Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of human cytochrome P450 isoenzymes involved in the metabolism of vinorelbine

Vinorelbine (VRL) (IV Navelbine®) is a semi‐synthetic vinca alkaloid, used in therapeutics for the treatment of non‐small‐cell lung cancer and advanced breast cancer. The aim of this study was to characterize the cytochrome P450 (CYP) isoenzymes involved in VRL metabolism. VRL was incubated at 1.28 × 10−5 m for 90 min with human hepatic microsomes prepared from 14 donors (one woman and 13 men aged from 27 to 76 years old) and characterized for CYP1A2, CYP2D6, CYP2E1 and CYP3A4 activities. A four‐combined‐approach study was performed, including correlation between CYP activities and VRL metabolism among the 14 batches of microsomes, inhibition of VRL biotransformation by isoform‐selective substrates and by specific inhibitory antibodies, and incubation with supersomes®. Analysis of unchanged VRL and its metabolites was performed using an HPLC method coupled with both radioactive and UV detections. No correlation between CYP1A2 or CYP2E1 and VRL metabolism was observed in the 14 batches of microsomes used. A correlation was shown between VRL metabolism and CYP3A4 activity as determined with the dextromethorphan N‐demethylase and nifedipine oxidase activities (r2 = 0.80 and 0.59, respectively). These results were strengthened by a correlation between the metabolism extent of VRL and CYP3A4 protein content determined by immunoblotting (r2 = 0.75). Furthermore, VRL biotransformation was inhibited by troleandomycine, the CYP3A4‐specific inhibitor substrate (80% of inhibition) and by anti‐CYP3A antibodies (36% of inhibition). On the contrary, a low correlation with CYP2D6 activity as determined by dextrometorphan O‐demethylation (r2 = 0.31) was established. CYP2D6 supersomes® did not metabolize the drug whereas 63.4% of VRL were metabolized by microsomes overexpressing CYP3A4 isoform. These data indicated that CYP3A4 is the main enzyme involved in the hepatic metabolism of VRL in human, whereas CYP2D6 is not involved.
Foreign Ownership and Performance in Sub‐Saharan African Manufacturing and Services

This paper tests for differences in performance between foreign‐owned and domestically owned firms in a sample of manufacturing and services firms from 19 sub‐Saharan African countries. Results indicate that foreign‐owned firms perform significantly better than domestically owned ones in sub‐Saharan Africa across several performance measures, with the foreign‐ownership premia usually being larger for services firms. The results further indicate that firms owned by a transnational corporation perform better than those owned by individual foreign entrepreneurs, although there is little evidence of differences in performance between joint ventures and wholly owned foreign enterprises. Copyright © 2014 John Wiley & Sons, Ltd.
Foreign direct investment, exports and economic growth: evidence from two panels of developing countries

Abstract The purpose of this article is to examine the causal relationship between foreign direct investment (FDI), exports and economic growth in two panels of developing countries (eight European developing countries and eight Asian developing countries). Panel-VECM causality is employed for investigating a tri-variate model of FDI, exports and GDP. Causality results in the European developing panel indicate bidirectional causality between GDP and FDI, and unidirectional causality from GDP and FDI to exports in the short-run. The empirical results of the Asian developing panel indicate bidirectional causality between exports and economic growth in the short-run. Moreover, there is evidence of long-run causality from export and FDI to economic growth, and long-run causality from economic growth and export to FDI for both of the aforementioned panels.
Application of Denaturing Gradient Gel Electrophoresis (DGGE) To Study the Diversity of Marine Picoeukaryotic Assemblages and Comparison of DGGE with Other Molecular Techniques

ABSTRACT We used denaturing gradient gel electrophoresis (DGGE) to study the diversity of picoeukaryotes in natural marine assemblages. Two eukaryote-specific primer sets targeting different regions of the 18S rRNA gene were tested. Both primer sets gave a single band when used with algal cultures and complex fingerprints when used with natural assemblages. The reproducibility of the fingerprints was estimated by quantifying the intensities of the same bands obtained in independent PCR and DGGE analyses, and the standard error of these estimates was less than 2% on average. DGGE fingerprints were then used to compare the picoeukaryotic diversity in samples obtained at different depths and on different dates from a station in the southwest Mediterranean Sea. Both primer sets revealed significant differences along the vertical profile, whereas temporal differences at the same depths were less marked. The phylogenetic composition of picoeukaryotes from one surface sample was investigated by excising and sequencing DGGE bands. The results were compared with an analysis of a clone library and a terminal restriction fragment length polymorphism fingerprint obtained from the same sample. The three PCR-based methods, performed with three different primer sets, revealed very similar assemblage compositions; the same main phylogenetic groups were present at similar relative levels. Thus, the prasinophyte group appeared to be the most abundant group in the surface Mediterranean samples as determined by our molecular analyses. DGGE bands corresponding to prasinophytes were always found in surface samples but were not present in deep samples. Other groups detected were prymnesiophytes, novel stramenopiles (distantly related to hyphochytrids or labyrinthulids), cryptophytes, dinophytes, and pelagophytes. In conclusion, the DGGE method described here provided a reasonably detailed view of marine picoeukaryotic assemblages and allowed tentative phylogenetic identification of the dominant members.
“She’s a dog at the end of the day”: Guide dog owners’ perspectives on the behaviour of their guide dog

A guide dog is a domestic dog (Canis familiaris) that is specifically educated to provide mobility support to a blind or visually impaired owner. Current dog suitability assessments focus on behavioural traits, including: trainability, reactivity or attention to environmental stimuli, low aggressiveness, fearfulness and stress behaviour, energy levels, and attachment behaviour. The aim of this study was to find out which aspects of guide dog behaviour are of key importance to guide dog owners themselves. Sixty-three semi-structured interview surveys were carried out with guide dog owners. Topics included the behaviour of their guide dog both within and outside their working role, and also focused on examples of behaviour which might be considered outside a guide dog owner’s typical expectations. Both positive and negative examples and situations were covered. This allowed for the discovery of new perspectives and emerging themes on living and working with a guide dog. Thematic analysis of the results reveals that a dog’s safe behaviour in the face of traffic was the most important positive aspect of a guide dog’s behaviour and pulling or high tension on the lead and /or harness was the most discussed negative aspect. Other aspects of guide dog behaviour were highlighted as particularly pleasing or disappointing by owners including attentiveness to the task, work, environment and owner; confidence in work and decision making (with confident dogs resulting in confident owners) obedience and control; calmness and locating objectives. The results reveal important areas of behaviour that are not currently considered priorities in guide dog assessments; these key areas were consistency of behaviour, the dog’s maturity and the dog’s behaviour in relation to children. The survey revealed a large range in what owners considered problematic or pleasing behaviours and this highlights the heterogeneity in guide dog owners and the potential multifarious roles of the guide dog. This study contributes to the literature on which behaviour is considered appropriate or inappropriate in dogs and on the nature of human-animal interactions.
The perception of tax concessions in retirement savings decisions

Purpose - Research to date has reported ambiguous results on the influence of tax concessions on retirement savings decisions. The purpose of this paper is to investigate the influence of tax concessions on private retirement investment decisions by analyzing actual retirement decision processes and the rationales behind these decisions in-depth. Design/methodology/approach - Qualitative semi-structured interviews on actual retirement savings decisions were conducted with private investors (17) and their respective bank advisors (5). Decision-making rationales are analysed by means of semantic and causal coding of verbal data as well as by highlighting the complexities of decision processes represented in individual investment narratives. Findings - Results indicate that taxes do not matter much, neither during the decision to join a private retirement plan, nor when choosing a specific investment product. Financial planning for retirement consists of saving disposable income instead of the required savings premium and choosing a secure type of investment which yields more than a savings account. Savers do not base their decisions on calculating and comparing rates of return or tax benefits. Instead, comparatively unqualified relatives as well as bank advisors and the desire for trust and security are of major relevance. Research limitations/implications - The generalization of results is limited in so far as they refer to a relatively small interview sample. The study shall thus prompt further research that takes the decision-making context and the interrelation between several context factors systematically into account. Originality/value - The study is of value in that it highlights the difficulties private investors' experience when making actual – rather than hypothetical – retirement savings decisions and the rationales behind seemingly “imperfect” decisions. It shows that retirement savings decisions are heavily linked with the social decision-making context. These results are closely linked to the recent debate on “responsibilization”, critical perspectives on the tendency of states to hold individuals increasingly accountable for aspects of market governance and social security.
Comparison of multigrid algorithms for high‐order continuous finite element discretizations

We present a comparison of different multigrid approaches for the solution of systems arising from high‐order continuous finite element discretizations of elliptic partial differential equations on complex geometries. We consider the pointwise Jacobi, the Chebyshev‐accelerated Jacobi, and the symmetric successive over‐relaxation smoothers, as well as elementwise block Jacobi smoothing. Three approaches for the multigrid hierarchy are compared: (1) high‐order h‐multigrid, which uses high‐order interpolation and restriction between geometrically coarsened meshes; (2) p‐multigrid, in which the polynomial order is reduced while the mesh remains unchanged, and the interpolation and restriction incorporate the different‐order basis functions; and (3) a first‐order approximation multigrid preconditioner constructed using the nodes of the high‐order discretization. This latter approach is often combined with algebraic multigrid for the low‐order operator and is attractive for high‐order discretizations on unstructured meshes, where geometric coarsening is difficult. Based on a simple performance model, we compare the computational cost of the different approaches. Using scalar test problems in two and three dimensions with constant and varying coefficients, we compare the performance of the different multigrid approaches for polynomial orders up to 16. Overall, both h‐multigrid and p‐multigrid work well; the first‐order approximation is less efficient. For constant coefficients, all smoothers work well. For variable coefficients, Chebyshev and symmetric successive over‐relaxation smoothing outperform Jacobi smoothing. While all of the tested methods converge in a mesh‐independent number of iterations, none of them behaves completely independent of the polynomial order. When multigrid is used as a preconditioner in a Krylov method, the iteration number decreases significantly compared with using multigrid as a solver. Copyright © 2015 John Wiley & Sons, Ltd.
Intake, Fecal Excretion, and Body Burden of Polychlorinated Dibenzo-p-dioxins and Dibenzofurans in Breast-Fed and Formula-Fed Infants

To assess toxicokinetics of polychlorinated dibenzo-p-dioxins(PCDDs) and dibenzofurans (PCDFs), oral intake and fecal excretion were measured in two breast-fed infants and one formula-fed infant during the 1st y of life. The intake of these compounds was up to 50 times higher in the breast-fed infants. In these children, fecal excretion of the main tetra- to hexachlorinated congeners was less than 9% of the intake at age of 1 and 5 mo, indicating almost complete intestinal absorption during breast-feeding. In contrast, distinctly higher fecal excretion rates were observed for the hepta- and octachlorinated compounds. Despite much lower PCDD/PCDF intake after weaning, concentrations in stool fat did not decrease substantially. We conclude that concentrations in fecal fat more or less reflect those in body fat. Additionally, PCDD/PCDF concentrations were measured in blood fat of all infants (and in a second formula-fed baby) at the age of 11 mo. International toxicity equivalent (1-TEq) concentrations in the formula-fed infants were less than 25% of maternal values and about 10 times lower than in the infants breast-fed for 6-7 mo. In the latter, a distinct accumulation was found for the tetra- to hexachlorinated congeners compared with maternal concentrations. We conclude that accumulation of PCDDs and PCDFs in infants is as high as expected on the basis of intake data and assuming complete absorption and negligible elimination during the 1st y of life.
A prospective study of maternal fatty acids, micronutrients and homocysteine and their association with birth outcome.

Our earlier studies both in animals and in humans have indicated that micronutrients (folic acid, vitamin B12) and long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), are interlinked in the one-carbon cycle, which plays an important role in fetal 'programming' of adult diseases. The present study examines the levels of maternal and cord plasma fatty acids, maternal folate, vitamin B12 and homocysteine in healthy mothers at various time points during pregnancy and also examine an association between them. A longitudinal study of 106 normal pregnant women was carried out, and maternal blood was collected at three time points, viz., T1 = 16-20th week, T2 = 26-30th week and T3 = at delivery. Cord blood was collected at delivery. Fatty acids were estimated using a gas chromatograph. Levels of folate, vitamin B12 and homocysteine were estimated by the chemiluminescent microparticle immunoassay (CMIA) technology. Maternal plasma folate (P < 0.05), vitamin B12 (P < 0.01) and DHA (P < 0.05) levels were lowest, while maternal homocysteine levels were highest (P < 0.01) at T3. There was a negative association between maternal DHA and homocysteine at T2 (P < 0.05) and T3 (P < 0.01). There was a positive association between plasma DHA in maternal blood at T3 and cord blood. Furthermore, there was a positive association between maternal folate and vitamin B12 at T3 and baby weight, whereas maternal homocysteine at T1 were inversely associated with baby weight at delivery. Our study provides evidence for the associations of folic acid, vitamin B12, homocysteine with DHA and baby weight, suggesting that a balanced dietary supplementation of folate-vitamin B12-DHA during pregnancy may be beneficial.
International Trade and Business Cycle Synchronization in Poland, the European Union and the Euro Zone

The analysis of business cycle synchronization levels has become a key point in the discussion of the processes of international economic integration. Economists show a particular interest in analyzing the frequency of processes of business cycle convergence and divergence (decoupling) in the European Union, especially in the Euro Zone. One of the factors determining business cycle convergence in economies is the intensity and structure of international trade. The aim of this paper is to analyze the influence exerted by international trade over the synchronization of business cycles in Poland, the European Union and the Euro Zone from 1995 to 2011. The analytical methods employed here encompass a review of the literature on macroeconomics and international finance, as well as econometric models (such as the Vector Autoregression Model). The results of empirical research indicate that an increase in trade turnover does not necessarily lead to greater business cycle synchronization in the economies under analysis. In fact, the impact of an increase in countries’ turnover on the synchronization of their business cycles depends predominantly on the structure of trade turnover and not solely on the intensity of trade.
Metabolism of xanthurenic acid in the rat.

The chromatographic pattem of metabolites of tryptophan and xanthurenic acid in urine of the normal rat has been described by Baglioni, Fasella, Turano & Siliprandi (1960). Administration of xanthurenic acid caused the excretion of three major components, one of which is xanthurenic acid. WVhen heated at 1000 in strongly acidic solutions, the other two compounds yielded xanthurenic acid. Dalgliesh (1952) reported the presence, in the urines of tryptophan-fed pyridoxine-deficient rats, of a compound in which xanthurenic acid is conjugated with sulphate and some other unknown residue. In the urine of xanthurenic acid-treated albino rats, Kotake & Nogami (1954) and Kotake (1957) found a double ethereal sulphate and a glucuronide derivative, and Rothstein & Greenberg (1957) found a diglucuronide-monoserine derivative and a monoglucuronide-monoserine derivative. In the present paper we describe the separation and identification of two metabolites of xanthurenic acid from rat urine.
Expression of extracellular matrix molecules and cell surface molecules in the olfactory nerve pathway during early development

The spatial and temporal expression patterns of several extracellular matrix molecules—laminin and fibronectin and cell surface molecules, neural cell adhesion molecule (NCAM), L1, tenascin, chondroitin sulfate proteoglycan, and peanut agglutinin (PNA) binding sites—were investigated during early olfactory nerve development. NCAM and L1 have similar patterns: They are expressed in the olfactory nerve and on the olfactory receptor neurons (ORNs) commencing with the earliest olfactory axon outgrowth (E12‐E15). Their expression patterns suggest that both NCAM and L1 are associated with extension and fasciculation of olfactory axons. A comparison of L1 and olfactory marker protein suggests that L1 is expressed predominantly on immature ORNs. Laminin has an unique punctate staining pattern in the developing olfactory pathway as early as E12. These laminin puncta might play a role in olfactory neurite outgrowth and guidance. At E14, when pioneer olfactory axons enter the brain, the laminin‐positive meninges on the surface of the olfactory bulb primordium break down but remain intact in the rest of the telencephalon. This suggests a functional interaction between the olfactory axons and the glial‐pial barrier. Fibronectin staining is diffuse throughout the cranial mesenchyme but is absent from the olfactory nerve pathway. No specific patterns of tenascin or chondroitin sulfate, were observed during early olfactory development. PNA binding sites were associated with olfactory axon fasciculation. The expression of several extracellular matrix molecules and cell surface molecules is spatially and temporally regulated in the developing olfactory system. These molecules, thus, may play functional roles in olfactory axon outgrowth, fasciculation, and/or guidance. ©1996 Wiley‐Liss, Inc.
Anatomic goals in the correction of female stress urinary incontinence.

The goal of stress incontinence surgery is to prevent opening of the urethra during increases in intra-abdominal pressure. Greater refinements in the understanding of the pathophysiology of incontinence and experience with newer treatments have extended surgical thinking beyond the familiar paradigm "to place the urethra in a high retropubic position. " When incontinence is associated with vaginal hypermobility, vaginal support may be sufficient to restore continence if the suburethral vaginal wall is sufficiently strong, an evaluation which must often be made by physical examination alone. However, when the vaginal wall is weak, the urethra will require an alternative form of support, usually a sling. If the urethra is intrinsically deficient, vaginal support may not be sufficient to prevent opening during increased intra-abdominal pressure, and coaptation by sling obstruction or periurethral bulking injection may be required. Most laparoscopic approaches to stress incontinence use Burch's method, which offers excellent urethral stability provided the suburethral vaginal wall is strong. Newer insights into the relation between vaginal mobility and urethral closure are discussed, as well as anatomic aspects of the Burch suspension relevant to laparoscopic repair.
Barriers to innovation and firm productivity

ABSTRACT The paper analyzes the effect of financial, knowledge, demand, market structure and regulation barriers to innovation on firms’ economic performance. It contributes to the literature on barriers to innovation by accounting for the heterogeneous effects that each barrier has on firms across the productivity distribution. We do so by employing both quantile regression techniques and matching estimators on this UK CIS panel 2002–2010 merged with the Business Structure Database. While we find evidence that both the cost and also the availability of finance negatively affect productivity across the whole distribution, the lack of qualified personnel mostly hinders high productivity firms. Moreover, quantile regression reveals some interesting variation in effect sizes across the (conditional) productivity distribution.
Enigma of Silence in Organizations: What Happens To Whom and Why?

Ozet: Organizational silence, which is defined as being employees remaining silent about their views, opinions and concerns about organizational problems, has recently started to receive due interest in organizational behavior literature. This phenomenon, which poses a great barrier to organizational change and development, is frequently experienced in many organizations. Organizational silence is a composition of various personal and organizational factors and thus has negative impacts and results on both individuals and organizations. This study is a qualitative research and has been conducted through face to face interviews with 10 employees who work at the marketing and export departments of a company active in automotive supply industry. Findings of the study suggest that employees experience the phenomenon of organizational silence and the causes that lead to it are in parallel with the ones elaborated on in the literature.