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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.