The puzzling symbiotic X-ray system 4U1700+24

Symbiotic X-ray binaries form a subclass of low-mass X-ray binary systems consisting of a neutron star accreting material from a red giant donor star via stellar wind or Roche lobe overflow. Only a few confirmed members are currently known; 4U 1700+24 is a good candidate as it is a relatively bright X-ray object, possibly associated with the late-type star V934 Her. We analysed the archive {\it XMM}-Newton and Swift/XRT observations of 4U 1700+24 in order to have a uniform high-energy ($0.3-10$ keV) view of the source. We confirmed the existence of a red-shifted O VIII Ly-$\alpha$ transition (already observed in the 2002 {\it XMM}-Newton data) in the high-resolution spectra collected via the RGS instruments. The red-shift of the line is found in all the analysed observations and, on average, it was estimated to be $\simeq 0.009$. We also observed a modulation of the centroid energy of the line on short time scales (a few days) and discuss the observations in the framework of different scenarios. If the modulation is due to the gravitational red-shift of the neutron star, it might arise from a sudden re-organization of the emitting $X$-ray matter on the scale of a few hundreds of km. Alternatively, we are witnessing a uni-polar jet of matter (with typical velocity of $1000-4000$ km s$^{-1}$) possibly emitted by the neutron star in an almost face-on system. The second possibility seems to be required by the apparent lack of any modulation in the observed $X$-ray light curve. We also note also that the low-resolution spectra (both {\it XMM}-Newton and Swift/XRT in the $0.3-10$ keV band) show the existence of a black body radiation emitted by a region (possibly associated with the neutron star polar cap) with typical size from a few tens to hundreds of meters. The size of this spot-like region reduces as the overall luminosity of 4U 1700+24 decreases.Comment: In press on A&

Harmonic theta series and the kodaira dimension of a6

We construct a basis of the space S14(Sp12(ℤ)) of Siegel cusp forms of degree 6 and weight 14 consisting of harmonic theta series. One of these functions has vanishing order 2 at the boundary which implies that the Kodaira dimension of A6 is nonnegative

Learning effect of humphrey matrix frequency doubling technology perimetry in patients with ocular hypertension

Aim: To evaluate the learning effect of Frequency Doubling Technology (FDT) perimetry using the Humphrey Matrix-FDT perimetry (Matrix) 24-2 full-threshold program on patients with 7 ocular hypertension experienced with standard automated perimetry. Methods: Twenty-four patients with Ocular hypertension underwent 5 full-threshold Matrix tests at intervals of 5 2 days. Learning effect was defined as an improvement at results for duration, perimetric indices, foveal sensitivity, Glaucoma Hemifield Test, and the number of points with a P < 5% and < 1% in the total and pattern deviation maps. Eccentricity, hemifield, and quadrant sensitivities were also addressed as Sources of differences in learning effect. Test-retest variability was also calculated for each repetition as the mean of the point-to-point interindividual standard deviations. Results: A learning effect was demonstrated for mean defect (P = 0.031, analysis of variance) and foveal sensitivity (P = 0.009) and it only affected the first test for both parameters. All the other parameters did not show any significant learning effect. The effect was independent From eccentricity and quadrant or hemifield sensitivities. Conclusions: The results of this study demonstrate that the learning effect for Matrix-FDT is mild and it may affect only the first test. Caution is needed in the analysis of the first Matrix-FDT examination and retest may be advisable in the presence of low mean defect

PAAT: a path to atherosclerosis

The artery wall consists ofintima, media, and adventitia, the latter gradually transiting into the periadventitial adipose tissue (PAAT). Although many paths lead to atherosclerosis, the prevailing paradigm at present is Russell Ross's response-to-injury hypothesis, which states that atherosclerosis is a chronic inflammatory disease. This hypothesis considers the intimal smooth muscle cell proliferation as a key event in the generation, development and complication of atherosclerosis. Thus the potentially important role played by adventitial fibroblasts/myofibroblasts in atherosclerosis and postangioplasty restenosis, suggesting therapeutic perspectives targeted to these particular cells, has been neglected. Here we go further away from the intima, and focus on the potential involvement of PAAT in the process of atherogenesis and angioplasty-induced restenosis.Biomedical Reviews 2002; 13: 63-65

An Evaluation of Therapeutic Noninferiority of 0.005% Latanoprost Ophthalmic Solution and Xalatan in Patients With Glaucoma or Ocular Hypertension.

PURPOSE: To assess the therapeutic noninferiority of 0.005% latanoprost ophthalmic solution versus Xalatan in the treatment of patients with primary open-angle glaucoma or ocular hypertension. PATIENTS AND METHODS: This was a double-masked, randomized, multicenter study. A total of 184 patients with a diagnosis of unilateral or bilateral primary open-angle glaucoma or ocular hypertension were randomly assigned to either 0.005% latanoprost ophthalmic solution or Xalatan for 12 weeks. The primary end-point was the change in intraocular pressure (IOP) at 12 weeks in the 2 groups. Noninferiority was reached if the 2-sided 95% confidence intervals (CI) for the difference between adjusted treatment means were entirely within the interval from -1.5 to +1.5 mm Hg. RESULTS: The difference between treatments in the change of IOP from baseline to the end of treatment was 0.12 mm Hg (95% CI: -0.47, 0.71) in the intention-to-treat population and 0 mm Hg (95% CI: -0.58, 0.57) in the per protocol population. There was no statistically significant difference between the 2 groups in terms of drug-related adverse events. The most commonly reported drug-related local adverse events were: ocular hyperemia, eyelashes growth, and eye irritation. CONCLUSIONS: This study demonstrates that 0.005% latanoprost ophthalmic solution is noninferior to Xalatan in lowering IOP and is generally well tolerate

Protease-activated receptor 2 sensitizes the capsaicin receptor transient receptor potential vanilloid receptor 1 to induce hyperalgesia

Inflammatory proteases (mast cell tryptase and trypsins) cleave protease-activated receptor 2 (PAR2) on spinal afferent neurons and cause persistent inflammation and hyperalgesia by unknown mechanisms. We determined whether transient receptor potential vanilloid receptor 1 (TRPV1), a cation channel activated by capsaicin, protons, and noxious heat, mediates PAR2-induced hyperalgesia. PAR2 was coexpressed with TRPV1 in small- to medium-diameter neurons of the dorsal root ganglia (DRG), as determined by immunofluorescence. PAR2 agonists increased intracellular [Ca2+] ([Ca2+]i) in these neurons in culture, and PAR2-responsive neurons also responded to the TRPV1 agonist capsaicin, confirming coexpression of PAR2 and TRPV1. PAR2 agonists potentiated capsaicin-induced increases in [Ca2+]i in TRPV1-transfected human embryonic kidney (HEK) cells and DRG neurons and potentiated capsaicin-induced currents in DRG neurons. Inhibitors of phospholipase C and protein kinase C (PKC) suppressed PAR2-induced sensitization of TRPV1-mediated changes in [Ca2+]i and TRPV1 currents. Activation of PAR2 or PKC induced phosphorylation of TRPV1 in HEK cells, suggesting a direct regulation of the channel. Intraplantar injection of a PAR2 agonist caused persistent thermal hyperalgesia that was prevented by antagonism or deletion of TRPV1. Coinjection of nonhyperalgesic doses of PAR2 agonist and capsaicin induced hyperalgesia that was inhibited by deletion of TRPV1 or antagonism of PKC. PAR2 activation also potentiated capsaicin-induced release of substance P and calcitonin gene-related peptide from superfused segments of the dorsal horn of the spinal cord, where they mediate hyperalgesia. We have identified a novel mechanism by which proteases that activate PAR2 sensitize TRPV1 through PKC. Antagonism of PAR2, TRPV1, or PKC may abrogate protease-induced thermal hyperalgesia

An evaluation of the role of miR-361-5p in senescence and systemic ageing

This is the final version. Available on open access from Elsevier via the DOI in this recordData availability: The data presented in this study are available upon reasonable request from the corresponding author. The data are not publicly available for reasons of intellectual property.Senescent cells are key regulators of ageing and age-associated disease. MicroRNAs (miRs) are a key component of the molecular machinery governing cellular senescence, with several known to regulate important genes associated with this process. We sought to identify miRs associated with both senescence and reversal by pinpointing those showing opposing directionality of effect in senescence and in response to senotherapy. Cellular senescence phenotypes were assessed in primary human endothelial cells following targeted manipulation of emergent miRNAs. Finally, the effect of conserved target gene knockdown on lifespan and healthspan was assessed in a C. elegans system in vivo. Three miRNAs (miR-5787, miR-3665 and miR-361-5p) demonstrated associations with both senescence and rejuvenation, but miR-361-5p alone demonstrated opposing effects in senescence and rescue. Treatment of late passage human endothelial cells with a miR-361-5p mimic caused a 14 % decrease in the senescent load of the culture. RNAi gene knockdown of conserved miR-361-5p target genes in a C. elegans model however resulted in adverse effects on healthspan and/or lifespan. Although miR-361-5p may attenuate aspects of the senescence phenotype in human primary endothelial cells, many of its validated target genes also play essential roles in the regulation or formation of the cytoskeletal network, or its interaction with the extracellular matrix. These processes are essential for cell survival and cell function. Targeting miR-361-5p alone may not represent a promising target for future senotherapy; more sophisticated approaches to attenuate its interaction with specific targets without roles in essential cell processes would be required.Al Jouf UniversitySaudi Arabia Cultural Bureau, UKNational Institute for Health and Care Research (NIHR