Moment-Fourier approach to ion parallel fluid closures and transport for a toroidally confined plasma

A general method of solving the drift kinetic equation is developed for an axisymmetric magnetic field. Expanding a distribution function in general moments a set of ordinary differential equations are obtained. Successively expanding the moments and magnetic-field involved quantities in Fourier series, a set of linear algebraic equations is obtained. The set of full (Maxwellian and non-Maxwellian) moment equations is solved to express the density, temperature, and flow velocity perturbations in terms of radial gradients of equilibrium pressure and temperature. Closure relations that connect parallel heat flux density and viscosity to the radial gradients and parallel gradients of temperature and flow velocity, are also obtained by solving the non-Maxwellian moment equations. The closure relations combined with the linearized fluid equations reproduce the same solution obtained directly from the full moment equations. The method can be generalized to derive closures and transport for an electron-ion plasma and a multi-ion plasma in a general magnetic field.Comment: 25 pages, 9 figure

Electron Parallel Closures for Various Ion Charge Numbers

Electron parallel closures for the ion charge number Z = 1 [J.-Y. Ji and E. D. Held, Phys. Plasmas 21, 122116 (2014)] are extended for 1 ≤ Z ≤ 10. Parameters are computed for various Z with the same form of the Z = 1 kernels adopted. The parameters are smoothly varying in Z and hence can be used to interpolate parameters and closures for noninteger, effective ion charge numbers

Electron Parallel Transport for Arbitrary Collisionality

Integral (nonlocal) closures [J.-Y. Ji and E. D. Held, Phys. Plasmas 21, 122116 (2014)] are combined with the momentum balance equation to derive electron parallel transport relations. For a single harmonic fluctuation, the relations take the same form as the classical Spitzer theory (with possible additional terms): the electric current and heat flux densities are connected to the modified electric field and temperature gradient by transport coefficients. In contrast to the classical theory, the dimensionless coefficients depend on the collisionality quantified by a Knudsen number, the ratio of the collision length to the angular wavelength. The key difference comes from the proper treatment of the viscosity and friction terms in the momentum balance equation, accurately reflecting the free streaming and collision terms in the kinetic equation. For an arbitrary fluctuation, the transport relations may be expressed by a Fourier series or transform. For low collisionality, the electric resistivity can be significantly larger than that of classical theory and may predict the correct timescale for fast magnetic reconnection

Epilepsy in Leigh Syndrome With Mitochondrial DNA Mutations

Background: Leigh syndrome is a mitochondrial cytopathy that presents as a neurodegenerative disease with apparent manifestation in the central nervous system. The aim of the present study was to describe its dominant neurological clinical features and analyze data related to epilepsy in Leigh syndrome accompanied by a mitochondrial DNA mutation.Methods: Whole mitochondrial sequencing was performed on 125 patients clinically suspected of Leigh syndrome. Among them, 25 patients were identified to have mitochondrial DNA associated Leigh syndrome. Electroencephalography (EEG) findings, semiology, brain imaging findings, and biochemical results, were evaluated. We also compared brain magnetic resonance imaging findings and biochemical features in patients with Leigh syndrome based on the presence of epilepsy.Results: Clinical seizures were observed in 14 out of 25 enrolled patients (56%), with focal seizures being the most common type (6/14, 42.8%). All patients were found to have slow and disorganized background neural activity while eight exhibited epileptic discharges on EEG. Mutations at base pairs 10,191 and 8,993 were revealed in a relatively larger number of patients of Leigh syndrome with epilepsy. The presence of gastrointestinal symptoms was significantly more frequent in the epilepsy group (P = 0.042). Diffuse cerebral atrophy was significantly increased (P = 0.042) and cortex signal abnormalities were also increased (P = 0.033) in the epilepsy group.Conclusions: Patients with Leigh syndrome and mitochondrial DNA mutations had a high proportion of central nervous system comorbidities, though the prevalence of epilepsy in this population was not particularly high. Various types of seizure and EEG findings are common in those with Leigh syndrome. Future imaging studies involving more patients and proper mitochondrial DNA mutation analyses are needed to further evaluate the natural course of Leigh syndrome with epilepsy

Genotype-phenotype correlations in pediatric patients with myotonic dystrophy type 1

Purpose Myotonic dystrophy, also known as dystrophia myotonica (DM), is an autosomal dominant disorder with 2 genetically distinct forms. DM type 1 (DM1) is the more common form and is caused by abnormal expansion of cytosine/thymine/guanine (CTG) repeats in the DM protein kinase (DMPK) gene. Our study aimed to determine whether the age of onset is correlated with CTG repeat length in a population of pediatric patients with DM1. Methods We retrospectively identified 30 pediatric patients with DM1 that underwent DMPK testing, of which the clinical data of 17 was sufficient. The cohort was divided into 2 subgroups based on the clinical phenotype (congenital-onset vs. late-onset) and number of CTG repeats (<1,000 vs. ≥1,000). Results We found no significant difference between the age of onset and CTG repeat length in our pediatric patient population. Based on clinical subgrouping, we found that the congenital-onset subgroup was statistically different with respect to several variables, including prematurity, rate of admission to neonatal intensive care unit, need for respiratory support at birth, hypotonia, dysphagia, ventilator dependence, and functional status on last visit, compared to the late-onset subgroup. Based on genetic subgrouping, we found a single variable (poor feeding in neonate) that was significantly different in the large CTG subgroup than that in the small CTG subgroup. Conclusion Clinical variables exhibiting statistically significant differences between the subgroups should be focused on prognosis and designing tailored management approaches for the patients; our findings will contribute to achieve this important goal for treating patients with DM1

Interpretation of personal genome sequencing data in terms of disease ranks based on mutual information

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Abstract Background The rapid advances in genome sequencing technologies have resulted in an unprecedented number of genome variations being discovered in humans. However, there has been very limited coverage of interpretation of the personal genome sequencing data in terms of diseases. Methods In this paper we present the first computational analysis scheme for interpreting personal genome data by simultaneously considering the functional impact of damaging variants and curated disease-gene association data. This method is based on mutual information as a measure of the relative closeness between the personal genome and diseases. We hypothesize that a higher mutual information score implies that the personal genome is more susceptible to a particular disease than other diseases. Results The method was applied to the sequencing data of 50 acute myeloid leukemia (AML) patients in The Cancer Genome Atlas. The utility of associations between a disease and the personal genome was explored using data of healthy (control) people obtained from the 1000 Genomes Project. The ranks of the disease terms in the AML patient group were compared with those in the healthy control group using "Leukemia, Myeloid, Acute" (C04.557.337.539.550) as the corresponding MeSH disease term. The mutual information rank of the disease term was substantially higher in the AML patient group than in the healthy control group, which demonstrates that the proposed methodology can be successfully applied to infer associations between the personal genome and diseases. Conclusions Overall, the area under the receiver operating characteristics curve was significantly larger for the AML patient data than for the healthy controls. This methodology could contribute to consequential discoveries and explanations for mining personal genome sequencing data in terms of diseases, and have versatility with respect to genomic-based knowledge such as drug-gene and environmental-factor-gene interactions

Curcumin induces expression of 15-hydroxyprostaglandin dehydrogenase in gastric mucosal cells and mouse stomach in vivo: AP-1 as a potential target

15-Hydroxyprostaglandin dehydrogenase (15-PGDH) catalyzes the conversion of oncogenic prostaglandin E-2 to non-tumerigenic 15-keto prostaglandin E-2. In the present study, we found that curcumin, a yellow coloring agent present in the rhizome of Curcuma Tonga Linn (Zingiberaceae), induced expression of 15-PGDH at the both transcriptional and translational levels in normal rat gastric mucosal cells. By using deletion constructs of 15-PGDH promoter, we were able to demonstrate that activator protein-1 (AP-1) is the principal transcription factor responsible for regulating curcumin-induced 15-PGDH expression. Curcumin enhanced the expression of c-jun and cFos that are functional subunits of AP-1, in the nuclear fraction of cells. Silencing of c-jun suppressed curcumin-induced expression of 15-PGDH. Moreover, the chromatin immunoprecipitation assay revealed curcumin-induced binding of c-Jun to the AP-1 consensus sequence present in the 15-PGDH promoter. Curaimin increased phosphorylation of ERK1/2 and JNK. and pharmacologic inhibition of these kinases abrogated the curcumin-induced phosphorylation of clun and 15-PGDH expression. In contrast, tetrahydrocurcumin which lacks the alpha,beta-unsaturated carbonyl group failed to induce 15-PGDH expression, suggesting that the electrophilic carbonyl group of curcumin is essential for its induction of 15-PGDH expression. Curcumin restored the expression of 15-PGDH which is down-regulated by Helicobater pylori through suppression of DNA methyltransferase 1. In addition, oral administration of curcumin increased the expression of 15-PGDH and its regulators such as p-ERK1/2, p-JNK and c-Jun in the mouse stomach. Taken together, these findings suggest that curcumin-induced upregulation of 15-PGDH may contribute to chemopreventive effects of this phytochemical on inflammation-associated gastric carcinogenesis. (C) 2020 Elsevier Inc. All rights reserved.

Association between MSX1 SNPs and Nonsyndromic Cleft Lip with or without Cleft Palate in the Korean Population

The purpose of this study was to investigate the contribution of MSX1 gene to the risk of nonsyndromic cleft lip with or without cleft palate (NS-CL +/- P) in the Korean population. The samples consisted of 142 NS-CL +/- P families (9 with cleft lip, 26 with cleft lip and alveolus, and 107 with cleft lip and palate; 76 trios and 66 dyads). Three single nucleotide polymorphisms (SNPs: rs3821949, rs12532, and rs4464513) were tested for association with NS-CL +/- P case-parent trios using transmission disequilibrium test (TDT) and conditional logistic regression models (CLRMs). Minor allele frequency, heterozygosity, chi(2) test for Hardy-Weinberg equilibrium, and pairwise linkage disequilibrium (LD) at each SNP were computed. The family- and haplotype-based association test programs were used to perform allelic and genotypic TDTs for individual SNPs and to fabricate sliding windows of haplotypes. Genotypic odds ratios (GORs) were obtained from CLRMs using R software. Although the family-based TDT indicated a meaningful association for rs3821949 (P = 0.028), the haplotype analysis did not reveal any significant association with rs3821949, rs12532, or rs4464513. The A allele at rs3821949 had a significant increased risk of NS-CL +/- P (GOR, 1.64; 95% confidence interval, 1.03-2.63; P = 0.038, additive model). A positive association is suggested between MSX1 rs3821949 and NS-CL +/- P in the Korean population.OAIID:oai:osos.snu.ac.kr:snu2013-01/102/0000004298/4SEQ:4PERF_CD:SNU2013-01EVAL_ITEM_CD:102USER_ID:0000004298ADJUST_YN:YEMP_ID:A072100DEPT_CD:852CITE_RATE:1.249FILENAME:kimny-cleft-msx1-manuscript-jkms-final.pdfDEPT_NM:치의과학과SCOPUS_YN:YCONFIRM:

The Expression of Adipophilin Is Frequently Found in Solid Subtype Adenocarcinoma and Is Associated with Adverse Outcomes in Lung Adenocarcinoma

Background The up-regulation of the lipogenic pathway has been reported in many types of malignant tumors. However, its pathogenic role or clinical significance is not fully understood. The objective of this study was to examine the expression levels of adipophilin and related hypoxic signaling proteins and to determine their prognostic impacts and associations with the pathologic characteristics of lung adenocarcinoma. Methods Expression levels of adipophilin, heat shock protein 27 (HSP27), carbonic anhydrase IX, and hypoxia-inducible factor 1α were examined by immunohistochemical staining using tissue microarray blocks. Correlations between protein expression levels and various clinicopathologic features were analyzed. Results A total of 230 cases of primary adenocarcinoma of the lung were enrolled in this study. Adipophilin expression was more frequent in males and with the solid histologic type. It was correlated with HSP27 expression. Patients with adipophilin-positive adenocarcinoma showed a shorter progression-free survival (PFS) (median PFS, 17.2 months vs 18.4 months) in a univariable survival analysis, whereas HSP27 positivity correlated with favorable overall survival (OS) and PFS. In a multivariable analysis, adipophilin and HSP27 were independent prognostic markers of both OS and PFS. Conclusions Activated lipid metabolism and the hypoxic signaling pathway might play a major role in the progression of lung adenocarcinoma, especially in the solid histologic type