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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.