Perforin and interferon-gamma activities independently control tumor initiation, growth, and metastasis

Perforin (pfp) and interferon-gamma (IFN-gamma) together in C57BL/6 (B6) and BALB/c mouse strains provided optimal protection in 3 separate tumor models controlled by innate immunity. Using experimental (B6, RM-1 prostate carcinoma) and spontaneous (BALB/c, DA3 mammary carcinoma) models of metastatic cancer, mice deficient in both pfp and IFN-gamma were significantly less proficient than pfp- or IFN-gamma -deficient mice in preventing metastasis of tumor cells to the lung. Pfp and IFN-gamma -deficient mice were as susceptible as mice depleted of natural killer (NK) cells in both tumor metastasis models, and IFN-gamma appeared to play an early role in protection from metastasis, Previous experiments in a model of fibrosarcoma induced by the chemical carcinogen methylcholanthrene indicated an important role for NK1.1(+) T cells, Herein, both pfp and IFN-gamma played critical and independent roles in providing the host with protection equivalent to that mediated by NK1.1+ T cells, Further analysis demonstrated that IFN-gamma, but not pfp, controlled the growth rate of sarcomas arising in these mice. Thus, this is the first study to demonstrate that host IFN-gamma, and direct cytotoxicity mediated by cytotoxic lymphocytes expressing pfp independently contribute antitumor effector functions that together control the initiation, growth, and spread of tumors in mice, (C) 2001 by The American Society of Hematology.

Hybrid modelling of coupled pore fluid-solid deformation problems

A hybrid formulation for coupled pore fluid-solid deformation problems is proposed. The scheme is a hybrid in the sense that we use a vertex centered finite volume formulation for the analysis of the pore fluid and a particle method for the solid in our model. The pore fluid formally occupies the same space as the solid particles. The size of the particles is not necessarily equal to the physical size of materials. A finite volume mesh for the pore fluid flow is generated by Delaunay triangulation. Each triangle possesses an initial porosity. Changes of the porosity are specified by the translations of the mass centers of particles. Net pore pressure gradients are applied to the particle centers and are considered in the particle momentum balance. The potential of our model is illustrated by means of a simulation of coupled fracture and fluid flow developed in porous rock under biaxial compression condition.

Finite element modelling of three-dimensional convection problems in fluid-saturated porous media heated from below

We use the finite element method to model three-dimensional convective pore-fluid flow in fluid-saturated porous media when they are heated from below. In particular, we employ the particle-tracking technique to mimic the trajectories of particles in three-dimensional fluid flow problems. The related numerical results demonstrated that: (1) The progressive asymptotic approach procedure, which was previously developed for the finite element modelling of two-dimensional convective pore-fluid flow problems, is equally applicable to the finite element modelling of three-dimensional convective pore-fluid flow in fluid-saturated porous media heated from below. (2) The perturbation of gravity at different planes has a significant effect on the pattern of three-dimensional convective pore-fluid flow and therefore, may influence the pattern of orebody formation and mineralization in three-dimensional hydrothermal systems. Copyright (C) 2001 John Wiley & Sons, Ltd.

Experimental methods for studying drug uptake in the head and brain

A number of techniques have been developed to study the disposition of drugs in the head and, in particular, the role of the blood-brain barrier (BBB) in drug uptake. The techniques can be divided into three groups: in-vitro, in-vivo and in-situ. The most suitable method depends on the purpose(s) and requirements of the particular study being conducted. In-vitro techniques involve the isolation of cerebral endothelial cells so that direct investigations of these cells can be carried out. The most recent preparations are able to maintain structural and functional characteristics of the BBB by simultaneously culturing endothelial cells with astrocytic cells,The main advantages of the in-vitro methods are the elimination of anaesthetics and surgery. In-vivo methods consist of a diverse range of techniques and include the traditional Brain Uptake Index and indicator diffusion methods, as well as microdialysis and positron emission tomography. In-vivo methods maintain the cells and vasculature of an organ in their normal physiological states and anatomical position within the animal. However, the shortcomings include renal acid hepatic elimination of solutes as well as the inability to control blood flow. In-situ techniques, including the perfused head, are more technically demanding. However, these models have the ability to vary the composition and flow rate of the artificial perfusate. This review is intended as a guide for selecting the most appropriate method for studying drug uptake in the brain.

Finite element modeling of fluid-rock interaction problems in pore-fluid saturated hydrothermal/sedimentary basins

In order to use the finite element method for solving fluid-rock interaction problems in pore-fluid saturated hydrothermal/sedimentary basins effectively and efficiently, we have presented, in this paper, the new concept and numerical algorithms to deal with the fundamental issues associated with the fluid-rock interaction problems. These fundamental issues are often overlooked by some purely numerical modelers. (1) Since the fluid-rock interaction problem involves heterogeneous chemical reactions between reactive aqueous chemical species in the pore-fluid and solid minerals in the rock masses, it is necessary to develop the new concept of the generalized concentration of a solid mineral, so that two types of reactive mass transport equations, namely, the conventional mass transport equation for the aqueous chemical species in the pore-fluid and the degenerated mass transport equation for the solid minerals in the rock mass, can be solved simultaneously in computation. (2) Since the reaction area between the pore-fluid and mineral surfaces is basically a function of the generalized concentration of the solid mineral, there is a definite need to appropriately consider the dependence of the dissolution rate of a dissolving mineral on its generalized concentration in the numerical analysis. (3) Considering the direct consequence of the porosity evolution with time in the transient analysis of fluid-rock interaction problems; we have proposed the term splitting algorithm and the concept of the equivalent source/sink terms in mass transport equations so that the problem of variable mesh Peclet number and Courant number has been successfully converted into the problem of constant mesh Peclet and Courant numbers. The numerical results from an application example have demonstrated the usefulness of the proposed concepts and the robustness of the proposed numerical algorithms in dealing with fluid-rock interaction problems in pore-fluid saturated hydrothermal/sedimentary basins. (C) 2001 Elsevier Science B.V. All rights reserved.

Hormonal factors and risk of aneurysmal subarachnoid hemorrhage - An international population-based, case-control study

Background and Purpose-Subarachnoid hemorrhage (SAH) is more common in women than in men, but the role of hormonal factors in its etiology remains uncertain. The aim of this study was to examine the relationship between hormonal factors and risk of SAH in women. Methods-This was a prospective, multicenter, population-based, case-control study performed in 4 major urban centers in Australia and New Zealand. Two hundred sixty-eight female cases of first-ever aneurysmal SAH occurred during 1995-1998. Controls were 286 frequency-matched women from the general population of each center. Outcome measures included risk of SAH associated with use of oral contraceptive pills (OCPs), hormone replacement therapy (HRT), and various endogenous hormonal factors including menstrual patterns, parity, age at birth of first child, and breast-feeding practices. Results-Cases and controls did not differ with regard to menstrual and reproductive history except in age at bir th of first child, where older age was associated with reduced risk of SAH (odds ratio [OR], 0.63; 95% CI, 0.43, 0.91). Relative to never use of HRT, the adjusted OR for over use of HRT was 0.64 (95% CI, 0.41, 0.98), which did not alter significantly after further adjustment for possible confounding factors. Borderline evidence of an inverse association was detected for past use of HRT (adjusted OR, 0.59; 95% CI, 0.30, 1.13) and current use of HRT (adjusted OR, 0.67; 95% CI, 0.40, 1.13), but there was no evidence of an association for use of OCPs (adjusted OR, 0.97; 95% CI, 0.58, 1.60). Conclusions-The risks of SAH are lower in women whose first pregnancy is at an older age and women who have ever used HRT but not OCPs. The findings suggest an independent etiologic role for hormonal factors in the pathogenesis of aneurysmal SAH and provide support for a protective role fur HRT on risk of SAH in postmenopausal women.

Employee reactions to behavioural control under conditions of stress: the moderating role of self-efficacy

Extensive research conducted in the occupational stress literature has failed to provide convincing support for the stress-buffering effects of work control on employee adjustment. Drawing on research conducted in the laboratory context, it was proposed that the stress-buffering effects of work control on employee adjustment would be more marked at high, rather than low, levels of self-efficacy. In a sample of 100 customer service representatives, a significant three-way interaction among role conflict, work control and self-efficacy (measured at Time 1) was observed on (low) depersonalization (measured at Time 2). Consistent with expectations, work control reduced the negative effects of work stress on this outcome measure only for employees who perceived high levels of self-efficacy at work. In addition, there was evidence to suggest that self-efficacy moderated the main effects of work control on job satisfaction and somatic health. These findings are discussed hi terms of their theoretical contribution to the job strain model, and also in relation to workplace interventions designed to improve levels of employee adjustment.

Biological control of the rabbit in Australia: lessons not learned?

The story of the spread of the European rabbit across Australia, and of the two viruses used to control it, is an interesting way to look at some of the issues associated with biological control. What can be learned from the way this system developed, and what has been learned, or not learned, from the mistakes made? Here, we look at these events and examine what insights can be gained from this history.

Finger and A-B ridge count, and fluctuating asymmetry in psychosis: A catchment area case-control study

Dermatoglyphic measures are of interest to schizophrenia research because they serve as persistent markers of deviant development in foetal life. Several studies have reported alterations in A–B ridge counts, total finger ridge counts and measures related to asymmetry in schizophrenia. The aim of this study was to assess these measures in an Australian catchment area, case-control study. Individuals with psychosisŽns246.were drawn from a catchment-area prevalence study, and well controlsŽns229. were recruited from the same area. Finger and palm prints were taken usingan inkless technique and all dermatoglyphic measures were assessed by a trained rater blind to case status. The dermatoglyphic measures Žfinger ridge count, A–B ridge count, and their derived asymmetry measures. were divided into quartiles based on the distribution of these variables in controls. The main analysis Žlogistic regression controlled for age and sex.examined all psychotic disorders, with planned subgroup analyses comparing controls with Ž1. nonaffective psychosis Žschizophrenia, delusional disorder, schizophreniform psychosis, atypical psychosis.andŽ2. affective psychosis Ždepression with psychosis, bipolar disorder, schizoaffective psychosis.. There were no statistically significant alterations in the odds of havinga psychotic disorder for any of the dermatoglyphic measures. The results did not change when we examined affective and nonaffective psychosis separately. The dermatoglyphic features that distinguish schizophreniar psychosis in other studies were not identified in this Australian study. Regional variations in these findings may provide clues to differential ethnicrgenetic and environmental factors that are associated with schizophrenia. The Stanley Foundation supported this project.

Finite element modelling of reactive fluids mixing and mineralization in pore-fluid saturated hydrothermal/sedimentary basins

We present the finite element simulations of reactive mineral carrying fluids mixing and mineralization in pore-fluid saturated hydrothermal/sedimentary basins. In particular we explore the mixing of reactive sulfide and sulfate fluids and the relevant patterns of mineralization for Load, zinc and iron minerals in the regime of temperature-gradient-driven convective flow. Since the mineralization and ore body formation may last quite a long period of time in a hydrothermal basin, it is commonly assumed that, in the geochemistry, the solutions of minerals are in an equilibrium state or near an equilibrium state. Therefore, the mineralization rate of a particular kind of mineral can be expressed as the product of the pore-fluid velocity and the equilibrium concentration of this particular kind of mineral Using the present mineralization rate of a mineral, the potential of the modern mineralization theory is illustrated by means of finite element studies related to reactive mineral-carrying fluids mixing problems in materially homogeneous and inhomogeneous porous rock basins.

Human response to environmental noise: The role of perceived control

Negative impacts of noise exposure on health and performance may result in part from learned helplessness, the syndrome of deficits typically produced by exposure to uncontrollable events. People may perceive environmental noise to be uncontrollable, and several effects of noise exposure appear to parallel learned helplessness deficits. In the present socioacoustic survey (N = 1,015), perceived control over aircraft noise correlated negatively with some effects of noise (though not others). Furthermore, these effects were better predicted by perceived control than by noise level. These observational data support the claim that learned helplessness contributes to the effects of noise exposure.

Effect of material anisotropy on the onset of convective flow in three-dimensional fluid-saturated faults

In order to investigate the effect of material anisotropy on convective instability of three-dimensional fluid-saturated faults, an exact analytical solution for the critical Rayleigh number of three-dimensional convective flow has been obtained. Using this critical Rayleigh number, effects of different permeability ratios and thermal conductivity ratios on convective instability of a vertically oriented three-dimensional fault have been examined in detail. It has been recognized that (1) if the fault material is isotropic in the horizontal direction, the horizontal to vertical permeability ratio has a significant effect on the critical Rayleigh number of the three-dimensional fault system, but the horizontal to vertical thermal conductivity ratio has little influence on the convective instability of the system, and (2) if the fault material is isotropic in the fault plane, the thermal conductivity ratio of the fault normal to plane has a considerable effect on the critical Rayleigh number of the three-dimensional fault system, but the effect of the permeability ratio of the fault normal to plane on the critical Rayleigh number of three-dimensional convective flow is negligible.