Harper-dorn creep and specimen size

Under conditions typical of Harper-Dorn (H-D) creep the statistical slip-length may become comparable to, or even exceed, the specimen diameter (a size effect). It is demonstrated that a consequence of such a size effect is that the rates of dislocation storage and dynamic recovery are reduced and the static recovery rate will exceed the dynamic one. Under such conditions, the analysis shows that the creep rate will scale linearly with the applied stress, a characteristic of H-D creep. This article is based on a presentation made in the workshop entitled “Mechanisms of Elevated Temperature Plasticity and Fracture,” which was held June 27–29, 2001, in San Diego, CA, concurrent with the 2001 Joint Applied Mechanics and Materials Summer Conference. The workshop was sponsored by Basic Energy Sciences of the United States Department of Energy.     

Selective employment of chemokine receptors as human immunodeficiency virus type 1 coreceptors determined by individual amino acids within the envelope V3 loop

The chemokine receptor CCR5 acts as an essential cofactor for cell entry by macrophage-tropic human immunodeficiency virus type 1 (HIV-1) strains, whereas CXCR4 acts as an essential cofactor for T-cell-line-adapted strains. We demonstrated that the specific amino acids in the V3 loop of the HIV-1 envelope protein that determine cellular tropism also regulate chemokine coreceptor preference for cell entry by the virus. Further, a strong correlation was found between HIV-1 strains classified as syncytium inducing in standard assays and those using CXCR4 as a coreceptor. These data support the hypothesis that progressive adaptation to additional coreceptors is a key molecular basis for HIV-1 phenotypic evolution in vivo.     

Insulin propeptides in conditions associated with insulin resistance in humans and their relevance to insulin measurements

Routine insulin assays measure not only biologically active insulin but also the relatively inactive propeptides, proinsulin and desdipeptide proinsulin. Such measurements may be misleading if insulin propeptide levels are increased, as has been reported in patients with non-insulin-dependent diabetes mellitus (NIDDM). Inferences regarding insulin resistance, based on hyperinsulinemia, could thus be invalidated where routine insulin assays have been used. We have measured plasma insulin levels using a routine assay, together with measurements of the major circulating insulin propeptides, intact proinsulin and des 31,32proinsulin, in various clinical situations associated with apparently increased insulin levels and insulin resistance. Major increases of insulin propeptide levels relative to insulin levels were not seen in obese subjects or in patients taking oral contraceptives or danazol, or in obese subjects compared with non-obese controls. Although the insulinemic responses observed with routine radioimmunoassay in these situations associated with insulin resistance are not confounded by major changes in the proportion of circulating insulin propeptides, further studies will be necessary to validate investigations in other insulin-resistant states.     

Resistance to atracurium in rats with experimental inflammation: role of protein binding

The influence of altered protein binding on the neuromuscular effect of atracurium has been studied in rats with experimental inflammation induced by subcutaneous injection of turpentine oil. Doses of atracurium ranging from 0.45 to 1.5 mg.kg-1 were administered to control (n = 30) and to experimental inflammation induced rats (n = 30). Neuromuscular transmission was monitored by recording the twitch tension of the tibialis-anterior muscle elicited by stimulation of the sciatic nerve. Three effect parameters were recorded: (i) intensity of the effect, measured as percentage depression of baseline twitch tension, (ii) duration of drug action (min) and (iii) recovery time (min). The dose-intensity of the effect relationship was modelled using a sigmoid Emax model. The ED50 (effective dose eliciting 50% of the maximum effect) was significantly increased (P < 0.01) in the inflammation group as compared to the control group (0.94 vs. 0.68 mg.kg-1). This change was reflected in a shift of the dose-response curve to the right in the pretreated rats. For equipotent doses ED95 (defined as the effective dose eliciting 95% of maximum effect), no differences were found in recovery time and duration of action between the two groups of rats. Mucoproteins levels (index of alpha 1-acid glycoprotein (AAG) and protein binding were significantly increased in rats with experimental inflammation as compared to control rats. Based on these results, altered serum protein binding of atracurium appears to be responsible, at least in part, for the resistance to atracurium.     

Changes in Δ5- and Δ7-sterols during germination and seedling development ofCucurbita maximaduring germination and seedling development ofCucurbita maxima

While seeds ofCucurbita maxima contain both Δ⁵- and Δ⁷-sterols, the former, which have been described earlier, now have been found to disappear during germination. This suggests that a function exists for the Δ⁵-compounds only in the early part of the life cycle ofC. maxima, unlike most of the other higher plants studied. In contrast to the Δ⁵-sterols, the level of Δ⁷-sterols increased during germination as well as during seedling development and maturation. The period of transition between germination and seedling development appeared to be of special importance in terms of sterol changes. This period represented a surge of sterol biosynthesis with an ontogenetic shift in sterol composition from approximately equal amounts of 24α- and 24β-ethyl stereochemistry to a predominance of the former. The sterol composition of the mature plants included only about 5% of the 24β-ethylsterols. The configurational relationships were demonstrated by high resolution¹H-NMR. The sterols of the mature plants were: 25(27)-dehydrochondrillasterol, 24β-ethyl-25(27)-dehydrolathosterol, avenasterol, spinasterol, 22-dihydrospinasterol and 24ξ-methyllathosterol. Based on the changes which occurred in the relative amounts of the Δ⁷-sterols, it did not appear that the Δ⁵-components were being converted to their Δ⁷-analogs. A portion of this work was presented at the meeting of the American Oil Chemists' Society in May, 1985 in Philadelphia.     

Phytohemagglutinin-induced gut hyperplasia and the growth of a mouse lymphosarcoma tumor

OBJECTIVE: To identify possible causes for the increased cardiovascular morbidity and mortality seen in patients with primary hyperparathyroidism. DESIGN: Prospective, blind study. SETTING: University hospital, Sweden. SUBJECTS: 44 Patients with primary hyperparathyroidism and 23 (sex and age matched) control patients with atoxic nodular goitres. INTERVENTIONS: Exploration of the neck with removal of pathological parathyroid glands or thyroid resection. Echocardiography before, and one year after, the operation. MAIN OUTCOME MEASURES: Blood pressure and echocardiographic findings. RESULTS: Hyperparathyroid patients had higher blood pressure and greater left atrial diameter than control patients preoperatively. They also had a significantly lower E:A ratio (mitral flow velocity pattern) than the controls (p = 0.02) indicating a disturbance in early diastolic filling of the left ventricle. The E:A ratio correlated negatively with the systolic blood pressure. 19 of the hyperparathyroid patients (43%) had cardiac calcifications as did 14 (61%) of the controls. Most of calcifications were located in the aortic and mitral valves; only a few patients had calcifications in the myocardium. No significant changes had occurred one year after parathyroidectomy, except for a reduction in systolic blood pressure, in the hyperparathyroid patients. CONCLUSION: Echocardiographic investigation of patients with primary hyperparathyroidism shows early signs of left ventricular dysfunction that may be of clinical importance.     

Investigation of I1-imidazoline receptors using microphysiometry and molecular modelling

A truncated form of SAG1, the immunodominant surface antigen of Toxoplasma gondii, has been produced in the methylotrophic yeast, Pichia pastoris. By construction, the recombinant protein lacks C-terminal residues 308-336 which, in native SAG1, encompass the glycosylphosphatidylinositol anchorage site. Secretion of anchor-less SAG1 proceeded via the yeast prepro alpha-mating factor signal peptide and yielded two immunoreactive protein species having apparent molecular masses of 31.5 and 34.5 kDa, respectively, and differing only by N-glycosylation of the single Asn-X-Ser site present in the molecule. Purification of the anchor-less SAG1 was achieved by a combination of ion-exchange and size-exclusion chromatographies. N-terminal amino acid sequencing of the products indicated the presence of additional residues glutamic acid--alanine at the N-terminal end of the products. Despite incomplete processing and unnatural glycosylation, anchor-less SAG1 proteins apparently adopted a suitable conformation recognized by monoclonal and human serum-derived antibodies, specific for the native SAG1. In addition, the recombinant anchor-less SAG1 proved competent for inducing proliferation, in vitro, of mononuclear cells from seropositive individuals. Finally, properly adjuvanted anchor-less SAG1 was able to induce protection of mice against a lethal challenge with T. gondii tachyzoites.     

Delayed conversion of squalene to sterols during development ofPinus pinea seeds

During germination of seeds of the gymnosperm,Pinus pinea, radioactivity from [2-¹⁴C]-mevalonate proceeded principally through the anaerobic reactions leading to squalene in the first 24 hr in both the haploid endosperm and the diploid embryo, and only with succeeding time (3–9 days) in both cases was label transferred to sterols in oxygen-requiring steps. The rates of turnover must be real and independent in the two tissues, since no consequential interchange of labelled lipids occurred between the endosperm and the embryo. Similar delayed conversion of squalene to sterols has been observed previously during germination of seeds of the angiosperm,Pisum sativum.