Refine
Year of publication
Document Type
- Article (30515) (remove)
Language
- English (15219)
- German (13289)
- Portuguese (696)
- French (387)
- Croatian (251)
- Spanish (250)
- Italian (133)
- Turkish (113)
- Multiple languages (36)
- Latin (35)
Has Fulltext
- yes (30515)
Keywords
- Deutsch (503)
- taxonomy (421)
- Literatur (297)
- Hofmannsthal, Hugo von (185)
- new species (179)
- Rezeption (178)
- Übersetzung (163)
- Filmmusik (155)
- Johann Wolfgang von Goethe (131)
- Vormärz (113)
Institute
- Medizin (5128)
- Physik (1728)
- Biowissenschaften (1108)
- Extern (1108)
- Biochemie und Chemie (1099)
- Gesellschaftswissenschaften (798)
- Frankfurt Institute for Advanced Studies (FIAS) (697)
- Geowissenschaften (582)
- Präsidium (453)
- Philosophie (448)
Ecological speciation assumes reproductive isolation to be the product of ecologically based divergent selection. Beside natural selection, sexual selection via phenotype-assortative mating is thought to promote reproductive isolation. Using the neotropical fish Poecilia mexicana from a system that has been described to undergo incipient ecological speciation in adjacent, but ecologically divergent habitats characterized by the presence or absence of toxic H2S and darkness in cave habitats, we demonstrate a gradual change in male body colouration along the gradient of light/darkness, including a reduction of ornaments that are under both inter- and intrasexual selection in surface populations. In dichotomous choice tests using video-animated stimuli, we found surface females to prefer males from their own population over the cave phenotype. However, female cave fish, observed on site via infrared techniques, preferred to associate with surface males rather than size-matched cave males, likely reflecting the female preference for better-nourished (in this case: surface) males. Hence, divergent selection on body colouration indeed translates into phenotype-assortative mating in the surface ecotype, by selecting against potential migrant males. Female cave fish, by contrast, do not have a preference for the resident male phenotype, identifying natural selection against migrants imposed by the cave environment as the major driver of the observed reproductive isolation.
B lymphocytes are an important cell population of the immune system. However, until recently it was not possible to transduce resting B lymphocytes with retro- or lentiviral vectors, making them unsusceptible for genetic manipulations by these vectors. Lately, we demonstrated that lentiviral vectors pseudotyped with modified measles virus (MV) glycoproteins hemagglutinin, responsible for receptor recognition, and fusion protein were able to overcome this transduction block. They use either the natural MV receptors, CD46 and signaling lymphocyte activation molecule (SLAM), for cell entry (MV-LV) or the vector particles were further modified to selectively enter via the CD20 molecule, which is exclusively expressed on B lymphocytes (CD20-LV). It has been shown previously that transduction by MV-LV does not induce B lymphocyte activation. However, if this is also true for CD20-LV is still unknown. Here, we generated a vector specific for another B lymphocyte marker, CD19, and compared its ability to transduce resting B lymphocytes with CD20-LV. The vector (CD19ds-LV) was able to stably transduce unstimulated B lymphocytes, albeit with a reduced efficiency of about 10% compared to CD20-LV, which transduced about 30% of the cells. Since CD20 as well as CD19 are closely linked to the B lymphocyte activation pathway, we investigated if engagement of CD20 or CD19 molecules by the vector particles induces activating stimuli in resting B lymphocytes. Although, activation of B lymphocytes often involves calcium influx, we did not detect elevated calcium levels. However, the activation marker CD71 was substantially up-regulated upon CD20-LV transduction and most importantly, B lymphocytes transduced with CD20-LV or CD19ds-LV entered the G1b phase of cell cycle, whereas untransduced or MV-LV transduced B lymphocytes remained in G0. Hence, CD20 and CD19 targeting vectors induce activating stimuli in resting B lymphocytes, which most likely renders them susceptible for lentiviral vector transduction.
Diabetes is characterized by a dysregulation of glucose homeostasis and platelets from patients with diabetes are known to be hyper-reactive and contribute to the accelerated development of vascular diseases. Since many of the deleterious effects of glucose have been attributed to its metabolite methylgyloxal (MG) rather than to hyperglycemia itself, the aim of the present study was to characterize the effects of MG on platelet function. Washed human platelets were pre-incubated for 15 min with MG and platelet aggregation, adhesion on matrix-coated slides and signaling (Western blot) were assessed ex vivo. In vivo, the effect of MG on thrombus formation was determined using the FeCl3-induced carotid artery injury model. MG potentiated thrombin-induced platelet aggregation and dense granule release, but inhibited platelet spreading on fibronectin and collagen. In vivo, MG accelerated thrombus formation but decreased thrombus stability. At the molecular level, MG increased intracellular Ca2+ and activated classical PKCs at the same time as inhibiting PI3K/Akt and the β3-integrin outside-in signaling. In conclusion, these findings indicate that the enhanced MG concentration measured in diabetic patients can directly contribute to the platelet dysfunction associated with diabetes characterized by hyperaggregability and reduced thrombus stability.
Novel treatment options are needed for the successful therapy of patients with high-risk neuroblastoma. Here, we investigated the cyclin-dependent kinase (CDK) inhibitor SNS-032 in a panel of 109 neuroblastoma cell lines consisting of 19 parental cell lines and 90 sublines with acquired resistance to 14 different anticancer drugs. Seventy-three percent of the investigated neuroblastoma cell lines and all four investigated primary tumor samples displayed concentrations that reduce cell viability by 50% in the range of the therapeutic plasma levels reported for SNS-032 (<754 nM). Sixty-two percent of the cell lines and two of the primary samples displayed concentrations that reduce cell viability by 90% in this concentration range. SNS-032 also impaired the growth of the multidrug-resistant cisplatin-adapted UKF-NB-3 subline UKF-NB-3rCDDP1000 in mice. ABCB1 expression (but not ABCG2 expression) conferred resistance to SNS-032. The antineuroblastoma effects of SNS-032 did not depend on functional p53. The antineuroblastoma mechanism of SNS-032 included CDK7 and CDK9 inhibition-mediated suppression of RNA synthesis and subsequent depletion of antiapoptotic proteins with a fast turnover rate including X-linked inhibitor of apoptosis (XIAP), myeloid cell leukemia sequence 1 (Mcl-1), baculoviral IAP repeat containing 2 (BIRC2; cIAP-1), and survivin. In conclusion, CDK7 and CDK9 represent promising drug targets and SNS-032 represents a potential treatment option for neuroblastoma including therapy-refractory cases.
Characteristically, most solid tumors exhibit an increased tumor interstitial fluid pressure (TIFP) that directly contributes to the lowered uptake of macromolecular therapeutics into the tumor interstitium. Abnormalities in the tumor-associated lymph vessels are a central brick in the development and prolonged sustaining of an increased TIFP. In the current study, vascular endothelial growth factor C (VEGF-C) was used to enhance tumor-associated lymphangiogenesis as a new mechanism to actively reduce the TIFP by increased lymphatic drainage of the tumor tissue. Human A431 epidermoid vulva carcinoma cells were inoculated in NMRI nu/nu mice to generate a xenograft mouse model. Seven days after tumor cell injection, VEGF-C was peritumorally injected to induce lymphangiogenesis. Tumor growth and TIFP was lowered significantly over time in VEGF-C-treated tumors in comparison to control or VEGF-A-treated animals. These data demonstrate for the first time that actively induced lymphangiogenesis can lower the TIFP in a xenograft tumor model and apparently reduce tumor growth. This model represents a novel approach to modulate biomechanical properties of the tumor interstitium enabling a lowering of TIFP in vivo.
The proportion of elderly women in the population is rising, and in tandem, the incidence of breast cancer rises with age. Because of health and tolerability concerns, as well as life expectancy, physicians may be reluctant to advise a standard treatment regimen for elderly patients with metastatic breast cancer. To elucidate this issue, we performed a literature review of clinical studies that included women with metastatic breast cancer who were over the age of 65. Our results show that although little clinical evidence exists, what is available suggests that standard treatment is tolerated and beneficial for patients meeting certain criteria. A geriatric assessment may identify specific patient groups (independent, dependent, or frail) and thereby guide treatment. Treatment recommendations for elderly patients with metastatic breast cancer are sparse, although first-line endocrine treatment, usually aromatase inhibitors or tamoxifen, is recommended for hormone-sensitive disease. In general, the evidence from clinical studies suggests that aromatase inhibitors are more effective than either tamoxifen or megestrol acetate as first- or second-line treatment in postmenopausal women with metastatic breast cancer. Ultimately, quality of life, treatment effects, and comorbidities are important aspects in this population and may guide treatment choice. To provide evidence-based treatment guidance, future clinical trials should include more patients over the age of 65 years.
Long-range angular correlations on the near and away side in p–Pb collisions at √sNN=5.02 TeV
(2013)
Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p–Pb collisions at a nucleon–nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5<pT,assoc<pT,trig<4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and pT bins, and the widths show no significant evolution with event multiplicity or pT. These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge.
Artificial environments for the co-translational stabilization of cell-free expressed proteins
(2013)
An approach for designing individual expression environments that reduce or prevent protein aggregation and precipitation is described. Inefficient folding of difficult proteins in unfavorable translation environments can cause significant losses of overexpressed proteins as precipitates or inclusion bodies. A number of chemical chaperones including alcohols, polyols, polyions or polymers are known to have positive effects on protein stability. However, conventional expression approaches can use such stabilizing agents only post-translationally during protein extraction and purification. Proteins that already precipitate inside of the producer cells cannot be addressed. The open nature of cell-free protein expression systems offers the option to include single chemicals or cocktails of stabilizing compounds already into the expression environment. We report an approach for systematic screening of stabilizers in order to improve the solubility and quality of overexpressed proteins co-translationally. A comprehensive list of representative protein stabilizers from the major groups of naturally occurring chemical chaperones has been analyzed and their concentration ranges tolerated by cell-free expression systems have been determined. As a proof of concept, we have applied the method to improve the yield of proteins showing instability and partial precipitation during cell-free synthesis. Stabilizers that co-translationally improve the solubility and functional folding of human glucosamine 6-phosphate N-acetyltransferase have been identified and cumulative effects of stabilizers have been studied.
Previous experimental measurements from nuclear collisions have indicated modifications of jets by interaction with the medium created in the collision. Observables from particle correlations in the ALICE detector continue to provide access to key properties of the hot deconfined nuclear matter. New results from two- and three-particle number and transverse momentum correlations are discussed. Specifically, correlation function properties are characterized as a function of transverse momentum and centrality and for different charge combinations. Fourier decompositions are performed, identified particle ratios are studied in the jet-like peak and in the bulk, and the away-side shape is looked at in three-particle correlations.
Der Bundestag hat in seiner gestrigen Plenardebatte theoretisch über Netzneutralität diskutiert. Theoretisch dadurch, dass die Debatte nur als "Reden zu Protokoll" stattfand, weil die Opposition wohl alle Plenardebatten-Kärtchen bereits gezogen hatte und die Regierungskoalition anscheinend kein großes Interesse an einer öffentlichen Debatte hatten. Konkret ging es um einen Gesetzentwurf der Linksfraktion, die Netzneutralität festzuschreiben. ...
BACKGROUND: In the heart, cytoplasmic actin networks are thought to have important roles in mechanical support, myofibrillogenesis, and ion channel function. However, subcellular localization of cytoplasmic actin isoforms and proteins involved in the modulation of the cytoplasmic actin networks are elusive. Mena and VASP are important regulators of actin dynamics. Due to the lethal phenotype of mice with combined deficiency in Mena and VASP, however, distinct cardiac roles of the proteins remain speculative. In the present study, we analyzed the physiological functions of Mena and VASP in the heart and also investigated the role of the proteins in the organization of cytoplasmic actin networks.
RESULTS: We generated a mouse model, which simultaneously lacks Mena and VASP in the heart. Mena/VASP double-deficiency induced dilated cardiomyopathy and conduction abnormalities. In wild-type mice, Mena and VASP specifically interacted with a distinct αII-Spectrin splice variant (SH3i), which is in cardiomyocytes exclusively localized at Z- and intercalated discs. At Z- and intercalated discs, Mena and β-actin localized to the edges of the sarcomeres, where the thin filaments are anchored. In Mena/VASP double-deficient mice, β-actin networks were disrupted and the integrity of Z- and intercalated discs was markedly impaired.
CONCLUSIONS: Together, our data suggest that Mena, VASP, and αII-Spectrin assemble cardiac multi-protein complexes, which regulate cytoplasmic actin networks. Conversely, Mena/VASP deficiency results in disrupted β-actin assembly, Z- and intercalated disc malformation, and induces dilated cardiomyopathy and conduction abnormalities.
Bei Zeit.de findet sich eine Übersicht der Verhandlungsführer für nun beginnenden Koalitionsverhandlungen für eine Große Koalition. Netzpolitik dürfte als Querschnittsthema in mehreren Arbeitsgruppen verhandelt werden. Zuallererst fällt natürlich die Unterarbeitsgruppe Digitale Agenda auf, die der Arbeitsgruppe Kultur zugeordnet ist. Das führte gestern erstmal zu viel Häme auf Twitter, aber diese Zuordnung muss ja erstmal nicht schlecht sein. Viel wichtiger als eine Zuordnung ist ja, wer da was verhandelt. ...
Die Koalition hat sich gestern über einen letzten Kompromiss zum Leistungsschutzrecht geeinigt, der heute im federführenden Rechtsausschuss abgestimmt werden soll. Geplant ist, diesen am Freitag nach zweiter und dritter Lesung im Bundestag abzustimmen. Dagegen wehrte sich die Opposition und forderte heute im Rechtsausschuss eine weitere Anhörung, um die veränderten Rahmenbedingungen diskutieren zu können. Das wurde aber mit der Mehrheit der Koalition abgelehnt. ...
The gauge principle is fundamental in formulating the Standard Model. Fermion–gauge-boson couplings are the inescapable consequence and the primary determining factor for observable phenomena. Vertices describing such couplings are simple in perturbation theory and yet the existence of strong-interaction bound-states guarantees that many phenomena within the Model are nonperturbative. It is therefore crucial to understand how dynamics dresses the vertices and thereby fundamentally alters the appearance of fermion–gauge-boson interactions. We consider the coupling of a dressed-fermion to an Abelian gauge boson, and describe a unified treatment and solution of the familiar longitudinal Ward–Green–Takahashi identity and its less well known transverse counterparts. Novel consequences for the dressed-fermion–gauge-boson vertex are exposed.
The role of the mRNA-binding protein human antigen R (HuR) in stabilization and translation of AU-rich elements (ARE) containing mRNAs is well established. However, the trafficking of HuR and bound mRNA cargo, which comprises a fundamental requirement for the aforementioned HuR functions is only poorly understood. By administering different cytoskeletal inhibitors, we found that the protein kinase Cδ (PKCδ)-triggered accumulation of cytoplasmic HuR by Angiotensin II (AngII) is an actin-myosin driven process functionally relevant for stabilization of ARE-bearing mRNAs. Furthermore, we show that the AngII-induced recruitment of HuR and its bound mRNA from ribonucleoprotein particles to free and cytoskeleton bound polysomes strongly depended on an intact actomyosin cytoskeleton. In addition, HuR allocation to free and cytoskeletal bound polysomes is highly sensitive toward RNase and PPtase and structurally depends on serine 318 (S318) located within the C-terminal RNA recognition motif (RRM3). Conversely, the trafficking of the phosphomimetic HuRS318D, mimicking HuR phosphorylation at S318 by the PKCδ remained PPtase resistant. Co-immunoprecipitation experiments with truncated HuR proteins revealed that the stimulus-induced association of HuR with myosin IIA is strictly RNA dependent and mediated via the RRM3. Our data implicate a microfilament dependent transport of HuR, which is relevant for stimulus-induced targeting of ARE-bearing mRNAs from translational inactive ribonucleoprotein particles to polysomes.
Natural killer (NK) cells are highly specialized effectors of the innate immune system that hold promise for adoptive cancer immunotherapy. Their cell killing activity is primarily mediated by the pro-apoptotic serine protease granzyme B (GrB), which enters targets cells with the help of the pore-forming protein perforin. We investigated expression of a chimeric GrB fusion protein in NK cells as a means to augment their antitumoral activity. For selective targeting to tumor cells, we fused the epidermal growth factor receptor (EGFR) peptide ligand transforming growth factor α (TGFα) to human pre-pro-GrB. Established human NKL natural killer cells transduced with a lentiviral vector expressed this GrB-TGFα (GrB-T) molecule in amounts comparable to endogenous wildtype GrB. Activation of the genetically modified NK cells by cognate target cells resulted in the release of GrB-T together with endogenous granzymes and perforin, which augmented the effector cells' natural cytotoxicity against NK-sensitive tumor cells. Likewise, GrB-T was released into the extracellular space upon induction of degranulation with PMA and ionomycin. Secreted GrB-T fusion protein displayed specific binding to EGFR-overexpressing tumor cells, enzymatic activity, and selective target cell killing in the presence of an endosomolytic activity. Our data demonstrate that ectopic expression of a targeted GrB fusion protein in NK cells is feasible and can enhance antitumoral activity of the effector cells.
Background and Aims: Mutations reducing the function of Nav1.7 sodium channels entail diminished pain perception and olfactory acuity, suggesting a link between nociception and olfaction at ion channel level. We hypothesized that if such link exists, it should work in both directions and gain-of-function Nav1.7 mutations known to be associated with increased pain perception should also increase olfactory acuity.
Methods: SCN9A variants were assessed known to enhance pain perception and found more frequently in the average population. Specifically, carriers of SCN9A variants rs41268673C>A (P610T; n = 14) or rs6746030C>T (R1150W; n = 21) were compared with non-carriers (n = 40). Olfactory function was quantified by assessing odor threshold, odor discrimination and odor identification using an established olfactory test. Nociception was assessed by measuring pain thresholds to experimental nociceptive stimuli (punctate and blunt mechanical pressure, heat and electrical stimuli).
Results: The number of carried alleles of the non-mutated SCN9A haplotype rs41268673C/rs6746030C was significantly associated with the comparatively highest olfactory threshold (0 alleles: threshold at phenylethylethanol dilution step 12 of 16 (n = 1), 1 allele: 10.6±2.6 (n = 34), 2 alleles: 9.5±2.1 (n = 40)). The same SCN9A haplotype determined the pain threshold to blunt pressure stimuli (0 alleles: 21.1 N/m2, 1 allele: 29.8±10.4 N/m2, 2 alleles: 33.5±10.2 N/m2).
Conclusions: The findings established a working link between nociception and olfaction via Nav1.7 in the gain-of-function direction. Hence, together with the known reduced olfaction and pain in loss-of-function mutations, a bidirectional genetic functional association between nociception and olfaction exists at Nav1.7 level.
Background and Aims: The Roadmap concept is a therapeutic framework in chronic hepatitis B for the intensification of nucleoside analogue monotherapy based on early virologic response. The efficacy and safety of this approach applied to telbivudine treatment has not been investigated.
Methods: A multinational, phase IV, single-arm open-label study (ClinicalTrials.gov ID NCT00651209) was undertaken in HBeAg-positive, nucleoside-naive adult patients with chronic hepatitis B. Patients received telbivudine (600 mg once-daily) for 24 weeks, after which those with undetectable serum HBV DNA (<300 copies/mL) continued to receive telbivudine alone while those with detectable DNA received telbivudine plus tenofovir (300 mg once-daily). Outcomes were assessed at Week 52.
Results: 105 patients commenced telbivudine monotherapy, of whom 100 were included in the efficacy analysis. Fifty-five (55%) had undetectable HBV DNA at Week 24 and continued telbivudine monotherapy; 45 (45%) received tenofovir intensification. At Week 52, the overall proportion of undetectable HBV DNA was 93% (93/100) by last-observation-carried-forward analysis (100% monotherapy group, 84% intensification group) and no virologic breakthroughs had occurred. ALT normalization occurred in 77% (87% monotherapy, 64% intensification), HBeAg clearance in 43% (65% monotherapy, 16% intensification), and HBeAg seroconversion in 39% (62% monotherapy, 11% intensification). Six patients had HBsAg clearance. Myalgia was more common in the monotherapy group (19% versus 7%). No decrease in the mean glomerular filtration rate occurred in either treatment group at Week 52.
Conclusions: Telbivudine therapy with tenofovir intensification at Week 24, where indicated by the Roadmap strategy, appears effective and well tolerated for the treatment of chronic hepatitis B.
Trial Registration: ClinicalTrials.gov NCT00651209
BACKGROUND: To report the clinical outcome of high dose rate brachytherapy as sole treatment for clinically localised prostate cancer.
METHODS: Between March 2004 and January 2008, a total of 351 consecutive patients with clinically localised prostate cancer were treated with transrectal ultrasound guided high dose rate brachytherapy. The prescribed dose was 38.0 Gy in four fractions (two implants of two fractions each of 9.5 Gy with an interval of 14 days between the implants) delivered to an intraoperative transrectal ultrasound real-time defined planning treatment volume. Biochemical failure was defined according to the Phoenix Consensus and toxicity evaluated using the Common Toxicity Criteria for Adverse Events version 3.
RESULTS: The median follow-up time was 59.3 months. The 36 and 60 month biochemical control and metastasis-free survival rates were respectively 98%, 94% and 99%, 98%. Toxicity was scored per event with 4.8% acute Grade 3 genitourinary and no acute Grade 3 gastrointestinal toxicity. Late Grade 3 genitourinary and gastrointestinal toxicity were respectively 3.4% and 1.4%. No instances of Grade 4 or greater acute or late adverse events were reported.
CONCLUSIONS: Our results confirm high dose rate brachytherapy as safe and effective monotherapy for clinically organ-confined prostate cancer.
Background. Incomplete revascularization negatively affects survival after coronary artery bypass surgery (CABG). Since gender and classification technique might impact outcome and reporting, we investigated their effect on revascularization patterns and mortality. Methods. A cohort of bypass patients (N = 1545, 23% women) was enrolled prospectively. The degree of revascularization was determined as mathematical difference between affected vessels upon diagnosis and number of grafts or the surgeon’s rating on the case file. Results. Although men displayed more triple-vessel disease, they obtained complete revascularization more frequently than women (85% versus 77%, P < 0.001). The two calculation methods identified analogous percentages of incompletely revascularized patients, yet there was only a 50% overlap between the two groups. Mathematically, more women, older patients, and patients with NYHA class III/IV appeared incompletely revascularized, while the surgeons identified more patients undergoing technically challenging procedures. Regardless of the definition, incompleteness was a significant risk factor for mortality in both genders (mathematical calculation: HR 2.62, 95% CI 1.76–3.89, P < 0.001; surgeon: HR 2.04, 95% CI 1.35–3.89, P = 0.001). Conclusions. Given the differences in identification patterns, we advise that the mathematical calculation be performed after-procedure in all patients regardless of the surgeons’ rating to uncover additional subjects at increased risk.
Fire is the primary disturbance factor in many terrestrial ecosystems. Wildfire alters vegetation structure and composition, affects carbon storage and biogeochemical cycling, and results in the release of climatically relevant trace gases including CO2, CO, CH4, NOx, and aerosols. One way of assessing the impacts of global wildfire on centennial to multi-millennial timescales is to use process-based fire models linked to dynamic global vegetation models (DGVMs). Here we present an update to the LPJ-DGVM and a new fire module based on SPITFIRE that includes several improvements to the way in which fire occurrence, behaviour, and the effects of fire on vegetation are simulated. The new LPJ-LMfire model includes explicit calculation of natural ignitions, the representation of multi-day burning and coalescence of fires, and the calculation of rates of spread in different vegetation types. We describe a new representation of anthropogenic biomass burning under preindustrial conditions that distinguishes the different relationships between humans and fire among hunter-gatherers, pastoralists, and farmers. We evaluate our model simulations against remote-sensing-based estimates of burned area at regional and global scale. While wildfire in much of the modern world is largely influenced by anthropogenic suppression and ignitions, in those parts of the world where natural fire is still the dominant process (e.g. in remote areas of the boreal forest and subarctic), our results demonstrate a significant improvement in simulated burned area over the original SPITFIRE. The new fire model we present here is particularly suited for the investigation of climate–human–fire relationships on multi-millennial timescales prior to the Industrial Revolution.
Inhibitors of Apoptosis Proteins (IAPs) are a class of highly conserved proteins predominantly known for the regulation of caspases and immune signaling. However, recent evidence suggests a crucial role for these molecules in the regulation of tumor cell shape and migration by controlling MAPK, NF-κB and Rho GTPases. IAPs directly control Rho GTPases, thus regulating cell shape and migration. For instance, XIAP and cIAP1 function as the direct E3 ubiquitin ligases of Rac1 and target it for proteasomal degradation. IAPs are differentially expressed in tumor cells and have been targeted by several cancer therapeutic drugs that are currently in clinical trials. Here, we summarize the current knowledge on the role of IAPs in the regulation of cell migration and discuss the possible implications of these observations in regulating tumor cell metastases.
Background: Cannabinoid receptor 1 (CB1) is expressed in certain types of malignancies. An analysis of CB1 expression and function in Hodgkin lymphoma (HL), one of the most frequent lymphomas, was not performed to date.
Design and Methods: We examined the distribution of CB1 protein in primary cases of HL. Using lymphoma derived cell lines, the role of CB1 signaling on cell survival was investigated.
Results: A predominant expression of CB1 was found in Hodgkin-Reed-Sternberg cells in a vast majority of classical HL cases. The HL cell lines L428, L540 and KM-H2 showed strong CB1-abundance and displayed a dose-dependent decline of viability under CB1 inhibition with AM251. Further, application of AM251 led to decrease of constitutively active NFκB/p65, a crucial survival factor of HRS-cells, and was followed by elevation of apoptotic markers in HL cells.
Conclusions: The present study identifies CB1 as a feature of HL, which might serve as a potential selective target in the treatment of Hodgkin lymphoma.
Objectives Tumour recurrence of glioblastoma multiforme (GBM) after initial treatment with surgical resection, radiotherapy and chemotherapy is an inevitable phenomenon. This retrospective cohort study compared the efficacy of interstitial high dose rate brachytherapy (HDR-BRT), re-resection and sole dose dense temozolomide chemotherapy (ddTMZ) in the treatment of recurrent glioblastoma after initial surgery and radiochemotherapy.
Design Retropective cohort study.
Setting Primary level of care with two participating centres. The geographical location was central Germany.
Participants From January 2005 to December 2010, a total of 111 patients developed recurrent GBM after initial surgery and radiotherapy with concomitant temozolomide. The inclusion criteria were as follows: (1) histology-proven diagnosis of primary GBM (WHO grade 4), (2) primary treatment with resection and radiochemotherapy, and (3) tumour recurrence/progression.
Interventions This study compared retrospectively the efficacy of interstitial HDR-BRT, re-resection and ddTMZ alone in the treatment of recurrent glioblastoma.
Primary and secondary outcome measures Median survival, progression free survival and complication rate.
Results Median survival after salvage therapy of the recurrence was 37, 30 and 26 weeks, respectively. The HDR-BRT group did significantly better than both the reoperation (p<0.05) and the ddTMZ groups (p<0.05). Moderate to severe complications in the HDR-BRT, reoperation and sole chemotherapy groups occurred in 5/50 (10%), 4/36 (11%) and 9/25 (36%) cases, respectively.
Conclusions CT-guided interstitial HDR-BRT attained higher survival benefits in the management of recurrent glioblastoma after initial surgery and radiotherapy with concurrent temozolomide in comparison with the other treatment modalities. The low risk of complications of the HDR-BRT and the fact that it can be delivered percutaneously in local anaesthesia render it a promissing treatment option for selected patients which should be further evaluated.
The prize-collecting vehicle routing problem with single and multiple depots and non-linear cost
(2013)
In this paper, we propose a new routing problem to model a highly relevant planning task in small package shipping. We consider the Prize-Collecting Vehicle Routing Problem with Non-Linear cost in its single and multi-depot version, which integrates the option of outsourcing customers to subcontractors instead of serving them with the private fleet. Thereby, a lower bound on the total customer demand to be served by the private fleet guarantees a high utilization of the fleet capacity. To represent the practical situation, where a discount is given by a subcontractor if larger amounts of packages are outsourced, subcontracting costs follow a non-linear function. The considered problem is NP-hard and we propose an Adaptive Variable Neighborhood Search algorithm to solve instances of realistic size. We propose new benchmark sets for the single and the multi-depot problem, which are adapted from test instances of the capacitated VRP and the closely related Multi-Depot VRP with Private fleet and Common carrier. In numerical studies, we investigate the performance of our algorithm on the newly generated test instances and on standard benchmark problems of related problems. Moreover, we study the effect of different cost functions and different values of the minimal demand to be served by the private fleet on the routing solutions obtained.
Im Rahmen eines umfangreichen Projekts zu Übersetzungsmöglichkeiten der deutschen Modalverben ins Portugiesische – und nachdem wir schon den Fall sollen behandelt haben (siehe Hörster/Athayde/Carecho 2011) – stellen wir in dieser Studie einige wesentliche Ergebnisse unserer Untersuchung bezüglich des Modalverbs müssen dar. Ziel unserer Arbeit war nicht die semantische und pragmatische Beschreibung der einzelnen Modalverben, ein Thema, das immer wieder im Mittelpunkt der wissenschaftlichen Diskussion steht. Vielmehr war es unsere Absicht, einen Beitrag zur zweisprachigen Lexikografie, zur Fremdsprachendidaktik und vor allem zur Übersetzungsdidaktik zu leisten.
Persistent neuropathic pain is a frequent consequence of peripheral nerve injuries, particularly in the elderly. Using the IntelliCage we studied if sciatic nerve injury obstructed learning and memory in young and aged mice, each in wild type and progranulin deficient mice, which develop premature signs of brain aging. Both young and aged mice developed long-term nerve injury-evoked hyperalgesia and allodynia. In both genotypes, aged mice with neuropathic pain showed high error rates in place avoidance acquisition tasks. However, once learnt, these aged mice with neuropathic pain showed a significantly stronger maintenance of the aversive memory. Nerve injury did not affect place preference behavior in neither genotype, neither in young nor aged mice. However, nerve injury in progranulin deficient mice impaired the learning of spatial sequences of awarded places, particularly in the aged mice. This task required a discrimination of clockwise and anti-clockwise sequences. The chaining failure occurred only in progranulin deficient mice after nerve injury, but not in sham operated or wildtype mice, suggesting that progranulin was particularly important for compensatory adaptations after nerve injury. In contrast, all aged mice with neuropathic pain, irrespective of the genotype, had a long maintenance of aversive memory suggesting a negative alliance and possibly mutual aggravation of chronic neuropathic pain and aversive memory at old age.
The inner structural Gag proteins and the envelope (Env) glycoproteins of human immunodeficiency virus (HIV-1) traffic independently to the plasma membrane, where they assemble the nascent virion. HIV-1 carries a relatively low number of glycoproteins in its membrane, and the mechanism of Env recruitment and virus incorporation is incompletely understood. We employed dual-color super-resolution microscopy visualizing Gag assembly sites and HIV-1 Env proteins in virus-producing and in Env expressing cells. Distinctive HIV-1 Gag assembly sites were readily detected and were associated with Env clusters that always extended beyond the actual Gag assembly site and often showed enrichment at the periphery and surrounding the assembly site. Formation of these Env clusters depended on the presence of other HIV-1 proteins and on the long cytoplasmic tail (CT) of Env. CT deletion, a matrix mutation affecting Env incorporation or Env expression in the absence of other HIV-1 proteins led to much smaller Env clusters, which were not enriched at viral assembly sites. These results show that Env is recruited to HIV-1 assembly sites in a CT-dependent manner, while Env(ΔCT) appears to be randomly incorporated. The observed Env accumulation surrounding Gag assemblies, with a lower density on the actual bud, could facilitate viral spread . Keeping Env molecules on the nascent virus low may be important for escape from the humoral immune response, while cell-cell contacts mediated by surrounding Env molecules could promote HIV-1 transmission through the virological synapse.
We searched for a drug capable of sensitization of sarcoma cells to doxorubicin (DOX). We report that the dual PI3K/mTOR inhibitor PI103 enhances the efficacy of DOX in several sarcoma cell lines and interacts with DOX in the induction of apoptosis. PI103 decreased the expression of MDR1 and MRP1, which resulted in DOX accumulation. However, the enhancement of DOX-induced apoptosis was unrelated to DOX accumulation. Neither did it involve inhibition of mTOR. Instead, the combination treatment of DOX plus PI103 activated Bax, the mitochondrial apoptosis pathway, and caspase 3. Caspase 3 activation was also observed in xenografts of sarcoma cells in nude mice upon combination of DOX with the specific PI3K inhibitor GDC-0941. Although the increase in apoptosis did not further impact on tumor growth when compared to the efficient growth inhibition by GDC-0941 alone, these findings suggest that inhibition of PI3K may improve DOX-induced proapoptotic effects in sarcoma. Taken together with similar recent studies of neuroblastoma- and glioblastoma-derived cells, PI3K inhibition seems to be a more general option to sensitize tumor cells to anthracyclines.
We report on new localities for Anolis gruuo Köhler, Ponce, Sunyer and Batista, 2007 along the Serranía de Tabasará in the Comarca Ngöbe-Buglé and Veraguas province of western Panama. These records extend the known geographic distribution of this lizard about 80 km eastward, and the known vertical distribution approximately 40 m lower and 630 m higher. We provide photos of specimens from different localities and comment on their morphology. Only the easternmost populations of this Panamanian endemic live inside a protected area.
Bei der Routinekontrolle von Laichgewässern von Kreuzkröten (Bufo calamita) auf dem Truppenübungsplatz Colbitz-Letzlinger Heide wurde auch eine Wasserführende Bodensenke begutachtet. Bei der vorsichtigen Annäherung an dieses Habitat konnten vier rufende Kreuzkrötenmännchen erfasst werden. Zusätzlich konnten Branchiopoden der Arten Triops cancriformis und Branchipus schaefferi bestimmt werden. Dieser neue Fund befindet sich weit im Süden des Truppenübungsplatzes und trägt damit zur Vervollständigung der Gesamtübersicht zur Verbreitung von Branchiopoden bei.
Eine Kartierfahrt zur Erfassung von Lebensräumen von Zauneidechsen (Lacerta agilis) und Schlingnattern (Coronella austriaca) führte in den Süden des Truppenübungsplatzes Colbitz-Letzlinger Heide. Die Begutachtung einer weiträumigen Kreuzung ergab eine auffallend große Anzahl an Witwenblumen (Kuatia arvensis)in den Randbereichen. Bei genauer Betrachtung des reichen Blütenpulkes konnten außerdem drei Borstige Dolchwespen (Scolia hirta) beobachtet werden, welche in den Roten Listen für Deutschland sowie auch für Sachsen-Anhalt aufgeführt ist.
Folding of RNA molecules into their functional three-dimensional structures is often supported by RNA chaperones, some of which can catalyse the two elementary reactions helix disruption and helix formation. Hfq is one such RNA chaperone, but its strand displacement activity is controversial. Whereas some groups found Hfq to destabilize secondary structures, others did not observe such an activity with their RNA substrates. We studied Hfq’s activities using a set of short RNAs of different thermodynamic stabilities (GC-contents from 4.8% to 61.9%), but constant length. We show that Hfq’s strand displacement as well as its annealing activity are strongly dependent on the substrate’s GC-content. However, this is due to Hfq’s preferred binding of AU-rich sequences and not to the substrate’s thermodynamic stability. Importantly, Hfq catalyses both annealing and strand displacement with comparable rates for different substrates, hinting at RNA strand diffusion and annealing nucleation being rate-limiting for both reactions. Hfq’s strand displacement activity is a result of the thermodynamic destabilization of the RNA through preferred single-strand binding whereas annealing acceleration is independent from Hfq’s thermodynamic influence. Therefore, the two apparently disparate activities annealing acceleration and duplex destabilization are not in energetic conflict with each other.
In vielen Fällen blühen Koniferen unauffällig. Ihre Blüten sind sparsam ausgestattet, vergleicht man sie mit denen der echten "Blütenpflanzen" (Angiospermen), also z. B. einer Rose oder einem Mohn. Es gibt bei den Koniferen keine Blütenblätter und es gibt auch keine Fruchtblätter: Die Samenanlagen stehen "nackt" in den Achseln oder auf der Fläche einer Zapfenschuppe, weswegen man die Koniferen zu der Gruppe der Nacktsamer (Gymnospermen) zählt. So braucht man bei vielen Koniferen einige Übung, die Blüten überhaupt zu finden.
BACKGROUND: There is agreement that the infectivity assay with the duck hepatitis B virus (DHBV) is a suitable surrogate test to validate disinfectants for hepatitis B virucidal activity. However, since this test is not widely used, information is necessary whether disinfectants with limited virucidal activity also inactivate DHBV. In general, disinfectants with limited virucidal activity are used for skin and sensitive surfaces while agents with full activity are more aggressive. The present study compares the activity of five different biocides against DHBV and the classical test virus for limited virucidal activity, the vaccinia virus strain Lister Elstree (VACV) or the modified vaccinia Ankara strain (MVA).
METHODS: Virucidal assay was performed as suspension test according to the German DVV/RKI guideline. Duck hepatitis B virus obtained from congenitally infected Peking ducks was propagated in primary duck embryonic hepatocytes and was detected by indirect immunofluorescent antigen staining.
RESULTS: The DHBV was inactivated by the use of 40% ethanol within 1-min and 30% isopropanol within 2-min exposure. In comparison, 40% ethanol within 2-min and 40% isopropanol within 1-min exposure were effective against VACV/MVA. These alcohols only have limited virucidal activity, while the following agents have full activity. 0.01% peracetic acid inactivated DHBV within 2 min and a concentration of 0.005% had virucidal efficacy against VACV/MVA within 1 min. After 2-min exposure, 0.05% glutardialdehyde showed a comparable activity against DHBV and VACV/MVA. This is also the case for 0.7% formaldehyde after a contact time of 30 min.
CONCLUSIONS: Duck hepatitis B virus is at least as sensitive to limited virucidal activity as VACV/MVA. Peracetic acid is less effective against DHBV, while the alcohols are less effective against VACV/MVA. It can be expected that in absence of more direct tests the results may be extrapolated to HBV.
Das Herbarium des Pfarrers Adolf Becker, gesammelt zwischen 1833 und 1863, wurde nachbestimmt. Bei der Mehrzahl der etwa 200 mit Fundorten versehenen Belege handelt es sich um Kulturpflanzen, die vornehmlich in Parkanlagen von Bad Homburg v. d. Höhe und Okarben gesammelt wurden. Diese geben einen Eindruck von den erstaunlich reichhaltigen Bepflanzungen jener Zeit. 81 von uns als Wildpflanzen klassifizierte Arten wurden zumeist um Okarben gesammelt. Wegen ihres Rückganges oder aktuellen Fehlens sind die Belege von Apium graveolens, A. nodiflorum, Juncus gerardii, Nigella arvensis und Oenanthe fistulosa bemerkenswert.
Festuca rhenana spec. nov. und Festuca heteropachys, zwei verkannte Schwingel der Flora Deutschlands
(2012)
Seit über vier Jahrzehnten werden kräftige Schwingel von Silikatfelsen des mittelrheinischen Raumes irrtümlich als Festuca heteropachys bezeichnet. Diese Pflanzen gehören zu keiner der bisher bekannten Sippen. Sie werden unter dem Namen F. rhenana als neue, in Deutschland endemische Art beschrieben. Im Nordpfälzer Bergland, im Nahe- , im Mittelrhein- und im Moseltal besiedelt F. rhenana extrem trocken-warme Felsstandorte auf ± basenreichen Silikatgesteinen (Rhyolith, Andesit, Oberrotliegendes, devonische Schiefer). Fast alle Fundorte liegen in Rheinland-Pfalz, zwei in Hessen. Die wahre F. heteropachys kommt ebenfalls in Deutschland vor, und zwar nur im südlichen Teil von Rheinland-Pfalz. F. heteropachys ist ein mesophiles bis schwach thermophiles, Halbschatten ertragendes Horstgras. Kennzeichnend sind die mit 30–50 cm oft sehr langen Grundblätter und die starke, deutlich bis über die Mitte der Halme reichende Beblätterung. Im Anschluss an die Vorkommen im Elsass findet sich F. heteropachys hauptsächlich im Pfälzer Wald auf ± sauren steinigen oder sandigen Böden über Buntsandstein. Unterscheidungsmerkmale von F. heteropachys, F. rhenana, F. lemanii und der häufigen F. guestfalica werden dargestellt.
Schriftenschau
(2012)
Vorkommen von Festuca pallens wurden 2011 und 2012 in Hessen nachgesucht. Für alle Populationen wurden die Chromosomenzahl und der Ploidiegrad ermittelt. Fast alle bekannten Vorkommen wurden in teilweise großen, ungefährdeten Beständen wiedergefunden. Bei den meisten Vorkommen erwiesen sich die Pflanzen als tetraploid und gehören damit zu F. csikhegyensis. Pflanzen von der Bodensteiner Lei westlich von Villmar (Landkreis Limburg-Weilburg) und von Basaltfelsen der Ruine Altenburg (Schwalm-Eder-Kreis) sind diploid und gehören zu F. pallens. Ein früheres Vorkommen von F. pallens am Kirchenfelsen in Dietkirchen (Landkreis Limburg-Weilburg) wurde bei Säuberungsmaßnahmen vernichtet.
2011 wurden Gräben der Oberrheinebene auf ihren Makrophytenbestand untersucht. Die Mehrzahl der Gräben wies keine bemerkenswerten Pflanzenvorkommen auf. Callitriche obtusangula gehört allerdings zu den im Gebiet offenbar relativ weit verbreiteten Arten. Bemerkenswert ist der Bereich innerhalb einer Altrheinschlinge zwischen Geinsheim, Leeheim und Wallerstädten, wo in kleinen Gräben, deren Umgebung intensiv ackerbaulich genutzt wird, bemerkenswerte Arten wie Nitella capillaris, Ranunculus lingua, Samolus valerandi und Utricularia vulgaris vorkommen. Die Neuanlage von Gräben in diesem Bereich wird empfohlen.
Angegeben wird jeweils das Sammeldatum des für die Chromosomenzählung verwendeten Materials (Lebendpflanze, Samen) zuzüglich eines eventuell gesammelten Beleges sowie – getrennt durch einen Schrägstrich – Sammeldatum und Aufbewahrungsort eines Beleges der gezählten Pflanze. Wird nur ein Datum angegeben, ist allein die Wildaufsammlung dokumentiert. Die Abkürzungen der Herbarien richten sich nach HOLMGREN & al. (1990, sowie Online- Nachträge, für die neuerdings B. Thiers verantwortlich zeichnet). Taxonomie und Nomenklatur richten sich nach der aktuellen deutschen Standardliste (BUTTLER & HAND 2008). Die Abbildungen zeigen Metaphasen, die an Quetschpräparaten von Wurzelspitzen gewonnen wurden (zur Methodik siehe VOGT & APARICIO 2000). Ralf Hand dankt Michael Meyer und seinem Gärtnerteam sowie Monika Lüchow und Marion Cubr (alle Botanischer Garten und Botanisches Museum Berlin-Dahlem) für Kultur, Dokumentation und Hilfe bei der Zählung von Material.
Es werden folgende Publikationen rezensiert: Chytrý: Vegetation of the Czech Republic 1, Chytrý: Vegetation of the Czech Republic 2, Chytrý: Vegetation of the Czech Republic 3, Eger & Kesper: Flechten zwischen Eder und Diemel, Gerster: Kräuterwissen, Meyer: Pflanzen Nordhessens, Mollenhauer: Gregor Kraus, Seibold: Schmeil-Fitschen, Suck & Bushart: Karte der Potentiellen Natürlichen Vegetation Deutschlands, Süß & al.: Ried und Sand.
Die jährlich im Vorfeld der DGfS-Tagung veranstaltete Arbeitstagung Linguistische Pragmatik fand 2012 vor besonderem Hintergrund statt: Es war zugleich die erste Jahrestagung des neu gegründeten, seit 01.01.2012 bestehenden Vereins Arbeitskreis Linguistische Pragmatik. Zu diesem Anlass haben die Organisatoren (Constanze Spieß, Elke Diedrichsen und Jörg Bücker) ein Rahmenthema gewählt, das pragmatisch orientierte Linguistinnen und Linguisten der verschiedensten Forschungsrichtungen zusammenbringt: Sprachkritik und Sprachwandel. ...
The Strongest Meaning Hypothesis (SMH henceforth), a pragmatic principle motivated in Dalrymple et al.'s (1998) study of reciprocals, has recently been applied to problems in implicatures (Chierchia et al. to appear) and Vagueness (Cobreros et al. 2011). In this snippet, I argue that the SMH can apply to embedded sentences, which is perhaps unusual for a pragmatic principle.
Albert Ostermaiers Werk nimmt eine Sonderstellung ein in der deutschsprachigen Gegenwartsliteratur: zum einen weil sich der Autor mit großer Selbstverständlichkeit in allen Gattungen bewegt und zum anderen, weil er intertextuelle und intermediale Bezüge ungewohnt offen verarbeitet und damit offensiv ausstellt, dass die schriftliche Literatur (zumal im 21. Jahrhundert) immer auch von anderen Künsten profitiert und aus diesen 'gemacht' ist. Vergleichbare Bezüge sind schon einigen Werktiteln zu entnehmen wenn Dramen 'Tatar Titus', 'The Making Of B.-Movie' bzw. 'Radio Noir' und Gedichtbände 'Autokino' und 'Wer sehen will' heißen. Bezüge zu Shakespeare klingen damit ebenso an wie zur amerikanischen Tradition der billigeren kleineren Filmproduktion, zum Hörmedium des Radios wie auch zu der einer bestimmten Form der Filmrezeption; und nicht zuletzt zur Photokunst, wenn sich in 'Wer sehen will' alle Gedichte auf die abgebildeten Photos Donzellis beziehen. Diese Mischung aus so genannter hohen und populärer Kultur ist kennzeichnend für Ostermaiers unbefangenen Umgang mit kulturellen und ästhetischen Traditionen. Das zeigt auch der kleine Band mit dem Titel 'Der Torwart' ist immer dort, wo es weh tut. Die Populärkultur des Sports wird in diesem Band gattungsübergreifend verhandelt: Die Sammlung beginnt mit drei lyrischen 'ode[n] an kahn'; findet später ihre Fortsetzung in einer dramatisch-dialogischen Szene 'Eins mit der eins' während im Rest des Bandes so genannte epische Texte dominieren und essayistisch-philosophische Gedanken versammeln, die um den Fußballsport kreisen. Dabei schreibt sich Ostermaier mit der Ode in eine lyrische Tradition ein, die schon in der Antike begonnen hat, während er in den epischen Texten über aktuelle und alltägliche Fußballangelegenheiten nachdenkt, über einen Sport also dem massenhafte Aufmerksamkeit zuteil wird und der globale schichten- und klassenübergreifende Beachtung findet.
This article is based on the observation that the linguistic expression of emotions has three basic categories: intensity, quality, and the temporal dimension. The latter category has not yet received sufficient attention from linguistic research. The article takes the example of contemporary theatrical texts to demonstrate the close correlation between the linguistic means used to express emotion and their temporal dimension. The analysis of the use of these means and their meaning in the given dramatic situation shows that temporality is a linguistic phenomenon which plays a key role in the linguistic expression of emotions in this type of text. It was also shown that the organization of a dramatic text – including an exposition phase or authorial notes – provides a suitable tool for the mediation of various temporal levels, the understanding of which plays an irreplaceable role in the total emotional potential of the text.
Background: 15-20% of all patients initially diagnosed with colorectal cancer develop metastatic disease and surgical resection remains the only potentially curative treatment available. Current 5-year survival following R0-resection of liver metastases is 28-39%, but recurrence eventually occurs in up to 70%. To date, adjuvant chemotherapy has not improved clinical outcomes significantly. The primary objective of the ongoing LICC trial (L-BLP25 In Colorectal Cancer) is to determine whether L-BLP25, an active cancer immunotherapy, extends recurrence-free survival (RFS) time over placebo in colorectal cancer patients following R0/R1 resection of hepatic metastases. L-BLP25 targets MUC1 glycoprotein, which is highly expressed in hepatic metastases from colorectal cancer. In a phase IIB trial, L-BLP25 has shown acceptable tolerability and a trend towards longer survival in patients with stage IIIB locoregional NSCLC.
Methods: This is a multinational, phase II, multicenter, randomized, double-blind, placebo-controlled trial with a sample size of 159 patients from 20 centers in 3 countries. Patients with stage IV colorectal adenocarcinoma limited to liver metastases are included. Following curative-intent complete resection of the primary tumor and of all synchronous/metachronous metastases, eligible patients are randomized 2:1 to receive either L-BLP25 or placebo. Those allocated to L-BLP25 receive a single dose of 300 mg/m2 cyclophosphamide (CP) 3 days before first L-BLP25 dose, then primary treatment with s.c. L-BLP25 930 mug once weekly for 8 weeks, followed by s.c. L-BLP25 930 mug maintenance doses at 6-week (years 1&2) and 12-week (year 3) intervals unless recurrence occurs. In the control arm, CP is replaced by saline solution and L-BLP25 by placebo. Primary endpoint is the comparison of recurrence-free survival (RFS) time between groups. Secondary endpoints are overall survival (OS) time, safety, tolerability, RFS/OS in MUC-1 positive cancers. Exploratory immune response analyses are planned. The primary endpoint will be assessed in Q3 2016. Follow-up will end Q3 2017. Interim analyses are not planned.
Discussion: The design and implementation of such a vaccination study in colorectal cancer is feasible. The study will provide recurrence-free and overall survival rates of groups in an unbiased fashion. Trial Registration EudraCT Number 2011-000218-20
Der Aufsatz arbeitet im Rückgriff auf Richard Alewyns bekannte Studie markante Modifikationen von Opitz' Antigone-Übersetzung auf syntaktischer, stilistischer und semantischer Ebene heraus: Während die sophokleische Tragödie vom Oxymoron geprägt ist, zeichnet sich Opitz' Übersetzung durch die Klärung des paradoxen Ausdrucks zur äußerlichen Antithese aus. Dank ihr kann die widerspruchsreiche Tragödie zum moralischen Exempel vereinfacht werden. Der Grund für diese Umdichtung wird – abweichend von Alewyn – im rhetorischen Sprachverständnis des Übersetzers gesucht: Die Eigenart seines "Teutschs" liegt in der zwiespältigen Orientierung an griechischer Tragödie und lateinischer Gerichtsrhetorik begründet. Dementsprechend kann auch die Charakteristik des "teutschen" Trauerspiels (das sich auf die griechische Tragödie beruft, aber zumeist ein religiöses Exempel statuiert) in diesem Zwiespalt einer neu zu schaffenden Trauerspielsprache verankert werden.
"In der Machination", so Walter Benjamin, "hat die neue Bühne den Gott." Das gilt nicht nur für die Theatermaschinerie, die den Gott auf der Barockbühne erscheinen lässt, sondern ebenso für die weiteren Bedeutungen des Wortes: "Machination" im Sinn des kunstfertigen Verstands und der trügerischen List, wie sie sich in der Intrige, dem dramatischen Kern des Trauerspiels, verkörpert. Der Aufsatz entfaltet den Zusammenhang zwischen Machination und Theophanie in einem Vergleich zwischen den barocken Dichtern Gryphius und Racine. Während die Spiele des Ersteren sich vorrangig auf die anschauliche Wirkung der Maschine stützen, um die Souveränität des 'christlichen' Gesetzes zu demonstrieren, präsentieren sich die Dramen des Letzteren als Musterbeispiele für ingeniöse Handlungsführung im Namen eines Regelwerks, dessen poetologische Autorität als 'göttlich' anerkannt wird. Zwischen diesen beiden Modellen theatralen Spiels vermittelt die Analyse einer Edition der aristotelischen Poetik, die Daniel Heinsius herausgegeben hat und einen besonderen Schwerpunkt auf die Deutung des deus ex machina legt.
Erinnerungen an ein menschenleeres Paradies : Urszenen literarischer Modernität im 19. Jahrhundert
(2012)
An der Schwelle zum 19. Jahrhundert stößt ein Aspekt des Kontinuums, in dem 'der Mensch' "seine Positivität bildet und bildet", an seine Grenze. Das romantische Büchermachen als Erbe einer religiös legitimierten eigentlichen Natur wird seiner Redundanz gewahr; die Ordnungen des Wissens beginnen in ihrer Form als Riesenbibliotheken zu ängstigen. In dieser Situation eröffnet die naturwissenschaftliche Beschäftigung mit der Physiologie des Gehirns und der Nervenbahnen, mit dem, was Aufschluss über die organischen Bedingtheiten des "Menschseins" allgemein zu liefern verspricht, aus anderer Warte eine Möglichkeit, "das im gedruckten Gehirn der Gemeinschaft erstarrte Denken" auf eine neue Stufe zu heben. Die Vorrang- und Vorreiterposition der französischen Psychiatrie im 19. Jahrhundert hat Robert Castel in die Formel 'L'Âge d'or de l'aliénisme' gefasst. Nietzsche hat diese "wissenschaftliche Lust des Menschen an sich selber" als "Lust am Ausnahmefall" denunziert, und konsequenterweise wandte sie sich auch dem zu, was noch unter dem schillernden Wort Genie firmierte, spezieller sogar dem 'génie im Medium der langue'.
Für die beiden Gründerväter der klinischen Psychiatrie Philippe Pinel und Jean Etienne Dominique Esquirol hatten in der Tradition der jüngeren Vergangenheit schon die Hypertrophien der Imagination allgemein zum eisernen prognostischen Bestand der Psychopathologie gehört; zu nennen wären hier als Anreger der berühmte William Cullen, der den folgenreichen Begriff Neurose prägte, sowie der englische Irrenarzt Sir Alexander Crichton, der als erster die damals revolutionäre These vertrat, dass die einzelnen Fähigkeiten der Seele, z.B. Aufmerksamkeit, Gedächtnis, Urteilskraft, Imagination etc., jede für sich allein erkranken könnten. Pinels Schüler Victor Broussais widmete in seinem Hauptwerk 'De l’irritation et de la folie' von 1828 einen langen Abschnitt der 'valeur des signes', in welchem er die Gültigkeit von sprachlichen Zeichen zur Selbstbeschreibung von psychischen Phänomenen untersucht. Sein Urteil: Begriffe wie 'moi', 'intelligence', 'imagination' seien nur der unvollkommene, laienhafte Versuch, die wechselnden physiologischen Zustände des Nervensystems unter eine chimärische Einheit zu zwingen, die selbst Züge des Wahnhaften trüge.
The notion of "presence" in contemporary debates about aesthetic experience ("ästhetisches Erleben") marks a turn against the premises of deconstruction. One of the most prominent figures in using the concept of "presence" is the german-american literary theorist Hans Ulrich Gumbrecht. In his works "presence" is not only a corporal experience in the aesthetic experience, it suspends sense and promotes the dimension of space against that of time. Moments of intensity in the observation of artworks can be read as moments of oscillation between sense and presence. This article outlines the main characteristics of Gumbrecht's notion of presence and discusses possibilities of reading literary texts with that concept in mind.
ABSTRACT: BACKGROUND: Particulate matter (PM) is assumed to exert a major burden on public health. Most studies that address levels of PM use stationary measure systems. By contrast, only few studies measure PM concentrations under mobile conditions to analyze individual exposure situations.
METHODS: By combining spatial-temporal analysis with a novel vehicle-mounted sensor system, the present Mobile Air Quality Study (MAQS) aimed to analyse effects of different driving conditions in a convertible vehicle. PM10 was continuously monitored in a convertible car, driven with roof open, roof closed, but windows open, or windows closed.
RESULTS: PM10 values inside the car were nearly always higher with open roof than with roof and windows closed, whereas no difference was seen with open or closed windows. During the day PM10 values varied with high values before noon, and occasional high median values or standard deviation values due to individual factors. Vehicle speed in itself did not influence the mean value of PM10; however, at traffic speed (10 -- 50 km/h) the standard deviation was large. No systematic difference was seen between PM10 values in stationary and mobile cars, nor was any PM10 difference observed between driving within or outside an environmental (low emission) zone.
CONCLUSIONS: he present study has shown the feasibility of mobile PM analysis in vehicles. Individual exposure of the occupants varies depending on factors like time of day as well as ventilation of the car; other specific factors are clearly identifiably and may relate to specific PM10 sources. This system may be used to monitor individual exposure ranges and provide recommendations for preventive measurements. Although differences in PM10 levels were found under certain ventilation conditions, these differences likely are not of concern for the safety and health of passengers.
U radu se raspravlja o leksikografskome statusu dvorječnih pozdrava dobro jutro, dobar dan, dobra večer i laku noć u hrvatskim rječnicima te se upućuje i na strane leksikografske pristupe. Naglasak je na značenjskim i komunikacijskim obilježjima pozdrava koja ih određuju kao posebnu leksičku skupinu te se predlaže da dvorječni pozdravi kao i jednorječni (zdravo, zbogom, doviđenja) postanu samostalne rječničke natuknice.
Urban health is potentially affected by particle emissions. The potential toxicity of nanoparticles is heavily debated and there is an enormous global increase in research activity in this field. In this respect, it is commonly accepted that nanoparticles may also be generated in processes occurring while driving vehicles. So far, a variety of studies addressed traffic-related particulate matter emissions, but only few studies focused on potential nanoparticles. Therefore, the present study analyzed the literature with regard to nanoparticles and cars. It can be stated that, to date, only a limited amount of research has been conducted in this area and more studies are needed to 1) address kind and sources of nanoparticles within automobiles and to 2) analyse whether there are health effects caused by these nanoparticles.
Depuis le milieu des années 1970, on assiste dans le monde entier à un retour en force des thématiques et problématiques relatives à la culture dans le champ de la sociologie. Ce regain d’intérêt va de pair avec le déclin croissant de la tradition, d’inspiration avant tout marxiste, de la théorie de la société, et s’inscrit dans un cultural turn global,qui a eu ces dernières années des répercussions sur la plupart des disciplines universitaires. ...
The tumour suppressor p53 controls transcription of various genes involved in apoptosis, cell-cycle arrest, DNA repair and metabolism. However, its DNA-recognition specificity is not nearly sufficient to explain binding to specific locations in vivo. Here, we present evidence that KLF4 increases the DNA-binding affinity of p53 through the formation of a loosely arranged ternary complex on DNA. This effect depends on the distance between the response elements of KLF4 and p53. Using nuclear magnetic resonance and fluorescence techniques, we found that the amino-terminal domain of p53 interacts with the KLF4 zinc fingers and mapped the interaction site. The strength of this interaction was increased by phosphorylation of the p53 N-terminus, particularly on residues associated with regulation of cell-cycle arrest genes. Taken together, the cooperative binding of KLF4 and p53 to DNA exemplifies a regulatory mechanism that contributes to p53 target selectivity.
Xenorhabdus and Photorhabdus spp. are bacterial symbionts of entomopathogenic nematodes (EPNs). In this study, we isolated and characterized Xenorhabdus and Photorhabdus spp. from across Thailand together with their associated nematode symbionts, and characterized their phylogenetic diversity. EPNs were isolated from soil samples using a Galleria-baiting technique. Bacteria from EPNs were cultured and genotyped based on recA sequence. The nematodes were identified based on sequences of 28S rDNA and internal transcribed spacer regions. A total of 795 soil samples were collected from 159 sites in 13 provinces across Thailand. A total of 126 EPNs isolated from samples taken from 10 provinces were positive for Xenorhabdus (n = 69) or Photorhabdus spp. (n = 57). Phylogenetic analysis separated the 69 Xenorhabdus isolates into 4 groups. Groups 1, 2 and 3 consisting of 52, 13 and 1 isolates related to X. stockiae, and group 4 consisting of 3 isolates related to X. miraniensis. The EPN host for isolates related to X. stockiae was S. websteri, and for X. miraniensis was S. khoisanae. The Photorhabdus species were identified as P. luminescens (n = 56) and P. asymbiotica (n = 1). Phylogenenic analysis divided P. luminescens into five groups. Groups 1 and 2 consisted of 45 and 8 isolates defined as subspecies hainanensis and akhurstii, respectively. One isolate was related to hainanensis and akhurstii, two isolates were related to laumondii, and one isolate was the pathogenic species P. asymbiotica subsp. australis. H. indica was the major EPN host for Photorhabdus. This study reveals the genetic diversity of Xenorhabdus and Photorhabdus spp. and describes new associations between EPNs and their bacterial symbionts in Thailand.
Die gesellschaftliche Wende 1989 hatte u. a. einen grundsätzlichen Umbau der bisherigen Verlagslandschaft in der Slowakei zur Folge. Wenn die Lage davor und danach verglichen wird, erscheinen markante Unterschiede, die neben anderen herausgegebenen Büchern auch die Übersetzungen aus der deutschsprachigen Literatur betreffen.
Assessing the uncertainties of simulation results of ecological models is becoming increasingly important, specifically if these models are used to estimate greenhouse gas emissions on site to regional/national levels. Four general sources of uncertainty effect the outcome of process-based models: (i) uncertainty of information used to initialise and drive the model, (ii) uncertainty of model parameters describing specific ecosystem processes, (iii) uncertainty of the model structure, and (iv) accurateness of measurements (e.g., soil-atmosphere greenhouse gas exchange) which are used for model testing and development.
The aim of our study was to assess the simulation uncertainty of the process-based biogeochemical model LandscapeDNDC. For this we set up a Bayesian framework using a Markov Chain Monte Carlo (MCMC) method, to estimate the joint model parameter distribution. Data for model testing, parameter estimation and uncertainty assessment were taken from observations of soil fluxes of nitrous oxide (N2O), nitric oxide (NO) and carbon dioxide (CO2) as observed over a 10 yr period at the spruce site of the Höglwald Forest, Germany. By running four independent Markov Chains in parallel with identical properties (except for the parameter start values), an objective criteria for chain convergence developed by Gelman et al. (2003) could be used.
Our approach shows that by means of the joint parameter distribution, we were able not only to limit the parameter space and specify the probability of parameter values, but also to assess the complex dependencies among model parameters used for simulating soil C and N trace gas emissions. This helped to improve the understanding of the behaviour of the complex LandscapeDNDC model while simulating soil C and N turnover processes and associated C and N soil-atmosphere exchange. In a final step the parameter distribution of the most sensitive parameters determining soil-atmosphere C and N exchange were used to obtain the parameter-induced uncertainty of simulated N2O, NO and CO2 emissions. These were compared to observational data of an calibration set (6 yr) and an independent validation set of 4 yr. The comparison showed that most of the annual observed trace gas emissions were in the range of simulated values and were predicted with a high certainty (Root-mean-squared error (RMSE) NO: 2.4 to 18.95 g N ha−1 d−1, N2O: 0.14 to 21.12 g N ha−1 d−1, CO2: 5.4 to 11.9 kg C ha−1 d−1). However, LandscapeDNDC simulations were sometimes still limited to accurately predict observed seasonal variations in fluxes.
In the title molecule, C18H17N5O2, the dihedral angle between the benzene plane and the benzimidazole plane is 19.8 (1)° and the angle between the benzene plane and the triazole plane is 16.7 (1)°. In the crystal, molecules are connected by O—H[cdots, three dots, centered]N hydrogen bonds, forming zigzag chains along the c-axis direction. The chains are connected by bifurcated N—H[cdots, three dots, centered](N,N) hydrogen bonds into layers parallel to (100). These layers are connected along the a-axis direction by weak C—H[cdots, three dots, centered]O contacts, forming a three-dimensional network.
Visual perception is highly variable and can be influenced by the surrounding world. Previous research has revealed that body perception can be biased due to adaptation to thin or fat body shapes. The aim of the present study was to show that adaptation to certain body shapes and the resulting perceptual biases transfer across different identities of adaptation and test stimuli. We designed two similar adaptation experiments in which healthy female participants adapted to pictures of either thin or fat bodies and subsequently compared more or less distorted pictures of their own body to their actual body shape. In the first experiment (n = 16) the same identity was used as adaptation and test stimuli (i.e. pictures of the participant’s own body) while in the second experiment (n = 16) we used pictures of unfamiliar thin or fat bodies as adaptation stimuli. We found comparable adaptation effects in both experiments: After adaptation to a thin body, participants rated a thinner than actual body picture to be the most realistic and vice versa. We therefore assume that adaptation to certain body shapes transfers across different identities. These results raise the questions of whether some type of natural adaptation occurs in everyday life. Natural and predominant exposure to certain bodily features like body shape – especially the thin ideal in Western societies – could bias perception for these features. In this regard, further research might shed light on aspects of body dissatisfaction and the development of body image disturbances in terms of eating disorders.
Am 1. Dezember 1988 führte ein Eisbruch zu erheblichen Auflichtungen in Buchenwäldern Ostwestfalens. Am Osthang eines Kalkbuchenwaldes am Ochsenberg (Eggegebirge/Nordrhein-Westfalen) wurden in einer Naturwaldzelle (NWZ) zwei Dauerprobeflächen (davon eine gezäunt) als sogenannte Kernflächen ausgepflockt, um Erkenntnisse über die natürliche Regeneration dieses Bestandes nach dem Eisbruch zu gewinnen. Neben dem Baumbestand (1989, 1999, 2009) wurden in beiden Kernflächen die Gehölzverjüngung (1989, 1993, 1997, 2011) und die Vegetation (1989, 1993, 1994, 2011) wiederholt aufgenommen. Ein Vergleich der vorliegenden Vegetations- und Verjüngungsaufnahmen zeigte nach dem Eisbruch zunächst die Etablierung einer Urtica-Rubus-Krautflur, die von den verbesserten Licht- und Nährstoffbedingungen profitierte. Arten des geschlossenen Waldes wurden von den Störungen kaum beeinträchtigt. Sie persistierten in vom Eisbruch unversehrten Bereichen, im Schutz von Totholzstrukturen und der aufkommenden Verjüngung. 20 Jahre nach dem Eisbruch hatte sich die Baumschicht regeneriert. Anfänglich deutliche erkennbare Unterschiede in der Artenzusammensetzung zwischen verschiedenen Kleinstandorten am Hang (Ober-, Mittel- und Unterhang) und Zäunungsvarianten (mit und ohne Zäunung) verringerten sich. Insbesondere die abnehmende Lichtverfügbarkeit führte zu einem erheblichen Rückgang der lichtliebenden Störzeiger und zu einer generellen Verringerung der Krautschichtdeckung. Konstante Deckungsgrade wiesen lediglich die Frühjahrsgeophyten Allium ursinum und Cardamine bulbifera auf, die vom dunkleren und feuchteren Mikroklima im sich regenerierenden Wald profitierten. Pionierbaumarten konnten sich nach der Störung nur geringfügig etablieren, da die Verjüngung stets von der Buche dominiert wurde. Dazu trugen umgestürzte Buchen bei, die neu austrieben, besonders aber die Eckernsaat der verbliebenen Altbuchen, in deren Schutz sich die meisten Jungbuchen ent - wickelten. Aufgrund der geringen Lichtverfügbarkeit in den heutigen Beständen verjüngt sich aber selbst die schattentolerante Buche nicht mehr. Die vorliegende Untersuchung dokumentiert die schnelle Regenerationsfähigkeit des Kalkbuchenwaldes auch nach großflächiger Störung. Die Wälder des Eggegebirges sind aufgrund der Luvlage und hoher Niederschläge anfällig für Schnee- und Eisbruch, so dass auch in der NWZ Ochsenberg mit weiteren Störungen zu rechnen ist. Eine regelmäßige wald- und vegetationskundliche Aufnahme der Kernflächen und eine Erweiterung der Dauerflächenuntersuchungen auf die gesamte NWZ Ochsenberg sind daher empfehlenswert, um zukünftige Störungen und unterschiedliche Sukzessionsstadien erfassen zu können. In Kombination mit Daten aus anderen Naturwaldreservaten können die Ergebnisse aus der NWZ Ochsenberg dabei helfen, natürliche Entwicklungsprozesse nach großflächigen Störungen zu analysieren und Rückschlüsse auf eine naturnahe Bewirtschaftung von Buchenwäldern zu ziehen.
The Romanian poet and essayist Ion Pillat (1891-1945) ranks among the relatively often translated writers of his generation (authors who were active during the interwar period). His works have kept the attention of the German readership several times: Two volumes by Ion Pillat, which appeared in 1943 and 1976 (containing translations by Konrad Richter and Bernhard Capesius, respectively by Wolf von Aichelburg), as well as varied publications in anthologies and other publications have contributed to the spread of his work in Germany and Austria. The author offers an overview of the existing translations and, in the end, refers to his own attempts at translating Ion Pillat’s poetry into German.
Two Romanian authors, Nora Iuga and Carmen Francesca Banciu have published their impressions about the German capital Berlin. Nora Iuga stayed there twice for a limited period of time (in 2000 and in 2010), whereas Carmen Francesca Banciu decided to live in Berlin after her scholarship there ended in 1991. This is why Carmen Francesca Banciu’s writing changed together with the changing city, which was then under construction not only literally but also in a figurative way integrating new influences due to the opening of Eastern Europe after the end of its isolation during the Cold War. She is one of those new elements which reshape Berlin adding new and different perspectives to its cultural life. Banciu publishes her impressions in Berlin ist mein Paris. Nora Iuga, on the other hand, remains nothing but a visitor. Her ideas about the City and about the Germans in general change a lot during her stays in Berlin. In the end, she leaves for Bucharest with new impressions, which are released in Romania in her book Berlinul meu e un monolog.
This succint introduction to Radu Vancu, the young poet and university lecturer invited to the reading organized by the Department of German Studies as part of its annual scientific conference, offers some biographical and exegetical points of reference for the author’s literary and professional evolution. For instance, there is the apprenticeship (rather a “friendshipin-love”) with the venerated master: the poet, gifted translator and man of culture Mircea Ivãnescu, whom he praises in his doctoral thesis as ”the poet of absolute discretion”. Then there is his editing activity at the “Transilvania” Cultural Journal, a publication of original critical and essayistic writings. His forceful, resourceful and sensitive lyrical work shows two dominant themes: on the one hand, the traumatising early loss of his father, and on the other hand, the birth and growing-up of his son Sebastian, for whom the poet builds, with endless affection and humour, a magical livresque universe, populated by fabulous creatures.
Seit einigen Jahren setzt die Filmwirtschaft wieder verstärkt darauf, das breite Publikum mit der Adaption von literarischen Texten in die Kinosäle zu locken. Das Interesse erstreckt sich sowohl auf Klassiker als auch auf Werke der Gegenwartsliteratur: Thomas Manns 'Buddenbrooks', Heinrich Manns 'Henri IV', Theodor Fontanes 'Effi Briest', Martin Walsers 'Ein fliehendes Pferd', Patrick Süskinds 'Das Parfum' und Bernhard Schlinks 'Der Vorleser' wurden innerhalb weniger Jahre auf die Leinwand gebracht. Die Liste lässt sich mit populären Titeln vor allem der jüngeren Literatur fortsetzen, etwa Thomas Brussigs 'Am kürzeren Ende der Sonnenallee', Judith Hermanns Erzählband 'Nichts als Gespenster' (vielleicht die gelungenste der hier genannten 'Literaturverfilmungen', Benjamin Leberts 'Crazy', Sven Regeners 'Herr Lehmann', Frank Goosens 'Liegen lernen' und Martin Suters Romane 'Small World' und 'Lila Lila'. Dieses neu erstarkte Interesse an der Literatur mag auch eine Reaktion auf den florierenden Diskurs über den angeblichen oder tatsächlichen deutschen Bildungsnotstand sein: Wenn die Schule als Bildungsinstitution versagt, muss die Unterhaltungsindustrie versuchen, die klaffenden Löcher zu stopfen, das Heer der Leseunwilligen via Bild mit einem gewissen Maß an Kanonischem zu versorgen. Ich konzentriere mich hier auf zwei 'Literaturverfilmungen', deren Macher offenbar auf eine in zahlreichen Ratgebern und Fachpublikationen zur filmischen Dramaturgie propagierte - aber auch kritisch diskutierte - 'Rezeptur' gesetzt haben, um die Chancen auf einen kommerziellen Erfolg zu erhöhen.
Background: After focal neuronal injury the endocannabinioid system becomes activated and protects or harms neurons depending on cannabinoid derivates and receptor subtypes. Endocannabinoids (eCBs) play a central role in controlling local responses and influencing neural plasticity and survival. However, little is known about the functional relevance of eCBs in long-range projection damage as observed in stroke or spinal cord injury (SCI).
Methods: In rat organotypic entorhino-hippocampal slice cultures (OHSC) as a relevant and suitable model for investigating projection fibers in the CNS we performed perforant pathway transection (PPT) and subsequently analyzed the spatial and temporal dynamics of eCB levels. This approach allows proper distinction of responses in originating neurons (entorhinal cortex), areas of deafferentiation/anterograde axonal degeneration (dentate gyrus) and putative changes in more distant but synaptically connected subfields (cornu ammonis (CA) 1 region).
Results: Using LC-MS/MS, we measured a strong increase in arachidonoylethanolamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) levels in the denervation zone (dentate gyrus) 24 hours post lesion (hpl), whereas entorhinal cortex and CA1 region exhibited little if any changes. NAPE-PLD, responsible for biosynthesis of eCBs, was increased early, whereas FAAH, a catabolizing enzyme, was up-regulated 48hpl.
Conclusion: Neuronal damage as assessed by transection of long-range projections apparently provides a strong time-dependent and area-confined signal for de novo synthesis of eCB, presumably to restrict neuronal damage. The present data underlines the importance of activation of the eCB system in CNS pathologies and identifies a novel site-specific intrinsic regulation of eCBs after long-range projection damage.
Molecules of the title compound, C20H14O2, show approximate C s symmetry with the approximate mirror plane perpendicular to the central ring. The torsion angles about the acyclic bonds are 30.05 (15) and 30.77 (15)° in one half compared to −36.62 (14) and −18.60 (15)° in the other half of the molecule. The central aromatic ring makes dihedral angles of 47.78 (4) and 51.68 (3)° with the two terminal rings.
In the title compound, [Ag(BF4)(C14H12N2O4)]n, the coordination of the Ag+ ion is trigonal–bipyramidal with the N atoms of two ethane-1,2-diyl bis(pyridine-3-carboxylate) ligands in the apical positions and three F atoms belonging to different tetrafluoridoborate anions in the equatorial plane. The material consists of infinite chains of [Ag(C14H12N2O4)] units running along [001], held together by BF4 − bridging anions.
Im Jahre 2012 wurde eine umfassende Bestandsaufnahme der ehemaligen und aktuellen hessischen Vorkommen des Moorglöckchens (Wahlenbergia hederacea) durchgeführt. Es konnten nur noch Restbestände ermittelt werden, die an den verbliebenen Wuchsorten stark gefährdet sind und bei denen ohne geeignete Hilfsmaßnahmen mit einem Erlöschen der Populationen zu rechnen ist.
Beim Übergang von der frühneuzeitlichen Ständegesellschaft hin zu den Nationalstaaten des 19. und 20. Jahrhunderts kommt der Herausbildung eines geographisch und politisch definierten Territoriums, des Territorialstaats, eine wichtige Funktion zu. Ein Zusammenschluss von Herrschaftsgebieten zu einer geographisch-politischen Einheit konnte sich in Form der Annexion des Schwächeren durch den Stärkeren vollziehen, war aber auch im gegenseitigen Einverständnis der politischen Entscheidungsträger denkbar. Im Fall einer Union unterschied man bereits sehr früh zwischen den Typen der Realunion und der Personalunion. Während in einer Realunion völkerrechtliche Vereinbarungen für beide Partner gleichermaßen galten, nahm die Personalunion einen besonderen Status ein, in der allein die Person des Herrschers die Verbindung zwischen beiden Staaten darstellte. Diese streng juristische Definition galt jedoch lediglich für die politischen Institutionen. Jenseits der staatlichen Ebenen fanden sich Formen des Transfers, die einer Personalunion einen besonderen, transnationalen Charakter verleihen konnten. Inwiefern solche Verbindungen, die unter dem Begriff des "composite statehood" zusammengefasst werden, eine gesamteuropäische Entwicklung darstellten, bleibt innerhalb der Forschung umstritten.
Der CDU-Bundestagsabgeordnete Thomas Jarzombek hat einen "sitzungswöchentlichen Video-Podcast". Titel des Formats: "Nachgefragt". In einem "Nachgefragt Spezial" hat Jarzombek nun am 07. März 2012 ein sehr interessantes Gespräch mit seinem Abgeordnetenkollegen aus dem Europäischen Parlament, Daniel Caspary, bei YouTube veröffentlicht.
Um die verworrene Lage im Regelungsdickicht aus Urheberrecht, Nutzungsbedingungen und Kopierschutz bei digitalen Downloads ging es bei iRights.info gerade ausführlich am Beispiel von Musik sowie Filmen und E-Books. In einer neuen Urheberrechts-Debattenreihe bei Süddeutsche.de hat sich heute CDU-Netzpolitiker Peter Tauber für ein Recht auf Privatkopie bei gekauften Downloads ausgesprochen ...
Les tâches d’une sociologie de la culture ne peuvent être définies sans prendre en considération la situation générale de la discipline. La conception dominante veut que la société puisse être définie par son organisation extérieure, par les divisions qui sont partout manifestes dans la vie sociale et qui sont aujourd’hui désignées sommairement comme sa structure. Ce concept de société, nous aurons à le montrer, est davantage le produit de différentes circonstances contingentes qu’il ne se fonde sur une décision de principe ou sur des preuves empiriques. Quoi qu’il en soit, il en résulte, en pratique, que la société est identifiée avec sa structure et que la sociologie, par suite, est réduite à une analyse de cette dernière. Cette conception de la société ne laisse pas de place à la culture comme donnée autonome ; la sociologie de la culture, de ce fait, en est réduite à la portion congrue. ...
Grenzenloser Reichtum und schier unerschöpfliche Geldquellen – diese Träume sind der Stoff, aus dem unzählige Geschichten narratives Kapital schlagen. Der Mythos von König Midas oder die Comics mit Dagobert Duck gehören zu den prominentesten Vertretern solcher Erzählungen. Der Fortunatus hingegen, in dem ein Geld produzierender Zauberbeutel die Geschicke bestimmt, ist weitgehend in Vergessenheit geraten. Dabei kann gerade dieser Roman, der 1509 in Augsburg anonym veröffentlicht wurde, in doppelter Hinsicht als ein Pionier der Literaturgeschichte gelten.
Eine der primären Aufgaben nicht nur der Komparatistik, sondern der Literaturwissenschaft im Allgemeinen sollte es sein, Literatur als ein globales Phänomen zu erfassen und zu beschreiben. Manifestiert sich der globale Charakter von Literatur auch am augenscheinlichsten im Rahmen einer Poetik der imitatio in motivischer, thematischer und gattungsgeschichtlicher Hinsicht, so besteht er dennoch auch dann, wenn bestimmte Techniken eine internationale Präsenz besitzen. Dies gilt beispielsweise für die Konkrete Poesie, deren Funktion als einer der Katalysatoren der Globalität von Literatur im Folgenden erläutert wird.
Konkrete Poesie ist per se ein internationales Phänomen, oder wie Eugen Gomringer es formuliert hat: „die konkrete poesie […] ist einer der konsequentesten versuche, poesie inter- und übernational zu begründen.“ Zunächst müssen wir – im Sinne wissenschaftlicher Eindeutigkeit – zwischen einem engeren und einem weiteren Begriff der Konkreten Poesie unterscheiden. Die Konkrete Poesie im engeren Sinne meint eine seit den 1970er Jahren historisch gewordene Dichtung. Ihre ‘Geburtsstunde’ lässt sich zu Recht als „transatlantic baptism“ , nämlich durch Eugen Gomringer und Décio Pignatari in der Hochschule für Gestaltung im Jahre 1955 in Ulm, bezeichnen. In den frühen 1950er Jahren sowohl in Deutschland als auch Brasilien entstanden, findet sie Aufnahme in fast allen europäischen Ländern, Nordamerika und Japan. Im Folgenden soll der Begriff der Konkreten Poesie jedoch nicht in diesem unnötig eingeschränkten historischen Sinn gebraucht werden, sondern in einem sehr viel umfassenderen Sinn: Er ist all jenen Gedichten vorbehalten, in denen eine Transpa-renz des Zeichengebrauchs nicht gegeben ist, sondern stattdessen die Materialität der jeweils eingesetzten Zeichen im Vordergrund steht, wie dies auf ähnliche Weise schon im Futurismus und Dadaismus betrieben wurde, bevor der Surrealismus diesen Experimenten ein jähes Ende bereitet hat. Gilt dies auch für die Bereiche der Lautdichtung, der Gedichtobjekte u. ä., so beschränken sich die folgenden Ausführungen auf den visuellen Bereich, und zwar auf visuelle Konkrete Poesie nach 1945, zumal in der Dichtung aus dieser Zeit eine starke Tendenz zu konkretistischen Verfahrensweisen herrscht.
Wie kommen Begriffe in die Welt? Auf diese Frage gibt es mehr als eine Antwort; eine davon aber verweist mit Sicherheit auf die akademische Welt. Ständig mit (vermeintlich) neuartigen Sachverhalten konfrontiert, erfindet diese unermüdlich neue Benennungen, um die zu analysierenden Phänomene beschreib- und fassbar zu machen. Dabei hat sich im Laufe der Zeit ein noch immer nicht abgeschlossener Katalog an Fachwörtern angesammelt. Dieser mag den Eindruck erwecken, die wissenschaftliche Begriffsbildung sei nur in den seltensten Fällen um besonders poetische oder eingängige Fachbegriffe bemüht. Doch es gibt eine unliebsame Verwandte der Wissenschaft, die Neologismen sehr zugetan ist, und deren sprachliche Welt von einem Hauch von Poesie belebt wird, die Science-Fiction. Sie steht zwischen Forschung und Fiktion, übernimmt Termini aus der Wissenschaftssprache, verfremdet sie, kombiniert sie neu, und trägt zu ihrer Popularisierung bei. Auch der Begriff "Klon" ist in diesem Kontext zu verorten, allerdings weicht er in seiner Charakteristik und Entwicklung von anderen Fachtermini ab. Gerade seine Besonderheiten machen ihn aber für die begriffsgeschichtliche Arbeit so interessant. Wie die Wissenschaftshistorikerin Christina Brandt zeigt, muss der "Klon" als "hybride Konstellation" historisch unterschiedlich gelagerter Bedeutungsebenen verstanden werden, in der die biowissenschaftliche Definition und wesentlich ältere religiöse, naturphilosophische Denkfiguren und kulturhistorische Narrative zueinander in Spannung geraten sind. Auch dieser Beitrag skizziert den "Klon" als einen Begriff, der in verschiedenen Diskursen und Disziplinen verortet ist und auf der Grundlage kulturhistorisch wesentlich älterer Narrative und Denkfiguren neue Bedeutungen generiert. Das nicht enden wollende Hin und Her um seine Auslegung und Verwendung kann aber auch als Hinweis auf bestimmte irrationale Elemente gelesen werden, die in diesem Streit um die Deutungshoheit eine Rolle zu spielen scheinen. So lässt sich nicht leugnen, dass von bestimmten Begriffen eine besondere Faszination ausgeht. Dies wird vor allem deutlich, wenn ein wissenschaftlicher Begriff in den allgemeinen Sprachgebrauch übergeht. Die Transferbewegung des "Klons" in den öffentlichenRaum der Alltagssprache ist – dies gilt es zu zeigen – zweifellos auch, wenn nicht gar in entscheidendem Maße, den meist äußerst phantasievollen visuellen Eindrücken zu verdanken, die in der populären Vorstellung an den Begriff gekoppelt wurden. Denn es sind vor allem Bilder, die eine unwiderstehliche Anziehungskraft ausüben, die Imagination beflügeln und vermeintlich leere Begriffe in einem einzigen Augenblick mit neuem Inhalt füllen. Im Unterschied zu bisherigen begriffsgeschichtlichen Arbeiten soll deshalb hier das Augenmerk auf dem Moment der Faszination und auf dem Visuellen liegen, um so die Korrespondenz historischer Denkfiguren, Mythen und Narrative zu ikonischen Semantiken und visuellen Bildkomplexen aufzuzeigen.
Background: Focused electron beam induced deposition (FEBID) is a direct-writing technique with nanometer resolution, which has received strongly increasing attention within the last decade. In FEBID a precursor previously adsorbed on a substrate surface is dissociated in the focus of an electron beam. After 20 years of continuous development FEBID has reached a stage at which this technique is now particularly attractive for several areas in both, basic and applied research. The present topical review addresses selected examples that highlight this development in the areas of charge-transport regimes in nanogranular metals close to an insulator-to-metal transition, the use of these materials for strain- and magnetic-field sensing, and the prospect of extending FEBID to multicomponent systems, such as binary alloys and intermetallic compounds with cooperative ground states.
Results: After a brief introduction to the technique, recent work concerning FEBID of Pt–Si alloys and (hard-magnetic) Co–Pt intermetallic compounds on the nanometer scale is reviewed. The growth process in the presence of two precursors, whose flux is independently controlled, is analyzed within a continuum model of FEBID that employs rate equations. Predictions are made for the tunability of the composition of the Co–Pt system by simply changing the dwell time of the electron beam during the writing process. The charge-transport regimes of nanogranular metals are reviewed next with a focus on recent theoretical advancements in the field. As a case study the transport properties of Pt–C nanogranular FEBID structures are discussed. It is shown that by means of a post-growth electron-irradiation treatment the electronic intergrain-coupling strength can be continuously tuned over a wide range. This provides unique access to the transport properties of this material close to the insulator-to-metal transition. In the last part of the review, recent developments in mechanical strain-sensing and the detection of small, inhomogeneous magnetic fields by employing nanogranular FEBID structures are highlighted.
Conclusion: FEBID has now reached a state of maturity that allows a shift of the focus towards the development of new application fields, be it in basic research or applied. This is shown for selected examples in the present review. At the same time, when seen from a broader perspective, FEBID still has to live up to the original idea of providing a tool for electron-controlled chemistry on the nanometer scale. This has to be understood in the sense that, by providing a suitable environment during the FEBID process, the outcome of the electron-induced reactions can be steered in a controlled way towards yielding the desired composition of the products. The development of a FEBID-specialized surface chemistry is mostly still in its infancy. Next to application development, it is this aspect that will likely be a guiding light for the future development of the field of focused electron beam induced deposition.
A careful analysis of the magneto-transport properties of epitaxial nanostructured Nb thin films in the normal and the mixed state is performed. The nanopatterns were prepared by focused ion beam (FIB) milling. They provide a washboard-like pinning potential landscape for vortices in the mixed state and simultaneously cause a resistivity anisotropy in the normal state. Two matching magnetic fields for the vortex lattice with the underlying nanostructures have been observed. By applying these fields, the most likely pinning sites along which the flux lines move through the samples have been selected. By this, either the background isotropic pinning of the pristine film or the enhanced isotropic pinning originating from the nanoprocessing have been probed. Via an Arrhenius analysis of the resistivity data the pinning activation energies for three vortex lattice parameters have been quantified. The changes in the electrical transport and the pinning properties have been correlated with the results of the microstructural and topographical characterization of the FIB-patterned samples. Accordingly, along with the surface processing, FIB milling has been found to alter the material composition and the degree of disorder in as-grown films. The obtained results provide further insight into the pinning mechanisms at work in FIB-nanopatterned superconductors, e.g. for fluxonic applications.
At the beginning of the 1970s, the literature in German language from Romania went through a radical process of change that transformed a largely epigonic and obedient literature into a dynamic, original and subversive one. The following paper analyses the context, the causes, and the mechanisms of this innovative period.
Wenn man an die Stelle des Titels "Georg Büchner und seine Zeit" "Georg Büchner in seiner Zeit" setzt, hat man den Unterschied der Lebenszeit Büchners (1813-1837) und seiner Wirkung über einen umfassenderen Zeitraum im Blick. Diese doppelte Perspektive versucht der Essay durchzuhalten: Er fragt zunächst, wie es möglich wurde, dass ein junger Mann, der mit 24 Jahren starb, nicht nur als Schriftsteller, sondern auch als Wissenschaftler und Revolutionär eine herausragende Rolle spielen konnte. Anschließend werden zwei avantgardistische Alternativen zu den von Büchner gewählten Dramenstoffen Danton und Woyzeck fiktiv vorgeführt.
The motif of the „sun wedding“, which has its origin in ancient mythology, can also be found in the Romanian folk ballad The sun and the moon, where the action takes place around the conflict with etiological meaning of the love between brother and sister. So, the ballad tries to explain some natural phenomena and tries to answer the question, why the sun never meets the moon in its way across the sky. Masterpiece of Romanian folk poetry, the ballad of the sun wedding with the moon raised the interest of German translators, who proved the size of their talent by translating the ballad in German and by popularizing it among the German readers in the country and abroad. The present study analyses the variants of translation of five authors in different centuries (the 19th and the 20th century) and aims to highlight the difficulties, the solutions and the takeovers of the time, as a result of the authors’ wish to translate the original text as accurately as possible and as close as possible to the spirit of the Romanian folk poetry.
This article deals with the difficulty of translating institution names. The translation of institution names from one language into another plays an important role at the translation of official documents. Institution names are stronger conventionalised than other proper names, because the judicial system is determined by the appropriate public institutions. The names of institutions arose in each speech community related to the judicial tradition and the legal history, which must be taken into account at translating them from one language into another and thus from one legal system into another. This article points out the difficulties that arise at different levels when translating institution names, it presents the advantages and disadvantages of the solutions offered so far in the specialized literature and proposes a surrogate solution.
This paper discusses and analyses the importance of oral history in offering a true image of reality. Referring to the tragic destiny of the German ethnic group in Romania after the second world war – their deportation in the Soviet Union – it presents an excerpt of the narration of contemporary witnesses.
The present study researches the literary materializations of the Heimat visions as they emerge from Herta Müller’s Atemschaukel and Aglaja Veteranyi’s Warum das Kind in der Polenta kocht. The Heimat concepts are narratologically constructed both as Erinnerungsräume and as imaginary geographies. Usage of these notions will be made according to the definitions of Aleida Assmann respectively Doris Bachmann-Medick. Heimat is seen as a space from the past, which is projected with the force of the memories in the present having an imaginary geography, that can be articulated on three aspects associated with this concept: shelter, food and possessions.
This study indicates research areas from the perspective of the German and Romanian language phraseology, areas that are exemplified within the phraseosemantic field of „communication”. The analysis of the current state of research indicates the partial or complete lack of preoccupation, on the one hand, with the metaphorization process and the predominance of the conceptual metaphors in the two languages or the dominance of some components and their analysis from a cultural-specific point of view, and, on the other hand, with the systematization of morphosyntactic or semantic restrictions.
Fascinated by the exotic India, Mircea Eliade decided to explore closely the culture and its subtleties. In 1929 he received a scholarship for five years to study the culture and religions of India under the guidance of the illustrious scholar Surendranah Dasgupta. During the time spent in the master‘s house, Eliade gets to know his daughter Maitreyi, whom he falls in love with and they will experience a beautiful and exciting love affair. This relationship will subsequently be the subject of the novel with the same name. Unique case in the history of world literature, the novel Maitreyi will receive a reply over the years, still under the form of a fascinating narration, whose author is the main character Maitreyi Devi herself. It Does Not Die (Love never dies, in Romanian translation; Die Liebe stirbt nicht, in German translation) will become the platform that will host the narrative duel of Eliade the author become character, and Maitreyi Devi, the character, who became author. In our analytical approach we tried to render the ways in which this intercultural dialogue at a distance was perceived in the German linguistic area.
The aim of the present paper is to describe the geographic diffusion of the family name Pfaff in Germany, starting from the telephone directory of 2005 and retracing the historic linguistic phenomena that led to the formation of this name. Pfaff (mhd. phaffe, md. paffe, nd. pape, southern German Pfaffe “priest” or “churchman”) is explained both as an agnomen and as the name of a profession. Our map represents an addition to the maps that have already appeared in dtv – Atlas Namenkunde (1999), Duden-Familiennamen (2005) and Deutscher Familiennamenatlas (2011), for it additionally and thoroughly renders not? only the geographic diffusion of the family name Pfaff in Germany but also in Transylvania, where the name also exists. [this surname also exists in Transylvania]. The type Pfaff (5056 telephone addresses) is spread all over Germany, but we notice two areas of high frequency: one, according to our expectations, in the southern part of the Benrath Line and on the right of the Germersheim Line, but also on the left of the latter, especially in the rectangle Koblenz – Kassel – Hof – Frankfurt and also in south-western Germany (in Schwarzwald –The Black Forest). The northern version Pape, approximately twice more frequent than Pfaff(e), did not adapt to standard German, due to the negative connotations of the appellative Pfaffe, Pfaffen, which appeared at the same time as the Church Reform in the 16th century. In some places in Transylvania, the surname Pfaff was replaced with the version Prediger. The appellative Pfaffe and the family name Pfaff (in the Saxon language – the Romanian “limba sãseascã”: faf, pfaf ) contributed to the formation of different rural toponyms in Transylvania. The surname Pfaff is spread not only in the German linguistic space, but also in areas where ethnic Germans live (France, Luxembourg, Belgium, Holland, Poland, Romania, USA, Canada, Argentina). In Romania, there are very few Pfaff surnames in telephone books for the 2008-2009 period, due to the massive migration of the German ethnics to Germany after 1990.
The present interview is rooted in the diverse aspects of interculturalism and of Romanian-German literary convergence – landmarks of both the works of fiction and non-fiction of the German author hailing from Sibiu. Special emphasis is placed upon the collection of essays Einen Halt suchen (En. In search of stability) and upon its translations from the Romanian into German, the main scope of the interview being to highlight the author’s opinions about the aforementioned aspects.
This study intends to analyze the barely known literary personality of Carmen Sylva, the first Romanian queen. Since Carmen Sylva was a German-born princess, yet lived almost her entire life in the Romanian cultural environment, the main point of this paper is to analyze the idea of writing while being split between two different cultures. Carmen Sylva’s self-assumed role of cultural mediator is in this respect obvisouly worth mentioning. However the main question of this study lies not necessarily in the role, but rather in the place of this writer with two homelands. Did she indeed manage to become a cultural mediator or was she her entire life nothing more than an outsider?
The current article deals with the feedback issue in the study of foreign languages, both from the perspective of traditional learning, as well as from the perspective of computer assisted learning. The possibilities and limits, advantages and disadvantages of each case are presented and compared, and the new demands and opportunities on the educational - and job market are being mentioned.
Translation exercises have always played an important role in teaching/learning foreign languages, ever since the Grammar-Translation method was developed. However, with the emergence of the communicative language teaching in the 70s which focussed on communicative competence as the ultimate goal of language learning, they were considered to be obsolete and inefficient. The present article suggests that the utility of translation – not only where teaching foreign languages is concerned, but also within the field of German studies – should be reassessed, showing that both ”pedagogical” as well as ”communicative” translation can support and improve the study of German language, literature and culture, increase students‘ awareness of both German language and their mother tongue and furthermore contribute to the enrichment of their general knowledge.
The title compound, C37H67NO13·2C2H6OS·1.43H2O, is a macrolide antibiotic with better solubility and better dermal penetration abilities than erythromycin A itself. The asymmetric unit of this form contains one erythromycin A molecule, two dimethyl sulfoxide (DMSO) solvent molecules, a fully occupied water molecule and a partially occupied water molecule with an occupancy factor of 0.432 (11). The 14-membered ring of the erythronolide fragment has a conformation which differs considerably from that in erythromycin A dihydrate [Stephenson, Stowell, Toma, Pfeiffer & Byrn (1997[Stephenson, G. A., Stowell, J. G., Toma, P. H., Pfeiffer, R. R. & Byrn, S. R. (1997). J. Pharm. Sci. 86, 1239-1244.]). J. Pharm. Sci. 86, 1239–1244]. One of the two DMSO molecules is disordered over two orientations; the orientation depends on the presence or absence of the second, partially occupied, water molecule. In the crystal, erythromycin molecules are connected by O—H⋯O hydrogen bonds involving the hydroxy groups and the fully occupied water molecule to form layers parallel to (010). These layers are connected along the b-axis direction only by a possible hydrogen-bonding contact involving the partially occupied water molecule.
Reconocimiento versus ethos
(2012)
El filósofo mexicano Bolívar Echeverría distingue cuatro ethe de la modernidad capitalista, entre ellos: el realista, hoy dominante, es el de la claridad; el barroco, es el de contradicciones, de doblesentidos. Según la teoría hegeliana del reconocimiento (Honneth/Habermas), la convivencia racional entre culturas sólo es posible dentro del ethos realista. Se parte del a priori dudoso de la posibilidad del reconocimiento dentro de la sociedad burguesa (entendiendo al racismo como algo accidental y no estructural). El ethos barroco, que existe en América Latina, implica la posibilidad de convivir con el otro sin reconocerlo en términos hegelianos, abriendo vías al mestizaje cultural. La falta de claridad de este ethos es la base de cierta convivencia intercultural bajo su actual imposibilidad estructural.
The biological effects of energetic heavy ions are attracting increasing interest for their applications in cancer therapy and protection against space radiation. The cascade of events leading to cell death or late effects starts from stochastic energy deposition on the nanometer scale and the corresponding lesions in biological molecules, primarily DNA. We have developed experimental techniques to visualize DNA nanolesions induced by heavy ions. Nanolesions appear in cells as “streaks” which can be visualized by using different DNA repair markers. We have studied the kinetics of repair of these “streaks” also with respect to the chromatin conformation. Initial steps in the modeling of the energy deposition patterns at the micrometer and nanometer scale were made with MCHIT and TRAX models, respectively.
Objective: Betahistine is a histamine H1-receptor agonist and H3-receptor antagonist that is administered to treat Menière’s disease. Despite widespread use, its pharmacological mode of action has not been entirely elucidated. This study investigated the effect of betahistine on guinea pigs at dosages corresponding to clinically used doses for cochlear microcirculation.
Methods: Thirty healthy Dunkin-Hartley guinea pigs were randomly assigned to five groups to receive betahistine dihydrochloride in a dose of 1,000 mg/kg b. w. (milligram per kilogram body weight), 0.100 mg/kg b. w., 0.010 mg/kg b. w., 0.001 mg/kg b. w. in NaCl 0.9% or NaCl 0.9% alone as placebo. Cochlear blood flow and mean arterial pressure were continuously monitored by intravital fluorescence microscopy and invasive blood pressure measurements 3 minutes before and 15 minutes after administration of betahistine.
Results: When betahistine was administered in a dose of 1.000 mg/kg b. w. cochlear blood flow was increased to a peak value of 1.340 arbitrary units (SD: 0.246; range: 0.933–1.546 arb. units) compared to baseline (p<0.05; Two Way Repeated Measures ANOVA/Bonferroni t-test). The lowest dosage of 0.001 mg/kg b. w. betahistine or NaCl 0.9% had the same effect as placebo. Nonlinear regression revealed that there was a sigmoid correlation between increase in blood flow and dosages.
Conclusions: Betahistine has a dose-dependent effect on the increase of blood flow in cochlear capillaries. The effects of the dosage range of betahistine on cochlear microcirculation corresponded well to clinically used single dosages to treat Menière’s disease. Our data suggest that the improved effects of higher doses of betahistine in the treatment of Menière’s disease might be due to a corresponding increase of cochlear blood flow.