1,320 research outputs found
Optimierung der Photonenselektion f\"{u}r die Suche nach dem Zerfall des Higgsbosons in zwei leichte CP-ungerade Skalare
No full textNanve Art Origins in 20th Century Germany: Artistic Tradition Specificity
No full textРассматриваются истоки наивного искусства Германии. К числу источников художественной традиции относятся вотивная живопись (ex voto), живопись на стекле, народное искусство и непрофессиональное искусство. Описывается творчество наиболее ярких художников-любителей XIX - начала XX в. - О. Брарена и его учеников, К-Х. Тегена, А. Трильхаза, Ф. Рамхольца и их взаимоотношений с профессиональным миром (к примеру, с объединением «Юная Рейнланд» в Дюссельдорфе).The article studies the origins of nanve art in Germany, its sources being votive painting (ex voto), glass painting, folk art and amateur art. The author describes the art of the most significant amateur painters of the 19th - early 20th century, O. Braren and his followers, K-Ch. Thegen, A. Trillhaase, F. Ramholz, and their relationships with the professional community (e.g., with Das Junge Rheinland (Young Rhineland group) in Dusseldorf)
Истоки наивного искусства Германии XX в.: специфика художественной традиции
No full textРассматриваются истоки наивного искусства Германии. К числу источников художественной традиции относятся вотивная живопись (ex voto), живопись на стекле, народное искусство и непрофессиональное искусство. Описывается творчество наиболее ярких художников-любителей XIX - начала XX в. - О. Брарена и его учеников, К-Х. Тегена, А. Трильхаза, Ф. Рамхольца и их взаимоотношений с профессиональным миром (к примеру, с объединением «Юная Рейнланд» в Дюссельдорфе).The article studies the origins of nanve art in Germany, its sources being votive painting (ex voto), glass painting, folk art and amateur art. The author describes the art of the most significant amateur painters of the 19th - early 20th century, O. Braren and his followers, K-Ch. Thegen, A. Trillhaase, F. Ramholz, and their relationships with the professional community (e.g., with Das Junge Rheinland (Young Rhineland group) in Dusseldorf)
Targeting PI3K/mTOR Signaling Displays Potent Antitumor Efficacy against Nonfunctioning Pituitary Adenomas
No full textPURPOSE: Novel therapeutic approaches are needed to improve the postoperative management of residual nonfunctioning pituitary adenomas (NFPA), given their high relapse rate. Here, we evaluated the antitumor efficacy of the dual PI3K/mTOR inhibitor NVP-BEZ235 in the only available model of spontaneous NFPAs (MENX rats).EXPERIMENTAL DESIGN: Organotypic cultures of rat primary NFPAs were incubated with NVP-BEZ235 and assessed for cell viability, proliferation, apoptosis, and PI3K/mTOR inhibition. NVP-BEZ235, or placebo, was administered to MENX rats and tumor response was monitored noninvasively by diffusion weighted-magnetic resonance imaging (DW-MRI). Following treatment, tumor tissues were investigated for cell proliferation, apoptosis, and PI3K/mTOR inhibition. Genes mediating the cytotoxic activity of NVP-BEZ235 were identified by gene-expression profiling. Among them, Defb1, encoding beta-defensin 1, was further studied for its role in pituitary cells and in human pancreatic neuroendocrine tumor (NET) cells.RESULTS: NVP-BEZ235 showed antiproliferative and pro-cell death activities against NFPAs both in vitro and in vivo, and the response to the drug correlated with inhibition of the PI3K pathway. DW-MRI identified early functional changes (decreased cellularity) in the adenomas before their size was affected and emerged as a useful modality to assess therapy response. The cytotoxic effect of PI3K/mTOR blockade in NFPA was mediated by several genes, including Defb1. NVP-BEZ235 treatment induced Defb1 expression in NFPAs in vitro and in vivo, and in pancreatic NET cells. High Defb1 levels sensitized NET cells to PI3K/mTOR inhibition.CONCLUSIONS: Our findings provide rationale for clinical investigation of PI3K/mTOR inhibition in NFPAs and identify novel effectors of PI3K-mediated neuroendocrine cell survival.</p
Assessing antiangiogenic therapy response by DCE-MRI: development of a physiology driven multi-compartment model using population pharmacometrics
No full textDynamic contrast enhanced (DCE-) MRI is commonly applied for the monitoring of antiangiogenic therapy in oncology. Established pharmacokinetic (PK) analysis methods of DCE-MRI data do not sufficiently reflect the complex anatomical and physiological constituents of the analyzed tissue. Hence, accepted endpoints such as Ktrans reflect an unknown multitude of local and global physiological effects often rendering an understanding of specific local drug effects impossible. In this work a novel multi-compartment PK model is presented, which for the first time allows the separation of local and systemic physiological effects. DCE-MRI data sets from multiple, simultaneously acquired tissues, i.e. spinal muscle, liver and tumor tissue, of hepatocellular carcinoma (HCC) bearing rats were applied for model development. The full Markov chain Monte Carlo (MCMC) Bayesian analysis method was applied for model parameter estimation and model selection was based on histological and anatomical considerations and numerical criteria. A population PK model (MTL3 model) consisting of 3 measured and 6 latent (unobserved) compartments was selected based on Bayesian chain plots, conditional weighted residuals, objective function values, standard errors of model parameters and the deviance information criterion. Covariate model building, which was based on the histology of tumor tissue, demonstrated that the MTL3 model was able to identify and separate tumor specific, i.e. local, and systemic, i.e. global, effects in the DCE-MRI data. The findings confirm the feasibility to develop physiology driven multi-compartment PK models from DCE-MRI data. The presented MTL3 model allowed the separation of a local, tumor specific therapy effect and thus has the potential for identification and specification of effectors of vascular and tissue physiology in antiangiogenic therapy monitoring
Strategies of construction and legitimization of an ethos in the causa veritatis: Michael Servetus and religious polemics in the sixteenth century
No full textEsta tese tem como objetivo apontar e comentar as estratégias de construção e de legitimação de um ethos de advogado da causa ueritatis nas polêmicas religiosas do século XVI. Trata-se aqui de defender uma posição num contexto em que só há um Deus e só há uma Verdade, e, portanto, somente uma interpretação é verdadeira. O autor cristão envolvido em polêmicas precisa, pois, provar que ele é o \"enviado\", o nuntius que proclama a mensagem com simplicidade, ao passo que seus oponentes são os \"falsos mestres\" que, para dissimular suas mentiras, ocultam-nas sob palavras artisticamente trabalhadas. Assim, não apenas a construção do ethos \"positivo\" de um está vinculada à desconstrução (ou destruição) do ethos do outro, mas ambas - construção e desconstrução - dão-se segundo o ideário da humilitas, a qual é, ao mesmo tempo, constitutiva da moral (ética) e da expressão discursiva (estética).The objective of this doctoral dissertation is to identify and comment on the strategies of construction and legitimization of an ethos of an advocate in the causa ueritatis in the religious polemics of the sixteenth century. It is a way of defending a position within a context in which there is only one God and only one Truth, and, therefore, only one true interpretation. The Christian author involved in such polemic needs to prove that he is the \"emissary,\" the nuntius who proclaims the message with simplicity, whereas his opponents are the \"false masters\" who, in order to dissimulate their lies, hide them under artistically woven words. Thus, not only is the construction of the positive ethos linked to the deconstruction (or destruction) of the other\'s ethos; but both, construction and deconstruction, happen according to the concept of humilitas, which is, at the same time, constitutive of morals (ethics) and of discursive expression (esthetics)
Impact of F-18-FDG-PET/CT on the identification of regional lymph node metastases and delineation of the primary tumor in esophageal squamous cell carcinoma patients.
No full textPurpose In patients undergoing chemoradiation for esophageal squamous cell carcinoma (ESCC), the extent of elective nodal irradiation (ENI) is still discussed controversially. This study aimed to analyze patterns of lymph node metastases and their correlation with the primary tumor using F-18-fludeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scans. Methods 102 ESCC patients with pre-treatment FDG-PET/CT scans were evaluated retrospectively. After exclusion of patients with low FDG uptake and patients without FDG-PET-positive lymph node metastases (LNM), 76 patients were included in the final analysis. All LNM were assigned to 16 pre-defined anatomical regions and classified according to their position relative to the primary tumor (above, at the same height, or below the primary tumor). In addition, the longitudinal distance to the primary tumor was measured for all LNM above or below the primary tumor. The craniocaudal extent (i.e., length) of the primary tumor was measured using FDG-PET imaging (L-PET) and also based on all other available clinical and imaging data (endoscopy, computed tomography, biopsy results) except FDG-PET (L-CT/EUS). Results Significantly more LNM were identified with F-18-FDG-PET/CT (177 LNM) compared to CT alone (131 LNM, p & x202f;< 0.001). The most common sites of LNM were paraesophageal (63% of patients, 37% of LNM) and paratracheal (33% of patients, 20% of LNM), while less than 5% of patients had supraclavicular, subaortic, diaphragmatic, or hilar LNM. With regard to the primary tumor, 51% of LNM were at the same height, while 25% and 24% of lymph node metastases were above and below the primary tumor, respectively. For thirty-three LNM (19%), the distance to the primary tumor was larger than 4 & x202f;cm. No significant difference was seen between L-CT/EUS (median 6 & x202f;cm) and L-PET (median 6 & x202f;cm, p & x202f;= 0.846) Conclusion F-18-FDG-PET can help to identify subclinical lymph node metastases which are located outside of recommended radiation fields. PET-based involved-field irradiation might be the ideal compromise between small treatment volumes and decreasing the risk of undertreatment of subclinical metastatic lymph nodes and should be further evaluated
Angpt2/Tie2 autostimulatory loop controls tumorigenesis
No full textInvasive nonfunctioning (NF) pituitary neuroendocrine tumors (PitNETs) are non-resectable neoplasms associated with frequent relapses and significant comorbidities. As the current therapies of NF-PitNETs often fail, new therapeutic targets are needed. The observation that circulating angiopoietin-2 (ANGPT2) is elevated in patients with NF-PitNET and correlates with tumor aggressiveness prompted us to investigate the ANGPT2/TIE2 axis in NF-PitNETs in the GH3 PitNET cell line, primary human NF-PitNET cells, xenografts in zebrafish and mice, and in MENX rats, the only autochthonous NF-PitNET model. We show that PitNET cells express a functional TIE2 receptor and secrete bioactive ANGPT2, which promotes, besides angiogenesis, tumor cell growth in an autocrine and paracrine fashion. ANGPT2 stimulation of TIE2 in tumor cells activates downstream cell proliferation signals, as previously demonstrated in endothelial cells (ECs). Tie2 gene deletion blunts PitNETs growth in xenograft models, and pharmacological inhibition of Angpt2/Tie2 signaling antagonizes PitNETs in primary cell cultures, tumor xenografts in mice, and in MENX rats. Thus, the ANGPT2/TIE2 axis provides an exploitable therapeutic target in NF-PitNETs and possibly in other tumors expressing ANGPT2/TIE2. The ability of tumor cells to coopt angiogenic signals classically viewed as EC-specific expands our view on the microenvironmental cues that are essential for tumor progression
- …
