Investigation of charged aerosol transport and deposition in human airway models

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.Several theoretical and experimental studies of charged aerosol deposition in human airways have been reported. These studies suggest that higher charge values on particles lead to improve deposition efficiency in the human lung, especially in the alveolar region. Most of the previous numerical studies in realistic 3D geometrical models have been investigated only for uncharged particles. Hence, this research was aimed at numerically investigating aerosol transport and deposition by including the effect of electrostatic forces (both space and image charge forces). The numerical models that have been developed and presented in this thesis, treat the aerodynamics and electrodynamics as a coupled problem and successfully integrate both mechanisms. The physical model of the human lung used for this research consists of three sub-models: a 3D bifurcation airway model, a 3D reconstructed airway model representing the tracheobronchial region, and a 2D alveolar airway model representing the alveolar region. The airflow dynamics in these geometrical models were carried out using a Computational Fluid Dynamic software (CFD) with given boundary conditions related to corresponding breathing conditions. The space charge force was calculated using the Particle Mesh (PM) method, and the image charge force was computed using the mesh configuration. Both airflow dynamics and electrodynamics are integrated in the newly developed software, and the particle trajectories are then calculated. The numerical study of electrostatic forces is primarily focused on the submicron particle. The numerical study in the 3D tubular airway model gives a better understanding of parameters affecting the predicted deposition efficiency. The numerical study in the 3D tubular airway model focuses on the transport and deposition of particles near the branching regions between the parent and daughter tubes, where airflow profile is significantly altered, and secondary airflow also arises. Many charged particles are deposited near the carinae by the strong skewed axial velocity and image charge force. The space charge will influence the deposition efficiency if the number concentration of particles is high. Similarly, the charged particles in the 3D reconstructed airway model tends to have the deposition pattern near the branching regions, depending on the local airflow and charge value. In the 2D alveolar model, the image charge force can improve deposition efficiency. The outcome of this research clearly shows how the electrostatic forces play an important role in aerosol transport and deposition in human airways. The integrated numerical model provides a valuable tool for respiratory clinicians and the pharmaceutical industry to study the complex mechanism of drug aerosol deposition in human airways. Although this model is adequate for the intended purpose, it can be further improved by extending this work to develop a complete 3D model of entire human airways incorporating the full breathing cycle. Such a model would require extensive computing facilities, nevertheless it would be an enormous benefit to develop a better treatment for respiratory diseases.Financial support obtained from the Overseas Research Students Awards Scheme (ORS)and System Engineering department

Investigation of charged aerosol transport and deposition in human airway models

Several theoretical and experimental studies of charged aerosol deposition in human airways have been reported. These studies suggest that higher charge values on particles lead to improve deposition efficiency in the human lung, especially in the alveolar region. Most of the previous numerical studies in realistic 3D geometrical models have been investigated only for uncharged particles. Hence, this research was aimed at numerically investigating aerosol transport and deposition by including the effect of electrostatic forces (both space and image charge forces). The numerical models that have been developed and presented in this thesis, treat the aerodynamics and electrodynamics as a coupled problem and successfully integrate both mechanisms. The physical model of the human lung used for this research consists of three sub-models: a 3D bifurcation airway model, a 3D reconstructed airway model representing the tracheobronchial region, and a 2D alveolar airway model representing the alveolar region. The airflow dynamics in these geometrical models were carried out using a Computational Fluid Dynamic software (CFD) with given boundary conditions related to corresponding breathing conditions. The space charge force was calculated using the Particle Mesh (PM) method, and the image charge force was computed using the mesh configuration. Both airflow dynamics and electrodynamics are integrated in the newly developed software, and the particle trajectories are then calculated. The numerical study of electrostatic forces is primarily focused on the submicron particle. The numerical study in the 3D tubular airway model gives a better understanding of parameters affecting the predicted deposition efficiency. The numerical study in the 3D tubular airway model focuses on the transport and deposition of particles near the branching regions between the parent and daughter tubes, where airflow profile is significantly altered, and secondary airflow also arises. Many charged particles are deposited near the carinae by the strong skewed axial velocity and image charge force. The space charge will influence the deposition efficiency if the number concentration of particles is high. Similarly, the charged particles in the 3D reconstructed airway model tends to have the deposition pattern near the branching regions, depending on the local airflow and charge value. In the 2D alveolar model, the image charge force can improve deposition efficiency. The outcome of this research clearly shows how the electrostatic forces play an important role in aerosol transport and deposition in human airways. The integrated numerical model provides a valuable tool for respiratory clinicians and the pharmaceutical industry to study the complex mechanism of drug aerosol deposition in human airways. Although this model is adequate for the intended purpose, it can be further improved by extending this work to develop a complete 3D model of entire human airways incorporating the full breathing cycle. Such a model would require extensive computing facilities, nevertheless it would be an enormous benefit to develop a better treatment for respiratory diseases.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Sox10 regulates enteric neural crest cell migration in the developing gut

Concurrent Sessions 1: 1.3 - Organs to organisms: Models of Human Diseases: abstract no. 1417th ISDB 2013 cum 72nd Annual Meeting of the Society for Developmental Biology, VII Latin American Society of Developmental Biology Meeting and XI Congreso de la Sociedad Mexicana de Biologia del Desarrollo. The Conference's web site is located at http://www.inb.unam.mx/isdb/Sox10 is a HMG-domain containing transcription factor which plays important roles in neural crest cell survival and differentiation. Mutations of Sox10 have been identified in patients with Waardenburg-Hirschsprung syndrome, who suffer from deafness, pigmentation defects and intestinal aganglionosis. Enteric neural crest cells (ENCCs) with Sox10 mutation undergo premature differentiation and fail to colonize the distal hindgut. It is unclear, however, whether Sox10 plays a role in the migration of ENCCs. To visualize the migration behaviour of mutant ENCCs, we generated a Sox10NGFP mouse model where EGFP is fused to the N-terminal domain of Sox10. Using time-lapse imaging, we found that ENCCs in Sox10NGFP/+ mutants displays lower migration speed and altered trajectories compared to normal controls. This behaviour was cell-autonomous, as shown by organotypic grafting of Sox10NGFP/+ gut segments onto control guts and vice versa. ENCCs encounter different extracellular matrix (ECM) molecules along the developing gut. We performed gut explant culture on various ECM and found that Sox10NGFP/+ ENCCs tend to form aggregates, particularly on fibronectin. Time-lapse imaging of single cells in gut explant culture indicated that the tightly-packed Sox10 mutant cells failed to exhibit contact inhibition of locomotion. We determined the expression of adhesion molecule families by qPCR analysis, and found integrin expression unaffected while L1-cam and selected cadherins were altered, suggesting that Sox10 mutation affects cell adhesion properties of ENCCs. Our findings identify a de novo role of Sox10 in regulating the migration behaviour of ENCCs, which has important implications for the treatment of Hirschsprung disease.postprin

Analysis of craniofacial defects in Six1/Eya1-associated Branchio-Oto-Renal Syndrome

Poster Session I - Morphogenesis: 205/B10117th ISDB 2013 cum 72nd Annual Meeting of the Society for Developmental Biology, 7th Latin American Society of Developmental Biology Meeting and 11th Congreso de la Sociedad Mexicana de Biologia del Desarrollo.Branchio-Oto-Renal (BOR) syndrome patients exhibit craniofacial and renal anomalies as well as deafness. BOR syndrome is caused by mutations in Six1 or Eya1, both of which regulate cell proliferation and differentiation. The molecular mechanism underlying the craniofacial and branchial arch (BA) defects in BOR syndrome is unclear. We have found that Hoxb3 is up-regulated in the second branchial arch (BA2) of Six1-/- mutants. Moreover, Hoxb3 over-expression in transgenic mice leads to BA abnormalities which are similar to the BA defects in Six1-/- or Eya1-/- mutants, suggesting a regulatory relationship among Six1, Eya1 and Hoxb3 genes. The aim of this study is to investigate the molecular mechanism underlying abnormal BA development in BOR syndrome using Six1 and Eya1 mutant mice. Two potential Six1 binding sites were identified on the Hoxb3 gene. In vitro and in vivo Chromatin IP assays showed that Six1 could directly bind to one of the sites specifically. Furthermore, using a chick in ovo luciferase assay we showed that Six1 could suppress gene expression through one of the specific binding sites. On the other hand, in Six1-/- mutants, we found that the Notch ligand Jag1 was up-regulated in BA2. Similarly, in Hoxb3 transgenic mice, ectopic expression of Jag1 could be also detected in BA2. To investigate the activation of Notch signaling pathway, we found that Notch intracellular domain (NICD), a direct indicator of Notch pathway activation, was up-regulated in BAs of Six1-/-; Eya1-/- double mutants. Our results indicate that Hoxb3 and Notch signaling pathway are involved in mediating the craniofacial defects of Six1/Eya1-associated Branchio-Oto-Renal Syndrome.postprin

Advancements and Breakthroughs in Ultrasound Imaging

Ultrasonic imaging is a powerful diagnostic tool available to medical practitioners, engineers and researchers today. Due to the relative safety, and the non-invasive nature, ultrasonic imaging has become one of the most rapidly advancing technologies. These rapid advances are directly related to the parallel advancements in electronics, computing, and transducer technology together with sophisticated signal processing techniques. This book focuses on state of the art developments in ultrasonic imaging applications and underlying technologies presented by leading practitioners and researchers from many parts of the world

Evaluation of the availability and applicability of computational approaches in the safety assessment of nanomaterials: Final report of the Nanocomput project

This is the final report of the Nanocomput project, the main aims of which were to review the current status of computational methods that are potentially useful for predicting the properties of engineered nanomaterials, and to assess their applicability in order to provide advice on the use of these approaches for the purposes of the REACH regulation. Since computational methods cover a broad range of models and tools, emphasis was placed on Quantitative Structure-Property Relationship (QSPR) and Quantitative Structure-Activity Relationship (QSAR) models, and their potential role in predicting NM properties. In addition, the status of a diverse array of compartment-based mathematical models was assessed. These models comprised toxicokinetic (TK), toxicodynamic (TD), in vitro and in vivo dosimetry, and environmental fate models. Finally, based on systematic reviews of the scientific literature, as well as the outputs of the EU-funded research projects, recommendations for further research and development were also made. The Nanocomput project was carried out by the European Commission’s Joint Research Centre (JRC) for the Directorate-General (DG) for Internal Market, Industry, Entrepreneurship and SMEs (DG GROW) under the terms of an Administrative Arrangement between JRC and DG GROW. The project lasted 39 months, from January 2014 to March 2017, and was supported by a steering group with representatives from DG GROW, DG Environment and the European Chemicals Agency (ECHA).JRC.F.3-Chemicals Safety and Alternative Method

Front Lines of Thoracic Surgery

Front Lines of Thoracic Surgery collects up-to-date contributions on some of the most debated topics in today's clinical practice of cardiac, aortic, and general thoracic surgery,and anesthesia as viewed by authors personally involved in their evolution. The strong and genuine enthusiasm of the authors was clearly perceptible in all their contributions and I'm sure that will further stimulate the reader to understand their messages. Moreover, the strict adhesion of the authors' original observations and findings to the evidence base proves that facts are the best guarantee of scientific value. This is not a standard textbook where the whole discipline is organically presented, but authors' contributions are simply listed in their pertaining subclasses of Thoracic Surgery. I'm sure that this original and very promising editorial format which has and free availability at its core further increases this book's value and it will be of interest to healthcare professionals and scientists dedicated to this field

CT Scanning

Since its introduction in 1972, X-ray computed tomography (CT) has evolved into an essential diagnostic imaging tool for a continually increasing variety of clinical applications. The goal of this book was not simply to summarize currently available CT imaging techniques but also to provide clinical perspectives, advances in hybrid technologies, new applications other than medicine and an outlook on future developments. Major experts in this growing field contributed to this book, which is geared to radiologists, orthopedic surgeons, engineers, and clinical and basic researchers. We believe that CT scanning is an effective and essential tools in treatment planning, basic understanding of physiology, and and tackling the ever-increasing challenge of diagnosis in our society