118 research outputs found

    Novel Approach to Repairing a Traumatic Aortic Arch Pseudoaneurysm Following a Fall.

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    Traumatic pseudoaneurysms of the aortic arch are often treated with surgical repair regardless of the lesion size or age. The authors report a simple, less invasive surgical repair in a patient who sustained blunt aortic injury following a fall

    Optimal B-spline Mapping of Flow Imaging Data for Imposing Patient-specific Velocity Profiles in Computational Hemodynamics.

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    OBJECTIVE: We propose a novel method to map patient-specific blood velocity profiles obtained from imaging data such as 2D flow MRI or 3D colour Doppler ultrasound) to geometric vascular models suitable to perform CFD simulations of haemodynamics. We describe the implementation and utilisation of the method within an open-source computational hemodynamics simulation software (CRIMSON). METHODS: The proposed method establishes point-wise correspondences between the contour of a fixed geometric model and time-varying contours containing the velocity image data, from which a continuous, smooth and cyclic deformation field is calculated. Our methodology is validated using synthetic data, and demonstrated using two different in-vivo aortic velocity datasets: a healthy subject with normal tricuspid valve and a patient with bicuspid aortic valve. RESULTS: We compare our method with the state-of-the-art Schwarz-Christoffel method, in terms of preservation of velocities and execution time. Our method is as accurate as the Schwarz-Christoffel method, while being over 8 times faster. CONCLUSIONS: Our mapping method can accurately preserve either the flow rate or the velocity field through the surface, and can cope with inconsistencies in motion and contour shape. SIGNIFICANCE: The proposed method and its integration into the CRIMSON software enable a streamlined approach towards incorporating more patient-specific data in blood flow simulations

    Two-Tone Optomechanical Instability and Its Fundamental Implications for Backaction-Evading Measurements

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    While quantum mechanics imposes a fundamental limit on the precision of interferometric measurements of mechanical motion due to measurement backaction, the nonlinear nature of the coupling also leads to parametric instabilities that place practical limits on the sensitivity by limiting the power in the interferometer. Such instabilities have been extensively studied in the context of gravitational wave detectors, and their presence has recently been reported in Advanced LIGO. Here, we observe experimentally and describe theoretically a new type of optomechanical instability that arises in two-tone backaction-evading (BAE) measurements, designed to overcome the standard quantum limit, and demonstrate the effect in the optical domain with a photonic crystal nanobeam, and in the microwave domain with a micromechanical oscillator coupled to a microwave resonator. In contrast to the well-known oscillatory parametric instability that occurs in single-tone, blue-detuned pumping, which is characterized by a vanishing effective mechanical damping, the parametric instability in balanced two-tone optomechanics is exponential, and is a result of small detuning errors in the two pump frequencies. Its origin can be understood in a rotating frame as the vanishing of the effective mechanical frequency due to an optical spring effect. Counterintuitively, the instability occurs even in the presence of perfectly balanced intracavity fields, and can occur for both signs of detuning. We find excellent quantitative agreement with our theoretical predictions. Since the constraints on tuning accuracy become stricter with increasing probe power, it imposes a fundamental limitation on BAE measurements, as well as other two-tone schemes. In addition to introducing a new limitation in two-tone BAE measurements, the results also introduce a new type of nonlinear dynamics in cavity optomechanics

    Fate of the Aortic Arch Following Surgery on Aortic Root and Ascending Aorta in Bicuspid Aortic Valve.

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    BACKGROUND: Recent guidelines support more aggressive surgery for aneurysms of the ascending aorta and root in patients with bicuspid aortic valve. However, the fate of the arch after surgery of the root and ascending aorta is unknown. We set out to assess outcomes following root and ascending aortic surgery and subsequent growth of the arch. METHODS: Between 2005 and 2016, 536 consecutive patients underwent surgery for aneurysm of the root and ascending aorta. 168 had bicuspid aortic valve. Patients with dissection were excluded. Arch diameter was measured before and after surgery, at six months and then annually. RESULTS: Of 168 patients, 127 (75.6%) had aortic root replacement and 41 (24.4%) had ascending replacement. Mean age was 57Β±12.8 years, 82.7% were males and five operations were performed during pregnancy. There was one (0.6%) hospital death. One (0.6%) patient had a stroke and one (0.6%) had re-sternotomy for bleeding. Median ICU and hospital stays were 1 and 6 days respectively. Follow-up was complete for 94% at a median of 5.9 years (1-139 months). Aortic arch diameter was 2.9 cm preoperatively and 3.0 cm at follow-up. There was 97% freedom from reoperation and none of the patients required surgery on the arch. CONCLUSIONS: Prophylactic arch replacement during aortic root and ascending aortic surgery in patients with bicuspid aortic valve is not supported. Our data does not support long term surveillance of the rest of the aorta in this population

    Inhibitors of Bcl-2 protein family deplete ER Ca2+ stores in pancreatic acinar cells

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    Physiological stimulation of pancreatic acinar cells by cholecystokinin and acetylcholine activate a spatial-temporal pattern of cytosolic [Ca+2] changes that are regulated by a coordinated response of inositol 1,4,5-trisphosphate receptors (IP3Rs), ryanodine receptors (RyRs) and calcium-induced calcium release (CICR). For the present study, we designed experiments to determine the potential role of Bcl-2 proteins in these patterns of cytosolic [Ca+2] responses. We used small molecule inhibitors that disrupt the interactions between prosurvival Bcl-2 proteins (i.e. Bcl-2 and Bcl-xl) and proapoptotic Bcl-2 proteins (i.e. Bax) and fluorescence microfluorimetry techniques to measure both cytosolic [Ca+2] and endoplasmic reticulum [Ca+2]. We found that the inhibitors of Bcl-2 protein interactions caused a slow and complete release of intracellular agonist-sensitive stores of calcium. The release was attenuated by inhibitors of IP3Rs and RyRs and substantially reduced by strong [Ca2+] buffering. Inhibition of IP3Rs and RyRs also dramatically reduced activation of apoptosis by BH3I-2β€². CICR induced by different doses of BH3I-2β€² in Bcl-2 overexpressing cells was markedly decreased compared with control. The results suggest that Bcl-2 proteins regulate calcium release from the intracellular stores and suggest that the spatial-temporal patterns of agonist-stimulated cytosolic [Ca+2] changes are regulated by differential cellular distribution of interacting pairs of prosurvival and proapoptotic Bcl-2 proteins

    Calcineurin Interacts with PERK and Dephosphorylates Calnexin to Relieve ER Stress in Mammals and Frogs

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    Background: The accumulation of misfolded proteins within the endoplasmic reticulum (ER) triggers a cellular process known as the Unfolded Protein Response (UPR). One of the earliest responses is the attenuation of protein translation. Little is known about the role that Ca 2+ mobilization plays in the early UPR. Work from our group has shown that cytosolic phosphorylation of calnexin (CLNX) controls Ca 2+ uptake into the ER via the sarco-endoplasmic reticulum Ca 2+-ATPase (SERCA) 2b. Methodology/Principal Findings: Here, we demonstrate that calcineurin (CN), a Ca 2+ dependent phosphatase, associates with the (PKR)-like ER kinase (PERK), and promotes PERK auto-phosphorylation. This association, in turn, increases the phosphorylation level of eukaryotic initiation factor-2 a (eIF2-a) and attenuates protein translation. Data supporting these conclusions were obtained from co-immunoprecipitations, pull-down assays, in-vitro kinase assays, siRNA treatments and [ 35 S]-methionine incorporation measurements. The interaction of CN with PERK was facilitated at elevated cytosolic Ca 2+ concentrations and involved the cytosolic domain of PERK. CN levels were rapidly increased by ER stressors, which could be blocked by siRNA treatments for CN-Aa in cultured astrocytes. Downregulation of CN blocked subsequent ER-stress-induced increases in phosphorylated elF2-a. CN knockdown in Xenopus oocytes predisposed them to induction of apoptosis. We also found that CLNX was dephosphorylated by CN when Ca 2+ increased. These data were obtained from [c 32 P]-CLN
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