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排序方式: 共有1455条查询结果,搜索用时 656 毫秒
41.
RE Georgescu JH Li ME Goldberg ML Tasayco AF Chaffotte 《Canadian Metallurgical Quarterly》1998,37(28):10286-10297
Oxidized Escherichia coli thioredoxin (Trx) is a small protein of 108 residues with one disulfide bond (C32-C35 essentially involved in the activity) and no prosthetic moieties, which folds into a structural motif containing a central twisted beta-sheet flanked by helices that is found in many larger proteins. The kinetics of refolding of Trx in vitro have been investigated using a newly developed active site titration assay and continuous or stopped-flow (SF) methods in conjunction with circular dichroism (CD) and fluorescence (Fl) spectroscopy. These studies revealed the presence of early folding intermediates with "molten globule or pre-molten globule" characteristics. Measurements of the ellipticity at 222 nm indicated that about 68% of the total change associated with refolding occurred during the dead time (4 ms) of the stopped-flow instrument, suggesting the formation of substantial secondary structure. The reconstruction of the far-UV CD spectrum of the burst intermediate using combined continuous and stopped-flow methods showed the formation of a defined secondary structure that contains more beta-structure than the native state. Kinetic measurements using SF far-UV CD and Fl over a wide range (0.087-6 M) of GuHCl concentrations at two temperatures (6 and 20 degreesC) demonstrated that the population formed during the 4 ms dead time contained multiple species that are stabilized mainly by hydrophobic interactions and undergo further folding along alternative pathways. One of these species leads directly and rapidly to the native state as demonstrated by active site titration, while the two others fold into a fourth intermediate that is slowly converted to the native protein. Double-jump experiments suggest that the heterogeneity in folding behavior results from proline isomerizations occurring in the unfolded state. Conversely, the accumulation of the burst intermediate does not depend on proline isomerizations. 相似文献
42.
During the last 7 years significant progress has been made in the identification of melanoma-associated antigens recognized by cytotoxic T lymphocytes (CTL). These antigens belong to three main groups: cancer/testis-specific antigens (MAGE, BAGE, GAGE, PRAME and NY-ESO-1), melanocyte differentiation antigens (tyrosinase, Melan-A/MART-1, gp100, TRP-1 and TRP-2), and mutated or aberrantly expressed antigens (MUM-1, CDK4, beta-catenin, gp100-in4, p15 and N-acetylglucosaminyltransferase V). In this review we have summarized the available data concerning the characterization of melanoma-associated antigens, focusing on their immunogenic and protective properties. The development of a strong immune response to differentiation antigens is limited by the existence of tolerance to these "self"-antigens, permitting the involvement of only T cells with low affinity T-cell receptors. Among the melanoma differentiation antigens, only gp100 has been shown to be a tumor regression antigen. The cancer/testis-specific antigens such as MAGE and PRAME should potentially be highly immunogenic antigens. They contain several potential HLA class I binding epitopes and are present only in the testes, which are not accessible to the cells of the immune system owing to the lack of direct contact with the immune cells and the lack of HLA class I expression on the surface of germ cells. But only two patients have been found who responded to these antigens in vivo, indicating their genuinely low immunogenicity. A comparison of the predicted secondary structures of these two groups of antigens (cancer/testis-specific and differentiation antigens) revealed enrichment of long alpha-helical stretches in the cancer/testis-specific antigens. We hypothesize that such highly organized stable structures could, first, reduce denaturation of the protein and, thus, ubiquitinylation as a degradation signal, and, second, diminish the efficiency of the protein unfolding - a necessary step in the proteolytic cleavage by proteasomes. High structural stability could therefore be responsible for the low immunogenicity of these proteins. In this case, modifications decreasing the stability of these proteins might be a means of improving the immune response to these potentially therapeutically useful antigens. 相似文献
43.
44.
II Wistuba C Behrens S Milchgrub AK Virmani J Jagirdar B Thomas HL Ioachim LA Litzky EM Brambilla JD Minna AF Gazdar 《Canadian Metallurgical Quarterly》1998,279(19):1554-1559
CONTEXT: Human immunodeficiency virus (HIV) infection has been associated with an increasing incidence of malignancy, and HIV-infected persons have an increased incidence of primary lung carcinoma compared with the general population. OBJECTIVE: To investigate the molecular changes present in HIV-associated lung tumors and compare them with those present in lung carcinomas arising in HIV-indeterminate subjects ("sporadic tumors"). DESIGN: Convenience sample. SUBJECTS: Archival tissues from 11 HIV-positive persons and from 35 persons of indeterminate HIV status. SETTING: University-based medical centers and affiliated hospitals. MAIN OUTCOME MEASURES: Analysis of frequency of loss of heterozygosity (LOH) and microsatellite alteration (MA) using polymerase chain reaction and 16 polymorphic microsatellite markers at 8 chromosomal regions frequently deleted in lung cancer. Presence of HIV and human papillomavirus (HPV) sequences. RESULTS: The overall frequency of LOH at all chromosomal regions tested and the frequencies at most of the individual regions were similar in the 2 groups. Frequency of MA present in the HIV-associated tumors (0.18) was 6-fold higher than in sporadic tumors (0.03) (P<.001). At least 1 MA was present in 10 (91%) of 11 HIV-associated tumors vs 17 (48%) of 35 sporadic tumors (P=.02). Molecular changes were independent of tumor stage and gender. HIV and HPV sequences were not detected in the HIV-associated lung carcinomas. CONCLUSIONS: Microsatellite alterations, which reflect widespread genomic instability, occur at greatly increased frequency in HIV-associated lung carcinomas. Although the mechanism underlying the development of increased MAs is unknown, it may play a crucial role in the development of many HIV-associated tumors. 相似文献
45.
L Fratiglioni AF Jorm M Grut M Viitanen K Holmén A Ahlbom B Winblad 《Canadian Metallurgical Quarterly》1993,46(3):281-287
Steroid hormone regulation and cell-type specific expression of the jun-D protooncogene in rat uterus was examined. Adult, ovariectomized rats were injected with progesterone, testosterone, 17beta-estradiol (E2-17beta), 16alpha-estradiol (E2-16alpha), dexamethasone or cycloheximide. Uteri were collected between 0 and 6 h post-treatment. Northern blot analysis of uterine RNA revealed that induction of jun-D was specific for estrogenic steroids, as progesterone and testosterone had no effect on expression of this member of the jun gene family. Treatment with E2-17beta increased jun-D mRNA levels by approx. 5-fold, with expression reaching peak levels at 3 h after treatment and declining thereafter. Administration of E2-16alpha, a short-acting estrogen that does not cause uterine cell proliferation, increased expression of jun-D but with different kinetics compared to the long-acting E2-17beta. The mRNA levels of jun-D increased by 3-fold 1 h after administration of E2-16alpha but declined soon after. Slight induction of jun-D mRNA by dexamethasone was apparent, but to a much lesser extent compared to estrogen. The protein synthesis inhibitor, cycloheximide, did not block jun-D induction, indicating that this is an "immediate early" response. Expression of Jun-D protein was examined by immunohistochemical methods. E2-17beta treatment activated jun-D primarily in the nuclei of luminal and glandular epithelial cells of the endometrium. These results demonstrate that hormonal induction of jun-D is specific for estrogens and that uterine expression of this protooncogene occurs in a cell-type specific manner. 相似文献
46.
The technique of continuous-flow solid-phase peptide synthesis using unsupported polymers has been extended to cover the use of N alpha-Fmoc protected amino acids. This approach to peptide synthesis uses (but is not limited to) a phenolic bead-form polymer at 5 mmol g-1 loading. The success of the technique is based upon "layered displacement" to efficiently remove spent reagents and washing solutions from within the flow reactor under low pressure conditions. This system has been successfully employed in synthesizing the test peptides, [Leu5]-enkephalin, neurotensin and the notoriously difficult decapeptide sequence (65-74) of the acyl carrier protein. 相似文献
47.
As demand for more power increases, compression ratios, and operating temperatures keep rising. High speeds combined with
high temperatures make turbomachinery sealing applications even more challenging. In order to confirm sufficient service life
material pairs should be tested under conditions similar to engine operating conditions. This study presents high temperature
friction and wear characteristics of cobalt/nickel superalloys, Haynes 25 (51Co–10Ni–20Cr–15W), Haynes 188 (39Co–22Ni–22Cr–14W),
and Haynes 214 (75Ni–16Cr–3Fe–0.5Mn) sheets when rubbed against Hastelloy X (47Ni–22Cr–18Fe–9Mo) pins. Tests are conducted
at 25, 200, 400, and 540 °C with a validated custom design linear reciprocating tribometer. Sliding speed and sliding distance
are 1 Hz and 1.2 km, respectively. Friction coefficients are calculated with friction force data acquired from a load cell.
Wear coefficients are calculated through weight loss measurements. Results indicate that Haynes 25 (H25) has the lowest friction
coefficients at all test temperatures. Above 400 °C, H25 and Haynes 188 (H188) exhibit the best wear resistance. Protective
cobalt oxide layers are formed on the H25 and H188 at 540 °C in addition to nickel, chrome, and tungsten oxides. Although,
it has better oxidation resistance, Haynes 214 has relatively higher wear rates than other tested materials especially at
low temperatures. However, its wear performance improves beyond 200 °C. 相似文献
48.
Healthcare facilities are often complex and overwhelming for visitors, and wayfinding in healthcare facilities can be challenging. As there is an increasing number of global citizens who travel to seek medical care in another country, it is critical to make wayfinding easy for visitors who are not familiar with the language in a foreign country. Among many wayfinding aids, symbols are helpful for those visitors who have limited ability to understand written language. This study tested universal healthcare symbols in the United States, South Korea, and Turkey to compare the comprehension of symbols cross-country and identify predictors of the correct comprehension. To explore statistically significant relationships between symbol comprehension and countries, Pearson's Chi-square tests, logistic regression, and ANOVA were conducted. The test results showed that ten symbols among 14 tested have significant relationship with countries. Results of this study demonstrate that symbol comprehension can be varied significantly in different countries. 相似文献
49.
50.
Gokhan Aydin Izzet Karakurt Coskun Hamzacebi 《The International Journal of Advanced Manufacturing Technology》2014,75(9-12):1321-1330
An experimental study is carried out for modeling the rock cutting performance of abrasive waterjet. Kerf angle (KA) is considered as a performance criteria and modeled using artificial neural network (ANN) and regression analysis based on operating variables. Three operating variables, including traverse speed, standoff distance, and abrasive mass flow rate, are studied for obtaining different results for the KA. Data belonging to the trials are used for construction of ANN and regression models. The developed models are then tested using a test data set which is not utilized during construction of models. Additionally, the regression model is validated using various statistical approaches. The results of regression analysis are also used to determine the significant operating variables affecting the KA. Furthermore, the performances of derived models are compared for showing the accuracy levels in prediction of the KA. As a result, it is concluded that both ANN and regression models can give adequate prediction for the KA with an acceptable accuracy level. The compared results reveal also that the corresponding ANN model is more reliable than the regression model. On the other hand, the standoff distance and traverse speed are statistically determined as dominant operating variables on the KA, respectively. 相似文献