Turbulent Scalar Mixing in a Skewed Jet in Crossflow: Experiments and Modeling

Turbulent mixing of an inclined, skewed jet injected into a crossflow is investigated using MRI-based experiments and a high-fidelity LES of the same configuration. The MRI technique provides three-dimensional fields of mean velocity and mean jet concentration. The 30° skew of the jet relative to the crossflow produces a single dominant vortex which introduces spanwise asymmetries to the velocity and concentration fields. The turbulent scalar transport of the skewed jet is investigated in further detail using the LES, which is validated against the experimental measurements. Mixing is found to be highly anisotropic throughout the jet region. Isotropic turbulent diffusivity and viscosity are used to calculate an optimal value of the turbulent Schmidt number, which varies widely over the jet region and lies mostly outside of the typically accepted range 0.7 ≤ Sct ≤ 0.9. Finally, three common scalar flux models of increasing complexity are evaluated based on their ability to capture the anisotropy and predict the scalar concentration field of the present configuration. The higher order models are shown to better represent the turbulent scalar flux vector, leading to more accurate calculations of the concentration field. While more complex models are better able to capture the turbulent mixing, optimization of model constants is shown to significantly affect the results

High-efficiency endovascular gene delivery via therapeutic ultrasound

AbstractOBJECTIVESWe studied enhancement of local gene delivery to the arterial wall by using an endovascular catheter ultrasound (US).BACKGROUNDUltrasound exposure is standard for enhancement of in vitro gene delivery. We postulate that in vivo endovascular applications can be safely developed.METHODSWe used a rabbit model of arterial mechanical overdilation injury. After arterial overdilation, US catheters were introduced in bilateral rabbit femoral arteries and perfused with plasmid- or adenovirus-expressing blue fluorescent protein (BFP) or phosphate buffered saline. One side received endovascular US (2 MHz, 50 W/cm2, 16 min), and the contralateral artery did not.RESULTSRelative to controls, US exposure enhanced BFP expression measured via fluorescence 12-fold for plasmid (1,502.1 ± 927.3 vs. 18,053.9 ± 11,612 μm2, p < 0.05) and 19-fold for adenovirus (877.1 ± 577.7 vs. 17,213.15 ± 3,892 μm2, p < 0.05) while increasing cell death for the adenovirus group only (26 ± 5.78% vs. 13 ± 2.55%, p < 0.012).CONCLUSIONSEndovascular US enhanced vascular gene delivery and increased the efficiency of nonviral platforms to levels previously attained only by adenoviral strategies

Cryopreserved homograft valves in the pulmonary position: Risk analysis for intermediate-term failure

AbstractObjective: The purpose of this study was to examine the durability of cryopreserved homografts used to replace the “pulmonary” valve and to identify factors associated with their late deterioration. Methods: We reviewed our entire experience (1985-1997) with 331 survivors in whom cryopreserved homograft valves (pulmonary, n = 304; aortic, n = 27) were used to reconstruct the pulmonary outflow tract. Median age was 14 years (range, 2 days–62 years). Operations included Ross operation (n = 259), tetralogy of Fallot (n = 41), truncus arteriosus (n = 14), Rastelli operation (n = 11), and others (n = 6). Median follow-up was 3.8 years (range, 0.2–11.2 years); late echographic follow-up was complete for 97% of patients. Homograft failure was defined as the need for explantation and valve-related death; homograft dysfunction was defined as a pulmonary insufficiency grade 3/4 or greater and a transvalvular gradient of 40 mm Hg or greater. Results: Homograft failure occurred in 9% (30 of 331 patients; Kaplan-Meier); freedom from failure was 82% ± 4% at 8 years. Homograft dysfunction occurred in 12% (39 of 331 patients), although freedom from dysfunction was 76% ± 4% at 8 years. For aortic homografts, this was 56% ± 11%, compared to 80% ± 4% for pulmonary homografts (P = .003). For patients aged less than 3 years (n = 38), this was 51% ± 12%, compared with 87% ± 4% for older patients (P = .0001). By multivariable analysis, younger age of homograft donors, non-Ross operation, and later year of operation were associated with homograft failure; younger age of homograft donors, later year of operation, and use of an aortic homograft were associated with homograft dysfunction. Conclusions: Homograft valves function satisfactorily in the pulmonary position at mid-term follow-up. The pulmonary homograft valve appears to be more durable than the aortic homograft valve in the pulmonary position. (J Thorac Cardiovasc Surg 1999;117:141-7

Validation of Immersed Boundary Simulations of Heart Valve Hemodynamics against In Vitro 4D Flow MRI Data

The immersed boundary (IB) method is a mathematical framework for fluid-structure interaction problems (FSI) that was originally developed to simulate flows around heart valves. Validation of FSI simulations around heart valves against experimental data is challenging, however, due to the difficulty of performing robust and effective simulations, the complications of modeling a specific physical experiment, and the need to acquire experimental data that is directly comparable to simulation data. In this work, we performed physical experiments of flow through a pulmonary valve in an in vitro pulse duplicator, and measured the corresponding velocity field using 4D flow MRI (4-dimensional flow magnetic resonance imaging). We constructed a computer model of this pulmonary artery setup, including modeling valve geometry and material properties via a technique called design-based elasticity, and simulated flow through it with the IB method. The simulated flow fields showed excellent qualitative agreement with experiments, excellent agreement on integral metrics, and reasonable relative error in the entire flow domain and on slices of interest. These results validate our design-based valve model construction, the IB solvers used and the immersed boundary method for flows around heart valves

Hemorrhagic stroke outcomes of KApSR patients with co-morbid diabetes and Alzheimer’s disease

Background: Vascular risk factors, such as diabetes mellitus (DM), are associated with poorer outcomes following many neurodegenerative diseases, including hemorrhagic stroke and Alzheimer’s disease (AD). Combined AD and DM co-morbidities are associated with an increased risk of hemorrhagic stroke and increased Medicare costs. Therefore, we hypothesized that patients with DM in combination with AD, termed DM/AD, would have increased hemorrhagic stroke severity. Methods: Kentucky Appalachian Stroke Registry (KApSR) is a database of demographic and clinical data from patients that live in Appalachia, a distinct region with increased health disparities and stroke severity. Inpatients with a primary indication of hemorrhagic stroke were selected from KApSR for retrospective analysis and were separated into four groups: DM only, AD only, neither, or both. Results: Hemorrhagic stroke patients (2,071 total) presented with either intracerebral hemorrhage (ICH), n=1,448, or subarachnoid hemorrhage (SAH), n=623. When examining all four groups, subjects with AD were significantly older (AD+, 80.9±6.6 yrs) (DM+/AD+, 77.4±10.0 yrs) than non AD subjects (DM-/AD-, 61.3±16.5 yrs) and (DM+, 66.0±12.5 yrs). A higher percentage of females were among the AD+ group and a higher percentage of males among the DM+/AD+ group. Interestingly, after adjusting for multiple comparison, DM+/AD+ subjects were ten times as likely to suffer a moderate to severe stroke based on a National Institute of Health Stroke (NIHSS) upon admission [odds ratio (95% CI)] compared to DM-/AD- [0.1 (0.02–0.55)], DM+ [0.11 (0.02–0.59)], and AD+ [0.09(0.01–0.63)]. The odds of DM+/AD+ subjects having an unfavorable discharge destination (death, hospice, long-term care) was significant (P Conclusions: In our retrospective analysis utilizing KApSR, regardless of adjusting for age, sex, and comorbidities, DM+/AD+ patients were significantly more likely to have had a moderate or severe stroke leading to an unfavorable outcome following hemorrhagic stroke

An integrated approach to supply chain risk analysis

Despite the increasing attention that supply chain risk management is receiving by both researchers and practitioners, companies still lack a risk culture. Moreover, risk management approaches are either too general or require pieces of information not regularly recorded by organisations. This work develops a risk identification and analysis methodology that integrates widely adopted supply chain and risk management tools. In particular, process analysis is performed by means of the standard framework provided by the Supply Chain Operations Reference Model, the risk identification and analysis tasks are accomplished by applying the Risk Breakdown Structure and the Risk Breakdown Matrix, and the effects of risk occurrence on activities are assessed by indicators that are already measured by companies in order to monitor their performances. In such a way, the framework contributes to increase companies' awareness and communication about risk, which are essential components of the management of modern supply chains. A base case has been developed by applying the proposed approach to a hypothetical manufacturing supply chain. An in-depth validation will be carried out to improve the methodology and further demonstrate its benefits and limitations. Future research will extend the framework to include the understanding of the multiple effects of risky events on different processe

Ribosomal oxygenases are structurally conserved from prokaryotes to humans

2-Oxoglutarate (2OG)-dependent oxygenases have important roles in the regulation of gene expression via demethylation of N-methylated chromatin components1,2 and in the hydroxylation of transcription factors3 and splicing factor proteins4. Recently, 2OG-dependent oxygenases that catalyse hydroxylation of transfer RNA5,6,7 and ribosomal proteins8 have been shown to be important in translation relating to cellular growth, TH17-cell differentiation and translational accuracy9,10,11,12. The finding that ribosomal oxygenases (ROXs) occur in organisms ranging from prokaryotes to humans8 raises questions as to their structural and evolutionary relationships. In Escherichia coli, YcfD catalyses arginine hydroxylation in the ribosomal protein L16; in humans, MYC-induced nuclear antigen (MINA53; also known as MINA) and nucleolar protein 66 (NO66) catalyse histidine hydroxylation in the ribosomal proteins RPL27A and RPL8, respectively. The functional assignments of ROXs open therapeutic possibilities via either ROX inhibition or targeting of differentially modified ribosomes. Despite differences in the residue and protein selectivities of prokaryotic and eukaryotic ROXs, comparison of the crystal structures of E. coli YcfD and Rhodothermus marinus YcfD with those of human MINA53 and NO66 reveals highly conserved folds and novel dimerization modes defining a new structural subfamily of 2OG-dependent oxygenases. ROX structures with and without their substrates support their functional assignments as hydroxylases but not demethylases, and reveal how the subfamily has evolved to catalyse the hydroxylation of different residue side chains of ribosomal proteins. Comparison of ROX crystal structures with those of other JmjC-domain-containing hydroxylases, including the hypoxia-inducible factor asparaginyl hydroxylase FIH and histone Nε-methyl lysine demethylases, identifies branch points in 2OG-dependent oxygenase evolution and distinguishes between JmjC-containing hydroxylases and demethylases catalysing modifications of translational and transcriptional machinery. The structures reveal that new protein hydroxylation activities can evolve by changing the coordination position from which the iron-bound substrate-oxidizing species reacts. This coordination flexibility has probably contributed to the evolution of the wide range of reactions catalysed by oxygenases

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes