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MA Nowak AL Lloyd GM Vasquez TA Wiltrout LM Wahl N Bischofberger J Williams A Kinter AS Fauci VM Hirsch JD Lifson 《Canadian Metallurgical Quarterly》1997,71(10):7518-7525
Mathematical modeling of viral replication dynamics, based on sequential measurements of levels of virion-associated RNA in plasma during antiretroviral treatment, has led to fundamental new insights into human immunodeficiency virus type 1 pathogenesis. We took advantage of the simian immunodeficiency virus (SIV)-infected macaque model to perform detailed measurements and mathematical modeling during primary infection and during treatment of established infection with the antiretroviral drug (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA). The calculated clearance half-life for productively infected cells during resolution of the peak viremia of primary infection was on the order of 1 day, with slightly shorter clearance half-lives calculated during PMPA treatment. Viral reproduction rates upon discontinuation of PMPA treatment after 2 weeks were approximately twofold greater than those obtained just prior to initiation of treatment in the same animals, likely reflecting accumulation of susceptible target cells during treatment. The basic reproductive ratio (R0) for the spread of SIV infection in vivo, which represents the number of productively infected cells derived from each productively infected cell at the beginning of infection, was also estimated. This parameter quantifies the extent to which antiviral therapy or vaccination must limit the initial spread of virus to prevent establishment of chronic disseminated infection. The results thus provide an important guide for efforts to develop vaccines against SIV and, by extension, human immunodeficiency virus. 相似文献
23.
对己二腈工业反应器提出了两釜串联带回流的模型,通过模拟计算得出模型的级间返混系数 f=6的结论。该模型能较好地预测工业反应器中物料组分浓度变化和气、液两相的流动特性;指出了现工业反应器的鼓泡中和段体积偏小是造成己二酸浓度偏高的关键;提出了可以通过增加串连一个鼓泡预反应段的改造方案,能有效地降低己二酸的浓度,从7%降至4%左右,从而能较好地减缓腐蚀和结焦。 相似文献
24.
LW Seymour H Soyez A De Marre MA Shoaibi EH Schacht 《Canadian Metallurgical Quarterly》1996,11(5):351-365
Prodrugs of mitomycin C (MMC) based on soluble poly-[N-(2-hydroxyethyl)-L-glutamine] (pHEG) polymers have been evaluated as tumour-targeted drugs. These materials are designed to exploit the enhanced permeability of tumour vasculature, combining a passive tumour tropism with decreased systemic liberation of free MMC. A tri- or tetrapeptide linkage (e.g. Gly-Phe-Ala-Leu) between pHEG and the aziridine nitrogen of MMC can combine good hydrolytic stability with rapid cleavage by lysosomal enzymes, releasing free MMC. The conjugates showed decreased systemic toxicity and could be administered to mice at a total MMC dose of 15 mg/kg i.v., compared with just 6 mg/kg for free MMC. Conjugates also showed better activity against animal models of established tumours, achieving up to 77% increased life span (ILS) against solid P388 leukaemia, compared with only 23% for free MMC, and up to 121% ILS against solid C26 colorectal carcinoma, compared with no activity for the free drug. Improving the therapeutic index of anticancer drugs by combining tumour tropism with decreased systemic toxicity is a versatile approach that should produce a new generation of improved anticancer agents. 相似文献
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Spontaneous resolution of deformities after excision of facial skin lesions has been known and used for a long time by plastic surgeons. The resorption mechanism of deformity is based on natural skin expansion, and seems to be directly related to the action of the muscles of facial expression and their skin relations. Natural expansion has been shown to be effective in children. Between 1990 and 1994 excision of skin lesions, including congenital nevi, leading to postoperative deformity of the cheek, labial commissure, nose, eyelid and forehead, was performed on 35 patients, aged from 3 month to 12 years. The average follow-up is 24 months. For 26 patients (74%), natural resorption was observed 4 or 6 weeks later with good aesthetic results. For 6 patients (17%), the deformity persisted 3 or 6 months later, but did not require any further surgery. For 3 patients (9%), a second operation was necessary. Using the skins natural capacity for expansion in the treatment of facial skin defects in children is a method of reconstruction which has already been used for excision in enforced position. The platysma and muscles of facial expression by their action on skin mobilisation, allow natural expansion. A better knowledge of cutaneous biomechanical properties enables plastic surgeons to find an alternative to other classical methods. 相似文献
27.
M Vives ME Garcia P Saenz MA Mora L Mata H Sabharwal C Svanborg 《Canadian Metallurgical Quarterly》1997,16(9):852-858
BACKGROUND: The establishment of the nasopharyngeal flora was followed in Costa Rican children from birth to 1 year of age. METHODS: Nasopharyngeal cultures were obtained at 1 (n = 413), 3 (n = 393), 6 (n = 376) and 12 months (n = 356) of age from children representative of the population in the Puriscal district. Weekly cultures were obtained from a subcohort of these children (n = 101). Mother-infant diads (n = 95) and preschool children (n = 208) attending day-care centers were also studied. RESULTS: The estimated proportion of colonized children in the population differed markedly depending on the frequency of culture. Quarterly cultures showed a slow increase in carrier rates from 3.9% for Haemophilus influenzae, 3.1% for Streptococcus pneumoniae and 6.5% for Moraxella catarrhalis at 1 month of age to 10.1% carrying H. influenzae and 19.4% carrying S. pneumoniae by the end of the first year. By quarterly culture the proportion of children colonized at least once was 36% for S. pneumoniae, 26% for H. influenzae and 28% for M. catarrhalis. In contrast weekly sampling showed that 95 to 100% of the children were colonized at least once during the first year of life with H. influenzae, S. pneumoniae or M. catarrhalis. Nasopharyngeal carriage of H. influenzae, S. pneumoniae and M. catarrhalis was low in the mothers, and very few mother-infant pairs carried identical bacteria at the same time. In contrast carrier rates were high in the siblings attending day care (H. influenzae 27.9%, S. pneumoniae 39.4%, both organisms 26.6%). Infants with siblings had significantly higher bacterial carriage at all ages than infants without siblings. CONCLUSIONS: Quarterly nasopharyngeal cultures showed that Costa Rican infants acquire their nasopharyngeal flora at a rate comparable with that for infants in developed countries and that siblings are an important source of the bacteria. Weekly samplings showed that virtually all children were colonized at least once during the first year of life. 相似文献
28.
29.
ME Sutherlin I Nishimori T Caffrey EP Bennett H Hassan U Mandel D Mack T Iwamura H Clausen MA Hollingsworth 《Canadian Metallurgical Quarterly》1997,57(21):4744-4748
The levels of mRNA expression of three UDP-N-acetyl-alpha-D-galactosamine:polypeptide GalNAc N-acetylgalactosaminyltransferases (GalNAc-transferases) were quantified for human adenocarcinoma cell lines from pancreas, colon, stomach, and breast. Two of the GalNAc-transferases, GalNAc-T1 and GalNAc-T2, were expressed constitutively and at low levels in most or all cell lines examined. A third GalNAc-transferase, GalNAc-T3, was differentially expressed. Well-differentiated adenocarcinoma cell lines expressed high levels and moderately differentiated cell lines expressed lower levels of GalNAc-T3. Cell lines classified as poorly differentiated failed to express GalNAc-T3 mRNA at levels that could be detected by Northern blot analysis. Differential expression of the GalNAc-T3 protein was confirmed in these cell lines by Western blotting. We propose that glycosylation in tumor cell lines may be regulated in part by differential expression of GalNAc-transferases, and we suggest that GalNAc-T3 gene expression may be a molecular indicator of differentiated adenocarcinoma. 相似文献
30.
用实验方法研究了Al_2O_3陶瓷缺口试件在循环载荷作用下的疲劳寿命。结果表明,缺口导致的应力集中效应显著降低了循环疲劳寿命;若用缺口根部最大应力为应力水平,则不同缺口半径陶瓷试件具有相同疲劳断裂规律,说明陶瓷材料的疲劳集中系数和理论应力集中系数相同。本文还分析讨论了陶瓷材料的循环疲劳寿命表达式和循环疲劳断裂机理。 相似文献