High expression of P-selectin induces neutrophil extracellular traps via the PSGL-1/Syk/Ca2+/PAD4 pathway to exacerbate acute pancreatitis

BackgroundExcessive neutrophil extracellular traps (NETs) is involved in the progression of acute pancreatitis (AP) but the mechanisms controlling NETs formation in AP are not fully understood. Therefore, our study sought to investigate the mechanism of the highly expressed P-selectin stimulating the formation of NETs in AP.MethodsNETs formation was detected by flow cytometry, immunofluorescence staining, and cf-DNA and MPO-DNA complexes were measured as biomarkers of NETs formation. Neutrophils treated with P-selectin and pharmacological inhibitors were examined by western blot, immunofluorescence staining and flow cytometry. Mouse model of AP was established by caerulein and the effect of inhibiting P-selectin by PSI-697 on the level of NETs and PAD4 in pancreatic tissue was observed. The severity of AP was evaluated by histopathological score and the detection of serum amylase and lipase.ResultsPatients with AP had elevated levels of NETs and P-selectin compared with healthy volunteers. Stimulation of P-selectin up-regulated the expression of PSGL-1, increased the phosphorylation of Syk, mediated intracellular calcium signal and led to the activation and expression of PAD4, which modulated NETs formation in neutrophils. Pretreament with PSI-697 blunted NETs formation and PAD4 expression in the pancreatic tissue, and ameliorated the severity of AP in mice.ConclusionTaken together, these results suggest that P-selectin induces NETs through PSGL-1 and its downstream Syk/Ca2+/PAD4 signaling pathway, and that targeting this pathway might be a promising strategy for the treatment of AP

Permutation Entropy and Bubble Entropy: Possible interactions and synergies between order and sorting relations

[EN] Despite its widely demonstrated usefulness, there is still room for improvement in the basic Permutation Entropy (PE) algorithm, as several subsequent studies have proposed in the recent years. For example, some improved PE variants try to address possible PE weaknesses, such as its only focus on ordinal information, and not on amplitude, or the possible detrimental impact of equal values in subsequences due to motif ambiguity. Other evolved PE methods try to reduce the influence of input parameters. A good representative of this last point is the Bubble Entropy (BE) method. BE is based on sorting relations instead of ordinal patterns, and its promising capabilities have not been extensively assessed yet. The objective of the present study was to comparatively assess the classification performance of this new method, and study and exploit the possible synergies between PE and BE. The claimed superior performance of BE over PE was first evaluated by conducting a series of time series classification tests over a varied and diverse experimental set. The results of this assessment apparently suggested that there is a complementary relationship between PE and BE, instead of a superior/inferior relationship. A second set of experiments using PE and BE simultaneously as the input features of a clustering algorithm, demonstrated that with a proper algorithm configuration, classification accuracy and robustness can benefit from both measures.Cuesta Frau, D.; Vargas-Rojo, B. (2020). Permutation Entropy and Bubble Entropy: Possible interactions and synergies between order and sorting relations. Mathematical Biosciences and Engineering. 17(2):1637-1658. https://doi.org/10.3934/mbe.2020086S163716581721. C. Bandt and B. Pompe, Permutation entropy: A natural complexity measure for time series, Phys. Rev. Lett., 88 (2002), 174102.2. M. Zanin, L. Zunino, O. A. Rosso and D. 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N-Methylimidazole Promotes The Reaction Of Homophthalic Anhydride With Imines

The addition of N-methylimidazole (NMI) to the reaction of homophthalic anhydride with imines such as pyridine-3-carboxaldehyde-N-trifluoroethylimine (9) reduces the amount of elimination byproduct and improves the yield of the formal cycloadduct, tetrahydroisoquinolonic carboxylate 10. Carboxanilides of such compounds are of interest as potential antimalarial agents. A mechanism that rationalizes the role of NMI is proposed, and a gram-scale procedure for the synthesis and resolution of 10 is also described

The Muon Anomalous Magnetic Moment and the Standard Model

The muon anomalous magnetic moment measurement, when compared with theory, can be used to test many extensions to the standard model. The most recent measurement made by the Brookhaven E821 Collaboration reduces the uncertainty on the world average of a_mu to 0.7 ppm, comparable in precision to theory. This paper describes the experiment and the current theoretical efforts to establish a correct standard model reference value for the muon anomaly.Comment: Plenary Talk; PANIC'02 XVI Particles and Nuclear International Conference, Osaka, Japan; Sept. 30 - Oct. 4, 2002; Report describes the published 0.7 ppm result and updates the theory statu

Full deflection profile calculation and Young’s modulus optimisation for engineered high performance materials

New engineered materials have critical applications in different fields in medicine, engineering and technology but their enhanced mechanical performances are significantly affected by the microstructural design and the sintering process used in their manufacture. This work introduces (i) a methodology for the calculation of the full deflection profile from video recordings of bending tests, (ii) an optimisation algorithm for the characterisation of Young’s modulus, (iii) a quantification of the effects of optical distortions and (iv) a comparison with other standard tests. The results presented in this paper show the capabilities of this procedure to evaluate the Young’s modulus of highly stiff materials with greater accuracy than previously possible with bending tests, by employing all the available information from the video recording of the tests. This methodology extends to this class of materials the possibility to evaluate both the elastic modulus and the tensile strength with a single mechanical test, without the need for other experimental tools

Supercapacitance from cellulose and carbon nanotube nanocomposite fibers

Copyright © 2013 American Chemical SocietyACS AuthorChoice open access articleMultiwalled carbon nanotube (MWNT)/cellulose composite nanofibers have been prepared by electrospinning a MWNT/cellulose acetate blend solution followed by deacetylation. These composite nanofibers were then used as precursors for carbon nanofibers (CNFs). The effect of nanotubes on the stabilization of the precursor and microstructure of the resultant CNFs were investigated using thermogravimetric analysis, transmission electron microscopy and Raman spectroscopy. It is demonstrated that the incorporated MWNTs reduce the activation energy of the oxidative stabilization of cellulose nanofibers from 230 to 180 kJ mol–1. They also increase the crystallite size, structural order, and electrical conductivity of the activated CNFs (ACNFs). The surface area of the ACNFs increased upon addition of nanotubes which protrude from the fiber leading to a rougher surface. The ACNFs were used as the electrodes of a supercapacitor. The electrochemical capacitance of the ACNF derived from pure cellulose nanofibers is demonstrated to be 105 F g–1 at a current density of 10 A g–1, which increases to 145 F g–1 upon the addition of 6% of MWNTs.The authors would like to thank the [Engineering and Physical Sciences Research Council] EPSRC (EP/F036914/1 and EP/I023879/1), Guangdong and Shenzhen Innovative Research Team Program (No. 2011D052,KYPT20121228160843692), National Natural Science Foundation of China (Grant No. 21201175), R&D Funds for basic Research Program of Shenzhen (Grant No. JCYJ20120615140007998), and the Universities of Exeter and Manchester for funding this research

Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications.

Analysis of DNA methylation patterns relies increasingly on sequencing-based profiling methods. The four most frequently used sequencing-based technologies are the bisulfite-based methods MethylC-seq and reduced representation bisulfite sequencing (RRBS), and the enrichment-based techniques methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylated DNA binding domain sequencing (MBD-seq). We applied all four methods to biological replicates of human embryonic stem cells to assess their genome-wide CpG coverage, resolution, cost, concordance and the influence of CpG density and genomic context. The methylation levels assessed by the two bisulfite methods were concordant (their difference did not exceed a given threshold) for 82% for CpGs and 99% of the non-CpG cytosines. Using binary methylation calls, the two enrichment methods were 99% concordant and regions assessed by all four methods were 97% concordant. We combined MeDIP-seq with methylation-sensitive restriction enzyme (MRE-seq) sequencing for comprehensive methylome coverage at lower cost. This, along with RNA-seq and ChIP-seq of the ES cells enabled us to detect regions with allele-specific epigenetic states, identifying most known imprinted regions and new loci with monoallelic epigenetic marks and monoallelic expression

What is 'Open'? An Economic Analysis of Open Institutions

By examining several different types of open institutions including open source software, open science, open square and (open) urban planning, this paper presents a general analysis of open institutional structure that is complementary to traditional proprietary mode. We argue that open institutions, in whatever forms, are essentially about decentralized production of a collective good (or “commons”) that relies on voluntary collaboration of highly variable human-related input. In addition to providing a general definition of open institutional structure, we submit there are two necessary conditions for open institutions. The first is the integration of consumers into production. The second condition is that the efficiency gain from “production” commons is the objective and the tragedy of anticommons becomes a serious problem. In this sense, open institutions represent a positive approach toward externality and uncertainty

Spanning Forests on Random Planar Lattices

The generating function for spanning forests on a lattice is related to the q-state Potts model in a certain q -> 0 limit, and extends the analogous notion for spanning trees, or dense self-avoiding branched polymers. Recent works have found a combinatorial perturbative equivalence also with the (quadratic action) O(n) model in the limit n -> -1, the expansion parameter t counting the number of components in the forest. We give a random-matrix formulation of this model on the ensemble of degree-k random planar lattices. For k = 3, a correspondence is found with the Kostov solution of the loop-gas problem, which arise as a reformulation of the (logarithmic action) O(n) model, at n = -2. Then, we show how to perform an expansion around the t = 0 theory. In the thermodynamic limit, at any order in t we have a finite sum of finite-dimensional Cauchy integrals. The leading contribution comes from a peculiar class of terms, for which a resummation can be performed exactly.Comment: 43 pages, Dedicated to Edouard Brezin and Giorgio Parisi, on the occasion of their special birthda