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.     

Modeling ion implantation of HgCdTe

Ion implantation of boron is used to create n on p photodiodes in vacancy-doped mercury cadmium telluride (MC.T). The junction is formed by Hg interstitials from the implant damage region diffusing into the MC.T and annihilating Hg vacancies. The resultant doping profile is n⁺/n^-/p, where the n⁺ region is near the surface and roughly coincides with the implant damage, the n^- region is where Hg vacancies have been annihilated revealing a residual grown-in donor, and the p region remains doped by Hg vacancy double acceptors. We have recently developed a new process modeling tool for simulating junction formation in MC.T by ion implantation. The interstitial source in the damage region is represented by stored interstitials whose distribution depends on the implant dose. These interstitials are released into the bulk at a constant, user defined rate. Once released, they diffuse away from the damage region and annihilate any Hg vacancies they encounter. In this paper, we present results of simulations using this tool and show how it can be used to quantitatively analyze the effects of variations in processing conditions, including implant dose, annealing temperature, and doping background.     

Evidence for the presence of sodium- and potassium-dependent adenosine triphosphatase alpha1 and beta1 subunit isoforms and their probable role in blastocyst expansion in the preattachment horse conceptus

Two Caribbean hair sheep breeds, the St. Croix (SC) and Barbados Blackbelly (BB), are found in the United States, and the SC has led to the development of the Katahdin (K), a synthetic breed of hair sheep. These breeds have mature ewe BW ranging from 32 to 54 kg (for BB and SC) and from 55 to 73 kg (K). Hair sheep and hair sheep crosses have lower rectal temperatures and respiration rates than wool breeds and a lower DMI and water intake. There are indications of increased resistance to internal parasites in hair sheep. Although hair sheep are seasonal breeders under U.S. photoperiodic conditions, they tend to perform better under accelerated lambing systems than traditional wool breeds. Fertility, prolificacy, and lamb survival is high in BB and SC, but hair x wool crossbred ewes tend to have a higher level of fertility than hair and wool parent breeds. Ewe productivity is also higher in hair x wool crosses than in wool crosses, particularly when adjusted for ewe BW or under accelerated lambing systems. Hair sheep have a lower ADG and intake of high-energy diets, as well as a lower gain/feed ratio, than wool breeds. Growth rates tend to be higher in SC than in BB. Differences in carcass characteristics are inconsistent between hair and wool breeds. Production characteristics of hair sheep, particularly hair x wool crosses, make them suitable for low-input, sustainable production systems that do not require high growth rates and large carcasses. There is a need to preserve the existing U.S. hair sheep germplasm base in support of such systems.     

UTEC and Ferut: the University of Toronto's computation centre

Although not well known, the University of Toronto had a very early computer-development program and in 1952 was one of the first few institutions with an operable computer in North America. This article describes the university's initial attempt to build the UTEC computer and how it acquired the pioneering Ferut machine     

Cell-mediated immunological responses in cervical and vaginal cancer patients immunized with a lipidated epitope of human papillomavirus type 16 E7

Human papillomavirus (HPV) infection has been causally associated with cervical cancer. We tested the effectiveness of an HLA-A*0201-restricted, HPV-16 E7 lipopeptide vaccine in eliciting cellular immune responses in vivo in women with refractory cervical cancer. In a nonrandomized Phase I clinical trial, 12 women expressing the HLA-A2 allele with refractory cervical or vaginal cancer were vaccinated with four E786-93 lipopeptide inoculations at 3-week intervals. HLA-A2 subtyping was also performed, and HPV typing was assessed on tumor specimens. Induction of epitope-specific CD8+ T-lymphocyte (CTL) responses was analyzed using peripheral blood leukapheresis specimens obtained before and after vaccination. CTL specificity was measured by IFN-gamma release assay using HLA-A*0201 matched target cells. Clinical responses were assessed by physical examination and radiographic images. All HLA-A*0201 patients were able to mount a cellular immune response to a control peptide. E786-93-specific CTLs were elicited in 4 of 10 evaluable HLA-A*0201 subjects before vaccination, 5 of 7 evaluable HLA-A*0201 patients after two vaccinations, and 2 of 3 evaluable HLA-A*0201 cultures after all four inoculations. Two of three evaluable patients' CTLs converted from unreactive to reactive after administration of all four inoculations. There were no clinical responses or treatment toxicities. The ability to generate specific cellular immune responses is retained in patients with advanced cervical cancer. Vaccination with a lipidated HPV peptide epitope appears capable of safely augmenting CTL reactivity. Although enhancements of cellular immune responses are needed to achieve therapeutic utility in advanced cervical cancer, this approach might prove useful in treating preinvasive disease.     

Deformation behavior of HCP Ti-Al alloy single crystals

Single crystals of Ti-Al alloys containing 1.4, 2.9, 5, and 6.6 pct Al (by weight) were oriented for 〈a〉 slip on either basal or prism planes or loaded parallel along the c-axis to enforce a nonbasal deformation mode. Most of the tests were conducted in compression and at temperatures between 77 and 1000 K. Trace analysis of prepolished surfaces enabled identification of the twin or slip systems primarily responsible for deformation. Increasing the deformation temperature, Al content, or both, acted to inhibit secondary twin and slip systems, thereby increasing the tendency toward strain accommodation by a single slip system having the highest resolved stress. In the crystals oriented for basal slip, transitions from twinning to multiple slip and, finally, to basal slip occurred with increasing temperature in the lower-Al-content alloys, whereas for Ti-6.6 pct Al, only basal slip was observed at all temperatures tested. A comparison of the critically resolved shear stress (CRSS) values for basal and prism slip as a function of Al content shows that prism slip is favored at room temperature in pure Ti, but the stress to activate these two systems becomes essentially equal in the Ti-6.6 pct Al crystals over a wide range of temperatures. Compression tests on crystals oriented so that the load was applied parallel to the c-axis showed extensive twinning in lower Al concentrations and 〈c+a〉 slip at higher Al concentrations, with a mixture of 〈c+a〉 slip and twinning at intermediate compositions. A few tests also were conducted in tension, with the load applied parallel to the c-axis. In these cases, twinning was observed, and the resolved shear for plastic deformation by twinning was much lower that that for 〈c+a〉 slip observed in compression loading. This article is based on a presentation made in the symposium entitled “Defect Properties and Mechanical Behavior of HCP Metals and Alloys” at the TMS Annual Meeting, February 11–15, 2001, in New Orleans, Louisiana, under the auspices of the following ASM committees: Materials Science and Critical Technology Sector, Structural Materials Division, Electronic, Magnetic & Photonic Materials Division, Chemistry & Physics of Materials Committee, Joint Nuclear Materials Committee, and Titanium Committee.     

Properties of Carbopol Solutions as Models for Yield-Stress Fluids

ABSTRACT: The effect of pH on the non-Newtonian viscosity (η)of aqueous Carbopol 940 solutions is presented with high resolution (pH increments about 0.4) between pH = 2.8 and 12.7. Aqueous NaOH was used to adjust pH of 1.48 wt % Carbopol solutions. A Contraves viscometer was used to measure steady-flow shear stress at known shear rate (γ) over the range γ= 8 to 195 s⁻¹. Yield stresses and shear-thinning η(γ) were observed. Data were fitted with a Herschel-Bulkley model, whose parameters (including yield stress) were expressed as functions of pH. Comparisons were made of η(γ) to the dynamic viscometric properties η'(ω) and η*(ω) for comparable ranges of γ and frequency (ω): A fairly close match was found between η and η* but η«η'. pH dependence included previously unreported extrema of h(pH) in the range of pH = 6.2 to 6.6. Because of sensitive control of rheological properties with pH, Carbopol solutions can be used to mimic a great range of shear-thinning and yield-stress behavior that should make them useful for model studies directed toward process and equipment design and evaluation.