248 research outputs found

    The Revenue Online System: Factors Influencing Adoption

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    This paper describes an ongoing study into the quality of service provided by the Irish Revenue Commisioners’ on-line tax filing and collection system. The Irish Revenue On-Line Service (ROS) site has won several awards. In this study, a version of the widely used SERVQUAL measuring instrument, adapted for use with on-line services, has been modified for the specific case of ROS. The theory behind this instrument is set out, the particular problems of evaluating revenue collecting on-line are examined and the rationale for this approach is explaine

    Information Technology and Government Research: A Brief History

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    Governments have been using computers since the early 1950s and academics have been writing about government’s use of computers for almost as long. This paper explores this literature and examines the evolution of research into and thinking about the use of information and communications technology (ICT) in government and public administration over the past 50 years. Questions asked include to what extent the technology of the time influenced this research, how themes and topic of interest have changed over this period and what lessons for future research can be drawn from a better knowledge of the past

    Administration by algorithm: a risk management framework

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    Algorithmic decision-making is neither a recent phenomenon nor one necessarily associated with artificial intelligence (AI), though advances in AI are increasingly resulting in what were heretofore human decisions being taken over by, or becoming dependent on, algorithms and technologies like machine learning. Such developments promise many potential benefits, but are not without certain risks. These risks are not always well understood. It is not just a question of machines making mistakes; it is the embedding of values, biases and prejudices in software which can discriminate against both individuals and groups in society. Such biases are often hard either to detect or prove, particularly where there are problems with transparency and accountability and where such systems are outsourced to the private sector. Consequently, being able to detect and categorise these risks is essential in order to develop a systematic and calibrated response. This paper proposes a simple taxonomy of decision-making algorithms in the public sector and uses this to build a risk management framework with a number of components including an accountability structure and regulatory governance. This framework is designed to assist scholars and practitioners interested in ensuring structured accountability and legal regulation of AI in the public sphere

    A malignant hyperthermia–inducing mutation in RYR1 (R163C): alterations in Ca2+ entry, release, and retrograde signaling to the DHPR

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    Bidirectional signaling between the sarcolemmal L-type Ca2+ channel (1,4-dihydropyridine receptor [DHPR]) and the sarcoplasmic reticulum (SR) Ca2+ release channel (type 1 ryanodine receptor [RYR1]) of skeletal muscle is essential for excitation–contraction coupling (ECC) and is a well-understood prototype of conformational coupling. Mutations in either channel alter coupling fidelity and with an added pharmacologic stimulus or stress can trigger malignant hyperthermia (MH). In this study, we measured the response of wild-type (WT), heterozygous (Het), or homozygous (Hom) RYR1-R163C knock-in mouse myotubes to maintained K+ depolarization. The new findings are: (a) For all three genotypes, Ca2+ transients decay during prolonged depolarization, and this decay is not a consequence of SR depletion or RYR1 inactivation. (b) The R163C mutation retards the decay rate with a rank order WT > Het > Hom. (c) The removal of external Ca2+ or the addition of Ca2+ entry blockers (nifedipine, SKF96365, and Ni2+) enhanced the rate of decay in all genotypes. (d) When Ca2+ entry is blocked, the decay rates are slower for Hom and Het than WT, indicating that the rate of inactivation of ECC is affected by the R163C mutation and is genotype dependent (WT > Het > Hom). (e) Reduced ECC inactivation in Het and Hom myotubes was shown directly using two identical K+ depolarizations separated by varying time intervals. These data suggest that conformational changes induced by the R163C MH mutation alter the retrograde signal that is sent from RYR1 to the DHPR, delaying the inactivation of the DHPR voltage sensor

    Pregabalin Suppresses Spinal Neuronal Hyperexcitability and Visceral Hypersensitivity in the Absence of Peripheral Pathophysiology

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    ABSTRACT Background: Opioid-induced hyperalgesia is recognized in the laboratory and the clinic, generating central hyperexcitability in the absence of peripheral pathology. We investigated pregabalin, indicated for neuropathic pain, and ondansetron, a drug that disrupts descending serotonergic processing in the central nervous system, on spinal neuronal hyperexcitability and visceral hypersensitivity in a rat model of opioid-induced hyperalgesia. Methods: Male Sprague-Dawley rats (180 -200 g) were implanted with osmotic mini-pumps filled with morphine (90 g ⅐ l Ϫ1 ⅐

    Structure of the hDmc1-ssDNA filament reveals the principles of its architecture

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    In eukaryotes, meiotic recombination is a major source of genetic diversity, but its defects in humans lead to abnormalities such as Down's, Klinefelter's and other syndromes. Human Dmc1 (hDmc1), a RecA/Rad51 homologue, is a recombinase that plays a crucial role in faithful chromosome segregation during meiosis. The initial step of homologous recombination occurs when hDmc1 forms a filament on single-stranded (ss) DNA. However the structure of this presynaptic complex filament for hDmc1 remains unknown. To compare hDmc1-ssDNA complexes to those known for the RecA/Rad51 family we have obtained electron microscopy (EM) structures of hDmc1-ssDNA nucleoprotein filaments using single particle approach. The EM maps were analysed by docking crystal structures of Dmc1, Rad51, RadA, RecA and DNA. To fully characterise hDmc1-DNA complexes we have analysed their organisation in the presence of Ca2+, Mg2+, ATP, AMP-PNP, ssDNA and dsDNA. The 3D EM structures of the hDmc1-ssDNA filaments allowed us to elucidate the principles of their internal architecture. Similar to the RecA/Rad51 family, hDmc1 forms helical filaments on ssDNA in two states: extended (active) and compressed (inactive). However, in contrast to the RecA/Rad51 family, and the recently reported structure of hDmc1-double stranded (ds) DNA nucleoprotein filaments, the extended (active) state of the hDmc1 filament formed on ssDNA has nine protomers per helical turn, instead of the conventional six, resulting in one protomer covering two nucleotides instead of three. The control reconstruction of the hDmc1-dsDNA filament revealed 6.4 protein subunits per helical turn indicating that the filament organisation varies depending on the DNA templates. Our structural analysis has also revealed that the N-terminal domain of hDmc1 accomplishes its important role in complex formation through domain swapping between adjacent protomers, thus providing a mechanistic basis for coordinated action of hDmc1 protomers during meiotic recombination

    Androgen profiles among Egyptian adults considering liver status

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    Background and aim:  Hepatitis C virus (HCV) and environmental hepatotoxins may have an indirect influence on health by altering the synthesis and function of hormones, particularly reproductive hormones. We aimed to evaluate liver diseases and sex steroid hormones in Egypt, which has the highest prevalence of HCV worldwide. Methods:  We measured markers of hepatitis B virus (HBV), HCV and schistosomiasis infection as well as liver function in 159 apparently healthy subjects. We measured total testosterone (T), sex-hormone binding globulin (SHBG) and albumin, and calculated the free androgen index. Results:  Anti-HCV antibodies were detected in 51% of men and 42% of women. Based on HCV reverse transcription PCR (RT-PCR) of 44 men and 33 women, 11% of men and 21% of women showed HCV viremia. There was schistosomiasis in 25% of men and 9% of women, and mixed HCV viremia and schistosomiasis in 57% of men and 52% of women. Compared with men with schistosomiasis only (mean 593.3 ± 73.4 ng/dL), T was higher in men with mixed HCV viremia and schistosomiasis (mean 854.5 ± 47.9 ng/dL; P  = 0.006) and men with mixed chronic HCV and schistosomiasis (mean 812.1 ± 43.3 ng/dL; P  = 0.001). Men with mixed chronic HCV and schistosomiasis had also significantly higher SHBG (mean 57.7 ± 3.9 ng/dL) than males with schistosomiasis only (mean 34.8 ± SE 4.5 ng/dL; P  = 0.0003). Conclusion:  Future investigations should consider that a high prevalence of asymptomatic liver disease may alter associations between hormone concentrations and chronic disease etiology.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72021/1/j.1440-1746.2007.04949.x.pd
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