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 effect of the length of a malarial epitope on its antigenicity and immunogenicity in an epitope presentation system using the Pseudomonas aeruginosa outer membrane protein OprF as the carrier

The phenotypic characteristics of three Serpulina pilosicoli strains isolated from humans with diarrhoea (WesB, Kar, Hrm7) and two porcine S. pilosicoli strains isolated from pigs with intestinal spirochaetosis (1648, 3295), were compared with the type strain of the species P43/6/78T (T = type strain) and other intestinal spirochaetes within the genus Serpulina. All S. pilosicoli strains had a characteristic ultrastructural appearance, displayed similar growth rates, hydrolysed hippurate, lacked beta-glucosidase activity, utilised D-ribose as a growth substrate, and had similar sensitivities to rifampicin and spiramycin. The only consistent phenotypic characteristic that differentiated human strains from porcine strains of S. pilosicoli was that the human strains all utilised the pentose sugar D-xylose. These distinguishing phenotypic traits appear useful for identifying S. pilosicoli.     

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.     

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.     

Comparison of two methods of surfactant administration and the effect on dosing-associated hypoxemia

OBJECTIVE: The purpose of our study was to test the hypothesis that surfactant dosing through a proximal sideport adapter on an endotracheal tube leads to more dosing-associated hypoxemia compared with a method of dosing that uses a double-lumen endotracheal tube. STUDY DESIGN: Using adequate sample size to compare significant changes in O2 saturation (power > 0.8, alpha < 0.05) we enrolled 36 infants with respiratory distress syndrome in this randomized trial. A 10% change in O2 saturation was considered clinically significant. Nineteen infants received 38 doses of surfactant through the sideport adapter. Seventeen infants received 31 doses of surfactant through the nonventilation lumen of a double-lumen endotracheal tube. Two main outcome measures were assessed: time-averaged O2 saturation values 30 minutes after dosing and the largest absolute fall in O2 saturation for each patient. RESULTS AND CONCLUSIONS: Time-averaged O2 saturation measures were higher in the proximal sideport group (p = 0.02), but the magnitude of difference was probably not clinically significant. No significant difference was detected between groups when we compared largest absolute drop in O2 saturation. Secondary analyses found no effect of birth weight or dose number (second vs third dose) on either outcome measure.     

Predicting bleaching results with computer imaging

Vital bleaching can be a relatively unpredictable treatment. Photographs of previous cases and cosmetic imaging, although useful, may lead to unrealistic expectations on the part of the patient. The high-tech mystique of computer imaging and viewing one's own teeth has a significant impact on the dental patient. Whether imaged by the dentist or an auxiliary, patients must be aware of alternatives that may exist both before and during treatment. Cosmetic imaging should be used as an adjunct to, not as the prime motivator for, treatment planning in bleaching cases. Excellent communication between the practitioner and patient is the most important factor in assuring positive bleaching results and patient satisfaction.