1,743 research outputs found
Nebulized Hyaluronan Ameliorates lung inflammation in cystic fibrosis mice.
No full textRATIONALE:
Chronic lung inflammation with increased susceptibility to bacterial infections cause much of the morbidity and mortality in patients with cystic fibrosis (CF), the most common severe, autosomal recessively inherited disease in the Caucasian population. Exogenous inhaled hyaluronan (HA) can exert a protective effect against injury and beneficial effects of HA have been shown in experimental models of chronic respiratory diseases. Our objective was to examine whether exogenous administration of nebulized HA might interfere with lung inflammation in CF.
STUDY DESIGN/METHODS:
F508del homozygous mice (Cftr(F508del) ) and transgenic mice overexpressing the ENaC channel β-subunit (Scnn1b-Tg) were treated with nebulized HA (0.5 mg/mouse/day for 7 days). Tumor necrosis factor-alpha (TNFα), macrophage inflammatory protein-2 (MIP-2), myeloperoxidase (MPO) levels, and macrophage infiltration were assessed on lung tissues. IB3-1 and CFBE41o-epithelial cell lines were cultured with HA (24 hr, 100 μg/ml) and Reactive Oxygen Species (ROS), Tissue Transglutaminase (TG2) SUMOylation and Peroxisome Proliferator Activated Receptor gamma (PPARγ) and phospho-p42/p44 levels were measured by dichlorodihydrofluorescein assay, or fluorescence resonance energy transfer (FRET) microscopy or immunoblots.
RESULTS:
Nebulized HA reduced TNFα expression (P < 0.005); TNFα, MIP-2, and MPO protein levels (P < 0.05); MPO activity (P < 0.05); and CD68+ cells counts (P < 0.005) in lung tissues of Cftr(F508del) and Scnn1b-Tg mice, compared with saline-treated mice. HA reduced ROS, TG2 SUMOylation, TG2 activity, phospho-p42-44, and increased PPARγ protein in both IB3-1 and CFBE41o cells (P < 0.05).
CONCLUSIONS:
Nebulized HA is effective in controlling inflammation in vivo in mice CF airways and in vitro in human airway epithelial cells. We provide the proof of concept for the use of inhaled HA as a potential anti-inflammatory drug in CF therapy. Pediatr Pulmonol. © 2012 Wiley Periodicals, Inc
Personalization of therapies in rare diseases: a translational approach for the treatment of cystic fibrosis.
No full textHigh variability in the response rates to treatments can make the interpretation of data from clinical trials very difficult, particularly in rare genetic diseases in which the enrolment of thousands of patients is problematic. Personalized medicine largely depends on the establishment of appropriate early detectors of drug efficacy that may guide the administration (or discontinuation) of specific treatments. Such biomarkers should be capable of predicting the therapeutic response of individual patients and of monitoring early benefits of candidate drugs before late clinical benefits become evident. The identification of these biomarkers implies a rigorous stepwise process of translation from preclinical evaluation in cultured cells, suitable animal models or patient-derived freshly isolated cells to clinical application. In this review, we will discuss how a process of research translation can lead to the implementation of functional and mechanistic diseaserelevant biomarkers. Moreover, we will address how preclinical data can be translated into the clinic in a personalized medical approach that can provide the right drug to the right patient within the right timeframe
Do different types of VR influence pedestrian route choice behaviour? A comparison study of Desktop VR and HMD VR
No full textVirtual Reality (VR) is a valuable tool for studying pedestrian behaviour in complex and realistic scenarios. However, it has remained unknown how different VR technology would influence pedestrian behaviour. This paper presents VR experiments that were conducted with 70 participants using a desktop VR or a HMD VR to perform four different wayfinding tasks in a multi-story building. Quantitative analysis of pedestrian behaviour data and user experience data were performed in order to investigate the impact of the technological differences between the two VR techniques. It was found that participants had better wayfinding task performance in the desktop group. However, the route and exit choice and user experience were overall similar between the two groups. The findings suggest that one could adopt more ‘simple’ VR technologies for studies featuring ‘simple’ wayfinding tasks.Accepted Author ManuscriptTransport and Plannin
Cystic fibrosis transmembrane conductance regulator (CFTR) and autophagy: hereditary defects in cystic fibrosis versus gluten-mediated inhibition in celiac disease
No full textCystic Fibrosis (CF) is the most frequent lethal monogenetic disease affecting humans. CF is characterized by mutations in cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel whose malfunction triggers the activation of transglutaminase-2 (TGM2), as well as the inactivation of the Beclin-1 (BECN1) complex resulting in disabled autophagy. CFTR inhibition, TGM2 activation and BECN1 sequestration engage in an 'infernal trio' that locks the cell in a pro-inflammatory state through anti-homeostatic feedforward loops. Thus, stimulation of CFTR function, TGM2 inhibition and autophagy stimulation can be used to treat CF patients. Several studies indicate that patients with CF have a higher incidence of celiac disease (CD) and that mice bearing genetically determined CFTR defects are particularly sensitive to the enteropathogenic effects of the orally supplied gliadin (a gluten-derived protein). A gluten/gliadin-derived peptide (P31-43) inhibits CFTR in mouse intestinal epithelial cells, causing a local stress response that contributes to the immunopathology of CD. In particular, P31-43-induced CFTR inhibition elicits an epithelial stress response perturbing proteostasis. This event triggers TGM2 activation, BECN1 sequestration and results in molecular crosslinking of CFTR and P31-43 by TGM2. Importantly, stimulation of CFTR function with a pharmacological potentiator (Ivacaftor), which is approved for the treatment of CF, could attenuate the autophagy-inhibition and pro-inflammatory effects of gliadin in preclinical models of CD. Thus, CD shares with CF a common molecular mechanism involving CFTR inhibition that might respond to drugs that intercept the "infernal trio". Here, we highlight how drugs available for CF treatment could be repurposed for the therapy of CD
VR Kepler orbit simulation: VR Astronomy simulation
No full textFor this project, we developed an educational Virtual Reality (VR) experience that will expose students to an immersive simulation of planetary motion. While there are many Solar System simulations available online, none of them focus on visualizing apparent retrograde motion in an educational setting. This VR experience is intended to fill that gap. The objective of this research project was to develop and implement an efficient and accurate simulation of Kepler orbits in VR for educational settings with a focus on the visualization of apparent retrograde motion. In particular, our main focus is on the ability to view the apparent retrograde motion of planets from the perspective of planets other than Earth. Our VR application is created using Unreal Engine 5, with code written in C++, and is designed to be used with the Meta Quest 2 VR headset. To the best of our knowledge, this is one of the first attempts in post-secondary education at creating an immersive experience for planetary motion in VR with a focus on apparent retrograde motion. Report submission was sponsored by Dr. Shahriar Khosravi, (Computing Science Department) for course CMPT 2367 and was presented at the New Westminster campus on April 12, 2023, for Student Research Days 2023.Not peer reviewe
VR Kepler orbit simulation: VR Astronomy simulation
No full textFor this project, we developed an educational Virtual Reality (VR) experience that will expose students to an immersive simulation of planetary motion. While there are many Solar System simulations available online, none of them focus on visualizing apparent retrograde motion in an educational setting. This VR experience is intended to fill that gap.
The objective of this research project was to develop and implement an efficient and accurate simulation of Kepler orbits in VR for educational settings with a focus on the visualization of apparent retrograde motion. In particular, our main focus is on the ability to view the apparent retrograde motion of planets from the perspective of planets other than Earth.
Our VR application is created using Unreal Engine 5, with code written in C++, and is designed to be used with the Meta Quest 2 VR headset. To the best of our knowledge, this is one of the first attempts in post-secondary education at creating an immersive experience for planetary motion in VR with a focus on apparent retrograde motion.
Video submission was sponsored by Dr. Shahriar Khosravi, (Computing Science Department) for course CMPT 2367 and was presented at the New Westminster campus on April 12, 2023, for Student Research Days 2023
Применение VR-технологий в обучении и развитии персонала
No full textТема исследования: Применение VR-технологий в обучении и развитии персонала. Документ содержит 76 страниц, на которых размещены 16 рисунков и 7 таблиц. Выпускная квалификационная работа включает 4 приложения. В процессе написания ВКР использовались 50 литературных источников. Объект исследования - публичное акционерное общество «Газпром нефть». Предмет исследования - программы обучения и развития персонала с использованием VR-технологий в ПАО «Газпром нефть».
Структура ВКР включает в себя введение, три главы основного текста, заключение, список используемых источников и приложения. Во введении сформированы цель и задачи, а также объект, предмет и методы исследования, обоснована актуальность выбранной темы выпускной квалификационной работы.
В первой главе «Теоретические основы обучения и развития персонала» описаны сущность, подходы, методологические принципы, цели и методы обучения и развития персонала, а также рассмотрен традиционный корпоративный университет как форма обучения и развития персонала. Вторая глава «Инновационные технологии обучения и развития персонала» посвящена описанию инновационных методов обучения персонала, а также изучению различных методик оценки эффективности программ обучения. В третьей главе «Применение VR-технологий в ПАО «Газпром нефть» описана деятельность компании, проанализирована организационная структура, а также характеристика персонала организации по различных критериям, отражены финансовые показатели компании. На основе данных внутренней документации и анкетирования сотрудников автором были проанализированы внедрённые программы обучения с применением VR-технологий и сформулированы рекомендации по совершенствованию реализуемых VR-курсов. Также в работе были предложены метрики для оценки экономической и социальной эффективности обучения с применением VR-технологий.
В заключении работы сформулированы итоги исследования и общие выводы.
Цель выпускной квалификационной работы: анализ реализуемых программ обучения с применением VR-технологий в ПАО «Газпром нефть» и разработка рекомендаций по их совершенствованию. Также были поставлены следующие задачи: исследовать дифференциацию понятий «обучение персонала» и «развитие персонала», изучить методы обучения и развития персонала, проанализировать методики оценки эффективности обучения и развития персонала и др.
Получены следующие выводы: выявлены высокая эффективность применения VR-технологий в обучении и развитии персонала в ПАО «Газпром нефть», а также возможные зоны развития, для совершенствования которых предложен ряд рекомендаций.Research topic: Application of VR technologies in personnel training and development. The document contains 76 pages containing 16 figures and 7 tables. The final qualifying work includes 4 applications. In the process of writing the work, 50 literary sources were used. The object of the research is the public joint stock company Gazprom Neft. The subject of the research is personnel training and development programs using VR technologies at Gazprom Neft PJSC.
The structure of the work includes an introduction, three chapters of the main text, a conclusion, a list of sources and applications. In the introduction, the goal and objectives, as well as the object, subject and methods of research are formed, the relevance of the chosen topic of the final qualifying work is substantiated.
The first chapter "Theoretical foundations of personnel training and development" describes the essence, approaches, methodological principles, goals and methods of personnel training and development, and also considers the traditional corporate university as a form of personnel training and development. The second chapter "Innovative technologies for personnel training and development" is devoted to the description of innovative methods of personnel training, as well as to the study of various methods for assessing the effectiveness of training programs. The third chapter, Application of VR technologies at PJSC Gazprom Neft, describes the company's activities, analyzes the organizational structure, as well as the characteristics of the organization's personnel according to various criteria, reflects the company's financial indicators. Based on the data of internal documentation and questionnaires of employees, the author analyzed the implemented training programs using VR technologies and formulated recommendations for improving the implemented VR courses. The work also proposed metrics for assessing the economic and social effectiveness of learning using VR technologies.
In the conclusion of the work, the results of the study and general conclusions are formulated.
The purpose of the final qualification work: analysis of the training programs being implemented using VR technologies at Gazprom Neft PJSC and the development of recommendations for their improvement. The following tasks were also set: to investigate the differentiation of the concepts of "personnel training" and "personnel development", to study the methods of training and personnel development, to analyze methods for assessing the effectiveness of training and personnel development, etc.
The following conclusions were obtained: high efficiency of the use of VR technologies in personnel training and development at Gazprom Neft PJSC was revealed, as well as possible development zones, for the improvement of which a number of recommendations were proposed
Social virtual reality (VR) applications and user experiences
No full textVirtual reality (VR) is the experience in a simulated interactive virtual space. It provides synthetic sensory feedback to users' actions that can physically and mentally immerse the users. Social VR is one type of VR system that allows multiple users to join a collaborative virtual environment and communicate with each other, usually by means of visual and audio cues. The virtual space can be a computer-generated 3D scene or a 360° scene captured by an omnidirectional camera. Each user is represented as a computer-generated avatar or using a virtual representation based on live capture. Social VR has shown to be a promising solution to enrich remote communication experiences in the face of increasing pressures to reduce travel and work remotely. In this chapter, we will showcase the design, implementation, and real-world deployment of a series of social VR applications, which are developed for immersive interactive communication and collaboration for multiple domains (e.g., healthcare, cultural heritage). Moreover, we discuss the experimental protocols for evaluating user experiences in this new medium.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Multimedia Computin
Wayfinding behaviour in a multi-level building: A comparative study of HMD VR and Desktop VR
No full textVirtual Reality (VR) provides the possibility to study pedestrian wayfinding behaviour in multi-level buildings. Although VR has been applied increasingly to study pedestrian behaviour, it has remained unclear how different VR technology would affect behavioural outcomes in a multi-level building. The study compares the adoption of different VR technologies for pedestrian wayfinding studies, via investigating the difference in pedestrian wayfinding behaviour and user experience. Wayfinding experiments with two groups of participants were conducted using either HMD VR or Desktop VR. Pedestrian movement trajectory data were collected via the VR system and user experience data were recorded via a questionnaire. These data allow for direct comparison and detailed analysis of pedestrian behaviour and user experience between the adoption of two VR technologies. The results showed that technological differences have a significant impact on wayfinding task performance and head rotation change. However, the route choice, exit choice and user experience were overall similar between the two groups. These results provide empirical evidence supporting researchers to choose between immersive and non-immersive VR when study pedestrian wayfinding behaviour.Transport and PlanningTransport and Plannin
Restoration of CFTR function in patients with cystic fibrosis carrying the F508del-CFTR mutation
No full textRestoration of BECN1/Beclin 1-dependent autophagy and depletion of SQSTM1/p62 by genetic manipulation or autophagy-stimulatory proteostasis regulators, such as cystamine, have positive effects on mouse models of human cystic fibrosis (CF). These measures rescue the functional expression of the most frequent pathogenic CFTR mutant, F508del, at the respiratory epithelial surface and reduce lung inflammation in CftrF508del homozygous mice. Cysteamine, the reduced form of cystamine, is an FDA-approved drug. Here, we report that oral treatment with cysteamine greatly reduces the mortality rate and improves the phenotype of newborn mice bearing the F508del-CFTR mutation. Cysteamine was also able to increase the plasma membrane expression of the F508del-CFTR protein in nasal epithelial cells from F508del homozygous CF patients, and these effects persisted for 24 h after cysteamine withdrawal. Importantly, this cysteamine effect after washout was further sustained by the sequential administration of epigallocatechin gallate (EGCG), a green tea flavonoid, both in vivo, in mice, and in vitro, in primary epithelial cells from CF patients. In a pilot clinical trial involving 10 F508del-CFTR homozygous CF patients, the combination of cysteamine and EGCG restored BECN1, reduced SQSTM1 levels and improved CFTR function from nasal epithelial cells in vivo, correlating with a decrease of chloride concentrations in sweat, as well as with a reduction of the abundance of TNF/TNF-alpha (tumor necrosis factor) and CXCL8 (chemokine [C-X-C motif] ligand 8) transcripts in nasal brushing and TNF and CXCL8 protein levels in the sputum. Altogether, these results suggest that optimal schedules of cysteamine plus EGCG might be used for the treatment of CF caused by the F508del-CFTR mutation.</p
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