789 research outputs found

    Finding and Resolving Security Misusability with Misusability Cases

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    Although widely used for both security and usability concerns, scenarios used in security design may not necessarily inform the design of usability, and vice- versa. One way of using scenarios to bridge security and usability involves explicitly describing how design deci- sions can lead to users inadvertently exploiting vulnera- bilities to carry out their production tasks. This paper describes how misusability cases, scenarios that describe how design decisions may lead to usability problems sub- sequently leading to system misuse, address this problem. We describe the related work upon which misusability cases are based before presenting the approach, and illus- trating its application using a case study example. Finally, we describe some findings from this approach that further inform the design of usable and secure systems

    A comparison of location of acute symptomatic vs. 'silent' small vessel lesions

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    Background: Acute lacunar ischaemic stroke, white matter hyperintensities, and lacunes are all features of cerebral small vessel disease. It is unclear why some small vessel disease lesions present with acute stroke symptoms, whereas others typically do not. Aim: To test if lesion location could be one reason why some small vessel disease lesions present with acute stroke, whereas others accumulate covertly. Methods: We identified prospectively patients who presented with acute lacunar stroke symptoms with a recent small subcortical infarct confirmed on magnetic resonance diffusion imaging. We compared the distribution of the acute infarcts with that of white matter hyperintensity and lacunes using computational image mapping methods. Results: In 188 patients, mean age 67 ± standard deviation 12 years, the lesions that presented with acute lacunar ischaemic stroke were located in or near the main motor and sensory tracts in (descending order): posterior limb of the internal capsule (probability density 0·2/mm3), centrum semiovale (probability density = 0·15/mm3), medial lentiform nucleus/lateral thalamus (probability density = 0·09/mm3), and pons (probability density = 0·02/mm3). Most lacunes were in the lentiform nucleus (probability density = 0·01–0·04/mm3) or external capsule (probability density = 0·05/mm3). Most white matter hyperintensities were in centrum semiovale (except for the area affected by the acute symptomatic infarcts), external capsules, basal ganglia, and brainstem, with little overlap with the acute symptomatic infarcts (analysis of variance, P < 0·01). Conclusions: Lesions that present with acute lacunar ischaemic stroke symptoms may be more likely noticed by the patient through affecting the main motor and sensory tracts, whereas white matter hyperintensity and asymptomatic lacunes mainly affect other areas. Brain location could at least partly explain the symptomatic vs. covert development of small vessel disease

    Towards comprehensive assessment of mitral regurgitation using cardiovascular magnetic resonance

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    Cardiovascular magnetic resonance (CMR) is increasingly used to assess patients with mitral regurgitation. Its advantages include quantitative determination of ventricular volumes and function and the mitral regurgitant fraction, and in ischemic mitral regurgitation, regional myocardial function and viability. In addition to these, identification of leaflet prolapse or restriction is necessary when valve repair is contemplated. We describe a systematic approach to the evaluation of mitral regurgitation using CMR which we have used in 149 patients with varying etiologies and severity of regurgitation over a 15 month period

    The appropriateness of gatekeeping in the provision of reproductive health care for adolescents in Lithuania:the general practice perspective

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    BACKGROUND: Adolescents' consultation of primary health care services remains problematic despite their accessibility. The reproductive health service seeking behavior of adolescents is the object of much research but little is known about how this behavior is influenced by the gatekeeping system. This study aimed to explore general practitioners' perceptions of the appropriateness of gatekeeping in adolescent reproductive health care. METHODS: Twenty in-depth interviews regarding factors affecting adolescent reproductive health care were carried out on a diverse sample of general practitioners and analyzed using grounded theory. RESULTS: The analysis identified several factors that shaped GPs' negative attitude to gatekeeping in adolescent reproductive health care. Its appropriateness in this field was questionable due to a lack of willingness on the part of GPs to provide reproductive health services for teenagers, their insufficient training, inadequately equipped surgeries and low perceived support for reproductive health service provision. CONCLUSION: Since factors for improving adolescent reproductive health concern not only physicians but also the health system and policy levels, complex measures should be designed to overcome these barriers. Discussion of a flexible model of gatekeeping, encompassing both co-ordination of care provided by GPs and the possibility of patients' self-referral, should be included in the political agenda. Adolescents tend to under-use rather than over-use reproductive health services and every effort should be made to facilitate the accessibility of such services

    Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

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    Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

    Requirements Engineering

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    Requirements Engineering (RE) aims to ensure that systems meet the needs of their stakeholders including users, sponsors, and customers. Often consid- ered as one of the earliest activities in software engineering, it has developed into a set of activities that touch almost every step of the software development process. In this chapter, we reflect on how the need for RE was first recognised and how its foundational concepts were developed. We present the seminal papers on four main activities of the RE process, namely (i) elicitation, (ii) modelling & analysis, (iii) as- surance, and (iv) management & evolution. We also discuss some current research challenges in the area, including security requirements engineering as well as RE for mobile and ubiquitous computing. Finally, we identify some open challenges and research gaps that require further exploration

    Human Telomerase Reverse Transcriptase (hTERT) Q169 Is Essential for Telomerase Function In Vitro and In Vivo

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    BACKGROUND:Telomerase is a reverse transcriptase that maintains the telomeres of linear chromosomes and preserves genomic integrity. The core components are a catalytic protein subunit, the telomerase reverse transcriptase (TERT), and an RNA subunit, the telomerase RNA (TR). Telomerase is unique in its ability to catalyze processive DNA synthesis, which is facilitated by telomere-specific DNA-binding domains in TERT called anchor sites. A conserved glutamine residue in the TERT N-terminus is important for anchor site interactions in lower eukaryotes. The significance of this residue in higher eukaryotes, however, has not been investigated. METHODOLOGY/PRINCIPAL FINDINGS:To understand the significance of this residue in higher eukaryotes, we performed site-directed mutagenesis on human TERT (hTERT) Q169 to create neutral (Q169A), conservative (Q169N), and non-conservative (Q169D) mutant proteins. We show that these mutations severely compromise telomerase activity in vitro and in vivo. The functional defects are not due to abrogated interactions with hTR or telomeric ssDNA. However, substitution of hTERT Q169 dramatically impaired the ability of telomerase to incorporate nucleotides at the second position of the template. Furthermore, Q169 mutagenesis altered the relative strength of hTERT-telomeric ssDNA interactions, which identifies Q169 as a novel residue in hTERT required for optimal primer binding. Proteolysis experiments indicate that Q169 substitution alters the protease-sensitivity of the hTERT N-terminus, indicating that a conformational change in this region of hTERT is likely critical for catalytic function. CONCLUSIONS/SIGNIFICANCE:We provide the first detailed evidence regarding the biochemical and cellular roles of an evolutionarily-conserved Gln residue in higher eukaryotes. Collectively, our results indicate that Q169 is needed to maintain the hTERT N-terminus in a conformation that is necessary for optimal enzyme-primer interactions and nucleotide incorporation. We show that Q169 is critical for the structure and function of human telomerase, thereby identifying a novel residue in hTERT that may be amenable to therapeutic intervention

    Different Human Copper-Zinc Superoxide Dismutase Mutants, SOD1G93A and SOD1H46R, Exert Distinct Harmful Effects on Gross Phenotype in Mice

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    Amyotrophic lateral sclerosis (ALS) is a heterogeneous group of fatal neurodegenerative diseases characterized by a selective loss of motor neurons in the brain and spinal cord. Creation of transgenic mice expressing mutant Cu/Zn superoxide dismutase (SOD1), as ALS models, has made an enormous impact on progress of the ALS studies. Recently, it has been recognized that genetic background and gender affect many physiological and pathological phenotypes. However, no systematic studies focusing on such effects using ALS models other than SOD1G93A mice have been conducted. To clarify the effects of genetic background and gender on gross phenotypes among different ALS models, we here conducted a comparative analysis of growth curves and lifespans using congenic lines of SOD1G93A and SOD1H46R mice on two different genetic backgrounds; C57BL/6N (B6) and FVB/N (FVB). Copy number of the transgene and their expression between SOD1G93A and SOD1H46R lines were comparable. B6 congenic mutant SOD1 transgenic lines irrespective of their mutation and gender differences lived longer than corresponding FVB lines. Notably, the G93A mutation caused severer disease phenotypes than did the H46R mutation, where SOD1G93A mice, particularly on a FVB background, showed more extensive body weight loss and earlier death. Gender effect on survival also solely emerged in FVB congenic SOD1G93A mice. Conversely, consistent with our previous study using B6 lines, lack of Als2, a murine homolog for the recessive juvenile ALS causative gene, in FVB congenic SOD1H46R, but not SOD1G93A, mice resulted in an earlier death, implying a genetic background-independent but mutation-dependent phenotypic modification. These results indicate that SOD1G93A- and SOD1H46R-mediated toxicity and their associated pathogenic pathways are not identical. Further, distinctive injurious effects resulted from different SOD1 mutations, which are associated with genetic background and/or gender, suggests the presence of several genetic modifiers of disease expression in the mouse genome
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