Bounds on solutions of the rotating, stratified, incompressible, non-hydrostatic, three-dimensional Boussinesq equations

We study the three-dimensional, incompressible, non-hydrostatic Boussinesq fluid equations, which are applicable to the dynamics of the oceans and atmosphere. These equations describe the interplay between velocity and buoyancy in a rotating frame. A hierarchy of dynamical variables is introduced whose members $\Omega_{m}(t)$ ($1 \leq m < \infty$) are made up from the respective sum of the $L^{2m}$-norms of vorticity and the density gradient. Each $\Omega_{m}(t)$ has a lower bound in terms of the inverse Rossby number, $Ro^{-1}$, that turns out to be crucial to the argument. For convenience, the $\Omega_{m}$ are also scaled into a new set of variables $D_{m}(t)$. By assuming the existence and uniqueness of solutions, conditional upper bounds are found on the $D_{m}(t)$ in terms of $Ro^{-1}$ and the Reynolds number $Re$. These upper bounds vary across bands in the $\{D_{1},\,D_{m}\}$ phase plane. The boundaries of these bands depend subtly upon $Ro^{-1}$, $Re$, and the inverse Froude number $Fr^{-1}$. For example, solutions in the lower band conditionally live in an absorbing ball in which the maximum value of $\Omega_{1}$ deviates from $Re^{3/4}$ as a function of $Ro^{-1},\,Re$ and $Fr^{-1}$.Comment: 24 pages, 3 figures and 1 tabl

Vlasov moments, integrable systems and singular solutions

The Vlasov equation for the collisionless evolution of the single-particle probability distribution function (PDF) is a well-known Lie-Poisson Hamiltonian system. Remarkably, the operation of taking the moments of the Vlasov PDF preserves the Lie-Poisson structure. The individual particle motions correspond to singular solutions of the Vlasov equation. The paper focuses on singular solutions of the problem of geodesic motion of the Vlasov moments. These singular solutions recover geodesic motion of the individual particles.Comment: 16 pages, no figures. Submitted to Phys. Lett.

Ionic Capillary Evaporation in Weakly Charged Nanopores

Using a variational field theory, we show that an electrolyte confined to a neutral cylindrical nanopore traversing a low dielectric membrane exhibits a first-order ionic liquid-vapor pseudo-phase-transition from an ionic-penetration "liquid" phase to an ionic-exclusion "vapor" phase, controlled by nanopore-modified ionic correlations and dielectric repulsion. For weakly charged nanopores, this pseudotransition survives and may shed light on the mechanism behind the rapid switching of nanopore conductivity observed in experiments.Comment: This version is accepted for publication in PR

A single H/ACA small nucleolar RNA mediates tumor suppression downstream of oncogenic RAS.

Small nucleolar RNAs (snoRNAs) are a diverse group of non-coding RNAs that direct chemical modifications at specific residues on other RNA molecules, primarily on ribosomal RNA (rRNA). SnoRNAs are altered in several cancers; however, their role in cell homeostasis as well as in cellular transformation remains poorly explored. Here, we show that specific subsets of snoRNAs are differentially regulated during the earliest cellular response to oncogenic RASG12V expression. We describe a novel function for one H/ACA snoRNA, SNORA24, which guides two pseudouridine modifications within the small ribosomal subunit, in RAS-induced senescence in vivo. We find that in mouse models, loss of Snora24 cooperates with RASG12V to promote the development of liver cancer that closely resembles human steatohepatitic hepatocellular carcinoma (HCC). From a clinical perspective, we further show that human HCCs with low SNORA24 expression display increased lipid content and are associated with poor patient survival. We next asked whether ribosomes lacking SNORA24-guided pseudouridine modifications on 18S rRNA have alterations in their biophysical properties. Single-molecule Fluorescence Resonance Energy Transfer (FRET) analyses revealed that these ribosomes exhibit perturbations in aminoacyl-transfer RNA (aa-tRNA) selection and altered pre-translocation ribosome complex dynamics. Furthermore, we find that HCC cells lacking SNORA24-guided pseudouridine modifications have increased translational miscoding and stop codon readthrough frequencies. These findings highlight a role for specific snoRNAs in safeguarding against oncogenic insult and demonstrate a functional link between H/ACA snoRNAs regulated by RAS and the biophysical properties of ribosomes in cancer

Eliminating Trachoma in Areas with Limited Disease

The common wisdom is that a trachoma program cannot eliminate ocular chlamydia from a community, just reduce infection to a level where there would be minimal blindness. We describe the success of multiple mass antibiotic treatments, demonstrating that complete elimination of infection may be an attainable goal in an area with modest disease

The structure of a resuscitation-promoting factor domain from Mycobacterium tuberculosis shows homology to lysozymes

Resuscitation-promoting factor (RPF) proteins reactivate stationary-phase cultures of (G+C)-rich Gram-positive bacteria including the causative agent of tuberculosis, Mycobacterium tuberculosis. We report the solution structure of the RPF domain from M. tuberculosis Rv1009 (RpfB) solved by heteronuclear multidimensional NMR. Structural homology with various glycoside hydrolases suggested that RpfB cleaved oligosaccharides. Biochemical studies indicate that a conserved active site glutamate is important for resuscitation activity. These data, as well as the presence of a clear binding pocket for a large molecule, indicate that oligosaccharide cleavage is probably the signal for revival from dormancy

Trachoma Decline and Widespread Use of Antimicrobial Drugs

Widespread use of antimicrobial drugs may be contributing to trachoma decline

Phenome-wide association study (PheWAS) in EMR-linked pediatric cohorts, genetically links PLCL1 to speech language development and IL5-IL13 to Eosinophilic Esophagitis

Objective: We report the first pediatric specific Phenome-Wide Association Study (PheWAS) using electronic medical records (EMRs). Given the early success of PheWAS in adult populations, we investigated the feasibility of this approach in pediatric cohorts in which associations between a previously known genetic variant and a wide range of clinical or physiological traits were evaluated. Although computationally intensive, this approach has potential to reveal disease mechanistic relationships between a variant and a network of phenotypes. Method: Data on 5049 samples of European ancestry were obtained from the EMRs of two large academic centers in five different genotyped cohorts. Recently, these samples have undergone whole genome imputation. After standard quality controls, removing missing data and outliers based on principal components analyses (PCA), 4268 samples were used for the PheWAS study. We scanned for associations between 2476 single-nucleotide polymorphisms (SNP) with available genotyping data from previously published GWAS studies and 539 EMR-derived phenotypes. The false discovery rate was calculated and, for any new PheWAS findings, a permutation approach (with up to 1,000,000 trials) was implemented. Results: This PheWAS found a variety of common variants (MAF > 10%) with prior GWAS associations in our pediatric cohorts including Juvenile Rheumatoid Arthritis (JRA), Asthma, Autism and Pervasive Developmental Disorder (PDD) and Type 1 Diabetes with a false discovery rate < 0.05 and power of study above 80%. In addition, several new PheWAS findings were identified including a cluster of association near the NDFIP1 gene for mental retardation (best SNP rs10057309, p = 4.33 × 10−7, OR = 1.70, 95%CI = 1.38 − 2.09); association near PLCL1 gene for developmental delays and speech disorder [best SNP rs1595825, p = 1.13 × 10−8, OR = 0.65(0.57 − 0.76)]; a cluster of associations in the IL5-IL13 region with Eosinophilic Esophagitis (EoE) [best at rs12653750, p = 3.03 × 10−9, OR = 1.73 95%CI = (1.44 − 2.07)], previously implicated in asthma, allergy, and eosinophilia; and association of variants in GCKR and JAZF1 with allergic rhinitis in our pediatric cohorts [best SNP rs780093, p = 2.18 × 10−5, OR = 1.39, 95%CI = (1.19 − 1.61)], previously demonstrated in metabolic disease and diabetes in adults. Conclusion: The PheWAS approach with re-mapping ICD-9 structured codes for our European-origin pediatric cohorts, as with the previous adult studies, finds many previously reported associations as well as presents the discovery of associations with potentially important clinical implications