Maximizing Adsorption Involving Three Solutes on Enhanced Adsorbents Using the Mixture-Process Variable Design

Unmodified (UN), acid-treated (AT) and microwave-acid-treated (MAT) activated carbons were optimized for their solute removal efficacies by adjusting feed mixture compositions and process conditions. Acetaminophen, benzotriazole, and caffeine were used either individually or as binary/ternary mixtures in this study. The process conditions considered were the pH, adsorbent dosage, and type of adsorbent. Experimental responses such as total adsorbent loading (qtotal) and total percentage removal (PRtotal) were fitted with empirical models that had high adjusted R2 (>0.95), insignificant lack of fit (p-value > 0.22), and high model predictive R2 (>0.93). Mixture compositions of the feed were found to interact significantly not only among themselves but with process variables as well. Hence, adsorption optimization must simultaneously consider mixture as well as process variables. The conventional response surface methodology for mixtures, termed as ridge analysis, optimizes mixture compositions at specified values of process variables. An improved steepest ascent method which considers mixture and process variables simultaneously was developed in this work. This could track the path of steepest ascent toward globally optimal settings, from any arbitrary starting point within the design space. For the chosen adsorbent, optimal settings for feed mixture compositions and pH were found to change along this steepest ascent path. The feed compositions, pH, and adsorbent dosage identified for maximum adsorbent utilization were usually quite different from those identified for maximum total percentage removal. When both these objectives were optimized together, the most favorable compromise solutions for qtotal and PRtotal were, respectively, 264.1 mg/g and 43.4% for UN, 294.9 mg/g and 52.5% for AT, and 336.6 mg/g and 55.9% for MAT

The Ubiquitin Proteasome System Acutely Regulates Presynaptic Protein Turnover and Synaptic Efficacy

AbstractBackground: The ubiquitin proteasome system (UPS) mediates regulated protein degradation and provides a mechanism for closely controling protein abundance in spatially restricted domains within cells. We hypothesized that the UPS may acutely determine the local concentration of key regulatory proteins at neuronal synapses as a means for locally modulating synaptic efficacy and the strength of neurotransmission communication.Results: We investigated this hypothesis at the Drosophila neuromuscular synapse by using an array of genetic and pharmacological tools. This study demonstrates that UPS components are present in presynaptic boutons and that the UPS functions locally in the presynaptic compartment to rapidly eliminate a conditional transgenic reporter of proteasome activity. We assayed a panel of synaptic proteins to determine whether the UPS acutely regulates the local abundance of native synaptic targets. Both acute pharmacological inhibition of the proteasome (<1 hr) and targeted genetic perturbation of proteasome function in the presynaptic neuron cause the specific accumulation of the essential synaptic vesicle-priming protein DUNC-13. Most importantly, acute pharmacological inhibition of the proteasome (<1 hr) causes a rapid strengthening of neurotransmission (an approximately 50% increase in evoked amplitude) because of increased presynaptic efficacy. The proteasome-dependent regulation of presynaptic protein abundance, both of the exogenous reporter and native DUNC-13, and the modulation of presynaptic neurotransmitter release occur on an intermediate, rapid (tens of minutes) timescale.Conclusions: Taken together, these studies demonstrate that the UPS functions locally within synaptic boutons to acutely control levels of presynaptic protein and that the rate of UPS-dependent protein degradation is a primary determinant of neurotransmission strength