The MDM2–p53–pyruvate carboxylase signalling axis couples mitochondrial metabolism to glucose-stimulated insulin secretion in pancreatic β-cells

published_or_final_versio

Effects of GnRH-a on the ovarian maturation of blue tang fish (Paracanthurus hepatus Linnaeus, 1776)

The effects of gonadotropin-releasing hormone – analogue (GnRH-a) injection on the ovarian maturation and steroid hormone level of blue tang (Paracanthurus hepatus) females were investigated. Pre-matured blue tang females were injected with GnRH-a at dosages of 150, 200 and 250 μg/kg body weight and were then observed for fluctuation of steroid hormone levels, including testosterone (T), estradiol (E2) and 17α,20β-dihydroxy-4-pregnen-3-one (DHP) in plasma and ovary after 2 and 7 days. Plasma T level was not significantly different among the treated groups at sampling times. However, the ovarian T levels in the fish injected with 200 and 250 μg/kg GnRH-a were higher than that of the non-administered GnRH-a and fish injected with 150 μg/kg after two days (P < 0.05). After seven days of the administration, the ovarian T level was lowest in the fish without GnRH-a injection and highest in the fish injected with 250 μg/kg (P < 0.05). The plasma and ovarian E2 levels were higher (P < 0.05) in the fish injected with 200 and 250 μg/kg of GnRH-a than in the control fish after 2 and 7 days of injection. Both the plasma and ovarian DHP levels in GnRH-a injected fish were significantly (P < 0.05) increased after day 2 and was highest in the fish injected with 250 μg/kg (P < 0.05). After 7 days of injection, the plasma and ovarian DHP levels remained higher in the GnRH-a injected fish than in the controlled group (P < 0.05). There was no difference in DHP levels among the GnRH-a-treated groups. The results indicate that the dosage of 200 µg/kg of GnRH-a is appropriate for inducing maturation of the blue tang fish

A prospective randomized, open-label trial comparing the safety and efficacy of dose sparing intradermal 2010/2011 trivalent influenza vaccine delivered by two different devices

Poster Abstract Session - Influenza Vaccines: no. 533BACKGROUND: We performed intradermal 2010/11 trivalent influenza vaccination (TIV) in adult subjects delivered by two different intradermal (ID) devices, using 20% and 60% of the standard dose and compared the immunogenicity and safety with full dose intramuscular (IM) immunization. METHODS: This is a prospective randomized trial conducted from December 2010 to March 2011, comprising chronically ill adults. Subjects were randomly assigned …postprin

The K526R substitution in viral protein ​PB2 enhances the effects of E627K on influenza virus replication

Host-adaptive strategies, such as the E627K substitution in the ​PB2 protein, are critical for replication of avian influenza A viruses in mammalian hosts. Here we show that mutation ​PB2-K526R is present in some human H7N9 influenza isolates, in nearly 80% of H5N1 human isolates from Indonesia and, in conjunction with E627K, in almost all seasonal H3N2 viruses since 1970. Polymerase complexes containing ​PB2-526R derived from H7N9, H5N1 or H3N2 viruses exhibit increased polymerase activity. ​PB2-526R also enhances viral transcription and replication in cells. In comparison with viruses carrying 627K, H7N9 viruses carrying both 526R and 627K replicate more efficiently in mammalian (but not avian) cells and in mouse lung tissues, and cause greater body weight loss and mortality in infected mice. ​PB2-K526R interacts with nuclear export protein and our results suggest that it contributes to enhance replication for certain influenza virus subtypes, particularly in combination with 627K.published_or_final_versio

UNCLES: Method for the identification of genes differentially consistently co-expressed in a specific subset of datasets

Background: Collective analysis of the increasingly emerging gene expression datasets are required. The recently proposed binarisation of consensus partition matrices (Bi-CoPaM) method can combine clustering results from multiple datasets to identify the subsets of genes which are consistently co-expressed in all of the provided datasets in a tuneable manner. However, results validation and parameter setting are issues that complicate the design of such methods. Moreover, although it is a common practice to test methods by application to synthetic datasets, the mathematical models used to synthesise such datasets are usually based on approximations which may not always be sufficiently representative of real datasets. Results: Here, we propose an unsupervised method for the unification of clustering results from multiple datasets using external specifications (UNCLES). This method has the ability to identify the subsets of genes consistently co-expressed in a subset of datasets while being poorly co-expressed in another subset of datasets, and to identify the subsets of genes consistently co-expressed in all given datasets. We also propose the M-N scatter plots validation technique and adopt it to set the parameters of UNCLES, such as the number of clusters, automatically. Additionally, we propose an approach for the synthesis of gene expression datasets using real data profiles in a way which combines the ground-truth-knowledge of synthetic data and the realistic expression values of real data, and therefore overcomes the problem of faithfulness of synthetic expression data modelling. By application to those datasets, we validate UNCLES while comparing it with other conventional clustering methods, and of particular relevance, biclustering methods. We further validate UNCLES by application to a set of 14 real genome-wide yeast datasets as it produces focused clusters that conform well to known biological facts. Furthermore, in-silico-based hypotheses regarding the function of a few previously unknown genes in those focused clusters are drawn. Conclusions: The UNCLES method, the M-N scatter plots technique, and the expression data synthesis approach will have wide application for the comprehensive analysis of genomic and other sources of multiple complex biological datasets. Moreover, the derived in-silico-based biological hypotheses represent subjects for future functional studies.The National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Number RP-PG-0310-1004)

G0^0 Electronics and Data Acquisition (Forward-Angle Measurements)

The G$^0$ parity-violation experiment at Jefferson Lab (Newport News, VA) is designed to determine the contribution of strange/anti-strange quark pairs to the intrinsic properties of the proton. In the forward-angle part of the experiment, the asymmetry in the cross section was measured for $\vec{e}p$ elastic scattering by counting the recoil protons corresponding to the two beam-helicity states. Due to the high accuracy required on the asymmetry, the G$^0$ experiment was based on a custom experimental setup with its own associated electronics and data acquisition (DAQ) system. Highly specialized time-encoding electronics provided time-of-flight spectra for each detector for each helicity state. More conventional electronics was used for monitoring (mainly FastBus). The time-encoding electronics and the DAQ system have been designed to handle events at a mean rate of 2 MHz per detector with low deadtime and to minimize helicity-correlated systematic errors. In this paper, we outline the general architecture and the main features of the electronics and the DAQ system dedicated to G$^0$ forward-angle measurements.Comment: 35 pages. 17 figures. This article is to be submitted to NIM section A. It has been written with Latex using \documentclass{elsart}. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment In Press (2007

CD8+ T Cells Mediate the Athero-Protective Effect of Immunization with an ApoB-100 Peptide

Immunization of hypercholesterolemic mice with selected apoB-100 peptide antigens reduces atherosclerosis but the precise immune mediators of athero-protection remain unclear. In this study we show that immunization of apoE (-/-) mice with p210, a 20 amino acid apoB-100 related peptide, reduced aortic atherosclerosis compared with PBS or adjuvant/carrier controls. Immunization with p210 activated CD8+ T cells, reduced dendritic cells (DC) at the site of immunization and within the plaque with an associated reduction in plaque macrophage immunoreactivity. Adoptive transfer of CD8+ T cells from p210 immunized mice recapitulated the athero-protective effect of p210 immunization in naïve, non-immunized mice. CD8+ T cells from p210 immunized mice developed a preferentially higher cytolytic response against p210-loaded dendritic cells in vitro. Although p210 immunization profoundly modulated DCs and cellular immune responses, it did not alter the efficacy of subsequent T cell dependent or independent immune response to other irrelevant antigens. Our data define, for the first time, a role for CD8+ T cells in mediating the athero-protective effects of apoB-100 related peptide immunization in apoE (-/-) mice

Measuring sub-mm structural displacements using QDaedalus: a digital clip-on measuring system developed for total stations

The monitoring of rigid structures of modal frequencies greater than 5 Hz and sub-mm displacement is mainly based so far on relative quantities from accelerometers, strain gauges etc. Additionally geodetic techniques such as GPS and Robotic Total Stations (RTS) are constrained by their low accuracy (few mm) and their low sampling rates. In this study the application of QDaedalus is presented, which constitutes a measuring system developed at the Geodesy and Geodynamics Lab, ETH Zurich and consists of a small CCD camera and Total Station, for the monitoring of the oscillations of a rigid structure. In collaboration with the Institute of Structural Engineering of ETH Zurich and EMPA, the QDaedalus system was used for monitoring of the sub-mm displacement of a rigid prototype beam and the estimation of its modal frequencies up to 30 Hz. The results of the QDaedalus data analysis were compared to those of accelerometers and proved to hold sufficient accuracy and suitably supplementing the existing monitoring techniques

Review: optical fiber sensors for civil engineering applications

Optical fiber sensor (OFS) technologies have developed rapidly over the last few decades, and various types of OFS have found practical applications in the field of civil engineering. In this paper, which is resulting from the work of the RILEM technical committee “Optical fiber sensors for civil engineering applications”, different kinds of sensing techniques, including change of light intensity, interferometry, fiber Bragg grating, adsorption measurement and distributed sensing, are briefly reviewed to introduce the basic sensing principles. Then, the applications of OFS in highway structures, building structures, geotechnical structures, pipelines as well as cables monitoring are described, with focus on sensor design, installation technique and sensor performance. It is believed that the State-of-the-Art review is helpful to engineers considering the use of OFS in their projects, and can facilitate the wider application of OFS technologies in construction industry