Distribution of lipid nanocapsules in different cochlear cell populations after round window membrane permeation

Hearing loss is a major public health problem, and its treatment with traditional therapy strategies is often unsuccessful due to limited drug access deep in the temporal bone. Multifunctional nanoparticles that are targeted to specified cell populations, biodegradable, traceable in vivo, and equipped with controlled drug/gene release may resolve this problem. We developed lipid core nanocapsules (LNCs) with sizes below 50 nm. The aim of the present study is to evaluate the ability of the LNCs to pass through the round window membrane and reach inner ear targets. FITC was incorporated as a tag for the LNCs and Nile Red was encapsulated inside the oily core to assess the integrity of the LNCs. The capability of LNCs to pass through the round window membrane and the distribution of the LNCs inside the inner ear were evaluated in rats via confocal microscopy in combination with image analysis using ImageJ. After round window membrane administration, LNCs reached the spiral ganglion cells, nerve fibers, and spiral ligament fibrocytes within 30 min. The paracellular pathway was the main approach for LNC penetration of the round window membrane. LNCs can also reach the vestibule, middle ear mucosa, and the adjacent artery. Nuclear localization was detected in the spiral ganglion, though infrequently. These results suggest that LNCs are potential vectors for drug delivery into the spiral ganglion cells, nerve fibers, hair cells, and spiral ligament

Symmetry Breaking of Relativistic Multiconfiguration Methods in the Nonrelativistic Limit

The multiconfiguration Dirac-Fock method allows to calculate the state of relativistic electrons in atoms or molecules. This method has been known for a long time to provide certain wrong predictions in the nonrelativistic limit. We study in full mathematical details the nonlinear model obtained in the nonrelativistic limit for Be-like atoms. We show that the method with sp+pd configurations in the J=1 sector leads to a symmetry breaking phenomenon in the sense that the ground state is never an eigenvector of L^2 or S^2. We thereby complement and clarify some previous studies.Comment: Final version, to appear in Nonlinearity. Nonlinearity (2010) in pres

Cigarette smoking, cytochrome P4501A1 polymorphisms, and breast cancer among African-American and white women

INTRODUCTION: Previous epidemiologic studies suggest that women with variant cytochrome P4501A1 (CYP1A1) genotypes who smoke cigarettes are at increased risk for breast cancer. METHODS: We evaluated the association of breast cancer with CYP1A1 polymorphisms and cigarette smoking in a population-based, case–control study of invasive breast cancer in North Carolina. The study population consisted of 688 cases (271 African Americans and 417 whites) and 702 controls (285 African Americans and 417 whites). Four polymorphisms in CYP1A1 were genotyped using PCR/restriction fragment length polymorphism analysis: M1 (also known as CYP1A1*2A), M2 (CYP1A1*2C), M3 (CYP1A1*3), and M4 (CYP1A1*4) RESULTS: No associations were observed for CYP1A1 variant alleles and breast cancer, ignoring smoking. Among women who smoked for longer than 20 years, a modest positive association was found among women with one or more M1 alleles (odds ratio [OR] = 2.1, 95% confidence interval [CI] = 1.2–3.5) but not among women with non-M1 alleles (OR = 1.2, 95% CI = 0.9–1.6). Odds ratios for smoking longer than 20 years were higher among African-American women with one or more M3 alleles (OR = 2.5, 95% CI = 0.9–7.1) compared with women with non-M3 alleles (OR = 1.3, 95% CI = 0.8–2.2). ORs for smoking in white women did not differ appreciably based upon M2 or M4 genotypes. CONCLUSIONS: Cigarette smoking increases breast cancer risk in women with CYP1A1 M1 variant genotypes and in African-American women with CYP1A1 M3 variant genotypes, but the modifying effects of the CYP1A1 genotype are quite weak

Light-Activated Metal-Coordinated Supramolecular Complexes with Charge-Directed Self-Assembly

This document is the Accepted Manuscript version of a Published Work that appeared in final form in The Journal of Physical Chemistry C, copyright © American Chemical Society after peer review and technical editing by publisher. To access the final edited and published work see http://dx.doi.org/10.1021/jp3121403Metal-coordinated materials are attractive for many applications including catalysis, sensing, and controlled release. Adenine and its derivatives have been widely used to generate many coordination complexes, polymers, and nanoparticles. However, few of these materials display fluorescence. Herein, we report fluorescent gold complexes and nanoclusters formed with adenosine, deoxyadenosine, AMP, and ATP, where the former two produced micrometer-sized particles and the latter two produced molecular clusters. Only weak fluorescence was produced with adenine, while no emission was observed with uridine, cytidine, or guanosine. We found that adding citrate and light exposure are two key factors to generate fluorescence, and their mechanistic roles have been explored. In all the products, the ratio between gold and adenine was determined to be 1:1 using UV–vis spectroscopy. Mass spectrometry showed clusters containing 2, 4, and 6 gold atoms in the gas phase. The fluorescence peak is around 470 nm for the AMP and ATP complex and 480 nm for the (deoxy)adenosine complexes. This work has provided a systematic approach to obtain fluorescent metal coordinated polymers and materials with tunable sizes, which will find applications in analytical chemistry, drug delivery, and imaging. The fundamental physical chemistry of these materials has been systematically explored.University of Waterloo || Canadian Foundation for Innovation || Ontario Ministry of Research & Innovation || Natural Sciences and Engineering Research Council |

Complete Result for Positronium Energy Levels at Order alpha^6 m

We have completed theoretical predictions for positronium energy levels through order alpha^6 m by the calculation of the spin independent, radiative recoil correction. This contribution is significant and amounts to 10.64 MHz for the 1S state. We further perform detailed comparison of theoretical predictions to experimental results for 1S-2S and 2S-2P transitions.Comment: 9 pages, 2 tables. Email: [email protected]