456 research outputs found

    The impact of empowering internal auditors on the quality of electronic internal audits: A case of Jordanian listed services companies

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    This study emphases on the top management empowerments to internal auditors, namely, general qualification, electronic qualification and independence, affecting quality of electronic internal audits in the Jordanian Listed Service Companies. This paper used 144 usable questionnaires from internal auditors in the Jordanian listed service companies. The gathered data were analysed utilizing ``Statistical Package for Social Sciences (SPSS)''. The results reveal that general qualification, electronic qualification and independence have a significant effect on the quality of electronic internal audits, as supported by the resource-based view. Due to the importance of the service companies’ sector in the context of Jordan, the results are helpful for the internal audit profession and decision makers in offering new legislation for the internal audit profession. Future research may consider other factors that may hinder the quality of electronic internal audits, such as audit task complexity or organizational culture

    Child injury mortality in Iran: A systematic review and meta-analysis

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    Background: Reducing child injury mortality is an important factor in directing national and international policy-makers to program appropriate cause-specific interventions. The systematic review and meta-analysis study was performed to provide a clear view of child injury mortality in Iran. Methods: A systematic electronic search of PubMed, Scopus, Web of Science, SID, and Elmnet was performed to identify the Persian and English articles published between 2005 and 2018. All studies reporting child injury mortality were gathered according to our inclusion and exclusion criteria. After quality appraisal, data were extracted and analyzed. Results: Twelve studies with an overall sample size of 22,721 met our inclusion criteria. The prevalence of mortality due to road accident, falling, drowning, poisoning and other causes of death were 56.8, 11.3, 8.6, 5.7 and, 17.6, respectively. The proportion of injury in all-cause mortality in 0�19 and 0�6 age groups were 11.9 and 16.9, respectively. Conclusion: Our findings suggest a relatively high mortality rate for road traffic accidents, which should be taken into account seriously. Developing preventive policies is essential to achieve better standards of road transportation and reduce related mortality in Iran. © 201

    Statistical Analysis of Readthrough Levels for Nonsense Mutations in Mammalian Cells Reveals a Major Determinant of Response to Gentamicin

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    The efficiency of translation termination depends on the nature of the stop codon and the surrounding nucleotides. Some molecules, such as aminoglycoside antibiotics (gentamicin), decrease termination efficiency and are currently being evaluated for diseases caused by premature termination codons. However, the readthrough response to treatment is highly variable and little is known about the rules governing readthrough level and response to aminoglycosides. In this study, we carried out in-depth statistical analysis on a very large set of nonsense mutations to decipher the elements of nucleotide context responsible for modulating readthrough levels and gentamicin response. We quantified readthrough for 66 sequences containing a stop codon, in the presence and absence of gentamicin, in cultured mammalian cells. We demonstrated that the efficiency of readthrough after treatment is determined by the complex interplay between the stop codon and a larger sequence context. There was a strong positive correlation between basal and induced readthrough levels, and a weak negative correlation between basal readthrough level and gentamicin response (i.e. the factor of increase from basal to induced readthrough levels). The identity of the stop codon did not affect the response to gentamicin treatment. In agreement with a previous report, we confirm that the presence of a cytosine in +4 position promotes higher basal and gentamicin-induced readthrough than other nucleotides. We highlight for the first time that the presence of a uracil residue immediately upstream from the stop codon is a major determinant of the response to gentamicin. Moreover, this effect was mediated by the nucleotide itself, rather than by the amino-acid or tRNA corresponding to the −1 codon. Finally, we point out that a uracil at this position associated with a cytosine at +4 results in an optimal gentamicin-induced readthrough, which is the therapeutically relevant variable

    Inferring viral quasispecies spectra from 454 pyrosequencing reads

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    <p>Abstract</p> <p>Background</p> <p>RNA viruses infecting a host usually exist as a set of closely related sequences, referred to as quasispecies. The genomic diversity of viral quasispecies is a subject of great interest, particularly for chronic infections, since it can lead to resistance to existing therapies. High-throughput sequencing is a promising approach to characterizing viral diversity, but unfortunately standard assembly software was originally designed for single genome assembly and cannot be used to simultaneously assemble and estimate the abundance of multiple closely related quasispecies sequences.</p> <p>Results</p> <p>In this paper, we introduce a new <b>Vi</b>ral <b>Sp</b>ectrum <b>A</b>ssembler (ViSpA) method for quasispecies spectrum reconstruction and compare it with the state-of-the-art ShoRAH tool on both simulated and real 454 pyrosequencing shotgun reads from HCV and HIV quasispecies. Experimental results show that ViSpA outperforms ShoRAH on simulated error-free reads, correctly assembling 10 out of 10 quasispecies and 29 sequences out of 40 quasispecies. While ShoRAH has a significant advantage over ViSpA on reads simulated with sequencing errors due to its advanced error correction algorithm, ViSpA is better at assembling the simulated reads after they have been corrected by ShoRAH. ViSpA also outperforms ShoRAH on real 454 reads. Indeed, 7 most frequent sequences reconstructed by ViSpA from a real HCV dataset are viable (do not contain internal stop codons), and the most frequent sequence was within 1% of the actual open reading frame obtained by cloning and Sanger sequencing. In contrast, only one of the sequences reconstructed by ShoRAH is viable. On a real HIV dataset, ShoRAH correctly inferred only 2 quasispecies sequences with at most 4 mismatches whereas ViSpA correctly reconstructed 5 quasispecies with at most 2 mismatches, and 2 out of 5 sequences were inferred without any mismatches. ViSpA source code is available at <url>http://alla.cs.gsu.edu/~software/VISPA/vispa.html</url>.</p> <p>Conclusions</p> <p>ViSpA enables accurate viral quasispecies spectrum reconstruction from 454 pyrosequencing reads. We are currently exploring extensions applicable to the analysis of high-throughput sequencing data from bacterial metagenomic samples and ecological samples of eukaryote populations.</p

    Large Scale Comparative Codon-Pair Context Analysis Unveils General Rules that Fine-Tune Evolution of mRNA Primary Structure

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    BACKGROUND: Codon usage and codon-pair context are important gene primary structure features that influence mRNA decoding fidelity. In order to identify general rules that shape codon-pair context and minimize mRNA decoding error, we have carried out a large scale comparative codon-pair context analysis of 119 fully sequenced genomes. METHODOLOGIES/PRINCIPAL FINDINGS: We have developed mathematical and software tools for large scale comparative codon-pair context analysis. These methodologies unveiled general and species specific codon-pair context rules that govern evolution of mRNAs in the 3 domains of life. We show that evolution of bacterial and archeal mRNA primary structure is mainly dependent on constraints imposed by the translational machinery, while in eukaryotes DNA methylation and tri-nucleotide repeats impose strong biases on codon-pair context. CONCLUSIONS: The data highlight fundamental differences between prokaryotic and eukaryotic mRNA decoding rules, which are partially independent of codon usage

    GDNF Secreting Human Neural Progenitor Cells Protect Dying Motor Neurons, but Not Their Projection to Muscle, in a Rat Model of Familial ALS

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    Amyotrophic lateral sclerosis (ALS) is a fatal, progressive neurodegenerative disease characterized by rapid loss of muscle control and eventual paralysis due to the death of large motor neurons in the brain and spinal cord. Growth factors such as glial cell line derived neurotrophic factor (GDNF) are known to protect motor neurons from damage in a range of models. However, penetrance through the blood brain barrier and delivery to the spinal cord remains a serious challenge. Although there may be a primary dysfunction in the motor neuron itself, there is also increasing evidence that excitotoxicity due to glial dysfunction plays a crucial role in disease progression. Clearly it would be of great interest if wild type glial cells could ameliorate motor neuron loss in these models, perhaps in combination with the release of growth factors such as GDNF.Human neural progenitor cells can be expanded in culture for long periods and survive transplantation into the adult rodent central nervous system, in some cases making large numbers of GFAP positive astrocytes. They can also be genetically modified to release GDNF (hNPC(GDNF)) and thus act as long-term 'mini pumps' in specific regions of the rodent and primate brain. In the current study we genetically modified human neural stem cells to release GDNF and transplanted them into the spinal cord of rats over-expressing mutant SOD1 (SOD1(G93A)). Following unilateral transplantation into the spinal cord of SOD1(G93A) rats there was robust cellular migration into degenerating areas, efficient delivery of GDNF and remarkable preservation of motor neurons at early and end stages of the disease within chimeric regions. The progenitors retained immature markers, and those not secreting GDNF had no effect on motor neuron survival. Interestingly, this robust motor neuron survival was not accompanied by continued innervation of muscle end plates and thus resulted in no improvement in ipsilateral limb use.The potential to maintain dying motor neurons by delivering GDNF using neural progenitor cells represents a novel and powerful treatment strategy for ALS. While this approach represents a unique way to prevent motor neuron loss, our data also suggest that additional strategies may also be required for maintenance of neuromuscular connections and full functional recovery. However, simply maintaining motor neurons in patients would be the first step of a therapeutic advance for this devastating and incurable disease, while future strategies focus on the maintenance of the neuromuscular junction

    Charged-particle multiplicity fluctuations in Pb–Pb collisions at √sNN = 2.76 TeV

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    Measurements of event-by-event fluctuations of charged-particle multiplicities in Pb–Pb collisions at √sNN = 2.76 TeV using the ALICE detector at the CERN Large Hadron Collider (LHC) are presented in the pseudorapidity range |η|<0.8 and transverse momentum 0.2<pT<2.0 GeV/c. The amplitude of the fluctuations is expressed in terms of the variance normalized by the mean of the multiplicity distribution. The η and pT dependences of the fluctuations and their evolution with respect to collision centrality are investigated. The multiplicity fluctuations tend to decrease from peripheral to central collisions. The results are compared to those obtained from HIJING and AMPT Monte Carlo event generators as well as to experimental data at lower collision energies. Additionally, the measured multiplicity fluctuations are discussed in the context of the isothermal compressibility of the high-density strongly-interacting system formed in central Pb–Pb collisions.publishedVersio

    Observation of flow angle and flow magnitude fluctuations in Pb-Pb collisions at sNN=5.02TeV at the CERN Large Hadron Collider

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    This Letter reports on the first measurements of transverse momentum dependent flow angle n and flow magnitude vn fluctuations determined using new four-particle correlators. The measurements are performed for various centralities in Pb–Pb collisions at a center-of-mass energy per nucleon pair of √s NN = 5.02 TeV with ALICE at the CERN Large Hadron Collider. Both flow angle and flow magnitude fluctuations are observed in the presented centrality ranges and are strongest in the most central collisions and for a transverse momentum pT > 2 GeV/c. Comparison with theoretical models, including iEBE-VISHNU, MUSIC, and AMPT, show that the measurements exhibit unique sensitivities to the initial state of heavy-ion collisions
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