1,324 research outputs found

    The Role of Deontic Logic in the Specification of Information Systems

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    In this paper we discuss the role that deontic logic plays in the specification of information systems, either because constraints on the systems directly concern norms or, and even more importantly, system constraints are considered ideal but violable (so-called `soft¿ constraints).\ud To overcome the traditional problems with deontic logic (the so-called paradoxes), we first state the importance of distinguishing between ought-to-be and ought-to-do constraints and next focus on the most severe paradox, the so-called Chisholm paradox, involving contrary-to-duty norms. We present a multi-modal extension of standard deontic logic (SDL) to represent the ought-to-be version of the Chisholm set properly. For the ought-to-do variant we employ a reduction to dynamic logic, and show how the Chisholm set can be treated adequately in this setting. Finally we discuss a way of integrating both ought-to-be and ought-to-do reasoning, enabling one to draw conclusions from ought-to-be constraints to ought-to-do ones, and show by an example the use(fulness) of this

    Transgenic expression of the dicotyledonous pattern recognition receptor EFR in rice leads to ligand-dependent activation of defense responses

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    Plant plasma membrane localized pattern recognition receptors (PRRs) detect extracellular pathogen-associated molecules. PRRs such as Arabidopsis EFR and rice XA21 are taxonomically restricted and are absent from most plant genomes. Here we show that rice plants expressing EFR or the chimeric receptor EFR::XA21, containing the EFR ectodomain and the XA21 intracellular domain, sense both Escherichia coli- and Xanthomonas oryzae pv. oryzae (Xoo)-derived elf18 peptides at sub-nanomolar concentrations. Treatment of EFR and EFR::XA21 rice leaf tissue with elf18 leads to MAP kinase activation, reactive oxygen production and defense gene expression. Although expression of EFR does not lead to robust enhanced resistance to fully virulent Xoo isolates, it does lead to quantitatively enhanced resistance to weakly virulent Xoo isolates. EFR interacts with OsSERK2 and the XA21 binding protein 24 (XB24), two key components of the rice XA21-mediated immune response. Rice-EFR plants silenced for OsSERK2, or overexpressing rice XB24 are compromised in elf18-induced reactive oxygen production and defense gene expression indicating that these proteins are also important for EFR-mediated signaling in transgenic rice. Taken together, our results demonstrate the potential feasibility of enhancing disease resistance in rice and possibly other monocotyledonous crop species by expression of dicotyledonous PRRs. Our results also suggest that Arabidopsis EFR utilizes at least a subset of the known endogenous rice XA21 signaling components

    Acute wound management: revisiting the approach to assessment, irrigation, and closure considerations

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    Abstract Background As millions of emergency department (ED) visits each year include wound care, emergency care providers must remain experts in acute wound management. The variety of acute wounds presenting to the ED challenge the physician to select the most appropriate management to facilitate healing. A complete wound history along with anatomic and specific medical considerations for each patient provides the basis of decision making for wound management. It is essential to apply an evidence‐based approach and consider each wound individually in order to create the optimal conditions for wound healing. Aims A comprehensive evidence‐based approach to acute wound management is an essential skill set for any emergency physician or acute care practitioner. This review provides an overview of current evidence and addresses frequent pitfalls. Methods A systematic review of the literature for acute wound management was performed. Results A structured MEDLINE search was performed regarding acute wound management including established wound care guidelines. The data obtained provided the framework for evidence‐based recommendations and current best practices for wound care. Conclusion Acute wound management varies based on the wound location and characteristics. No single approach can be applied to all wounds; however, a systematic approach to acute wound care integrated with current best practices provides the framework for exceptional wound management

    Phosphorylation and Ubiquitination Regulate Protein Phosphatase 5 Activity and Its Prosurvival Role in Kidney Cancer

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    The serine/threonine protein phosphatase 5 (PP5) regulates multiple cellular signaling networks. A number of cellular factors, including heat shock protein 90 (Hsp90), promote the activation of PP5. However, it is unclear whether post-translational modifications also influence PP5 phosphatase activity. Here, we show an “on/off switch” mechanism for PP5 regulation. The casein kinase 1δ (CK1δ) phosphorylates T362 in the catalytic domain of PP5, which activates and enhances phosphatase activity independent of Hsp90. Overexpression of the phosphomimetic T362E-PP5 mutant hyper-dephosphorylates substrates such as the co-chaperone Cdc37 and glucocorticoid receptor in cells. Our proteomic approach revealed that the tumor suppressor von Hippel-Lindau protein (VHL) interacts with and ubiquitinates K185/K199-PP5 for proteasomal degradation in a hypoxia- and prolyl-hydroxylation-independent manner. Finally, VHL-deficient clear cell renal cell carcinoma (ccRCC) cell lines and patient tumors exhibit elevated PP5 levels. Downregulation of PP5 causes ccRCC cells to undergo apoptosis, suggesting a prosurvival role for PP5 in kidney cancer

    Alcohol and marijuana use while driving-an unexpected crash risk in Pakistani commercial drivers: a cross-sectional survey

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    Background:A significant proportion of road traffic crashes are attributable to alcohol and marijuana use while driving globally. Sale and use of both substances is illegal in Pakistan and is not considered a threat for road traffic injuries. However literature hints that this may not be the case. We did this study to assess usage of alcohol and marijuana in Pakistani commercial drivers.Methods:A sample of 857 commercial bus and truck drivers was interviewed in October 2008 at the largest commercial vehicle station in Rawalpindi and Islamabad, Pakistan. Time location cluster sampling was used to select the subjects and a structured questionnaire was used to assess the basic demographic profile, substance abuse habits of the drivers while on the road, and reasons for usage of illicit substances while driving were recorded. Self reported information was collected after obtaining informed consent. Chi square and fisher exact tests were used to assess differences between groups and logistic regression was used to identify significant associations between driver characteristics and alcohol and marijuana use.Results:Almost 10% of truck drivers use alcohol while driving on Pakistani roads. Marijuana use is almost 30% in some groups. Statistically different patterns of usage are seen between population subgroups based on age, ethnicity, education, and marital status. Regression analysis shows association of alcohol and marijuana use with road rage and error behaviours, and also with an increased risk of being involved in road crashes. The reported reasons for using alcohol or marijuana show a general lack of awareness of the hazardous nature of this practice among the commercial driver population.Conclusion:Alcohol and marijuana use is highly prevalent in Pakistani commercial drivers. The issue needs to be recognized by concerned authorities and methods such as random breath tests and sobriety check points need to be employed for proper law enforcement

    Arabidopsis MKS1 Is Involved in Basal Immunity and Requires an Intact N-terminal Domain for Proper Function

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    Innate immune signaling pathways in animals and plants are regulated by mitogen-activated protein kinase (MAPK) cascades. MAP kinase 4 (MPK4) functions downstream of innate immune receptors via a nuclear substrate MKS1 to regulate the activity of the WRKY33 transcription factor, which in turn controls the production of anti-microbial phytoalexins.We investigate the role of MKS1 in basal resistance and the importance of its N- and C-terminal domains for MKS1 function. We used the information that mks1 loss-of-function partially suppresses the mpk4 loss-of-function phenotype, and that transgenic expression of functional MKS1 in mpk4/mks1 double mutants reverted the mpk4 dwarf phenotype. Transformation of mks1/mpk4 with mutant versions of MKS1 constructs showed that a single amino acid substitution in a putative MAP kinase docking domain, MKS1-L32A, or a truncated MKS1 version unable to interact with WRKY33, were deficient in reverting the double mutant to the mpk4 phenotype. These results demonstrate functional requirement in MKS1 for the interaction with MPK4 and WRKY33. In addition, nuclear localization of MKS1 was shown to depend on an intact N-terminal domain. Furthermore, loss-of-function mks1 mutants exhibited increased susceptibility to strains of Pseudomonas syringae and Hyaloperonospora arabidopsidis, indicating that MKS1 plays a role in basal defense responses.Taken together, our results indicate that MKS1 function and subcellular location requires an intact N-terminus important for both MPK4 and WRKY33 interactions

    The empirical analysis of non-problematic video gaming and cognitive skills: a systematic review

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    Videogames have become one of the most popular leisure activities worldwide, including multiple game genres with different characteristics and levels of involvement required. Although a small minority of excessive players suffer detrimental consequences including impairment of several cognitive skills (e.g., inhibition, decision-making), it has also been demonstrated that playing videogames can improve different cognitive skills. Therefore, the current paper systematically reviewed the empirical studies experimentally investigating the positive impact of videogames on cognitive skills. Following a number of inclusion and exclusion criteria, a total of 32 papers were identified as empirically investigating three specific skills: taskswitching (eight studies), attentional control (22 studies), and sub-second time perception (two studies). Results demonstrated that compared to control groups, non-problematic use of videogames can lead to improved task-switching, more effective top-down attentional control and processing speed and increased sub-second time perception. Two studies highlighted the impact of gaming on cognitive skills differs depends upon game genre. The studies reviewed suggest that videogame play can have a positive impact on cognitive processes for players

    Predicting microbiologically defined infection in febrile neutropenic episodes in children : global individual participant data multivariable meta-analysis

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    BACKGROUND: Risk-stratified management of fever with neutropenia (FN), allows intensive management of high-risk cases and early discharge of low-risk cases. No single, internationally validated, prediction model of the risk of adverse outcomes exists for children and young people. An individual patient data (IPD) meta-analysis was undertaken to devise one. METHODS: The 'Predicting Infectious Complications in Children with Cancer' (PICNICC) collaboration was formed by parent representatives, international clinical and methodological experts. Univariable and multivariable analyses, using random effects logistic regression, were undertaken to derive and internally validate a risk-prediction model for outcomes of episodes of FN based on clinical and laboratory data at presentation. RESULTS: Data came from 22 different study groups from 15 countries, of 5127 episodes of FN in 3504 patients. There were 1070 episodes in 616 patients from seven studies available for multivariable analysis. Univariable analyses showed associations with microbiologically defined infection (MDI) in many items, including higher temperature, lower white cell counts and acute myeloid leukaemia, but not age. Patients with osteosarcoma/Ewings sarcoma and those with more severe mucositis were associated with a decreased risk of MDI. The predictive model included: malignancy type, temperature, clinically 'severely unwell', haemoglobin, white cell count and absolute monocyte count. It showed moderate discrimination (AUROC 0.723, 95% confidence interval 0.711-0.759) and good calibration (calibration slope 0.95). The model was robust to bootstrap and cross-validation sensitivity analyses. CONCLUSIONS: This new prediction model for risk of MDI appears accurate. It requires prospective studies assessing implementation to assist clinicians and parents/patients in individualised decision making
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