A Fourier Continuation Method for the Solution of Elliptic Eigenvalue Problems in General Domains

We present a new computational method for the solution of elliptic eigenvalue problems with variable coefficients in general two-dimensional domains. The proposed approach is based on use of the novel Fourier continuation method (which enables fast and highly accurate Fourier approximation of nonperiodic functions in equispaced grids without the limitations arising from the Gibbs phenomenon) in conjunction with an overlapping patch domain decomposition strategy and Arnoldi iteration. A variety of examples demonstrate the versatility, accuracy, and generality of the proposed methodology

DUSP9 Modulates DNA Hypomethylation in Female Mouse Pluripotent Stem Cells

Blastocyst-derived embryonic stem cells (ESCs) and gonad-derived embryonic germ cells (EGCs) represent two classic types of pluripotent cell lines, yet their molecular equivalence remains incompletely understood. Here, we compare genome-wide methylation patterns between isogenic ESC and EGC lines to define epigenetic similarities and differences. Surprisingly, we find that sex rather than cell type drives methylation patterns in ESCs and EGCs. Cell fusion experiments further reveal that the ratio of X chromosomes to autosomes dictates methylation levels, with female hybrids being hypomethylated and male hybrids being hypermethylated. We show that the X-linked MAPK phosphatase DUSP9 is upregulated in female compared to male ESCs, and its heterozygous loss in female ESCs leads to male-like methylation levels. However, male and female blastocysts are similarly hypomethylated, indicating that sex-specific methylation differences arise in culture. Collectively, our data demonstrate the epigenetic similarity of sex-matched ESCs and EGCs and identify DUSP9 as a regulator of female-specific hypomethylation

Multi-omic studies on missense PLG variants in families with otitis media

Otitis media (OM), a very common disease in young children, can result in hearing loss. In order to potentially replicate previously reported associations between OM and PLG, exome and Sanger sequencing, RNA-sequencing of saliva and middle ear samples, 16S rRNA sequencing, molecular modeling, and statistical analyses including transmission disequilibrium tests (TDT) were performed in a multi-ethnic cohort of 718 families and simplex cases with OM. We identified four rare PLG variants c.112A > G (p.Lys38Glu), c.782G > A (p.Arg261His), c.1481C > T (p.Ala494Val) and c.2045 T > A (p.Ile682Asn), and one common variant c.1414G > A (p.Asp472Asn). However TDT analyses for these PLG variants did not demonstrate association with OM in 314 families. Additionally PLG expression is very low or absent in normal or diseased middle ear in mouse and human, and salivary expression and microbial a-diversity were non-significant in c.1414G > A (p.Asp472Asn) carriers. Based on molecular modeling, the novel rare variants particularly c.782G > A (p.Arg261His) and c.2045 T > A (p.Ile682Asn) were predicted to affect protein structure. Exploration of other potential disease mechanisms will help elucidate how PLG contributes to OM susceptibility in humans. Our results underline the importance of following up findings from genome-wide association through replication studies, preferably using multi-omic datasets.Peer reviewe

Derivation and maintenance of mouse haploid embryonic stem cells.

Ploidy represents the number of chromosome sets in a cell. Although gametes have a haploid genome (n), most mammalian cells have diploid genomes (2n). The diploid status of most cells correlates with the number of probable alleles for each autosomal gene and makes it difficult to target these genes via mutagenesis techniques. Here, we describe a 7-week protocol for the derivation of mouse haploid embryonic stem cells (hESCs) from female gametes that also outlines how to maintain the cells once derived. We detail additional procedures that can be used with cell lines obtained from the mouse Haplobank, a biobank of >100,000 individual mouse hESC lines with targeted mutations in 16,970 genes. hESCs can spontaneously diploidize and can be maintained in both haploid and diploid states. Mouse hESCs are genomically and karyotypically stable, are innately immortal and isogenic, and can be derived in an array of differentiated cell types; they are thus highly amenable to genetic screens and to defining molecular connectivity pathways.UK Dementia Research Institute fellowship (MC_PC_17111)

Rapid syndromic PCR testing in patients with respiratory tract infections reduces time to results and improves microbial yield

Lack of rapid and comprehensive microbiological diagnosis in patients with community acquired pneumonia (CAP) hampers appropriate antimicrobial therapy. This study evaluates the real-world performance of the BioFire FilmArray Pneumonia panel plus (FAP plus) and explores the feasibility of evaluation in a randomised controlled trial. Patients presenting to hospital with suspected CAP were recruited in a prospective feasibility study. An induced sputum or an endotracheal aspirate was obtained from all participants. The FAP plus turnaround time (TAT) and microbiological yield were compared with standard diagnostic methods (SDs). 96/104 (92%) enrolled patients had a respiratory tract infection (RTI); 72 CAP and 24 other RTIs. Median TAT was shorter for the FAP plus, compared with in-house PCR (2.6 vs 24.1 h, p < 0.001) and sputum cultures (2.6 vs 57.5 h, p < 0.001). The total microbiological yield by the FAP plus was higher compared to SDs (91% (162/179) vs 55% (99/179), p < 0.0001). Haemophilus influenzae, Streptococcus pneumoniae and influenza A virus were the most frequent pathogens. In conclusion, molecular panel testing in adults with CAP was associated with a significant reduction in time to actionable results and increased microbiological yield. The impact on antibiotic use and patient outcome should be assessed in randomised controlled trials.publishedVersio

Net Benefits to Agriculture from the Trinity River Project, Texas

The purpose of this study was to estimate the agricultural benefits due to flood protection provided by the proposed Trinity River Project. The area examined was the land located between the 100-year flood plain with the project and without the project. Benefits of the project were defined as reduced flood damages on current land uses and alternatively as increased net returns assuming a shift to a profit maximizing land use with flood protection provided. Annual flood damages were calculated by applying published seasonal flood damage factors and flood frequency as developed from a producer survey to annual gross returns. Annual net benefits were calculated as net returns with flood protection less net returns without flood protection. The reduction in net returns without flood protection represented annual flood damages with a constant land use assumption. The two estimates of flood protection benefits were developed for evaluation reaches 1 through 6 separately as well as on an aggregate basis. Total annual net benefits of the Trinity River Project were $676,392.43 assuming current land use and$4,579,688.55 assuming profit maximizing land use after flood protection. These benefits were capitalized to a present value using interest rates of 3 1/4% and 9%. Under current land use the total benefits were $20,812,074 at 3 1/4$7,515,471 at 9%. Similarity flood protection benefits were $140,913,493 and$50,885,429 respectively assuming the profit maximizing land use. Applying regional income multipliers, the increased annual household income was $2,171,796.66 assuming current land use and$12,163,887.68 assuming all land in the profit maximizing enterprise. The capitalized values of the regional impact were $66,824,513 and$24,131,075 under current land use, and $374,273,469 and$135,154,308 under profit maximizing land use at 3 1/4% and 9% respectively

Multidimensional Conservation Laws: Overview, Problems, and Perspective

Some of recent important developments are overviewed, several longstanding open problems are discussed, and a perspective is presented for the mathematical theory of multidimensional conservation laws. Some basic features and phenomena of multidimensional hyperbolic conservation laws are revealed, and some samples of multidimensional systems/models and related important problems are presented and analyzed with emphasis on the prototypes that have been solved or may be expected to be solved rigorously at least for some cases. In particular, multidimensional steady supersonic problems and transonic problems, shock reflection-diffraction problems, and related effective nonlinear approaches are analyzed. A theory of divergence-measure vector fields and related analytical frameworks for the analysis of entropy solutions are discussed.Comment: 43 pages, 3 figure

Effects of Place of Articulation Changes on Auditory Neural Activity: A Magnetoencephalography Study

In casual speech, phonemic segments often assimilate such that they adopt features from adjacent segments, a typical feature being their place of articulation within the vocal tract (e.g., labial, coronal, velar). Place assimilation (e.g., from coronal /n/ to labial /m/: rainbow→*raimbow) alters the surface form of words. Listeners' ability to perceptually compensate for such changes seems to depend on the phonemic context, on whether the adjacent segment (e.g., the /b/ in “rainbow”) invites the particular change. Also, some assimilations occur frequently (e.g., /n/→/m/), others are rare (e.g., /m/→/n/). We investigated the effects of place assimilation, its contextual dependency, and its frequency on the strength of auditory evoked mismatch negativity (MMN) responses, using pseudowords. Results from magnetoencephalography (MEG) revealed that the MMN was modulated both by the frequency and contextual appropriateness of assimilations

The effect of the UP4FUN pilot intervention on objectively measured sedentary time and physical activity in 10-12 year old children in Belgium: the ENERGY-project

<p>Abstract</p> <p>Bakckground</p> <p>The first aim was to examine the effect of the UP4FUN pilot intervention on children’s total sedentary time. The second aim was to investigate if the intervention had an effect on children’s physical activity (PA) level. Finally, we aimed to investigate demographic differences (i.e. age, gender, ethnicity, living status and having siblings) between children in the intervention group who improved in sedentary time and PA at post-test and children in the intervention group who worsened in sedentary time and PA at post-test.</p> <p>Methods</p> <p>The six weeks UP4FUN intervention was tested in a randomized controlled trial with pre-test post-test design with five intervention and five control schools in Belgium and included children of the 5^th and 6^th grade. The children wore accelerometers for seven days at pre- and post-test. Analyses included children with valid accelerometer data for at least two weekdays with minimum 10h-wearing time and one weekend day with 8h-wearing time.</p> <p>Result</p> <p>Final analyses included 372 children (60% girls, mean age = 10.9 ± 0.7 years). There were no significant differences in the change in sedentary time or light PA between intervention and control schools for the total sample or for the subgroup analyses by gender. However, children (specifically girls) in the intervention group had a higher decrease in moderate-to-vigorous PA than children in the control group. In the intervention group, children who lived with both parents and children with one or more siblings were less likely to reduce sedentary time after exposure to the intervention. Older children, girls and children who lived with both parents were less likely to increase light PA after the intervention.</p> <p>Conclusion</p> <p>The UP4FUN intervention did not result in an effect on children’s sedentary time. Based on the high amounts of accelerometer-derived sedentary time in this age group, more efforts are needed to develop strategies to reduce children’s sedentary time.</p