Brinkman-type Operators on Riemannian Manifolds: Transmission Problems in Lipschitz and <Emphasis Type="Italic">C</Emphasis><Superscript>1</Superscript> Domains

In this paper we use the method of boundary integral equations to treat some transmission problems for Brinkman-type operators on Lipschitz and C ¹ domains in Riemannian manifolds.     

New Approach to the Synthesis of the Natural Product Aripuanin

Abstract

Aripuanin is a megastigmane that exists in the leaves of Ficus aripuanensis C.C. Berg (Moraceae). The present study describes a new approach to the total synthesis of this natural product starting from the readily available β-ionone. The proposed synthetic route provided racemic aripuanin in moderate yields (~31%). This route can be applied to the synthesis of other natural products bearing the megastigmane moiety, as well as to the enantioselective synthesis of aripuanin derivatives.     

Orbitrap mass spectrometry for monitoring the ganglioside pattern in human cerebellum development and aging

We have developed here a superior approach based on high‐resolution (HR) mass spectrometry (MS) for monitoring the changes occurring with development and aging in the composition and structure of cerebellar gangliosidome. The experiments were focused on the comparative screening and structural analysis of gangliosides expressed in fetal and aged cerebellum by Orbitrap MS with nanoelectrospray ionization (nanoESI) in the negative ion mode. The employed ultrahigh‐resolution MS platform allowed the discrimination, without the need of previous separation, of 159 ions corresponding to 120 distinct species in the native ganglioside mixtures from fetal and aged cerebellar biopsies, many more than detected before, when MS platforms of lower resolution were employed. A number of gangliosides, in particular polysialylated belonging to GT, GQ, GP, and GS classes, modified by O‐fucosylation, O‐acetylation, or CH₃COO^? were discovered here, for the first time in human cerebellum. These components, found differently expressed in fetal and aged tissues, indicated that the ganglioside profile in cerebellum is development stage‐ and age‐specific. Following the fragmentation analysis by high‐energy collision‐induced dissociation (HCD) tandem MS (MS/MS), we have also observed that the intimate structure of certain compounds has not changed during the development and aging of the brain, an aspect which could open new directions in the investigation of ganglioside biomarkers in cerebellar tissue.     

Rare-Earth Metal Complexes of the Antibacterial Drug Oxolinic Acid: Synthesis,Characterization, DNA/Protein Binding and Cytotoxicity Studies

“Drug repositioning” is a current trend which proved useful in the search for new applications for existing, failed, no longer in use or abandoned drugs, particularly when addressing issues such as bacterial or cancer cells resistance to current therapeutic approaches. In this context, six new complexes of the first-generation quinolone oxolinic acid with rare-earth metal cations (Y³⁺, La³⁺, Sm³⁺, Eu³⁺, Gd³⁺, Tb³⁺) have been synthesized and characterized. The experimental data suggest that the quinolone acts as a bidentate ligand, binding to the metal ion via the keto and carboxylate oxygen atoms; these findings are supported by DFT (density functional theory) calculations for the Sm³⁺ complex. The cytotoxic activity of the complexes, as well as the ligand, has been studied on MDA-MB 231 (human breast adenocarcinoma), LoVo (human colon adenocarcinoma) and HUVEC (normal human umbilical vein endothelial cells) cell lines. UV-Vis spectroscopy and competitive binding studies show that the complexes display binding affinities (K_b) towards double stranded DNA in the range of 9.33 × 10⁴ − 10.72 × 10⁵. Major and minor groove-binding most likely play a significant role in the interactions of the complexes with DNA. Moreover, the complexes bind human serum albumin more avidly than apo-transferrin.     

Boundary Value Problems of Robin Type for the Brinkman and Darcy–Forchheimer–Brinkman Systems in Lipschitz Domains

The purpose of this paper is to study boundary value problems of Robin type for the Brinkman system and a semilinear elliptic system, called the Darcy–Forchheimer–Brinkman system, on Lipschitz domains in Euclidean setting. In the first part of the paper, we exploit a layer potential analysis and a fixed point theorem to show the existence and uniqueness of the solution to the nonlinear Robin problem for the Darcy–Forchheimer–Brinkman system on a bounded Lipschitz domain in \({\mathbb{R}^n}\) \({(n \in \{2,3\})}\) with small data in L ²-based Sobolev spaces. In the second part, we show an existence result for the mixed Dirichlet–Robin problem for the same semilinear Darcy–Forchheimer-Brinkman system on a bounded creased Lipschitz domain in \({\mathbb{R}^3}\) with small L ²-boundary data. We also study mixed Dirichlet–Robin problems and boundary value problems of mixed Dirichlet–Robin and transmission type for Brinkman systems on bounded creased Lipschitz domains in \({\mathbb{R}^n}\) (n ≥ 3). Finally, we show the well-posedness of the Navier problem for the Brinkman system with boundary data in some L ²-based Sobolev spaces on a bounded Lipschitz domain in \({\mathbb{R}^3}\) .     

Ultrasound-assisted butyl acetate synthesis catalyzed by Novozym 435: Enhanced activity and operational stability

The influence of low-frequency ultrasound (40 kHz) in the esterification reaction between acetic acid and butanol for flavor ester synthesis catalyzed by the commercial immobilized lipase B from Candida antarctica (Novozym 435) was evaluated. A central composite design and the response surface methodology were used to analyze the effects of the reaction parameters (temperature, substrate molar ratio, enzyme content and added water) and their response (yields of conversion in 2.5 h of reaction). The reaction was carried out using n-hexane as solvent. The optimal conditions for ultrasound-assisted butyl acetate synthesis were found to be: temperature of 46 °C; substrate molar ratio of 3.6:1 butanol:acetic acid; enzyme content of 7%; added water of 0.25%, conditions that are slightly different from those found using mechanical mixing. Over 94% of conversion was obtained in 2.5 h under these conditions. The optimal acid concentration for the reaction was determined to be 2.0 M, compared to 0.3 M without ultrasound treatment. Enzyme productivity was significantly improved to around 7.5-fold for each batch when comparing ultrasound and standard mechanical agitation. The biocatalyst could be directly reused for 14 reactions cycles keeping around 70% of its original activity, while activity was virtually zeroed in the third cycle using the standard mixing system. Thus, compared to the traditional mechanical agitation, ultrasound technology not only improves the process productivity, but also enhances enzyme recycling and stability in the presence of acetic acid, being a powerful tool to improve biocatalyst performance in this type of reaction.     

Identification and structural characterization of novel O‐ and N‐glycoforms in the urine of a Schindler disease patient by Orbitrap mass spectrometry

Schindler disease is an inherited metabolic disorder caused by the deficient activity of α‐N‐acetylgalactosaminidase enzyme. An accurate diagnosis requires, besides clinical examination, complex and costly biochemical and molecular genetic tests. In the last years, mass spectrometry (MS) based on nanofluidics and high‐resolution instruments has become a successful alternative for disease diagnosis based on the investigation of O‐glycopeptides in patient urine. A complex mixture of glycoforms extracted from the urine of a 3‐year‐old patient was investigated by Orbitrap MS equipped with Nanospray Flex Ion Source in the negative ion mode. For structural characterization of several molecular species, collision‐induced dissociation MS²–MS³ was carried out using collision energy values within 20–60 eV range. By our approach, 39 novel species associated to this condition were identified, among which O‐glycopeptides, free O‐glycans and one structure corresponding to an N‐glycan never characterized in the context of Schindler disease. The experiments conducted at a resolution of 60 000 allowed the discrimination and identification of a total number of 69 different species with an average mass accuracy of 9.87 ppm, an in‐run reproducibility of almost 100%, an experiment‐to‐experiment and day‐to‐day reproducibility of about 95%. This study brings contributions in the diagnosis of Schindler disease through the elucidation of potential biomarker species in urine. Our multistage MS results completed with 39 new glycoforms the inventory of potential biomarker structures associated to Schindler disease. For the first time, an N‐glycan was identified and structurally characterized in Schindler patient urine, which opens new research directions in the field. Copyright © 2015 John Wiley & Sons, Ltd.     

Withaferin A—A Promising Phytochemical Compound with Multiple Results in Dermatological Diseases

Withaferin A (WFA) was identified as the most active phytocompound of the plant Withania somnifera (WS) and as having multiple therapeutic/ameliorating properties (anticancer, antiangiogenic, anti-invasive, anti-inflammatory, proapoptotic, etc.) in case of various diseases. In drug chemistry, WFA in silico approaches have identified favorite biological targets, stimulating and accelerating research to evaluate its pharmacological activity—numerous anticancer effects manifested in various organs (breast, pancreas, skin, colon, etc.), antivirals, anti-infective, etc., which are not yet sufficiently explored. This paper is a synthesis of the most relevant specialized papers in the field that are focused on the use of WFA in dermatological diseases, describing its mechanism of action while providing, at the same time, details about the results of its testing in in vitro/in vivo studies.     

Development and validation of an HPLC method for the determination of endocrine disruptors bisphenol A and benzophenone in thermochromic printing inks

The endocrine disruptors bisphenol A (BPA) and benzophenone (BFN) could be important ingredients in thermochromic printing inks in significant amounts. Due to patent protection and use of the inks, manufacturers are not obliged to state their precise chemical composition. These substances in increasingly used thermochromic printing inks present a hazard for human health and environment in the case of inappropriate application and waste disposal. In this work we enabled identification of the inks that contain these hazardous substances by developing a new method for the analysis of BPA and BFN in thermochromic printing inks. The method is based on the reversed-phase liquid chromatography (LC) with UV detection at 226 and 254?nm. Ultrasound-assisted sample extraction in methanol was proven to be the most suitable and effective among several other solvents. The method was completely validated with satisfactory results. The specificity of the method was proven by the additional LC–tandem mass spectrometry analysis. A representative group of 15 ink samples from various manufacturers, curing and printing modes was analyzed. BPA was found in three samples with mass fractions of about 2% while BFN was found in two samples with mass fractions of 0.34 and 0.66%.     

Dehydrocoupling Polymerization: Poly(silylether) Synthesis by Using an Iron β-Diketiminate Catalyst

We describe the iron-catalyzed polymerizations of diol and silane monomers to obtain fourteen different poly(silylether) products with number average molecular weights (M_n) up to 36.3 kDa. The polymerization reactions developed in this study are operationally simple and applicable to 1° and 2° silane monomer substrates and a range of benzylic and aliphatic diol substrates as well as one polyol example. The polymers were characterized by IR spectroscopy, DSC and TGA and, where solubility allowed, ¹H, ¹³C{¹H}, ²⁹Si{¹H} NMR spectroscopies, GPC and MALDI-TOF were also employed. The materials obtained displayed low T_g values (−70.6 to 19.1 °C) and were stable upon heating up to T_–5%,Ar 421.6 °C. A trend in T_–5%,Ar was observed whereby use of a 2° silane leads to higher T_–5%,Ar compared to those obtained using a 1° silane. Reaction monitoring was undertaken by in situ gas evolution studies coupled with GPC analysis to follow the progression of chain-length growth which confirmed a condensation polymerization-type mechanism.