69 research outputs found

    Development of a Real-Time, Secure and Reliable Automobile Service Center

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    Lack of ambition will prevent you from moving forward in life, as much like a car without petrol. The majority of people on earth isobsessed with automobiles. We have provided you with a web application for Real time automobile service that functions effectively on all the platforms. Occasionally, automobiles and other motorized vehicles require maintenance. They must be maintained clean, just as humans practice proper hygiene. They run on dirty streets and in polluted environment. They are subjected to loads that harm them since they travel on uneven roads with obstacles. Therefore, it is necessary to maintain automobiles and other motorized vehicles on a regular basis. This project aims to keep service centers running smoothly in terms of things like vehicle maintenance, customer quotation generation, vehicle servicing, spare parts sales, customer information, and customer feedback. The system is efficient at generating reports that will make service center routine maintenance easy.Additionally, it can handle car repairs, insurance, payments, delivery, etc. This project will be very helpful to customers who want to fix or repair their cars. As a result, we develop a software that is both compatible and unique

    EQ-5D-3L Derived Population Norms for Health Related Quality of Life in Sri Lanka

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    Background Health Related Quality of Life (HRQoL) is an important outcome measure in health economic evaluation that guides health resource allocations. Population norms for HRQoL are an essential ingredient in health economics and in the evaluation of population health. The aim of this study was to produce EQ-5D-3L-derived population norms for Sri Lanka. Method A population sample (n =  780) was selected from four districts of Sri Lanka. A stratified cluster sampling approach with probability proportionate to size was employed. Twenty six clusters of 30 participants each were selected; each participant completed the EQ-5D-3L in a face-to-face interview. Utility weights for their EQ-5D-3L health states were assigned using the Sri Lankan EQ-5D-3L algorithm. The population norms are reported by age and socio-economic variables. Results The EQ-5D-3L was completed by 736 people, representing a 94% response rate. Sixty per cent of the sample reported being in full health. The percentage of people responding to any problems in the five EQ-5D-3L dimensions increased with age. The mean EQ-5D-3L weight was 0.85 (SD 0.008; 95%CI 0.84-0.87). The mean EQ-5D-3L weight was significantly associated with age, housing type, disease experience and religiosity. People above 70 years of age were 7.5 times more likely to report mobility problems and 3.7 times more likely to report pain/discomfort than those aged 18-29 years. Those with a tertiary education were five times less likely to report any HRQoL problems than those without a tertiary education. A person living in a shanty was 4.3 more likely to have problems in usual activities than a person living in a single house. Conclusion The population norms in Sri Lanka vary with socio-demographic characteristics. The socioeconomically disadvantaged have a lower HRQoL. The trends of population norms observed in this lower middle income country were generally similar to those previously reported in high income countries

    Cre-dependent DNA recombination activates a STING-dependent innate immune response

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    Gene-recombinase technologies, such as Cre/loxP-mediated DNA recombination, are important tools in the study of gene function, but have potential side effects due to damaging activity on DNA. Here we show that DNA recombination by Cre instigates a robust antiviral response in mammalian cells, independent of legitimate loxP recombination. This is due to the recruitment of the cytosolic DNA sensor STING, concurrent with Cre-dependent DNA damage and the accumulation of cytoplasmic DNA. Importantly, we establish a direct interplay between this antiviral response and cell-cell interactions, indicating that low cell densities in vitro could be useful to help mitigate these effects of Cre. Taking into account the wide range of interferon stimulated genes that may be induced by the STING pathway, these results have broad implications in fields such as immunology, cancer biology, metabolism and stem cell research. Further, this study sets a precedent in the field of gene-engineering, possibly applicable to other enzymatic-based genome editing technologies

    Cre-dependent DNA recombination activates a STING-dependent innate immune response

    Get PDF
    Gene-recombinase technologies, such as Cre/loxP-mediated DNA recombination, are important tools in the study of gene function, but have potential side effects due to damaging activity on DNA. Here we show that DNA recombination by Cre instigates a robust antiviral response in mammalian cells, independent of legitimate loxP recombination. This is due to the recruitment of the cytosolic DNA sensor STING, concurrent with Cre-dependent DNA damage and the accumulation of cytoplasmic DNA. Importantly, we establish a direct interplay between this antiviral response and cell-cell interactions, indicating that low cell densities in vitro could be useful to help mitigate these effects of Cre. Taking into account the wide range of interferon stimulated genes that may be induced by the STING pathway, these results have broad implications in fields such as immunology, cancer biology, metabolism and stem cell research. Further, this study sets a precedent in the field of gene-engineering, possibly applicable to other enzymatic-based genome editing technologies

    ONC201 in combination with paxalisib for the treatment of H3K27-altered diffuse midline glioma

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    Diffuse midline gliomas (DMG), including diffuse intrinsic pontine gliomas (DIPGs), are the most lethal of childhood cancers. Palliative radiotherapy is the only established treatment, with median patient survival of 9-11 months. ONC201 is a DRD2 antagonist and ClpP agonist that has shown preclinical and emerging clinical efficacy in DMG. However, further work is needed to identify the mechanisms of response of DIPGs to ONC201 treatment and to determine whether recurring genomic features influence response. Using a systems-biological approach, we showed that ONC201 elicits potent agonism of the mitochondrial protease ClpP to drive proteolysis of electron transport chain and tricarboxylic acid cycle proteins. DIPGs harboring PIK3CA-mutations showed increased sensitivity to ONC201, while those harboring TP53-mutations were more resistant. Metabolic adaptation and reduced sensitivity to ONC201 was promoted by redox-activated PI3K/Akt signaling, which could be counteracted using the brain penetrant PI3K/Akt inhibitor, paxalisib. Together, these discoveries coupled with the powerful anti-DIPG/DMG pharmacokinetic and pharmacodynamic properties of ONC201 and paxalisib have provided the rationale for the ongoing DIPG/DMG phase II combination clinical trial NCT05009992

    A splenic artery aneurysm presenting with multiple episodes of upper gastrointestinal bleeding: a case report

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    Abstract Background Splenic artery aneurysm is rare and its diagnosis is challenging due to the nonspecific nature of the clinical presentation. We report a case of a splenic artery aneurysm in which the patient presented with chronic dyspepsia and multiple episodes of minor intragastric bleeding. Case presentation A 60-year-old, previously healthy Sri Lankan man presented with four episodes of hematemesis and severe dyspeptic symptoms over a period of 6 months. The results of two initial upper gastrointestinal endoscopies and an abdominal ultrasound scan were unremarkable. A third upper gastrointestinal endoscopy detected a pulsatile bulge at the posterior wall of the gastric antrum. A contrast-enhanced computed tomogram of his abdomen detected a splenic artery aneurysm measuring 3 × 3 × 2.5 cm. While awaiting routine surgery, he developed a torrential upper gastrointestinal bleeding and shock, leading to emergency laparotomy. Splenectomy and en bloc resection of the aneurysm with the posterior stomach wall were performed. Histology revealed evidence for a true aneurysm without overt, acute, or chronic inflammation of the surrounding gastric mucosa. He became completely asymptomatic 2 weeks after the surgery. Conclusions Splenic artery aneurysms can result in recurrent upper gastrointestinal bleeding. The possibility of impending catastrophic bleeding should be remembered when managing patients with splenic artery aneurysms after a minor bleeding. Negative endoscopy and ultrasonography should require contrast-enhanced computed tomography to look for the cause of recurrent upper gastrointestinal bleeding

    Unilateral Cervical Lymphadenopathy due to Cladosporium oxysporum: A Case Report and Review of the Literature

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    Phaeohyphomycosis is a fungal infection caused by Dermatiacae group of fungi, by Cladosporium spp. The term phaeohyphomycosis was introduced by Ajello et al. in 1974 to designate infections by brown pigmented filamentous fungi. Cladosporium oxysporum is a very rare etiological agent in humans. Phaeohyphomycosis of the cervical lymph node in an immunocompetent individual is a very rare clinical entity. To the best of our knowledge we report the first case of phaeohyphomycosis caused by Cladosporium oxysporum in the absence of other systemic manifestations in a 16-year-old male
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