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.     

Moderators of nonverbal indicators of deception: A meta-analytic synthesis.

In many legal proceedings, fact finders scrutinize the demeanor of a defendant or witness, particularly his or her nonverbal behavior, for indicators of deception. This meta-analysis investigated directly observable nonverbal correlates of deception as a function of different moderator variables. Although lay people and professionals alike assume that many nonverbal behaviors are displayed more frequently while lying, of 11 different behaviors observable in the head and body area, only 3 were reliably associated with deception. Nodding, foot and leg movements, and hand movements were negatively related to deception in the overall analyses weighted by sample size. Most people assume that nonverbal behaviors increase while lying; however, these behaviors decreased, whereas others showed no change. There was no evidence that people avoid eye contact while lying, although around the world, gaze aversion is deemed the most important signal of deception. Most effect sizes were found to be heterogeneous. Analyses of moderator variables revealed that many of the observed relationships varied as a function of content, motivation, preparation, sanctioning of the lie, experimental design, and operationalization. Existing theories cannot readily account for the heterogeneity in findings. Thus, practitioners are cautioned against using these indicators in assessing the truthfulness of oral reports. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Vector-entropy optimization-based neural-network approach to imagereconstruction from projections

In this paper we propose a multiobjective decision making based neural-network model and algorithm for image reconstruction from projections. This model combines the Hopfield's model and multiobjective decision making approach. We develop a weighted sum optimization based neural-network algorithm. The dynamical process of the net is based on minimization of a weighted sum energy function and Euler's iteration, and apply this algorithm to image reconstruction from computer-generated noisy projections and Siemens Somatson DR scanner data, respectively. Reconstructions based on this method is shown to be superior to conventional iterative reconstruction algorithms such as the multiplicate algebraic reconstruction technique (MART) and convolution from the point of view of accuracy of reconstruction. Computer simulation using the multiobjective method shows a significant improvement in image quality and convergence behavior over the conventional algorithms     

Gene amplification in a p53-deficient cell line requires cell cycle progression under conditions that generate DNA breakage

Amplification of genes involved in signal transduction and cell cycle control occurs in a significant fraction of human cancers. Loss of p53 function has been proposed to enable cells with gene amplification to arise spontaneously during growth in vitro. However, this conclusion derives from studies employing the UMP synthesis inhibitor N-phosphonacetyl-L-aspartate (PALA), which, in addition to selecting for cells containing extra copies of the CAD locus, enables p53-deficient cells to enter S phase and acquire the DNA breaks that initiate the amplification process. Thus, it has not been possible to determine if gene amplification occurs spontaneously or results from the inductive effects of the selective agent. The studies reported here assess whether p53 deficiency leads to spontaneous genetic instability by comparing cell cycle responses and amplification frequencies of the human fibrosarcoma cell line HT1080 when treated with PALA or with methotrexate, an antifolate that, under the conditions used, should not generate DNA breaks. p53-deficient HT1080 cells generated PALA-resistant variants containing amplified CAD genes at a frequency of >10(-5). By contrast, methotrexate selection did not result in resistant cells at a detectable frequency (<10(-9)). However, growth of HT1080 cells under conditions that induced DNA breakage prior to selection generated methotrexate-resistant clones containing amplified dihydrofolate reductase sequences at a high frequency. These data demonstrate that, under standard growth conditions, p53 loss is not sufficient to enable cells to produce the DNA breaks that initiate amplification. We propose that p53-deficient cells must proceed through S phase under conditions that induce DNA breakage for genetic instability to occur.     

Uncertainty of Predictions of Embankment Dam Breach Parameters

Risk assessment studies considering the failure of embankment dams often require the prediction of basic geometric and temporal parameters of a breach, or the estimation of peak breach outflows. Many of the relations most commonly used to make these predictions were developed from statistical analyses of data collected from historic dam failures. The prediction uncertainties of these methods are widely recognized to be very large, but have never been specifically quantified. This paper presents an analysis of the uncertainty of many of these breach parameter and peak flow prediction methods. Application of the methods and the uncertainty analysis are illustrated through a case study of a risk assessment recently performed by the Bureau of Reclamation for a large embankment dam in North Dakota.     

Maternal complications from tocolytic treatment with beta-mimetics. Three cases of pulmonary edema

We report three cases of pulmonary edema associated with prolonged intravenous tocolytic therapy with beta 2-adrenergic agonists among patients with multiple pregnancies. Although beta 2-adrenergic agonists may have direct myocardial side-effects, the underlying pathophysiologic mechanisms are mainly noncardiogenic. The most important one appears to be the fluid overload, related to amounts of fluids given intravenously and to direct result of beta-sympathomimetic therapy on renal excretion of sodium and water. Neonatal benefit of prolonged tocolytic therapy remains hypothetical. If this strategy is used, the prevention of cardiovascular adverse effects requires an intensive maternal supervision, especially in case of multiple pregnancy, the use of beta 2-adrenergic agonists in concentrated solution in order to reduce the amounts of fluids given intravenously, and the association with progesterone therapy which can reduce the infusion rate and the duration of tocolytic therapy.     

Exact solutions for characterization of electro-elastically graded materials

The present paper deals with a class of functionally graded materials (FGM), called active FGM that has electro-elastically graded material phases. An active FGM system leads to minimization of stress concentration that arises due to mismatch in the electrical and elastic properties of the constituent phases. This work focuses on the characterization of the through thickness stresses of an active FGM subjected to electrical excitation. The structure is comprised of a substrate, an electro-elastically graded layer and an active layer. A formulation for exact solutions of the system based on Euler–Bernoulli theory is presented. Power-law variation of the composition of the two phases in the graded layer is considered. Performance of linearly gradient FGM for a range of stiffness and electrical property ratios of the active and substrate materials have been studied. It is observed that the electrical strain component and the compositional gradation significantly influence the stress characteristics of the active FGM.     

"即连即铸"的奥钢联连铸技术

1前言 生产率和作业率方面的收益以及可能性调整的灵活性是提高钢铁工业竞争力的关键因素.     

Influence of high titers of maternal antibody on the serologic response of infants to diphtheria vaccination at three, five and twelve months of age

Diphtheria antitoxin was determined in serum from 44 pregnant women, of whom 26 had received one injection of diphtheria toxoid during pregnancy. Their infants were vaccinated with a combined diphtheria-tetanus vaccine at 3, 5 and 12 months of age. This vaccination schedule has been used in Sweden since 1986, replacing the old schedule of vaccination at 3, 4.5 and 6 months of age originally designed for diphtheria-tetanus-pertussis vaccine, which had not been used after cessation of general vaccination against pertussis in 1979. Serum samples from the infants were obtained at 3, 7 and 18 months of age. After 2 injections infants of mothers with high antitoxin titers, > or = 0.1 IU/ml, tended to have lower antitoxin titers than infants of mothers with low antitoxin concentrations (P = 0.067). All children had, however, antitoxin above the minimum protective level of 0.01 IU/ml. Median antitoxin titers were 1.6 IU/ml in both groups after the third booster injection. Four infants of mothers who had been vaccinated during pregnancy and who had titers of > or = 0.4 IU/ml did not reach the 0.1 IU/ml level after 2 injections: all 4 responded with high antitoxin titers after the third dose. Thus all infants were primed by 2 doses of vaccine, irrespective of maternal antibody concentration. The repressive effect of maternal antibody on titers noted after 2 doses was no longer observed after the third, booster dose.