The interaction of amyloid A beta(1-40) with lipid bilayers and ganglioside as studied by P-31 solid-state NMR

Amyloid P-peptide (A beta) is a major component of plaques in Alzheimer's disease, and formation of senile plaques has been suggested to originate fro m regions of neuronal membrane rich in gangliosides. We analyzed the mode of interaction of A beta with lipid bilayers by multinuclear NMR using P-31 nuclei. We found that A beta (1-40) strongly perturbed the bilayer structure of dimyristoylphosphatidylcholine (DMPQ, to form a non-lamellar phase (most likely micellar). The ganglioside GM1 potentiated the effect of A beta (1-40), as viewed from P-31 NMR. The difference of the isotropic peak intensity between DMPC/A beta and DMPC/GM1/A beta suggests a specific interaction between A beta and GM1. We show that in the DMPC/GM1/A beta system there are three lipid phases, namely a lamellar phase, a hexagonal phase and non-oriented lipids. The latter two phases are induced by the presence of the A beta peptide, and facilitated by GM1. 9) 2008 Elsevier Ireland Ltd. All rights reserved

Are Investors Warned by Disclosure of Conflicts of Interest? The Moderating Effect of Investment Horizon

Financial analysts are required to disclose conflicts of interest (COI) in their research reports, but there is limited evidence on the effectiveness of COI disclosures. We investigate whether the influence of disclosing COI in analyst reports on investors' decision making depends on investment horizon. Experimental results show that short-term investors who view a COI disclosure are significantly less willing to invest in the recommended stock compared to short-term investors who do not view such a disclosure, while the presence of a COI disclosure does not significantly affect long-term investors’ willingness to invest. Results further demonstrate that the COI disclosure decreases short-term investors’ willingness to invest by reducing their perception of analysts’ trustworthiness and expertness. This study provides evidence on when and how the COI disclosure can influence investors’ behavior and enhances our understanding of investors’ reactions to cautionary disclaimers

Genomic homogeneity in fibrolamellar carcinomas

Background-Fibrolamellar carcinoma (FLC) is a variant of hepatocellular carcinoma (HCC) with distinctive clinical and histological features. To date there have been few studies on the genotypic aspects of FLC and no previous attempts have been made to use the arbitrarily primed-polymerase chain reaction (AF-FCR) technique to detect genetic alterations in this disease.Aim-The aim of this study was to assess the degree of genomic heterogeneity of FEC using the AP-PCR technique. Methods-A fetal of 50 tissue samples of primary and metastatic FLCs from seven patients were microdissected. AP-PCR amplification of each genomic DNA sample was carried out using two arbitrary primers.Results-DNA fingerprints of the primary FLCs and all their metastatic lesions (both synchronous and metachronous disease) were identical in an individual patient. The fingerprints were different between tumours of different patients. No evidence of intratumour heterogeneity was observed.Conclusions-Such genomic homogeneity in FLCs may explain their indolent growth. The absence of clonal evolution, which is present in other tumours (particularly HCCs), may explain the distinct behaviour in this tumour. The tumorigenic pathway and degree of somatic genomic changes in this disease may be less complex than in HCC

Comparison of the urinary excretion of quercetin glycosides from red onion and aglycone from dietary supplements in healthy subjects: A randomized, single-blinded, cross-over study.

Some intervention studies have shown that quercetin supplementation can regulate certain biomarkers, but it is not clear how the doses given relate to dietary quercetin (e.g. from onion). We conducted a two-period, two-sequence crossover study to compare the bioavailability of quercetin when administered in the form of a fresh red onion meal (naturally glycosylated quercetin) or dietary supplement (aglycone quercetin) under fasting conditions. Six healthy, non-smoking, adult males with BMI 22.7 ± 4.0 kg m(-2) and age 35.3 ± 12.3 y were grouped to take the two study meals in random order. In each of the 2 study periods, one serving of onion soup (made from 100 g fresh red onion, providing 156.3 ± 3.4 μmol (47 mg) quercetin) or a single dose of a quercetin dihydrate tablet (1800 ± 150 μmol (544 mg) of quercetin) were administered following 3 d washout. Urine samples were collected up to 24 h, and after enzyme deconjugation, quercetin was quantified by LC-MS. The 24 h urinary excretion of quercetin (1.69 ± 0.79 μmol) from red onion in soup was not significantly different to that (1.17 ± 0.44 μmol) for the quercetin supplement tablet (P = 0.065, paired t-test). This means that, in practice, 166 mg of quercetin supplement would be comparable to about 10 mg of quercetin aglycone equivalents from onion. These data allow intervention studies on quercetin giving either food or supplements to be more effectively compared

Towards a killer app for the Semantic Web

Killer apps are highly transformative technologies that create new markets and widespread patterns of behaviour. IT generally, and the Web in particular, has benefited from killer apps to create new networks of users and increase its value. The Semantic Web community on the other hand is still awaiting a killer app that proves the superiority of its technologies. There are certain features that distinguish killer apps from other ordinary applications. This paper examines those features in the context of the Semantic Web, in the hope that a better understanding of the characteristics of killer apps might encourage their consideration when developing Semantic Web applications

Development of a Consensus Statement for the Definition, Diagnosis, and Treatment of Acute Exacerbations of Idiopathic Pulmonary Fibrosis Using the Delphi Technique.

© 2015, The Author(s).Introduction: There is a lack of agreed and established guidelines for the treatment of acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF). This reflects, in part, the limited evidence-base underpinning the management of AE-IPF. In the absence of high-quality evidence, the aim of this research was to develop a clinician-led consensus statement for the definition, diagnosis and treatment of AE-IPF. Methods: A literature review was conducted to obtain published material on the definition and treatment of AE-IPF. The results of this review were circulated to an online panel of clinicians for review. Statements were then shared with ten expert respiratory clinicians who regularly treat patients with IPF. A Delphi technique was then used to develop a consensus statement for the definition, diagnosis and treatment of AE-IPF. During the first round of review, clinicians rated the clarity of each statement, the extent to which the statement should be included and provided comments. In two subsequent rounds of review, clinicians were provided with the group median inclusion rating for each statement, and any revised wording of statements to aid clarity. Clinicians were asked to repeat the clarity and inclusion ratings for the revised statements. Results: The literature review, online panel discussion, and face-to-face meeting generated 65 statements covering the definition, diagnosis, and management of AE-IPF. Following three rounds of blind review, 90% of clinicians agreed 39 final statements. These final statements included a definition of AE-IPF, approach to diagnosis, and treatment options, specifically: supportive measures, use of anti-microbials, immunosuppressants, anti-coagulants, anti-fibrotic therapy, escalation, transplant management, and long-term management including discharge planning. Conclusion: This clinician-led consensus statement establishes the ‘best practice’ for the management and treatment of AE-IPF based on current knowledge, evidence, and available treatments. Funding: Boehringer Ingelheim Ltd., Bracknell, West Berkshire, UK

Cholecystitis Without Gallstones

10.1155/1990/89848HPB Surgery2283-10

Decision region approximation by polynomials or neural networks

We give degree of approximation results for decision regions which are defined by polynomial and neural network parametrizations. The volume of the misclassified region is used to measure the approximation error, and results for the degree of L1 approximation of functions are used. For polynomial parametrizations, we show that the degree of approximation is at least 1, whereas for neural network parametrizations we prove the slightly weaker result that the degree of approximation is at least r, where r can be any number in the open interval (0, 1)