An analytic Green's function for a lined circular duct containing uniform mean flow

An analytic Green’s function is derived for a lined circular duct, both hollow and annular, containing uniform mean flow, from first principles by Fourier transformation. The derived result takes the form of a common mode series. All modes are assumed to decay in their respective direction of propagation. A more comprehensive causality analysis suggests the possibility of upstream modes being really downstream instabilities. As their growth rates are usually exceptionally large, this possibility is not considered in the present study. We show that the analytic Green’s function for a lined hollow circular duct, containing uniform mean flow, is essentially identical to that used by Tester e.a. in the Cargill splice scattering model. The Green’s function for the annular duct is new. Comparisons between the numerically obtained modal amplitudes of Alonso e.a. and the present analytic results for a lined, hollow circular duct show good agreement without flow, irrespective of how many modes are included in the matrix inversion for the numerical mode amplitudes. With flow, the mode amplitudes do not agree but as the number of modes included in the matrix inversion is increased the numerically obtained modal amplitudes of Alonso e.a. appear to be converging to the present analytical result. In practical applications our closed form analytic Green’s function will be computationally more efficient, especially at high frequencies of practical interest to aero-engine applications, and the analytic form for the mode amplitudes could permit future modelling advances not possible from the numerical equivalent

An analytic Green's function for a lined circular duct containing uniform mean flow

An analytic Green’s function is derived for a lined circular duct, both hollow and annular, containing uniform mean flow, from first principles by Fourier transformation. The derived result takes the form of a common mode series. All modes are assumed to decay in their respective direction of propagation. A more comprehensive causality analysis suggests the possibility of upstream modes being really downstream instabilities. As their growth rates are usually exceptionally large, this possibility is not considered in the present study. We show that the analytic Green’s function for a lined hollow circular duct, containing uniform mean flow, is essentially identical to that used by Tester e.a. in the Cargill splice scattering model. The Green’s function for the annular duct is new. Comparisons between the numerically obtained modal amplitudes of Alonso e.a. and the present analytic results for a lined, hollow circular duct show good agreement without flow, irrespective of how many modes are included in the matrix inversion for the numerical mode amplitudes. With flow, the mode amplitudes do not agree but as the number of modes included in the matrix inversion is increased the numerically obtained modal amplitudes of Alonso e.a. appear to be converging to the present analytical result. In practical applications our closed form analytic Green’s function will be computationally more efficient, especially at high frequencies of practical interest to aero-engine applications, and the analytic form for the mode amplitudes could permit future modelling advances not possible from the numerical equivalent

Characterization of <em>SEMA3A</em>-encoded semaphorin as a naturally occurring Kv4.3 protein inhibitor and its contribution to Brugada syndrome.

RATIONALE: Semaphorin 3A (SEMA3A)-encoded semaphorin is a chemorepellent that disrupts neural patterning in the nervous and cardiac systems. In addition, SEMA3A has an amino acid motif that is analogous to hanatoxin, an inhibitor of voltage-gated K channels. SEMA3A-knockout mice exhibit an abnormal ECG pattern and are prone to ventricular arrhythmias and sudden cardiac death. OBJECTIVE:: Our aim was to determine whether SEMA3A is a naturally occurring protein inhibitor of Kv4.3 (Ito) channels and its potential contribution to Brugada syndrome. METHODS AND RESULTS:: Kv4.3, Nav1.5, Cav1.2, or Kv4.2 were coexpressed or perfused with SEMA3A in HEK293 cells, and electrophysiological properties were examined via whole-cell patch clamp technique. SEMA3A selectively altered Kv4.3 by significantly reducing peak current density without perturbing Kv4.3 cell surface protein expression. SEMA3A also reduced Ito current density in cardiomyocytes derived from human-induced pluripotent stem cells. Disruption of a putative toxin binding domain on Kv4.3 was used to assess physical interactions between SEMA3A and Kv4.3. These findings in combination with coimmunoprecipitations of SEMA3A and Kv4.3 revealed a potential direct binding interaction between these proteins. Comprehensive mutational analysis of SEMA3A was performed on 198 unrelated SCN5A genotype-negative patients with Brugada syndrome, and 2 rare SEMA3A missense mutations were identified. The SEMA3A mutations disrupted SEMA3A&#39;s ability to inhibit Kv4.3 channels, resulting in a significant gain of Kv4.3 current compared with wild-type SEMA3A. CONCLUSIONS:: This study is the first to demonstrate SEMA3A as a naturally occurring protein that selectively inhibits Kv4.3 and SEMA3A as a possible Brugada syndrome susceptibility gene through a Kv4.3 gain-of-function mechanism

Loss-of-function of the voltage-gated sodium channel NaV1.5 (Channelopathies) in patients with irritable bowel syndrome

Background &amp;amp; Aims SCN5A encodes the α-subunit of the voltage-gated sodium channel NaV1.5. Many patients with cardiac arrhythmias caused by mutations in SCN5A also have symptoms of irritable bowel syndrome (IBS). We investigated whether patients with IBS have SCN5A variants that affect the function of NaV1.5. Methods We performed genotype analysis of SCN5A in 584 persons with IBS and 1380 without IBS (controls). Mutant forms of SCN5A were expressed in human embryonic kidney-293 cells, and functions were assessed by voltage clamp analysis. A genome-wide association study was analyzed for an association signal for the SCN5A gene, and replicated in 1745 patients in 4 independent cohorts of IBS patients and controls. Results Missense mutations were found in SCN5A in 13 of 584 patients (2.2%, probands). Diarrhea-predominant IBS was the most prevalent form of IBS in the overall study population (25%). However, a greater percentage of individuals with SCN5A mutations had constipation-predominant IBS (31%) than diarrhea-predominant IBS (10%; P &amp;lt;.05). Electrophysiologic analysis showed that 10 of 13 detected mutations disrupted NaV1.5 function (9 loss-of-function and 1 gain-of-function function). The p. A997T-NaV1.5 had the greatest effect in reducing NaV1.5 function. Incubation of cells that expressed this variant with mexiletine restored their sodium current and administration of mexiletine to 1 carrier of this mutation (who had constipation-predominant IBS) normalized their bowel habits. In the genome-wide association study and 4 replicated studies, the SCN5A locus was strongly associated with IBS. Conclusions About 2% of patients with IBS carry mutations in SCN5A. Most of these are loss-of-function mutations that disrupt Na V1.5 channel function. These findings provide a new pathogenic mechanism for IBS and possible treatment options. © 2014 by the AGA Institute