Encapsulation of Lornoxicam into spermaceti microspheres and comparative bioavailability study

In this study, Lornoxicam (LX) loaded spermaceti (SC) microspheres were prepared using meltable emulsified dispersion cooling induced solidification technique and the bioavailability of the marketed product (Flexispaz® capsule-reference-product A) was compared with the optimized formulation (lornoxicam loaded spermaceti microspheres–test–product B). Morphological studies of wax microspheres were evaluated using scanning electron microscopy (SEM). The SEM images showed the spherical shape of wax microspheres and more than 97% of the isolated microspheres were in the size range 309-317 μm. Differential scanning calorimetry (DSC), Fourier transforms infrared (FTIR) spectroscopy and stability studies showed that the drug after encapsulation with SC microspheres was stable and compatible. A single dose, randomized, complete cross over study of LX (8mg) microspheres were carried out on 10 healthy male and female Albino sheep’s under fasting conditions. Plasma LX concentrations and other pharmacokinetic parameters obtained were statistically analyzed. Based on this study, it can be concluded that drug loaded LX microspheres and Flexispaz® capsule are bioequivalent in term of the rate and extent of absorption.Key words: Lornoxicam; Wax microspheres; Release kinetics; Bioavailability; Bioequivalence

Encapsulation of Lornoxicam into spermaceti microspheres and comparative bioavailability study

In this study, Lornoxicam (LX) loaded spermaceti (SC) microspheres were prepared using meltable emulsified dispersion cooling induced solidification technique and the bioavailability of the marketed product (Flexispaz® capsule-reference-product A) was compared with the optimized formulation (lornoxicam loaded spermaceti microspheres–test–product B). Morphological studies of wax microspheres were evaluated using scanning electron microscopy (SEM). The SEM images showed the spherical shape of wax microspheres and more than 97% of the isolated microspheres were in the size range 309-317 μm. Differential scanning calorimetry (DSC), Fourier transforms infrared (FTIR) spectroscopy and stability studies showed that the drug after encapsulation with SC microspheres was stable and compatible. A single dose, randomized, complete cross over study of LX (8mg) microspheres were carried out on 10 healthy male and female Albino sheep’s under fasting conditions. Plasma LX concentrations and other pharmacokinetic parameters obtained were statistically analyzed. Based on this study, it can be concluded that drug loaded LX microspheres and Flexispaz® capsule are bioequivalent in term of the rate and extent of absorption.Key words: Lornoxicam; Wax microspheres; Release kinetics; Bioavailability; Bioequivalence

Toward physical realizations of thermodynamic resource theories

Conventional statistical mechanics describes large systems and averages over many particles or over many trials. But work, heat, and entropy impact the small scales that experimentalists can increasingly control, e.g., in single-molecule experiments. The statistical mechanics of small scales has been quantified with two toolkits developed in quantum information theory: resource theories and one-shot information theory. The field has boomed recently, but the theorems amassed have hardly impacted experiments. Can thermodynamic resource theories be realized experimentally? Via what steps can we shift the theory toward physical realizations? Should we care? I present eleven opportunities in physically realizing thermodynamic resource theories.Comment: Publication information added. Cosmetic change

Facile Synthesis of High Quality Graphene Nanoribbons

Graphene nanoribbons have attracted attention for their novel electronic and spin transport properties1-6, and because nanoribbons less than 10 nm wide have a band gap that can be used to make field effect transistors. However, producing nanoribbons of very high quality, or in high volumes, remains a challenge. Here, we show that pristine few-layer nanoribbons can be produced by unzipping mildly gas-phase oxidized multiwalled carbon nanotube using mechanical sonication in an organic solvent. The nanoribbons exhibit very high quality, with smooth edges (as seen by high-resolution transmission electron microscopy), low ratios of disorder to graphitic Raman bands, and the highest electrical conductance and mobility reported to date (up to 5e2/h and 1500 cm2/Vs for ribbons 10-20 nm in width). Further, at low temperature, the nanoribbons exhibit phase coherent transport and Fabry-Perot interference, suggesting minimal defects and edge roughness. The yield of nanoribbons was ~2% of the starting raw nanotube soot material, which was significantly higher than previous methods capable of producing high quality narrow nanoribbons1. The relatively high yield synthesis of pristine graphene nanoribbons will make these materials easily accessible for a wide range of fundamental and practical applications.Comment: Nature Nanotechnology in pres

A frequentist framework of inductive reasoning

Reacting against the limitation of statistics to decision procedures, R. A. Fisher proposed for inductive reasoning the use of the fiducial distribution, a parameter-space distribution of epistemological probability transferred directly from limiting relative frequencies rather than computed according to the Bayes update rule. The proposal is developed as follows using the confidence measure of a scalar parameter of interest. (With the restriction to one-dimensional parameter space, a confidence measure is essentially a fiducial probability distribution free of complications involving ancillary statistics.) A betting game establishes a sense in which confidence measures are the only reliable inferential probability distributions. The equality between the probabilities encoded in a confidence measure and the coverage rates of the corresponding confidence intervals ensures that the measure's rule for assigning confidence levels to hypotheses is uniquely minimax in the game. Although a confidence measure can be computed without any prior distribution, previous knowledge can be incorporated into confidence-based reasoning. To adjust a p-value or confidence interval for prior information, the confidence measure from the observed data can be combined with one or more independent confidence measures representing previous agent opinion. (The former confidence measure may correspond to a posterior distribution with frequentist matching of coverage probabilities.) The representation of subjective knowledge in terms of confidence measures rather than prior probability distributions preserves approximate frequentist validity.Comment: major revisio

Lactic acid production from lime-treated wheat straw by Bacillus coagulans: neutralization of acid by fed-batch addition of alkaline substrate

Conventional processes for lignocellulose-to-organic acid conversion requires pretreatment, enzymatic hydrolysis, and microbial fermentation. In this study, lime-treated wheat straw was hydrolyzed and fermented simultaneously to lactic acid by an enzyme preparation and Bacillus coagulans DSM 2314. Decrease in pH because of lactic acid formation was partially adjusted by automatic addition of the alkaline substrate. After 55 h of incubation, the polymeric glucan, xylan, and arabinan present in the lime-treated straw were hydrolyzed for 55%, 75%, and 80%, respectively. Lactic acid (40.7 g/l) indicated a fermentation efficiency of 81% and a chiral l(+)-lactic acid purity of 97.2%. In total, 711 g lactic acid was produced out of 2,706 g lime-treated straw, representing 43% of the overall theoretical maximum yield. Approximately half of the lactic acid produced was neutralized by fed-batch feeding of lime-treated straw, whereas the remaining half was neutralized during the batch phase with a Ca(OH)2 suspension. Of the lime added during the pretreatment of straw, 61% was used for the neutralization of lactic acid. This is the first demonstration of a process having a combined alkaline pretreatment of lignocellulosic biomass and pH control in fermentation resulting in a significant saving of lime consumption and avoiding the necessity to recycle lime

Presenting the Uncertainties of Odds Ratios Using Empirical-Bayes Prediction Intervals

Quantifying exposure-disease associations is a central issue in epidemiology. Researchers of a study often present an odds ratio (or a logarithm of odds ratio, logOR) estimate together with its confidence interval (CI), for each exposure they examined. Here the authors advocate using the empirical-Bayes-based ‘prediction intervals’ (PIs) to bound the uncertainty of logORs. The PI approach is applicable to a panel of factors believed to be exchangeable (no extra information, other than the data itself, is available to distinguish some logORs from the others). The authors demonstrate its use in a genetic epidemiological study on age-related macular degeneration (AMD). The proposed PIs can enjoy straightforward probabilistic interpretations—a 95% PI has a probability of 0.95 to encompass the true value, and the expected number of true values that are being encompassed is for a total of 95% PIs. The PI approach is theoretically more efficient (producing shorter intervals) than the traditional CI approach. In the AMD data, the average efficiency gain is 51.2%. The PI approach is advocated to present the uncertainties of many logORs in a study, for its straightforward probabilistic interpretations and higher efficiency while maintaining the nominal coverage probability

Etching and Narrowing of Graphene from the Edges

Large scale graphene electronics desires lithographic patterning of narrow graphene nanoribbons (GNRs) for device integration. However, conventional lithography can only reliably pattern ~20nm wide GNR arrays limited by lithography resolution, while sub-5nm GNRs are desirable for high on/off ratio field-effect transistors (FETs) at room temperature. Here, we devised a gas phase chemical approach to etch graphene from the edges without damaging its basal plane. The reaction involved high temperature oxidation of graphene in a slightly reducing environment to afford controlled etch rate (\leq ~1nm/min). We fabricated ~20-30nm wide GNR arrays lithographically, and used the gas phase etching chemistry to narrow the ribbons down to <10nm. For the first time, high on/off ratio up to ~10^4 was achieved at room temperature for FETs built with sub-5nm wide GNR semiconductors derived from lithographic patterning and narrowing. Our controlled etching method opens up a chemical way to control the size of various graphene nano-structures beyond the capability of top-down lithography.Comment: 18 pages, 4 figures, to appear in Nature Chemistr

IL-21 Limits Peripheral Lymphocyte Numbers through T Cell Homeostatic Mechanisms

IL-21, a member of the common gamma-chain utilizing family of cytokines, participates in immune and inflammatory processes. In addition, the cytokine has been linked to autoimmunity in humans and rodents.To investigate the mechanism whereby IL-21 affects the immune system, we investigated its role in T cell homeostasis and autoimmunity in both non-autoimmune C57BL/6 and autoimmune NOD mice. Our data indicate that IL-21R knockout C57BL/6 and NOD mice show increased size of their lymphocyte population and decreased homeostatic proliferation. In addition, our experimental results demonstrate that IL-21 inhibits T cell survival. These data suggest that IL-21 acts to limit the size of the T cell pool. Furthermore, our data suggest IL-21 may contribute to the development of autoimmunity.Taken together, our results suggest that IL-21 plays a global role in regulating T cell homeostasis, promoting the continuous adaptation of the T cell lymphoid space