXCL5), the prostanoid synthesising enzyme COX-2 and members of the keratin gene family. Overall there was a strong positive and significant correlation in gene expression between the human and rat (R = 0.8022). In contrast to the skin, only 39 genes were significantly dysregulated in the rat L4 and L5 DRGs, the majority of which had small fold change values. Amongst the most up-regulated genes in DRG were REG3B, CCL2 and VGF. Overall, our data shows that numerous genes were up-regulated in UVB irradiated skin at the peak of hyperalgesia in both human and rats. Many of the top up-regulated genes were cytokines and chemokines, highlighting again their potential as pain mediators. However many other genes were also up-regulated and might play a role in UVB-induced hyperalgesia. In addition, the strong gene expression correlation between species re-emphasises the value of the UVB model as translational tool to study inflammatory pain.
Hypoxia enhances the antiglioma cytotoxicity of b10, a glycosylated derivative of betulinic acid
(2014)
B10 is a glycosylated derivative of betulinic acid with promising activity against glioma cells. Lysosomal cell death pathways appear to be essential for its cytotoxicity. We investigated the influence of hypoxia, nutrient deprivation and current standard therapies on B10 cytotoxicity. The human glioma cell lines LN-308 and LNT-229 were exposed to B10 alone or together with irradiation, temozolomide, nutrient deprivation or hypoxia. Cell growth and viability were evaluated by crystal violet staining, clonogenicity assays, propidium iodide uptake and LDH release assays. Cell death was examined using an inhibitor of lysosomal acidification (bafilomycin A1), a cathepsin inhibitor (CA074-Me) and a short-hairpin RNA targeting cathepsin B. Hypoxia substantially enhanced B10-induced cell death. This effect was sensitive to bafilomycin A1 and thus dependent on hypoxia-induced lysosomal acidification. Cathepsin B appeared to mediate cell death because either the inhibitor CA074-Me or cathepsin B gene silencing rescued glioma cells from B10 toxicity under hypoxia. B10 is a novel antitumor agent with substantially enhanced cytotoxicity under hypoxia conferred by increased lysosomal cell death pathway activation. Given the importance of hypoxia for therapy resistance, malignant progression, and as a result of antiangiogenic therapies, B10 might be a promising strategy for hypoxic tumors like malignant glioma.
Treatment with inhibitors of the receptor tyrosine kinase FLT3 are currently studied as promising therapies in acute myeloid leukemia (AML). However, only a subset of patients benefit from these treatments and the presence of activating mutations within FLT3 can predict response to a certain extent only. ...
Background: Health Authorities recommend influenza vaccination of healthcare personnel (HCP) to decrease the transmission of influenza to vulnerable patients. Recent studies have almost exclusively used quantitative questionnaires in order to identify determinants of vaccination behaviour. Interviews enable HCP to express freely why they think they are (not) willing to get vaccinated against influenza.
Methods: By means of semi-structured one-on-one interviews with 123 Belgian, Dutch and German HCP, reasons for and against vaccination, experiences with influenza vaccination, intention to get vaccinated and possible barriers, as well as willingness to advice influenza vaccination to patients were investigated. Data were processed with QSR NVivo 8.0 and analysed using a combination of a deductive and a general inductive approach.
Results: Across countries, self-protection, patient protection, and protection of family members were reported as most important reasons to get vaccinated against influenza. Reasons to not get vaccinated against influenza were fear of side effects caused by the vaccine, a low risk-perception, the disbelief in the effectiveness of influenza vaccination, organizational barriers, misconceptions, and undefined negative emotions.
Conclusions: The social cognitive variables underlying the decision of HCP to get vaccinated against influenza (or not) seem to be similar in Belgium, Germany, and the Netherlands, even though some differences surfaced. A quantitative investigation of those social cognitive variables is needed in order to determine the importance of the social cognitive variables in explaining the intention to get vaccinated and the importance of the similarities and differences between countries that have been found in this study.
Poster presentation at 1st International Workshop on Odor Spaces.
Mice are exceptional in their ability to capture their chemical environment, mapping the olfactory world into a basic sensory representation with over one thousand different types of chemical sensors, that is, olfactory sensory neurons (OSNs). OSNs of each type converge in the olfactory bulb onto exclusive distinct physiological areas called glomeruli. The glomeruli constitute the first relay station of olfactory stimulus representation in the mouse brain. Thus, the stimulus induced glomerular input pattern spatially embodies an important part of the sensory representation in the olfactory bulb. Still, topographic organization principles (chemotopy, tunotopy) are under debate. One reason might be that investigation are, due to experimental limitations, only performed on stimuli sets in the size of one hundred odors. But this represents only a tiny snapshot of the vast amount of molecules in the olfactory world and topographic relationships might be disguised in the incomplete representation of molecular receptive ranges (MRR). Therefore we investigated the problem with the MOR18-2 glomerulus as point of reference: First we determined it's MRR. Then, based on a measurement set covering this MRR, we elucidated the topographic embedding. It shows that MOR18-2 is embedded in a hierarchy of patchy tunotopic domains.
Background: Chronic particulate matter (PM) exposure is correlated to various health effects, even at low amounts. WHO has defined PM concentration limits as daily and annual mean values which were made legally binding in the European Union. While many studies have focused on PM concentrations in special environments, little is known about the average PM- exposure for both employees and passengers in the German public transportation system.
Methods: Particulate matter (PM10, PM2.5, PM1) - concentrations were monitored for 30 minutes at 15 different areas in Frankfurt am Main with major public traffic. Maximum and mean concentrations and, as a surrogate for the inhaled dosage, the Area Under the Curve (AUC) for 15 minutes of exposure were calculated.
Results: The WHO limits for PM10 and PM2.5 were exceeded at nearly all times and areas. Highest maximum concentrations were found at underground stations, subterranean railway stations and subterranean shopping arcades with much lower values obtained at surface points. In one measurement at a surface test point smokers who neglected the non-smoking policy could be identified as a major cause for a at least temporary strong increase of PM-load as seen in high maximum values and normal averages.
Conclusions: Subterranean areas have high particulate matter contamination exceeding WHO limits. Improvement may be achieved by increased ventilation. Subterranean shops and kiosks, being workplaces with long term exposure, should be equipped with external air supply. The non- smoking policy of the "Deutsche Bahn" for public spaces should be enforced.
Die zentralen Objekte der Dissertation sind Translationsflächen. Dabei handelt es sich um Riemann’sche Flächen, die aus in die euklidische Ebene eingebetteten Polygonen durch Verkleben von parallelen gleichlangen Seiten entstehen. Zwei Translationsflächen sind gleich, wenn es möglich ist, die Polygone durch ”Zerschneiden und mittels Translationen neu Zusammenkleben“ ineinander zu überführen. Die Gruppe GL_2(R) operiert auf der Menge der Translationsflächen via der linearen Abbildungen auf den Polygonen. Der Stabilisator einer Translationsfläche X unter dieser Operation wird die Veech-Gruppe von X genannt und mit SL(X) bezeichnet. Die Veech-Gruppe ist eine diskrete Untergruppe von SL_2(R) und damit eine Fuchs’sche Gruppe.
Fuchs’sche Gruppen werden je nach ihrer Limesmenge in elementare und nicht-elementare Gruppen eingeteilt. Letztere wiederum unterteilt man in Gruppen erster oder zweiter Art. Fuchs’sche Gruppen mit endlichem co-Volumen heißen Gitter und sind genau die endlich erzeugten Gruppen erster Art. Translationsflächen, deren Veech-Gruppe ein Gitter ist, heißen Veech-Flächen und sind von besonderem Interesse, da für sie die Veech Alternative gilt.
Ein feineres Maß für die Größe einer Fuchs’schen Gruppe ist der kritische Exponent. Er ist definiert als das Infimum aller reellen Zahlen, für die die Poincaré Reihe konvergiert und liegt für alle unendlichen Fuchs’schen Gruppen zwischen 0 und 1. Hauptziel der Dissertation ist der Beweis von Theorem 1. Es gibt Translationsflächen, für die der kritische Exponent ihrer Veech-Gruppe echt zwischen 1/2 und 1 liegt.
Der kritische Exponent von elementaren Gruppen ist höchstens 1/2, Translationsflächen mit elementaren Veech-Gruppen sind also als Kandidaten für das Theorem ausgeschlossen. Der kritische Exponent von Gittern ist 1. Also scheiden auch Veech-Flächen für das Theorem aus.
Bis zum Jahr 2003 waren Gitter die einzigen bekannten nicht-elementaren Veech-Gruppen. McMullen klassifizierte die Veech-Flächen vom Geschlecht 2 und zeigte, dass jede solche Fläche, die nur eine Singularität besitzt, in der GL_2(R)-Bahn der Fläche L_D liegt, die aus einem L-förmigen Polygon mit geeigneten von D abhängigen Seitenlängen entsteht.
Während auch heute noch keine Translationsfläche mit Veech-Gruppe zweiter Art bekannt ist, fanden McMullen und unabhängig davon Hubert und Schmidt Konstruktionen unendlich erzeugter Veech-Gruppen erster Art. Eine Abschätzung des kritischen Exponenten dieser Gruppen war 10 Jahre lang eine wichtige offene Frage, die nun durch Theorem 1 beantwortet wird.
Zentral in der Konstruktion von Hubert und Schmidt sind spezielle Punkte, nämlich Verbindungspunkte. Hubert und Schmidt konstruieren Translationsflächen, deren Veech-Gruppen kommensurabel zum Stabilisator SL(X;P) von P sind und damit den gleichen kritischen Exponenten haben. Für Verbindungspunkte mit unendlicher SL(X)- Bahn (diese Punkte heißen nicht-periodisch) ist SL(X;P) unendlich erzeugt und von erster Art.
Wir zeigen Theorem 1, indem wir zeigen, dass für jedes D kongruent 0 mod 4, (kein Quadrat), und jeden nicht-periodischen Verbindungspunkt P in L_D der kritische Exponent der Gruppe SL(L_D;P) echt zwischen 1/2 und 1 liegt.
Eine natürliche Frage in diesem Zusammenhang ist die Abhängigkeit von P: Punkte Q in der SL(L_D)-Bahn von P sind auch er nicht-periodische Verbindungspunkte und die zugehö̈rigen Gruppen SL(L_D;P) und SL(L_D;Q) sind konjugiert zueinander. Daher widmen wir uns in Kapitel 4 der Bestimmung der Bahnen nicht-periodischer Verbindungspunkte.
Die Verbindungspunkte haben die Form P=(x_r+x_iw;y_r+y_iw) mit x_r,x_i,y_r,y_i aus Q. Wir zeigen, dass der Hauptnenner N(P) dieser (gekürzten) Brüche eine Invariante der Bahn ist. Daraus folgt:
Theorem 2. Es gibt unendlich viele verschiedene Bahnen von Verbindungspunkten von L_D.
Wir kennen die Operation der horizontalen und der vertikalen Scherungen A und B aus SL(L_D). Im Spezialfall D=8 erzeugen diese beiden Elemente die ganze Gruppe und wir geben je ein Verfahren an, um eine untere und eine obere Schranke an die Anzahl der Bahnen von nicht-periodischen Verbindungspunkten P mit fixiertem Hauptnenner N(P) zu finden. Damit zeigen wir:
Theorem 3. Die Menge der Verbindungspunkte P mit festem Wert N(P) zerfällt in eine endliche Anzahl von SL(L_8)-Bahnen.
Im Beweis von Theorem 1 ist es nötig, die Nicht-Mittelbarkeit eines Graphen zu zeigen. Da wir nur sehr wenige Informationen über dessen Struktur in unserer konkreten Situation haben, entwickeln wir in Kapitel 1 die folgende Methode:
Theorem 4. Sei G ein Graph, den man durch Weglassen von Kanten in einen Wald G′ ohne Blätter überführen kann, bei dem das Supremum der Längen von zusammenhängenden Valenz-2-Teilgraphen von G′ beschränkt ist. Dann ist G nicht mittelbar.
Um diese Methode anzuwenden, ordnen wir jeder Ecke P von G ein Komplexitätsmaß s(P) zu und weisen nach, dass dieser Wert für die Operation von Worten in A- und B-Potenzen mit wachsender Wortlänge ”tendenziell wächst“.
Die Arbeit „Zwischen Kooperation und Wetteifer – Interaktionen und mediale Organisation von Kreativität am Beispiel des koopetitiven Ideennetzwerks jovoto“ untersucht internetbasierte Kokreativität – die gemeinsame Ideenentwicklung im Mediennetzwerk. Im Unterschied zu vorangegangen Untersuchungen, die sich mit den Motiven für die häufig unentgeltlichen kokreativen Aktivitäten und dem Innovationspotential dieser Organisationsform beschäftigten, liegt der Fokus dieser Studie auf der Kommunikation der Akteure untereinander während der Kokreation. Als Fallbeispiel wird die Design-Ideenplattform jovoto ausgewählt, die Kreativität auf der Basis von Koopetition – der Gleichzeitigkeit von Kooperation und Wettbewerb – unter den Teilnehmern fördert. Die Ideenautoren im Netzwerk von jovoto entwickeln kreative Lösungen in den Bereichen Produktdesign, Kampagnen, Innovation und Architektur. Die Teilnehmer treten mit ihren Ideen im Wettbewerb gegeneinander an; gleichzeitig kommentieren und bewerten sie sich gegenseitig im Prozess der Ideenentwicklung. Aus den Bewertungen der Community ergeben sich die Gewinner des ausgeschriebenen Preisgeldes. Aus dieser Gleichzeitigkeit von Wettbewerb und Kooperation ergibt sich die Forschungsfrage dieser Untersuchung: Wie ist das Verhältnis zwischen Kooperation und Wettbewerb im Kokreationsnetzwerk jovoto bestimmt, und wie wirkt dies auf Kreativität? Um diese Frage zu beantworten, untersuche ich die auf der Plattform dokumentierten Interaktionen (Kommentar-Threads) zwischen den Ideenentwicklern und anderen Community-Mitgliedern mit qualitativen und quantitativen Methoden und analysiere zwanzig von mir geführte halbstrukturierte Leitfaden-Interviews mit den Ideenautoren auf jovoto. Zur theoretischen Einordnung der beobachteten Phänomene stütze ich mich sowohl auf Kultur- und Kommunikationstheorien des radikal-konstruktivistischen Erkenntnismodells als auch auf die kulturellen Spieltheorien von Johan Huizinga und Roger Caillois. Ich beziehe zudem Ansätze ein, die Kokreativität als eine Form der kulturellen Produktivität beschreiben. Einen weiteren Anhaltspunkt bilden Studien, die sich mit der produktiven Beziehung zwischen Kooperation und Wettbewerb auseinandersetzen. Ergänzt werden diese Erkenntnisse bspw. durch die These zur Intelligenz der Crowd in heterogenen Gruppen von Entscheidern und durch Untersuchungen zum positiven Einfluss von Differenzen und Konflikten auf die Gruppenkreativität. Ich führe diese Vorarbeiten zu einer Modellvorstellung zusammen: In dieser verknüpft der koopetitive Handlungskontext ein Kooperationsspiel mit einem Wettbewerbsspiel, und zwar mithilfe von Kreativität: Diese ermöglicht, dass der Fokus im Spiel – von der Betonung und Vergrößerung des Gemeinsamen zwischen den Teilnehmern zur Betonung ihrer Differenzen – wechseln kann. Hieraus leite ich Hypothesen ab, die ich empirisch überprüfe: Während einer sechsmonatigen Beobachtung des Plattformgeschehens habe ich Daten zu 135 Wettbewerben auf jovoto erhoben. Die Analyse von über 2.400 Kommentaren ergibt, dass die beiden Leitkategorien „Bestätigung“ und „Herausforderung“ das kokreative Kommunikationsgeschehen charakterisieren. Hiervon ausgehende qualitative und quantitative Untersuchungen zu 54 Diskussions-Threads ergeben: In der Platzierung erfolgreiche Ideen werden von intensiveren Diskussionen begleitet als weniger erfolgreiche. Bemerkenswert ist, dass sie nicht nur eine größere Zahl bestätigender Kommentare erhalten, sondern auch mehr Herausforderungen. Die im Schnitt höchste Punktzahl geht mit einem Verhältnis von rund acht Bestätigungen je Herausforderung einher. Dieses Ergebnis bestätigt die Ausgangshypothese, dass es sich bei den Ideenwettbewerben um ein Kommunikationsspiel mit kooperativer, wetteifernder und kreativer Komponente handelt: In den Interaktionen zu den Ideenbeiträgen, insbesondere den erfolgreichen, herrscht ein Wechsel zwischen Bestätigungen und Herausforderungen vor. Aus den Aussagen der Ideenautoren in den geführten Interviews wird ein zentraler Konflikt deutlich: Die Tätigkeit bringt einen hohen Aufwand und wenig Aussicht auf Gewinn mit sich. Unterm Strich scheint sie jedoch lohnenswert, da die Akteure wichtige Lernerfahrungen im Netzwerk sammeln können und die eigenen Fähigkeiten einzuschätzen lernen. Dass die kreativen Beiträge anderer Wettbewerbsteilnehmer von anderen rege diskutiert werden, belegt den Erfolg des Organisationsmodells der Kokreation. Dieser verhält sich konträr zu den Vorhersagen herkömmlicher ökonomischer Theorie, die rein eigennützige Akteure annimmt, und deutet auf die Relevanz von Theorien hin, die wechselseitiges Feedback und dessen Gratifikationen als Faktoren in der netzwerkbasierte Produktion zentral berücksichtigen.
Gerichtliche und nicht gerichtliche Konfliktlösung in zivilrechtlichen Streitigkeiten – Deutschland
(2014)
Das Arbeitspapier zeigt die Entwicklung des deutschen Zivilprozessrechts von der Preußischen Allgemeinen Gerichtsordnung von 1795 an bis zum aktuellen Zivilprozessrecht auf. Schwerpunkte sind die Rezeption des französischen Zivilprozessrechts von 1806, die Vereinheitlichung des deutschen Zivilprozessrechts durch die ZPO (1877/98) und die Prozessrechtsreformen der Weimarer Zeit und der NS-Zeit. Ausführlich behandelt wird die zivilprozessuale Reformdiskussion in der NS-Zeit (Akademie für Deutsches Recht; 1934-1943) und in der Frühzeit der Bundesrepublik Deutschland. Weitere Themen des Arbeitspapiers sind der (obligatorische) Güteversuch durch das Gericht, das schiedsrichterliche Verfahren, das außergerichtliche Güteverfahren vor einem Schiedsmann und die außergerichtliche Streitbeilegung durch Gütestellen und die Mediation (1980-2012).
Acute kidney injury (AKI) is one of the most important complications in hospitalized patients and its pathomechanisms are not completely elucidated. We hypothesize that signaling via toll-like receptor (TLR)-3, a receptor that is activated upon binding of double-stranded nucleotides, might play a crucial role in the pathogenesis of AKI following ischemia and reperfusion (IR). Male adult C57Bl6 wild-type (wt) mice and TLR-3 knock-out (-/-) mice were subjected to 30 minutes bilateral selective clamping of the renal artery followed by reperfusion for 30 min 2.5h and 23.5 hours or subjected to sham procedures. TLR-3 down-stream signaling was activated already within 3 h of ischemia and reperfusion in post-ischemic kidneys of wt mice lead to impaired blood perfusion followed by a strong pro-inflammatory response with significant neutrophil invasion. In contrast, this effect was absent in TLR-3-/- mice. Moreover, the quick TLR-3 activation resulted in kidney damage that was histomorphologically associated with significantly increased apoptosis and necrosis rates in renal tubules of wt mice. This finding was confirmed by increased kidney injury marker NGAL in wt mice and a better preserved renal perfusion after IR in TLR-3-/- mice than wt mice. Overall, the absence of TLR-3 is associated with lower cumulative kidney damage and maintained renal blood perfusion within the first 24 hours of reperfusion. Thus, we conclude that TLR-3 seems to participate in the pathogenesis of early acute kidney injury.
Vasointestinal peptide metabolism plays a key physiological role in multimodular levels of vasodilatory, smooth muscle cell proliferative, parenchymal, and inflammatory lung reactions. In animal studies, vasointestinal peptide relaxes isolated pulmonary arterial segments from several mammalian species in vitro and neutralizes the pulmonary vasoconstrictor effect of endothelin. In some animal models, it reduces pulmonary vascular resistance in vivo and in monocrotaline-induced pulmonary hypertension. A 58-year-old woman presented with dyspnea and mild edema of the lower extremities. A bronchoscopy was performed without any suspicious findings suggesting a central tumor or other infiltrative disease. Endobronchial ultrasound revealed enlarged pulmonary arteries containing thrombi, a few enlarged lymph nodes, and enlarged mediastinal tissue anatomy with suspicion for mediastinal infiltration of a malignant process. We estimated that less than 10% of the peripheral vascular bed of the lung was involved in direct consolidated fibrosis as demonstrated in the left upper lobe apex. Further, direct involvement of fibrosis around the main stems of the pulmonary arteries was assumed to be low from positron emission tomography and magnetic resonance imaging scans. Assuming a positive influence of low-dose radiation, it was not expected that this could have reduced pulmonary vascular resistance by over two thirds of the initial result. However; it was noted that this patient had idiopathic pulmonary arterial hypertension mixed with "acute" (mediastinal) fibrosis which could have contributed to the unexpected success of reduction of pulmonary vascular resistance. To the best of our knowledge, this is the first report of successful treatment of idiopathic pulmonary arterial hypertension, probably as a result of low-dose radiation to the pulmonary arterial main stems. The patient continues to have no specific complaints concerning her idiopathic pulmonary arterial hypertension.
Background: Anemia is a common condition in the elderly and a significant risk factor for increased morbidity and mortality, reducing not only functional capacity and mobility but also quality of life. Currently, few data are available regarding anemia in hospitalized geriatric patients. Our retrospective study investigated epidemiology and causes of anemia in 405 hospitalized geriatric patients.
Methods: Data analysis was performed using laboratory parameters determined during routine hospital admission procedures (hemoglobin, ferritin, transferrin saturation, C-reactive protein, vitamin B12, folic acid, and creatinine) in addition to medical history and demographics.
Results: Anemia affected approximately two-thirds of subjects. Of 386 patients with recorded hemoglobin values, 66.3% were anemic according to WHO criteria, mostly (85.1%) in a mild form. Anemia was primarily due to iron deficiency (65%), frequently due to underlying chronic infection (62.1%), or of mixed etiology involving a combination of chronic disease and iron deficiency, with absolute iron deficiency playing a comparatively minor role.
Conclusion: Greater awareness of anemia in the elderly is warranted due to its high prevalence and negative effect on outcomes, hospitalization duration, and mortality. Geriatric patients should be routinely screened for anemia and etiological causes of anemia individually assessed to allow timely initiation of appropriate therapy.
Background: Acute leukemia in early age (EAL) is characterized by acquired genetic alterations such as MLL rearrangements (MLL-r). The aim of this case-controlled study was to investigate whether single nucleotide polymorphisms (SNPs) of IKZF1, ARID5B, and CEBPE could be related to the onset of EAL cases (<24 months-old at diagnosis).
Methods: The SNPs (IKZF1 rs11978267, ARID5B rs10821936 and rs10994982, CEBPE rs2239633) were genotyped in 265 cases [169 acute lymphoblastic leukemia (ALL) and 96 acute myeloid leukaemia (AML)] and 505 controls by Taqman allelic discrimination assay. Logistic regression was used to evaluate the association between SNPs of cases and controls, adjusted on skin color and/or age. The risk was determined by calculating odds ratios (ORs) with 95% confidence interval (CI).
Results: Children with the IKZF1 SNP had an increased risk of developing MLL-germline ALL in white children. The heterozygous/mutant genotype in ARID5B rs10994982 significantly increased the risk for MLL-germline leukemia in white and non-white children (OR 2.60, 95% CI: 1.09-6.18 and OR 3.55, 95% CI: 1.57-8.68, respectively). The heterozygous genotype in ARID5B rs10821936 increased the risk for MLL-r leukemia in both white and non-white (OR 2.06, 95% CI: 1.12-3.79 and OR 2.36, 95% CI: 1.09-5.10, respectively). Furthermore, ARID5B rs10821936 conferred increased risk for MLL-MLLT3 positive cases (OR 7.10, 95% CI:1.54-32.68). Our data do not show evidence that CEBPE rs2239633 confers increased genetic susceptibility to EAL.
Conclusions: IKZF1 and CEBPE variants seem to play a minor role in genetic susceptibility to EAL, while ARID5B rs10821936 increased the risk of MLL-MLLT3. This result shows that genetic susceptibility could be associated with the differences regarding MLL breakpoints and partner genes.
Background: In Germany, about 20% of the total population have a migration background. Differences exist between migrants and non-migrants in terms of health care access and utilisation. Colorectal cancer is the second most common malignant tumour in Germany, and incidence, staging and survival chances depend, amongst other things, on ethnicity and lifestyle. The current study investigates whether stage at diagnosis differs between migrants and non-migrants with colorectal cancer in an area of high migration and attempts to identify factors that can explain any differences.
Methods/Design: Data on tumour and migration status will be collected for 1,200 consecutive patients that have received a new, histologically verified diagnosis of colorectal cancer in a high migration area in Germany in the previous three months. The recruitment process is expected to take 16 months and will include gastroenterological private practices and certified centres for intestinal diseases. Descriptive and analytical analysis will be performed: the distribution of variables for migrants versus non-migrants and participants versus non-participants will be analysed using appropriate χ2-, t-, F- or Wilcoxon tests. Multivariable, logistic regression models will be performed, with the dependent variable being the dichotomized stage of the tumour (UICC stage I versus more advanced than UICC stage I). Odds ratios and associated 95%-confidence intervals will be calculated. Furthermore, ordered logistic regression models will be estimated, with the exact stage of the tumour at diagnosis as the dependent variable. Predictors used in the ordered logistic regression will be patient characteristics that are specific to migrants as well as patient characteristics that are not. Interaction models will be estimated in order to investigate whether the effects of patient characteristics on stage of tumour at the time of the initial diagnosis is different in migrants, compared to non-migrants.
Discussion: An association of migration status or other socioeconomic variables with stage at diagnosis of colorectal cancer would be an important finding with respect to equal health care access among migrants. It would point to access barriers or different symptom appraisal and, in the long term, could contribute to the development of new health care concepts for migrants.
Trial registration: German Clinical Trials Register DRKS00005056.
Background: Multimorbidity is a common phenomenon in primary care. Until now, no clinical guidelines for multimorbidity exist. For the development of these guidelines, it is necessary to know whether or not patients are aware of their diseases and to what extent they agree with their doctor. The objectives of this paper are to analyze the agreement of self-reported and general practitioner-reported chronic conditions among multimorbid patients in primary care, and to discover which patient characteristics are associated with positive agreement.
Methods: The MultiCare Cohort Study is a multicenter, prospective, observational cohort study of 3,189 multimorbid patients, ages 65 to 85. Data was collected in personal interviews with patients and GPs. The prevalence proportions for 32 diagnosis groups, kappa coefficients and proportions of specific agreement were calculated in order to examine the agreement of patient self-reported and general practitioner-reported chronic conditions. Logistic regression models were calculated to analyze which patient characteristics can be associated with positive agreement.
Results: We identified four chronic conditions with good agreement (e.g. diabetes mellitus κ = 0.80;PA = 0,87), seven with moderate agreement (e.g. cerebral ischemia/chronic stroke κ = 0.55;PA = 0.60), seventeen with fair agreement (e.g. cardiac insufficiency κ = 0.24;PA = 0.36) and four with poor agreement (e.g. gynecological problems κ = 0.05;PA = 0.10).Factors associated with positive agreement concerning different chronic diseases were sex, age, education, income, disease count, depression, EQ VAS score and nursing care dependency. For example: Women had higher odds ratios for positive agreement with their GP regarding osteoporosis (OR = 7.16). The odds ratios for positive agreement increase with increasing multimorbidity in almost all of the observed chronic conditions (OR = 1.22-2.41).
Conclusions: For multimorbidity research, the knowledge of diseases with high disagreement levels between the patients' perceived illnesses and their physicians' reports is important. The analysis shows that different patient characteristics have an impact on the agreement. Findings from this study should be included in the development of clinical guidelines for multimorbidity aiming to optimize health care. Further research is needed to identify more reasons for disagreement and their consequences in health care.
A third Supplement to the 1992 Catalog of the Scolytidae and Platypodidae (Coleoptera) of the World (Wood and Bright 1992) is presented. This Supplement updates the taxonomy, distribution, and biology pertaining to these families of Coleoptera from 2000 to the end of 2010. A few 2011 taxonomic references are included in order to make the nomenclature as current as possible. The format of this Supplement differs slightly from the format of the original 1992 Catalog and the two previous Supplements. Only references relating to general biology, systematics and distribution were selected to be included. Tribal arrangement follows the scheme established in the 1992 World Catalog, with additions. Each genus is listed alphabetically under the current tribe and the species are listed alphabetically under the current genus. Additional information on figures, distribution, hosts, and references relating to the above are given. The bibliography used with this Supplement lists 580 references, most published from 2000 to the end of 2010. New synonymy proposed: Phloeotribus carinatus Burgos and Equihua, 2003 (= Phloeotribus ebeneus Wood, 2007). New combinations proposed: Phloeosinus kinabaluensis Bright to Hyledius; Phloeosinus phyllocladus Bright to Hyledius.
An argument is made for the retention of the family status of the Scolytidae and Platypodidae as members of the superfamily Curculionoidea. A new subfamily and tribal arrangement is proposed: SCOLYTIDAE comprising 13 subfamilies, Hylesininae, with 12 tribes, Hyorrhynchinae, with one tribe; Scolytinae, with one tribe; Hexacolinae, with one tribe; Cylindrobrotinae, with one tribe; Scolytoplatypodinae, with one tribe; Cactopininae, with one tribe; Carphodicticinae, with one tribe; Micracidinae, with one tribe; Crypturginae, with one tribe; Ipinae, with six tribes; Cryphalinae, with one tribe and Corthylinae, with two tribes and PLATYPODIDAE comprising three subfamilies, Coptonotinae, with three tribes; Tesserocerinae, with two tribes and Platypodinae, with one tribe.
The term compensation is widely used in every-day language, in psychological research, and also discussed in the context of Attention Deficit Hyperactivity Disorder (ADHD). However, few studies have looked at psychological compensation in ADHD systematically and theory based. Compensation can be inferred if a deficit (i.e., a mismatch between skill and environmental demand) is counterbalanced by the investment of more effort, the utilization of latent or the acquisition of new skills. Based on the application of a theoretical framework (Bäckman & Dixon, 1992) to ADHD, I developed the following aims: (1) To reassess the awareness of deficits in ADHD and (2) to explore psychological compensation in a group with ADHD that accomplishes high achievement.
The results of Study 1 showed that children with ADHD did not overestimate their own skills compared to a group matched for academic achievement. In Study 2, college students with ADHD reported higher achievement motivation compared to college students without ADHD. Furthermore, results indicated that women with ADHD compensate by adopting compensatory effort and obsessive-compulsive behavior. Study 3 showed that female college students compensate for possible deficits in solving a flanker task by being overly cautious, which may reflect more obsessive-compulsive behavior.
The studies are discussed within the framework of psychological compensation. They add to the understanding of compensation in ADHD by (1) the reassessment of awareness of deficits in ADHD by including a group without ADHD but with low achievement, and by (2) suggesting that overly cautious behavior could be a form of psychological compensation in females with ADHD enabling them to enter college, leading to a late diagnosis and to good performance in cognitive tasks (i.e., flanker task).
Limitations are, that I did not test all components of the theoretical framework in one study and that I did not include adults with ADHD that did not enter college in Study 2 and 3 to test if achievement motivation or overly cautious behavior explains why some adults with ADHD gain admittance to higher education and show good performance in cognitive tasks and others do not.
Background: Health-related and disease-specific quality of life (HRQoL) has been increasingly valued as relevant clinical parameter in cystic fibrosis (CF) clinical care and clinical trials. HRQoL measures should assess – among other domains – daily functioning from a patient’s perspective. However, validation studies for the most frequently used HRQoL questionnaire in CF, the Cystic Fibrosis Questionnaire (CFQ), have not included measures of physical activity or fitness. The objective of this study was, therefore, to determine the cross-sectional and longitudinal relationships between HRQoL, physical activity and fitness in patients with CF.
Methods: Baseline (n = 76) and 6-month follow-up data (n = 70) from patients with CF (age ≥12 years, FEV1 ≥35%) were analysed. Patients participated in two multi-centre exercise intervention studies with identical assessment methodology. Outcome variables included HRQoL (German revised multi-dimensional disease-specific CFQ (CFQ-R)), body composition, pulmonary function, physical activity, short-term muscle power, and aerobic fitness by peak oxygen uptake and aerobic power.
Results: Peak oxygen uptake was positively related to 7 of 13 HRQoL scales cross-sectionally (r = 0.30-0.46). Muscle power (r = 0.25-0.32) and peak aerobic power (r = 0.24-0.35) were positively related to 4 scales each, and reported physical activity to 1 scale (r = 0.29). Changes in HRQoL-scores were directly and significantly related to changes in reported activity (r = 0.35-0.39), peak aerobic power (r = 0.31-0.34), and peak oxygen uptake (r = 0.26-0.37) in 3 scales each. Established associates of HRQoL such as FEV1 or body mass index correlated positively with fewer scales (all 0.24 < r < 0.55).
Conclusions: HRQoL was associated with physical fitness, especially aerobic fitness, and to a lesser extent with reported physical activity. These findings underline the importance of physical fitness for HRQoL in CF and provide an additional rationale for exercise testing in this population.
Trial registration: ClinicalTrials.gov, NCT00231686
pH and Na+ homeostasis in all cells requires Na+/H+ antiporters. The crystal structure, obtained at pH 4, of NhaA, the main antiporter of Escherichia coli, has provided general insights into an antiporter mechanism and its unique pH regulation. Here, we describe a general method to select various NhaA mutants from a library of randomly mutagenized NhaA. The selected mutants, A167P and F267C are described in detail. Both mutants are expressed in Escherichia coli EP432 cells at 70–95% of the wild type but grow on selective medium only at neutral pH, A167P on Li+ (0.1 M) and F267C on Na+ (0.6 M). Surprising for an electrogenic secondary transporter, and opposed to wild type NhaA, the rates of A167P and F267C are almost indifferent to membrane potential. Detailed kinetic analysis reveals that in both mutants the rate limiting step of the cation exchange cycle is changed from an electrogenic to an electroneutral reaction.
Background: Diabetes mellitus and thyroid diseases frequently coexist. In order to evaluate how thyroid disorders interfere with glycemic control, we analysed insulin-treated type 2 diabetes patients with thyroid disease.
Methods: Diabetes patients (n = 1.957) were retrospectively investigated. We focused on type 2 diabetes patients who had been admitted for insulin-treatment and diagnosed thyroid diseases (n = 328). Patients were divided into three groups according to thyroid disease manifestation in relation to diabetes onset: prior to (group 1), same year (group 2) and thyroid disease following diabetes (group 3).
Results: Out of all diabetes patients 27.3% had a thyroid disorder with more women (62.2%) being affected (p < 0.001). Thyroid disease was predominantly diagnosed after diabetes onset. Patients with type 2 diabetes and prior appearance of thyroid disease required insulin therapy significantly earlier (median insulin-free period: 2.5 yrs; Q1 = 0.0, Q3 = 8.25) compared to patients who had thyroid dysfunction after diabetes onset (median insulin-free period: 8.0 yrs; Q1 = 3.0, Q3 = 12.0; p < 0.001). Age at diabetes onset correlated with insulin-free period (p < 0.001).
Conclusions: Thyroid disease may be a marker of a distinct metabolic trait in type 2 diabetes potentially requiring earlier insulin treatment.
Synaptic dysfunction and synapse loss are key features of Alzheimer's pathogenesis. Previously, we showed an essential function of APP and APLP2 for synaptic plasticity, learning and memory. Here, we used organotypic hippocampal cultures to investigate the specific role(s) of APP family members and their fragments for dendritic complexity and spine formation of principal neurons within the hippocampus. Whereas CA1 neurons from APLP1-KO or APLP2-KO mice showed normal neuronal morphology and spine density, APP-KO mice revealed a highly reduced dendritic complexity in mid-apical dendrites. Despite unaltered morphology of APLP2-KO neurons, combined APP/APLP2-DKO mutants showed an additional branching defect in proximal apical dendrites, indicating redundancy and a combined function of APP and APLP2 for dendritic architecture. Remarkably, APP-KO neurons showed a pronounced decrease in spine density and reductions in the number of mushroom spines. No further decrease in spine density, however, was detectable in APP/APLP2-DKO mice. Mechanistically, using APPsalpha-KI mice lacking transmembrane APP and expressing solely the secreted APPsalpha fragment we demonstrate that APPsalpha expression alone is sufficient to prevent the defects in spine density observed in APP-KO mice. Collectively, these studies reveal a combined role of APP and APLP2 for dendritic architecture and a unique function of secreted APPs for spine density.
Background: The positive association between parental socio-economic position (PSEP) and health among adolescents may be partly explained by physical activity behaviour. We investigated the associations between physical activity, aerobic fitness and PSEP in a population based sample of German adolescents.
Methods: 5,251 participants, aged 11-17 years, in the German Health Interview and Examination Survey for Children and Adolescents 2003-2006 (KiGGS) underwent a sub-maximal cycle ergometer test and completed a questionnaire obtaining information on physical activity and media use. The associations between physical activity, media use, aerobic fitness and PSEP were analysed with multivariate logistic regression models for boys and girls separately. Odds ratios (ORs) of PSEP (education, occupation and income) on the outcomes were calculated adjusted for age, region, and other influencing factors.
Results: Parental education was more strongly associated with the outcome variables than parental occupation and income. After adjusting for age and region, a higher parental education level was associated with better aerobic fitness - with an OR of 1.5 (95% CI 1.2-1.9) for girls whose parents had secondary education and 1.9 (1.4-2.5) for girls whose parents had tertiary education compared to girls whose parents had primary education. The corresponding ORs for boys were 1.3 (1.0-1.6) and 1.6 (1.2-2.1), respectively. Higher parental education level was associated with lower media use: an OR of 2.1 (1.5-3.0) for girls whose parents had secondary education and 2.7 (1.8-4.1) for girls whose parents had primary education compared to girls whose parents had tertiary education. The corresponding ORs for boys were 1.5 (1.2-1.9) and 1.9 (1.5-2.5), respectively. Higher parental education level was associated with a higher physical activity level only among girls: an OR of 1.3 (1.0-1.6) for girls whose parents had secondary education and 1.2 (0.9-1.5) for girls whose parents had tertiary education compared to girls whose parents had primary education. The corresponding ORs for boys were 0.9 (0.8-1.2) and 0.8 (0.6-1.0), respectively.
Conclusions: Adolescents of parents with low SEP showed a lower level of aerobic fitness and higher levels of media use than adolescents of parents with higher SEP. Health-promotion interventions need to reach adolescents of parents with low PSEP and stimulate physical activity.
The phylogeny of the genus Gazella and the phylogeography and population genetics of arabian species
(2014)
Biodiversity is caused by a fundamental evolutionary process: speciation. When species can spread into new habitats and are allowed to colonize new ecological niches, speciation can become accelerated and is then called radiation. This can happen, e.g., when formerly separated land masses become connected. A prime example of such a scenario is the Arabian Peninsula that connects Africa and Asia since the Oligocene (approx. 30 Ma ago). Since then, the peninsula promoted several faunal exchanges between both continents. The mammalian genus Gazella is an excellent candidate for investigating this faunal exchange. Species are distributed on both, the African and Asian continent as well as on the Arabian Peninsula that is located in between. The aim of my thesis was to cast new light on the evolution and speciation of the genus and, furthermore, to evaluate the currently problematic taxonomy to infer suggestions for improved conservation actions for threatened gazelle species. Therefore, I investigated the taxon Gazella genetically and identified factors that promoted the speciation of this diverse genus. I assessed intraspecific genetic variability for species that inhabited the Arabian Peninsula to infer the past demography of those species and to estimate the history of species divergence and past population parameters.
In the first part of my thesis I inferred a mitochondrial phylogeny based on cytochrome b gene sequences using samples of all nine extant species of Gazella and also of closely related taxa (chapter 2). Besides the monophyly of the genus Gazella two reciprocally monophyletic clades were detected that evolved in allopatry: one predominantly African and one predominantly Asian clade. Within both clades species pairs could be inferred with species being ecologically adapted to different habitats: one species is a desert-dweller (probably the ancestral character state combination), while the other one is adapted to rather mountainous and humid habitats. These adaptations also correlate with the behavior of the species with the mountainous forms being sedentary, territorial and living in small groups and the desert forms being migratory, non-territorial and living in larger herds.
The second part of my thesis focuses on the Arabian gazelle species. In a study about G. subgutturosa I could show that the Arabian form G. marica (sand gazelle)—previously recognized as a subspecies of G. subgutturosa—is genetically distinct from the nominate form (chapter 3). Moreover, a phylogenetic tree based on cytochrome b gene sequences revealed a polyphyly of G. subgutturosa and G. marica with sand gazelles being more closely related to G. leptoceros and G. cuvieri of North Africa. Consequently, I suggested the restoration to full species level for G. marica corroborating earlier conservation practices of breeding both taxa separately in captivity.
In case of G. dorcas such a genetic differentiation could not be detected (chapter 4). Despite the large distribution range from Mali in the west to Saudi Arabia in the east only low genetic variation was detectable in mitochondrial sequence data. Statistically parsimony network analyses revealed pronounced haplotype sharing across regions. Using a coalescence approach I observed a steep population decline that started about 25,000 years ago and which is still ongoing. The decline could be correlated with human hunting activities in the Sahara. Hence, hunting of G. dorcas (already in ancient times) had a much larger impact on gazelle populations than previously thought and even led to the extinction of the Arabian form of G. dorcas.
In chapter 5 of my thesis I provided a rigorous test to genetically distinguish between the potential species G. gazella and G. arabica. Previously recognized as a single species mitochondrial sequence analyses provided first hints for the separation of both taxa. But without the investigation of nuclear loci the observed pattern could also be the result of male biased dispersal combined with female philopatry. Therefore, I amplified mitochondrial sequence markers and nuclear microsatellite loci for both taxa and found support for the earlier view of two separate species. No signs of recurrent gene flow could be detected between neighboring populations of G. arabica and G. gazella. The split of both species could be estimated one million years ago and the recommendation of breeding both taxa separately in captivity for conservation purposes is fully justified.
Several populations of G. arabica suffer from a severe decline. In chapter 6 I asked whether the population occurring on the Farasan archipelago—being at stable individual numbers for decades—may serve as potential source for future reintroduction on the Arabian mainland, although the gazelles show a reduced body size. Analyzing the genetic differentiation of Farasan gazelles, a genetic cluster could be inferred being endemic to the archipelago. However, only approx. 70% of Farasan individuals were assigned to this specific cluster, while the others showed at least intermediate or even complete assignment to the mainland cluster. This indicates ongoing introgression that is probably mediated by human translocations of gazelles from and onto the islands. Considering the uniform dwarfism of Farasan gazelles, reasons for the smaller body size might be direct consequences of resource limitations, i.e., phenotypic plasticity. If the population decline on the mainland will hold on Farasan gazelles could serve as stocks for future reintroductions.
The extinction of conditioned fear depends on an efficient interplay between the amygdala and the medial prefrontal cortex (mPFC). In rats, high-frequency electrical mPFC stimulation has been shown to improve extinction by means of a reduction of amygdala activity. However, so far it is unclear whether stimulation of homologues regions in humans might have similar beneficial effects. Healthy volunteers received one session of either active or sham repetitive transcranial magnetic stimulation (rTMS) covering the mPFC while undergoing a 2-day fear conditioning and extinction paradigm. Repetitive TMS was applied offline after fear acquisition in which one of two faces (CS+ but not CS−) was associated with an aversive scream (UCS). Immediate extinction learning (day 1) and extinction recall (day 2) were conducted without UCS delivery. Conditioned responses (CR) were assessed in a multimodal approach using fear-potentiated startle (FPS), skin conductance responses (SCR), functional near-infrared spectroscopy (fNIRS), and self-report scales. Consistent with the hypothesis of a modulated processing of conditioned fear after high-frequency rTMS, the active group showed a reduced CS+/CS− discrimination during extinction learning as evident in FPS as well as in SCR and arousal ratings. FPS responses to CS+ further showed a linear decrement throughout both extinction sessions. This study describes the first experimental approach of influencing conditioned fear by using rTMS and can thus be a basis for future studies investigating a complementation of mPFC stimulation to cognitive behavioral therapy (CBT).
During cell stress, the transcription and translation of immediate early genes are prioritized, while most other messenger RNAs (mRNAs) are stored away in stress granules or degraded in processing bodies (P-bodies). TIA-1 is an mRNA-binding protein that needs to translocate from the nucleus to seed the formation of stress granules in the cytoplasm. Because other stress granule components such as TDP-43, FUS, ATXN2, SMN, MAPT, HNRNPA2B1, and HNRNPA1 are crucial for the motor neuron diseases amyotrophic lateral sclerosis (ALS)/spinal muscular atrophy (SMA) and for the frontotemporal dementia (FTD), here we studied mouse nervous tissue to identify mRNAs with selective dependence on Tia1 deletion. Transcriptome profiling with oligonucleotide microarrays in comparison of spinal cord and cerebellum, together with independent validation in quantitative reverse transcriptase PCR and immunoblots demonstrated several strong and consistent dysregulations. In agreement with previously reported TIA1 knock down effects, cell cycle and apoptosis regulators were affected markedly with expression changes up to +2-fold, exhibiting increased levels for Cdkn1a, Ccnf, and Tprkb vs. decreased levels for Bid and Inca1 transcripts. Novel and surprisingly strong expression alterations were detected for fat storage and membrane trafficking factors, with prominent +3-fold upregulations of Plin4, Wdfy1, Tbc1d24, and Pnpla2 vs. a −2.4-fold downregulation of Cntn4 transcript, encoding an axonal membrane adhesion factor with established haploinsufficiency. In comparison, subtle effects on the RNA processing machinery included up to 1.2-fold upregulations of Dcp1b and Tial1. The effect on lipid dynamics factors is noteworthy, since also the gene deletion of Tardbp (encoding TDP-43) and Atxn2 led to fat metabolism phenotypes in mouse. In conclusion, genetic ablation of the stress granule nucleator TIA-1 has a novel major effect on mRNAs encoding lipid homeostasis factors in the brain, similar to the fasting effect.
Recognizing individual faces is an important human ability that highly depends on experience. This is reflected in the so called other-race effect; adults are better at recognizing faces from their own ethnic group, while very young infants do not show this specialization yet. Two experiments examined whether 3-year-old children from two different cultural backgrounds show the other-race effect. In Experiment 1, German children (N = 41) were presented with a forced choice paradigm where they were asked to recognize female Caucasian or African faces. In Experiment 2, 3-year-olds from Cameroon (N = 66) participated in a similar task using the same stimulus material. In both cultures the other-race effect was present; children were better at recognizing individual faces from their own ethnic group. In addition, German children performed at a higher overall level of accuracy than Cameroonians. The results are discussed in relation to cultural aspects in particular.
The use of reporter gene fusions to assess cellular processes such as protein targeting and regulation of transcription or translation is established technology in archaeal, bacterial, and eukaryal genetics. Fluorescent proteins or enzymes resulting in chromogenic substrate turnover, like β -galactosidase, have been particularly useful for microscopic and screening purposes. However, application of such methodology is of limited use for strictly anaerobic organisms due to the requirement of molecular oxygen for chromophore formation or color development. We have developed β -lactamase from Escherichia coli (encoded by bla) in conjunction with the chromogenic substrate nitrocefin into a reporter system usable under anaerobic conditions for the methanogenic archaeon Methanosarcina acetivorans. By using a signal peptide of a putative flagellin from M. acetivorans and different catabolic promoters, we could demonstrate growth substrate-dependent secretion of β -lactamase, facilitating its use in colony screening on agar plates. Furthermore, a series of fusions comprised of a constitutive promoter and sequences encoding variants of the synthetic tetracycline-responsive riboswitch (tc-RS) was created to characterize its influence on translation initiation in M. acetivorans. One tc-RS variant resulted in more than 11-fold tetracycline-dependent regulation of bla expression, which is in the range of regulation by naturally occurring riboswitches. Thus, tc-RS fusions represent the first solely cis-active, that is, factor-independent system for controlled gene expression in Archaea.
Permanent conflict resolution at the high courts was one of the Holy Roman Empire’s main characteristics. This applies even to conflicts between rural communities and their lords, who could be dealt with, at least under certain circumstances, at the Imperial Chamber Court or the Aulic Council. These trials, however, were embedded in complicated processes of establishing and legitimizing claims on a local level as well as attempts to achieve a solution by violence or by arbitration. Researchers have stated that conflict resolution underwent, in the long run, a process of “juridification” (“Verrechtlichung”). This working paper proposes a method, based on Niklas Luhmann’s theory of procedural legitimation (“Legitimation durch Verfahren”), which possibly allows to detect elements of juridification and conflict resolution in the actions of parties and courts.
From the late middle ages to early modern times (ca. 1200-1600) the Lübeck City Council was the most important courthouse in the Baltic. About 100 cities and towns on its shores lived according to the law of Lübeck. The paper deals with the old theory that Imperial law, i.e. mainly the learned Ius commune, was generally rejected by the council on the grounds of its foreign nature. The paper rejects this view with the help of 8 case studies. There exist rather spectacular statements against Imperial Law, but a closer look reveals that they have to be seen in the light of a specific practical context. They must not be confounded with general statements in which the council had no interest. Its attitude towards Learned Law was flexible and purely pragmatic.
Das pragmatische Verhältnis des Lübecker Rats zum kaiserlichen Recht im Mittelalter und in der frühen Neuzeit ist das Thema des Aufsatzes. Anhand von acht Fallstudien lässt sich zeigen, wie flexibel der Rat, der zugleich das wichtigste Gericht für die rund hundert nach lübischem Recht lebenden Städte im Ostseeraum war, mit dieser eigentlich übergeordneten, da vom kaiserlichen Stadtherren der Reichsstadt gesetzten Rechtsordnung umging. Auch plakative Stellungnahmen gegen das angeblich mit dem Charakter der Stadt nicht vereinbare römische Recht sind nicht wirklich grundsätzlich gemeint. Ihre gelegentlich vorgeschlagene Interpretation im Sinne einer fundamentalen Ablehnung fremden Rechts in Norddeutschland ist deshalb verfehlt.
Im Jahr 2005 entschied das Bundesverfassungsgericht, dass die bestehenden Regelungen im Versicherungsvertrags- und Versicherungsaufsichtsgesetz zur Überschussbeteiligung in der Lebensversicherung den Anforderungen des Grundgesetzes nicht genügen. Denn sie sicherten die Ansprüche der Versicherten nicht angemessen gegen einseitige Gestaltungsmöglichkeiten der Versicherer ab. Nach dem Urteil änderte der Gesetzgeber die einschlägigen Regelungen, insbesondere erließ die Bundesanstalt für Finanzdienstdienstleistungsaufsicht BAFin eine neue Mindestzuführungsverordnung. Der Beitrag untersucht die Rechtslage auf dem Stand von April 2012 daraufhin, ob nun den Anforderungen des Bundesverfassungsgerichts genüge getan wird. Er kommt zu dem Ergebnis, dass dies nicht der Fall ist.
Die Private Krankenversicherung ist explizit seit Einführung der Versicherungspflicht im Jahr 2008 neben der Gesetzlichen Krankenversicherung zweite Säule eines umfassenden Krankenversicherungsschutzes in Deutschland. Sie ist – auch schon traditionell – umfassend reguliert; Versichertenwettbewerb innerhalb der PKV aber auch zur GKV findet in entsprechend enger rechtlicher Strukturierung statt. In den letzten Jahren wird die PKV zudem auch immer stärker bei der Regulierung der Leistungserbringer berücksichtigt bzw. einbezogen. Der Beitrag gibt einen komprimierten Überblick über die Regulierung der PKV als Teil des Gesundheitssystems.
Der Deutsche Juristentag 2012 ließ begutachten, wie der Wettbewerb in der Gesetzlichen Krankenversicherung zu regeln sei. Der vorliegende Beitrag ist als Begleitaufsatz hierzu erschienen. Er spürt den Motiven des Gesetzgebers und den theoretischen und konzeptionellen Gründen für Wettbewerb nach, um daraus Antworten auf die Frage nach der Wettbewerbsregulierung im Gesundheitswesen zu entwickeln. Sein Ergebnis ist, dass die spezifische Funktion von Wettbewerb innerhalb des sozialrechtlichen Krankenversicherungssystems ein spezifisches Regulierungsrecht erfordert. Dies ist gegenüber einer generellen Zuordnung dieses Sozialsystems zum allgemeinen Wettbewerbs- und Kartellrecht vorzugswürdig. Außerdem wird die Zuordnung zu den Sozialgerichten befürwortet.
Wettbewerbsrecht der GKV
(2014)
Seit inzwischen 20 Jahren führt der Gesetzgeber in die Binnenordnung der Gesetzlichen Krankenversicherung Wettbewerbselemente ein. Ausgangspunkt ist die Kassenwahlfreiheit der Versicherten. Die Krankenkassen agieren dadurch immer stärker als Wettbewerber um Versicherte. Seit einigen Jahren ist der Rechtsrahmen dieses Wettbewerbs in der Diskussion und auch prozessual und politisch umstritten. Inwieweit das allgemeine Kartellrecht, konkret die Fusionskontrolle, oder das allgemeine Lauterkeitsrecht Anwendung finden soll, ist noch nicht abschließend geklärt. Weniger grundsätzliche Probleme bereitet hingegen das Vergaberecht. Der Beitrag beschreibt die sich im Fluss befindliche Rechtsgrundlage des GKV-Wettbewerbsrechts in ihrer bisherigen Entwicklung und auf dem Stand von 2013.
In dieser Arbeit wurden eine Reihe neuer organischer Ladungstransfer (CT)-Verbindungen in Form von Einkristallen und Dünnschichten synthetisiert und grundlegend charakterisiert.
Für die Synthese kamen verschiedene bekannte und bislang unbekannte Donor- und Akzeptormoleküle zum Einsatz. Während einige bekannte Materialien wie TTF und TCNQ kommerziell erworben werden konnten, bestand im Rahmen der Kollaboration mit dem MPI für Polymerforschung zudem Zugang zu mehreren neuen Molekülen wie TMP und HATCN, die besonders mit Blick auf die Möglichkeit zur Dünnschichtpräparation ausgewählt wurden. Auf dieser Grundlage konnten zum einen mittels verschiedener Varianten der Lösungszüchtung erfolgreich neue CT-Komplexe als Einkristalle gezüchtet werden. Dabei kamen mehrere unterschiedliche Lösungsmittel zur Anwendung, die z.T. auch die gezielte Synthese bestimmter Kristallphasen erlaubten. Zum zweiten gelang die Präparation eines Teils dieser Systeme als Dünnschicht über die Methode der Molekularstrahldeposition mit verschiedenen Isolatoren wie SiO2 als Substratmaterial. Hierbei wurde zum Teil zuvor gezüchtetes Material eingesetzt, zum Teil entstand die neue Verbindung erst über diesen Prozess.
Die Proben der neuen Verbindungen wurden zunächst mittels verschiedener Methoden morphologisch und kristallographisch untersucht. Die Kristallzüchtung lieferte in vielen Fällen eine gute Kristallqualität, die sowohl für die Strukturbestimmung als auch die späteren elektrischen Messungen ausreichend war. Die Kristallstruktur konnte für mehrere neue Systeme ermittelt werden und ergab in allen Fällen eine Anordnung mit gemischten Donor-Akzeptor-Stapeln. Für die präparierten Dünnschichten konnte bei einem Großteil der Verbindungen gemäß der Untersuchungen mittels Röntgendiffraktion die gleiche(n) kristalline(n) Struktur(en) wie in den Einkristallen festgestellt werden. Es ließen sich zwei wesentliche Beobachtungen machen: a) Die Morphologie der Schichten besitzt eine ausgeprägte Tendenz zu rauem Inselwachstum; b) In praktisch allen Fällen bilden sich innerhalb der Schicht mindestens zwei stabile CT-Phasen parallel. Beide Verhaltensweisen traten nahezu unabhängig von Substrat, dessen Temperatur, Ausgangszustand (Material vorreagiert oder nicht) und Depositionstemperatur auf.
Die elektronischen Transportmessungen bestanden primär aus temperaturabhängigen Messungen
der elektrischen Leitfähigkeit, während Feldeffektmessungen mit organischen Transistorstrukturen
lediglich den Charakter einer Grundsteinlegung für tiefergehende Untersuchungen mit optimierten Schichten hatten. Die Kryostat-Messungen bis hinunter zu rund 1,5 Kelvin zeigten bei keiner der Verbindungen ein klares Anzeichen für einen Phasenübergang. Die absoluten Werte der Leitfähigkeit bei Raumtemperatur passten qualitativ zu der typischen Erwartung an ein gemischt gestapeltes CT-System, nämlich ein halbleitendes oder isolierendes Verhalten, was durch das arrhenius-artige Temperaturverhalten auch bestätigt wurde.
Dielektrische Messungen mit Kondensatorstrukturen wurden für die neuen Systeme TMP-TCNQ
und ET-DTF in der Dünnschichtform vorgenommen. Im Vordergrund stand dabei die Suche nach neuen Verbindungen, die einen neutral-ionischen Phasenübergang zeigen, der sich im Idealfall durch eine starke, peakförmige Anomalie in der Temperaturabhängigkeit der Dielektrizitätskonstanten bemerkbar machen sollte. Während sich in TMP-TCNQ keinerlei Hinweise auf einen Übergang zeigten, lieferte ET-DTF einen Verlauf, der einen strukturellen
Übergang andeutet, dessen Identität aber noch ungeklärt ist.
Zur Ergänzung wurden mit Hilfe mehrerer Kooperationspartner weitere Untersuchungen zwecks
Charakterisierung der neuen CT-Systeme vorgenommen. Die Bestimmung des Ladungstransfergrades δ mittels IR-Absorption lieferte im Wesentlichen eine Bestätigung der Beobachtung, dass die inspizierten Verbindungen gemischt gestapelte Systeme halbleitender oder
isolierender Natur sind, da δ nur geringe Werte von max. ca. 0,2 zeigte, die für solche Systeme
typisch sind. In ähnlicher Weise bestätigten Bandstruktur-Rechnungen dieses Verhalten, da die Bänder allgemein nur eine eher geringe elektronische Bandbreite zeigten. Zudem ergab sich für die trikline Phase von ET-DTF und das System TMP-F4TCNQ eine deutliche Anisotropie hinsichtlich der Dispersion, da diese erheblich verstärkt entlang der zur Stapelachse des Systems korrespondierenden Richtung des k-Raumes auftritt, also (im Einklang mit den Leitfähigkeitsdaten) 1D-Charakter besitzt. Ein weiterer Beitrag zur Suche nach neuen NI-Verbindungen entstand durch Messung der charakteristischen CT-Absorption einiger Systeme im optischen bzw. IR-Spektrum. In Kombination mit den Werten für Ionisierungsenergie und Elektronenaffinität konnte eine Einordnung in das von Torrance et al. entwickelte, sog. V-Diagramm vorgenommen werden, mit dessen Hilfe sich aussichtsreiche Molekülkombinationen für ein neues NI-System eruieren ließen.
Background: Cichlid fishes show considerable diversity in swim bladder morphology. In members of the subfamily Etroplinae, the connection between anterior swim bladder extensions and the inner ears enhances sound transmission and translates into an improved hearing ability. We tested the hypothesis that those swim bladder modifications coincide with differences in inner ear morphology and thus compared Steatocranus tinanti (vestigial swim bladder), Hemichromis guttatus (large swim bladder without extensions), and Etroplus maculatus (intimate connection between swim bladder and inner ears).
Methodology and results: We applied immunostaining together with confocal imaging and scanning electron microscopy for the investigation of sensory epithelia, and high-resolution, contrast-enhanced microCT imaging for characterizing inner ears in 3D, and evaluated otolith dimensions. Compared to S. tinanti and H. guttatus, inner ears of E. maculatus showed an enlargement of all three maculae, and a particularly large lacinia of the macula utriculi. While our analysis of orientation patterns of ciliary bundles on the three macula types using artificially flattened maculae uncovered rather similar orientation patterns of ciliary bundles, interspecific differences became apparent when illustrating the orientation patterns on the 3D models of the maculae: differences in the shape and curvature of the lacinia of the macula utriculi, and the anterior arm of the macula lagenae resulted in an altered arrangement of ciliary bundles.
Conclusions: Our results imply that improved audition in E. maculatus is associated not only with swim bladder modifications but also with altered inner ear morphology. However, not all modifications in E. maculatus could be connected to enhanced auditory abilities, and so a potential improvement of the vestibular sense, among others, also needs to be considered. Our study highlights the value of analyzing orientation patterns of ciliary bundles in their intact 3D context in studies of inner ear morphology and physiology.
Selection of higher order regression models in the analysis of multi-factorial transcription data
(2014)
Introduction: Many studies examine gene expression data that has been obtained under the influence of multiple factors, such as genetic background, environmental conditions, or exposure to diseases. The interplay of multiple factors may lead to effect modification and confounding. Higher order linear regression models can account for these effects. We present a new methodology for linear model selection and apply it to microarray data of bone marrow-derived macrophages. This experiment investigates the influence of three variable factors: the genetic background of the mice from which the macrophages were obtained, Yersinia enterocolitica infection (two strains, and a mock control), and treatment/non-treatment with interferon-γ.
Results: We set up four different linear regression models in a hierarchical order. We introduce the eruption plot as a new practical tool for model selection complementary to global testing. It visually compares the size and significance of effect estimates between two nested models. Using this methodology we were able to select the most appropriate model by keeping only relevant factors showing additional explanatory power. Application to experimental data allowed us to qualify the interaction of factors as either neutral (no interaction), alleviating (co-occurring effects are weaker than expected from the single effects), or aggravating (stronger than expected). We find a biologically meaningful gene cluster of putative C2TA target genes that appear to be co-regulated with MHC class II genes.
Conclusions: We introduced the eruption plot as a tool for visual model comparison to identify relevant higher order interactions in the analysis of expression data obtained under the influence of multiple factors. We conclude that model selection in higher order linear regression models should generally be performed for the analysis of multi-factorial microarray data.
Background: Endometriosis is characterized by the presence of functional endometrial tissue outside of the uterine cavity. It affects 1 in 10 women of reproductive age. This chronic condition commonly leads to consequences such as pelvic pain, dysmenorrhea, infertility and an elevated risk of epithelial ovarian cancer. Despite the prevalence of endometriosis and its impact on women's lives, there are relatively few in vitro and in vivo models available for studying the complex disease biology, pathophysiology, and for use in the preclinical development of novel therapies. The goal of this study was to develop a novel three-dimensional (3D) cell culture model of ovarian endometriosis and to test whether it is more reflective of endometriosis biology than traditional two dimensional (2D) monolayer cultures.
Methods: A novel ovarian endometriosis epithelial cell line (EEC16) was isolated from a 34-year old female with severe endometriosis. After characterization of cells using in vitro assays, western blotting and RNA-sequencing, this cell line and a second, already well characterized endometriosis cell line, EEC12Z, were established as in vitro 3D spheroid models. We compared biological features of 3D spheroids to 2D cultures and human endometriosis lesions using immunohistochemistry and real-time semi-quantitative PCR.
Results: In comparison to normal ovarian epithelial cells, EEC16 displayed features of neoplastic transformation in in vitro assays. When cultured in 3D, EEC16 and EEC12Z showed differential expression of endometriosis-associated genes compared to 2D monolayer cultures, and more closely mimicked the molecular and histological features of human endometriosis lesions.
Conclusions: To our knowledge, this represents the first report of an in vitro spheroid model of endometriosis. 3D endometriosis models represent valuable experimental tools for studying EEC biology and the development of novel therapeutic approaches.
Fünfzehnhundertsiebenundachtzig : Literatur, Geschichte und die Historia von D. Johann Fausten
(2014)
Ausgehend von der Beobachtung, dass die 1587 in Frankfurt am Main erschienene »Historia von D. Johann Fausten« überaus erfolgreich war, wird die These formuliert, dass dieser Erfolg auf der dichten Vernetzung mit zeitgenössischen Techniken, Praktiken und Diskursen beruht. Um Teile dieses Netzwerks zu rekonstruieren, beschränkt sich der Beobachtungszeitraum auf die 1580er und frühen 1590er Jahre. Innerhalb dieses Zeitraums wird etwa untersucht, wie man am »Faustbuch« weiterschreibt, welche Rolle die Hexen- und Zaubererverfolgung spielt, wie es um den Einfluss der Transformationen des Postsystems und des Kalenders bestellt ist und was man von außergewöhnlichen Zeichen zu halten hat, die auf dem Körperäußeren erscheinen. Methodisch ist die Arbeit dem New Historicism verpflichtet, dessen vermittelnde Stellung zwischen ›Literatur‹ und ›Geschichte‹ auch dazu genutzt wird, gängige disziplinäre Grenzziehungen in Frage zu stellen.
The multifunctional molecule netrin-1 is upregulated in various malignancies and has recently been presented as a major general player in tumorigenesis leading to tumor progression and maintenance in various animal models. However, there is still a lack of clinico-epidemiological data related to netrin-1 expression. Therefore, the aim of our study was to elucidate the association of netrin-1 expression and patient survival in brain metastases since those constitute one of the most limiting factors for patient prognosis. We investigated 104 brain metastases cases for netrin-1 expression using in-situ hybridization and immunohistochemistry with regard to clinical parameters such as patient survival and MRI data. Our data show that netrin-1 is strongly upregulated in most cancer subtypes. Univariate analyses revealed netrin-1 expression as a significant factor associated with poor patient survival in the total cohort of brain metastasis patients and in sub-entities such as non-small cell lung carcinomas. Interestingly, many cancer samples showed a strong nuclear netrin-1 signal which was recently linked to a truncated netrin-1 variant that enhances tumor growth. Nuclear netrin-1 expression was associated with poor patient survival in univariate as well as in multivariate analyses. Our data indicate both total and nuclear netrin-1 expression as prognostic factors in brain metastases patients in contrast to other prognostic markers in oncology such as patient age, number of brain metastases or Ki67 proliferation index. Therefore, nuclear netrin-1 expression constitutes one of the first reported molecular biomarkers for patient survival in brain metastases. Furthermore, netrin-1 may constitute a promising target for future anti-cancer treatment approaches in brain metastases.
The haloarchaeon Haloferax volcanii was shown to contain 145 intergenic and 45 antisense sRNAs. In a comprehensive approach to unravel various biological roles of haloarchaeal sRNAs in vivo, 27 sRNA genes were selected and deletion mutants were generated. The phenotypes of these mutants were compared to that of the parent strain under ten different conditions, i.e. growth on four different carbon sources, growth at three different salt concentrations, and application of four different stress conditions. In addition, cell morphologies in exponential and stationary phase were observed. Furthermore, swarming of 17 mutants was analyzed. 24 of the 27 mutants exhibited a difference from the parent strain under at least one condition, revealing that haloarchaeal sRNAs are involved in metabolic regulation, growth under extreme conditions, regulation of morphology and behavior, and stress adaptation. Notably, 7 deletion mutants showed a gain of function phenotype, which has not yet been described for any other prokaryotic sRNA gene deletion mutant. Comparison of the transcriptomes of one sRNA gene deletion mutant and the parent strain led to the identification of differentially expressed genes. Genes for flagellins and chemotaxis were up-regulated in the mutant, in accordance with its gain of function swarming phenotype. While the deletion mutant analysis underscored that haloarchaeal sRNAs are involved in many biological functions, the degree of conservation is extremely low. Only 3 of the 27 genes are conserved in more than 10 haloarchaeal species. 22 of the 27 genes are confined to H. volcanii, indicating a fast evolution of haloarchaeal sRNA genes.
Genome-wide association studies are widely used to correlate phenotypic traits with genetic variants. These studies usually compare the genetic variation between two groups to single out certain Single Nucleotide Polymorphisms (SNPs) that are linked to a phenotypic variation in one of the groups. However, it is necessary to have a large enough sample size to find statistically significant correlations. Direct-To-Consumer (DTC) genetic testing can supply additional data: DTC-companies offer the analysis of a large amount of SNPs for an individual at low cost without the need to consult a physician or geneticist. Over 100,000 people have already been genotyped through Direct-To-Consumer genetic testing companies. However, this data is not public for a variety of reasons and thus cannot be used in research. It seems reasonable to create a central open data repository for such data. Here we present the web platform openSNP, an open database which allows participants of Direct-To-Consumer genetic testing to publish their genetic data at no cost along with phenotypic information. Through this crowdsourced effort of collecting genetic and phenotypic information, openSNP has become a resource for a wide area of studies, including Genome-Wide Association Studies. openSNP is hosted at http://www.opensnp.org, and the code is released under MIT-license at http://github.com/gedankenstuecke/snpr.
Three neonicotinoids, imidacloprid, clothianidin and thiacloprid, agonists of the nicotinic acetylcholine receptor in the central brain of insects, were applied at non-lethal doses in order to test their effects on honeybee navigation. A catch-and-release experimental design was applied in which feeder trained bees were caught when arriving at the feeder, treated with one of the neonicotinoids, and released 1.5 hours later at a remote site. The flight paths of individual bees were tracked with harmonic radar. The initial flight phase controlled by the recently acquired navigation memory (vector memory) was less compromised than the second phase that leads the animal back to the hive (homing flight). The rate of successful return was significantly lower in treated bees, the probability of a correct turn at a salient landscape structure was reduced, and less directed flights during homing flights were performed. Since the homing phase in catch-and-release experiments documents the ability of a foraging honeybee to activate a remote memory acquired during its exploratory orientation flights, we conclude that non-lethal doses of the three neonicotinoids tested either block the retrieval of exploratory navigation memory or alter this form of navigation memory. These findings are discussed in the context of the application of neonicotinoids in plant protection.
Objective: The objective of this study was to describe and analyze the effects of depression on health care utilization and costs in a sample of multimorbid elderly patients.
Method: This cross-sectional analysis used data of a prospective cohort study, consisting of 1,050 randomly selected multimorbid primary care patients aged 65 to 85 years. Depression was defined as a score of six points or more on the Geriatric Depression Scale (GDS-15). Subjects passed a geriatric assessment, including a questionnaire for health care utilization. The impact of depression on health care costs was analyzed using multiple linear regression models. A societal perspective was adopted.
Results: Prevalence of depression was 10.7%. Mean total costs per six-month period were €8,144 (95% CI: €6,199-€10,090) in patients with depression as compared to €3,137 (95% CI: €2,735-€3,538; p<0.001) in patients without depression. The positive association between depression and total costs persisted after controlling for socio-economic variables, functional status and level of multimorbidity. In particular, multiple regression analyses showed a significant positive association between depression and pharmaceutical costs.
Conclusion: Among multimorbid elderly patients, depression was associated with significantly higher health care utilization and costs. The effect of depression on costs was even greater than reported by previous studies conducted in less morbid patients.
Hepatitis C virus (HCV) infection leads to the development of hepatic diseases, as well as extrahepatic disorders such as B-cell non-Hodgkin's lymphoma (B-NHL). To reveal the molecular signalling pathways responsible for HCV-associated B-NHL development, we utilised transgenic (Tg) mice that express the full-length HCV genome specifically in B cells and develop non-Hodgkin type B-cell lymphomas (BCLs). The gene expression profiles in B cells from BCL-developing HCV-Tg mice, from BCL-non-developing HCV-Tg mice, and from BCL-non-developing HCV-negative mice were analysed by genome-wide microarray. In BCLs from HCV-Tg mice, the expression of various genes was modified, and for some genes, expression was influenced by the gender of the animals. Markedly modified genes such as Fos, C3, LTβR, A20, NF-κB and miR-26b in BCLs were further characterised using specific assays. We propose that activation of both canonical and alternative NF-κB signalling pathways and down-regulation of miR-26b contribute to the development of HCV-associated B-NHL.
I analyze a critical illness insurance in a consumption-investment model over the life cycle. I solve a model with stochastic mortality risk and health shock risk numerically. These shocks are interpreted as critical illness and can negatively affect the expected remaining lifetime, the health expenses, and the income. In order to hedge the health expense effect of a shock, the agent has the possibility to contract a critical illness insurance. My results highlight that the critical illness insurance is strongly desired by the agents. With an insurance profit of 20%, nearly all agents contract the insurance in the working stage of the life cycle and more than 50% of the agents contract the insurance during retirement. With an insurance profit of 200%, still nearly all working agents contract the insurance, whereas there is little demand in the retirement stage.
I numerically solve realistically calibrated life cycle consumption-investment problems in continuous time featuring stochastic mortality risk driven by jumps, unspanned labor income as well as short-sale and liquidity constraints and a simple insurance. I compare models with deterministic and stochastic hazard rate of death to a model without mortality risk. Mortality risk has only minor effects on the optimal controls early in the life cycle but it becomes crucial in later years. A diffusive component in the hazard rate of death has no significant impact, whereas a jump component is desired by the agent and influences optimal controls and wealth evolution. The insurance is used to ensure optimal bequest such that there is no accidental bequest. In the absence of the insurance, the biggest part of bequest is accidental.
We explore the sources of household balance sheet adjustment following the collapse of the housing market in 2006. First, we use microdata from the Federal Reserve Board’s Senior Loan Officer Opinion Survey to document that banks cumulatively tightened consumer lending standards more in counties that experienced a house price boom in the mid-2000s than in non-boom counties. We then use the idea that renters, unlike homeowners, did not experience an adverse wealth shock when the housing market collapsed to examine the relative importance of two explanations for the observed deleveraging and the sluggish pickup in consumption after 2008. First, households may have optimally adjusted to lower wealth by reducing their demand for debt and implicitly, their demand for consumption. Alternatively, banks may have been more reluctant to lend in areas with pronounced real estate declines. Our evidence is consistent with the second explanation. Renters with low risk scores, compared to homeowners in the same markets, reduced their levels of nonmortgage debt and credit card debt more in counties where house prices fell more. The contrast suggests that the observed reductions in aggregate borrowing were more driven by cutbacks in the provision of credit than by a demand-based response to lower housing wealth.
This paper solves a dynamic model of households' mortgage decisions incorporating labor income, house price, inflation, and interest rate risk. It uses a zero-profit condition for mortgage lenders to solve for equilibrium mortgage rates given borrower characteristics and optimal decisions. The model quantifies the effects of adjustable vs. fixed mortgage rates, loan-to-value ratios, and mortgage affordability measures on mortgage premia and default. Heterogeneity in borrowers' labor income risk is important for explaining the higher default rates on adjustable-rate mortgages during the recent US housing downturn, and the variation in mortgage premia with the level of interest rates.
Die Dissertation gliedert sich in zwei Teile – einen methodisch-wissenschaftstheoretischen bzw. biografisch-dogmenhistorischen und einen wirtschaftsethischen Bereich. Beide Abschnitte sind wechselseitig miteinander verzahnt. Im ersten Teil geht es vorwiegend um biografische und theoriegeschichtliche Fragestellungen. Der erste Aufsatz – On the Affiliation of Phenomenology and Ordoliberalism – beschäftigt sich mit dem wechselseitigen Einfluss von Husserl, Rudolf und Walter Eucken. Der erste Aufsatz – On the Affiliation of Phenomenology and Ordoliberalism – beschäftigt sich mit dem wechselseitigen Einfluss von Husserl, Rudolf und Walter Eucken. Dabei wird eine Drei-Ebenen-Unterscheidung vorgenommen: Einflüsse lassen sich demnach nicht nur auf der biografischen, sondern gleichfalls auf der wissenschaftstheoretischen und sozialphilosophischen Ebene ausmachen. Dennoch ist Vorsicht geboten, denn der Einfluss der Phänomenologie auf das Werk Walter Euckens sollte nicht überbetont werden, in dem Sinne, dass man Eucken als angewandten Phänomenologen und die Husserlsche Phänomenologie als Metatheorie des Ordoliberalismus darstellt. Vielmehr ist von einem eklektischen Denkmuster in den Schriften Euckens auszugehen, das maßgeblich vom Werk seines Vaters beeinflusst wurde (d.i., Walter Eucken als Rudolf Euckenianer) – und dies sowohl im Bereich der Wissenschaftstheorie und Methodik als auch im Kontext des sozialphilosophischen Topos der Gesellschaftskrisis. Der zweite Aufsatz – An Ordoliberal Interpretation of Adam Smith – geht den Parallelen im Denken Adam Smiths und Euckens nach. Auffallend ist, dass Eucken Smith meist im Zusammenhang mit seiner Kritik am laissez faire- respektive Paläoliberalismus zitiert. Dabei ist seine Bezugnahme auf Smith von verzerrten Stereotypen geprägt – und dies obwohl es einige bemerkenswerte Parallelen nicht nur zwischen Eucken und Smith, sondern auch zwischen Smith und Kant gibt. Der Übergang vom sogenannten Paläo- bzw. klassischen Liberalismus hin zum Ordoliberalismus ist somit gradueller, nicht jedoch revolutionärer Art. Im Mittelpunkt des zweiten Hauptteils stehen wirtschaftsethische Themenstellungen, die eine große Affinität zum Forschungsprogramm des Exzellenzclusters 'Die Herausbildung normativer Ordnungen' aufweisen. Dabei geht es wesentlich um die Herausarbeitung des ethischen Gehalts und der stark normativen Komponenten des Ordoliberalismus. Die ersten Essays im zweiten Teilbereich der Dissertation beziehen sich primär auf Eucken und die Freiburger Schule. Die letzten beiden Aufsätze jedoch sind bestrebt, über Eucken hinauszugehen und den Ordoliberalismus i.e.S. um den Soziologischen Neoliberalismus bzw. den Wirtschafts- und Sozialhumanismus Rüstows und Röpkes zu erweitern. Die Aufsätze 'Über die normativen Implikationen des Ordoliberalismus für die moderne Wirtschaftsethik' und 'On the Economic Ethics of Walter Eucken' geben dem Leser einen Überblick über die Wirtschaftsethik der Freiburger Schule im Allgemeinen und Walter Euckens im Besonderen. Dabei wird insbesondere das ordoliberale Staats- sowie das (in der kantischen Tradition stehende) Freiheitsverständnis herausgearbeitet und der Versuch unternommen, Eucken für die moderne Wirtschaftsethik anschlussfähig zu machen. Als Ergebnis wird Euckens Ordoliberalismus, dem es um ein ausgewogenes Verhältnis von Eigeninteresse und Gemeinwohl und die Realisierung des Ideals einer funktionsfähigen und menschenwürdigen Gesellschaftsordnung geht, im Spannungsfeld von Homannscher Moralökonomik und Ulrichs Integrativer Wirtschaftsethik porträtiert. Ergänzt wird dieser Einblick in die ordoliberale Wirtschaftsethik durch das Kapitel 'Von Hayek and Ordoliberalism on Justice', das die Gerechtigkeitskonzeptionen Euckens, Rüstows und Röpkes mit derjenigen von von Hayek kontrastiert. Derart werden u.a. die Unterschiede zwischen Ordoliberalismus und Evolutorischem Liberalismus deutlich. Das Kapitel 'Individual versus Regulatory Ethics: An Economic-Ethical and Theoretical-Historical Analysis of German Neoliberalism' untersucht im Anschluss an Foucaults ‚Ambiguitätsthese‘ das Verhältnis von Individual- und Ordnungsethik und kommt zu dem Ergebnis, dass es die Besonderheit des Ordoliberalismus ist, eine weitreichende, integrative Einheit beider Ebenen vorzunehmen. Aufbauend auf der Unterscheidung von Individual- und Ordnungsethik werden im vorletzten Kapitel – 'Ordoliberalism and the Evolution of Norms' – schließlich die divergierenden Normengenese-Prozesse im Ordoliberalismus einer Analyse unterzogen. Das verblüffende Resultat lautet, dass im Ordoliberalismus zwei unterschiedliche Arten der Entstehung von Normen nebeneinander existieren – eine kulturell-evolutionäre und eine elitär-expertokratische. Mithilfe dieser Unterscheidung ist eine weitere Differenzierung zwischen von Hayek und dem Ordoliberalismus möglich. Das letzte Kapitel – Beyond Ordoliberalism? – fasst zentrale Kritikpunkte am Ordoliberalismus noch einmal zusammen und geht der Frage nach, inwiefern es realistisch erscheint, auf eine Renaissance eines aktualisierten Ordoliberalismus zu hoffen?