Materials modelling: A bridge from atoms to bulk properties

The use of molecular-level materials modelling techniques in the development of advanced performance polymers is discussed, with particular emphasis upon bridging the large difference in the scales of dimensions between atomic structure and fabricated parts. The advantages and disadvantages of bulk quantitative structure-property relations and atomistic modelling are assessed, and the method of group interaction modelling is suggested as a means of bridging the dimensional scales.After a brief introduction to the concept of group interaction modelling, examples of modelling the engineering properties of polymers are presented which are difficult to model quantitatively by any other means. The important phase transitions from the crystal and glassy states of matter to those of rubber- and liquidlike states are shown quantitatively to be due to the same isoenergetic condition. The viscoelastic properties of a polymer are critical for many applications and expressions are derived for the loss and storage components of the complex modulus, with reference to failure initiation conditions. The effect of crosslinking in thermosets upon the glass transition temperature and viscoelastic properties is outlined. Finally, the scaling of time from atomic vibrations to the years involved in creep and ageing effects are discussed.     

Proceedings of the Joint US/EU Workshop: urinary biomarkers to detect significant effects of environmental and occupational exposure to nephrotoxins

Tear cytokines and growth factors are likely to modulate the wound healing process following corneal epithelial injury. Hepatocyte growth factor (HGF) is a paracrine mediator of epithelial proliferation, motility, and differentiation that is produced by keratocytes and the lacrimal gland. Tear samples were collected preoperatively and one, two, and seven days postoperatively in eyes undergoing excimer laser surface ablation [photorefractive keratoplasty (PRK) or phototherapeutic keratoplasty (PTK)]. Tear HGF concentration was measured with a sensitive ELISA assay. Tear HGF production was calculated using the tear flow rate in the collection capillary and HGF concentration. Although the instantaneous concentration of HGF in tears decreased significantly in the days following PRK, a large increase in tear flow resulted in a marked increase in HGF bioavailability. The heparin-binding characteristics of HGF would result in increased binding to glycosaminoglycans and other heparin-like matrix components and, therefore, increased growth factor availability to the cognate recptor. This is the first report documenting changes in tear film HGF production. HGF may have an important function in maintenance and wound healing of the ocular surface epithelium since HGF is present in the normal tear film and the HGF secretion rate increases markedly in parallel with aqueous tear production following corneal surgical injury.     

Identification of the blood-borne somatotroph-differentiating factor during chicken embryonic development

Somatotrophs become a significant population by day 16 of chicken embryonic development. We have previously demonstrated that an earlier induction of GH cell differentiation is possible with the addition of day 16 embryonic serum to cultures of day 12 pituitary cells, an age when somatotrophs are rare. The present study was designed to identify the blood-borne signal(s) responsible for the serum activity, using reverse hemolytic plaque assays to identify individual GH-secreting cells. The activity was found to be a heat-stable, ether-soluble compound(s) that is bound or inhibited by a trypsin-sensitive protein. The extent of GH cell differentiation was greater (P < 0.05; n = 3) in response to the ether phases of heated day 16 (14.1 +/- 0.4% of all cells) and day 12 sera (9.3 +/- 0.4%) than with untreated serum from days 16 and 12 (6.1 +/- 0.4% and 0.82 +/- 0.4%, respectively). Furthermore, ether-extracted day 16 serum was more effective than ether-extracted day 12 serum, which was also different from basal (0.85 +/- 0.4%; P < 0.05). Based on this biochemical profile, the abilities of various steroids to stimulate differentiation were tested. Three steroids were found to stimulate somatotroph differentiation in vitro: 17beta-estradiol, corticosterone, and progesterone. However, the estradiol receptor antagonist, tamoxifen, while abolishing the effect of estradiol, had no effect on the induction of differentiation by day 16 serum. In contrast, RU486, a specific glucocorticoid receptor antagonist in chickens, blocked the stimulatory effects of corticosterone, progesterone, and day 16 serum on somatotroph differentiation. We next tested whether the active compound in day 16 embryonic serum was corticosterone, the predominant glucocorticoid in chickens. Incubation of day 16 serum with corticosterone antiserum, but not control antiserum, suppressed day 16 serum-induced GH cell differentiation. Therefore, we conclude that corticosterone is the blood-borne signal capable of stimulating somatotroph differentiation in vitro. The present findings together with previous reports indicate that somatotroph differentiation during embryonic development may result from an increase in circulating glucocorticoid concentrations.     

Surface localization of the sea urchin egg receptor for sperm

The sea urchin egg receptor for sperm is thought to be involved in species-specific sperm-egg interactions at the egg surface. Recent revisions in the deduced amino acid sequence of the cloned cDNAs indicate that the protein encoded does not possess the common structural hallmarks of a membrane protein. Thus, investigation of the localization and association of the protein with the egg surface is crucial. We describe and characterize a new monoclonal antibody raised against recombinant sperm receptor protein. This antibody, in conjunction with several polyclonal antibodies, was used to study the receptor protein in eggs. Immunoprecipitation studies indicated that the antibodies recognize the high Mr (ca. 350 K) sperm receptor protein which copurified with egg plasma membrane-vitelline layer complexes. The sperm receptor protein was solubilized only by detergents and not by treatments designed to solubilize peripherally associated or lipid-anchored membrane proteins, suggesting a tight association with the membrane fraction. Confocal immunofluorescence microscopy of live eggs indicated surface staining. Finally, lysylendoproteinase C treatment of live eggs resulted in a loss of the high Mr receptor protein epitopes, and the concomitant release of a 70-kDa proteolytic fragment, which correlated with a reduced ability of the eggs to be fertilized. Taken together, these data indicate that at least some fraction of the sperm receptor protein is present on the egg surface, a requisite locale for a sperm binding protein.     

Cytoplasmic tail deletion of T cell receptor (TCR) beta-chain results in its surface expression as glycosylphosphatidylinositol-anchored polypeptide on mature T cells in the absence of TCR-alpha

Surface expression of the T cell antigen receptor (TCR) in mature T cells requires the association of a variable heterodimer (alpha.beta or gamma.delta) with six invariant CD3 polypeptides (gamma, delta, epsilon-epsilon, zeta-zeta, or zeta-eta). We described here that deletion of the cytoplasmic tail polypeptide sequence (Lys-Lys-Lys-Asn-Ser) of TCR beta-chain (beta CT) results in expression of the truncated beta-chain on the surface of a mature T cell hybridoma line, in the absence of TCR-alpha, as a glycophosphatidylinositol (GPI)-anchored monomeric polypeptide. The GPI-anchored TCR-beta CT is not associated with CD3-epsilon and is incapable of conventional signal transduction. Association with TCR-alpha prevents beta CT from GPI-linkage formation. The alpha beta CT heterodimer binds the CD3 polypeptides, and the resultant TCR alpha beta CT/CD3 complex is capable of signal transduction. Our data show that a signal sequence for GPI-linkage formation is present in TCR-beta, and this alternative membrane anchoring mechanism can be utilized by beta-chain polypeptide lacking the CT sequence. We conclude therefore that in the absence of TCR-alpha expression, the beta-chain CT sequence plays an essential function in hindering GPI-linkage formation, thereby preventing escape of incompletely assembled TCR beta-chain to the cell surface of mature T cells.     

Ventricular perforation associated with central venous introducer-dilator systems

BACKGROUND: An erythrocyte sedimentation rate (ESR) of at least 40 mm/h is considered an important requisite for the diagnosis of polymyalgia rheumatica (PMR). However, the relative frequency and clinical features of PMR in patients without a significantly increased ESR are unclear. METHODS: We performed a retrospective study of patients diagnosed as having PMR at the rheumatology divisions of 3 teaching hospitals. The diagnosis of PMR was established, regardless of the ESR, in 201 consecutive patients fulfilling the following criteria: (1) age 50 years or older, (2) severe proximal pain for more than 1 month in at least 2 of 3 areas: neck, shoulder, and/or pelvic girdles, and (3) rapid resolution of the syndrome while taking low-dose prednisone. Patients with giant cell arteritis were previously excluded from the study. The frequency and clinical features of patients with PMR and an ESR lower than 40 mm/h were analyzed. A comparative study between these patients and those with high ESRs was performed. RESULTS: An ESR lower than 40 mm/h was found in 41 patients (20.4%). These patients were younger (P = .02), were more frequently men (P = .006), and experienced a lower frequency of fever (P = .003) and weight loss (P = .07). Furthermore, these patients were characterized by an absence of anemia (P = .002) and a lower frequency of abnormal protein electrophoresis results (P < .001). Otherwise, their clinical syndrome, response to therapy, and frequency of relapses were similar to those of patients with classic PMR. In the entire population of 201 patients, the ESR was related to the length of treatment, number of areas involved, presence of fever, weight loss, and laboratory test result abnormalities, but it was unrelated to the duration of the illness prior to diagnosis. CONCLUSIONS: It is not uncommon to find a patient with PMR with an ESR lower than 40 mm/h. This syndrome is more frequent in men and it is clinically less severe than the classic form of PMR. Its recognition will allow these patients to benefit from an effective treatment with low-dose corticosteroids.     

The stationary-phase-exit defect of cydC (surB) mutants is due to the lack of a functional terminal cytochrome oxidase

The surB gene was identified as a gene product required for Escherichia coli cells to exit stationary phase at 37 degrees C under aerobic conditions. surB was shown to be the same as cydC, whose product is required for the proper assembly and activity of cytochrome d oxidase. Cytochrome d oxidase, encoded by the cydAB operon, is one of two alternate terminal cytochrome oxidases that function during aerobic electron transport in E. coli. Mutations inactivating the cydAB operon also cause a temperature-sensitive defect in exiting stationary phase, but the phenotype is not as severe as it is for surB mutants. In this study, we examined the phenotypes of surB1 delta(cydAB) double mutants and the ability of overexpression of cytochrome o oxidase to suppress the temperature-sensitive stationary-phase-exit defect of surB1 and delta(cydAB) mutants and analyzed spontaneous suppressors of surB1. Our results indicate that the severe temperature-sensitive defect in exiting stationary phase of surB1 mutants is due both to the absence of terminal cytochrome oxidase activity and to the presence of a defective cytochrome d oxidase. Membrane vesicles prepared from wild-type, surB1, and delta(cydAB) strains produced superoxide radicals at the same rate in vitro. Therefore, the aerobic growth defects of the surB1 and delta(cydAB) strains are not due to enhanced superoxide production resulting from the block in aerobic electron transport.