2,602 research outputs found

    Complement activation and protein adsorption by carbon nanotubes

    Get PDF
    As a first step to validate the use of carbon nanotubes as novel vaccine or drug delivery devices, their interaction with a part of the human immune system, complement, has been explored. Haemolytic assays were conducted to investigate the activation of the human serum complement system via the classical and alternative pathways. Western blot and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) techniques were used to elucidate the mechanism of activation of complement via the classical pathway, and to analyse the interaction of complement and other plasma proteins with carbon nanotubes. We report for the first time that carbon nanotubes activate human complement via both classical and alternative pathways. We conclude that complement activation by nanotubes is consistent with reported adjuvant effects, and might also in various circumstances promote damaging effects of excessive complement activation, such as inflammation and granuloma formation. C1q binds directly to carbon nanotubes. Protein binding to carbon nanotubes is highly selective, since out of the many different proteins in plasma, very few bind to the carbon nanotubes. Fibrinogen and apolipoproteins (AI, AIV and CIII) were the proteins that bound to carbon nanotubes in greatest quantit

    Implementation and Utilization of Mobile Technology In Adolescent Bariatric Surgery Patients

    Get PDF
    Obesity is the most prevalent chronic disease of childhood. Obese adolescents are likely to become obese adults with significant associated co-morbidities and early mortality. In Massachusetts, 30% of children ages 10-17 are overweight or obese. It is projected that 48% of Massachusetts’ adults will be obese by 2030. In March of 2015, the Good Fit Adolescent Weight and Wellness Center opened, with a goal of addressing this issue with a proven multidisciplinary approach. Mobile technology continues to develop at a rapid pace. Adolescent access to mobile technology on smart phones and tablets continues to increase. Mobile fitness tracker applications are numerous and easy to use for today’s tech savvy teens. Successful weight loss and health maintenance is variable and has been difficult to validate with this technology so far. The purpose of this study is to evaluate existing mobile applications to be used by adolescent patients in the Good Fit Center. Our aim is to determine whether adolescent patients will be compliant with diet and exercise challenges sent through a mobile application and social media platform. We will work closely with dietitians, physicians and surgeons to evaluate feasibility and compliance within the first year of this project. In the second year, we will then test the functionality of this mobile application as it relates to patient success in the Good Fit program. The proposed research is a novel multimodal study combining behavioral sciences research, clinical outcomes research, and mobile technology to help to better understand the fitness management of adolescents struggling with morbid obesity. The findings of our research may have a number of important implications. These include the refinement of existing fitness strategies, as well as the development of a new useful piece of technology to combat obesity and improve the health and clinical outcomes of our nation’s children

    Enhancing the Laser Scanning Confocal Microscopic Visualization of Lucifer Yellow Filled Cells in Whole-Mounted Tissue

    Get PDF
    The laser scanning confocal microscope (LSCM) is an extremely useful tool that allows fluorescently labelled cells to be visualized in whole-mount preparations. This is particularly advantageous, for example, in studying the dendritic trees of neurons with respect to their environment. One of the most popular, and easiest, ways to visualize a cell is to inject it intracellularly with the fluorophore Lucifer Yellow (LY). However, the argon gas lasers of most LSCM\u27s are not well matched to the excitation spectrum of aqueous LY. When this largely inappropriate excitation is combined with standard filters, designed for fluorescein fluorescence rather than Lucifer Yellow, the resulting image is poor. We report that clearing LY-injected neurons in methyl salicylate and mounting them in Entellan, a non-aqueous medium of high refractive index, enhances their visualization on a Bio-Rad LSCM with standard fluorescein (FITC) filters to an unexpected degree. This technique also leads to a substantial reduction in photobleaching

    X-ray crystallographic structure of a complex between a synthetic protease of human immunodeficiency virus 1 and a substrate-based hydroxyethylamine inhibitor

    Get PDF
    The structure of a crystal complex of the chemically synthesized protease of human immunodeficiency virus 1 with a heptapeptide-derived inhibitor bound in the active site has been determined. The sequence of the inhibitor JG-365 is Ac-Ser-Leu-Asn-Phe-ψ[CH(OH)CH_2N]-Pro-Ile-Val-OMe; the K_i is 0.24 nM. The hydroxyethylamine moiety, in place of the normal scissile bond of the substrate, is believed to mimic a tetrahedral reaction intermediate. The structure of the complex has been refined to an R factor of 0.146 at 2.4-Å resolution by using restrained least squares with rms deviations in bond lengths of 0.02 Å and bond angles of 4. The bound inhibitor diastereomer has the S configuration at the hydroxyethylamine chiral carbon, and the hydroxyl group is positioned between the active site aspartate carboxyl groups within hydrogen bonding distance. Comparison of this structure with a reduced peptide bond inhibitor-protease complex indicates that these contacts confer the exceptional binding strength of JG-365

    The Influence of Different Light Angles During Standardized Patient Photographic Assessment on the Aesthetic Perception of the Face

    Get PDF
    BACKGROUND 2D baseline and follow-up clinical images are potentially subject to inconsistency due to alteration of imaging parameters. However, no study to date has attempted to quantify the magnitude by which such images can be influenced. OBJECTIVE The objective of the present study is to identify the magnitude by which images can be influenced by changing the imaging light angle. METHODS This study is based on the evaluation of 2D frontal images of the face and included a total of 51 subjects of which n = 14 were males and n = 37 were females. Faces were photographed at 0°, 30°, and 60° light angle under identical and standardized conditions. Images were randomized and rated by 27 blinded raters for age, facial attractiveness, body mass index (BMI), temporal hollowing, lower cheek fullness, nasolabial sulcus severity, and jawline contour. RESULTS Facial attractiveness decreased, facial unattractiveness increased and the evaluated BMI (based on facial assessment) increased statistically significantly at 60°. The assessment of regional facial scores, i.e., temporal hollowing, lower cheek fullness, and jawline contour, showed no statistically meaningful changes both at 30° and at 60° light angle. CONCLUSION The results indicate that there might be an observed blind range in light angle (0°-30°) which does not influence facial assessment. Increasing the light angle past the threshold value to 60° might result in a statistically significant impact on facial perception which should be accounted for when documenting and/or presenting facial 2D images. LEVEL OF EVIDENCE V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266

    Nonclassic lipoid congenital adrenal hyperplasia masquerading as familial glucocorticoid deficiency

    Get PDF
    Context: Familial glucocorticoid deficiency (FGD) is an autosomal recessive disorder resulting from resistance to the action of ACTH on the adrenal cortex. Affected individuals are deficient in cortisol and, if untreated, are likely to succumb to hypoglycemia and/or overwhelming infection. Mutations of the ACTH receptor (MC2R) and the melanocortin 2 receptor accessory protein (MRAP), FGD types 1 and 2 respectively, account for approximately 45% of cases. Objective: A locus on chromosome 8 has previously been linked to the disease in three families, but no underlying gene defect has to date been identified. Design: The study design comprised single-nucleotide polymorphism genotyping and mutation detection. Setting: The study was conducted at secondary and tertiary referral centers. Patients: Eighty probands from families referred for investigation of the genetic cause of FGD participated in the study. Interventions: There were no interventions. Results: Analysis by single-nucleotide polymorphism array of the genotype of one individual with FGD previously linked to chromosome 8 revealed a large region of homozygosity encompassing the steroidogenic acute regulatory protein gene, STAR. We identified homozygous STAR mutations in this patient and his affected siblings. Screening of our total FGD patient cohort revealed homozygous STAR mutations in a further nine individuals from four other families. Conclusions: Mutations in STAR usually cause lipoid congenital adrenal hyperplasia, a disorder characterized by both gonadal and adrenal steroid deficiency. Our results demonstrate that certain mutations in STAR (R192C and the previously reported R188C) can present with a phenotype indistinguishable from that seen in FGD

    Accounting for Calibration Uncertainties in X-ray Analysis: Effective Areas in Spectral Fitting

    Full text link
    While considerable advance has been made to account for statistical uncertainties in astronomical analyses, systematic instrumental uncertainties have been generally ignored. This can be crucial to a proper interpretation of analysis results because instrumental calibration uncertainty is a form of systematic uncertainty. Ignoring it can underestimate error bars and introduce bias into the fitted values of model parameters. Accounting for such uncertainties currently requires extensive case-specific simulations if using existing analysis packages. Here we present general statistical methods that incorporate calibration uncertainties into spectral analysis of high-energy data. We first present a method based on multiple imputation that can be applied with any fitting method, but is necessarily approximate. We then describe a more exact Bayesian approach that works in conjunction with a Markov chain Monte Carlo based fitting. We explore methods for improving computational efficiency, and in particular detail a method of summarizing calibration uncertainties with a principal component analysis of samples of plausible calibration files. This method is implemented using recently codified Chandra effective area uncertainties for low-resolution spectral analysis and is verified using both simulated and actual Chandra data. Our procedure for incorporating effective area uncertainty is easily generalized to other types of calibration uncertainties.Comment: 61 pages double spaced, 8 figures, accepted for publication in Ap
    • …
    corecore