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In many markets, design is one of the key factors in determining a product’s success. The present research offers insights into the role of design for the success of cars, and offers procedures to measure the quality of the designs objectively. The authors show that visual design plays a major role in a product’s success in the automobile market. In the study, two visual design aspects were already sufficient to significantly improve traditional sales forecasting models for cars. Visual prototypicality and visual complexity both had a positive impact on sales, and designs that were perceived as both prototypical and complex were the ones that displayed the best results. Most design evaluation used to be based on subjective measures, but the researcher applied a new, objective procedure to measure prototypicality and complexity. While the latter was detected by the disk space needed by the compressed image file, the new approach for measuring prototypicality was even more sophisticated. It relied on the technique of image morphing. Morphing is a technique that allows the construction of a visual synthesis – or average picture – from a number of individual pictures. Once a car morph is developed, one can determine the visual similarity of different car models to the morph in order to obtain its prototypicality. In principle, this procedure can be automated completely, and including a large number of versions is possible. These measures therefore seem suitable for supporting design decision processes in practice.
OBJECTIVES: Outcome of aortic valve replacement may be influenced by the choice of bioprosthesis. Pericardial heart valves are described to have a favourable haemodynamic profile compared with porcine valves, although the clinical notability of this finding is still controversially debated. Herein, we compared the long-term results of two commonly implanted bioprosthesis at a single centre.
METHODS: All consecutive patients undergoing isolated aortic valve replacement with either a Carpentier-Edwards Magna pericardial prosthesis or a Medtronic Mosaic porcine prosthesis between 2002 and 2008 were analysed regarding preoperative characteristics, short- and long-term survival, valve-related complications and echocardiographic findings.
RESULTS: The Medtronic Mosaic was implanted in 163 patients and the Carpentier-Edwards Magna in 295 patients. The sizes of implanted valves were 22.4 ± 1.5 mm for the Mosaic and 21.8 ± 1.8 mm for the Magna (P = 0.001). The long-term survival rate was 76 and 56% after 5 and 10 years for the Medtronic Mosaic, which was comparable with the Carpentier-Edwards Magna (77 and 57%; P = 0.92). Overall long-term survival was comparable with an age- and sex-matched Austrian general population for both groups. Valve-related adverse events were similar between groups. The postoperative mean transvalvular gradient was significantly increased in the Mosaic group (24 ± 9 mmHg vs 17 ± 7 mmHg; P < 0.001).
CONCLUSIONS: Both types of aortic bioprostheses offer excellent results after isolated aortic valve replacement. Despite relevant differences in gradients, long-term survival was comparable with the expected normal survival for both bioprostheses. Patients with a porcine heart valve had a higher postoperative transvalvular gradient.
The paper is aimed at contributing to an empirically grounded understanding of the psychosocial dynamics that underlie the relation between heteronormative images of masculinity, internalized heterosexism and health behavior of gay men in the global North. It is based on a qualitative interview study that focuses on the consequences of the internalization of dominant images of masculinity for the identity constructions of gay men and their HIV-related sexual risk behavior in Germany. In the paper it will be argued that 1) the tension between the authoritative image of masculinity that is determined by heteronormative discourses one the one hand and the gendered self-image that is shaped and threatened by connotations of a non-masculine homosexuality on the other constitutes a decisive issue of gay identity constructions, 2) a higher sexual risk behavior can be understood as a possible consequence of the internalization of masculine images and its impact on the self-esteem, if the self-image does not match the male ideal, and 3) this may include a paradoxical desire for the imagined masculinity that is experienced as violent with regard to one’s own psychodynamics. Finally, perspectives on gay masculinities that may transgress dominant heteronormative modes of subjectification are discussed.
CD4+CD25+ regulatory T cells (Tregs) represent a specialized subpopulation of T cells, which are essential for maintaining peripheral tolerance and preventing autoimmunity. The immunomodulatory effects of Tregs depend on their activation status. Here we show that, in contrast to conventional anti-CD4 monoclonal antibodies (mAbs), the humanized CD4-specific monoclonal antibody tregalizumab (BT-061) is able to selectively activate the suppressive properties of Tregs in vitro. BT-061 activates Tregs by binding to CD4 and activation of signaling downstream pathways. The specific functionality of BT-061 may be explained by the recognition of a unique, conformational epitope on domain 2 of the CD4 molecule that is not recognized by other anti-CD4 mAbs. We found that, due to this special epitope binding, BT-061 induces a unique phosphorylation of T-cell receptor complex-associated signaling molecules. This is sufficient to activate the function of Tregs without activating effector T cells. Furthermore, BT-061 does not induce the release of pro-inflammatory cytokines. These results demonstrate that BT-061 stimulation via the CD4 receptor is able to induce T-cell receptor-independent activation of Tregs. Selective activation of Tregs via CD4 is a promising approach for the treatment of autoimmune diseases where insufficient Treg activity has been described. Clinical investigation of this new approach is currently ongoing.
Brain activity reveals exquisite coordination across spatial scales, from local microcircuits to brain-wide networks. Understanding how the brain represents, transforms and communicates information requires simultaneous recordings from distributed nodes of whole brain networks with single-cell resolution. Realizing multi-site recordings from communicating populations is hampered by the need to isolate clusters of interacting cells, often on a day-to-day basis. Chronic implantation of multi-electrode arrays allows long-term tracking of activity. Lithography on thin films provides a means to produce arrays of variable resolution, a high degree of flexibility, and minimal tissue displacement. Sequential application of surface arrays to monitor activity across brain-wide networks and subsequent implantation of laminar arrays to target specific populations enables continual refinement of spatial scale while maintaining coverage.
Generating functionals may guide the evolution of a dynamical system and constitute a possible route for handling the complexity of neural networks as relevant for computational intelligence.We propose and explore a new objective function, which allows to obtain plasticity rules for the afferent synaptic weights. The adaption rules are Hebbian, self-limiting, and result from the minimization of the Fisher information with respect to the synaptic flux. We perform a series of simulations examining the behavior of the new learning rules in various circumstances.The vector of synaptic weights aligns with the principal direction of input activities, whenever one is present. A linear discrimination is performed when there are two or more principal directions; directions having bimodal firing-rate distributions, being characterized by a negative excess kurtosis, are preferred. We find robust performance and full homeostatic adaption of the synaptic weights results as a by-product of the synaptic flux minimization. This self-limiting behavior allows for stable online learning for arbitrary durations.The neuron acquires new information when the statistics of input activities is changed at a certain point of the simulation, showing however, a distinct resilience to unlearn previously acquired knowledge. Learning is fast when starting with randomly drawn synaptic weights and substantially slower when the synaptic weights are already fully adapted.
Polo-like kinase 1 regulates the stability of the mitotic centromere-associated kinesin in mitosis
(2014)
Proper bi-orientation of chromosomes is critical for the accurate segregation of chromosomes in mitosis. A key regulator of this process is MCAK, the mitotic centromere-associated kinesin. During mitosis the activity and localization of MCAK are regulated by mitotic key kinases including Plk1 and Aurora B. We show here that S621 in the MCAK’s C-terminal domain is the major phosphorylation site for Plk1. This phosphorylation regulates MCAK’s stability and facilitates its recognition by the ubiquitin/proteasome dependent APC/CCdc20 pathway leading to its D-box dependent degradation in mitosis. While phosphorylation of S621 does not directly affect its microtubule depolymerising activity, loss of Plk1 phosphorylation on S621 indirectly enhances its depolymerization activity in vivo by stabilizing MCAK, leading to an increased level of protein. Interfering with phosphorylation at S621 causes spindle formation defects and chromosome misalignments. Therefore, this study suggests a new mechanism by which Plk1 regulates MCAK: by regulating its degradation and hence controlling its turnover in mitosis.
Global Governance ist in: Klingt neuartig, global ist eigentlich auch alles und wer will sich schon vorwerfen lassen, noch im „methodologischen Nationalismus“ verhaftet zu sein? Dies ist überspitzt formuliert, doch wie sich zeigte nicht ganz unberechtigt. Nichtsdestotrotz waren die OrganisatorInnen des ersten Weltkongresses der International Association of Political Science Students (IAPSS) wohl selbst überrascht als zur Tagung mit dem Titel „The Limits of Global Governance“ rund 200 Anmeldungen von Studierenden kamen. In Thessaloniki, der europäischen Jugendhauptstadt 2014, wurde vier Tage über Global Governance debattiert und in den insgesamt sieben studentischen Panels, zahlreichen Vorträgen von etablierten WissenschaftlerInnen und weiteren Veranstaltungen zeigte sich vor allem die Vielfalt und Breite des Themas. Wir werden daher im Folgenden Schlaglichter auf interessante Veranstaltungen und Inhalte werfen und abschließend ein kritisch-konstruktives Fazit der Tagung ziehen.
Objective: To investigate the impact of HPV status in patients with locally advanced head and neck squamous cell carcinoma (HNSCC), who received surgery and cisplatin-based postoperative radiochemotherapy.
Materials and methods: For 221 patients with locally advanced squamous cell carcinoma of the hypopharynx, oropharynx or oral cavity treated at the 8 partner sites of the German Cancer Consortium, the impact of HPV DNA, p16 overexpression and p53 expression on outcome were retrospectively analysed. The primary endpoint was loco-regional tumour control; secondary endpoints were distant metastases and overall survival.
Results: In the total patient population, univariate analyses revealed a significant impact of HPV16 DNA positivity, p16 overexpression, p53 positivity and tumour site on loco-regional tumour control. Multivariate analysis stratified for tumour site showed that positive HPV 16 DNA status correlated with loco-regional tumour control in patients with oropharyngeal carcinoma (p = 0.02) but not in the oral cavity carcinoma group. Multivariate evaluation of the secondary endpoints in the total population revealed a significant association of HPV16 DNA positivity with overall survival (p < 0.01) but not with distant metastases.
Conclusions: HPV16 DNA status appears to be a strong prognosticator of loco-regional tumour control after postoperative cisplatin-based radiochemotherapy of locally advanced oropharyngeal carcinoma and is now being explored in a prospective validation trial.
Late stage cancer is often associated with reduced immune recognition and a highly immunosuppressive tumor microenvironment. The presence of tumor infiltrating lymphocytes (TILs) and specific gene-signatures prior to treatment are linked to good prognosis, while the opposite is true for extensive immunosuppression. The use of adenoviruses as cancer vaccines is a form of active immunotherapy to initialise a tumor-specific immune response that targets the patient’s unique tumor antigen repertoire. We report a case of a 68-year-old male with asbestos-related malignant pleural mesothelioma who was treated in a Phase I study with a granulocyte-macrophage colony‑stimulating factor (GM-CSF)-expressing oncolytic adenovirus, Ad5/3-D24-GMCSF (ONCOS-102). The treatment resulted in prominent infiltration of CD8C lymphocytes to tumor, marked induction of systemic antitumor CD8C T-cells and induction of Th1- type polarization in the tumor. These results indicate that ONCOS-102 treatment sensitizes tumors to other immunotherapies by inducing a T-cell positive phenotype to an initially T-cell negative tumor.
"Kapabel, miserabel, aimabel" : Funktionen der französischen Sprachelemente in Heinrich Heines Lyrik
(2014)
Durch das gesamte Werk Heinrich Heines ziehen sich fremdsprachige Einstreuungen, wobei diejenigen in französischer Sprache das größte Gewicht einnehmen. Nach einem Rekurs auf Heines biographische Situation und sein Verhältnis zur deutschen und französischen Sprache werden Form und Funktion der französischen Einsprengsel – vor allem Adjektive, substantivierte Verben und Interjektionen – in Heines lyrischen Texten untersucht. Anhand zahlreicher Beispiele zeigt der Beitrag, dass die französischen Elemente offensichtlich bewusst eingesetzt wurden, um bestimmte semantische Strategien zu verfolgen. Dabei können vor allem sprach-spielerische und gesellschaftskritische Funktionen nachgewiesen werden.
Response to Kriticos et al.
(2014)
Various aspects of uncertainty have become topical in pest risk modelling discussions. A recent contribution to the literature sought to explore the effect of taxonomic uncertainty on modelled pest risk. The case study involved a high profile plant pathogen Puccinia psidii, which causes a major disease of plants within the Myrtaceae family. Consequently, the results and recommendations may attract a wide range of interest in the biosecurity and pest risk modelling communities. We found the study by Elith et al. (2013) included a number of methodological issues that limit some of the specific and general conclusions reached in the paper. We discuss these issues and the ensuing implications for biosecurity management. We also draw attention to the need for pest risk modellers and biosecurity managers to find ways to communicate more effectively. We urge modellers and managers alike to develop a better understanding of the challenges and limitations of modelling species potential distributions across novel climates, and to be able to appreciate the meanings and limitations of models framed in different ways.
This dataset represents a registry of species that are not native but recorded to live in the wild of at least one of the four countries that comprise the Two Seas Area, i.e. Great Britain, France, Belgium and the Netherlands. For each of the 6,661 species, subspecies and hybrids listed, we provide detailed information on its status in each country, taxonomic affiliation and environment inhabited. The data were collected by review of 36 web- and print-based sources over an eight-month period. Further systematic scanning of three of the most relevant scientific journals, i.e. Neobiota, Aquatic Invasions and BioInvasions Records, recovered 19 additional relevant publications from which information was included in the registry. As a result, the registry will serve as a basis for developing effective, cross-boundary strategies to manage and control non-native species, which can have severe ecological and economic impacts. The registry can further be used as a general reference for both scientists and practitioners, as well as a tool to assess reliability and comprehensiveness of other well-known databases such as the DAISIE portal.
The article reviews distribution records of Deroceras invadens (previously called D. panormitanum and D. caruanae), adding significant unpublished records from the authors’ own collecting, museum samples, and interceptions on goods arriving in the U.S.A. By 1940 D. invadens had already arrived in Britain, Denmark, California, Australia and probably New Zealand; it has turned up in many further places since, including remote oceanic islands, but scarcely around the eastern Mediterranean (Egypt and Crete are the exceptions), nor in Asia. Throughout much of the Americas its presence seems to have been previously overlooked, probably often being mistaken for D. laeve. New national records include Mexico, Costa Rica, and Ecuador, with evidence from interceptions of its presence in Panama, Peru, and Kenya. The range appears limited by cold winters and dry summers; this would explain why its intrusion into eastern Europe and southern Spain has been rather slow and incomplete. At a finer geographic scale, the occurrence of the congener D. reticulatum provides a convenient comparison to control for sampling effort; D. invadens is often about half as frequently encountered and sometimes predominates. Deroceras invadens is most commonly found in synanthropic habitats, particularly gardens and under rubbish, but also in greenhouses, and sometimes arable land and pasture. It may spread into natural habitats, as in Britain, South Africa,
Australia and Tenerife. Many identifications have been checked in the light of recent taxonomic revision, revealing that the sibling species D. panormitanum s.s. has spread much less extensively. A number of published or online records, especially in Australia, have turned out to be misidentifications of D. laeve.
Non-neuronal acetylcholine plays a substantial role in the human skin by influencing adhesion, migration, proliferation and differentiation of keratinocytes. These processes are regulated by the Mitogen-Activated Protein (MAP) kinase cascade. Here we show that in HaCaT keratinocytes all five muscarinic receptor subtypes are expressed, but M1 and M3 are the subtypes involved in mitogenic signaling. Stimulation with the cholinergic agonist carbachol leads to activation of the MAP kinase extracellular signal regulated kinase, together with the protein kinase Akt. The activation is fully dependent on the transactivation of the epidermal growth factor receptor (EGFR), which even appears to be the sole pathway for the muscarinic receptors to facilitate MAP kinase activation in HaCaT cells. The transactivation pathway involves a triple-membrane-passing process, based on activation of matrix metalloproteases, and extracellular ligand release; whereas phosphatidylinositol 3-kinase, Src family kinases or protein kinase C do not appear to be involved in MAP kinase activation. Furthermore, phosphorylation, ubiquitination and endocytosis of the EGF receptor after cholinergic transactivation are different from that induced by a direct stimulation with EGF, suggesting that ligands other than EGF itself mediate the cholinergic transactivation.
Im Aufsatz versucht der Autor, nach einer textgestützten Interpretation von Martial II 51, zu zeigen, wie der Epigrammatiker die Fabel des augusteischen Historikers Livius vom Magen und den Gliedern (II 32,9ff.) in eine frivole Parodie überführt und sie zu einer witzigen und grotesken Karikatur verformt – ein spöttisches Spiel mit gattungs- und literaturgeschichtlichen Elementen.
Die bisher vorliegenden Lesungen einer fragmentarischen Weihinschrift aus Solothurn/Salodurum (CIL XIII 5170) müssen in einigen Punkten korrigiert werden. So ist die Lesung des Personennamens [O]pilius, Ma[o]pilius, Ma[ga]pilius oder Mapilius zu verwerfen. Wahrscheinlich führte der Dedikant der Inschrift den Namen M(arcus) A(urelius) [Ap]rilius. Das Gentilnomen Aprilius ist in den germanischen Provinzen und der Gallia Belgica mehrfach bezeugt.
In den römischen Grabinschriften 2. N. Nr.129 (Mittelstrimmig) und CIL XIII 6202 (Schwarzerden) sollte D•F zu d(e)f(unctis) bzw. d(e)f(uncto) aufgelöst werden und nicht zu D(ecimi) f(ilio) bzw. d(efuncto) f(ecit). Die Wendung defunctus kommt im gallisch-germanischen Raum vor allem in Bordeaux/Burdigala und im Gebiet von Trier/Augusta Treverorum vor.
It has become increasingly apparent over the last decades that cooking pottery played a considerable role as a trade commodity in ancient times, yet relatively little research has yet been done on this topic for its own sake. By taking a closer look at the cooking pottery found in Priene, a small city in southern Ionia re-founded in the middle of the 4th century BCE, we want to trace some of the broader developments within the cooking wares that were used over a period of roughly 300 years. The aim is not only to outline the general shapes that were in use over this period of time, but also to register if and how these shapes correlate with the different fabrics observed in Priene so far.
The title compound, [Li2(C25H23BN4OP)2], features a centrosymmetric dimeric complex. The four-memberered Li2O2 ring is exactly planar due to symmetry. The Li atom is four-coordinated by two O atoms and by two N atoms of two different pyrazole rings. The dihedral angle between two pyrazole rings bonded to the same B atom is 45.66 (9)°. The B—N—N—Li—N—N metalla ring adopts a boat conformation. The crystal packing is stabilized by van der Waals interactions only.
The structure of the title compound, C8H16N4, which consists of four fused seven-membered rings, has been redetermined at 173 K. This redetermination corrects the orientation of two H atoms, which were located at unrealistic positions in the original room-temperature study [Murray-Rust (1974[Murray-Rust, P. (1974). J. Chem. Soc. Perkin Trans. 2, pp. 1136-1141.]). J. Chem. Soc. Perkin Trans. 2, pp. 1136–1141]. The complete molecule is generated by -42m symmetry, with one quarter of a molecule [one N atom (site symmetry m), two C atoms (one with site symmetry m and the other with site symmetry 2) and two H atoms] in the asymmetric unit. No directional interactions beyond van der Waals contacts are apparent in the crystal structure.
In the title compound, C40H76Si, the Si atom is located on a special position of site symmetry -4. Thus, there is just a quarter of a molecule in the asymmetric unit. The C=C double bonds exhibit a trans configuration. The Si atom and the tert-butyl group are located on the same side of the plane formed by the C=C double bond and its four substituents. The crystal packing shows no short contacts between the molecules and despite the low crystal density (0.980 Mg m−3), there are no significant voids in the structure.
In the title compound, C19H24N2O2, a di-Mannich base derived from 2-methylphenol and 1,3,6,8-tetraazatricyclo[4.4.1.13,8]dodecane, the imidazolidine ring adopts a twist conformation, with a twist about the ring N—C bond [C—N—C—C torsion angle = −44.34 (14)°]. The two 2-hydroxy-3-methylbenzyl groups are located in trans positions with respect to the imidazolidine fragment. The structure displays two intramolecular O—H⋯N hydrogen bonds, which each form an S(6) ring motif. In the crystal, the molecules are linked by weak C—H⋯O interactions with a bifurcated acceptor, forming a three-dimensional network.
In the title solvate, C14H12N2O·0.5C6H6, the complete benzene molecule is generated by a crystallographic inversion centre. The dihedral angle between the planes of the benzimidazole moiety and the phenol substituent is 75.28 (3)°. In the crystal, O—H⋯N hydrogen bonds link the molecules into parallel chains propagating along [100]. The molecules are further connected by C—H⋯π interactions.
Background: The invasive eel parasite Anguillicoloides crassus (syn. Anguillicola crassus) is considered one of the major causes for the decline of the European eel (Anguilla anguilla) panmictic population. It impairs the swim bladder function and reduces swimming performance of its host. The life cycle of this parasite involves different intermediate and paratenic hosts. Despite an efficient immune system of the paratenic fish hosts acting against infections with A. crassus, levels of parasitized eels remain high in European river systems. Recently, the round goby Neogobius melanostomus (Gobiidae) has become dominant in many rivers in Europe and is still spreading at a rapid pace. This highly invasive species might potentially act as an important, so far neglected paratenic fish host for A. crassus.
Methods: Based on own observations and earlier single sightings of A. crassus in N. melanostomus, 60 fresh individuals of N. melanostomus were caught in the Rhine River and examined to assess the infection levels with metazoan parasites, especially A. crassus. Glycerin preparations were used for parasite identification.
Results: The parasite most frequently found in N. melanostomus was the acanthocephalan Pomphorhynchus sp. (subadult stage) which occurred mainly encysted in the mesenteries and liver. Every third gobiid (P = 31.7%) was infected by A. crassus larvae (L3) which exclusively occurred inside the acanthocephalan cysts. No intact or degenerated larvae of A. crassus were detected elsewhere in the goby, neither in the body cavity and mesenteries nor in other organs. Affected cysts contained the acanthocephalan larvae and 1-12 (mI =3) living A. crassus larvae. Additionally, encysted larvae of the nematode Raphidascaris acus were detected in the gobies, but only in the body cavity and not inside the acanthocephalan cysts.
Conclusions: Based on our observations, we suggest that A. crassus might actively bypass the immune response of N. melanostomus by invading the cysts of acanthocephalan parasites of the genus Pomphorhynchus using them as "Trojan horses". Providing that eels prey on the highly abundant round goby and that the latter transfers viable infective larvae of A. crassus, the new paratenic host might have a strong impact on the epidemiology of A. crassus.
The late physicist Carl Sagan, whom I quote in the first part of my title, skillfully phrased the common sense view on evidence in the mature sciences. In linguistics, however, evidence has become a controversial issue, especially so when it comes to the investigation of less well studied languages. In this paper, I argue that Sagan's principle should be applied to linguistics. The growing accessibility of a wide array of experimental techniques and computational tools to analyze such data makes it feasible to back up extraordinary claims with evidence from a variety of sources. At the same time, it is in many cases possible to agree on what constitutes an ordinary claim and focus the extra effort on extraordinary claims. For non-controversial claims no more than the minimum effort to establish the claim and properly document the evidence is necessary.
Im Folgenden soll kurz geklärt werden, was Genus ist (Kap. 2) und – auch wenn diese Frage nicht mit unserem derzeitigen Wissen beantwortbar ist – woher Genus kommen könnte (Kap. 3). Hauptsächlich stellt sich jedoch die Frage: Was tun mit Genus, das heute das Endstadium einer langen Grammatikalisierung darstellt (Kap. 4)? Hier wird die wichtigste Antwort lauten: Genus hat eine neue, eine syntaktische Nutzung erfahren, indem es maßgeblich daran beteiligt ist, unsere berühmten Nominalklammern zu bauen (4.1). Außerdem gibt es weitere "Recyclingmöglichkeiten" von Genus, nämlich: a) Objekte, die Namen tragen, zu klassifizieren (die Kaiser Wilhelm), b) Beziehungen zwischen namentragenden und namenverwendenden Personen zu qualifizieren (der Peterle, das Anna) oder sogar c) Personen zu degradieren (das Merkel). Mit Punkt a) begebe ich mich in die Onomastik, mit Punkt b) in die Dialektologie, und mit Punkt c) werde ich mit der Genderlinguistik enden.
Mapping is an important tool for the management of plant invasions. If landscapes are mapped in an appropriate way, results can help managers decide when and where to prioritize their efforts. We mapped vegetation with the aim of providing key information for managers on the extent, density and rates of spread of multiple invasive species across the landscape. Our case study focused on an area of Galapagos National Park that is faced with the challenge of managing multiple plant invasions. We used satellite imagery to produce a spatially explicit database of plant species densities in the canopy, finding that 92% of the humid highlands had some degree of invasion and 41% of the canopy was comprised of invasive plants. We also calculated the rate of spread of eight invasive species using known introduction dates, finding that species with the most limited dispersal ability had the slowest spread rates while those able to disperse long distances had a range of spread rates. Our results on spread rate fall at the lower end of the range of published spread rates of invasive plants. This is probably because most studies are based on the entire geographic extent, whereas our estimates took plant density into account. A spatial database of plant species densities, such as the one developed in our case study, can be used by managers to decide where to apply management actions and thereby help curtail the spread of current plant invasions. For example, it can be used to identify sites containing several invasive plant species, to find the density of a particular species across the landscape or to locate where native species make up the majority of the canopy. Similar databases could be developed elsewhere to help inform the management of multiple plant invasions over the landscape.
The deregulation of Polo-like kinase 1 is inversely linked to the prognosis of patients with diverse human tumors. Targeting Polo-like kinase 1 has been widely considered as one of the most promising strategies for molecular anticancer therapy. While the preclinical results are encouraging, the clinical outcomes are rather less inspiring by showing limited anticancer activity. It is thus of importance to identify molecules and mechanisms responsible for the sensitivity of Polo-like kinase 1 inhibition. We have recently shown that p21Cip1/CDKN1A is involved in the regulation of mitosis and its loss prolongs the mitotic duration accompanied by defects in chromosome segregation and cytokinesis in various tumor cells. In the present study, we demonstrate that p21 affects the efficacy of Polo-like kinase 1 inhibitors, especially Poloxin, a specific inhibitor of the unique Polo-box domain. Intriguingly, upon treatment with Polo-like kinase 1 inhibitors, p21 is increased in the cytoplasm, associated with anti-apoptosis, DNA repair and cell survival. By contrast, deficiency of p21 renders tumor cells more susceptible to Polo-like kinase 1 inhibition by showing a pronounced mitotic arrest, DNA damage and apoptosis. Furthermore, long-term treatment with Plk1 inhibitors induced fiercely the senescent state of tumor cells with functional p21. We suggest that the p21 status may be a useful biomarker for predicting the efficacy of Plk1 inhibition.
The transcription factor Tal1 is a critical activator or repressor of gene expression in hematopoiesis and leukaemia. The mechanism by which Tal1 differentially influences transcription of distinct genes is not fully understood. Here we show that Tal1 interacts with the peptidylarginine deiminase IV (PADI4). We demonstrate that PADI4 can act as an epigenetic coactivator through influencing H3R2me2a. At the Tal1/PADI4 target gene IL6ST the repressive H3R2me2a mark triggered by PRMT6 is counteracted by PADI4, which augments the active H3K4me3 mark and thus increases IL6ST expression. In contrast, at the CTCF promoter PADI4 acts as a repressor. We propose that the influence of PADI4 on IL6ST transcription plays a role in the control of IL6ST expression during lineage differentiation of hematopoietic stem/progenitor cells. These results open the possibility to pharmacologically influence Tal1 in leukaemia.
Predominant polarity in bipolar disorder and validation of the polarity index in a German sample
(2014)
Background: A large number of patients with bipolar disorder (BD) can be characterized by predominant polarity (PP), which has important implications for relapse prevention. Recently, Popovic et al. (EUR NEUROPSYCHOPHARM 22(5): 339¿346, 2012) proposed the Polarity Index (PI) as a helpful tool in the maintenance treatment of BD. As a numeric expression, it reflects the efficacy of drugs used in treatment of BD. In the present retrospective study, we aimed to validate this Index in a large and well characterized German bipolar sample.
Methods: We investigated 336 bipolar patients (BP) according to their PP and calculated the PI for each patient in order to prove if maintenance treatment differs according to their PP. Furthermore, we analysed whether PP is associated with demographic and clinical characteristics of BP.
Results: In our sample, 63.9% of patients fulfilled criteria of PP: 169 patients were classified as depressive predominant polarity (DPP), 46 patients as manic predominant polarity (MPP). The two groups differed significantly in their drug regime: Patients with DPP were more often medicated with lamotrigine and antidepressants, patients with MPP were more often treated with lithium, valproate, carbamazepine and first generation antipsychotics. However, patients with DPP and MPP did not differ significantly with respect to the PI, although they received evidence-based and guideline-driven treatment.
Conclusion: The reason for this negative finding might well be that for several drugs, which were used frequently, no PI value is available. Nevertheless we suggest PP as an important concept in the planning of BD maintenance treatment.
Background: In this study, we examined patients who had non-progressive disease for at least 2 years after diagnosis of inoperable locoregional recurrent or metastatic breast cancer under continuous trastuzumab treatment. Our primary goal was to assess the long-term outcome of patients with durable response to trastuzumab.
Methods: 268 patients with HER2-positive inoperable locally recurrent or metastatic breast cancer and non-progressive disease for at least 2 years under trastuzumab treatment were documented retrospectively or prospectively in the HER-OS registry, an online documentation tool, between December 2006 and September 2010 by 71 German oncology centers. The study end point was time to tumor progression.
Results: Overall, 47.1% of patients (95% confidence interval (CI): 39.9–54.1%) remained in remission for more than 5 years, while the median time to progression was 4.5 years (95% CI: 4.0–6.6 years). Lower age (<50 years) and good performance status (ECOG 0) at time of trastuzumab treatment initiation as well as complete remission after initial trastuzumab treatment were associated with longer time to progression. Interruption of trastuzumab therapy correlated with shorter time to progression.
Conclusions: HER2-positive patients, who initially respond to palliative treatment with trastuzumab, can achieve a long-term tumor remission of several years.
Zur Flora von Deutschland gehören sieben Arten der Wintergrüngewächse, die alle auch in Sachsen-Anhalt heimisch sind: Dolden-Winterlieb (Chimaphila umbellata [L.] BARTON), Einblütiges Wintergrün (Moneses uniflora [L.] A. GRAY), Birngrün (Orthilia secunda [L.] HOUSE), Grünblütiges Wintergrün (Pyrola chlorantha SW.), Mittleres Wintergrün (Pyrola media SW.), Kleines Wintergrün (Pyrola minor L.) und Rundblättriges Wintergrün (Pyrola rotundifolia L.). Im Mittelpunkt dieses Beitrages steht nur die aktuelle Verbreitung im Bundesland mit Bezug auf MTB-Q4, und zwar bezogen auf zwei Perioden von jeweils 10 Jahren: Nachweise im MTB-Q4 von 2005 bis 2014, sowie Nachweise im MTB-Q4 von 1995 bis 2004.
Die Mauerkronen der Nicolai-Kirche in Zerbst wurden im Jahr 2001 mit unterschiedlichen Methoden begrünt. Das Ziel dieser Maßnahmen war die Pufferung extremer Temperaturunterschiede, die häufig zu starken Schäden am Mauerwerk führen. In Vorbereitung von anstehenden Sanierungsmaßnahmen wurde der Artenbestand auf repräsentativen Abschnitten der Mauern erfasst. Auf diese Weise konnte ermittelt werden, welche Arten mit den extremen Standortbedingungen, wie Hitze, Trockenheit und große Temperaturunterschiede gut zurechtkommen und daher bei der Sanierung an Fehlstellen erfolgversprechend angesiedelt werden können.
Das Vorkommen von Bunias orientalis (Orientalische Zackenschote) konzentriert sich auf den Südwesten Sachsen-Anhalts. Bisher ist die Art vorrangig aus dem Straßenbegleitgrün bekannt, doch zunehmend kann das Einwandern in Halbtrockenrasen und Frischwiesen beobachtet werden. Ein Beispiel dafür ist die 2011 eingerichtete und ca. 24 ha große Ganzjahresstandweide bei Hainrode. 2013 konnten hier 58 Fundpunkte mit 644 Sprossen dokumentiert werden. Die Art wird von den weidenden Salers angenommen und verbissen. Das Abfressen führt zu geringeren Wuchshöhen und vermutlich ist die Reproduktion über Samen auch bei Neuaustrieb deutlich herabgesetzt. Es wird die Möglichkeit, mittels Beweidung der Südharzer Frischwiesen die weitere Ausbreitung von Bunias orientalis zu verhindern bzw. die Art über eine Beweidung zurückzudrängen, diskutiert.
Oscillations play a critical role in cognitive phenomena and have been observed in many brain regions. Experimental evidence indicates that classes of neurons exhibit properties that could promote oscillations, such as subthreshold resonance and electrical gap junctions. Typically, these two properties are studied separately but it is not clear which is the dominant determinant of global network rhythms. Our aim is to provide an analytical understanding of how these two effects destabilize the fluctuation-driven state, in which neurons fire irregularly, and lead to an emergence of global synchronous oscillations. Here we show how the oscillation frequency is shaped by single neuron resonance, electrical and chemical synapses.The presence of both gap junctions and subthreshold resonance are necessary for the emergence of oscillations. Our results are in agreement with several experimental observations such as network responses to oscillatory inputs and offer a much-needed conceptual link connecting a collection of disparate effects observed in networks.
A measurement of the transverse momentum spectra of jets in Pb-Pb collisions at sNN−−−√=2.76 TeV is reported. Jets are reconstructed from charged particles using the anti-kT jet algorithm with jet resolution parameters R of 0.2 and 0.3 in pseudo-rapidity |η|<0.5. The transverse momentum pT of charged particles is measured down to 0.15 GeV/c which gives access to the low pT fragments of the jet. Jets found in heavy-ion collisions are corrected event-by-event for average background density and on an inclusive basis (via unfolding) for residual background fluctuations and detector effects. A strong suppression of jet production in central events with respect to peripheral events is observed. The suppression is found to be similar to the suppression of charged hadrons, which suggests that substantial energy is radiated at angles larger than the jet resolution parameter R=0.3 considered in the analysis. The fragmentation bias introduced by selecting jets with a high pT leading particle, which rejects jets with a soft fragmentation pattern, has a similar effect on the jet yield for central and peripheral events. The ratio of jet spectra with R=0.2 and R=0.3 is found to be similar in Pb-Pb and simulated PYTHIA pp events, indicating no strong broadening of the radial jet structure in the reconstructed jets with R<0.3.
This study investigates the diabetes-associated alterations present in cardiac mesenchymal cells (CMSC) obtained from normoglycemic (ND-CMSC) and type 2 diabetic patients (D-CMSC), identifying the histone acetylase (HAT) activator pentadecylidenemalonate 1b (SPV106) as a potential pharmacological intervention to restore cellular function. D-CMSC were characterized by a reduced proliferation rate, diminished phosphorylation at histone H3 serine 10 (H3S10P), decreased differentiation potential, and premature cellular senescence. A global histone code profiling of D-CMSC revealed that acetylation on histone H3 lysine 9 (H3K9Ac) and lysine 14 (H3K14Ac) was decreased, whereas the trimethylation of H3K9Ac and lysine 27 significantly increased. These observations were paralleled by a downregulation of the GCN5-related N-acetyltransferases (GNAT) p300/CBP-associated factor and its isoform 5-α general control of amino acid synthesis (GCN5a), determining a relative decrease in total HAT activity. DNA CpG island hypermethylation was detected at promoters of genes involved in cell growth control and genomic stability. Remarkably, treatment with the GNAT proactivator SPV106 restored normal levels of H3K9Ac and H3K14Ac, reduced DNA CpG hypermethylation, and recovered D-CMSC proliferation and differentiation. These results suggest that epigenetic interventions may reverse alterations in human CMSC obtained from diabetic patients.
Cytokine-regulated GADD45G induces differentiation and lineage selection in hematopoietic stem cells
(2014)
The balance of self-renewal and differentiation in long-term repopulating hematopoietic stem cells (LT-HSC) must be strictly controlled to maintain blood homeostasis and to prevent leukemogenesis. Hematopoietic cytokines can induce differentiation in LT-HSCs; however, the molecular mechanism orchestrating this delicate balance requires further elucidation. We identified the tumor suppressor GADD45G as an instructor of LT-HSC differentiation under the control of differentiation-promoting cytokine receptor signaling. GADD45G immediately induces and accelerates differentiation in LT-HSCs and overrides the self-renewal program by specifically activating MAP3K4-mediated MAPK p38. Conversely, the absence of GADD45G enhances the self-renewal potential of LT-HSCs. Videomicroscopy-based tracking of single LT-HSCs revealed that, once GADD45G is expressed, the development of LT-HSCs into lineage-committed progeny occurred within 36 hr and uncovered a selective lineage choice with a severe reduction in megakaryocytic-erythroid cells. Here, we report an unrecognized role of GADD45G as a central molecular linker of extrinsic cytokine differentiation and lineage choice control in hematopoiesis.
Use of drug-eluting balloon coronary intervention prior to living donor kidney transplantation
(2014)
Background: Kidney transplantation is the gold standard of therapy in patients with terminal renal insufficiency. Living donor transplantation is a well-established option in this field. Enlarging the donor's pool implicates the acceptance of an increased rate of comorbidities. Among them, coronary artery disease is a growing problem. An increasing number of patients, undergoing living donation, receive antiplatelet therapies due to coronary disease.
Case presentation: Here we report about the perioperative treatment with a drug-eluting balloon in a patient with major cardiac risk factors who underwent kidney transplantation.
Conclusion: At the current time no recommendation can be given for the routine use of drug-eluting balloons.
Linear Ubiquitin chain Assembly Complex (LUBAC) is an E3 ligase complex that generates linear ubiquitin chains and is important for tumour necrosis factor (TNF) signaling activation. Mice lacking Sharpin, a critical subunit of LUBAC, spontaneously develop inflammatory lesions in the skin and other organs. Here we show that TNF receptor 1 (TNFR1)-associated death domain (TRADD)-dependent TNFR1 signaling in epidermal keratinocytes drives skin inflammation in Sharpin-deficient mice. Epidermis-restricted ablation of Fas-associated protein with death domain (FADD) combined with receptor-interacting protein kinase 3 (RIPK3) deficiency fully prevented skin inflammation, while single RIPK3 deficiency only delayed and partly ameliorated lesion development in Sharpin-deficient mice, showing that inflammation is primarily driven by TRADD- and FADD-dependent keratinocyte apoptosis while necroptosis plays a minor role. At the cellular level, Sharpin deficiency sensitized primary murine keratinocytes, human keratinocytes, and mouse embryonic fibroblasts to TNF-induced apoptosis. Depletion of FADD or TRADD in Sharpin-deficient HaCaT cells suppressed TNF-induced apoptosis, indicating the importance of FADD and TRADD in Sharpin-dependent anti-apoptosis signaling in keratinocytes.
Ziel: Die Evaluation der DEGUM-Mammasonografiekurse nach objektivierbaren Kriterien war Ziel dieser Arbeit. Damit sollte die Qualität der Kurse überprüft werden, um eine flächendeckende Fort- und Weiterbildung auf hohem Niveau anzubieten.
Material und Methoden: 10 Qualitätskriterien, orientierend an den Vorgaben der KBV-Ultraschallvereinbarungen wurden als Qualitätsparameter definiert. Alle Kursleiter des Arbeitskreises Mammasonografie der DEGUM wurden angeschrieben. Dabei wurden die 10 definierten Qualitätskriterien überprüft.
Ergebnisse: Alle Kurse erfüllten die Voraussetzungen bezüglich der Qualität des Kursleiters, der Kursdauer und Unterrichtseinheiten sowie der Anzahl an Kursteilnehmern pro Ultraschallgerät. In 1 von 9 Kursen wurde die Zeit der praktischen Übungen, gefordert sind 50 %, unterschritten. Die Voraussetzungen für den Abschlusskurs (200 selbst durchgeführte und dokumentierte Fälle) sind in den Kursankündigungen zum Teil nicht klar definiert. Ein strukturierter Lehrkatalog fehlt.
Schlussfolgerung: Die DEGUM-Mammasonografiekurse werden auf hohem Niveau angeboten und erfüllen zum größten Teil die Anforderungen der KBV. Trotz der hohen Qualität der DEGUM-Kurse sind Optimierungsoptionen im Bereich Kursankündigung und strukturierter Lehrkatalog möglich.
Dil öğretiminde geleneksel öğretmen merkezli ve dilbilgisi ağırlıklı metotlardan gitgide uzaklaşılmaktadır. Bu çalışmada işitsel ve görsel araçlardan biri olarak tiyatronun ders dışı sosyal aktivite olarak kullanımı ve öğrenimi hızlandırıcı etkisi incelenmiştir.
Bu amaç ile Akdeniz Üniversitesi Yabancı Diller Yüksekokulu tarafından Türkiye Burslusu 43 farklı ülkeden 70 öğrenciye (Tablo1) 30 Eylül 2013-27 Haziran 2014 tarihleri arasında verilen Türkçe eğitimi programı kullanılmıştır. Öğrencilere 960 saat Türkçe eğitimi verilmesinin yanı sıra haftada 2 saatten az olmamak üzere sosyal aktivite adı altında ek çalışmalara (koro, dans, tiyatro vs.) yönlendirilmişlerdir.
Bu çalışmada, hedef dilin öğretilmesinde tiyatro tekniğinin/ çalışmalarının öğrencinin hedef dildeki performansına etkisini belirlemek amacıyla ön test-son test kontrol gruplu yarı deneysel araştırma deseni kullanılmıştır.
Çalışma sonunda; Konuşma becerisi açısından bakıldığında Yabancı Dil Olarak Türkçe'nin Öğretilmesi (YDT) konusunda Akdeniz Üniversitesi Yabancı Diller Yüksekokulu bünyesinde ders dışında ‒ sosyal etkinlik olarak ‒ uygulanmakta olan Tiyatro Çalışmalarının öğrencilerin dil edinme performanslarına etkisinin olumlu olduğu bulgusuna ulaşılmıştır. Bununla beraber, üç alt bulgu da tespit edilmiştir: Konuşma becerisi açısından bakıldığında tiyatro çalışmalarını takip eden öğrenciler ile bu çalışmalara katılmayan öğrencilerin sınav sonuçları arasında belirli bir farklılığın olduğu sınav sonuçlarının analizi ile ortaya konulmuştur. Ayrıca, Yeterlik sınav sonucu değerlendirildiğinde tiyatro çalışmalarını takip eden öğrenciler ile bu çalışmalara katılmayan öğrencilerin sınav sonuçları arasında belirli bir farklılığın da tespiti yapılmıştır. Bunlara ek olarak, "Motivasyon açısından bakıldığında, tiyatro çalışmalarını takip eden öğrenciler ile bu çalışmalara katılmayan öğrencilerin sınav sonuçları arasında belirli bir farklılık var mıdır?" alt hipotezi de tiyatro çalışmalarının öğrenci motivasyonunu arttırdığı belirlenmiştir.
Bu bağlamda, her hafta hazırlanan öğrenci gelişim raporu ile öğrencinin dil gelişimi, motivasyonu ve öğrencinin ilgi alanları (müzik, dans, drama vs.) danışman öğretim elemanları tarafından değerlendirilmesi uygulamalarına gelecek akademik yıllarda da devam edilmesi kurumca kararlaştırılmıştır.
2013 yılında ilk kez gerçekleştirilen Öğretmenler için Alan Bilgisi (ÖABT) Almanca sınavı üniversitelerin Alman Dili Eğitimi Anabilim Dallarında ve Alman Dili ve Edebiyatı Bölümlerinde okuyan lisans öğrencileri için umut kapısı olmuştur. Bu bölümlerin öğrencileri önceki yıllarda "mezun olup diploma sahibi olmak" gibi bir amaçla okuduklarından dolayı derslere karşı motivasyonları düşük kalmaktaydı. ÖABT ve beraberinde getirdiği Almanca öğretmeni olarak atanma fırsatı sayesinde bu öğrenciler artık lisans eğitimlerini daha fazla ciddiye almaya ve olabildiğince donanımlı bir şekilde mezun olmaya çalışmaktadır.
Yukarıdaki bilgilerden hareketle bu çalışmamızda öncelikli olarak ÖABT Almanca sınavının içeriği, kapsamı, alanlara göre soru dağılımı ve puan ağırlıkları incelenecek, daha sonra da Eğitim Fakültelerinin Alman Dili Eğitimi Anabilim Dallarının müfredatı ele alınacak ve böylelikle bu bölümlerde okutulan derslerin ÖABT Almanca sınavının içeriğiyle ne derece uyumlu ve sınavı kazanıp atanabilmek adına ne derece yeterli olduğu tartışılacaktır. Çanakkale Onsekiz Mart Üniversitesi lmanca Öğretmenliği öğrencileri ile yapılan anket çalışması ışığında da öğrencilerin sınava dair görüşleri ve beklentileri analiz edilmiş ve çalışmaya monte edilmiştir.
Redensarten sind für die Deutsch als Fremdsprache Studierenden im hohen Grad interpretationsbedürftig. Auch der Muttersprachler braucht für sie häufig eine nähere Erklärung, die im vorliegenden Fall formal (Redensart veraltet und wegen antisemitischer Sicht nicht verwendbar) und inhaltlich (Zusammenhänge, die kaum einer ahnt) sein muss. Redensarten können einen weitreichenden kulturellen Hintergrund haben und sie sind selbst, entsprechend analysiert, Quelle zur Sprach- und Kulturgeschichte. Die Redensart "... wie in der Judenschule" verrät uns zudem überraschenderweise etwas über die Frühform literarischer Entwicklung im Kulturprozess von der Mündlichkeit zur Schriftlichkeit.
D. Seleskovitch ve M. Lederer'in birlikte geliştirmiş oldukları Yorumlayıcı Çeviri (Anlam) Kuramı, çevirmeni merkeze koyan bir yaklaşım gösterir. Çeviriye ilişkin kuramsallaşmanın tarihine bakılırsa; önceki yüzyıllardan günümüze değin çevirmenin rolünü öne çıkaran görüş ve düşüncelere rastlanmaktadır. 90'lı yıllardan sonra belirginleşen bilişsel yaklaşımlar, alana yeni kazanımlar sağlamış, çeviribilim araştırmalarının uygulama alanına yansıyarak kültürlerarası veya dillerarası aktarımın başat aktörü olarak 'çevirmen'in bilişsel bakımdan yeniden değerlendirilmesine zemin hazırlamıştır. Bilişsel odaklı bir görünüm sergileyen çevirmen merkezli yaklaşımlar, çevirinin başarısının çevirmene bağlı olduğu görüşünden hareketle çevirmenin çeviri eylemi sırasında zihninde olup bitenlerin, bilişsel süreçlerinin işleyişinin ve dili kullanma mekanizmasının açıklığa kavuşturulmasını öngörür.
Bu çalışmanın amacı, Yorumlayıcı Çeviri Kuramı doğrultusunda 'anlama'nın koşulları olarak öne çıkan saptamaları ortaya koyarak çevirmenin sahip olması gereken özniteliklere ilişkin izdüşümleri serimlemektir. Bu amaç doğrultusunda, anlamın kavranması sürecinde çevirmenin zihinsel süreçlerinin nasıl işlediği, çevirmenin bu süreçleri nasıl yönettiği betimlenmeye ve söylem çözümlemesine dayanan Yorumlayıcı Çeviri Kuramı ve Yorumlayıcı Çeviri Yöntemi'nde yer alan düşünsel veriler görünür kılınmaya çalışılacaktır.
Eine immer dringlicher geforderte kultur- und medienwissenschaftliche Orientierung der interkulturellen Germanistik erfordert zugleich auch eine Auseinandersetzung mit neueren Konzepten, die differenzierende, dynamische und multiperspektivische Ansätze anbieten. So bemühen sich neuere kulturphilosophische Konzepte wie die Hyperkulturalität und Transdifferenz über rigide binäre Unterscheidungen zwischen "Eigenem" und "Fremden" hinauszugehen und der Durchlässigkeit der Grenzen und der internen Heterogenität von Gesellschaften im Zeitalter der Globalisierung in angemessener Weise gerecht zu werden. Vor diesem Hintergrund untersuche ich in meinem Beitrag den Film "Almanya – Willkommen in Deutschland" (Samdereli 2011) im Rahmen einer diskursiven Auseinandersetzung mit diesen Begrifflichkeiten. Entgegen bisheriger Darstellungen im so genannten türkisch-deutschen Migrantenkino fokussiert dieses Filmbeispiel verstärkt eine (postmigrantische) Perspektive, die mit tradierten Sichtweisen und Klischees bricht. Grundsätzlich soll herausgestellt werden, wie kollektive und individuelle Phänomene von Zugehörigkeit und Identitiätskonstruktion mit filmischen Mitteln dargestellt werden. Zur Diskussion gestellt soll dabei die Frage, inwiefern neuere kulturtheoretische Konzepte dabei greifen.
Bu çalışmada geleneksel Türk namus anlayışı, biçimleri ve toplumda ve ailede erkek ve kadının konumu ile görevleri üzerine etkisi tartışılacaktır. Burada özellikle, genel olarak ve göçmenlik yaşamında namus cinayetlerini teşvik eden ve bu suçun toplum tarafından görmezlikten gelinmesini sağlayan faktörler açığa çıkarılacaktır. Bu amaçla yazar, Feo Aladag'ın sosyal açıdan ilginç ve göçmenliği konu edinen ve böylece tartışmaların bir parçası olan "Die Fremde" adlı filmini ele alacaktır. Söz konusu film, gerçeğe yakın sahneleri ile gündemdeki olguyu objektif ve eleştirel olarak tartışmaktadır.
In Ernst Jüngers Werk spielt der Topos des Niemandslandes von Anfang an eine außerordentliche Rolle. Gleich ob es sich um den umkämpften Raum zwischen den erstarrten Fronten des ersten Weltkrieges, die Imagination tropischer Zonen, die Überschreitung jeder Normalität im Drogenrausch oder den Entschluß zur Desertation aus dem bürgerlichen Alltag im "Waldgang" handelt -, stets fasziniert das Niemandsland durch die Abwesenheit von Sicherheit und die Nötigung zu freier Aktion. Seinen geheimen Fluchtpunkt findet der Topos der "Terra nullius" aber in der Idee eines Schreibens, das dem Tod, dem eigentlichen Niemandsland, eine Stimme geben könnte.
Nach dem letzten Germanistikkongress 2009 in Izmir wurde der zwölfte Germanistikkongress unter dem Motto "Migration und kulturelle Diversität" vom 12. bis 14. Mai 2014 an der Universität Kocaeli veranstaltet. Bei der Veranstaltung des Kongresses hat der türkische Germanistenverband GERDER aktiv mitgewirkt. Der DAAD, das Goethe Institut Ankara, das Österreichische Kulturinstitut und das Schweizer Konsulat Istanbul haben zur Organisation des Kongresses beigetragen, indem sie die Einladung von Professoren zu Plenarvorträgen und die Verwirklichung kultureller sowie sozialer Aktivitäten, wie Konzert und Abendessen unterstützen.
Türkiye'de Akademik Açık Erişim Dergi Yayıncılığı ve Çeviribilim Alanındaki Açık Erişim Dergiler
(2014)
Bu çalışmada Türkiye'nin akademik açık erişim dergi yayıncılığında geldiği noktayı ortaya koymak, 70'li yıllardan itibaren dilbilim ve filolojiden ayrılarak kendi bilimsel çerçevesini çizen ve kendi bilimsel iletişim sistemini oluşturan Çeviribilim alanının, bilimsel iletişim sisteminin en önemli araçlarından biri olan akademik açık erişim dergicilik konusunda aldığı mesafeyi görmek, bu konuda mevcut eksiklikleri tespit etmek ve bunlara çözüm önerilerinde bulunmak amaçlanmaktadır. Bu amaçla ulusal ve uluslararası açık erişim veritabanları incelenerek elde edilen bilgiler değerlendirilmeye çalışıldı. Çalışmanın birinci aşamasında Türkiye'nin akademik açık erişim dergicilik konusundaki mevcut durumu değerlendirilirken ikinci aşamada Çeviribilim alanının durumu ele alındı. Son aşamada ise elde edilen verilerden anlamlı sonuçlar çıkarılarak genel bir değerlendirme yapıldı ve çeşitli öneriler sunuldu.
Die Anwendung von Social Media im Fremdsprachenunterricht am Beispiel von "Twitter" Microblogging
(2014)
"Sosyal medya" sözcüğü günümüzün sloganı haline gelmiştir. Teknik olarak sosyal ağları destekleyen Web 2,0 hizmetlerinin uygulaması ile blog ve microblog hizmetleri her alanda kullanılmaya ve hiç olmadığı kadar iletişim kurulmaya başlanmıştır.
Twitter da, bu hizmetlerin ortak paydası olan dünyadan haberdar olma, olaylara katılma, bu amaçla da, fazla teknik bilgi gerektirmeden içerik oluşturma ve yayınlama özelliğini kullanıcılarına sunmaktadır. Nasıl ve ne şekilde iletişim kurulduğu çok farklılık göstermekle birlikte, paylaşılanlar çok basit önemsiz konuşmalardan, eğlendirici, bilgilendirici politik ve ticari içeriklere kadar uzanıp, zaman zaman da kutuplaşmalara sebep olmaktadır. Öyle ki bazıları bu içerikleri önemsiz ve gereksiz görürken, diğerleri 'devrim' yaratan nitelikte bulabilmektedir. Gerçek olan, bu kanallar aracılığı ile birçok bilginin ve içeriğin paylaşılıyor, iletişim kuruluyor olmasıdır.
Bu çalışmanın amacı Microblogging hizmeti [uygulaması] olan Twitter'ın tanıtılması, anlaşılır hale getirilmesidir. Bunu için öncelikle tarihçesi ve var olan durum açıklanmış, hesap oluşturma ve uygulamaları üzerinde durulmuştur. Ayrıca "internet dili", bu dilin gençler üzerindeki etkileri ile medya okuryazarlığının önemine ve meslek edinme sürecindeki etkilerine kısaca değinilmiştir. Son olarak örnek bir uygulama üzerinden Twitter'ın ders ortamlarında kullanılabilirlik özelliği işlenmiştir.
Eğitim, Öğretme ve Öğrenme konuları uluslararası eğitim alanında olduğu gibi Türkiye'de de son yıllarda en fazla konuşulan, tartışılan ve değişime uğrayan temadır. Öyle ki artan bilgi yoğunluğu, hızlı teknolojik kazanımlar ve buna bağlı olarak farklılaşan anlayış ve beklentiler eğitimin sürekli ve nitel açıdan irdelenmesini zorunlu kılmaktadır. Çalışmada eğitim konusunun temel sorun ve soruları, uluslararası eğitim standartları ve değişen eğitim stratejileri, öğrenme ve etkin öğretme ile ilgili yeni yaklaşımları, öğretmen tanımlamaları, öğretmen-öğrenci ve veli iletişimin önemi, öğretmen kazanımları ve yeterlilikleri gibi geniş bir perspektif taranmaktadır. Çalışmada yüksek öğretim reformu kapsamında eğitim fakülteleri ve öğretmen yetiştirme modelleri ve bu çalışmaların uluslararası uyumu değerlendirilmekte ve daha iyi bir eğitim, daha etkin öğretme ve öğrenme için öneriler sunulmaktadır.
Das Ziel dieser Arbeit ist über historische und soziale Beziehungen zwischen Brasilien und Deutschland zu diskutieren, die bei den frühesten iberischen Expeditionen im 16. Jahrhundert, bei der Entdeckung Brasiliens, stattfanden, und sich mit dem offiziellen Beginn der deutschen Auswanderung nach Brasilien, im Jahr 1824, mit der Gründung der Kolonie von São Leopoldo im Bundesstaat Rio Grande do Sul, verstärkte. Im Hinblick darauf, dass die Deutschen ihre Traditionen, Sprache und Kultur, deren Unterschiede die brasilianische Heterogenität intensivierte, nicht vollständig verloren haben, bezieht sich der zweite Teil dieses Textes auf ein konkretes Beispiel einer brasilianischen Stadt namens Marechal Câdido Rondon. Die Stadt liegt in Südbrasilien und wurde von deutschstämmigen Auswanderern gegründet. Trotz diesen germanischen Wurzeln, welche sich durchaus in der Architektur und den Volksfesten bemerkbar machen, zeigt die Gemeinde keine Auffälligkeiten hinsichtlich der deutschen Sprache aufgrund der Förderung der Zweisprachigkeit.
Das Faktum, dass in der Komikproduktion "Türkisch für Anfänger" Verhaltens- und Sprachpraktiken des türkischstämmigen männlichen Jugendlichen namens Cem Öztürk als standardfern angesehen und so dargestellt werden, und der Betroffene demnach im komischen Modus stets mit dem Affen bzw. Affenmenschen verglichen wird, wurde für die Autorin der vorliegenden Arbeit zum Auslöser für den Vergleich seiner mit Bourroughs' Protagonisten Tarzan. Dies wiederum eröffnet Reflexion und Debatte über Machtverhältnisse/Positionierungen in der deutschen Einwanderergesellschaft einen freien Raum.
Bu makalede Şebnem İşigüzel ve Elfriede Jelinek'in kitaplarından yola çıkılarak annelerin anne – kız arasındaki ilişkinin niteliklerini nasıl ve ne yönde etkiledikleri karşılaştırmalı olarak ortaya konmaya çalışılmıştır. Her iki tarafın da dişil bir kimliğe sahip olmasına rağmen, annelerin baskın otoriteleri ile bu ilişkiye şiddeti dahil etmeleri sonucu bunun kendi kızları, dolayısı ile kadın bedeni ve iç dünyası üzerindeki yansımaları ve algılanışları kitaplardan alınan alıntılarla örneklendirilmiştir. Bu örneklendirme her iki kitabın romanların ana teması, figürlerin özellikleri, belirli imgeler ile yazarın üslup özellikleri gibi başlıklar rehberliğinde gerçekleştirilmiştir.
Bellek ve tarih ilişkisinin irdelendiği bir çok araştırmada, doksanlı yılların başından beri tüm dünyada bir bellek ve anımsama furyasının yaşandığı belirtilmekte ve ana nedenlerinden biri olarak da yazılı tarihin kaydettiği en ağır felaketlerin yaşandığı 20. Yüzyılın sona ermesi gösterilmektedir. 2000'li yıllardan bu yana gerek Avrupa kıtasında yazılan romanlara gerekse Türkiye'de yayımlanan romanlara bakıldığında, metinlerin odak noktasına yakın geçmişi yerleştiren tarihsel romanların sayısı küçümsenmeyecek kadar artmıştır. Yakın tarihe bugünden bakarak tarihsel durumların yeniden değerlendirilmesi, dolayısıyla belleklerde saklanan ancak şimdi dile gelen anıların öykülendirilmesi söz konusudur.
Tarihsel romanların yanı sıra bir ya da birden fazla ailenin kuşaklar boyu belleklerinde sakladıkları ve büyük tarihin yanında bugün "oral history" olarak yeniden önem kazanan bireysel/kollektif bellek, özellikle tarihsel romanların bir uzantısı olan "yeni" aile romanlarında gittikçe daha fazla yer bulmaktadır. 2011'in Mart ayında yayımlanan, Zülfü Livanel'nin "Serenad" adlı romanı da içerdiği tarihsel düzlem ve bu tarihin bireysel ve kollektif belleklerin bir parçası olarak aile üyelerinin anımsaması yoluyla okuyucuya açımlanması nedeniyle, çerçevesini tarihsel olguların oluşturduğu bir aile romanıyla karşı karşıya olduğumuzu göstermektedir.
Bu çalışmada romanda yer alan figürlerin tarihle ilişkileri yeni aile romanı çerçevesinde incelenecektir.
Als Weltautor ist der deutsche Dichter Johann Wolfgang von Goethe mit seinen Werken "Werther" und "Faust" unumstritten ein weit beliebter und prominenter Autor des 18. Jh.s. Ein ebenso beliebtes Werk des Autors ist die Ballade vom "Erlkönig", eine typisch lyrische Gattung der deutschen Dichtung der Romantik. Dass es sich hierbei nicht um ein rein zum Tanzen gesungenes Lied handelt, sondern vielmehr eine in sich geschlossene Welt von Symbolen dargestellt wird, ist bereits dem Titel zu entnehmen.
Begriff, Bedeutung und Funktion der Figuration "Erlkönig" stehen so als Thema und Fragestellung im Mittelpunkt der Diskussion des Beitrags. Handelt es sich bei dem benannten Begriff und Titeltext um eine Inspiration Goethes aufgrund einer missverstandenen Übersetzung Herders? Oder ist unter dieser Begrifflichkeit doch ein Geisterwesen, gar ein König der Geister zu verstehen, was wiederum die Bedeutungsvielfalt und die Symbolwelt des Volkstümlich-Mythologischen als Grundwissen voraussetzt. In diesem Sinne kommt der gesamte Bedeutungskomplex des Textes dem türkischen Volksglauben vom Alkarısı (wörtlich "Rote Frau") einerseits und Karabasan (wörtlich "Schwarz-Druck") andererseits nahe, zumal der Text mit dem tragischen Schicksal des fiebernden und halluzinierenden Kindes ein Ende nimmt.
Ziel des Beitrages ist so die Aufdeckung der verschlüsselten Botschaften des Textes; Symbole, kulturelle Werte und Handlungsmuster der Textstruktur sollen im Rahmen der volkskundlich-kritischen Textanalyse unter Einbeziehung der Hermeneutik anhand von Fallbeispielen der deutschen und türkischen Volksdichtung herausgearbeitet werden.
Schiller'in Edebiyat Görüşü
(2014)
Schiller'in edebiyat üzerine yazdığı makalesi "Über naive und sentimentalische Dichtung", Goethe ile yakın ve verimli dostluğuna dayanır. Mektuplaşmalarında eserleri hakkında karşılıklı ifadeleri bunu göstermektedir. Schiller'in çıkardığı "Die Horen" adlı edebi ve felsefi dergi, Goethe'nin katkısıyla nerdeyse Alman Klasisizminin program dergisi olmuştur. Felsefeye olan büyük merakı ile Schiller Goethe'nin eserlerini ve "Horen" dergisindeki yazılarını okuyunca, kendisi ile onun arasında önemli bir farkı keşfetmek durumunda kalmıştır. Doğalcı ve düşünselci edebiyat hakkında yazdığı görüşleri bunun kanıtlarıdır.
Eine deutsche Volksballade aus Bayern mit einem Türken-Thema und ihr Verhältnis zur Geschichte
(2014)
Volksballaden sind interessante kulturhistorische Belege; sie spiegeln Zeitgeschehen und Mentalitäten – historisch sind sie nicht, auch wenn sie als 'wahr' empfundene Ereignisse aufgreifen. Die deutsche Volksballade vom "Dollinger" wurde unter dem Eindruck der über Jahrhunderte andauernden Türkengefahr überliefert und jeweils neu aktualisiert; sie hat eine in Regensburg lokalisierte Stadtsage zum Inhalt, wie ein christlicher Held nur mit Mühe den heidnischen Türken (oder Ungarn, Osmanen usw.) überwindet und damit die Stadt (das Land) rettet.
Aus dem nun mehr als sechzig Jahre zurück liegenden Streit zwischen Staiger und Heidegger über das rechte Verständnis einer Verszeile von Eduard Mörike, der im Laufe der Jahre immer neue Stellungnahmen provozierte, läßt sich Aufschluß über die blicklenkenden Kategorien hermeneutischer Interpretation gewinnen, wenn man die Position einer Beobachtung zweiter Ordnung einnimmt. Es zeigt sich dann in großer Klarheit, daß die Interpretation literarischer Polyvalenzen und Ambiguitäten ihre Eindeutigkeit aus der Zuhilfenahme regulativer Ideen gewinnt, die nicht dem literarischen Text, sondern ästhetischen Vorlieben, philosophischen Axiomen oder politisch – moralischen Überzeugungen entstammen. Sie erzielen Sinneffekte, weil sie sich mehr oder weniger erfolgreich als subjektive Setzungen unsichtbar machen und aus der "Sache" heraus zu sprechen vorgeben. Werden diese regulativen Ideen aus der Perspektive einer Beobachtung zweiter Ordnung ins Sichtfeld gerückt, erscheint die Kontingenz jeder Interpretation, die immer auch anders möglich ist. Sie hat sich freilich am Wortlaut des literarischen Werkes zu bewähren, der jedem Konstruktivismus eine unüberschreitbare Grenze setzt. So verstanden ist die berühmte und nicht selten auch bespöttelte Kontroverse zwischen Heidegger und Staiger noch heute eine anregende Hilfestellung für jeden Versuch eines neuen Verständnisses von Mörikes Gedicht und eine grundsätzliche Herausforderung der Reflexion auf die Voraussetzungen literaturwissenschaftlicher Interpretation.
Sanat ve ahlâk arasındaki ilişki Antik dönemden bu yana tartışılan en eski felsefi sorunlardan birisi olarak görülebilir. Bu iki alan arasında varolduğu düşünülen doğrudan bağı kabul etmeyen ve "çıkarsız hoşa gitme" kavramıyla sanatın özerkliğini ilan eden Kant'ın estetiğiyle birlikte sorun kısmen çözülmüştür. Sanatın özgürlüğü anlamına gelen bu ayrım 20. Yüzyılın ikinci yarısından itibaren relativizm ve postmodernizm akımlarının yardımıyla daha da kabul edilebilir hale gelmesiyle günümüzde bu iki alan arasındaki ilişkiye vurgu yapmak nerdeyse imkansız hale geldi. Jauss'un bu konudaki düşünceleri bu nedenle neredeyse bir istisnaya karşılık gelirler. Jauss'un kuramı sanat ve edebiyatı okur ve alımlayıcı açısından ele alır ve sanat ve edebiyat aracılığıyla okur ya da alımlayıcının ahlâki yargılar oluşturduklarını söyler.
This article deals with the topic of dyslexia in adults and its consequences for learning German during university studies; the author explores the extent to which an optimized German text influences understanding. The results of research on dyslexia and psycholinguistic research on text understanding show that depending on the text structure and the simplicity of the linguistic means used, different levels of text understanding may be expected. The main tool of the research is text optimization based on a practical application of the "Hamburg concept of understandability", involving four text properties which make the text understandable to different extents.
Textkompetenz in mehreren Sprachen : Forschungsergebnisse und weiterführende Forschungsansätze
(2014)
The article presents results of an empirical study which examines productive transfer in the area of text skills competence and the associated writing skill which could be attributed to the learners' contact with several languages. The research was conducted within the research project "Multilingualism in the Czech Republik: Learning and Teaching German after English." After a short presentation of the key concepts in the development of the study and a presentation of selected results, implications and a modell for further research in multilingual writing and on transfer processes between languages are introduced.
Kunigunda of Galicia, the second wife of the Bohemian King Otokar II and later the second wife of the powerful nobleman Záviš of Falkenstein, suffers from a very poor reputation due to her depiction in medieval chronicles, especially the Styrian Rhymed Chronicle written by Ottokar aus der Gaal. Her image as a domineering and morally dubious figure is also echoed in Franz Grillparzer's play "König Ottokars Glück und Ende", which draws partly on the Styrian chronicle as source material. This study attempts to answer the question of what role Kunigunda plays in Grillparzer's drama, and whether she genuinely deserves to be known as a "whore" – a designation which was applied to her immediately after the play's premiere. Grillparzer's version of Kunigunda is also compared with her depiction in the tragedy "Král Přemysl Otakar Druhý" by František Zavřel.
The unique situation in which job seekers and employers find themselves results in the necessity to formulate and accept refusal letters. Employers frequently express their emotions in such letters. They are, however, in the form of clichés which apparently do not contain any genuine emotions. The subject of this analysis is genuine German refusal letters collected in the years between 2000 and 2012. Our objective is to indicate the types of emotions verbalized in the analyzed text type and to present the linguistic means utilized to express those emotions.
The article focuses on two objectives. First it addresses current trends in the lexical development of the German language. This investigation is based on changes within the section Fernsehabend to Fernsehzuschauerin in the "Duden – Deutsches Universalwörterbuch" between 1996 and 2011. Secondly, on the basis of the given section, the article examines to what extent this dictionary reflects current vocabulary.
"Jelen přeplotil skok" : kontrastiver Vergleich von Wortspielen und idiomatischen Wortverbindungen
(2014)
The article presents some of the outcomes of the contrastive comparison of the Czech original text and its German translation. It tries to show some hidden implications as well as many other peculiarities of wordplay and idiomatic phrases that a reader of the translated text may be deprived of.
This article examines the use of the standard German language in German speaking Switzerland with focus on the spoken language. It brings to attention sociolinguistic concepts of the Swiss language environment and the role of the standard German language in Switzerland. The goal of the article is to evaluate the role of the standard German language in German speaking Switzerland on the base of theoretical assumptions and empirical research. The article presents the results of an analysis which was performed on the examples of TV broadcast of the Swiss television.
Ziel des vorliegenden Artikels ist die Analyse von Motivationsschreiben, einer Textsorte, die bei der Bewerbung um einen Masterstudienplatz oder um ein Stipendium häufig eingereicht werden muss. Anhand eines Korpus von 30 Motivationsschreiben, welche im Rahmen der Masterarbeit von November 2013 bis Mai 2014 gesammelt wurden, sollen die Relevanz, der Kommunikationskontext und die Textfunktionen der offenen Textsorte aufgezeigt werden.
O objetivo principal deste artigo é apresentar uma visão geral dos resultados obtidos em uma pesquisa empírica envolvendo aprendizes adultos de alemão como língua estrangeira com conhecimentos prévios de inglês. O foco deste artigo recai sobre os processos envolvidos no ensino/aprendizagem de terceiras línguas, levando-se em consideração que a língua alemã é comumente aprendida como uma segunda língua estrangeira após o inglês. Os principais questionamentos da pesquisa estão baseados em processos de transferência positiva, bem como na interferência linguística observada em um grupo de 50 aprendizes de alemão dos níveis A1 a B1 do Quadro Europeu Comum de Referência para as Línguas. Ao que concerne a relação entre as línguas alemã e inglesa, a afirmação de que o inglês exerce um papel importante na aprendizagem de alemão pôde ser confirmada, sendo o parentesco etimológico entre as duas línguas um dos mais importantes fatores para se determinar a ocorrência de influência interlinguística. Por outro lado, a interferência linguística resultante da coexistência de ambas as línguas demanda o desenvolvimento de uma didática do plurilinguismo que compreenda métodos alternativos para o ensino/aprendizagem de alemão como segunda língua estrangeira no Brasil.
"Great technology, football and ..." : Malaysian language learners' stereotypes about Germany
(2014)
This study focuses on stereotypes about Germany, its culture and people, held by learners of German in a big public university in Malaysia. It examines not only the stereotypical representations of the target language country but also assesses its favourability and salience, which has not been done previously. The findings revealed that the students' stereotypes about Germany were varied and diverse. Also, they were overwhelmingly positive. The top three salient categories of images about Germany were related to technology, famous personalities – for the most part football players and scientists – and cars. The findings also indicated that very few references had been made to German culture and to its great cultural figures. The results of the present study suggest that students could benefit from a wider and deeper exposure to German culture in the language classroom.
Der Aufsatz untersucht das syntaktische Verhalten nicht-satzförmiger Adverbialia im Deutschen und im brasilianischen Portugiesisch in vergleichender Perspektive. Behandelt werden Adverbialia aus sechs Klassen, deren semantische Funktionen von der Sachverhaltsbeschreibung bis zur Beschreibung von Handlungsabsichten des Sprechers reichen. Insgesamt zeigen sich große Ähnlichkeiten zwischen den Vergleichssprachen. Im Deutschen scheint eine etwas stärkere Tendenz zu bestehen, Adverbialia syntaktisch zu integrieren, während es im Portugiesischen mehr Möglichkeiten gibt, sie desintegriert zu verwenden.
Este artigo recapitula as traduções de Wilhelm Busch publicadas no Brasil e aponta que determinadas circunstâncias de publicação levaram a uma recepção unilateral de sua obra exclusivamente como literatura infantil nesse país. Entre outras estratégias que poderiam estender para uma faixa etária adulta o público leitor da poesia humorística buschiana, propõe-se que o Knittelvers seja traduzido para o português como decassílabo iâmbico. Uma tradução anotada do poema "Hänsel und Gretel" nesse padrão métrico-acentual testa em que medida a escolha consciente de um ritmo e o aproveitamento de associações culturais desencadeadas por ele podem destacar o efeito irônico desse pseudoconto-de-fada.
O presente texto lida com a forma do juízo em Hölderlin e Hegel, focalizando principalmente seus momentos de divisão e unificação. Inicialmente, unificação e divisão são aqui tratadas a partir de temáticas desenvolvidas em torno do amor no séc. XVIII. O juízo é analisado basicamente no âmbito da Ciência da lógica, de Hegel, de prefácios do romance Hyperion e do texto "Juízo e Ser", de Hölderlin. A análise visa expor as passagens entre esses momentos do juízo nos textos supracitados, as quais mobilizam relações entre singular, particular e geral. Considerando essas relações, propõe-se uma interpretação do romance acima mencionado.
A influência de Bertolt Brecht sobre Walter Benjamin é comumente atribuída à assimilação da tradição de crítica marxista pelo último. O presente artigo busca realizar uma crítica imanente e teórica da obra de ambos com o fito de investigar outras faces possíveis dessa influência. Sendo assim, o objetivo é demonstrar que o "Efeito de distanciamento" (em alemão "Verfremdungseffekt") utilizado por Brecht em seu teatro épico tem um papel fundamental na leitura que Benjamin fará do cinema e aparece nas quatro versões do ensaio sobre "A obra de arte na época de sua reprodutibilidade técnica", bem como na sua teoria sobre a "aura".
Franz Kafka's (1883-1924) "Die Brücke" is one of the less well-known texts by one of the most prolific authors of literary modernity. However, this short prose text embodies prevalent questions of literary modernity and philosophy as it reflects the crisis of language in regard of identity, communication, and literary production. Placed in the context of fin-de-siècle's discourse of language crisis, this article provides a dialogue between Kafka's "Die Brücke" and Hannah Arendt's (1906-1975) philosophy of thinking and speaking in "The Life of the Mind". Contrary to Arendt's understanding of the metaphor as "a carrying over" between the mental activities of the solitude thinker and a reconciliation with the pluralistic world shared with others, this article argues for a deconstructionist reading of "Die Brücke" as a tool to reevaluate Arendt"s notion of a shared human experience ensured through language and illustrates the advantages of poetic texts within philosophical discourses.
Seven years after the launch of the European Paediatric Medicine Regulation, limited progress in paediatric oncology drug development remains a major concern amongst stakeholders – academics, industry, regulatory authorities, parents, patients and caregivers. Restricted increases in early phase paediatric oncology trials, legal requirements and regulatory pressure to propose early Paediatric Investigation Plans (PIPs), missed opportunities to explore new drugs potentially relevant for paediatric malignancies, lack of innovative trial designs and no new incentives to develop drugs against specific paediatric targets are some unmet needs. Better access to new anti-cancer drugs for paediatric clinical studies and improved collaboration between stakeholders are essential. The Cancer Drug Development Forum (CDDF), previously Biotherapy Development Association (BDA), with Innovative Therapy for Children with Cancer Consortium (ITCC), European Society for Paediatric Oncology (SIOPE) and European Network for Cancer Research in Children and Adolescents (ENCCA) has created a unique Paediatric Oncology Platform, involving multiple stakeholders and the European Union (EU) Commission, with an urgent remit to improve paediatric oncology drug development. The Paediatric Oncology Platform proposes to recommend immediate changes in the implementation of the Regulation and set the framework for its 2017 revision; initiatives to incentivise drug development against specific paediatric oncology targets, and repositioning of drugs not developed in adults. Underpinning these changes is a strategy for mechanism of action and biology driven selection and prioritisation of potential paediatric indications rather than the current process based on adult cancer indications. Pre-competitive research and drug prioritisation, early portfolio evaluation, cross-industry cooperation and multi-compound/sponsor trials are being explored, from which guidance for innovative trial designs will be provided.
Structure and regulatory interactions of the cytoplasmic terminal domains of serotonin transporter
(2014)
Uptake of neurotransmitters by sodium-coupled monoamine transporters of the NSS family is required for termination of synaptic transmission. Transport is tightly regulated by protein–protein interactions involving the small cytoplasmic segments at the amino- and carboxy-terminal ends of the transporter. Although structures of homologues provide information about the transmembrane regions of these transporters, the structural arrangement of the terminal domains remains largely unknown. Here, we combined molecular modeling, biochemical, and biophysical approaches in an iterative manner to investigate the structure of the 82-residue N-terminal and 30-residue C-terminal domains of human serotonin transporter (SERT). Several secondary structures were predicted in these domains, and structural models were built using the Rosetta fragment-based methodology. One-dimensional 1H nuclear magnetic resonance and circular dichroism spectroscopy supported the presence of helical elements in the isolated SERT N-terminal domain. Moreover, introducing helix-breaking residues within those elements altered the fluorescence resonance energy transfer signal between terminal cyan fluorescent protein and yellow fluorescent protein tags attached to full-length SERT, consistent with the notion that the fold of the terminal domains is relatively well-defined. Full-length models of SERT that are consistent with these and published experimental data were generated. The resultant models predict confined loci for the terminal domains and predict that they move apart during the transport-related conformational cycle, as predicted by structures of homologues and by the “rocking bundle” hypothesis, which is consistent with spectroscopic measurements. The models also suggest the nature of binding to regulatory interaction partners. This study provides a structural context for functional and regulatory mechanisms involving SERT terminal domains.
Background: Despite improvements in liver surgery over the past decades, hemostasis during hepatic resections remains challenging. This multicenter randomized study compares the hemostatic effect of a collagen hemostat vs. a carrier-bound fibrin sealant after hepatic resection.
Methods: Patients scheduled for elective liver resection were randomized intraoperatively to receive either the collagen hemostat (COLL) or the carrier-bound fibrin sealant (CBFS) for secondary hemostasis. The primary endpoint was the proportion of patients with hemostasis after 3 min. Secondary parameters were the proportions of patients with hemostasis after 5 and 10 min, the total time to hemostasis, and the complication rates during a 3 months follow-up period.
Results: A total of 128 patients were included. In the COLL group, 53 out of 61 patients (86.9 %) achieved complete hemostasis within 3 min after application of the hemostat compared to 52 out of 65 patients (80.0 %) in the CBFS group. The 95 % confidence interval for this difference [−6.0 %, 19.8 %] does not include the lower noninferiority margin (−10 %). Thus, the COLL treatment can be regarded as noninferior to the comparator. The proportions of patients with hemostasis after 3, 5, and 10 min were not significantly different between the two study arms. Postoperative mortality and morbidity were similar in both treatment groups.
Conclusion: The collagen hemostat is as effective as the carrier-bound fibrin sealant in obtaining secondary hemostasis during liver resection with a comparable complication rate.
A cell-based high-throughput screen that assessed the cellular stability of a tumor suppressor protein PDCD4 (Programmed cell death 4) was used to identify a new guanidine-containing marine alkaloid mirabilin K (3), as well as the known compounds mirabilin G (1) and netamine M (2). The structures of these tricyclic guanidine alkaloids were established from extensive spectroscopic analyses. Compounds 1 and 2 inhibited cellular degradation of PDCD4 with EC50 values of 1.8 μg/mL and 2.8 μg/mL, respectively. Mirabilin G (1) and netamine M (2) are the first marine natural products reported to stabilize PDCD4 under tumor promoting conditions.
Resveratrol shows beneficial effects in inflammation-based diseases like cancer, cardiovascular and chronic inflammatory diseases. Therefore, the molecular mechanisms of the anti-inflammatory resveratrol effects deserve more attention. In human epithelial DLD-1 and monocytic Mono Mac 6 cells resveratrol decreased the expression of iNOS, IL-8 and TNF-α by reducing mRNA stability without inhibition of the promoter activity. Shown by pharmacological and siRNA-mediated inhibition, the observed effects are SIRT1-independent. Target-fishing and drug responsive target stability experiments showed selective binding of resveratrol to the RNA-binding protein KSRP, a central post-transcriptional regulator of pro-inflammatory gene expression. Knockdown of KSRP expression prevented resveratrol-induced mRNA destabilization in human and murine cells. Resveratrol did not change KSRP expression, but immunoprecipitation experiments indicated that resveratrol reduces the p38 MAPK-related inhibitory KSRP threonine phosphorylation, without blocking p38 MAPK activation or activity. Mutation of the p38 MAPK target site in KSRP blocked the resveratrol effect on pro-inflammatory gene expression. In addition, resveratrol incubation enhanced KSRP-exosome interaction, which is important for mRNA degradation. Finally, resveratrol incubation enhanced its intra-cellular binding to the IL-8, iNOS and TNF-α mRNA. Therefore, modulation of KSRP mRNA binding activity and, thereby, enhancement of mRNA degradation seems to be the common denominator of many anti-inflammatory effects of resveratrol.
Observation and tracking of fluorescently labeled molecules and particles in living cells reveals detailed information about intracellular processes on the molecular level. Whereas light microscopic particle observation is usually limited to two-dimensional projections of short trajectory segments, we report here image-based real-time three-dimensional single particle tracking in an active feedback loop with single molecule sensitivity. We tracked particles carrying only 1-3 fluorophores deep inside living tissue with high spatio-temporal resolution. Using this approach, we succeeded to acquire trajectories containing several hundred localizations. We present statistical methods to find significant deviations from random Brownian motion in such trajectories. The analysis allowed us to directly observe transitions in the mobility of ribosomal (r)RNA and Balbiani ring (BR) messenger (m)RNA particles in living Chironomus tentans salivary gland cell nuclei. We found that BR mRNA particles displayed phases of reduced mobility, while rRNA particles showed distinct binding events in and near nucleoli.
The knowledge of phenotypic variation in the European range of the highly allergenic Ambrosia artemisiifolia L. (common ragweed) is not entirely complete, even though it is an invasive species of utmost concern. We hypothesized the prevalence of phenotypic differentiations between common ragweed populations in the introduced range, and we assumed that those differentiations were related to environmental conditions at the points of origin. Using a common garden experiment, we investigated biomass allocation, growth rates, and flowering phenology of 38 European common ragweed populations originating from a major geographical gradient. We observed considerable phenotypic variation in growth parameters and flowering phenology, e.g. mean aboveground biomass varied from 23.3 to 47.3 g between the populations. We were able to relate most measured traits with environmental parameters prevailing at the points of origin. For example, early growth of ruderal populations was highly correlated with temperature and precipitation at the point of origin. Late growth and flowering phenology were highly correlated with latitude, i.e. individuals from northern populations grew smaller and flowered and dispersed their pollen and seeds up to 5 weeks earlier than individuals from southern populations. We also found a longitudinal gradient in flowering phenology which has not yet been described. The existence of such a high variability in the introduced range may facilitate further range expansion. We suggest that the correlation with environmental variables rests upon genetic variation possibly due to adaptations to the respective environment. To clarify if such adaptation results from multiple events of introduction or as evolutionary response after introduction, genetic investigations are needed.
Molecular tumour targeting has significantly improved anti-cancer protocols. Still, the addition of molecular targeting to the treatment regime has not led to a curative breakthrough. Combined mammalian target of Rapamycin (mTOR) and histone deacetylase (HDAC) inhibition has been shown not only to enhance anti-tumour potential, but also to prevent resistance development seen under mono-drug therapy. This investigation was designed to evaluate whether cross-communication exists between mTOR signalling and epigenetic events regulated by HDAC. DU-145 prostate cancer cells were treated with insulin-like growth factor (IGF) to activate the Akt-mTOR cascade or with the HDAC-inhibitor valproic acid (VPA) to induce histone H3 and H4 acetylation (aH3, aH4). Subsequently, mTOR, Rictor, Raptor, p70s6k, Akt (all: total and phosphorylated), H3 and H4 (total and acetylated) were analysed by western blotting. Both techniques revealed a link between mTOR and the epigenetic machinery. IGF activated mTOR, Rictor, Raptor, p70s6k and Akt, but also enhanced aH3 and aH4. Inversely, IGFr blockade and knock-down blocked the Akt-mTOR axis, but simultaneously diminished aH3 and aH4. VPA treatment up-regulated histone acetylation, but also activated mTOR-Akt signalling. HDAC1 and 2 knock-down revealed that the interaction with the mTOR system is initiated by histone H3 acetylation. HDAC-mTOR communication, therefore, is apparent whereby tumour-promoting (Akt/mTORhigh, aH3/aH4low) and tumour-suppressing signals (Akt/mTORlow, aH3/aH4high) are activated in parallel. Combined use of an HDAC- and mTOR inhibitor might then diminish pro-tumour effects triggered by the HDAC- (Akt/mTORhigh) or mTOR inhibitor (aH3/aH4low) alone.
Background: Following acute coronary syndrome (ACS), the risk for future cardiovascular events is high and is related to levels of low-density lipoprotein cholesterol (LDL-C) even within the setting of intensive statin treatment. Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates LDL receptor expression and circulating levels of LDL-C. Antibodies to PCSK9 can produce substantial and sustained reductions of LDL-C. The ODYSSEY Outcomes trial tests the hypothesis that treatment with alirocumab, a fully human monoclonal antibody to PCSK9, improves cardiovascular outcomes after ACS.
Design: This Phase 3 study will randomize approximately 18,000 patients to receive biweekly injections of alirocumab (75-150 mg) or matching placebo beginning 1 to 12 months after an index hospitalization for acute myocardial infarction or unstable angina. Qualifying patients are treated with atorvastatin 40 or 80 mg daily, rosuvastatin 20 or 40 mg daily, or the maximum tolerated and approved dose of one of these agents and fulfill one of the following criteria: LDL-C ≥ 70 mg/dL, non-high-density lipoprotein cholesterol ≥ 100 mg/dL, or apolipoprotein B ≥ 80 mg/dL. The primary efficacy measure is time to first occurrence of coronary heart disease death, acute myocardial infarction, hospitalization for unstable angina, or ischemic stroke. The trial is expected to continue until 1613 primary end point events have occurred with minimum follow-up of at least 2 years, providing 90% power to detect a 15% hazard reduction. Adverse events of special interest include allergic events and injection site reactions. Interim analyses are planned when approximately 50% and 75% of the targeted number of primary end points have occurred.
Summary: ODYSSEY Outcomes will determine whether the addition of the PCSK9 antibody alirocumab to intensive statin therapy reduces cardiovascular morbidity and mortality after ACS.
Background: HER2 status assessment is a prerequisite for the establishment of an appropriate treatment strategy in gastric cancer. Gastric cancers are very heterogeneous and separate evaluations of gene amplification and protein expression lead to uncertainties in localizing distinct clones and are time consuming. This study evaluates the equivalence of the novel method combining both gene and protein platforms on one slide.
Methods: Immunohistochemistry (IHC) and HER2 dual-colour silver in situ hybridization (SISH) as single methods (IHC/SISH) and gene-protein platform combining both methods on one slide (gene/protein) were performed in randomly collected 100 cases of gastric adenocarcinoma. Results of IHC/SISH were compared with gene/protein staining.
Results: 96 of 100 samples were assessable. In the gene/protein staining, pathologists were able to assess gene amplification and consequent protein expression at the single cell level. In comparison trials, gene amplification was observed in 14.6% by both, conventional SISH and gene/protein platform (agreement 100%; Kappa-coefficient κ = 1.0). Protein expression scores by IHC were 70.8% (0), 10.4% (1+), 9.4% (2+), and 9.4% (3+). Protein expression by gene/protein method were: 70.8% (0), 11.5% (1+), 7.3% (2+) and 10.4% (3+) of patients. There were complete concordances in IHC assessment of cases with score 0 (100.0%; κ = 1). High concordances are shown in score 1+ (98.96%; κ = 0.947) and 3+ (96.88%; κ = 0.825) cases and good concordances in 2+ cases (95.83%; κ = 0.728).
Conclusions: This novel combined platform has the advantage of being able to evaluate both gene and the protein status in the same cancer cell and may be of particular interest for research and patient's care.
Considering the review by Puspitasari and colleagues, an additional discussion of the endpoints of the Se supplementation studies described would be helpful. In our view, selenium can safely be given to selenium-deficient cancer patients prior to and during radiotherapy. Therefore, in order to help the radiation oncologist in decision making, we strongly advocate to determine the selenium status prior to and during a potential adjuvant selenium supplementation, e.g. when trying to ease the side-effects of radiation treatment or in the aftercare situation when the selenium status may become insufficient.
Irrigation intensifies land use by increasing crop yield but also impacts water resources. It affects water and energy balances and consequently the microclimate in irrigated regions. Therefore, knowledge of the extent of irrigated land is important for hydrological and crop modelling, global change research, and assessments of resource use and management. Information on the historical evolution of irrigated lands is limited. The new global Historical Irrigation Dataset (HID) provides estimates of the temporal development of the area equipped for irrigation (AEI) between 1900 and 2005 at 5 arc-minute resolution. We collected subnational irrigation statistics from various sources and found that the global extent of AEI increased from 63 million ha (Mha) in 1900 to 112 Mha in 1950 and 306 Mha in 2005. We developed eight gridded versions of time series of AEI by combining subnational irrigation statistics with different data sets on the historical extent of cropland and pasture. Different rules were applied to maximize consistency of the gridded products to subnational irrigation statistics or to historical cropland and pasture data sets. The HID reflects very well the spatial patterns of irrigated land in the western United States as shown on historical maps. Mean aridity on irrigated land increased and river discharge decreased from 1900–1950 whereas aridity decreased from 1950–2005. The dataset and its documentation are made available in an open data repository at https://mygeohub.org/publications/8 (doi:10.13019/M2MW2G).
We have isolated a cDNA coding for a putative invertebrate-type dopamine receptor (Peadop2) from P. americana brain by using a PCR-based strategy. The mRNA is present in samples from brain and salivary glands. We analyzed the distribution of the PeaDOP2 receptor protein with specific affinity-purified polyclonal antibodies. On Western blots, PeaDOP2 was detected in protein samples from brain, subesophageal ganglion, thoracic ganglia, and salivary glands. In immunocytochemical experiments, we detected PeaDOP2 in neurons with their somata being located at the anterior edge of the medulla bilaterally innervating the optic lobes and projecting to the ventro-lateral protocerebrum. In order to determine the functional and pharmacological properties of the cloned receptor, we generated a cell line constitutively expressing PeaDOP2. Activation of PeaDOP2-expressing cells with dopamine induced an increase in intracellular cAMP. In contrast, a C-terminally truncated splice variant of this receptor did not exhibit any functional property by itself. The molecular and pharmacological characterization of the first dopamine receptor from P. americana provides the basis for forthcoming studies focusing on the significance of the dopaminergic system in cockroach behavior and physiology.
Conventional radar-based image reconstruction techniques fail when they are applied to heterogeneous breast tissue, since the underlying in-breast relative permittivity is unknown or assumed to be constant. This results in a systematic error during the process of image formation. A recent trend in microwave biomedical imaging is to extract the relative permittivity from the object under test to improve the image reconstruction quality and thereby to enhance the diagnostic assessment. In this paper, we present a novel radar-based methodology for microwave breast cancer detection in heterogeneous breast tissue integrating a 3D map of relative permittivity as a priori information. This leads to a novel image reconstruction formulation where the delay-and-sum focusing takes place in time rather than range domain. Results are shown for a heterogeneous dense (class-4) and a scattered fibroglandular (class-2) numerical breast phantom using Bristol's 31-element array configuration.
Multimorbidity is a health issue mostly dealt with in primary care practice. As a result of their generalist and patient-centered approach, long-lasting relationships with patients, and responsibility for continuity and coordination of care, family physicians are particularly well placed to manage patients with multimorbidity. However, conflicts arising from the application of multiple disease oriented guidelines and the burden of diseases and treatments often make consultations challenging. To provide orientation in decision making in multimorbidity during primary care consultations, we developed guiding principles and named them after the Greek mythological figure Ariadne. For this purpose, we convened a two-day expert workshop accompanied by an international symposium in October 2012 in Frankfurt, Germany. Against the background of the current state of knowledge presented and discussed at the symposium, 19 experts from North America, Europe, and Australia identified the key issues of concern in the management of multimorbidity in primary care in panel and small group sessions and agreed upon making use of formal and informal consensus methods. The proposed preliminary principles were refined during a multistage feedback process and discussed using a case example. The sharing of realistic treatment goals by physicians and patients is at the core of the Ariadne principles. These result from i) a thorough interaction assessment of the patient’s conditions, treatments, constitution, and context; ii) the prioritization of health problems that take into account the patient's preferences – his or her most and least desired outcomes; and iii) individualized management realizes the best options of care in diagnostics, treatment, and prevention to achieve the goals. Goal attainment is followed-up in accordance with a re-assessment in planned visits. The occurrence of new or changed conditions, such as an increase in severity, or a changed context may trigger the (re-)start of the process. Further work is needed on the implementation of the formulated principles, but they were recognized and appreciated as important by family physicians and primary care researchers.
Purpose: Prostate specific antigen is not reliable in diagnosing prostate cancer (PCa), making the identification of novel, precise diagnostic biomarkers important. Since chemokines are associated with more aggressive disease and poor prognosis in diverse malignancies, we aimed to investigate the diagnostic relevance of chemokines in PCa.
Materials and methods: Preoperative and early postoperative serum samples were obtained from 39 consecutive PCa patients undergoing radical prostatectomy. Serum from 15 healthy volunteers served as controls. Concentrations of CXCL12, CXCL13, CX3CL1, CCL2, CCL5, and CCL20 were measured in serum by Luminex. The expression activity of CXCR3, CXCR4, CXCR5, CXCR7, CXCL12, CXCL13, CX3CR1, CXCL1, CCR2, CCR5, CCR6, CCR7, CCL2, and CCL5 mRNA was assessed in tumor and adjacent normal tissue of prostatectomy specimens by quantitative real-time polymerase chain reaction. The associations of these chemokines with clinical and histological parameters were tested.
Results: The gene expression activity of CCL2 and CCR6 was significantly higher in tumor tissue compared to adjacent normal tissue. CCL2 was also significantly higher in the blood samples of PCa patients, compared to controls. CCL5, CCL20, and CX3CL1 were lower in patient serum, compared to controls. CCR2 tissue mRNA was negatively correlated with the Gleason score and grading.
Conclusion: Chemokines are significantly modified during tumorigenesis of PCa, and CCL2 is a promising diagnostic biomarker.
A versatile synthetic procedure is described to prepare the benzimidazole-fused 1,2,4-thiadiazoles 2a–c via a methanesulfonyl chloride initiated multistep cyclization involving the intramolecular reaction of an in-situ generated carbodiimide with a thiourea unit. The structure of the intricate heterocycle 2a was confirmed by single-crystal X-ray analysis and its mechanism of formation supported by DFT computations.