The stretch zone of automotive steel sheets

The paper deals with an experimental determination of the stretch zone dimensions in the notch tip in thin steel sheets. The stretch zone dimensions depend on steel grade, on the rolling direction as well as on the loading rate. Stretch zones were observed and measured on three steel grades. Fracture area and stretch zones were analysed by SEM. Stable crack growth was monitored by videoextensometry techniques on CT (Compact Tension) specimens. Specimens were loaded under two loading rates by eccentric tension, whereby the deformation in the notch surrounding area was recorded using a non-contact measurement–videoextensometry technique. Linear relation between the stretch zone dimensions was determined.     

Chemometrics can be applied to mechanical testing data to characterise stem toughness and stiffness in crop plants

Mechanical tests have been used to assess the engineering properties of pea (Pisum sativum L) stems. Measurements were made on plants of three different genotypes at four different stages of development and at five defined locations along the stem. The force–displacement curves obtained were used to estimate values of the engineering properties of toughness and flexural modulus, from cutting and flexure mechanical tests respectively. Specimens of all genotypes showed an increase in toughness with age and generally also with stem height. However, there were marked differences in flexural modulus between genotypes. One genotype, known to exhibit a ‘stiff straw’ characteristic, showed a consistent increase in modulus with age and stem height, and at and beyond fruiting had substantially the greatest flexural modulus. The remaining genotypes showed decreasing flexural modulus with age. Chemometric methods were used to analyse sets of complete force–displacement curves, following suitable pre‐processing to allow the application of linear algebra methods. Whereas univariate consideration of the engineering quantities allowed trends to be observed, multivariate analysis of force–distance curves was able to model empirically the genotype differences so that individual specimens could be largely correctly classified. Examination of some of the model coefficients suggested that the ability to discriminate between genotypes is related to structural features of the specimens and that cutting tests in particular are sensitive to the anatomy of the specimen. This is the first time that chemometric methods have been applied to such data and suggests the potential of mechanical tests combined with multivariate analysis to form the basis of a screening system for phenotypic properties of new lines and varieties. Copyright © 2004 Society of Chemical Industry     

Regulation of cardiac myocyte contractile function by inducible nitric oxide synthase (iNOS): mechanisms of contractile depression by nitric oxide

Inflammatory cytokines have been implicated in the reversible depression of cardiac contractile function accompanying local or systemic immune stimulation. Incubation of cardiac myocytes with soluble components in the supernatant from cultured rat lung macrophages activated with endotoxin decreases their contractile response to beta-adrenergic stimulation through the induction of iNOS and the subsequent production of nitric oxide by these cells. In the present study, we characterize the mechanisms underlying NO's attenuation of adrenergic responsiveness in cardiac myocytes. iNOS was induced in cultured ventricular myocytes from adult rats by incubation for 20 h with conditioned medium from lipopolysaccharide (LPS)-activated macrophages. iNOS induction did not induce any alteration in beta-adrenergic receptor density or affinity, Galphai protein abundance, or adenylyl cyclase activity in cultured myocytes. Myocyte exposure to activated macrophage-conditioned medium markedly attenuated the elevation of cAMP in response to isoproterenol (Iso, 2 nM). Induction of iNOS with the macrophage-conditioned medium also potentiated the Iso-induced increase in myocyte cGMP. This cGMP increase was totally abolished by NOS inhibitors. NOS inhibition also returned the attenuated cAMP response to 2 nM Iso to levels observed in control cells. Pre-incubation of the cells in isobutylmethylxanthine (IBMX), a phosphodiesterase inhibitor, also partly reversed the attenuation of cAMP increase with 2 nM Iso in cells expressing iNOS. Brief (15 min) exposure of myocytes to the NO donor, S-nitrosoacetylcysteine (SNAC, 100 micro M) which produced a three-fold increase in intracellular cGMP, also decreased by half the contractile response of cardiac myocytes to Iso (2 nM). We conclude that NO endogenously produced by iNOS decreases the intracellular levels of cAMP in response to beta-adrenergic stimulation in isolated cardiac myocytes, in part through a cGMP-mediated mechanism. This effect may participate in the NO-dependent depression of cardiac function following cytokine exposure.     

Bordetella pertussis adenylate cyclase toxin: proCyaA and CyaC proteins synthesised separately in Escherichia coli produce active toxin in vitro

We analyzed the role of Fyn tyrosine kinase in cell cycle progression of B lymphocyte progenitor (pro B cell). Whereas there were no substantial defects in the intramarrow B cell genesis in the fyn(-) mouse, and long-term proliferation of fyn(-) pro B cells was maintained in vitro under a serum containing culture condition, the cell cycle was arrested at G2/M upon serum deprivation. Morphological analyses demonstrated that the cytokinesis of fyn(-) pro B cells was retarded in the presence of serum and that the entry of fyn(-) pro B cells into late telophase was completely blocked under the serum-free condition. In contrast, the earlier phases of mitosis of fyn(-) pro B cells proceeded normally without FCS. This failure to initiate late telophase resulted in the accumulation of elliptical binucleated cells that might be the outcome of the nuclear division without cytokinesis. Consistent with this defect in the progression of cytokinesis, Fyn was localized in the midspace of dividing pro B cells at anaphase. These results suggested that Fyn localizes at the midspace of dividing pro B cells and regulates the progression of cytokinesis.     

Plasmid DNA is protected against ultrasonic cavitation-induced damage when complexed to cationic liposomes

Cationic liposomes bound to plasmid DNA are currently used for in vitro and in vivo gene therapy applications, but such complexes readily form large, heterogeneous aggregates that are not appropriate for pharmaceutical development. More importantly, size heterogeneity makes studies focused on optimizing gene transfer to cells difficult to conduct or understand. For this reason we have evaluated the effect of microprobe sonication on these complexes in an effort to achieve process-controlled size homogeneity. Complexes were prepared using a 7.2 kb reporter plasmid and the following liposomal lipid combinations: DDAB/DOPE (50:50 mol %), DDAB/DOPE/PEG-PE (50:45:5 mol %), DDAB/EPC (50:50 mol %), DDAB/EPC/PEG-PE (50:45:5, 50:40:10, 50:35:15 mol %), DODAC/DOPE (50:50 mol %), and DODAC/EPC (50:50 mol %) (DDAB, dimethyldioctadecylammonium bromide; DOPE, dioleoylphosphatidylethanolamine; PEG-PE, monomethoxypolyethylene glycol2000 succinate- distearoylphosphatidylethanolamine; EPC, egg phosphatidylcholine; DODAC, dioleoyldimethylammonium chloride). The influence of complex composition and lipid:DNA ratio was evaluated. Particle size was determined before and after complexation and again after sonication using the quasi-elastic light scattering technique. DNA integrity was assessed via agarose gel electrophoresis. Finally, gene transfection was evaluated using CHO cells that were transfected in vitro with sonicated and unsonicated complexes. It is established in this study that size reduction can occur, but this is dependent on cationic and neutral lipid composition and, in some cases, lipid:DNA ratio. Surprisingly, the process of sonication leaves a significant percentage of the plasmid DNA intact and capable of in vitro transfection. This study shows that plasmid DNA can be protected from damage due to sonication by liposome complex formation. This may indicate that more common pharmaceutical methods for size reduction which subject particles to mechanical stress may be applicable in preparation of liposome/DNA formulations for in vivo application.     

Cytotoxic effects of topotecan combined with various anticancer agents in human cancer cell lines

BACKGROUND: Topotecan (TPT) is a topoisomerase I poison that exhibits antineoplastic activity. Analysis of the cytotoxic effects of combinations of TPT and other anticancer agents has been limited. PURPOSE: We assessed the cytotoxic effects produced by combinations of TPT and other antineoplastic agents in experiments involving multiple human cancer cell lines of diverse histologic origins. METHODS: The cytotoxic effects of various antimetabolites (fluorouracil, methotrexate, or cytarabine), antimicrotubule agents (vincristine or paclitaxel [Taxol]), DNA alkylating agents (melphalan, bis[chloroethyl]nitrosourea [BCNU], or 4-hydroperoxycyclophosphamide [4HC]), and a DNA-platinating agent (cisplatin), alone and in combination with TPT, were measured in clonogenic (i.e., colony-forming) assays. HCT8 ileocecal adenocarcinoma, A549 non-small-cell lung carcinoma, NCI-H82ras(H) lung cancer, T98G glioblastoma, and MCF-7 breast cancer cell lines were used in these assays. The data were analyzed by the median effect method, primarily under the assumption that drug mechanisms of action were mutually nonexclusive (i.e., completely independent of one another). For each level of cytotoxicity (ranging from 5% to 95%), a drug combination index (CI) was calculated. A CI less than 1 indicated synergy (i.e., the effect of the combination was greater than that expected from the additive effects of the component agents), a CI equal to 1 indicated additivity, and a CI greater than 1 indicated antagonism (the effect of the combination was less than that expected from the additive effects of the component agents). RESULTS: When the mechanisms of drug action were assumed to be mutually nonexclusive, virtually all CIs for combinations of TPT and either antimetabolites or antimicrotubule agents revealed cytotoxic effects that were less than additive. The CIs calculated at low-to-intermediate levels of cytotoxicity for combinations of TPT and the DNA alkylating agents melphalan, BCNU, and 4HC also showed drug effects that were less than additive; in most cases, however, nearly additive or even synergistic effects were observed with these same drug combinations at high levels of cytotoxicity (i.e., at > or = 90% inhibition of colony formation). Results obtained with combinations of TPT and cisplatin varied according to the cell line examined. With A549 cells, less than additive effects were seen at low-to-intermediate levels of cytotoxicity, and more than additive effects were seen at high levels of cytotoxicity. With NCI-H82ras(H) cells, synergy was observed over most of the cytotoxicity range. CONCLUSIONS AND IMPLICATIONS: TPT cytotoxicity appears to be enhanced more by combination with certain DNA-damaging agents than by combination with antimetabolites or antimicrotubule agents. Interactions between TPT and other drugs can vary depending on the cell type examined. Further investigation is required to determine the basis of the observed effects and to determine whether these in vitro findings are predictive of results obtained in vivo.     

Controlled-release products for the control of the estrus cycle in cattle, sheep, goats, deer, pigs, and horses

This paper describes the estrus cycles of a number of livestock breeds and reviews the controlled-release drug delivery systems that are currently available for the purpose of controlled breeding. The bovine estrus cycle is reviewed in detail, and the estrus cycles of other species are described in a manner that highlights similarities and differences between species. Pertinent formulation and pharmacokinetic information about current drug delivery systems is presented and discussed, and recent advances in this area are also described.     

Design,Capital and Operating Costs of Mineral Processing Plants

This paper reviews important aspects of the design of mineral processing plants, emphasizing the different factors which seem to be most important today, when labour and energy represent a high proportion of total costs. Such items as autogenous and semi-autogenous grinding, two-stage classification, large flotation cells, pressure filtration, etc., are discussed. Recent examples of flotation plants are described

Capital cost evaluation is briefly surveyed, as well as generally accepted procedures; relationships with flowsheeting and mill design are specially pointed out

Distribution of operating costs is reported on the basis of processes and elements, and a few examples are fully detailed.     

Development of an epitaxial lift-off technology for II-VI nanostructures using ZnMgSSe alloys

An epitaxial lift-off technique for removing wide bandgap II-VI heterostructures from GaAs substrates has previously been demonstrated using lattice-matched MgS as the sacrificial layer. However, using MgS as an etch release layer prevents its use as a wide bandgap barrier in the rest of the structure. Here, we describe the use of the etch-resistant alloy Zn_.2Mg_.8S_.64Se_.36 which we have developed as a replacement for MgS. We demonstrate that this alloy can be grown by MBE together with MgS in heterostructures and used as a barrier for ZnSe. A ZnSe quantum well with Zn_.2Mg_.8S_.64Se_.36 barriers shows no decrease in photoluminescence intensity after the etching process but shows a shift in emission wavelength associated with the changing strain state.     

Sex cord-stromal and steroid cell tumors of the ovary

Gonadal cell types that derive from the coelomic epithelium (sex cords) or mesenchymal cells of the embryonic gonads include granulosa cells, theca cells, fibroblasts, Leydig cells, and Sertoli cells. Ovarian tumors of these cell types are called sex cord-stromal tumors. This group of tumors represents approximately 8% of ovarian neoplasms and affects all age groups. The more common types are granulosa cell tumors (GCTs), fibrothecomas, and Sertoli-Leydig cell tumors. Sex cord-stromal tumors are of interest partly because of their hormonal effects, which are rare for other ovarian neoplasms. These effects include estrogenic effects (pseudoprecocious puberty, endometrial bleeding, endometrial hyperplasia and carcinoma) and virilization. The variety of gross appearances of these tumors, ranging from large multicystic masses to small solid masses, would appear to preclude a specific radiologic diagnosis. However, in many patients, both clinical and radiologic clues can suggest the diagnosis, including predominantly fibrous content at ultrasound or magnetic resonance imaging (fibrothecoma), large hemorrhagic multicystic mass in a child with pseudoprecocious puberty (juvenile GCT), and associated syndromes such as Peutz-Jeghers syndrome (sex cord tumor with annular tubules) or Ollier disease and Maffucci syndrome (juvenile GCT).