Chimeric human papilloma virus-simian/human immunodeficiency virus virus-like-particle vaccines: Immunogenicity and protective efficacy in macaques

Vaccines to efficiently block or limit sexual transmission of both HIV and human papilloma virus (HPV) are urgently needed. Chimeric virus-like-particle (VLP) vaccines consisting of both multimerized HPV L1 proteins and fragments of SIV gag p27, HIV-1 tat, and HIV-1 rev proteins (HPV-SHIV VLPs) were constructed and administered to macaques both systemically and mucosally. An additional group of macaques first received a priming vaccination with DNA vaccines expressing the same SIV and HIV-1 antigens prior to chimeric HPV-SHIV VLP boosting vaccinations. Although HPV L1 antibodies were induced in all immunized macaques, weak antibody or T cell responses to the chimeric SHIV antigens were detected only in animals receiving the DNA prime/HPV-SHIV VLP boost vaccine regimen. Significant but partial protection from a virulent mucosal SHIV challenge was also detected only in the prime/boosted macaques and not in animals receiving the HPV-SHIV VLP vaccines alone, with three of five prime/boosted animals retaining some CD4+ T cells following challenge. Thus, although some immunogenicity and partial protection was observed in non-human primates receiving both DNA and chimeric HPV-SHIV VLP vaccines, significant improvements in vaccine design are required before we can confidently proceed with this approach to clinical trials. (C) 2002 Elsevier Science (USA).

On the fast approximation of Green's functions in MPIE formulations for planar layered media

The numerical implementation of the complex image approach for the Green's function of a mixed-potential integralequation formulation is examined and is found to be limited to low values of k(0) rho (in this context k(0) rho = 2 pirho/ lambda(0), where rho is the distance between the source and the field points of the Green's function and lambda(0) is the free space wavelength). This is a clear limitation for problems of large dimension or high frequency where this limit is easily exceeded. This paper examines the various strategies and proposes a hybrid method whereby most of the above problems can be avoided. An efficient integral method that is valid for large k(0) rho is combined with the complex image method in order to take advantage of the relative merits of both schemes. It is found that a wide overlapping region exists between the two techniques allowing a very efficient and consistent approach for accurately calculating the Green's functions. In this paper, the method developed for the computation of the Green's function is used for planar structures containing both lossless and lossy media.

Atom lasers, coherent states, and coherence II. Maximally robust ensembles of pure states

As discussed in the preceding paper [Wiseman and Vaccaro, preceding paper, Phys. Rev. A 65, 043605 (2002)], the stationary state of an optical or atom laser far above threshold is a mixture of coherent field states with random phase, or, equivalently, a Poissonian mixture of number states. We are interested in which, if either, of these descriptions of rho(ss) as a stationary ensemble of pure states, is more natural. In the preceding paper we concentrated upon the question of whether descriptions such as these are physically realizable (PR). In this paper we investigate another relevant aspect of these ensembles, their robustness. A robust ensemble is one for which the pure states that comprise it survive relatively unchanged for a long time under the system evolution. We determine numerically the most robust ensembles as a function of the parameters in the laser model: the self-energy chi of the bosons in the laser mode, and the excess phase noise nu. We find that these most robust ensembles are PR ensembles, or similar to PR ensembles, for all values of these parameters. In the ideal laser limit (nu=chi=0), the most robust states are coherent states. As the phase noise or phase dispersion is increased through nu or the self-interaction of the bosons chi, respectively, the most robust states become more and more amplitude squeezed. We find scaling laws for these states, and give analytical derivations for them. As the phase diffusion or dispersion becomes so large that the laser output is no longer quantum coherent, the most robust states become so squeezed that they cease to have a well-defined coherent amplitude. That is, the quantum coherence of the laser output is manifest in the most robust PR ensemble being an ensemble of states with a well-defined coherent amplitude. This lends support to our approach of regarding robust PR ensembles as the most natural description of the state of the laser mode. It also has interesting implications for atom lasers in particular, for which phase dispersion due to self-interactions is expected to be large.

Electric-field-induced Mott insulating states in organic field-effect transistors

We consider the possibility that the electrons injected into organic field-effect transistors are strongly correlated. A single layer of acenes can be modeled by a Hubbard Hamiltonian similar to that used for the κ-(BEDT-TTF)2X family of organic superconductors. The injected electrons do not necessarily undergo a transition to a Mott insulator state as they would in bulk crystals when the system is half-filled. We calculate the fillings needed for obtaining insulating states in the framework of the slave-boson theory and in the limit of large Hubbard repulsion U. We also suggest that these Mott states are unstable above some critical interlayer coupling or long-range Coulomb interaction.

Apoptosis in the pathogenesis of renal disease with a focus on tubulointerstitial injury

Renal cell apoptosis is important not only in normal physiological conditions of the kidney but also in pathological processes. In normal renal development, it removes unwanted, damaged or harmful cells, and in the healthy adult kidney, it maintains cellular homeostasis by regulating the balance between cell proliferation and cell loss. The apoptotic process has now been described in the pathogenesis and prognosis of certain renal diseases with both beneficial and detrimental roles. It causes deletion of cells intrinsic to the kidney after, for example, toxic, ischaemic, immune or radiation damage, and this loss can be destructive and can cause significant reduction of renal function. In contrast, it can control and limit inflammatory processes in both the acute and chronic phases of renal disease. Information on the positive and negative outcomes of renal cell apoptosis, plus the thousands of publications on more general aspects of apoptosis mechanisms, have now presented real opportunities for the development of therapies that selectively delete or protect certain renal cell populations. This review will discuss some of the more general aspects of renal cell apoptosis and then concentrate on the detrimental or beneficial roles of apoptosis in the initiation, progression or resolution of selected, mainly tubulointerstitial, renal diseases.

Interacting roles of myofibroblasts, apoptosis and fibrogenic growth factors in the pathogenesis of renal tubulo-interstitial fibrosis

The interrelationship between myofibroblasts and fibrogenic growth factors in the pathogenesis of renal fibrosis is poorly defined. A temporal and spatial analysis of myofibroblasts, their proliferation and death, and presence of transforming growth factor-beta1 (TGF-beta1) and platelet-derived growth factor-B (PDGF-B) was carried out in an established rodent model in which chronic renal scarring and fibrosis occurs after healed renal papillary necrosis (RPN), similar to that seen with analgesic nephropathy. Treated and control groups (N = 6 and 4, respectively) were compared at 2, 4, 8 and 12 weeks. A positive relationship was found between presence of tubulo-interstitial myofibroblasts and development of fibrosis. Apoptotic myofibroblasts were identified in the interstitium and their incidence peaked 2 weeks after treatment. Levels of interstitial cell apoptosis and fibrosis were negatively correlated over time (r = -0.57, p < 0.01 ), suggesting that as apoptosis progressively failed to limit myofibroblast numbers, fibrosis increased. In comparison with the diminishing apoptosis in the interstitium, the tubular epithelium had progressively increasing levels of apoptosis over time, indicative of developing atrophy of nephrons. TGF-beta1 protein expression had a close spatial and temporal association with fibrosis and myofibroblasts, whilst PDGF-B appeared to have a closer link with populations of other chronic inflammatory cells such as infiltrating lymphocytes. Peritubular myofibroblasts were often seen near apoptotic cells in the tubular epithelium, suggestive of a paracrine toxic effect of factor/s secreted by the myofibroblasts. In vitro , TGF-beta1 was found to be toxic to renal tubular epithelial cells. These findings suggest an interaction between myofibroblasts, their deletion by apoptosis, and the presence of the fibrogenic growth factor TGF-beta1 in renal fibrosis, whereby apoptotic deletion of myofibroblasts could act as a controlling factor in progression of fibrosis.

Computation of the linear elastic properties of random porous materials with a wide variety of microstructure

A finite-element method is used to study the elastic properties of random three-dimensional porous materials with highly interconnected pores. We show that Young's modulus, E, is practically independent of Poisson's ratio of the solid phase, nu(s), over the entire solid fraction range, and Poisson's ratio, nu, becomes independent of nu(s) as the percolation threshold is approached. We represent this behaviour of nu in a flow diagram. This interesting but approximate behaviour is very similar to the exactly known behaviour in two-dimensional porous materials. In addition, the behaviour of nu versus nu(s) appears to imply that information in the dilute porosity limit can affect behaviour in the percolation threshold limit. We summarize the finite-element results in terms of simple structure-property relations, instead of tables of data, to make it easier to apply the computational results. Without using accurate numerical computations, one is limited to various effective medium theories and rigorous approximations like bounds and expansions. The accuracy of these equations is unknown for general porous media. To verify a particular theory it is important to check that it predicts both isotropic elastic moduli, i.e. prediction of Young's modulus alone is necessary but not sufficient. The subtleties of Poisson's ratio behaviour actually provide a very effective method for showing differences between the theories and demonstrating their ranges of validity. We find that for moderate- to high-porosity materials, none of the analytical theories is accurate and, at present, numerical techniques must be relied upon.

Model specification tests in nonparametric stochastic regression models

In this paper, we consider testing for additivity in a class of nonparametric stochastic regression models. Two test statistics are constructed and their asymptotic distributions are established. We also conduct a small sample study for one of the test statistics through a simulated example. (C) 2002 Elsevier Science (USA).

Racialised schooling, 'ethnic success' and Asian-Australian students

Based on discussions with Asian-Australian young women at a mixed-sex, Australia State high school, this article argues that the pro-school conformity of Asian-Australian young women sets them in a problematic and precarious relationship to the material and symbolic and processes of racialisation. The first part of the article identifies the limitations of research into the pro-school/anti-school orientations of minority students, arguing that most accounts are based on theories of culture, acculturation, class and gender, and class and race that neglect an analysis of race and sex. I then argue that practices of racialisation and sexualisation actually sustain pro-school culture and Asian female group associations. While these formations are effective in securing Asian female educational success, they are also problematic because they limit the educational possibilities and employment opportunities of Asian young women in Australia.

Propagation of nonstationary curved and stretched premixed flames with multistep reaction mechanisms

The propagation speed of a thin premixed flame disturbed by an unsteady fluid flow of a larger scale is considered. The flame may also have a general shape but the reaction zone is assumed to be thin compared to the flame thickness. Unlike in preceding publications, the presented asymptotic analysis is performed for a general multistep reaction mechanism and, at the same time, the flame front is curved by the fluid flow. The resulting equations define the propagation speed of disturbed flames in terms of the properties of undisturbed planar flames and the flame stretch. Special attention is paid to the near-equidiffusion limit. In this case, the flame propagation speed is shown to depend on the effective Zeldovich number Z(f) , and the flame stretch. Unlike the conventional Zeldovich number, the effective Zeldovich number is not necessarily linked directly to the activation energies of the reactions. Several examples of determining the effective Zeldovich number for reduced combustion mechanisms are given while, for realistic reactions, the effective Zeldovich number is determined from experiments. Another feature of the present approach is represented by the relatively simple asymptotic technique based on the adaptive generalized curvilinear system of coordinates attached to the flame (i.e., intrinsic disturbed flame equations [IDFE]).

Determinants of tissue Doppler measures of regional diastolic function during dobutamine stress echocardiography

Background Diastolic dysfunction induced by ischemia may alter transmitral blood flow, but this reflects global ventricular function, and pseudonormalization may occur with increased preload. Tissue Doppler may assess regional diastolic function and is relatively load-independent, but limited data exist regarding its application to stress testing. We sought to examine the stress response of regional diastolic parameters to dobutomine echocardiography (DbE). Methods Sixty-three patients underwent study with DbE: 20 with low probability of coronary artery disease (CAD) and 43 with CAD who underwent angiography. A standard DbE protocol was used, and segments were categorized as ischemic, scar, or normal. Color tissue Doppler was acquired at baseline and peak stress, and waveforms in the basal and mid segments were used to measure early filling (Em), late filling (Am), and E deceleration time. Significant CAD was defined by stenoses >50% vessel diameter. Results Diastolic parameters had limited feasibility because of merging of Em and Am waves at high heart rates and limited reproducibility. Nonetheless, compared with normal segments, segments subtended with significant stenoses showed a lower Em velocity at rest (6.2 +/- 2.6 cm/s vs 4.8 +/- 2.2 cm/s, P < .0001) and peak (7.5 +/- 4.2 cm/s vs 5.1 +/- 3.6 cm/s, P < .0001), Abnormal segments also showed a shorter E deceleration time (51 +/- 27 ms vs 41 +/- 27 ms, P = .0001) at base and peak. No changes were documented in Am. The same pattern was seen with segments identified as ischemic with wall motion score. However, in the absence of ischemia, segments of patients with left ventricular hypertrophy showed a lower Em velocity, with blunted Em responses to stress. Conclusion Regional diastolic function is sensitive to ischemia. However, a number of practical limitations limit the applicability of diastolic parameters for the quantification of stress echocardiography.

Enterohepatic circulation - Physiological, pharmacokinetic and clinical implications

Enterohepatic recycling occurs by biliary excretion and intestinal reabsorption of a solute, sometimes with hepatic conjugation and intestinal deconjugation. Cycling is often associated with multiple peaks and a longer apparent half-life in a plasma concentration-time profile. Factors affecting biliary excretion include drug characteristics (chemical structure, polarity and molecular size), transport across sinusoidal plasma membrane and canniculae membranes, biotransformation and possible reabsorption from intrahepatic bile ductules. Intestinal reabsorption to complete the enterohepatic cycle may depend on hydrolysis of a drug conjugate by gut bacteria. Bioavailability is also affected by the extent of intestinal absorption, gut-wall P-glycoprotein efflux and gut-wall metabolism. Recently, there has been a considerable increase in our understanding of the role of transporters, of gene expression of intestinal and hepatic enzymes, and of hepatic zonation. Drugs, disease and genetics may result in induced or inhibited activity of transporters and metabolising enzymes. Reduced expression of one transporter, for example hepatic canalicular multidrug resistance-associated protein (MRP) 2, is often associated with enhanced expression of others, for example the usually quiescent basolateral efflux MRP3, to limit hepatic toxicity. In addition, physiologically relevant pharmacokinetic models, which describe enterohepatic recirculation in terms of its determinants (such as sporadic gall bladder emptying), have been developed. In general, enterohepatic recirculation may prolong the pharmacological effect of certain drugs and drug metabolites. Of particular importance is the potential amplifying effect of enterohepatic variability in defining differences in the bioavailability, apparent volume of distribution and clearance of a given compound. Genetic abnormalities, disease states, orally administered adsorbents and certain coadministered drugs all affect enterohepatic recycling.

Detection of West Nile virus antigen in mosquitoes and avian tissues by a monoclonal antibody-based capture enzyme immunoassay

An antigen capture immunoassay to detect West Nile (WN) virus antigen in infected mosquitoes and avian tissues has been developed. With this assay purified WN virus was detected at a concentration of 32 pg/0.1 ml, and antigen in infected suckling mouse brain and laboratory-infected mosquito pools could be detected when the WN virus titer was 10(2.1) to 10(3.7) PFU/0.1 ml. In a blindly coded set of field-collected mosquito pools (n = 100), this assay detected WN virus antigen in 12 of 18 (66.7%) TaqMan-positive pools, whereas traditional reverse transcriptase PCR detected 10 of 18 (55.5%) positive pools. A sample set of 73 organ homogenates from naturally infected American crows was also examined by WN virus antigen capture immunoassay and TaqMan for the presence of WN virus. The antigen capture assay detected antigen in 30 of 34 (88.2%) TaqMan-positive tissues. Based upon a TaqMan-generated standard curve of infectious WN virus, the limit of detection in the antigen capture assay for avian tissue homogenates was approximately 10(3) PFU/0.1 ml. The recommended WN virus antigen capture protocol, which includes a capture assay followed by a confirmatory inhibition assay used to retest presumptive positive samples, could distinguish between the closely related WN and St. Louis encephalitis viruses in virus-infected mosquito pools and avian tissues. Therefore, this immunoassay demonstrates adequate sensitivity and specificity for surveillance of WN virus activity in mosquito vectors and avian hosts, and, in addition, it is easy to perform and relatively inexpensive compared with the TaqMan assay.

Ab initio modelling of basal plane oxidation of graphenes and implications for modelling char combustion

Ab initio calculations have been performed to determine the energetics of oxygen atoms adsorbed onto graphene planes and the possible reaction path extracting carbon atorns in the form of carbon monoxide. Front the energetics it is confirmed that this reaction path will not significantly contribute to the gasification of well ordered carbonaceous chars. Modelling results which explore this limit Lire presented. (C) 2002 Elsevier Science Ltd, All rights reserved.

Implementing the quantum random walk

Recently, several groups have investigated quantum analogues of random walk algorithms, both on a line and on a circle. It has been found that the quantum versions have markedly different features to the classical versions. Namely, the variance on the line, and the mixing time on the circle increase quadratically faster in the quantum versions as compared to the classical versions. Here, we propose a scheme to implement the quantum random walk on a line and on a circle in an ion trap quantum computer. With current ion trap technology, the number of steps that could be experimentally implemented will be relatively small. However, we show how the enhanced features of these walks could be observed experimentally. In the limit of strong decoherence, the quantum random walk tends to the classical random walk. By measuring the degree to which the walk remains quantum, '' this algorithm could serve as an important benchmarking protocol for ion trap quantum computers.