Numerical simulation of transpiration cooling on stagnation line in thermochemical non-equilibrium

Sharp leading edges offer drag and maneuverability advantages for hypersonic applications such as powered flight and some gliding trajectories. The reduction in standoff distance resulting from the adoption of sharp edges, however, results in increased surface convective heating that needs to be managed. Ablative layers are unfeasible as a cooling strategy for sharp edges because they lead to a change in surface curvature radius and render systems non-reusable. Among possible strategies, transpiration cooling has been presented as an attractive option in terms of cooling effectiveness and system complexity. In this study, a method is presented for the numerical simulation of transpiration cooling in proximity of the stagnation point of sharp leading edges or tips. The method is suited to both equilibrium and non-equilibrium flight regimes and is based on stagnation line theory presented by Cheng. Transport properties are determined through rigorous Chapman-Enskog theory. Non-equilibrium cases are handled with Park’s two temperature model. The solver explicitly represents coolant flow through a porous medium. Detailed temperature profiles and mole fractions in the shock layer and within the porous medium can be evaluated, with variations in in these profiles computed as functions of flight altitude, speed, leading edge radius, and coolant flow rate and composition. Argon, helium, and nitrogen are tested for their efficacy. The ability of different coolant mixtures to limit the transport of catalytic species to the surface is studied

Association of MRI Volume Parameters in Predicting Patient Outcome at Time of Initial Diagnosis of Glioblastoma

Purpose: Patients with glioblastoma (GBM) may demonstrate varying patterns of infiltration and relapse. Improving the ability to predict these patterns may influence the management strategies at the time of initial diagnosis. This study aims to examine the impact of the ratio (T2/T1) of the non-enhancing volume in T2-weighted images (T2) to the enhancing volume in MRI T1-weighted gadolinium-enhanced images (T1gad) on patient outcome. Methods and Materials: A retrospective audit was performed from established prospective databases in patients managed consecutively with radiation therapy (RT) for GBM between 2016 and 2019. Patient, tumour and treatment-related factors were assessed in relation to outcome. Volumetric data from the initial diagnostic MRI were obtained via the manual segmentation of the T1gd and T2 abnormalities. A T2/T1 ratio was calculated from these volumes. The initial relapse site was assessed on MRI in relation to the site of the original T1gad volume and surgical cavity. The major endpoints were median relapse-free survival (RFS) from the date of diagnosis and site of initial relapse (defined as either local at the initial surgical site or any distance more than 20 mm from initial T1gad abnormality). The analysis was performed for association between known prognostic factors as well as the radiological factors using log-rank tests for subgroup comparisons, with correction for multiple comparisons. Results: One hundred and seventy-seven patients with GBM were managed consecutively with RT between 2016 and 2019 and were eligible for the analysis. The median age was 62 years. Seventy-four percent were managed under a 60Gy (Stupp) protocol, whilst 26% were on a 40Gy (Elderly) protocol. Major neuroanatomical subsites were Lateral Temporal (18%), Anterior Temporal (13%) and Medial Frontal (10%). Median volumes on T1gd and T2 were 20 cm3 (q1–3:8–43) and 37 cm3 (q1–3: 17–70), respectively. The median T2/T1 ratio was 2.1. For the whole cohort, the median OS was 16.0 months (95%CI:14.1–18.0). One hundred and forty-eight patients have relapsed with a median RFS of 11.4 months (95%CI:10.4–12.5). A component of distant relapse was evident in 43.9% of relapses, with 23.6% isolated relapse. Better ECOG performance Status (p = 0.007), greater extent of resection (p = 0.020), MGMT methylation (p p = 0.050) were associated with improved RFS. Although the continuous variable of initial T1gd volume (p = 0.39) and T2 volume (p = 0.23) were not associated with RFS, the lowest T2/T1 quartile (reflecting a relatively lower T2 volume compared to T1gd volume) was significantly associated with improved RFS (p = 0.016) compared with the highest quartile. The lowest T2/T1 ratio quartile was also associated with a lower risk of distant relapse (p = 0.031). Conclusion: In patients diagnosed with GBM, the volumetric parameters of the diagnostic MRI with a ratio of T2 and T1gad abnormality may assist in the prediction of relapse-free survival and patterns of relapse. A further understanding of these relationships has the potential to impact the design of future radiation therapy target volume delineation protocols

Facile Aerobic Alkylation of Rhodium Porphyrins with Alkyl Halides

Alkylation of rhodium porphyrins was achieved in moderate to high yields in the presence of air and water. With this facile alkylation method, various alkyl Rh^III(por) species, including those with tertiary alkyl, were synthesized. Mechanistic investigations suggest a parallel S_N2 via [Rh^I(ttp)]⁻ with halogen atom transfer pathway via [Rh^II(ttp)]^•

Molecular Mechanisms and New Treatment Paradigm for Atrial Fibrillation

BACKGROUND: Atrial fibrillation (AF) represents the most common arrhythmia leading to increased morbidity and mortality, yet, current treatment strategies have proven inadequate. Conventional treatment with antiarrhythmic drugs carries a high risk for proarrhythmias. The soluble epoxide hydrolase enzyme (sEH) catalyzes the hydrolysis of anti-inflammatory epoxy fatty acids including epoxyeicosatrienoic acids (EETs) from arachidonic acid to the corresponding pro-inflammatory diols. Therefore, the goal of the study is to directly test the hypotheses that inhibition of the sEH enzyme can result in an increase in the levels of EETs leading to the attenuation of atrial structural and electrical remodeling and the prevention of AF. METHODS AND RESULTS: For the first time, we report findings that inhibition of sEH reduces inflammation, oxidative stress, atrial structural and electrical remodeling. Treatment with sEH inhibitor significantly reduces the activation of key inflammatory signaling molecules, including the transcription factor nuclear factor κ-light-chain-enhancer (NF-κB), mitogen-activated protein kinase (MAPK) and transforming growth factor-β (TGF-β). CONCLUSIONS: This study provides insights into the underlying molecular mechanisms leading to AF by inflammation and represents a paradigm shift from conventional antiarrhythmic drugs which block downstream events to a novel upstream therapeutic target by counteracting the inflammatory processes in AF

Molecular Mechanisms and New Treatment Paradigm for Atrial Fibrillation.

Atrial fibrillation represents the most common arrhythmia leading to increased morbidity and mortality, yet, current treatment strategies have proven inadequate. Conventional treatment with antiarrhythmic drugs carries a high risk for proarrhythmias. The soluble epoxide hydrolase enzyme catalyzes the hydrolysis of anti-inflammatory epoxy fatty acids, including epoxyeicosatrienoic acids from arachidonic acid to the corresponding proinflammatory diols. Therefore, the goal of the study is to directly test the hypotheses that inhibition of the soluble epoxide hydrolase enzyme can result in an increase in the levels of epoxyeicosatrienoic acids, leading to the attenuation of atrial structural and electric remodeling and the prevention of atrial fibrillation. For the first time, we report findings that inhibition of soluble epoxide hydrolase reduces inflammation, oxidative stress, atrial structural, and electric remodeling. Treatment with soluble epoxide hydrolase inhibitor significantly reduces the activation of key inflammatory signaling molecules, including the transcription factor nuclear factor κ-light-chain-enhancer, mitogen-activated protein kinase, and transforming growth factor-β. This study provides insights into the underlying molecular mechanisms leading to atrial fibrillation by inflammation and represents a paradigm shift from conventional antiarrhythmic drugs, which block downstream events to a novel upstream therapeutic target by counteracting the inflammatory processes in atrial fibrillation