252 research outputs found

    Neutron activation analysis of pottery samples from Abila of the Decapolis

    Full text link
    Instrumental neutron activation analyses have been performed on samples of pottery from Abila of the Decapolis (northern Jordan) ranging in age from Early Bronze to Islamic (Abassid). Preliminary results suggest several groupings of samples from each of twelve major archaeological periods, implying a common source of raw materials for ceramic manufacture at Abila for specimens within each grouping, and different sources of raw materials for specimens from different groupings.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43131/1/10967_2005_Article_898.pd

    UK Housing Market: Time Series Processes with Independent and Identically Distributed Residuals

    Get PDF
    The paper examines whether a univariate data generating process can be identified which explains the data by having residuals that are independent and identically distributed, as verified by the BDS test. The stationary first differenced natural log quarterly house price index is regressed, initially with a constant variance and then with a conditional variance. The only regression function that produces independent and identically distributed standardised residuals is a mean process based on a pure random walk format with Exponential GARCH in mean for the conditional variance. There is an indication of an asymmetric volatility feedback effect but higher frequency data is required to confirm this. There could be scope for forecasting the index but this is tempered by the reduction in the power of the BDS test if there is a non-linear conditional variance process

    Self-oligomerization Regulates Stability of Survival Motor Neuron Protein Isoforms by Sequestering an SCF\u3csup\u3eSlmb\u3c/sup\u3e Degron

    Get PDF
    Spinal muscular atrophy (SMA) is caused by homozygous mutations in human SMN1. Expression of a duplicate gene (SMN2) primarily results in skipping of exon 7 and production of an unstable protein isoform, SMNΔ7. Although SMN2 exon skipping is the principal contributor to SMA severity, mechanisms governing stability of survival motor neuron (SMN) isoforms are poorly understood. We used a Drosophila model system and label-free proteomics to identify the SCFSlmb ubiquitin E3 ligase complex as a novel SMN binding partner. SCFSlmb interacts with a phosphor degron embedded within the human and fruitfly SMN YG-box oligomerization domains. Substitution of a conserved serine (S270A) interferes with SCFSlmb binding and stabilizes SMNΔ7. SMA-causing missense mutations that block multimerization of full-length SMN are also stabilized in the degron mutant background. Overexpression of SMNΔ7S270A, but not wild-type (WT) SMNΔ7, provides a protective effect in SMA model mice and human motor neuron cell culture systems. Our findings support a model wherein the degron is exposed when SMN is monomeric and sequestered when SMN forms higher-order multimers

    Methods for economic evaluation of a factorial-design cluster randomised controlled trial of a nutrition supplement and an exercise programme among healthy older people living in Santiago, Chile: the CENEX study

    Get PDF
    BACKGROUND: In an effort to promote healthy ageing and preserve health and function, the government of Chile has formulated a package of actions into the Programme for Complementary Food in Older People (Programa de Alimentación Complementaria para el Adulto Mayor - PACAM). The CENEX study was designed to evaluate the impact, cost and cost-effectiveness of the PACAM and a specially designed exercise programme on pneumonia incidence, walking capacity and body mass index in healthy older people living in low- to medium-socio-economic status areas of Santiago. The purpose of this paper is to describe in detail the methods that will be used to estimate the incremental costs and cost-effectiveness of the interventions. METHODS AND DESIGN: The base-case analysis will adopt a societal perspective, including the direct medical and non-medical costs borne by the government and patients. The cost of the interventions will be calculated by the ingredients approach, in which the total quantities of goods and services actually employed in applying the interventions will be estimated, and multiplied by their respective unit prices. Relevant information on costs of interventions will be obtained mainly from administrative records. The costs borne by patients will be collected via exit and telephone interviews. An annual discount rate of 8% will be used, consistent with the rate recommended by the Government of Chile. All costs will be converted from Chilean Peso to US dollars with the 2007 average period exchange rate of US$1 = 522.37 Chilean Peso. To test the robustness of model results, we will vary the assumptions over a plausible range in sensitivity analyses. DISCUSSION: The protocol described here indicates our intent to conduct an economic evaluation alongside the CENEX study. It provides a detailed and transparent statement of planned data collection methods and analyses. TRIAL REGISTRATION: ISRCTN48153354

    Self-oligomerization regulates stability of survival motor neuron protein isoforms by sequestering an SCF<sup>Slmb</sup> degron

    Get PDF
    Spinal muscular atrophy (SMA) is caused by homozygous mutations in human SMN1. Expression of a duplicate gene (SMN2) primarily results in skipping of exon 7 and production of an unstable protein isoform, SMNΔ7. Although SMN2 exon skipping is the principal contributor to SMA severity, mechanisms governing stability of survival motor neuron (SMN) isoforms are poorly understood. We used a Drosophila model system and label-free proteomics to identify the SCFSlmb ubiquitin E3 ligase complex as a novel SMN binding partner. SCFSlmb interacts with a phosphor degron embedded within the human and fruitfly SMN YG-box oligomerization domains. Substitution of a conserved serine (S270A) interferes with SCFSlmb binding and stabilizes SMNΔ7. SMA-causing missense mutations that block multimerization of full-length SMN are also stabilized in the degron mutant background. Overexpression of SMNΔ7S270A, but not wild-type (WT) SMNΔ7, provides a protective effect in SMA model mice and human motor neuron cell culture systems. Our findings support a model wherein the degron is exposed when SMN is monomeric and sequestered when SMN forms higher-order multimers

    Non-destructive characterisation and classification of ceramic artefacts using pEDXRF and statistical pattern recognition

    Get PDF
    Background: Portable energy dispersive X-ray fluorescence (pEDXRF) spectrometry analysis was applied for the characterisation of archaeological ceramic findings from three Neolithic sites in Serbia. Two dimension reduction techniques, principal component analysis (PCA) and scattering matrices-based dimension reduction were used to examine the possible classification of those findings, and to extract the most discriminant features. Results: A decision-making procedure is proposed, whose goal is to classify unknown ceramic findings based on their elemental compositions derived by pEDXRF spectrometry. As a major part of decision-making procedure, the possibilities of two dimension reduction methods were tested. Scattering matrices-based dimension reduction was found to be the more efficient method for the purpose. Linear classifiers designed based on the desired output allowed for 7 of 8 unknown samples from the test set to be correctly classified. Conclusions: Based on the results, the conclusion is that despite the constraints typical of the applied analytical technique, the elemental composition can be considered as viable information in provenience studies. With a fully-developed procedure, ceramic artefacts can be classified based on their elemental composition and well-known provenance

    Mechanism of Splicing Regulation of Spinal Muscular Atrophy Genes

    Get PDF
    Spinal muscular atrophy (SMA) is one of the major genetic disorders associated with infant mortality. More than 90% cases of SMA result from deletions or mutations of Survival Motor Neuron 1 (SMN1) gene. SMN2, a nearly identical copy of SMN1, does not compensate for the loss of SMN1due to predominant skipping of exon 7. However, correction of SMN2 exon 7 splicing has proven to confer therapeutic benefits in SMA patients. The only approved drug for SMA is an antisense oligonucleotide (Spinraza™/Nusinersen), which corrects SMN2 exon 7 splicing by blocking intronic splicing silencer N1 (ISS-N1) located immediately downstream of exon 7. ISS-N1 is a complex regulatory element encompassing overlapping negative motifs and sequestering a cryptic splice site. More than 40 protein factors have been implicated in the regulation of SMN exon 7 splicing. There is evidence to support that multiple exons of SMN are alternatively spliced during oxidative stress, which is associated with a growing number of pathological conditions. Here, we provide the most up to date account of the mechanism of splicing regulation of the SMN genes
    corecore