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排序方式: 共有266条查询结果,搜索用时 140 毫秒
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Siebert HC André S Asensio JL Cañada FJ Dong X Espinosa JF Frank M Gilleron M Kaltner H Kozár T Bovin NV von Der Lieth CW Vliegenthart JF Jiménez-Barbero J Gabius HJ 《Chembiochem : a European journal of chemical biology》2000,1(3):181-195
This study documents the feasibility of switching to an aprotic medium in sugar receptor research. The solvent change offers additional insights into mechanistic details of receptor--carbohydrate ligand interactions. If a receptor retained binding capacity in an aprotic medium, solvent-exchangeable protons of the ligand would not undergo transfer and could act as additional sensors, thus improving the level of reliability in conformational analysis. To probe this possibility, we first focused on hevein, the smallest lectin found in nature. The NMR-spectroscopic measurements verified complexation, albeit with progressively reduced affinity by more than 1.5 orders of magnitude, in mixtures of up to 50% dimethyl sulfoxide (DMSO). Since hevein lacks the compact beta-strand arrangement of other sugar receptors, such a structural motif may confer enhanced resistance to solvent exchange. Two settings of solid-phase activity assays proved this assumption for three types of alpha- and/or beta-galactoside-binding proteins, that is, a human immunoglobulin G (IgG) subfraction, the mistletoe lectin, and a member of the galectin family of animal lectins. Computer-assisted calculations and NMR experiments also revealed no conspicuous impact of the solvent on the conformational properties of the tested ligands. To define all possible nuclear Overhauser effect (NOE) contacts in a certain conformation and to predict involvement of exchangeable protons, we established a new screening protocol applicable during a given molecular dynamics (MD) trajectory and calculated population densities of distinct contacts. Experimentally, transferred NOE (tr-NOE) experiments with IgG molecules and the disaccharide Gal'alpha1-3Galbeta1-R in DMSO as solvent disclosed that such an additional crosspeak, that is, Gal'OH2--GalOH4, was even detectable for the bound ligand under conditions in which spin diffusion effects are suppressed. Further measurements with the plant lectin and galectins confirmed line broadening of ligand signals and gave access to characteristic crosspeaks in the aprotic solvent and its mixtures with water. Our combined biochemical, computational, and NMR-spectroscopical strategy is expected to contribute notably to the precise elucidation of the geometry of ligands bound to compactly folded sugar receptors and of the role of water molecules in protein--ligand (carbohydrate) recognition, with relevance to areas beyond the glycosciences. 相似文献
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This paper presents an innovative approach for initiating processes of a transactive memory system in newly formed groups of experts collaborating computer-supported in a complex problem-solving task. Our empirical study compared 15 experimental and 15 control groups, each consisting of triads. In the experimental condition, the triads were provided with a tool for fostering knowledge and information awareness, that is, being informed about the knowledge and the underlying information of the collaboration partners in form of digital concept maps. In the control condition, the groups had no access to this tool. Results confirmed the potential of the tool to initiate processes of a transactive memory system: shared agreement of the knowledge of the other group members’ knowledge proved to influence group performance positively. In addition, previous findings of the tool’s potential to establish knowledge and information awareness and to augment group performance could be replicated. However, the postulated mediating effect of processes of a transactive memory system concerning the impact of knowledge and information awareness on group performance did not reach statistical significance. Aspects for future studies and implications of these findings regarding their practical implementation, for example, in teams of organizations, are discussed. 相似文献
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h –p–adaptive projection with respect to any prescribed threshold value for the visual error. This projection can then be processed
by various local rendering methods, e.g. color coding of data or isosurface extraction. Especially for color coding purposes
modern texture capabilities are used to directly render higher polynomial data by superposition of polynomial basis function
textures and final color look-up tables. Numerical experiments from CFD clearly demonstrate the applicability and efficiency
of our approach.
Received September 25, 2001; revised March 31, 2003
Published online: May 26, 2003
The authors acknowledge the valuable hints of the anonymous referees. 相似文献
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Ramona Erber Steffen Spoerl Andreas Mamilos Rosemarie Krupar Arndt Hartmann Matthias Ruebner Juergen Taxis Mareike Wittenberg Torsten E. Reichert Gerrit Spanier Silvia Spoerl 《International journal of molecular sciences》2022,23(1)
Oral cancer often presents with aggressive behavior and a high risk of recurrence and metastasis. For oral squamous cell carcinoma (OSCC), which is the most frequent histological subtype, therapy strategies include surgery, radiation therapy, chemotherapy, immune checkpoint inhibitors, and EGFR inhibitors. Recently, a Trop-2 antibody-drug conjugate (ADC) has been approved in the United States of America for the treatment of advanced triple-negative breast cancer. However, this ADC has also been tested in other solid tumors including head & neck squamous cell carcinoma. The prognostic impact of Trop-2 has already been reported for several cancers. We studied the prognostic influence of Trop-2 protein expression on OSCC patients’ survival. The cohort comprised n = 229 OSCC patients with available archived tumor tissue and corresponding non-neoplastic oral mucosa tissue. Using immunohistochemistry, we investigated Trop-2 expression in both the central and peripheral regions of each tumor and in corresponding non-neoplastic oral mucosa. In patients suffering from OSCC with combined high central and low peripheral Trop-2 expression, five-year overall survival (OS) was 41.2%, whereas 55.6% of OSCC patients who presented lower central and/or higher peripheral tumoral Trop-2 expression were alive after five years (p = 0.075). In multivariate Cox regression, the expression pattern of high central tumoral and lower peripheral Trop-2 expression was significantly correlated with impaired OS (HR = 1.802, 95%-CI: 1.134–2.864; p = 0.013) and recurrence-free survival (RFS) (HR = 1.633, 95%-CI: 1.042–2.560; p = 0.033), respectively, when adjusting for co-variables. Hence, Trop-2 may serve as an independent prognostic biomarker in OSCC. In subsequent studies, the pathophysiological meaning of downregulated Trop-2 expression in the OSCC periphery has to be analyzed. 相似文献
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Stephan Bose-O'Reilly Gustav Drasch Saulo Rodrigues-Filho Beate Lettmeier Alexandra Maydl Uwe Siebert 《The Science of the total environment》2010,408(4):713-1000
Small scale miners use mercury to extract gold from ore in many countries. An environmental and health assessment was performed in Indonesia in two regions, Galangan in Central Kalimantan and Talawaan in Northern Sulawesi. The environmental assessment showed severe mercury contamination of the sediments, and increased mercury levels in local fish. For the health investigation 281 volunteers were recruited and examined by a standardized questionnaire, a neurological examination and neuro-psychological tests. A medical score was used consisting of significant factors of mercury intoxication. Mercury exposed workers showed typical symptoms of mercury intoxication, such as movement disorders (ataxia, tremor, dysdiadochokinesia, etc.). Blood, urine and hair samples were taken from any participant and analyzed for mercury. The mercury concentration in the biomonitors was high, partly extreme high in the working population, increased in the population living in the same habitat and low in the control group. By a standard protocol which includes a combination of threshold values of mercury in the biomonitors and a medical sum score the diagnosis of chronic mercury intoxication was made for highly burdened workers (amalgam smelters) in 55% in Sulawesi and in 62% in Kalimantan. Less exposed mineral processors and the general population in the mining areas were also intoxicated to a high percentage. 相似文献