Forward and inverse problems for creep models in viscoelasticity.

This study examines a class of time-dependent constitutive equations used to describe viscoelastic materials under creep in solid mechanics. In nonlinear elasticity, the strain response to the applied stress is expressed via an implicit graph allowing multi-valued functions. For coercive and maximal monotone graphs, the existence of a solution to the quasi-static viscoelastic problem is proven by applying the Browder-Minty fixed point theorem. Moreover, for quasi-linear viscoelastic problems, the solution is constructed as a semi-analytic formula. The inverse viscoelastic problem is represented by identification of a design variable from non-smooth measurements. A non-empty set of optimal variables is obtained based on the compactness argument by applying Tikhonov regularization in the space of bounded measures and deformations. Furthermore, an illustrative example is given for the inverse problem of isotropic kernel identification. This article is part of the theme issue 'Non-smooth variational problems with applications in mechanics'.

Effective epidemic model for COVID-19 using accumulated deaths.

The severe acute respiratory syndrome COVID-19 has been in the center of the ongoing global health crisis in 2020. The high prevalence of mild cases facilitates sub-notification outside hospital environments and the number of those who are or have been infected remains largely unknown, leading to poor estimates of the crude mortality rate of the disease. Here we use a simple model to describe the number of accumulated deaths caused by COVID-19. The close connection between the proposed model and an approximate solution of the SIR model provides estimates of epidemiological parameters. We find values for the crude mortality between 10 - 4 and 10 - 3 which are lower than estimated numbers obtained from laboratory-confirmed patients. We also calculate quantities of practical interest such as the basic reproduction number and subsequent increment after relaxation of lockdown and other control measures.

Levy geometric graphs.

We present a family of graphs with remarkable properties. They are obtained by connecting the points of a random walk when their distance is smaller than a given scale. Their degree (number of neighbors) does not depend on the graph's size but only on the considered scale. It follows a gamma distribution and thus presents an exponential decay. Levy flights are particular random walks with some power-law increments of infinite variance. When building the geometric graphs from them, we show from dimensional arguments that the number of connected components (clusters) follows an inverse power of the scale. The distribution of the size of their components, properly normalized, is scale invariant, which reflects the self-similar nature of the underlying process. This allows to test if a graph (including nonspatial ones) could possibly result from an underlying Levy process. When the scale increases, these graphs never tend towards a single cluster, the giant component. In other words, while the autocorrelation of the process scales as a power of the distance, they never undergo a phase transition of percolation type. The Levy graphs may find applications in community detection and in the analysis of collective behaviors as in face-to-face interaction networks.

Expression of the 180-kD ribosome receptor induces membrane proliferation and increased secretory activity in yeast.

Expression of the canine 180-kD ribosome receptor (p180) in yeast cells resulted in a marked proliferation of intracellular membranes. The type of membranes observed varied with the expression of specific portions of p180. Rough membranes predominated when the ribosome binding domain of p180 was present, whereas expression constructs lacking this region resulted in smooth membranes. Northern analysis indicated that expression of the NH(2)-terminal 767 amino acids (DeltaCT), which include the ribosome binding domain, upregulated the transcription and translation of genes involved in exocytosis. The membranes that were proliferated were functional as these cells overcame a temperature-sensitive translocation defect. Most significantly, cells that overexpressed DeltaCT and proliferated rough endoplasmic reticulum exhibited severalfold higher levels of secretion of an ectopically expressed secretory protein. We conclude that p180 expression triggers a cascade of events leading to an increase in secretory potential akin to the terminal differentiation of mammalian secretory cells and tissues.

Neutralization of the AIDS retrovirus by antibodies to a recombinant envelope glycoprotein.

Mammalian cell lines have been engineered to produce a secreted form of the AIDS retrovirus envelope glycoprotein. The recombinant protein has been isolated from growth-conditioned culture media and used to immunize animals. Antibodies directed against the recombinant molecule were found to react with the envelope glycoprotein produced in virus-infected cells. Furthermore, these antibodies were able to directly inactivate the AIDS retrovirus in a neutralization assay in vitro. The expression system reported here should provide sufficient quantities of the AIDS retrovirus envelope protein for biological and vaccination studies.

Comparison of the immune response to recombinant gp120 in humans and chimpanzees.

OBJECTIVE: To assess similarities and differences in antibody responses to recombinant (r) HIV-1IIIB gp120 in chimpanzees, previously protected from HIV-1 infection, and human volunteers immunized in connection with a Phase I clinical trial. METHODS: Frozen sera from humans immunized with rgp120 from HIV-1IIIB and chimpanzees immunized with the same antigen or recombinant soluble gp160 were compared in a variety of serologic assays. RESULTS: The magnitude of the antibody response to gp120 was similar in both species; however, the half-life of the antibody response to rgp120 was approximately 4.5 times longer in humans (9 weeks) than in chimpanzees (2 weeks). Antibodies to gp120 in both species were broadly cross-reactive with gp120 from diverse isolates of HIV-1 and were effective in blocking the binding of gp120 to CD4. Antibody binding to native gp120 was greater than to denatured gp120 in both species. Antibody responses to the principal neutralizing determinant (V3 domain) and virus neutralization titers were approximately 10-fold lower in humans than chimpanzees. The relative avidity of antibody binding to gp120 was higher in the sera from the immunized chimpanzees than in the immunized humans. CONCLUSIONS: While the antibody responses to rgp120 elicited in man and chimpanzees were in many ways similar, significant differences did occur. Predictions made on the basis of chimpanzee immunogenicity studies over-estimated the potency of the virus neutralizing titers and under-estimated the duration of the antibody response achieved in humans.

Environment: peculiar pigment cell neoplasm in fish.

Chromatophoroma in the croaker (Nibea mitsukurii) showed a unique geographic distribution. The contribution of environmental chemicals to the cause of chromatophoroma in the feral croaker is considered likely on the basis of the following results in our studies. 1) Chromatophoroma was induced in tank-reared N. mitsukurii by administration of certain kinds of known carcinogens such as 7,12-dimethyl-benz(a)anthracene, N-methyl-N'-nitro-N-nitrosoguanidine, and nifurpirinol. 2) Local accumulation of pigment-cell hyperplasia in the catfish (Protosus anguillaris) showed similar tendencies to those of chromatophoroma in N. mitsukurii. 3) Removal of contaminated sediment from the harbor and the river appeared to reduce the incidence from 47% in 1973-1983 to about 20% in 1985-1987. 4) Waste water from a factory located at the station where the incidence of the neoplasm was the highest contained mutagenic substances such as chloroacetones and glyoxals [5]. Exposure of catfish to the waste water induced pigment-cell hyperplasia on the skin.

Binding protein-3-selective insulin-like growth factor I variants: engineering, biodistributions, and clearance.

Insulin-like growth factor I (IGF-I) is a potent anabolic peptide that mediates most of its pleiotropic effects through association with the IGF type I receptor. Biological availability and plasma half-life of IGF-I are modulated by soluble binding proteins (IGFBPs), which sequester free IGF-I into high affinity complexes. Elevated levels of specific IGFBPs have been observed in several pathological conditions, resulting in inhibition of IGF-I activity. Administration of IGF-I variants that are unable to bind to the up-regulated IGFBP species could potentially counteract this effect. We engineered two IGFBP-selective variants that demonstrated 700- and 80,000-fold apparent reductions in affinity for IGFBP-1 while preserving low nanomolar affinity for IGFBP-3, the major carrier of IGF-I in plasma. Both variants displayed wild-type-like potency in cellular receptor kinase assays, stimulated human cartilage matrix synthesis, and retained their ability to associate with the acid-labile subunit in complex with IGFBP-3. Furthermore, pharmacokinetic parameters and tissue distribution of the IGF-I variants in rats differed from those of wild-type IGF-I as a function of their IGFBP affinities. These IGF-I variants may potentially be useful for treating disease conditions associated with up-regulated IGFBP-1 levels, such as chronic or acute renal and hepatic failure or uncontrolled diabetes. More generally, these results suggest that the complex biology of IGF-I may be clarified through in vivo studies of IGFBP-selective variants.

The influence of carbohydrate structure on the clearance of recombinant tissue-type plasminogen activator.

Modification of the carbohydrate structures of recombinant tissue-type plasminogen activator (rt-PA) can increase or decrease its rate of clearance in rabbits. When rt-PA was treated with sodium periodate to oxidize carbohydrate residues, the rate of clearance was decreased from 9.6 +/- 1.9 ml min-1 kg-1 to 3.5 +/- 0.6 ml min-1 kg-1 (mean +/- SD, n = 5). A similar change in the clearance of rt-PA was introduced by the use of endo-beta-N-acetyl-glucosaminidase H (Endo-H), which selectively removes high mannose asparagine-linked oligosaccharides; the clearance of Endo-H-treated rt-PA was 5.0 +/- 0.5 ml min-1 kg-1. A mutant of rt-PA was produced with an amino acid substitution at position 117 (Asn replaced with Gln) to remove a potential glycosylation site that normally contains a high mannose structure. The clearance of this material was also decreased, similar to the periodate and Endo-H-treated rt-PA. Conversely, when rt-PA was produced in the CHO 15B cell line, which can produce only high mannose oligosaccharide structures on glycoproteins, the clearance was increased by a factor of 1.8. These results demonstrate that the removal of rt-PA from the blood depends significantly upon the nature of its oligosaccharide structures.

Adhesion mediated by intercellular adhesion molecule 1 attenuates the potency of antibodies that block HIV-1 gp160-dependent syncytium formation.

Several lines of evidence suggest that leukocyte adhesion molecules can promote HIV-1-mediated cell fusion and syncytium formation. In the present studies, the human kidney cell line, 293, was transfected with the envelope glycoprotein gene of the MN strain of HIV-1 alone or cotransfected with a cDNA encoding intercellular adhesion molecule 1 (ICAM-1). It was found that 293 cells transfected with the HIV-1MN env gene expressed the HIV-1 polyglycoprotein precursor, gp160, and the mature gp120-gp41 complex. When mixed with a CD4+ T cell line (CEM), the gp160-transfected cells mediated heterotypic cell fusion and formed multinucleate syncytia. Virus-neutralizing monoclonal antibodies to the V2 and V3 domains of gp120 were able to inhibit syncytium formation, as were monoclonal antibodies to CD4. When ICAM-1 was coexpressed with gp160, syncytium formation between the transfected kidney cells and uninfected CD$+ T cells was markedly enhanced. Inhibitors of HIV-1 infectivity (e.g., monoclonal antibodies to gp120, recombinant soluble CD4) were able to prevent syncytium formation; however, the syncytium-blocking activity of these agents was significantly attenuated in cultures in which ICAM-1 was cotransfected with gp160. These results confirm that leukocyte adhesion molecules can promote gp160-mediated syncytium formation and demonstrate, for the first time, that adhesive interactions mediated by ICAM-1 and its contrareceptor, LFA-1, attenuate the syncytium-inhibiting activity of virus-neutralizing monoclonal antibodies and soluble CD4. These findings suggest that the type and magnitude of leukocyte adhesion molecules expressed on cells may be a significant variable in in vitro HIV-1 neutralization assays.

Monoclonal antibodies to the extracellular domain of HIV-1IIIB gp160 that neutralize infectivity, block binding to CD4, and react with diverse isolates.

Ten monoclonal antibodies prepared against a soluble, recombinant form of gp160, derived from the IIIB isolate of HIV-1, were characterized. Four of the antibodies neutralized HIV-1IIIB infectivity in vitro, three blocked the binding of recombinant gp120 to CD4, three were reactive with gp41, and one preferentially reacted with an epitope on gp120 within the gp160 precursor. All three CD4 blocking antibodies bound to distinct epitopes, with one mapping to the C1 domain, one mapping to the C4 domain, and one reactive with a conformation-dependent, discontinuous epitope. Of these, the antibody reactive with the discontinuous epitope exhibited neutralizing activity against homologous and heterologous strains of HIV-1. The binding of these monoclonal antibodies to a panel of seven recombinant gp120s prepared from diverse isolates of HIV-1 was measured, and monoclonal antibodies with broad cross reactivity were identified. The epitopes recognized by 7 of the 10 monoclonal antibodies studied were localized by their reactivity with synthetic peptides and with fragments of gp120 expressed as fusion proteins in a lambda gt-11 gp160 epitope library.

Regional differences of phospholipase A2 activity in the rabbit oviductal epithelium.

To evaluate the biosynthesis of prostaglandins in the oviducts, phospholipase A2 (EC 3.1.1.4) activities were first measured in the epithelial cells obtained from rabbit oviducts. At least four kinds of phospholipase A2 (PLA2) activities with respect to calcium dependency and pH requirement were observed. There were two calcium-dependent, pH optima of 7.5 and 8.5 activities, and two calcium-independent, pH optima of 4.0 and 8.0 activities. One of those activities, a calcium-dependent and alkaline active PLA2 activity of the epithelial cells was then compared between the ampullary portion and the isthmic portion of the oviducts. The activity was significantly higher in the ampullary epithelium than in the isthmic epithelium (223.2 +/- 57.2 or 103.8 +/- 32.3 pmol/min/mg, p < 0.05). These results support the idea that the production of prostaglandins, which is dependent upon the activity of the arachidonate cascades, was higher in the ampullary portion of oviduct than that in the isthmic portion. The PLA2 activity of the ampullary epithelium may thus play an important role in the regulation of smooth muscle contractility and ciliary movement.

Changes in phospholipase A2 activity of the rabbit ampullary epithelium by ovarian steroids.

Phospholipase A2 (EC 3.1.1.4) activity of the ampullary epithelium from rabbit oviducts was compared in the presence of various ovarian steroids to assess how they could modulate prostaglandins (PG) biosynthesis in the oviduct. The phospholipase A2 (PLA2) activity of the cells from ovariectomized rabbits (control) was 190.8 +/- 9.8 pmol/min/mg. The PLA2 activity of the cells from progesterone-treated rabbits was 156.0 +/- 41.8 pmol/min/mg and was not significantly different from the control activity. However, the PLA2 activity of the cells from the estrogen-treated rabbits was 233.5 +/- 29.0 pmol/min/mg, which was significantly higher than the control activity (p < 0.05). On the other hand, the PLA2 activity of the cells from progesterone-treated rabbits after being primed with estrogen was 116.3 +/- 25.9 pmol/min/mg, which was significantly lower than the control activity (p < 0.01). These results suggest that the effects on PLA2 activity of ovarian steroids could regulate the local production of PG which plays a role in both smooth muscle contractility and ciliary activity.

Effects of two different doses of leuprolide acetate depot on uterine cavity area in patients with uterine leiomyomata.

OBJECTIVE: To compare the effects of two different doses of a monthly depot injection of a GnRH agonist (GnRH-a) on uterine cavity area in patients with uterine leiomyomata. DESIGN: Prospective, randomized study. SETTING: Hospital department of obstetrics and gynecology. PATIENTS: Thirty-six premenopausal women, 25 to 52 years of age, with uterine leiomyomata. INTERVENTION: Leuprolide acetate (LA) depot, 1.88 or 3.75 mg, was administered SC every 4 weeks for 24 weeks. MAIN OUTCOME MEASURE: Uterine cavity area before and after treatment was assessed by hysterosalpingography. RESULTS: The 1.88- and 3.75-mg LA depots significantly reduced uterine cavity area by 40.8% and 40.2%, respectively. No significant difference was observed between the two groups. CONCLUSION: Monthly injection of 1.88 or 3.75 mg LA depots appears to reduce uterine cavity area to a similar extent in patients with uterine leiomyomata.

Efficacy of a low-dose leuprolide acetate depot in the treatment of uterine leiomyomata in Japanese women.

OBJECTIVE: To compare the efficacy of two different doses, 1.88 mg and 3.75 mg, of a monthly depot injection of a gonadotropin-releasing hormone agonist (GnRH-a) in the treatment of uterine leiomyomata. DESIGN: A prospective randomized study. SETTING: Hospital department of gynecology and obstetrics. PATIENTS: Forty-one premenopausal Japanese women, 25 to 53 years of age, with uterine leiomyomata. INTERVENTIONS: Depot type of GnRH-a, leuprolide acetate (LA) 1.88 mg or 3.75 mg was administered subcutaneously every 4 weeks for 24 weeks. MAIN OUTCOME MEASURES: Efficacy of treatment was assessed in terms of uterine volume, serum levels of estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and adverse symptoms during treatment. RESULTS: In both groups, a significant reduction in uterine volume, 52% in 1.88 mg group and 47% in 3.75 mg group, was obtained at week 24, with near maximal reduction (41%, 45%) apparent by 12 weeks. No significant difference was observed between the groups in percent uterine volume reduction at each treatment week. Both groups showed significant and equal suppression of serum levels of E2, LH, and FSH. In addition, the incidence of adverse symptoms was not significantly different between the two groups. CONCLUSIONS: Monthly injection of 1.88 mg or 3.75 mg LA depot has equivalent treatment efficacy in reducing uterine volume. Twelve weeks of treatment is enough to obtain near maximal reduction.

Vascular pedicle transposition of an ovary with subsequent intrauterine pregnancy.

In a patient who underwent both a right salpingectomy because of right tubal pregnancy and left ovarian cystectomy due to an ovarian cyst, we performed an operation whereupon the normal right ovary was shifted toward the position of the left ovary together with the pelvic infundibular ligament. By observation of the ovarian follicle through ultrasonic tomography, the follicle, as seen only from the right preoperatively, was seen only from the left after the operation. The patient delivered a baby by normal pregnancy 3 months after the operation. This method requires no complicated technique and could prove to be a promising therapeutic procedure treating patients with infertility.

Correlation between microvessel density and tumor cell proliferation with clinical factors in breast carcinomas.

Fifty-nine methacarn-fixed, paraffin-embedded human breast carcinomas were immunostained by QB-END/10 (an antibody to CD34 antigen) to observe microvessels and by PC10 (an antibody to proliferating cell nuclear antigen; PCNA) to determine tumor cell proliferation; 9 normal human breast tissue specimens were also immunostained by QB-END/10. The number of microvessels in the periphery of the breast carcinoma was significantly greater than both that in the center of the breast carcinoma and that in the normal breast. There was also a significant relationship between the number of microvessels in the periphery of breast carcinomas and the histological tumor size and lymph node status. However, there was no significant relationship between the tumor cell proliferation activity (PCNA positive cell ratio) and any clinical or histopathological variables. The number of microvessels and the tumor cell proliferation activity showed a weak negative correlation.

Immunohistochemical study of mammary and extramammary Paget's disease.

Immunophenotypes of mammary (MPD) and extramammary Paget's disease (EPD) are still not well understood. Thirty-four formalin-fixed paraffin-embedded tissue sections from 33 patients with 6 MPD and 28 EPD were studied immunohistochemically with the use of polyclonal c-erbB-2 and pS2 antisera, and monoclonal nm23, B6.2, GCDFP-15, and p53 antibodies. Cases of MPD expressed a high incidence of c-erbB-2 and nm23 compared with those of EPD (100% vs. 29%; p < 0.01, and 83% vs. 29%; p < 0.05, respectively). Although high expression of B6.2 (> 83%) and moderate expression of GCDFP-15 (33-39%), pS2 (33-46%) and p53 (39-50%) were seen, the positivity was not significantly different between MPD and EPD. These findings indicate that MPD and EPD share immunohistochemical features but partially differ in their patterns of antigen expression.

High prevalence of Chlamydia trachomatis, Neisseria gonorrhoeae and Mycoplasma genitalium in female commercial sex workers in Japan.

Our objectives were to explore the prevalence of Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma genitalium in Japanese female commercial sex workers (CSWs), in comparison with pregnant women as controls. A high-risk group of 174 female CSWs and 90 asymptomatic pregnant women were enrolled in this study. Detection of C. trachomatis, N. gonorrhoeae, and M. genitalium on the endocervix of the women was performed mainly by using polymerase chain reaction (PCR)-based assays. The prevalence rates of C. trachomatis, N. gonorrhoeae, and M. genitalium were 19.0%, 32.8%, and 12.6%, respectively, in the CSWs, compared with 5.6%, 0%, and 1.1% respectively, in the pregnant women. These results suggest a high prevalence of C. trachomatis, N. gonorrhoeae, and M. genitalium in Japanese CSWs. We conclude that continued close monitoring of the prevalence of C. trachomatis, N. gonorrhoeae, and M. genitalium infection in CSWs is important for preventing the dissemination of these microorganisms, and that further investigation of M. genitalium as a sexually transmitted pathogen in women is needed.

Effects of storage of jaws in saline and of velocity of loading on the force required to extract the rat mandibular first molar.

Storage of jaws in cold saline for up to 32 h did not cause significant changes in the ultimate loads required to extract the rat mandibular first molar. The mean ultimate loads were 33.05, 34.91 and 36.38 newtons at the extension rates 1, 5 and 25 mm/min respectively, though the differences were not significant between groups. The force required to extract the tooth would be fairly constant even after the storage of the dissected jaws in cold saline for longer periods of time. Changes in the force required were not detectable within the range of the velocities of loading employed.