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排序方式: 共有868条查询结果,搜索用时 15 毫秒
21.
Eline A. M. Ruigrok Nicole S. Verkaik Erik de Blois Corrina de Ridder Debra Stuurman Stefan J. Roobol Dik C. Van Gent Marion de Jong Wytske M. Van Weerden Julie Nonnekens 《International journal of molecular sciences》2022,23(14)
Prostate specific membrane antigen targeted radionuclide therapy (PSMA-TRT) is a promising novel treatment for prostate cancer (PCa) patients. However, PSMA-TRT cannot be used for curative intent yet, thus additional research on how to improve the therapeutic efficacy is warranted. A potential way of achieving this, is combining TRT with poly ADP-ribosylation inhibitors (PARPi), which has shown promising results for TRT of neuroendocrine tumor cells. Currently, several clinical trials have been initiated for this combination for PCa, however so far, no evidence of synergism is available for PCa. Therefore, we evaluated the combination of PSMA-TRT with three classes of PARPi in preclinical PCa models. In vitro viability and survival assays were performed using PSMA-expressing PCa cell lines PC3-PIP and LNCaP to assess the effect of increasing concentrations of PARPi veliparib, olaparib or talazoparib in combination with PSMA-TRT compared to single PARPi treatment. Next, DNA damage analyses were performed by quantifying the number of DNA breaks by immunofluorescent stainings. Lastly, the potential of the combination treatments was studied in vivo in mice bearing PC3-PIP xenografts. Our results show that combining PSMA-TRT with PARPi did not synergistically affect the in vitro clonogenic survival or cell viability. DNA-damage analysis revealed only a significant increase in DNA breaks when combining PSMA-TRT with veliparib and not in the other combination treatments. Moreover, PSMA-TRT with PARPi treatment did not improve tumor control compared to PSMA-TRT monotherapy. Overall, the data presented do not support the assumption that combining PSMA-TRT with PARPi leads to a synergistic antitumor effect in PCa. These results underline that extensive preclinical research using various PCa models is imperative to validate the applicability of the combination strategy for PCa, as it is for other cancer types. 相似文献
22.
The numbers of English public houses or “pubs” have reduced significantly in the last two decades. Politicians have called on the planning system to resist their closure but, at the same time, demand further controls over high-street bars. This paper explores the reasons for the decline and the rationale for supporting the continuation of the “traditional” English pub. Using evidence drawn from a wider study of the relationships between places and youth drinking cultures, the paper discusses young adults' use of pubs. While recognising the adverse effects of heavy drinking, arguments are put forward in support of the traditional pub as a site for restrained and responsible social interaction for young adults. The paper discusses the issues this raises for the UK planning system in the context of responsibilities for social sustainability and public health. 相似文献
23.
Jian Cao Ekkard Brinksmeier Mingwang Fu Robert X. Gao Biao Liang Marion Merklein Michael Schmidt Jun Yanagimoto 《CIRP Annals》2019,68(2):605-628
Forming is widely used due to its high efficiency in material utilization and its high production rate in general. Most forming processes control the geometry of final products through a set of tooling. The increasing demands on lightweight products have challenged the performances and functionalities of tooling. This paper provides a systematic review of recent advancements related to tooling performance and functionalities, including tool materials, tooling fabrication processes (e.g., machining, heat treatment, coating, surface texturing, and additive manufacturing), sensing, and data analytics. Finally, recommendations on future research directions for metal forming tooling are provided. 相似文献
24.
Fei Huang Tomáš Halenkovič Marion Baillieul Virginie Nazabal Petr Němec Josef Havel 《Journal of the American Ceramic Society》2022,105(3):1992-2000
Quaternary germanium-antimony-selenium-tellurium (Ge-Sb-Se-Te) thin films deposited from Ge19.4Sb16.7Se63.9−xTex (x = 5, 10, 15, and 20) glass-ceramics targets by radio frequency magnetron sputtering were studied using laser ablation quadrupole ion trap time of flight mass spectrometry. Binary, ternary, and quaternary GeaSbbSecTed clusters were formed and their stoichiometry was determined. By comparison of the clusters obtained from quaternary Ge-Sb-Se-Te thin films and those from ternary Ge-Sb-Te materials, we found that Ge-Te species are not detected from the quaternary system. Furthermore, Ge-Se and Se-Te species are missing in mass spectra generated from Ge-Sb-Se-Te thin films. From the Ge-Sb-Se-Te thin films, 16 clusters were detected while ternary Ge-Sb-Se glasses yielded 26 species. This might be considered as a signal of higher stability of Ge-Sb-Se-Te thin films which is increasing with a higher content of Te. The missing (Se2+, GeaSb+ (a = 1–4), and GeSec+ (c = 1, 2)) and new (Ge+ and SbbTe+ (b = 1–3)) clusters may indicate that some of the structural features of the films (Ge2Se6/2 and Se2Sb-SbSe2) were replaced by (GeSe4−xTex and SbSe3−xTex) ones. In addition, when comparing the stoichiometry of clusters formed from Ge-Sb-Se-Te thin films with those from the mixtures of the elements, only Sb3+ and SbSe+ were observed in both cases. The knowledge gained concerning clusters stoichiometry contributes to the elucidation of the processes proceeding during plasma formation used for the chalcogenide thin films deposition. 相似文献
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27.
M. Merklein 《CIRP Annals》2008,57(1):269-274
The enhancement of material modeling in fields of sheet metal forming is essential for finite element-based designing of processes and dimensioning of parts. Since new lightweight materials, e.g. aluminum and magnesium wrought alloys show anisotropic and temperature-dependent forming behavior adequate testing methods and evaluation strategies have to be developed to obtain the reliable material data. For that purpose an experimental setup has been designed at the Chair of Manufacturing Technology which enables biaxial tensile testing of sheet metal at elevated temperatures. In this paper, the setup is introduced and the obtained results, i.e. experimentally determined yield loci and subsequent yield loci as a function of temperature are given for the well-known aluminum alloy AA6016 as well as the magnesium alloy AZ31. 相似文献
28.
M. Geiger F. Micari M. Merklein L. Fratini D. Contorno A. Giera D. Staud 《International Journal of Machine Tools and Manufacture》2008,48(5):515
To develop steel aluminium-tailored hybrids in a butt joint for sheets in a thickness of about 1 mm conventional Friction Stir Welding is not feasible due to a high distortion of the welded specimen. Contrary to Friction Stir Welding the tool used for Friction Stir Knead Welding has no pin wherefore higher welding speeds can be realised. Due to the fact that this is a newer process, applied for patent in 2005, the cut contours of the edges and their variations have to be optimised by numerical analysis to transfer a maximum of load in order to improve the formability. The examined materials in this paper are steel DC04, as well as the aluminium alloys AA5182 and AA6016 in sheet thicknesses of 1 mm. Accompanying experimental investigations, as tensile tests, will evaluate the quality of the welding mechanism. As the mechanics of the new welding technology is not fundamentally investigated until now, metallographic investigations are performed, and additionally micro hardness measurements are carried out to verify the changes in the hardness distribution in the welding zone after stirring and welding. 相似文献
29.
Florenza Lüder Ripoli Annika Mohr Susanne Conradine Hammer Saskia Willenbrock Marion Hewicker-Trautwein Silvia Hennecke Hugo Murua Escobar Ingo Nolte 《International journal of molecular sciences》2016,17(5)
Mammary neoplasms are the tumors most affecting female dogs and women. Formalin-fixed, paraffin-embedded (FFPE) tissues are an invaluable source of archived biological material. Fresh frozen (FF) tissue is considered ideal for gene expression analysis. However, strategies based on FFPE material offer several advantages. Branched-DNA assays permit a reliable and fast workflow when analyzing gene expression. The aim of this study was to assess the comparability of the branched-DNA assay when analyzing certain gene expression patterns between FF and FFPE samples in canine mammary tumors. RNA was isolated from 109 FFPE samples and from 93 FF samples of different canine mammary tissues. Sixteen (16) target genes (Tp53; Myc; HMGA1; Pik3ca; Mcl1; MAPK3; FOXO3; PTEN; GATA4; PFDN5; HMGB1; MAPK1; BRCA2; BRCA1; HMGA2; and Her2) were analyzed via branched-DNA assay (b-DNA). ACTB, GAPDH, and HPRT1 were used as data normalizers. Overall, the relative gene expression of the two different origins of samples showed an agreement of 63%. Still, care should be taken, as FFPE specimens showed lower expression of the analyzed targets when compared to FF samples. The fact that the gene expression in FFPE proved to be lower than in FF specimens is likely to have been caused by the effect of storage time. ACTB had the best performance as a data normalizer. 相似文献
30.
Characterization of activated sludge flocs by confocal laser scanning microscopy and image analysis 总被引:7,自引:0,他引:7
Schmid M Thill A Purkhold U Walcher M Bottero JY Ginestet P Nielsen PH Wuertz S Wagner M 《Water research》2003,37(9):2043-2052
In this study we present a new approach to determine volumes, heterogeneity factors, and compositions of the bacterial population of activated sludge flocs by 3D confocal imaging. After staining the fresh flocs with fluorescein-isothiocyanate, 75 stacks of images (containing approx. 3000 flocs) were acquired with a confocal laser scanning microscope. The self-developed macro 3D volume and surface determination for the KS 400 software package combined the images of one stack to a 3D image and calculated the real floc volume and surface. We determined heterogeneity factors like the ratio of real floc surface to the surface of a sphere with the respective volume and the fractal dimension (D(f)). According to their significant influence on floc integrity and quality, we also investigated the chemical composition of flocs and quantified their bacterial population structure by using group-specific rRNA-targeted probes for fluorescence in situ hybridization. By a settling experiment we enriched flocs with poor settling properties and determined the above-mentioned parameters. This approach revealed shifts in floc volume, heterogeneity, and bacterial and chemical composition according to the settling quality of the flocs. 相似文献