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排序方式: 共有651条查询结果,搜索用时 312 毫秒
1.
S Bastian JL Paquet C Robert B Cremers B Loillier JF Larrivée DR Bachvarov F Marceau D Pruneau 《Canadian Metallurgical Quarterly》1998,253(3):750-755
Near-haploidy is a rare cytogenetic finding in childhood acute lymphoblastic leukaemia (ALL) and is associated with a poor prognosis. A second hyperdiploid line, occurring presumably by endoreduplication of the near-haploid stemline, is often observed. We present a case of common ALL in relapse characterized morphologically by a dual population of small and large lymphoblasts. Cytogenetic analysis supplemented with fluorescence in-situ hybridization (FISH) studies localized near-haploidy and hyperdiploidy to the small and large blast population respectively. DNA ploidy determination confirmed two abnormal clones with near-haploidy as the predominant one. A novel t(9;12)(q11;q13) was present in the near-haploid clone and was duplicated in the hyperdiploid clone. This finding identified cells bearing near-haploidy to be the clonogenic population following malignant transformation and confirmed endoreduplication as the mechanism for the presence of associated hyperdiploidy. 相似文献
2.
Ann-Kathrin Eichelmann George C. Mayne Karen Chiam Steven L. Due Isabell Bastian Frederike Butz Tingting Wang Pamela J. Sykes Nicholas J. Clemons David S. Liu Michael Z. Michael Christos S. Karapetis Richard Hummel David I. Watson Damian J. Hussey 《International journal of molecular sciences》2021,22(11)
TP53 gene mutations occur in 70% of oesophageal adenocarcinomas (OACs). Given the central role of p53 in controlling cellular response to therapy we investigated the role of mutant (mut-) p53 and SLC7A11 in a CRISPR-mediated JH-EsoAd1 TP53 knockout model. Response to 2 Gy irradiation, cisplatin, 5-FU, 4-hydroxytamoxifen, and endoxifen was assessed, followed by a TaqMan OpenArray qPCR screening for differences in miRNA expression. Knockout of mut-p53 resulted in increased chemo- and radioresistance (2 Gy survival fraction: 38% vs. 56%, p < 0.0001) and in altered miRNA expression levels. Target mRNA pathways analyses indicated several potential mechanisms of treatment resistance. SLC7A11 knockdown restored radiosensitivity (2 Gy SF: 46% vs. 73%; p = 0.0239), possibly via enhanced sensitivity to oxidative stress. Pathway analysis of the mRNA targets of differentially expressed miRNAs indicated potential involvement in several pathways associated with apoptosis, ribosomes, and p53 signaling pathways. The data suggest that mut-p53 in JH-EsoAd1, despite being classified as non-functional, has some function related to radio- and chemoresistance. The results also highlight the important role of SLC7A11 in cancer metabolism and redox balance and the influence of p53 on these processes. Inhibition of the SLC7A11-glutathione axis may represent a promising approach to overcome resistance associated with mut-p53. 相似文献
3.
Paula Bracco Hein J. Wijma Bastian Nicolai Jhon Alexander Rodriguez Buitrago Thomas Klünemann Agustina Vila Patrick Schrepfer Wulf Blankenfeldt Dick B. Janssen Prof. Dr. Anett Schallmey 《Chembiochem : a European journal of chemical biology》2021,22(6):1099-1110
CYP154C5 from Nocardia farcinica is a P450 monooxygenase able to hydroxylate a range of steroids with high regio- and stereoselectivity at the 16α-position. Using protein engineering and substrate modifications based on the crystal structure of CYP154C5, an altered regioselectivity of the enzyme in steroid hydroxylation had been achieved. Thus, conversion of progesterone by mutant CYP154C5 F92A resulted in formation of the corresponding 21-hydroxylated product 11-deoxycorticosterone in addition to 16α-hydroxylation. Using MD simulation, this altered regioselectivity appeared to result from an alternative binding mode of the steroid in the active site of mutant F92A. MD simulation further suggested that the entrance of water to the active site caused higher uncoupling in this mutant. Moreover, exclusive 15α-hydroxylation was observed for wild-type CYP154C5 in the conversion of 5α-androstan-3-one, lacking an oxy-functional group at C17. Overall, our data give valuable insight into the structure–function relationship of this cytochrome P450 monooxygenase for steroid hydroxylation. 相似文献
4.
5.
Heiko Koziolek Bastian Schlich Steffen Becker Michael Hauck 《Empirical Software Engineering》2013,18(4):746-790
During software system evolution, software architects intuitively trade off the different architecture alternatives for their extra-functional properties, such as performance, maintainability, reliability, security, and usability. Researchers have proposed numerous model-driven prediction methods based on queuing networks or Petri nets, which claim to be more cost-effective and less error-prone than current practice. Practitioners are reluctant to apply these methods because of the unknown prediction accuracy and work effort. We have applied a novel model-driven prediction method called Q-ImPrESS on a large-scale process control system from ABB consisting of several million lines of code. This paper reports on the achieved performance prediction accuracy and reliability prediction sensitivity analyses as well as the effort in person hours for achieving these results. 相似文献
6.
This paper studies a new class of single-machine scheduling problems, which are faced by Just-in-Time-suppliers satisfying a given demand. In these models the processing of jobs leads to a release of a predefined number of product units into inventory. Consumption is triggered by predetermined time-varying, and product-specific demand requests. While all demands have to be fulfilled, the objective is to minimize the resulting product inventory. We investigate different subproblems of this general setting with regard to their computational complexity. For more restricted problem versions strongly polynomial time algorithms are presented. In contrast to this, NP-hardness in the strong sense is proven for more general problem versions. Moreover, for the most general version, even finding a feasible solution is shown to be strongly NP-hard. 相似文献
7.
Andreas Goralczyk Sofya Savicheva Ramin Montazeri Simona Fine Fadoua Mayoussi Pang Zhu Kay Steffen Frederik Kotz-Helmer Dorothea Helmer Bastian E. Rapp 《Advanced Engineering Materials》2023,25(8):2201314
Superhydrophobic coatings are widely applicable, e.g., as self-cleaning surfaces or water–oil separation membranes, yet their wider usage is impeded due to costs of fabrication, size, or substrate limitation. Spray-coating is a versatile coating procedures and might offer a good solution for the fabrication of these superhydrophobic coatings, due to the fact that coatings can be fabricated on various materials in a simple, fast, and inexpensive manner. Most procedures rely on hybrid coatings of hydrophobized nanoparticles and a polymeric matrix, which have several drawbacks including the easy loss of nanoparticles and difficult waste handling. Here, the fabrication of the superhydrophobic material, called Fluoropor, for the first time, by spray-coating on various substrates including metals, tissues, concrete, and glass is presented. It is fabricated by spray-coating a mixture of a highly fluorinated monomer blended with porogens followed by photopolymerization. The superhydrophobicity of the material relies on the porous structure on the micro-/nanoscale across the bulk material and does not require any nanoparticles. Excellent self-cleaning ability of these coatings, resistance against thermal and abrasive impact, and their application as oil–water separation membranes are shown. This versatile applicability is highly promising for real-world application as self-cleaning coatings or oil–water separating membranes. 相似文献
8.
P Brown L Cervenáková L McShane LG Goldfarb K Bishop F Bastian J Kirkpatrick P Piccardo B Ghetti DC Gajdusek 《Canadian Metallurgical Quarterly》1998,50(3):684-688
A 53-year-old man died of sporadic Creutzfeldt-Jakob disease (CJD) after a 1.5-year clinical course. Four and a half years later, his then 55-year-old widow died from CJD after a 1-month illness. Both patients had typical clinical and neuropathologic features of the disease, and pathognomonic proteinase-resistant amyloid protein ("prion" protein, or PrP) was present in both brains. Neither patient had a family history of neurologic disease, and molecular genetic analysis of their PrP genes was normal. No medical, surgical, or dietary antecedent of CJD was identified; therefore, we are left with the unanswerable alternatives of human-to-human transmission or the chance occurrence of sporadic CJD in a husband and wife. 相似文献
9.
10.
Malte Krack Marc Secanell Pierre Mertiny 《Structural and Multidisciplinary Optimization》2011,44(1):57-73
A procedure to find the optimal design of a flywheel with a split-type hub is presented. Since cost plays a decisive role
in stationary flywheel energy storage applications, a trade-off between energy and cost is required. Applying a scaling technique,
the multi-objective design problem is reduced to the maximization of the energy-per-cost ratio as the single objective. Both
an analytical and a finite element model were studied. The latter was found to be more than three orders of magnitude more
computationally expensive than the analytical model, while the analytical model can only be regarded as a coarse approximation.
Multifidelity approaches were examined to reduce the computational expense while retaining the high accuracy and large modeling
depth of the finite element model. Using a surrogate-based optimization strategy, the computational cost was reduced to only
one third in comparison to using only the finite element model. A nonlinear interior-point method was employed to find the
optimal rim thicknesses and rotational speed. The benefits of the split-type hub architecture were demonstrated. 相似文献