LEMDA: A Lagrangian-Eulerian Multiscale Data Assimilation Framework

Lagrangian trajectories are widely used as observations for recovering the underlying flow field via Lagrangian data assimilation (DA). However, the strong nonlinearity in the observational process and the high dimensionality of the problems often cause challenges in applying standard Lagrangian DA. In this paper, a Lagrangian-Eulerian multiscale DA (LEMDA) framework is developed. It starts with exploiting the Boltzmann kinetic description of the particle dynamics to derive a set of continuum equations, which characterize the statistical quantities of particle motions at fixed grids and serve as Eulerian observations. Despite the nonlinearity in the continuum equations and the processes of Lagrangian observations, the time evolutions of the posterior distribution from LEMDA can be written down using closed analytic formulae. This offers an exact and efficient way of carrying out DA, which avoids using ensemble approximations and the associated tunings. The analytically solvable properties also facilitate the derivation of an effective reduced-order Lagrangian DA scheme that further enhances computational efficiency. The Lagrangian DA within the framework has advantages when a moderate number of particles is used, while the Eulerian DA can effectively save computational costs when the number of particle observations becomes large. The Eulerian DA is also valuable when particles collide, such as using sea ice floe trajectories as observations. LEMDA naturally applies to multiscale turbulent flow fields, where the Eulerian DA recovers the large-scale structures, and the Lagrangian DA efficiently resolves the small-scale features in each grid cell via parallel computing. Numerical experiments demonstrate the skilful results of LEMDA and its two components

Genome-Wide Association Study of Tanning Phenotype in a Population of European Ancestry

We conducted a multistage genome-wide association study (GWAS) of tanning response after exposure to sunlight in over 9,000 men and women of European ancestry who live in the United States. An initial analysis of 528,173 single-nucleotide polymorphisms (SNPs) genotyped on 2,287 women identified LOC401937 (rs966321) on chromosome 1 as a novel locus highly associated with tanning ability, and we confirmed this association in 870 women controls from a skin cancer case–control study with joint P-value=1.6 × 10−9. We further genotyped this SNP in two subsequent replication studies (one with 3,750 women and the other with 2,405 men). This association was not replicated in either of these two studies. We found that several SNPs reaching the genome-wide significance level are located in or adjacent to the loci previously known as pigmentation genes: MATP, IRF4, TYR, OCA2, and MC1R. Overall, these tanning ability–related loci are similar to the hair color–related loci previously reported in the GWAS of hair color

Whirling Hexagons and Defect Chaos in Hexagonal Non-Boussinesq Convection

We study hexagon patterns in non-Boussinesq convection of a thin rotating layer of water. For realistic parameters and boundary conditions we identify various linear instabilities of the pattern. We focus on the dynamics arising from an oscillatory side-band instability that leads to a spatially disordered chaotic state characterized by oscillating (whirling) hexagons. Using triangulation we obtain the distribution functions for the number of pentagonal and heptagonal convection cells. In contrast to the results found for defect chaos in the complex Ginzburg-Landau equation and in inclined-layer convection, the distribution functions can show deviations from a squared Poisson distribution that suggest non-trivial correlations between the defects.Comment: 4 mpg-movies are available at http://www.esam.northwestern.edu/~riecke/lit/lit.html submitted to New J. Physic

Quantitative real-time RT-PCR validation of differential mRNA expression of SPARC, FADD, Fascin, COL7A1, CK4, TGM3, ECM1, PPL and EVPL in esophageal squamous cell carcinoma

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most malignant tumors and typically presents at an advanced and rapidly fatal stage. To better understand the role of genetics in the etiology and prevention of ESCC and to identify potential susceptibility genes as well as early detection markers, we previously compared tumor and matched normal tissues from ESCC patients from a high-risk area of China using cDNA expression microarrays and identified 41 differentially-expressed genes (13 over-expressed and 28 under-expressed). METHODS: In the current study, we validated and quantitated differential mRNA expression in a sample of nine of these 41 genes, including four that were over-expressed (SPARC, FADD, Fascin, COL7A1), and five that were under-expressed (CK4, TGM3, ECM1, PPL, EVPL), in 75 new ESCC patients using quantitative Real-time RT-PCR and the 2(-ΔΔCT )method to examine both tumor and matched normal tissue. In addition, we examined expression patterns for these genes by selected demographic and clinical characteristics. RESULTS: Four previously over-expressed (tumor ≥2-fold normal) genes were all increased in the majority of new ESCC patients: SPARC was increased in 71% of patients, Fascin in 70%, FADD in 63%, and COL7A1 in 57%. Five previously under-expressed (tumor ≤0.5-fold normal) genes similarly showed decreased mRNA expression in two-thirds or more of patients: CK4 was decreased in 83% of patients, TGM3 in 77%, ECM1 in 73%, and PPL and EVPL in 67% each. In subset analyses, associations with age (for COL7A1), family history (for PPL and ECM1), and alcohol use (for SPARC and Fascin) were also noted. CONCLUSION: These data indicate that these nine genes have consistent differential mRNA expression, validating results of our previous cDNA array results, and affirming their potential role in the early detection of ESCC

Influence of Genetic Background and Tissue Types on Global DNA Methylation Patterns

Recent studies have shown a genetic influence on gene expression variation, chromatin, and DNA methylation. However, the effects of genetic background and tissue types on DNA methylation at the genome-wide level have not been characterized extensively. To study the effect of genetic background and tissue types on global DNA methylation, we performed DNA methylation analysis using the Affymetrix 500K SNP array on tumor, adjacent normal tissue, and blood DNA from 30 patients with esophageal squamous cell carcinoma (ESCC). The use of multiple tissues from 30 individuals allowed us to evaluate variation of DNA methylation states across tissues and individuals. Our results demonstrate that blood and esophageal tissues shared similar DNA methylation patterns within the same individual, suggesting an influence of genetic background on DNA methylation. Furthermore, we showed that tissue types are important contributors of DNA methylation states

Revealing missing human protein isoforms based on Ab initio prediction, RNA-seq and proteomics

Biological and biomedical research relies on comprehensive understanding of protein-coding transcripts. However, the total number of human proteins is still unknown due to the prevalence of alternative splicing. In this paper, we detected 31,566 novel transcripts with coding potential by filtering our ab initio predictions with 50 RNA-seq datasets from diverse tissues/cell lines. PCR followed by MiSeq sequencing showed that at least 84.1% of these predicted novel splice sites could be validated. In contrast to known transcripts, the expression of these novel transcripts were highly tissue-specific. Based on these novel transcripts, at least 36 novel proteins were detected from shotgun proteomics data of 41 breast samples. We also showed L1 retrotransposons have a more significant impact on the origin of new transcripts/genes than previously thought. Furthermore, we found that alternative splicing is extraordinarily widespread for genes involved in specific biological functions like protein binding, nucleoside binding, neuron projection, membrane organization and cell adhesion. In the end, the total number of human transcripts with protein-coding potential was estimated to be at least 204,950.publishedVersio

Control region mutations and the 'common deletion' are frequent in the mitochondrial DNA of patients with esophageal squamous cell carcinoma

BACKGROUND: North central China has some of the highest rates of esophageal squamous cell carcinoma in the world with cumulative mortality surpassing 20%. Mitochondrial DNA (mtDNA) accumulates more mutations than nuclear DNA and because of its high abundance has been proposed as a early detection device for subjects with cancer at various sites. We wished to examine the prevalence of mtDNA mutation and polymorphism in subjects from this high risk area of China. METHODS: We used DNA samples isolated from tumors, adjacent normal esophageal tissue, and blood from 21 esophageal squamous cell carcinoma cases and DNA isolated from blood from 23 healthy persons. We completely sequenced the control region (D-Loop) from each of these samples and used a PCR assay to assess the presence of the 4977 bp common deletion. RESULTS: Direct DNA sequencing revealed that 7/21 (33%, 95% CI = 17–55%) tumor samples had mutations in the control region, with clustering evident in the hyper-variable segment 1 (HSV1) and the homopolymeric stretch surrounding position 309. The number of mutations per subject ranged from 1 to 16 and there were a number of instances of heteroplasmy. We detected the 4977 bp 'common deletion' in 92% of the tumor and adjacent normal esophageal tissue samples examined, whereas no evidence of the common deletion was found in corresponding peripheral blood samples. CONCLUSIONS: Control region mutations were insufficiently common to warrant attempts to develop mtDNA mutation screening as a clinical test for ESCC. The common deletion was highly prevalent in the esophageal tissue of cancer cases but absent from peripheral blood. The potential utility of the common deletion in an early detection system will be pursued in further studies

Family history of cancer and risk for esophageal and gastric cancer in Shanxi, China

<p>Abstract</p> <p>Background</p> <p>Family history (FH) by different relative types and risk of upper gastrointestinal (UGI) cancers has been only rarely reported; the data on UGI cancer survival are sparse.</p> <p>Methods</p> <p>600 esophageal squamous cell carcinoma (ESCC) cases, 598 gastric cardia adenocarcinoma cases, and 316 gastric non-cardia adenocarcinoma cases, and 1514 age-, gender-, and neighborhood-matched controls were asked for FH in first degree relatives and non-blood relatives. Odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regressions, and hazard ratios (HRs) from Cox proportional hazard regressions were estimated.</p> <p>Results</p> <p>Increased ESCC risk was associated with FH of any cancer (OR = 1.72, 95% CI = 1.39–2.12), FH of any UGI cancer (OR = 2.28, 95%CI = 1.77–2.95) and FH of esophageal cancer (OR = 2.84, 95%CI = 2.09–3.86), but not FH of non-UGI cancer. Individuals with two or more affected first-degree relatives had 10-fold increased ESCC risk. FH of gastric cardia cancer was associated with an increased risk of all three cancers. Cancer in non-blood relatives was not associated with risk of any UGI cancer. FH of UGI cancer was associated with a poorer survival rate among younger ESCC cases (HR = 1.82, 95%CI = 1.01–3.29).</p> <p>Conclusion</p> <p>These data provide strong evidence that shared susceptibility is involved in esophageal carcinogenesis and also suggest a role in prognosis.</p

Short Body Height and Pre-pregnancy Overweight for Increased Risk of Gestational Diabetes Mellitus: A Population-Based Cohort Study

Background: Short height is associated with gestational diabetes mellitus (GDM) but the underlying mechanism remains unknown. This study aims to explore whether short height has a synergistic effect with pre-pregnancy overweight/obesity and undue weight gain on the risk of GDM.Methods: We recruited 19,962 singleton pregnant women from their first antenatal care visit in urban Tianjin, China, between October 2010 to August 2012. At 24–28 weeks of gestation, women underwent a 50-g 1-h glucose challenge test (GCT) followed by a 75-g 2-h oral glucose tolerance test (OGTT) if the GCT result was ≥7.8 mmol/L. GDM was defined by the International Association of Diabetes and Pregnancy Study Group's cut-points. Univariable and multivariable logistic regression analyses were performed to obtain odds ratios (ORs) and 95% confidence intervals (CIs). Restricted cubic spline (RCS) analysis nested in the logistic regression analysis was used to identify a cutoff point of height for GDM. Additive interaction was used to test interactions between short height, pregnancy overweight/obesity and undue weight gain.Results: A total of 1,517 (or 7.6%) women developed GDM. The risk of GDM increased rapidly with a decreasing height from 158 cm and downwards. Using height ≥158 cm as the reference group, women with &lt; 158 cm of height were at increased GDM risk (adjusted OR: 1.44, 95%CI: 1.18–1.75). Maternal overweight/obesity at the first antenatal care visit greatly enhanced the OR of short height for GDM (adjusted OR: 3.78, 95%CI: 2.84–5.03) with significant additive interaction (P &lt; 0.05). However, the interaction between short height and undue weight gain was non-significant (P &gt; 0.05).Conclusions: In Chinese pregnant women in urban Tianjin, height &lt; 158 cm had a synergistic effect with pre-pregnancy overweight/obesity on the risk of GDM