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Der angezeigte Aufsatzband ist aus einer Tagung hervorgegangen, die im Mai 2011 an der McGill University in Montreal/Kanada veranstaltet wurde. In der "Introduction" (9- 17) skizzieren die Herausgeber die Zielsetzung der Konferenz und ihrer Akten: Untersucht werden soll, "how economic power and 'real' capital influenced and augmented the nature of aristocratic power at Rome and the driving forces behind the Republic’s foreign expansion" (12). Zwar gebe es einige wenige Studien, die sich dieser Thematik gewidmet hätten (verwiesen wird auf Publikationen von H. Schneider und I. Shatzmann), viele Detailfragen seien jedoch bislang ungeklärt. Im Anschluss an die kurze Einführung der Herausgeber folgt eine knappe inhaltliche Wiedergabe der dreizehn abgedruckten Artikel (13-17)...
Rezension zu: Verena Schulz, Die Stimme in der antiken Rhetorik, Hypomnemata 194 (Göttingen 2014)
(2017)
Die Stimme als vornehmlich akustisches Phänomen im Rahmen der antiken Rhetorik darstellen zu wollen, war schon den antiken Schriftstellern nach ein schwieriges Unterfangen, und umso willkommener ist eine derartige Darstellung zu begrüßen, insbesondere wenn sie sich, wie im Fall der vorliegenden Dissertation von Verena Schulz, eines interdisziplinären Ansatzes bedient. Bei der fast 400 Seiten starken Monographie handelt es sich einerseits um einen philologischen Kommentar zu den beiden ausführlichsten Quellentexten zur antiken Rhetorik, namentlich den Ausführungen des Auctor ad Herennium und denen des Quintilian. Andererseits aber stellt die Monographie eine Materialsammlung unter chronologischen und systematischen Gesichtspunkten dar, die die wesentlichen antiken Quellenstellen zur Stimme aus philologischer, medizinischer, musikalischer und historischer Perspektive in sich vereint und somit verschiedene Lesergruppen ansprechen soll. Ergänzt und erweitert um Exkurse, die sich dem heutigen Verständnis der Stimmphysiologie (S. 79-83), der antiken Terminologie von actio und pronuntiatio (S. 107-109) und den begrifflichen Vorstellungen der akustisch-physikalischen Stimmfaktoren zu Lautstärke und Tonhöhe (S. 178- 184) widmen, wird damit auf äußerst gelungene Weise eine Brücke von der Antike in die Rezeptionsgeschichte von Stimme und Rhetorik geschlagen, die abgrenzend zur bestehenden Forschung insbesondere um den medizinhistorischen Blickwinkel erweitert wurde...
Der Erzählforscher Johannes Merkel hat unlängst (2015) einen bemerkenswerten Überblick zur Gesamttradition des mündlichen Erzählens vorgelegt. Die folgenden Überlegungen, von einer Teilbesprechung dieser Neuerscheinung ausgehend, zielen grundsätzlich auf eine kritische Überprüfung von verschiedenen in der bisherigen Forschung für selbstverständlich gehaltenen Basisfaktoren (insbesondere den theoretischen Ansätzen von Nilsson und Parry). Dabei geht es zunächst einmal um jene allgemein vorausgesetzte vorgriechische Phase von oral poetry, auf die sich auch Merkel im 3. Kapitel unter dem Titel ‚Das singende Gedächtnis: Epenvortrag in Mittelasien und auf dem Balkan‘ bezog (105-148). Die neuere Forschung tendiert bekanntlich dazu, es habe eine längere oral poetry in den sog. "dunklen Jahrhunderten" zwischen 1200 und 850 v. Chr. noch vor Ausbildung der frühgriechischen Kultur gegeben; so z.B. der englische Althistoriker Robin Lane Fox (2008/11): "Ilias und Odyssee sind im Wesentlichen Werke der Mündlichkeit, die letzten in einem langen 'Zeitalter der Mündlichkeit'…". Eng damit verbunden waren Martin P. Nilssons Hypothese "The Mycenaen Origin of Greek Mythology" (1932) und der von Milman Parry seit 1928 konstituierte, von seinem Schüler Arthur B. Lord weiter entwickelte Ansatz, dass für frühgriechische Epen eine Vergleichbarkeit mit neueren Phasen mündlicher Epik z.B. auf dem Balkan gegeben sei. Merkels jüngste Ausführungen verstärken meine früheren Bedenken gegen dieses Gesamtkonzept.
In den Jahren 1886 und 1887 fanden sich in Avenches (Schweiz, Kanton Waadt), der ehemaligen römischen Colonia Pia Flavia Constans Emerita Helvetiorum Foederata, mehrere Fragmente einer Grabinschrift aus Marmor, die schon häufiger das Interesse der Forschung geweckt haben, da auf der Grabplatte anscheinend eine kaiserliche Gouvernante, eine educatrix Augusti nostri, genannt wird...
The paper assesses current rising reparations claims for the Maafa/ Maangamizi (‘African holocaust,’ comprising transatlantic slavery, colonialism and neo-colonialism) from two angles. First, it explores the connectivity of reparations and global justice, peace and security. Second, it discusses how the claim is justified in international law. The concept of reparations in international law is also explored, revealing that reparations cannot be limited to financial compensation due to the nature of the damage and international law prescriptions. Comprehensive reparations based in international law require the removal of structures built on centuries of illegal acts and aggression, in the forms of transatlantic slavery, colonialism and neo-colonialism. Reparations must also lead to the restitution of sovereignty to African and indigenous peoples globally. They are indispensable to halt the destruction of the earth as human habitat, caused by the violent European cultural, political, socio-economic system known as apitalism that is rooted in transatlantic slavery.
From reparations for slavery to international racial justice: a critical republican perspective
(2017)
This paper focuses on demands for reparations for colonial slavery and their public reception in France. It argues that this bottom-up, context-sensitive approach to theorising reparations enables us to formulate a critical republican theory of international racial justice. It contrasts the critical republican perspective on reparations with a nation-state centred approach in which reparations activists are accused of threatening the French republic’s sense of homogeneity and unity, thus undermining the national narrative on the French identity. It also rejects the liberal egalitarian perspective, which itself rejects reparations in favour of focusing on present disadvantages. In so doing, this paper illustrates how the notion of non-domination offers a superior way of conceptualising global racial injustices compared to more traditional distributive outlooks.
If Third World women form ‘the bedrock of a certain kind of global exploitation of labour,’ as Chandra Mohanty argues, how can our theoretical definitions of exploitation account for this? This paper argues that liberal theories of exploitation are insufficiently structural and that Marxian accounts are structural but are insufficiently intersectional. What we need is a structural and intersectional definition of exploitation in order to correctly identify global structural exploitation. Drawing on feminist, critical race/post-colonial and post-Fordist critiques of the Marxist definition and the intersectional accounts of Maria Mies and Iris Marion Young, this paper offers the following definition of structural exploitation: structural exploitation refers to the forced transfer of the productive powers of groups positioned as socially inferior to the advantage of groups positioned as socially superior. Global structural exploitation is a form of global injustice because it is a form of oppression.
Many theories of global distributive justice are based on the assumption that all humans hold common ownership of the earth. As the earth is finite and our actions interconnect, we need a system of justice that regulates the potential appropriation of the common earth to ensure fairness. According to these theories, imposing limits and distributive obligations on private and public property arrangements may be the best mechanism for governing common ownership. We present a critique of the assumption that this issue can be solved within the private–public property regime, arguing that the boundaries of this regime should not be taken for granted and that the growing literature on the democratic commons movement suggests how this can be accomplished. We consider that, if the earth is defined as a common, the private– public property paradigm must be open to questioning, and democratic commoners’ activities should be considered.
All cosmopolitan approaches to global distributive justice are premised on the idea that humans are the primary units of moral concern. In this paper, I argue that neither relational nor non-relational cosmopolitans can unquestioningly assume the moral primacy of humans. Furthermore, I argue that, by their own lights, cosmopolitans must extend the scope of justice to most, if not all, nonhuman animals. To demonstrate that cosmopolitans cannot simply ‘add nonhuman animals and stir,’ I examine the cosmopolitan position developed by Martha Nussbaum in Frontiers of Justice. I argue that while Nussbaum explicitly includes nonhuman animals within the scope of justice, her account is marked by an unjustifiable anthropocentric bias. I ultimately conclude that we must radically reconceptualise the primary unit of cosmopolitan moral concern to encompass most, if not all, sentient animals.
For some time now, structural macroeconomic models used at central banks have been predominantly New Keynesian DSGE models featuring nominal rigidities and forwardlooking decision-making. While these features are widely deemed crucial for policy evaluation exercises, most central banks have added more detailed characterizations of the financial sector to these models following the Great Recession in order to improve their fit to the data and their forecasting performance. We employ a comparative approach to investigate the characteristics of this new generation of New Keynesian DSGE models and document an elevated degree of model uncertainty relative to earlier model generations. Policy transmission is highly heterogeneous across types of financial frictions and monetary policy causes larger effects, on average. The New Keynesian DSGE models we analyze suggest that a simple policy rule robust to model uncertainty involves a weaker response to inflation and the output gap in the presence of financial frictions as compared to earlier generations of such models. Leaning-against-the-wind policies in models of this class estimated for the Euro Area do not lead to substantial gains. With regard to forecasting performance, the inclusion of financial frictions can generate improvements, if conditioned on appropriate data. Looking forward, we argue that model-averaging and embracing alternative modelling paradigms is likely to yield a more robust framework for the conduct of monetary policy.
We study the general equilibrium implications of different fiscal policies on macroeconomic quantities, asset prices, and welfare by utilizing two endogenous growth models. The expanding variety model features only homogeneous innovations by entrants. The Schumpeterian growth model features heterogeneous innovations: "incremental" innovations by incumbents and "radical" innovations by entrants. The government levies taxes on labor income and corporate profits and supplies subsidies to consumption, capital investment, and investments in research and development by entrants and, if applicable, incumbents. With these models at hand, we provide new insights on the interplay of innovation dynamics and fiscal policy.
Exploiting NASDAQ order book data and difference-in-differences methodology, we identify the distinct effects of trading pause mechanisms introduced on U.S. stock exchanges after May 2010. We show that the mere existence of such a regulation constitutes a safeguard which makes market participants behave differently in anticipation of a pause. Pauses tend to break local price trends, make liquidity suppliers revise positions, and enhance price discovery. In contrast, pauses do not have a “cool off” effect on markets, but rather accelerate volatility and bid-ask spreads. This implies a regulatory trade-off between the protective role of trading pauses and their adverse effects on market quality.
Rezension inside islam
(2017)
Für balancierte, irreduzible Pólya-Urnen-Modelle sind Grenzwertsätze für die normalisierte Anzahl von Kugeln einer Farbe bekannt. Für eine spezielle Urne, deren Dynamik mit "Randomised-Play-the-Winner Rule" bezeichnet wird, werden im Rahmen der bekannten Grenzwertsätze Konvergenzraten in Wasserstein-Metriken und in der Kolmogorov-Metrik im Falle eines nicht-normalverteilten Grenzwerts hergeleitet.
Hintergrund: Die Interaktion zwischen β-HCG und TSH in der Schwangerschaft stellt ein differentialdiagnostisches Problem dar, weil die Wertung von supprimierten TSH-Spiegeln erschwert wird. Dies kann im schlimmsten Fall zu Fehlinterpretationen führen. Ziel der vorliegenden Arbeit war, diese Interaktion an einem großen Kollektiv in einen zeitlichen Kontext mit dem Verlauf der Schwangerschaft zu bringen, da der Zeitpunkt des Screenings entscheidenden Einfluss auf die Höhe des TSH-Spiegels hat. Zusätzlich wurden anhand der vorliegenden Daten Referenzbereiche für Schwangere berechnet und der Einfluss einer Jodmedikation untersucht.
Patienten und Methoden: Aus einem unselektionierten Pool von Patientinnen eines nuklearmedizinischen Praxisverbundes wurden die Daten von 1283 schilddrüsengesunden Schwangeren zwischen 16 und 48 Jahren ausgewertet. Neben der TSH-Bestimmung lag ein Schwerpunkt auf dem zeitlichen Verlauf, so dass die Schwangeren in Untergruppen von je 2 Wochen analysiert wurden. Untersucht wurde der Einfluss der Jodmedikation auf die TSH-Werte. Am Ende erfolgte mit Hilfe der logarithmischen Transformation unter Verwendung der 2-Sigma-Grenzen die Bestimmung neuer TSH-Referenzbereiche für Schwangere.
Ergebnisse: Es zeigt sich zu Beginn der Schwangerschaft ein Anstieg der mittleren TSH-Werte von 1,22 mU/l in der 2. SSW bis auf 1,7 mU/l um die 7. SSW mit einem konsekutiven Abfall der TSH-Werte bis auf 0,9 mU/l bis zur 16. SSW (entsprechend 52,9%). Der größte Abfall findet sich in der 12. bis 14. SSW, also zum Zeitpunkt des ersten Screenings. Die Jodmedikation hat keinen maßgeblichen Einfluss auf den TSH-Wert. Die Berechnung schwangerschaftskorrigierter Referenzbereiche zeigt im ersten Drittel TSH-Werte von 0,08 – 3,67 mU/l, im 2. Drittel 0,04 – 2,88 mU/l und im 3. Trimenon 0,17 – 3,19 mU/l.
Schlussfolgerungen: Die Arbeit zeigt, dass die niedrigsten TSH-Werte zum Zeitpunkt des ersten Screenings zu erwarten sind und deswegen möglicherweise zu Fehlentscheidungen führen können. Ein relevanter Zusammenhang der Jodmedikation mit dem TSH-Wert lässt sich nicht nachweisen. Neue Referenzbereiche für Schwangere könnten hilfreich sein, dieses diagnostische Dilemma zu vermeiden.
Excessive neutrophil activation accompanied by delayed apoptotic cell death in inflammatory conditions causes progressive damage of cells and tissues, leading to life-threatening multiple organ dysfunction syndrome. Previous work suggested that circulating serum factors during inflammation are critically involved in the suppression of neutrophil cell death although the identity of these antiapoptotic mediators remained elusive. In this study, we identified the acute phase protein α-1 Antitrypsin (AAT) as a potent suppressor of staurosporine (STS)-induced apoptosis in human neutrophils through a mechanism implicating caspases-independent pathways. We show here that serum levels of AAT, potentially in part released by stimulated neutrophils, are markedly elevated in major trauma patients suffering from systemic inflammatory response syndrome (SIRS). Notably, AAT depletion from serum increased sensitivity of human neutrophils for STS-induced cell death. In fact, AAT was demonstrated to confer intrinsic apoptosis resistance by preventing PKC/Akt inactivation and subsequent proteasomal degradation of antiapoptotic Mcl-1 protein in response to STS treatment. Neither MAP kinase ERK1/2 nor caspases were found to be involved in AAT-triggered antiapoptotic pathways in neutrophils. In summary, these results establish a novel pivotal role of circulating AAT in mediating survival by antagonizing the proapoptotic action of the PKC inhibitor STS and should be considered for AAT augmentation therapies in future.
Natural killer (NK) cells are a promising tool for the use in adoptive immunotherapy, since they efficiently recognize and kill tumor cells. In this context, ex vivo cultivation is an attractive option to increase NK cells in numbers and to improve their antitumor potential prior to clinical applications. Consequently, various strategies to generate NK cells for adoptive immunotherapy have been developed. Here, we give an overview of different NK cell cultivation approaches and their impact on shaping the NK cell antitumor activity. So far, the cytokines interleukin (IL)-2, IL-12, IL-15, IL-18, and IL-21 are used to culture and expand NK cells. The selection of the respective cytokine combination is an important factor that directly affects NK cell maturation, proliferation, survival, distribution of NK cell subpopulations, activation, and function in terms of cytokine production and cytotoxic potential. Importantly, cytokines can upregulate the expression of certain activating receptors on NK cells, thereby increasing their responsiveness against tumor cells that express the corresponding ligands. Apart from using cytokines, cocultivation with autologous accessory non-NK cells or addition of growth-inactivated feeder cells are approaches for NK cell cultivation with pronounced effects on NK cell activation and expansion. Furthermore, ex vivo cultivation was reported to prime NK cells for the killing of tumor cells that were previously resistant to NK cell attack. In general, NK cells become frequently dysfunctional in cancer patients, for instance, by downregulation of NK cell activating receptors, disabling them in their antitumor response. In such scenario, ex vivo cultivation can be helpful to arm NK cells with enhanced antitumor properties to overcome immunosuppression. In this review, we summarize the current knowledge on NK cell modulation by different ex vivo cultivation strategies focused on increasing NK cytotoxicity for clinical application in malignant diseases. Moreover, we critically discuss the technical and regulatory aspects and challenges underlying NK cell based therapeutic approaches in the clinics.
Background and Purpose: This review aims to provide a comprehensive overview of the literature and elucidate open questions for future clinical trials concerning diagnostics and treatment modalities for cervical cancer of unknown primary (CUP).
Methods: A literature search for head and neck CUP was performed with focus on diagnostics and therapies as well as molecular markers.
Results: High level evidence on CUP is limited. However, it seems that a consensus exists regarding the optimal diagnostic procedures. The correct implementation of biomarkers for patient stratification and treatment remains unclear. An even greater dispute dominates about the ideal treatment with publications ranging from sole surgery to surgery with postoperative bilateral radiotherapy with inclusion of the mucosa and concomitant chemotherapy.
Conclusions: Cervical CUP represents a very heterogeneous malignant disease. On this account many aspects concerning treatment optimization remain unclear, despite a considerable number of publications in the past. Future research in form of prospective randomized trials is needed in order to better define patient stratification criteria and enable tailored treatment.
Diffusion tensor imaging (DTI) is amongst the simplest mathematical models available for diffusion magnetic resonance imaging, yet still by far the most used one. Despite the success of DTI as an imaging tool for white matter fibers, its anatomical underpinnings on a microstructural basis remain unclear. In this study, we used 65 myelin-stained sections of human premotor cortex to validate modeled fiber orientations and oft used microstructure-sensitive scalar measures of DTI on the level of individual voxels. We performed this validation on high spatial resolution diffusion MRI acquisitions investigating both white and gray matter. We found a very good agreement between DTI and myelin orientations with the majority of voxels showing angular differences less than 10°. The agreement was strongest in white matter, particularly in unidirectional fiber pathways. In gray matter, the agreement was good in the deeper layers highlighting radial fiber directions even at lower fractional anisotropy (FA) compared to white matter. This result has potentially important implications for tractography algorithms applied to high resolution diffusion MRI data if the aim is to move across the gray/white matter boundary. We found strong relationships between myelin microstructure and DTI-based microstructure-sensitive measures. High FA values were linked to high myelin density and a sharply tuned histological orientation profile. Conversely, high values of mean diffusivity (MD) were linked to bimodal or diffuse orientation distributions and low myelin density. At high spatial resolution, DTI-based measures can be highly sensitive to white and gray matter microstructure despite being relatively unspecific to concrete microarchitectural aspects.
Epigenetic signatures such as methylation of the monoamine oxidase A (MAOA) gene have been found to be altered in panic disorder (PD). Hypothesizing temporal plasticity of epigenetic processes as a mechanism of successful fear extinction, the present psychotherapy-epigenetic study for we believe the first time investigated MAOA methylation changes during the course of exposure-based cognitive behavioral therapy (CBT) in PD. MAOA methylation was compared between N=28 female Caucasian PD patients (discovery sample) and N=28 age- and sex-matched healthy controls via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells. MAOA methylation was furthermore analyzed at baseline (T0) and after a 6-week CBT (T1) in the discovery sample parallelized by a waiting time in healthy controls, as well as in an independent sample of female PD patients (N=20). Patients exhibited lower MAOA methylation than healthy controls (P<0.001), and baseline PD severity correlated negatively with MAOA methylation (P=0.01). In the discovery sample, MAOA methylation increased up to the level of healthy controls along with CBT response (number of panic attacks; T0–T1: +3.37±2.17%), while non-responders further decreased in methylation (−2.00±1.28%; P=0.001). In the replication sample, increases in MAOA methylation correlated with agoraphobic symptom reduction after CBT (P=0.02–0.03). The present results support previous evidence for MAOA hypomethylation as a PD risk marker and suggest reversibility of MAOA hypomethylation as a potential epigenetic correlate of response to CBT. The emerging notion of epigenetic signatures as a mechanism of action of psychotherapeutic interventions may promote epigenetic patterns as biomarkers of lasting extinction effects.
Background: Cell salvage is commonly used as part of a blood conservation strategy. However concerns among clinicians exist about the efficacy of transfusion of washed cell salvage.
Methods: We performed a meta-analysis of randomized controlled trials in which patients, scheduled for all types of surgery, were randomized to washed cell salvage or to a control group with no cell salvage. Data were independently extracted, risk ratio (RR), and weighted mean differences (WMD) with 95% confidence intervals (CIs) were calculated. Data were pooled using a random effects model. The primary endpoint was the number of patients exposed to allogeneic red blood cell (RBC) transfusion.
Results: Out of 1140 search results, a total of 47 trials were included. Overall, the use of washed cell salvage reduced the rate of exposure to allogeneic RBC transfusion by a relative 39% (RR = 0.61; 95% CI 0.57 to 0.65; P < 0.001), resulting in an average saving of 0.20 units of allogeneic RBC per patient (weighted mean differences [WMD] = -0.20; 95% CI -0.22 to -0.18; P < 0.001), reduced risk of infection by 28% (RR = 0.72; 95% CI 0.54 to 0.97; P = 0.03), reduced length of hospital stay by 2.31 days (WMD = -2.31; 95% CI -2.50 to -2.11; P < 0.001), but did not significantly affect risk of mortality (RR = 0.92; 95% CI 0.63 to 1.34; P = 0.66). No statistical difference could be observed in the number of patients exposed to re-operation, plasma, platelets, or rate of myocardial infarction and stroke.
Conclusions: Washed cell salvage is efficacious in reducing the need for allogeneic RBC transfusion and risk of infection in surgery.
Background: The oral administration of the gum resin extracts of Indian frankincense (Boswellia serrata Roxb. ex Colebr) results in very low plasma concentrations of boswellic acids (BAs), being far below the pharmacologically active concentrations required in vitro for anti-inflammatory activity. For that reason the use of Indian frankincense in clinical practice and pharmaceutical development has substantially lagged behind. Recently the application of new formulation technologies resulted in a formulation of frankincense extract with lecithin, which revealed improved absorption and tissue penetration of BAs in a rodent study, leading for the first time to plasma concentrations of BAs in the range of their anti-inflammatory activity.
Purpose: In order to verify these encouraging results in humans, the absorption of a standardized Boswellia serrata extract (BE) and its lecithin formulation (CSP) was comparatively investigated in healthy volunteers.
Study design: According to a randomized cross-over design with two treatments, two sequences and two periods, 12 volunteers alternatively received the lecithin-formulated Boswellia extract (CSP) or the non-formulated Boswellia extract (BE) at a dosage of 2 × 250 mg capsules.
Methods: The plasma concentrations of the six major BAs (KBA, AKBA, βBA, αBA, AβBA, AαBA) were determined using LC/MS.
Results: With the exception of KBA, a significantly higher (both in terms of weight-to-weight and molar comparison) and quicker absorption of BAs from the lecithin formulation was observed, leading to Cmax in the range required for the interaction with their molecular targets.
Conclusion: These findings pave the way to further studies evaluating the clinical potential of BAs, and verify the beneficial effect of lecithin formulation to improve the absorption of poorly soluble phytochemicals.
Type I interferons (IFNs), including IFN-α, upregulate an array of IFN-stimulated genes (ISGs) and potently suppress Human immunodeficiency virus type 1 (HIV-1) infectivity in CD4(+) T cells, monocyte-derived macrophages, and dendritic cells. Recently, we and others identified ISG myxovirus resistance 2 (MX2) as an inhibitor of HIV-1 nuclear entry. However, additional antiviral blocks exist upstream of nuclear import, but the ISGs that suppress infection, e.g., prior to (or during) reverse transcription, remain to be defined. We show here that the HIV-1 CA mutations N74D and A105T, both of which allow escape from inhibition by MX2 and the truncated version of cleavage and polyadenylation specific factor 6 (CPSF6), as well as the cyclophilin A (CypA)-binding loop mutation P90A, all increase sensitivity to IFN-α-mediated inhibition. Using clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 technology, we demonstrate that the IFN-α hypersensitivity of these mutants in THP-1 cells is independent of MX2 or CPSF6. As expected, CypA depletion had no additional effect on the behavior of the P90A mutant but modestly increased the IFN-α sensitivity of wild-type virus. Interestingly, the infectivity of wild-type or P90A virus could be rescued from the MX2-independent IFN-α-induced blocks in THP-1 cells by treatment with cyclosporine (Cs) or its nonimmunosuppressive analogue SDZ-NIM811, indicating that Cs-sensitive host cell cyclophilins other than CypA contribute to the activity of IFN-α-induced blocks. We propose that cellular interactions with incoming HIV-1 capsids help shield the virus from recognition by antiviral effector mechanisms. Thus, the CA protein is a fulcrum for the dynamic interplay between cell-encoded functions that inhibit or promote HIV-1 infection.
Medium range hydrological forecasts in mesoscale catchments are only possible with the use of hydrological models driven by meteorological forecasts, which in particular contribute quantitative precipitation forecasts (QPF). QPFs are accompanied by large uncertainties, especially for longer lead times, which are propagated within the hydrometeorological model system. To deal with this limitation of predictability, a probabilistic forecasting system is tested, which is based on a hydrological-meteorological ensemble prediction system. The meteorological component of the system is the operational limited-area ensemble prediction system COSMO-LEPS that downscales the global ECMWF ensemble to a horizontal resolution of 10 km, while the hydrological component is based on the semi-distributed hydrological model PREVAH with a spatial resolution of 500 m.
Earlier studies have mostly addressed the potential benefits of hydrometeorological ensemble systems in short case studies. Here we present an analysis of hydrological ensemble hindcasts for two years (2005 and 2006). It is shown that the ensemble covers the uncertainty during different weather situations with an appropriate spread-skill relationship. The ensemble also shows advantages over a corresponding deterministic forecast, even under consideration of an artificial spread.
Volatile organic compounds (VOCs) were analyzed in air and snow samples at the Jungfraujoch high alpine research station in Switzerland as part of CLACE 5 (CLoud and Aerosol Characterization Experiment) during February/March 2006. The fluxes of individual compounds in ambient air were calculated from gas phase concentrations and wind speed. The highest flux values were observed for the aromatic hydrocarbons benzene (14.3 µg m−2s−1), 1,3,5-trimethylbenzene (5.27 µg m−2s−1), toluene (4.40 µg m−2s−1), and the aliphatic hydrocarbons i-butane (7.87 µg m−2s−1), i-pentane (3.61 µg m−2s−1) and n-butane (3.23 µg m−2s−1). The fluxes were used to calculate the efficiency of removal of VOCs by snow, and the effect of temperature on removal efficiency. The removal efficiency was calculated at – 24◦C (−13.7◦C) and ranged from 37% (35%) for o-xylene to 93% (63%) for i-pentane. The distribution coefficients of VOCs between the air and snow phases were derived from published poly-parameter linear free energy relationship (pp-LFER) data, and compared with distribution coef- ficients obtained from the simultaneous measurements of VOC concentrations in air and snow at Jungfraujoch. The coefficients calculated from pp-LFER exceeded those values measured in the present study, which indicates more efficient snow scavenging of the VOCs investigated than suggested by theoretical predictions.
We explored the characteristics and motivations of people who, having obtained their genetic or genomic data from Direct-To-Consumer genetic testing (DTC-GT) companies, voluntarily decide to share them on the publicly accessible web platform openSNP. The study is the first attempt to describe open data sharing activities undertaken by individuals without institutional oversight. In the paper we provide a detailed overview of the distribution of the demographic characteristics and motivations of people engaged in genetic or genomic open data sharing. The geographical distribution of the respondents showed the USA as dominant. There was no significant gender divide, the age distribution was broad, educational background varied and respondents with and without children were equally represented. Health, even though prominent, was not the respondents’ primary or only motivation to be tested. As to their motivations to openly share their data, 86.05% indicated wanting to learn about themselves as relevant, followed by contributing to the advancement of medical research (80.30%), improving the predictability of genetic testing (76.02%) and considering it fun to explore genotype and phenotype data (75.51%). Whereas most respondents were well aware of the privacy risks of their involvement in open genetic data sharing and considered the possibility of direct, personal repercussions troubling, they estimated the risk of this happening to be negligible. Our findings highlight the diversity of DTC-GT consumers who decide to openly share their data. Instead of focusing exclusively on health-related aspects of genetic testing and data sharing, our study emphasizes the importance of taking into account benefits and risks that stretch beyond the health spectrum. Our results thus lend further support to the call for a broader and multi-faceted conceptualization of genomic utility.
In evidence-based weight-loss programs weight regain is common after an initial weight reduction. Eating slowly significantly lowers meal energy intake and hunger ratings. Despite this knowledge, obese individuals do not implement this behaviour. We, thus tested the hypothesis of changing eating behaviour with an intra-oral medical device leading to constant weight reduction in overweight and obesity.
Six obese patients (6 men, age 56 ± 14, BMI 29 ± 2 kg / m2) with increased CVRF profile were included in this prospective study. All patients had been treated for obesity during the last 10 years in a single centre and had at least 3 frustrate evidence-based diets. Patients received a novel non-invasive intra-oral medical device to slow eating time. Further advice included not to count calories, to avoid any other form of diet, to take their time with their meals, and to eat whatever they liked.
This device was used only during meals for the first 4 to 8 weeks for a total of 88 [20–160] hours. Follow-up period was 23 [15–38] months. During this period, patients lost 11% [5–20%] (p<0.001) of their initial weight. At 12 months, all patients had lost >5%, and 67% (4/6) achieved a >10% bodyweight loss. In the course of the study, altered eating patterns were observed. There were no complications with the medical device. Of note, all patients continued to lose weight after the initial intervention period (p<0.001) and none of them had weight regain.
With this medical device, overweight and obese patients with a history of previously frustrating attempts to lose weight achieved a significant and sustained weight loss over two years. These results warrant the ongoing prospective randomised controlled trial to prove concept and mechanism of action.
Ziel der vorliegenden Arbeit war es, vor- und nachbereitenden Unterricht zu Biodiversitätsführungen an den vier außerschulischen Lernorten Palmengarten, Senckenbergmuseum, Stadtwaldhaus und Zoo Frankfurt zu evaluieren. Durch den Unterricht mithilfe neu entwickelter Arbeitsmaterialien sollte die aktuelle Motivation der Schüler und weitere pädagogisch-psychologische Lernvariablen gefördert werden. Es stellte sich die Frage, ob so eine erhöhte Auseinandersetzung mit dem Themenkomplex Biodiversität erreicht werden kann und welche Einflussfaktoren dabei eine Rolle spielen.
Theoretische Grundlage war dabei das Risikowahlmodell der Leistungsmotivation nach Atkinson, das von Rheinberg zum handlungstheoretischen Modell der Motivation erweitert wurde (Rheinberg & Vollmeyer, 2012). Auf dieses bezieht sich der von Rheinberg et al. (2001) entwickelte und hier eingesetzte Fragebogen zur aktuellen Motivation (FAM).
Die Stichprobe setzte sich aus insgesamt 523 Schülern der Klassen 5 bis 9 zusammen. Davon nahm jeweils die Hälfte mit (Versuchsgruppe) und die andere ohne (Kontrollgruppe) vor- und nachbereitendem Unterricht an den Biodiversitätsführungen teil. Die Erhebung der aktuellen Motivation, des erworbenen Fachwissens und weiterer Variablen erfolgte in einem Pre/Post/Follow-Up-Design mit Fragebögen, deren Auswertung analytisch statistisch durgeführt wurde.
Es zeigte sich, dass in der Gesamtstichprobe die Teilnahme an der Biodiversitätsführung die aktuelle Motivation der Schüler erhöhte. Dauerhafte Lernparameter wie die Biologieeinstellung und die Interessenshandlung wurden jedoch nicht signifikant verändert. Ein eindeutiger Effekt der unterrichtlichen Vorbereitung konnte jedoch nicht ermittelt werden. Einzig beim gemessen Fachwissen zu den Führungsinhalten schnitt die Versuchsgruppe signifikant besser ab. Insgesamt wird angenommen, dass der Effekt des Besuchs des außerschulischen Lernortes an sich den Effekt der Vor- und Nachbereitung überdeckt oder vom Einfluss anderer Parameter beeinflusst wird. Hier stach besonders das Alter der Jugendlichen hervor, das vor allem in der hier evaluierten Schülergruppe bedingt durch die Pubertät eine große Rolle spielt. Weitere Einflussfaktoren waren die Biologieeinstellung und die Unterrichtsvariablen der Führung. In den Stichproben der einzelnen außerschulischen Lernorte zeigten sich leichte Abweichungen von der Gesamtstichprobe. Diese waren meist auf die leicht unterschiedliche Zusammensetzung der Stichproben zurückzuführen. Aber auch Besonderheiten der Lernorte hatten dabei ein bedeutendes Gewicht.
Bezüglich der Lernbedingungen für die Lernorte ließen sich aus den Ergebnissen vor allem zwei Komponenten ermitteln: Zum einen die Architektur/räumliche Struktur der Lernorte. Hier können Faktoren wie drinnen/ draußen, Größe und die räumliche Orientierung unterschieden werden. All dies hat Auswirkungen auf das physische Wohlbefinden der Schüler, was wiederum eine Voraussetzung für eine hohe Lernmotivation ist. Die andere Hauptkomponente ist das am Lernort behandelte Thema. Hier kann grob zwischen Pflanzen und Tieren unterschieden werden. Pflanzen wurden dabei in mehreren Studien von den Schülern als weniger attraktiv eingeschätzt. Trotzdem sollten aber die Möglichkeiten, auch botanische Themen außerhalb der Schule zu behandeln, von den Lehrkräften zur Vermittlung biologischer Vielfalt genutzt werden.
Als Konsequenz der Ergebnisse kann der Besuch eines außerschulischen Lernrotes im Biologieunterricht bezüglich der Förderung der Lernmotivation unbedingt empfohlen werden. Da kein klarer Effekt des vor- und nachbereitenden Unterrichts der Biodiversitätsführungen erkennbar war, wären hier weitere Untersuchungen vonnöten, um genauere Aussagen machen zu können. Hier böten sich Studien mit Schülern anderer Altersgruppen und der Vergleich nur zweier außerschulischer Lernorte an.
Der vorliegende Beitrag konzentriert sich nicht auf die interessanten, etwas späteren Vorbilder einer italienischen 'hybriden' Rezeption des Gotischen bzw. Phantastischen, die gleichzeitig einer neuen Sensibilität bzw. Ästhetik den Weg ebnete und die das Interesse der Forschung schon erweckte, sondern er verfolgt das Ziel, die weniger erforschten Wurzeln des Genres in Italien zu ergründen. Diese sind unerwartet in 'Fermo e Lucia', d.h. in jener unvollkommenen ersten bzw. 'Ur'-Fassung von Manzonis Prosameisterstück 'I promessi sposi' zu finden.
1896, kurz nach dem Tod Paul Verlaines, veröffentlicht der tschechische Künstler Karel Hlaváček seinen Gedichtband 'Pozdě k ránu' ('Spät, gegen Morgen'). Hlaváček wirkt im Kreis Arnošt Procházkas und Jiři Karásek ze Lvovices, Begründer und Herausgeber der Literaturzeitschrift 'Moderní Revue', die mit ihrer dezidiert europäischen Ausrichtung ein Gegengewicht zum nationalistisch-patriotischen Literaturbetrieb in Prag um 1900 bildet. Durch seine Verbindungen zum eher national konservativ orientierten Sokol ist das Verhältnis zu Arnošt Procházka zeitweilig angespannt, wenngleich die Missstimmung weniger konträren politischen Überzeugungen der beiden Männer als den divergierenden Attitüden von 'Moderní Revue' und Sokol geschuldet ist. Seit der Gründung der Zeitschrift 1894 entwirft der junge Hlaváček mehrere Cover für die 'Revue' und ist vorrangig an der Illustration des Blattes beteiligt. Das Oeuvre des mit 23 Jahren früh an Tuberkulose verstorbenen Tschechen ist überschaubar: neben Literaturkritiken und kürzeren Essays und den genannten Gedichtbänden sind 'Mstíva kantiléna' ('Die Rache der Kantilene') und die posthum veröffentlichen 'Žalmy' ('Psalme') seine einzigen Werke. In 'Pozdě k ránu' findet sich das Prosagedicht 'Subtilnost smutku', das nicht nur in einzigartiger Weise eine Auseinandersetzung der in Westeuropa beliebten Topoi und Schreibverfahren der Décadence darstellt, sondern darüber hinaus als kritischer Kommentar zum intellektuellen Milieu im Prag des ausgehenden 19. Jahrhunderts betrachtet werden kann. Der Wahnsinn fungiert in diesem Text im gleichen Maße als komplexe Metapher wie als strukturierendes Leitmotiv und stellt einen Knotenpunkt der verschiedenen Disziplinen, in denen der Begriff "Décadence" im Fin de siècle ungeheure Popularität erlangt, dar. Wenn der Kritiker Herben mit seiner polemischen Kritik versucht, Hlaváček als geisteskrank zu diskreditieren, so verfehlt er seine Absicht dergestalt, dass er nicht nur die Antihaltung des Künstlers befeuert, sondern er identifiziert darüberhinaus das Element, welches sich als Schlüssel zur Dechiffrierung der Stellung von 'Subtilnost smutku' in einem europäischen Rahmen erweisen soll.
Im alltäglichen Gespräch lässt sich beobachten, dass bei vielen in der Bundesrepublik aufgewachsenen Personen die Kinderbücher Astrid Lindgrens einen hohen Stellenwert und einen starken Einfluss auf Lebensvorstellungen und Werte des zwischenmenschlichen Miteinanders haben. Wenn die eigene Lebenswelt - wie etwa bestimmte Situationen, Lebensumstände, zwischenmenschliche Beziehungen, die äußere Umwelt, das Lebensgefühl - als besonders beglückend, ja geradezu als ideal empfunden werden, ziehen viele Menschen Parallelen zu den in den Texten Astrid Lindgrens modellierten Lebenswelten. Umgekehrt wird auch versucht, die eigene Lebenswelt nach dem Muster dieser Textwelten zu gestalten, um das Leben so schön, harmonisch und beglückend zu gestalten, wie es die Figuren in den Texten vorleben. Da Texte, die einen solch prägenden Eindruck auf uns ausüben und einen so hohen Stellenwert für die eigenen Lebensvorstellungen und die Lebensgestaltung haben, in der Regel auch an die Nachkommen weitergegeben werden, werden die in den Büchern modellierten Lebensvorstellungen und Werte häufig über mehrere Generationen hinweg tradiert und erhalten einen wichtigen identitätsstabilisierenden Platz im kollektiven Gedächtnis. So können bestimmte Welt-, Lebens- und Wertkonstrukte innerhalb einer Gesellschaft über einen längeren Zeitraum Bestand haben und ein fester Teil des gesellschaftlichen Diskurses werden. Ausgehend von diesen Beobachtungen und Hypothesen scheint es lohnend zu sein, folgende Fragen zu stellen: 1. Lässt sich die eingangs formulierte Alltagsbeobachtung von der Wichtigkeit der Bücher Astrid Lindgrens für die Lebensvorstellungen vieler Deutscher auch durch eine umfassende Untersuchung, also durch konkretes Zahlenmaterial, bestätigen? Oder allgemeiner gefragt: Gibt es Bücher, in denen viele Menschen eine ideale Lebenswelt wiederfinden? 2. Falls es wirklich eines oder mehrere solcher Bücher gibt: Wie genau sieht eine solche ideale Lebenswelt für uns aus? Um diese Fragen zu beantworten, wende ich eine Untersuchungsmethode an, die aus drei Schritten besteht: erstens einer quantitativen Befragung zur Ermittlung eines Textkorpus; zweitens einer literaturwissenschaftlichen Analyse der so ermittelten Texte zur Untersuchung der Rezeptionsangebote dieser Texte; drittens Leitfadeninterviews, um herauszuarbeiten, welche der Textangebote tatsächlich von den Rezipienten aktualisiert werden.
Decreased STARD10 expression is associated with defective insulin secretion in humans and mice
(2017)
Genetic variants near ARAP1 (CENTD2) and STARD10 influence type 2 diabetes (T2D) risk. The risk alleles impair glucose-induced insulin secretion and, paradoxically but characteristically, are associated with decreased proinsulin:insulin ratios, indicating improved proinsulin conversion. Neither the identity of the causal variants nor the gene(s) through which risk is conferred have been firmly established. Whereas ARAP1 encodes a GTPase activating protein, STARD10 is a member of the steroidogenic acute regulatory protein (StAR)-related lipid transfer protein family. By integrating genetic fine-mapping and epigenomic annotation data and performing promoter-reporter and chromatin conformational capture (3C) studies in β cell lines, we localize the causal variant(s) at this locus to a 5 kb region that overlaps a stretch-enhancer active in islets. This region contains several highly correlated T2D-risk variants, including the rs140130268 indel. Expression QTL analysis of islet transcriptomes from three independent subject groups demonstrated that T2D-risk allele carriers displayed reduced levels of STARD10 mRNA, with no concomitant change in ARAP1 mRNA levels. Correspondingly, β-cell-selective deletion of StarD10 in mice led to impaired glucose-stimulated Ca2+ dynamics and insulin secretion and recapitulated the pattern of improved proinsulin processing observed at the human GWAS signal. Conversely, overexpression of StarD10 in the adult β cell improved glucose tolerance in high fat-fed animals. In contrast, manipulation of Arap1 in β cells had no impact on insulin secretion or proinsulin conversion in mice. This convergence of human and murine data provides compelling evidence that the T2D risk associated with variation at this locus is mediated through reduction in STARD10 expression in the β cell.
Objective: ACPAs are associated with bone destruction in RA. The aim of this study was to evaluate the association between ACPA and bone destruction in patients with a distinct inflammatory disorder, PsA.
Methods: We used baseline data from a large observational study of PsA patients preparing to initiate treatment with adalimumab to analyse demographic and disease characteristics by ACPA status. To ensure a homogeneous PsA study population, only patients with active psoriatic skin manifestations who met Classification of Psoriatic Arthritis criteria for PsA were included in the analyses, thereby minimizing the risk of including misdiagnosed RA patients. Multiple logistic regression analyses were used to explore potential associations between ACPA seropositivity and bone destruction.
Results: Of 1996 PsA patients who met the strict inclusion criteria, 105 (5.3%) were positive for ACPA. ACPA-positive patients had significantly higher swollen joint counts and 28-joint DAS values than ACPA-negative patients and significantly higher rates of erosive changes and dactylitis. Multiple logistic regression analysis confirmed the association of ACPA seropositivity with a 2.8-fold increase in the risk of erosive disease.
Conclusion: As has been previously shown for RA, ACPA is associated with bone destruction in PsA, suggesting that the osteocatabolic effect of ACPA is not confined to RA but is also detectable in the different pathogenetic context of a distinct disease entity.
Trial registration: ClinicalTrials.gov, NCT01111240.
Rationale: The AMP-activated protein kinase (AMPK) is stimulated by hypoxia, and although the AMPKα1 catalytic subunit has been implicated in angiogenesis, little is known about the role played by the AMPKα2 subunit in vascular repair.
Objective: To determine the role of the AMPKα2 subunit in vascular repair.
Methods and Results: Recovery of blood flow after femoral artery ligation was impaired (>80%) in AMPKα2-/- versus wild-type mice, a phenotype reproduced in mice lacking AMPKα2 in myeloid cells (AMPKα2ΔMC). Three days after ligation, neutrophil infiltration into ischemic limbs of AMPKα2ΔMC mice was lower than that in wild-type mice despite being higher after 24 hours. Neutrophil survival in ischemic tissue is required to attract monocytes that contribute to the angiogenic response. Indeed, apoptosis was increased in hypoxic neutrophils from AMPKα2ΔMC mice, fewer monocytes were recruited, and gene array analysis revealed attenuated expression of proangiogenic proteins in ischemic AMPKα2ΔMC hindlimbs. Many angiogenic growth factors are regulated by hypoxia-inducible factor, and hypoxia-inducible factor-1α induction was attenuated in AMPKα2-deficient cells and accompanied by its enhanced hydroxylation. Also, fewer proteins were regulated by hypoxia in neutrophils from AMPKα2ΔMC mice. Mechanistically, isocitrate dehydrogenase expression and the production of α-ketoglutarate, which negatively regulate hypoxia-inducible factor-1α stability, were attenuated in neutrophils from wild-type mice but remained elevated in cells from AMPKα2ΔMC mice.
Conclusions: AMPKα2 regulates α-ketoglutarate generation, hypoxia-inducible factor-1α stability, and neutrophil survival, which in turn determine further myeloid cell recruitment and repair potential. The activation of AMPKα2 in neutrophils is a decisive event in the initiation of vascular repair after ischemia.
MRI-detection rate and incidence of lumbar bleeding sources in 190 patients with non-aneurysmal SAH
(2017)
Background: Up to 15% of all spontaneous subarachnoid hemorrhages (SAH) have a non-aneurysmal SAH (NASAH). The evaluation of SAH patients with negative digital subtraction angiography (DSA) is sometimes a diagnostic challenge. Our goal in this study was to reassess the yield of standard MR-imaging of the complete spinal axis to rule out spinal bleeding sources in patients with NASAH.
Methods: We retrospectively analyzed the spinal MRI findings in 190 patients with spontaneous NASAH, containing perimesencephalic (PM) and non-perimesencephalic (NPM) SAH, diagnosed by computer tomography (CT) and/or lumbar puncture (LP), and negative 2nd DSA.
Results: 190 NASAH patients were included in the study, divided into PM-SAH (n = 87; 46%) and NPM-SAH (n = 103; 54%). Overall, 23 (22%) patients had a CT negative SAH, diagnosed by positive LP. MR-imaging of the spinal axis detected two patients with lumbar ependymoma (n = 2; 1,05%). Both patients complained of radicular sciatic pain. The detection rate raised up to 25%, if only patients with radicular sciatic pain received an MRI.
Conclusion: Routine radiological investigation of the complete spinal axis in NASAH patients is expensive and can not be recommended for standard procedure. However, patients with clinical signs of low-back/sciatic pain should be worked up for a spinal pathology.
Human beings are assumed to possess an approximate number system (ANS) dedicated to extracting and representing approximate numerical magnitude information. The ANS is assumed to be fundamental to arithmetic learning and has been shown to be associated with arithmetic performance. It is, however, still a matter of debate whether better arithmetic skills are reflected in the ANS. To address this issue, Chinese and German adults were compared regarding their performance in simple arithmetic tasks and in a non-symbolic numerical magnitude comparison task. Chinese participants showed a better performance in solving simple arithmetic tasks and faster reaction times in the non-symbolic numerical magnitude comparison task without making more errors than their German peers. These differences in performance could not be ascribed to differences in general cognitive abilities. Better arithmetic skills were thus found to be accompanied by a higher speed of retrieving non-symbolic numerical magnitude knowledge but not by a higher precision of non-symbolic numerical magnitude representations. The group difference in the speed of retrieving non-symbolic numerical magnitude knowledge was fully mediated by the performance in arithmetic tasks, suggesting that arithmetic skills shape non-symbolic numerical magnitude processing skills.
The acidification of the oceans could potentially alter marine plankton communities with consequences for ecosystem functioning. While several studies have investigated effects of ocean acidification on communities using traditional methods, few have used genetic analyses. Here, we use community barcoding to assess the impact of ocean acidification on the composition of a coastal plankton community in a large scale, in situ, long-term mesocosm experiment. High-throughput sequencing resulted in the identification of a wide range of planktonic taxa (Alveolata, Cryptophyta, Haptophyceae, Fungi, Metazoa, Hydrozoa, Rhizaria, Straminipila, Chlorophyta). Analyses based on predicted operational taxonomical units as well as taxonomical compositions revealed no differences between communities in high CO2 mesocosms (~ 760 μatm) and those exposed to present-day CO2 conditions. Observed shifts in the planktonic community composition were mainly related to seasonal changes in temperature and nutrients. Furthermore, based on our investigations, the elevated CO2 did not affect the intraspecific diversity of the most common mesozooplankter, the calanoid copepod Pseudocalanus acuspes. Nevertheless, accompanying studies found temporary effects attributed to a raise in CO2. Differences in taxa composition between the CO2 treatments could, however, only be observed in a specific period of the experiment. Based on our genetic investigations, no compositional long-term shifts of the plankton communities exposed to elevated CO2 conditions were observed. Thus, we conclude that the compositions of planktonic communities, especially those in coastal areas, remain rather unaffected by increased CO2.
Background: Legionella pneumophila (L. pneumophila) is a causative agent of severe pneumonia. It is highly adapted to intracellular replication and manipulates host cell functions like vesicle trafficking and mRNA translation to its own advantage. However, it is still unknown to what extent microRNAs (miRNAs) are involved in the Legionella-host cell interaction.
Methods: WT and MyD88-/- murine bone marrow-derived macrophages (BMM) were infected with L. pneumophila, the transcriptome was analyzed by high throughput qPCR array (microRNAs) and conventional qPCR (mRNAs), and mRNA-miRNA interaction was validated by luciferase assays with 3´-UTR mutations and western blot.
Results: L. pneumophila infection caused a pro-inflammatory reaction and significant miRNA changes in murine macrophages. In MyD88-/- cells, induction of inflammatory markers, such as Ccxl1/Kc, Il6 and miR-146a-5p was reduced. Induction of miR-125a-3p was completely abrogated in MyD88-/- cells. Target prediction analyses revealed N-terminal asparagine amidase 1 (NTAN1), a factor from the n-end rule pathway, to be a putative target of miR-125a-3p. This interaction could be confirmed by luciferase assay and western blot.
Conclusion: Taken together, we characterized the miRNA regulation in L. pneumophila infection with regard to MyD88 signaling and identified NTAN1 as a target of miR-125a-3p. This finding unravels a yet unknown feature of Legionella-host cell interaction, potentially relevant for new treatment options.
Introduction: Preclinical CT-guided radiotherapy platforms are increasingly used but the CT images are characterized by poor soft tissue contrast. The aim of this study was to develop a robust and accurate method of MRI-guided radiotherapy (MR-IGRT) delivery to abdominal targets in the mouse.
Methods: A multimodality cradle was developed for providing subject immobilisation and its performance was evaluated. Whilst CT was still used for dose calculations, target identification was based on MRI. Each step of the radiotherapy planning procedure was validated initially in vitro using BANG gel dosimeters. Subsequently, MR-IGRT of normal adrenal glands with a size-matched collimated beam was performed. Additionally, the SK-N-SH neuroblastoma xenograft model and the transgenic KPC model of pancreatic ductal adenocarcinoma were used to demonstrate the applicability of our methods for the accurate delivery of radiation to CT-invisible abdominal tumours.
Results: The BANG gel phantoms demonstrated a targeting efficiency error of 0.56 ± 0.18 mm. The in vivo stability tests of body motion during MR-IGRT and the associated cradle transfer showed that the residual body movements are within this MR-IGRT targeting error. Accurate MR-IGRT of the normal adrenal glands with a size-matched collimated beam was confirmed by γH2AX staining. Regression in tumour volume was observed almost immediately post MR-IGRT in the neuroblastoma model, further demonstrating accuracy of x-ray delivery. Finally, MR-IGRT in the KPC model facilitated precise contouring and comparison of different treatment plans and radiotherapy dose distributions not only to the intra-abdominal tumour but also to the organs at risk.
Conclusion: This is, to our knowledge, the first study to demonstrate preclinical MR-IGRT in intra-abdominal organs. The proposed MR-IGRT method presents a state-of-the-art solution to enabling robust, accurate and efficient targeting of extracranial organs in the mouse and can operate with a sufficiently high throughput to allow fractionated treatments to be given.
Glial cell line-derived neurotrophic factor (GDNF) is a ligand that activates, through co-receptor GDNF family receptor alpha-1 (GFRα1) and receptor tyrosine kinase “RET”, several signaling pathways crucial in the development and sustainment of multiple neuronal populations. We decided to study whether non-mammalian orthologs of these three proteins have conserved their function: can they activate the human counterparts? Using the baculovirus expression system, we expressed and purified Danio rerio RET, and its binding partners GFRα1 and GDNF, and Drosophila melanogaster RET and two isoforms of co-receptor GDNF receptor-like. Our results report high-level insect cell expression of post-translationally modified and dimerized zebrafish RET and its binding partners. We also found that zebrafish GFRα1 and GDNF are comparably active as mammalian cell-produced ones. We also report the first measurements of the affinity of the complex to RET in solution: at least for zebrafish, the Kd for GFRα1-GDNF binding RET is 5.9 μM. Surprisingly, we also found that zebrafish GDNF as well as zebrafish GFRα1 robustly activated human RET signaling and promoted the survival of cultured mouse dopaminergic neurons with comparable efficiency to mammalian GDNF, unlike E. coli-produced human proteins. These results contradict previous studies suggesting that mammalian GFRα1 and GDNF cannot bind and activate non-mammalian RET and vice versa.
Cixidia fusca and Synecdoche impunctata (Hemiptera: Achilidae) are reported from Missouri for the first time, new state records. Ecological and trapping information is also provided.
The eight species in the genus Tomarus Erichson (Coleoptera: Scarabaeidae) in Argentina, Chile, and Uruguay are reviewed. Tomarus roigjunenti new species and Tomarus spinipenis new species are described from Argentina. We include a key to species, representative habitus illustrations for all species, character illustrations, and distribution maps for each, as well as commentary about the natural history and distributions for each species. Diagnostic characters are discussed for each species, and species relationships are hypothesized based on the analysis of internal and external morphological characters. The male of T. bidentulus (Fairmaire) is described for fi rst time. The following taxonomic changes are made: Tomarus guianucai Dechambre and Lumaret, 1985 is a new junior synonym of Tomarus rubripes (Boheman, 1858), which was formerly and incorrectly cited as occurring in Argentina.
Descriptions and illustrations of the triungulin, 5th instar, and prepupal larval forms for Nematodes penetrans (LeConte, 1852) (Coleoptera: Eucnemidae: Macraulacinae: Nematodini) are given. The descriptions are based on triungulins collected in a plastic vial as well as 5th instars and prepupal larval stages collected from hard sections of sugar maple (Acer saccharum Marshall; Aceraceae) logs and limbs. Adults were reared from those pieces placed in plastic bags. Biological information is provided, based on literature search and personal observations.
Comparative studies between larvae of N. penetrans and the European species, Nematodes fi lum (Fabricius, 1801) along with other Nearctic larval forms are briefl y discussed. This discovery represents the fi rst larval description for the genus in the Nearctic region.
Four new species of Chrysina Kirby (Coleoptera: Scarabaeidae: Rutelinae) from Guatemala and Honduras
(2017)
Four new species of the genus Chrysina Kirby (Coleoptera: Scarabaeidae: Rutelinae) are described from cloud forests of Guatemala and Honduras. The Guatemalan species are C. alexae n. sp. from Purulhá, Baja Verapáz in the central mountains and C. woodruffi n. sp. from Bulej, Huehuetenango in Los Cuchumatanes Mountains at elevations from 1500 to 2000 meters. The species from Honduras are C. antonkozlovi n. sp. from Celaque, Lempira and C. maishei n. sp. from El Güisayote, Ocotepeque, at elevations between 2000 and 2600 meters above sea level.
Species descriptions, keys to genera and species, and geographical distributions are presented for 43 species of the family Bruchidae (Coleoptera: Chrysomeloidea) for Chile. Of these species, seven are described as new:
Acanthoscelides aricae sp. nov., Lithraeus chillan sp. nov., L. comptus sp. nov., L. elguetai sp. nov., L. limari sp. nov., L. lonquimay sp. nov., and L. penai sp. nov. Eight species are endemic to Chile. A list of true host plants and floral records for those with known host associations is presented. Habitus photographs and drawings of pertinent body parts, including male genitalia, are provided. References pertaining to the previously described species are listed.
The genus Paraphloeolaemus Thomas (Coleoptera: Cucujoidea: Laemophloeidae) is described for two new Neotropical species, P. vorticosus Thomas, new species, and P. pterosiagon Thomas, new species. Diagnoses and illustrations are provided.
The following 16 species are transferred from Laemophloeus Dejean (s. l.) to Phloeolaemus Casey: Phloeolaemus anticus (Sharp, 1899: 518) [= Laemophloeus anticus Sharp, 1899], new combination; Phloeolaemus boops (Sharp, 1899: 517) [= Laemophloeus boops Sharp, 1899], new combination; Phloeolaemus castaneipennis (Grouvelle, 1876: 494) [= Laemophloeus castaneipennis Grouvelle, 1876: 494], new combination; Phloeolaemus championi (Sharp, 1899: 516) [= Laemophloeus championi Sharp, 1899], new combination; Phloeolaemus curtus (Grouvelle, 1876: xxxiii) [= Laemophloeus curtus Grouvelle, 1876], new combination; Phloeolaemus endomychus (Sharp, 1899: 519) [= Laemophloeus endomychus Sharp, 1899], new combination; Phloeolaemus hoplites (Sharp, 1899: 517) [= Laemophloeus hoplites Sharp, 1899], new combination; Phloeolaemus ignobilis (Sharp, 1899: 518) [= Laemophloeus ignobilis Sharp, 1899], new combination; Phloeolaemus impressus (Grouvelle, 1876: xxxiii) [= Laemophloeus impressus Grouvelle, 1876], new combination; Phloeolaemus lacerdae (Grouvelle, 1877: 211) [= Laemophloeus lacerdae Grouvelle, 1877], new combination; Phloeolaemus macrocephalus (Schaeffer, 1910: 214) [= Laemophloeus macrocephalus Schaeffer, 1910], new combination; Phloeolaemus punctulaticollis (Hetschko, 1929: 94) [= Laemophloeus punctulaticollis Hetschko, 1929], new combination; Phloeolaemus reitteri (Grouvelle, 1877: 210) [= Laemophloeus reitteri Grouvelle, 1877], new combination; Phloeolaemus semiflavus (Grouvelle, 1876: 497) [= Laemophloeus semiflavus Grouvelle, 1876], new combination; Phloeolaemus sharpi (Hetschko, 1929: 41) [= Laemophloeus sharpi Hetschko, 1929], new combination; Phloeolaemus straminipennis (Reitter, 1876: 47) [= Laemophloeus straminipennis Reitter, 1876], new combination; Phloeolaemus teapensis (Grouvelle, 1876: 494) [= Laemophloeus teapensis Grouvelle, 1876], new combination.
A new genus and two new species of Argentine Rhinotragini
(Coleoptera, Cerambycidae, Cerambycinae)
(2017)
Rhopalessa irwini sp.nov. and Rhinion parkeri gen. nov., sp. nov. (Coleoptera, Cerambycidae, Cerambycinae, Rhinotragini) are described from Argentina. A key to species of Rhopalessa is provided.
Six annotated lists are presented: A, a checklist of the butterflies (Lepidoptera, Papilionoidea) of Tobago (150 species); B, species for which there are no records in the last 80 years (49 species); C, species needing confi rmation from Tobago (5 species); D, species not accepted from Tobago (12 species); E, species which are likely to occur in Tobago, but have not been recorded (6 species); and F, species and subspecies recorded from Tobago, but not from Trinidad (2 species and 2 subspecies). Remarkably, 33% of the 150 recorded species have not been reported
in the last 80 years. While it is possible that some of these are not resident or have become extinct, it seems more likely that most have simply not been found in the last 80 years. The butterfly fauna of Tobago merits further study; year-round collecting in different habitats and areas, using a variety of techniques, will surely fi ll in many of the apparent gaps in our knowledge. Ouleus fridericus sheldoni ssp. nov. (Hesperiidae, Pyrginae) is described from Tobago, with illustrations of adults and male genitalia, and is compared to O. fridericus sinepunctis (Kaye) from Trinidad. Danaus plexippus tobagi A.H. Clark, 1941 is a syn. nov. of D. plexippus nigrippus (Haensch, 1909) (Nymphalidae, Danainae).
The female of Callichroma magnifi cum Napp and Martins, 2009 (Coleoptera: Cerambycidae: Cerambycinae: Callichromatini) is described and illustrated for the fi rst time. The geographical distribution of the species is expanded to the Colombian Caribbean and information on the collection site is provided.
The Republic of Panama currently has 21 recorded species of stoneflies, all in the genus Anacroneuria (Plecoptera: Perlidae). Herein, we record five species of this genus from the Mount Totumas Cloud Forest and Biological Reserve, in the upper reaches of the Río Chiriquí Viejo watershed. One of these species, A. plutonis (Banks), represents a new country record for Panama. These results are part of an ongoing effort to characterize the aquatic insect fauna of Panama, and to evaluate that country’s major watersheds.
A new genus, Dejunaleon Miller and Stange, is described with two new species: Dejunaleon loja Miller and Dejunaleon maculosus Stange (Neuroptera: Myrmeleontidae: Brachynemurini). A key to species is provided as well as distributional data. A description of the larva of Dejunaleon loja is given. A key to genera of the tribe Brachynemurini is provided based on larvae and adults.
Aphis elena Lagos-Kutz and Voegtlin, sp. nov. (Hemiptera: Aphididae), is described from specimens collected in Illinois, USA, on the North American native plant, Pycnanthemum virginianum (L.) T. Dur. & B.D. Jacks. ex B.L. Rob. & Fernald (Family: Lamiaceae). Both apterous and alate viviparae are described and illustrated, and a dichotomous key is provided to apterous and alate viviparae of the six species of Aphis that have been recorded on plants in the family Lamiaceae in North America. Neighbor-joining analysis of cytochrome oxidase 1 (Cox1) indicated a close relationship of the new species with Aphis monardae Oestlund, which also feeds on a member of Lamiaceae. The range of pair-wise distances for DNA barcoding of these species is 0.17–0.33%. The newly described Aphis elena is morphologically more similar to Aphis gossypii Glover than it is to Aphis monardae.
Females of Traumatomutilla André (Hymenoptera: Mutillidae) are organized into 14 species groups; 136 of the 138 Traumatomutilla taxa known from females were studied. Of these species groups, only the inermis species group was adequately established and diagnosed in the literature (Casal 1969). The remaining newly established species groups are as follows: americana, auriculata, bellica, bifurca, diabolica, gemella, indica, integella, juvenilis, quadrinotata, tabapua, trochanterata, and vitelligera. Diagnoses and lists of included species are provided for each species group. Eighty-three new country records are provided for 49 species.
Effective island conservation depends on thorough biodiversity surveys and species assessment. The U.S. Fish and Wildlife Service in coordination with Point Blue Conservation Science undertook a two-year insect survey of the Farallon Islands, California, in order to catalog current insect and spider species on the island and to gather information that will be used to examine prey dynamics to aid in the conservation of the endemic salamander Aneides lugubris (Hallowell). The report lists 11 insect orders representing 60 families, 107 genera and 112 insect species on Southeast Farallon Island. Holometabolous orders were the most represented on the island with Coleoptera and Diptera being the most abundant, followed by Lepidoptera and Diptera. One spider order was identified, representing six genera and six species.
Nine new species of Rhinotragini (Coleoptera: Cerambycidae: Cerambycinae) are described from the Neotropical region: Odontocera galileoae (Mexico); Odontocera mthomasi (Guatemala); Ecliptoides vandenberghei (Nicaragua); Eclipta ricei and Odontocera skelleyi (Costa Rica); Eclipta nearnsi (Panama); Odontocera stangei (Venezuela); Chariergodes lingafelteri and Ischasia martinsi (Costa Rica and Panama). Ischasia rufi na Thomson, 1864 is formally excluded from the fauna of Costa Rica and Panama, and Nicaragua is added as a new country record for Eclipta fi cta Bezark, Martins and Santos-Silva, 2013. Notes on Ecliptoides monostigma (Bates, 1869)
are provided in the “Diagnosis” of E. vandenberghei.
The genus Speorthus Chamberlin is revalidated for S. tuganbius Chamberlin and S. reyesi, new species (Diplopoda, Polydesmida, Macrosternodesmidae). The families Polydesmidae and Macrosternodesmidae (as they occur in North America) are briefly discussed, and their component North American genera listed. The validity of Macrosternodesmidae is reaffi rmed; the family is predominantly North American. Nearctodesminae, new status, is formally designated as a subfamily of Macrosternodesmidae. The superfamily Trichopolydesmoidea is synonymized with the superfamily Polydesmoidea, new combination.
This revision concerns a small group of Western Palaearctic Copris species (Coleoptera: Scarabaeoidea:
Scarabaeidae) distinguished by having three lateral teeth on the foretibae. According to the literature, this group consists of four taxa: Copris armeniacus Faldermann, 1835, C. felschei Reitter, 1892, C. pueli Mollandin de Boissy, 1905 and C. umbilicatus Abeille de Perrin, 1901. Copris armeniacus is herein deemed a species inquirenda, and C. felschei, for which a neotype is designated, is deemed valid. Copris umbilicatus is recorded for the fi rst time from Turkey. A key to all species of the genus Copris known from the Western Palaearctic is provided. Variability of the cephalic and pronotal armature, and morphology of the parameres are illustrated.
The melon fly, Bactrocera cucurbitae (Coquillett) (Diptera: Tephritidae), is a widespread, economically important tephritid fruit fly species. Bactrocera cucurbitae infests fruits and vegetables of a number of different plant species, with many host plants in the plant family Cucurbitaceae, but with additional hosts scattered across many other plant families. Although thought to be native to India, its distribution has spread throughout many countries in Oriental Asia, into a number of Pacifi c Island nations, and into Africa. The documented introductions into countries outside its native distribution show that this species could establish in other countries where it does not presently occur, particularly through the movement of infested fruit. As with other tephritid fruit fly species, establishment of B. cucurbitae can have signifi cant economic consequences, including damage and loss of food production, as well as requirements for implementation of costly quarantine treatments to permit export of commodities susceptible to infestation by B. cucurbitae and inspection of susceptible imported commodities. In order to avoid these adverse economic consequences, one needs to prevent the entry, establishment and spread of B. cucurbitae into a new habitat. To successfully achieve this, an accurate knowledge of the fly’s host plants is essential. Cognizant of this need, we prepared, and present here, a worldwide list of host plants for B. cucurbitae, with annotations on reported laboratory and fi eld infestation data. Overall, 136 plant taxa from 62 plant genera and 30 plant families are identifi ed as hosts of B. cucurbitae, based on reported fi eld infestation data. The predominant family, as expected, is Cucurbitaceae, with 56 plant taxa (41.2% of all host plant taxa) in which fi eld infestation by B. cucurbitae has been documented. The family with the 2nd highest number of documented infested plant taxa is Solanaceae, for which there are published fi eld infestation data for 20 plant taxa (14.7% of plant taxa for which there is documented fi eld infestation). Papers that list plants as hosts of B. cucurbitae based only on laboratory data, those that list plants as a host but do not report any fi eld infestation data, and those that report interception data add an additional 137 host plant taxa, representing a total of 80 genera and 39 plant families, 20 of which are additional plant families beyond those for which there is fi eld infestation data. These additional species must be considered “undetermined” hosts for which additional data are needed to document actual host status. This paper is a comprehensive documentation of host plants of the melon fly based on recorded infestations in laboratory and/or fi eld, interceptions at ports of entry, or “listing only” associations. Host records presented here will be used in vetting and developing the offi cial USDA list of host plants of the melon fly, which will be published by APHIS as a federal order.
Im Folgenden soll die besondere Bedeutung von Musik und Geräuschen für den Roman 'Sound' aufgezeigt werden. Es gilt dabei nachzuweisen, auf welchen Ebenen und durch welche Elemente Klang Eingang in den Text findet, aber auch zu zeigen, wie die typographische Gestaltung des Romans zu einer besonderen Rezeptionsweise führt, die beim Leser auditive Prozesse einleitet. In diesem Zusammenhang soll analysiert werden, inwiefern die vom Protagonisten thematisierte Musik, also die Rezeption von Musik im Text, die Rezeption des Textes beeinflusst.
Dass Max Aubs Biographie über den Maler Jusep Torres Campalans einer fiktiven Person gilt, dass nicht nur die hier gebotenen Informationen zum Leben und Wirken dieser Figur fingiert sind, sondern auch das im Zusammenhang damit präsentierte 'OEuvre' des Künstlers von Max Aub selbst stammt, sieht man dem Buch Aubs zunächst einmal nicht an; auf den zweiten Blick mögen sich Auffälligkeiten ergeben (wie etwa nicht zueinander stimmende Detailangaben), aber dergleichen kann ja auch Nachlässigkeiten bei der Recherche, beim Lektorieren oder bei der Drucklegung geschuldet sein. Der Roman wird in Form und Ausstattung nach dem Vorbild einer Künstlerbiographie gestaltet. Dazu gehören neben den biografisch-narrativen Teilen des Buchs diverse Abschnitte, die den Duktus faktografischer Darstellungen imitieren; so ein chronikalischer Teil, der JTCs Leben und Wirken in Form einer annalistischen Tabelle in das zeitgenössische historische und kunsthistorische Umfeld einordnet, ferner auch ein umfangreicher Anmerkungsteil, der die Ausführungen weiter historisch und forschungsgeschichtlich kontextualisiert. Und dazu gehören insbesondere auch Reproduktionen und Beschreibungen angeblicher Werke des fiktiven Protagonisten, welche die Suggestion der Existenz dieses Malers schon insofern verstärken, als hier Beschreibung und Beschriebenes, Bildteil und Katalog gemeinsam präsentiert werden. Bilder, die man sieht, so die immanente Logik der Suggestion, sind evidenterweise ‚wirkliche‘ Bilder. Und wenn man, hiervon ausgehend, akzeptiert, dass die Kommentare zu diesen Bildern 'faktografisch' sind, dann ist es nur ein weiterer Schritt zur Akzeptanz auch der übrigen Mitteilungen als 'faktografisch': ein Analogieschluss zwar, aber ein naheliegender.
Compact stars can be treated as the ultimate laboratories for testing theories of dense matter. They are not only extremely dense objects, but they are known to be associated with strong magnetic fields, fast rotation and, in certain cases, with very high temperatures. Here, we present several different approaches to model numerically the signatures and properties of these stars, namely:
•The effects of strong magnetic fields on hybrid stars by using a fully general relativistic approach. We solved the coupled Maxwell-Einstein equations in a self-consistent way, taking into consideration the anisotropy of the energy-momentum tensor due purely to the magnetic field, magnetic field effects on equation of state and the interaction between matter and the magnetic field (magnetization). We showed that the effects of the magnetization and the magnetic field on the equation of state for matter do not play an important role on global properties of neutron stars (only the pure magnetic _eld contribution does). In addition, the magnetic field breaks the spherical symmetry of stars, inducing major changes in the populated degrees of freedom inside these objects and, potentially, converting a hybrid star into a hadronic star over time.
•The effects of magnetic fields and rotation on the structure and composition of proto-neutron stars. We found that the magnetic field not only deforms these stars, but also significantly alters the number of trapped neutrinos in the stellar interior, together with the strangeness content and temperature in each evolution stage from a hot proto-neutron star to a cold neutron star.
•The influence of the quark-hadron phase transitions in neutron stars. In particular, previous calculations have shown that fast rotating neutron stars, when subjected to a quark-hadron phase transition in their interiors, could give rise to the backbending phenomenon characterized by a spin-up era. In this work, we obtained the interesting backbending phenomenon for fast spinning neutron stars. More importantly, we showed that a magnetic field, which is assumed to be axisymmetric and poloidal, can also be enhanced due to the phase transition from normal hadronic matter to quark matter on highly magnetized neutron stars. Therefore, in parallel to the spin-up era, classes of neutron stars endowed with strong magnetic fields may go through a `magnetic-up era' in their lives.
•Finally, we were also able to calculate super-heavy white dwarfs in the presence of strong magnetic fields. White dwarfs are the progenitors of supernova Type Ia explosions and they are widely used as candles to show that the Universe is expanding and accelerating. However, observations of ultraluminous supernovae have suggested that the progenitor of such an explosion should be a white dwarf with mass above the well-known Chandrasekhar limit ~ 1.4 M. In corroboration with other works, but by using a fully general relativistic framework, we obtained also strongly magnetized white dwarfs with masses M ~ 2:0 M.
MoSyD-Jahresbericht 2015 : Drogentrends in Frankfurt am Main : Monitoring-System Drogentrends
(2016)
Der Nucleus suprachiasmaticus (SCN) ist ein Kerngebiet des Hypothalamus mit der Funktion des zentralen Taktgebers für die Generierung der circadianen Rhythmik. Zahlreiche petale Verbindungen zum SCN dienen der Synchronisierung der circadianen Uhr mit der tatsächlichen Tagesphase. Fugale Verbindungen des SCN dienen der Verteilung der Tageszeiteninformation über das Gehirn, insbesondere in vegetativen Zentren. So werden beispielsweise die physiologischen Vorgänge des Kreislaufsystems, Hormonausschüttung, der Schlaf-Wach-Zyklus etc. kontrolliert und mit Tag-Nacht-Wechsel synchronisiert. Obwohl viele dieser Verbindungen verstanden und beschrieben sind, sind die nahen Verbindungen in der unmittelbaren Nähe des SCN und des-sen intrinsische Verbindung nicht genau untersucht. Zur Darstellung dieser nahen Verbindungen wurden DiI-Tracer-Studien an Gehirnschnitten von Mäusen durchgeführt. Untersucht wurde parallel zu der DiI-Färbung das Neuropeptid Vasopressin innerhalb und außerhalb des SCN bei Mäusen von zwei verschiedenen Mäusestämmen (C3H und C57BL); C57BL ist defizient für das photoperiodische sezernierte Epiphysenhormon Melatonin, C3H-Mäuse er-blinden im frühen Lebensalter. Die immunzytochemische Untersuchung des Vasopressin-Systems belegte einen Unterschied in der Zytoarchitektur des SCN zwischen den C3H und C57BL Mäusen. Obwohl einige Elemente ähnliche Lokalisations- und Reaktivitätscharakteristika aufwiesen z.B. die dorsomediale Verteilung der Vasopressin-Perikaryen im Kerngebiet, so zeigte sich bei den C57BL-Mäusen eine deutlich schwächere Reaktivität des Neuropeptids AVP in diesem Bereich und ferner eine deutliche inhomogenere Verteilung der Vasopressin-Elemente im gesamten Kerngebiet. Die Tracing Untersuchung zeigte bei beiden Mäuse-Stämmen die gleichen Verbindungswege des SCN mit der nahen Periphere. Zum einen zeigen die Ergebnisse, dass der Hauptpassage des SCN im dorsomedialen, also im periventrikulären Bereich lokalisiert ist und das der SCN multiple Zugänge an seiner dorsalen und lateralen Grenze zur subparaventrikulären Zone besitzt. Ferner konnte auch gezeigt werden, dass beide bilateralen SCN-Kerne direkt über ausgeprägte Kommissurfaserverbindungen miteinander kommunizieren. Diese Kommissuren dürften dafür verantwortlich sein, den SCN einer Seite mit dem SCN der kontralateralen Seite zu synchronisieren. Obwohl in der vorliegenden Arbeit der Tracer nur einseitig appliziert wurde, ist dennoch von einer gekreuzten kontralateralen Verbindung auszugehen. Hier liegen Ansätze für weitere Un-tersuchungen. Ein weiterer Aspekt der Untersuchungen zeigen Faserverbin-dungen in die Area hypothalamica lateralis (AHL), die eine wichtige Rolle in der Kontrolle der zentralen Nahrungsaufnahme besitzt. Diese Faserverbin-dungen haben ihren Ursprung im SCN bzw. Nucl. paraventricularis und dem Nucl. arcuatus. Diese Verbindungen dienen am ehesten der Modulation der zentralen Regulation der Nahrungsaufnahme und spielen daher eine besondere Rolle in der Krankheitsentstehung wie Adipositas, Diabetes und Herz-Kreislauf-Erkrankung bei gestörter circadianen Rhythmik. Neu ist der Befund einer beachtlichen Anzahl von suprachiasmaticopetalen Fasern aus der sub-paraventrikulären Zone. Diese könnten die Einbindung des limbischen Systems in die Modulation der inneren Uhr erklären, die darüber hinaus ursächlich für zahlreiche Pathologien sein könnten.
In China and other countries of East Asia, so-called Ling-zhi or Reishi mushrooms are used in traditional medicine since several centuries. Although the common practice to apply the originally European name ‘Ganoderma lucidum’ to these fungi has been questioned by several taxonomists, this is still generally done in recent publications and with commercially cultivated strains. In the present study, two commercially sold strains of ‘G. lucidum’, M9720 and M9724 from the company Mycelia bvba (Belgium), are compared for their fruiting body (basidiocarp) morphology combined with molecular phylogenetic analyses, and for their secondary metabolite profile employing an ultra-performance liquid chromatography–electrospray ionization mass spectrometry (UPLC–ESIMS) in combination with a high resolution electrospray ionization mass spectrometry (HR-ESI-MS). According to basidiocarp morphology, the strain M9720 was identified as G. lucidum s.str. whereas M9724 was determined as Ganoderma lingzhi. In molecular phylogenetic analyses, the M9720 ITS and beta-tubulin sequences grouped with sequences of G. lucidum s.str. from Europe whereas those from M9724 clustered with sequences of G. lingzhi from East Asia. We show that an ethanol extract of ground basidiocarps from G. lucidum (M9720) contains much less triterpenic acids than found in the extract of G. lingzhi (M9724). The high amount of triterpenic acids accounts for the bitter taste of the basidiocarps of G. lingzhi (M9724) and of its ethanol extract. Apparently, triterpenic acids of G. lucidum s.str. are analyzed here for the first time. These results demonstrate the importance of taxonomy for commercial use of fungi.
The term superconductivity describes the phenomenon of vanishing electrical resistivity in a certain material, then called a superconductor, below a critical typically very low temperature. Since the discovery of superconductivity in mercury in 1911 many other superconductors have been found and the critical temperature below which superconductivity occurs could recently be raised to the temperatures encountered in a cold antarctic winter.
Superconductors are promising materials for applications. They can serve as nearly loss-free cables for energy transmission, in coils for the generation of high magnetic fields or in various electronic devices, such as detectors for magnetic fields. Despite their obvious advantages, the cost for using superconductors, however, depends a lot on the cooling effort needed to realize the superconducting state. Therefore, the search for a superconductor with critical temperature above room-temperature, which would avoid the need for any specialized cooling system, is one of the main projects of contemporary research in condensed matter physics.
While a theory of superconductivity in simple metals has already been developed in the 1950s, it has meanwhile been recognized that many superconductors are unconventional in the sense that their behavior does not follow the aforementioned theory. Unconventional superconductors differ from conventional superconductors mainly by the momentum- and real-space symmetry of the order parameter, which is associated with the superconducting state. While conventional superconductors have a uniform order parameter, unconventional superconductors can have an order parameter that bears structure. Of course, alternative theoretical descriptions have been suggested, but the discussion on the right theory for unconventional superconductivity has not yet been settled. Ultimately, this lack of a general theory of superconductivity prevents a targeted search for the room-temperature superconductor. Any new theoretical approach must, however, prove its value by correctly predicting the structure of the superconducting order parameter and further material properties.
In this work we participate in the search for a theory of unconventional superconductivity. We discuss the theory of superconductivity mediated by electron-electron interactions, which has been popular in the last few decades due to its success in explaining various properties of the copper-based superconductors that emerged in the 1980s. We give a detailed derivation of the so-called random phase approximation for the Hubbard model in terms of a diagrammatic many-body theory and apply it in conjunction with low-energy kinetic Hamiltonians, which we construct from first principles calculations in the framework of density functional theory. Density functional theory is an established technique for calculating the electronic and magnetic properties of materials solely based on their crystal structure. Its practical implementations in computer codes, however, do for example not describe complicated many-electron phenomena like the superconducting state that we are interested in here. Nevertheless, it can provide important information about the properties of the normal state of the material, which superconductivity emerges from. In our theory we use these information and approach the superconducting state from the normal state.
Such an interfacing of different calculational techniques requires a lot of implementation work in the form of computer code. Inclusion of the computer code into this work would consume by far too much space, but since some of the decisions on approximations in the calculational formalism are guided by the feasibility of the associated computer calculations, we discuss the numerical implementation in great detail.
We apply the developed methods to quasi-two-dimensional organic charge transfer salts and iron-based superconductors. Finally, we discuss implications of our findings for the interpretation of various experiments.
For a chaotic system pairs of initially close-by trajectories become eventually fully uncorrelated on the attracting set. This process of decorrelation can split into an initial exponential decrease and a subsequent diffusive process on the chaotic attractor causing the final loss of predictability. Both processes can be either of the same or of very different time scales. In the latter case the two trajectories linger within a finite but small distance (with respect to the overall extent of the attractor) for exceedingly long times and remain partially predictable. Standard tests for chaos widely use inter-orbital correlations as an indicator. However, testing partially predictable chaos yields mostly ambiguous results, as this type of chaos is characterized by attractors of fractally broadened braids. For a resolution we introduce a novel 0-1 indicator for chaos based on the cross-distance scaling of pairs of initially close trajectories. This test robustly discriminates chaos, including partially predictable chaos, from laminar flow. Additionally using the finite time cross-correlation of pairs of initially close trajectories, we are able to identify laminar flow as well as strong and partially predictable chaos in a 0-1 manner solely from the properties of pairs of trajectories.
Background: The Objective Structured Clinical Examination (OSCE) is increasingly used at medical schools to assess practical competencies. To compare the outcomes of students at different medical schools, we introduced standardized OSCE stations with identical checklists.
Methods: We investigated examiner bias at standardized OSCE stations for knee- and shoulder-joint examinations, which were implemented into the surgical OSCE at five different medical schools. The checklists for the assessment consisted of part A for knowledge and performance of the skill and part B for communication and interaction with the patient. At each medical faculty, one reference examiner also scored independently to the local examiner. The scores from both examiners were compared and analysed for inter-rater reliability and correlation with the level of clinical experience. Possible gender bias was also evaluated.
Results: In part A of the checklist, local examiners graded students higher compared to the reference examiner; in part B of the checklist, there was no trend to the findings. The inter-rater reliability was weak, and the scoring correlated only weakly with the examiner’s level of experience. Female examiners rated generally higher, but male examiners scored significantly higher if the examinee was female.
Conclusions: These findings of examiner effects, even in standardized situations, may influence outcome even when students perform equally well. Examiners need to be made aware of these biases prior to examining.
Aim: We investigated the long-term impact of adjunctive systemic antibiotics on periodontal disease progression. Periodontal therapy is frequently supplemented by systemic antibiotics, although its impact on the course of disease is still unclear.
Material & Methods: This prospective, randomized, double-blind, placebo-controlled multi-centre trial comprising patients suffering from moderate to severe periodontitis evaluated the impact of rational adjunctive use of systemic amoxicillin 500 mg plus metronidazole 400 mg (3x/day, 7 days) on attachment loss. The primary outcome was the percentage of sites showing further attachment loss (PSAL) ≥1.3 mm after the 27.5 months observation period. Standardized therapy comprised mechanical debridement in conjunction with antibiotics or placebo administration, and maintenance therapy at 3 months intervals.
Results: From 506 participating patients, 406 were included in the intention to treat analysis. Median PSAL observed in placebo group was 7.8% compared to 5.3% in antibiotics group (Q25 4.7%/Q75 14.1%; Q25 3.1%/Q75 9.9%; p < 0.001 respectively).
Conclusions: Both treatments were effective in preventing disease progression. Compared to placebo, the prescription of empiric adjunctive systemic antibiotics showed a small absolute, although statistically significant, additional reduction in further attachment loss. Therapists should consider the patient's overall risk for periodontal disease when deciding for or against adjunctive antibiotics prescription.
Parkinson's disease (PD) is a frequent neurodegenerative process in old age. Accumulation and aggregation of the lipid-binding SNARE complex component α-synuclein (SNCA) underlies this vulnerability and defines stages of disease progression. Determinants of SNCA levels and mechanisms of SNCA neurotoxicity have been intensely investigated. In view of the physiological roles of SNCA in blood to modulate vesicle release, we studied blood samples from a new large pedigree with SNCA gene duplication (PARK4 mutation) to identify effects of SNCA gain of function as potential disease biomarkers. Downregulation of complexin 1 (CPLX1) mRNA was correlated with genotype, but the expression of other Parkinson's disease genes was not. In global RNA-seq profiling of blood from presymptomatic PARK4 indviduals, bioinformatics detected significant upregulations for platelet activation, hemostasis, lipoproteins, endocytosis, lysosome, cytokine, Toll-like receptor signaling and extracellular pathways. In PARK4 platelets, stimulus-triggered degranulation was impaired. Strong SPP1, GZMH and PLTP mRNA upregulations were validated in PARK4. When analysing individuals with rapid eye movement sleep behavior disorder, the most specific known prodromal stage of general PD, only blood CPLX1 levels were altered. Validation experiments confirmed an inverse mutual regulation of SNCA and CPLX1 mRNA levels. In the 3′-UTR of the CPLX1 gene we identified a single nucleotide polymorphism that is significantly associated with PD risk. In summary, our data define CPLX1 as a PD risk factor and provide functional insights into the role and regulation of blood SNCA levels. The new blood biomarkers of PARK4 in this Turkish family might become useful for PD prediction.
Patient-reported outcomes (PROs) such as quality of life and work productivity are important for measuring patient's experience. We assessed PROs during and after treatment of hepatitis C virus (HCV) patients.Data were obtained from a phase 3 open label study of sofosbuvir and ribavirin (SOF + RBV) with and without interferon (IFN). Patients completed 4 PRO assessment instruments (SF-36, Functional Assessment of Chronic Illness Therapy-Fatigue, Chronic Liver Disease Questionnaire- HCV, Work Productivity and Activity-Specific Health Problem) before, during, and after treatment.A total of 533 patients with chronic HCV were enrolled; 28.9% treatment-naïve, 23.1% cirrhotic, 219 received IFN + SOF + RBV and 314 received IFN-free SOF + RBV. At baseline, there were no differences in PROs between the IFN-free and IFN-containing treatment arms (all P > 0.05). During treatment, patients receiving IFN + SOF + RBV had a substantial impairment in their PROs (up to -24.4% by treatment week 12, up to -8.3% at week 4 post-treatment). The PRO decrements seen in the SOF + RBV arm were smaller in magnitude (up to -7.1% by treatment week 12), and all returned to baseline or improved by post-treatment week 4. By 12 weeks after treatment cessation, patients who achieved sustained viral response-12 showed some improvement of PRO scores regardless of the regimen (up to +7.1%, P < 0.0001) or previous treatment experience. In multivariate analysis, the use of IFN was independently associated with lower PROs.IFN-based regimens have a profoundly negative impact to PROs. By contrast, the impact of RBV on these PROs is relatively modest. Achieving HCV cure is associated with improvement of most of the PRO scores.
Expression, perception and recognition of intense emotions in healthy and depressed individuals
(2017)
Die Fähigkeit die Gefühle anderer zu erkennen und einzuordnen ermöglicht es soziale Situationen richtig einzuschätzen und soziale Beziehungen aufzubauen. Da Emotionen also in unserem Leben eine wichtige Rolle spielen, kann eine Dysregulation der Emotionsverarbeitung auch zu elementaren Einschränkungen führen. Menschen, die unter depressiven Episoden leiden, durchleben beispielsweise regelmäßig Phasen intensiver und anhaltender Traurigkeit. Jedoch ist noch nicht vollständig erklärt, wie es zu dieser verzerrten Emotionswahrnehmung kommt. Diese Dissertation hatte deshalb das Ziel, den Ausdruck, die Wahrnehmung und das Erkennen extremer Emotionen genauer zu beleuchten.
In Studie 1 wurden der Ausdruck und das Erkennen extremer Emotionen untersucht.
Hierbei dienten aus dem Internet bezogene Videosequenzen von Kindern und Erwachsenen als Basis, in denen diese sich in Situationen befanden, die sie extrem negative oder extrem positive Emotionen durchleben ließen. Die Gesichtsausdrücke der Kinder und Erwachsenen wurden dann zum Zeitpunkt der stärksten emotionalen Erregung in ein Bild umgewandelt und von unabhängigen Ratern auf ihre Valenz und ihr Arousal eingeschätzt. Es wurde beobachtet, dass - entgegen der Vorhersage etablierter Emotionstheorien (z.B. Ekman, 1993) – Emotionen hoher positiver und negativer Intensität schwer auseinander zu halten sind. Tatsächlich wurden positive Emotionsausdrücke häufig als negativ eingeschätzt. Eine mögliche Erklärung dafür liefern Aragón und Kollegen (2015). Sie schätzen den Ausdruck negativer Emotionen in positiven Situationen als Emotionsregulationsstrategie ein, die dazu dient ein emotionales Equilibrium wieder herzustellen, das durch die überwältigenden positiven Emotionen aus dem Gleichgewicht gebracht wurde.
In Studie 2 und 3 wurde die Wahrnehmung negativer Emotionen bei depressiven Menschen im Vergleich zu gesunden Kontrollprobanden auf subjektiver und physiologischer Ebene untersucht. Hierbei wurde zunächst im Rahmen von Studie 2 untersucht, ob Parameter des autonomen Nervensystems (ANS) sich zwischen depressiven und gesunden Probanden unterscheiden. ANS-Parameter umfassten Hormone (Cortisol und DHEA), Herzratenvariabilität (HRV), Hautleitfähigkeit (GSR), Hauttemperatur (TEMP) und Atemfrequenz (RSP). Es konnten erhöhte DHEA-Werte, eine erhöhte Hauttemperatur und eine reduzierte Atemfrequenz in der Patientengruppe gefunden werden. Eine erhöhte Hauttemperatur korrelierte zudem mit der Ausprägung depressiver Symptome und der aktuellen Stimmung. Reduzierte HRV-Werte wurden hauptsächlich auf antidepressive Medikation zurückgeführt.
In Studie 3 wurde dann die Reaktion der Probanden auf emotionsevozierende Stimuli verschiedener Valenzkategorien (neutral, leicht negative, hoch negative) untersucht. Hierbei wurden sowohl physiologische Parameter (TEMP, HRV, GSR, RSP) als auch die subjektive Einschätzung der Stimuli bezüglich ihrer Valenz und ihres Arousal erhoben. Die Befunde bezüglich Hauttemperatur und HRV-Werte aus Studie 2 konnten in Studie 3 repliziert
werden. Zudem zeigte sich eine akzentuierte Reaktion der RSP sowie höhere Valenz- und Arousalratings in der Patientengruppe. Das subjektiv intensivere Empfinden der Stimuli bei den Patienten hing zusätzlich mit emotionaler und sozialer Kompetenz zusammen.
In dieser Dissertation konnte gezeigt werden, dass Ausdrücke intensiver Emotionen im Gesicht oft als zweideutig wahrgenommen werden. Um ein genaueres Verständnis der Emotionswahrnehmung bei depressiven Menschen zu erlangen, konnten zudem mehrere Parameter des ANS identifiziert werden, die teils noch nicht untersucht wurden und einer intensiveren Emotionswahrnehmung bei depressiven Patienten zugrunde liegen könnten.
Hierbei wurden zusätzlich Zusammenhänge zu weiteren Aspekten der Depression, wie Defiziten in sozialen Kompetenzen, aufgezeigt. Damit gibt diese Dissertation umfassende Aufschlüsse über Emotionsverarbeitungsprozesse bei gesunden und depressiven Menschen.
Background: Detailed injury data are not available for international tournaments in field hockey. We investigated the epidemiology of field hockey injuries during major International Hockey Federation (Fédération Internationale de Hockey, FIH) tournaments in 2013.
Materials: and methods FIH injury reports were used for data collection. All major FIH tournaments for women (n=5) and men (n=11) in 2013 were included. The main focus of this study was to assess the pattern, time, site on the pitch, body site and mechanism of each of the injuries. We calculated the average number of injuries per match and the number of injuries per 1000 player match hours.
Results: The average number of injuries was 0.7 (95% CI 0.5 to 1.0) per match in women's tournaments and 1.2 (95% CI 0.8 to 1.7) per match in men's tournaments. The number of injuries per 1000 player match hours ranged from 23.4 to 44.2 (average 29.1; 95% CI 18.6 to 39.7) in women and 20.8 to 90.9 (average 48.3; 95% CI 30.9 to 65.8) in men. Most injuries occurred in the circle (n=25, 50%, in women, n=95, 51%, in men). The rate of injuries increased after the first quarter. Injuries to the head and face (n=20, 40%) were most common in women. The head/face (n=51, 27%) and the thigh/knee (n=52, 28%) were equally affected in men. The ball caused the most injuries, followed by the stick, collisions and tripping/falling. There were no deaths or injuries that required hospital treatment in the entire cohort.
Summary: Field hockey has a low incidence of acute injuries during competition.
Ocular gene therapy approaches have been developed for a variety of different diseases. In particular, clinical gene therapy trials for RPE65 mutations, X-linked retinoschisis, and choroideremia have been conducted at different centers in recent years, showing that adeno-associated virus (AAV)-mediated gene therapy is safe, but limitations exist as to the therapeutic benefit and long-term duration of the treatment. The technique of vector delivery to retinal cells relies on subretinal injection of the vector solution, causing a transient retinal detachment. Although retinal detachments are known to cause remodeling of retinal neuronal structures as well as significant cell loss, the possible effects of this short-term therapeutic retinal detachment on retinal structure and circuitry have not yet been studied in detail. In this study, retinal morphology and apoptotic status were examined in healthy rat retinas following AAV-mediated gene transfer via subretinal injection with AAV2/5.CMV.d2GFP or sham injection with fluorescein. Outer plexiform layer (OPL) morphology was assessed by immunohistochemical labeling, laser scanning confocal microscopy, and electron microscopy. The number of synaptic contacts in the OPL was quantified after labeling with structural markers. To assess the apoptotic status, inflammatory and pro-apoptotic markers were tested and TUNEL assay for the detection of apoptotic nuclei was performed. Pre- and postsynaptic structures in the OPL, such as synaptic ribbons or horizontal and bipolar cell processes, did not differ in size or shape in injected versus non-injected areas and control retinas. Absolute numbers of synaptic ribbons were not altered. No signs of relevant gliosis were detected. TUNEL labeling of retinal cells did not vary between injected and non-injected areas, and apoptosis-inducing factor was not delocalized to the nucleus in transduced areas. The neuronal circuits in the OPL of healthy rat retinas undergoing AAV-mediated gene transfer were not altered by the temporary retinal detachment caused by subretinal injection, the presence of viral particles, or the expression of green fluorescent protein as a transgene. This observation likely requires further investigations in the dog model for RPE65 deficiency in order to determine the impact of RPE65 transgene expression on diseased retinas in animals and men.
Hyponatremia is the most common and by far underestimated electrolyte disorder in clinical practice. Especially in elderly patients, treatment of symptomatic hyponatremia is challenging. Herein we describe the case of an octogenarian with recurrent symptomatic hyponatremia due to idiopathic syndrome of inappropriate antidiuretic hormone release (SIADH). Fluid restriction was insufficient to prevent repeated episodes of hyponatremia complicated by falls and coma. After introduction of a low-dose therapy with tolvaptan, serum sodium levels as well as the clinical condition were stable under vaptan therapy, without any relapse for more than six years now. This case demonstrates that long-term tolvaptan treatment for hyponatremia caused by SIADH is safe and well tolerated, even in the elderly.
We have developed a new in vitro skin irritation test based on an open source reconstructed epidermis (OS-REp) with openly accessible protocols for tissue production and test performance. Due to structural, mechanistic and procedural similarity, a blinded catch-up validation study for skin irritation according to OECD Performance Standards (PS) was conducted in three laboratories to promote regulatory acceptance, with OS-REp models produced at a single production site only. While overall sensitivity and predictive capacity met the PS requirements, overall specificity was only 57%. A thorough analysis of the test results led to the assumption that some of the false-positive classifications could have been evoked by volatile skin-irritating chemicals tested in the same culture plate as the non-irritants falsely predicted as irritants. With GC/MS and biological approaches the cross-contamination effect was confirmed and the experimental set-up adapted accordingly. Retesting of the affected chemicals with the improved experimental set-up and otherwise identical protocol resulted in correct classifications as non-irritants. Taking these re-test results into account, 93% overall sensitivity, 70% specificity and 82% accuracy was achieved, which is in accordance with the OECD PS. A sufficient reliability of the method was indicated by a within-laboratory-reproducibility of 85–95% and a between-laboratory-reproducibility of 90%.
The first myrmecophilous fl ea beetle genus (Myrmeconycha Konstantinov and Tishechkin, new genus) with four new species (M. erwini Konstantinov and Tishechkin, new species – Ecuador, M. gordoni Konstantinov and Tishechkin, new species – Brazil, M. pakaluki Konstantinov and Tishechkin, new species – Panama, and M. pheidole Konstantinov and Tishechkin, new species – Costa Rica) is described and illustrated. It is compared with fl ea beetles of the subtribe Disonychina (Coleoptera: Chrysomelidae: Galerucinae: Alticini) and may be easily differentiated based on the external and internal features, which include the waxy surface of the head and pronotum, reticulated surface of the pronotum, and four longitudinal ridges on each elytron.