Two problems of binomial sums involving harmonic numbers

AbstractTwo open problems recently proposed by Xi and Luo (Adv. Differ. Equ. 2021:38, 2021) are resolved by evaluating explicitly three binomial sums involving harmonic numbers, that are realized mainly by utilizing the generating function method and symmetric functions

Hydro-chemical modelling of in situ behaviour of bituminized radioactive waste in Boom Clay

The hydro-chemical (CH) interaction between swelling Eurobitum bituminized radioactive waste (BW) and Boom Clay was investigated to assess the feasibility of geological disposal for the long-term management of this waste. First, the long-term behaviour of BW in contact with water was studied. A CH formulation of chemically and hydraulically coupled flow processes in porous materials containing salt crystals is discussed. The formulation incorporates the strong dependence of the osmotic efficiency of the bitumen membrane on porosity and assumes the existence of high salt concentration gradients that are maintained for a long time and that influence the density and motion of the fluid. The impacts of temporal and spatial variations of key transport parameters (i.e. osmotic efficiency (s), intrinsic permeability (k), diffusion, etc.) were investigated. Porosity was considered the basic variable. For BW porosity varies in time because of the water uptake and subsequent processes (i.e. dissolution of salt crystals, swelling of hydrating layers, compression of highly leached layers). New expressions of s and k describing the dependence of these parameters on porosity are proposed. Several cases were analysed. The numerical analysis was proven to be able to furnish a satisfactory representation of the main observed patterns of the behaviour in terms of osmotic-induced swelling, leached mass of NaNO3 and progression of the hydration front when heterogeneous porosity and crystal distributions have been assumed. Second, the long-term behaviour of real Eurobitum drums in disposal conditions, and in particular its interaction with the surrounding clay, was investigated. Results of a CH analysis are presented.Peer ReviewedPostprint (published version

Multifold convolutions of binomial coefficients

A class of the multifold convolutions of binomial coefficients will be evaluated by employing a pair of Lambert series. The corresponding multisums on Abel coefficients will also be examine

Double-Peaked Low-Ionization Emission Lines in Active Galactic Nuclei

We present a new sample of 116 double-peaked Balmer line Active Galactic Nuclei (AGN) selected from the Sloan Digital Sky Survey. Double-peaked emission lines are believed to originate in the accretion disks of AGN, a few hundred gravitational radii (Rg) from the supermassive black hole. We investigate the properties of the candidate disk emitters with respect to the full sample of AGN over the same redshifts, focusing on optical, radio and X-ray flux, broad line shapes and narrow line equivalent widths and line flux-ratios. We find that the disk-emitters have medium luminosities (~10^44erg/s) and FWHM on average six times broader than the AGN in the parent sample. The double-peaked AGN are 1.6 times more likely to be radio-sources and are predominantly (76%) radio quiet, with about 12% of the objects classified as LINERs. Statistical comparison of the observed double-peaked line profiles with those produced by axisymmetric and non-axisymmetric accretion disk models allows us to impose constraints on accretion disk parameters. The observed Halpha line profiles are consistent with accretion disks with inclinations smaller than 50 deg, surface emissivity slopes of 1.0-2.5, outer radii larger than ~2000 Rg, inner radii between 200-800Rg, and local turbulent broadening of 780-1800 km/s. The comparison suggests that 60% of accretion disks require some form of asymmetry (e.g., elliptical disks, warps, spiral shocks or hot spots).Comment: 60 pages, 19 figures, accepted for publication in AJ. For high quality figures and full tables, please see http://astro.princeton.edu/~iskra/disks.htm

Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser.

G-protein-coupled receptors (GPCRs) signal primarily through G proteins or arrestins. Arrestin binding to GPCRs blocks G protein interaction and redirects signalling to numerous G-protein-independent pathways. Here we report the crystal structure of a constitutively active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin, determined by serial femtosecond X-ray laser crystallography. Together with extensive biochemical and mutagenesis data, the structure reveals an overall architecture of the rhodopsin-arrestin assembly in which rhodopsin uses distinct structural elements, including transmembrane helix 7 and helix 8, to recruit arrestin. Correspondingly, arrestin adopts the pre-activated conformation, with a ∼20° rotation between the amino and carboxy domains, which opens up a cleft in arrestin to accommodate a short helix formed by the second intracellular loop of rhodopsin. This structure provides a basis for understanding GPCR-mediated arrestin-biased signalling and demonstrates the power of X-ray lasers for advancing the frontiers of structural biology

The Pharmacogenomics of Inhaled Corticosteroids and Lung Function Decline in COPD

Inhaled corticosteroids (ICS) are widely prescribed for patients with chronic obstructive pulmonary disease (COPD), yet with variable outcomes and adverse reactions which may be genetically determined. The primary aim of the study was to identify the genetic determinants for FEV1 changes related to ICS therapy. In the Lung Health Study 2 (LHS-2), 1116 COPD patients were randomised to the ICS, triamcinolone acetonide (n=559), or placebo (n=557) with spirometry performed every 6 months for 3 years. We performed a pharmacogenomic genome-wide association study (GWAS) for the genotype-by-ICS treatment effect on 3 years of forced expiratory volume in 1 s (FEV1) changes (estimated as slope) in 802 genotyped LHS-2 participants. Replication was performed in 199 COPD patients randomised to the ICS, fluticasone or placebo. A total of five loci showed genotype-by-ICS interaction at p&lt;5×10-6; of these, SNP rs111720447 on chromosome 7 was replicated (discovery p=4.8×10-6, replication p=5.9×10-5) with the same direction of interaction effect. ENCODE data revealed that in glucocorticoid treated (dexamethasone) A549 alveolar cell line, glucocorticoid receptor binding sites were located near SNP rs111720447. In stratified analyses of LHS-2, genotype at SNP rs111720447 was significantly associated with rate of FEV1 decline in patients taking ICS (C allele beta=56.35 mL·year-1, 95% confidence interval (CI)=29.96, 82.76 mL·yr-1) and also in patients who were assigned to placebo, though the relationship was weaker and in the opposite direction than that in the ICS group (C allele beta=-27.57 mL·year-1, 95% CI=-53.27, -1.87 mL·yr-1). The study uncovered genetic factors associated with FEV1 changes related to ICS in COPD patients, which may provide new insight on the potential biology of steroid responsiveness in COPD.</p

Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function.

BACKGROUND: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function. METHODS: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis. RESULTS: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10(-7)). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10(-8)) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively. CONCLUSIONS: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function

Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations.

Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10(-9)). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma

iNKT cell development is orchestrated by different branches of TGF-β signaling

Invariant natural killer T (iNKT) cells constitute a distinct subset of T lymphocytes exhibiting important immune-regulatory functions. Although various steps of their differentiation have been well characterized, the factors controlling their development remain poorly documented. Here, we show that TGF-β controls the differentiation program of iNKT cells. We demonstrate that TGF-β signaling carefully and specifically orchestrates several steps of iNKT cell development. In vivo, this multifaceted role of TGF-β involves the concerted action of different pathways of TGF-β signaling. Whereas the Tif-1γ branch controls lineage expansion, the Smad4 branch maintains the maturation stage that is initially repressed by a Tif-1γ/Smad4-independent branch. Thus, these three different branches of TGF-β signaling function in concert as complementary effectors, allowing TGF-β to fine tune the iNKT cell differentiation program