The nitric oxide-sensitive p21Ras-ERK pathway mediates S-nitrosoglutathione-induced apoptosis

p21Ras protein plays a critical role in cellular signaling that induces either cell cycle progression or apoptosis. Nitric oxide (NO) has been consistently reported to activate p21Ras through the redox sensitive cysteine residue (118). In this study, we demonstrated that the p21Ras-ERK pathway regulates THP-1 monocyte/macrophage apoptosis induced by S-nitrosoglutathione (SNOG). This was apparent from studies in THP-1 cells expressing NO-insensitive p21Ras (p21Ras(C118S)) where the pro-apoptotic action of SNOG was almost abrogated. Three major MAP kinase pathways (ERK, JNK, and p38) that are downstream to p21Ras were investigated. It was observed that only the activation of ERK1/2 MAP kinases by SNOG in THP-1 cells was attributable to p21Ras. The inhibition of the ERK pathway by PD98059 markedly attenuated apoptosis in SNOG-treated THP-1 cells, but had a marginal effect on SNOG-treated THP-1 cells expressing NO-inserisitive p21Ras. The inhibition of the JNK and p38 pathways by selective inhibitors had no marked effects on the percentage of apoptosis. The induction of p21Waf1 expression by SNOG was observed in THP-1 cells harboring mutant and wild-type p21Ras, however in cells expressing mutant Ras, the expression of p21Waf1 was significantly attenuated. The treatment of THP-1 cells expressing wild-type p21Ras with PD98059 resulted in significant attenuation of p21Waf1 expression. These results indicate that the redox sensitive p21Ras-ERK pathway plays a critical role in sensing and delivering the pro-apoptotic signaling mediated by SNOG. (C) 2008 Elsevier Inc. All rights reserved.

Growth Response of Various Perennial Grasses to Increasing Salinity

Although the effect of salinity on plant growth has been the focus of a substantive research effort, much of this research has failed to adequately separate the various growth limiting aspects of salinity; thus the results are confounded by multiple factors. Eight perennial grass species were grown in a sand culture system dominated by NaCl (electrical conductivities (ECs) between 1.4 and 38 dS m 1), with sufficient Ca added to each treatment to ensure that Na-induced Ca deficiency did not reduce growth. Of the eight perennial grass species examined, Chloris gayana cv. Pioneer (Rhodes grass) was the most salt tolerant species, whilst in comparison, Chrysopogon zizanioides cv. Monto (vetiver) was of only moderate tolerance. However, observed salinity tolerances tended to be lower than those expected from published values based on the threshold salinity model (bent stick model). This discrepancy may be due in part to differences in the evapotranspirational demand between studies; an increase in demand accelerating the accumulation of Na in the shoots and hence decreasing apparent salinity tolerance. It was also observed that the use of a non-saline growth period to allow seed germination and establishment results in the overestimation of vegetative salinity tolerance if not taken into consideration. This is particularly true for species of low salt tolerance due to their comparatively rapid growth in the non-saline medium compared to that at full salinity.

Sources of information about HIV/AIDS and perceived risk of infection among heterosexual young adults: 1989 and 1994

This paper reports a study of sources of information about HIV/AIDS and trust of the sources among heterosexuals in 1989 (113 females and 91 males) and 1994 (185 females and 66 males). We also examined whether perceived personal risk of HIV infection was predicted by sources of information about HIV/AIDS, trust of the sources, how informed about AIDS people believed they were, and perceived risk of infection to others, as well as whether there was a relationship between perceived personal risk and safe sex behaviour Participants received most of their information about AIDS/HIV from magazines, newspapers, and television, but placed most trust on sources such as doctors and HIV/AIDS organisations. Perceived personal risk was influenced most by perceived risk to friends and to people with the same sexual practices. In the 1994 sample, perceived personal risk was correlated with the amount of condom use among participants with sexual experience. These results indicate ther has been. relative stability across a five-year period. They also point to the continuing discrepancy among young heterosexuals between the most-used and most-trusted sources of information, as well as to the importance of peer influence on perceptions of personal risk of HIV infection.

Factors controlling the origin of gas in Australian Bowen Basin coals

Open system pyrolysis (heating rate 10 degrees C/min) of coal maturity (vitrinite reflectance, VR) sequence (0.5%, 0.8% and 1.4% VR) demonstrates that there are two stages of thermogenic methane generation from Bowen Basin coals. The first and major stage shows a steady increase in methane generation maximising at 570 degrees C, corresponding to a VR of 2-2.5%. This is followed by a less intense methane generation which has not as yet maximised by 800 degrees C (equivalent to VR of 5%). Heavier (C2+) hydrocarbons are generated up to 570 degrees C after which only the C-1 (CH4, CO and CO2) gases are produced. The main phase of heavy hydrocarbon generation occurs between 420 and 510 degrees C. Over this temperature range,methane generation accounts for only a minor component, whereas the wet gases (C-2-C-5) are either in equal abundance or are more abundant by a factor of two than the liquid hydrocarbons. The yields of non-hydrocarbon gases CO2 and CO are greater then methane during the early stages of gas generation from an immature coal, subordinate to methane during the main phase of methane generation after which they are again dominant. Compositional data for desorbed and produced coal seam gases from the Bowen show that CO2 and wet gases are a minor component. This discrepancy between the proportion of wet gas components produced during open system pyrolysis and that observed in naturally matured coals may be the result of preferential migration of wet gas components, by dilution of methane generated during secondary cracking of bitumen, or kinetic effects associated with different activations for production of individual hydrocarbon gases. Extrapolation of results of artificial pyrolysis of the main organic components in coal to geological significant heating rates suggests that isotopically light methane to delta(13)C of -50 parts per thousand can be generated. Carbon isotope depletions in C-13 are further enhanced, however, as a result of trapping of gases over selected rank levels (instantaneous generation) which is a probable explanation for the range of delta(13)C values we have recorded in methane desorbed from Bowen Basin coals (-51 +/- 9 parts per thousand). Pervasive carbonate-rich veins in Bowen Basin coals are the product of magmatism-related hydrothermal activity. Furthermore, the pyrolysis results suggest an additional organic carbon source front CO2 released at any stage during the maturation history could mix in varying proportions with CO2 from the other sources. This interpretation is supported by C and O isotopic ratios, of carbonates that indicate mixing between magmatic and meteoric fluids. Also, the steep slope of the C and O isotope correlation trend suggests that the carbonates were deposited over a very narrow temperature interval basin-wide, or at relatively high temperatures (i.e., greater than 150 degrees C) where mineral-fluid oxygen isotope fractionations are small. These temperatures are high enough for catagenic production of methane and higher hydrocarbons from the coal and coal-derived bitumen. The results suggests that a combination of thermogenic generation of methane and thermodynamic processes associated with CH4/CO2 equilibria are the two most important factors that control the primary isotope and molecular composition of coal seam gases in the Bowen Basin. Biological process are regionally subordinate but may be locally significant. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.

Putative beta(4)-adrenoceptors in rat ventricle mediate increases in contractile force and cell Ca2+: comparison with atrial receptors and relationship to (-)-[H-3]-CGP 12177 binding

1 We identified putative beta(4)-adrenoceptors by radioligand binding, measured increases in ventricular contractile force by (-)-CGP 12177 and (+/-)-cyanopindolol and demonstrated increased Ca2+ transients by (-)-CGP 12177 in rat cardiomyocytes. 2 (-)-[H-3]-CGP 12177 labelled 13-22 fmol mg(-1) protein ventricular beta(1), beta(2)-adrenoceptors (pK(D) similar to 9.0) and 50-90 fmol mg(-1) protein putative beta(4)-adrenoceptors (pK(D) similar to 7.3). The affinity values (PKi) for (beta(1),beta(2)-) and putative beta(4)-adrenoceptors, estimated from binding inhibition, were (-)-propranolol 8.4, 5.7; (-)-bupranolol 9.7, 5.8; (+/-)-cyanopindolol 10.0,7.4. 3 In left ventricular papillary muscle, in the presence of 30 mu M 3-isobutyl-1-methylxanthine, (-)CGP 12177 and (+/-)-cyanopindolol caused positive inotropic effects, (pEC(50) (-)-CGP 12177, 7.6; (+/-)-cyanopindolol, 7.0) which were antagonized by (-)-bupranolol (pK(B) 6.7-7.0) and (-)-CGP 20712A (pK(B) 6.3-6.6). The cardiostimulant effects of(-)-CGP 12177 in papillary muscle, left and right atrium were antagonized by (+/-)-cyanopindolol (pK(i), 7.0-7.4). 4 (-)-CGP 12177 (1 mu M) in the presence of 200 nM (-)-propranolol increased Ca2+ transient amplitude by 56% in atrial myocytes, but only caused a marginal increase in ventricular myocytes. In the presence of 1 mu M 3-isobutyl-1-methylxanthine and 200 nM (-)-propranolol, 1 mu M (-)-CGP 12177 caused a 73% increase in Ca2+ transient amplitude in ventricular myocytes. (-)-CGP 12177 elicited arrhythmic transients in some atrial and ventricular myocytes. 5 Probably by preventing cyclic AMP hydrolysis, 3-isobutyl-1-methylxanthine facilitates the inotropic function of ventricular putative beta(4)-adrenoceptors. suggesting coupling to G(s) protein-adenylyl cyclase. The receptor-mediated increases in contractile force are related to increases of Ca2+ in atrial and ventricular myocytes. The agreement of binding affinities of agonists with cardiostimulant potencies is consistent with mediation through putative beta(4)-adrenoceptors labelled with (-)-[H-3]-CGP 12177.

Modeling of hepatic elimination and organ distribution kinetics with the extended convection-dispersion model

The conventional convection-dispersion (also called axial dispersion) model is widely used to interrelate hepatic availability (F) and clearance (Cl) with the morphology and physiology of the liver and to predict effects such as changes in liver blood flow on F and Cl. An extended form of the convection-dispersion model has been developed to adequately describe the outflow concentration-time profiles for vascular markers at both short and long times after bolus injections into perfused livers. The model, based on flux concentration and a convolution of catheters and large vessels, assumes that solute elimination in hepatocytes follows either fast distribution into or radial diffusion in hepatocytes. The model includes a secondary vascular compartment, postulated to be interconnecting sinusoids. Analysis of the mean hepatic transit time (MTT) and normalized variance (CV2) of solutes with extraction showed that the discrepancy between the predictions of MTT and CV2 for the extended and conventional models are essentially identical irrespective of the magnitude of rate constants representing permeability, volume, and clearance parameters, providing that there is significant hepatic extraction. In conclusion, the application of a newly developed extended convection-dispersion model has shown that the unweighted conventional convection-dispersion model can be used to describe the disposition of extracted solutes and, in particular, to estimate hepatic availability and clearance in booth experimental and clinical situations.

Numerical modelling of single-layer folding: clarification of an issue regarding the possible effect of computer codes and the influence of initial irregularities

The influence of initial perturbation geometry and material propel-ties on final fold geometry has been investigated using finite-difference (FLAC) and finite-element (MARC) numerical models. Previous studies using these two different codes reported very different folding behaviour although the material properties, boundary conditions and initial perturbation geometries were similar. The current results establish that the discrepancy was not due to the different computer codes but due to the different strain rates employed in the two previous studies (i.e. 10(-6) s(-1) in the FLAC models and 10(-14) s(-1) in the MARC models). As a result, different parts of the elasto-viscous rheological field were bring investigated. For the same material properties, strain rate and boundary conditions, the present results using the two different codes are consistent. A transition in Folding behaviour, from a situation where the geometry of initial perturbation determines final fold shape to a situation where material properties control the final geometry, is produced using both models. This transition takes place with increasing strain rate, decreasing elastic moduli or increasing viscosity (reflecting in each case the increasing influence of the elastic component in the Maxwell elastoviscous rheology). The transition described here is mechanically feasible but is associated with very high stresses in the competent layer (on the order of GPa), which is improbable under natural conditions. (C) 2000 Elsevier Science Ltd. All rights reserved.

Using stochastic dynamic programming to determine optimal fire management for Banksia ornata

1. A model of the population dynamics of Banksia ornata was developed, using stochastic dynamic programming (a state-dependent decision-making tool), to determine optimal fire management strategies that incorporate trade-offs between biodiversity conservation and fuel reduction. 2. The modelled population of B. ornata was described by its age and density, and was exposed to the risk of unplanned fires and stochastic variation in germination success. 3. For a given population in each year, three management strategies were considered: (i) lighting a prescribed fire; (ii) controlling the incidence of unplanned fire; (iii) doing nothing. 4. The optimal management strategy depended on the state of the B. ornata population, with the time since the last fire (age of the population) being the most important variable. Lighting a prescribed fire at an age of less than 30 years was only optimal when the density of seedlings after a fire was low (< 100 plants ha(-1)) or when there were benefits of maintaining a low fuel load by using more frequent fire. 5. Because the cost of management was assumed to be negligible (relative to the value of the persistence of the population), the do-nothing option was never the optimal strategy, although lighting prescribed fires had only marginal benefits when the mean interval between unplanned fires was less than 20-30 years.

Prediction of promiscuous peptides that bind HLA class I molecules

Promiscuous T-cell epitopes make ideal targets for vaccine development. We report here a computational system, multipred, for the prediction of peptide binding to the HLA-A2 supertype. It combines a novel representation of peptide/MHC interactions with a hidden Markov model as the prediction algorithm. multipred is both sensitive and specific, and demonstrates high accuracy of peptide-binding predictions for HLA-A*0201, *0204, and *0205 alleles, good accuracy for *0206 allele, and marginal accuracy for *0203 allele. multipred replaces earlier requirements for individual prediction models for each HLA allelic variant and simplifies computational aspects of peptide-binding prediction. Preliminary testing indicates that multipred can predict peptide binding to HLA-A2 supertype molecules with high accuracy, including those allelic variants for which no experimental binding data are currently available.

An economic evaluation of plasma production via erythroplasmapheresis and whole blood collection

This paper presents cost-effectiveness analyses (CEAs) of plasma collection via two alternative methods: whole blood collection (WBC) and erythroplasmapheresis collection (EPC). The objective of the study is to provide an answer to the question 'What is the least-cost method of plasma production'. This question is answered, both from the viewpoint of the blood collection agency (using financial CEA) and from that of 'society' as a whole (using economic CEA). We employ detailed financial data and economic survey data for collections made by a blood collection agency and to WBC and EPC donors in Brisbane, Australia. The results indicate that, despite the superior yield provided by EPC, WBC is actually more cost-effective. This result is robust to thorough sensitivity analysis and arises regardless of whether an economic or financial perspective is taken. We conclude that, ceteris paribus, the cost of recruiting new plasma donors would need to be quite substantial for marginal investments in EPC to be considered cost-effective. Crown Copyright (C) 2002 Published by Elsevier Science Ltd. All rights reserved.

Undergraduate student experience in dental service delivery in rural South Australia: An analysis of costs and benefits

Background, Rural experience for dental students can provide valuable clinical education, change attitudes to rural practice, and make a valuable contribution to clinical service provision. The aim of this paper is to assess the costs and benefits of service delivery by students through rural training programmes Methods: Groups of two students worked in the public dental clinics in adjacent rural centres where there had been long-term difficulties in recruiting staff. The costs and benefits of the programme were assessed by the impact on waiting lists, the total cost per patient of, a course of care and by the marginal cost of adding service provision by students to existing arrangements. Results: The total costs of emergency and complete treatment provided by students were greater than the costs of treatment provided by public-sector dentists but less than the costs of private providers treating public patients. However, the value of services were greater when care was provided by students or private providers and the marginal cost of students providing services was 50-70 per cent of the cost of care provided by public dentists. Conclusion: This assessment suggests that the service benefits achieved compliment the primary objective of influencing the attitude of students to rural practice.

Predicting energy requirements in the clinical setting: Are current methods evidence based?

Estimating energy requirements is necessary in clinical practice when indirect calorimetry is impractical. This paper systematically reviews current methods for estimating energy requirements. Conclusions include: there is discrepancy between the characteristics of populations upon which predictive equations are based and current populations; tools are not well understood, and patient care can be compromised by inappropriate application of the tools. Data comparing tools and methods are presented and issues for practitioners are discussed. (C) 2003 International Life Sciences Institute.

Image calibration to like-values in mapping shallow water quality from multitemporal data

The applicability of image calibration to like-values in mapping water quality parameters from multitemporal images is explored, Six sets of water samples were collected at satellite overpasses over Moreton Bay, Brisbane, Australia. Analysis of these samples reveals that waters in this shallow bay are mostly TSS-dominated, even though they are occasionally dominated by chlorophyll as well. Three of the images were calibrated to a reference image based on invariant targets. Predictive models constructed from the reference image were applied to estimating total suspended sediment (TSS) and Secchi depth from another image at a discrepancy of around 35 percent. Application of the predictive model for TSS concentration to another image acquired at a time of different water types resulted in a discrepancy of 152 percent. Therefore, image calibration to like-values could be used to reliably map certain water quality parameters from multitemporal TM images so long as the water type under study remains unchanged. This method is limited in that the mapped results could be rather inaccurate if the water type under study has changed considerably. Thus, the approach needs to be refined in shallow water from multitemporal satellite imagery.

The Mesozoic and Cenozoic motion of Adria (central Mediterranean): a review of constraints and limitations

This paper presents kinematic analysis on the motion of Adria, which is the continental mass that bridges Africa and Europe in the central Mediterranean. Palaeomagnetic data show a general coherence between the motion of Adria and Africa since the Late Paleozoic. This mutual motion, for the period from 120 Ma and the present, is verified by comparing inferred palaeolatitudes from relatively stable parts of Adria (Apulia, Gargano, Istria, and the Southern Alps) and the Hyblean Plateau, with latitudinal changes that are calculated from the motion of Africa with respect to hotspots. Additional constraints on the motion of Adria are provided from the Late Paleozoic-Early Mesozoic passive margin of Adria in the Ionian Sea. The seismic structure of the floor of the Ionian Sea resembles the structure of the oceanic crust in marginal back-arc basins, suggesting that it formed as a small ocean basin. Furthermore, the Ionian lithosphere in the Calabrian arc has been subjected to rapid rollback, which commonly occurs only when the subducting slab is made of oceanic lithosphere. This oceanic domain marks the Pennian-Triassic to Jurassic plate boundary between Adria and Africa, suggesting that a small amount of independent motion between Adria and Africa took place at that time. Since the Jurassic, Adria and Africa have shared a relatively coherent motion path. (C) 2004 Lavoisier SAS. All rights reserved.

Bayesian analysis of the error correction model

This paper presents a method for estimating the posterior probability density of the cointegrating rank of a multivariate error correction model. A second contribution is the careful elicitation of the prior for the cointegrating vectors derived from a prior on the cointegrating space. This prior obtains naturally from treating the cointegrating space as the parameter of interest in inference and overcomes problems previously encountered in Bayesian cointegration analysis. Using this new prior and Laplace approximation, an estimator for the posterior probability of the rank is given. The approach performs well compared with information criteria in Monte Carlo experiments. (C) 2003 Elsevier B.V. All rights reserved.