Highlights d In adipose tissue (AT), PDGFRb expression is not specific to mural cells d Mural and endothelial cells have no significant adipogenic potential d Fibroblasts have significant adipogenic potential in both white and brown AT d Fibroblasts significantly contribute to the beiging of white AT
Highlights
Negative pressure isolation space is an effective method to meet needed surge capacity during the COVID-19 pandemic and future pandemics
Planning for how and where to rapidly create a negative pressure isolation space is needed in congregate living areas such as skilled nursing facilities
This demonstration shows the feasibility of using low-cost and in-house systems to quickly create negative pressure within a skilled nursing facility hallway and to maintain these conditions, minimizing disease transmission between residents and staff
Stroke caused by an embolism accounts for about a third of all stroke cases. Understanding the source and cause of the embolism is critical for diagnosis and long-term treatment of such stroke cases. The complex nature of the transport of an embolus within large arteries is a primary hindrance to a clear understanding of embolic stroke etiology. Recent advances in medical image-based computational hemodynamics modeling have rendered increasing utility to such techniques as a probe into the complex flow and transport phenomena in large arteries. In this work, we present a novel, patient-specific, computational framework for understanding embolic stroke etiology, by combining image-based hemodynamics with discrete particle dynamics and a sampling-based analysis. The framework allows us to explore the important question of how embolism source manifests itself in embolus distribution across the various major cerebral arteries. Our investigations illustrate prominent numerical evidence regarding (i) the size/inertia-dependent trends in embolus distribution to the brain; (ii) the relative distribution of cardiogenic versus aortogenic emboli among the anterior, middle, and posterior cerebral arteries; (iii) the left versus right brain preference in cardio-emboli and aortic-emboli transport; and (iv) the source-destination relationship for embolisms affecting the brain.
We describe a patient-specific simulation based investigation on the role of Circle of Willis anatomy in cardioembolic stroke. Our simulation framework consists of medical image-driven modeling of patient anatomy including the Circle, 3D blood flow simulation through patient vasculature, embolus transport modeling using a discrete particle dynamics technique, and a sampling based approach to incorporate parametric variations. A total of 24 (four patients and six Circle anatomies including the complete Circle) models were considered, with cardiogenic emboli of varying sizes and compositions released virtually and tracked to compute distribution to the brain. The results establish that Circle anatomical variations significantly influence embolus distribution to the six major cerebral arteries. Embolus distribution to MCA territory is found to be least sensitive to the influence of anatomical variations. For varying Circle topologies, differences in flow through cervical vasculature are observed. This incoming flow is recruited differently across the communicating arteries of the Circle for varying anastomoses. Emboli interact with the routed flow, and can undergo significant traversal across the Circle arterial segments, depending upon their inertia and density ratio with respect to blood. This interaction drives the underlying biomechanics of embolus transport across the Circle, explaining how Circle anatomy influences embolism risk.
A hybrid, multiscale, particle-continuum numerical method is developed for resolving the interaction of a realistic thrombus geometry with unsteady hemodynamics typically occurring within large arteries. The method is based on a discrete particle/element description of the thrombus, coupled to blood flow using a fictitious domain finite element method. The efficacy of the discrete element approach in representing thrombi with arbitrary aggregate morphology and microstructure is demonstrated. The various features of the method are illustrated using a series of numerical experiments with a model system consisting of an occlusion embedded in a channel. The results from these numerical experiments establish that this approach can resolve the complex macroscale flow structures emanating from unsteady hemodynamics interacting with a thrombus. Simultaneously, it can also resolve micromechanical features, and microscale intra-thrombus flow and perfusion. Using a staggering algorithm, the method can further capture hemodynamics around time-varying thrombus manifolds. This is established using a numerical simulation of lysis of an idealized clot. The hybrid particle-continuum description of thrombus-hemodynamics interaction mechanics, and the unified treatment of macroscale as well as microscale flow and transport, renders significant advantages to the proposed method in enabling further investigations of physiological interest in thrombosis within patient-specific settings.
EP300 is a member of the EP300/CBP family of lysine acetyltransferases (KATs) with multiple roles in development and physiology. Loss of EP300/CBP activity in humans causes a very rare congenital disorder called Rubinstein Taybi Syndrome (RSTS). The zebrafish genome has two co-orthologs of lysine acetyltransferase EP300 (KAT3B) in zebrafish viz. ep300a and ep300b. Chemical inhibition of Ep300 with C646, a competitive inhibitor and morpholino-based genetic knockdown of ep300a and ep300b cause defects in embryonic development reminiscent of the human RSTS syndrome. Remarkably, overexpression of Ep300a KAT domain results in near complete rescue of the jaw development defects, a characteristic feature of RSTS in human suggesting the dispensability of the protein-interaction and DNA-binding domains for at least some developmental roles of Ep300. We also perform a chemical screen and identify two inhibitors of deacetylases, CHIC35 and HDACi III, that can partially rescue the RSTS-like phenotypes. Thus, modeling rare human genetic disorders in zebrafish allows for functional understanding of the genes involved and can also yield small molecule candidates towards therapeutic goals.
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