150 research outputs found

    Ontology mapping of business process modeling based on formal temporal logic

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    A business process is the combination of a set of activities with logical order and dependence, whose objective is to produce a desired goal. Business process modeling (BPM) using knowledge of the available process modeling techniques enable a common understanding and analysis of a business process. Industry and academics use informal and formal methods respectively to represent business processes (BP), having the main objective to support an organization. Despite both are aiming at BPM but the methods used are quite different in their semantics. While carrying out literature research, it has been found that there is no general representation of business process modeling is available that is expressive than the commercial modeling tools and techniques. Therefore, it is primarily conceived to provide an ontology mapping of modeling terms of Business Process Modeling Notation (BPMN), Unified Modeling Language (UML) Activity Diagrams (AD) and Event Driven Process Chains (EPC) to temporal logic. Being a formal system, first order logic assists in thorough understanding of process modeling and its application. However, our contribution is to devise a versatile conceptual categorization of modeling terms/constructs and also formalizing them, based on well accepted business notions, such as action, event, process, sub-process, connector and flow. It is demonstrated that the new categorization of modeling terms mapped to formal temporal logic, provides the expressive power to subsume business process modeling techniques i.e. BPMN, UML AD and EPC

    Phenolic Profile, Nutritional Composition, Functional Properties and Antioxidant Activity of Newly Grown Parthenocarpic and Normal Seeded Tomato

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    The aim of the study was to compare the physico-chemical parameters, sugar, vitamin C, and phenolic profiles in five genotypes of local indeterminate tunnel tomato hybrid (LITTH) (LITTH-778, LITTH-784, LITTH-786, LITTH-788 and LITTH-790) of natural parthenocarpic tomato (NPT) and normal seeded tomato (NST). Samples were collected from the experimental fields of Ayub Agricultural Research Institute, Faisalabad, Pakistan. Physical parameters (fruit shape, fruit weight, fruit length, fruit width, number of seeds per fruit, shelf life), chemical composition (moisture, ash, crude fat, crude fibre, total carbohydrate, crude protein, vitamin C), ofNPT and NST were analyzed by reported methods. The methanolic extracts of tomato pulp were prepared by shaking and extracts were assayed for antioxidant activity. Sugars contents and phenolic profile of NPT and NST were estimatedusing HPLC method.Weight and size of NPT were less and smaller than the NST. Moreover, NPT were seedless with longer shelf-life and had more phenolic and flavonoid contents than the NST.HPLC analysis revealed that chlorogenic acid, gallic acid, p-coumeric acid were major phenolics in methanol (polar solvent) extracts of NST whereas, caffeic acid, gallic acid, p-coumeric acid in NPT extract.NPT contained higher concentration of sugar contents, but lower concentration of vitamin C than NST. In 2,2-diphenyl-1-picrylhydrazyl(DPPH) free-radical-scavenging assay, NPT fruits extracts showed high scavenging activity with the 50% inhibitory concentration (IC50)value of 22.56 µg/mL than NSTfruit extracts having IC50 29.49 µg/mL. This study provided useful information for farmers and nutritionists

    Transformation of UML Activity Diagram for Enhanced Reasoning

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    IT industry has adopted the unified modelling language activity diagram (UML-AD) as a de facto standard. UML AD facilitates modellers to graphically represent and document business processes to show the flow of activities and behaviour of a system. However, UML AD has many drawbacks such as lack of formal semantics i.e. ontology used for the constructs based on intuition, that vaguely describes processes and no provision for verifiability. Petri Net (PN) has been around for decades and used to model the workflow systems but PNs and its variants are too complex for business process modellers with no prior experience. A logical foundation is desirable to construct a business process with a precision that facilitates in transforming UML AD into a formal mechanism supported by verifiability capabilities for enhanced reasoning. Therefore, in this paper, we will provide a framework that will provide formal definitions for UML AD core terms and constructs used for modelling, and subsequently transform them to formal representation called point graph(PG). This will provide an insight into UML AD and will improve the overall functionality required from a modelling tool. A case study is conducted at King’s College Hospital trust’ to improve their patient flows of an accident and emergency (A&E) department

    Evidence that talin alternative splice variants from Ciona intestinalis have different roles in cell adhesion

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    BACKGROUND: Talins are large, modular cytoskeletal proteins found in animals and amoebozoans such as Dictyostelium discoideum. Since the identification of a second talin gene in vertebrates, it has become increasingly clear that vertebrate Talin1 and Talin2 have non-redundant roles as essential links between integrins and the actin cytoskeleton in distinct plasma membrane-associated adhesion complexes. The conserved C-terminal I/LWEQ module is important for talin function. This structural element mediates the interaction of talins with F-actin. The I/LWEQ module also targets mammalian Talin1 to focal adhesion complexes, which are dynamic multicomponent assemblies required for cell adhesion and cell motility. Although Talin1 is essential for focal adhesion function, Talin2 is not targeted to focal adhesions. The nonvertebrate chordate Ciona intestinalis has only one talin gene, but alternative splicing of the talin mRNA produces two proteins with different C-terminal I/LWEQ modules. Thus, C. intestinalis contains two talins, Talin-a and Talin-b, with potentially different activities, despite having only one talin gene. RESULTS: We show here that, based on their distribution in cDNA libraries, Talin-a and Talin-b are differentially expressed during C. intestinalis development. The I/LWEQ modules of the two proteins also have different affinities for F-actin. Consistent with the hypothesis that Talin-a and Talin-b have different roles in cell adhesion, the distinct I/LWEQ modules of Talin-a and Talin-b possess different subcellular targeting determinants. The I/LWEQ module of Talin-a is targeted to focal adhesions, where it most likely serves as the link between integrin and the actin cytoskeleton. The Talin-b I/LWEQ module is not targeted to focal adhesions, but instead preferentially labels F-actin stress fibers. These different properties of C. intestinalis the Talin-a and Talin-b I/LWEQ modules mimic the differences between mammalian Talin1 and Talin2. CONCLUSION: Vertebrates and D. discoideum contain two talin genes that encode proteins with different functions. The urochordate C. intestinalis has a single talin gene but produces two separate talins by alternative splicing that vary in a domain crucial for talin function. This suggests that multicellular organisms require multiple talins as components of adhesion complexes. In C. intestinalis, alternative splicing, rather than gene duplication followed by neo-functionalization, accounts for the presence of multiple talins with different properties. Given that C. intestinalis is an excellent model system for chordate biology, the study of Talin-a and Talin-b will lead to a deeper understanding of cell adhesion in the chordate lineage and how talin functions have been parceled out to multiple proteins during metazoan evolution

    MicroRNA-Related Cofilin Abnormality in Alzheimer's Disease

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    Rod-like structures composed of actin and the actin-binding protein cofilin are found in Alzheimer's disease (AD) patients. However, the mechanisms underlying formation of these structures and their pathological consequences are still largely unknown. We found that microRNAs 103 and 107 repress translation of cofilin, and that reduced levels of miR-103 or miR-107 are associated with elevated cofilin protein levels and formation of rod-like structures in a transgenic mouse model of AD. These results suggest that microRNAs may play an important role in cytoskeletal pathology in AD

    Sodium/myo-Inositol Transporters: Substrate Transport Requirements and Regional Brain Expression in the TgCRND8 Mouse Model of Amyloid Pathology

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    Inositol stereoisomers, myo- and scyllo-inositol, are known to enter the brain and are significantly elevated following oral administration. Elevations in brain inositol levels occur across a concentration gradient as a result of active transport from the periphery. There are two sodium/myo-inositol transporters (SMIT1, SMIT2) that may be responsible for regulating brain inositol levels. The goals of this study were to determine the effects of aging and Alzheimer's disease (AD)-like amyloid pathology on transporter expression, to compare regional expression and to analyze substrate requirements of the inositol transporters. QPCR was used to examine expression of the two transporters in the cortex, hippocampus and cerebellum of TgCRND8 mice, a mouse model of amyloid pathology, in comparison to non-transgenic littermates. In addition, we examined the structural features of inositol required for active transport, utilizing a cell-based competitive uptake assay. Disease pathology did not alter transporter expression in the cortex or hippocampus (p>0.005), with only minimal effects of aging observed in the cerebellum (SMIT1: F2,26 = 12.62; p = 0.0002; SMIT2: F2,26 = 8.71; p = 0.0015). Overall, brain SMIT1 levels were higher than SMIT2, however, regional differences were observed. For SMIT1, at 4 and 6 months cerebellar SMIT1 levels were significantly higher than cortical and hippocampal levels (p<0.05). For SMIT2, at all three ages both cortical and cerebellar SMIT2 levels were significantly higher than hippocampal levels (p<0.05) and at 4 and 6 months of age, cerebellar SMIT2 levels were also significantly higher than cortical levels (p<0.05). Inositol transporter levels are stably expressed as a function of age, and expression is unaltered with disease pathology in the TgCRND8 mouse. Given the fact that scyllo-inositol is currently in clinical trials for the treatment of AD, the stable expression of inositol transporters regardless of disease pathology is an important finding

    Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

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    Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

    Antibodies Targeted to the Brain with Image-Guided Focused Ultrasound Reduces Amyloid-β Plaque Load in the TgCRND8 Mouse Model of Alzheimer's Disease

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    Immunotherapy for Alzheimer's disease (AD) relies on antibodies directed against toxic amyloid-beta peptide (Aβ), which circulate in the bloodstream and remove Aβ from the brain [1], [2]. In mouse models of AD, the administration of anti-Aβ antibodies directly into the brain, in comparison to the bloodstream, was shown to be more efficient at reducing Aβ plaque pathology [3], [4]. Therefore, delivering anti-Aβ antibodies to the brain of AD patients may also improve treatment efficiency. Transcranial focused ultrasound (FUS) is known to transiently-enhance the permeability of the blood-brain barrier (BBB) [5], allowing intravenously administered therapeutics to enter the brain [6]–[8]. Our goal was to establish that anti-Aβ antibodies delivered to the brain using magnetic resonance imaging-guided FUS (MRIgFUS) [9] can reduce plaque pathology. To test this, TgCRND8 mice [10] received intravenous injections of MRI and FUS contrast agents, as well as anti-Aβ antibody, BAM-10. MRIgFUS was then applied transcranially. Within minutes, the MRI contrast agent entered the brain, and BAM-10 was later found bound to Aβ plaques in targeted cortical areas. Four days post-treatment, Aβ pathology was significantly reduced in TgCRND8 mice. In conclusion, this is the first report to demonstrate that MRIgFUS delivery of anti-Aβ antibodies provides the combined advantages of using a low dose of antibody and rapidly reducing plaque pathology

    Lithium Improves Hippocampal Neurogenesis, Neuropathology and Cognitive Functions in APP Mutant Mice

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    Background: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive deterioration of cognitive functions, extracellular b-amyloid (Ab) plaques and intracellular neurofibrillary tangles within neocortex and hippocampus. Adult hippocampal neurogenesis plays an important role in learning and memory processes and its abnormal regulation might account for cognitive impairments associated with AD. Methodology/Principal Findings: The double transgenic (Tg) CRND8 mice (overexpressing the Swedish and Indiana mutations in the human amyloid precursor protein), aged 2 and 6 months, were used to examine in vivo the effects of 5 weeks lithium treatment. BrdU labelling showed a decreased neurogenesis in the subgranular zone of Tg mice compared to non-Tg mice. The decrease of hippocampal neurogenesis was accompanied by behavioural deficits and worsened with age and pathology severity. The differentiation into neurons and maturation of the proliferating cells were also markedly impaired in the Tg mice. Lithium treatment to 2-month-old Tg mice significantly stimulated the proliferation and neuron fate specification of newborn cells and fully counteracted the transgene-induced impairments of cognitive functions. The drug, by the inhibition of GSK-3b and subsequent activation of Wnt/ß-catenin signalling promoted hippocampal neurogenesis. Finally, the data show that the lithium’s ability to stimulate neurogenesis and cognitive functions was lost in the aged Tg mice, thus indicating that the lithium-induced facilitation of neurogenesis and cognitive functions declines a
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