Regenerative Pharmacology for COPD

Regenerative pharmacology for COPDXinhui Wu investigated novel therapeutic targets for chronic obstructive pulmonary disease (COPD). COPD is one of the most common lung diseases worldwide. It is characterized by airflow obstruction in the lung that causes breathing difficulties, cough, mucus (sputum) production and wheezing. The main causes of COPD are tobacco smoke and air pollution. They key problem in COPD is defective tissue repair, causing chronic bronchitis and emphysema, which are the two most common conditions resulting from airway and/or alveolar abnormalities. However, the current treatments for COPD can only reduce the symptoms and do not reverse or slow down the progression of the disease. Ms. Wu focused her research on the mechanisms underlying cigarette smoke and air pollution-induced dysfunctional lung repair and discovered several potential regenerative drug targets beneficial to lung repair in COPD.By using novel tools, such as 3D organoids and the precision-cut-lung slices (PCLS), to model different pathological conditions, Ms. Wu identified that cigarette smoke and air pollution both cause defective lung repair, but with different mechanisms. Molecular pathways such WNT-5A/B signaling, TGF- signaling, growth factors related signaling, cell death related signaling and circadian clock signaling all appear to play fundamental roles in the defective functions of alveolar epithelial progenitors. Several pharmacological strategies, such as ROCK inhibitors; antioxidants such as NAC and MitoQ; the analogues of PGE2 and PGI2 were discovered as potential regenerative therapeutic targets in lung repair for COPD

Analysis, design and implementation of high performance control schemes for three phase PWM AC-DC voltage source converter

Ph.DDOCTOR OF PHILOSOPH

High order entropy stable schemes for the quasi-one-dimensional shallow water and compressible Euler equations

High order schemes are known to be unstable in the presence of shock discontinuities or under-resolved solution features for nonlinear conservation laws. Entropy stable schemes address this instability by ensuring that physically relevant solutions satisfy a semi-discrete entropy inequality independently of discretization parameters. This work extends high order entropy stable schemes to the quasi-1D shallow water equations and the quasi-1D compressible Euler equations, which model one-dimensional flows through channels or nozzles with varying width. We introduce new non-symmetric entropy conservative finite volume fluxes for both sets of quasi-1D equations, as well as a generalization of the entropy conservation condition to non-symmetric fluxes. When combined with an entropy stable interface flux, the resulting schemes are high order accurate, conservative, and semi-discretely entropy stable. For the quasi-1D shallow water equations, the resulting schemes are also well-balanced

Pericytes:The lung-forgotten cell type

Pericytes are a heterogeneous population of mesenchymal cells located on the abluminal surface of microvessels, where they provide structural and biochemical support. Pericytes have been implicated in numerous lung diseases including pulmonary arterial hypertension (PAH) and allergic asthma due to their ability to differentiate into scar-forming myofibroblasts, leading to collagen deposition and matrix remodelling and thus driving tissue fibrosis. Pericyte-extracellular matrix interactions as well as other biochemical cues play crucial roles in these processes. In this review, we give an overview of lung pericytes, the key pro-fibrotic mediators they interact with, and detail recent advances in preclinical studies on how pericytes are disrupted and contribute to lung diseases including PAH, allergic asthma, and chronic obstructive pulmonary disease (COPD). Several recent studies using mouse models of PAH have demonstrated that pericytes contribute to these pathological events; efforts are currently underway to mitigate pericyte dysfunction in PAH by targeting the TGF-β, CXCR7, and CXCR4 signalling pathways. In allergic asthma, the dissociation of pericytes from the endothelium of blood vessels and their migration towards inflamed areas of the airway contribute to the characteristic airway remodelling observed in allergic asthma. Although several factors have been suggested to influence this migration such as TGF-β, IL-4, IL-13, and periostin, recent evidence points to the CXCL12/CXCR4 pathway as a potential therapeutic target. Pericytes might also play an essential role in lung dysfunction in response to ageing, as they are responsive to environmental risk factors such as cigarette smoke and air pollutants, which are the main drivers of COPD. However, there is currently no direct evidence delineating the contribution of pericytes to COPD pathology. Although there is a lack of human clinical data, the recent available evidence derived from in vitro and animal-based models shows that pericytes play important roles in the initiation and maintenance of chronic lung diseases and are amenable to pharmacological interventions. Therefore, further studies in this field are required to elucidate if targeting pericytes can treat lung diseases.</p