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.     

Applications of a super element model for non-linear analysis of stiffened box structures

Numerical investigations are carried out to verify the new super element model developed in Reference 1 for non-linear analysis of stiffened box structures. The results presented here are obtained from a variety of examples which are chosen to illustrate the accuracy and convergence of the model in various applications. Good agreement is obtained for most of the problems considered and the present formulation is found to be accurate and economical for preliminary engineering design.     

Effect of crosslinking agent content, monomer functionality, and repeat unit chemistry on properties of unfilled resins

Seven mechanical/physical properties were used to evaluate 10 unfilled resins: eight aromatic dimethacrylates and two urethane dimethacrylates. Physical property tests included compressive strength, Young's modulus in compression, uniaxial tensile strength, intrinsic yield point, toothbrush abrasion, Knoop hardness, and water sorption. Controlled changes were made in the following four material parameters: amount of crosslinking diluent present in the uncured monomer, functionality of the monomer, repeat unit chemistry of the monomer (urethane vs. aromatic structure) and mode of activation (chemical vs. visible light). Polymers containing a high concentration of crosslinking agent (50 wt%) were found to be tougher and to possess lower hardness than materials containing lesser amounts of crosslinking agent. This was attributed to the flexible nature of the triethylene glycol dimethacrylate crosslinking molecule. Exposure to water plasticized the highly crosslinked materials to the degree that the yield point and elastic modulus were effectively lowered. Most of the tested properties were unaffected by differences in functionality except resistance to toothbrush abrasion, which was enhanced for polymers derived from high functionality monomers. The urethane-based polymers sorbed substantially more water than the aromatic-based materials, which presumably resulted in lower values for surface hardness. However, the urethane resins were very tough, and excellent resistance to toothbrush abrasion was observed. Property differences caused by differences in activation mode were small, although the visible light materials did sorb more water.     

Edible vaccine protects mice against Escherichia coli heat-labile enterotoxin (LT): potatoes expressing a synthetic LT-B gene

The authors have designed and constructed a plant-optimize synthetic gene encoding the Escherichia coli heat-labile enterotoxin B subunit (LT-B), for use in transgenic plants as an edible vaccine against enterotoxigenic E. coli. Expression of the synthetic LT-B gene in potato plants under the control of a constitutive promoter yielded increased accumulation of LT-B in leaves and tubers, as compared to the bacterial LT-B gene. The plant-derived LT-B assembled into native pentameric structures as evidenced by its ability to bind ganglioside. The authors demonstrated immunogenicity by feeding mice the raw tubers and comparing the anti-LT-B serum IgG and faecal IgA to that produced in mice gavaged with bacterial LT-B. Mice were fed three weekly doses of 5 g tuber tissue containing either 20 or 50 micrograms LT-B, or gavaged weekly with 5 micrograms of LT-B from recombinant E. coli. One week after the third dose, mice immunized with potato LT-B had higher levels of serum and mucosal anti-LT-B than those gavaged with bacterial LT-B. Mice were challenged by oral administration of 25 micrograms LT, and protection assessed by comparing the gut/carcass mass ratios. Although none of the mice were completely protected, the higher dose potato vaccine compared favourably with the bacterial vaccine. These findings show that an edible vaccine against E. coli LT-B is feasible.     

Memory in sub-clinical obsessive-compulsive checkers

In a series of experiments we extended the research on possible memory deficits in subclinical obsessive-compulsive Ss who reported excessive checking. Using a variety of memory tests we compared 20 subclinical checkers to 20 Ss without obsessive-compulsive symptomatology. Contrary to hypothesis, checkers remembered self-generated words better than read words just as much as did normals, but they were more likely than normals to report thinking they had studied words that, in fact, had not been on the study list. Further, they more often confused whether they read or generated the words at study. Checkers did not appear to perseverate on already-recalled words on repeated free recall tests any more than did normals. However, checkers remembered fewer actions overall and more often misremembered whether they had performed, observed, or written these actions. Such memory deficits may contribute to the development of excessive checking.     

Human thalamic nucleus mediating taste and multiple other sensations related to ingestive behavior

Until now, taste was the only primary sensory modality for which the human central nervous system pathways were unknown. We report sensations evoked by stimulation at microampere current levels in the region of the human thalamic nucleus (ventralis caudalis parvocellularis internis) corresponding to the monkey taste relay nucleus. Stimulation in this region during awake neurosurgical procedures evoked special visceral/somatic (taste/pungent smell), general visceral (fullness of a hollow viscus), as well as painful and nonpainful general somatic sensations. General somatic or visceral sensation was evoked by stimulation at 80% of sites where special visceral/somatic sensation was evoked. These results suggest that primate taste relay mediates multiple sensations in addition to taste.     

Stereotactic radiosurgery of malignant and benign intracranial lesions utilizing a patient rotator

The objective of this survey was to demonstrate whether a primary care track internal medicine residency program emphasizing community-based health care of the urban sick poor trains physicians who will continue to practice in general internal medicine or similar fields. Thirty-five primary care residents (100% of graduates) who trained from 1976 through 1993 in the Adult Primary Care Track of the Internal Medicine Residency Program at St. Vincent's Hospital, New York were used as participants.     

Quantitative patterns in the clinical manifestations of radiation sickness in large laboratory animals exposed to radiation at superlethal doses. The quantitative patterns in the manifestations of radiation sickness in dogs

Radiation sickness manifestations have been studied in dogs exposed to electrons (electron energy 25 MeV) and gamma-neutron radiation (neutron energies of 0.37 and 1.2 MeV) in a wide dose range. Dose-response relationships have been calculated for mortality and some clinical manifestations of the intestinal and cerebral forms of radiation sickness. With regard to mortality, the highest effect has been observed for gamma-neutron radiation with a neutron energy of 1.2 MeV. For equal physical doses and for those equally effective in relation to mortality, clinical manifestations of damage are more prominent following exposure to electrons.