Heterogeneous asymmetric reactions. 23. Enantioselective hydrogenation of ethyl pyruvate over cinchonine- and α-isocinchonine-modified platinum catalysts

The enantioselective hydrogenation of ethyl pyruvate to (S)-ethyl lactate over cinchonine- and -isocinchonine-modified Pt/Al₂O₃ catalysts was studied as a function of modifier concentration and reaction temperature. The maximum enantioselectivities obtained under the applied mild conditions were 89% ee using cinchonine (0.014 mmoldm^–3, 1 bar H₂, 23°C, 6% AcOH in toluene), and 76% ee in the case of -isocinchonine (0.14 mmoldm^–3, 1 bar H₂, –10°C, 6% AcOH in toluene). Since -isocinchonine of rigid structure exists only in anti-open conformation these data provide additional experimental evidence to support the former suggestion concerning the dominating role of anti-open conformation in these cinchona-modified enantioselective hydrogenations.     

On the Black-Box Complexity of Sperner’s Lemma

We present several results on the complexity of various forms of Sperner’s Lemma in the black-box model of computing. We give a deterministic algorithm for Sperner problems over pseudo-manifolds of arbitrary dimension. The query complexity of our algorithm is linear in the separation number of the skeleton graph of the manifold and the size of its boundary. As a corollary we get an deterministic query algorithm for the black-box version of the problem 2D-SPERNER, a well studied member of Papadimitriou’s complexity class PPAD. This upper bound matches the deterministic lower bound of Crescenzi and Silvestri. The tightness of this bound was not known before. In another result we prove for the same problem an lower bound for its probabilistic, and an lower bound for its quantum query complexity, showing that all these measures are polynomially related. Research supported by the European Commission IST Integrated Project Qubit Application (QAP) 015848, the OTKA grants T42559 and T46234, and by the ANR Blanc AlgoQP grant of the French Research Ministry.     

Quality through Managed Improvement and Measurement (QMIM): Towards a Phased Development and Implementation of a Quality Management System for a Software Company

The paper describes results of a longitudinal study of developments in the area of software product and process quality improvement within a Hungarian software company, IQSOFT Ltd. This company has been active in this area since 1993, trying to build, introduce and maintain an efficiently working quality management system which, e.g., fulfils the ISO 9001 requirements, allows steady software process improvement and, at the same time, conforms to company's own needs. Over the last eight years five phases could be distinguished. Each phase is described shortly, following the same structure, namely: basic starting points, key problem areas, literature consulted, activities and design executed, reflections on what happened and why. The lessons resulting from the analysis of this case have been formulated in terms of guidelines. We feel that these are applicable to any low maturity software development organisation embarking on a product or process quality improvement endeavour. These guidelines are developed around a framework containing the basic issues of software production (project management, technical processes and products). The guidelines advocate a careful step-by-step development of definitions, quality characteristics, and metrics related to these objects while at the same time developing and introducing the associated process.     

Metabolic Adaptation as Potential Target in Papillary Renal Cell Carcinomas Based on Their In Situ Metabolic Characteristics

Metabolic characteristics of kidney cancers have mainly been obtained from the most frequent clear cell renal cell carcinoma (CCRCC) studies. Moreover, the bioenergetic perturbances that affect metabolic adaptation possibilities of papillary renal cell carcinoma (PRCC) have not yet been detailed. Therefore, our study aimed to analyze the in situ metabolic features of PRCC vs. CCRCC tissues and compared the metabolic characteristics of PRCC, CCRCC, and normal tubular epithelial cell lines. The protein and mRNA expressions of the molecular elements in mammalian target of rapamycin (mTOR) and additional metabolic pathways were analyzed in human PRCC cases compared to CCRCC. The metabolic protein expression pattern, metabolite content, mTOR, and metabolic inhibitor sensitivity of renal carcinoma cell lines were also studied and compared with tubular epithelial cells, as “normal” control. We observed higher protein expressions of the “alternative bioenergetic pathway” elements, in correlation with the possible higher glutamine and acetate consumption in PRCC cells instead of higher glycolytic and mTOR activity in CCRCCs. Increased expression of certain metabolic pathway markers correlates with the detected differences in metabolite ratios, as well. The lower lactate/pyruvate, lactate/malate, and higher pyruvate/citrate intracellular metabolite ratios in PRCC compared to CCRCC cell lines suggest that ACHN (PRCC) have lower Warburg glycolytic capacity, less pronounced pyruvate to lactate producing activity and shifted OXPHOS phenotype. However, both studied renal carcinoma cell lines showed higher mTOR activity than tubular epithelial cells cultured in vitro, the metabolite ratio, the enzyme expression profiles, and the higher mitochondrial content also suggest increased importance of mitochondrial functions, including mitochondrial OXPHOS in PRCCs. Additionally, PRCC cells showed significant mTOR inhibitor sensitivity and the used metabolic inhibitors increased the effect of rapamycin in combined treatments. Our study revealed in situ metabolic differences in mTOR and metabolic protein expression patterns of human PRCC and CCRCC tissues as well as in cell lines. These underline the importance in the development of specific new treatment strategies, new mTOR inhibitors, and other anti-metabolic drug combinations in PRCC therapy.     

Model complexity reduction of chemical reaction networks using mixed-integer quadratic programming

The model complexity reduction problem of large chemical reaction networks under isobaric and isothermal conditions is considered. With a given detailed kinetic mechanism and measured data of the key species over a finite time horizon, the complexity reduction is formulated in the form of a mixed-integer quadratic optimization problem where the objective function is derived from the parametric sensitivity matrix. The proposed method sequentially eliminates reactions from the mechanism and simultaneously tunes the remaining parameters until the pre-specified tolerance limit in the species concentration space is reached. The computational efficiency and numerical stability of the optimization are improved by a pre-reduction step followed by suitable scaling and initial conditioning of the Hessian involved. The proposed complexity reduction method is illustrated using three well-known case studies taken from reaction kinetics literature.     

Electrospray ionization mass spectrometry fingerprinting of Brazilian cacha?as produced in copper alembic and in stainless-steel column stills

Brazilian cacha?a can be produced in two different ways: distilled in stainless steel column or in copper alembic stills. We evaluated 36 samples of commercial non-aged cacha?as: 18 samples of sweetened cacha?as distilled in stainless steel column, and 18 samples distilled in copper alembic stills. Fingerprints were obtained through electrospray ionization mass spectrometry by recording the intensity of the 15 most abundant ions. Principal component analysis was applied to the data and separated the samples in two groups. However, after sample standardization with sugar (20?g?L^?1), it was not possible to group them by type of distillation. The results showed that the technique applied did not allow differentiation of cacha?as based on the distillation system, but for the presence or absence of sugar in them.     

Shape memory crosslinked polyurethanes containing thermoreversible Diels‐Alder couplings

Crosslinked polyurethanes (PUs) containing irreversible (allophanate) and reversible Diels‐Alder chemical bonds were synthesized using various diisocyanates (methylene diphenyl diisocyanate MDI, 1,6‐hexamethylenediisocyanate HDI) and poly(?‐caprolactone) ((PCL) with different molecular weights (M_n = 10 kg/mol, 25 kg/mol, 50 kg/mol) as diol component. The melting/crystallization of PCL and the reversible DA bonds acted as temperature‐activated switches for shape memory performances, while allophanate network provided the permanent crosslinks for these PUs. The reversible DA bonds were obtained by the reaction of diisocyanate‐ended prepolymers with furfurylamine (FA) followed by the addition of bismaleimide (BMI). The permanent crosslinks between the linear chains containing DA bonds were achieved using additional amounts of diisocyanates (MDI or HDI). The above reaction path was supported by infrared spectroscopic results and swelling experiments. Tensile mechanical and shape memory properties in tension of the PUs were determined and discussed as a function of composition and crosslink densities deduced from swelling and dynamic mechanical analysis. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 44145.     

Comparison of Two Analytical Methods for Assessing Antioxidant Capacity of Rapeseed and Olive Oils

The oxygen radical absorbance capacity (ORAC) and the ferric reducing antioxidant power (FRAP) methods were used for the determination of antioxidant capacities (AC) of rapeseed oils at different steps of technological process and olive oils. The mean ORAC and FRAP results obtained for rapeseed oils (1,106–160 and 552–95.6 μmol TE/100 g) were higher than for olive oils (949–123 and 167–32.1 μmol TE/100 g). Although, FRAP values were lower than ORAC values for all studied oils, there is a linear and significant correlation between these two analytical methods (r = 0.9665 and 0.9298, P < 0.0005) for rapeseed and olive oils, respectively). Also, total phenolic compounds in rapeseed oils and olives correlated with antioxidant capacities (correlation coefficient ranged between 0.9470 and 0.8049). The refining process of rapeseed oils decreased the total phenolics content and antioxidant capacities by about 80%.     

Rosuvastatin Enhances the Catabolism of LDL apoB‐100 in Subjects with Combined Hyperlipidemia in a Dose Dependent Manner

Dose‐associated effects of rosuvastatin on the metabolism of apolipoprotein (apo) B‐100 in triacylglycerol rich lipoprotein (TRL, d < 1.019 g/ml) and low density lipoprotein (LDL) and of apoA‐I in high density lipoprotein (HDL) were assessed in subjects with combined hyperlipidemia. Our primary hypothesis was that maximal dose rosuvastatin would decrease the apoB‐100 production rate (PR), as well as increase apoB‐100 fractional catabolic rate (FCR). Eight subjects received placebo, rosuvastatin 5 mg/day, and rosuvastatin 40 mg/day for 8 weeks each in sequential order. The kinetics of apoB‐100 in TRL and LDL and apoA‐I in HDL were determined at the end of each phase using stable isotope methodology, gas chromatography‐mass spectrometry, and multicompartmental modeling. Rosuvastatin at 5 and 40 mg/day decreased LDL cholesterol by 44 and 54 % (both P < 0.0001), triacylglycerol by 14 % (ns) and 35 % (P < 0.01), apoB by 30 and 36 % (both P < 0.0001), respectively, and had no significant effects on HDL cholesterol or apoA‐I levels. Significant decreases in plasma markers of cholesterol synthesis and increases in cholesterol absorption markers were observed. Rosuvastatin 5 and 40 mg/day increased TRL apoB‐100 FCR by 36 and 46 % (both ns) and LDL apoB‐100 by 63 and 102 % (both P < 0.05), respectively. HDL apoA‐I PR increased with low dose rosuvastatin (12 %, P < 0.05) but not with maximal dose rosuvastatin. Neither rosuvastatin dose altered apoB‐100 PR or HDL apoA‐I FCR. Our data indicate that maximal dose rosuvastatin treatment in subjects with combined hyperlipidemia resulted in significant increases in the catabolism of LDL apoB‐100, with no significant effects on apoB‐100 production or HDL apoA‐I kinetics.