A Dual Consistent Finite Difference Method with Narrow Stencil Second Derivative Operators

We study the numerical solutions of time-dependent systems of partial differential equations, focusing on the implementation of boundary conditions. The numerical method considered is a finite difference scheme constructed by high order summation by parts operators, combined with a boundary procedure using penalties (SBP–SAT). Recently it was shown that SBP–SAT finite difference methods can yield superconvergent functional output if the boundary conditions are imposed such that the discretization is dual consistent. We generalize these results so that they include a broader range of boundary conditions and penalty parameters. The results are also generalized to hold for narrow-stencil second derivative operators. The derivations are supported by numerical experiments.     

Senescence-Independent Anti-Inflammatory Activity of the Senolytic Drugs Dasatinib,Navitoclax, and Venetoclax in Zebrafish Models of Chronic Inflammation

Telomere shortening is the main molecular mechanism of aging, but not the only one. The adaptive immune system also ages, and older organisms tend to develop a chronic pro-inflammatory status with low-grade inflammation characterized by chronic activation of the innate immune system, called inflammaging. One of the main stimuli that fuels inflammaging is a high nutrient intake, triggering a metabolic inflammation process called metainflammation. In this study, we report the anti-inflammatory activity of several senolytic drugs in the context of chronic inflammation, by using two different zebrafish models: (i) a chronic skin inflammation model with a hypomorphic mutation in spint1a, the gene encoding the serine protease inhibitor, kunitz-type, 1a (also known as hai1a) and (ii) a non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH) model with inflammation induced by a high-fat diet. Our results show that, although these models do not manifest premature aging, the senolytic drugs dasatinib, navitoclax, and venetoclax have an anti-inflammatory effect that results in the amelioration of chronic inflammation.     

Accuracy of FIB-4 to Detect Elevated Liver Stiffness Measurements in Patients with Non-Alcoholic Fatty Liver Disease: A Cross-Sectional Study in Referral Centers

The identification of advanced fibrosis by applying noninvasive tests is still a key component of the diagnostic algorithm of NAFLD. The aim of this study is to assess the concordance between the FIB-4 and liver stiffness measurement (LSM) in patients referred to two liver centers for the ultrasound-based diagnosis of NAFLD. Fibrosis 4 Index for Liver Fibrosis (FIB-4) and LSM were assessed in 1338 patients. A total of 428 (32%) had an LSM ≥ 8 kPa, whereas 699 (52%) and 113 (9%) patients had an FIB-4 < 1.3 and >3.25, respectively. Among 699 patients with an FIB-4 < 1.3, 118 (17%) had an LSM ≥ 8 kPa (false-negative FIB-4). This proportion was higher in patients ≥60 years, with diabetes mellitus (DM), arterial hypertension or a body mass index (BMI) ≥ 27 kg/m². In multiple adjusted models, age ≥ 60 years (odds ratio (OR) = 1.96, 95% confidence interval (CI) 1.19–3.23)), DM (OR = 2.59, 95% CI 1.63–4.13), body mass index (BMI) ≥ 27 kg/m² (OR = 2.17, 95% CI 1.33–3.56) and gamma-glutamyltransferase ≥ 25 UI/L (OR = 2.68, 95% CI 1.49–4.84) were associated with false-negative FIB-4. The proportion of false-negative FIB-4 was 6% in patients with none or one of these risk factors and increased to 16, 31 and 46% among those with two, three and four concomitant risk factors, respectively. FIB-4 is suboptimal to identify patients to refer to liver centers, because about one-fifth may be false negative at FIB-4, having instead an LSM ≥ 8 KPa.     

Phenylvinilbisquinolines as fluorescent markers in functionalized polypropylene films

Polymer Bulletin - In this work, polypropylene films (PP) and maleic anhydride graft polypropylene (PPgMA) at different concentrations of a photoluminescent dye 2,2′-(1,4-phenylenedivinylene)...     

Expression and Roles of Individual HIF Prolyl 4-Hydroxylase Isoenzymes in the Regulation of the Hypoxia Response Pathway along the Murine Gastrointestinal Epithelium

The HIF prolyl 4-hydroxylases (HIF-P4H) control hypoxia-inducible factor (HIF), a powerful mechanism regulating cellular adaptation to decreased oxygenation. The gastrointestinal epithelium subsists in “physiological hypoxia” and should therefore have an especially well-designed control over this adaptation. Thus, we assessed the absolute mRNA expression levels of the HIF pathway components, Hif1a, HIF2a, Hif-p4h-1, 2 and 3 and factor inhibiting HIF (Fih1) in murine jejunum, caecum and colon epithelium using droplet digital PCR. We found a higher expression of all these genes towards the distal end of the gastrointestinal tract. We detected mRNA for Hif-p4h-1, 2 and 3 in all parts of the gastrointestinal tract. Hif-p4h-2 had significantly higher expression levels compared to Hif-p4h-1 and 3 in colon and caecum epithelium. To test the roles each HIF-P4H isoform plays in the gut epithelium, we measured the gene expression of classical HIF target genes in Hif-p4h-1^−/−, Hif-p4h-2 hypomorph and Hif-p4h-3^−/− mice. Only Hif-p4h-2 hypomorphism led to an upregulation of HIF target genes, confirming a predominant role of HIF-P4H-2. However, the abundance of Hif-p4h-1 and 3 expression in the gastrointestinal epithelium implies that these isoforms may have specific functions as well. Thus, the development of selective inhibitors might be useful for diverging therapeutic needs.     

Synthesis and Biological Studies of Pyrazolyl‐Diamine PtII Complexes Containing Polyaromatic DNA‐Binding Groups

New [PtCl(pz*NN)]ⁿ⁺ complexes anchored by pyrazolyl‐diamine (pz*NN) ligands incorporating anthracenyl or acridine orange DNA‐binding groups have been synthesized so as to obtain compounds that would display synergistic effects between platination and intercalation of DNA. Study of their interaction with supercoiled DNA indicated that the anthracenyl‐containing complex L²Pt displays a covalent type of binding, whereas the acridine orange counterpart L³Pt shows a combination of intercalative and covalent binding modes with a strong contribution from the former. L²Pt showed a very strong cytotoxic effect on ovarian carcinoma cell lines A2780 and A2780cisR, which are, respectively, sensitive to and resistant to cisplatin. In these cell lines, L²Pt is nine to 27 times more cytotoxic than cisplatin. In the sensitive cell line, L³Pt showed a cytotoxic activity similar to that of cisplatin, but like L²Pt was able significantly to overcome cisplatin cross‐resistance. Cell‐uptake studies showed that L²Pt accumulates preferentially in the cytoplasm, whereas L³Pt reaches the cell nucleus more easily, as clearly visualized by time‐lapse confocal imaging of live A2870 cells. Altogether, these findings seem to indicate that interaction with biological targets other than DNA might be involved in the mechanism of action of L²Pt because this compound, despite having a weaker ability to target the cell nucleus than L³Pt , as well as an inferior DNA affinity, is nevertheless more cytotoxic. Furthermore, ultrastructural studies of A2870 cells exposed to L²Pt and L³Pt revealed that these complexes induce different alterations in cell morphology, thus indicating the involvement of different modes of action in cell death.     

Hydrogen‐Bonding‐Driven Enantioselective Resolution against the Kazlauskas Rule To Afford γ‐Amino Alcohols by Candida rugosa Lipase

Most lipases resolve secondary alcohols in accordance with the “Kazlauskas rule” to give the R enantiomers. In a similar manner to other lipases, Candida rugosa lipase (CRL) exhibits R enantioselectivity towards heptan‐2‐ol, although the enantiomeric ratio (E) is low (E=1.6). However, unexpected enantioselectivity (i.e., S enantioselectivity, E=58) of CRL towards 4‐(tert‐butoxycarbonylamino)butan‐2‐ol, which has a similar chain length to heptan‐2‐ol, has been observed. To develop a deeper understanding of the molecular basis for this unusual enantioselectivity, we have conducted a series of molecular modeling and substrate engineering experiments. The results of these computational and experimental analyses indicated that a hydrogen bond between the Ser450 residue and the nitrogen atom of the carbamate group is critical to stabilize the transition state of the S enantiomer.     

Influence of chemical structure of hardener on mechanical and adhesive properties of epoxy polymers

The mechanical and adhesive properties of epoxy formulations based on diglycidyl ether of bisphenol A cured with various aliphatic amines were evaluated in the glass state. Impact and uniaxial compression tests were used to determine the impact energy, elastic modulus and yield stress, respectively. The adhesion tests were carried out in steel–steel joints using single‐lap shear, T‐peel, and impact adhesive joints geometry. The better mechanical and adhesive behavior of the networks is obtained when exists high flexibility of chain between crosslink and/or high elastic modulus. The 1‐(2‐aminoethyl)piperazine epoxy network presents the best adhesive properties, high flexibility, and the largest impact energy. However, it possesses low elastic modulus and yield stress. Also, exhibits increases in peel strength and impact energy while reductions in lap shear strength. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

The Effect of the Ionizing Radiation on Hydroxyapatite–Polydimethylsiloxane Layers

The bio hydroxyapatite (HAp) was used from a long time in different medical and environmental applications. The HAp layers with a uniform surface were used for various medical applications such as orthopedic and dental metal implants. In this work, we reported on the influence of X‐ray radiation on the structural and morphological properties of composite layers based on HAp and polydimethylsiloxane (PDMS) deposited on titanium substrates. The HAp:PDMS layers were investigated by different complementary methods such as scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and glow discharge optical emission spectrometry (GDOES). FTIR spectral analysis showed that the molecular structure of the coatings was not changed after their irradiation even though, the depth profile analysis performed by GDOES indicated a depletion of Ca and P elements from the HAp:PDMS irradiated samples. By SEM, we showed that the morphological features of the coatings were also changed, as the irradiated layers are delaminated. The biological assays confirmed that the antibacterial activity of HAp:PDMS composite layers increased after irradiation. The results obtained in this study highlighted that the biological properties of HAp:PDMS layers could be influenced by irradiation. POLYM. ENG. SCI., 59:2406–2412, 2019. © 2019 Society of Plastics Engineers