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"Parsons, David"
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Epithelial mesenchymal transition (EMT): a universal process in lung diseases with implications for cystic fibrosis pathophysiology
Cystic Fibrosis (CF) is a genetic disorder that arises due to mutations in the Cystic Fibrosis Transmembrane Conductance Regulator gene, which encodes for a protein responsible for ion transport out of epithelial cells. This leads to a disruption in transepithelial Cl-, Na + and HCO
3
− ion transport and the subsequent dehydration of the airway epithelium, resulting in infection, inflammation and development of fibrotic tissue. Unlike in CF, fibrosis in other lung diseases including asthma, chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis has been well characterised. One of the driving forces behind fibrosis is Epithelial Mesenchymal Transition (EMT), a process where epithelial cells lose epithelial proteins including E-Cadherin, which is responsible for tight junctions. The cell moves to a more mesenchymal phenotype as it gains mesenchymal markers such as N-Cadherin (providing the cells with migration potential), Vimentin and Fibronectin (proteins excreted to help form the extracellular matrix), and the fibroblast proliferation transcription factors Snail, Slug and Twist. This review paper explores the EMT process in a range of lung diseases, details the common links that these have to cystic fibrosis, and explores how understanding EMT in cystic fibrosis may open up novel methods of treating patients with cystic fibrosis.
Journal Article
Short‐Duration Extreme Rainfall Events in the Central and Eastern United States During the Summer: 2003–2023 Trends and Variability
Extreme rainfall events (EREs) caused by convection are a major prediction challenge and can lead to deadly flash flooding. This study investigates EREs from 2003 to 2023 over the central and eastern United States using high‐resolution (4‐km) Stage IV precipitation analyses. EREs were defined where 12‐hr accumulations exceeded the 10‐year average recurrence interval thresholds. Summertime (June–August) EREs exhibited pronounced interannual variability, but with statistically significant increasing trends in annual frequency, particularly among those caused by mesoscale convective systems. Significant relationships were also found between summertime convective EREs over the central United States and enhanced poleward moisture transport, consistent with a westward expansion of the climatological North Atlantic Subtropical High. This relationship may aid in medium‐ and long‐range forecasting. However, the spatial scale of EREs often included localized or narrow bands of extreme accumulations, revealing significant challenges in the accurate representation of EREs in weather and climate models. Plain Language Summary Extreme rainfall events often result from slow‐moving thunderstorms that drop heavy rain over the same area for several hours, which can cause deadly flash flooding. This study defines an extreme rainfall event where the 12‐hr accumulation would only exceed that amount once every 10 years on average, with a focus on the summer months over the central and eastern United States from 2003 to 2023. Our results show a significant increasing trend in the number of extreme events, especially those caused by larger, longer‐duration storms. Our use of a high‐resolution rainfall data set also revealed that extreme rainfall often occurs due to nighttime thunderstorms producing heavy rainfall over highly localized areas or narrow (20–40 km wide) swaths. These characteristics present a challenge for global weather and climate models. The frequency of these summertime extreme events also significantly varied from year to year. Summers with more extreme events were associated with a greater northward transport of moist air around the western edge of an area of high pressure that extends westward from the Atlantic Ocean. The relationship between this flow pattern and extreme rainfall suggests a possible path for improving forecasts of extreme rainfall. Key Points High‐resolution rainfall data reveal an increasing trend in extreme summertime rainfall, especially from mesoscale convective systems More events occurred during summers with greater southerly moisture transport driven by differences in the North Atlantic Subtropical High The relatively small scale of extreme convective rainfall presents a challenge for representing these events in weather and climate models
Journal Article
التمويل الحكومي للتعليم العالي : سياقات متغيرة ومسوغات جديدة
يتناول هذا الكتاب قضايا متعلقة بكل من تطوير مهارات الأساتذة ورؤساء الوحدات الأكاديمية والإداريين في أكثر الجامعات العالمية تقدما، كما تناول هذه الكتاب أيضا قضايا مثل : التعليم الإلكتروني والتعليم عن بعد ومهارات التعليم والتعلم وتقنيات التعليم الحديثة والتخطيط الإستراتيجي الخاص بالتعليم والاختبارات والتقويم ومواءمة مخرجات التعليم العالي لسوق العمل وتحقيق الجودة في مدخلات ومخرجات التعليم العالي وغير ذلك من الموضوعات ذات العلاقة.
BOOK
Wave Disturbances and Their Role in the Maintenance, Structure, and Evolution of a Mesoscale Convection System
This study investigates a nocturnal mesoscale convective system (MCS) observed during the Plains Elevated Convection At Night (PECAN) field campaign. A series of wavelike features were observed ahead of this MCS with extensive convective initiation (CI) taking place in the wake of one of these disturbances. Simulations with the WRF-ARW Model were utilized to understand the dynamics of these disturbances and their impact on the MCS. In these simulations, an “elevated bore” formed within an inversion layer aloft in response to the layer being lifted by air flowing up and over the cold pool. As the bore propagated ahead of the MCS, the lifting created an environment more conducive to deep convection allowing the MCS to discretely propagate due to CI in the bore’s wake. The Scorer parameter was somewhat favorable for trapping of this wave energy, although aspects of the environment evolved to be consistent with the expectations for an n = 2 mode deep tropospheric gravity wave. A bore within an inversion layer aloft is reminiscent of disturbances predicted by two-layer hydraulic theory, contrasting with recent studies that suggest bores are frequently initiated by the interaction between the flow within stable nocturnal boundary layer and convectively generated cold pools. Idealized simulations that expand upon this two-layer approach with orography and a well-mixed layer below the inversion suggest that elevated bores provide a possible mechanism for daytime squall lines to remove the capping inversion often found over the Great Plains, particularly in synoptically disturbed environments where vertical shear could create a favorable trapping of wave energy.
Journal Article
Developing disaster leaders for contemporary times
In 2017, the New Zealand Government completed its review of the country's emergency response capabilities. The review was to make sure New Zealand’s emergency response capabilities and frameworks are well placed to meet future challenges.
Journal Article
Airway disease phenotypes in animal models of cystic fibrosis
In humans, cystic fibrosis (CF) lung disease is characterised by chronic infection, inflammation, airway remodelling, and mucus obstruction. A lack of pulmonary manifestations in CF mouse models has hindered investigations of airway disease pathogenesis, as well as the development and testing of potential therapeutics. However, recently generated CF animal models including rat, ferret and pig models demonstrate a range of well characterised lung disease phenotypes with varying degrees of severity. This review discusses the airway phenotypes of currently available CF animal models and presents potential applications of each model in airway-related CF research.
Journal Article
Gene Therapy for Cystic Fibrosis Lung Disease: Overcoming the Barriers to Translation to the Clinic
Cystic fibrosis (CF) is a progressive, chronic and debilitating genetic disease caused by mutations in the CF Transmembrane-Conductance Regulator (
) gene. Unrelenting airway disease begins in infancy and produces a steady deterioration in quality of life, ultimately leading to premature death. While life expectancy has improved, current treatments for CF are neither preventive nor curative. Since the discovery of
the vision of correcting the underlying genetic defect - not just treating the symptoms - has been developed to where it is poised to become a transformative technology. Addition of a properly functioning
gene into defective airway cells is the only biologically rational way to prevent or treat CF airway disease for
mutation classes. While new gene editing approaches hold exciting promise, airway gene-addition therapy remains the most encouraging therapeutic approach for CF. However, early work has not yet progressed to large-scale clinical trials. For clinical trials to begin in earnest the field must demonstrate that gene therapies are safe in CF lungs; can provide clear health benefits and alter the course of lung disease; can be repeatedly dosed to boost effect; and can be scaled effectively from small animal models into human-sized lungs. Demonstrating the durability of these effects demands relevant CF animal models and accurate and reliable techniques to measure benefit. In this review, illustrated with data from our own studies, we outline recent technological developments and discuss these key questions that we believe must be answered to progress CF airway gene-addition therapies to clinical trials.
Journal Article
Impact of Assimilating PECAN Profilers on the Prediction of Bore-Driven Nocturnal Convection: A Multiscale Forecast Evaluation for the 6 July 2015 Case Study
Using data from the 6 July 2015 PECAN case study, this paper provides the first objective assessment of how the assimilation of ground-based remote sensing profilers affects the forecasts of bore-driven convection. To account for the multiscale nature of the phenomenon, data impacts are examined separately with respect to (i) the bore environment, (ii) the explicitly resolved bore, and (iii) the bore-initiated convection. The findings from this work suggest that remote sensing profiling instruments provide considerable advantages over conventional in situ observations, especially when the retrieved data are assimilated at a high temporal frequency. The clearest forecast improvements are seen in terms of the predicted bore environment where the assimilation of kinematic profilers reduces a preexisting bias in the structure of the low-level jet. Data impacts with respect to the other two forecast components are mixed in nature. While the assimilation of thermodynamic retrievals from the Atmospheric Emitted Radiance Interferometer (AERI) results in the best convective forecast, it also creates a positive bias in the height of the convectively generated bore. Conversely, the assimilation of wind profiler data improves the characteristics of the explicitly resolved bore, but tends to further exacerbate the lack of convection in the control forecasts. Various dynamical diagnostics utilized throughout this study provide a physical insight into the data impact results and demonstrate that a successful prediction of bore-driven convection requires an accurate depiction of the internal bore structure as well as the ambient environment ahead of it.
Journal Article