Analysis of folding of bladder structures

Analysis of folding bladder structure

Insights into the regulation of DMSP synthesis in the diatom Thalassiosira pseudonana through APR activity, proteomics and gene expression analyses on cells acclimating to changes in salinity, light and nitrogen

Despite the importance of dimethylsulphoniopropionate (DMSP) in the global sulphur cycle and climate regulation, the biological pathways underpinning its synthesis in marine phytoplankton remain poorly understood. The intracellular concentration of DMSP increases with increased salinity, increased light intensity and nitrogen starvation in the diatom Thalassiosira pseudonana. We used these conditions to investigate DMSP synthesis at the cellular level via analysis of enzyme activity, gene expression and proteome comparison. The activity of the key sulphur assimilatory enzyme, adenosine 5′- phosphosulphate reductase was not coordinated with increasing intracellular DMSP concentration. Under all three treatments coordination in the expression of sulphur assimilation genes was limited to increases in sulphite reductase transcripts. Similarly, proteomic 2D gel analysis only revealed an increase in phosphoenolpyruvate carboxylase following increases in DMSP concentration. Our findings suggest that increased sulphur assimilation might not be required for increased DMSP synthesis, instead the availability of carbon and nitrogen substrates may be important in the regulation of this pathway. This contrasts with the regulation of sulphur metabolism in higher plants, which generally involves upregulation of several sulphur assimilatory enzymes. In T. pseudonana changes relating to sulphur metabolism were specific to the individual treatments and, given that little coordination was seen in transcript and protein responses across the three growth conditions, different patterns of regulation might be responsible for the increase in DMSP concentration seen under each treatment

Anti-inflammatory agents and monoHER protect against DOX-induced cardiotoxicity and accumulation of CML in mice

Cardiac damage is the major limiting factor for the clinical use of doxorubicin (DOX). Preclinical studies indicate that inflammatory effects may be involved in DOX-induced cardiotoxicity. Nɛ-(carboxymethyl) lysine (CML) is suggested to be generated subsequent to oxidative stress, including inflammation. Therefore, the aim of this study was to investigate whether CML increased in the heart after DOX and whether anti-inflammatory agents reduced this effect in addition to their possible protection on DOX-induced cardiotoxicity. These effects were compared with those of the potential cardioprotector 7-monohydroxyethylrutoside (monoHER)

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study

Background Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2–11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75–1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58–1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91–1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70–1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11–0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50–0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38–0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45–0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. Funding Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health

Deformation of an Inertia-Loaded Thin Ring in a Rigid Cavity With Initial Clearance

BRIEF NOTES characteristics were observed for the limiting case of a rigid substrate considered by It may be observed that the load-deflection curves flatten and Q c decreases with decreasing values of the substrate stiffness K, and also that the unstable portion of each curve lies above those with higher K. This would seem to indicate that although buckling of the ring occurs at a lower load for a more compliant substrate, it appears to be accompanied by a less extensive &quot;jump&quot; in the deflection. This may be attributed to the smaller build up of strain energy preceding buckling for the more compliant system. We note here that, within the resolution of the figure, the curve corresponding to K/C= 10 3 in Let us first separate the systems considered into two categories, the first such that K&gt; C the substrates of which shall be referred to as &quot;stiff&quot; substrates, and the second category such that K&lt; C the substrates of which shall be said to be &quot;compliant.&quot; One may first observe from For the compliant substrates (K&lt;Q we observe a shifting to the right, of the corresponding load-deflection and loadinterface angle curves, as K decreases. This phenomenon offers the explanation that as the ring stiffness to substrate stiffness ratio increases, the system (initially) tends toward the behavior of a rigid ring confined by a compliant substrate, where for a rigid ring &lt;j&gt; = ir/2 for all finite K. We also observe, for K&lt;C, that #-&lt;j&gt; mi n as &lt;2 0 -*0 + and that the positive slopes of the corresponding Q 0 -&lt;f&gt; curves decrease with increasing K, indicating that the ring bends aways from the substrate with increasing Q 0 , immediately following the initial shrink dominated phase and that this behavior is more pronounced as if decreases. Chicurel, R., 1968, &quot;Shrink Buckling of Circular Rings,&quot; ASME JOURNAL OF APPLIED MECHANICS, Vol. 35, El-Bayoumy, L., 1972, &quot;Buckling of a Circular Elastic Ring Confined to a Uniformly Contracting Boundary,&quot; ASME JOURNAL OF APPLIED MECHANICS, Vol. 39, pp. 758-766. Hsu, P. T., Elkon, J., and Pian, T. H. H., 1964, &quot;Note on the Instability of Circular Rings Confined to a Rigid Boundary,&quot; ASME JOURNAL OF APPLIED MECHANICS, Vol. Propagation of steady waves and shocks in viscoelastic materials has been reviewed by where we have now set x = 0. The variables e, v, and a are required to vanish as f --oo. The quantity a in (1) is now the stress divided by the constant mass density. Because of the small range of strains and times involved in laboratory measurements of steady waves in real viscoelastic materials The function/(e) is asymptotic to e when the strain is small. For the present discussion we suppose that /(e)/e is an increasing function of e, and for illustrative purposes we use the form f(e)=e[l + (e/e c ) p ](P&gt;0). The asterisk in (2) denotes convolution over the interval (-oo, + oo), and the derivatives J&apos; and a&apos; are treated as generalized functions. J(t) is the compliance multiplied by the mass density. It is identically zero for /&lt;0, with initial value J 0 = 7(0 +) = 0. For t&gt; 0, J is an increasing function of t, with J&apos; decreasing. Experimentally determined compliances for some real materials are given in Ferry&apos;s book BRIEF NOTES form Ct&quot; J(t)=J 0 + J,(t/t r y (0&lt;p&lt;l). (4) Combining Note from (1) that v(t), which is more likely to be the observed quantity, is proportional to e(t). Warhola (1988) has devised a numerical algorithm for the solution of The quasi-elastic approximation furnishes a rigorous upper bound on the exact solution, and in cases of the type that are of main physical interest, the error in e q (t) is very small When P = 1 (a quadratic nonlinearity in/,) the wave form has the same shape as &lt;/(/). Schuler&apos;s (1970) observed wave forms are like those given by using (7) with a power-law compliance (4) with small p J&apos;*e = J[T(t)]e(t), T(t) must be approximately equal to t when the strain history is nearly a simple step at time zero. A closer approximation e a (t) can be obtained by using a more refined estimate of T, Since /(T) is the average value of J(s) with respect to the weight function e&apos; (t-s)/e(t), we estimate T as the average value of s itself with respect to the same weight function. With an integration by parts, this leads to the prescription with t (t)T(t)=\&apos; e a (s)ds f(e a )/e a = lPJ(T). Integration of (10) with appropriate initial conditions then gives t as a function of e a . This procedure gives the exact solution if J has the form (4) with p = 0 or p = 1. For real materials with J concave, e a lies between e q and the exact solution e if U&gt;U 0 . To test the accuracy of e q and e a , in some cases in which the exact solution is known, we use the forms (3) and (4) in For critical waves For P= 1, the factor K is unity at p = Q but 1/2 at p= 1, so e g (t) is accurate only at small/?. In contrast, the ratio e/e a is unity at both p = 0 and p= 1, and it is never less than about 0. with the upper sign for subcritical waves and the lower sign for supercritical waves. &lt;2(rj) is defined as tf /p\. To test the approximation e a (t) in a subcritical case, let A{r)) be the correspondingly scaled version of e a {t), and let T be the scaled version of T. Then, in place of The integration can be carried out in finite form if p=l/N with N an integer. To lighten the notation, let us take P= 1. This is the exact solution when N=$p=$. For N=20(p = 0.05), the exact and approximate solutions are compared in Acknowledgment We are grateful for the support from NSF grant DMS-8702866 and from the U.S. Air Force