That\u27s An Irish Lullaby (Too-ra-loo-ra-loo-ral)

[Verse 1] Over in Killarney, Many years ago, Me Mither sang a song to me In tones so sweet and low, Just a simple little ditty, In her good ould Irish way, And I’d give the world if she could sing That song to me this day. [Chorus] “Too-ra-loo-ra-loo-ral, Too-ra-loo-ra-li, Too-ra-loo-ra-loo-ral, Hush now, don’t you cry! Too-ra-loo-ra-loo-ral, Too-ra-loo-ra-li, Too-ra-loo-ra-loo-ral, That’s an Irish lullaby.” [Verse 2] Oft, in dreams, I wander To that cot again, I feel her arms a huggin’ me As when she held me then. And I hear her voice a hummin’ To me as in days of yore, When she used to tuck me fast asleep Outside the cabin door. [Chorus

A Global Treatment Of VMD Physics Up To The ϕ\phi: I. e+e−e^+e^- Annihilations, Anomalies And Vector Meson Partial Widths

The HLS Model, equipped with a mechanism providing the breaking of U(3)/SU(3) symmetry and an isospin symmetry breaking leading naturally to vector meson mixing, has been recently shown to successfully account for e^+ e^- \ra \pi^+\pi^- cross section and for the dipion spectrum in $\tau$ decay. The present study shows that the full anomalous sector of the HLS model can be considered and is validated by the experimental data. Indeed, this extended model provides a successful simultaneous fit to the e^+ e^- \ra \pi^+\pi^- data together with the available data on e^+ e^- \ra \pi^0\gamma, e^+ e^- \ra \eta\gamma and e^+ e^- \ra \pi^0 \pi^+\pi^- cross sections. It is shown that the fit of these data sets also predicts an accurate description of the \eta/\eta^\prime \ra \pi^+ \pi^- \gamma decays fully consistent with the reported information on their branching fractions and spectra. Finally, one also derives from our global fits products of widths of the form \Gamma (V \ra f_1)\Gamma(V \ra e^+ e^-) and ratios of the form \Gamma (V \ra f_1)/\Gamma (V \ra f_2) describing decays of vector mesons to several non--leptonic final states.Comment: 58 pages, 10 figures Corrected a few misprints. Footnote 10 change

Rheumatoid Arthritis Naive T Cells Share Hypermethylation Sites With Synoviocytes.

ObjectiveTo determine whether differentially methylated CpGs in synovium-derived fibroblast-like synoviocytes (FLS) of patients with rheumatoid arthritis (RA) were also differentially methylated in RA peripheral blood (PB) samples.MethodsFor this study, 371 genome-wide DNA methylation profiles were measured using Illumina HumanMethylation450 BeadChips in PB samples from 63 patients with RA and 31 unaffected control subjects, specifically in the cell subsets of CD14+ monocytes, CD19+ B cells, CD4+ memory T cells, and CD4+ naive T cells.ResultsOf 5,532 hypermethylated FLS candidate CpGs, 1,056 were hypermethylated in CD4+ naive T cells from RA PB compared to control PB. In analyses of a second set of CpG candidates based on single-nucleotide polymorphisms from a genome-wide association study of RA, 1 significantly hypermethylated CpG in CD4+ memory T cells and 18 significant CpGs (6 hypomethylated, 12 hypermethylated) in CD4+ naive T cells were found. A prediction score based on the hypermethylated FLS candidates had an area under the curve of 0.73 for association with RA case status, which compared favorably to the association of RA with the HLA-DRB1 shared epitope risk allele and with a validated RA genetic risk score.ConclusionFLS-representative DNA methylation signatures derived from the PB may prove to be valuable biomarkers for the risk of RA or for disease status

Microbiota and bile acid profiles in retinoic acid-primed mice that exhibit accelerated liver regeneration.

Background & aimsAll-trans Retinoic acid (RA) regulates hepatic lipid and bile acid homeostasis. Similar to bile acid (BA), RA accelerates partial hepatectomy (PHx)-induced liver regeneration. Because there is a bidirectional regulatory relationship between gut microbiota and BA synthesis, we examined the effect of RA in altering the gut microbial population and BA composition and established their relationship with hepatic biological processes during the active phases of liver regeneration.MethodsC57BL/6 mice were treated with RA orally followed by 2/3 PHx. The roles of RA in shifting gut microbiota and BA profiles as well as hepatocyte metabolism and proliferation were studied.ResultsRA-primed mice exhibited accelerated hepatocyte proliferation revealed by higher numbers of Ki67-positive cells compared to untreated mice. Firmicutes and Bacteroidetes phyla dominated the gut microbial community (>85%) in both control and RA-primed mice after PHx. RA reduced the ratio of Firmicutes to Bacteroidetes, which was associated with a lean phenotype. Consistently, RA-primed mice lacked transient lipid accumulation normally found in regenerating livers. In addition, RA altered BA homeostasis and shifted BA profiles by increasing the ratio of hydrophilic to hydrophobic BAs in regenerating livers. Accordingly, metabolic regulators fibroblast growth factor 21, Sirtuin1, and their downstream targets AMPK and ERK1/2 were more robustly activated in RA-primed than unprimed regenerating livers.ConclusionsPriming mice with RA resulted in a lean microbiota composition and hydrophilic BA profiles, which were associated with facilitated metabolism and enhanced cell proliferation

Citrullinated vimentin as an important antigen in immune complexes from synovial fluid of rheumatoid arthritis patients with antibodies against citrullinated proteins

Introduction: Rheumatoid arthritis (RA) is an inflammatory disease, which results in destruction of the joint. The presence of immune complexes (IC) in serum and synovial fluid of RA patients might contribute to this articular damage through different mechanisms, such as complement activation. Therefore, identification of the antigens from these IC is important to gain more insight into the pathogenesis of RA. Since RA patients have antibodies against citrullinated proteins (ACPA) in their serum and synovial fluid (SF) and since elevated levels of citrullinated proteins are detected in the joints of RA patients, citrullinated antigens are possibly present in IC from RA patients. Methods: IC from serum of healthy persons, serum of RA patients and IC from synovial fluid of RA patients and Spondyloarthropathy (SpA) patients were isolated by immunoprecipitation. Identification of the antigens was performed by SDS-PAGE, mass spectrometry and immunodetection. The presence of citrullinated proteins was evaluated by anti-modified citrulline (AMC) staining. Results: Circulating IC in the serum of RA patients and healthy controls contain fibrinogen beta and fibronectin, both in a non-citrullinated form. Additionally, in IC isolated from RA SF, fibrinogen. and vimentin were identified as well. More importantly, vimentin and a minor portion of fibrinogen beta were found to be citrullinated in the isolated complexes. Moreover these citrullinated antigens were only found in ACPA+ patients. No citrullinated antigens were found in IC from SF of SpA patients. Conclusions: Citrullinated fibrinogen beta and citrullinated vimentin were found in IC from SF of ACPA+ RA patients, while no citrullinated antigens were found in IC from SF of ACPA-RA patients or SpA patients or in IC from serum of RA patients or healthy volunteers. The identification of citrullinated vimentin as a prominent citrullinated antigen in IC from SF of ACPA+ RA patients strengthens the hypothesis that citrullinated vimentin plays an important role in the pathogenesis of RA

Regulating Retinoic Acid Availability during Development and Regeneration: The Role of the CYP26 Enzymes.

This review focuses on the role of the Cytochrome p450 subfamily 26 (CYP26) retinoic acid (RA) degrading enzymes during development and regeneration. Cyp26 enzymes, along with retinoic acid synthesising enzymes, are absolutely required for RA homeostasis in these processes by regulating availability of RA for receptor binding and signalling. Cyp26 enzymes are necessary to generate RA gradients and to protect specific tissues from RA signalling. Disruption of RA homeostasis leads to a wide variety of embryonic defects affecting many tissues. Here, the function of CYP26 enzymes is discussed in the context of the RA signalling pathway, enzymatic structure and biochemistry, human genetic disease, and function in development and regeneration as elucidated from animal model studies

Interleukin-7 deficiency in rheumatoid arthritis: consequences for therapy-induced lymphopenia

We previously demonstrated prolonged, profound CD4+ T-lymphopenia in rheumatoid arthritis (RA) patients following lymphocyte-depleting therapy. Poor reconstitution could result either from reduced de novo T-cell production through the thymus or from poor peripheral expansion of residual T-cells. Interleukin-7 (IL-7) is known to stimulate the thymus to produce new T-cells and to allow circulating mature T-cells to expand, thereby playing a critical role in T-cell homeostasis. In the present study we demonstrated reduced levels of circulating IL-7 in a cross-section of RA patients. IL-7 production by bone marrow stromal cell cultures was also compromised in RA. To investigate whether such an IL-7 deficiency could account for the prolonged lymphopenia observed in RA following therapeutic lymphodepletion, we compared RA patients and patients with solid cancers treated with high-dose chemotherapy and autologous progenitor cell rescue. Chemotherapy rendered all patients similarly lymphopenic, but this was sustained in RA patients at 12 months, as compared with the reconstitution that occurred in cancer patients by 3–4 months. Both cohorts produced naïve T-cells containing T-cell receptor excision circles. The main distinguishing feature between the groups was a failure to expand peripheral T-cells in RA, particularly memory cells during the first 3 months after treatment. Most importantly, there was no increase in serum IL-7 levels in RA, as compared with a fourfold rise in non-RA control individuals at the time of lymphopenia. Our data therefore suggest that RA patients are relatively IL-7 deficient and that this deficiency is likely to be an important contributing factor to poor early T-cell reconstitution in RA following therapeutic lymphodepletion. Furthermore, in RA patients with stable, well controlled disease, IL-7 levels were positively correlated with the T-cell receptor excision circle content of CD4+ T-cells, demonstrating a direct effect of IL-7 on thymic activity in this cohort

Joint Multi-Cell Resource Allocation Using Pure Binary-Integer Programming for LTE Uplink

Due to high system capacity requirement, 3GPP Long Term Evolution (LTE) is likely to adopt frequency reuse factor 1 at the cost of suffering severe inter-cell interference (ICI). One of combating ICI strategies is network cooperation of resource allocation (RA). For LTE uplink RA, requiring all the subcarriers to be allocated adjacently complicates the RA problem greatly. This paper investigates the joint multi-cell RA problem for LTE uplink. We model the uplink RA and ICI mitigation problem using pure binary-integer programming (BIP), with integrative consideration of all users' channel state information (CSI). The advantage of the pure BIP model is that it can be solved by branch-and-bound search (BBS) algorithm or other BIP solving algorithms, rather than resorting to exhaustive search. The system-level simulation results show that it yields 14.83% and 22.13% gains over single-cell optimal RA in average spectrum efficiency and 5th percentile of user throughput, respectively.Comment: Accepted to IEEE Vehicular Technology Conference (VTC Spring), Seoul, Korea, May, 201