Different Expression of Mitochondrial and Endoplasmic Reticulum Stress Genes in Epicardial Adipose Tissue Depends on Coronary Atherosclerosis

The aim of our study was to analyze mitochondrial and endoplasmic reticulum (ER) gene expression profiles in subcutaneous (SAT) and epicardial (EAT) adipose tissue, skeletal muscle, and myocardium in patients with and without CAD undergoing elective cardiac surgery. Thirty-eight patients, 27 with (CAD group) and 11 without CAD (noCAD group), undergoing coronary artery bypass grafting and/or valvular surgery were included in the study. EAT, SAT, intercostal skeletal muscle, and right atrium tissue and blood samples were collected at the start and end of surgery; mRNA expression of selected mitochondrial and ER stress genes was assessed using qRT-PCR. The presence of CAD was associated with decreased mRNA expression of most of the investigated mitochondrial respiratory chain genes in EAT, while no such changes were seen in SAT or other tissues. In contrast, the expression of ER stress genes did not differ between the CAD and noCAD groups in almost any tissue. Cardiac surgery further augmented mitochondrial dysfunction in EAT. In our study, CAD was associated with decreased expression of mitochondrial, but not endoplasmic reticulum stress genes in EAT. These changes may contribute to the acceleration of coronary atherosclerosis.     

Evaluation of Floxuridine Oligonucleotide Conjugates Carrying Potential Enhancers of Cellular Uptake

Conjugation of small molecules such as lipids or receptor ligands to anti-cancer drugs has been used to improve their pharmacological properties. In this work, we studied the biological effects of several small-molecule enhancers into a short oligonucleotide made of five floxuridine units. Specifically, we studied adding cholesterol, palmitic acid, polyethyleneglycol (PEG 1000), folic acid and triantennary N-acetylgalactosamine (GalNAc) as potential enhancers of cellular uptake. As expected, all these molecules increased the internalization efficiency with different degrees depending on the cell line. The conjugates showed antiproliferative activity due to their metabolic activation by nuclease degradation generating floxuridine monophosphate. The cytotoxicity and apoptosis assays showed an increase in the anti-cancer activity of the conjugates related to the floxuridine oligomer, but this effect did not correlate with the internalization results. Palmitic and folic acid conjugates provide the highest antiproliferative activity without having the highest internalization results. On the contrary, cholesterol oligomers that were the best-internalized oligomers had poor antiproliferative activity, even worse than the unmodified floxuridine oligomer. Especially relevant is the effect induced by palmitic and folic acid derivatives generating the most active drugs. These results are of special interest for delivering other therapeutic oligonucleotides.     

Interplay between Coumarin Accumulation,Iron Deficiency and Plant Resistance to Dickeya spp.

Coumarins belong to a group of secondary metabolites well known for their high biological activities including antibacterial and antifungal properties. Recently, an important role of coumarins in plant resistance to pathogens and their release into the rhizosphere upon pathogen infection was discovered. It is also well documented that coumarins play a crucial role in the Arabidopsis thaliana growth under Fe-limited conditions. However, the mechanisms underlying interplay between plant resistance, accumulation of coumarins and Fe status, remain largely unknown. In this work, we investigated the effect of both mentioned factors on the disease severity using the model system of Arabidopsis/Dickeya spp. molecular interactions. We evaluated the disease symptoms in Arabidopsis plants, wild-type Col-0 and its mutants defective in coumarin accumulation, grown in hydroponic cultures with contrasting Fe regimes and in soil mixes. Under all tested conditions, Arabidopsis plants inoculated with Dickeya solani IFB0099 strain developed more severe disease symptoms compared to lines inoculated with Dickeya dadantii 3937. We also showed that the expression of genes encoding plant stress markers were strongly affected by D. solani IFB0099 infection. Interestingly, the response of plants to D. dadantii 3937 infection was genotype-dependent in Fe-deficient hydroponic solution.     

Characterization of Apo-Form Selective Inhibition of Indoleamine 2,3-Dioxygenase**

Indoleamine-2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme that catalyzes the rate-limiting step in the kynurenine pathway of tryptophan (TRP) metabolism. As it is an inflammation-induced immunoregulatory enzyme, pharmacological inhibition of IDO1 activity is currently being pursued as a potential therapeutic tool for the treatment of cancer and other disease states. As such, a detailed understanding of the mechanism of action of IDO1 inhibitors with various mechanisms of inhibition is of great interest. Comparison of an apo-form-binding IDO1 inhibitor (GSK5628) to the heme-coordinating compound, epacadostat (Incyte), allows us to explore the details of the apo-binding inhibition of IDO1. Herein, we demonstrate that GSK5628 inhibits IDO1 by competing with heme for binding to a heme-free conformation of the enzyme (apo-IDO1), whereas epacadostat coordinates its binding with the iron atom of the IDO1 heme cofactor. Comparison of these two compounds in cellular systems reveals a long-lasting inhibitory effect of GSK5628, previously undescribed for other known IDO1 inhibitors. Detailed characterization of this apo-binding mechanism for IDO1 inhibition might help design superior inhibitors or could confer a unique competitive advantage over other IDO1 inhibitors vis-à-vis specificity and pharmacokinetic parameters.     

Effect of Ca2+ and Mg2+ ions on the sintering and spectroscopic properties of cr-doped yttrium aluminum garnet ceramics

In this work, we investigated the effects of Ca²⁺ and Mg²⁺ ions and annealing temperature on the spectroscopic parameters of chromium-doped yttrium aluminum garnet ceramics (Cr:YAG). Samples were obtained with either a separate or a simultaneous addition of calcium and magnesium oxides. To achieve this, aqueous suspensions were prepared using Y₂O₃, Al₂O₃, Cr₂O₃, MgO, and CaO high-purity powders as raw materials. The obtained suspensions were freeze-granulated, pressed into pellets, debinded, and subjected to reactive sintering in vacuum at 1715°C for 6 h. Each material was annealed in air with temperatures between 1300 and 1700°C. Samples were also compared to Cr:YAG ceramics with the addition of silica as a sintering aid. All the materials obtained were then exposed to 445 nm excitation, and emission spectra in the visible and infrared wavelengths were recorded. The results showed that the emission spectra of Cr:YAG ceramics varied according to the annealing conditions: as-sintered samples exhibited strong emissions of around 680 nm and, after air annealing, of around 1400 nm. This phenomenon is attributed to the Cr³⁺→Cr⁴⁺ transition. Samples doped solely with MgO exhibited the highest emission intensity in the infrared region. Thus, Mg²⁺ ions provided the best conversion efficiency of chromium ions.     

Effect of Density and Processing Conditions on Oxide Transformations and Mechanical Properties in Cr–Mo-Alloyed PM steels

To improve the mechanical properties and performances of water-atomized powder metallurgy steels, it is necessary to enhance the density. Consolidating water-atomized steel powders via conventional pressing and sintering to a relative density level > 95 pct involves processing challenges. Consolidation of gas-atomized powders to full density by hot isostatic pressing (HIP) is an established process route but utilizing water-atomized powders in HIP involves challenges that result in the formation of prior particle boundaries due to higher oxygen content. In this study, the effect of density and processing conditions on the oxide transformations and mechanical properties from conventional press and sintering, and HIP are evaluated. Hence, water-atomized Cr–Mo-alloyed powder is used and consolidated into different density levels between 6.8 and 7.3 g cm⁻³ by conventional die pressing and sintering. Fully dense material produced through HIP is evaluated not only of mechanical properties but also for microstructural and fractographic analysis. An empirical model based on power law is fitted to the sintered material properties to estimate and predict the properties up to full density at different sintering conditions. A model describing the mechanism of oxide transformation during sintering and HIP is proposed. The challenges when it comes to the HIP of water-atomized powder are addressed and the requirements for successful HIP processing are discussed.

     

Evaluation and characterization of ammoniumpolyphosphate–pentaerythritol‐based systems for intumescent coatings

Intumescent coatings are increasingly used as a method of passive fire protection on steel constructions. By forming a carbon network and releasing a blowing agent, the thin intumescent film swells 100‐fold at elevated temperatures. The highly insulating foam effectively prevents the load bearing steel from reaching its critical temperature at which it looses its mechanical properties and collapses. The role of the carbon donor in intumescent coatings has been studied. Comparison in temperature development, foaming ratios, and rheological behavior has been performed between formulations containing pentaerythritol (penta), di–penta, and tri–penta. A simulated fire test, in which the temperature development during intumescence was studied, showed that the formulations containing penta were considerably more efficient in keeping a low temperature throughout the process. A more rapid temperature development was displayed when using di–penta and tri–penta as the carbon donor. Rheometer tests indicate that penta formulations enter the intumescent process at a lower temperature and stays in it for a longer time than di–penta and tri–penta formulations. Furthermore, the crossover temperature and maximum phase angle are shifted towards higher temperatures by replacing penta with di–penta and with tri–penta in the formulations, respectively. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 748–753, 2007     

Mining non-derivable hypercliques

A hyperclique (Xiong et al. in Proceedings of the IEEE international conference on data mining, pp 387–394, 2003) is an itemset containing items that are strongly correlated with each other, based on a user-specified threshold. Hypercliques (HCs) have been successfully used in a number of applications, for example, clustering (Xiong et al. in Proceedings of the 4th SIAM international conference on data mining, pp 279–290, 2004) and noise removal (Xiong et al. in IEEE Trans Knowl Data Eng 18(3):304–319, 2006). Even though HC has been shown to respond well to datasets with skewed support distribution and low support threshold, it may still grow very large for dense datasets and lower h-confidence threshold. In this paper, we propose a new pruning method based on combining HCs and non-derivable itemsets (NDIs) (Calders and Goethals in Proceedings of the PKDD international conference on principles of data mining and knowledge discovery, pp 74–85, 2002) in order to substantially reduce the amount of generated HCs. Specifically, we propose a new collection of HCs, called non-derivable hypercliques (NDHCs). The NDHC collection is a lossless representation of HCs, that is, given the itemsets in NDHCs, we can generate the complete HC collection and their support, without additional scanning of the dataset. We present an efficient algorithm to mine all NDHC sets, NDHCMiner, and an algorithm to derive all HC sets and their support from NDHCs, NDHCDeriveAll. We experimentally compare our collection, NDHC with HC, with respect to runtime performance as well as total number of generated sets, using real and artificial data. We also show comparisons with another condensed representation of HCs, maximal hyperclique patterns (MHPs). Our experiments show that the NDHC collection offers substantial advantages over HCs, and even MHPs, especially for dense datasets and lower h-confidence values.     

A Dynamic Network Oligopoly Model with Transportation Costs,Product Differentiation,and Quality Competition

This paper develops a new dynamic model of Cournot–Nash oligopolistic competition that includes production and transportation costs, product differentiation, and quality levels in a network framework. The production costs capture the total quality cost, which, in turn, can also represent the R&D cost. We first present the equilibrium version and derive alternative variational inequality formulations. We then construct the projected dynamical systems model, which provides a continuous-time evolution of the firms’ product shipments and product quality levels, and whose set of stationary points coincides with the set of solutions to the variational inequality problem. We establish stability analysis results using a monotonicity approach and construct a discrete-time version of the continuous-time adjustment process, which yields an algorithm, with closed form expressions at each iteration. The algorithm is then utilized to compute solutions to several numerical examples. The framework can serve as the foundation for the modeling and analysis of competition among firms in industries ranging from food to pharmaceuticals to durable goods and high tech products, as well as Internet services, where quality and product differentiation are seminal.     

Anonymity preserving sequential pattern mining

The increasing availability of personal data of a sequential nature, such as time-stamped transaction or location data, enables increasingly sophisticated sequential pattern mining techniques. However, privacy is at risk if it is possible to reconstruct the identity of individuals from sequential data. Therefore, it is important to develop privacy-preserving techniques that support publishing of really anonymous data, without altering the analysis results significantly. In this paper we propose to apply the Privacy-by-design paradigm for designing a technological framework to counter the threats of undesirable, unlawful effects of privacy violation on sequence data, without obstructing the knowledge discovery opportunities of data mining technologies. First, we introduce a k-anonymity framework for sequence data, by defining the sequence linking attack model and its associated countermeasure, a k-anonymity notion for sequence datasets, which provides a formal protection against the attack. Second, we instantiate this framework and provide a specific method for constructing the k-anonymous version of a sequence dataset, which preserves the results of sequential pattern mining, together with several basic statistics and other analytical properties of the original data, including the clustering structure. A comprehensive experimental study on realistic datasets of process-logs, web-logs and GPS tracks is carried out, which empirically shows how, in our proposed method, the protection of privacy meets analytical utility.