Digital sculpture : technical and aesthetic considerations applicable to current input and output modes of additive fabricated sculpture

Published ArticleThis article examines the synergy between aesthetic and technical issues surrounding current input and output modes applicable to digital sculpture built by means of additive fabrication technologies. The scope is limited to select sculptural aspects that either transcend, question or fall short when measured against traditional manufacturing and aesthetic modes. Presented are a range of technical as well as aesthetic aspects that have impacted on this ''new form'' of sculpture delivery. It is indicated that irrespective of current strengths and weaknesses, for the evolving sculptor, an interactive creative partnership between technologies equally positions this ''new form'' of sculpture delivery as a leading role player towards defining a new digital aesthetic

Biochemical evaluation of the nutrition status of Urban Primary school children: riboflavin status

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Biochemical investigation of the nutrition status of urban school children aged 12 -15 years: Protein status

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Biochemical evaluation of the nutrition status of urban primary school children: Vitamin-A status

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Biochemical evaluation of the nutrition status of urban school children of 12-15 years - riboflavin status

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The effect of dietary therapy on abnormal carbohydrate and fat metabolism

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Reductive atmospheric acid leaching of lateritic smectite/nontronite ores in H2SO4/Cu(II)/SO2 solutions

Despite the success of reductive atmospheric acid leaching (RAAL) of limonitic nickel laterite ores in recent studies limited attempt has been made to apply this method to smectite/nontronite ores of different mineralogies. A comparative study of four smectite/nontronite ores in this study showed that the use of 700 kg H2SO4/ton dry ore leaches only 74-86% Ni, 37-76% Co, 47-58% Fe and 24-66% Mn at 90 °C from slurries of 20-35% (w/w) pulp density even after 10 h, depending upon the mineralogy. These values increased to 90-97% Ni, 94-97% Co, 92-98% Mn and 72-85% Fe in the presence of Cu(II)/SO2. The first order dependence of initial fraction of iron, aluminium and nickel leached from a typical smectite ore in the first 0.5 h on the initial acid concentration provides evidence for the involvement of hydrogen ions in the surface reaction. Low activation energy of 10 kJ/mol based on the fraction of nickel leached in the first 0.5 h indicates a diffusion controlled reaction. This is supported by the applicability of a shrinking core kinetic model for metal dissolution over the first 2 h, with different apparent rate constants (kap) depending upon the iron oxide content, mineralogy and porosity. A log-log plot of kap for ores with high iron content as a function of acid concentration agrees reasonably well with the correlation already established for the leaching of nickel from limonitic laterite and manganese nodules. Thus, initial fast leaching can be related to the higher porosity and a rate controlling step which involves the diffusion of H+ through a thickening solid layer. The slow leaching at latter stages is a result of low remnant acid, thickening solid layer and changes in mineral composition

Receptor activation using multi-biomarker pharmacokinetic/pharmacodynamic modelling

receptor activation was evaluated using quinpirole as a paradigm compound. ), as well as plasma concentrations of 13 hormones and neuropeptides, were measured. Experiments were performed at day 1 and repeated after 7-day s.c. drug administration. PK/PD modelling was applied to identify the in vivo concentration-effect relations and neuroendocrine dynamics. receptor expression levels on the pituitary hormone-releasing cells predicted the concentration-effect relationship differences. Baseline levels (ACTH, prolactin, TSH), hormone release (ACTH) and potency (TSH) changed with treatment duration. agonists in clinical practice. Further development towards quantitative systems pharmacology models will eventually facilitate mechanistic drug development. BACKGROUND AND PURPOSE EXPERIMENTAL APPROACH KEY RESULTS CONCLUSIONS AND IMPLICATION

A novel CCR2 antagonist inhibits atherogenesis in apoE deficient mice by achieving high receptor occupancy

CC Chemokine Receptor 2 (CCR2) and its endogenous ligand CCL2 are involved in a number of diseases, including atherosclerosis. Several CCR2 antagonists have been developed as potential therapeutic agents, however their in vivo clinical efficacy was limited. In this report, we aimed to determine whether 15a, an antagonist with a long residence time on the human CCR2, is effective in inhibiting the development of atherosclerosis in a mouse disease model. First, radioligand binding assays were performed to determine affinity and binding kinetics of 15a on murine CCR2. To assess the in vivo efficacy, western-type diet fed apoE-/- mice were treated daily with 15a or vehicle as control. Treatment with 15a reduced the amount of circulating CCR2+ monocytes and the size of the atherosclerotic plaques in both the carotid artery and the aortic root. We then showed that the long pharmacokinetic half-life of 15a combined with the high drug concentrations ensured prolonged CCR2 occupancy. These data render 15a a promising compound for drug development and confirms high receptor occupancy as a key parameter when targeting chemokine receptors

Diurnal variation in P-glycoprotein-mediated transport and cerebrospinal fluid turnover in the brain.

Nearly all bodily processes exhibit circadian rhythmicity. As a consequence, the pharmacokinetic and pharmacodynamic properties of a drug may also vary with time of day. The objective of this study was to investigate diurnal variation in processes that regulate drug concentrations in the brain, focusing on P-glycoprotein (P-gp). This efflux transporter limits the distribution of many drugs in the brain. To this end, the exposure to the P-gp substrate quinidine was determined in the plasma and brain tissue after intravenous administration in rats at six different time points over the 24-h period. Our results indicate that time of administration significantly affects the exposure to quinidine in the brain. Upon inhibition of P-gp, exposure to quinidine in brain tissue is constant over the 24-h period. To gain more insight into processes regulating brain concentrations, we used intracerebral microdialysis to determine the concentration of quinidine in brain extracellular fluid (ECF) and cerebrospinal fluid (CSF) after intravenous administration at two different time points. The data were analyzed by physiologically based pharmacokinetic modeling using NONMEM. The model shows that the variation is due to higher activity of P-gp-mediated transport from the deep brain compartment to the plasma compartment during the active period. Furthermore, the analysis reveals that CSF flux is higher in the resting period compared to the active period. In conclusion, we show that the exposure to a P-gp substrate in the brain depends on time of administration, thereby providing a new strategy for drug targeting to the brain.Pharmacolog