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  • 1
    Keywords: Forschungsbericht
    Type of Medium: Online Resource
    Pages: Online-Ressource (PDF-Datei: 212 S., 5,97 MB) , Ill., graph. Darst.
    Edition: [Online-Ausg.]
    Language: German
    Note: Förderkennzeichen BMELV 22004907 [neu] - 07NR049 [alt] , Unterschiede zwischen dem gedruckten Dokument und der elektronischen Ressource können nicht ausgeschlossen werden. - Auch als gedr. Ausg. vorhanden , Systemvoraussetzungen: Acrobat reader.
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  • 2
    Keywords: Forschungsbericht ; Silphium ; Biogasanlage
    Type of Medium: Online Resource
    Pages: Online-Ressource (PDF-Datei: 49 S., 662 KB) , Ill., graph. Darst.
    Edition: [Online-Ausg.]
    Language: German
    Note: Förderkennzeichen BMBF 22004307 , Unterschiede zwischen dem gedruckten Dokument und der elektronischen Ressource können nicht ausgeschlossen werden , Auch als gedr. Ausg. erschienen , Systemvoraussetzungen: Acrobat reader.
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  • 3
    Publication Date: 2011-09-29
    Description: SUMMARY We propose a class of spherical wavelet bases for the analysis of geophysical models and for the tomographic inversion of global seismic data. Its multiresolution character allows for modelling with an effective spatial resolution that varies with position within the Earth. Our procedure is numerically efficient and can be implemented with parallel computing. We discuss two possible types of discrete wavelet transforms in the angular dimension of the cubed sphere. We describe benefits and drawbacks of these constructions and apply them to analyse the information in two published seismic wave speed models of the mantle, using the statistics of wavelet coefficients across scales. The localization and sparsity properties of wavelet bases allow finding a sparse solution to inverse problems by iterative minimization of a combination of the ℓ 2 norm of the data residuals and the ℓ 1 norm of the model wavelet coefficients. By validation with realistic synthetic experiments we illustrate the likely gains from our new approach in future inversions of finite-frequency seismic data.
    Print ISSN: 0956-540X
    Electronic ISSN: 1365-246X
    Topics: Geosciences
    Published by Oxford University Press on behalf of The Deutsche Geophysikalische Gesellschaft (DGG) and the Royal Astronomical Society (RAS).
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  • 4
    Publication Date: 2011-05-21
    Description: ABSTRACT Riffle-pool sequences are a common feature of gravel-bed rivers. However, mechanisms of their generation and maintenance are still not fully understood. In this study a monitoring approach similar to the one of Andrews (1979 and 1982) is employed. It focuses on analysing cross-sectional and longitudinal channel geometry of a large floodplain river (Vereinigte Mulde, Sachsen-Anhalt, Germany) with a high temporal and spatial resolution, in order to conclude from stage-dependant morphometric changes to riffle and pool maintaining processes. In accordance with Richards (1976a), Andrews (1979 and 1982) among others, pool cross sections of the Mulde River are narrow and riffle cross sections are wide suggesting that they should rather be addressed as two general types of channel cross-sections than solely as bedforms. At high flows, riffles and pools in the study reaches changed in length and height but not in position. Pools were scoured and riffles aggraded, a development which was reversed during receding flows below the threshold of 0.4·Q bf (40% bankfull discharge). An index for the longitudinal amplitude of riffle-pool sequences, the bed undulation intensity or bedform amplitude, is introduced and proved to be highly significant as a form parameter, its first derivative as a process parameter. The process of pool scour and riffle fill is addressed as bedform maintenance or bedform accentuation. It is indicated by increasing longitudinal bed amplitudes. According to the observed dynamics of bed amplitudes, maintenance of riffle-pool sequences lags behind discharge peaks. Maximum bed amplitudes may be reached with a delay of several days after peak discharges. Increasing bed undulation intensity is interpreted to indicate bed mobility. Post-flood decrease of the bed undulation intensity indicates a retrograde phase when transport from pools to riffles has ceased and bed mobility is restricted to riffle tails and heads of pools. This type of transport behaviour is referred to as disconnected mobility. The comparison of two river reaches, one with undisturbed sediment supply, the other with sediment deficit, suggests that high bed undulation intensity values at low flows indicate sediment deficit and potentially channel degrading conditions. It is more generally hypothesised that channel bed undulations constitute a major component of form roughness and that increased bed amplitudes are an important feature of channel bed adjustment to sediment deficit be it temporally during late floods or permanently due to a supply limitation of bedload. Copyright © 2011 John Wiley & Sons, Ltd.
    Print ISSN: 0197-9337
    Electronic ISSN: 1096-9837
    Topics: Geography , Geosciences
    Published by Wiley-Blackwell
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  • 5
    Publication Date: 2013-01-23
    Description: We evaluated the impact of staging procedures to detect asymptomatic distant metastases (DM) in the management of women with operable invasive breast cancer (BC, entire cohort: n = 866). Out of 472 patients with lymph node (LN)-negative disease (pN0), DM were found in four cases (detection rate: 0.8%). All four patients presented with established risk factors: hormone receptor (HR)-negative status, HER2-positive status, n = 3; ‘triple-negative’ disease, n = 1. Considering the subgroup of LN-negative patients whose tumors showed the risk factor ‘negative HR status’ ( n = 66), the detection rate of DM was 6%. The detection rates of DM in higher pN categories were as follows: pN1:1.7%; pN2:9.5%; pN3:13.5%. We generally support the international guidelines, including those published by the European Society for Medical Oncology (ESMO) which emphasize that patients with early-stage BC do not profit from radiological staging for the detection of DM and recommend refraining from this. However, we would expand these guidelines and propose that screening should be carried out in node-negative patients whose tumors show established tumor-related risk factors (e.g. HR-negative and HER2-positive status), since in this particular subcohort, the detection rate of DM is with 6% similarly high as that of patients with four to nine positive LNs.
    Print ISSN: 0923-7534
    Electronic ISSN: 1569-8041
    Topics: Medicine
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  • 6
    Publication Date: 2012-12-18
    Description: We report on the calibration of the one-dimensional hydrodynamic lake model DYRESM to simulate the water temperature conditions of the pre-alpine Lake Ammersee (South-east Germany) which is representative of deep and large lakes in this region. Special focus is given to the calibration in order to reproduce the correct thermal distribution and stratification including the time of onset and duration of summer stratification. To ensure the application of the model to investigate the impact of climate change on lakes, an analysis of the model sensitivity under stepwise modification of meteorological input parameters (air temperature, wind speed, precipitation, global radiation, cloud cover, vapor pressure, and tributary water temperature) was conducted. The total mean error of the calibration results is –0.23 °C, the root mean square error amounts to 1.012 °C. All characteristics of the annual stratification cycle were reproduced accurately by the model. Additionally, the simulated deviations for all applied modifications of the input parameters for the sensitivity analysis can be differentiated in the high temporal resolution of monthly values for each specific depth. The smallest applied alteration to each modified input parameter caused a maximum deviation in the simulation results of at least 0.26 °C. The most sensitive reactions of the model can be observed through modifications of the input parameters air temperature and wind speed. Hence the results show that further investigations at Lake Ammersee, such as coupling the hydrodynamic model with chemo-dynamic models to assess the impact of changing climate on biochemical conditions within lakes, can be carried out using DYRESM. Copyright © 2012 John Wiley & Sons, Ltd.
    Print ISSN: 0885-6087
    Electronic ISSN: 1099-1085
    Topics: Architecture, Civil Engineering, Surveying , Geography
    Published by Wiley-Blackwell
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  • 7
    Publication Date: 2014-09-17
    Description: Background Peripheral neuropathy is the major dose-limiting side effect of cisplatin and oxaliplatin, and there are currently no effective treatments available. The aim of this study was to assess the pharmacological mechanisms underlying chemotherapy-induced neuropathy in novel animal models based on intraplantar administration of cisplatin and oxaliplatin and to systematically evaluate the analgesic efficacy of a range of therapeutics. Methods Neuropathy was induced by a single intraplantar injection of cisplatin or oxaliplatin in C57BL/6J mice and assessed by quantification of mechanical and thermal allodynia. The pharmacological basis of cisplatin-induced neuropathy was characterized using a range of selective pharmacological inhibitors. The analgesic effects of phenytoin, amitriptyline, oxcarbazepine, mexiletine, topiramate, retigabine, gabapentin, fentanyl, and Ca 2+/ Mg 2+ were assessed 24 hours after induction of neuropathy. Results Intraplantar administration of cisplatin led to the development of mechanical allodynia, mediated through Na v 1.6-expressing sensory neurons. Unlike intraplantar injection of oxaliplatin, cold allodynia was not observed with cisplatin, consistent with clinical observations. Surprisingly, only fentanyl was effective at alleviating cisplatin-induced mechanical allodynia despite a lack of efficacy in oxaliplatin-induced cold allodynia. Conversely, lamotrigine, phenytoin, retigabine, and gabapentin were effective at reversing oxaliplatin-induced cold allodynia but had no effect on cisplatin-induced mechanical allodynia. Oxcarbazepine, amitriptyline, mexiletine, and topiramate lacked efficacy in both models of acute chemotherapy-induced neuropathy. Conclusion This study established a novel animal model of cisplatin-induced mechanical allodynia consistent with the A-fiber neuropathy seen clinically. Systematic assessment of a range of therapeutics identified several candidates that warrant further clinical investigation.
    Print ISSN: 1522-8517
    Electronic ISSN: 1523-5866
    Topics: Medicine
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  • 8
    Publication Date: 2012-06-12
    Description: In response to gonadectomy certain inbred mouse strains develop sex steroidogenic adrenocortical neoplasms. One of the hallmarks of neoplastic transformation is expression of GATA4, a transcription factor normally present in gonadal but not adrenal steroidogenic cells of the adult mouse. To show that GATA4 directly modulates adrenocortical tumorigenesis and is not merely a marker of gonadal-like differentiation in the neoplasms, we studied mice with germline or conditional loss-of-function mutations in the Gata4 gene. Germline Gata4 haploinsufficiency was associated with attenuated tumor growth and reduced expression of sex steroidogenic genes in the adrenal glands of ovariectomized B6D2F1 and B6AF1 mice. At 12 months after ovariectomy, wild-type B6D2F1 mice had biochemical and histological evidence of adrenocortical estrogen production, whereas Gata4 +/– B6D2F1 mice did not. Germline Gata4 haploinsufficiency exacerbated the secondary phenotype of postovariectomy obesity in B6D2F1 mice, presumably by limiting ectopic estrogen production in the adrenal glands. Amhr2 -cre-mediated deletion of floxed Gata4 ( Gata4 F ) in nascent adrenocortical neoplasms of ovariectomized B6.129 mice reduced tumor growth and the expression of gonadal-like markers in a Gata4 F dose-dependent manner. We conclude that GATA4 is a key modifier of gonadectomy-induced adrenocortical neoplasia, postovariectomy obesity, and sex steroidogenic cell differentiation.
    Print ISSN: 0013-7227
    Topics: Medicine
    Published by Oxford University Press on behalf of The Endocrine Society.
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  • 9
    Publication Date: 2012-02-28
    Description: Histone post-translational modifications play an important role in regulating chromatin structure and gene expression in vivo . Extensive studies investigated the post-translational modifications of the core histones H3 and H4 or the linker histone H1. Much less is known on the regulation of H2A and H2B modifications. Here, we show that a major modification of H2B in Drosophila melanogaster is the methylation of the N-terminal proline, which increases during fly development. Experiments performed in cultured cells revealed higher levels of H2B methylation when cells are dense, regardless of their cell cycle distribution. We identified dNTMT (CG1675) as the enzyme responsible for H2B methylation. We also found that the level of N-terminal methylation is regulated by dART8, an arginine methyltransferase that physically interacts with dNTMT and asymmetrically methylates H3R2. Our results demonstrate the existence of a complex containing two methyltransferases enzymes, which negatively influence each other’s activity.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 10
    Publication Date: 2012-05-02
    Description: Background: KLF6-SV1 ( SV1 ), the major splice variant of KLF6 , antagonizes the KLF6 tumor suppressor by an unknown mechanism. Decreased KLF6 expression in human hepatocellular carcinoma (HCC) correlates with increased mortality, but the contribution of increased SV1 is unknown. We sought to define the impact of SV1 on human outcomes and experimental murine hepatocarcinogenesis, and to elucidate its mechanism of action. Results: In HCV-related HCC, an increased ratio of SV1/KLF6 within the tumor was associated with more features of more advanced disease. Six months after a single injection of diethylnitrosamine (DEN), SV1 hepatocyte transgenic mice developed more histologically advanced tumors, whereas Klf6 -depleted mice developed bigger tumors compared to the Klf6 fl(+/+) control mice. Nine months after DEN, SV1 transgenic-mice with Klf6 -depletion had the greatest tumor burden. Primary mouse hepatocytes from both the SV1 transgenic animals and those with hepatocyte-specific Klf6 depletion displayed increased DNA synthesis, with an additive effect in hepatocytes harboring both SV1 over-expression and Klf6 depletion. Parallel results were obtained by viral SV1-transduction- and depletion of Klf6 through adenovirus-Cre infection of primary Klf6 fl(+/+) hepatocytes. Increased DNA synthesis was due to both enhanced cell proliferation and increased ploidy. Co-IP studies in 293T cells uncovered a direct interaction of transfected SV1 with KLF6 . Accelerated KLF6 degradation in the presence of SV1 was abrogated by the proteasome inhibitor MG132. Conclusion: Increased SV1/KLF6 ratio correlates with more aggressive HCC. In mice, an increased SV1/KLF6 ratio, generated either by increasing SV1, decreasing KLF6, or both, accelerates hepatic carcinogenesis. Moreover, SV1 binds directly to KLF6 and accelerates its degradation. These findings represent a novel mechanism underlying the antagonism of tumor suppressor gene function by a splice variant of the same gene. (H EPATOLOGY 2012.)
    Print ISSN: 0270-9139
    Electronic ISSN: 1527-3350
    Topics: Medicine
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