Common variants in signaling transcription-factor-binding sites drive phenotypic variability in red blood cell traits

Genome-wide association studies identify genomic variants associated with human traits and diseases. Most trait-associated variants are located within cell-type-specific enhancers, but the molecular mechanisms governing phenotypic variation are less well understood. Here, we show that many enhancer variants associated with red blood cell (RBC) traits map to enhancers that are co-bound by lineage-specific master transcription factors (MTFs) and signaling transcription factors (STFs) responsive to extracellular signals. The majority of enhancer variants reside on STF and not MTF motifs, perturbing DNA binding by various STFs (BMP/TGF-β-directed SMADs or WNT-induced TCFs) and affecting target gene expression. Analyses of engineered human blood cells and expression quantitative trait loci verify that disrupted STF binding leads to altered gene expression. Our results propose that the majority of the RBC-trait-associated variants that reside on transcription-factor-binding sequences fall in STF target sequences, suggesting that the phenotypic variation of RBC traits could stem from altered responsiveness to extracellular stimuli

Measurement of concentration profiles using confocal Raman spectroscopy in multicomponent polymeric coatings-model validation

Concentrations of the solvents were measured using confocal laser Raman Spectroscopy for two ternary systems, poly(styrene)tetrahydrofuranp-xylene and poly(methyl methacrylate)ethylbenzenetetrahydrofuran, during drying at room temperature. The concentrations were compared with predictions of drying models, which utilize several existing theories for mutual diffusion coefficients for polymer solvent systems. Of the nine free volume parameters required to predict diffusion coefficients of binary systems, four for each of the four pairs studied here were estimated as suggested by the literature. Estimation was done by minimizing the difference between predictions of the model and experimental weight loss data for each binary pair. It is found that the predictions of the models which include cross term diffusion coefficients are in better agreement with measured concentrations than those which ignore the cross terms. (c) 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 201

Analysis of Sensitivity of Equilibrium Constant to Reaction Conditions for Esterification of Fatty Acids with Alcohols

The equilibrium constant (K-eq) depends on temperature only, but reported measurements for esterification reactions show that it also depends on reactant concentration and amount of catalyst. In this work, analysis of sensitivity of K-eq to errors in equilibrium composition of esterification reactions at different reaction conditions is presented. Rigorous error and Taguchi analyses showed that K-eq is indeed a function of temperature only and not of molar ratio (MR) of the reactants and catalyst loading; reported dependency of K-eq on reactants concentrations and catalyst loadings is due to errors in analysis of equilibrium composition. Sensitivity of K-eq to these errors depends strongly on molar ratio (MR), and calculations show that K-eq is least sensitive to error at 1.5 MR. However, phase separation of the reaction mixture is possible at 1.5 MR which can cause errors in measured equilibrium composition. K-eq of esterification reactions should be obtained through kinetic data fitting to the rate model. For sulfuric acid-catalyzed esterification of oleic acid with methanol, a single K-eq value for each reaction temperature is obtained through kinetics data fitting as 1.53 (+/-0.05), 1.67 (+/-0.04), and 1.91 (+/-0.06) at 313, 323, and 338 K, respectively. Equilibrium compositions are calculated reasonably well with these K-eq values

Near-Optimization of Operating Conditions and Residence Times in Multizone Dryers for Polymer Coatings

Several polymeric coatings are dried by blowing jets of hot air on them from the top and bottom sides in multizone dryers. The goal of quickly removing solvent from a coating by manipulating air flow and temperature, together called operating conditions in this work, conflicts with the goal of producing blister-free coatings. Optimum operating conditions ensure both minimum residual solvent and no defects. Determining optimum conditions for multizone dryers is a difficult task with severe convergence problems. In this work, an easy method is developed to determine near-optimum operating conditions and residence times. The results indicate that the air flow on the top side should always be lower than or equal to that on the bottom side; the minimum residence time in first zone should be such that, toward the end, the solvent concentration starts to fall at the bottom. As long as the residence times are reasonably long, several different combinations of residence times in the second and subsequent zones nearly minimize residual solvent

Robust Silica Aerogel Microspheres from Rice Husk Ash to Enhance the Dissolution Rate of Poorly Water-Soluble Drugs

The present paper demonstrates the capability of specially prepared robust silica aerogel microspheres (RSAMs) to enhance the dissolution rate of poorly water-soluble drugs. A sol-gel/mineral oil emulsion method has been developed for RSAMs from rice husk ash (RHA), a biogenic source. The particles were characterized for their Brunauer-Emmett-Teller (BET) specific surface area, Barrett, Joyner and Halenda (BJH) pore volume and pore diameter, and morphology by optical microscopy and scanning electron microscopy (SEM). The dissolution rate of ibuprofen, a poorly water-soluble drug, was investigated by adsorbing it onto RSAMs upon dissolving it in supercritical carbon dioxide (scCO(2)) at 150 bar and 40 degrees C. This resulted in a loading of similar to 0.13 g ibuprofen/g loaded RSAMs in 24 h. X-ray diffraction analysis was used to characterize the nature of the adsorbed ibuprofen onto RSAMs. It was observed that the loaded drug on the aerogels is in amorphous form. An in vitro drug-release kinetic studies confirmed a significant enhancement in the dissolution rate, namely similar to 100% of the loaded ibuprofen released as compared to that of similar to 11% of crystalline ibuprofen in 15 min

Concentration-independent rate constant for biodiesel synthesis from homogeneous-catalytic esterification of free fatty acid

Dependence of the second-order rate constant (SRC) on the reactants' concentration, for esterification or Fatty acids, is found empirically in the published reports. Taguchi method is used to study dependency of the rate constant on temperature, reactants' concentration, and catalyst loading for the synthesis of biodiesel from sulfuric acid-catalyzed esterification of free fatty acid (ETA) with methanol. On the basis of general literature on dependency of rate constant on reactants' concentration and the esterification-rate determining step, concentration term embedded in the units of SRC has been identified as catalyst concentration. Accordingly SRC has been modified to include the catalyst concentration in the rate law, which is consistent with the general mass-action rate law reported by Blum and bus (1964) and Pikar (2011). Analysis of the modified rate constant showed it to be independent of the reactants' concentration, It is thus named as 'concentration independent rate constant (ClRC)'. The predictions of kinetics of the esterification of FFA are better using CIRC than other commonly used rate forms. The modified rate constant is shown to be equivalent to Bronsted-Bjerrum relation. Moreover, the modified rate constant is more general than the reported ones for esterification of fatty acids and it predicts kinetics well over a wide range of reaction parameters. (C) 2014 Elsevier Ltd. All rights reserved

Parametric effects on kinetics of esterification for biodiesel production: A Taguchi approach

Parametric-effects On kinetics for biodiesel production from H2SO4-catalyzed esterification of free fatty acids (FFA) with methanol are evaluated at different intervals of reaction using Taguchi method. The parameters studied with orthogonal array design are catalyst loading, temperature, and methanol-to-FFA mole ratio (MR). Within the range of the parameters studied, each parameter has positive effect on conversion of FFA (X-FFA) throughout the reaction wherein trans-esterification of oil is found negligible. But relative-contribution of temperature to X-FFA declined similar to 23.5% (from 55.77% at 10 min to 32.39% at 180 min) and that of MR increased similar to 29%. (from 21.46% at 10 min to 50.45% at 180 min). Catalyst loading has minimal effect on X-FFA throughout the reaction (contribution varied within 15-24%) and has constant effect on FFA-esterification rate beyond 75 min. The relative effect of reaction time (as an independent parameter) along with other parameters is also evaluated at different reaction-phases and the orders of parametric-effects are compared with the results of the detailed analyses (using Taguchi approach) of esterification-kinetics data of published works for biodiesel synthesis. The relative parametric-effects on kinetics are found to be a I-Unction of reaction duration; parametric-order changes as reaction progresses toward equilibrium. However, temperature and MR are the more dominant parameters than catalyst loading and reaction time. Taguchi additivity model is validated with experiments and the predictions deviated within +/- 5%. (C) 2013 Elsevier Ltd. All rights reserved

Encapsulation of nanoparticles using CO2-expanded liquids

A new process for encapsulation based on the principle of precipitation of nanoparticles by pressure reduction of CO2 gas-expanded liquids (PPRGEL) is presented here. Encapsulation has been studied for two types of core solid nanoparticles, namely suspended and in situ produced particles from solution. Mechanisms for both types of encapsulations have been proposed: for the former type deposition happens because of mass transfer from the bulk solution; for the latter type encapsulation happens if the supersaturation profiles of the core and coating solutes are staggered in time in order that the core solute precipitates first and the coating solute deposits on it by mass transfer. A model for the process that includes nucleation and growth has been developed to select systems and process conditions that favor encapsulation. The mechanisms have been experimentally verified at 52 bar and 303 K for (i) encapsulation of suspended nanoparticles of silica with ascorbylpalmitate (AP) dissolved acetone and (ii) encapsulation of in situ produced tartaric acid (TA) nanoparticles with AP, both initially dissolved in acetone. A uniform coating of about 10-20 nm of AP is formed on the 250 nm silica particles. For the two-solute system it is observed that AP deposits on TA resulting in encapsulated particles of an average size of about 520 nm. (C) 2013 Elsevier B.V. All rights reserved

Mechanism for formation of Hollow and Granular Silica Aerogel Microspheres from rice husk ash for drug delivery

The present work describes a method for preparation of Hollow Silica Aerogel Microspheres (HSAMs) and Granular Silica Aerogel Microparticles (GSAMs) for drug delivery, from rice husk ash (RHA), an inexpensive source of bio-compatible silica. This method involves a two-step sol-gel process for preparation of wet gel microspheres using an improved sol-gel/mineral-oil emulsion (containing dual surfactants), followed by solvent exchange and aging in aqueous ethanol, to replace water in the microspheres with ethanol. It is shown that the amount and concentration of the ammonium hydroxide (NH4OH) solution added during gelation process determine if hollow or granular wet gel particles form. A mechanism for the formation of HSAMs or GSAMs is proposed and validated by experiments. The wet gel particles are subsequently dried with supercritical carbon dioxide at 150 bar and 50 degrees C to obtain HSAMs or GSAMs. HSAMs afford high loading of drugs as illustrated by loading of 0.47 g ibuprofen per g of HSAM. Further, a fast release of ibuprofen from loaded HSAMs compared to pure crystalline ibuprofen and other loaded forms, indicates that HSAMs produced by the present method are good drug delivery vehicles. (C) 2015 Elsevier B.V. All rights reserved