Quantitative and qualitative influences of tapasin on the class I peptide repertoire

Tapasin is critical for efficient loading and surface expression of most HLA class I molecules. The high level surface expression of HLA-B*2705 on tapasin-deficient 721.220 cells allowed the influence of this chaperone on peptide repertoire to be examined. Comparison of peptides bound to HLA-B*2705 expressed on tapasin-deficient and -proficient cells by mass spectrometry revealed an overall reduction in the recovery of B*2705-bound peptides isolated from tapasin-deficient cells despite similar yields of B27 heavy chain and beta (2)-microglobulin. This indicated that a proportion of suboptimal ligands were associated with B27, and they were lost during the purification process. Notwithstanding this failure to recover these suboptimal peptides, there was substantial overlap in the repertoire and biochemical properties of peptides recovered from B27 complexes derived from tapasin-positive and -negative cells. Although many peptides were preferentially or uniquely isolated from B*2705 in tapasin-positive cells, a number of species were preferentially recovered in the absence of tapasin, and some of these peptide ligands have been sequenced. In general, these ligands did not exhibit exceptional binding affinity, and we invoke an argument based on lumenal availability and affinity to explain their tapasin independence. The differential display of peptides in tapasin-negative and -positive cells was also apparent in the reactivity of peptide-sensitive alloreactive CTL raised against tapasin-positive and -negative targets, demonstrating the functional relevance of the biochemical observation of changes in peptide repertoire in the tapasin-deficient APC. Overall, the data reveal that tapasin quantitatively and qualitatively influences ligand selection by class I molecules.

Developments in the understanding of South African style SAG mills

The South African style SAG (RoM) mills operate in a window that is almost exclusive from the operation of the Australian and North American mills that have been used for the development of SAG mill models. Combining good quality, test data from the RoM mills is extending and improving these models, and assisting in a practical manner in improving our understanding of SAG/AG milling. Data from high mill loads, both in absolute filling and ball loading, have been used to extend and improve the JK SAG mill model. This improved understanding has been successfully applied to increasing the throughput of a mill by 8%. Data is presented on relationships between power and load for high mill loading. Slurry pooling is common in closed-circuit RoM mills, and the detrimental effect of this has been dramatically demonstrated at ALCOA with a mill throughput increase of over 20%. Techniques for calculating the effects of slurry pooling have been developed and a new pulp lifter system designed to give optimal slurry discharge. The influence of mill speed in shifting the product size distribution has also been measured. (C) 2001 Elsevier Science Ltd. All rights reserved.

Population pharmacokinetics of magnesium in preeclampsia

OBJECTIVE: The purpose of this study was to determine the population pharmacokinetics of magnesium from sparse observational data in patients with preeclampsia. STUDY DESIGN: Serum magnesium concentrations (1-11 per patient) were obtained retrospectively from the records of 116 patients with preeclampsia who had a loading dose of magnesium sulfate (16 or 20 mmol), followed by a maintenance dose (1 mmol/h) over an average of 28 hours. Population clearance, volume of distribution, and the baseline magnesium concentration were estimated using the NONMEM program. RESULTS: The following population typical values, together with the interpatient variability (expressed as coefficient of variation) were obtained with the use of a 1-compartment model: systemic clearance, 4.28 L/h (37.3%); volume of distribution, 32.3 L (32.1%); baseline concentration, 0.811 mmol/L (18.5%). The average half-life was 5.2 hours. Clonus was not obtunded in 4 patients whose serum magnesium concentrations were similar to the average concentration of 1.7 mmol/L. The variability remaining unexplained after the population model was fitted to the data was 6.5% to 10.8%. CONCLUSION: This study extended knowledge of the pharmacokinetic disposition of magnesium in preeclampsia. The results are potentially useful for the calculation of loading and maintenance doses, particularly when the relationship between serum concentration and effect in preeclampsia is clarified.

Effects of short-duration and long-duration exercise on lipoprotein(a)

Purpose: Most studies that use either a single exercise session, exercise training, or a cross-sectional design have failed to find a relationship between exercise and plasma lipoprotein(a) [Lp(a)] concentrations. However, a few studies investigating the effects of longer and/or more strenuous exercise have shown elevated Lp(a) concentrations, possibly as an acute-phase reactant to muscle damage. Based on the assumption that greater muscle damage would occur with exercise of longer duration, the purpose of the present study was to determine whether exercise of longer duration would increase Lp(a) concentration and creatine kinase. (CK) activity more than exercise of shorter duration. Methods: Ten endurance-trained men (mean +/- SD: age, 27 +/- 6 yr; maximal oxygen consumption [(V)over dotO(2max)], 57 +/- 7 mL(.)kg(-1) min(-1)) completed two separate exercise sessions at 70% (V)over dotO(2max). One session required 900 kcal of energy expenditure (60 +/- 6 min), and the other required 1500 kcal (112 +/- 12 min). Fasted blood samples were taken immediately before (0-pre), immediately after (0-post), 1 d after (1-post), and 2 d after (2-post) each exercise session. Results: CK activity increased after both exercise sessions (mean +/- SE; 800 kcal: 0-pre 55 +/- 11, 1-post 168 +/- 64 U(.)L(-1.)min(-1); 1500 kcal: 0-pre 51 +/- 5, 1-post 187 +/- 30, 2-post 123 +/- 19 U(.)L(-1.)min(-1); P < 0.05). However, median Lp(a) concentrations were not altered by either exercise session (800 kcal: 0-pre 5.0 mg(.)dL(-1), 0-post 3.2 mg(.)dL(-1), 1-post 4.0 mg(.)dL(-1), 2-post 3.4 mg(.)dL(-1); 1500 kcal: 0-pre 5.8 mg(.)dL(-1), 0-post 4.3 mg(.)dL(-1), 1-post 3.2 mg(.)dL(-1), 2-post 5.3 mg(.)dL(-1)). In addition, no relationship existed between exercise-induced changes in CK activity and Lp(a) concentration (800 kcal: r = -0.26; 1500 kcal: r = -0.02). Conclusion: These results suggest that plasma Lp(a) concentration will not increase in response to minor exercise-induced muscle damage in endurance-trained runners.

Mechanical effects on the skeleton: Are there clinical implications?

The basic morphology of the skeleton is determined genetically, but its final mass and architecture are modulated by adaptive mechanisms sensitive to mechanical factors. When subjected to loading, the ability of bones to resist fracture depends on their mass, material properties, geometry and tissue quality. The contribution of altered bone geometry to fracture risk is unappreciated by clinical assessment using absorptiometry because it fails to distinguish geometry and density. For example, for the same bone area and density, small increases in the diaphyseal radius effect a disproportionate influence on torsional strength of bone. Mechanical factors are clinically relevant because of their ability to influence growth, modeling and remodeling activities that can maximize, or maintain, the determinants of fracture resistance. Mechanical loads, greater than those habitually encountered by the skeleton, effect adaptations in cortical and cancellous bone, reduce the rate of bone turnover, and activate new bone formation on cortical and trabecular surfaces. In doing so, they increase bone strength by beneficial adaptations in the geometric dimensions and material properties of the tissue. There is no direct evidence to demonstrate anti-fracture efficacy for mechanical loading, but the geometric alterations engendered undoubtedly increase the structural properties of bone as an organ, increasing the resistance to fracture. Like all interventions, issues of safety also arise. Physical activities involving high strain rates, heavy lifting or impact loading may be detrimental to the joints, leading to osteoarthritis; may stimulate fatigue damage leading with some to stress fractures; or may interact pharmaceutical interventions to increase the rate of microdamage within cortical or trabecular bone.

Surface diffusion and adsorption of hydrocarbons in activated carbon

Adsorption and diffusion in a porous media were studied theoretically and experimentally with a differential transient permeation method. The porous medium is allowed to equilibrate at some specified loading, and then the time trajectory of the permeation process is followed after a small difference between the pressures at the end faces of the porous medium is introduced at time t = 0 +. Such a trajectory us. time would contain adsorption and diffusion characteristics of the system. By studying this for various surface loadings, pore and surface diffusions can be fully characterized. Mathematical modeling of transient permeation is detailed for pure gases or vapors diffusion and adsorption in porous media. Effects of nonlinearity of adsorption isotherm, pressure, temperature and heat effects were considered in the model. Experimental data of diffusion and adsorption of propane, n-butane and n-hexane in activated carbon at different temperatures and loadings show the potential of this method as a useful tool to study adsorption kinetics in porous media. Validity of the model is best tested against the transient data where the kinetics curves exhibit sigmoidal shape, which is a result of the diffusion and adsorption rate during the initial stage of permeation.

Heat of desorption measured by means of electrical heat excitation

A new method of measuring heat of desorption is proposed in this Letter. The principle of the method is to measure the amount of mass released when a controlled amount of energy is supplied directly to a solid adsorbent. This is in contrast to conventional methods such as microcalorimetry, where heat released upon adsorption is measured. In this method, a quantified heat supply is generated by passing a de current through a carbon pellet, which is equilibrated with a gas phase confined in a closed vessel. As a consequence of the heating, the particle temperature is increased, resulting in partial desorption of adsorbed molecules. The variations of pellet temperature and the system pressure with respect to time are used to determine the heat of desorption as a function of loading.

The Dubinin-Radushkevich equation and the underlying microscopic adsorption description

The Dubinin-Radushkevich (DR) equation is widely used for description of adsorption in microporous materials, especially those of a carbonaceous origin. The equation has a semi-empirical origin and is based on the assumptions of a change in the potential energy between the gas and adsorbed phases and a characteristic energy of a given solid. This equation yields a macroscopic behaviour of adsorption loading for a given pressure. In this paper, we apply a theory developed in our group to investigate the underlying mechanism of adsorption as an alternative to the macroscopic description using the DR equation. Using this approach, we are able to establish a detailed picture of the adsorption in the whole range of the micropore system. This is different from the DR equation, which provides an overall description of the process. (C) 2001 Elsevier Science Ltd. All rights reserved.

On the surface diffusion of hydrocarbons in microporous activated carbon

This paper addresses the current status of the various diffusion theories for surface diffusion in the literature. The inadequacy of these models to explain the surface diffusion of many hydrocarbons in microporous activated carbon is shown in this paper. They all can explain the increase of the surface diffusivity (D-mu) with loading, but cannot explain the increase of the surface permeability (D(mu)partial derivativeC(mu)/partial derivativeP) with loading as observed in our data of diffusion of hydrocarbons in activated carbon, even when the surface heterogeneity is accounted for in those models. The explanation for their failure was presented, and we have put forward a theory to explain the increase of surface diffusion permeability with loading. This new theory assumes the variation of the activation energy for surface diffusion with surface loading, and it is validated with diffusion data of propane, n-butane, n-hexane, benzene and ethanol in activated carbon. (C) 2001 Elsevier Science Ltd. All rights reserved.

Surface diffusion of hydrocarbons in activated carbon: Comparison between constant molar flow, differential permeation and differential adsorption bed methods

This paper presents the comparison of surface diffusivities of hydrocarbons in activated carbon. The surface diffusivities are obtained from the analysis of kinetic data collected using three different kinetics methods- the constant molar flow, the differential adsorption bed and the differential permeation methods. In general the values of surface diffusivity obtained by these methods agree with each other, and it is found that the surface diffusivity increases very fast with loading. Such a fast increase can not be accounted for by a thermodynamic Darken factor, and the surface heterogeneity only partially accounts for the fast rise of surface diffusivity versus loading. Surface diffusivities of methane, ethane, propane, n-butane, n-hexane, benzene and ethanol on activated carbon are reported in this paper.

A new diffusion and flow theory for activated carbon from low pressure to capillary condensation range

In this paper, we develop a theory for diffusion and flow of pure sub-critical adsorbates in microporous activated carbon over a wide range of pressure, ranging from very low to high pressure, where capillary condensation is occurring. This theory does not require any fitting parameter. The only information needed for the prediction is the complete pore size distribution of activated carbon. The various interesting behaviors of permeability versus loading are observed such as the maximum permeability at high loading (occurred at about 0.8-0.9 relative pressure). The theory is tested with diffusion and flow of benzene through a commercial activated carbon, and the agreement is found to be very good in the light that there is no fitting parameter in the model. (C) 2001 Elsevier Science B.V. All rights reserved.

Credibility and staff conduct make or break bank customer service quality

Service quality is assessed by customers along the dimensions of staff conduct, credibility, communication, and access to teller services. Credibility and staff conduct emerge as the highest loading first-order factors. This highlights the significance of rectifying mistakes while keeping customers informed, and employing branch staff that are responsive and civilized in their conduct. Discovery of a valid second-order factor, namely, overall customer service quality, underscores the importance of providing quality service across all its dimensions. For example, if the bank fails to rectify mistakes and keep customers informed but excels in all other dimensions, its overall customer service quality can still be rated poorly.

Managing the Brisbane River and Moreton Bay: an integrated research/management program to reduce impacts on an Australian estuary

The Brisbane River and Moreton Bay Study, an interdisciplinary study of Moreton Bay and its major tributaries, was initiated to address water quality issues which link sewage and diffuse loading with environmental degradation. Runoff and deposition of fine-grained sediments into Moreton Bay, followed by resuspension, have been linked with increased turbidity and significant loss of seagrass habitat. Sewage-derived nutrient enrichment, particularly nitrogen (N), has been linked to algal blooms by sewage plume maps. Blooms of a marine cyanobacterium, Lyngbya majuscula, in Moreton Bay have resulted in significant impacts on human health (e.g., contact dermatitis) and ecological health (e.g., seagrass loss), and the availability of dissolved iron from acid sulfate soil runoff has been hypothesised. The impacts of catchment activities resulting in runoff of sediments, nutrients and dissolved iron on the health of the Moreton Bay waterways are addressed. The Study, established by 6 local councils in association with two state departments in 1994, forms a regional component of a national and state program to achieve ecologically sustainable use of the waterways by protecting and enhancing their health, while maintaining economic and social development. The Study framework illustrates a unique integrated approach to water quality management whereby scientific research, community participation and the strategy development were done in parallel with each other. This collaborative effort resulted in a water quality management strategy which focuses on the integration of socioeconomic and ecological values of the waterways. This work has led to significant cost savings in infrastructure by providing a clear focus on initiatives towards achieving healthy waterways. The Study's Stage 2 initiatives form the basis for this paper.

ENCORE: The effect of nutrient enrichment on coral reefs. Synthesis of results and conclusions

Coral reef degradation resulting from nutrient enrichment of coastal waters is of increasing global concern. Although effects of nutrients on coral reef organisms have been demonstrated in the laboratory, there is little direct evidence of nutrient effects on coral reef biota in situ. The ENCORE experiment investigated responses of coral reef organisms and processes to controlled additions of dissolved inorganic nitrogen (N) and/or phosphorus (P) on an offshore reef(One Tree Island) at the southern end of the Great Barrier Reef, Australia. A multi-disciplinary team assessed a variety of factors focusing on nutrient dynamics and biotic responses. A controlled and replicated experiment was conducted over two years using twelve small patch reefs ponded at low tide by a coral rim. Treatments included three control reefs (no nutrient addition) and three + N reefs (NH4Cl added), three + P reefs (KH2PO4 added), and three + N + P reefs. Nutrients were added as pulses at each low tide (ca twice per day) by remotely operated units. There were two phases of nutrient additions. During the initial, low-loading phase of the experiment nutrient pulses (mean dose = 11.5 muM NH4+; 2.3 muM PO4-3) rapidly declined, reaching near-background levels (mean = 0.9 muM NH4+; 0.5 muM PO4-3) within 2-3 h. A variety of biotic processes, assessed over a year during this initial nutrient loading phase, were not significantly affected, with the exception of coral reproduction, which was affected in all nutrient treatments. In Acropora longicyathus and A. aspera, fewer successfully developed embryos were formed, and in A. longicyathus fertilization rates and lipid levels decreased. In the second, high-loading, phase of ENCORE an increased nutrient dosage (mean dose = 36.2 muM NH4+; 5.1 muM PO4-3 declining to means of 11.3 muM NH4+ and 2.4 muM PO4-3 at the end of low tide) was used for a further year, and a variety of significant biotic responses occurred. Encrusting algae incorporated virtually none of the added nutrients. Organisms containing endosymbiotic zooxanthellae (corals and giant clams) assimilated dissolved nutrients rapidly and were responsive to added nutrients. Coral mortality, not detected during the initial low-loading phase, became evident with increased nutrient dosage, particularly in Pocillopora damicornis. Nitrogen additions stunted coral growth, and phosphorus additions had a variable effect. Coral calcification rate and linear extension increased in the presence of added phosphorus but skeletal density was reduced, making corals more susceptible to breakage. Settlement of all coral larvae was reduced in nitrogen treatments, yet settlement of larvae from brooded species was enhanced in phosphorus treatments. Recruitment of stomatopods, benthic crustaceans living in coral rubble, was reduced in nitrogen and nitrogen plus phosphorus treatments. Grazing rates and reproductive effort of various fish species were not affected by the nutrient treatments. Microbial nitrogen transformations in sediments,were responsive to nutrient loading with nitrogen fixation significantly increased in phosphorus treatments and denitrification increased in all treatments to which nitrogen had been added. Rates of bioerosion and grazing showed no significant effects of added nutrients, ENCORE has shown that reef organisms and processes investigated ill situ were impacted by elevated nutrients. Impacts mere dependent on dose level, whether nitrogen and/or phosphorus mere elevated and were often species-specific. The impacts were generally sub-lethal and subtle and the treated reefs at the end of the experiment mere visually similar to control reefs. Rapid nutrient uptake indicates that nutrient concentrations alone are not adequate to assess nutrient condition of reefs. Sensitive and quantifiable biological indicators need to be developed for coral reef ecosystems. The potential bioindicators identified in ENCORE should be tested in future research on coral reef/nutrient interactions. Synergistic and cumulative effects of elevated nutrients and other environmental parameters, comparative studies of intact vs. disturbed reefs, offshore vs, inshore reefs, or the ability of a nutrient-stressed reef to respond to natural disturbances require elucidation. An expanded understanding of coral reef responses to anthropogenic impacts is necessary, particularly regarding the subtle, sub-lethal effects detected in the ENCORE studies. (C) 2001 Published by Elsevier Science Ltd.

A new approach for detecting and mapping sewage impacts

Increased nitrogen loading has been implicated in eutrophication occurrences worldwide. Much of this loading is attributable to the growing human population along the world's coastlines. A significant component of this nitrogen input is from sewage effluent, and delineation of the distribution and biological impact of sewage-derived nitrogen is becoming increasingly important. Here, we show a technique that identifies the source, extent and fate of biologically available sewage nitrogen in coastal marine ecosystem. This method is based on the uptake of sewage nitrogen by marine plants and subsequent analysis of the sewage signature (elevated delta N-15) in plant tissues. Spatial analysis is used to create maps of delta N-15 and establish coefficient of variation estimates of the mapped values. We show elevated delta N-15 levels in marine plants near sewage outfalls in Moreton Bay, Australia, a semi-enclosed bay receiving multiple sewage inputs. These maps of sewage nitrogen distribution are being used to direct nutrient reduction strategies in the region and will assist in monitoring the effectiveness of environmental protection measures. (C) 2001 Elsevier Science Ltd. All rights reserved.