Viral dynamics of primary viremia and antiretroviral therapy in simian immunodeficiency virus infection

Mathematical modeling of viral replication dynamics, based on sequential measurements of levels of virion-associated RNA in plasma during antiretroviral treatment, has led to fundamental new insights into human immunodeficiency virus type 1 pathogenesis. We took advantage of the simian immunodeficiency virus (SIV)-infected macaque model to perform detailed measurements and mathematical modeling during primary infection and during treatment of established infection with the antiretroviral drug (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA). The calculated clearance half-life for productively infected cells during resolution of the peak viremia of primary infection was on the order of 1 day, with slightly shorter clearance half-lives calculated during PMPA treatment. Viral reproduction rates upon discontinuation of PMPA treatment after 2 weeks were approximately twofold greater than those obtained just prior to initiation of treatment in the same animals, likely reflecting accumulation of susceptible target cells during treatment. The basic reproductive ratio (R0) for the spread of SIV infection in vivo, which represents the number of productively infected cells derived from each productively infected cell at the beginning of infection, was also estimated. This parameter quantifies the extent to which antiviral therapy or vaccination must limit the initial spread of virus to prevent establishment of chronic disseminated infection. The results thus provide an important guide for efforts to develop vaccines against SIV and, by extension, human immunodeficiency virus.     

Scheduling DAG's for asynchronous multiprocessor execution

A new approach is given for scheduling a sequential instruction stream for execution “in parallel” on asynchronous multiprocessors. The key idea in our approach is to exploit the fine grained parallelism present in the instruction stream. In this context, schedules are constructed by a careful balancing of execution and communication costs at the level of individual instructions, and their data dependencies. Three methods are used to evaluate our approach. First, several existing methods are extended to the fine grained situation. Our approach is then compared to these methods using both static schedule length analyses, and simulated executions of the scheduled code. In each instance, our method is found to provide significantly shorter schedules. Second, by varying parameters such as the speed of the instruction set, and the speed/parallelism in the interconnection structure, simulation techniques are used to examine the effects of various architectural considerations on the executions of the schedules. These results show that our approach provides significant speedups in a wide-range of situations. Third, schedules produced by our approach are executed on a two-processor Data General shared memory multiprocessor system. These experiments show that there is a strong correlation between our simulation results, and these actual executions, and thereby serve to validate the simulation studies. Together, our results establish that fine grained parallelism can be exploited in a substantial manner when scheduling a sequential instruction stream for execution “in parallel” on asynchronous multiprocessors     

The effects of pressure on the isothermal fluid behavior of bituminous coals

An investigation into the effects of pressure (helium gas) on the isothermal fluid behavior includes: (1) the effect of pressure on the rate of melting and coking as evidenced by the rate constants k(melt) and k(coke); (2) the effect of pressure on the energies of activation of melting and coking; (3) the effects of pressure on the characteristic times; (4) the effects of pressure on the maximum isothermal fluidity. Results from the effects of pressure on k(melt) revealed that it was generally the high total sulfur, low nitrogen, low reactives/mineral matter ratio, medium rank coals which show the greatest increase in k(melt), whereas the highest rank coals show the least decrease in k(coke). The energies of activation of melting and coking were not significantly affected by pressure. The investigation also reveals increases or decreases in the respective times of softening, maximum fluidity, resolidification and total time of fluid behavior under isothermal pressurized conditions. There appears the possibility that these shifts may be rank dependent. Additionally, the lower rank coals show the largest relative increase in their fluidities when subjected to pressure. Empirical relationships were derived in order to quantitatively predict the maximum isothermal fluidity for most (fluid) coals at a given pressure.     

Analytical pyrolysis as a tool for the study of plastic coals

The technique of analytical pyrolysis has been used to characterize 40 similar mid-rank western Kentucky coals of widely differing ASTM Gieseler plasticity. Certain pyrolysis/g.c. variables were shown to correlate well with both ASTM Gieseler and isothermal plasticity. Highly plastic coals were shown to exhibit certain characteristic peaks in the 450 °C pyrogram which were absent in the pyrogram of the non-plastic coals. Two coals, representing the two extremes in plasticity, were selected for further study. After extraction with solvents such as DMF the characteristic peaks were absent in the 450 °C pyrogram of the extraction residue of the highly plastic coal. These peaks were also shown to decrease with increasing severity of air oxidation of the plastic coal. This technique appears to be a useful tool for the analysis of mid-rank plastic coals and supports the view that the substances contained in the bitumen fraction of these coals are involved in the development of the plastic state.     

Artefactual cleavage of E coli H-NS by OmpT

In the bacterium Escherichia coli, H-NS-(H1, H1a) is a heat-stable protein with a molecular mass of 15.5 kDa involved in nucleoid organisation and gene regulation linked to certain signal transduction pathways. We have shown that, following addition of preparations of everted inner membrane vesicles, heat-stable cleavage products of approximately 10 kDa of H-NS are formed in vitro from newly synthesised, radio-labelled H-NS and from purified H-NS. The 15.5 kDa protein and its cleavage products were also recovered from a minicell system. These results raised the possibility that cleavage of H-NS is physiologically significant. However, the cleavage of H-NS observed appears to occur during cell breakage and to depend on the method of protein extraction and the presence of the outer membrane protease, OmpT. Nevertheless, the results indicate that H-NS may contain at least two separate domains with cleavage occurring between these domains at a preferred OmpT site. Failure to take account of H-NS cleavage in sample preparation and analysis can lead to serious underestimation of H-NS levels.     

Na/K pump current in guinea pig cardiac myocytes and the effect of Na leak

INTRODUCTION: Steady-state Na/K pump current (Ip) in adult guinea pig ventricular myocytes was studied to determine the effect on the Na/K pump of transmembrane Na leak, membrane potential, and pipette Na concentration. METHODS AND RESULTS: Using conventional whole cell, patch clamp techniques, Ip was identified as either Ko-sensitive or ouabain-sensitive current when most other membrane currents were inhibited. Control experiments showed that there were no Ko-sensitive currents other than Ip under the conditions of our experiments. Ip was found to be similar to that reported by others being voltage dependent between -130 and 0 mV and having a half maximal activation by Nai of 28 mM. Ouabain sensitivity was also measured, and it was found that there were two binding sites with the high affinity site comprising 5% to 10% of the total and having an apparent affinity 1000-fold higher than the low affinity site. Apparent affinity of both sites was shifted about 10-fold (higher affinity) by increasing Nai from 10 to 85 mM. When internally perfused with 0 Na solution, Na leak through the membrane was found to be linearly related to Na/K pump activity. In contrast to prior suggestions, Ip was not correlated with series resistance when there was a large transmembrane Na gradient. CONCLUSION: These data suggest that, under conditions of high transmembrane Na gradient, Na leak through the membrane plays a significant role in determining Na/K pump activity.     

Gastric ECL-cell hyperplasia produces enhanced basal and stimulated gastric acid output but not gastric erosion formation in the rat

Cervical involvement is one of the major prognostic factors in carcinoma of the endometrium confined to the uterus. The purpose of this study was to determine whether intrauterine ultrasound with a high-frequency miniature probe can depict the degree of cervical involvement of the disease. Thirty-two women with endometrial carcinoma underwent preoperative transvaginal and intrauterine sonography. By both scans, the degree of cervical involvement was prospectively evaluated. Sonograms were compared with the findings from histologic examination. Intrauterine sonography was completed in 30 of the 32 patients. In these 30 patients, the degree of cervical involvement (none, endocervical gland, or cervical stroma) based on transvaginal scan was correct in 23 cases (77%), and that based on intrauterine scan was correct in 26 cases (87%). Three tumors with endocervical glandular involvement were correctly diagnosed by intrauterine sonography, whereas they were incorrectly diagnosed by transvaginal scan. The specificity and positive predictive value of intrauterine sonography for the assessment of the presence of cervical stromal invasion are 100% (26/26 and 3/3, respectively). Although this study is preliminary, our experience with intrauterine sonography shows that it has potential for assessing cervical stromal invasion in endometrial carcinoma.     

Mechanomyography and oxygen consumption during incremental cycle ergometry

Brucella abortus strain RB51 was recently approved as an official brucellosis calfhood vaccine for cattle by the Animal and Plant Health Inspection Service branch of the United States Department of Agriculture. Currently available serologic surveillance tests for B. abortus do not detect seroconversion following SRB51 vaccination. The purpose of this study was to evaluate a dot-blot assay using gamma-irradiated strain RB51 bacteria for its specificity and sensitivity to detect antibody responses of cattle vaccinated with strain RB51. Dot-blot titers of sera at a recommended dosage (10(10) colony-forming units) were similar to those of sera from cattle vaccinated with similar numbers of B. abortus strain 19 and greater (P < 0.05) than titers of nonvaccinated cattle. In the first 12 weeks after vaccination with 10(10) colony-forming units of strain RB51, the RB51 dot-blot assay had 100% specificity for titers of 80 or less and a 53% sensitivity for titers of 160 or greater. Sensitivity of the RB51 dot-blot assay peaked at 4 weeks after vaccination with 10(10) colony-forming units of strain RB51. Dot-blot responses of sera from cattle vaccinated with a reduced dosage of strain RB51 (10(9) colony-forming units) did not differ (P > 0.05) from titers of sera from nonvaccinated cattle. Following intraconjunctival challenge with B. abortus strain 2308, titers on the RB51 dot-blot assay did not differ (P > 0.05) between nonvaccinated cattle and cattle vaccinated at calfhood with strain 19 or strain RB51.