Construction project control under resources constraints by fuzzy linear programming

Fuzzy linear programming (FLP) provides an alternative method of programming and the authors claim improvements in flexibility more appropriate to construction situations, but believe this is an area that needs further research.     

Prospective randomized study of early versus delayed laparoscopic cholecystectomy for acute cholecystitis

We asked whether the likelihood for mice of the C57BL/6J strain to develop glucose intolerance when fed a high-fat diet is related to the increase in circulating levels of leptin or free fatty acids (FFA). We therefore administered a high-fat diet (58% fat) or a control diet (11% fat) for 1.5 years. NMRI mice were used as a more glucose-tolerant control group. After a high-fat diet, the area under the glucose curve following an intraperitoneal glucose challenge (1 g/kg) increased more markedly in C57BL/6J mice (by 42+/-8%) than in NMRI mice (by 21+/-3%, P = 0.007). Plasma levels of insulin, leptin and FFA increased in both strains of mice, whereas plasma glucose levels were elevated after the high-fat diet only in C57BL/6J mice. The slope of the relationship between body weight and plasma leptin was higher in C57BL/6J mice than in NMRI mice. suggesting leptin insensitivity. Circulating leptin correlated to circulating insulin in both strains of mice, whereas plasma FFA correlated to plasma insulin in NMRI mice but not in C57BL/6J mice. These correlations remained significant after adjustment for body weight. The results show that elevated leptin and FFA levels evolve after high-fat feeding in mice, in conjunction with evolvement of glucose intolerance and hyperglycemia.     

Metabolic activation and carcinogen-DNA adduct detection in human larynx

Putative carcinogen-DNA adducts in human larynx tissues (n = 25) from smoker and non/ex-smoker patients were examined by 32P-postlabeling and compared with the metabolic activation capacity of larynx microsomes and cytosols from the same tissues. Hydrophobic DNA adducts were evident only in smokers, and chromatographic profiles of the adducts were similar using either the butanol extraction or nuclease P1 enhancement method, which suggested that the adducts may be derived from polycyclic aromatic hydrocarbons but not aromatic amines. Immunoblots of larynx microsomes using anti-cytochrome P450 1A1/1A2, 2C, 3A4, 2E1, and 2A6 antibodies showed intensities ranging from 1-10% of that typically observed with human liver microsomes. Enzymatic assays of larynx microsomes showed appreciable activity for benzo(a)pyrene hydroxylation (P450 1A1 and 2C) but not for 4-aminobiphenyl N-oxidation (P450 1A2), which indicated that the observed immunoreactivity was for P450 1A1; this represents the highest level of this P450 yet detected in human extrahepatic tissues. Accordingly, total DNA adduct levels in the larynx correlated strongly with levels of P450 2C, 1A1, and 3A4 but not with P450 2E1 or 2A6. Larynx cytosols also showed appreciable aromatic amine N-acetyl-transferase activity for p-aminobenzoic acid (NAT-1) but not for sulfamethazine (NAT-2); however, NAT-1 activity was not correlated with total DNA adducts, which is again consistent with the lack of aromatic amine-DNA adducts detected by 32P-postlabeling. Thus, these results suggest that the DNA adducts detected in human larynx are largely derived from metabolic activation of polycyclic aromatic hydrocarbons in cigarette smoke by P450 2C, 3A4, and/or 1A1.     

Immunohistochemical analysis of mycosis fungoides on paraffin-embedded tissue sections

Mycosis fungoides (MF) is typically characterized by dermal and epidermal infiltration of T lymphocytes with a helper/inducer phenotype. Immunophenotypic analysis of such cases was traditionally performed by flow cytometry or immunohistochemistry on cryostat sections. With the advent of new monoclonal antibodies developed against T-cell antigens, including CD3, CD4, CD5, and CD8, it is now possible to immunophenotype T-cell subpopulations in paraffin-embedded tissues. To investigate the potential use of these antibodies for the evaluation of cutaneous lesions, 35 specimens (34 skin and 1 lymph node) from 29 patients with MF were retrospectively reviewed and immunophenotyped in paraffin sections with antibodies to CD3 (T-cell CD3), CD4 (NCL-CD4-1F6), CD5 (NCL-CD5-4C7), CD8 (CD8/144B), and CD20 (L26). Epidermal and dermal distribution of T and B cells were analyzed, and we assessed the ratios of CD4+ to CD8+ T cells. All of our 35 cases demonstrated a predominant CD3+ T-cell population. In 32 cases, the neoplastic cells expressed CD3, CD4, and CD5 consistent with a T-helper/inducer phenotype. In three cutaneous cases, the neoplastic CD4+ T cells showed minimal or absent expression of CD5, indicating an aberrant phenotype. In the majority of cases, minimal CD8+ T cells were present in the background, but in four cases, the CD4:CD8 ratios were 2:1 or less. Thirty-two cutaneous cases demonstrated epidermotropism exclusively by CD4+ T cells; one case showed both CD4+ and CD8+ T cells. In 17 cutaneous cases, scattered dermal CD20+ B cells were found individually or in small clusters within the background surrounding the neoplastic infiltrates. We concluded, therefore, that the immunophenotypic analysis of T-cell subpopulations using monoclonal antibodies of CD3, CD4, CD5, and CD8 was useful for histologic evaluation and confirmation of MF lesions in paraffin-embedded tissue. These antibodies might also provide an effective method of immunophenotyping other neoplastic and non-neoplastic T-cell populations in paraffin-embedded tissues.     

A comparative study of prothrombinase and thrombin inhibitors in a novel rabbit model of non-occlusive deep vein thrombosis

A quantitative and non-occlusive deep vein thrombosis model was developed in rabbits. We used this model to test the antithrombotic activity of the prothrombinase complex inhibitors factor rXai and its chemical analog glutamyl-glycyl-arginyl chloromethyl ketone inactivated human factor Xa (EGR-Xai), along with the thrombin inhibitors D-phenylalanyl-prolyl-arginyl chloromethyl ketone (PPACK) and heparin. Dose dependent effects of the inhibitors during constant infusion were monitored. Measurements included thrombus weights, hemostatic parameters and both cuticle and ear bleeding times. In this model, factor rXai and EGR-Xai had comparable in-vivo efficacy, and showed 80%-93% inhibition at plasma levels of 6.5 nM (rXai) and 8 nM (EGR-Xai). Effects on ex-vivo clotting times varied among the inhibitors. At 80-100% thrombus inhibition, factor rXai and EGR-Xai had no statistically significant effect, while PPACK extended thrombin clotting time (TCT) times 2.3-fold, and heparin prolonged both activated partial thromboplastin time (APTT), prothrombin time (PT) and TCT ex-vivo clotting times 6.9-, 1.2-, and 7-fold respectively. At these dosages, cuticle and ear bleeding times were prolonged for all inhibitors and showed increases of 177%-389% (cuticle) and 45%-129% (ear). Our results demonstrate that direct inhibition of prothrombinase complex assembly is effective in arresting venous thrombosis.     

A study of the association of Epstein-Barr virus with Burkitt''s lymphoma occurring in a Chinese population

Several (carbamoylalkenyl)- and (carbamoylalkenyl)phenyloxy carboxylic acids (Table 1) and some of their ethyl esters (Table 2) were synthesized and evaluated in vitro as inhibitors of steroid 5 alpha-reductase. Inhibitors of this enzyme may be useful in treating dihydrotestosterone-related diseases such as prostate cancer and benign prostatic hyperplasia. Using an enzyme preparation obtained from human prostate carcinoma tissue, the inhibition values ranged from 0 to 57% at the given dose of 100 microM. In the series of free acids, surprisingly, the compounds showed only modest inhibitory potency (0-26%). By contrast, the ethyl esters displayed inhibition values up to 57%. Structure-activity relationships are discussed.     

Historical Records of Metal Pollution in Sediments of Toronto and Hamilton Harbours

The sediments of Hamilton and Toronto Harbours contain some of the oldest records of metal pollution in the Great Lakes basin. The fluxes of Cd, Cr, Cu, Ni, Pb, Zn, Fe, and Mn into the two harbours have been estimated from the analyses of core samples dated by the Pb-210 technique. The contrasting metal levels in the two harbour sediments are viewed in relation to the differences in the disposal strategies of the dredged spoils and the sources of metal pollution in the harbours. The Zn and Fe concentrations of 5 to 8 mg g^?1 and 10 to 13 % dry wt. in Hamilton Harbour sediments, which are among the highest recorded in any harbour, can be related to effluent discharges from the large local iron and steel plants. An inventory of the sources and sinks of pollutant metals in Hamilton Bay shows a substantive export of the metals to Lake Ontario.     

Structural elucidation by electrospray mass spectrometry: an approach to the in vitro metabolism of the macrolide immunosuppressant SDZ RAD

SDZ RAD [40-O-(2-hydroxyethyl)rapamycin] is a macrolide immunosuppressant that is currently under clinical investigation after organ transplantation. The elucidation of its metabolic pathway is essential to improve the understanding of its therapeutic potentials and safety. In this article we describe investigations on the structural identification of some major metabolites of the drug produced by human liver microsomes in vitro. The principles described may be generally applicable for the structural elucidation of complex compound mixtures in biological matrices. Under the conditions of electron impact ionization, SDZ RAD undergoes extensive fragmentation and no information sufficient for structural elucidation is obtained. Therefore, mass spectrometry based on soft electrospray ionization (ESI) in conjunction with collision-induced fragmentation was the method of choice. High-performance liquid chromatography coupled to an ESI mass spectrometer resulted in separation and identification of 16-O-demethyl-SDZ RAD, the ring-opened form of SDZ RAD, and its dehydrate. Additionally, we characterized several demethylated and hydroxylated metabolites.     

Separation-bubble flow solution using Euler/Navier-Stokes zonal approach with downstream compatibility conditions

An Euler/Navier-Stokes zonal scheme is developed to numerically simulate the two-dimensional flow over a blunt leading-edge plate. The computational domain has been divided into inner and outer regions where the Navier-Stokes and Euler equations are used, respectively. On the downstream boundary, compatibility conditions derived from the boundary-layer equations are used. The grid is generated by using conformal mapping and the problem is solved by using a compressible Navier-Stokes code, which has been modified to treat Euler and Navier-Stokes regions. The accuracy of the solution is determined by the reattachment location. Bench-mark solutions have been obtained using the Navier-Stokes equations throughout the optimum computational domain and size. The problem is recalculated with sucessive decrease of the computational domain from the downstream side where the compatibility conditions are used, and with successive decrease of the Navier-Stokes computational region. The results of the zonal scheme are in excellent agreement with those of the benchmark solutions and the experimental data. The CPU time saving is about 15%.