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Sample records for empirically derived metabolic

  1. Derivatives in South Africa – an empirical investigation

    Directory of Open Access Journals (Sweden)

    Stefan Schwegler

    2011-03-01

    Full Text Available This paper, which is the second of a two-part series, presents the empirical findings of testing a number of variables influencing investors’ decisions to use derivatives in their portfolios. Five variables were deemed very important by a sample of 21 experts in the financial services industry in South Africa. These were: the level of information available (including the transparency of price determination; investor’s knowledge of different derivative instruments; investor’s level of risk tolerance; the level of liquidity in the market; and investor’s knowledge of and familiarity with financial markets. Education is required to change negative sentiments regarding derivatives and more regulation is called for, especially in over-the-counter markets.

  2. Empirically derived climate predictability over the extratropical northern hemisphere

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    J. B. Elsner

    1994-01-01

    Full Text Available A novel application of a technique developed from chaos theory is used in describing seasonal to interannual climate predictability over the Northern Hemisphere (NH. The technique is based on an empirical forecast scheme - local approximation in a reconstructed phase space - for time-series data. Data are monthly 500 hPa heights on a latitude-longitude grid covering the NH from 20° N to the equator. Predictability is estimated based on the linear correlation between actual and predicted heights averaged over a forecast range of one- to twelve.month lead. The method is capable of extracting the major climate signals on this time scale including ENSO and the North Atlantic Oscillation.

  3. EMPIRICALLY DERIVED INTEGRATED STELLAR YIELDS OF Fe-PEAK ELEMENTS

    International Nuclear Information System (INIS)

    Henry, R. B. C.; Cowan, John J.; Sobeck, Jennifer

    2010-01-01

    We present here the initial results of a new study of massive star yields of Fe-peak elements. We have compiled from the literature a database of carefully determined solar neighborhood stellar abundances of seven iron-peak elements, Ti, V, Cr, Mn, Fe, Co, and Ni, and then plotted [X/Fe] versus [Fe/H] to study the trends as functions of metallicity. Chemical evolution models were then employed to force a fit to the observed trends by adjusting the input massive star metallicity-sensitive yields of Kobayashi et al. Our results suggest that yields of Ti, V, and Co are generally larger as well as anticorrelated with metallicity, in contrast to the Kobayashi et al. predictions. We also find the yields of Cr and Mn to be generally smaller and directly correlated with metallicity compared to the theoretical results. Our results for Ni are consistent with theory, although our model suggests that all Ni yields should be scaled up slightly. The outcome of this exercise is the computation of a set of integrated yields, i.e., stellar yields weighted by a slightly flattened time-independent Salpeter initial mass function and integrated over stellar mass, for each of the above elements at several metallicity points spanned by the broad range of observations. These results are designed to be used as empirical constraints on future iron-peak yield predictions by stellar evolution modelers. Special attention is paid to the interesting behavior of [Cr/Co] with metallicity-these two elements have opposite slopes-as well as the indirect correlation of [Ti/Fe] with [Fe/H]. These particular trends, as well as those exhibited by the inferred integrated yields of all iron-peak elements with metallicity, are discussed in terms of both supernova nucleosynthesis and atomic physics.

  4. Student Response to Faculty Instruction (SRFI): An Empirically Derived Instrument to Measure Student Evaluations of Teaching

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    Beitzel, Brian D.

    2013-01-01

    The Student Response to Faculty Instruction (SRFI) is an instrument designed to measure the student perspective on courses in higher education. The SRFI was derived from decades of empirical studies of student evaluations of teaching. This article describes the development of the SRFI and its psychometric attributes demonstrated in two pilot study…

  5. Deriving Multidimensional Poverty Indicators: Methodological Issues and an Empirical Analysis for Italy

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    Coromaldi, Manuela; Zoli, Mariangela

    2012-01-01

    Theoretical and empirical studies have recently adopted a multidimensional concept of poverty. There is considerable debate about the most appropriate degree of multidimensionality to retain in the analysis. In this work we add to the received literature in two ways. First, we derive indicators of multiple deprivation by applying a particular…

  6. Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism.

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    Zhao, Hongyun; Yang, Lifeng; Baddour, Joelle; Achreja, Abhinav; Bernard, Vincent; Moss, Tyler; Marini, Juan C; Tudawe, Thavisha; Seviour, Elena G; San Lucas, F Anthony; Alvarez, Hector; Gupta, Sonal; Maiti, Sourindra N; Cooper, Laurence; Peehl, Donna; Ram, Prahlad T; Maitra, Anirban; Nagrath, Deepak

    2016-02-27

    Cancer-associated fibroblasts (CAFs) are a major cellular component of tumor microenvironment in most solid cancers. Altered cellular metabolism is a hallmark of cancer, and much of the published literature has focused on neoplastic cell-autonomous processes for these adaptations. We demonstrate that exosomes secreted by patient-derived CAFs can strikingly reprogram the metabolic machinery following their uptake by cancer cells. We find that CAF-derived exosomes (CDEs) inhibit mitochondrial oxidative phosphorylation, thereby increasing glycolysis and glutamine-dependent reductive carboxylation in cancer cells. Through 13C-labeled isotope labeling experiments we elucidate that exosomes supply amino acids to nutrient-deprived cancer cells in a mechanism similar to macropinocytosis, albeit without the previously described dependence on oncogenic-Kras signaling. Using intra-exosomal metabolomics, we provide compelling evidence that CDEs contain intact metabolites, including amino acids, lipids, and TCA-cycle intermediates that are avidly utilized by cancer cells for central carbon metabolism and promoting tumor growth under nutrient deprivation or nutrient stressed conditions.

  7. Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism

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    Zhao, Hongyun; Yang, Lifeng; Baddour, Joelle; Achreja, Abhinav; Bernard, Vincent; Moss, Tyler; Marini, Juan C; Tudawe, Thavisha; Seviour, Elena G; San Lucas, F Anthony; Alvarez, Hector; Gupta, Sonal; Maiti, Sourindra N; Cooper, Laurence; Peehl, Donna; Ram, Prahlad T; Maitra, Anirban; Nagrath, Deepak

    2016-01-01

    Cancer-associated fibroblasts (CAFs) are a major cellular component of tumor microenvironment in most solid cancers. Altered cellular metabolism is a hallmark of cancer, and much of the published literature has focused on neoplastic cell-autonomous processes for these adaptations. We demonstrate that exosomes secreted by patient-derived CAFs can strikingly reprogram the metabolic machinery following their uptake by cancer cells. We find that CAF-derived exosomes (CDEs) inhibit mitochondrial oxidative phosphorylation, thereby increasing glycolysis and glutamine-dependent reductive carboxylation in cancer cells. Through 13C-labeled isotope labeling experiments we elucidate that exosomes supply amino acids to nutrient-deprived cancer cells in a mechanism similar to macropinocytosis, albeit without the previously described dependence on oncogenic-Kras signaling. Using intra-exosomal metabolomics, we provide compelling evidence that CDEs contain intact metabolites, including amino acids, lipids, and TCA-cycle intermediates that are avidly utilized by cancer cells for central carbon metabolism and promoting tumor growth under nutrient deprivation or nutrient stressed conditions. DOI: http://dx.doi.org/10.7554/eLife.10250.001 PMID:26920219

  8. Human reliability under sleep deprivation: Derivation of performance shaping factor multipliers from empirical data

    International Nuclear Information System (INIS)

    Griffith, Candice D.; Mahadevan, Sankaran

    2015-01-01

    This paper develops a probabilistic approach that could use empirical data to derive values of performance shaping factor (PSF) multipliers for use in quantitative human reliability analysis (HRA). The proposed approach is illustrated with data on sleep deprivation effects on performance. A review of existing HRA methods reveals that sleep deprivation is not explicitly included at present, and expert opinion is frequently used to inform HRA model multipliers. In this paper, quantitative data from empirical studies regarding the effect of continuous hours of wakefulness on performance measures (reaction time, accuracy, and number of lapses) are used to develop a method to derive PSF multiplier values for sleep deprivation, in the context of the SPAR-H model. Data is extracted from the identified studies according to the meta-analysis research synthesis method and used to investigate performance trends and error probabilities. The error probabilities in test and control conditions are compared, and the resulting probability ratios are suggested for use in informing the selection of PSF multipliers in HRA methods. Although illustrated for sleep deprivation, the proposed methodology is general, and can be applied to other performance shaping factors. - Highlights: • Method proposed to derive performance shaping factor multipliers from empirical data. • Studies reporting the effect of sleep deprivation on performance are analyzed. • Test data using psychomotor vigilance tasks are analyzed. • Error probability multipliers computed for reaction time, lapses, and accuracy measures.

  9. A metabolic derivation of tritium transfer factors in animal products

    International Nuclear Information System (INIS)

    Galeriu, D.; Melintescu, A.; Crout, N. M. J.; Bersford, N. A.; Peterson, S. R.; Hess, M. van

    2001-01-01

    Tritium is a potentially important environmental contaminant arising from the nuclear industry. Because tritium is an isotope of hydrogen, its behaviour in the environment is controlled by the behaviour of hydrogen. Chronic releases of tritium to the atmosphere, in particular, will result in tritium-to-hydrogen (T/H) ratios in plants and animals that are more or less in equilibrium with T/H ratios in the air moisture. Tritium is thus a potentially important contaminant of plant and animal food products. The transfer of tritium from air moisture to plants is quite well understood. In contrast, although a number of regulatory agencies have published transfer coefficient values for diet tritium transfer for a limited number of animal products, a fresh evaluation of these transfers needs to be made In this paper we present an approach for the derivation of tritium transfer coefficients which is based on the metabolism of hydrogen in animals in conjunction with experimental data on tritium transfer. The derived transfer coefficients separately account for transfer to and from free (i.e. water) and organically bound tritium. The predicted transfer coefficients are compared to available data independent of model development. Agreement is good, with the exception of the transfer coefficient for transfer from tritiated water to organically bound tritium in ruminants, which may be attributable to the particular characteristics of ruminant digestion. We show that transfer coefficients will vary in response to the metabolic status of an animal (e.g. stage of lactation, digestibility of diet, etc.) and that the use of a single transfer coefficient from diet to animal product is not appropriate for tritium. It is possible to derive concentration ratio values which relate the concentration of tritiated water and organically bound tritium in an animal product to the corresponding concentrations in the animals diet. These concentration ratios are shown to be less subject to

  10. Arachidonic acid metabolism in fibroblasts derived from canine myocardium

    International Nuclear Information System (INIS)

    Weber, D.R.; Prescott, S.M.

    1986-01-01

    Canine fibroblasts from normal or healing infarcted myocardium were grown in culture. The cells were morphologically indistinguishable, but the doubling time of cells from healing myocardium was 39.6 +/- 3.5 hr whereas that of normals was 24 +/- 3.7 (n=5, p 3 H]arachidonate (AA) into phospholipids. Calcium ionophore A23187 (10 μM) caused release and metabolism of [ 3 H] AA. A23187 or AA (10μM) induced production of 6-keto PGF1α, PGE2, and a hydroxy metabolite of AA. RIA of 6-keto PGF1α showed that subconfluent cells from healing myocardium produced 1202 +/- 354 pg/mg protein whereas that of normals was 551 +/- 222 (n=7, p 3 H]AA released but did not metabolize [ 3 H]AA. In coincubations, fibroblasts incorporated myocyte-derived AA. Subsequent stimulation of the fibroblasts with A23187 induced the synthesis of 6-keto PGF1α, PGE2 and a hydroxy metabolite. The fibroblast content of healing myocardium was 35-1000 times that of normal tissue (n=7). Thus even a moderate change in AA metabolism, amplified by the AA released from deteriorating myocytes, may be a significant physiologic or pathologic event

  11. Metabolic Activity of Radish Sprouts Derived Isothiocyanates in Drosophila melanogaster

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    Nieves Baenas

    2016-02-01

    Full Text Available We used Drosophila melanogaster as a model system to study the absorption, metabolism and potential health benefits of plant bioactives derived from radish sprouts (Raphanus sativus cv. Rambo, a Brassicaceae species rich in glucosinolates and other phytochemicals. Flies were subjected to a diet supplemented with lyophilized radish sprouts (10.6 g/L for 10 days, containing high amounts of glucoraphenin and glucoraphasatin, which can be hydrolyzed by myrosinase to the isothiocyanates sulforaphene and raphasatin, respectively. We demonstrate that Drosophila melanogaster takes up and metabolizes isothiocyanates from radish sprouts through the detection of the metabolite sulforaphane-cysteine in fly homogenates. Moreover, we report a decrease in the glucose content of flies, an upregulation of spargel expression, the Drosophila homolog of the mammalian PPARγ-coactivator 1 α, as well as the inhibition of α-amylase and α-glucosidase in vitro. Overall, we show that the consumption of radish sprouts affects energy metabolism in Drosophila melanogaster which is reflected by lower glucose levels and an increased expression of spargel, a central player in mitochondrial biogenesis. These processes are often affected in chronic diseases associated with aging, including type II diabetes mellitus.

  12. Metabolic Activity of Radish Sprouts Derived Isothiocyanates in Drosophila melanogaster

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    Baenas, Nieves; Piegholdt, Stefanie; Schloesser, Anke; Moreno, Diego A.; García-Viguera, Cristina; Rimbach, Gerald; Wagner, Anika E.

    2016-01-01

    We used Drosophila melanogaster as a model system to study the absorption, metabolism and potential health benefits of plant bioactives derived from radish sprouts (Raphanus sativus cv. Rambo), a Brassicaceae species rich in glucosinolates and other phytochemicals. Flies were subjected to a diet supplemented with lyophilized radish sprouts (10.6 g/L) for 10 days, containing high amounts of glucoraphenin and glucoraphasatin, which can be hydrolyzed by myrosinase to the isothiocyanates sulforaphene and raphasatin, respectively. We demonstrate that Drosophila melanogaster takes up and metabolizes isothiocyanates from radish sprouts through the detection of the metabolite sulforaphane-cysteine in fly homogenates. Moreover, we report a decrease in the glucose content of flies, an upregulation of spargel expression, the Drosophila homolog of the mammalian PPARγ-coactivator 1 α, as well as the inhibition of α-amylase and α-glucosidase in vitro. Overall, we show that the consumption of radish sprouts affects energy metabolism in Drosophila melanogaster which is reflected by lower glucose levels and an increased expression of spargel, a central player in mitochondrial biogenesis. These processes are often affected in chronic diseases associated with aging, including type II diabetes mellitus. PMID:26901196

  13. An Empirically Derived Taxonomy for Personality Diagnosis: Bridging Science and Practice in Conceptualizing Personality

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    Westen, Drew; Shedler, Jonathan; Bradley, Bekh; DeFife, Jared A.

    2013-01-01

    Objective The authors describe a system for diagnosing personality pathology that is empirically derived, clinically relevant, and practical for day-to-day use. Method A random national sample of psychiatrists and clinical psychologists (N=1,201) described a randomly selected current patient with any degree of personality dysfunction (from minimal to severe) using the descriptors in the Shedler-Westen Assessment Procedure–II and completed additional research forms. Results The authors applied factor analysis to identify naturally occurring diagnostic groupings within the patient sample. The analysis yielded 10 clinically coherent personality diagnoses organized into three higher-order clusters: internalizing, externalizing, and borderline-dysregulated. The authors selected the most highly rated descriptors to construct a diagnostic prototype for each personality syndrome. In a second, independent sample, research interviewers and patients’ treating clinicians were able to diagnose the personality syndromes with high agreement and minimal comorbidity among diagnoses. Conclusions The empirically derived personality prototypes described here provide a framework for personality diagnosis that is both empirically based and clinically relevant. PMID:22193534

  14. Bacterial metabolism of human polymorphonuclear leukocyte-derived arachidonic acid.

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    Sorrell, T C; Muller, M; Sztelma, K

    1992-05-01

    Evidence for transcellular bacterial metabolism of phagocyte-derived arachidonic acid was sought by exposing human blood polymorphonuclear leukocytes, prelabelled with [3H]arachidonic acid, to opsonized, stationary-phase Pseudomonas aeruginosa (bacteria-to-phagocyte ratio of 50:1) for 90 min at 37 degrees C. Control leukocytes were stimulated with the calcium ionophore A23187 (5 microM) for 5 min. Radiochromatograms of arachidonic acid metabolites, extracted from A23187-stimulated cultures and then separated by reverse-phase high-performance liquid chromatography, revealed leukotriene B4, its omega-oxidation products, and 5-hydroxy-eicosatetraenoic acid. In contrast, two major metabolite peaks, distinct from known polymorphonuclear leukocyte arachidonic acid products by high-performance liquid chromatography or by thin-layer chromatography, were identified in cultures of P. aeruginosa with [3H]arachidonic acid-labelled polymorphonuclear leukocytes. Respective chromatographic characteristics of these novel products were identical to those of two major metabolite peaks produced by incubation of stationary-phase P. aeruginosa with [3H]arachidonic acid. Production of the metabolites was dependent upon pseudomonal viability. UV spectral data were consistent with a conjugated diene structure. Metabolism of arachidonic acid by P. aeruginosa was not influenced by the presence of catalase, superoxide dismutase, nordihydroguaiaretic acid, ethanol, dimethyl sulfoxide, or ferrous ions but was inhibited by carbon monoxide, ketoconazole, and 1,2-epoxy-3,3,3-trichloropropane. Our data suggest that pseudomonal metabolism of polymorphonuclear leukocyte-derived arachidonic acid occurs during phagocytosis, probably by enzymatic epoxidation and hydroxylation via an oxygenase. By this means, potential proinflammatory effects of arachidonic acid or its metabolites may be modulated by P. aeruginosa at sites of infection in vivo.

  15. SU-F-BRD-07: Empirical Derivation of Site-Specific Margin Formulas

    International Nuclear Information System (INIS)

    Conroy, L; Smith, W; Quirk, S

    2014-01-01

    Purpose: To empirically derive margin formulas from existing clinical radiotherapy plans accounting for respiratory motion and setup uncertainties. Methods: We simulated realistic treatment scenarios, including respiratory motion and setup errors. Individual probability density functions (PDF) from respiratory data were used to simulate respiratory motion. Random (σ) and systematic (Σ) setup errors were modeled as Gaussian distributions. One-dimensional dose profiles were extracted from existing radiotherapy plans and convolved with respiratory PDFs and random error distributions to produce blurred dose profiles. Each blurred dose profile was then shifted 1000 times by randomly sampling the simulated systematic error distribution. Margins were determined from the distance between the simulated treatment and the original 95% isodose level. An equation was fit for each (σ, Σ) combination to derive margin formulas for 90% of the population receiving 95% dose. This methodology can be applied to different tumor sites. Here, dose profiles were extracted from partial breast 3DCRT plans in the anterior-posterior (AP) and superior-inferior (SI) directions. Respiratory motion data was from healthy volunteers, and a clinically relevant range of random and systematic setup errors (standard deviations 1 – 4 mm) was determined from the literature. Results: The PBI margin formulas in the AP and SI directions for 95% dose coverage for 90% of the population were very similar: M= 0.68σ + 1.54Σ and M= 0.72σ + 1.50Σ, respectively. Systematic setup errors had the largest influence on required margin size, whereas realistic respiratory amplitude had minimal impact. The derived formulas resulted in a smaller systematic component than commonly-used theoretical margin recipes. Conclusion: We have demonstrated a method to derive empirical margin formulas from existing patient radiotherapy plans, incorporating realistic respiratory motion and appropriate ranges of random and

  16. [Thiamine and its derivatives in the regulation of cell metabolism].

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    Tylicki, Adam; Siemieniuk, Magdalena

    2011-07-06

    For over 70 years thiamine (vitamin B1) has aroused the interest of biologists, biochemists and medical doctors because of its multilateral participation in key biochemical and physiological processes. The thiamine molecule is composed of pyrimidine and thiazole rings which are linked by a methylene bridge. It is synthesized by microorganisms, fungi and plants, whereas animals and humans have to obtain it from food. There are several known forms of vitamin B1 inside cells: free thiamine, three phosphate esters (mono-, di-, and triphosphate), and the recently found adenosine thiamine triphosphate. Thiamine has a dual, coenzymatic and non-coenzymatic role. First of all, it is a precursor of thiamin diphosphate, which is a coenzyme for over 20 characterized enzymes which are involved in cell bioenergetic processes leading to the synthesis of ATP. Moreover, these enzymes take part in the biosynthesis of pentose (required for the synthesis of nucleotides), amino acids and other organic compounds of cell metabolism. On the other hand, recent discoveries show the non-coenzymatic role of thiamine derivatives in the process of regulation of gene expression (riboswitches in microorganisms and plants), the stress response, and perhaps so far unknown signal transduction pathways associated with adverse environmental conditions, or transduction of nerve signals with participation of thiamine triphosphate and adenosine thiamine triphosphate. From the clinical point of view thiamine deficiency is related to beri-beri, Parkinson disease, Alzheimer disease, Wernicke-Korsakoff syndrome and other pathologies of the nervous system, and it is successfully applied in medical practice. On the other hand, identifying new synthetic analogues of thiamine which could be used as cytostatics, herbicides or agents preventing deficiency of vitamin B1 is currently the major goal of the research. In this paper we present the current state of knowledge of thiamine and its derivatives, indicating

  17. Semi-Empirical Predictions on the Structure and Properties of ent-Kaurenoic Acid and Derivatives

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    Jose Isagani B. Janairo

    2011-01-01

    Full Text Available The physicochemical properties of ent- kaurenoic acid model derivatives, which possibly influence its therapeutic application, were calculated. Results revealed that the molecule possess favourable attributes which renders it possible to be considered as a drug lead only that its very hydrophobic nature can result to poor bioavailabilty, low absorption and poor systemic circulation. In silico simulations revealed that this setback can be overcome by introduction of hydroxyl group to the tertiary carbon of ent-kaurenoic acid employing m-CPBA catalyzed hydroxylation, thus, unleashing its full drug potency. Moreover, molecular similarity analyses derived from semi-empirical calculations between ent-kaurenoic acid and a set of kaurane diterpenoids showed differences in hydrophobic complementarity, size and electronic properties despite possessing nearly identical molecular frameworks, thus, arriving in a generalization for their observed mechanistic differences on acting on different targets.

  18. The performance of selected semi-empirical and DFT methods in studying C60 fullerene derivatives

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    Sikorska, Celina; Puzyn, Tomasz

    2015-11-01

    The capability of reproducing the open circuit voltages (V oc) of 15 representative C60 fullerene derivatives was tested using the selected quantum mechanical methods (B3LYP, PM6, and PM7) together with the two one-electron basis sets. Certain theoretical treatments (e.g. PM6) were found to be satisfactory for preliminary estimates of the open circuit voltages (V oc), whereas the use of the B3LYP/6-31G(d) approach has been proven to assure highly accurate results. We also examined the structural similarity of 19 fullerene derivatives by employing principle component analysis (PCA). In order to express the structural features of the studied compounds we used molecular descriptors calculated with semi-empirical (PM6 and PM7) and density functional (B3LYP/6-31G(d)) methods separately. In performing PCA, we noticed that semi-empirical methods (i.e. PM6 and PM7) seem satisfactory for molecules, in which one can distinguish the aromatic and the aliphatic parts in the cyclopropane ring of PCBM (phenyl-C61-buteric acid methyl ester) and they significantly overestimate the energy of the highest occupied molecular orbital (E HOMO). The use of the B3LYP functional, however, is recommended for studying methanofullerenes, which closely resemble the structure of PCBM, and for their modifications.

  19. The performance of selected semi-empirical and DFT methods in studying C60 fullerene derivatives

    International Nuclear Information System (INIS)

    Sikorska, Celina; Puzyn, Tomasz

    2015-01-01

    The capability of reproducing the open circuit voltages (V oc ) of 15 representative C 60 fullerene derivatives was tested using the selected quantum mechanical methods (B3LYP, PM6, and PM7) together with the two one-electron basis sets. Certain theoretical treatments (e.g. PM6) were found to be satisfactory for preliminary estimates of the open circuit voltages (V oc ), whereas the use of the B3LYP/6-31G(d) approach has been proven to assure highly accurate results. We also examined the structural similarity of 19 fullerene derivatives by employing principle component analysis (PCA). In order to express the structural features of the studied compounds we used molecular descriptors calculated with semi-empirical (PM6 and PM7) and density functional (B3LYP/6-31G(d)) methods separately. In performing PCA, we noticed that semi-empirical methods (i.e. PM6 and PM7) seem satisfactory for molecules, in which one can distinguish the aromatic and the aliphatic parts in the cyclopropane ring of PCBM (phenyl-C 61 -buteric acid methyl ester) and they significantly overestimate the energy of the highest occupied molecular orbital (E HOMO ). The use of the B3LYP functional, however, is recommended for studying methanofullerenes, which closely resemble the structure of PCBM, and for their modifications. (paper)

  20. Patterns of alcohol use and consequences among empirically derived sexual minority subgroups.

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    Talley, Amelia E; Sher, Kenneth J; Steinley, Douglas; Wood, Phillip K; Littlefield, Andrew K

    2012-03-01

    The current study develops an empirically determined classification of sexual orientation developmental patterns based on participants' annual reports of self-identifications, sexual attractions, and sexual behaviors during the first 4 years of college. A secondary aim of the current work was to examine trajectories of alcohol involvement among identified subgroups. Data were drawn from a subsample of a longitudinal study of incoming first-time college students at a large, public university (n = 2,068). Longitudinal latent class analysis was used to classify sexual minority participants into empirically derived subgroups based on three self-reported facets of sexual orientation. Multivariate repeated-measures analyses were conducted to examine how trajectories of alcohol involvement varied by sexual orientation class membership. Four unique subclasses of sexual orientation developmental patterns were identified for males and females: one consistently exclusively heterosexual group and three sexual minority groups. Despite generally similar alcohol use patterns among subclasses, certain sexual minority subgroups reported elevated levels of alcohol-related negative consequences and maladaptive motivations for use throughout college compared with their exclusively heterosexual counterparts. Elevations in coping and conformity motivations for alcohol use were seen among those subgroups that also evidenced heightened negative alcohol-related consequences. Implications and limitations of the current work are discussed.

  1. Computational optogenetics: empirically-derived voltage- and light-sensitive channelrhodopsin-2 model.

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    John C Williams

    Full Text Available Channelrhodospin-2 (ChR2, a light-sensitive ion channel, and its variants have emerged as new excitatory optogenetic tools not only in neuroscience, but also in other areas, including cardiac electrophysiology. An accurate quantitative model of ChR2 is necessary for in silico prediction of the response to optical stimulation in realistic tissue/organ settings. Such a model can guide the rational design of new ion channel functionality tailored to different cell types/tissues. Focusing on one of the most widely used ChR2 mutants (H134R with enhanced current, we collected a comprehensive experimental data set of the response of this ion channel to different irradiances and voltages, and used these data to develop a model of ChR2 with empirically-derived voltage- and irradiance- dependence, where parameters were fine-tuned via simulated annealing optimization. This ChR2 model offers: 1 accurate inward rectification in the current-voltage response across irradiances; 2 empirically-derived voltage- and light-dependent kinetics (activation, deactivation and recovery from inactivation; and 3 accurate amplitude and morphology of the response across voltage and irradiance settings. Temperature-scaling factors (Q10 were derived and model kinetics was adjusted to physiological temperatures. Using optical action potential clamp, we experimentally validated model-predicted ChR2 behavior in guinea pig ventricular myocytes. The model was then incorporated in a variety of cardiac myocytes, including human ventricular, atrial and Purkinje cell models. We demonstrate the ability of ChR2 to trigger action potentials in human cardiomyocytes at relatively low light levels, as well as the differential response of these cells to light, with the Purkinje cells being most easily excitable and ventricular cells requiring the highest irradiance at all pulse durations. This new experimentally-validated ChR2 model will facilitate virtual experimentation in neural and

  2. Plant-derived therapeutics for the treatment of metabolic syndrome.

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    Graf, Brittany L; Raskin, Ilya; Cefalu, William T; Ribnicky, David M

    2010-10-01

    Metabolic syndrome is defined as a set of coexisting metabolic disorders that increase an individual's likelihood of developing type 2 diabetes, cardiovascular disease and stroke. Medicinal plants, some of which have been used for thousands of years, serve as an excellent source of bioactive compounds for the treatment of metabolic syndrome because they contain a wide range of phytochemicals with diverse metabolic effects. In order for botanicals to be effectively used against metabolic syndrome, however, botanical preparations must be characterized and standardized through the identification of their active compounds and respective modes of action, followed by validation in controlled clinical trials with clearly defined endpoints. This review assesses examples of commonly known and partially characterized botanicals to describe specific considerations for the phytochemical, preclinical and clinical characterization of botanicals associated with metabolic syndrome.

  3. Corporate interest rate risk management with derivatives in Australia: empirical results

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    Luiz Augusto Ferreira Carneiro

    2008-04-01

    Full Text Available Financial and insurance theories explain that large widely-held corporations manage corporate risks if doing so is costective to reduce frictional costs such as taxes, agency costs and financial distress costs. A large number of previous empirical studies, most in the U.S., have tested the hypotheses underlying corporate risk management with financial derivative instruments. In order to quantify corporate hedge demand, most previous studies have used the ratio of principal notional amount of derivatives to company size, although they recognize that company size is not an appropriate proxy for financial risk. This paper analyzes the interest-rate-risk hedge demand by Australian companies, measured through the ratio of principal notional amount of interest rate derivatives to interest-rate-riskbearing liabilities. Modern panel data methods are used, with two panel data sets from 1998 to 2003 (1102 and 465 observations, respectively. Detailed information about interest-rate-risk exposures was available after manual data collection from financial annual reports, which was only possible due to specific reporting requirements in Australian accounting standards. Regarding the analysis of the extent of hedge, our measurement of interest-rate-risk exposures generates some significant results di erent from those found in previous studies. For example, this study shows that total leverage (total debt ratio is not significantly important to interest-rate-risk hedge demand and that, instead, this demand is related to the specific risk exposure in the interest bearing part of the firms liabilities. This study finds significant relations of interest-rate-risk hedge to company size, floating-interest-rate debt ratio, annual log returns, and company industry type (utilities and non-banking financial institutions.

  4. Empirically Derived and Simulated Sensitivity of Vegetation to Climate Across Global Gradients of Temperature and Precipitation

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    Quetin, G. R.; Swann, A. L. S.

    2017-12-01

    Successfully predicting the state of vegetation in a novel environment is dependent on our process level understanding of the ecosystem and its interactions with the environment. We derive a global empirical map of the sensitivity of vegetation to climate using the response of satellite-observed greenness and leaf area to interannual variations in temperature and precipitation. Our analysis provides observations of ecosystem functioning; the vegetation interactions with the physical environment, across a wide range of climates and provide a functional constraint for hypotheses engendered in process-based models. We infer mechanisms constraining ecosystem functioning by contrasting how the observed and simulated sensitivity of vegetation to climate varies across climate space. Our analysis yields empirical evidence for multiple physical and biological mediators of the sensitivity of vegetation to climate as a systematic change across climate space. Our comparison of remote sensing-based vegetation sensitivity with modeled estimates provides evidence for which physiological mechanisms - photosynthetic efficiency, respiration, water supply, atmospheric water demand, and sunlight availability - dominate the ecosystem functioning in places with different climates. Earth system models are generally successful in reproducing the broad sign and shape of ecosystem functioning across climate space. However, this general agreement breaks down in hot wet climates where models simulate less leaf area during a warmer year, while observations show a mixed response but overall more leaf area during warmer years. In addition, simulated ecosystem interaction with temperature is generally larger and changes more rapidly across a gradient of temperature than is observed. We hypothesize that the amplified interaction and change are both due to a lack of adaptation and acclimation in simulations. This discrepancy with observations suggests that simulated responses of vegetation to

  5. Empirically derived personality subtyping for predicting clinical symptoms and treatment response in bulimia nervosa.

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    Haynos, Ann F; Pearson, Carolyn M; Utzinger, Linsey M; Wonderlich, Stephen A; Crosby, Ross D; Mitchell, James E; Crow, Scott J; Peterson, Carol B

    2017-05-01

    Evidence suggests that eating disorder subtypes reflecting under-controlled, over-controlled, and low psychopathology personality traits constitute reliable phenotypes that differentiate treatment response. This study is the first to use statistical analyses to identify these subtypes within treatment-seeking individuals with bulimia nervosa (BN) and to use these statistically derived clusters to predict clinical outcomes. Using variables from the Dimensional Assessment of Personality Pathology-Basic Questionnaire, K-means cluster analyses identified under-controlled, over-controlled, and low psychopathology subtypes within BN patients (n = 80) enrolled in a treatment trial. Generalized linear models examined the impact of personality subtypes on Eating Disorder Examination global score, binge eating frequency, and purging frequency cross-sectionally at baseline and longitudinally at end of treatment (EOT) and follow-up. In the longitudinal models, secondary analyses were conducted to examine personality subtype as a potential moderator of response to Cognitive Behavioral Therapy-Enhanced (CBT-E) or Integrative Cognitive-Affective Therapy for BN (ICAT-BN). There were no baseline clinical differences between groups. In the longitudinal models, personality subtype predicted binge eating (p = 0.03) and purging (p = 0.01) frequency at EOT and binge eating frequency at follow-up (p = 0.045). The over-controlled group demonstrated the best outcomes on these variables. In secondary analyses, there was a treatment by subtype interaction for purging at follow-up (p = 0.04), which indicated a superiority of CBT-E over ICAT-BN for reducing purging among the over-controlled group. Empirically derived personality subtyping appears to be a valid classification system with potential to guide eating disorder treatment decisions. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:506-514). © 2016 Wiley Periodicals, Inc.

  6. Empirically Derived Lessons Learned about What Makes Peer-Led Exercise Groups Flourish.

    Science.gov (United States)

    Fletcher, Kathlyn E; Ertl, Kristyn; Ruffalo, Leslie; Harris, LaTamba; Whittle, Jeff

    2017-01-01

    Physical exercise confers many health benefits, but it is difficult to motivate people to exercise. Although community exercise groups may facilitate initiation and persistence in an exercise program, reports regarding factors that allow such groups to flourish are limited. We performed a prospective qualitative evaluation of our experience starting a program of community-based, peer-led exercise groups for military veterans to identify important lessons learned. We synthesized data from structured observations, post-observation debriefings, and focus groups. Our participants were trained peer leaders and exercise group members. Our main outcomes consisted of empirically derived lessons learned during the implementation of a peer-led group exercise program for veterans at multiple community sites. We collected and analyzed data from 40 observation visits (covering 14 sites), 7 transcribed debriefings, and 5 focus groups. We identified five lessons learned. (1) The camaraderie and social aspect of the exercise groups provided motivation for people to stay involved. (2) Shared responsibility and commitment to each other by the group members was instrumental to success. (3) Regular meeting times encouraged participation. (4) Variety, especially getting outdoors, was very popular for some groups. (5) Modest involvement of professionals encouraged ongoing engagement with the program. Both social and programmatic issues influence implementation of group exercise programs for older, predominantly male, veterans. These results should be confirmed in other settings.

  7. Testing an empirically derived mental health training model featuring small groups, distributed practice and patient discussion.

    Science.gov (United States)

    Murrihy, Rachael C; Byrne, Mitchell K; Gonsalvez, Craig J

    2009-02-01

    Internationally, family doctors seeking to enhance their skills in evidence-based mental health treatment are attending brief training workshops, despite clear evidence in the literature that short-term, massed formats are not likely to improve skills in this complex area. Reviews of the educational literature suggest that an optimal model of training would incorporate distributed practice techniques; repeated practice over a lengthy time period, small-group interactive learning, mentoring relationships, skills-based training and an ongoing discussion of actual patients. This study investigates the potential role of group-based training incorporating multiple aspects of good pedagogy for training doctors in basic competencies in brief cognitive behaviour therapy (BCBT). Six groups of family doctors (n = 32) completed eight 2-hour sessions of BCBT group training over a 6-month period. A baseline control design was utilised with pre- and post-training measures of doctors' BCBT skills, knowledge and engagement in BCBT treatment. Family doctors' knowledge, skills in and actual use of BCBT with patients improved significantly over the course of training compared with the control period. This research demonstrates preliminary support for the efficacy of an empirically derived group training model for family doctors. Brief CBT group-based training could prove to be an effective and viable model for future doctor training.

  8. Examining the Stability of "DSM-IV" and Empirically Derived Eating Disorder Classification: Implications for "DSM-5"

    Science.gov (United States)

    Peterson, Carol B.; Crow, Scott J.; Swanson, Sonja A.; Crosby, Ross D.; Wonderlich, Stephen A.; Mitchell, James E.; Agras, W. Stewart; Halmi, Katherine A.

    2011-01-01

    Objective: The purpose of this investigation was to derive an empirical classification of eating disorder symptoms in a heterogeneous eating disorder sample using latent class analysis (LCA) and to examine the longitudinal stability of these latent classes (LCs) and the stability of DSM-IV eating disorder (ED) diagnoses. Method: A total of 429…

  9. Expression profiling and comparative sequence derived insights into lipid metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Callow, Matthew J.; Rubin, Edward M.

    2001-12-19

    Expression profiling and genomic DNA sequence comparisons are increasingly being applied to the identification and analysis of the genes involved in lipid metabolism. Not only has genome-wide expression profiling aided in the identification of novel genes involved in important processes in lipid metabolism such as sterol efflux, but the utilization of information from these studies has added to our understanding of the regulation of pathways participating in the process. Coupled with these gene expression studies, cross species comparison, searching for sequences conserved through evolution, has proven to be a powerful tool to identify important non-coding regulatory sequences as well as the discovery of novel genes relevant to lipid biology. An example of the value of this approach was the recent chance discovery of a new apolipoprotein gene (apo AV) that has dramatic effects upon triglyceride metabolism in mice and humans.

  10. Diet index-based and empirically derived dietary patterns are associated with colorectal cancer risk.

    Science.gov (United States)

    Miller, Paige E; Lazarus, Philip; Lesko, Samuel M; Muscat, Joshua E; Harper, Gregory; Cross, Amanda J; Sinha, Rashmi; Ryczak, Karen; Escobar, Gladys; Mauger, David T; Hartman, Terryl J

    2010-07-01

    Previous studies have derived patterns by measuring compliance with preestablished dietary guidance or empirical methods, such as principal components analysis (PCA). Our objective was to examine colorectal cancer risk associated with patterns identified by both methods. The study included 431 incident colorectal cancer cases (225 men, 206 women) and 726 healthy controls (330 men, 396 women) participating in a population-based, case-control study. PCA identified sex-specific dietary patterns and the Healthy Eating Index-2005 (HEI-05) assessed adherence to the 2005 Dietary Guidelines for Americans. A fruits and vegetables pattern and a meat, potatoes, and refined grains pattern were identified among men and women; a third pattern (alcohol and sweetened beverages) was identified in men. The fruits and vegetables pattern was inversely associated with risk among men [odds ratio (OR) = 0.38, 95% CI = 0.21-0.69 for the highest compared with the lowest quartile] and women (OR = 0.35, 95% CI = 0.19-0.65). The meat, potatoes, and refined grains pattern was positively associated with risk in women (OR = 2.20, 95% CI = 1.08-4.50) and there was a suggestion of a positive association among men (OR = 1.56, 95% CI = 0.84-2.90; P-trend = 0.070). Men and women with greater HEI-05 scores had a significantly reduced risk of colorectal cancer (OR = 0.56, 95% CI = 0.31-0.99; OR = 0.44, 95% CI = 0.24-0.77, respectively). Following the Dietary Guidelines or a dietary pattern lower in meat, potatoes, high fat, and refined foods and higher in fruits and vegetables may reduce colorectal cancer risk.

  11. Empirical Derivation of Correction Factors for Human Spiral Ganglion Cell Nucleus and Nucleolus Count Units.

    Science.gov (United States)

    Robert, Mark E; Linthicum, Fred H

    2016-01-01

    Profile count method for estimating cell number in sectioned tissue applies a correction factor for double count (resulting from transection during sectioning) of count units selected to represent the cell. For human spiral ganglion cell counts, we attempted to address apparent confusion between published correction factors for nucleus and nucleolus count units that are identical despite the role of count unit diameter in a commonly used correction factor formula. We examined a portion of human cochlea to empirically derive correction factors for the 2 count units, using 3-dimensional reconstruction software to identify double counts. The Neurotology and House Histological Temporal Bone Laboratory at University of California at Los Angeles. Using a fully sectioned and stained human temporal bone, we identified and generated digital images of sections of the modiolar region of the lower first turn of cochlea, identified count units with a light microscope, labeled them on corresponding digital sections, and used 3-dimensional reconstruction software to identify double-counted count units. For 25 consecutive sections, we determined that double-count correction factors for nucleus count unit (0.91) and nucleolus count unit (0.92) matched the published factors. We discovered that nuclei and, therefore, spiral ganglion cells were undercounted by 6.3% when using nucleolus count units. We determined that correction factors for count units must include an element for undercounting spiral ganglion cells as well as the double-count element. We recommend a correction factor of 0.91 for the nucleus count unit and 0.98 for the nucleolus count unit when using 20-µm sections. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

  12. Using Whole-House Field Tests to Empirically Derive Moisture Buffering Model Inputs

    Energy Technology Data Exchange (ETDEWEB)

    Woods, J.; Winkler, J.; Christensen, D.; Hancock, E.

    2014-08-01

    Building energy simulations can be used to predict a building's interior conditions, along with the energy use associated with keeping these conditions comfortable. These models simulate the loads on the building (e.g., internal gains, envelope heat transfer), determine the operation of the space conditioning equipment, and then calculate the building's temperature and humidity throughout the year. The indoor temperature and humidity are affected not only by the loads and the space conditioning equipment, but also by the capacitance of the building materials, which buffer changes in temperature and humidity. This research developed an empirical method to extract whole-house model inputs for use with a more accurate moisture capacitance model (the effective moisture penetration depth model). The experimental approach was to subject the materials in the house to a square-wave relative humidity profile, measure all of the moisture transfer terms (e.g., infiltration, air conditioner condensate) and calculate the only unmeasured term: the moisture absorption into the materials. After validating the method with laboratory measurements, we performed the tests in a field house. A least-squares fit of an analytical solution to the measured moisture absorption curves was used to determine the three independent model parameters representing the moisture buffering potential of this house and its furnishings. Follow on tests with realistic latent and sensible loads showed good agreement with the derived parameters, especially compared to the commonly-used effective capacitance approach. These results show that the EMPD model, once the inputs are known, is an accurate moisture buffering model.

  13. Collagen-derived markers of bone metabolism in osteogenesis imperfecta

    DEFF Research Database (Denmark)

    Lund, A M; Hansen, M; Kollerup, Gina Birgitte

    1998-01-01

    )] were measured in 78 osteogenesis imperfecta (OI) patients to investigate bone metabolism in vivo and relate marker concentrations to phenotype and in vitro collagen I defects, as shown by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). PICP and PINP were generally low...

  14. Metabolic engineering toward 1-butanol derivatives in solvent producing clostridia

    NARCIS (Netherlands)

    Siemerink, M.A.J.

    2010-01-01

    Chapter 1 of this thesis gives an overview about the history of the acetone, butanol and ethanol (ABE) fermentation. The responsible solventogenic clostridia with their central metabolism are briefly discussed. Despite the fact that scientific research on the key organisms of the ABE process has

  15. The need of data harmonization to derive robust empirical relationships between soil conditions and vegetation.

    NARCIS (Netherlands)

    Bartholomeus, R.P.; Witte, J.P.M.; van Bodegom, P.M.; Aerts, R.

    2008-01-01

    Question: Is it possible to improve the general applicability and significance of empirical relationships between abiotic conditions and vegetation by harmonization of temporal data? Location: The Netherlands. Methods: Three datasets of vegetation, recorded after periods with different

  16. Collagen-derived markers of bone metabolism in osteogenesis imperfecta

    DEFF Research Database (Denmark)

    Lund, A M; Hansen, M; Kollerup, Gina Birgitte

    1998-01-01

    )] were measured in 78 osteogenesis imperfecta (OI) patients to investigate bone metabolism in vivo and relate marker concentrations to phenotype and in vitro collagen I defects, as shown by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). PICP and PINP were generally low....... The in vivo findings correlated with in vitro results of collagen I SDS-PAGE. Bone turnover is reduced in OI children and mildly affected OI adults, whereas bone resorption is elevated in severely affected adults. These findings may prove helpful for diagnosis and decision-making regarding therapy in OI....

  17. Hydroxylamine derivatives for regulation of spermine and spermidine metabolism.

    Science.gov (United States)

    Khomutov, M A; Weisell, J; Hyvönen, M; Keinänen, T A; Vepsäläinen, J; Alhonen, L; Khomutov, A R; Kochetkov, S N

    2013-12-01

    The biogenic polyamines spermine, spermidine, and their precursor putrescine are present in micro-to-millimolar concentrations in all cell types and are vitally important for their normal growth. High intracellular content of spermine and spermidine determines the multiplicity of the cellular functions of the polyamines. Many of these functions are not well characterized at the molecular level, ensuring the ongoing development of this field of biochemistry. Tumor cells have elevated polyamine level if compared with normal cells, and this greatly stimulates the search for new opportunities to deplete the intracellular pool of spermine and spermidine resulting in decrease in cell growth and even cell death. O-Substituted hydroxylamines occupy their own place among chemical regulators of the activity of the enzymes of polyamine metabolism. Varying the structure of the alkyl substituent made it possible to obtain within one class of chemical compounds highly effective inhibitors and regulators of the activity of all the enzymes of putrescine, spermine and spermidine metabolism (with the exception of FAD-dependent spermine oxidase and acetylpolyamine oxidase), effectors of the polyamine transport system, and even actively transported in cells "proinhibitor" of ornithine decarboxylase. Some principles for the design of specific inhibitors of these enzymes as well as the peculiarities of cellular effects of corresponding O-substituted hydroxylamines are discussed.

  18. Libor and Swap Market Models for the Pricing of Interest Rate Derivatives : An Empirical Analysis

    NARCIS (Netherlands)

    de Jong, F.C.J.M.; Driessen, J.J.A.G.; Pelsser, A.

    2000-01-01

    In this paper we empirically analyze and compare the Libor and Swap Market Models, developed by Brace, Gatarek, and Musiela (1997) and Jamshidian (1997), using paneldata on prices of US caplets and swaptions.A Libor Market Model can directly be calibrated to observed prices of caplets, whereas a

  19. Empirical studies on the pricing of bonds and interest rate derivatives

    NARCIS (Netherlands)

    Driessen, J.J.A.G.

    2001-01-01

    Nowadays, both large financial and non-financial institutions use models for the term structure of interest rates for risk management and pricing purposes. This thesis focuses on these two important applications of term structure models. In the first part, the empirical performance of several term

  20. Microbiota-Derived Metabolic Factors Reduce Campylobacteriosis in Mice.

    Science.gov (United States)

    Sun, Xiaolun; Winglee, Kathryn; Gharaibeh, Raad Z; Gauthier, Josee; He, Zhen; Tripathi, Prabhanshu; Avram, Dorina; Bruner, Steven; Fodor, Anthony; Jobin, Christian

    2018-05-01

    Campylobacter jejuni, a prevalent foodborne bacterial pathogen, exploits the host innate response to induce colitis. Little is known about the roles of microbiota in C jejuni-induced intestinal inflammation. We investigated interactions between microbiota and intestinal cells during C jejuni infection of mice. Germ-free C57BL/6 Il10 -/- mice were colonized with conventional microbiota and infected with a single dose of C jejuni (10 9 colony-forming units/mouse) via gavage. Conventional microbiota were cultured under aerobic, microaerobic, or anaerobic conditions and orally transplanted into germ-free Il10 -/- mice. Colon tissues were collected from mice and analyzed by histology, real-time polymerase chain reaction, and immunoblotting. Fecal microbiota and bile acids were analyzed with 16S sequencing and high-performance liquid chromatography with mass spectrometry, respectively. Introduction of conventional microbiota reduced C jejuni-induced colitis in previously germ-free Il10 -/- mice, independent of fecal load of C jejuni, accompanied by reduced activation of mammalian target of rapamycin. Microbiota transplantation and 16S ribosomal DNA sequencing experiments showed that Clostridium XI, Bifidobacterium, and Lactobacillus were enriched in fecal samples from mice colonized with microbiota cultured in anaerobic conditions (which reduce colitis) compared with mice fed microbiota cultured under aerobic conditions (susceptible to colitis). Oral administration to mice of microbiota-derived secondary bile acid sodium deoxycholate, but not ursodeoxycholic acid or lithocholic acid, reduced C jejuni-induced colitis. Depletion of secondary bile acid-producing bacteria with antibiotics that kill anaerobic bacteria (clindamycin) promoted C jejuni-induced colitis in specific pathogen-free Il10 -/- mice compared with the nonspecific antibiotic nalidixic acid; colitis induction by antibiotics was associated with reduced level of luminal deoxycholate. We identified a

  1. Skeletal Muscle Derived IL-6 in Liver and Adipose Tissue Metabolism

    DEFF Research Database (Denmark)

    Knudsen, Jakob Grunnet

    Summary Physical activity can lead to metabolic disease and treatment of several metabolic diseases include exercise training. Skeletal muscle has, due to its central role in glucose and fat metabolism at rest and during exercise been studied in detail with regard to exercise training. The role...... of both liver and adipose tissue regulation in whole body metabolism has come in to focus and it has been shown that both tissues are subject to exercise training-induced adaptations. However, the contribution of endocrine factors to the regulation of exercise training-induced adaptations in liver...... and adipose tissue metabolism is unknown. It has been suggested that myokines, such as IL-6, released from skeletal muscle affects liver and adipose tissue and are involved in the regulation of exercise training adaptations. Thus, the aim of this thesis was to investigate the role of skeletal muscle derived...

  2. Derivation of an empirical formula for determining water content of mixed uranyl nitrate-thorium nitrate solutions

    International Nuclear Information System (INIS)

    Min, Duck Kee; Choi, Byung Il; Ro, Seung Gy; Eom, Tae Yoon; Kim, Zong Goo

    1986-01-01

    Densities of a large number of mixed uranyl nitrate-thorium nitrate solutions were measured with pycnometer. By the least squares analysis of the experimental result, an empirical formula for determining water content of mixed uranyl nitrate-thorium nitrate solutions as functions of uranium concentration, thorium concentration and nitric acid normality is derived; W=1.0-0.3580 C u -0.4538 C Th -0.0307H + where W, C u , C Th , and H + stand for water content(g/cc), uranium concentration (g/cc), thorium concentration(g/cc), and nitric acid normality, respectively. Water contents of the mixed uranyl nitrate-thorium nitrate solutions are calculated by using the empirical formular, and compared with the values calculated by Bouly's equation in which an additional data, solution density, is required. The two results show good agreements within 2.7%. (Author)

  3. RISK MANAGEMENT WITH FINANCIAL DERIVATIVES: EMPIRICAL EVIDENCE FROM ROMANIAN NON-FINANCIAL FIRMS

    Directory of Open Access Journals (Sweden)

    Sorin Gabriel Anton

    2016-12-01

    Full Text Available Financial risk management has rapidly evolved over the past two decades and has become an indispensable function in many institutions from different area of activities. In the last two decades, as the financial markets have become more and more mature, an increasing number of firms from emerging economies have chosen to use derivatives to hedge financial risks. As a result, risk management with financial derivatives has attracted much attention recently, becoming an important topic in the financial literature. However, we know little about the use of financial derivatives by firms from emerging economies and about the effect of these instruments on firms’ risk and value. The aim of the paper is to provide new insights into the use of financial derivatives for hedging purpose by non-financial firms from emerging markets. We analyzed risk management practices on a sample of 68 non-financial firms listed at Bucharest Stock Exchange (BSE over a long time frame (2001 to 2011. We found that Romanian non-financial firms from our sample are exposed mainly to commodity price risk, currency risk, interest rate risk, and liquidity risk. More than half of the firms in our sample (55.88% publish in their annual reports the goal of risk management process. Our results show that 10.29% of non-financial firms in our sample use financial derivatives to hedge their currency, interest rate or commodity price risks. We also found that the volatility caused by the global financial crisis determined many firms to use financial derivatives over the period 2007-2011. Nevertheless, the use of financial derivatives by Romanian non-financial firms is low relative to values registered for other emerging economies. The most important factors that hindered the use of financial derivatives have been the low liquidity of exchange derivatives markets, high hedging costs, and the lack of risk management expertise. The traditional approach of managing risks individually is

  4. Metabolic cost of neuronal information in an empirical stimulus-response model

    Czech Academy of Sciences Publication Activity Database

    Košťál, Lubomír; Lánský, Petr; McDonnell, M.D.

    2013-01-01

    Roč. 107, č. 3 (2013), s. 355-365 ISSN 0340-1200 R&D Projects: GA ČR(CZ) GBP304/12/G069; GA ČR(CZ) GAP103/11/0282; GA ČR(CZ) GPP103/12/P558 Institutional support: RVO:67985823 Keywords : information capacity * metabolic cost * stimulus-response curve Subject RIV: FH - Neurology Impact factor: 1.933, year: 2013

  5. Untargeted Metabolic Profiling of Winery-Derived Biomass Waste Degradation by Penicillium chrysogenum.

    Science.gov (United States)

    Karpe, Avinash V; Beale, David J; Godhani, Nainesh B; Morrison, Paul D; Harding, Ian H; Palombo, Enzo A

    2015-12-16

    Winery-derived biomass waste was degraded by Penicillium chrysogenum under solid state fermentation over 8 days in a (2)H2O-supplemented medium. Multivariate statistical analysis of the gas chromatography-mass spectrometry (GC-MS) data resulted in the identification of 94 significant metabolites, within 28 different metabolic pathways. The majority of biomass sugars were utilized by day 4 to yield products such as sugars, fatty acids, isoprenoids, and amino acids. The fungus was observed to metabolize xylose to xylitol, an intermediate of ethanol production. However, enzyme inhibition and autolysis were observed from day 6, indicating 5 days as the optimal time for fermentation. P. chrysogenum displayed metabolism of pentoses (to alcohols) and degraded tannins and lignins, properties that are lacking in other biomass-degrading ascomycetes. Rapid fermentation (3-5 days) may not only increase the pentose metabolizing efficiency but also increase the yield of medicinally important metabolites, such as syringate.

  6. The performance of selected semi-empirical and DFT methods in studying C₆₀ fullerene derivatives.

    Science.gov (United States)

    Sikorska, Celina; Puzyn, Tomasz

    2015-11-13

    The capability of reproducing the open circuit voltages (V(oc)) of 15 representative C60 fullerene derivatives was tested using the selected quantum mechanical methods (B3LYP, PM6, and PM7) together with the two one-electron basis sets. Certain theoretical treatments (e.g. PM6) were found to be satisfactory for preliminary estimates of the open circuit voltages (V(oc)), whereas the use of the B3LYP/6-31G(d) approach has been proven to assure highly accurate results. We also examined the structural similarity of 19 fullerene derivatives by employing principle component analysis (PCA). In order to express the structural features of the studied compounds we used molecular descriptors calculated with semi-empirical (PM6 and PM7) and density functional (B3LYP/6-31G(d)) methods separately. In performing PCA, we noticed that semi-empirical methods (i.e. PM6 and PM7) seem satisfactory for molecules, in which one can distinguish the aromatic and the aliphatic parts in the cyclopropane ring of PCBM (phenyl-C61-buteric acid methyl ester) and they significantly overestimate the energy of the highest occupied molecular orbital (E(HOMO)). The use of the B3LYP functional, however, is recommended for studying methanofullerenes, which closely resemble the structure of PCBM, and for their modifications.

  7. An Empirical Derivation of the Run Time of the Bubble Sort Algorithm.

    Science.gov (United States)

    Gonzales, Michael G.

    1984-01-01

    Suggests a moving pictorial tool to help teach principles in the bubble sort algorithm. Develops such a tool applied to an unsorted list of numbers and describes a method to derive the run time of the algorithm. The method can be modified to run the times of various other algorithms. (JN)

  8. Empirically Derived Dietary Patterns in UK Adults Are Associated with Sociodemographic Characteristics, Lifestyle, and Diet Quality

    Science.gov (United States)

    Cade, Janet; Dawson, Jeremy; Holdsworth, Michelle

    2018-01-01

    The aim of this study was to examine empirical dietary patterns in UK adults and their association with sociodemographic characteristics, lifestyle factors, self-reported nutrient intake, nutrient biomarkers, and the Nutrient-based Diet Quality Score (NDQS) using National Diet and Nutrition Survey data 2008–2012 (n = 2083; mean age 49 years; 43.3% male). Four patterns explained 13.6% of the total variance: ‘Snacks, fast food, fizzy drinks’ (SFFFD), ‘Fruit, vegetables, oily fish’ (FVOF), ‘Meat, potatoes, beer’ (MPB), and ‘Sugary foods, dairy’ (SFD). ‘SFFFD’ was associated positively with: being male; smoking; body mass index (BMI); urinary sodium; intake of non-milk extrinsic sugars (NMES), fat and starch; and negatively with: age; plasma carotenoids; and NDQS. ‘FVOF’ was associated positively with: being non-white; age; income; socioeconomic classification (National Statistics Socio-economic Classifications; NSSEC); plasma carotenoids; intake of non-starch polysaccharides and polyunsaturated fatty acids. It was negatively associated with: being male, smoking, BMI, urinary sodium, intake of saturated fat; and NMES and NDQS. Whilst the patterns explained only 13.6% of the total variance, they were associated with self-reported nutrient intake, biomarkers of nutrient intake, sociodemographic and lifestyle variables, and the NDQS. These findings provide support for dietary patterns analyses as a means of exploring dietary intake in the UK population to inform public health nutrition policy and guidance. PMID:29415478

  9. New GRACE-Derived Storage Change Estimates Using Empirical Mode Extraction

    Science.gov (United States)

    Aierken, A.; Lee, H.; Yu, H.; Ate, P.; Hossain, F.; Basnayake, S. B.; Jayasinghe, S.; Saah, D. S.; Shum, C. K.

    2017-12-01

    Estimated mass change from GRACE spherical harmonic solutions have north/south stripes and east/west banded errors due to random noise and modeling errors. Low pass filters like decorrelation and Gaussian smoothing are typically applied to reduce noise and errors. However, these filters introduce leakage errors that need to be addressed. GRACE mascon estimates (JPL and CSR mascon solutions) do not need decorrelation or Gaussian smoothing and offer larger signal magnitudes compared to the GRACE spherical harmonics (SH) filtered results. However, a recent study [Chen et al., JGR, 2017] demonstrated that both JPL and CSR mascon solutions also have leakage errors. We developed a new postprocessing method based on empirical mode decomposition to estimate mass change from GRACE SH solutions without decorrelation and Gaussian smoothing, the two main sources of leakage errors. We found that, without any post processing, the noise and errors in spherical harmonic solutions introduced very clear high frequency components in the spatial domain. By removing these high frequency components and reserve the overall pattern of the signal, we obtained better mass estimates with minimum leakage errors. The new global mass change estimates captured all the signals observed by GRACE without the stripe errors. Results were compared with traditional methods over the Tonle Sap Basin in Cambodia, Northwestern India, Central Valley in California, and the Caspian Sea. Our results provide larger signal magnitudes which are in good agreement with the leakage corrected (forward modeled) SH results.

  10. Empirical Derivation and Validation of a Clinical Case Definition for Neuropsychological Impairment in Children and Adolescents.

    Science.gov (United States)

    Beauchamp, Miriam H; Brooks, Brian L; Barrowman, Nick; Aglipay, Mary; Keightley, Michelle; Anderson, Peter; Yeates, Keith O; Osmond, Martin H; Zemek, Roger

    2015-09-01

    Neuropsychological assessment aims to identify individual performance profiles in multiple domains of cognitive functioning; however, substantial variation exists in how deficits are defined and what cutoffs are used, and there is no universally accepted definition of neuropsychological impairment. The aim of this study was to derive and validate a clinical case definition rule to identify neuropsychological impairment in children and adolescents. An existing normative pediatric sample was used to calculate base rates of abnormal functioning on eight measures covering six domains of neuropsychological functioning. The dataset was analyzed by varying the range of cutoff levels [1, 1.5, and 2 standard deviations (SDs) below the mean] and number of indicators of impairment. The derived rule was evaluated by bootstrap, internal and external clinical validation (orthopedic and traumatic brain injury). Our neuropsychological impairment (NPI) rule was defined as "two or more test scores that fall 1.5 SDs below the mean." The rule identifies 5.1% of the total sample as impaired in the assessment battery and consistently targets between 3 and 7% of the population as impaired even when age, domains, and number of tests are varied. The NPI rate increases in groups known to exhibit cognitive deficits. The NPI rule provides a psychometrically derived method for interpreting performance across multiple tests and may be used in children 6-18 years. The rule may be useful to clinicians and scientists who wish to establish whether specific individuals or clinical populations present within expected norms versus impaired function across a battery of neuropsychological tests.

  11. An Empirical Ultraviolet Template for Iron Emission in Quasars as Derived from I Zw 1

    DEFF Research Database (Denmark)

    Vestergaard, Marianne; Wilkes, B. J.

    2001-01-01

    contaminant in optical--UV spectra of AGNs. Its presence complicates and limits the accuracy of measurements of both strong and weak emission lines and the continuum emission, affecting studies of line and continuum interrelations, the ionization structure, and elemental abundances in AGNs. Despite the wealth...... iron spectrum make the template particularly suitable for use with most AGN spectra. The iron emission spectrum and the line identifications and measurements are presented and compared with the work of Laor et al. We illustrate the application of the derived FeII and FeIII templates by fitting...

  12. An approach to derive some simple empirical equations to calibrate nuclear and acoustic well logging tools.

    Science.gov (United States)

    Mohammad Al Alfy, Ibrahim

    2018-01-01

    A set of three pads was constructed from primary materials (sand, gravel and cement) to calibrate the gamma-gamma density tool. A simple equation was devised to convert the qualitative cps values to quantitative g/cc values. The neutron-neutron porosity tool measures the qualitative cps porosity values. A direct equation was derived to calculate the porosity percentage from the cps porosity values. Cement-bond log illustrates the cement quantities, which surround well pipes. This log needs a difficult process due to the existence of various parameters, such as: drilling well diameter as well as internal diameter, thickness and type of well pipes. An equation was invented to calculate the cement percentage at standard conditions. This equation can be modified according to varying conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Internal Control of Derivatives Usage by Spanish Savings Banks: An Empirical Survey

    Directory of Open Access Journals (Sweden)

    Ana Fernández-Laviada

    2007-12-01

    Full Text Available Global derivatives activity continues to expand although they have provided some of the most devastating financial disasters. The debate on their regulation has always been present and is still unresolved. However, without undervaluing the importance of regulation and the usefulness of an adequate external control, a sound internal control system is essential to prevent new financial scandals. First of all, this paper, through the review of existing recommendations, rules, regulation and academic literature, studies and analyses the need and importance of internal control in derivative usage for risk management. And secondly, through a questionnaire about established policies, procedures and internal controls, it provides evidence related to its usage and control by Spanish savings banks.El uso de los derivados sigue en expansión a pesar de haber ocasionado alguno de los mayoresescándalos financieros.El debate sobre su regulación, todavía sin resolver, ha estado siempre presente. No obstante,y sin menospreciar la importancia de la regulación y la utilidad de un adecuado controlexterno, un buen sistema de control interno es esencial para prevenir nuevos desastres.Este trabajo, en primer lugar, a través de la revisión de las recomendaciones, normas,regulación y literatura académica existente, estudia y analiza la necesidad e importancia delcontrol interno en el uso de los derivados para la gestión del riesgo. Y en segundo lugar, através de un cuestionario sobre las políticas, procedimientos y controles internos establecidos,aporta evidencia sobre el uso y control de los mismos por las cajas de ahorros españolas.

  14. Empirically derived dimensional syndromes of self-reported psychopathology: Cross-cultural comparisons of Portuguese and US elders.

    Science.gov (United States)

    Ivanova, Masha Y; Achenbach, Thomas; Leite, Manuela; Almeida, Vera; Caldas, Carlos; Turner, Lori; Dumas, Julie A

    2018-05-01

    As the world population ages, mental health professionals increasingly need empirically supported assessment instruments for older adult psychopathology. This study tested the degree to which syndromes derived from self-ratings of psychopathology by elders in the US would fit self-ratings by elders in Portugal. The Older Adult Self-Report (OASR) was completed by 352 60- to 102-year-olds in Portuguese community and residential settings. Confirmatory factor analyses tested the fit of the 7-syndrome OASR model to self-ratings by Portuguese elders. The primary fit index (Root Mean Square Error of Approximation) showed good fit, while secondary fit indices (the Comparative Fit Index and the Tucker-Lewis Index) showed acceptable fit. Loadings of 95 of the 97 items on their expected syndromes were statistically significant (mean = .63), indicating that the items measured the syndromes well. Correlations between latent factors, ie, between the hypothesized syndrome constructs measured by the items, averaged .66. The correlations between syndromes reflect varying degrees of comorbidity between problems comprising particular pairs of syndromes. The results support the syndrome structure of the OASR for Portuguese elders, offering Portuguese clinicians and researchers a useful instrument for assessing a broad spectrum of psychopathology. The results also offer a core of empirically supported taxonomic constructs of later life psychopathology as a basis for advancing clinical practice, training, and cross-cultural research. Copyright © 2017 John Wiley & Sons, Ltd.

  15. Precision comparison of the erosion rates derived from 137Cs measurements models with predictions based on empirical relationship

    International Nuclear Information System (INIS)

    Yang Mingyi; Liu Puling; Li Liqing

    2004-01-01

    The soil samples were collected in 6 cultivated runoff plots with grid sampling method, and the soil erosion rates derived from 137 Cs measurements were calculated. The models precision of Zhang Xinbao, Zhou Weizhi, Yang Hao and Walling were compared with predictions based on empirical relationship, data showed that the precision of 4 models is high within 50m slope length except for the slope with low slope angle and short length. Relatively, the precision of Walling's model is better than that of Zhang Xinbao, Zhou Weizhi and Yang Hao. In addition, the relationship between parameter Γ in Walling's improved model and slope angle was analyzed, the ralation is: Y=0.0109 X 1.0072 . (authors)

  16. Minimal variance hedging of natural gas derivatives in exponential Lévy models: Theory and empirical performance

    International Nuclear Information System (INIS)

    Ewald, Christian-Oliver; Nawar, Roy; Siu, Tak Kuen

    2013-01-01

    We consider the problem of hedging European options written on natural gas futures, in a market where prices of traded assets exhibit jumps, by trading in the underlying asset. We provide a general expression for the hedging strategy which minimizes the variance of the terminal hedging error, in terms of stochastic integral representations of the payoffs of the options involved. This formula is then applied to compute hedge ratios for common options in various models with jumps, leading to easily computable expressions. As a benchmark we take the standard Black–Scholes and Merton delta hedges. We show that in natural gas option markets minimal variance hedging with underlying consistently outperform the benchmarks by quite a margin. - Highlights: ► We derive hedging strategies for European type options written on natural gas futures. ► These are tested empirically using Henry Hub natural gas futures and options data. ► We find that our hedges systematically outperform classical benchmarks

  17. Empirically derived dietary patterns and health-related quality of life in the SUN project.

    Directory of Open Access Journals (Sweden)

    Cristina Ruano

    Full Text Available The analysis of dietary patterns has become a valuable tool to examine diet-disease relationships but little is known about their effects on quality of life. Our aim was to ascertain the association between major dietary patterns and mental and physical quality of life after 4 years of follow-up.This analysis included 11,128 participants from the "Seguimiento Universidad de Navarra" (SUN cohort. Dietary habits were assessed using a validated food-frequency questionnaire. Factor analysis was used to derive dietary patterns. Quality of life was measured with the validated Spanish version of the SF-36 Health Survey.Two major dietary patterns were identified, the 'Western' dietary pattern (rich in red meats, processed pastries and fast-food and the "Mediterranean" dietary pattern (high in fruits, vegetables and olive oil. After controlling for confounders, the Western dietary pattern was associated with quality of life in all domains. The magnitude of these differences between the subjects in the highest (quintile 5 and the lowest quintile of adherence to the Western pattern ranged from -0.8 (for mental health to -3.5 (for vitality. On the contrary, the Mediterranean dietary pattern was associated with better quality of life domains: differences ranged from +1.3 (for physical functioning to +3.4 (for vitality when comparing extreme quintiles of adherence. Additional sensitivity analyses did not change the reported differences.Whereas baseline adherence to a Western dietary pattern was inversely associated with self-perceived quality of life after 4 years of follow-up, baseline adherence to a Mediterranean dietary pattern was directly associated with better scores in quality of life four years later in the SUN Project.

  18. Empirically derived dietary patterns and health-related quality of life in the SUN project.

    Science.gov (United States)

    Ruano, Cristina; Henriquez, Patricia; Martínez-González, Miguel Ángel; Bes-Rastrollo, Maira; Ruiz-Canela, Miguel; Sánchez-Villegas, Almudena

    2013-01-01

    The analysis of dietary patterns has become a valuable tool to examine diet-disease relationships but little is known about their effects on quality of life. Our aim was to ascertain the association between major dietary patterns and mental and physical quality of life after 4 years of follow-up. This analysis included 11,128 participants from the "Seguimiento Universidad de Navarra" (SUN) cohort. Dietary habits were assessed using a validated food-frequency questionnaire. Factor analysis was used to derive dietary patterns. Quality of life was measured with the validated Spanish version of the SF-36 Health Survey. Two major dietary patterns were identified, the 'Western' dietary pattern (rich in red meats, processed pastries and fast-food) and the "Mediterranean" dietary pattern (high in fruits, vegetables and olive oil). After controlling for confounders, the Western dietary pattern was associated with quality of life in all domains. The magnitude of these differences between the subjects in the highest (quintile 5) and the lowest quintile of adherence to the Western pattern ranged from -0.8 (for mental health) to -3.5 (for vitality). On the contrary, the Mediterranean dietary pattern was associated with better quality of life domains: differences ranged from +1.3 (for physical functioning) to +3.4 (for vitality) when comparing extreme quintiles of adherence. Additional sensitivity analyses did not change the reported differences. Whereas baseline adherence to a Western dietary pattern was inversely associated with self-perceived quality of life after 4 years of follow-up, baseline adherence to a Mediterranean dietary pattern was directly associated with better scores in quality of life four years later in the SUN Project.

  19. Correcting orbital drift signal in the time series of AVHRR derived convective cloud fraction using rotated empirical orthogonal function

    Directory of Open Access Journals (Sweden)

    A. Devasthale

    2012-02-01

    Full Text Available The Advanced Very High Resolution Radiometer (AVHRR instruments onboard the series of National Oceanic and Atmospheric Administration (NOAA satellites offer the longest available meteorological data records from space. These satellites have drifted in orbit resulting in shifts in the local time sampling during the life span of the sensors onboard. Depending upon the amplitude of the diurnal cycle of the geophysical parameters derived, orbital drift may cause spurious trends in their time series. We investigate tropical deep convective clouds, which show pronounced diurnal cycle amplitude, to estimate an upper bound of the impact of orbital drift on their time series. We carry out a rotated empirical orthogonal function analysis (REOF and show that the REOFs are useful in delineating orbital drift signal and, more importantly, in subtracting this signal in the time series of convective cloud amount. These results will help facilitate the derivation of homogenized data series of cloud amount from NOAA satellite sensors and ultimately analyzing trends from them. However, we suggest detailed comparison of various methods and rigorous testing thereof applying final orbital drift corrections.

  20. A tryptophan derivative, ITE, enhances liver cell metabolic functions in vitro.

    Science.gov (United States)

    Zhang, Xiaoqian; Lu, Juan; He, Bin; Tang, Lingling; Liu, Xiaoli; Zhu, Danhua; Cao, Hongcui; Wang, Yingjie; Li, Lanjuan

    2017-01-01

    Cell encapsulation provides a three-dimensional support by incorporating isolated cells into microcapsules with the goal of simultaneously maintaining cell survival and function, as well as providing active transport for a bioreactor in vitro similarly to that observed in vivo. However, the biotra-nsformation and metabolic functions of the encapsulated cells are not satisfactory for clinical applications. For this purpose, in this study, hepatoma-derived Huh7 cells/C3A cells were treated with 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), an endogenous non-toxic ligand for aryl hydrocarbon receptor, in monolayer cultures and on microspheres. The mRNA and protein levels, as well as the metabolic activities of drug metabolizing enzymes, albumin secretion and urea synthesis were determined. When the Huh7 and C3A cells cultured in a monolayer on two‑dimensional surfaces, ITE enhanced the protein levels and the metabolic activities of the major cytochrome P450 (CYP450) enzymes, CYP1A1, CYP1A2, CYP3A4 and CYP1B1, and slightly increased albumin secretion and urea synthesis. Moreover, when cultured on microspheres, ITE also substantially increased the protein levels and metabolic activities of CYP1A1, CYP1A2, CYP3A4 and CYP1B1 in both liver cell lines. On the whole, our findings indicate that ITE enhances the enzymatic activities of major CYP450 enzymes and the metabolic functions of liver cells cultured in monolayer or on microspheres, indicating that it may be utilized to improve the functions of hepatocytes. Thus, it may be used in the future for the treatment of liver diseases.

  1. A tryptophan derivative, ITE, enhances liver cell metabolic functions in vitro

    Science.gov (United States)

    Zhang, Xiaoqian; Lu, Juan; He, Bin; Tang, Lingling; Liu, Xiaoli; Zhu, Danhua; Cao, Hongcui; Wang, Yingjie; Li, Lanjuan

    2017-01-01

    Cell encapsulation provides a three-dimensional support by incorporating isolated cells into microcapsules with the goal of simultaneously maintaining cell survival and function, as well as providing active transport for a bioreactor in vitro similarly to that observed in vivo. However, the biotransformation and metabolic functions of the encapsulated cells are not satisfactory for clinical applications. For this purpose, in this study, hepatoma-derived Huh7 cells/C3A cells were treated with 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), an endogenous non-toxic ligand for aryl hydrocarbon receptor, in monolayer cultures and on microspheres. The mRNA and protein levels, as well as the metabolic activities of drug metabolizing enzymes, albumin secretion and urea synthesis were determined. When the Huh7 and C3A cells cultured in a monolayer on two-dimensional surfaces, ITE enhanced the protein levels and the metabolic activities of the major cytochrome P450 (CYP450) enzymes, CYP1A1, CYP1A2, CYP3A4 and CYP1B1, and slightly increased albumin secretion and urea synthesis. Moreover, when cultured on microspheres, ITE also substantially increased the protein levels and metabolic activities of CYP1A1, CYP1A2, CYP3A4 and CYP1B1 in both liver cell lines. On the whole, our findings indicate that ITE enhances the enzymatic activities of major CYP450 enzymes and the metabolic functions of liver cells cultured in monolayer or on microspheres, indicating that it may be utilized to improve the functions of hepatocytes. Thus, it may be used in the future for the treatment of liver diseases. PMID:27959388

  2. Derivation of a semi-empirical formula for the quantum efficiency of forward secondary electron emission from γ-irradiated metals. 2

    International Nuclear Information System (INIS)

    Nakamura, Masamoto; Katoh, Yoh

    1994-01-01

    An empirical formula for the quantum efficiency of electrons irradiated with 60 Co γ-rays was reported in a previous paper, but its physical meaning was not made clear. Then, a simple model was assumed, from which a formula for calculating the efficiency was theoretically derived. Some parameters in the formula were determined so that the calculated results might fit the experimental data. The above empirical formula was shown to be the same as the formula physically derived this time. Results from the semiempirical formula and experimental data for Al and Pb sample were in agreement within the limits of 5%. (author)

  3. Bioactive Compounds Derived from the Yeast Metabolism of Aromatic Amino Acids during Alcoholic Fermentation

    Directory of Open Access Journals (Sweden)

    Albert Mas

    2014-01-01

    Full Text Available Metabolites resulting from nitrogen metabolism in yeast are currently found in some fermented beverages such as wine and beer. Their study has recently attracted the attention of researchers. Some metabolites derived from aromatic amino acids are bioactive compounds that can behave as hormones or even mimic their role in humans and may also act as regulators in yeast. Although the metabolic pathways for their formation are well known, the physiological significance is still far from being understood. The understanding of this relevance will be a key element in managing the production of these compounds under controlled conditions, to offer fermented food with specific enrichment in these compounds or even to use the yeast as nutritional complements.

  4. A preliminary study of the metabolic stability of a series of benzoxazinone derivatives as potent neuropeptide Y5 antagonists.

    Science.gov (United States)

    Dordal, Alberto; Lipkin, Mike; Macritchie, Jackie; Mas, Josep; Port, Adriana; Rose, Sally; Salgado, Leonardo; Savic, Vladimir; Schmidt, Wolfgang; Serafini, Maria Teresa; Spearing, William; Torrens, Antoni; Yeste, Sandra

    2005-08-15

    The metabolic stability of benzoxazinone derivatives, a potent series of NPY Y5 antagonists, has been investigated. This study resulted in the identification of the structural moieties prone to metabolic transformations and which strongly influenced the in vitro half-life. This provides opportunities to optimize the structure of this new class of NPY Y5 antagonists.

  5. Brain-derived neurotrophic factor, impaired glucose metabolism, and bipolar disorder course

    DEFF Research Database (Denmark)

    Mansur, Rodrigo B; Santos, Camila M; Rizzo, Lucas B

    2016-01-01

    OBJECTIVES: The neurotrophin brain-derived neurotrophic factor (BDNF) has been proposed as a potential biomarker in bipolar disorder (BD). However, current evidence is limited and results have been highly heterogeneous. This study aimed to assess the moderating effect of impaired glucose metabolism......, alcohol use, and IGM (P=.046). There was no effect of IGM (P=.860) and no interaction between BD diagnosis and IGM (P=.893). Peripheral BDNF levels were positively correlated with lifetime depressive episodes (Psuicide attempts (P=.021). IGM moderated...... the association between BDNF and the number of previous mood episodes (P

  6. Induced Pluripotent Stem Cell-Derived Endothelial Cells in Insulin Resistance and Metabolic Syndrome.

    Science.gov (United States)

    Carcamo-Orive, Ivan; Huang, Ngan F; Quertermous, Thomas; Knowles, Joshua W

    2017-11-01

    Insulin resistance leads to a number of metabolic and cellular abnormalities including endothelial dysfunction that increase the risk of vascular disease. Although it has been particularly challenging to study the genetic determinants that predispose to abnormal function of the endothelium in insulin-resistant states, the possibility of deriving endothelial cells from induced pluripotent stem cells generated from individuals with detailed clinical phenotyping, including accurate measurements of insulin resistance accompanied by multilevel omic data (eg, genetic and genomic characterization), has opened new avenues to study this relationship. Unfortunately, several technical barriers have hampered these efforts. In the present review, we summarize the current status of induced pluripotent stem cell-derived endothelial cells for modeling endothelial dysfunction associated with insulin resistance and discuss the challenges to overcoming these limitations. © 2017 American Heart Association, Inc.

  7. Diagnostic Classification of Eating Disorders in Children and Adolescents: How Does DSM-IV-TR Compare to Empirically-Derived Categories?

    Science.gov (United States)

    Eddy, Kamryn T.; Le Grange, Daniel; Crosby, Ross D.; Hoste, Renee Rienecke; Doyle, Angela Celio; Smyth, Angela; Herzog, David B.

    2010-01-01

    Objective: The purpose of this study was to empirically derive eating disorder phenotypes in a clinical sample of children and adolescents using latent profile analysis (LPA), and to compare these latent profile (LP) groups to the DSM-IV-TR eating disorder categories. Method: Eating disorder symptom data collected from 401 youth (aged 7 through 19…

  8. Effect of brain-derived neurotrophic factor (BDNF) on hepatocyte metabolism.

    Science.gov (United States)

    Genzer, Yoni; Chapnik, Nava; Froy, Oren

    2017-07-01

    Brain-derived neurotrophic factor (BDNF) plays crucial roles in the development, maintenance, plasticity and homeostasis of the central and peripheral nervous systems. Perturbing BDNF signaling in mouse brain results in hyperphagia, obesity, hyperinsulinemia and hyperglycemia. Currently, little is known whether BDNF affects liver tissue directly. Our aim was to determine the metabolic signaling pathways activated after BDNF treatment in hepatocytes. Unlike its effect in the brain, BDNF did not lead to activation of the liver AKT pathway. However, AMP protein activated kinase (AMPK) was ∼3 times more active and fatty acid synthase (FAS) ∼2-fold less active, suggesting increased fatty acid oxidation and reduced fatty acid synthesis. In addition, cAMP response element binding protein (CREB) was ∼3.5-fold less active together with its output the gluconeogenic transcript phosphoenolpyruvate carboxykinase (Pepck), suggesting reduced gluconeogenesis. The levels of glycogen synthase kinase 3b (GSK3b) was ∼3-fold higher suggesting increased glycogen synthesis. In parallel, the expression levels of the clock genes Bmal1 and Cry1, whose protein products play also a metabolic role, were ∼2-fold increased and decreased, respectively. In conclusion, BDNF binding to hepatocytes leads to activation of catabolic pathways, such as fatty acid oxidation. In parallel gluconeogenesis is inhibited, while glycogen storage is triggered. This metabolic state mimics that of after breakfast, in which the liver continues to oxidize fat, stops gluconeogenesis and replenishes glycogen stores. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Metabolic Engineering of Yeast to Produce Fatty Acid-derived Biofuels: Bottlenecks and Solutions

    Directory of Open Access Journals (Sweden)

    Jiayuan eSheng

    2015-06-01

    Full Text Available Fatty acid-derived biofuels can be a better solution than bioethanol to replace petroleum fuel, since they have similar energy content and combustion properties as current transportation fuels. The environmentally friendly microbial fermentation process has been used to synthesize advanced biofuels from renewable feedstock. Due to their robustness as well as the high tolerance to fermentation inhibitors and phage contamination, yeast strains such as Saccharomyces cerevisiae and Yarrowia lipolytica have attracted tremendous attention in recent studies regarding the production of fatty acid-derived biofuels, including fatty acids, fatty acid ethyl esters, fatty alcohols, and fatty alkanes. However, the native yeast strains cannot produce fatty acids and fatty acid-derived biofuels in large quantities. To this end, we have summarized recent publications in this review on metabolic engineering of yeast strains to improve the production of fatty acid-derived biofuels, identified the bottlenecks that limit the productivity of biofuels, and categorized the appropriate approaches to overcome these obstacles.

  10. Octulosonic acid derivatives from Roman chamomile (Chamaemelum nobile) with activities against inflammation and metabolic disorder.

    Science.gov (United States)

    Zhao, Jianping; Khan, Shabana I; Wang, Mei; Vasquez, Yelkaira; Yang, Min Hye; Avula, Bharathi; Wang, Yan-Hong; Avonto, Cristina; Smillie, Troy J; Khan, Ikhlas A

    2014-03-28

    Six new octulosonic acid derivatives (1-6) were isolated from the flower heads of Roman chamomile (Chamaemelum nobile). Their structures were elucidated by means of spectroscopic interpretation. The biological activity of the isolated compounds was evaluated toward multiple targets related to inflammation and metabolic disorder such as NAG-1, NF-κB, iNOS, ROS, PPARα, PPARγ, and LXR. Similar to the action of NSAIDs, all the six compounds (1-6) increased NAG-1 activity 2-3-fold. They also decreased cellular oxidative stress by inhibiting ROS generation. Compounds 3, 5, and 6 activated PPARγ 1.6-2.1-fold, while PPARα was activated 1.4-fold by compounds 5 and 6 only. None of the compounds showed significant activity against iNOS or NF-κB. This is the first report of biological activity of octulosonic acid derivatives toward multiple pathways related to inflammation and metabolic disorder. The reported anti-inflammatory, hypoglycemic, antiedemic, and antioxidant activities of Roman chamomile could be partly explained as due to the presence of these constituents.

  11. Metabolism and toxicological evaluation of the aromatic amide herbicide propanil and its derivatives

    International Nuclear Information System (INIS)

    McMillian, D.C.

    1989-01-01

    Since propanil is structurally similar to other carcinogenic arylamides, the potential chronic toxicity of propanil and its derivatives were examined in short-term assays for genotoxicity. Propanil, 3,4-dichloroaniline, and their N-oxidized derivatives were inactive in the Salmonella typhimurium reversion, Chinese hamster ovary/hypoxanthine guanine phosphoribosyl transferase (CHO/HGPRT), and rat hepatocyte/DNA repair assays. The metabolism of propanil and 3,4-dichloroaniline was subsequently examined in liver microsomes from males Sprague-Dawley rats to identify metabolites that may be involved in the acute toxicity of propanil. The major pathway of propanil metabolism was acylamidase-catalyzed hydrolysis to 3,4-dichloroaniline. Oxidized metabolites were isolated by high performance liquid chromatography, and identified as 2'-hydroxy-propanil and 6-hydroxy-propanil by comparison of their mass and nuclear magnetic resonance spectra to synthetic standards. Experiments were performed to determine if propanil exposure could be monitored by the analysis of hemoglobin binding. Administration of [ring-U- 14 C]propanil to rats increased methemoglobin formation in a dose-dependent manner. Concomitant with methemoglobin formation, dose-dependent covalent binding of radiolabeled propanil to hemoglobin was detected. HPLC analysis indicated that the hemoglobin adducts were sulfinic acid esters, and these data suggest that human exposure to propanil may be monitored by the analysis of propanil metabolites bound to hemoglobin

  12. Acclimation of aerobic-activated sludge degrading benzene derivatives and co-metabolic degradation activities of trichloroethylene by benzene derivative-grown aerobic sludge.

    Science.gov (United States)

    Wang, Shizong; Yang, Qi; Bai, Zhiyong; Wang, Shidong; Wang, Yeyao; Nowak, Karolina M

    2015-01-01

    The acclimation of aerobic-activated sludge for degradation of benzene derivatives was investigated in batch experiments. Phenol, benzoic acid, toluene, aniline and chlorobenzene were concurrently added to five different bioreactors which contained the aerobic-activated sludge. After the acclimation process ended, the acclimated phenol-, benzoic acid-, toluene-, aniline- and chlorobenzene-grown aerobic-activated sludge were used to explore the co-metabolic degradation activities of trichloroethylene (TCE). Monod equation was employed to simulate the kinetics of co-metabolic degradation of TCE by benzene derivative-grown sludge. At the end of experiments, the mixed microbial communities grown under different conditions were identified. The results showed that the acclimation periods of microorganisms for different benzene derivatives varied. The maximum degradation rates of TCE for phenol-, benzoic acid-, toluene-, aniline- and chlorobenzene-grown aerobic sludge were 0.020, 0.017, 0.016, 0.0089 and 0.0047 mg g SS(-1) h(-1), respectively. The kinetic of TCE degradation in the absence of benzene derivative followed Monod equation well. Also, eight phyla were observed in the acclimated benzene derivative-grown aerobic sludge. Each of benzene derivative-grown aerobic sludge had different microbial community composition. This study can hopefully add new knowledge to the area of TCE co-metabolic by mixed microbial communities, and further the understanding on the function and applicability of aerobic-activated sludge.

  13. Modeling Cerebrovascular Pathophysiology in Amyloid-β Metabolism using Neural-Crest-Derived Smooth Muscle Cells

    Directory of Open Access Journals (Sweden)

    Christine Cheung

    2014-10-01

    Full Text Available Summary: There is growing recognition of cerebrovascular contributions to neurodegenerative diseases. In the walls of cerebral arteries, amyloid-beta (Aβ accumulation is evident in a majority of aged people and patients with cerebral amyloid angiopathy. Here, we leverage human pluripotent stem cells to generate vascular smooth muscle cells (SMCs from neural crest progenitors, recapitulating brain-vasculature-specific attributes of Aβ metabolism. We confirm that the lipoprotein receptor, LRP1, functions in our neural-crest-derived SMCs to mediate Aβ uptake and intracellular lysosomal degradation. Hypoxia significantly compromises the contribution of SMCs to Aβ clearance by suppressing LRP1 expression. This enabled us to develop an assay of Aβ uptake by using the neural crest-derived SMCs with hypoxia as a stress paradigm. We then tested several vascular protective compounds in a high-throughput format, demonstrating the value of stem-cell-based phenotypic screening for novel therapeutics and drug repurposing, aimed at alleviating amyloid burden. : The contribution of blood vessel pathologies to neurodegenerative disorders is relatively neglected, partly due to inadequate human tissues for research. By using human stem cells, Cheung et al. establish a method of generating vascular smooth muscle cells (SMCs from neural crest progenitors, the primary precursors that give rise to brain blood vessels. These stem-cell-derived SMCs display defective amyloid processing under chronic hypoxia, a phenomenon well documented in the cerebral vasculatures of aged people and patients with Alzheimer’s disease.

  14. Characterization of energy and neurotransmitter metabolism in cortical glutamatergic neurons derived from human induced pluripotent stem cells: A novel approach to study metabolism in human neurons.

    Science.gov (United States)

    Aldana, Blanca I; Zhang, Yu; Lihme, Maria Fog; Bak, Lasse K; Nielsen, Jørgen E; Holst, Bjørn; Hyttel, Poul; Freude, Kristine K; Waagepetersen, Helle S

    2017-06-01

    Alterations in the cellular metabolic machinery of the brain are associated with neurodegenerative disorders such as Alzheimer's disease. Novel human cellular disease models are essential in order to study underlying disease mechanisms. In the present study, we characterized major metabolic pathways in neurons derived from human induced pluripotent stem cells (hiPSC). With this aim, cultures of hiPSC-derived neurons were incubated with [U- 13 C]glucose, [U- 13 C]glutamate or [U- 13 C]glutamine. Isotopic labeling in metabolites was determined using gas chromatography coupled to mass spectrometry, and cellular amino acid content was quantified by high-performance liquid chromatography. Additionally, we evaluated mitochondrial function using real-time assessment of oxygen consumption via the Seahorse XF e 96 Analyzer. Moreover, in order to validate the hiPSC-derived neurons as a model system, a metabolic profiling was performed in parallel in primary neuronal cultures of mouse cerebral cortex and cerebellum. These serve as well-established models of GABAergic and glutamatergic neurons, respectively. The hiPSC-derived neurons were previously characterized as being forebrain-specific cortical glutamatergic neurons. However, a comparable preparation of predominantly mouse cortical glutamatergic neurons is not available. We found a higher glycolytic capacity in hiPSC-derived neurons compared to mouse neurons and a substantial oxidative metabolism through the mitochondrial tricarboxylic acid (TCA) cycle. This finding is supported by the extracellular acidification and oxygen consumption rates measured in the cultured human neurons. [U- 13 C]Glutamate and [U- 13 C]glutamine were found to be efficient energy substrates for the neuronal cultures originating from both mice and humans. Interestingly, isotopic labeling in metabolites from [U- 13 C]glutamate was higher than that from [U- 13 C]glutamine. Although the metabolic profile of hiPSC-derived neurons in vitro was

  15. Marine-derived nutrients, bioturbation, and ecosystem metabolism: reconsidering the role of salmon in streams.

    Science.gov (United States)

    Holtgrieve, Gordon W; Schindler, Daniel E

    2011-02-01

    In coastal areas of the North Pacific Ocean, annual returns of spawning salmon provide a substantial influx of nutrients and organic matter to streams and are generally believed to enhance the productivity of recipient ecosystems. Loss of this subsidy from areas with diminished salmon runs has been hypothesized to limit ecosystem productivity in juvenile salmon rearing habitats (lakes and streams), thereby reinforcing population declines. Using five to seven years of data from an Alaskan stream supporting moderate salmon densities, we show that salmon predictably increased stream water nutrient concentrations, which were on average 190% (nitrogen) and 390% (phosphorus) pre-salmon values, and that primary producers incorporated some of these nutrients into tissues. However, benthic algal biomass declined by an order of magnitude despite increased nutrients. We also measured changes in stream ecosystem metabolic properties, including gross primary productivity (GPP) and ecosystem respiration (ER), from three salmon streams by analyzing diel measurements of oxygen concentrations and stable isotopic ratios (delta O-O2) within a Bayesian statistical model of oxygen dynamics. Our results do not support a shift toward higher primary productivity with the return of salmon, as is expected from a nutrient fertilization mechanism. Rather, net ecosystem metabolism switched from approximately net autotrophic (GPP > or = ER) to a strongly net heterotrophic state (GPP disturbance enhanced in situ heterotrophic respiration. Salmon also changed the physical properties of the stream, increasing air-water gas exchange by nearly 10-fold during peak spawning. We suggest that management efforts to restore salmon ecosystems should consider effects on ecosystem metabolic properties and how salmon disturbance affects the incorporation of marine-derived nutrients into food webs.

  16. Metabolic engineering of a haploid strain derived from a triploid industrial yeast for producing cellulosic ethanol.

    Science.gov (United States)

    Kim, Soo Rin; Skerker, Jeffrey M; Kong, In Iok; Kim, Heejin; Maurer, Matthew J; Zhang, Guo-Chang; Peng, Dairong; Wei, Na; Arkin, Adam P; Jin, Yong-Su

    2017-03-01

    Many desired phenotypes for producing cellulosic biofuels are often observed in industrial Saccharomyces cerevisiae strains. However, many industrial yeast strains are polyploid and have low spore viability, making it difficult to use these strains for metabolic engineering applications. We selected the polyploid industrial strain S. cerevisiae ATCC 4124 exhibiting rapid glucose fermentation capability, high ethanol productivity, strong heat and inhibitor tolerance in order to construct an optimal yeast strain for producing cellulosic ethanol. Here, we focused on developing a general approach and high-throughput screening method to isolate stable haploid segregants derived from a polyploid parent, such as triploid ATCC 4124 with a poor spore viability. Specifically, we deleted the HO genes, performed random sporulation, and screened the resulting segregants based on growth rate, mating type, and ploidy. Only one stable haploid derivative (4124-S60) was isolated, while 14 other segregants with a stable mating type were aneuploid. The 4124-S60 strain inherited only a subset of desirable traits present in the parent strain, same as other aneuploids, suggesting that glucose fermentation and specific ethanol productivity are likely to be genetically complex traits and/or they might depend on ploidy. Nonetheless, the 4124-60 strain did inherit the ability to tolerate fermentation inhibitors. When additional genetic perturbations known to improve xylose fermentation were introduced into the 4124-60 strain, the resulting engineered strain (IIK1) was able to ferment a Miscanthus hydrolysate better than a previously engineered laboratory strain (SR8), built by making the same genetic changes. However, the IIK1 strain showed higher glycerol and xylitol yields than the SR8 strain. In order to decrease glycerol and xylitol production, an NADH-dependent acetate reduction pathway was introduced into the IIK1 strain. By consuming 2.4g/L of acetate, the resulting strain (IIK1A

  17. Empirically Derived Dehydration Scoring and Decision Tree Models for Children With Diarrhea: Assessment and Internal Validation in a Prospective Cohort Study in Dhaka, Bangladesh

    OpenAIRE

    Levine, Adam C; Glavis-Bloom, Justin; Modi, Payal; Nasrin, Sabiha; Rege, Soham; Chu, Chieh; Schmid, Christopher H; Alam, Nur H

    2015-01-01

    Introduction: Diarrhea remains one of the most common and most deadly conditions affecting children worldwide. Accurately assessing dehydration status is critical to determining treatment course, yet no clinical diagnostic models for dehydration have been empirically derived and validated for use in resource-limited settings. Methods: In the Dehydration: Assessing Kids Accurately (DHAKA) prospective cohort study, a random sample of children under 5 with acute diarrhea was enrolled between Feb...

  18. Uncertainty in Measurement: A Review of Monte Carlo Simulation Using Microsoft Excel for the Calculation of Uncertainties Through Functional Relationships, Including Uncertainties in Empirically Derived Constants

    Science.gov (United States)

    Farrance, Ian; Frenkel, Robert

    2014-01-01

    The Guide to the Expression of Uncertainty in Measurement (usually referred to as the GUM) provides the basic framework for evaluating uncertainty in measurement. The GUM however does not always provide clearly identifiable procedures suitable for medical laboratory applications, particularly when internal quality control (IQC) is used to derive most of the uncertainty estimates. The GUM modelling approach requires advanced mathematical skills for many of its procedures, but Monte Carlo simulation (MCS) can be used as an alternative for many medical laboratory applications. In particular, calculations for determining how uncertainties in the input quantities to a functional relationship propagate through to the output can be accomplished using a readily available spreadsheet such as Microsoft Excel. The MCS procedure uses algorithmically generated pseudo-random numbers which are then forced to follow a prescribed probability distribution. When IQC data provide the uncertainty estimates the normal (Gaussian) distribution is generally considered appropriate, but MCS is by no means restricted to this particular case. With input variations simulated by random numbers, the functional relationship then provides the corresponding variations in the output in a manner which also provides its probability distribution. The MCS procedure thus provides output uncertainty estimates without the need for the differential equations associated with GUM modelling. The aim of this article is to demonstrate the ease with which Microsoft Excel (or a similar spreadsheet) can be used to provide an uncertainty estimate for measurands derived through a functional relationship. In addition, we also consider the relatively common situation where an empirically derived formula includes one or more ‘constants’, each of which has an empirically derived numerical value. Such empirically derived ‘constants’ must also have associated uncertainties which propagate through the functional

  19. Uncertainty in measurement: a review of monte carlo simulation using microsoft excel for the calculation of uncertainties through functional relationships, including uncertainties in empirically derived constants.

    Science.gov (United States)

    Farrance, Ian; Frenkel, Robert

    2014-02-01

    The Guide to the Expression of Uncertainty in Measurement (usually referred to as the GUM) provides the basic framework for evaluating uncertainty in measurement. The GUM however does not always provide clearly identifiable procedures suitable for medical laboratory applications, particularly when internal quality control (IQC) is used to derive most of the uncertainty estimates. The GUM modelling approach requires advanced mathematical skills for many of its procedures, but Monte Carlo simulation (MCS) can be used as an alternative for many medical laboratory applications. In particular, calculations for determining how uncertainties in the input quantities to a functional relationship propagate through to the output can be accomplished using a readily available spreadsheet such as Microsoft Excel. The MCS procedure uses algorithmically generated pseudo-random numbers which are then forced to follow a prescribed probability distribution. When IQC data provide the uncertainty estimates the normal (Gaussian) distribution is generally considered appropriate, but MCS is by no means restricted to this particular case. With input variations simulated by random numbers, the functional relationship then provides the corresponding variations in the output in a manner which also provides its probability distribution. The MCS procedure thus provides output uncertainty estimates without the need for the differential equations associated with GUM modelling. The aim of this article is to demonstrate the ease with which Microsoft Excel (or a similar spreadsheet) can be used to provide an uncertainty estimate for measurands derived through a functional relationship. In addition, we also consider the relatively common situation where an empirically derived formula includes one or more 'constants', each of which has an empirically derived numerical value. Such empirically derived 'constants' must also have associated uncertainties which propagate through the functional relationship

  20. Metabolism

    Science.gov (United States)

    ... Are More Common in People With Type 1 Diabetes Metabolic Syndrome Your Child's Weight Healthy Eating Endocrine System Blood Test: Basic Metabolic Panel (BMP) Activity: Endocrine System Growth Disorders Diabetes Center Thyroid Disorders Your Endocrine System Movie: Endocrine ...

  1. Immunosuppressive activity enhances central carbon metabolism and bioenergetics in myeloid-derived suppressor cells in vitro models

    Directory of Open Access Journals (Sweden)

    Hammami Ines

    2012-07-01

    Full Text Available Abstract Background The tumor microenvironment contains a vast array of pro- and anti-inflammatory cytokines that alter myelopoiesis and lead to the maturation of immunosuppressive cells known as myeloid-derived suppressor cells (MDSCs. Incubating bone marrow (BM precursors with a combination of granulocyte-macrophage colony-stimulating factor (GM-CSF and interleukin-6 (IL-6 generated a tumor-infiltrating MDSC-like population that impaired anti-tumor specific T-cell functions. This in vitro experimental approach was used to simulate MDSC maturation, and the cellular metabolic response was then monitored. A complementary experimental model that inhibited L-arginine (L-Arg metabolizing enzymes in MSC-1 cells, an immortalized cell line derived from primary MDSCs, was used to study the metabolic events related to immunosuppression. Results Exposure of BM cells to GM-CSF and IL-6 activated, within 24 h, L-Arg metabolizing enzymes which are responsible for the MDSCs immunosuppressive potential. This was accompanied by an increased uptake of L-glutamine (L-Gln and glucose, the latter being metabolized by anaerobic glycolysis. The up-regulation of nutrient uptake lead to the accumulation of TCA cycle intermediates and lactate as well as the endogenous synthesis of L-Arg and the production of energy-rich nucleotides. Moreover, inhibition of L-Arg metabolism in MSC-1 cells down-regulated central carbon metabolism activity, including glycolysis, glutaminolysis and TCA cycle activity, and led to a deterioration of cell bioenergetic status. The simultaneous increase of cell specific concentrations of ATP and a decrease in ATP-to-ADP ratio in BM-derived MDSCs suggested cells were metabolically active during maturation. Moreover, AMP-activated protein kinase (AMPK was activated during MDSC maturation in GM-CSF and IL-6–treated cultures, as revealed by the continuous increase of AMP-to-ATP ratios and the phosphorylation of AMPK. Likewise, AMPK activity was

  2. Synthesis of a metabolically stable modified long-chain fatty acid salt and its photolabile derivative

    Energy Technology Data Exchange (ETDEWEB)

    Stoll, G.H.; Voges, R.; Gerok, W.; Kurz, G. (Institut fuer Organische Chemie and Biochemie, Universitaet Freiburg (Germany))

    1991-05-01

    An analogue of the long-chain fatty acid salt, sodium stearate, was synthesized in which the hydrogen atoms at carbons 2, 3, and 18 were replaced by fluorine. The key step in the synthesis was the addition of 3-iodo-2,2,3,3-tetrafluoropropanoic acid amide to 15,15,15-trifluoro-1-pentadecene. Radioactivity was introduced by catalytic reduction of 2,2,3,3,18,18,18-heptafluoro-4-octadecenoic acid amide with carrier-free tritium gas yielding a product with the specific radioactivity of 2.63 TBq/mmol. The resulting 2,2,3,3,18,18,18-heptafluoro-4-octadecenoic acid has a pKa of about 0.5 and is completely dissociated under normal physiological conditions. The fluorinated fatty acid salt analogue is readily taken up into hepatocytes and proved to be metabolically inert. In an approach to the identification of proteins involved in long-chain fatty acid salt transport across membranes and intracellular compartments, the photolabile derivative 11,11-azo-2,2,3,3,18,18,18-heptafluoro(G-3H)octadecanoic acid sodium salt was synthesized with a specific radioactivity of 2.63 TBq/mmol. Photolysis of the photolabile derivative, using a light source with a maximum emission at 350 nm, occurred with a half-life of 1.5 min. The generated carbene reacted with 14C-labeled methanol and acetonitrile with covalent bond formation of 6-13%. Its efficacy for photoaffinity labeling was demonstrated by incorporation into serum albumin, the extracellular fatty acid salt-binding protein, as well as into the intracellular fatty acid salt-binding protein (FABP) of rat liver with the molecular weight of 14,000.

  3. Pharmacological Classification and Activity Evaluation of Furan and Thiophene Amide Derivatives Applying Semi-Empirical ab initio Molecular Modeling Methods

    Directory of Open Access Journals (Sweden)

    Leszek Bober

    2012-05-01

    Full Text Available Pharmacological and physicochemical classification of the furan and thiophene amide derivatives by multiple regression analysis and partial least square (PLS based on semi-empirical ab initio molecular modeling studies and high-performance liquid chromatography (HPLC retention data is proposed. Structural parameters obtained from the PCM (Polarizable Continuum Model method and the literature values of biological activity (antiproliferative for the A431 cells expressed as LD50 of the examined furan and thiophene derivatives was used to search for relationships. It was tested how variable molecular modeling conditions considered together, with or without HPLC retention data, allow evaluation of the structural recognition of furan and thiophene derivatives with respect to their pharmacological properties.

  4. Metabolism of periplasmic membrane-derived oligosaccharides by the predatory bacterium Bdellovibrio bacteriovorus 109J

    International Nuclear Information System (INIS)

    Ruby, E.G.; McCabe, J.B.

    1988-01-01

    Membrane-derived oligosaccharides (MDO), a class of osmotically active carbohydrates, are the major organic solutes present in the periplasm of Escherichia coli and many other gram-negative bacteria when cells are grown in a medium of low osmolarity. Analyses of growing cells of Bdellovibrio bacteriovorus, a gram-negative predator of other bacteria, have confirmed that they also synthesize a characteristic MDO-like class of oligosaccharides. The natural growth environment of bdellovibrios is the periplasm of other gram-negative bacteria. Because of this location, prey cell MDO constitute a potential source of organic nutrients for growing bdellovibrios. Using cells of E. coli whose MDO were 3 H labeled, we examined the extent to which B. bacteriovorus 109J metabolizes these prey cell components. Interestingly, there was neither significant degradation nor incorporation of prey cell MDO by bdellovibrios during the course of their intracellular growth. In fact, bdellovibrios had little capability either to degrade extracellular MDO that was made available to them or to transport glucose, the major monomeric constituent of prey cell MDO. Instead, periplasmic MDO were irreversibly lost to the extracellular environment during the period of bdellovibrio attack and penetration. Thus, although prey cell periplasmic proteins are retained, other important periplasmic components are released early in the bdellovibrio growth cycle. The loss of these MDO may aid in the destabilization of the prey cell plasma membrane, increasing the availability of cytoplasmic constituents to the periplasmic bdellovibrio

  5. Estimating the effects of 17α-ethinylestradiol on stochastic population growth rate of fathead minnows: a population synthesis of empirically derived vital rates

    Science.gov (United States)

    Schwindt, Adam R.; Winkelman, Dana L.

    2016-01-01

    Urban freshwater streams in arid climates are wastewater effluent dominated ecosystems particularly impacted by bioactive chemicals including steroid estrogens that disrupt vertebrate reproduction. However, more understanding of the population and ecological consequences of exposure to wastewater effluent is needed. We used empirically derived vital rate estimates from a mesocosm study to develop a stochastic stage-structured population model and evaluated the effect of 17α-ethinylestradiol (EE2), the estrogen in human contraceptive pills, on fathead minnow Pimephales promelas stochastic population growth rate. Tested EE2 concentrations ranged from 3.2 to 10.9 ng L−1 and produced stochastic population growth rates (λ S ) below 1 at the lowest concentration, indicating potential for population decline. Declines in λ S compared to controls were evident in treatments that were lethal to adult males despite statistically insignificant effects on egg production and juvenile recruitment. In fact, results indicated that λ S was most sensitive to the survival of juveniles and female egg production. More broadly, our results document that population model results may differ even when empirically derived estimates of vital rates are similar among experimental treatments, and demonstrate how population models integrate and project the effects of stressors throughout the life cycle. Thus, stochastic population models can more effectively evaluate the ecological consequences of experimentally derived vital rates.

  6. Estimation of Aboveground Biomass in Alpine Forests: A Semi-Empirical Approach Considering Canopy Transparency Derived from Airborne LiDAR Data

    Directory of Open Access Journals (Sweden)

    Martin Rutzinger

    2010-12-01

    Full Text Available In this study, a semi-empirical model that was originally developed for stem volume estimation is used for aboveground biomass (AGB estimation of a spruce dominated alpine forest. The reference AGB of the available sample plots is calculated from forest inventory data by means of biomass expansion factors. Furthermore, the semi-empirical model is extended by three different canopy transparency parameters derived from airborne LiDAR data. These parameters have not been considered for stem volume estimation until now and are introduced in order to investigate the behavior of the model concerning AGB estimation. The developed additional input parameters are based on the assumption that transparency of vegetation can be measured by determining the penetration of the laser beams through the canopy. These parameters are calculated for every single point within the 3D point cloud in order to consider the varying properties of the vegetation in an appropriate way. Exploratory Data Analysis (EDA is performed to evaluate the influence of the additional LiDAR derived canopy transparency parameters for AGB estimation. The study is carried out in a 560 km2 alpine area in Austria, where reference forest inventory data and LiDAR data are available. The investigations show that the introduction of the canopy transparency parameters does not change the results significantly according to R2 (R2 = 0.70 to R2 = 0.71 in comparison to the results derived from, the semi-empirical model, which was originally developed for stem volume estimation.

  7. Synthesis of N-(6-(4-(Piperazin-1-ylphenoxypyridin-3-ylbenzenesulfonamide Derivatives for the Treatment of Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Nabajyoti Deka

    2013-01-01

    Full Text Available Metabolic syndrome is a widely prevalent multifactorial disorder associated with an increased risk of cardiovascular disease and type 2 diabetes mellitus. High plasma levels of insulin and glucose due to insulin resistance are a major component of the metabolic disorder. Thiazolidinediones (TZDs are potent PPARγ ligand and used as insulin sensitizers in the treatment of type 2 diabetes mellitus. They are potent insulin-sensitizing agents but due to adverse effects like hepatotoxicity, a safer alternative of TZDs is highly demanded. Here we report synthesis of N-(6-(4-(piperazin-1-ylphenoxypyridin-3-ylbenzenesulfonamide derivatives as an alternate remedy for insulin resistance.

  8. Metabolic Disorder in Chronic Obstructive Pulmonary Disease (COPD) Patients: Towards a Personalized Approach Using Marine Drug Derivatives.

    Science.gov (United States)

    Lamonaca, Palma; Prinzi, Giulia; Kisialiou, Aliaksei; Cardaci, Vittorio; Fini, Massimo; Russo, Patrizia

    2017-03-20

    Metabolic disorder has been frequently observed in chronic obstructive pulmonary disease (COPD) patients. However, the exact correlation between obesity, which is a complex metabolic disorder, and COPD remains controversial. The current study summarizes a variety of drugs from marine sources that have anti-obesity effects and proposed potential mechanisms by which lung function can be modulated with the anti-obesity activity. Considering the similar mechanism, such as inflammation, shared between obesity and COPD, the study suggests that marine derivatives that act on the adipose tissues to reduce inflammation may provide beneficial therapeutic effects in COPD subjects with high body mass index (BMI).

  9. EMPIRICAL TESTING OF MODIFIED BLACK-SCHOLES OPTION PRICING MODEL FORMULA ON NSE DERIVATIVE MARKET IN INDIA

    Directory of Open Access Journals (Sweden)

    Ambrish Gupta

    2013-01-01

    Full Text Available The main objectives of this paper are to incorporate modification in Black-Scholes option pricing model formula by adding some new variables on the basis of given assumption related to risk-free interest rate, and also shows the calculation process of new risk-free interest rate on the basis of modified variable. This paper also identifies the various situations in empirical testing of modified and original Black-Scholes formula with respect to the market value on the basis of assumed and calculated risk-free interest rate.

  10. Derivative Process Model of Development Power in Industry: Empirical Research and Forecast for Chinese Software Industry and US Economy

    OpenAIRE

    Feng Dai; Bao- hua Sun; Jie Sun

    2004-01-01

    Based on concept and theory of Development Power [1], this paper analyzes the transferability and the diffusibility of industrial development power, points out that the chaos is the extreme of DP releasing and order is the highest degree of DP accumulating, puts forward A-C strength, the index of adjusting and controlling strength, and sets up the derivative process model for industrial development power on the Partial Distribution [2]-[4]. By the derivative process model, a kind of time seri...

  11. Endothelial cell-derived matrix promotes the metabolic functional maturation of hepatocyte via integrin-Src signalling.

    Science.gov (United States)

    Guo, Xinyue; Li, Weihong; Ma, Minghui; Lu, Xin; Zhang, Haiyan

    2017-11-01

    The extracellular matrix (ECM) microenvironment is involved in the regulation of hepatocyte phenotype and function. Recently, the cell-derived extracellular matrix has been proposed to represent the bioactive and biocompatible materials of the native ECM. Here, we show that the endothelial cell-derived matrix (EC matrix) promotes the metabolic maturation of human adipose stem cell-derived hepatocyte-like cells (hASC-HLCs) through the activation of the transcription factor forkhead box protein A2 (FOXA2) and the nuclear receptors hepatocyte nuclear factor 4 alpha (HNF4α) and pregnane X receptor (PXR). Reducing the fibronectin content in the EC matrix or silencing the expression of α5 integrin in the hASC-HLCs inhibited the effect of the EC matrix on Src phosphorylation and hepatocyte maturation. The inhibition of Src phosphorylation using the inhibitor PP2 or silencing the expression of Src in hASC-HLCs also attenuated the up-regulation of the metabolic function of hASC-HLCs in a nuclear receptor-dependent manner. These data elucidate integrin-Src signalling linking the extrinsic EC matrix signals and metabolic functional maturation of hepatocyte. This study provides a model for studying the interaction between hepatocytes and non-parenchymal cell-derived matrix. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  12. Data regarding association between serum osteoprotegerin level, numerous of circulating endothelial-derived and mononuclear-derived progenitor cells in patients with metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Alexander E. Berezin

    2016-09-01

    Full Text Available Metabolic syndrome (MetS is defined as cluster of multiple metabolic and cardiovascular (CV abnormalities included abdominal obesity, high-normal blood pressure, dyslipidaemia, and impaired fasting glucose tolerance that exhibits has a growing prevalence worldwide. We investigated whether an elevated level of osteoprotegerin (OPG predicts imbalance between different phenotypes of circulating endothelial (EPCs and mononuclear (MPCs progenitor cells in MetS patients. We have analyzed data regarding dysmetabolic disorder subjects without known CV disease, as well as with known type two diabetes mellitus. All patients have given their informed written consent for participation in the study. This article contains data on the independent predictors of depletion in numerous of circulating EPCs and MPCs in MetS patients. The data are supplemental to our original research article describing detailed associations of elevated OPG level in MetS patients with numerous of EPCs and MPCs beyond traditional CV risk factors. Keywords: Metabolic syndrome, Osteoprotegerin, Circulating endothelial derived progenitor cells, Mononuclear-derived progenitor cells

  13. The Assimilation of Diazotroph-Derived Nitrogen by Scleractinian Corals Depends on Their Metabolic Status

    Directory of Open Access Journals (Sweden)

    Vanessa N. Bednarz

    2017-01-01

    Full Text Available Tropical corals are associated with a diverse community of dinitrogen (N2-fixing prokaryotes (diazotrophs providing the coral an additional source of bioavailable nitrogen (N in oligotrophic waters. The overall activity of these diazotrophs changes depending on the current environmental conditions, but to what extent it affects the assimilation of diazotroph-derived N (DDN by corals is still unknown. Here, in a series of 15N2 tracer experiments, we directly quantified DDN assimilation by scleractinian corals from the Red Sea exposed to different environmental conditions. We show that DDN assimilation strongly varied with the corals’ metabolic status or with phosphate availability in the water. The very autotrophic shallow-water (~5 m corals showed low or no DDN assimilation, which significantly increased under elevated phosphate availability (3 µM. Corals that depended more on heterotrophy (i.e., bleached and deep-water [~45 m] corals assimilated significantly more DDN, which contributed up to 15% of the corals’ N demand (compared to 1% in shallow corals. Furthermore, we demonstrate that a substantial part of the DDN assimilated by deep corals was likely obtained from heterotrophic feeding on fixed N compounds and/or diazotrophic cells in the mucus. Conversely, in shallow corals, the net release of mucus, rich in organic carbon compounds, likely enhanced diazotroph abundance and activity and thereby the release of fixed N to the pelagic and benthic reef community. Overall, our results suggest that DDN assimilation by corals varies according to the environmental conditions and is likely linked to the capacity of the coral to acquire nutrients from seawater.

  14. Metabolism

    Science.gov (United States)

    ... lin), which signals cells to increase their anabolic activities. Metabolism is a complicated chemical process, so it's not ... how those enzymes or hormones work. When the metabolism of body chemicals is ... Hyperthyroidism (pronounced: hi-per-THIGH-roy-dih-zum). Hyperthyroidism ...

  15. Using in vitro derived enzymatic reaction rates of metabolism to inform pesticide body burdens in amphibians

    Science.gov (United States)

    Understanding how pesticide exposure to non-target species influences toxicity is necessary to accurately assess the ecological risks these compounds pose. To assess the potential metabolic activation of broad use pesticides in amphibians, in vitro and in vivo metabolic rate cons...

  16. Association between empirically derived dietary patterns with blood lipids, fasting blood glucose and blood pressure in adults - the India migration study.

    Science.gov (United States)

    Shridhar, Krithiga; Satija, Ambika; Dhillon, Preet K; Agrawal, Sutapa; Gupta, Ruby; Bowen, Liza; Kinra, Sanjay; Bharathi, A V; Prabhakaran, D; Srinath Reddy, K; Ebrahim, Shah

    2018-02-08

    Dietary patterns (DPs) in India are heterogenous. To date, data on association of indigenous DPs in India with risk factors of nutrition-related noncommunicable diseases (cardiovascular disease and diabetes), leading causes of premature death and disability, are limited. We aimed to evaluate the associations of empirically-derived DPs with blood lipids, fasting glucose and blood pressure levels in an adult Indian population recruited across four geographical regions of India. We used cross-sectional data from the Indian Migration Study (2005-2007). Study participants included urban migrants, their rural siblings and urban residents and their urban siblings from Lucknow, Nagpur, Hyderabad and Bangalore (n = 7067, mean age 40.8 yrs). Information on diet (validated interviewer-administered, 184-item semi-quantitative food frequency questionnaire), tobacco consumption, alcohol intake, physical activity, medical history, as well as anthropometric measurements were collected. Fasting-blood samples were collected for estimation of blood lipids and glucose. Principal component analysis (PCA) was used to identify major DPs based on eigenvalue> 1 and component interpretability. Robust standard error multivariable linear regression models were used to investigate the association of DPs (tertiles) with total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides, fasting-blood glucose (FBG), systolic and diastolic blood pressure (SBP and DBP) levels. Three major DPs were identified: 'cereal-savoury' (cooked grains, rice/rice-based dishes, snacks, condiments, soups, nuts), 'fruit-vegetable-sweets-snacks' (Western cereals, vegetables, fruit, fruit juices, cooked milk products, snacks, sugars, sweets) and 'animal food' (red meat, poultry, fish/seafood, eggs) patterns. High intake of the 'animal food' pattern was positively associated with levels of TC (β = 0.10 mmol/L; 95% CI: 0.02, 0.17 mmol/L; p

  17. Exosome-derived microRNAs in cancer metabolism: possible implications in cancer diagnostics and therapy.

    Science.gov (United States)

    Tomasetti, Marco; Lee, Wan; Santarelli, Lory; Neuzil, Jiri

    2017-01-20

    Malignant progression is greatly affected by dynamic cross-talk between stromal and cancer cells. Exosomes are secreted nanovesicles that have key roles in cell-cell communication by transferring nucleic acids and proteins to target cells and tissues. Recently, MicroRNAs (miRs) and their delivery in exosomes have been implicated in physiological and pathological processes. Tumor-delivered miRs, interacting with stromal cells in the tumor microenvironment, modulate tumor progression, angiogenesis, metastasis and immune escape. Altered cell metabolism is one of the hallmarks of cancer. A number of different types of tumor rely on mitochondrial metabolism by triggering adaptive mechanisms to optimize their oxidative phosphorylation in relation to their substrate supply and energy demands. Exogenous exosomes can induce metabolic reprogramming by restoring the respiration of cancer cells and supress tumor growth. The exosomal miRs involved in the modulation of cancer metabolism may be potentially utilized for better diagnostics and therapy.

  18. UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells

    Science.gov (United States)

    2018-03-15

    Adrenoleukodystrophy; Batten Disease; Mucopolysaccharidosis II; Leukodystrophy, Globoid Cell; Leukodystrophy, Metachromatic; Neimann Pick Disease; Pelizaeus-Merzbacher Disease; Sandhoff Disease; Tay-Sachs Disease; Brain Diseases, Metabolic, Inborn; Alpha-Mannosidosis; Sanfilippo Mucopolysaccharidoses

  19. Sympathetic nervous system control of triglyceride metabolism: novel concepts derived from recent studies

    NARCIS (Netherlands)

    Geerling, Janine J.; Boon, Mariëtte R.; Kooijman, Sander; Parlevliet, Edwin T.; Havekes, Louis M.; Romijn, Johannes A.; Meurs, Illiana M.; Rensen, Patrick C. N.

    2014-01-01

    Important players in triglyceride (TG) metabolism include the liver (production), white adipose tissue (WAT) (storage), heart and skeletal muscle (combustion to generate ATP), and brown adipose tissue (BAT) (combustion toward heat), the collective action of which determine plasma TG levels.

  20. Deriving metabolic engineering strategies from genome-scale modeling with flux ratio constraints.

    Science.gov (United States)

    Yen, Jiun Y; Nazem-Bokaee, Hadi; Freedman, Benjamin G; Athamneh, Ahmad I M; Senger, Ryan S

    2013-05-01

    Optimized production of bio-based fuels and chemicals from microbial cell factories is a central goal of systems metabolic engineering. To achieve this goal, a new computational method of using flux balance analysis with flux ratios (FBrAtio) was further developed in this research and applied to five case studies to evaluate and design metabolic engineering strategies. The approach was implemented using publicly available genome-scale metabolic flux models. Synthetic pathways were added to these models along with flux ratio constraints by FBrAtio to achieve increased (i) cellulose production from Arabidopsis thaliana; (ii) isobutanol production from Saccharomyces cerevisiae; (iii) acetone production from Synechocystis sp. PCC6803; (iv) H2 production from Escherichia coli MG1655; and (v) isopropanol, butanol, and ethanol (IBE) production from engineered Clostridium acetobutylicum. The FBrAtio approach was applied to each case to simulate a metabolic engineering strategy already implemented experimentally, and flux ratios were continually adjusted to find (i) the end-limit of increased production using the existing strategy, (ii) new potential strategies to increase production, and (iii) the impact of these metabolic engineering strategies on product yield and culture growth. The FBrAtio approach has the potential to design "fine-tuned" metabolic engineering strategies in silico that can be implemented directly with available genomic tools. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. An empirically-derived approach for investigating Health Information Technology: the Elementally Entangled Organisational Communication (EEOC) framework.

    Science.gov (United States)

    Georgiou, Andrew; Westbrook, Johanna I; Braithwaite, Jeffrey

    2012-07-12

    The purpose of this paper is to illustrate the Elementally Entangled Organisational Communication (EEOC) framework by drawing on a set of three case studies which assessed the impact of new Health Information Technology (HIT) on a pathology service. The EEOC framework was empirically developed as a tool to tackle organisational communication challenges in the implementation and evaluation of health information systems. The framework was synthesised from multiple research studies undertaken across a major metropolitan hospital pathology service during the period 2005 to 2008. These studies evaluated the impact of new HIT systems in pathology departments (Laboratory Information System) and an Emergency Department (Computerised Provider Order Entry) located in Sydney, Australia. Key dimensions of EEOC are illustrated by the following case studies: 1) the communication infrastructure between the Blood Bank and the ward for the coordination and distribution of blood products; 2) the organisational environment in the Clinical Chemistry and Haematology departments and their attempts to organise, plan and control the processing of laboratory specimens; and 3) the temporal make up of the organisation as revealed in changes to the way the Central Specimen Reception allocated, sequenced and synchronised work tasks. The case studies not only highlight the pre-existing communication architecture within the organisation but also the constitutive role communication plays in the way organisations go about addressing their requirements. HIT implementation involves a mutual transformation of the organisation and the technology. This is a vital consideration because of the dangers associated with poor organisational planning and implementation of HIT, and the potential for unintended adverse consequences, workarounds and risks to the quality and safety of patient care. The EEOC framework aims to account for the complex range of contextual factors and triggers that play a role in the

  2. Empirical Hamiltonians

    International Nuclear Information System (INIS)

    Peggs, S.; Talman, R.

    1987-01-01

    As proton accelerators get larger, and include more magnets, the conventional tracking programs which simulate them run slower. The purpose of this paper is to describe a method, still under development, in which element-by-element tracking around one turn is replaced by a single man, which can be processed far faster. It is assumed for this method that a conventional program exists which can perform faithful tracking in the lattice under study for some hundreds of turns, with all lattice parameters held constant. An empirical map is then generated by comparison with the tracking program. A procedure has been outlined for determining an empirical Hamiltonian, which can represent motion through many nonlinear kicks, by taking data from a conventional tracking program. Though derived by an approximate method this Hamiltonian is analytic in form and can be subjected to further analysis of varying degrees of mathematical rigor. Even though the empirical procedure has only been described in one transverse dimension, there is good reason to hope that it can be extended to include two transverse dimensions, so that it can become a more practical tool in realistic cases

  3. Identifying nurse staffing research in Medline: development and testing of empirically derived search strategies with the PubMed interface.

    Science.gov (United States)

    Simon, Michael; Hausner, Elke; Klaus, Susan F; Dunton, Nancy E

    2010-08-23

    term "nurse staffing") could improve the precision of future searches in this field. Empirically selected search terms can help to develop effective search strategies. The high consistency between all test sets confirmed the validity of our approach.

  4. The Cognitive Assessment Interview (CAI): development and validation of an empirically derived, brief interview-based measure of cognition.

    Science.gov (United States)

    Ventura, Joseph; Reise, Steven P; Keefe, Richard S E; Baade, Lyle E; Gold, James M; Green, Michael F; Kern, Robert S; Mesholam-Gately, Raquelle; Nuechterlein, Keith H; Seidman, Larry J; Bilder, Robert M

    2010-08-01

    Practical, reliable "real world" measures of cognition are needed to supplement neurocognitive performance data to evaluate possible efficacy of new drugs targeting cognitive deficits associated with schizophrenia. Because interview-based measures of cognition offer one possible approach, data from the MATRICS initiative (n=176) were used to examine the psychometric properties of the Schizophrenia Cognition Rating Scale (SCoRS) and the Clinical Global Impression of Cognition in Schizophrenia (CGI-CogS). We used classical test theory methods and item response theory to derive the 10-item Cognitive Assessment Interview (CAI) from the SCoRS and CGI-CogS ("parent instruments"). Sources of information for CAI ratings included the patient and an informant. Validity analyses examined the relationship between the CAI and objective measures of cognitive functioning, intermediate measures of cognition, and functional outcome. The rater's score from the newly derived CAI (10 items) correlate highly (r=.87) with those from the combined set of the SCoRS and CGI-CogS (41 items). Both the patient (r=.82) and the informant (r=.95) data were highly correlated with the rater's score. The CAI was modestly correlated with objectively measured neurocognition (r=-.32), functional capacity (r=-.44), and functional outcome (r=-.32), which was comparable to the parent instruments. The CAI allows for expert judgment in evaluating a patient's cognitive functioning and was modestly correlated with neurocognitive functioning, functional capacity, and functional outcome. The CAI is a brief, repeatable, and potentially valuable tool for rating cognition in schizophrenia patients who are participating in clinical trials. Copyright 2010 Elsevier B.V. All rights reserved.

  5. Association of Empirically Derived Dietary Patterns with Cardiovascular Risk Factors: A Comparison of PCA and RRR Methods.

    Directory of Open Access Journals (Sweden)

    Nicolas Sauvageot

    Full Text Available Principal component analysis is used to determine dietary behaviors of a population whereas reduced rank regression is used to construct disease-related dietary patterns. This study aimed to compare both types of DP and theirs associations with cardiovascular risk factors (CVRF.Data were derived from the cross sectional NESCAV (Nutrition, Environment and Cardiovascular Health study, aiming to describe the cardiovascular health of the Greater region's population (Grand duchy of Luxembourg, Wallonia (Belgium, Lorraine (France. 2298 individuals were included for this study and dietary intake was assessed using a 134-item food frequency questionnaire.We found that CVRF-related patterns also reflect eating behaviours of the population. Comparing concordant food groups between both dietary pattern methods, a diet high in fruits, oleaginous and dried fruits, vegetables, olive oil, fats rich in omega 6 and tea and low in fried foods, lean and fatty meat, processed meat, ready meal, soft drink and beer was associated with lower prevalence of CVRF. In the opposite, a pattern characterized by high intakes of fried foods, meat, offal, beer, wine and aperitifs and spirits, and low intakes of cereals, sugar and sweets and soft drinks was associated with higher prevalence of CVRF.In sum, we found that a "Prudent" and "Animal protein and alcohol" patterns were both associated with CVRF and behaviourally meaningful. Moreover, the relationships of those dietary patterns with lifestyle characteristics support the theory that food choices are part of a larger pattern of healthy lifestyle.

  6. Detection of transketolase in bone marrow-derived insulin-producing cells: benfotiamine enhances insulin synthesis and glucose metabolism.

    Science.gov (United States)

    Oh, Seh-Hoon; Witek, Rafal P; Bae, Si-Hyun; Darwiche, Houda; Jung, Youngmi; Pi, Liya; Brown, Alicia; Petersen, Bryon E

    2009-01-01

    Adult bone marrow (BM)-derived insulin-producing cells (IPCs) are capable of regulating blood glucose levels in chemically induced hyperglycemic mice. Using cell transplantation therapy, fully functional BM-derived IPCs help to mediate treatment of diabetes mellitus. Here, we demonstrate the detection of the pentose phosphate pathway enzyme, transketolase (TK), in BM-derived IPCs cultured under high-glucose conditions. Benfotiamine, a known activator of TK, was not shown to affect the proliferation of insulinoma cell line, INS-1; however, when INS-1 cells were cultured with oxythiamine, an inhibitor of TK, cell proliferation was suppressed. Treatment with benfotiamine activated glucose metabolism in INS-1 cells in high-glucose culture conditions, and appeared to maximize the BM-derived IPCs ability to synthesize insulin. Benfotiamine was not shown to induce the glucose receptor Glut-2, however it was shown to activate glucokinase, the enzyme responsible for conversion of glucose to glucose-6-phosphate. Furthermore, benfotiamine-treated groups showed upregulation of the downstream glycolytic enzyme, glyceraldehyde phosphate dehydrogenase (GAPDH). However, in cells where the pentose phosphate pathway was blocked by oxythiamine treatment, there was a clear downregulation of Glut-2, glucokinase, insulin, and GAPDH. When benfotiamine was used to treat mice transplanted with BM-derived IPCs transplanted, their glucose level was brought to a normal range. The glucose challenge of normal mice treated with benfotiamine lead to rapidly normalized blood glucose levels. These results indicate that benfotiamine activates glucose metabolism and insulin synthesis to prevent glucose toxicity caused by high concentrations of blood glucose in diabetes mellitus.

  7. Detection of Transketolase in Bone Marrow—Derived Insulin-Producing Cells: Benfotiamine Enhances Insulin Synthesis and Glucose Metabolism

    Science.gov (United States)

    Witek, Rafal P.; Bae, Si-Hyun; Darwiche, Houda; Jung, Youngmi; Pi, Liya; Brown, Alicia; Petersen, Bryon E.

    2009-01-01

    Adult bone marrow (BM)-derived insulin-producing cells (IPCs) are capable of regulating blood glucose levels in chemically induced hyperglycemic mice. Using cell transplantation therapy, fully functional BM-derived IPCs help to mediate treatment of diabetes mellitus. Here, we demonstrate the detection of the pentose phosphate pathway enzyme, transketolase (TK), in BM-derived IPCs cultured under high-glucose conditions. Benfotiamine, a known activator of TK, was not shown to affect the proliferation of insulinoma cell line, INS-1; however, when INS-1 cells were cultured with oxythiamine, an inhibitor of TK, cell proliferation was suppressed. Treatment with benfotiamine activated glucose metabolism in INS-1 cells in high-glucose culture conditions, and appeared to maximize the BM-derived IPCs ability to synthesize insulin. Benfotiamine was not shown to induce the glucose receptor Glut-2, however it was shown to activate glucokinase, the enzyme responsible for conversion of glucose to glucose-6-phosphate. Furthermore, benfotiamine-treated groups showed upregulation of the downstream glycolytic enzyme, glyceraldehyde phosphate dehydrogenase (GAPDH). However, in cells where the pentose phosphate pathway was blocked by oxythiamine treatment, there was a clear downregulation of Glut-2, glucokinase, insulin, and GAPDH. When benfotiamine was used to treat mice transplanted with BM-derived IPCs transplanted, their glucose level was brought to a normal range. The glucose challenge of normal mice treated with benfotiamine lead to rapidly normalized blood glucose levels. These results indicate that benfotiamine activates glucose metabolism and insulin synthesis to prevent glucose toxicity caused by high concentrations of blood glucose in diabetes mellitus. PMID:18393672

  8. [Effect of a new derivative of glutamic and apovincaminic acids on brain metabolism in post-ischemic period].

    Science.gov (United States)

    Makarova, L M; Prikhod'ko, M A; Pogorelyĭ, V E; Skachilova, S Ia; Mirzoian, R S

    2014-01-01

    Neuroprotective properties of the new derivative of glutamic and apovincaminic acids, ethyl -(3-alpha,16-alpha)-eburnamenin-14-carbopxylate of 2-aminopentadionic acid (LHT 1-02) were studied on a model of acute brain ischemia in cats. LHT 1-02 has proved to be more effective than the reference drugs vinpocetin and glycine in preventing the reperfusive damage, which was manifested by decreased postischemic hyperglycemia, activated utilization of oxygen in the brain, and suppressed postischemic metabolic lactate acidosis. Thus, the results of this comparative study show expediency of further investigations of LHT 1 - 02 as a potential neuroprotective drug.

  9. Detoxification of biomass derived acetate via metabolic conversion to ethanol, acetone, isopropanol, or ethyl acetate

    Science.gov (United States)

    Sillers, William Ryan; Van Dijken, Hans; Licht, Steve; Shaw, IV, Arthur J.; Gilbert, Alan Benjamin; Argyros, Aaron; Froehlich, Allan C.; McBride, John E.; Xu, Haowen; Hogsett, David A.; Rajgarhia, Vineet B.

    2017-03-28

    One aspect of the invention relates to a genetically modified thermophilic or mesophilic microorganism, wherein a first native gene is partially, substantially, or completely deleted, silenced, inactivated, or down-regulated, which first native gene encodes a first native enzyme involved in the metabolic production of an organic acid or a salt thereof, thereby increasing the native ability of said thermophilic or mesophilic microorganism to produce lactate or acetate as a fermentation product. In certain embodiments, the aforementioned microorganism further comprises a first non-native gene, which first non-native gene encodes a first non-native enzyme involved in the metabolic production of lactate or acetate. Another aspect of the invention relates to a process for converting lignocellulosic biomass to lactate or acetate, comprising contacting lignocellulosic biomass with a genetically modified thermophilic or mesophilic microorganism.

  10. The Effect of Marine Derived n-3 Fatty Acids on Adipose Tissue Metabolism and Function

    Directory of Open Access Journals (Sweden)

    Marijana Todorčević

    2015-12-01

    Full Text Available Adipose tissue function is key determinant of metabolic health, with specific nutrients being suggested to play a role in tissue metabolism. One such group of nutrients are the n-3 fatty acids, specifically eicosapentaenoic acid (EPA; 20:5n-3 and docosahexaenoic acid (DHA; 22:6n-3. Results from studies where human, animal and cellular models have been utilised to investigate the effects of EPA and/or DHA on white adipose tissue/adipocytes suggest anti-obesity and anti-inflammatory effects. We review here evidence for these effects, specifically focusing on studies that provide some insight into metabolic pathways or processes. Of note, limited work has been undertaken investigating the effects of EPA and DHA on white adipose tissue in humans whilst more work has been undertaken using animal and cellular models. Taken together it would appear that EPA and DHA have a positive effect on lowering lipogenesis, increasing lipolysis and decreasing inflammation, all of which would be beneficial for adipose tissue biology. What remains to be elucidated is the duration and dose required to see a favourable effect of EPA and DHA in vivo in humans, across a range of adiposity.

  11. Charge-associated effects of fullerene derivatives on microbialstructural integrity and central metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Yinjie J.; Ashcroft, Jared M.; Chen, Ding; Min, Guangwei; Kim, Chul; Murkhejee, Bipasha; Larabell, Carolyn; Keasling, Jay D.; Chen,Fanqing Frank

    2007-01-23

    The effects of four types of fullerene compounds (C60,C60-OH, C60-COOH, C60-NH2) were examined on two model microorganisms(Escherichia coli W3110 and Shewanella oneidensis MR-1). Positivelycharged C60-NH2 at concentrations as low as 10 mg/L inhibited growth andreduced substrate uptake for both microorganisms. Scanning ElectronMicroscopy (SEM) revealed damage to cellular structures.Neutrally-charged C60 and C60-OH had mild negative effects on S.oneidensis MR-1, whereas the negatively-charged C60-COOH did not affecteither microorganism s growth. The effect of fullerene compounds onglobal metabolism was further investigated using [3-13C]L-lactateisotopic labeling, which tracks perturbations to metabolic reaction ratesin bacteria by examining the change in the isotopic labeling pattern inthe resulting metabolites (often amino acids).1-3 The 13C isotopomeranalysis from all fullerene-exposed cultures revealed no significantdifferences in isotopomer distributions from unstressed cells. Thisresult indicates that microbial central metabolism is robust toenvironmental stress inflicted by fullerene nanoparticles. In addition,although C60-NH2 compounds caused mechanical stress on the cell wall ormembrane, both S. oneidensis MR-1 and E. coli W3110 can efficientlyalleviate such stress by cell aggregation and precipitation of the toxicnanoparticles. The results presented here favor the hypothesis thatfullerenes cause more membrane stress4, 5, 6 than perturbation to energymetabolism7

  12. Analysis of glucose metabolism in patients with diabetes mellitus by using functional images derived from 18F-FDG PET

    International Nuclear Information System (INIS)

    Ohtake, Tohru; Yokoyama, Ikuo; Watanabe, Toshiaki; Kosaka, Noboru; Momose, Toshimitsu; Nishikawa, Jun-ichi; Serizawa, Takashi; Sasaki, Yasuhito

    1993-01-01

    Functional images of K complex (KC) and regional myocardial glucose utilization rates (rMGU), derived from F-18-fluoro-deoxy-glucose (F-18-FDG) positron emission computed tomography, were prepared. Using functional images obtained, myocardial glucose metabolism was examined in the fasting state, oral glucose loading (OG), and insulin clamp (IC) condition. The subjects were 10 patients with diabetes mellitus (DM), consisting of 8 with non-insulin dependent DM and 2 with insulin dependent DM, and 4 normal persons. Image quality, derived from both OG and IC approaches, was favorable in the normal group. In the groups of non-insulin dependent DM and insulin dependent DM patients, however, image quality was good with IC method but not with OG method. In the group of non-insulin dependent DM, rMGU derived by IC method was relatively high, but was significantly lower than that in the control group, suggesting a decreased function in glucose transporter. When using OG method, rMGU was even more decreased due to high blood sugar and low insulin. In the group of insulin dependent DM, both IC and OG approaches achieved the same rMGU as that in the control group, with the exception of KC derived by OG method that was decreased due to high blood sugar. In moderate or severe DM, myocardial viability seems to be difficult to evaluate because F-18-FDG uptake is decreased in the ischemic area associated with fasting high blood sugar. Mismatching between blood flow and metabolism is also difficult to detect due to high insulin or glucose load. Thus, myocardial viability should be evaluated in the condition of slightly loaded insulin by decreasing blood sugar. (N.K.)

  13. Different response to hypoxia of adipose-derived multipotent cells from obese subjects with and without metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    Wilfredo Oliva-Olivera

    Full Text Available Multiple studies suggest that hypoxia, together with inflammation, could be one of the phenomena involved in the onset and progression of obesity-related insulin resistance. In addition, dysfunction of adipose tissue in obese subjects with metabolic syndrome is associated with decreased angiogenesis. However, some subjects with a high body mass index do not develop metabolic abnormalities associated with obesity. The aim of the current study was to examine the neovascular properties of visceral adipose tissue-derived multipotent mesenchymal cells subjected to hypoxia (hypox-visASCs from normal-weight subjects (Nw and obese patients with metabolic syndrome (MS and without metabolic syndrome (NonMS.This was a 2-year study to enroll subjects who underwent bariatric surgery or cholecystectomy. Eight patients who underwent either bariatric surgery or cholecystectomy (27 patients participated in the study. Visceral adipose tissue samples from Nw, MS and NonMS subjects were processed by enzymatic digestion. VisASCs cultured under hypoxic conditions were characterized by tubule formation assay, ELISA, flow cytometry, migration rate, and qRT-PCR, and the effects of visASCs-conditioned medium on survival and endothelial cell tubule formation were evaluated.Hypox-visASCs from NonMS subjects showed a greater capacity for tubule formation than hypox-visASCs from Nw and MS subjects. The lower percentage of CD140b+/CD44+ and CD140b+/CD184+ cells observed in hypox-visASCs from NonMS subjects compared to MS subjects was accompanied not only by a lower migration rate from the chemotactic effects of stromal cell derived factor 1α, but also by lower levels of NOX5 mRNA expression. While the levels of monocyte chemoattractant protein 1 mRNA expressed by hypox-visASCs correlated positively with the body mass index and waist circumference of the subjects, the concentration of vascular endothelial growth factor present in hypox-visASC-conditioned culture medium

  14. Different response to hypoxia of adipose-derived multipotent cells from obese subjects with and without metabolic syndrome

    Science.gov (United States)

    Moreno-Indias, Isabel; Coín-Aragüez, Leticia; Lhamyani, Said; Alcaide Torres, Juan; Fernández-Veledo, Sonia; Vendrell, Joan; Camargo, Antonio; El Bekay, Rajaa; Tinahones, Francisco José

    2017-01-01

    Background/Objectives Multiple studies suggest that hypoxia, together with inflammation, could be one of the phenomena involved in the onset and progression of obesity-related insulin resistance. In addition, dysfunction of adipose tissue in obese subjects with metabolic syndrome is associated with decreased angiogenesis. However, some subjects with a high body mass index do not develop metabolic abnormalities associated with obesity. The aim of the current study was to examine the neovascular properties of visceral adipose tissue-derived multipotent mesenchymal cells subjected to hypoxia (hypox-visASCs) from normal-weight subjects (Nw) and obese patients with metabolic syndrome (MS) and without metabolic syndrome (NonMS). Methods This was a 2-year study to enroll subjects who underwent bariatric surgery or cholecystectomy. Eight patients who underwent either bariatric surgery or cholecystectomy (27 patients) participated in the study. Visceral adipose tissue samples from Nw, MS and NonMS subjects were processed by enzymatic digestion. VisASCs cultured under hypoxic conditions were characterized by tubule formation assay, ELISA, flow cytometry, migration rate, and qRT-PCR, and the effects of visASCs-conditioned medium on survival and endothelial cell tubule formation were evaluated. Results Hypox-visASCs from NonMS subjects showed a greater capacity for tubule formation than hypox-visASCs from Nw and MS subjects. The lower percentage of CD140b+/CD44+ and CD140b+/CD184+ cells observed in hypox-visASCs from NonMS subjects compared to MS subjects was accompanied not only by a lower migration rate from the chemotactic effects of stromal cell derived factor 1α, but also by lower levels of NOX5 mRNA expression. While the levels of monocyte chemoattractant protein 1 mRNA expressed by hypox-visASCs correlated positively with the body mass index and waist circumference of the subjects, the concentration of vascular endothelial growth factor present in hypox

  15. Metabolic fate of endogenous molecular damage: Urinary glutathione conjugates of DNA-derived base propenals as markers of inflammation.

    Science.gov (United States)

    Jumpathong, Watthanachai; Chan, Wan; Taghizadeh, Koli; Babu, I Ramesh; Dedon, Peter C

    2015-09-01

    Although mechanistically linked to disease, cellular molecules damaged by endogenous processes have not emerged as significant biomarkers of inflammation and disease risk, due in part to poor understanding of their pharmacokinetic fate from tissue to excretion. Here, we use systematic metabolite profiling to define the fate of a common DNA oxidation product, base propenals, to discover such a biomarker. Based on known chemical reactivity and metabolism in liver cell extracts, 15 candidate metabolites were identified for liquid chromatography-coupled tandem mass spectrometry (LC-MS/MS) quantification in urine and bile of rats treated with thymine propenal (Tp). Analysis of urine revealed three metabolites (6% of Tp dose): thymine propenoate and two mercapturate derivatives of glutathione conjugates. Bile contained an additional four metabolites (22% of Tp dose): cysteinylglycine and cysteine derivatives of glutathione adducts. A bis-mercapturate was observed in urine of untreated rats and increased approximately three- to fourfold following CCl4-induced oxidative stress or treatment with the DNA-cleaving antitumor agent, bleomycin. Systematic metabolite profiling thus provides evidence for a metabolized DNA damage product as a candidate biomarker of inflammation and oxidative stress in humans.

  16. Patient-Specific Seizure Detection in Long-Term EEG Using Signal-Derived Empirical Mode Decomposition (EMD)-based Dictionary Approach.

    Science.gov (United States)

    Kaleem, Muhammad; Gurve, Dharmendra; Guergachi, Aziz; Krishnan, Sridhar

    2018-06-25

    The objective of the work described in this paper is development of a computationally efficient methodology for patient-specific automatic seizure detection in long-term multi-channel EEG recordings. Approach: A novel patient-specific seizure detection approach based on signal-derived Empirical Mode Decomposition (EMD)-based dictionary approach is proposed. For this purpose, we use an empirical framework for EMD-based dictionary creation and learning, inspired by traditional dictionary learning methods, in which the EMD-based dictionary is learned from the multi-channel EEG data being analyzed for automatic seizure detection. We present the algorithm for dictionary creation and learning, whose purpose is to learn dictionaries with a small number of atoms. Using training signals belonging to seizure and non-seizure classes, an initial dictionary, termed as the raw dictionary, is formed. The atoms of the raw dictionary are composed of intrinsic mode functions obtained after decomposition of the training signals using the empirical mode decomposition algorithm. The raw dictionary is then trained using a learning algorithm, resulting in a substantial decrease in the number of atoms in the trained dictionary. The trained dictionary is then used for automatic seizure detection, such that coefficients of orthogonal projections of test signals against the trained dictionary form the features used for classification of test signals into seizure and non-seizure classes. Thus no hand-engineered features have to be extracted from the data as in traditional seizure detection approaches. Main results: The performance of the proposed approach is validated using the CHB-MIT benchmark database, and averaged accuracy, sensitivity and specificity values of 92.9%, 94.3% and 91.5%, respectively, are obtained using support vector machine classifier and five-fold cross-validation method. These results are compared with other approaches using the same database, and the suitability

  17. Solar-wind predictions for the Parker Solar Probe orbit. Near-Sun extrapolations derived from an empirical solar-wind model based on Helios and OMNI observations

    Science.gov (United States)

    Venzmer, M. S.; Bothmer, V.

    2018-03-01

    Context. The Parker Solar Probe (PSP; formerly Solar Probe Plus) mission will be humanitys first in situ exploration of the solar corona with closest perihelia at 9.86 solar radii (R⊙) distance to the Sun. It will help answer hitherto unresolved questions on the heating of the solar corona and the source and acceleration of the solar wind and solar energetic particles. The scope of this study is to model the solar-wind environment for PSPs unprecedented distances in its prime mission phase during the years 2018 to 2025. The study is performed within the Coronagraphic German And US SolarProbePlus Survey (CGAUSS) which is the German contribution to the PSP mission as part of the Wide-field Imager for Solar PRobe. Aim. We present an empirical solar-wind model for the inner heliosphere which is derived from OMNI and Helios data. The German-US space probes Helios 1 and Helios 2 flew in the 1970s and observed solar wind in the ecliptic within heliocentric distances of 0.29 au to 0.98 au. The OMNI database consists of multi-spacecraft intercalibrated in situ data obtained near 1 au over more than five solar cycles. The international sunspot number (SSN) and its predictions are used to derive dependencies of the major solar-wind parameters on solar activity and to forecast their properties for the PSP mission. Methods: The frequency distributions for the solar-wind key parameters, magnetic field strength, proton velocity, density, and temperature, are represented by lognormal functions. In addition, we consider the velocity distributions bi-componental shape, consisting of a slower and a faster part. Functional relations to solar activity are compiled with use of the OMNI data by correlating and fitting the frequency distributions with the SSN. Further, based on the combined data set from both Helios probes, the parameters frequency distributions are fitted with respect to solar distance to obtain power law dependencies. Thus an empirical solar-wind model for the inner

  18. Novel benzimidazole derivatives as phosphodiesterase 10A (PDE10A) inhibitors with improved metabolic stability.

    Science.gov (United States)

    Chino, Ayaka; Masuda, Naoyuki; Amano, Yasushi; Honbou, Kazuya; Mihara, Takuma; Yamazaki, Mayako; Tomishima, Masaki

    2014-07-01

    In this study, we report the identification of potent benzimidazoles as PDE10A inhibitors. We first identified imidazopyridine 1 as a high-throughput screening hit compound from an in-house library. Next, optimization of the imidazopyridine moiety to improve inhibitory activity gave imidazopyridinone 10b. Following further structure-activity relationship development by reducing lipophilicity and introducing substituents, we acquired 35, which exhibited both improved metabolic stability and reduced CYP3A4 time-dependent inhibition. Copyright © 2014. Published by Elsevier Ltd.

  19. Empirically Derived Dehydration Scoring and Decision Tree Models for Children With Diarrhea: Assessment and Internal Validation in a Prospective Cohort Study in Dhaka, Bangladesh.

    Science.gov (United States)

    Levine, Adam C; Glavis-Bloom, Justin; Modi, Payal; Nasrin, Sabiha; Rege, Soham; Chu, Chieh; Schmid, Christopher H; Alam, Nur H

    2015-08-18

    Diarrhea remains one of the most common and most deadly conditions affecting children worldwide. Accurately assessing dehydration status is critical to determining treatment course, yet no clinical diagnostic models for dehydration have been empirically derived and validated for use in resource-limited settings. In the Dehydration: Assessing Kids Accurately (DHAKA) prospective cohort study, a random sample of children under 5 with acute diarrhea was enrolled between February and June 2014 in Bangladesh. Local nurses assessed children for clinical signs of dehydration on arrival, and then serial weights were obtained as subjects were rehydrated. For each child, the percent weight change with rehydration was used to classify subjects with severe dehydration (>9% weight change), some dehydration (3-9%), or no dehydration (Dehydration Score and DHAKA Dehydration Tree, respectively. Models were assessed for their accuracy using the area under their receiver operating characteristic curve (AUC) and for their reliability through repeat clinical exams. Bootstrapping was used to internally validate the models. A total of 850 children were enrolled, with 771 included in the final analysis. Of the 771 children included in the analysis, 11% were classified with severe dehydration, 45% with some dehydration, and 44% with no dehydration. Both the DHAKA Dehydration Score and DHAKA Dehydration Tree had significant AUCs of 0.79 (95% CI = 0.74, 0.84) and 0.76 (95% CI = 0.71, 0.80), respectively, for the diagnosis of severe dehydration. Additionally, the DHAKA Dehydration Score and DHAKA Dehydration Tree had significant positive likelihood ratios of 2.0 (95% CI = 1.8, 2.3) and 2.5 (95% CI = 2.1, 2.8), respectively, and significant negative likelihood ratios of 0.23 (95% CI = 0.13, 0.40) and 0.28 (95% CI = 0.18, 0.44), respectively, for the diagnosis of severe dehydration. Both models demonstrated 90% agreement between independent raters and good

  20. Assessment of Energy Metabolic Changes in Adipose Tissue-Derived Stem Cells

    NARCIS (Netherlands)

    Hajmousa, Ghazaleh; Harmsen, Martin C; Di Nardo, Paolo; Dhingra, Sanjiv; Singla, Dinender K.

    2017-01-01

    Adipose tissue-derived stem cells (ADSC) are promising candidates for therapeutic applications in cardiovascular regenerative medicine. By definition, the phenotype ADSCs, e.g., the ubiquitous secretion of growth factors, cytokines, and extracellular matrix components is not met in vivo, which

  1. Empirically derived dietary patterns and incident type 2 diabetes mellitus: a systematic review and meta-analysis on prospective observational studies.

    Science.gov (United States)

    Maghsoudi, Zahra; Ghiasvand, Reza; Salehi-Abargouei, Amin

    2016-02-01

    To systematically review prospective cohort studies about the association between dietary patterns and type 2 diabetes mellitus (T2DM) incidence, and to quantify the effects using a meta-analysis. Databases such as PubMed, ISI Web of Science, SCOPUS and Google Scholar were searched up to 15 January 2015. Cohort studies which tried to examine the association between empirically derived dietary patterns and incident T2DM were selected. The relative risks (RR) and their 95 % confidence intervals for diabetes among participants with highest v. lowest adherence to derived dietary patterns were incorporated into meta-analysis using random-effects models. Ten studies (n 404 528) were enrolled in the systematic review and meta-analysis; our analysis revealed that adherence to the 'healthy' dietary patterns significantly reduced the risk of T2DM (RR=0·86; 95 % CI 0·82, 0·90), while the 'unhealthy' dietary patterns adversely affected diabetes risk (RR=1·30; 95 % CI 1·18, 1·43). Subgroup analysis showed that unhealthy dietary patterns in which foods with high phytochemical content were also loaded did not significantly increase T2DM risk (RR=1·06; 95 % CI 0·87, 1·30). 'Healthy' dietary patterns containing vegetables, fruits and whole grains can lower diabetes risk by 14 %. Consuming higher amounts of red and processed meats, high-fat dairy and refined grains in the context of 'unhealthy' dietary patterns will increase diabetes risk by 30 %; while including foods with high phytochemical content in these patterns can modify this effect.

  2. CHARACTERIZING THE HEAVY ELEMENTS IN GLOBULAR CLUSTER M22 AND AN EMPIRICAL s-PROCESS ABUNDANCE DISTRIBUTION DERIVED FROM THE TWO STELLAR GROUPS

    International Nuclear Information System (INIS)

    Roederer, I. U.; Marino, A. F.; Sneden, C.

    2011-01-01

    We present an empirical s-process abundance distribution derived with explicit knowledge of the r-process component in the low-metallicity globular cluster M22. We have obtained high-resolution, high signal-to-noise spectra for six red giants in M22 using the Magellan Inamori Kyocera Echelle spectrograph on the Magellan-Clay Telescope at Las Campanas Observatory. In each star we derive abundances for 44 species of 40 elements, including 24 elements heavier than zinc (Z = 30) produced by neutron-capture reactions. Previous studies determined that three of these stars (the 'r+s group') have an enhancement of s-process material relative to the other three stars (the 'r-only group'). We confirm that the r+s group is moderately enriched in Pb relative to the r-only group. Both groups of stars were born with the same amount of r-process material, but s-process material was also present in the gas from which the r+s group formed. The s-process abundances are inconsistent with predictions for asymptotic giant branch (AGB) stars with M ≤ 3 M ☉ and suggest an origin in more massive AGB stars capable of activating the 22 Ne(α,n) 25 Mg reaction. We calculate the s-process 'residual' by subtracting the r-process pattern in the r-only group from the abundances in the r+s group. In contrast to previous r- and s-process decompositions, this approach makes no assumptions about the r- and s-process distributions in the solar system and provides a unique opportunity to explore s-process yields in a metal-poor environment.

  3. Characterizing the Heavy Elements in Globular Cluster M22 and an Empirical s-process Abundance Distribution Derived from the Two Stellar Groups

    Science.gov (United States)

    Roederer, I. U.; Marino, A. F.; Sneden, C.

    2011-11-01

    We present an empirical s-process abundance distribution derived with explicit knowledge of the r-process component in the low-metallicity globular cluster M22. We have obtained high-resolution, high signal-to-noise spectra for six red giants in M22 using the Magellan Inamori Kyocera Echelle spectrograph on the Magellan-Clay Telescope at Las Campanas Observatory. In each star we derive abundances for 44 species of 40 elements, including 24 elements heavier than zinc (Z = 30) produced by neutron-capture reactions. Previous studies determined that three of these stars (the "r+s group") have an enhancement of s-process material relative to the other three stars (the "r-only group"). We confirm that the r+s group is moderately enriched in Pb relative to the r-only group. Both groups of stars were born with the same amount of r-process material, but s-process material was also present in the gas from which the r+s group formed. The s-process abundances are inconsistent with predictions for asymptotic giant branch (AGB) stars with M <= 3 M ⊙ and suggest an origin in more massive AGB stars capable of activating the 22Ne(α,n)25Mg reaction. We calculate the s-process "residual" by subtracting the r-process pattern in the r-only group from the abundances in the r+s group. In contrast to previous r- and s-process decompositions, this approach makes no assumptions about the r- and s-process distributions in the solar system and provides a unique opportunity to explore s-process yields in a metal-poor environment. This paper includes data gathered with the 6.5 m Magellan Telescopes located at Las Campanas Observatory, Chile.

  4. Long Distance Metabolic Regulation through Adipose-Derived Circulating Exosomal miRNAs: A Trail for RNA-Based Therapies?

    Directory of Open Access Journals (Sweden)

    Farah Fatima

    2017-08-01

    Full Text Available The contribution of non-coding RNAs, such as microRNAs (miRNAs in regulating physiological and pathological states has been intensively elucidated during last 15 years. The discovery of circulating miRNAs (cir-miRNAs in variety of body fluids, is, however a recent focus of interest in understanding pathophysiological states of their originating cells/organs. Yet another stimulating debate that takes miRNAs to the next level is their presence in exosomes, and this is truly interesting area of research. Exosomes are cell-derived extracellular vesicles, and are naturally equipped biological vehicles that not only enable functional transfer of miRNAs between cells (horizontal transfer but also foster inter-organ communication, presumably guided by organ specific receptors—decorated on their surface. However, understandings on inter-organ communication elicited by tissue specific exosomal-miRNA fingerprints remain elusive. Recently, Thomou et al., has discovered that adipose tissue contributes a large fraction of adipose specific exosomal-miRNA fingerprints in blood circulation. Experimental evidence emphasize adipose tissue as major depot of cir-miRNAs that sail through blood flow and reach to distal organs—primarily in the liver, where they regulate gene expression of host tissue and elicit metabolic control. This appears to be a genetic form of adipokines (endocrine factors secreted from adipose tissue. We review such offshore metabolic insults, and make an effort to address few important missing links between miRNAs processing and their incorporation into exosomes. We provide potential perspectives on how this knowledge could be steered towards RNA-based therapeutics for monitoring complex metabolic diseases and beyond.

  5. Preliminary evaluation of MRI-derived input function for quantitative measurement of glucose metabolism in an integrated PET-MRI

    International Nuclear Information System (INIS)

    Anazodo, Udunna; Kewin, Matthew; Finger, Elizabeth; Thiessen, Jonathan; Hadway, Jennifer; Butler, John; Pavlosky, William; Prato, Frank; Thompson, Terry; St Lawrence, Keith

    2015-01-01

    PET semi-quantitative methods such as relative uptake value can be robust but offer no biological information and do not account for intra-subject variability in tracer administration or clearance. Simultaneous multimodal measurements that combine PET and MRI not only permit crucial multiparametric measurements, it provides means of applying tracer kinetic modelling without the need for serial arterial blood sampling. In this study we adapted an image-derived input function (IDIF) method to improve characterization of glucose metabolism in an ongoing dementia study. Here we present preliminary results in a small group of frontotemporal dementia patients and controls. IDIF was obtained directly from dynamic PET data guided by regions of interest drawn on carotid vessels on high resolution T1-weighted MR Images. IDIF was corrected for contamination of non-arterial voxels. A validation of the method was performed in a porcine model in a PET-CT scanner comparing IDIF to direct arterial blood samples. Metabolic rate of glucose (CMRglc) was measured voxel-by-voxel in gray matter producing maps that were compared between groups. Net influx rate (Ki) and global mean CMRglc are reported. A good correlation (r = 0.9 p<0.0001) was found between corrected IDIF and input function measured from direct arterial blood sampling in the validation study. In 3 FTD and 3 controls, a trend towards hypometabolism was found in frontal, temporal and parietal lobes similar to significant differences previously reported by other groups. The global mean CMRglc and Ki observed in control subjects are in line with previous reports. In general, kinetic modelling of PET-FDG using an MR-IDIF can improve characterization of glucose metabolism in dementia. This method is feasible in multimodal studies that aim to combine PET molecular imaging with MRI as dynamic PET can be acquired along with multiple MRI measurements.

  6. Relationship between Levels of Brain-Derived Neurotrophic Factor and Metabolic Parameters in Patients with Type 2 Diabetes Mellitus

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    Banu Boyuk

    2014-01-01

    Full Text Available Background and Aim. Studies have suggested that brain-derived neurotrophic factor (BDNF plays a role in glucose and lipid metabolism and inflammation. The aim of this study was to evaluate the relationship between serum BDNF levels and various metabolic parameters and inflammatory markers in patients with type 2 diabetes mellitus (T2DM. Materials and Methods. The study included 88 T2DM patients and 33 healthy controls. Fasting blood samples were obtained from the patients and the control group. The serum levels of BDNF were measured with an ELISA kit. The current paper introduces a receiver-operating characteristic (ROC generalization curve to identify cut-off for the BDNF values in type 2 diabetes patients. Results. The serum levels of BDNF were significantly higher in T2DM patients than in the healthy controls (206.81 ± 107.32 pg/mL versus 130.84 ± 59.81 pg/mL; P<0.001. They showed a positive correlation with the homeostasis model assessment of insulin resistance (HOMA-IR (r=0.28; P<0.05, the triglyceride level (r=0.265; P<0.05, and white blood cell (WBC count (r=0.35; P<0.001. In logistic regression analysis, age (P<0.05, body mass index (BMI (P<0.05, C-reactive protein (CRP (P<0.05, and BDNF (P<0.01 were independently associated with T2DM. In ROC curve analysis, BDNF cut-off was 137. Conclusion. The serum BDNF level was higher in patients with T2DM. The BDNF had a cut-off value of 137. The findings suggest that BDNF may contribute to glucose and lipid metabolism and inflammation.

  7. Preliminary evaluation of MRI-derived input function for quantitative measurement of glucose metabolism in an integrated PET-MRI

    Energy Technology Data Exchange (ETDEWEB)

    Anazodo, Udunna; Kewin, Matthew [Lawson Health Research Institute, Department of Medical Biophysics, Western University, London, Ontario (Canada); Finger, Elizabeth [Department of Clinical Neurological Sciences, Western University, London, Ontario (Canada); Thiessen, Jonathan; Hadway, Jennifer; Butler, John [Lawson Health Research Institute, Department of Medical Biophysics, Western University, London, Ontario (Canada); Pavlosky, William [Diagnostic Imaging, St Joseph' s Health Care, London, Ontario (Canada); Prato, Frank; Thompson, Terry; St Lawrence, Keith [Lawson Health Research Institute, Department of Medical Biophysics, Western University, London, Ontario (Canada)

    2015-05-18

    PET semi-quantitative methods such as relative uptake value can be robust but offer no biological information and do not account for intra-subject variability in tracer administration or clearance. Simultaneous multimodal measurements that combine PET and MRI not only permit crucial multiparametric measurements, it provides means of applying tracer kinetic modelling without the need for serial arterial blood sampling. In this study we adapted an image-derived input function (IDIF) method to improve characterization of glucose metabolism in an ongoing dementia study. Here we present preliminary results in a small group of frontotemporal dementia patients and controls. IDIF was obtained directly from dynamic PET data guided by regions of interest drawn on carotid vessels on high resolution T1-weighted MR Images. IDIF was corrected for contamination of non-arterial voxels. A validation of the method was performed in a porcine model in a PET-CT scanner comparing IDIF to direct arterial blood samples. Metabolic rate of glucose (CMRglc) was measured voxel-by-voxel in gray matter producing maps that were compared between groups. Net influx rate (Ki) and global mean CMRglc are reported. A good correlation (r = 0.9 p<0.0001) was found between corrected IDIF and input function measured from direct arterial blood sampling in the validation study. In 3 FTD and 3 controls, a trend towards hypometabolism was found in frontal, temporal and parietal lobes similar to significant differences previously reported by other groups. The global mean CMRglc and Ki observed in control subjects are in line with previous reports. In general, kinetic modelling of PET-FDG using an MR-IDIF can improve characterization of glucose metabolism in dementia. This method is feasible in multimodal studies that aim to combine PET molecular imaging with MRI as dynamic PET can be acquired along with multiple MRI measurements.

  8. Toxicokinetics of amphetamines: metabolism and toxicokinetic data of designer drugs, amphetamine, methamphetamine, and their N-alkyl derivatives.

    Science.gov (United States)

    Kraemer, Thomas; Maurer, Hans H

    2002-04-01

    This paper reviews the toxicokinetics of amphetamines. The designer drugs MDA (methylenedioxy-amphetamine, R,S-1-(3;,4;-methylenedioxyphenyl)2-propanamine), MDMA (R,S-methylenedioxymethamphetamine), and MDE (R,S-methylenedioxyethylamphetamine), as well as BDB (benzodioxolylbutanamine; R,S-1-(1;,3;-benzodioxol-5;-yl)-2-butanamine or R,S-1-(3;,4;-methylenedioxyphenyl)-2-butanamine) and MBDB (R,S-N-methyl-benzodioxolylbutanamine), were taken into consideration, as were the following N-alkylated amphetamine derivatives: amphetaminil, benzphetamine, clobenzorex, dimethylamphetamine, ethylamphetamine, famprofazone, fencamine, fenethylline, fenproporex, furfenorex, mefenorex, mesocarb, methamphetamine, prenylamine, and selegiline. English-language publications from 1995 to 2000 were reviewed. Papers describing identification of metabolites or cytochrome P450 isoenzyme-dependent metabolism and papers containing pharmacokinetic/toxicokinetic data were considered and summarized. The implications of toxicokinetics for toxicologic assessment or for interpretation in forensic cases are discussed.

  9. Synthesis and biological evaluation of novel 5-hydroxylaminoisoxazole derivatives as lipoxygenase inhibitors and metabolism enhancing agents.

    Science.gov (United States)

    Averina, Elena B; Vasilenko, Dmitry A; Gracheva, Yulia A; Grishin, Yuri K; Radchenko, Eugene V; Burmistrov, Vladimir V; Butov, Gennady M; Neganova, Margarita E; Serkova, Tatyana P; Redkozubova, Olga M; Shevtsova, Elena F; Milaeva, Elena R; Kuznetsova, Tamara S; Zefirov, Nikolay S

    2016-02-15

    A versatile synthesis of novel 5-hydroxylaminoisoxazoles bearing adamantane moieties has been accomplished using the heterocyclization reactions of readily available unsaturated esters by the treatment with tetranitromethane in the presence of triethylamine and subsequent reduction of resulting 5-nitroisoxazoles by SnCl2 with the participation of THF. A number of obtained isoxazole derivatives were evaluated for their antioxidative activity, inhibition of lipoxygenases and impact on the rat liver mitochondria. The majority of tested compounds demonstrated moderate antiradical activity in DPPH test (up to EC50 16μM). The same compounds strongly inhibited soybean lipoxygenase (up to IC50 0.4μM) and Fe(2+)- and Fe(3+)-induced lipid peroxidation (LP) of rat brain cortex homogenate (up to IC50 0.3μM). All tested isoxazole derivatives promoted the phosphorylating respiratory activity simultaneously with maximal stimulated respiratory activity of mitochondria and do not reveal any toxicity towards the primary culture of rat cortex neurons. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Chlorophyll-derived fatty acids regulate expression of lipid metabolizing enzymes in liver - a nutritional opportunity

    Directory of Open Access Journals (Sweden)

    Wolfrum Christian

    2001-01-01

    Full Text Available Nutritional values of fatty acid classes are normally discussed on the basis of their saturated, monounsaturated and polyunsaturated structures with implicit understanding that they are straight-chain. Here we focus on chlorophyll-derived phytanic and pristanic acids that are minor isoprenoid branched-chain lipid constituents in food, but of unknown nutritional value. After describing the enzyme machinery that degrades these nutrient fatty acids in the peroxisome, we show by the criteria of a mouse model and of a human cell culture model that they induce with high potency expression of enzymes responsible for beta-oxidation of straight-chain fatty acids in the peroxisome. We summarize present mechanistic knowledge on fatty acid signaling to the nucleus, which involves protein/protein contacts between peroxisome proliferator activated receptor (PPAR and fatty acid binding protein (FABP. In this signaling event the branched-chain fatty acids are the most effective ones. Finally, on the basis of this nutrient-gene interaction we discuss nutritional opportunities and therapeutic aspects of the chlorophyll-derived fatty acids.

  11. Metabolic Symbiosis and Immunomodulation: How Tumor Cell-Derived Lactate May Disturb Innate and Adaptive Immune Responses

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    Alexandre Morrot

    2018-03-01

    Full Text Available The tumor microenvironment (TME is composed by cellular and non-cellular components. Examples include the following: (i bone marrow-derived inflammatory cells, (ii fibroblasts, (iii blood vessels, (iv immune cells, and (v extracellular matrix components. In most cases, this combination of components may result in an inhospitable environment, in which a significant retrenchment in nutrients and oxygen considerably disturbs cell metabolism. Cancer cells are characterized by an enhanced uptake and utilization of glucose, a phenomenon described by Otto Warburg over 90 years ago. One of the main products of this reprogrammed cell metabolism is lactate. “Lactagenic” or lactate-producing cancer cells are characterized by their immunomodulatory properties, since lactate, the end product of the aerobic glycolysis, besides acting as an inducer of cellular signaling phenomena to influence cellular fate, might also play a role as an immunosuppressive metabolite. Over the last 10 years, it has been well accepted that in the TME, the lactate secreted by transformed cells is able to compromise the function and/or assembly of an effective immune response against tumors. Herein, we will discuss recent advances regarding the deleterious effect of high concentrations of lactate on the tumor-infiltrating immune cells, which might characterize an innovative way of understanding the tumor-immune privilege.

  12. Metabolic Engineering of the Shikimate Pathway for Production of Aromatics and Derived Compounds—Present and Future Strain Construction Strategies

    Directory of Open Access Journals (Sweden)

    Nils J. H. Averesch

    2018-03-01

    Full Text Available The aromatic nature of shikimate pathway intermediates gives rise to a wealth of potential bio-replacements for commonly fossil fuel-derived aromatics, as well as naturally produced secondary metabolites. Through metabolic engineering, the abundance of certain intermediates may be increased, while draining flux from other branches off the pathway. Often targets for genetic engineering lie beyond the shikimate pathway, altering flux deep in central metabolism. This has been extensively used to develop microbial production systems for a variety of compounds valuable in chemical industry, including aromatic and non-aromatic acids like muconic acid, para-hydroxybenzoic acid, and para-coumaric acid, as well as aminobenzoic acids and aromatic α-amino acids. Further, many natural products and secondary metabolites that are valuable in food- and pharma-industry are formed outgoing from shikimate pathway intermediates. (Reconstruction of such routes has been shown by de novo production of resveratrol, reticuline, opioids, and vanillin. In this review, strain construction strategies are compared across organisms and put into perspective with requirements by industry for commercial viability. Focus is put on enhancing flux to and through shikimate pathway, and engineering strategies are assessed in order to provide a guideline for future optimizations.

  13. Autism as a disorder of deficiency of brain-derived neurotrophic factor and altered metabolism of polyunsaturated fatty acids.

    Science.gov (United States)

    Das, Undurti N

    2013-10-01

    Autism has a strong genetic and environmental basis in which inflammatory markers and factors concerned with synapse formation, nerve transmission, and information processing such as brain-derived neurotrophic factor (BDNF), polyunsaturated fatty acids (PUFAs): arachidonic (AA), eicosapentaenoic (EPA), and docosahexaenoic acids (DHA) and their products and neurotransmitters: dopamine, serotonin, acetylcholine, γ-aminobutyric acid, and catecholamines and cytokines are altered. Antioxidants, vitamins, minerals, and trace elements are needed for the normal metabolism of neurotrophic factors, eicosanoids, and neurotransmitters, supporting reports of their alterations in autism. But, the exact relationship among these factors and their interaction with genes and proteins concerned with brain development and growth is not clear. It is suggested that maternal infections and inflammation and adverse events during intrauterine growth of the fetus could lead to alterations in the gene expression profile and proteomics that results in dysfunction of the neuronal function and neurotransmitters, alteration(s) in the metabolism of PUFAs and their metabolites resulting in excess production of proinflammatory eicosanoids and cytokines and a deficiency of anti-inflammatory cytokines and bioactive lipids that ultimately results in the development of autism. Based on these evidences, it is proposed that selective delivery of BDNF and methods designed to augment the production of anti-inflammatory cytokines and eicosanoids and PUFAs may prevent, arrest, or reverse the autism disease process. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Diverse and Abundant Secondary Metabolism Biosynthetic Gene Clusters in the Genomes of Marine Sponge Derived Streptomyces spp. Isolates

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    Stephen A. Jackson

    2018-02-01

    Full Text Available The genus Streptomyces produces secondary metabolic compounds that are rich in biological activity. Many of these compounds are genetically encoded by large secondary metabolism biosynthetic gene clusters (smBGCs such as polyketide synthases (PKS and non-ribosomal peptide synthetases (NRPS which are modular and can be highly repetitive. Due to the repeats, these gene clusters can be difficult to resolve using short read next generation datasets and are often quite poorly predicted using standard approaches. We have sequenced the genomes of 13 Streptomyces spp. strains isolated from shallow water and deep-sea sponges that display antimicrobial activities against a number of clinically relevant bacterial and yeast species. Draft genomes have been assembled and smBGCs have been identified using the antiSMASH (antibiotics and Secondary Metabolite Analysis Shell web platform. We have compared the smBGCs amongst strains in the search for novel sequences conferring the potential to produce novel bioactive secondary metabolites. The strains in this study recruit to four distinct clades within the genus Streptomyces. The marine strains host abundant smBGCs which encode polyketides, NRPS, siderophores, bacteriocins and lantipeptides. The deep-sea strains appear to be enriched with gene clusters encoding NRPS. Marine adaptations are evident in the sponge-derived strains which are enriched for genes involved in the biosynthesis and transport of compatible solutes and for heat-shock proteins. Streptomyces spp. from marine environments are a promising source of novel bioactive secondary metabolites as the abundance and diversity of smBGCs show high degrees of novelty. Sponge derived Streptomyces spp. isolates appear to display genomic adaptations to marine living when compared to terrestrial strains.

  15. Metabolism of arachidonic acid derivatives (prostaglandins and related compounds). Radioimmunological methods to measure certain of these compounds

    International Nuclear Information System (INIS)

    Sors, Herve.

    1978-06-01

    The detection of prostaglandins, present in tissues at concentrations of about 10 -7 to 10 -11 g/g and able to induce physiological effects at concentrations of the picomole order, sets the analyst a particularly difficult problem. Owing to the complexity of their metabolism, the existence of many structurally similar compounds and the low concentrations present, it is necessary to develop highly specific and sensitive methods. Suitable techniques are: the biological activity test or biotest; gas-liquid chromatogaphy combined with mass spectrometry; the radioimmunological method. The radioimmunological analysis procedure is developed: preparation of immunogens and immunisation; preparation of tracers; treatment of biological samples. The different radioimmunological systems are presented: determination of antiserum affinity constants; dose-response curves and sensitivities; specificities; applications to biological measurements. Some remarks are called for concerning the RIA of prostaglandins: the difficulty of obtaining antisera seems to depend on the nature of the PG, a good anti-PGB or PGFα is easier to get than an anti-PGA or PGE. The analysis of each compound implies the use of a corresponding immunoserum and it is therefore essential to have a range of immunosera in order to study as large a number of biosynthesis derivatives as possible; too many physiological investigations are still viewed in relation to one PG only (often a primary PG) at the expense of other derivatives [fr

  16. GABA and Topiramate Inhibit the Formation of Human Macrophage-Derived Foam Cells by Modulating Cholesterol-Metabolism-Associated Molecules

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    Ying Yang

    2014-04-01

    Full Text Available Aims: γ-aminobutyric acid (GABA, the principal inhibitory neurotransmitter, acts on GABA receptors to play an important role in the modulation of macrophage functions. The present study examined the effects of GABA and a GABA receptor agonist on modulating cholesterol-metabolism-associated molecules in human monocyte-derived macrophages (HMDMs. Methods: ORO stain, HPLC, qRT-PCR, Western blot and EMSA were carried out using HMDMs exposed to ox-LDL with or without GABAergic agents as the experimental model. Results: GABA and topiramate reduced the percentage of cholesterol ester in lipid-laden HMDMs by down-regulating SR-A, CD36 and LOX-1 expression and up-regulating ABCA1, ABCG1 and SR-BI expression in lipid-laden HMDMs. The production of TNF-a was decreased in GABA-and topiramate-treated lipid-laden HMDMs, and levels of interleukin (IL-6 did not change. The activation of two signaling pathways, p38MAPK and NF-γB, was repressed by GABA and topiramate in lipid-laden HMDMs. Conclusion: GABA and topiramate inhibit the formation of human macrophage-derived foam cells and may be a possibility for macrophage targeted therapy of atherosclerotic lesions.

  17. Metformin inhibits Branched Chain Amino Acid (BCAA) derived ketoacidosis and promotes metabolic homeostasis in MSUD.

    Science.gov (United States)

    S Sonnet, Davis; N O'Leary, Monique; A Gutierrez, Mark; M Nguyen, Steven; Mateen, Samiha; Hsu, Yuehmei; P Mitchell, Kylie; J Lopez, Antonio; Vockley, Jerry; K Kennedy, Brian; Ramanathan, Arvind

    2016-07-04

    Maple Syrup Urine Disease (MSUD) is an inherited disorder caused by the dysfunction in the branched chain keto-acid dehydrogenase (BCKDH) enzyme. This leads to buildup of branched-chain keto-acids (BCKA) and branched-chain amino acids (BCAA) in body fluids (e.g. keto-isocaproic acid from the BCAA leucine), leading to numerous clinical features including a less understood skeletal muscle dysfunction in patients. KIC is an inhibitor of mitochondrial function at disease relevant concentrations. A murine model of intermediate MSUD (iMSUD) shows significant skeletal muscle dysfunction as by judged decreased muscle fiber diameter. MSUD is an orphan disease with a need for novel drug interventions. Here using a 96-well plate (liquid chromatography- mass spectrometry (LC-MS) based drug-screening platform we show that Metformin, a widely used anti-diabetic drug, reduces levels of KIC in patient-derived fibroblasts by 20-50%. This Metformin-mediated effect was conserved in vivo; Metformin-treatment significantly reduced levels of KIC in the muscle (by 69%) and serum (by 56%) isolated from iMSUD mice, and restored levels of mitochondrial metabolites (e.g. AMP and other TCA). The drug also decreased the expression of mitochondrial branched chain amino transferase (BCAT) which produces KIC in skeletal muscle. This suggests that Metformin can restore skeletal muscle homeostasis in MSUD by decreasing mitochondrial KIC production.

  18. Metabolic and functional diversity of saponins, biosynthetic intermediates and semi-synthetic derivatives

    Science.gov (United States)

    Moses, Tessa; Papadopoulou, Kalliope K.

    2014-01-01

    Saponins are widely distributed plant natural products with vast structural and functional diversity. They are typically composed of a hydrophobic aglycone, which is extensively decorated with functional groups prior to the addition of hydrophilic sugar moieties, to result in surface-active amphipathic compounds. The saponins are broadly classified as triterpenoids, steroids or steroidal glycoalkaloids, based on the aglycone structure from which they are derived. The saponins and their biosynthetic intermediates display a variety of biological activities of interest to the pharmaceutical, cosmetic and food sectors. Although their relevance in industrial applications has long been recognized, their role in plants is underexplored. Recent research on modulating native pathway flux in saponin biosynthesis has demonstrated the roles of saponins and their biosynthetic intermediates in plant growth and development. Here, we review the literature on the effects of these molecules on plant physiology, which collectively implicate them in plant primary processes. The industrial uses and potential of saponins are discussed with respect to structure and activity, highlighting the undoubted value of these molecules as therapeutics. PMID:25286183

  19. Targeting progesterone metabolism in breast cancer with l-proline derived new 14-azasteroids.

    Science.gov (United States)

    Singh, Jyotsana; Singh, Ritesh; Gupta, Preeti; Rai, Smita; Ganesher, Asha; Badrinarayan, Preethi; Sastry, G Narahari; Konwar, Rituraj; Panda, Gautam

    2017-08-15

    Breast cancer cell proliferation is promoted by a variety of mitogenic signals. Classically estrogen is considered as most predominant mitogenic signal in hormone-dependent breast cancer and progesterone is primarily considered to have protective effect. However, it is suggested that some progesterone metabolite may promote breast cancer and progesterone metabolites like 5α-pregnane and 4-pregnene could serve as regulators of estrogen-responsiveness of breast cancer cells. Here, we estimated the potential of alternate targeting of breast cancer via progesterone signalling. l-Proline derived novel 14-azasteroid compounds were screened against MCF-7 and MDA-MB-231 cell lines using MTT assay. In silico studies, cell cycle, Annexin-V-FITC/PI, JC-1 mitochondrial assay, ROS analysis were performed to analyse the impact of hit compound 3b on breast cancer cells. Further, we analysed the impact of hit 3b on the progesterone, its metabolites and enzymes responsible for the conversion of progesterone and its metabolites using ELISA. Data suggests that compound 3b binds and down regulates of 5α-reductase by specifically inhibiting production of progesterone metabolites that are capable of promoting breast cancer proliferation, epithelial mesenchymal transition and migration. This study establishes the proof of concept and generation of new leads for additional targeting of breast cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Metabolism of a plant derived galactose‐containing polysaccharide by Bifidobacterium breve UCC2003

    Science.gov (United States)

    O'Connell Motherway, Mary; Fitzgerald, Gerald F.; van Sinderen, Douwe

    2011-01-01

    Summary In this study, we describe the functional characterization of the Bifidobacterium breve UCC2003 gal locus, which is dedicated to the utilization of galactan, a plant‐derived polysaccharide. Using a combination of molecular approaches we conclude that the galA gene of B. breve UCC2003 encodes a β‐1,4‐endogalactanase producing galacto‐oligosaccharides, which are specifically internalized by an ABC transport system, encoded by galBCDE, and which are then hydrolysed to galactose moieties by a dedicated intracellular β‐galactosidase, specified by galG. The generated galactose molecules are presumed to be fed into the fructose‐6‐phosphate phosphoketolase pathway via the Leloir pathway, thereby allowing B. breve UCC2003 to use galactan as its sole carbon and energy source. In addition to these findings we demonstrate that GalR is a LacI‐type DNA‐binding protein, which not only appears to control transcription of the galCDEGR operon, but also that of the galA gene. PMID:21375716

  1. Metabolism of a plant derived galactose-containing polysaccharide by Bifidobacterium breve UCC2003.

    Science.gov (United States)

    O'Connell Motherway, Mary; Fitzgerald, Gerald F; van Sinderen, Douwe

    2011-05-01

    In this study, we describe the functional characterization of the Bifidobacterium breve UCC2003 gal locus, which is dedicated to the utilization of galactan, a plant-derived polysaccharide. Using a combination of molecular approaches we conclude that the galA gene of B. breve UCC2003 encodes a β-1,4-endogalactanase producing galacto-oligosaccharides, which are specifically internalized by an ABC transport system, encoded by galBCDE, and which are then hydrolysed to galactose moieties by a dedicated intracellular β-galactosidase, specified by galG. The generated galactose molecules are presumed to be fed into the fructose-6-phosphate phosphoketolase pathway via the Leloir pathway, thereby allowing B. breve UCC2003 to use galactan as its sole carbon and energy source. In addition to these findings we demonstrate that GalR is a LacI-type DNA-binding protein, which not only appears to control transcription of the galCDEGR operon, but also that of the galA gene. © 2010 University College Cork. Journal compilation © 2010 Society for Applied Microbiology and Blackwell Publishing Ltd.

  2. Dietary pattern associated with selenoprotein P and MRI-derived body fat volumes, liver signal intensity, and metabolic disorders.

    Science.gov (United States)

    di Giuseppe, Romina; Plachta-Danielzik, Sandra; Koch, Manja; Nöthlings, Ute; Schlesinger, Sabrina; Borggrefe, Jan; Both, Marcus; Müller, Hans-Peter; Kassubek, Jan; Jacobs, Gunnar; Lieb, Wolfgang

    2018-02-14

    The association of complex dietary patterns with circulating selenoprotein P (SELENOP) levels in humans is unknown. In a general population sample, we aimed to identify a dietary pattern explaining inter-individual variation in circulating SELENOP concentrations and to study this pattern in relation to prevalent diabetes, metabolic syndrome (MetS), MRI-determined total volumes of visceral (VAT) and subcutaneous (SAT) abdominal adipose tissue, and liver signal intensity/fatty liver disease. In this cross-sectional study, serum SELENOP levels were measured in 853 individuals. In a subsample of 553 participants, whole-body MRI was performed to assess body fat distribution and liver fat. Dietary intake was assessed by a self-administered food frequency questionnaire and the dietary pattern identified using reduced-rank regression (RRR). Multivariable linear and logistic regressions were used to investigate associations between dietary pattern score and metabolic traits. Characterized by high intake of fruit, vegetables and antioxidant beverages, the RRR-derived dietary pattern displayed inverse associations with VAT, SAT, MetS, and prevalent diabetes in multivariable-adjusted restricted cubic splines. Each unit increase in dietary pattern score was associated with 31% higher SELENOP levels, 12% lower VAT (95% CI: - 19%; - 5%), 13% (95% CI: - 20%; - 6%) lower SAT values and 46% (95% CI: 27%; 60%) and 53% (95% CI: 22%; 72%) lower odds of having MetS or diabetes, respectively. No meaningful relations were observed between the dietary pattern and liver traits. Our observations propose diet-related regulation in SELENOP levels and that the identified dietary pattern is inversely related to VAT, SAT, MetS, and prevalent diabetes.

  3. Thiamin diphosphate in biological chemistry: new aspects of thiamin metabolism, especially triphosphate derivatives acting other than as cofactors.

    Science.gov (United States)

    Bettendorff, Lucien; Wins, Pierre

    2009-06-01

    Prokaryotes, yeasts and plants synthesize thiamin (vitamin B1) via complex pathways. Animal cells capture the vitamin through specific high-affinity transporters essential for internal thiamin homeostasis. Inside the cells, thiamin is phosphorylated to higher phosphate derivatives. Thiamin diphosphate (ThDP) is the best-known thiamin compound because of its role as an enzymatic cofactor. However, in addition to ThDP, at least three other thiamin phosphates occur naturally in most cells: thiamin monophosphate, thiamin triphosphate (ThTP) and the recently discovered adenosine thiamin triphosphate. It has been suggested that ThTP has a specific neurophysiological role, but recent data favor a much more basic metabolic function. During amino acid starvation, Escherichia coli accumulate ThTP, possibly acting as a signal involved in the adaptation of the bacteria to changing nutritional conditions. In animal cells, ThTP can phosphorylate some proteins, but the physiological significance of this mechanism remains unknown. Adenosine thiamin triphosphate, recently discovered in E. coli, accumulates during carbon starvation and might act as an alarmone. Among the proteins involved in thiamin metabolism, thiamin transporters, thiamin pyrophosphokinase and a soluble 25-kDa thiamin triphosphatase have been characterized at the molecular level, in contrast to thiamin mono- and diphosphatases whose specificities remain to be proven. A soluble enzyme catalyzing the synthesis of adenosine thiamin triphosphate from ThDP and ADP or ATP has been partially characterized in E. coli, but the mechanism of ThTP synthesis remains elusive. The data reviewed here illustrate the complexity of thiamin biochemistry, which is not restricted to the cofactor role of ThDP.

  4. Factor Structure of Indices of the Second Derivative of the Finger Photoplethysmogram with Metabolic Components and Other Cardiovascular Risk Indicators

    Directory of Open Access Journals (Sweden)

    Tomoyuki Kawada

    2013-02-01

    Full Text Available BackgroundThe second derivative of the finger photoplethysmogram (SDPTG is an indicator of arterial stiffness. The present study was conducted to clarify the factor structure of indices of the SDPTG in combination with components of the metabolic syndrome (MetS, to elucidate the significance of the SDPTG among various cardiovascular risk factors.MethodsThe SDPTG was determined in the second forefinger of the left hand in 1,055 male workers (mean age, 44.2±6.4 years. Among 4 waves of SDPTG components, the ratios of the height of the "a" wave to that of the "b" and "d" waves were expressed as b/a and d/a, and used as SDPTG indices for the analysis.ResultsPrincipal axis factoring analysis was conducted using age, SDPTG indices, components of MetS, and the serum levels of C-reactive protein (CRP and uric acid. Three factors were extracted, and the SDPTG indices were categorized in combination with age as the third factor. Metabolic components and the SDPTG indices were independently categorized. These three factors explained 44.4% of the total variation. Multiple logistic regression analysis revealed age, d/a, serum uric acid, serum CRP, and regular exercise as independent determinants of the risk of MetS. The odds ratios (95% confidence intervals were 1.08 (1.04 to 1.11, 0.10 (0.01 to 0.73, 1.24 (1.06 to 1.44, 3.59 (2.37 to 5.42, and 0.48 (0.28 to 0.82, respectively.ConclusionThe SDPTG indices were categorized in combination with age, and they differed in characteristics from components of MetS or inflammatory markers. In addition, this cross-sectional study also revealed decrease of the d/a as a risk factor for the development of MetS.

  5. Calibrated image-derived input functions for the determination of the metabolic uptake rate of glucose with [18F]-FDG PET

    DEFF Research Database (Denmark)

    Christensen, Anders Nymark; Reichkendler, Michala H.; Larsen, Rasmus

    2014-01-01

    We investigated the use of a simple calibration method to remove bias in previously proposed approaches to image-derived input functions (IDIFs) when used to calculate the metabolic uptake rate of glucose (Km) from dynamic [18F]-FDG PET scans of the thigh. Our objective was to obtain nonbiased, low...

  6. KENeV: A web-application for the automated reconstruction and visualization of the enriched metabolic and signaling super-pathways deriving from genomic experiments

    Directory of Open Access Journals (Sweden)

    Eleftherios Pilalis

    2015-01-01

    In conclusion, KENeV (available online at http://www.grissom.gr/kenev provides an integrative tool, suitable for users with no programming experience, for the functional interpretation, at both the metabolic and signaling level, of differentially expressed gene subsets deriving from genomic experiments.

  7. Molecular docking studies of 3-bromopyruvate and its derivatives to metabolic regulatory enzymes: Implication in designing of novel anticancer therapeutic strategies.

    Science.gov (United States)

    Yadav, Saveg; Pandey, Shrish Kumar; Singh, Vinay Kumar; Goel, Yugal; Kumar, Ajay; Singh, Sukh Mahendra

    2017-01-01

    Altered metabolism is an emerging hallmark of cancer, as malignant cells display a mammoth up-regulation of enzymes responsible for steering their bioenergetic and biosynthetic machinery. Thus, the recent anticancer therapeutic strategies focus on the targeting of metabolic enzymes, which has led to the identification of specific metabolic inhibitors. One of such inhibitors is 3-bromopyruvate (3-BP), with broad spectrum of anticancer activity due to its ability to inhibit multiple metabolic enzymes. However, the molecular characterization of its binding to the wide spectrum of target enzymes remains largely elusive. Therefore, in the present study we undertook in silico investigations to decipher the molecular nature of the docking of 3-BP with key target enzymes of glycolysis and TCA cycle by PatchDock and YASARA docking tools. Additionally, derivatives of 3-BP, dibromopyruvate (DBPA) and propionic acid (PA), with reported biological activity, were also investigated for docking to important target metabolic enzymes of 3-BP, in order to predict their therapeutic efficacy versus that of 3-BP. A comparison of the docking scores with respect to 3-BP indicated that both of these derivatives display a better binding strength to metabolic enzymes. Further, analysis of the drug likeness of 3-BP, DBPA and PA by Lipinski filter, admetSAR and FAF Drug3 indicated that all of these agents showed desirable drug-like criteria. The outcome of this investigation sheds light on the molecular characteristics of the binding of 3-BP and its derivatives with metabolic enzymes and thus may significantly contribute in designing and optimizing therapeutic strategies against cancer by using these agents.

  8. Molecular docking studies of 3-bromopyruvate and its derivatives to metabolic regulatory enzymes: Implication in designing of novel anticancer therapeutic strategies.

    Directory of Open Access Journals (Sweden)

    Saveg Yadav

    Full Text Available Altered metabolism is an emerging hallmark of cancer, as malignant cells display a mammoth up-regulation of enzymes responsible for steering their bioenergetic and biosynthetic machinery. Thus, the recent anticancer therapeutic strategies focus on the targeting of metabolic enzymes, which has led to the identification of specific metabolic inhibitors. One of such inhibitors is 3-bromopyruvate (3-BP, with broad spectrum of anticancer activity due to its ability to inhibit multiple metabolic enzymes. However, the molecular characterization of its binding to the wide spectrum of target enzymes remains largely elusive. Therefore, in the present study we undertook in silico investigations to decipher the molecular nature of the docking of 3-BP with key target enzymes of glycolysis and TCA cycle by PatchDock and YASARA docking tools. Additionally, derivatives of 3-BP, dibromopyruvate (DBPA and propionic acid (PA, with reported biological activity, were also investigated for docking to important target metabolic enzymes of 3-BP, in order to predict their therapeutic efficacy versus that of 3-BP. A comparison of the docking scores with respect to 3-BP indicated that both of these derivatives display a better binding strength to metabolic enzymes. Further, analysis of the drug likeness of 3-BP, DBPA and PA by Lipinski filter, admetSAR and FAF Drug3 indicated that all of these agents showed desirable drug-like criteria. The outcome of this investigation sheds light on the molecular characteristics of the binding of 3-BP and its derivatives with metabolic enzymes and thus may significantly contribute in designing and optimizing therapeutic strategies against cancer by using these agents.

  9. Enhanced production of resveratrol derivatives in tobacco plants by improving the metabolic flux of intermediates in the phenylpropanoid pathway.

    Science.gov (United States)

    Jeong, Yu Jeong; An, Chul Han; Woo, Su Gyeong; Park, Ji Hye; Lee, Ki-Won; Lee, Sang-Hoon; Rim, Yeonggil; Jeong, Hyung Jae; Ryu, Young Bae; Kim, Cha Young

    2016-09-01

    The biosynthesis of flavonoids such as anthocyanin and stilbenes has attracted increasing attention because of their potential health benefits. Anthocyanins and stilbenes share common phenylpropanoid precursor pathways. We previously reported that the overexpression of sweetpotato IbMYB1a induced anthocyanin pigmentation in transgenic tobacco (Nicotiana tabacum) plants. In the present study, transgenic tobacco (Nicotiana tabacum SR1) plants (STS-OX and ROST-OX) expressing the RpSTS gene encoding stilbene synthase from rhubarb (Rheum palmatum L. cv. Jangyeop) and the RpSTS and VrROMT genes encoding resveratrol O-methyltransferase from frost grape (Vitis riparia) were generated under the control of 35S promoter. Phenotypic alterations in floral organs, such as a reduction in floral pigments and male sterility, were observed in STS-OX transgenic tobacco plants. However, we failed to obtain STS-OX and ROST-OX plants with high levels of resveratrol compounds. Therefore, to improve the production of resveratrol derivatives in plants, we cross-pollinated flowers of STS-OX or ROST-OX and IbMYB1a-OX transgenic lines (SM and RSM). Phenotypic changes in vegetative and reproductive development of SM and RSM plants were observed. Furthermore, by HPLC and LC-MS analyses, we found enhanced production of resveratrol derivatives such as piceid, piceid methyl ether, resveratrol methyl ether O-hexoside, and 5-methyl resveratrol-3,4'-O-β-D-diglucopyranoside in SM and RSM cross-pollinated lines. Here, total contents of trans- and cis-piceids ranged from approximately 104-240 µg/g fresh weight in SM (F2). Collectively, we suggest that coexpression of RpSTS and IbMYB1a via cross-pollination can induce enhanced production of resveratrol compounds in plants by increasing metabolic flux into stilbenoid biosynthesis.

  10. The regulation of growth and metabolism of kidney stem cells with regional specificity using extracellular matrix derived from kidney.

    Science.gov (United States)

    O'Neill, John D; Freytes, Donald O; Anandappa, Annabelle J; Oliver, Juan A; Vunjak-Novakovic, Gordana V

    2013-12-01

    Native extracellular matrix (ECM) that is secreted and maintained by resident cells is of great interest for cell culture and cell delivery. We hypothesized that specialized bioengineered niches for stem cells can be established using ECM-derived scaffolding materials. Kidney was selected as a model system because of the high regional diversification of renal tissue matrix. By preparing the ECM from three specialized regions of the kidney (cortex, medulla, and papilla; whole kidney, heart, and bladder as controls) in three forms: (i) intact sheets of decellularized ECM, (ii) ECM hydrogels, and (iii) solubilized ECM, we investigated how the structure and composition of ECM affect the function of kidney stem cells (with mesenchymal stem cells, MSCs, as controls). All three forms of the ECM regulated KSC function, with differential structural and compositional effects. KSCs cultured on papilla ECM consistently displayed lower proliferation, higher metabolic activity, and differences in cell morphology, alignment, and structure formation as compared to KSCs on cortex and medulla ECM, effects not observed in corresponding MSC cultures. These data suggest that tissue- and region-specific ECM can provide an effective substrate for in vitro studies of therapeutic stem cells. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. T Follicular Helper Cells Promote a Beneficial Gut Ecosystem for Host Metabolic Homeostasis by Sensing Microbiota-Derived Extracellular ATP.

    Science.gov (United States)

    Perruzza, Lisa; Gargari, Giorgio; Proietti, Michele; Fosso, Bruno; D'Erchia, Anna Maria; Faliti, Caterina Elisa; Rezzonico-Jost, Tanja; Scribano, Daniela; Mauri, Laura; Colombo, Diego; Pellegrini, Giovanni; Moregola, Annalisa; Mooser, Catherine; Pesole, Graziano; Nicoletti, Mauro; Norata, Giuseppe Danilo; Geuking, Markus B; McCoy, Kathy D; Guglielmetti, Simone; Grassi, Fabio

    2017-03-14

    The ATP-gated ionotropic P2X7 receptor regulates T follicular helper (Tfh) cell abundance in the Peyer's patches (PPs) of the small intestine; deletion of P2rx7, encoding for P2X7, in Tfh cells results in enhanced IgA secretion and binding to commensal bacteria. Here, we show that Tfh cell activity is important for generating a diverse bacterial community in the gut and that sensing of microbiota-derived extracellular ATP via P2X7 promotes the generation of a proficient gut ecosystem for metabolic homeostasis. The results of this study indicate that Tfh cells play a role in host-microbiota mutualism beyond protecting the intestinal mucosa by induction of affinity-matured IgA and suggest that extracellular ATP constitutes an inter-kingdom signaling molecule important for selecting a beneficial microbial community for the host via P2X7-mediated regulation of B cell help. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  12. T Follicular Helper Cells Promote a Beneficial Gut Ecosystem for Host Metabolic Homeostasis by Sensing Microbiota-Derived Extracellular ATP

    Directory of Open Access Journals (Sweden)

    Lisa Perruzza

    2017-03-01

    Full Text Available The ATP-gated ionotropic P2X7 receptor regulates T follicular helper (Tfh cell abundance in the Peyer’s patches (PPs of the small intestine; deletion of P2rx7, encoding for P2X7, in Tfh cells results in enhanced IgA secretion and binding to commensal bacteria. Here, we show that Tfh cell activity is important for generating a diverse bacterial community in the gut and that sensing of microbiota-derived extracellular ATP via P2X7 promotes the generation of a proficient gut ecosystem for metabolic homeostasis. The results of this study indicate that Tfh cells play a role in host-microbiota mutualism beyond protecting the intestinal mucosa by induction of affinity-matured IgA and suggest that extracellular ATP constitutes an inter-kingdom signaling molecule important for selecting a beneficial microbial community for the host via P2X7-mediated regulation of B cell help.

  13. The expression of xenobiotic-metabolizing enzymes in human prostate and in prostate epithelial cells (PECs) derived from primary cultures.

    Science.gov (United States)

    Al-Buheissi, S Z; Cole, K J; Hewer, A; Kumar, V; Bryan, R L; Hudson, D L; Patel, H R; Nathan, S; Miller, R A; Phillips, D H

    2006-06-01

    Dietary heterocyclic amines (HCAs) are carcinogenic in rodent prostate requiring activation by enzymes such as cytochrome P450 (CYP) and N-acetyltransferase (NAT). We investigated by Western blotting and immunohistochemistry the expression of CYP1A1, CYP1A2, and NAT1 in human prostate and in prostate epithelial cells (PECs) derived from primary cultures and tested their ability to activate the dietary carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and its N-hydroxy metabolite (N-OH-IQ) to DNA-damaging moieties. Western blotting identified CYP1A1, CYP1A2, and NAT1. Immunohistochemistry localized NAT1 to the cytoplasm of PECs. Inter-individual variation was observed in the expression levels of CYP1A1, 1A2, and NAT1 (11, 75, and 35-fold, respectively). PECs expressed CYP1A1 and NAT1 but not CYP1A2. When incubated with IQ or N-OH-IQ, PECs formed DNA adducts indicating their ability to metabolically activate these compounds. Prostate cells possess the capacity to activate dietary carcinogens. PECs may provide a useful model system to study their role in prostate carcinogenesis.

  14. Inglorious Empire

    DEFF Research Database (Denmark)

    Khair, Tabish

    2017-01-01

    Review of 'Inglorious Empire: What the British did to India' by Shashi Tharoor, London, Hurst Publishers, 2017, 296 pp., £20.00......Review of 'Inglorious Empire: What the British did to India' by Shashi Tharoor, London, Hurst Publishers, 2017, 296 pp., £20.00...

  15. Abscisic acid and the accumulation, biological activity and metabolism of four derivatives of [3H] gibberellin A1 in barley aleurone layers

    International Nuclear Information System (INIS)

    Stolp, C.F.; Nadeau, R.; Rappaport, L.

    1977-01-01

    Tritiated GA 1 and four of its synthetic derivatives were studied in relation to their biological activity, uptake and metabolism by barley alcurone layers. Incubation was done in the presence and absence of abscisic acid (ABA). Tentative identification of some of the metabolites was made by TLC and GLC radiocounting of the metabolite and its acid hydrolyzed derivative. Only GA 1 promoted α-amylase synthesis. Uptake ranged from 20 to 42%, varying with the derivative. ABA enhanced uptake of [ 3 H] GA 1 and [ 3 H] pseudoGA 1 and inhibited uptake of [ 3 H] ketoGA 1 , the Wagner-Meerwein rearrangement product of [ 3 H]GA 1 . Uptake of [ 3 H] GA 1 methyl ester ([ 3 H] GA 1 -Me) and [ 3 H] dihydroGA 1 was unaffected by ABA. [ 3 H] GA 1 was converted to an amphoteric GA 1 derivative [ 3 H] amphoGA 1 ) and [ 3 H] GA 1 -glycosyl ester. GA 1 -Me was metabolized to four products, all of them GA 1 derivatives including an apparent amphoteric GA 1 derivative. DihydroGA 1 was quite stable; only one metabolite was produced in sufficient yield to analyze. This product did not cochromatograph with either of the expected acid hydrolyzed epimers of [ 3 H] - dihydroGA 1 . [ 3 H] ketoGA 1 was readily metabolized to one product, probably the glycoside. [ 3 H] pseudoGA 1 remained essentially unmetabolized. Metabolism of all compounds tested was not dramatically affected by ABA. Surprisingly, no metabolites from hydroxylation at the 2-position were found. (auth.)

  16. Catabolism of biomass-derived sugars in fungi and metabolic engineering as a tool for organic acid production

    Energy Technology Data Exchange (ETDEWEB)

    Koivistoinen, O.

    2013-11-01

    gene ladB was identified and the deletion of the gene resulted in growth arrest on galactitol indicating that the enzyme is an essential part of the oxido-reductive galactose pathway in fungi. The last step of this pathway converts D-sorbitol to D-fructose by sorbitol dehydrogenase encoded by sdhA gene. Sorbitol dehydrogenase was found to be a medium chain dehydrogenase and transcription analysis suggested that the enzyme is involved in D-galactose and D-sorbitol catabolism. The thesis also demonstrates how the understanding of cell metabolism can be used to engineer yeast to produce glycolic acid. Glycolic acid is a chemical, which can be used for example in the cosmetic industry and as a precursor for biopolymers. Currently, glycolic acid is produced by chemical synthesis in a process requiring toxic formaldehyde and fossil fuels. Thus, a biochemical production route would be preferable from a sustainability point of view. Yeasts do not produce glycolic acid under normal conditions but it is a desired production host for acid production because of its natural tolerance to low pH conditions. As a proof of concept, pure model substrates, e.g. D-xylose and ethanol, were used as starting materials for glycolic acid production but the knowledge can be further applied to an expanded substrate range such as biomass derived sugars. Already the introduction of a heterologous glyoxylate reductase gene resulted in glycolic acid production in the yeasts S. cerevisiae and Kluyveromyces lactis. Further modifications of the glyoxylate cycle increased the production of glycolic acid and it was successfully produced in bioreactor cultivation. The challenge of biotechnology is to produce high value products from cheap raw materials in an economically feasible way. This thesis gives more basic understanding to the topic in the form of new information regarding L-rhamnose and D-galactose metabolism in eukaryotic microbes as well as provides an example on how cell metabolism can be

  17. Empirical likelihood

    CERN Document Server

    Owen, Art B

    2001-01-01

    Empirical likelihood provides inferences whose validity does not depend on specifying a parametric model for the data. Because it uses a likelihood, the method has certain inherent advantages over resampling methods: it uses the data to determine the shape of the confidence regions, and it makes it easy to combined data from multiple sources. It also facilitates incorporating side information, and it simplifies accounting for censored, truncated, or biased sampling.One of the first books published on the subject, Empirical Likelihood offers an in-depth treatment of this method for constructing confidence regions and testing hypotheses. The author applies empirical likelihood to a range of problems, from those as simple as setting a confidence region for a univariate mean under IID sampling, to problems defined through smooth functions of means, regression models, generalized linear models, estimating equations, or kernel smooths, and to sampling with non-identically distributed data. Abundant figures offer vi...

  18. 68Ga-PSMA-11 PET/CT-derived metabolic parameters for determination of whole-body tumor burden and treatment response in prostate cancer.

    Science.gov (United States)

    Schmidkonz, Christian; Cordes, Michael; Schmidt, Daniela; Bäuerle, Tobias; Goetz, Theresa Ida; Beck, Michael; Prante, Olaf; Cavallaro, Alexander; Uder, Michael; Wullich, Bernd; Goebell, Peter; Kuwert, Torsten; Ritt, Philipp

    2018-05-03

    We aimed at evaluating the role of 68 Ga-PSMA-11 PET/CT-derived metabolic parameters for assessment of whole-body tumor burden and its capability to determine therapeutic response in patients with prostate cancer. A total of 142 patients with biochemical recurrence of prostate cancer underwent PET/CT with [ 68 Ga]Ga-PSMA-HBED-CC ( 68 Ga-PSMA-11). Quantitative assessment of all 641 68 Ga-PSMA-11-positive lesions in the field of view was performed to calculate PSMA-derived parameters, including whole-body PSMA tumor volume (PSMA-TV) and whole-body total lesion PSMA (TL-PSMA), as well as the established SUVmax and SUVmean values. All PET-derived parameters were tested for correlation with serum PSA levels and for association with Gleason scores. In 23 patients who underwent 68 Ga-PSMA-11 PET/CT before and after therapy with either external beam radiation, androgen deprivation, or docetaxel chemotherapy, SUVmax and TL-PSMA were compared to radiographic response assessment of CT images based on RECIST 1.1 criteria and to biochemical response determined by changes of serum PSA levels. PSMA-TV and TL-PSMA demonstrated a significant correlation with serum PSA levels (P PET and biochemical response was 87% (95% confidence interval, 0.66-0.97; Cohen's κ = 0.78; P PET and CT were most likely due to limitations of CT and RECIST in rating small lymph nodes as metastases, as well as bone involvement, which was sometimes not detectable in CT. 68 Ga-PSMA-11 PET/CT-derived metabolic tumor parameters showed promising results for evaluation of treatment response. Especially, TL-PSMA demonstrated higher agreement rates with biochemical response compared to SUVmax. Larger, ideally prospective trials are needed to help to reveal the full potential of metabolic parameters derived from PET imaging with 68 Ga-PSMA-11.

  19. Analytic, empirical and delta method temperature derivatives of D-D and D-T fusion reactivity formulations, as a means of verification

    Energy Technology Data Exchange (ETDEWEB)

    Langenbrunner, James R. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Booker, Jane M. [Booker Scientific, Fredericksburg, TX (United States)

    2017-07-21

    We examine the derivatives with respect to temperature, for various deuterium-tritium (DT) and deuterium-deuterium (D-D) fusion-reactivity formulations. Langenbrunner and Makaruk [1] had studied this as a means of understanding the time and temperature domain of reaction history measured in dynamic fusion experiments. Presently, we consider the temperature derivative dependence of fusion reactivity as a means of exercising and verifying the consistency of the various reactivity formulations.

  20. A novel Bayesian approach to accounting for uncertainty in fMRI-derived estimates of cerebral oxygen metabolism fluctuations.

    Science.gov (United States)

    Simon, Aaron B; Dubowitz, David J; Blockley, Nicholas P; Buxton, Richard B

    2016-04-01

    Calibrated blood oxygenation level dependent (BOLD) imaging is a multimodal functional MRI technique designed to estimate changes in cerebral oxygen metabolism from measured changes in cerebral blood flow and the BOLD signal. This technique addresses fundamental ambiguities associated with quantitative BOLD signal analysis; however, its dependence on biophysical modeling creates uncertainty in the resulting oxygen metabolism estimates. In this work, we developed a Bayesian approach to estimating the oxygen metabolism response to a neural stimulus and used it to examine the uncertainty that arises in calibrated BOLD estimation due to the presence of unmeasured model parameters. We applied our approach to estimate the CMRO2 response to a visual task using the traditional hypercapnia calibration experiment as well as to estimate the metabolic response to both a visual task and hypercapnia using the measurement of baseline apparent R2' as a calibration technique. Further, in order to examine the effects of cerebral spinal fluid (CSF) signal contamination on the measurement of apparent R2', we examined the effects of measuring this parameter with and without CSF-nulling. We found that the two calibration techniques provided consistent estimates of the metabolic response on average, with a median R2'-based estimate of the metabolic response to CO2 of 1.4%, and R2'- and hypercapnia-calibrated estimates of the visual response of 27% and 24%, respectively. However, these estimates were sensitive to different sources of estimation uncertainty. The R2'-calibrated estimate was highly sensitive to CSF contamination and to uncertainty in unmeasured model parameters describing flow-volume coupling, capillary bed characteristics, and the iso-susceptibility saturation of blood. The hypercapnia-calibrated estimate was relatively insensitive to these parameters but highly sensitive to the assumed metabolic response to CO2. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. A novel Bayesian approach to accounting for uncertainty in fMRI-derived estimates of cerebral oxygen metabolism fluctuations

    Science.gov (United States)

    Simon, Aaron B.; Dubowitz, David J.; Blockley, Nicholas P.; Buxton, Richard B.

    2016-01-01

    Calibrated blood oxygenation level dependent (BOLD) imaging is a multimodal functional MRI technique designed to estimate changes in cerebral oxygen metabolism from measured changes in cerebral blood flow and the BOLD signal. This technique addresses fundamental ambiguities associated with quantitative BOLD signal analysis; however, its dependence on biophysical modeling creates uncertainty in the resulting oxygen metabolism estimates. In this work, we developed a Bayesian approach to estimating the oxygen metabolism response to a neural stimulus and used it to examine the uncertainty that arises in calibrated BOLD estimation due to the presence of unmeasured model parameters. We applied our approach to estimate the CMRO2 response to a visual task using the traditional hypercapnia calibration experiment as well as to estimate the metabolic response to both a visual task and hypercapnia using the measurement of baseline apparent R2′ as a calibration technique. Further, in order to examine the effects of cerebral spinal fluid (CSF) signal contamination on the measurement of apparent R2′, we examined the effects of measuring this parameter with and without CSF-nulling. We found that the two calibration techniques provided consistent estimates of the metabolic response on average, with a median R2′-based estimate of the metabolic response to CO2 of 1.4%, and R2′- and hypercapnia-calibrated estimates of the visual response of 27% and 24%, respectively. However, these estimates were sensitive to different sources of estimation uncertainty. The R2′-calibrated estimate was highly sensitive to CSF contamination and to uncertainty in unmeasured model parameters describing flow-volume coupling, capillary bed characteristics, and the iso-susceptibility saturation of blood. The hypercapnia-calibrated estimate was relatively insensitive to these parameters but highly sensitive to the assumed metabolic response to CO2. PMID:26790354

  2. iAB-RBC-283: A proteomically derived knowledge-base of erythrocyte metabolism that can be used to simulate its physiological and patho-physiological states.

    Science.gov (United States)

    Bordbar, Aarash; Jamshidi, Neema; Palsson, Bernhard O

    2011-07-12

    The development of high-throughput technologies capable of whole cell measurements of genes, proteins, and metabolites has led to the emergence of systems biology. Integrated analysis of the resulting omic data sets has proved to be hard to achieve. Metabolic network reconstructions enable complex relationships amongst molecular components to be represented formally in a biologically relevant manner while respecting physical constraints. In silico models derived from such reconstructions can then be queried or interrogated through mathematical simulations. Proteomic profiling studies of the mature human erythrocyte have shown more proteins present related to metabolic function than previously thought; however the significance and the causal consequences of these findings have not been explored. Erythrocyte proteomic data was used to reconstruct the most expansive description of erythrocyte metabolism to date, following extensive manual curation, assessment of the literature, and functional testing. The reconstruction contains 281 enzymes representing functions from glycolysis to cofactor and amino acid metabolism. Such a comprehensive view of erythrocyte metabolism implicates the erythrocyte as a potential biomarker for different diseases as well as a 'cell-based' drug-screening tool. The analysis shows that 94 erythrocyte enzymes are implicated in morbid single nucleotide polymorphisms, representing 142 pathologies. In addition, over 230 FDA-approved and experimental pharmaceuticals have enzymatic targets in the erythrocyte. The advancement of proteomic technologies and increased generation of high-throughput proteomic data have created the need for a means to analyze these data in a coherent manner. Network reconstructions provide a systematic means to integrate and analyze proteomic data in a biologically meaning manner. Analysis of the red cell proteome has revealed an unexpected level of complexity in the functional capabilities of human erythrocyte metabolism.

  3. iAB-RBC-283: A proteomically derived knowledge-base of erythrocyte metabolism that can be used to simulate its physiological and patho-physiological states

    Directory of Open Access Journals (Sweden)

    Palsson Bernhard O

    2011-07-01

    Full Text Available Abstract Background The development of high-throughput technologies capable of whole cell measurements of genes, proteins, and metabolites has led to the emergence of systems biology. Integrated analysis of the resulting omic data sets has proved to be hard to achieve. Metabolic network reconstructions enable complex relationships amongst molecular components to be represented formally in a biologically relevant manner while respecting physical constraints. In silico models derived from such reconstructions can then be queried or interrogated through mathematical simulations. Proteomic profiling studies of the mature human erythrocyte have shown more proteins present related to metabolic function than previously thought; however the significance and the causal consequences of these findings have not been explored. Results Erythrocyte proteomic data was used to reconstruct the most expansive description of erythrocyte metabolism to date, following extensive manual curation, assessment of the literature, and functional testing. The reconstruction contains 281 enzymes representing functions from glycolysis to cofactor and amino acid metabolism. Such a comprehensive view of erythrocyte metabolism implicates the erythrocyte as a potential biomarker for different diseases as well as a 'cell-based' drug-screening tool. The analysis shows that 94 erythrocyte enzymes are implicated in morbid single nucleotide polymorphisms, representing 142 pathologies. In addition, over 230 FDA-approved and experimental pharmaceuticals have enzymatic targets in the erythrocyte. Conclusion The advancement of proteomic technologies and increased generation of high-throughput proteomic data have created the need for a means to analyze these data in a coherent manner. Network reconstructions provide a systematic means to integrate and analyze proteomic data in a biologically meaning manner. Analysis of the red cell proteome has revealed an unexpected level of complexity in

  4. Circulating brain-derived neurotrophic factor and indices of metabolic and cardiovascular health: data from the Baltimore Longitudinal Study of Aging.

    Directory of Open Access Journals (Sweden)

    Erin Golden

    2010-04-01

    Full Text Available Besides its well-established role in nerve cell survival and adaptive plasticity, brain-derived neurotrophic factor (BDNF is also involved in energy homeostasis and cardiovascular regulation. Although BDNF is present in the systemic circulation, it is unknown whether plasma BDNF correlates with circulating markers of dysregulated metabolism and an adverse cardiovascular profile.To determine whether circulating BDNF correlates with indices of metabolic and cardiovascular health, we measured plasma BDNF levels in 496 middle-age and elderly subjects (mean age approximately 70, in the Baltimore Longitudinal Study of Aging. Linear regression analysis revealed that plasma BDNF is associated with risk factors for cardiovascular disease and metabolic syndrome, regardless of age. In females, BDNF was positively correlated with BMI, fat mass, diastolic blood pressure, total cholesterol, and LDL-cholesterol, and inversely correlated with folate. In males, BDNF was positively correlated with diastolic blood pressure, triglycerides, free thiiodo-thyronine (FT3, and bioavailable testosterone, and inversely correlated with sex-hormone binding globulin, and adiponectin.Plasma BDNF significantly correlates with multiple risk factors for metabolic syndrome and cardiovascular dysfunction. Whether BDNF contributes to the pathogenesis of these disorders or functions in adaptive responses to cellular stress (as occurs in the brain remains to be determined.

  5. Metabolic Heterogeneity Evidenced by MRS among Patient-Derived Glioblastoma Multiforme Stem-Like Cells Accounts for Cell Clustering and Different Responses to Drugs

    Directory of Open Access Journals (Sweden)

    Sveva Grande

    2018-01-01

    Full Text Available Clustering of patient-derived glioma stem-like cells (GSCs through unsupervised analysis of metabolites detected by magnetic resonance spectroscopy (MRS evidenced three subgroups, namely clusters 1a and 1b, with high intergroup similarity and neural fingerprints, and cluster 2, with a metabolism typical of commercial tumor lines. In addition, subclones generated by the same GSC line showed different metabolic phenotypes. Aerobic glycolysis prevailed in cluster 2 cells as demonstrated by higher lactate production compared to cluster 1 cells. Oligomycin, a mitochondrial ATPase inhibitor, induced high lactate extrusion only in cluster 1 cells, where it produced neutral lipid accumulation detected as mobile lipid signals by MRS and lipid droplets by confocal microscopy. These results indicate a relevant role of mitochondrial fatty acid oxidation for energy production in GSCs. On the other hand, further metabolic differences, likely accounting for different therapy responsiveness observed after etomoxir treatment, suggest that caution must be used in considering patient treatment with mitochondria FAO blockers. Metabolomics and metabolic profiling may contribute to discover new diagnostic or prognostic biomarkers to be used for personalized therapies.

  6. Carbon-flux distribution within Streptomyces coelicolor metabolism: a comparison between the actinorhodin-producing strain M145 and its non-producing derivative M1146.

    Directory of Open Access Journals (Sweden)

    Fabien Coze

    Full Text Available Metabolic Flux Analysis is now viewed as essential to elucidate the metabolic pattern of cells and to design appropriate genetic engineering strategies to improve strain performance and production processes. Here, we investigated carbon flux distribution in two Streptomyces coelicolor A3 (2 strains: the wild type M145 and its derivative mutant M1146, in which gene clusters encoding the four main antibiotic biosynthetic pathways were deleted. Metabolic Flux Analysis and (13C-labeling allowed us to reconstruct a flux map under steady-state conditions for both strains. The mutant strain M1146 showed a higher growth rate, a higher flux through the pentose phosphate pathway and a higher flux through the anaplerotic phosphoenolpyruvate carboxylase. In that strain, glucose uptake and the flux through the Krebs cycle were lower than in M145. The enhanced flux through the pentose phosphate pathway in M1146 is thought to generate NADPH enough to face higher needs for biomass biosynthesis and other processes. In both strains, the production of NADPH was higher than NADPH needs, suggesting a key role for nicotinamide nucleotide transhydrogenase for redox homeostasis. ATP production is also likely to exceed metabolic ATP needs, indicating that ATP consumption for maintenance is substantial.Our results further suggest a possible competition between actinorhodin and triacylglycerol biosynthetic pathways for their common precursor, acetyl-CoA. These findings may be instrumental in developing new strategies exploiting S. coelicolor as a platform for the production of bio-based products of industrial interest.

  7. Detection of Transketolase in Bone Marrow—Derived Insulin-Producing Cells: Benfotiamine Enhances Insulin Synthesis and Glucose Metabolism

    OpenAIRE

    Oh, Seh-Hoon; Witek, Rafal P.; Bae, Si-Hyun; Darwiche, Houda; Jung, Youngmi; Pi, Liya; Brown, Alicia; Petersen, Bryon E.

    2009-01-01

    Adult bone marrow (BM)-derived insulin-producing cells (IPCs) are capable of regulating blood glucose levels in chemically induced hyperglycemic mice. Using cell transplantation therapy, fully functional BM-derived IPCs help to mediate treatment of diabetes mellitus. Here, we demonstrate the detection of the pentose phosphate pathway enzyme, transketolase (TK), in BM-derived IPCs cultured under high-glucose conditions. Benfotiamine, a known activator of TK, was not shown to affect the prolife...

  8. Association between abnormal myocardial fatty acid metabolism and cardiac-derived death among patients undergoing hemodialysis: results from a cohort study in Japan.

    Science.gov (United States)

    Moroi, Masao; Tamaki, Nagara; Nishimura, Masato; Haze, Kazuo; Nishimura, Tsunehiko; Kusano, Eiji; Akiba, Takashi; Sugimoto, Tokuichiro; Hase, Hiroki; Hara, Kazuhiro; Nakata, Tomoaki; Kumita, Shinichiro; Nagai, Yoji; Hashimoto, Akiyoshi; Momose, Mitsuru; Miyakoda, Keiko; Hasebe, Naoyuki; Kikuchi, Kenjiro

    2013-03-01

    Detecting myocardial ischemia in hemodialysis patients is crucial given the high incidence of silent ischemia and the high cardiovascular mortality rates. Abnormal myocardial fatty acid metabolism as determined by imaging with (123)I-labeled BMIPP (β-methyl iodophenyl-pentadecanoic acid) might be associated with cardiac-derived death in hemodialysis patients. Prospective observational study. Asymptomatic hemodialysis patients with one or more cardiovascular risk factors, but without known coronary artery disease, were followed up for 3 years at 48 Japanese hospitals (406 men, 271 women; mean age, 64 years). Baseline BMIPP summed scores semiquantified using a 17-segment 5-point system (normal, 0; absent, 4). Cardiac-derived death, including cardiac and sudden death. HRs were estimated using a Cox model for associations between BMIPP summed scores and cardiac-derived death, adjusting for potential confounders of age, sex, body mass index, dialysis duration, and cardiovascular risk factors. Rates of all-cause mortality and cardiac-derived death were 18.5% and 6.8%, respectively. Cardiac-derived death (acute myocardial infarction [n = 10], congestive heart failure [n = 13], arrhythmia [n = 2], valvular heart disease [n = 1], and sudden death [n = 20]) accounted for 36.8% of all-cause deaths. Cardiac-derived death (n = 46) was associated with age, history of heart failure, and BMIPP summed scores of 4 or higher (HR, 2.9; P death-free survival rates were 95.7%, 90.6%, and 78.8% when BMIPP summed scores were 3 or lower, 4-8, and 9 or higher, respectively. BMIPP summed score also was a predictor of all-cause death (HR, 1.6; P = 0.009). Sudden death of unknown cause was considered to have been cardiac derived, although a coronary origin was not confirmed. Abnormal myocardial fatty acid metabolism is associated with cardiac-derived death in hemodialysis patients. BMIPP single-proton emission computed tomography appears clinically useful for predicting cardiac-derived death

  9. Characterization of energy and neurotransmitter metabolism in cortical glutamatergic neurons derived from human induced pluripotent stem cells

    DEFF Research Database (Denmark)

    Aldana, Blanca I; Zhang, Yu; Lihme, Maria Fog

    2017-01-01

    pathways in neurons derived from human induced pluripotent stem cells (hiPSC). With this aim, cultures of hiPSC-derived neurons were incubated with [U-(13)C]glucose, [U-(13)C]glutamate or [U-(13)C]glutamine. Isotopic labeling in metabolites was determined using gas chromatography coupled to mass...

  10. The interrelationship of metabolic syndrome and neurodegenerative diseases with focus on brain-derived neurotrophic factor (BDNF): Kill two birds with one stone.

    Science.gov (United States)

    Motamedi, Shima; Karimi, Isaac; Jafari, Fariba

    2017-06-01

    The brain-derived neurotrophic factor (BDNF) is involved in metabolic syndrome (MetS) and neurodegenerative diseases (NDD) like Alzheimer's disease, Huntington's disease, Parkinson's disease and depression. If one factor plays an essential role in the pathogenesis of two diseases, it can be concluded that there might be a common root in these two diseases, as well. This review was aimed to highlight the crucial roles of BDNF in the pathogenesis of MetS and NDD and to introduce sole prophylactic or therapeutic applications, BDNF gene therapy and BDFN administration, in controlling MetS and NDD.

  11. Field metabolic rate and PCB adipose tissue deposition efficiency in East Greenland polar bears derived from contaminant monitoring data.

    Science.gov (United States)

    Pavlova, Viola; Nabe-Nielsen, Jacob; Dietz, Rune; Svenning, Jens-Christian; Vorkamp, Katrin; Rigét, Frank Farsø; Sonne, Christian; Letcher, Robert J; Grimm, Volker

    2014-01-01

    Climate change will increasingly affect the natural habitat and diet of polar bears (Ursus maritimus). Understanding the energetic needs of polar bears is therefore important. We developed a theoretical method for estimating polar bear food consumption based on using the highly recalcitrant polychlorinated biphenyl (PCB) congener, 2,2',4,4',55-hexaCB (CB153) in bear adipose tissue as an indicator of food intake. By comparing the CB153 tissue concentrations in wild polar bears with estimates from a purposely designed individual-based model, we identified the possible combinations of field metabolic rates (FMR) and CB153 deposition efficiencies in East Greenland polar bears. Our simulations indicate that if 30% of the CB153 consumed by polar bear individuals were deposited into their adipose tissue, the corresponding FMR would be only two times the basal metabolic rate. In contrast, if the modelled CB153 deposition efficiency were 10%, adult polar bears would require six times more energy than that needed to cover basal metabolism. This is considerably higher than what has been assumed for polar bears in previous studies though it is similar to FMRs found in other marine mammals. An implication of this result is that even relatively small reductions in future feeding opportunities could impact the survival of East Greenland polar bears.

  12. Field metabolic rate and PCB adipose tissue deposition efficiency in East Greenland polar bears derived from contaminant monitoring data.

    Directory of Open Access Journals (Sweden)

    Viola Pavlova

    Full Text Available Climate change will increasingly affect the natural habitat and diet of polar bears (Ursus maritimus. Understanding the energetic needs of polar bears is therefore important. We developed a theoretical method for estimating polar bear food consumption based on using the highly recalcitrant polychlorinated biphenyl (PCB congener, 2,2',4,4',55-hexaCB (CB153 in bear adipose tissue as an indicator of food intake. By comparing the CB153 tissue concentrations in wild polar bears with estimates from a purposely designed individual-based model, we identified the possible combinations of field metabolic rates (FMR and CB153 deposition efficiencies in East Greenland polar bears. Our simulations indicate that if 30% of the CB153 consumed by polar bear individuals were deposited into their adipose tissue, the corresponding FMR would be only two times the basal metabolic rate. In contrast, if the modelled CB153 deposition efficiency were 10%, adult polar bears would require six times more energy than that needed to cover basal metabolism. This is considerably higher than what has been assumed for polar bears in previous studies though it is similar to FMRs found in other marine mammals. An implication of this result is that even relatively small reductions in future feeding opportunities could impact the survival of East Greenland polar bears.

  13. Temporal stability in the genetic structure of Sarcoptes scabiei under the host-taxon law: empirical evidences from wildlife-derived Sarcoptes mite in Asturias, Spain

    Directory of Open Access Journals (Sweden)

    Rossi Luca

    2011-07-01

    Full Text Available Abstract Background Implicitly, parasite molecular studies assume temporal genetic stability. In this study we tested, for the first time to our knowledge, the extent of changes in genetic diversity and structure of Sarcoptes mite populations from Pyrenean chamois (Rupicapra pyrenaica in Asturias (Spain, using one multiplex of 9 microsatellite markers and Sarcoptes samples from sympatric Pyrenean chamois, red deer (Cervus elaphus, roe deer (Capreolus capreolus and red fox (Vulpes vulpes. Results The analysis of an 11-years interval period found little change in the genetic diversity (allelic diversity, and observed and expected heterozygosity. The temporal stability in the genetic diversity was confirmed by population structure analysis, which was not significantly variable over time. Population structure analysis revealed temporal stability in the genetic diversity of Sarcoptes mite under the host-taxon law (herbivore derived- and carnivore derived-Sarcoptes mite among the sympatric wild animals from Asturias. Conclusions The confirmation of parasite temporal genetic stability is of vital interest to allow generalizations to be made, which have further implications regarding the genetic structure, epidemiology and monitoring protocols of the ubiquitous Sarcoptes mite. This could eventually be applied to other parasite species.

  14. Benchmarking DFT and semi-empirical methods for a reliable and cost-efficient computational screening of benzofulvene derivatives as donor materials for small-molecule organic solar cells.

    Science.gov (United States)

    Tortorella, Sara; Talamo, Maurizio Mastropasqua; Cardone, Antonio; Pastore, Mariachiara; De Angelis, Filippo

    2016-02-24

    A systematic computational investigation on the optical properties of a group of novel benzofulvene derivatives (Martinelli 2014 Org. Lett. 16 3424-7), proposed as possible donor materials in small molecule organic photovoltaic (smOPV) devices, is presented. A benchmark evaluation against experimental results on the accuracy of different exchange and correlation functionals and semi-empirical methods in predicting both reliable ground state equilibrium geometries and electronic absorption spectra is carried out. The benchmark of the geometry optimization level indicated that the best agreement with x-ray data is achieved by using the B3LYP functional. Concerning the optical gap prediction, we found that, among the employed functionals, MPW1K provides the most accurate excitation energies over the entire set of benzofulvenes. Similarly reliable results were also obtained for range-separated hybrid functionals (CAM-B3LYP and wB97XD) and for global hybrid methods incorporating a large amount of non-local exchange (M06-2X and M06-HF). Density functional theory (DFT) hybrids with a moderate (about 20-30%) extent of Hartree-Fock exchange (HFexc) (PBE0, B3LYP and M06) were also found to deliver HOMO-LUMO energy gaps which compare well with the experimental absorption maxima, thus representing a valuable alternative for a prompt and predictive estimation of the optical gap. The possibility of using completely semi-empirical approaches (AM1/ZINDO) is also discussed.

  15. Benchmarking DFT and semi-empirical methods for a reliable and cost-efficient computational screening of benzofulvene derivatives as donor materials for small-molecule organic solar cells

    International Nuclear Information System (INIS)

    Tortorella, Sara; Talamo, Maurizio Mastropasqua; Cardone, Antonio; Pastore, Mariachiara; De Angelis, Filippo

    2016-01-01

    A systematic computational investigation on the optical properties of a group of novel benzofulvene derivatives (Martinelli 2014 Org. Lett. 16 3424–7), proposed as possible donor materials in small molecule organic photovoltaic (smOPV) devices, is presented. A benchmark evaluation against experimental results on the accuracy of different exchange and correlation functionals and semi-empirical methods in predicting both reliable ground state equilibrium geometries and electronic absorption spectra is carried out. The benchmark of the geometry optimization level indicated that the best agreement with x-ray data is achieved by using the B3LYP functional. Concerning the optical gap prediction, we found that, among the employed functionals, MPW1K provides the most accurate excitation energies over the entire set of benzofulvenes. Similarly reliable results were also obtained for range-separated hybrid functionals (CAM-B3LYP and wB97XD) and for global hybrid methods incorporating a large amount of non-local exchange (M06-2X and M06-HF). Density functional theory (DFT) hybrids with a moderate (about 20–30%) extent of Hartree–Fock exchange (HFexc) (PBE0, B3LYP and M06) were also found to deliver HOMO–LUMO energy gaps which compare well with the experimental absorption maxima, thus representing a valuable alternative for a prompt and predictive estimation of the optical gap. The possibility of using completely semi-empirical approaches (AM1/ZINDO) is also discussed. (paper)

  16. An empirically derived dietary pattern associated with breast cancer risk is validated in a nested case-control cohort from a randomized primary prevention trial.

    Science.gov (United States)

    Hidaka, Brandon H; Kimler, Bruce F; Fabian, Carol J; Carlson, Susan E

    2017-02-01

    We reported an association between cytologic atypia, a reversible biomarker of breast cancer risk, and lower omega-3/omega-6 fatty acid ratio in blood and breast tissue. Our goal was to develop and validate a dietary pattern index in this high-risk sample of U.S. women, and test its capacity to predict incidence in a nested case-control cohort of Canadian women from a randomized trial of a low-fat dietary intervention for primary prevention of breast cancer. Food intake was measured by food frequency questionnaire in the U.S. sample (n = 65) and multiple dietary recalls in the Canadian sample (n = 220 cases; 440 controls). Principal component analysis identified a dietary pattern associated with atypia. We measured differences among dietary pattern tertiles in (a) fatty acid composition in blood lipids and breast tissue in the U.S. sample, and (b) risk of breast cancer subtypes in the Canadian cohort. Registered under ClinicalTrials.gov Identifier: NCT00148057. A Modern diet was characterized as consuming more grains, dairy, and sugar and less vegetables, fish and poultry; these women had lower tissue omega-3 fatty acids and higher omega-6 and trans fatty acids. The low-fat intervention increased the likelihood of a Modern diet after randomization. A Modern diet at baseline and post-randomization was associated with estrogen-receptor negative (ER-) breast cancer risk among those at least 160 cm tall. A Traditional diet (the reciprocal of Modern) at baseline was associated with lower ER-positive (ER+) risk in the comparison group, but not the low-fat intervention group. A Modern diet (high in grains, dairy, and sugar and low in vegetables, fish, and poultry) is associated with ER- breast cancer risk among taller women. Recommending dietary fat reduction may have untoward effects on breast cancer risk. Copyright © 2016 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

  17. Fuels derived from starch digestion have different effects on energy intake and metabolic responses of cows in the postpartum period.

    Science.gov (United States)

    Gualdrón-Duarte, Laura B; Allen, Michael S

    2018-03-07

    Absorbed fuels from the digestion of starch include propionic acid (PA) produced by ruminal fermentation and glucose (GLU) from intestinal digestion, which may be partially metabolized to lactic acid (LA) by intestinal tissues. Our objective was to evaluate the effects of these fuels on dry matter intake (DMI) and feeding behavior of cows in the postpartum period. We hypothesized that these fuels affect feed intake differently and that their effects are related to differences in their hepatic metabolism. Glucose was expected to have little effect on feed intake because little or no GLU is extracted from the blood by the liver. Whereas both LA and PA are anaplerotic and can stimulate oxidation of acetyl CoA in hepatocytes, hepatic extraction of PA is greater than LA, which depends on cytosolic redox state. Continuous isoenergetic infusions (150 kcal of ME/h) of PA, LA, or GLU or no infusion were administered abomasally to 8 ruminally cannulated multiparous Holstein cows (12.4 ± 6.2 d postpartum) in a duplicate 4 × 4 Latin square design experiment, with four 1-d infusion periods, balanced for carry-over effects. Treatment sequences were assigned to cows randomly, and treatments included control (CON, no infusion), PA (0.41 mol/h), LA (0.46 mol/h), and GLU (0.22 mol/h). Solutions containing treatments were infused at 500 mL/h for 22 h/d and provided ~3.3 Mcal/d. Feeding behavior was recorded by a computerized data acquisition system. Gross energy digestibility of the diet was determined for each cow and used to calculate metabolizable energy intake (MEI) from the diet. Total MEI was calculated as the sum of MEI from the diet plus energy from infusions. Data were analyzed statistically with a mixed model including the fixed effect of treatment and random effects of block and cow within block. Each treatment was compared with CON by contrasts. Compared with CON, PA decreased DMI by 24% (14.3 vs. 18.9 kg/d) and total MEI by 13% (34.8 vs. 40.2 Mcal/d) with a tendency to

  18. Empirical Hamiltonians

    International Nuclear Information System (INIS)

    Peggs, S.; Talman, R.

    1986-08-01

    As proton accelerators get larger, and include more magnets, the conventional tracking programs which simulate them run slower. At the same time, in order to more carefully optimize the higher cost of the accelerators, they must return more accurate results, even in the presence of a longer list of realistic effects, such as magnet errors and misalignments. For these reasons conventional tracking programs continue to be computationally bound, despite the continually increasing computing power available. This limitation is especially severe for a class of problems in which some lattice parameter is slowly varying, when a faithful description is only obtained by tracking for an exceedingly large number of turns. Examples are synchrotron oscillations in which the energy varies slowly with a period of, say, hundreds of turns, or magnet ripple or noise on a comparably slow time scale. In these cases one may with to track for hundreds of periods of the slowly varying parameter. The purpose of this paper is to describe a method, still under development, in which element-by-element tracking around one turn is replaced by a single map, which can be processed far faster. Similar programs have already been written in which successive elements are ''concatenated'' with truncation to linear, sextupole, or octupole order, et cetera, using Lie algebraic techniques to preserve symplecticity. The method described here is rather more empirical than this but, in principle, contains information to all orders and is able to handle resonances in a more straightforward fashion

  19. The regulation of growth and metabolism of kidney stem cell with regional specificity using extracellular matrix derived from kidney

    OpenAIRE

    O’Neill, John D.; Freytes, Donald O.; Anandappa, Annabelle; Oliver, Juan A.; Vunjak-Novakovic, Gordana

    2013-01-01

    Native extracellular matrix (ECM) that is secreted and maintained by resident cells is of great interest for cell culture and cell delivery. We hypothesized that specialized bioengineered niches for stem cells can be established using ECM-derived scaffolding materials. Kidney was selected as a model system because of the high regional diversification of renal tissue matrix. By preparing the ECM from three specialized regions of the kidney (cortex, medulla, and papilla; whole kidney, heart, an...

  20. Galactomannan from Schizolobium amazonicum seed and its sulfated derivatives impair metabolism in HepG2 cells.

    Science.gov (United States)

    Cunha de Padua, Monique Meyenberg; Suter Correia Cadena, Silvia Maria; de Oliveira Petkowicz, Carmen Lucia; Martinez, Glaucia Regina; Rodrigues Noleto, Guilhermina

    2017-08-01

    This study evaluated the effects of native galactomannan from Schizolobium amazonicum seeds and its sulfated forms on certain metabolic parameters of HepG2 cells. Aqueous extraction from S. amazonicum seeds furnished galactomannan with 3.2:1 Man:Gal ratio (SAGM) and molar mass of 4.34×10 5 g/mol. The SAGM fraction was subjected to sulfation using chlorosulfonic acid to obtain SAGMS1 and SAGMS2 with DS of 0.4 and 0.6, respectively. Cytotoxicity of SAGM, SAGMS1, and SAGMS2 was evaluated in human hepatocellular carcinoma cells (HepG2). After 72h, SAGM decreased the viability of HepG2 cells by 50% at 250μg/mL, while SAGMS1 reduced it by 30% at the same concentration. SAGM, SAGMS1, and SAGMS2 promoted a reduction in oxygen consumption and an increase in lactate production in non-permeabilized HepG2 cells after 72h of treatment. These results suggest that SAGM, SAGMS1, and SAGMS2 could be recognized by HepG2 cells and might trigger alterations that impair its survival. These effects could be implicated in the modification of the oxidative phosphorylation process in HepG2 cells and activation of the glycolytic pathway. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Metabolic Interactions of Purine Derivatives with Human ABC Transporter ABCG2: Genetic Testing to Assess Gout Risk.

    Science.gov (United States)

    Ishikawa, Toshihisa; Aw, Wanping; Kaneko, Kiyoko

    2013-11-04

    In mammals, excess purine nucleosides are removed from the body by breakdown in the liver and excretion from the kidneys. Uric acid is the end product of purine metabolism in humans. Two-thirds of uric acid in the human body is normally excreted through the kidney, whereas one-third undergoes uricolysis (decomposition of uric acid) in the gut. Elevated serum uric acid levels result in gout and could be a risk factor for cardiovascular disease and diabetes. Recent studies have shown that human ATP-binding cassette transporter ABCG2 plays a role of renal excretion of uric acid. Two non-synonymous single nucleotide polymorphisms (SNPs), i.e., 421C>A (major) and 376C>T (minor), in the ABCG2 gene result in impaired transport activity, owing to ubiquitination-mediated proteosomal degradation and truncation of ABCG2, respectively. These genetic polymorphisms are associated with hyperuricemia and gout. Allele frequencies of those SNPs are significantly higher in Asian populations than they are in African and Caucasian populations. A rapid and isothermal genotyping method has been developed to detect the SNP 421C>A, where one drop of peripheral blood is sufficient for the detection. Development of simple genotyping methods would serve to improve prevention and early therapeutic intervention for high-risk individuals in personalized healthcare.

  2. Metabolic Interactions of Purine Derivatives with Human ABC Transporter ABCG2: Genetic Testing to Assess Gout Risk

    Directory of Open Access Journals (Sweden)

    Kiyoko Kaneko

    2013-11-01

    Full Text Available In mammals, excess purine nucleosides are removed from the body by breakdown in the liver and excretion from the kidneys. Uric acid is the end product of purine metabolism in humans. Two-thirds of uric acid in the human body is normally excreted through the kidney, whereas one-third undergoes uricolysis (decomposition of uric acid in the gut. Elevated serum uric acid levels result in gout and could be a risk factor for cardiovascular disease and diabetes. Recent studies have shown that human ATP-binding cassette transporter ABCG2 plays a role of renal excretion of uric acid. Two non-synonymous single nucleotide polymorphisms (SNPs, i.e., 421C>A (major and 376C>T (minor, in the ABCG2 gene result in impaired transport activity, owing to ubiquitination-mediated proteosomal degradation and truncation of ABCG2, respectively. These genetic polymorphisms are associated with hyperuricemia and gout. Allele frequencies of those SNPs are significantly higher in Asian populations than they are in African and Caucasian populations. A rapid and isothermal genotyping method has been developed to detect the SNP 421C>A, where one drop of peripheral blood is sufficient for the detection. Development of simple genotyping methods would serve to improve prevention and early therapeutic intervention for high-risk individuals in personalized healthcare.

  3. Niacin and olive oil promote skewing to the M2 phenotype in bone marrow-derived macrophages of mice with metabolic syndrome.

    Science.gov (United States)

    Montserrat-de la Paz, Sergio; Naranjo, Maria C; Lopez, Sergio; Abia, Rocio; Muriana, Francisco J G; Bermudez, Beatriz

    2016-05-18

    Metabolic syndrome (MetS) is associated with obesity, dyslipemia, type 2 diabetes and chronic low-grade inflammation. The aim of this study was to determine the role of high-fat low-cholesterol diets (HFLCDs) rich in SFAs (HFLCD-SFAs), MUFAs (HFLCD-MUFAs) or MUFAs plus omega-3 long-chain PUFAs (HFLCD-PUFAs) on polarisation and inflammatory potential in bone marrow-derived macrophages (BMDMs) from niacin (NA)-treated Lep(ob/ob)LDLR(-/-) mice. Animals fed with HFLCD-SFAs had increased weight and serum triglycerides, and their BMDMs accumulated triglycerides over the animals fed with HFLCD-MUFAs or -PUFAs. Furthermore, BMDMs from animals fed with HFLCD-SFAs were polarised towards the M1 phenotype with functional competence to produce pro-inflammatory cytokines, whereas BMDMs from animals fed with HFLCD-MUFAs or -PUFAs were skewed to the anti-inflammatory M2 phenotype. These findings open opportunities for developing novel nutritional strategies with olive oil as the most important dietary source of MUFAs (notably oleic acid) to prevent development and progression of metabolic complications in the NA-treated MetS.

  4. A liquid chromatography – tandem mass spectrometry method to measure a selected panel of uremic retention solutes derived from endogenous and colonic microbial metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Loor, Henriette de; Poesen, Ruben [KU Leuven – University of Leuven, Department of Microbiology and Immunology, Laboratory of Nephrology, B-3000 Leuven (Belgium); De Leger, Wout; Dehaen, Wim [KU Leuven – University of Leuven, Department of Chemistry, Division of Molecular Design and Synthesis, B-3000 Leuven (Belgium); Augustijns, Patrick [KU Leuven – University of Leuven, Department of Pharmaceutical and Pharmacological Sciences, Drug Delivery and Disposition, B-3000 Leuven (Belgium); Evenepoel, Pieter [KU Leuven – University of Leuven, Department of Microbiology and Immunology, Laboratory of Nephrology, B-3000 Leuven (Belgium); University Hospitals Leuven, Department of Nephrology and Renal Transplantation, B-3000 Leuven (Belgium); Meijers, Björn, E-mail: bjorn.meijers@uzleuven.be [KU Leuven – University of Leuven, Department of Microbiology and Immunology, Laboratory of Nephrology, B-3000 Leuven (Belgium); University Hospitals Leuven, Department of Nephrology and Renal Transplantation, B-3000 Leuven (Belgium)

    2016-09-14

    Chronic kidney disease (CKD) is associated with an increased risk of mortality and cardiovascular disease, which is, at least partly, mediated by the accumulation of so-called uremic retention solutes. Although there has been an increasing interest in the behavior of these solutes, derived from both the endogenous and colonic microbial metabolism, methods to simultaneously and accurately measure a broad panel of relevant uremic retention solutes remain scarce. We developed a highly sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. A high throughput sample preparation was used with extraction of analytes from 50 μl serum using Ostro plate technology. For most solutes, stable isotopes labelled metabolites were used as internal standards. Chromatography was achieved using an Acquity UPLC CSH Fluoro Phenyl column. The total run time was 8 min, the mobile phase was a gradient of 0.1% formic acid in Milli-Q water and pure methanol at a flow rate of 0.5 ml min{sup −1}. Detection was performed using a tandem mass spectrometer with alternated positive and negative electrospray ionization. Calibration curves were linear for all solutes. Precision was assessed according to the NCCLS EP5-T guideline, being below 15% for all metabolites. Mean recoveries were between 83 and 104% for all metabolites. The validated method was successfully applied in a cohort of 488 patients with CKD. We developed and validated a sensitive and robust UPLC-MS/MS method for quantification of 15 uremic retention solutes derived from endogenous and colonic microbial metabolism. This method allows for studying the behavior and relevance of these solutes in patients with CKD. - Highlights: • Simultaneous quantification of fifteen relevant uremic retention solutes. • Comprehensive validation, highly sensitive and high through-put LC-MSMS method. • Comparison of different blood tubes. • Freeze-thaw stability. • Successful implementation in a

  5. Modulation of Metabolic Detoxification Pathways Using Foods and Food-Derived Components: A Scientific Review with Clinical Application

    Directory of Open Access Journals (Sweden)

    Romilly E. Hodges

    2015-01-01

    Full Text Available Research into human biotransformation and elimination systems continues to evolve. Various clinical and in vivo studies have been undertaken to evaluate the effects of foods and food-derived components on the activity of detoxification pathways, including phase I cytochrome P450 enzymes, phase II conjugation enzymes, Nrf2 signaling, and metallothionein. This review summarizes the research in this area to date, highlighting the potential for foods and nutrients to support and/or modulate detoxification functions. Clinical applications to alter detoxification pathway activity and improve patient outcomes are considered, drawing on the growing understanding of the relationship between detoxification functions and different disease states, genetic polymorphisms, and drug-nutrient interactions. Some caution is recommended, however, due to the limitations of current research as well as indications that many nutrients exert biphasic, dose-dependent effects and that genetic polymorphisms may alter outcomes. A whole-foods approach may, therefore, be prudent.

  6. Methoxypyrazines biosynthesis and metabolism in grape: A review.

    Science.gov (United States)

    Lei, Yujuan; Xie, Sha; Guan, Xueqiang; Song, Changzheng; Zhang, Zhenwen; Meng, Jiangfei

    2018-04-15

    This review summarizes research on the discovery, biosynthesis, accumulation, transport, and metabolism of 3-alkyl-2-methoxypyrazines (MPs) in grape. The MPs are a family of potent volatile compounds distributed throughout biological kingdoms. These compounds impart herbaceous/green/vegetal sensory attributes to certain varieties of wine. Generally, high levels of MPs in wine are derived mainly from the corresponding grapes. Although two pathways for MPs biosynthesis have been proposed, only the final step and the enzymes that catalyze it has been confirmed in grape, and the metabolic intermediates and key enzymes involved in other steps are still unknown. The limited understanding of MPs metabolism has restricted research on these compounds, and some empirical results cannot be explained by the current knowledge of MPs metabolism. This review provides insights into research on MPs biosynthesis and metabolism, and proposes directions for further research on this important class of flavour/odour compounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Decreased Serum Levels of Ghrelin and Brain-Derived Neurotrophic Factor in Premenopausal Women With Metabolic Syndrome.

    Science.gov (United States)

    Jabbari, Masoumeh; Kheirouri, Sorayya; Alizadeh, Mohammad

    2018-03-21

    We aimed to investigate the association between serum levels of ghrelin and brain-derived neurotrophic factor (BDNF) with MetS and its components in premenopausal women. 43 patients with MetS and 43 healthy controls participated in this study. Participants' body mass index (BMI), waist circumference (WC), systolic and diastolic blood pressure (SBP and DBP) were measured. Serum levels of total cholesterol (TC), triglyceride (TG), low and high density lipoprotein cholesterol (LDL-C and HDL-C), fasting blood sugar (FBS), insulin, BDNF and ghrelin determined. Homeostasis model assessment insulin resistance index (HOMA-IR) was also calculated. Participants in MetS group had higher waist-to-hip ratios, elevated SBP and DBP, and higher serum levels of TG, FBS and insulin when compared with the control group. Serum ghrelin and BDNF levels were significantly lower in participants with MetS than in the healthier control subjects. There was a strong, positive correlation between serum ghrelin and BDNF levels. Both proteins negatively correlated with TG, FBS, HOMA-IR and positively with HDL-C. Furthermore, serum BDNF levels negatively associated with insulin levels. The findings indicate that variations occur in the circulating level of ghrelin and BDNF proteins in MetS patients. A strong correlation between serum ghrelin and BDNF suggests that production, release or practice of these 2 proteins might be related mechanically.

  8. KDT501, a derivative from hops, normalizes glucose metabolism and body weight in rodent models of diabetes.

    Directory of Open Access Journals (Sweden)

    Veera R Konda

    Full Text Available AIMS/HYPOTHESIS: We developed KDT501, a novel substituted 1,3-cyclopentadione chemically derived from hop extracts, and evaluated it in various in vitro and in vivo models of diabetes and insulin sensitivity. METHODS: KDT501 was evaluated for anti-inflammatory effects in monocyte/macrophage cells; agonistic activity for peroxisome proliferator-activated receptors (PPAR; lipogenesis and gene expression profile in human subcutaneous adipocytes. Body composition, glucose, insulin sensitivity, and lipids were assessed in diet-induced obesity (DIO mice and Zucker Diabetic Fatty (ZDF rats after oral administration. RESULTS: KDT501 mediated lipogenesis in 3T3L1 and human subcutaneous adipocytes; however, the gene expression profile of KDT501 differed from that of the full PPARγ agonist rosiglitazone, suggesting that KDT501 has pleiotropic biological activities. In addition, KDT501 showed only modest, partial PPARγ agonist activity and exhibited anti-inflammatory effects in monocytes/macrophages that were not observed with rosiglitazone. In a DIO mouse model, oral administration of KDT501 significantly reduced fed blood glucose, glucose/insulin AUC following an oral glucose bolus, and body fat. In ZDF rats, oral administration of KDT501 significantly reduced fed glucose, fasting plasma glucose, and glucose AUC after an oral glucose bolus. Significant, dose-dependent reductions of plasma hemoglobin A1c, weight gain, total cholesterol, and triglycerides were also observed in animals receiving KDT501. CONCLUSION: These results indicate that KDT501 produces a unique anti-diabetic profile that is distinct in its spectrum of pharmacological effects and biological mechanism from both metformin and pioglitazone. KDT501 may thus constitute a novel therapeutic agent for the treatment of Type 2 diabetes and associated conditions.

  9. The effects of ultraviolet light on aspects of DNA metabolism in cell lines derived from plodia interpunctella and Trichoplusia ni

    International Nuclear Information System (INIS)

    Styer, S.C.

    1991-01-01

    Insect cells are significantly more resistant to the lethal effects of 254 nm ultraviolet light (UV) than mammalian cells. The predominant photoproduct produced by UV is the (5-6) cyclobutyl pyrimidine dimer. There is controversy whether this lesion, or another, the pyrimidine (6-4) pyrimidone, is responsible for the biological effects of UV. Insect cells contain a photolyase which selectively removes the (5-6), but not the (6-4) lesion, so that the relative roles of these lesions can be studied. Insect cell lines derived from the cabbage looper and the Indian meal moth were exposed to UV and analyzed for their ability to incorporate 3 H-thymidine. After exposure, cells from the Indian meal moth exhibited a rapid and prolonged depression in the rate of thymidine incorporation, whereas cells from the cabbage looper showed only a slight drop in incorporation and a rapid recovery. The extent of depression in thymidine incorporation was not correlated to the amount of cell killing by UV in these cell lines. Blockage of fork progression was correlated to the depression in thymidine incorporation. Photoreactivation did not entirely relieve blockage, depression in thymidine incorporation or cell killing, indicating that although the (5-6) dimer appears to be the major lesion responsible for these effects, other lesions, such as the (6-4) photoproduct, may play a role. In addition, activation of alternative sites of replicon initiation appeared to correlate with the depression in thymidine incorporation and the excision capabilities in these cells. The resistance to UV in these insect cells compared to mammalian cells may be due to their ability to rapidly remove the (5-6) lesion, which is the critical lesion in these insect cells

  10. Association of pharmacokinetic and metabolic parameters derived using simultaneous PET/MRI: Initial findings and impact on response evaluation in breast cancer.

    Science.gov (United States)

    Jena, Amarnath; Taneja, Sangeeta; Singh, Aru; Negi, Pradeep; Mehta, Shashi Bhushan; Ahuja, Aashim; Singhal, Manish; Sarin, Ramesh

    2017-07-01

    To study relationships among pharmacokinetic and 18 F-fluorodeoxyglucose ( 18 F-FDG) PET parameters obtained through simultaneous PET/MRI in breast cancer patients and evaluate their combined potential for response evaluation. The study included 41 breast cancer patients for correlation study and 9 patients (pre and post therapy) for response evaluation. All patients underwent simultaneous PET/MRI with dedicated breast imaging. Pharmacokinetic parameters and PET parameters for tumor were derived using an in- house developed and vendor provided softwares respectively. Relationships between SUV and pharmacokinetic parameters and clinical as well as histopathologic parameters were evaluated using Spearman correlation analysis. Response to chemotherapy was derived as percentage reduction in size and in parameters post therapy. Significant correlations were observed between SUVmean, max, peak, TLG with K trans (ρ=0.446, 0.417, 0.491, 0.430; p≤0.01); with Kep(ρ=0.303, ρ=0.315, ρ=0.319; p≤0.05); and with iAUC(ρ=0.401, ρ=0.410, ρ=0.379; p≤0.05, p≤0.01). The ratio of ve/iAUC showed significant negative correlation to SUVmean, max, peak and TLG (ρ=0.420, 0.446, 0.443, 0.426; p≤0.01). Ability of SUV as well as pharmacokinetic parameters to predict response to therapy matched the RECIST criteria in 9 out of 11 lesions in 9 patients. Maximum post therapy quantitative reduction was observed in SUVpeak, TLG and K trans . Simultaneous PET/MRI enables illustration of close interactions between glucose metabolism and pharmacokinetic parameters in breast cancer patients and potential of their simultaneity in response assessment to therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Tools for the identification of bioactives impacting the metabolic syndrome: Screening of a botanical extract library using subcutaneous and visceral human adipose-derived stem cell based assays

    Science.gov (United States)

    Buehrer, Benjamin M.; Duffin, David J.; Lea-Currie, Y. Renee; Ribnicky, David; Raskin, Ilya; Stephens, Jacqueline M.; Cefalu, William T.; Gimble, Jeffrey M.

    2011-01-01

    Plant extracts continue to represent an untapped source of renewable therapeutic compounds for the treatment and prevention of illnesses including chronic metabolic disorders. With the increase in worldwide obesity and its related morbidities, the need for identifying safe and effective treatments is also rising. As such, use of primary human adipose-derived stem cells represents a physiologically relevant cell system to screen for bioactive agents in the prevention and treatment of obesity and its related complications. By using these cells in a primary screen, the risk and cost of identifying artifacts due to interspecies variation and immortalized cell lines is eliminated. We demonstrate that these cells can be formatted into 384-well high throughput screens to rapidly identify botanical extracts that affect lipogenesis and lipolysis. Additionally, counterscreening with human primary stem cells from distinct adipose depots can be routinely performed to identify tissue specific responses. In our study, over 500 botanical extracts were screened and 16 (2.7%) were found to affect lipogenesis and 4 (0.7%) affected lipolysis. PMID:21543201

  12. The vapor pressure and vaporization enthalpy of R-(+)-menthofuran, a hepatotoxin metabolically derived from the abortifacient terpene, (R)-(+)-pulegone by correlation gas chromatography

    International Nuclear Information System (INIS)

    Gobble, Chase; Chickos, James S.

    2016-01-01

    Highlights: • The vaporization enthalpy and vapor pressure of R-(+) menthofuran is evaluated. • The normal boiling temperature is predicted and compared to experimental and predicted values. • A vapor pressure equation as a function of temperature for menthofuran is evaluated. - Abstract: The vapor pressure as a function of temperature and its vaporization enthalpy at T = 298.15 K of R-(+)-menthofuran, a substance metabolically derived from R-(+)-pulegone that is both a flavoring agent at low concentrations and a hepatotoxin at larger ones, is evaluated by correlation-gas chromatography. A vapor pressure p/Pa = (36 ± 12) has been evaluated at T = 298.15 K, and a normal boiling temperature of T_b/K = 482.4 K is predicted. A boiling temperature of T_b/K = 374.3 compares with the literature value of T_b/K = 371.2 at reduced pressure, p/kPa = 2.93. The vaporization enthalpy of (56.5 ± 3.0) kJ·mol"−"1 compares to an estimated value of (57.8 ± 2.9) kJ·mol"−"1.

  13. Effect of six weeks of endurance exercise and following detraining on serum brain derived neurotrophic factor and memory performance in middle aged males with metabolic syndrome.

    Science.gov (United States)

    Babaei, P; Azali Alamdari, K; Soltani Tehrani, B; Damirchi, A

    2013-08-01

    Brain derived neurotrophic factor (BDNF) and physical inactivity contribute to the development of metabolic syndrome (MetS). Aerobic training has been reported to improve MetS, however less attention has been directed toward the role of training and detraining on cognitive function in MetS. Twenty one healthy middle-aged males and 21 with MetS were distributed into four groups: MetS exercise (ME), MetS control (MC), Healthy exercise (HE) and healthy control (HC). Both ME and HE, followed a 6-week aerobic training program (3 sessions/week). Digit Span memory test and blood sampling were conducted pre training, post training and also following a six weeks detraining. Data were analyzed using spearman, pearson and repeated measure ANOVA tests. Baseline serum BDNF level was positively correlated with waist circumference (r=0.383, P=0.012) and showed significant elevation in MetS compared with healthy subjects (1101.66±61.34 vs. 903.72±46.57 pg/mL, P=0.014). After aerobic exercise BDNF level significantly increased in HE, but decreased in ME group (P=0.001). Both short and mid term memory significantly increased (PExercise induced cognitive improvement might be mediated via BDNF-linked mechanisms in healthy people. However, the health status of individuals should be considered.

  14. Part I. Naltrexone-derived conjugate addition ligands for opioid receptors. Part II. Chemical and enantioselective aspects of the metabolism of verapamil

    International Nuclear Information System (INIS)

    Olsen, L.D.

    1987-01-01

    Selective chemoaffinity ligands to aid in identification and purification of opioid receptor subtypes were prepared from 6α- and 6β-naltrexol, obtained stereoselectively from the μ-receptor antagonist naltrexone. The targets were the 6α- and 6β-methacrylate ethers and 6α- and 6β-methacrylate esters prepared from reaction of 6α- and 6β-naltrexol with methyl α-(bromomethyl)acrylate or methacryloyl chloride. Of three methacrylate derivatives, the 6α-ether was the most potent in an opioid receptor binding assay with [ 3 H]-naltrexone. In the presence of sodium ion, preincubation of the 6α-ether resulted in recovery of about 60% of original [ 3 H]-naltrexone binding suggesting some irreversible effects. The methacrylate esters precipitated withdrawal in morphine dependent monkeys. The enantiomers of verapamil, a calcium channel antagonist, have different pharmacological and pharmacokinetic properties. The oxidative metabolism of verapamil was studied in rat and human liver microsomes and in man after a single oral dose

  15. Part I. Naltrexone-derived conjugate addition ligands for opioid receptors. Part II. Chemical and enantioselective aspects of the metabolism of verapamil

    Energy Technology Data Exchange (ETDEWEB)

    Olsen, L.D.

    1987-01-01

    Selective chemoaffinity ligands to aid in identification and purification of opioid receptor subtypes were prepared from 6..cap alpha..- and 6..beta..-naltrexol, obtained stereoselectively from the ..mu..-receptor antagonist naltrexone. The targets were the 6..cap alpha..- and 6..beta..-methacrylate ethers and 6..cap alpha..- and 6..beta..-methacrylate esters prepared from reaction of 6..cap alpha..- and 6..beta..-naltrexol with methyl ..cap alpha..-(bromomethyl)acrylate or methacryloyl chloride. Of three methacrylate derivatives, the 6..cap alpha..-ether was the most potent in an opioid receptor binding assay with (/sup 3/H)-naltrexone. In the presence of sodium ion, preincubation of the 6..cap alpha..-ether resulted in recovery of about 60% of original (/sup 3/H)-naltrexone binding suggesting some irreversible effects. The methacrylate esters precipitated withdrawal in morphine dependent monkeys. The enantiomers of verapamil, a calcium channel antagonist, have different pharmacological and pharmacokinetic properties. The oxidative metabolism of verapamil was studied in rat and human liver microsomes and in man after a single oral dose.

  16. Further studies on the intermediary metabolism of bone in vitro and a monoclonal cell line (MMB-1) derived from bone: effects of parathyroid hormone and acetazolamide

    International Nuclear Information System (INIS)

    Nichols, F.C.

    1981-01-01

    The mechanism/mechanisms by which PTH affects Ca homeostasis between blood and bone have not been clearly established. Most studies of metabolic acid production in bone took place during the late 1950s and early 1960s. Since that time, assay techniques for metabolic acid production have been improved for greater sensitivity, more has been learned as to how PTH mediates its cellular responses, and techniques for cell isolation and culture have dramatically improved. These improvements have made possible new approaches to the study of short term effects of PTH on metabolic acid production in bone. Chapter 1 explores the potential of bone to utilize substrates other than glucose for metabolic energy transfer. Chapter 2 characterizes glucose metabolism in mouse calvaria in vitro and explores effects of PTH, acetazolamide, and C1 13,850 on calvaria oxidative metabolism. Chapter 3 describes PTH effects on glucose metabolism of MMB-1 cells, a monoclonal cell line reported to possess osteoblast-like characteristics

  17. Differences in the expression of xenobiotic-metabolizing enzymes between islets derived from the ventral and dorsal anlage of the pancreas.

    Science.gov (United States)

    Standop, Jens; Ulrich, Alexis B; Schneider, Matthias B; Büchler, Markus W; Pour, Parviz M

    2002-01-01

    Chronic pancreatitis and pancreatic cancer have been linked to the exposure of environmental chemicals (xenobiotics), which generally require metabolic activation to highly reactive toxic or carcinogenic intermediates. The primary enzyme system involved is made up of numerous cytochrome P450 mono-oxygenases (CYP). Glutathione S-transferases (GST) belong to the enzyme systems that catalyze the conjugation of the reactive intermediates produced by CYPs to less toxic or readily excretable metabolites. Because the majority of chronic pancreatitis and pancreatic cancers develop in the organ's head, we compared the expression of selected CYP and GST enzymes between the tissues deriving from the ventral anlage (head) and dorsal anlage (corpus, tail). A total of 20 normal pancreatic tissue specimen from organ donors and early autopsy cases were processed immunohistochemically by using antibodies to CYP 1A1, 1A2, 2B6, 2C8/9/19, 2D6, 2E1, 3A1, 3A2 and 3A4, GST-alpha, GST-mu and GST-pi, and the NADPH cytochrome P450 oxido-reductase (NA-OR), the specificity of which has been verified in our previous study by Western blot and RT-PCR analyses. In all pancreatic regions, most of the enzymes were expressed in islet cells. However, more islets in the head region expressed CYP 2B6, 2C8/9/19, 2E1 and the NA-OR, than those in the body and tail. Moreover, the expression of CYP 2B6 and 2E1 was restricted to the pancreatic polypeptide (PP) cells, and the concentration of CYP 3A1 and 3A4 was stronger in PP cells than in other islet cells. On the other hand, GST-mu and GST-pi were expressed primarily in islet cells of the body and tail. The greater content of xenobiotic-metabolizing and carcinogen-activating CYP enzymes and a lower expression of detoxifying GST enzymes in the head of the pancreas could be one reason for the greater susceptibility of this region for inflammatory and malignant diseases. Copyright 2002 S. Karger AG, Basel and IAP

  18. Icariin reverses corticosterone-induced depression-like behavior, decrease in hippocampal brain-derived neurotrophic factor (BDNF) and metabolic network disturbances revealed by NMR-based metabonomics in rats.

    Science.gov (United States)

    Gong, Meng-Juan; Han, Bin; Wang, Shu-mei; Liang, Sheng-wang; Zou, Zhong-jie

    2016-05-10

    Previously published reports have revealed the antidepressant-like effects of icariin in a chronic mild stress model of depression and in a social defeat stress model in mice. However, the therapeutic effect of icariin in an animal model of glucocorticoid-induced depression remains unclear. This study aimed to investigate antidepressant-like effect and the possible mechanisms of icariin in a rat model of corticosterone (CORT)-induced depression by using a combination of behavioral and biochemical assessments and NMR-based metabonomics. The depression model was established by subcutaneous injections of CORT for 21 consecutive days in rats, as evidenced by reduced sucrose intake and hippocampal brain-derived neurotrophic factor (BDNF) levels, together with an increase in immobility time in a forced swim test (FST). Icariin significantly increased sucrose intake and hippocampal BDNF level and decreased the immobility time in FST in CORT-induced depressive rats, suggesting its potent antidepressant activity. Moreover, metabonomic analysis identified eight, five and three potential biomarkers associated with depression in serum, urine and brain tissue extract, respectively. These biomarkers are primarily involved in energy metabolism, lipid metabolism, amino acid metabolism and gut microbe metabolism. Icariin reversed the pathological process of CORT-induced depression, partially via regulation of the disturbed metabolic pathways. These results provide important mechanistic insights into the protective effects of icariin against CORT-induced depression and metabolic dysfunction. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Advancing Empirical Scholarship to Further Develop Evaluation Theory and Practice

    Science.gov (United States)

    Christie, Christina A.

    2011-01-01

    Good theory development is grounded in empirical inquiry. In the context of educational evaluation, the development of empirically grounded theory has important benefits for the field and the practitioner. In particular, a shift to empirically derived theory will assist in advancing more systematic and contextually relevant evaluation practice, as…

  20. The Metabolic Fate of Deoxynivalenol and Its Acetylated Derivatives in a Wheat Suspension Culture: Identification and Detection of DON-15-O-Glucoside, 15-Acetyl-DON-3-O-Glucoside and 15-Acetyl-DON-3-Sulfate

    Directory of Open Access Journals (Sweden)

    Clemens Schmeitzl

    2015-08-01

    Full Text Available Deoxynivalenol (DON is a protein synthesis inhibitor produced by the Fusarium species, which frequently contaminates grains used for human or animal consumption. We treated a wheat suspension culture with DON or one of its acetylated derivatives, 3-acetyl-DON (3-ADON, 15-acetyl-DON (15-ADON and 3,15-diacetyl-DON (3,15-diADON, and monitored the metabolization over a course of 96 h. Supernatant and cell extract samples were analyzed using a tailored LC-MS/MS method for the quantification of DON metabolites. We report the formation of tentatively identified DON-15-O-β-D-glucoside (D15G and of 15-acetyl-DON-3-sulfate (15-ADON3S as novel deoxynivalenol metabolites in wheat. Furthermore, we found that the recently identified 15-acetyl-DON-3-O-β-D-glucoside (15-ADON3G is the major metabolite produced after 15-ADON challenge. 3-ADON treatment led to a higher intracellular content of toxic metabolites after six hours compared to all other treatments. 3-ADON was exclusively metabolized into DON before phase II reactions occurred. In contrast, we found that 15-ADON was directly converted into 15-ADON3G and 15-ADON3S in addition to metabolization into deoxynivalenol-3-O-β-D-glucoside (D3G. This study highlights significant differences in the metabolization of DON and its acetylated derivatives.

  1. In vivo cardiac glucose metabolism in the high-fat fed mouse: Comparison of euglycemic–hyperinsulinemic clamp derived measures of glucose uptake with a dynamic metabolomic flux profiling approach

    International Nuclear Information System (INIS)

    Kowalski, Greg M.; De Souza, David P.; Risis, Steve; Burch, Micah L.; Hamley, Steven; Kloehn, Joachim; Selathurai, Ahrathy; Lee-Young, Robert S.; Tull, Dedreia; O'Callaghan, Sean; McConville, Malcolm J.; Bruce, Clinton R.

    2015-01-01

    Rationale: Cardiac metabolism is thought to be altered in insulin resistance and type 2 diabetes (T2D). Our understanding of the regulation of cardiac substrate metabolism and insulin sensitivity has largely been derived from ex vivo preparations which are not subject to the same metabolic regulation as in the intact heart in vivo. Studies are therefore required to examine in vivo cardiac glucose metabolism under physiologically relevant conditions. Objective: To determine the temporal pattern of the development of cardiac insulin resistance and to compare with dynamic approaches to interrogate cardiac glucose and intermediary metabolism in vivo. Methods and results: Studies were conducted to determine the evolution of cardiac insulin resistance in C57Bl/6 mice fed a high-fat diet (HFD) for between 1 and 16 weeks. Dynamic in vivo cardiac glucose metabolism was determined following oral administration of [U- 13 C] glucose. Hearts were collected after 15 and 60 min and flux profiling was determined by measuring 13 C mass isotopomers in glycolytic and tricarboxylic acid (TCA) cycle intermediates. Cardiac insulin resistance, determined by euglycemic–hyperinsulinemic clamp, was evident after 3 weeks of HFD. Despite the presence of insulin resistance, in vivo cardiac glucose metabolism following oral glucose administration was not compromised in HFD mice. This contrasts our recent findings in skeletal muscle, where TCA cycle activity was reduced in mice fed a HFD. Similar to our report in muscle, glucose derived pyruvate entry into the TCA cycle in the heart was almost exclusively via pyruvate dehydrogenase, with pyruvate carboxylase mediated anaplerosis being negligible after oral glucose administration. Conclusions: Under experimental conditions which closely mimic the postprandial state, the insulin resistant mouse heart retains the ability to stimulate glucose metabolism. - Highlights: • Insulin clamp was used to determine the evolution of cardiac insulin

  2. In vivo cardiac glucose metabolism in the high-fat fed mouse: Comparison of euglycemic–hyperinsulinemic clamp derived measures of glucose uptake with a dynamic metabolomic flux profiling approach

    Energy Technology Data Exchange (ETDEWEB)

    Kowalski, Greg M., E-mail: greg.kowalski@deakin.edu.au [Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria 3125 (Australia); De Souza, David P. [Metabolomics Australia, Department of Biochemistry and Molecular Biology, Bio21 Institute of Molecular Science and Biotechnology, University of Melbourne, Parkville, Victoria 3010 (Australia); Risis, Steve [Cellular and Molecular Metabolism Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004 (Australia); Burch, Micah L. [Brigham and Women' s Hospital, Department of Medicine, Boston, MA (United States); Hamley, Steven [Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria 3125 (Australia); Kloehn, Joachim [Metabolomics Australia, Department of Biochemistry and Molecular Biology, Bio21 Institute of Molecular Science and Biotechnology, University of Melbourne, Parkville, Victoria 3010 (Australia); Selathurai, Ahrathy [Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria 3125 (Australia); Lee-Young, Robert S. [Cellular and Molecular Metabolism Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004 (Australia); Tull, Dedreia; O' Callaghan, Sean; McConville, Malcolm J. [Metabolomics Australia, Department of Biochemistry and Molecular Biology, Bio21 Institute of Molecular Science and Biotechnology, University of Melbourne, Parkville, Victoria 3010 (Australia); Bruce, Clinton R. [Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria 3125 (Australia)

    2015-08-07

    Rationale: Cardiac metabolism is thought to be altered in insulin resistance and type 2 diabetes (T2D). Our understanding of the regulation of cardiac substrate metabolism and insulin sensitivity has largely been derived from ex vivo preparations which are not subject to the same metabolic regulation as in the intact heart in vivo. Studies are therefore required to examine in vivo cardiac glucose metabolism under physiologically relevant conditions. Objective: To determine the temporal pattern of the development of cardiac insulin resistance and to compare with dynamic approaches to interrogate cardiac glucose and intermediary metabolism in vivo. Methods and results: Studies were conducted to determine the evolution of cardiac insulin resistance in C57Bl/6 mice fed a high-fat diet (HFD) for between 1 and 16 weeks. Dynamic in vivo cardiac glucose metabolism was determined following oral administration of [U-{sup 13}C] glucose. Hearts were collected after 15 and 60 min and flux profiling was determined by measuring {sup 13}C mass isotopomers in glycolytic and tricarboxylic acid (TCA) cycle intermediates. Cardiac insulin resistance, determined by euglycemic–hyperinsulinemic clamp, was evident after 3 weeks of HFD. Despite the presence of insulin resistance, in vivo cardiac glucose metabolism following oral glucose administration was not compromised in HFD mice. This contrasts our recent findings in skeletal muscle, where TCA cycle activity was reduced in mice fed a HFD. Similar to our report in muscle, glucose derived pyruvate entry into the TCA cycle in the heart was almost exclusively via pyruvate dehydrogenase, with pyruvate carboxylase mediated anaplerosis being negligible after oral glucose administration. Conclusions: Under experimental conditions which closely mimic the postprandial state, the insulin resistant mouse heart retains the ability to stimulate glucose metabolism. - Highlights: • Insulin clamp was used to determine the evolution of cardiac

  3. Metabolic Syndrome Derived from Principal Component Analysis and Incident Cardiovascular Events: The Multi Ethnic Study of Atherosclerosis (MESA and Health, Aging, and Body Composition (Health ABC

    Directory of Open Access Journals (Sweden)

    Subhashish Agarwal

    2012-01-01

    Full Text Available Background. The NCEP metabolic syndrome (MetS is a combination of dichotomized interrelated risk factors from predominantly Caucasian populations. We propose a continuous MetS score based on principal component analysis (PCA of the same risk factors in a multiethnic cohort and compare prediction of incident CVD events with NCEP MetS definition. Additionally, we replicated these analyses in the Health, Aging, and Body composition (Health ABC study cohort. Methods and Results. We performed PCA of the MetS elements (waist circumference, HDL, TG, fasting blood glucose, SBP, and DBP in 2610 Caucasian Americans, 801 Chinese Americans, 1875 African Americans, and 1494 Hispanic Americans in the multiethnic study of atherosclerosis (MESA cohort. We selected the first principal component as a continuous MetS score (MetS-PC. Cox proportional hazards models were used to examine the association between MetS-PC and 5.5 years of CVD events (n=377 adjusting for age, gender, race, smoking and LDL-C, overall and by ethnicity. To facilitate comparison of MetS-PC with the binary NCEP definition, a MetS-PC cut point was chosen to yield the same 37% prevalence of MetS as the NCEP definition (37% in the MESA cohort. Hazard ratio (HR for CVD events were estimated using the NCEP and Mets-PC-derived binary definitions. In Cox proportional models, the HR (95% CI for CVD events for 1-SD (standard deviation of MetS-PC was 1.71 (1.54–1.90 (P<0.0001 overall after adjusting for potential confounders, and for each ethnicity, HRs were: Caucasian, 1.64 (1.39–1.94, Chinese, 1.39 (1.06–1.83, African, 1.67 (1.37–2.02, and Hispanic, 2.10 (1.66-2.65. Finally, when binary definitions were compared, HR for CVD events was 2.34 (1.91–2.87 for MetS-PC versus 1.79 (1.46–2.20 for NCEP MetS. In the Health ABC cohort, in a fully adjusted model, MetS-PC per 1-SD (Health ABC remained associated with CVD events (HR=1.21, 95%CI 1.12–1.32 overall, and for each ethnicity, Caucasian (HR

  4. Metabolic Syndrome Derived from Principal Component Analysis and Incident Cardiovascular Events: The Multi Ethnic Study of Atherosclerosis (MESA) and Health, Aging, and Body Composition (Health ABC).

    Science.gov (United States)

    Agarwal, Subhashish; Jacobs, David R; Vaidya, Dhananjay; Sibley, Christopher T; Jorgensen, Neal W; Rotter, Jerome I; Chen, Yii-Der Ida; Liu, Yongmei; Andrews, Jeanette S; Kritchevsky, Stephen; Goodpaster, Bret; Kanaya, Alka; Newman, Anne B; Simonsick, Eleanor M; Herrington, David M

    2012-01-01

    Background. The NCEP metabolic syndrome (MetS) is a combination of dichotomized interrelated risk factors from predominantly Caucasian populations. We propose a continuous MetS score based on principal component analysis (PCA) of the same risk factors in a multiethnic cohort and compare prediction of incident CVD events with NCEP MetS definition. Additionally, we replicated these analyses in the Health, Aging, and Body composition (Health ABC) study cohort. Methods and Results. We performed PCA of the MetS elements (waist circumference, HDL, TG, fasting blood glucose, SBP, and DBP) in 2610 Caucasian Americans, 801 Chinese Americans, 1875 African Americans, and 1494 Hispanic Americans in the multiethnic study of atherosclerosis (MESA) cohort. We selected the first principal component as a continuous MetS score (MetS-PC). Cox proportional hazards models were used to examine the association between MetS-PC and 5.5 years of CVD events (n = 377) adjusting for age, gender, race, smoking and LDL-C, overall and by ethnicity. To facilitate comparison of MetS-PC with the binary NCEP definition, a MetS-PC cut point was chosen to yield the same 37% prevalence of MetS as the NCEP definition (37%) in the MESA cohort. Hazard ratio (HR) for CVD events were estimated using the NCEP and Mets-PC-derived binary definitions. In Cox proportional models, the HR (95% CI) for CVD events for 1-SD (standard deviation) of MetS-PC was 1.71 (1.54-1.90) (P definitions were compared, HR for CVD events was 2.34 (1.91-2.87) for MetS-PC versus 1.79 (1.46-2.20) for NCEP MetS. In the Health ABC cohort, in a fully adjusted model, MetS-PC per 1-SD (Health ABC) remained associated with CVD events (HR = 1.21, 95%CI 1.12-1.32) overall, and for each ethnicity, Caucasian (HR = 1.24, 95%CI 1.12-1.39) and African Americans (HR = 1.16, 95%CI 1.01-1.32). Finally, when using a binary definition of MetS-PC (cut point 0.505) designed to match the NCEP definition in terms of prevalence in the Health ABC cohort (35

  5. Comparative metabolism of [14C]benzene to excretable products and bioactivation to DNA-binding derivatives in maternal and neonatal mice

    International Nuclear Information System (INIS)

    Iba, M.M.; Ghosal, A.; Snyder, R.

    2001-01-01

    Lactating adult female mice treated with a single dose of 880 mg/kg i.p. [ 14 C]benzene, and their 2-day-old sucklings similarly treated or nursed by their treated dams were compared in terms of their ability to metabolize benzene to urinary products or reactive intermediates as assessed by covalently-bound benzene derivatives in whole blood or liver DNA. Six metabolite fractions were identified in the urine of sucklings by high performance liquid chromatographic (HPLC) analysis at 5 h following intraperitoneal (direct) treatment with benzene. Three of the metabolite fractions co-chromatographed with authentic phenol, phenyl glucuronide, and muconic acid, and contributed 11, 6.9 and 0.6%, respectively, to the total urinary benzene metabolites. Two of the fractions were unidentified. The sixth and most polar fraction consisted of multiple metabolites, 21% of which were conjugates, and accounted for 72% of the total urinary metabolites. A similar metabolite profile was observed in 24-h urine samples from treated dams with the exception that one of the unidentified fractions in the sucklings was absent and levels of the metabolites were quantitatively higher than those observed in sucklings 5 h following their treatment with benzene. Furthermore, 78% of the most polar fraction from the dams consisted of conjugates compared with 21% of that from the sucklings. The metabolite pattern in urine of sucklings nursed by treated dams was qualitatively similar to, but quantitatively different from the pattern in treated dams. Five hours following intraperitoneal treatment with benzene, covalent binding of the compound to DNA (expressed as pmol benzene equivalents/mg DNA) in sucklings was slightly higher in whole blood (1.15±0.07) than in liver (0.77±0.07), whereas in the dam, it was slightly lower in whole blood (0.88±0.48) than in liver (1.63±0.61). Twenty four hours following benzene exposure in sucklings of benzene-treated dams, DNA binding by the compound in whole

  6. Empirical Test Case Specification

    DEFF Research Database (Denmark)

    Kalyanova, Olena; Heiselberg, Per

    This document includes the empirical specification on the IEA task of evaluation building energy simulation computer programs for the Double Skin Facades (DSF) constructions. There are two approaches involved into this procedure, one is the comparative approach and another is the empirical one. I....... In the comparative approach the outcomes of different software tools are compared, while in the empirical approach the modelling results are compared with the results of experimental test cases....

  7. Detoxification of ammonia in mouse cortical GABAergic cell cultures increases neuronal oxidative metabolism and reveals an emerging role for release of glucose-derived alanine

    DEFF Research Database (Denmark)

    Leke, Renata; Bak, Lasse Kristoffer; Anker, Malene

    2011-01-01

    Cerebral hyperammonemia is believed to play a pivotal role in the development of hepatic encephalopathy (HE), a debilitating condition arising due to acute or chronic liver disease. In the brain, ammonia is thought to be detoxified via the activity of glutamine synthetase, an astrocytic enzyme....... Moreover, it has been suggested that cerebral tricarboxylic acid (TCA) cycle metabolism is inhibited and glycolysis enhanced during hyperammonemia. The aim of this study was to characterize the ammonia-detoxifying mechanisms as well as the effects of ammonia on energy-generating metabolic pathways...... in a mouse neuronal-astrocytic co-culture model of the GABAergic system. We found that 5 mM ammonium chloride affected energy metabolism by increasing the neuronal TCA cycle activity and switching the astrocytic TCA cycle toward synthesis of substrate for glutamine synthesis. Furthermore, ammonia exposure...

  8. Spirulina platensis Improves Mitochondrial Function Impaired by Elevated Oxidative Stress in Adipose-Derived Mesenchymal Stromal Cells (ASCs) and Intestinal Epithelial Cells (IECs), and Enhances Insulin Sensitivity in Equine Metabolic Syndrome (EMS) Horses.

    Science.gov (United States)

    Nawrocka, Daria; Kornicka, Katarzyna; Śmieszek, Agnieszka; Marycz, Krzysztof

    2017-08-03

    Equine Metabolic Syndrome (EMS) is a steadily growing life-threatening endocrine disorder linked to insulin resistance, oxidative stress, and systemic inflammation. Inflammatory microenvironment of adipose tissue constitutes the direct tissue milieu for various cell populations, including adipose-derived mesenchymal stromal cells (ASCs), widely considered as a potential therapeutic cell source in the course of the treatment of metabolic disorders. Moreover, elevated oxidative stress induces inflammation in intestinal epithelial cells (IECs)-the first-line cells exposed to dietary compounds. In the conducted research, we showed that in vitro application of Spirulina platensis contributes to the restoration of ASCs' and IECs' morphology and function through the reduction of cellular oxidative stress and inflammation. Enhanced viability, suppressed senescence, and improved proliferation of ASCs and IECs isolated from metabolic syndrome-affected individuals were evident following exposition to Spirulina. A protective effect of the investigated extract against mitochondrial dysfunction and degeneration was also observed. Moreover, our data demonstrate that Spirulina extract effectively suppressed LPS-induced inflammatory responses in macrophages. In vivo studies showed that horses fed with a diet based on Spirulina platensis supplementation lost weight and their insulin sensitivity improved. Thus, our results indicate the engagement of Spirulina platensis nourishing as an interesting alternative approach for supporting the conventional treatment of equine metabolic syndrome.

  9. Comparison of the effect of cortisol on aromatase activity and androgen metabolism in two human fibroblast cell lines derived from the same individual

    DEFF Research Database (Denmark)

    Svenstrup, B; Brünner, N; Dombernowsky, P

    1990-01-01

    The effect of preincubation with cortisol on estrogen and androgen metabolism was investigated in human fibroblast monolayers grown from biopsies of genital and non-genital skin of the same person. The activity in the cells of aromatase, 5 alpha-reductase, 17 beta-hydroxysteroid oxidoreductase.......5-1.0 x 10(-6) M in both cell lines. When preincubation with cortisol was omitted no estrogen synthesis was detected. The formation of androgen was not altered after preincubation with cortisol. Pronounced differences were found in estrogen and in androgen metabolism in the two cell lines suggesting...

  10. Synthesis of benzo[b]fluoranthene derivatives and their application in research on the metabolic activation of benzo[b]fluoranthene

    International Nuclear Information System (INIS)

    Amin, S.; Huie, K.; Hussain, N.; Balanikas, G.; Geddie, J.E.; LaVoie, E.J.; Hecht, S.S.

    1986-01-01

    Our earlier studies on benzo[b]fluoranthene (BbF) have shown that dihydrodiols and phenols are formed metabolically in rat liver and mouse skin. The dihydrodiols were identified by comparison to synthetic standards as 1,2-dihydro-1,2-dihydroxyBbF and 11,12-dihydro-11,12-dihydroxyBbF. In the present study, the authors developed syntheses for BbF phenols and have used these standards to identify the metabolically formed phenols. In addition, they have prepared several methylated analogs of BbF and have tested their activities as tumor initiators on mouse skin

  11. Empirical Philosophy of Science

    DEFF Research Database (Denmark)

    Mansnerus, Erika; Wagenknecht, Susann

    2015-01-01

    knowledge takes place through the integration of the empirical or historical research into the philosophical studies, as Chang, Nersessian, Thagard and Schickore argue in their work. Building upon their contributions we will develop a blueprint for an Empirical Philosophy of Science that draws upon...... qualitative methods from the social sciences in order to advance our philosophical understanding of science in practice. We will regard the relationship between philosophical conceptualization and empirical data as an iterative dialogue between theory and data, which is guided by a particular ‘feeling with......Empirical insights are proven fruitful for the advancement of Philosophy of Science, but the integration of philosophical concepts and empirical data poses considerable methodological challenges. Debates in Integrated History and Philosophy of Science suggest that the advancement of philosophical...

  12. Detoxification of ammonia in mouse cortical GABAergic cell cultures increases neuronal oxidative metabolism and reveals an emerging role for release of glucose-derived alanine.

    Science.gov (United States)

    Leke, Renata; Bak, Lasse K; Anker, Malene; Melø, Torun M; Sørensen, Michael; Keiding, Susanne; Vilstrup, Hendrik; Ott, Peter; Portela, Luis V; Sonnewald, Ursula; Schousboe, Arne; Waagepetersen, Helle S

    2011-04-01

    Cerebral hyperammonemia is believed to play a pivotal role in the development of hepatic encephalopathy (HE), a debilitating condition arising due to acute or chronic liver disease. In the brain, ammonia is thought to be detoxified via the activity of glutamine synthetase, an astrocytic enzyme. Moreover, it has been suggested that cerebral tricarboxylic acid (TCA) cycle metabolism is inhibited and glycolysis enhanced during hyperammonemia. The aim of this study was to characterize the ammonia-detoxifying mechanisms as well as the effects of ammonia on energy-generating metabolic pathways in a mouse neuronal-astrocytic co-culture model of the GABAergic system. We found that 5 mM ammonium chloride affected energy metabolism by increasing the neuronal TCA cycle activity and switching the astrocytic TCA cycle toward synthesis of substrate for glutamine synthesis. Furthermore, ammonia exposure enhanced the synthesis and release of alanine. Collectively, our results demonstrate that (1) formation of glutamine is seminal for detoxification of ammonia; (2) neuronal oxidative metabolism is increased in the presence of ammonia; and (3) synthesis and release of alanine is likely to be important for ammonia detoxification as a supplement to formation of glutamine.

  13. The Role of Glucose, Serum, and Three-Dimensional Cell Culture on the Metabolism of Bone Marrow-Derived Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Byron Deorosan

    2011-01-01

    factors in the metabolic response of the cells. However, cells cultured in low density collagen exhibited considerable cell death, likely because of physical contraction of the collagen hydrogel which was not observed in the higher density collagen. These findings will be useful to the development of in vitro cell culture models that properly mimic in vivo physiological processes.

  14. Circadian control of p75 neurotrophin receptor leads to alternate activation of Nrf2 and c-Rel to reset energy metabolism in astrocytes via brain-derived neurotrophic factor.

    Science.gov (United States)

    Ishii, Tetsuro; Warabi, Eiji; Mann, Giovanni E

    2018-05-01

    Circadian clock genes regulate energy metabolism partly through neurotrophins in the body. The low affinity neurotrophin receptor p75 NTR is a clock component directly regulated by the transcriptional factor Clock:Bmal1 complex. Brain-derived neurotrophic factor (BDNF) is expressed in the brain and plays a key role in coordinating metabolic interactions between neurons and astrocytes. BDNF transduces signals through TrkB and p75 NTR receptors. This review highlights a novel molecular mechanism by which BDNF via circadian control of p75 NTR leads to daily resetting of glucose and glycogen metabolism in brain astrocytes to accommodate their functional interaction with neurons. Astrocytes store glycogen as an energy reservoir to provide active neurons with the glycolytic metabolite lactate. Astrocytes predominantly express the truncated receptor TrkB.T1 which lacks an intracellular receptor tyrosine kinase domain. TrkB.T1 retains the capacity to regulate cell morphology through regulation of Rho GTPases. In contrast, p75 NTR mediates generation of the bioactive lipid ceramide upon stimulation with BDNF and inhibits PKA activation. As ceramide directly activates PKCζ, we discuss the importance of the TrkB.T1-p75 NTR -ceramide-PKCζ signaling axis in the stimulation of glycogen and lipid synthesis and activation of RhoA. Ceramide-PKCζ-casein kinase 2 signaling activates Nrf2 to support oxidative phosphorylation via upregulation of antioxidant enzymes. In the absence of p75 NTR , TrkB.T1 functionally interacts with adenosine A 2A R and dopamine D1R receptors to enhance cAMP-PKA signaling and activate Rac1 and NF-κB c-Rel, favoring glycogen hydrolysis, gluconeogenesis and aerobic glycolysis. Thus, diurnal changes in p75 NTR levels in astrocytes resets energy metabolism via BDNF to accommodate their metabolic interaction with neurons. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Intracellular trafficking of the free cholesterol derived from LDL cholesteryl ester is defective in vivo in Niemann-Pick C disease: insights on normal metabolism of HDL and LDL gained from the NP-C mutation.

    Science.gov (United States)

    Shamburek, R D; Pentchev, P G; Zech, L A; Blanchette-Mackie, J; Carstea, E D; VandenBroek, J M; Cooper, P S; Neufeld, E B; Phair, R D; Brewer, H B; Brady, R O; Schwartz, C C

    1997-12-01

    Niemann-Pick C disease (NP-C) is a rare inborn error of metabolism with hepatic involvement and neurological sequelae that usually manifest in childhood. Although in vitro studies have shown that the lysosomal distribution of LDL-derived cholesterol is defective in cultured cells of NP-C subjects, no unusual characteristics mark the plasma lipoprotein profiles. We set out to determine whether anomalies exist in vivo in the cellular distribution of newly synthesized, HDL-derived or LDL-derived cholesterol under physiologic conditions in NP-C subjects. Three affected and three normal male subjects were administered [14C]mevalonate as a tracer of newly synthesized cholesterol and [3H]cholesteryl linoleate in either HDL or LDL to trace the distribution of lipoprotein-derived free cholesterol. The rate of appearance of free [14C]- and free [3H]cholesterol in the plasma membrane was detected indirectly by monitoring their appearance in plasma and bile. The plasma disappearance of [3H]cholesteryl linoleate was slightly faster in NP-C subjects regardless of its lipoprotein origin. Appearance of free [14C] cholesterol ill the plasma (and in bile) was essentially identical in normal and affected individuals as was the initial appearance of free [3H]cholesterol derived from HDL, observed before extensive exchange occurred of the [3H]cholesteryl linoleate among lipoproteins. In contrast, the rate of appearance of LDL-derived free [3H]cholesterol in the plasma membrane of NP-C subjects, as detected in plasma and bile, was retarded to a similar extent that LDL cholesterol metabolism was defective in cultured fibroblasts of these affected subjects. These findings show that intracellular distribution of both newly synthesized and HDL-derived cholesterol are essentially unperturbed by the NP-C mutation, and therefore occur by lysosomal-independent paths. In contrast, in NP-C there is defective trafficking of LDL-derived cholesterol to the plasma membrane in vivo as well as in vitro

  16. Life Writing After Empire

    DEFF Research Database (Denmark)

    A watershed moment of the twentieth century, the end of empire saw upheavals to global power structures and national identities. However, decolonisation profoundly affected individual subjectivities too. Life Writing After Empire examines how people around the globe have made sense of the post...... in order to understand how individual life writing reflects broader societal changes. From far-flung corners of the former British Empire, people have turned to life writing to manage painful or nostalgic memories, as well as to think about the past and future of the nation anew through the personal...

  17. Theological reflections on empire

    Directory of Open Access Journals (Sweden)

    Allan A. Boesak

    2009-11-01

    Full Text Available Since the meeting of the World Alliance of Reformed Churches in Accra, Ghana (2004, and the adoption of the Accra Declaration, a debate has been raging in the churches about globalisation, socio-economic justice, ecological responsibility, political and cultural domination and globalised war. Central to this debate is the concept of empire and the way the United States is increasingly becoming its embodiment. Is the United States a global empire? This article argues that the United States has indeed become the expression of a modern empire and that this reality has considerable consequences, not just for global economics and politics but for theological refl ection as well.

  18. Environmental and nutritional factors that affect growth and metabolism of the pneumococcal serotype 2 strain D39 and its nonencapsulated derivative strain R6.

    Directory of Open Access Journals (Sweden)

    Sandra M Carvalho

    Full Text Available Links between carbohydrate metabolism and virulence in Streptococcus pneumoniae have been recurrently established. To investigate these links further we developed a chemically defined medium (CDM and standardized growth conditions that allowed for high growth yields of the related pneumococcal strains D39 and R6. The utilization of the defined medium enabled the evaluation of different environmental and nutritional factors on growth and fermentation patterns under controlled conditions of pH, temperature and gas atmosphere. The same growth conditions impacted differently on the nonencapsulated R6, and its encapsulated progenitor D39. A semi-aerobic atmosphere and a raised concentration of uracil, a fundamental component of the D39 capsule, improved considerably D39 growth rate and biomass. In contrast, in strain R6, the growth rate was enhanced by strictly anaerobic conditions and uracil had no effect on biomass. In the presence of oxygen, the difference in the growth rates was mainly attributed to a lower activity of pyruvate oxidase in strain D39. Our data indicate an intricate connection between capsule production in strain D39 and uracil availability. In this study, we have also successfully applied the in vivo NMR technique to study sugar metabolism in S. pneumoniae R6. Glucose consumption, end-products formation and evolution of intracellular metabolite pools were monitored online by (13C-NMR. Additionally, the pools of NTP and inorganic phosphate were followed by (31P-NMR after a pulse of glucose. These results represent the first metabolic profiling data obtained non-invasively for S. pneumoniae, and pave the way to a better understanding of regulation of central metabolism.

  19. Effect of Vegan Fecal Microbiota Transplantation on Carnitine- and Choline-Derived Trimethylamine-N-Oxide Production and Vascular Inflammation in Patients With Metabolic Syndrome.

    Science.gov (United States)

    Smits, Loek P; Kootte, Ruud S; Levin, Evgeni; Prodan, Andrei; Fuentes, Susana; Zoetendal, Erwin G; Wang, Zeneng; Levison, Bruce S; Cleophas, Maartje C P; Kemper, E Marleen; Dallinga-Thie, Geesje M; Groen, Albert K; Joosten, Leo A B; Netea, Mihai G; Stroes, Erik S G; de Vos, Willem M; Hazen, Stanley L; Nieuwdorp, Max

    2018-03-26

    Intestinal microbiota have been found to be linked to cardiovascular disease via conversion of the dietary compounds choline and carnitine to the atherogenic metabolite TMAO (trimethylamine-N-oxide). Specifically, a vegan diet was associated with decreased plasma TMAO levels and nearly absent TMAO production on carnitine challenge. We performed a double-blind randomized controlled pilot study in which 20 male metabolic syndrome patients were randomized to single lean vegan-donor or autologous fecal microbiota transplantation. At baseline and 2 weeks thereafter, we determined the ability to produce TMAO from d 6 -choline and d 3 -carnitine (eg, labeled and unlabeled TMAO in plasma and 24-hour urine after oral ingestion of 250 mg of both isotope-labeled precursor nutrients), and fecal samples were collected for analysis of microbiota composition. 18 F-fluorodeoxyglucose positron emission tomography/computed tomography scans of the abdominal aorta, as well as ex vivo peripheral blood mononuclear cell cytokine production assays, were performed. At baseline, fecal microbiota composition differed significantly between vegans and metabolic syndrome patients. With vegan-donor fecal microbiota transplantation, intestinal microbiota composition in metabolic syndrome patients, as monitored by global fecal microbial community structure, changed toward a vegan profile in some of the patients; however, no functional effects from vegan-donor fecal microbiota transplantation were seen on TMAO production, abdominal aortic 18 F-fluorodeoxyglucose uptake, or ex vivo cytokine production from peripheral blood mononuclear cells. Single lean vegan-donor fecal microbiota transplantation in metabolic syndrome patients resulted in detectable changes in intestinal microbiota composition but failed to elicit changes in TMAO production capacity or parameters related to vascular inflammation. URL: http://www.trialregister.nl. Unique identifier: NTR 4338. © 2018 The Authors. Published on

  20. Classification of Marital Relationships: An Empirical Approach.

    Science.gov (United States)

    Snyder, Douglas K.; Smith, Gregory T.

    1986-01-01

    Derives an empirically based classification system of marital relationships, employing a multidimensional self-report measure of marital interaction. Spouses' profiles on the Marital Satisfaction Inventory for samples of clinic and nonclinic couples were subjected to cluster analysis, resulting in separate five-group typologies for husbands and…

  1. Empirical Evidence from Kenya

    African Journals Online (AJOL)

    FIRST LADY

    2011-01-18

    Jan 18, 2011 ... Empirical results reveal that consumption of sugar in. Kenya varies ... experiences in trade in different regions of the world. Some studies ... To assess the relationship between domestic sugar retail prices and sugar sales in ...

  2. Mathematical modelling of metabolism

    DEFF Research Database (Denmark)

    Gombert, Andreas Karoly; Nielsen, Jens

    2000-01-01

    Mathematical models of the cellular metabolism have a special interest within biotechnology. Many different kinds of commercially important products are derived from the cell factory, and metabolic engineering can be applied to improve existing production processes, as well as to make new processes...... availability of genomic information and powerful analytical techniques, mathematical models also serve as a tool for understanding the cellular metabolism and physiology....... available. Both stoichiometric and kinetic models have been used to investigate the metabolism, which has resulted in defining the optimal fermentation conditions, as well as in directing the genetic changes to be introduced in order to obtain a good producer strain or cell line. With the increasing...

  3. The position of imidazopyridine and metabolic activation are pivotal factors in the antimutagenic activity of novel imidazo[1,2-a]pyridine derivatives.

    Science.gov (United States)

    El-Sayed, Wael M; Hussin, Warda A; Al-Faiyz, Yasair S; Ismail, Mohamed A

    2013-09-05

    The antimutagenic activity of eight novel imidazo[1,2-a]pyridine derivatives (I-VIII) against sodium azide (NaN3) and benzo[a]pyrene (B[a]P) was evaluated using the Salmonella reverse mutation assay. At non-toxic concentrations (12.5-50 µM), imidazopyridines I, II, III, and V with a terminal imidazopyridine group were mutagenic, while derivatives VII and VIII with a central imidazopyridine group were not mutagenic. Compounds IV, VII, and VIII exerted a moderate antimutagenic activity against NaN3 under pre-exposure conditions, and a strong activity (>40%) against B[a]P in the presence of S9 under both pre- and co-exposure conditions and mostly independent on the dose. Imidazopyridines possibly inhibited the microsomal-dependent activation of B[a]P. The demethylated derivative VII was the most active antimutagen. All imidazopyridines had a low to moderate antioxidant activity. The antibacterial activity of imidazopyridines was sporadic and moderate probably due to the failure of bacteria to convert imidazopyridines into active metabolites. The position of imidazopyridine was a pivotal factor in the mutagenic/antimutagenic activity. The strong antimutagenic compounds were dicationic planar compounds with a centered imidazo[1,2-a]pyridine spacer. With LD50 of 60 mg/kg in mice for both derivatives VII and VIII, it is safe to investigate the anticancer activity of these derivatives in animal models. © 2013 Elsevier B.V. All rights reserved.

  4. Retention of tritium in reference persons: a metabolic model. Derivation of parameters and application of the model to the general public and to workers

    International Nuclear Information System (INIS)

    Galeriu, D; Melintescu, A

    2010-01-01

    Tritium ( 3 H) is a radioactive isotope of hydrogen that is ubiquitous in environmental and biological systems. Following debate on the human health risk from exposure to tritium, there have been claims that the current biokinetic model recommended by the International Commission on Radiological Protection (ICRP) may underestimate tritium doses. A new generic model for tritium in mammals, based on energy metabolism and body composition, together with all its input data, has been described in a recent paper and successfully tested for farm and laboratory mammals. That model considers only dietary intake of tritium and was extended to humans. This paper presents the latest development of the human model with explicit consideration of brain energy metabolism. Model testing with human experimental data on organically bound tritium (OBT) in urine after tritiated water (HTO) or OBT intakes is presented. Predicted absorbed doses show a moderate increase for OBT intakes compared with doses recommended by the ICRP. Infants have higher tritium retention-a factor of 2 longer than the ICRP estimate. The highest tritium concentration is in adipose tissue, which has a very low radiobiological sensitivity. The ranges of uncertainty in retention and doses are investigated. The advantage of the new model is its ability to be applied to the interpretation of bioassay data.

  5. Retention of tritium in reference persons: a metabolic model. Derivation of parameters and application of the model to the general public and to workers

    Energy Technology Data Exchange (ETDEWEB)

    Galeriu, D; Melintescu, A, E-mail: galdan@ifin.nipne.r, E-mail: dangaler@yahoo.co [' Horia Hulubei' National Institute for Physics and Nuclear Engineering, Department of Life and Environmental Physics, 407 Atomistilor Street, Bucharest-Magurele, POB MG-6, RO-077125 (Romania)

    2010-09-15

    Tritium ({sup 3}H) is a radioactive isotope of hydrogen that is ubiquitous in environmental and biological systems. Following debate on the human health risk from exposure to tritium, there have been claims that the current biokinetic model recommended by the International Commission on Radiological Protection (ICRP) may underestimate tritium doses. A new generic model for tritium in mammals, based on energy metabolism and body composition, together with all its input data, has been described in a recent paper and successfully tested for farm and laboratory mammals. That model considers only dietary intake of tritium and was extended to humans. This paper presents the latest development of the human model with explicit consideration of brain energy metabolism. Model testing with human experimental data on organically bound tritium (OBT) in urine after tritiated water (HTO) or OBT intakes is presented. Predicted absorbed doses show a moderate increase for OBT intakes compared with doses recommended by the ICRP. Infants have higher tritium retention-a factor of 2 longer than the ICRP estimate. The highest tritium concentration is in adipose tissue, which has a very low radiobiological sensitivity. The ranges of uncertainty in retention and doses are investigated. The advantage of the new model is its ability to be applied to the interpretation of bioassay data.

  6. Psychological Models of Art Reception must be Empirically Grounded

    DEFF Research Database (Denmark)

    Nadal, Marcos; Vartanian, Oshin; Skov, Martin

    2017-01-01

    We commend Menninghaus et al. for tackling the role of negative emotions in art reception. However, their model suffers from shortcomings that reduce its applicability to empirical studies of the arts: poor use of evidence, lack of integration with other models, and limited derivation of testable...... hypotheses. We argue that theories about art experiences should be based on empirical evidence....

  7. MRO CRISM TARGETED EMPIRICAL RECORD V1.0

    Data.gov (United States)

    National Aeronautics and Space Administration — This volume contains the CRISM Targeted Empirical Record (TER) archive, a collection of multiband image cubes derived from targeted (gimbaled) observations of Mars'...

  8. Empirical philosophy of science

    DEFF Research Database (Denmark)

    Wagenknecht, Susann; Nersessian, Nancy J.; Andersen, Hanne

    2015-01-01

    A growing number of philosophers of science make use of qualitative empirical data, a development that may reconfigure the relations between philosophy and sociology of science and that is reminiscent of efforts to integrate history and philosophy of science. Therefore, the first part...... of this introduction to the volume Empirical Philosophy of Science outlines the history of relations between philosophy and sociology of science on the one hand, and philosophy and history of science on the other. The second part of this introduction offers an overview of the papers in the volume, each of which...... is giving its own answer to questions such as: Why does the use of qualitative empirical methods benefit philosophical accounts of science? And how should these methods be used by the philosopher?...

  9. Empire vs. Federation

    DEFF Research Database (Denmark)

    Gravier, Magali

    2011-01-01

    The article discusses the concepts of federation and empire in the context of the European Union (EU). Even if these two concepts are not usually contrasted to one another, the article shows that they refer to related type of polities. Furthermore, they can be used at a time because they shed light...... on different and complementary aspects of the European integration process. The article concludes that the EU is at the crossroads between federation and empire and may remain an ‘imperial federation’ for several decades. This could mean that the EU is on the verge of transforming itself to another type...

  10. Empirical comparison of theories

    International Nuclear Information System (INIS)

    Opp, K.D.; Wippler, R.

    1990-01-01

    The book represents the first, comprehensive attempt to take an empirical approach for comparative assessment of theories in sociology. The aims, problems, and advantages of the empirical approach are discussed in detail, and the three theories selected for the purpose of this work are explained. Their comparative assessment is performed within the framework of several research projects, which among other subjects also investigate the social aspects of the protest against nuclear power plants. The theories analysed in this context are the theory of mental incongruities and that of the benefit, and their efficiency in explaining protest behaviour is compared. (orig./HSCH) [de

  11. Empirical Music Aesthetics

    DEFF Research Database (Denmark)

    Grund, Cynthia M.

    The toolbox for empirically exploring the ways that artistic endeavors convey and activate meaning on the part of performers and audiences continues to expand. Current work employing methods at the intersection of performance studies, philosophy, motion capture and neuroscience to better understand...... musical performance and reception is inspired by traditional approaches within aesthetics, but it also challenges some of the presuppositions inherent in them. As an example of such work I present a research project in empirical music aesthetics begun last year and of which I am a team member....

  12. Empirical research through design

    NARCIS (Netherlands)

    Keyson, D.V.; Bruns, M.

    2009-01-01

    This paper describes the empirical research through design method (ERDM), which differs from current approaches to research through design by enforcing the need for the designer, after a series of pilot prototype based studies, to a-priori develop a number of testable interaction design hypothesis

  13. Essays in empirical microeconomics

    NARCIS (Netherlands)

    Péter, A.N.

    2016-01-01

    The empirical studies in this thesis investigate various factors that could affect individuals' labor market, family formation and educational outcomes. Chapter 2 focuses on scheduling as a potential determinant of individuals' productivity. Chapter 3 looks at the role of a family factor on

  14. Worship, Reflection, Empirical Research

    OpenAIRE

    Ding Dong,

    2012-01-01

    In my youth, I was a worshipper of Mao Zedong. From the latter stage of the Mao Era to the early years of Reform and Opening, I began to reflect on Mao and the Communist Revolution he launched. In recent years I’ve devoted myself to empirical historical research on Mao, seeking the truth about Mao and China’s modern history.

  15. Trade and Empire

    DEFF Research Database (Denmark)

    Bang, Peter Fibiger

    2007-01-01

    This articles seeks to establish a new set of organizing concepts for the analysis of the Roman imperial economy from Republic to late antiquity: tributary empire, port-folio capitalism and protection costs. Together these concepts explain better economic developments in the Roman world than the...

  16. Empirically sampling Universal Dependencies

    DEFF Research Database (Denmark)

    Schluter, Natalie; Agic, Zeljko

    2017-01-01

    Universal Dependencies incur a high cost in computation for unbiased system development. We propose a 100% empirically chosen small subset of UD languages for efficient parsing system development. The technique used is based on measurements of model capacity globally. We show that the diversity o...

  17. Biochemical and ultrastructural analysis of β-VLDL and AC-LDL metabolism by pigeon monocyte-derived macrophages in culture

    International Nuclear Information System (INIS)

    Henson, D.A.

    1987-01-01

    It is proposed that monocyte-derived foam cells in atherosclerotic lesions of White Carneau pigeons become lipid-filled through the uptake of lipoproteins including β-migrating very low density lipoproteins (β-VLDL) and acetylated low density lipoproteins (Ac-LDL). Using iodinated forms of the above lipoproteins, specific and saturable receptors for both β-VLDL and Ac-LDL were detected on the surface of White Carneau pigeon monocyte-derived macrophages in culture. Competition studies demonstrated the high degree of binding specificity for 125 I-Ac-LDL. Likewise, binding of 125 I-β-VLDL to its receptor was significantly inhibited by excess β-VLDL, however LDL from both hyper- and normocholesterolemic pigeons were also recognized by the receptor. Upon binding of β-VLDL and Ac-LDL to their respective receptors, the lipoproteins were rapidly internalized and delivered to intracellular sites of degradation. As measured by the amount of 14 C-oleate incorporated into cholesteryl 14 C-oleate, the cholesterole liberated from the degradation of both β-VLDL and Ac-LDL stimulated cholesteryl ester synthesis in the pigeon cells. Using lipoproteins conjugated to colloidal gold of visualization with transmission electron microscopy, a major difference in the binding and uptake properties of β-VLDL-Gold and Ac-LDL-Gold was documented

  18. Interaction between Marine-Derived n-3 Long Chain Polyunsaturated Fatty Acids and Uric Acid on Glucose Metabolism and Risk of Type 2 Diabetes Mellitus: A Case-Control Study.

    Science.gov (United States)

    Li, Kelei; Wu, Kejian; Zhao, Yimin; Huang, Tao; Lou, Dajun; Yu, Xiaomei; Li, Duo

    2015-08-26

    The present case-control study explored the interaction between marine-derived n-3 long chain polyunsaturated fatty acids (n-3 LC PUFAs) and uric acid (UA) on glucose metabolism and risk of type 2 diabetes mellitus (T2DM). Two hundred and eleven healthy subjects in control group and 268 T2DM subjects in case group were included. Plasma phospholipid (PL) fatty acids and biochemical parameters were detected by standard methods. Plasma PL C22:6n-3 was significantly lower in case group than in control group, and was negatively correlated with fasting glucose (r = -0.177, p < 0.001). Higher plasma PL C22:6n-3 was associated with lower risk of T2DM, and the OR was 0.32 (95% confidence interval (CI), 0.12 to 0.80; p = 0.016) for per unit increase of C22:6n-3. UA was significantly lower in case group than in control group. UA was positively correlated with fasting glucose in healthy subjects, but this correlation became negative in T2DM subjects. A significant interaction was observed between C22:6n-3 and UA on fasting glucose (p for interaction = 0.005): the lowering effect of C22:6n-3 was only significant in subjects with a lower level of UA. In conclusion, C22:6n-3 interacts with UA to modulate glucose metabolism.

  19. Integrated empirical ethics: loss of normativity?

    Science.gov (United States)

    van der Scheer, Lieke; Widdershoven, Guy

    2004-01-01

    An important discussion in contemporary ethics concerns the relevance of empirical research for ethics. Specifically, two crucial questions pertain, respectively, to the possibility of inferring normative statements from descriptive statements, and to the danger of a loss of normativity if normative statements should be based on empirical research. Here we take part in the debate and defend integrated empirical ethical research: research in which normative guidelines are established on the basis of empirical research and in which the guidelines are empirically evaluated by focusing on observable consequences. We argue that in our concrete example normative statements are not derived from descriptive statements, but are developed within a process of reflection and dialogue that goes on within a specific praxis. Moreover, we show that the distinction in experience between the desirable and the undesirable precludes relativism. The normative guidelines so developed are both critical and normative: they help in choosing the right action and in evaluating that action. Finally, following Aristotle, we plead for a return to the view that morality and ethics are inherently related to one another, and for an acknowledgment of the fact that moral judgments have their origin in experience which is always related to historical and cultural circumstances.

  20. Autobiography After Empire

    DEFF Research Database (Denmark)

    Rasch, Astrid

    of the collective, but insufficient attention has been paid to how individuals respond to such narrative changes. This dissertation examines the relationship between individual and collective memory at the end of empire through analysis of 13 end of empire autobiographies by public intellectuals from Australia......Decolonisation was a major event of the twentieth century, redrawing maps and impacting on identity narratives around the globe. As new nations defined their place in the world, the national and imperial past was retold in new cultural memories. These developments have been studied at the level......, the Anglophone Caribbean and Zimbabwe. I conceive of memory as reconstructive and social, with individual memory striving to make sense of the past in the present in dialogue with surrounding narratives. By examining recurring tropes in the autobiographies, like colonial education, journeys to the imperial...

  1. Gazprom: the new empire

    International Nuclear Information System (INIS)

    Guillemoles, A.; Lazareva, A.

    2008-01-01

    Gazprom is conquering the world. The Russian industrial giant owns the hugest gas reserves and enjoys the privilege of a considerable power. Gazprom edits journals, owns hospitals, airplanes and has even built cities where most of the habitants work for him. With 400000 workers, Gazprom represents 8% of Russia's GDP. This inquiry describes the history and operation of this empire and show how its has become a masterpiece of the government's strategy of russian influence reconquest at the world scale. Is it going to be a winning game? Are the corruption affairs and the expected depletion of resources going to weaken the empire? The authors shade light on the political and diplomatic strategies that are played around the crucial dossier of the energy supply. (J.S.)

  2. Use of BMI as marker of adiposity in a metabolic syndrome severity score: derivation and validation in predicting long-term disease outcomes.

    Science.gov (United States)

    Gurka, Matthew J; Filipp, Stephanie L; Musani, Solomon K; Sims, Mario; DeBoer, Mark D

    2018-02-01

    Estimates of adiposity in evaluating the metabolic syndrome (MetS) have traditionally utilized measures of waist circumference (WC), whereas body mass index (BMI) is more commonly used clinically. Our objective was to determine if a MetS severity Z-score employing BMI as its measure of adiposity (MetS-Z-BMI) would perform similarly to a WC-based score (MetS-Z-WC) in predicting future disease. To formulate the MetS-Z-BMI, we performed confirmatory factor analysis on a sex- and race/ethnicity-specific basis on MetS-related data for 6870 adult participants of the National Health and Nutrition Survey 1999-2010. We then validated this score and compared it to MetS-Z-WC in assessing correlations with future coronary heart disease (CHD) and Type 2 diabetes mellitus (T2DM) using Cox proportional hazard analysis of 13,094 participants of the Atherosclerosis Risk in Communities study and Jackson Heart Study. Loading factors, which represent the relative contribution of each component to the latent MetS factor, were lower for BMI than for WC in formulating the two respective scores (MetS-Z-BMI and MetS-Z-WC). Nevertheless, MetS-Z-BMI and MetS-Z-WC exhibited similar hazard ratios (HR) toward future disease. For each one standard-deviation-unit increase in MetS-Z-BMI, HR for CHD was 1.76 (95% confidence interval [CI]: 1.65, 1.88) and HR for T2DM was 3.39 (CI 3.16, 3.63) (both p BMI scores in their associations with future CHD and T2DM. A MetS severity Z-score utilizing BMI as its measure of adiposity operated similarly to a WC-based score in predicting future CHD and T2DM, suggesting overall similarity in MetS-based risk as estimated by both measures of adiposity. This indicates potential clinical usefulness of MetS-Z-BMI in assessing and following MetS-related risk over time. Copyright © 2018. Published by Elsevier Inc.

  3. Phase I metabolism of the carbazole derived synthetic cannabinoids EG-018, EG-2201 and MDMB-CHMCZCA and detection in human urine samples.

    Science.gov (United States)

    Mogler, Lukas; Franz, Florian; Wilde, Maurice; Huppertz, Laura M; Halter, Sebastian; Angerer, Verena; Moosmann, Bjoern; Auwärter, Volker

    2018-05-04

    Synthetic cannabinoids (SCs) are a structurally diverse class of new psychoactive substances. Most SCs used for recreational purposes are based on indole or indazole core structures. EG-018 (naphthalen-1-yl(9-pentyl-9H-carbazol-3-yl)methanone), EG-2201 ((9-(5-fluoropentyl)-9H-carbazol-3-yl)(naphthalen-1-yl)methanone) and MDMB-CHMCZCA (methyl 2-(9-(cyclohexylmethyl)-9H-carbazole-3-carboxamido)-3,3-dimethylbutanoate) are three representatives of a structural subclass of SCs, characterized by a carbazole core system. In vitro and in vivo phase I metabolism studies were conducted to identify the most suitable metabolites for the detection of these substances in urine screening. Detection and characterization of metabolites were performed by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) and liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry (LC-ESI-QToF-MS). Eleven in vivo metabolites were detected in urine samples positive for metabolites of EG-018 (n=8). A hydroxypentyl metabolite, most probably the 4-hydroxypentyl isomer, and an N-dealkylated metabolite mono-hydroxylated at the carbazole core system were most abundant. In vitro studies of EG-018 and EG-2201 indicated that oxidative defluorination of the 5-fluoropentyl side chain of EG-2201 as well as dealkylation led to common metabolites with EG-018. This has to be taken into account for interpretation of analytical findings. A differentiation between EG-018 and EG-2201 (n=1) uptake is possible by the detection of compound-specific in vivo phase I metabolites evaluated in this study. Out of 30 metabolites detected in urine samples of MDMB-CHMCZCA users (n=20), one metabolite mono-hydroxylated at the cyclohexyl methyl tail is considered the most suitable compound-specific consumption marker while a biotransformation product of mono-hydroxylation in combination with hydrolysis of the terminal methyl ester function provides best sensitivity

  4. The metabolism of L-arginine and its significance for the biosynthesis of endothelium-derived relaxing factor: L-glutamine inhibits the generation of L-arginine by cultured endothelial cells

    International Nuclear Information System (INIS)

    Sessa, W.C.; Hecker, M.; Mitchell, J.A.; Vane, J.R.

    1990-01-01

    The mechanism by which L-glutamine (L-Gln) inhibits the release of endothelium-derived factor from bovine aortic cultured endothelial cells was investigated. The intracellular concentration of L-arginine (L-Arg) in Arg-depleted endothelial cells was inversely related to the level of L-Gln. Removal of L-Gln from the culture medium (usually containing L-Gln at 2 mM) abolished the inhibitory effect of the culture medium on L-Arg generation. L-Gln (0.2 and 2 mM) but not D-Gln inhibited the generation of L-Arg by both Arg-depleted and nondepleted endothelial cells. L-Gln did not interfere with the uptake of L-Arg or the metabolism of L-Arg-L-Phe to L-Arg but inhibited the formation of L-Arg from L-citrulline (L-Cit), L-Cit-L-Phe, and N G -monomethyl-L-arginine. L-Gln also inhibited the conversion of L-[ 14 C]Cit to L-[ 14 C]Arg by Arg-depleted endothelial cells. However, L-Gln did not inhibit the conversion of L-argininosuccinic acid to L-Arg by endothelial cell homogenates. Thus, L-Gln interferes with the conversion of L-Cit to L-Arg probably by acting on argininosuccinate synthetase rather than argininosuccinate lyase. L-Gln also inhibited the generation of L-Arg by the monocyte-macrophage cell line J774 but had no effect on the conversion of L-Cit to L-Arg by these cells. As the release of endothelium-derived relaxing factor from cultured and non-cultured endothelial cells is limited by the availability of L-Arg, endogenous L-Gln may play a regulatory role in the biosynthesis of endothelium-derived relaxing factor

  5. Empirical limits to antigravity

    International Nuclear Information System (INIS)

    Ericson, T.E.O.; Richter, A.

    1990-01-01

    An upper bound of one part in 10 6 /10 7 is derived for the violation of the equivalence principle for antimatter in the form of antiprotons based on existing data for bulk matter, electrons, positrons, neutrons and protons

  6. Epistemology and Empirical Investigation

    DEFF Research Database (Denmark)

    Ahlström, Kristoffer

    2008-01-01

    Recently, Hilary Kornblith has argued that epistemological investigation is substantially empirical. In the present paper, I will ¿rst show that his claim is not contingent upon the further and, admittedly, controversial assumption that all objects of epistemological investigation are natural kinds....... Then, I will argue that, contrary to what Kornblith seems to assume, this methodological contention does not imply that there is no need for attending to our epistemic concepts in epistemology. Understanding the make-up of our concepts and, in particular, the purposes they ¿ll, is necessary...

  7. Empirical microeconomics action functionals

    Science.gov (United States)

    Baaquie, Belal E.; Du, Xin; Tanputraman, Winson

    2015-06-01

    A statistical generalization of microeconomics has been made in Baaquie (2013), where the market price of every traded commodity, at each instant of time, is considered to be an independent random variable. The dynamics of commodity market prices is modeled by an action functional-and the focus of this paper is to empirically determine the action functionals for different commodities. The correlation functions of the model are defined using a Feynman path integral. The model is calibrated using the unequal time correlation of the market commodity prices as well as their cubic and quartic moments using a perturbation expansion. The consistency of the perturbation expansion is verified by a numerical evaluation of the path integral. Nine commodities drawn from the energy, metal and grain sectors are studied and their market behavior is described by the model to an accuracy of over 90% using only six parameters. The paper empirically establishes the existence of the action functional for commodity prices that was postulated to exist in Baaquie (2013).

  8. What 'empirical turn in bioethics'?

    Science.gov (United States)

    Hurst, Samia

    2010-10-01

    Uncertainty as to how we should articulate empirical data and normative reasoning seems to underlie most difficulties regarding the 'empirical turn' in bioethics. This article examines three different ways in which we could understand 'empirical turn'. Using real facts in normative reasoning is trivial and would not represent a 'turn'. Becoming an empirical discipline through a shift to the social and neurosciences would be a turn away from normative thinking, which we should not take. Conducting empirical research to inform normative reasoning is the usual meaning given to the term 'empirical turn'. In this sense, however, the turn is incomplete. Bioethics has imported methodological tools from empirical disciplines, but too often it has not imported the standards to which researchers in these disciplines are held. Integrating empirical and normative approaches also represents true added difficulties. Addressing these issues from the standpoint of debates on the fact-value distinction can cloud very real methodological concerns by displacing the debate to a level of abstraction where they need not be apparent. Ideally, empirical research in bioethics should meet standards for empirical and normative validity similar to those used in the source disciplines for these methods, and articulate these aspects clearly and appropriately. More modestly, criteria to ensure that none of these standards are completely left aside would improve the quality of empirical bioethics research and partly clear the air of critiques addressing its theoretical justification, when its rigour in the particularly difficult context of interdisciplinarity is what should be at stake.

  9. Metabolic Syndrome

    Science.gov (United States)

    Metabolic syndrome is a group of conditions that put you at risk for heart disease and diabetes. These conditions ... agree on the definition or cause of metabolic syndrome. The cause might be insulin resistance. Insulin is ...

  10. Empirical methods for estimating future climatic conditions

    International Nuclear Information System (INIS)

    Anon.

    1990-01-01

    Applying the empirical approach permits the derivation of estimates of the future climate that are nearly independent of conclusions based on theoretical (model) estimates. This creates an opportunity to compare these results with those derived from the model simulations of the forthcoming changes in climate, thus increasing confidence in areas of agreement and focusing research attention on areas of disagreements. The premise underlying this approach for predicting anthropogenic climate change is based on associating the conditions of the climatic optimums of the Holocene, Eemian, and Pliocene with corresponding stages of the projected increase of mean global surface air temperature. Provided that certain assumptions are fulfilled in matching the value of the increased mean temperature for a certain epoch with the model-projected change in global mean temperature in the future, the empirical approach suggests that relationships leading to the regional variations in air temperature and other meteorological elements could be deduced and interpreted based on use of empirical data describing climatic conditions for past warm epochs. Considerable care must be taken, of course, in making use of these spatial relationships, especially in accounting for possible large-scale differences that might, in some cases, result from different factors contributing to past climate changes than future changes and, in other cases, might result from the possible influences of changes in orography and geography on regional climatic conditions over time

  11. The effect of loss functions on empirical Bayes reliability analysis

    Directory of Open Access Journals (Sweden)

    Camara Vincent A. R.

    1998-01-01

    Full Text Available The aim of the present study is to investigate the sensitivity of empirical Bayes estimates of the reliability function with respect to changing of the loss function. In addition to applying some of the basic analytical results on empirical Bayes reliability obtained with the use of the “popular” squared error loss function, we shall derive some expressions corresponding to empirical Bayes reliability estimates obtained with the Higgins–Tsokos, the Harris and our proposed logarithmic loss functions. The concept of efficiency, along with the notion of integrated mean square error, will be used as a criterion to numerically compare our results. It is shown that empirical Bayes reliability functions are in general sensitive to the choice of the loss function, and that the squared error loss does not always yield the best empirical Bayes reliability estimate.

  12. EGG: Empirical Galaxy Generator

    Science.gov (United States)

    Schreiber, C.; Elbaz, D.; Pannella, M.; Merlin, E.; Castellano, M.; Fontana, A.; Bourne, N.; Boutsia, K.; Cullen, F.; Dunlop, J.; Ferguson, H. C.; Michałowski, M. J.; Okumura, K.; Santini, P.; Shu, X. W.; Wang, T.; White, C.

    2018-04-01

    The Empirical Galaxy Generator (EGG) generates fake galaxy catalogs and images with realistic positions, morphologies and fluxes from the far-ultraviolet to the far-infrared. The catalogs are generated by egg-gencat and stored in binary FITS tables (column oriented). Another program, egg-2skymaker, is used to convert the generated catalog into ASCII tables suitable for ingestion by SkyMaker (ascl:1010.066) to produce realistic high resolution images (e.g., Hubble-like), while egg-gennoise and egg-genmap can be used to generate the low resolution images (e.g., Herschel-like). These tools can be used to test source extraction codes, or to evaluate the reliability of any map-based science (stacking, dropout identification, etc.).

  13. Empirical P-L-C relations for delta Scuti stars

    International Nuclear Information System (INIS)

    Gupta, S.K.

    1978-01-01

    Separate P-L-C relations have been empirically derived by sampling the delta Scuti stars according to their pulsation modes. The results based on these relations have been compared with those estimated from the model based P-L-C relations and the other existing empirical P-L-C relations. It is found that a separate P-L-C relation for each pulsation mode provides a better correspondence with observations. (Auth.)

  14. Empirical limits to antigravity

    Energy Technology Data Exchange (ETDEWEB)

    Ericson, T.E.O. (European Organization for Nuclear Research, Geneva (CH)); Richter, A. (Technische Hochschule Darmstadt (DE). Inst. fuer Kernphysik)

    1990-02-01

    An upper bound of one part in 10{sup 6}/10{sup 7} is derived for the violation of the equivalence principle for antimatter in the form of antiprotons based on existing data for bulk matter, electrons, positrons, neutrons and protons.

  15. Pluvials, Droughts, Energetics, and the Mongol Empire

    Science.gov (United States)

    Hessl, A. E.; Pederson, N.; Baatarbileg, N.

    2012-12-01

    The success of the Mongol Empire, the largest contiguous land empire the world has ever known, is a historical enigma. At its peak in the late 13th century, the empire influenced areas from the Hungary to southern Asia and Persia. Powered by domesticated herbivores, the Mongol Empire grew at the expense of agriculturalists in Eastern Europe, Persia, and China. What environmental factors contributed to the rise of the Mongols? What factors influenced the disintegration of the empire by 1300 CE? Until now, little high resolution environmental data have been available to address these questions. We use tree-ring records of past temperature and water to illuminate the role of energy and water in the evolution of the Mongol Empire. The study of energetics has long been applied to biological and ecological systems but has only recently become a theme in understanding modern coupled natural and human systems (CNH). Because water and energy are tightly linked in human and natural systems, studying their synergies and interactions make it possible to integrate knowledge across disciplines and human history, yielding important lessons for modern societies. We focus on the role of energy and water in the trajectory of an empire, including its rise, development, and demise. Our research is focused on the Orkhon Valley, seat of the Mongol Empire, where recent paleoenvironmental and archeological discoveries allow high resolution reconstructions of past human and environmental conditions for the first time. Our preliminary records indicate that the period 1210-1230 CE, the height of Chinggis Khan's reign is one of the longest and most consistent pluvials in our tree ring reconstruction of interannual drought. Reconstructed temperature derived from five millennium-long records from subalpine forests in Mongolia document warm temperatures beginning in the early 1200's and ending with a plunge into cold temperatures in 1260. Abrupt cooling in central Mongolia at this time is

  16. The Cladophora glomerata Enriched by Biosorption Process in Cr(III Improves Viability, and Reduces Oxidative Stress and Apoptosis in Equine Metabolic Syndrome Derived Adipose Mesenchymal Stromal Stem Cells (ASCs and Their Extracellular Vesicles (MV’s

    Directory of Open Access Journals (Sweden)

    Krzysztof Marycz

    2017-12-01

    Full Text Available This study investigated in vitro effects of freshwater alga Cladophora glomerata water extract enriched during a biosorption process in Cr(III trivalent chromium and chromium picolinate on adipose-derived mesenchymal stromal stem cells (ASCs and extracellular microvesicles (MVs in equine metabolic syndrome-affected horses. Chemical characterisation of natural Cladophora glomerata was performed with special emphasis on: vitamin C, vitamin E, total phenols, fatty acids, free and protein-bound amino acids as well as measured Cr in algal biomass. To examine the influence of Cladophora glomerata water extracts, in vitro viability, oxidative stress factor accumulation, apoptosis, inflammatory response, biogenesis of mitochondria, autophagy in ASCs of EMS and secretory activity manifested by MV release were investigated. For this purpose, various methods of molecular biology and microscopic observations (i.e., immunofluorescence staining, SEM, TEM, FIB observations, mRNA and microRNA expression by RT-qPCR were applied. The extract of Cladophora glomerata enriched with Cr(III ions reduced apoptosis and inflammation in ASCs of EMS horses through improvement of mitochondrial dynamics, decreasing of PDK4 expression and reduction of endoplastic reticulum stress. Moreover, it was found, that Cladophora glomerata and Cr(III induce antioxidative protection coming from enhanced SOD activity Therefore, Cladophora glomerata enriched with Cr(III ions might become an interesting future therapeutic agent in the pharmacological treatment of EMS horses.

  17. Proteomic Analysis Reveals Distinct Metabolic Differences Between Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) and Macrophage Colony Stimulating Factor (M-CSF) Grown Macrophages Derived from Murine Bone Marrow Cells.

    Science.gov (United States)

    Na, Yi Rang; Hong, Ji Hye; Lee, Min Yong; Jung, Jae Hun; Jung, Daun; Kim, Young Won; Son, Dain; Choi, Murim; Kim, Kwang Pyo; Seok, Seung Hyeok

    2015-10-01

    Macrophages are crucial in controlling infectious agents and tissue homeostasis. Macrophages require a wide range of functional capabilities in order to fulfill distinct roles in our body, one being rapid and robust immune responses. To gain insight into macrophage plasticity and the key regulatory protein networks governing their specific functions, we performed quantitative analyses of the proteome and phosphoproteome of murine primary GM-CSF and M-CSF grown bone marrow derived macrophages (GM-BMMs and M-BMMs, respectively) using the latest isobaric tag based tandem mass tag (TMT) labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Strikingly, metabolic processes emerged as a major difference between these macrophages. Specifically, GM-BMMs show significant enrichment of proteins involving glycolysis, the mevalonate pathway, and nitrogen compound biosynthesis. This evidence of enhanced glycolytic capability in GM-BMMs is particularly significant regarding their pro-inflammatory responses, because increased production of cytokines upon LPS stimulation in GM-BMMs depends on their acute glycolytic capacity. In contrast, M-BMMs up-regulate proteins involved in endocytosis, which correlates with a tendency toward homeostatic functions such as scavenging cellular debris. Together, our data describes a proteomic network that underlies the pro-inflammatory actions of GM-BMMs as well as the homeostatic functions of M-BMMs. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. The Cladophora glomerata Enriched by Biosorption Process in Cr(III) Improves Viability, and Reduces Oxidative Stress and Apoptosis in Equine Metabolic Syndrome Derived Adipose Mesenchymal Stromal Stem Cells (ASCs) and Their Extracellular Vesicles (MV's).

    Science.gov (United States)

    Marycz, Krzysztof; Michalak, Izabela; Kocherova, Ievgeniia; Marędziak, Monika; Weiss, Christine

    2017-12-08

    This study investigated in vitro effects of freshwater alga Cladophora glomerata water extract enriched during a biosorption process in Cr(III) trivalent chromium and chromium picolinate on adipose-derived mesenchymal stromal stem cells (ASCs) and extracellular microvesicles (MVs) in equine metabolic syndrome-affected horses. Chemical characterisation of natural Cladophora glomerata was performed with special emphasis on: vitamin C, vitamin E, total phenols, fatty acids, free and protein-bound amino acids as well as measured Cr in algal biomass. To examine the influence of Cladophora glomerata water extracts, in vitro viability, oxidative stress factor accumulation, apoptosis, inflammatory response, biogenesis of mitochondria, autophagy in ASCs of EMS and secretory activity manifested by MV release were investigated. For this purpose, various methods of molecular biology and microscopic observations (i.e., immunofluorescence staining, SEM, TEM, FIB observations, mRNA and microRNA expression by RT-qPCR) were applied. The extract of Cladophora glomerata enriched with Cr(III) ions reduced apoptosis and inflammation in ASCs of EMS horses through improvement of mitochondrial dynamics, decreasing of PDK4 expression and reduction of endoplastic reticulum stress. Moreover, it was found, that Cladophora glomerata and Cr(III) induce antioxidative protection coming from enhanced SOD activity Therefore, Cladophora glomerata enriched with Cr(III) ions might become an interesting future therapeutic agent in the pharmacological treatment of EMS horses.

  19. The Cladophora glomerata Enriched by Biosorption Process in Cr(III) Improves Viability, and Reduces Oxidative Stress and Apoptosis in Equine Metabolic Syndrome Derived Adipose Mesenchymal Stromal Stem Cells (ASCs) and Their Extracellular Vesicles (MV’s)

    Science.gov (United States)

    Marycz, Krzysztof; Marędziak, Monika; Weiss, Christine

    2017-01-01

    This study investigated in vitro effects of freshwater alga Cladophora glomerata water extract enriched during a biosorption process in Cr(III) trivalent chromium and chromium picolinate on adipose-derived mesenchymal stromal stem cells (ASCs) and extracellular microvesicles (MVs) in equine metabolic syndrome-affected horses. Chemical characterisation of natural Cladophora glomerata was performed with special emphasis on: vitamin C, vitamin E, total phenols, fatty acids, free and protein-bound amino acids as well as measured Cr in algal biomass. To examine the influence of Cladophora glomerata water extracts, in vitro viability, oxidative stress factor accumulation, apoptosis, inflammatory response, biogenesis of mitochondria, autophagy in ASCs of EMS and secretory activity manifested by MV release were investigated. For this purpose, various methods of molecular biology and microscopic observations (i.e., immunofluorescence staining, SEM, TEM, FIB observations, mRNA and microRNA expression by RT-qPCR) were applied. The extract of Cladophora glomerata enriched with Cr(III) ions reduced apoptosis and inflammation in ASCs of EMS horses through improvement of mitochondrial dynamics, decreasing of PDK4 expression and reduction of endoplastic reticulum stress. Moreover, it was found, that Cladophora glomerata and Cr(III) induce antioxidative protection coming from enhanced SOD activity Therefore, Cladophora glomerata enriched with Cr(III) ions might become an interesting future therapeutic agent in the pharmacological treatment of EMS horses. PMID:29292726

  20. The effect of loss functions on empirical Bayes reliability analysis

    Directory of Open Access Journals (Sweden)

    Vincent A. R. Camara

    1999-01-01

    Full Text Available The aim of the present study is to investigate the sensitivity of empirical Bayes estimates of the reliability function with respect to changing of the loss function. In addition to applying some of the basic analytical results on empirical Bayes reliability obtained with the use of the “popular” squared error loss function, we shall derive some expressions corresponding to empirical Bayes reliability estimates obtained with the Higgins–Tsokos, the Harris and our proposed logarithmic loss functions. The concept of efficiency, along with the notion of integrated mean square error, will be used as a criterion to numerically compare our results.

  1. Birds of the Mongol Empire

    OpenAIRE

    Eugene N. Anderson

    2016-01-01

    The Mongol Empire, the largest contiguous empire the world has ever known, had, among other things, a goodly number of falconers, poultry raisers, birdcatchers, cooks, and other experts on various aspects of birding. We have records of this, largely in the Yinshan Zhengyao, the court nutrition manual of the Mongol empire in China (the Yuan Dynasty). It discusses in some detail 22 bird taxa, from swans to chickens. The Huihui Yaofang, a medical encyclopedia, lists ten taxa used medicinally. Ma...

  2. Empirically derived neighbourhood rules for urban land-use modelling

    DEFF Research Database (Denmark)

    Hansen, Henning Sten

    2012-01-01

    Land-use modelling and spatial scenarios have gained attention as a means to meet the challenge of reducing uncertainty in spatial planning and decision making. Many of the recent modelling efforts incorporate cellular automata to accomplish spatially explicit land-use-change modelling. Spatial...

  3. Empirically derived lifespan polytraumatization typologies: A systematic review.

    Science.gov (United States)

    Contractor, Ateka A; Caldas, Stephanie; Fletcher, Shelley; Shea, M Tracie; Armour, Cherie

    2018-07-01

    Polytraumatization classes based on trauma endorsement patterns relate to distinct clinical outcomes. Person-centered approaches robustly evaluate the nature, and construct validity of polytraumatization classes. Our review examined evidence for the nature and construct validity of lifespan polytraumatization typologies. In September 2016, we searched Pubmed, PSYCINFO, PSYC ARTICLES, Academic Search Complete, PILPTS, Web of Science, CINAHL, Medline, PsycEXTRA, and PBSC. Search terms included "latent profile," "latent class," "latent analysis," "person-centered," "polytrauma," "polyvictimization," "traumatization," "lifetime," "cooccurring," "complex," "typology," "multidimensional," "sequential," "multiple," "subtype," "(re)victimization," "cumulative," "maltreatment," "abuse," and "stressor." Inclusionary criteria included: peer-reviewed; latent class/latent profile analyses (LCA/LPA) of lifespan polytrauma classes; adult samples of size greater than 200; only trauma types as LCA/LPA indicators; mental health correlates of typologies; and individual-level trauma assessment. Of 1,397 articles, nine met inclusion criteria. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, research assistants completed a secondary reference search, and independently extracted data with standardized coding forms. Three-class (n = 5) or four-class (n = 4) solutions were found. Seven studies found a class characterized by higher trauma endorsement (high-trauma). All studies found a class characterized by lower trauma endorsement (low-trauma), and predominance of specific traumas (specific-trauma; e.g., childhood maltreatment). High-trauma versus low-trauma classes and specific-trauma versus low-trauma classes differed on mental health correlates. Evidence supports the prevalence of a high-trauma class experiencing poorer mental health, and the detrimental impact of aggregated interpersonal and other traumas. We highlight the clinical importance of addressing polytraumatization classes, and comprehensively assessing the impact of all traumas. © 2018 Wiley Periodicals, Inc.

  4. Empirical techniques in finance

    CERN Document Server

    Bhar, Ramaprasad

    2005-01-01

    This book offers the opportunity to study and experience advanced empi- cal techniques in finance and in general financial economics. It is not only suitable for students with an interest in the field, it is also highly rec- mended for academic researchers as well as the researchers in the industry. The book focuses on the contemporary empirical techniques used in the analysis of financial markets and how these are implemented using actual market data. With an emphasis on Implementation, this book helps foc- ing on strategies for rigorously combing finance theory and modeling technology to extend extant considerations in the literature. The main aim of this book is to equip the readers with an array of tools and techniques that will allow them to explore financial market problems with a fresh perspective. In this sense it is not another volume in eco- metrics. Of course, the traditional econometric methods are still valid and important; the contents of this book will bring in other related modeling topics tha...

  5. Final Empirical Test Case Specification

    DEFF Research Database (Denmark)

    Kalyanova, Olena; Heiselberg, Per

    This document includes the empirical specification on the IEA task of evaluation building energy simulation computer programs for the Double Skin Facades (DSF) constructions. There are two approaches involved into this procedure, one is the comparative approach and another is the empirical one....

  6. Remembrances of Empires Past

    Directory of Open Access Journals (Sweden)

    Robert Aldrich

    2010-03-01

    Full Text Available This paper argues that the colonial legacy is ever present in contemporary Europe. For a generation, most Europeans largely tried, publicly, to forget the colonial past, or remembered it only through the rose-coloured lenses of nostalgia; now the pendulum has swung to memory of that past – even perhaps, in the views of some, to a surfeit of memory, where each group agitates for its own version of history, its own recognition in laws and ceremonies, its own commemoration in museums and monuments, the valorization or repatriation of its own art and artefacts. Word such as ‘invasion,’ ‘racism’ and ‘genocide’ are emotional terms that provoke emotional reactions. Whether leaders should apologize for wrongs of the past – and which wrongs – remains a highly sensitive issue. The ‘return of the colonial’ thus has to do with ethics and politics as well as with history, and can link to statements of apology or recognition, legislation about certain views of history, monetary compensation, repatriation of objects, and—perhaps most importantly—redefinition of national identity and policy. The colonial flags may have been lowered, but many barricades seem to have been raised. Private memories—of loss of land, of unacknowledged service, of political, economic, social and cultural disenfranchisement, but also on the other side of defeat, national castigation and self-flagellation—have been increasingly public. Monuments and museums act not only as sites of history but as venues for political agitation and forums for academic debate – differences of opinion that have spread to the streets. Empire has a long after-life.

  7. Empirical Support for Perceptual Conceptualism

    Directory of Open Access Journals (Sweden)

    Nicolás Alejandro Serrano

    2018-03-01

    Full Text Available The main objective of this paper is to show that perceptual conceptualism can be understood as an empirically meaningful position and, furthermore, that there is some degree of empirical support for its main theses. In order to do this, I will start by offering an empirical reading of the conceptualist position, and making three predictions from it. Then, I will consider recent experimental results from cognitive sciences that seem to point towards those predictions. I will conclude that, while the evidence offered by those experiments is far from decisive, it is enough not only to show that conceptualism is an empirically meaningful position but also that there is empirical support for it.

  8. Empire as a Geopolitical Figure

    DEFF Research Database (Denmark)

    Parker, Noel

    2010-01-01

    This article analyses the ingredients of empire as a pattern of order with geopolitical effects. Noting the imperial form's proclivity for expansion from a critical reading of historical sociology, the article argues that the principal manifestation of earlier geopolitics lay not in the nation...... but in empire. That in turn has been driven by a view of the world as disorderly and open to the ordering will of empires (emanating, at the time of geopolitics' inception, from Europe). One implication is that empires are likely to figure in the geopolitical ordering of the globe at all times, in particular...... after all that has happened in the late twentieth century to undermine nationalism and the national state. Empire is indeed a probable, even for some an attractive form of regime for extending order over the disorder produced by globalisation. Geopolitics articulated in imperial expansion is likely...

  9. What is Metabolic Syndrome?

    Science.gov (United States)

    ... Intramural Research Home / Metabolic Syndrome Metabolic Syndrome Also known as What Is Metabolic syndrome ... metabolic risk factors to be diagnosed with metabolic syndrome. Metabolic Risk Factors A Large Waistline Having a large ...

  10. Urea metabolism in plants.

    Science.gov (United States)

    Witte, Claus-Peter

    2011-03-01

    Urea is a plant metabolite derived either from root uptake or from catabolism of arginine by arginase. In agriculture, urea is intensively used as a nitrogen fertilizer. Urea nitrogen enters the plant either directly, or in the form of ammonium or nitrate after urea degradation by soil microbes. In recent years various molecular players of plant urea metabolism have been investigated: active and passive urea transporters, the nickel metalloenzyme urease catalyzing the hydrolysis of urea, and three urease accessory proteins involved in the complex activation of urease. The degradation of ureides derived from purine breakdown has long been discussed as a possible additional metabolic source for urea, but an enzymatic route for the complete hydrolysis of ureides without a urea intermediate has recently been described for Arabidopsis thaliana. This review focuses on the proteins involved in plant urea metabolism and the metabolic sources of urea but also addresses open questions regarding plant urea metabolism in a physiological and agricultural context. The contribution of plant urea uptake and metabolism to fertilizer urea usage in crop production is still not investigated although globally more than half of all nitrogen fertilizer is applied to crops in the form of urea. Nitrogen use efficiency in crop production is generally well below 50% resulting in economical losses and creating ecological problems like groundwater pollution and emission of nitric oxides that can damage the ozone layer and function as greenhouse gasses. Biotechnological approaches to improve fertilizer urea usage bear the potential to increase crop nitrogen use efficiency. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  11. Birds of the Mongol Empire

    Directory of Open Access Journals (Sweden)

    Eugene N. Anderson

    2016-09-01

    Full Text Available The Mongol Empire, the largest contiguous empire the world has ever known, had, among other things, a goodly number of falconers, poultry raisers, birdcatchers, cooks, and other experts on various aspects of birding. We have records of this, largely in the Yinshan Zhengyao, the court nutrition manual of the Mongol empire in China (the Yuan Dynasty. It discusses in some detail 22 bird taxa, from swans to chickens. The Huihui Yaofang, a medical encyclopedia, lists ten taxa used medicinally. Marco Polo also made notes on Mongol bird use. There are a few other records. This allows us to draw conclusions about Mongol ornithology, which apparently was sophisticated and detailed.

  12. Mapping sediment thickness of Islamabad city using empirical ...

    Indian Academy of Sciences (India)

    A number of studies in recent years have demonstrated that frequency and ... sediment thicknesses derived from empirical relations developed in this study with ... Location map of the study area, the bold light grey line shows the boundary of the Islamabad region. .... frequency disturbances (wind blowing, in case of near tall ...

  13. [Metabolic acidosis].

    Science.gov (United States)

    Regolisti, Giuseppe; Fani, Filippo; Antoniotti, Riccardo; Castellano, Giuseppe; Cremaschi, Elena; Greco, Paolo; Parenti, Elisabetta; Morabito, Santo; Sabatino, Alice; Fiaccadori, Enrico

    2016-01-01

    Metabolic acidosis is frequently observed in clinical practice, especially among critically ill patients and/or in the course of renal failure. Complex mechanisms are involved, in most cases identifiable by medical history, pathophysiology-based diagnostic reasoning and measure of some key acid-base parameters that are easily available or calculable. On this basis the bedside differential diagnosis of metabolic acidosis should be started from the identification of the two main subtypes of metabolic acidosis: the high anion gap metabolic acidosis and the normal anion gap (or hyperchloremic) metabolic acidosis. Metabolic acidosis, especially in its acute forms with elevated anion gap such as is the case of lactic acidosis, diabetic and acute intoxications, may significantly affect metabolic body homeostasis and patients hemodynamic status, setting the stage for true medical emergencies. The therapeutic approach should be first aimed at early correction of concurrent clinical problems (e.g. fluids and hemodynamic optimization in case of shock, mechanical ventilation in case of concomitant respiratory failure, hemodialysis for acute intoxications etc.), in parallel to the formulation of a diagnosis. In case of severe acidosis, the administration of alkalizing agents should be carefully evaluated, taking into account the risk of side effects, as well as the potential need of renal replacement therapy.

  14. Empirical Legality and Effective Reality

    Directory of Open Access Journals (Sweden)

    Hernán Pringe

    2015-08-01

    Full Text Available The conditions that Kant’s doctrine establishes are examined for the predication of the effective reality of certain empirical objects. It is maintained that a for such a predication, it is necessary to have not only perception but also a certain homogeneity of sensible data, and b the knowledge of the existence of certain empirical objects depends on the application of regulative principles of experience.

  15. Empirical logic and quantum mechanics

    International Nuclear Information System (INIS)

    Foulis, D.J.; Randall, C.H.

    1976-01-01

    This article discusses some of the basic notions of quantum physics within the more general framework of operational statistics and empirical logic (as developed in Foulis and Randall, 1972, and Randall and Foulis, 1973). Empirical logic is a formal mathematical system in which the notion of an operation is primitive and undefined; all other concepts are rigorously defined in terms of such operations (which are presumed to correspond to actual physical procedures). (Auth.)

  16. Empirical Research In Engineering Design

    DEFF Research Database (Denmark)

    Ahmed, Saeema

    2007-01-01

    Increasingly engineering design research involves the use of empirical studies that are conducted within an industrial environment [Ahmed, 2001; Court 1995; Hales 1987]. Research into the use of information by designers or understanding how engineers build up experience are examples of research...... of research issues. This paper describes case studies of empirical research carried out within industry in engineering design focusing upon information, knowledge and experience in engineering design. The paper describes the research methods employed, their suitability for the particular research aims...

  17. Computational prediction of binding affinity for CYP1A2-ligand complexes using empirical free energy calculations

    DEFF Research Database (Denmark)

    Poongavanam, Vasanthanathan; Olsen, Lars; Jørgensen, Flemming Steen

    2010-01-01

    , and methods based on statistical mechanics. In the present investigation, we started from an LIE model to predict the binding free energy of structurally diverse compounds of cytochrome P450 1A2 ligands, one of the important human metabolizing isoforms of the cytochrome P450 family. The data set includes both...... substrates and inhibitors. It appears that the electrostatic contribution to the binding free energy becomes negligible in this particular protein and a simple empirical model was derived, based on a training set of eight compounds. The root mean square error for the training set was 3.7 kJ/mol. Subsequent......Predicting binding affinities for receptor-ligand complexes is still one of the challenging processes in computational structure-based ligand design. Many computational methods have been developed to achieve this goal, such as docking and scoring methods, the linear interaction energy (LIE) method...

  18. Drug Metabolism

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 19; Issue 3. Drug Metabolism: A Fascinating Link Between Chemistry and Biology. Nikhil Taxak Prasad V Bharatam. General Article Volume 19 Issue 3 March 2014 pp 259-282 ...

  19. Drug Metabolism

    Indian Academy of Sciences (India)

    IAS Admin

    behind metabolic reactions, importance, and consequences with several ... required for drug action. ... lism, which is catalyzed by enzymes present in the above-men- ... catalyze the transfer of one atom of oxygen to a substrate produc-.

  20. Metabolic Myopathies.

    Science.gov (United States)

    Tarnopolsky, Mark A

    2016-12-01

    Metabolic myopathies are genetic disorders that impair intermediary metabolism in skeletal muscle. Impairments in glycolysis/glycogenolysis (glycogen-storage disease), fatty acid transport and oxidation (fatty acid oxidation defects), and the mitochondrial respiratory chain (mitochondrial myopathies) represent the majority of known defects. The purpose of this review is to develop a diagnostic and treatment algorithm for the metabolic myopathies. The metabolic myopathies can present in the neonatal and infant period as part of more systemic involvement with hypotonia, hypoglycemia, and encephalopathy; however, most cases present in childhood or in adulthood with exercise intolerance (often with rhabdomyolysis) and weakness. The glycogen-storage diseases present during brief bouts of high-intensity exercise, whereas fatty acid oxidation defects and mitochondrial myopathies present during a long-duration/low-intensity endurance-type activity or during fasting or another metabolically stressful event (eg, surgery, fever). The clinical examination is often normal between acute events, and evaluation involves exercise testing, blood testing (creatine kinase, acylcarnitine profile, lactate, amino acids), urine organic acids (ketones, dicarboxylic acids, 3-methylglutaconic acid), muscle biopsy (histology, ultrastructure, enzyme testing), MRI/spectroscopy, and targeted or untargeted genetic testing. Accurate and early identification of metabolic myopathies can lead to therapeutic interventions with lifestyle and nutritional modification, cofactor treatment, and rapid treatment of rhabdomyolysis.

  1. Animal metabolism

    International Nuclear Information System (INIS)

    Walburg, H.E.

    1977-01-01

    Studies on placental transport included the following: clearance of tritiated water as a baseline measurement for transport of materials across perfused placentas; transport of organic and inorganic mercury across the perfused placenta of the guinea pig in late gestation; and transport of cadmium across the perfused placenta of the guinea pig in late gestation. Studies on cadmium absorption and metabolism included the following: intestinal absorption and retention of cadmium in neonatal rats; uptake and distribution of an oral dose of cadmium in postweanling male and female, iron-deficient and normal rats; postnatal viability and growth in rat pups after oral cadmium administration during gestation; and the effect of calcium and phosphorus on the absorption and toxicity of cadmium. Studies on gastrointestinal absorption and mineral metabolism included: uptake and distribution of orally administered plutonium complex compounds in male mice; gastrointestinal absorption of 144 Ce in the newborn mouse, rat, and pig; and gastrointestinal absorption of 95 Nb by rats of different ages. Studies on iodine metabolism included the following: influence of thyroid status and thiocyanate on iodine metabolism in the bovine; effects of simulated fallout radiation on iodine metabolism in dairy cattle; and effects of feeding iodine binding agents on iodine metabolism in the calf

  2. Protection against the Metabolic Syndrome by Guar Gum-Derived Short-Chain Fatty Acids Depends on Peroxisome Proliferator-Activated Receptor γ and Glucagon-Like Peptide-1.

    Science.gov (United States)

    den Besten, Gijs; Gerding, Albert; van Dijk, Theo H; Ciapaite, Jolita; Bleeker, Aycha; van Eunen, Karen; Havinga, Rick; Groen, Albert K; Reijngoud, Dirk-Jan; Bakker, Barbara M

    2015-01-01

    The dietary fiber guar gum has beneficial effects on obesity, hyperglycemia and hypercholesterolemia in both humans and rodents. The major products of colonic fermentation of dietary fiber, the short-chain fatty acids (SCFAs), have been suggested to play an important role. Recently, we showed that SCFAs protect against the metabolic syndrome via a signaling cascade that involves peroxisome proliferator-activated receptor (PPAR) γ repression and AMP-activated protein kinase (AMPK) activation. In this study we investigated the molecular mechanism via which the dietary fiber guar gum protects against the metabolic syndrome. C57Bl/6J mice were fed a high-fat diet supplemented with 0% or 10% of the fiber guar gum for 12 weeks and effects on lipid and glucose metabolism were studied. We demonstrate that, like SCFAs, also guar gum protects against high-fat diet-induced metabolic abnormalities by PPARγ repression, subsequently increasing mitochondrial uncoupling protein 2 expression and AMP/ATP ratio, leading to the activation of AMPK and culminating in enhanced oxidative metabolism in both liver and adipose tissue. Moreover, guar gum markedly increased peripheral glucose clearance, possibly mediated by the SCFA-induced colonic hormone glucagon-like peptide-1. Overall, this study provides novel molecular insights into the beneficial effects of guar gum on the metabolic syndrome and strengthens the potential role of guar gum as a dietary-fiber intervention.

  3. Protection against the Metabolic Syndrome by Guar Gum-Derived Short-Chain Fatty Acids Depends on Peroxisome Proliferator-Activated Receptor γ and Glucagon-Like Peptide-1.

    Directory of Open Access Journals (Sweden)

    Gijs den Besten

    Full Text Available The dietary fiber guar gum has beneficial effects on obesity, hyperglycemia and hypercholesterolemia in both humans and rodents. The major products of colonic fermentation of dietary fiber, the short-chain fatty acids (SCFAs, have been suggested to play an important role. Recently, we showed that SCFAs protect against the metabolic syndrome via a signaling cascade that involves peroxisome proliferator-activated receptor (PPAR γ repression and AMP-activated protein kinase (AMPK activation. In this study we investigated the molecular mechanism via which the dietary fiber guar gum protects against the metabolic syndrome. C57Bl/6J mice were fed a high-fat diet supplemented with 0% or 10% of the fiber guar gum for 12 weeks and effects on lipid and glucose metabolism were studied. We demonstrate that, like SCFAs, also guar gum protects against high-fat diet-induced metabolic abnormalities by PPARγ repression, subsequently increasing mitochondrial uncoupling protein 2 expression and AMP/ATP ratio, leading to the activation of AMPK and culminating in enhanced oxidative metabolism in both liver and adipose tissue. Moreover, guar gum markedly increased peripheral glucose clearance, possibly mediated by the SCFA-induced colonic hormone glucagon-like peptide-1. Overall, this study provides novel molecular insights into the beneficial effects of guar gum on the metabolic syndrome and strengthens the potential role of guar gum as a dietary-fiber intervention.

  4. Global Derivatives

    DEFF Research Database (Denmark)

    Andersen, Torben Juul

    approaches to dealing in the global business environment." - Sharon Brown-Hruska, Commissioner, Commodity Futures Trading Commission, USA. "This comprehensive survey of modern risk management using derivative securities is a fine demonstration of the practical relevance of modern derivatives theory to risk......" provides comprehensive coverage of different types of derivatives, including exchange traded contracts and over-the-counter instruments as well as real options. There is an equal emphasis on the practical application of derivatives and their actual uses in business transactions and corporate risk...... management situations. Its key features include: derivatives are introduced in a global market perspective; describes major derivative pricing models for practical use, extending these principles to valuation of real options; practical applications of derivative instruments are richly illustrated...

  5. Improving an Empirical Formula for the Absorption of Sound in the Sea

    National Research Council Canada - National Science Library

    Moll, C. A. van; Ainslie, M. A; Janmaat, J

    2008-01-01

    A new empirical formula for the absorption of sound in seawater is derived. The starting point of this investigation is the formula proposed by Ainslie and McColm for attenuation due to the boron and magnesium relaxations...

  6. Umayyad Relations with Byzantium Empire

    Directory of Open Access Journals (Sweden)

    Mansoor Haidari

    2017-06-01

    Full Text Available This research investigates the political and military relations between Umayyad caliphates with the Byzantine Empire. The aim of this research is to clarify Umayyad caliphate’s relations with the Byzantine Empire. We know that these relations were mostly about war and fight. Because there were always intense conflicts between Muslims and the Byzantine Empire, they had to have an active continuous diplomacy to call truce and settle the disputes. Thus, based on the general policy of the Umayyad caliphs, Christians were severely ignored and segregated within Islamic territories. This segregation of the Christians was highly affected by political relationships. It is worthy of mentioning that Umayyad caliphs brought the governing style of the Sassanid kings and Roman Caesar into the Islamic Caliphate system but they didn’t establish civil institutions and administrative organizations.

  7. [Metabolic myopathies].

    Science.gov (United States)

    Papazian, Óscar; Rivas-Chacón, Rafael

    2013-09-06

    To review the metabolic myopathies manifested only by crisis of myalgias, cramps and rigidity of the muscles with decreased voluntary contractions and normal inter crisis neurologic examination in children and adolescents. These metabolic myopathies are autosomic recessive inherited enzymatic deficiencies of the carbohydrates and lipids metabolisms. The end result is a reduction of intra muscle adenosine triphosphate, mainly through mitochondrial oxidative phosphorylation, with decrease of available energy for muscle contraction. The one secondary to carbohydrates intra muscle metabolism disorders are triggered by high intensity brief (fatty acids metabolism disorders are triggered by low intensity prolonged (> 10 min) exercises. The conditions in the first group in order of decreasing frequency are the deficiencies of myophosforilase (GSD V), muscle phosphofructokinase (GSD VII), phosphoglycerate mutase 1 (GSD X) and beta enolase (GSD XIII). The conditions in the second group in order of decreasing frequency are the deficiencies of carnitine palmitoyl transferase II and very long chain acyl CoA dehydrogenase. The differential characteristics of patients in each group and within each group will allow to make the initial presumptive clinical diagnosis in the majority and then to order only the necessary tests to achieve the final diagnosis. Treatment during the crisis includes hydration, glucose and alkalinization of urine if myoglobin in blood and urine are elevated. Prevention includes avoiding exercise which may induce the crisis and fasting. The prognosis is good with the exception of rare cases of acute renal failure due to hipermyoglobinemia because of severe rabdomyolisis.

  8. Do all roads lead to Rome? A comparison of brain networks derived from inter-subject volumetric and metabolic covariance and moment-to-moment hemodynamic correlations in old individuals.

    Science.gov (United States)

    Di, Xin; Gohel, Suril; Thielcke, Andre; Wehrl, Hans F; Biswal, Bharat B

    2017-11-01

    Relationships between spatially remote brain regions in human have typically been estimated by moment-to-moment correlations of blood-oxygen-level dependent signals in resting-state using functional MRI (fMRI). Recently, studies using subject-to-subject covariance of anatomical volumes, cortical thickness, and metabolic activity are becoming increasingly popular. However, question remains on whether these measures reflect the same inter-region connectivity and brain network organizations. In the current study, we systematically analyzed inter-subject volumetric covariance from anatomical MRI images, metabolic covariance from fluorodeoxyglucose positron emission tomography images from 193 healthy subjects, and resting-state moment-to-moment correlations from fMRI images of a subset of 44 subjects. The correlation matrices calculated from the three methods were found to be minimally correlated, with higher correlation in the range of 0.31, as well as limited proportion of overlapping connections. The volumetric network showed the highest global efficiency and lowest mean clustering coefficient, leaning toward random-like network, while the metabolic and resting-state networks conveyed properties more resembling small-world networks. Community structures of the volumetric and metabolic networks did not reflect known functional organizations, which could be observed in resting-state network. The current results suggested that inter-subject volumetric and metabolic covariance do not necessarily reflect the inter-regional relationships and network organizations as resting-state correlations, thus calling for cautions on interpreting results of inter-subject covariance networks.

  9. Utilizing time-lapse micro-CT-correlated bisphosphonate binding kinetics and soft tissue-derived input functions to differentiate site-specific changes in bone metabolism in vivo.

    Science.gov (United States)

    Tower, R J; Campbell, G M; Müller, M; Glüer, C C; Tiwari, S

    2015-05-01

    The turnover of bone is a tightly regulated process between bone formation and resorption to ensure skeletal homeostasis. This process differs between bone types, with trabecular bone often associated with higher turnover than cortical bone. Analyses of bone by micro-computed tomography (micro-CT) reveal changes in structure and mineral content, but are limited in the study of metabolic activity at a single time point, while analyses of serum markers can reveal changes in bone metabolism, but cannot delineate the origin of any aberrant findings. To obtain a site-specific assessment of bone metabolic status, bisphosphonate binding kinetics were utilized. Using a fluorescently-labeled bisphosphonate, we show that early binding kinetics monitored in vivo using fluorescent molecular tomography (FMT) can monitor changes in bone metabolism in response to bone loss, stimulated by ovariectomy (OVX), or bone gain, resulting from treatment with the anabolic bone agent parathyroid hormone (PTH), and is capable of distinguishing different, metabolically distinct skeletal sites. Using time-lapse micro-CT, longitudinal bone turnover was quantified. The spine showed a significantly greater percent resorbing volume and surface in response to OVX, while mice treated with PTH showed significantly greater resorbing volume per bone surface in the spine and significantly greater forming surfaces in the knee. Correlation studies between binding kinetics and micro-CT suggest that forming surfaces, as assessed by time-lapse micro-CT, are preferentially reflected in the rate constant values while forming and resorbing bone volumes primarily affect plateau values. Additionally, we developed a blood pool correction method which now allows for quantitative multi-compartment analyses to be conducted using FMT. These results further expand our understanding of bisphosphonate binding and the use of bisphosphonate binding kinetics as a tool to monitor site-specific changes in bone metabolism in

  10. Metabolism during flight in two species of bats, Phyllostomus hastatus and Pteropus gouldii.

    Science.gov (United States)

    Thomas, S P

    1975-08-01

    The energetic cost of flight in a wind-tunnel was measured at various combinations of speed and flight angle from two species of bats whose body masses differ by almost an order of magnitude. The highest mean metabolic rate per unit body mass measured from P. hastatus (mean body mass, 0.093 kg) was 130.4 Wkg-1, and that for P. gouldii (mean body mass, 0.78 kg) was 69.6 Wkg-1. These highest metabolic rates, recorded from flying bats, are essentially the same as those predicted for flying birds of the same body masses, but are from 2.5 to 3.0 times greater than the highest metabolic rates of which similar-size exercising terrestrial mammals appear capable. The lowest mean rate of energy utilization per unit body mass P. hastatus required to sustain level flight was 94.2 Wkg-1 and that for P. gouldii was 53.4 Wkg-1. These data from flying bats together with comparable data for flying birds all fall along a straight line when plotted on double logarithmic coordinates as a function of body mass. Such data show that even the lowest metabolic requirements of bats and birds during level flight are about twice the highest metabolic capabilities of similar-size terrestrial mammals. Flying bats share with flying birds the ability to move substantially greater distance per unit energy consumed than walking or running mammals. Calculations show that P. hastatus requires only one-sixth the energy to cover a given distance as does the same-size terrestrial mammal, while P. gouldii requires one-fourth the energy of the same-size terrestrial mammal. An empirically derived equation is presented which enables one to make estimates of the metabolic rates of bats and birds during level flight in nature from body mass data alone. Metabolic data obtained in this study are compared with predictions calculated from an avian flight theory.

  11. Financial Derivatives

    DEFF Research Database (Denmark)

    Wigan, Duncan

    2013-01-01

    Contemporary derivatives mark the development of capital and constitute a novel form of ownership. By reconfiguring the temporal, spatial and legal character of ownership derivatives present a substantive challenge to the tax collecting state. While fiscal systems are nationally bounded...... and inherently static, capital itself is unprecedentedly mobile, fluid and fungible. As such derivatives raise the specter of ‘financial weapons of mass destruction’....

  12. Financial Derivatives

    OpenAIRE

    Janečková, Alena

    2011-01-01

    1 Abstract/ Financial derivatives The purpose of this thesis is to provide an introduction to financial derivatives which has been, from the legal perspective, described in a not satisfactory manner as quite little literature that can be found about this topic. The main objectives of this thesis are to define the term "financial derivatives" and its particular types and to analyse legal nature of these financial instruments. The last objective is to try to draft future law regulation of finan...

  13. Gazprom the new russian empire

    International Nuclear Information System (INIS)

    Cosnard, D.

    2004-01-01

    The author analyzes the economical and political impacts of the great Gazprom group, leader in the russian energy domain, in Russia. Already number one of the world gas industry, this Group is becoming the right-hand of the Kremlin. Thus the author wonders on this empire transparency and limits. (A.L.B.)

  14. Phenomenology and the Empirical Turn

    NARCIS (Netherlands)

    Zwier, Jochem; Blok, Vincent; Lemmens, Pieter

    2016-01-01

    This paper provides a phenomenological analysis of postphenomenological philosophy of technology. While acknowledging that the results of its analyses are to be recognized as original, insightful, and valuable, we will argue that in its execution of the empirical turn, postphenomenology forfeits

  15. Empirical ethics as dialogical practice

    NARCIS (Netherlands)

    Widdershoven, G.A.M.; Abma, T.A.; Molewijk, A.C.

    2009-01-01

    In this article, we present a dialogical approach to empirical ethics, based upon hermeneutic ethics and responsive evaluation. Hermeneutic ethics regards experience as the concrete source of moral wisdom. In order to gain a good understanding of moral issues, concrete detailed experiences and

  16. Teaching "Empire of the Sun."

    Science.gov (United States)

    Riet, Fred H. van

    1990-01-01

    A Dutch teacher presents reading, film viewing, and writing activities for "Empire of the Sun," J. G. Ballard's autobiographical account of life as a boy in Shanghai and in a Japanese internment camp during World War II (the subject of Steven Spielberg's film of the same name). Includes objectives, procedures, and several literature,…

  17. Empirical Specification of Utility Functions.

    Science.gov (United States)

    Mellenbergh, Gideon J.

    Decision theory can be applied to four types of decision situations in education and psychology: (1) selection; (2) placement; (3) classification; and (4) mastery. For the application of the theory, a utility function must be specified. Usually the utility function is chosen on a priori grounds. In this paper methods for the empirical assessment…

  18. Empirical Productivity Indices and Indicators

    NARCIS (Netherlands)

    B.M. Balk (Bert)

    2016-01-01

    textabstractThe empirical measurement of productivity change (or difference) by means of indices and indicators starts with the ex post profit/loss accounts of a production unit. Key concepts are profit, leading to indicators, and profitability, leading to indices. The main task for the productivity

  19. EMPIRICAL RESEARCH AND CONGREGATIONAL ANALYSIS ...

    African Journals Online (AJOL)

    empirical research has made to the process of congregational analysis. 1 Part of this ... contextual congegrational analysis – meeting social and divine desires”) at the IAPT .... methodology of a congregational analysis should be regarded as a process. ... essential to create space for a qualitative and quantitative approach.

  20. Empirical processes: theory and applications

    OpenAIRE

    Venturini Sergio

    2005-01-01

    Proceedings of the 2003 Summer School in Statistics and Probability in Torgnon (Aosta, Italy) held by Prof. Jon A. Wellner and Prof. M. Banerjee. The topic presented was the theory of empirical processes with applications to statistics (m-estimation, bootstrap, semiparametric theory).

  1. Empirical laws, regularity and necessity

    NARCIS (Netherlands)

    Koningsveld, H.

    1973-01-01

    In this book I have tried to develop an analysis of the concept of an empirical law, an analysis that differs in many ways from the alternative analyse's found in contemporary literature dealing with the subject.

    1 am referring especially to two well-known views, viz. the regularity and

  2. Empirical analysis of consumer behavior

    NARCIS (Netherlands)

    Huang, Yufeng

    2015-01-01

    This thesis consists of three essays in quantitative marketing, focusing on structural empirical analysis of consumer behavior. In the first essay, he investigates the role of a consumer's skill of product usage, and its imperfect transferability across brands, in her product choice. It shows that

  3. Lipoprotein metabolism indicators improve cardiovascular risk prediction

    NARCIS (Netherlands)

    Schalkwijk, D.B. van; Graaf, A.A. de; Tsivtsivadze, E.; Parnell, L.D.; Werff-van der Vat, B.J.C. van der; Ommen, B. van; Greef, J. van der; Ordovás, J.M.

    2014-01-01

    Background: Cardiovascular disease risk increases when lipoprotein metabolism is dysfunctional. We have developed a computational model able to derive indicators of lipoprotein production, lipolysis, and uptake processes from a single lipoprotein profile measurement. This is the first study to

  4. Nucleotide Metabolism

    DEFF Research Database (Denmark)

    Martinussen, Jan; Willemoës, M.; Kilstrup, Mogens

    2011-01-01

    Metabolic pathways are connected through their utilization of nucleotides as supplier of energy, allosteric effectors, and their role in activation of intermediates. Therefore, any attempt to exploit a given living organism in a biotechnological process will have an impact on nucleotide metabolis...

  5. Generalized empirical likelihood methods for analyzing longitudinal data

    KAUST Repository

    Wang, S.

    2010-02-16

    Efficient estimation of parameters is a major objective in analyzing longitudinal data. We propose two generalized empirical likelihood based methods that take into consideration within-subject correlations. A nonparametric version of the Wilks theorem for the limiting distributions of the empirical likelihood ratios is derived. It is shown that one of the proposed methods is locally efficient among a class of within-subject variance-covariance matrices. A simulation study is conducted to investigate the finite sample properties of the proposed methods and compare them with the block empirical likelihood method by You et al. (2006) and the normal approximation with a correctly estimated variance-covariance. The results suggest that the proposed methods are generally more efficient than existing methods which ignore the correlation structure, and better in coverage compared to the normal approximation with correctly specified within-subject correlation. An application illustrating our methods and supporting the simulation study results is also presented.

  6. Predicting acid dew point with a semi-empirical model

    International Nuclear Information System (INIS)

    Xiang, Baixiang; Tang, Bin; Wu, Yuxin; Yang, Hairui; Zhang, Man; Lu, Junfu

    2016-01-01

    Highlights: • The previous semi-empirical models are systematically studied. • An improved thermodynamic correlation is derived. • A semi-empirical prediction model is proposed. • The proposed semi-empirical model is validated. - Abstract: Decreasing the temperature of exhaust flue gas in boilers is one of the most effective ways to further improve the thermal efficiency, electrostatic precipitator efficiency and to decrease the water consumption of desulfurization tower, while, when this temperature is below the acid dew point, the fouling and corrosion will occur on the heating surfaces in the second pass of boilers. So, the knowledge on accurately predicting the acid dew point is essential. By investigating the previous models on acid dew point prediction, an improved thermodynamic correlation formula between the acid dew point and its influencing factors is derived first. And then, a semi-empirical prediction model is proposed, which is validated with the data both in field test and experiment, and comparing with the previous models.

  7. Guidelines for using empirical studies in software engineering education

    Directory of Open Access Journals (Sweden)

    Fabian Fagerholm

    2017-09-01

    Full Text Available Software engineering education is under constant pressure to provide students with industry-relevant knowledge and skills. Educators must address issues beyond exercises and theories that can be directly rehearsed in small settings. Industry training has similar requirements of relevance as companies seek to keep their workforce up to date with technological advances. Real-life software development often deals with large, software-intensive systems and is influenced by the complex effects of teamwork and distributed software development, which are hard to demonstrate in an educational environment. A way to experience such effects and to increase the relevance of software engineering education is to apply empirical studies in teaching. In this paper, we show how different types of empirical studies can be used for educational purposes in software engineering. We give examples illustrating how to utilize empirical studies, discuss challenges, and derive an initial guideline that supports teachers to include empirical studies in software engineering courses. Furthermore, we give examples that show how empirical studies contribute to high-quality learning outcomes, to student motivation, and to the awareness of the advantages of applying software engineering principles. Having awareness, experience, and understanding of the actions required, students are more likely to apply such principles under real-life constraints in their working life.

  8. Empirically Testing Thematic Analysis (ETTA)

    DEFF Research Database (Denmark)

    Gildberg, Frederik Alkier; Bradley, Stephen K.; Tingleff, Elllen B.

    2015-01-01

    Text analysis is not a question of a right or wrong way to go about it, but a question of different traditions. These tend to not only give answers to how to conduct an analysis, but also to provide the answer as to why it is conducted in the way that it is. The problem however may be that the li...... for themselves. The advantage of utilizing the presented analytic approach is argued to be the integral empirical testing, which should assure systematic development, interpretation and analysis of the source textual material....... between tradition and tool is unclear. The main objective of this article is therefore to present Empirical Testing Thematic Analysis, a step by step approach to thematic text analysis; discussing strengths and weaknesses, so that others might assess its potential as an approach that they might utilize/develop...

  9. Metabolic Surgery

    DEFF Research Database (Denmark)

    Pareek, Manan; Schauer, Philip R; Kaplan, Lee M

    2018-01-01

    The alarming rise in the worldwide prevalence of obesity is paralleled by an increasing burden of type 2 diabetes mellitus. Metabolic surgery is the most effective means of obtaining substantial and durable weight loss in individuals with obesity. Randomized trials have recently shown...... the superiority of surgery over medical treatment alone in achieving improved glycemic control, as well as a reduction in cardiovascular risk factors. The mechanisms seem to extend beyond the magnitude of weight loss alone and include improvements in incretin profiles, insulin secretion, and insulin sensitivity....... Moreover, observational data suggest that the reduction in cardiovascular risk factors translates to better patient outcomes. This review describes commonly used metabolic surgical procedures and their current indications and summarizes the evidence related to weight loss and glycemic outcomes. It further...

  10. Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Sevil Ikinci

    2010-10-01

    Full Text Available Metabolic Syndrome is a combination of risk factors including common etiopathogenesis. These risk factors play different roles in occurence of atherosclerotic diseases, type 2 diabetes, and cancers. Although a compromise can not be achieved on differential diagnosis for MS, the existence of any three criterias enable to diagnose MS. These are abdominal obesity, dislipidemia (hypertrigliceridemia, hypercholesterolemia, and reduced high density lipoprotein hypertension, and elevated fasting blood glucose. According to the results of Metabolic Syndrome Research (METSAR, the overall prevalence of MS in Turkey is 34%; in females 40%, and in males it is 28%. As a result of “Western” diet, and increased frequency of obesity, MS is observed in children and in adolescents both in the world and in Turkey. Resulting in chronic diseases, it is thought that the syndrome can be prevented by healthy lifestyle behaviours. [TAF Prev Med Bull 2010; 9(5.000: 535-540

  11. Essays in empirical industrial organization

    OpenAIRE

    Aguiar de Luque, Luis

    2013-01-01

    My PhD thesis consists of three chapters in Empirical Industrial Organization. The first two chapters focus on the relationship between firrm performance and specific public policies. In particular, we analyze the cases of cooperative research and development (R&D) in the European Union and the regulation of public transports in France. The third chapter focuses on copyright protection in the digital era and analyzes the relationship between legal and illegal consumption of di...

  12. Empirical research on Waldorf education

    OpenAIRE

    Randoll, Dirk; Peters, Jürgen

    2015-01-01

    Waldorf education began in 1919 with the first Waldorf School in Stuttgart and nowadays is widespread in many countries all over the world. Empirical research, however, has been rare until the early nineties and Waldorf education has not been discussed within educational science so far. This has changed during the last decades. This article reviews the results of surveys during the last 20 years and is mainly focused on German Waldorf Schools, because most investigations have been done in thi...

  13. Empirical distribution function under heteroscedasticity

    Czech Academy of Sciences Publication Activity Database

    Víšek, Jan Ámos

    2011-01-01

    Roč. 45, č. 5 (2011), s. 497-508 ISSN 0233-1888 Grant - others:GA UK(CZ) GA402/09/0557 Institutional research plan: CEZ:AV0Z10750506 Keywords : Robustness * Convergence * Empirical distribution * Heteroscedasticity Subject RIV: BB - Applied Statistics , Operational Research Impact factor: 0.724, year: 2011 http://library.utia.cas.cz/separaty/2011/SI/visek-0365534.pdf

  14. Expert opinion vs. empirical evidence

    OpenAIRE

    Herman, Rod A; Raybould, Alan

    2014-01-01

    Expert opinion is often sought by government regulatory agencies when there is insufficient empirical evidence to judge the safety implications of a course of action. However, it can be reckless to continue following expert opinion when a preponderance of evidence is amassed that conflicts with this opinion. Factual evidence should always trump opinion in prioritizing the information that is used to guide regulatory policy. Evidence-based medicine has seen a dramatic upturn in recent years sp...

  15. Cellular metabolism

    International Nuclear Information System (INIS)

    Hildebrand, C.E.; Walters, R.A.

    1977-01-01

    Progress is reported on the following research projects: chromatin structure; the use of circular synthetic polydeoxynucleotides as substrates for the study of DNA repair enzymes; human cellular kinetic response following exposure to DNA-interactive compounds; histone phosphorylation and chromatin structure in cell proliferation; photoaddition products induced in chromatin by uv light; pollutants and genetic information transfer; altered RNA metabolism as a function of cadmium accumulation and intracellular distribution in cultured cells; and thymidylate chromophore destruction by water free radicals

  16. Empirical isotropic chemical shift surfaces

    International Nuclear Information System (INIS)

    Czinki, Eszter; Csaszar, Attila G.

    2007-01-01

    A list of proteins is given for which spatial structures, with a resolution better than 2.5 A, are known from entries in the Protein Data Bank (PDB) and isotropic chemical shift (ICS) values are known from the RefDB database related to the Biological Magnetic Resonance Bank (BMRB) database. The structures chosen provide, with unknown uncertainties, dihedral angles φ and ψ characterizing the backbone structure of the residues. The joint use of experimental ICSs of the same residues within the proteins, again with mostly unknown uncertainties, and ab initio ICS(φ,ψ) surfaces obtained for the model peptides For-(l-Ala) n -NH 2 , with n = 1, 3, and 5, resulted in so-called empirical ICS(φ,ψ) surfaces for all major nuclei of the 20 naturally occurring α-amino acids. Out of the many empirical surfaces determined, it is the 13C α ICS(φ,ψ) surface which seems to be most promising for identifying major secondary structure types, α-helix, β-strand, left-handed helix (α D ), and polyproline-II. Detailed tests suggest that Ala is a good model for many naturally occurring α-amino acids. Two-dimensional empirical 13C α - 1 H α ICS(φ,ψ) correlation plots, obtained so far only from computations on small peptide models, suggest the utility of the experimental information contained therein and thus they should provide useful constraints for structure determinations of proteins

  17. Two concepts of empirical ethics.

    Science.gov (United States)

    Parker, Malcolm

    2009-05-01

    The turn to empirical ethics answers two calls. The first is for a richer account of morality than that afforded by bioethical principlism, which is cast as excessively abstract and thin on the facts. The second is for the facts in question to be those of human experience and not some other, unworldly realm. Empirical ethics therefore promises a richer naturalistic ethics, but in fulfilling the second call it often fails to heed the metaethical requirements related to the first. Empirical ethics risks losing the normative edge which necessarily characterizes the ethical, by failing to account for the nature and the logic of moral norms. I sketch a naturalistic theory, teleological expressivism (TE), which negotiates the naturalistic fallacy by providing a more satisfactory means of taking into account facts and research data with ethical implications. The examples of informed consent and the euthanasia debate are used to illustrate the superiority of this approach, and the problems consequent on including the facts in the wrong kind of way.

  18. The impact of regional environmental regulations on empirical vessel speeds

    OpenAIRE

    Ådland, Roar Os; Fonnes, Gro; Jia, Haiying; Daae Lampe, Ove; Strandenes, Siri Pettersen

    2017-01-01

    Economic theory suggests that the use of more expensive low-sulphur fuel within an Emission Control Area (ECA) should result in lower vessel speeds. The objective of this paper is to investigate empirically, for the first time, whether the introduction of an ECA affects vessel speeds. We utilize a dataset of observed vessel speeds derived from the Automated Information System (AIS) for nearly 7000 ECA boundary crossings over a three-year period. Our results suggest that introducing stricter s...

  19. Engineering microbial fatty acid metabolism for biofuels and biochemicals

    DEFF Research Database (Denmark)

    Marella, Eko Roy; Holkenbrink, Carina; Siewers, Verena

    2017-01-01

    microbial catalysis. This review summarizes the recent advances in the engineering of microbial metabolism for production of fatty acid-derived products. We highlight the efforts in engineering the central carbon metabolism, redox metabolism, controlling the chain length of the products, and obtaining...

  20. Empirical Phenomenology: A Qualitative Research Approach (The ...

    African Journals Online (AJOL)

    Empirical Phenomenology: A Qualitative Research Approach (The Cologne Seminars) ... and practical application of empirical phenomenology in social research. ... and considers its implications for qualitative methods such as interviewing ...

  1. Derivative chameleons

    International Nuclear Information System (INIS)

    Noller, Johannes

    2012-01-01

    We consider generalized chameleon models where the conformal coupling between matter and gravitational geometries is not only a function of the chameleon field φ, but also of its derivatives via higher order co-ordinate invariants (such as ∂ μ φ∂ μ φ,□φ,...). Specifically we consider the first such non-trivial conformal factor A(φ,∂ μ φ∂ μ φ). The associated phenomenology is investigated and we show that such theories have a new generic mass-altering mechanism, potentially assisting the generation of a sufficiently large chameleon mass in dense environments. The most general effective potential is derived for such derivative chameleon setups and explicit examples are given. Interestingly this points us to the existence of a purely derivative chameleon protected by a shift symmetry for φ → φ+c. We also discuss potential ghost-like instabilities associated with mass-lifting mechanisms and find another, mass-lowering and instability-free, branch of solutions. This suggests that, barring fine-tuning, stable derivative models are in fact typically anti-chameleons that suppress the field's mass in dense environments. Furthermore we investigate modifications to the thin-shell regime and prove a no-go theorem for chameleon effects in non-conformal geometries of the disformal type

  2. Derivative chameleons

    Energy Technology Data Exchange (ETDEWEB)

    Noller, Johannes, E-mail: johannes.noller08@imperial.ac.uk [Theoretical Physics, Blackett Laboratory, Imperial College London, Prince Consort Road, London, SW7 2BZ (United Kingdom)

    2012-07-01

    We consider generalized chameleon models where the conformal coupling between matter and gravitational geometries is not only a function of the chameleon field φ, but also of its derivatives via higher order co-ordinate invariants (such as ∂{sub μ}φ∂{sup μ}φ,□φ,...). Specifically we consider the first such non-trivial conformal factor A(φ,∂{sub μ}φ∂{sup μ}φ). The associated phenomenology is investigated and we show that such theories have a new generic mass-altering mechanism, potentially assisting the generation of a sufficiently large chameleon mass in dense environments. The most general effective potential is derived for such derivative chameleon setups and explicit examples are given. Interestingly this points us to the existence of a purely derivative chameleon protected by a shift symmetry for φ → φ+c. We also discuss potential ghost-like instabilities associated with mass-lifting mechanisms and find another, mass-lowering and instability-free, branch of solutions. This suggests that, barring fine-tuning, stable derivative models are in fact typically anti-chameleons that suppress the field's mass in dense environments. Furthermore we investigate modifications to the thin-shell regime and prove a no-go theorem for chameleon effects in non-conformal geometries of the disformal type.

  3. Empirical yield tables for Michigan.

    Science.gov (United States)

    Jerold T. Hahn; Joan M. Stelman

    1984-01-01

    Describes the tables derived from the 1980 Forest Survey of Michigan and presents ways the tables can be used. These tables are broken down according to Michigan's four Forest Survey Units, 14 forest types, and 5 site-index classes.

  4. Empirical yield tables for Wisconsin.

    Science.gov (United States)

    Jerold T. Hahn; Joan M. Stelman

    1989-01-01

    Describes the tables derived from the 1983 Forest Survey of Wisconsin and presents ways the tables can be used. These tables are broken down according to Wisconsin`s five Forest Survey Units and 14 forest types.

  5. Electricity derivatives

    CERN Document Server

    Aïd, René

    2015-01-01

    Offering a concise but complete survey of the common features of the microstructure of electricity markets, this book describes the state of the art in the different proposed electricity price models for pricing derivatives and in the numerical methods used to price and hedge the most prominent derivatives in electricity markets, namely power plants and swings. The mathematical content of the book has intentionally been made light in order to concentrate on the main subject matter, avoiding fastidious computations. Wherever possible, the models are illustrated by diagrams. The book should allow prospective researchers in the field of electricity derivatives to focus on the actual difficulties associated with the subject. It should also offer a brief but exhaustive overview of the latest techniques used by financial engineers in energy utilities and energy trading desks.

  6. Science and the British Empire.

    Science.gov (United States)

    Harrison, Mark

    2005-03-01

    The last few decades have witnessed a flowering of interest in the history of science in the British Empire. This essay aims to provide an overview of some of the most important work in this area, identifying interpretative shifts and emerging themes. In so doing, it raises some questions about the analytical framework in which colonial science has traditionally been viewed, highlighting interactions with indigenous scientific traditions and the use of network-based models to understand scientific relations within and beyond colonial contexts.

  7. Empirical logic and tensor products

    International Nuclear Information System (INIS)

    Foulis, D.J.; Randall, C.H.

    1981-01-01

    In our work we are developing a formalism called empirical logic to support a generalization of conventional statistics; the resulting generalization is called operational statistics. We are not attempting to develop or advocate any particular physical theory; rather we are formulating a precision 'language' in which such theories can be expressed, compared, evaluated, and related to laboratory experiments. We believe that only in such a language can the connections between real physical procedures (operations) and physical theories be made explicit and perspicuous. (orig./HSI)

  8. Empirical reality, empirical causality, and the measurement problem

    International Nuclear Information System (INIS)

    d'Espagnat, B.

    1987-01-01

    Does physics describe anything that can meaningfully be called independent reality, or is it merely operational? Most physicists implicitly favor an intermediate standpoint, which takes quantum physics into account, but which nevertheless strongly holds fast to quite strictly realistic ideas about apparently obvious facts concerning the macro-objects. Part 1 of this article, which is a survey of recent measurement theories, shows that, when made explicit, the standpoint in question cannot be upheld. Part 2 brings forward a proposal for making minimal changes to this standpoint in such a way as to remove such objections. The empirical reality thus constructed is a notion that, to some extent, does ultimately refer to the human means of apprehension and of data processing. It nevertheless cannot be said that it reduces to a mere name just labelling a set of recipes that never fail. It is shown that their usual notion of macroscopic causality must be endowed with similar features

  9. Genome-Scale Reconstruction of the Human Astrocyte Metabolic Network

    OpenAIRE

    Mart?n-Jim?nez, Cynthia A.; Salazar-Barreto, Diego; Barreto, George E.; Gonz?lez, Janneth

    2017-01-01

    Astrocytes are the most abundant cells of the central nervous system; they have a predominant role in maintaining brain metabolism. In this sense, abnormal metabolic states have been found in different neuropathological diseases. Determination of metabolic states of astrocytes is difficult to model using current experimental approaches given the high number of reactions and metabolites present. Thus, genome-scale metabolic networks derived from transcriptomic data can be used as a framework t...

  10. Transformation of an empirical distribution to normal distribution by the use of Johnson system of translation and symmetrical quantile method

    OpenAIRE

    Ludvík Friebel; Jana Friebelová

    2006-01-01

    This article deals with approximation of empirical distribution to standard normal distribution using Johnson transformation. This transformation enables us to approximate wide spectrum of continuous distributions with a normal distribution. The estimation of parameters of transformation formulas is based on percentiles of empirical distribution. There are derived theoretical probability distribution functions of random variable obtained on the base of backward transformation standard normal ...

  11. Proposed empirical gas geothermometer using multidimensional approach

    Energy Technology Data Exchange (ETDEWEB)

    Supranto; Sudjatmiko; Toha, Budianto; Wintolo, Djoko; Alhamid, Idrus

    1996-01-24

    Several formulas of surface gas geothermometer have been developed to utilize in geothermal exploration, i.e. by D'Amore and Panichi (1980) and by Darling and Talbot (1992). This paper presents an empirical gas geothermometer formula using multidimensional approach. The formula was derived from 37 selected chemical data of the 5 production wells from the Awibengkok Geothermal Volcanic Field in West Java. Seven components, i.e., gas volume percentage, CO2, H2S, CH4, H2, N2, and NH3, from these data are utilize to developed three model equations which represent relationship between temperature and gas compositions. These formulas are then tested by several fumarolic chemical data from Sibual-buali Area (North Sumatera) and from Ringgit Area (South Sumatera). Preliminary result indicated that gas volume percentage, H2S and CO2 concentrations have a significant role in term of gas geothermometer. Further verification is currently in progress.

  12. Empirical particle transport model for tokamaks

    International Nuclear Information System (INIS)

    Petravic, M.; Kuo-Petravic, G.

    1986-08-01

    A simple empirical particle transport model has been constructed with the purpose of gaining insight into the L- to H-mode transition in tokamaks. The aim was to construct the simplest possible model which would reproduce the measured density profiles in the L-regime, and also produce a qualitatively correct transition to the H-regime without having to assume a completely different transport mode for the bulk of the plasma. Rather than using completely ad hoc constructions for the particle diffusion coefficient, we assume D = 1/5 chi/sub total/, where chi/sub total/ ≅ chi/sub e/ is the thermal diffusivity, and then use the κ/sub e/ = n/sub e/chi/sub e/ values derived from experiments. The observed temperature profiles are then automatically reproduced, but nontrivially, the correct density profiles are also obtained, for realistic fueling rates and profiles. Our conclusion is that it is sufficient to reduce the transport coefficients within a few centimeters of the surface to produce the H-mode behavior. An additional simple assumption, concerning the particle mean-free path, leads to a convective transport term which reverses sign a few centimeters inside the surface, as required by the H-mode density profiles

  13. Expert opinion vs. empirical evidence

    Science.gov (United States)

    Herman, Rod A; Raybould, Alan

    2014-01-01

    Expert opinion is often sought by government regulatory agencies when there is insufficient empirical evidence to judge the safety implications of a course of action. However, it can be reckless to continue following expert opinion when a preponderance of evidence is amassed that conflicts with this opinion. Factual evidence should always trump opinion in prioritizing the information that is used to guide regulatory policy. Evidence-based medicine has seen a dramatic upturn in recent years spurred by examples where evidence indicated that certain treatments recommended by expert opinions increased death rates. We suggest that scientific evidence should also take priority over expert opinion in the regulation of genetically modified crops (GM). Examples of regulatory data requirements that are not justified based on the mass of evidence are described, and it is suggested that expertise in risk assessment should guide evidence-based regulation of GM crops. PMID:24637724

  14. Large wood influence on stream metabolism at a reach-scale in the Assabet River, Massachusetts

    Science.gov (United States)

    David, G. C. L.; Snyder, N. P.; Rosario, G. M.

    2016-12-01

    Total stream metabolism (TSM) represents the transfer of carbon through a channel by both primary production and respiration, and thus represents the movement of energy through a watershed. Large wood (LW) creates geomorphically complex channels by diverting flows, altering shear stresses on the channel bed and banks, and pool development. The increase in habitat complexity around LW is expected to increase TSM, but this change has not been directly measured. In this study, we measured changes in TSM around a LW jam in a Massachusetts river. Dissolved oxygen (DO) time series data are used to quantify gross primary production (GPP), ecosystem respiration (ER), which equal TSM when summed. Two primary objectives of this study are to (1) assess changes in TSM around LW and (2) compare empirical methods of deriving TSM to Grace et al.'s (2015) BASE model. We hypothesized that LW would increase TSM by providing larger pools, increasing coverage for fish and macroinvertebrates, increasing organic matter accumulation, and providing a place for primary producers to anchor and grow. The Assabet River is a 78 km2 drainage basin in central Massachusetts that provides public water supply to 7 towns. A change in TSM over a reach-scale was assessed using two YSI 6-Series Multiparameter Water Quality sondes over a 140 m long pool-riffle open meadow section. The reach included 6 pools and one LW jam. Every two weeks from July to November 2015, the sondes were moved to different pools. The sondes collected DO, temperature, depth, pH, salinity, light intensity, and turbidity at 15-minute intervals. Velocity (V) and discharge (Q) were measured weekly around the sondes and at established cross sections. Instantaneous V and Q were calculated for each sonde by modeling flows in HEC-RAS. Overall, TSM was heavily influenced by the pool size and indirectly to the LW jam which was associated with the largest pool. The largest error in TSM calculations is related to the empirically

  15. A Balanced Theoretical and Empirical Approach for the Development of a Design Support Tool

    DEFF Research Database (Denmark)

    Jensen, Thomas Aakjær; Hansen, Claus Thorp

    1996-01-01

    The introduction of a new design support system may change the engineering designer's work situation. Therefore, it may not be possible to derive all the functionalities for a design support system from solely empirical studies of manual design work. Alternatively the design support system could ...... system, indicating a proposal for how to balance a theoretical and empirical approach. The result of this research will be utilized in the development of a Designer's Workbench to support the synthesis activity in mechanical design....

  16. Carnitine derivatives: clinical usefulness.

    Science.gov (United States)

    Malaguarnera, Mariano

    2012-03-01

    Carnitine and its derivatives are natural substances involved in both carbohydrate and lipid metabolism. This review summarizes the recent progress in the field in relation to the molecular mechanisms. The pool of different carnitine derivatives is formed by acetyl-L-carnitine (ALC), propionyl-L-carnitine (PLC), and isovaleryl-carnitine. ALC may have a preferential effect on the brain tissue. ALC represents a compound of great interest for its wide clinical application in various neurological disorders: it may be of benefit in treating Alzheimer's dementia, depression in the elderly, HIV infection, chronic fatigue syndrome, peripheral neuropathies, ischemia and reperfusion of the brain, and cognitive impairment associated with various conditions. PLC has been demonstrated to replenish the intermediates of the tricarboxylic acid cycle by the propionyl-CoA moiety, a greater affinity for the sarcolemmal carrier, peripheral vasodilator activity, a greater positive inotropism, and more rapid entry into myocytes. Most studies of the therapeutic use of PLC are focused on the prevention and treatment of ischemic heart disease, congestive heart failure, hypertrophic heart disease, and peripheral arterial disease. ALC and PLC are considered well tolerated without significant side-effects. A number of therapeutic effects possibly come from the interaction of carnitine and its derivatives with the elements of cellular membranes.

  17. An empirical algorithm to estimate spectral average cosine of underwater light field from remote sensing data in coastal oceanic waters.

    Digital Repository Service at National Institute of Oceanography (India)

    Talaulika, M.; Suresh, T.; Desa, E.S.; Inamdar, A.

    parameters from the coastal waters off Goa, India, and eastern Arabian Sea and the optical parameters derived using the radiative transfer code using these measured data. The algorithm was compared with two earlier reported empirical algorithms of Haltrin...

  18. Empirical yield tables for Minnesota.

    Science.gov (United States)

    Jerold T. Hahn; Gerhard K. Raile

    1982-01-01

    Describes the tables derived from the 1977 Forest Survey of Minnesota and presents examples of how the tables can be used. These tables are broken down according to Minnesota's four Forest Survey Units, 14 forest types, and 5 site index classes. Presents 210 of the 350 possible tables that contained sufficient data to justify publication.

  19. Dithiobiuret metabolism in the rat

    International Nuclear Information System (INIS)

    Williams, K.D.; Porter, W.R.; Peterson, R.E.

    1982-01-01

    Our main objective was to describe the metabolism of dithiobiuret (DTB) in the adult, male rat. Based on the thin-layer chromatographic analysis of urine from animals treated with [ 14 C] or [ 35 S] labeled DTB, two pathways for metabolism are proposed. One pathway is reversible and involves the oxidation of DTB to thiuret and the reduction of thiuret back to DTB. The other pathway consists of the desulfurization of DTB to monothiobiuret. The liver appears to desulfurate DTB because DTB-derived [35S] was eliminated from the liver more rapidly than [ 14 C]. The liver was the only tissue where the elimination kinetics of [ 35 S] and [ 14 C] DTB were different. DTB-derived radioactivity in urine that co-chromatographed with DTB, monothiobiuret, thiuret and sulfate was quantitated along with that of three uncharacterized metabolites. The presence of these unknown metabolites suggests that DTB metabolism is complex. The present study is the first description of the metabolic fate of DTB in the rat and serves as a starting point for determining whether DTB neurotoxicity is caused by the parent compound or a metabolite

  20. Carbohydrate Metabolism Disorders

    Science.gov (United States)

    ... metabolic disorder, something goes wrong with this process. Carbohydrate metabolism disorders are a group of metabolic disorders. Normally your enzymes break carbohydrates down into glucose (a type of sugar). If ...

  1. Comprehensive metabolic panel

    Science.gov (United States)

    Metabolic panel - comprehensive; Chem-20; SMA20; Sequential multi-channel analysis with computer-20; SMAC20; Metabolic panel 20 ... Chernecky CC, Berger BJ. Comprehensive metabolic panel (CMP) - blood. In: ... Tests and Diagnostic Procedures . 6th ed. St Louis, MO: ...

  2. Econometric Analysis of Financial Derivatives : An overview

    NARCIS (Netherlands)

    C-L. Chang (Chia-Lin); M.J. McAleer (Michael)

    2014-01-01

    markdownabstract__Abstract__ One of the fastest growing areas in empirical finance, and also one of the least rigorously analyzed, especially from a financial econometrics perspective, is the econometric analysis of financial derivatives, which are typically complicated and difficult to analyze.

  3. Econometric Analysis of Financial Derivatives: An Overview

    NARCIS (Netherlands)

    C-L. Chang (Chia-Lin); M.J. McAleer (Michael)

    2014-01-01

    markdownabstract__Abstract__ One of the fastest growing areas in empirical finance, and also one of the least rigorously analyzed, especially from a financial econometrics perspective, is the econometric analysis of financial derivatives, which are typically complicated and difficult to analyze.

  4. Risk Management and Financial Derivatives: An Overview

    NARCIS (Netherlands)

    S.M. Hammoudeh (Shawkat); M.J. McAleer (Michael)

    2012-01-01

    textabstractRisk management is crucial for optimal portfolio management. One of the fastest growing areas in empirical finance is the expansion of financial derivatives. The purpose of this special issue on “Risk Management and Financial Derivatives” is to highlight some areas in which novel

  5. Equine Metabolic Syndrome Affects Viability, Senescence, and Stress Factors of Equine Adipose-Derived Mesenchymal Stromal Stem Cells: New Insight into EqASCs Isolated from EMS Horses in the Context of Their Aging

    Directory of Open Access Journals (Sweden)

    Krzysztof Marycz

    2016-01-01

    Full Text Available Currently, equine metabolic syndrome (EMS, an endocrine disease linked to insulin resistance, affects an increasing number of horses. However, little is known about the effect of EMS on mesenchymal stem cells that reside in adipose tissue (ASC. Thus it is crucial to evaluate the viability and growth kinetics of these cells, particularly in terms of their application in regenerative medicine. In this study, we investigated the proliferative capacity, morphological features, and accumulation of oxidative stress factors in mesenchymal stem cells isolated from healthy animals (ASCN and horses suffering from EMS (ASCEMS. ASCEMS displayed senescent phenotype associated with β-galactosidase accumulation, enlarged cell bodies and nuclei, increased apoptosis, and reduced heterochromatin architecture. Moreover, we observed increased amounts of nitric oxide (NO and reactive oxygen species (ROS in these cells, accompanied by reduced superoxide dismutase (SOD activity. We also found in ASCEMS an elevated number of impaired mitochondria, characterized by membrane raptures, disarrayed cristae, and vacuole formation. Our results suggest that the toxic compounds, accumulating in the mitochondria under oxidative stress, lead to alternations in their morphology and may be partially responsible for the senescent phenotype and decreased proliferation potential of ASCEMS.

  6. Pluvials, droughts, the Mongol Empire, and modern Mongolia.

    Science.gov (United States)

    Pederson, Neil; Hessl, Amy E; Baatarbileg, Nachin; Anchukaitis, Kevin J; Di Cosmo, Nicola

    2014-03-25

    Although many studies have associated the demise of complex societies with deteriorating climate, few have investigated the connection between an ameliorating environment, surplus resources, energy, and the rise of empires. The 13th-century Mongol Empire was the largest contiguous land empire in world history. Although drought has been proposed as one factor that spurred these conquests, no high-resolution moisture data are available during the rapid development of the Mongol Empire. Here we present a 1,112-y tree-ring reconstruction of warm-season water balance derived from Siberian pine (Pinus sibirica) trees in central Mongolia. Our reconstruction accounts for 56% of the variability in the regional water balance and is significantly correlated with steppe productivity across central Mongolia. In combination with a gridded temperature reconstruction, our results indicate that the regional climate during the conquests of Chinggis Khan's (Genghis Khan's) 13th-century Mongol Empire was warm and persistently wet. This period, characterized by 15 consecutive years of above-average moisture in central Mongolia and coinciding with the rise of Chinggis Khan, is unprecedented over the last 1,112 y. We propose that these climate conditions promoted high grassland productivity and favored the formation of Mongol political and military power. Tree-ring and meteorological data also suggest that the early 21st-century drought in central Mongolia was the hottest drought in the last 1,112 y, consistent with projections of warming over Inner Asia. Future warming may overwhelm increases in precipitation leading to similar heat droughts, with potentially severe consequences for modern Mongolia.

  7. Pluvials, droughts, the Mongol Empire, and modern Mongolia

    Science.gov (United States)

    Pederson, Neil; Hessl, Amy E.; Baatarbileg, Nachin; Anchukaitis, Kevin J.; Di Cosmo, Nicola

    2014-01-01

    Although many studies have associated the demise of complex societies with deteriorating climate, few have investigated the connection between an ameliorating environment, surplus resources, energy, and the rise of empires. The 13th-century Mongol Empire was the largest contiguous land empire in world history. Although drought has been proposed as one factor that spurred these conquests, no high-resolution moisture data are available during the rapid development of the Mongol Empire. Here we present a 1,112-y tree-ring reconstruction of warm-season water balance derived from Siberian pine (Pinus sibirica) trees in central Mongolia. Our reconstruction accounts for 56% of the variability in the regional water balance and is significantly correlated with steppe productivity across central Mongolia. In combination with a gridded temperature reconstruction, our results indicate that the regional climate during the conquests of Chinggis Khan’s (Genghis Khan’s) 13th-century Mongol Empire was warm and persistently wet. This period, characterized by 15 consecutive years of above-average moisture in central Mongolia and coinciding with the rise of Chinggis Khan, is unprecedented over the last 1,112 y. We propose that these climate conditions promoted high grassland productivity and favored the formation of Mongol political and military power. Tree-ring and meteorological data also suggest that the early 21st-century drought in central Mongolia was the hottest drought in the last 1,112 y, consistent with projections of warming over Inner Asia. Future warming may overwhelm increases in precipitation leading to similar heat droughts, with potentially severe consequences for modern Mongolia. PMID:24616521

  8. Pluvials, droughts, the Mongol Empire, and modern Mongolia

    Science.gov (United States)

    Pederson, Neil; Hessl, Amy E.; Baatarbileg, Nachin; Anchukaitis, Kevin J.; Di Cosmo, Nicola

    2014-03-01

    Although many studies have associated the demise of complex societies with deteriorating climate, few have investigated the connection between an ameliorating environment, surplus resources, energy, and the rise of empires. The 13th-century Mongol Empire was the largest contiguous land empire in world history. Although drought has been proposed as one factor that spurred these conquests, no high-resolution moisture data are available during the rapid development of the Mongol Empire. Here we present a 1,112-y tree-ring reconstruction of warm-season water balance derived from Siberian pine (Pinus sibirica) trees in central Mongolia. Our reconstruction accounts for 56% of the variability in the regional water balance and is significantly correlated with steppe productivity across central Mongolia. In combination with a gridded temperature reconstruction, our results indicate that the regional climate during the conquests of Chinggis Khan's (Genghis Khan's) 13th-century Mongol Empire was warm and persistently wet. This period, characterized by 15 consecutive years of above-average moisture in central Mongolia and coinciding with the rise of Chinggis Khan, is unprecedented over the last 1,112 y. We propose that these climate conditions promoted high grassland productivity and favored the formation of Mongol political and military power. Tree-ring and meteorological data also suggest that the early 21st-century drought in central Mongolia was the hottest drought in the last 1,112 y, consistent with projections of warming over Inner Asia. Future warming may overwhelm increases in precipitation leading to similar heat droughts, with potentially severe consequences for modern Mongolia.

  9. Fibroblast Growth Factor Signaling in Metabolic Regulation.

    Science.gov (United States)

    Nies, Vera J M; Sancar, Gencer; Liu, Weilin; van Zutphen, Tim; Struik, Dicky; Yu, Ruth T; Atkins, Annette R; Evans, Ronald M; Jonker, Johan W; Downes, Michael Robert

    2015-01-01

    The prevalence of obesity is a growing health problem. Obesity is strongly associated with several comorbidities, such as non-alcoholic fatty liver disease, certain cancers, insulin resistance, and type 2 diabetes, which all reduce life expectancy and life quality. Several drugs have been put forward in order to treat these diseases, but many of them have detrimental side effects. The unexpected role of the family of fibroblast growth factors in the regulation of energy metabolism provides new approaches to the treatment of metabolic diseases and offers a valuable tool to gain more insight into metabolic regulation. The known beneficial effects of FGF19 and FGF21 on metabolism, together with recently discovered similar effects of FGF1 suggest that FGFs and their derivatives carry great potential as novel therapeutics to treat metabolic conditions. To facilitate the development of new therapies with improved targeting and minimal side effects, a better understanding of the molecular mechanism of action of FGFs is needed. In this review, we will discuss what is currently known about the physiological roles of FGF signaling in tissues important for metabolic homeostasis. In addition, we will discuss current concepts regarding their pharmacological properties and effector tissues in the context of metabolic disease. Also, the recent progress in the development of FGF variants will be reviewed. Our goal is to provide a comprehensive overview of the current concepts and consensuses regarding FGF signaling in metabolic health and disease and to provide starting points for the development of FGF-based therapies against metabolic conditions.

  10. An Empirical Mass Function Distribution

    Science.gov (United States)

    Murray, S. G.; Robotham, A. S. G.; Power, C.

    2018-03-01

    The halo mass function, encoding the comoving number density of dark matter halos of a given mass, plays a key role in understanding the formation and evolution of galaxies. As such, it is a key goal of current and future deep optical surveys to constrain the mass function down to mass scales that typically host {L}\\star galaxies. Motivated by the proven accuracy of Press–Schechter-type mass functions, we introduce a related but purely empirical form consistent with standard formulae to better than 4% in the medium-mass regime, {10}10{--}{10}13 {h}-1 {M}ȯ . In particular, our form consists of four parameters, each of which has a simple interpretation, and can be directly related to parameters of the galaxy distribution, such as {L}\\star . Using this form within a hierarchical Bayesian likelihood model, we show how individual mass-measurement errors can be successfully included in a typical analysis, while accounting for Eddington bias. We apply our form to a question of survey design in the context of a semi-realistic data model, illustrating how it can be used to obtain optimal balance between survey depth and angular coverage for constraints on mass function parameters. Open-source Python and R codes to apply our new form are provided at http://mrpy.readthedocs.org and https://cran.r-project.org/web/packages/tggd/index.html respectively.

  11. Toward a feline-optimized culture medium: impact of ions, carbohydrates, essential amino acids, vitamins, and serum on development and metabolism of in vitro fertilization-derived feline embryos relative to embryos grown in vivo.

    Science.gov (United States)

    Herrick, Jason R; Bond, Jennifer B; Magarey, Genevieve M; Bateman, Helen L; Krisher, Rebecca L; Dunford, Susan A; Swanson, William F

    2007-05-01

    The objective of this study was to define the physiologic needs of domestic cat embryos to facilitate development of a feline-specific culture medium. In a series of factorial experiments, in vivo-matured oocytes (n = 2040) from gonadotropin-treated domestic cats were inseminated in vitro to generate embryos (n = 1464) for culture. In the initial study, concentrations of NaCl (100.0 vs. 120.0 mM), KCl (4.0 vs. 8.0 mM), KH(2)PO(4) (0.25 vs. 1.0 mM), and the ratio of CaCl(2) to MgSO(4)-7H(2)O (1.0:2.0 mM vs. 2.0:1.0 mM) in the medium were evaluated during Days 1-6 (Day 0: oocyte recovery and in vitro fertilization [IVF]) of culture. Subsequent experiments assessed the effects of varying concentrations of carbohydrate (glucose, 1.5, 3.0, or 6.0 mM; l-lactate, 3.0, 6.0, or 12.0 mM; and pyruvate, 0.1 or 1.0 mM) and essential amino acids (EAAs; 0, 0.5, or 1.0x) in the medium during Days 1-3 and Days 3-6 of culture. Inclusion of vitamins (0 vs. 1.0x) and fetal calf serum (FCS; 0 vs. 5% [v/v]) in the medium also was evaluated during Days 3-6. Development and metabolism of IVF embryos on Day 3 or Day 6 were compared to age-matched in vivo embryos recovered from naturally mated queens. A feline-optimized culture medium (FOCM) was formulated based on these results (100.0 mM NaCl, 8.0 mM KCl, 1.0 mM KH(2)PO(4), 2.0 mM CaCl(2), 1.0 mM MgSO(4), 1.5 mM glucose, 6.0 mM L-lactate, 0.1 mM pyruvate, and 0x EAAs with 25.0 mM NaHCO(3), 1.0 mM alanyl-glutamine, 0.1 mM taurine, and 1.0x nonessential amino acids) with 0.4% (w/v) BSA from Days 0-3 and 5% FCS from Days 3-6. Using this medium, ~70% of cleaved embryos developed into blastocysts with profiles of carbohydrate metabolism similar to in vivo embryos. Our results suggest that feline embryos have stage-specific responses to carbohydrates and are sensitive to EAAs but are still reliant on one or more unidentified components of FCS for optimal blastocyst development.

  12. Effect of Creosote Bush-Derived NDGA on Expression of Genes Involved in Lipid Metabolism in Liver of High-Fructose Fed Rats: Relevance to NDGA Amelioration of Hypertriglyceridemia and Hepatic Steatosis.

    Directory of Open Access Journals (Sweden)

    Haiyan Zhang

    Full Text Available Nordihydroguaiaretic acid (NDGA, the main metabolite of Creosote bush, has been shown to have profound effects on the core components of the metabolic syndrome (MetS, lowering blood glucose, free fatty acids (FFA and triglyceride (TG levels in several models of dyslipidemia, as well as improving body weight (obesity, insulin resistance, diabetes and hypertension, and ameliorating hepatic steatosis. In the present study, a high-fructose diet (HFrD fed rat model of hypertriglyceridemia was employed to further delineate the underlying mechanism by which NDGA exerts its anti-hypertriglyceridemic action. In the HFrD treatment group, NDGA administration by oral gavage decreased plasma levels of TG, glucose, FFA, and insulin, increased hepatic mitochondrial fatty acid oxidation and attenuated hepatic TG accumulation. qRT-PCR measurements indicated that NDGA treatment increased the mRNA expression of key fatty acid transport (L-FABP, CD36, and fatty acid oxidation (ACOX1, CPT-2, and PPARα transcription factor genes and decreased the gene expression of enzymes involved in lipogenesis (FASN, ACC1, SCD1, L-PK and ChREBP and SREBP-1c transcription factors. Western blot analysis indicated that NDGA administration upregulated hepatic insulin signaling (P-Akt, AMPK activity (P-AMPK, MLYCD, and PPARα protein levels, but decreased SCD1, ACC1 and ACC2 protein content and also inactivated ACC1 activity (increased P-ACC1. These findings suggest that NDGA ameliorates hypertriglyceridemia and hepatic steatosis primarily by interfering with lipogenesis and promoting increased channeling of fatty acids towards their oxidation.

  13. Empirical STORM-E Model. [I. Theoretical and Observational Basis

    Science.gov (United States)

    Mertens, Christopher J.; Xu, Xiaojing; Bilitza, Dieter; Mlynczak, Martin G.; Russell, James M., III

    2013-01-01

    Auroral nighttime infrared emission observed by the Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) instrument onboard the Thermosphere-Ionosphere-Mesosphere Energetics and Dynamics (TIMED) satellite is used to develop an empirical model of geomagnetic storm enhancements to E-region peak electron densities. The empirical model is called STORM-E and will be incorporated into the 2012 release of the International Reference Ionosphere (IRI). The proxy for characterizing the E-region response to geomagnetic forcing is NO+(v) volume emission rates (VER) derived from the TIMED/SABER 4.3 lm channel limb radiance measurements. The storm-time response of the NO+(v) 4.3 lm VER is sensitive to auroral particle precipitation. A statistical database of storm-time to climatological quiet-time ratios of SABER-observed NO+(v) 4.3 lm VER are fit to widely available geomagnetic indices using the theoretical framework of linear impulse-response theory. The STORM-E model provides a dynamic storm-time correction factor to adjust a known quiescent E-region electron density peak concentration for geomagnetic enhancements due to auroral particle precipitation. Part II of this series describes the explicit development of the empirical storm-time correction factor for E-region peak electron densities, and shows comparisons of E-region electron densities between STORM-E predictions and incoherent scatter radar measurements. In this paper, Part I of the series, the efficacy of using SABER-derived NO+(v) VER as a proxy for the E-region response to solar-geomagnetic disturbances is presented. Furthermore, a detailed description of the algorithms and methodologies used to derive NO+(v) VER from SABER 4.3 lm limb emission measurements is given. Finally, an assessment of key uncertainties in retrieving NO+(v) VER is presented

  14. Essays on empirical likelihood in economics

    NARCIS (Netherlands)

    Gao, Z.

    2012-01-01

    This thesis intends to exploit the roots of empirical likelihood and its related methods in mathematical programming and computation. The roots will be connected and the connections will induce new solutions for the problems of estimation, computation, and generalization of empirical likelihood.

  15. Empirical training for conditional random fields

    NARCIS (Netherlands)

    Zhu, Zhemin; Hiemstra, Djoerd; Apers, Peter M.G.; Wombacher, Andreas

    2013-01-01

    In this paper (Zhu et al., 2013), we present a practi- cally scalable training method for CRFs called Empir- ical Training (EP). We show that the standard train- ing with unregularized log likelihood can have many maximum likelihood estimations (MLEs). Empirical training has a unique closed form MLE

  16. Intermodal connectivity in Europe, an empirical exploration

    NARCIS (Netherlands)

    de Langen, P.W.; Lases Figueroa, D.M.; van Donselaar, K.H.; Bozuwa, J.

    2017-01-01

    In this paper we analyse the intermodal connectivity in Europe. The empirical analysis is to our knowledge the first empirical analysis of intermodal connections, and is based on a comprehensive database of intermodal connections in Europe. The paper focuses on rail and barge services, as they are

  17. Empirical Moral Philosophy and Teacher Education

    Science.gov (United States)

    Schjetne, Espen; Afdal, Hilde Wågsås; Anker, Trine; Johannesen, Nina; Afdal, Geir

    2016-01-01

    In this paper, we explore the possible contributions of empirical moral philosophy to professional ethics in teacher education. We argue that it is both possible and desirable to connect knowledge of how teachers empirically do and understand professional ethics with normative theories of teachers' professional ethics. Our argument is made in…

  18. Empirical ethics, context-sensitivity, and contextualism.

    Science.gov (United States)

    Musschenga, Albert W

    2005-10-01

    In medical ethics, business ethics, and some branches of political philosophy (multi-culturalism, issues of just allocation, and equitable distribution) the literature increasingly combines insights from ethics and the social sciences. Some authors in medical ethics even speak of a new phase in the history of ethics, hailing "empirical ethics" as a logical next step in the development of practical ethics after the turn to "applied ethics." The name empirical ethics is ill-chosen because of its associations with "descriptive ethics." Unlike descriptive ethics, however, empirical ethics aims to be both descriptive and normative. The first question on which I focus is what kind of empirical research is used by empirical ethics and for which purposes. I argue that the ultimate aim of all empirical ethics is to improve the context-sensitivity of ethics. The second question is whether empirical ethics is essentially connected with specific positions in meta-ethics. I show that in some kinds of meta-ethical theories, which I categorize as broad contextualist theories, there is an intrinsic need for connecting normative ethics with empirical social research. But context-sensitivity is a goal that can be aimed for from any meta-ethical position.

  19. The emerging empirics of evolutionary economic geography

    NARCIS (Netherlands)

    Boschma, R.A.; Frenken, K.

    2011-01-01

    Following last decade’s programmatic papers on Evolutionary Economic Geography, we report on recent empirical advances and how this empirical work can be positioned vis-a`-vis other strands of research in economic geography. First, we review studies on the path dependent nature of clustering, and

  20. The emerging empirics of evolutionary economic geography

    NARCIS (Netherlands)

    Boschma, R.A.; Frenken, K.

    2010-01-01

    Following last decade’s programmatic papers on Evolutionary Economic Geography, we report on recent empirical advances and how this empirical work can be positioned vis-à-vis other strands of research in economic geography. First, we review studies on the path dependent nature of clustering, and how

  1. The emerging empirics of evolutionary economic geography.

    NARCIS (Netherlands)

    Boschma, R.A.; Frenken, K.

    2011-01-01

    Following last decade’s programmatic papers on Evolutionary Economic Geography, we report on recent empirical advances and how this empirical work can be positioned vis-a`-vis other strands of research in economic geography. First, we review studies on the path dependent nature of clustering, and

  2. Computational mate choice: theory and empirical evidence.

    Science.gov (United States)

    Castellano, Sergio; Cadeddu, Giorgia; Cermelli, Paolo

    2012-06-01

    The present review is based on the thesis that mate choice results from information-processing mechanisms governed by computational rules and that, to understand how females choose their mates, we should identify which are the sources of information and how they are used to make decisions. We describe mate choice as a three-step computational process and for each step we present theories and review empirical evidence. The first step is a perceptual process. It describes the acquisition of evidence, that is, how females use multiple cues and signals to assign an attractiveness value to prospective mates (the preference function hypothesis). The second step is a decisional process. It describes the construction of the decision variable (DV), which integrates evidence (private information by direct assessment), priors (public information), and value (perceived utility) of prospective mates into a quantity that is used by a decision rule (DR) to produce a choice. We make the assumption that females are optimal Bayesian decision makers and we derive a formal model of DV that can explain the effects of preference functions, mate copying, social context, and females' state and condition on the patterns of mate choice. The third step of mating decision is a deliberative process that depends on the DRs. We identify two main categories of DRs (absolute and comparative rules), and review the normative models of mate sampling tactics associated to them. We highlight the limits of the normative approach and present a class of computational models (sequential-sampling models) that are based on the assumption that DVs accumulate noisy evidence over time until a decision threshold is reached. These models force us to rethink the dichotomy between comparative and absolute decision rules, between discrimination and recognition, and even between rational and irrational choice. Since they have a robust biological basis, we think they may represent a useful theoretical tool for

  3. Empirical high-latitude electric field models

    International Nuclear Information System (INIS)

    Heppner, J.P.; Maynard, N.C.

    1987-01-01

    Electric field measurements from the Dynamics Explorer 2 satellite have been analyzed to extend the empirical models previously developed from dawn-dusk OGO 6 measurements (J.P. Heppner, 1977). The analysis embraces large quantities of data from polar crossings entering and exiting the high latitudes in all magnetic local time zones. Paralleling the previous analysis, the modeling is based on the distinctly different polar cap and dayside convective patterns that occur as a function of the sign of the Y component of the interplanetary magnetic field. The objective, which is to represent the typical distributions of convective electric fields with a minimum number of characteristic patterns, is met by deriving one pattern (model BC) for the northern hemisphere with a +Y interplanetary magnetic field (IMF) and southern hemisphere with a -Y IMF and two patterns (models A and DE) for the northern hemisphere with a -Y IMF and southern hemisphere with a +Y IMF. The most significant large-scale revisions of the OGO 6 models are (1) on the dayside where the latitudinal overlap of morning and evening convection cells reverses with the sign of the IMF Y component, (2) on the nightside where a westward flow region poleward from the Harang discontinuity appears under model BC conditions, and (3) magnetic local time shifts in the positions of the convection cell foci. The modeling above was followed by a detailed examination of cases where the IMF Z component was clearly positive (northward). Neglecting the seasonally dependent cases where irregularities obscure pattern recognition, the observations range from reasonable agreement with the new BC and DE models, to cases where different characteristics appeared primarily at dayside high latitudes

  4. The Role of Empirical Research in Bioethics

    Science.gov (United States)

    Kon, Alexander A.

    2010-01-01

    There has long been tension between bioethicists whose work focuses on classical philosophical inquiry and those who perform empirical studies on bioethical issues. While many have argued that empirical research merely illuminates current practices and cannot inform normative ethics, others assert that research-based work has significant implications for refining our ethical norms. In this essay, I present a novel construct for classifying empirical research in bioethics into four hierarchical categories: Lay of the Land, Ideal Versus Reality, Improving Care, and Changing Ethical Norms. Through explaining these four categories and providing examples of publications in each stratum, I define how empirical research informs normative ethics. I conclude by demonstrating how philosophical inquiry and empirical research can work cooperatively to further normative ethics. PMID:19998120

  5. Empirical modeling of dynamic behaviors of pneumatic artificial muscle actuators.

    Science.gov (United States)

    Wickramatunge, Kanchana Crishan; Leephakpreeda, Thananchai

    2013-11-01

    Pneumatic Artificial Muscle (PAM) actuators yield muscle-like mechanical actuation with high force to weight ratio, soft and flexible structure, and adaptable compliance for rehabilitation and prosthetic appliances to the disabled as well as humanoid robots or machines. The present study is to develop empirical models of the PAM actuators, that is, a PAM coupled with pneumatic control valves, in order to describe their dynamic behaviors for practical control design and usage. Empirical modeling is an efficient approach to computer-based modeling with observations of real behaviors. Different characteristics of dynamic behaviors of each PAM actuator are due not only to the structures of the PAM actuators themselves, but also to the variations of their material properties in manufacturing processes. To overcome the difficulties, the proposed empirical models are experimentally derived from real physical behaviors of the PAM actuators, which are being implemented. In case studies, the simulated results with good agreement to experimental results, show that the proposed methodology can be applied to describe the dynamic behaviors of the real PAM actuators. Copyright © 2013 ISA. Published by Elsevier Ltd. All rights reserved.

  6. Empirical complexities in the genetic foundations of lethal mutagenesis.

    Science.gov (United States)

    Bull, James J; Joyce, Paul; Gladstone, Eric; Molineux, Ian J

    2013-10-01

    From population genetics theory, elevating the mutation rate of a large population should progressively reduce average fitness. If the fitness decline is large enough, the population will go extinct in a process known as lethal mutagenesis. Lethal mutagenesis has been endorsed in the virology literature as a promising approach to viral treatment, and several in vitro studies have forced viral extinction with high doses of mutagenic drugs. Yet only one empirical study has tested the genetic models underlying lethal mutagenesis, and the theory failed on even a qualitative level. Here we provide a new level of analysis of lethal mutagenesis by developing and evaluating models specifically tailored to empirical systems that may be used to test the theory. We first quantify a bias in the estimation of a critical parameter and consider whether that bias underlies the previously observed lack of concordance between theory and experiment. We then consider a seemingly ideal protocol that avoids this bias-mutagenesis of virions-but find that it is hampered by other problems. Finally, results that reveal difficulties in the mere interpretation of mutations assayed from double-strand genomes are derived. Our analyses expose unanticipated complexities in testing the theory. Nevertheless, the previous failure of the theory to predict experimental outcomes appears to reside in evolutionary mechanisms neglected by the theory (e.g., beneficial mutations) rather than from a mismatch between the empirical setup and model assumptions. This interpretation raises the specter that naive attempts at lethal mutagenesis may augment adaptation rather than retard it.

  7. Protein-Ligand Empirical Interaction Components for Virtual Screening.

    Science.gov (United States)

    Yan, Yuna; Wang, Weijun; Sun, Zhaoxi; Zhang, John Z H; Ji, Changge

    2017-08-28

    A major shortcoming of empirical scoring functions is that they often fail to predict binding affinity properly. Removing false positives of docking results is one of the most challenging works in structure-based virtual screening. Postdocking filters, making use of all kinds of experimental structure and activity information, may help in solving the issue. We describe a new method based on detailed protein-ligand interaction decomposition and machine learning. Protein-ligand empirical interaction components (PLEIC) are used as descriptors for support vector machine learning to develop a classification model (PLEIC-SVM) to discriminate false positives from true positives. Experimentally derived activity information is used for model training. An extensive benchmark study on 36 diverse data sets from the DUD-E database has been performed to evaluate the performance of the new method. The results show that the new method performs much better than standard empirical scoring functions in structure-based virtual screening. The trained PLEIC-SVM model is able to capture important interaction patterns between ligand and protein residues for one specific target, which is helpful in discarding false positives in postdocking filtering.

  8. Explaining Innovation. An Empirical Analysis of Industry Data from Norway

    Directory of Open Access Journals (Sweden)

    Torbjørn Lorentzen

    2016-01-01

    Full Text Available The objective of the paper is to analyse why some firms innovate while others do not. The paper combines different theories of innovation by relating innovation to internal, firm specific assets and external, regional factors. Hypotheses are derived from theories and tested empirically by using logistic regression. The empirical analysis indicates that internal funding of R&D and size of the firm are the most important firm specific attributes for successful innovation. External, regional factors are also important. The analysis shows that firms located in large urban regions have significantly higher innovation rates than firms located in the periphery, and firms involved in regional networking are more likely to innovate compared to firms not involved in networking. The analysis contributes to a theoretical and empirical understanding of factors that influence on innovation and the role innovation plays in the market economy. Innovation policy should be targeted at developing a tax system and building infrastructure which give firms incentives to invest and allocate internal resources to R&D-activities and collaborate with others in innovation. From an economic policy perspective, consideration should be given to allocating more public resources to rural areas in order to compensate for the asymmetric distribution of resources between the centre and periphery. The paper contributes to the scientific literature of innovation by combining the firm oriented perspective with weight on firm specific, internal resources and a system perspective which focuses on external resources and networking as the most important determinants of innovation in firms.

  9. Empirical essays on energy economics

    Energy Technology Data Exchange (ETDEWEB)

    Thoenes, Stefan

    2013-06-13

    The main part of this thesis consists of three distinct essays that empirically analyze economic issues related to energy markets in the United States and Europe. The first chapter provides an introduction and discusses the motivation for the different analyses pursued in this thesis. The second chapter examines attention effects in the market for hybrid vehicles. We show that local media coverage, gasoline price changes and unprecedented record gasoline prices have a significant impact on the consumers' attention. As attention is not directly observable, we analyze online search behavior as a proxy for the revealed consumer attention. Our study is based on a unique weekly panel dataset for 19 metropolitan areas in the US. Additionally, we use monthly state-level panel data to show that the adoption rate of hybrid vehicles is robustly related to our measure of attention. Our results show that the consumers' attention fluctuates strongly and systematically. The third chapter shows how the effect of fuel prices varies with the level of electricity demand. It analyzes the relationship between daily prices of electricity, natural gas and carbon emission allowances with a semiparametric varying smooth coefficient cointegration model. This model is used to analyze the market impact of the nuclear moratorium by the German Government in March 2011. Futures prices of electricity, natural gas and emission allowances are used to show that the market efficiently accounts for the suspended capacity and correctly expects that several nuclear plants will not be switched on after the moratorium. In the fourth chapter, we develop a structural vector autoregressive model (VAR) for the German natural gas market. In particular, we illustrate the usefulness of our approach by disentangling the effects of different fundamental influences during four specific events: The financial crisis starting in 2008, the Russian-Ukrainian gas dispute in January 2009, the Libyan civil war

  10. Empirical essays on energy economics

    International Nuclear Information System (INIS)

    Thoenes, Stefan

    2013-01-01

    The main part of this thesis consists of three distinct essays that empirically analyze economic issues related to energy markets in the United States and Europe. The first chapter provides an introduction and discusses the motivation for the different analyses pursued in this thesis. The second chapter examines attention effects in the market for hybrid vehicles. We show that local media coverage, gasoline price changes and unprecedented record gasoline prices have a significant impact on the consumers' attention. As attention is not directly observable, we analyze online search behavior as a proxy for the revealed consumer attention. Our study is based on a unique weekly panel dataset for 19 metropolitan areas in the US. Additionally, we use monthly state-level panel data to show that the adoption rate of hybrid vehicles is robustly related to our measure of attention. Our results show that the consumers' attention fluctuates strongly and systematically. The third chapter shows how the effect of fuel prices varies with the level of electricity demand. It analyzes the relationship between daily prices of electricity, natural gas and carbon emission allowances with a semiparametric varying smooth coefficient cointegration model. This model is used to analyze the market impact of the nuclear moratorium by the German Government in March 2011. Futures prices of electricity, natural gas and emission allowances are used to show that the market efficiently accounts for the suspended capacity and correctly expects that several nuclear plants will not be switched on after the moratorium. In the fourth chapter, we develop a structural vector autoregressive model (VAR) for the German natural gas market. In particular, we illustrate the usefulness of our approach by disentangling the effects of different fundamental influences during four specific events: The financial crisis starting in 2008, the Russian-Ukrainian gas dispute in January 2009, the Libyan civil war in 2011 as

  11. Perspectives in metabolic engineering: understanding cellular regulation towards the control of metabolic routes.

    Science.gov (United States)

    Zadran, Sohila; Levine, Raphael D

    2013-01-01

    Metabolic engineering seeks to redirect metabolic pathways through the modification of specific biochemical reactions or the introduction of new ones with the use of recombinant technology. Many of the chemicals synthesized via introduction of product-specific enzymes or the reconstruction of entire metabolic pathways into engineered hosts that can sustain production and can synthesize high yields of the desired product as yields of natural product-derived compounds are frequently low, and chemical processes can be both energy and material expensive; current endeavors have focused on using biologically derived processes as alternatives to chemical synthesis. Such economically favorable manufacturing processes pursue goals related to sustainable development and "green chemistry". Metabolic engineering is a multidisciplinary approach, involving chemical engineering, molecular biology, biochemistry, and analytical chemistry. Recent advances in molecular biology, genome-scale models, theoretical understanding, and kinetic modeling has increased interest in using metabolic engineering to redirect metabolic fluxes for industrial and therapeutic purposes. The use of metabolic engineering has increased the productivity of industrially pertinent small molecules, alcohol-based biofuels, and biodiesel. Here, we highlight developments in the practical and theoretical strategies and technologies available for the metabolic engineering of simple systems and address current limitations.

  12. Metabolism of organically bound tritium

    International Nuclear Information System (INIS)

    Travis, C.C.

    1984-01-01

    The classic methodology for estimating dose to man from environmental tritium ignores the fact that organically bound tritium in foodstuffs may be directly assimilated in the bound compartment of tissues without previous oxidation. We propose a four-compartment model consisting of a free body water compartment, two organic compartments, and a small, rapidly metabolizing compartment. The utility of this model lies in the ability to input organically bound tritium in foodstuffs directly into the organic compartments of the model. We found that organically bound tritium in foodstuffs can increase cumulative total body dose by a factor of 1.7 to 4.5 times the free body water dose alone, depending on the bound-to-loose ratio of tritium in the diet. Model predictions are compared with empirical measurements of tritium in human urine and tissue samples, and appear to be in close agreement. 10 references, 4 figures, 3 tables

  13. Empirical data and moral theory. A plea for integrated empirical ethics.

    Science.gov (United States)

    Molewijk, Bert; Stiggelbout, Anne M; Otten, Wilma; Dupuis, Heleen M; Kievit, Job

    2004-01-01

    Ethicists differ considerably in their reasons for using empirical data. This paper presents a brief overview of four traditional approaches to the use of empirical data: "the prescriptive applied ethicists," "the theorists," "the critical applied ethicists," and "the particularists." The main aim of this paper is to introduce a fifth approach of more recent date (i.e. "integrated empirical ethics") and to offer some methodological directives for research in integrated empirical ethics. All five approaches are presented in a table for heuristic purposes. The table consists of eight columns: "view on distinction descriptive-prescriptive sciences," "location of moral authority," "central goal(s)," "types of normativity," "use of empirical data," "method," "interaction empirical data and moral theory," and "cooperation with descriptive sciences." Ethicists can use the table in order to identify their own approach. Reflection on these issues prior to starting research in empirical ethics should lead to harmonization of the different scientific disciplines and effective planning of the final research design. Integrated empirical ethics (IEE) refers to studies in which ethicists and descriptive scientists cooperate together continuously and intensively. Both disciplines try to integrate moral theory and empirical data in order to reach a normative conclusion with respect to a specific social practice. IEE is not wholly prescriptive or wholly descriptive since IEE assumes an interdepence between facts and values and between the empirical and the normative. The paper ends with three suggestions for consideration on some of the future challenges of integrated empirical ethics.

  14. Bile Acid Metabolism and Signaling

    Science.gov (United States)

    Chiang, John Y. L.

    2015-01-01

    Bile acids are important physiological agents for intestinal nutrient absorption and biliary secretion of lipids, toxic metabolites, and xenobiotics. Bile acids also are signaling molecules and metabolic regulators that activate nuclear receptors and G protein-coupled receptor (GPCR) signaling to regulate hepatic lipid, glucose, and energy homeostasis and maintain metabolic homeostasis. Conversion of cholesterol to bile acids is critical for maintaining cholesterol homeostasis and preventing accumulation of cholesterol, triglycerides, and toxic metabolites, and injury in the liver and other organs. Enterohepatic circulation of bile acids from the liver to intestine and back to the liver plays a central role in nutrient absorption and distribution, and metabolic regulation and homeostasis. This physiological process is regulated by a complex membrane transport system in the liver and intestine regulated by nuclear receptors. Toxic bile acids may cause inflammation, apoptosis, and cell death. On the other hand, bile acid-activated nuclear and GPCR signaling protects against inflammation in liver, intestine, and macrophages. Disorders in bile acid metabolism cause cholestatic liver diseases, dyslipidemia, fatty liver diseases, cardiovascular diseases, and diabetes. Bile acids, bile acid derivatives, and bile acid sequestrants are therapeutic agents for treating chronic liver diseases, obesity, and diabetes in humans. PMID:23897684

  15. Pluvials, Droughts, the Mongol Empire, and Modern Mongolia

    Science.gov (United States)

    Hessl, A. E.; Pederson, N.; Baatarbileg, N.; Anchukaitis, K. J.

    2013-12-01

    Understanding the connections between climate, ecosystems, and society during historical and modern climatic transitions requires annual resolution records with high fidelity climate signals. Many studies link the demise of complex societies with deteriorating climate conditions, but few have investigated the connection between climate, surplus energy, and the rise of empires. Inner Asia in the 13th century underwent a major political transformation requiring enormous energetic inputs that altered human history. The Mongol Empire, centered on the city of Karakorum, became the largest contiguous land empire in world history (Fig. 1 inset). Powered by domesticated grazing animals, the empire grew at the expense of sedentary agriculturalists across Asia, the Middle East, and Eastern Europe. Although some scholars and conventional wisdom agree that dry conditions spurred the Mongol conquests, little paleoenvironmental data at annual resolution are available to evaluate the role of climate in the development of the Mongol Empire. Here we present a 2600 year tree-ring reconstruction of warm-season, self-calibrating Palmer Drought Severity Index (scPDSI), a measure of water balance, derived from 107 live and dead Siberian pine (Pinus sibirica) trees growing on a Holocene lava flow in central Mongolia. Trees growing on the Khorgo lava flow today are stunted and widely spaced, occurring on microsites with little to no soil development. These trees are extremely water-stressed and their radial growth is well-correlated with both drought (scPDSI) and grassland productivity (Normalized Difference Vegetation Index (NDVI)). Our reconstruction, calibrated and validated on instrumental June-September scPDSI (1959-2009) accounts for 55.8% of the variability in the regional scPDSI when 73% of the annual rainfall occurs. Our scPDSI reconstruction places historic and modern social change in Mongolia in the context of the range of climatic variability during the Common Era. Our record

  16. Empirical method to calculate Clinch River Breeder Reactor (CRBR) inlet plenum transient temperatures

    International Nuclear Information System (INIS)

    Howarth, W.L.

    1976-01-01

    Sodium flow enters the CRBR inlet plenum via three loops or inlets. An empirical equation was developed to calculate transient temperatures in the CRBR inlet plenum from known loop flows and temperatures. The constants in the empirical equation were derived from 1/4 scale Inlet Plenum Model tests using water as the test fluid. The sodium temperature distribution was simulated by an electrolyte. Step electrolyte transients at 100 percent model flow were used to calculate the equation constants. Step electrolyte runs at 50 percent and 10 percent flow confirmed that the constants were independent of flow. Also, a transient was tested which varied simultaneously flow rate and electrolyte. Agreement of the test results with the empirical equation results was good which verifies the empirical equation

  17. Physico-empirical approach for mapping soil hydraulic behaviour

    Directory of Open Access Journals (Sweden)

    G. D'Urso

    1997-01-01

    Full Text Available Abstract: Pedo-transfer functions are largely used in soil hydraulic characterisation of large areas. The use of physico-empirical approaches for the derivation of soil hydraulic parameters from disturbed samples data can be greatly enhanced if a characterisation performed on undisturbed cores of the same type of soil is available. In this study, an experimental procedure for deriving maps of soil hydraulic behaviour is discussed with reference to its application in an irrigation district (30 km2 in southern Italy. The main steps of the proposed procedure are: i the precise identification of soil hydraulic functions from undisturbed sampling of main horizons in representative profiles for each soil map unit; ii the determination of pore-size distribution curves from larger disturbed sampling data sets within the same soil map unit. iii the calibration of physical-empirical methods for retrieving soil hydraulic parameters from particle-size data and undisturbed soil sample analysis; iv the definition of functional hydraulic properties from water balance output; and v the delimitation of soil hydraulic map units based on functional properties.

  18. Haloacetonitriles: metabolism and toxicity.

    Science.gov (United States)

    Lipscomb, John C; El-Demerdash, Ebtehal; Ahmed, Ahmed E

    2009-01-01

    The haloacetonitriles (HANs) exist in drinking water exclusively as byproducts of disinfection. HANs are found in drinking water more often, and in higher concentrations, when surface water is treated by chloramination. Human exposure occurs through consumption of finished drinking water; oral and dermal contact also occurs, and results from showering, swimming and other activities. HANs are reactive and are toxic to gastrointestinal tissues following oral administration. Such toxicity is characterized by GSH depletion, increased lipid peroxidation, and covalent binding of HAN-associated radioactivity to gut tissues. The presence of GSH in cells is an important protective mechanism against HAN toxicity; depletion of cellular GSH results in increased toxicity. Some studies have demonstrated an apparently synergistic effect between ROS and HAN administration, that may help explain effects observed in GI tissues. ROS are produced in gut tissues, and in vitro evidence indicates that ROS may contribute to the degradation and formation of reactive intermediates from HANs. The rationale for ROS involvement may involve HAN-induced depletion of GSH and the role of GSH in scavenging ROS. In addition to effects on GI tissues, studies show that HAN-derived radiolabel is found covalently bound to proteins and DNA in several organs and tissues. The addition of antioxidants to biologic systems protects against HAN-induced DNA damage. The protection offered by antioxidants supports the role of oxidative stress and the potential for a threshold in han-induced toxicity. However, additional data are needed to substantiate evidence for such a threshold. HANs are readily absorbed from the GI tract and are extensively metabolized. Elimination occurs primarily in urine, as unconjugated one-carbon metabolites. Evidence supports the involvement of mixed function oxidases, the cytochrome P450 enzyme family and GST, in HAN metabolism. Metabolism represents either a detoxification or

  19. Causation and the origin of life. Metabolism or replication first?

    Science.gov (United States)

    Pross, Addy

    2004-06-01

    The conceptual gulf that separates the 'metabolism first' and 'replication first' mechanisms for the emergence of life continues to cloud the origin of life debate. In the present paper we analyze this aspect of the origin of life problem and offer arguments in favor of the 'replication first' school. Utilizing Wicken's two-tier approach to causation we argue that a causal connection between replication and metabolism can only be demonstrated if replication would have preceded metabolism. In conjunction with existing empirical evidence and theoretical reasoning, our analysis concludes that there is no substantive evidence for a 'metabolism first' mechanism for life's emergence, while a coherent case can be made for the 'replication first' group of mechanisms. The analysis reaffirms our conviction that life is an extreme expression of kinetic control, and that the emergence of metabolic pathways can be understood by considering life as a manifestation of 'replicative chemistry'.

  20. Deriving Empirically-Based Design Guidelines for Advanced Learning Technologies that Foster Disciplinary Comprehension / Définir des lignes directrices fondées sur des données empiriques pour les technologies d’apprentissage avancé qui favorisent la compr

    Directory of Open Access Journals (Sweden)

    Eric Poitras

    2012-02-01

    Full Text Available Planning, conducting, and reporting leading-edge research requires professionals who are capable of highly skilled reading. This study reports the development of an empirically informed computer-based learning environment designed to foster the acquisition of reading comprehension strategies that mediate expertise in the social sciences. Empirical data were gathered in a mixed-methods explanatory sequential design that examined the reading comprehension strategies used by an expert social scientist while reading a professional-level text. Process data were collected through a concurrent think-aloud protocol and coded according to reading comprehension processes. We combined both quantitative and qualitative analyses to identify, describe, and explain patterns in the expert’s use of reading strategies. Our findings indicate that highly-skilled reading is characterized by critiquing text information, relating information to prior knowledge, and evaluating one’s own understanding of text information. Findings are used to inform the design of worked-examples and a pedagogical agent embedded within the Highly-Skilled Reading Tutor. Le type de planification, de réalisation et l’analyse qui caractérise une recherche d’avant-garde nécessite des professionnels en mesure d’effectuer des lectures hautement spécialisées. La présente étude dresse un rapport sur l’élaboration d’un milieu d’apprentissage informatisé conçu pour favoriser l’acquisition de stratégies de compréhension en lecture permettant d’assurer la transmission des connaissances spécialisées en sciences sociales. La collecte de données empiriques s’est effectuée suivant une conception séquentielle explicative fondée sur une méthode mixte, qui étudiait les stratégies de compréhension de lecture utilisées par un expert en sciences sociales lors de sa lecture d’un texte de calibre professionnel. La collecte des données sur le processus s

  1. An Empirical Typology of Narcissism and Mental Health in Late Adolescence

    Science.gov (United States)

    Lapsley, Daniel K.; Aalsma, Matthew C.

    2006-01-01

    A two-step cluster analytic strategy was used in two studies to identify an empirically derived typology of narcissism in late adolescence. In Study 1, late adolescents (N=204) responded to the profile of narcissistic dispositions and measures of grandiosity (''superiority'') and idealization (''goal instability'') inspired by Kohut's theory,…

  2. Empirical rate equation model and rate calculations of hydrogen generation for Hanford tank waste

    International Nuclear Information System (INIS)

    HU, T.A.

    1999-01-01

    Empirical rate equations are derived to estimate hydrogen generation based on chemical reactions, radiolysis of water and organic compounds, and corrosion processes. A comparison of the generation rates observed in the field with the rates calculated for twenty eight tanks shows agreement within a factor of two to three

  3. An empirical InSAR-optical fusion approach to mapping vegetation canopy height

    Science.gov (United States)

    Wayne S. Walker; Josef M. Kellndorfer; Elizabeth LaPoint; Michael Hoppus; James Westfall

    2007-01-01

    Exploiting synergies afforded by a host of recently available national-scale data sets derived from interferometric synthetic aperture radar (InSAR) and passive optical remote sensing, this paper describes the development of a novel empirical approach for the provision of regional- to continental-scale estimates of vegetation canopy height. Supported by data from the...

  4. Synergy between 13C-metabolic flux analysis and flux balance analysis for understanding metabolic adaption to anaerobiosis in e. coli

    Science.gov (United States)

    Genome-based Flux Balance Analysis (FBA, constraints based flux analysis) and steady state isotopic-labeling-based Metabolic Flux Analysis (MFA) are complimentary approaches to predicting and measuring the operation and regulation of metabolic networks. Here a genome-derived model of E. coli metabol...

  5. Introducing Empirical Exercises into Principles of Economics.

    Science.gov (United States)

    McGrath, Eileen L.; Tiemann, Thomas K.

    1985-01-01

    A rationale for requiring undergraduate students to become familiar with the empirical side of economics is presented, and seven exercises that can be used in an introductory course are provided. (Author/RM)

  6. Review essay: empires, ancient and modern.

    Science.gov (United States)

    Hall, John A

    2011-09-01

    This essay drews attention to two books on empires by historians which deserve the attention of sociologists. Bang's model of the workings of the Roman economy powerfully demonstrates the tributary nature of per-industrial tributary empires. Darwin's analysis concentrates on modern overseas empires, wholly different in character as they involved the transportation of consumption items for the many rather than luxury goods for the few. Darwin is especially good at describing the conditions of existence of late nineteenth century empires, noting that their demise was caused most of all by the failure of balance of power politics in Europe. Concluding thoughts are offered about the USA. © London School of Economics and Political Science 2011.

  7. Inland empire logistics GIS mapping project.

    Science.gov (United States)

    2009-01-01

    The Inland Empire has experienced exponential growth in the area of warehousing and distribution facilities within the last decade and it seems that it will continue way into the future. Where are these facilities located? How large are the facilitie...

  8. Teaching Empirical Software Engineering Using Expert Teams

    DEFF Research Database (Denmark)

    Kuhrmann, Marco

    2017-01-01

    Empirical software engineering aims at making software engineering claims measurable, i.e., to analyze and understand phenomena in software engineering and to evaluate software engineering approaches and solutions. Due to the involvement of humans and the multitude of fields for which software...... is crucial, software engineering is considered hard to teach. Yet, empirical software engineering increases this difficulty by adding the scientific method as extra dimension. In this paper, we present a Master-level course on empirical software engineering in which different empirical instruments...... an extra specific expertise that they offer as service to other teams, thus, fostering cross-team collaboration. The paper outlines the general course setup, topics addressed, and it provides initial lessons learned....

  9. Size structure, not metabolic scaling rules, determines fisheries reference points

    DEFF Research Database (Denmark)

    Andersen, Ken Haste; Beyer, Jan

    2015-01-01

    Impact assessments of fishing on a stock require parameterization of vital rates: growth, mortality and recruitment. For 'data-poor' stocks, vital rates may be estimated from empirical size-based relationships or from life-history invariants. However, a theoretical framework to synthesize...... these empirical relations is lacking. Here, we combine life-history invariants, metabolic scaling and size-spectrum theory to develop a general size- and trait-based theory for demography and recruitment of exploited fish stocks. Important concepts are physiological or metabolic scaled mortalities and flux...... is that larger species have a higher egg production per recruit than small species. This means that density dependence is stronger for large than for small species and has the consequence that fisheries reference points that incorporate recruitment do not obey metabolic scaling rules. This result implies...

  10. Oscillospira and related bacteria - from metagenomics species to metabolic features

    DEFF Research Database (Denmark)

    Gophna, Uri; Konikoff, Tom; Nielsen, Henrik Bjørn

    2017-01-01

    and manual metabolic pathway curation to decipher key metabolic features of this intriguing bacterial genus. We infer that Oscillospira species are butyrate producers, and at least some of them have the ability to utilize glucuronate, a common animal-derived sugar that is both produced by the human host...

  11. Detection by radio-auto-histography of the β-indolylacetic acid and its metabolic derivatives. Test of application to the search for their histological and cytological location; Detection, par radioautohistographie, de l'acide β-indolylacetique et de ses derives metaboliques. Essai d'application a la recherche de leur localisation histologique et cytologique

    Energy Technology Data Exchange (ETDEWEB)

    Figier, Jacques

    1961-02-04

    After having given an overview of research works in biophysics and biochemistry related to the study of the auxinic action within a cell, this research thesis reports the use of radio-auto-histography to detect the βindolylacetic acid within tissues and within a cell. The author reports experiments performed by using this acid either in its normal status, or marked either with carbon 14 or with tritium. Growth tests have been performed by using different plants. The author also presents insolubilization techniques which have been applied to the acid for this study. In vivo tests have been performed with the radioactive acid and other precipitation compounds (lead acetate, mercury nitrate). The acid detection technique is presented, and results are discussed [French] Dans le but de detecter, par radioautohistographie, l'acide β-indolylacetique marque au tritium et ses derives metaboliques, nous avons mis au point des techniques nouvelles d'insolubilisation de l'A.I.A. L'acide picrique et l'acetate de plomb donnant avec l'auxine un precipite insoluble dans les liquides de fixation (Formol neutre-Liquide de Bouin) et d'inclusion, nous avons reussi a conserver dans des epicotyles de pois et de haricot, des racines de feve et de pois, des coleoptiles d'avoine, une importante fraction de l'A.I.A. marque fourni a ces tissus (a des concentrations superieures ou egales a 10 mg/l). Cette detection etant satisfaisante, nous avons essaye de localiser l'A.I.A. et ses derives, avec plus de precision, dans la cellule en particulier. Mais il fallait alors tenir compte de plusieurs causes d'erreur possible: l'effet nocif eventuel du liquide precipitant (acide picrique ou acetate de plomb), - la diffusion d'A.I.A. dans ce liquide, - la cytologie imparfaite et en particulier l'incertitude sur la limite vacuole-cytoplasme. Compte tenu de ces critiques, il nous semble que la radioactivite (due a la presence d'A.I.A. et des produits derives) se localise plus particulierement au

  12. Principles Involving Marketing Policies: An Empirical Assessment

    OpenAIRE

    JS Armstrong; Randall L. Schultz

    2005-01-01

    We examined nine marketing textbooks, published since 1927, to see if they contained useful marketing principles. Four doctoral students found 566 normative statements about pricing, product, place, or promotion in these texts. None of these stateinents were supported by empirical evidence. Four raters agreed on only twenty of these 566 statements as providing meaningful principles. Twenty marketing professors rated whether the twenty meaningful principles were correct, supported by empirical...

  13. Sources of Currency Crisis: An Empirical Analysis

    OpenAIRE

    Weber, Axel A.

    1997-01-01

    Two types of currency crisis models coexist in the literature: first generation models view speculative attacks as being caused by economic fundamentals which are inconsistent with a given parity. Second generation models claim self-fulfilling speculation as the main source of a currency crisis. Recent empirical research in international macroeconomics has attempted to distinguish between the sources of currency crises. This paper adds to this literature by proposing a new empirical approach ...

  14. Agency Theory and Franchising: Some Empirical Results

    OpenAIRE

    Francine Lafontaine

    1992-01-01

    This article provides an empirical assessment of various agency-theoretic explanations for franchising, including risk sharing, one-sided moral hazard, and two-sided moral hazard. The empirical models use proxies for factors such as risk, moral hazard, and franchisors' need for capital to explain both franchisors' decisions about the terms of their contracts (royalty rates and up-front franchise fees) and the extent to which they use franchising. In this article, I exploit several new sources...

  15. Gun Laws and Crime: An Empirical Assessment

    OpenAIRE

    Matti Viren

    2012-01-01

    This paper deals with the effect of gun laws on crime. Several empirical analyses are carried to investigate the relationship between five different crime rates and alternative law variables. The tests are based on cross-section data from US sates. Three different law variables are used in the analysis, together with a set of control variables for income, poverty, unemployment and ethnic background of the population. Empirical analysis does not lend support to the notion that crime laws would...

  16. Empirical direction in design and analysis

    CERN Document Server

    Anderson, Norman H

    2001-01-01

    The goal of Norman H. Anderson's new book is to help students develop skills of scientific inference. To accomplish this he organized the book around the ""Experimental Pyramid""--six levels that represent a hierarchy of considerations in empirical investigation--conceptual framework, phenomena, behavior, measurement, design, and statistical inference. To facilitate conceptual and empirical understanding, Anderson de-emphasizes computational formulas and null hypothesis testing. Other features include: *emphasis on visual inspection as a basic skill in experimental analysis to help student

  17. An Empirical Taxonomy of Crowdfunding Intermediaries

    OpenAIRE

    Haas, Philipp; Blohm, Ivo; Leimeister, Jan Marco

    2014-01-01

    Due to the recent popularity of crowdfunding, a broad magnitude of crowdfunding intermediaries has emerged, while research on crowdfunding intermediaries has been largely neglected. As a consequence, existing classifications of crowdfunding intermediaries are conceptual, lack theoretical grounding, and are not empirically validated. Thus, we develop an empirical taxonomy of crowdfunding intermediaries, which is grounded in the theories of two-sided markets and financial intermediation. Integr...

  18. An empirical analysis of Diaspora bonds

    OpenAIRE

    AKKOYUNLU, Şule; STERN, Max

    2018-01-01

    Abstract. This study is the first to investigate theoretically and empirically the determinants of Diaspora Bonds for eight developing countries (Bangladesh, Ethiopia, Ghana, India, Lebanon, Pakistan, the Philippines, and Sri-Lanka) and one developed country - Israel for the period 1951 and 2008. Empirical results are consistent with the predictions of the theoretical model. The most robust variables are the closeness indicator and the sovereign rating, both on the demand-side. The spread is ...

  19. Circulating follistatin in relation to energy metabolism

    DEFF Research Database (Denmark)

    Hansen, Jakob Schiøler; Plomgaard, Peter

    2016-01-01

    a relation to energy metabolism. In this narrative review, we attempt to reconcile the existing findings on circulating follistatin with the novel concept that circulating follistatin is a liver-derived molecule regulated by the glucagon-to-insulin ratio. The picture emerging is that conditions associated...

  20. Metabolism and disease

    National Research Council Canada - National Science Library

    Grodzicker, Terri; Stewart, David J; Stillman, Bruce

    2011-01-01

    ...), cellular, organ system (cardiovascular, bone), and organismal (timing and life span) scales. Diseases impacted by metabolic imbalance or dysregulation that were covered in detail included diabetes, obesity, metabolic syndrome, and cancer...

  1. Intermittent metabolic switching, neuroplasticity and brain health

    Science.gov (United States)

    Mattson, Mark P.; Moehl, Keelin; Ghena, Nathaniel; Schmaedick, Maggie; Cheng, Aiwu

    2018-01-01

    During evolution, individuals whose brains and bodies functioned well in a fasted state were successful in acquiring food, enabling their survival and reproduction. With fasting and extended exercise, liver glycogen stores are depleted and ketones are produced from adipose-cell-derived fatty acids. This metabolic switch in cellular fuel source is accompanied by cellular and molecular adaptations of neural networks in the brain that enhance their functionality and bolster their resistance to stress, injury and disease. Here, we consider how intermittent metabolic switching, repeating cycles of a metabolic challenge that induces ketosis (fasting and/or exercise) followed by a recovery period (eating, resting and sleeping), may optimize brain function and resilience throughout the lifespan, with a focus on the neuronal circuits involved in cognition and mood. Such metabolic switching impacts multiple signalling pathways that promote neuroplasticity and resistance of the brain to injury and disease. PMID:29321682

  2. Genetics of homocysteine metabolism and associated disorders

    Directory of Open Access Journals (Sweden)

    S. Brustolin

    2010-01-01

    Full Text Available Homocysteine is a sulfur-containing amino acid derived from the metabolism of methionine, an essential amino acid, and is metabolized by one of two pathways: remethylation or transsulfuration. Abnormalities of these pathways lead to hyperhomocysteinemia. Hyperhomocysteinemia is observed in approximately 5% of the general population and is associated with an increased risk for many disorders, including vascular and neurodegenerative diseases, autoimmune disorders, birth defects, diabetes, renal disease, osteoporosis, neuropsychiatric disorders, and cancer. We review here the correlation between homocysteine metabolism and the disorders described above with genetic variants on genes coding for enzymes of homocysteine metabolism relevant to clinical practice, especially common variants of the MTHFR gene, 677C>T and 1298A>C. We also discuss the management of hyperhomocysteinemia with folic acid supplementation and fortification of folic acid and the impact of a decrease in the prevalence of congenital anomalies and a decline in the incidence of stroke mortality.

  3. Metabolic Engineering X Conference

    Energy Technology Data Exchange (ETDEWEB)

    Flach, Evan [American Institute of Chemical Engineers

    2015-05-07

    The International Metabolic Engineering Society (IMES) and the Society for Biological Engineering (SBE), both technological communities of the American Institute of Chemical Engineers (AIChE), hosted the Metabolic Engineering X Conference (ME-X) on June 15-19, 2014 at the Westin Bayshore in Vancouver, British Columbia. It attracted 395 metabolic engineers from academia, industry and government from around the globe.

  4. An update on the "empirical turn" in bioethics: analysis of empirical research in nine bioethics journals.

    Science.gov (United States)

    Wangmo, Tenzin; Hauri, Sirin; Gennet, Eloise; Anane-Sarpong, Evelyn; Provoost, Veerle; Elger, Bernice S

    2018-02-07

    A review of literature published a decade ago noted a significant increase in empirical papers across nine bioethics journals. This study provides an update on the presence of empirical papers in the same nine journals. It first evaluates whether the empirical trend is continuing as noted in the previous study, and second, how it is changing, that is, what are the characteristics of the empirical works published in these nine bioethics journals. A review of the same nine journals (Bioethics; Journal of Medical Ethics; Journal of Clinical Ethics; Nursing Ethics; Cambridge Quarterly of Healthcare Ethics; Hastings Center Report; Theoretical Medicine and Bioethics; Christian Bioethics; and Kennedy Institute of Ethics Journal) was conducted for a 12-year period from 2004 to 2015. Data obtained was analysed descriptively and using a non-parametric Chi-square test. Of the total number of original papers (N = 5567) published in the nine bioethics journals, 18.1% (n = 1007) collected and analysed empirical data. Journal of Medical Ethics and Nursing Ethics led the empirical publications, accounting for 89.4% of all empirical papers. The former published significantly more quantitative papers than qualitative, whereas the latter published more qualitative papers. Our analysis reveals no significant difference (χ2 = 2.857; p = 0.091) between the proportion of empirical papers published in 2004-2009 and 2010-2015. However, the increasing empirical trend has continued in these journals with the proportion of empirical papers increasing from 14.9% in 2004 to 17.8% in 2015. This study presents the current state of affairs regarding empirical research published nine bioethics journals. In the quarter century of data that is available about the nine bioethics journals studied in two reviews, the proportion of empirical publications continues to increase, signifying a trend towards empirical research in bioethics. The growing volume is mainly attributable to two

  5. Reflective equilibrium and empirical data: third person moral experiences in empirical medical ethics.

    Science.gov (United States)

    De Vries, Martine; Van Leeuwen, Evert

    2010-11-01

    In ethics, the use of empirical data has become more and more popular, leading to a distinct form of applied ethics, namely empirical ethics. This 'empirical turn' is especially visible in bioethics. There are various ways of combining empirical research and ethical reflection. In this paper we discuss the use of empirical data in a special form of Reflective Equilibrium (RE), namely the Network Model with Third Person Moral Experiences. In this model, the empirical data consist of the moral experiences of people in a practice. Although inclusion of these moral experiences in this specific model of RE can be well defended, their use in the application of the model still raises important questions. What precisely are moral experiences? How to determine relevance of experiences, in other words: should there be a selection of the moral experiences that are eventually used in the RE? How much weight should the empirical data have in the RE? And the key question: can the use of RE by empirical ethicists really produce answers to practical moral questions? In this paper we start to answer the above questions by giving examples taken from our research project on understanding the norm of informed consent in the field of pediatric oncology. We especially emphasize that incorporation of empirical data in a network model can reduce the risk of self-justification and bias and can increase the credibility of the RE reached. © 2009 Blackwell Publishing Ltd.

  6. Physics of metabolic organization

    Science.gov (United States)

    Jusup, Marko; Sousa, Tânia; Domingos, Tiago; Labinac, Velimir; Marn, Nina; Wang, Zhen; Klanjšček, Tin

    2017-03-01

    We review the most comprehensive metabolic theory of life existing to date. A special focus is given to the thermodynamic roots of this theory and to implications that the laws of physics-such as the conservation of mass and energy-have on all life. Both the theoretical foundations and biological applications are covered. Hitherto, the foundations were more accessible to physicists or mathematicians, and the applications to biologists, causing a dichotomy in what always should have been a single body of work. To bridge the gap between the two aspects of the same theory, we (i) adhere to the theoretical formalism, (ii) try to minimize the amount of information that a reader needs to process, but also (iii) invoke examples from biology to motivate the introduction of new concepts and to justify the assumptions made, and (iv) show how the careful formalism of the general theory enables modular, self-consistent extensions that capture important features of the species and the problem in question. Perhaps the most difficult among the introduced concepts, the utilization (or mobilization) energy flow, is given particular attention in the form of an original and considerably simplified derivation. Specific examples illustrate a range of possible applications-from energy budgets of individual organisms, to population dynamics, to ecotoxicology.

  7. Metabolism of designer drugs of abuse.

    Science.gov (United States)

    Staack, Roland F; Maurer, Hans H

    2005-06-01

    Abuse of designer drugs is widespread among young people, especially in the so-called "dance club scene" or "rave scene", worldwide. Severe and even fatal poisonings have been attributed to the consumption of such drugs of abuse. However, in contrast to new medicaments, which are extensively studied in controlled clinical studies concerning metabolism, including cytochrome P450 isoenzyme differentiation, and further pharmacokinetics, designer drugs are consumed without any safety testing. This paper reviews the metabolism of new designer drugs of abuse that have emerged on the black market during the last years. Para-methoxyamphetamine (PMA), para-methoxymethamphetamine (PMMA) and 4-methylthioamphetamine (4-MTA), were taken into consideration as new "classical" amphetamine-derived designer drugs. Furthermore, N-benzylpiperazine (BZP), 1-(3, 4-methylenedioxybenzyl)piperazine (MDBP), 1-(3-trifluoromethylphenyl)piperazine (TFMPP), 1-(3-chlorophenyl)piperazine (mCPP) and 1-(4-methoxyphenyl)piperazine (MeOPP) were taken into consideration as derivatives of the class of piperazine-derived designer drugs, as well as alpha-pyr-rolidinopropiophenone (PPP), 4'-methoxy-alpha-pyrrolidinopropiophenone (MOPPP), 3', 4'-methylenedioxy-alpha-pyrrolidino-propiophenone (MDPPP), 4'-methyl-alpha-pyrrolidinopropiophenone (MPPP), and 4'-methyl-alpha-pyrrolidinoexanophenone (MPHP) as derivatives of the class of alpha-pyrrolidinophenone-derived designer drugs. Papers describing identification of in vivo or in vitro human or animal metabolites and cytochrome P450 isoenzyme dependent metabolism have been considered and summarized.

  8. Altered metabolism in cancer

    Directory of Open Access Journals (Sweden)

    Locasale Jason W

    2010-06-01

    Full Text Available Abstract Cancer cells have different metabolic requirements from their normal counterparts. Understanding the consequences of this differential metabolism requires a detailed understanding of glucose metabolism and its relation to energy production in cancer cells. A recent study in BMC Systems Biology by Vasquez et al. developed a mathematical model to assess some features of this altered metabolism. Here, we take a broader look at the regulation of energy metabolism in cancer cells, considering their anabolic as well as catabolic needs. See research article: http://www.biomedcentral.com/1752-0509/4/58/

  9. Engineering Cellular Metabolism

    DEFF Research Database (Denmark)

    Nielsen, Jens; Keasling, Jay

    2016-01-01

    Metabolic engineering is the science of rewiring the metabolism of cells to enhance production of native metabolites or to endow cells with the ability to produce new products. The potential applications of such efforts are wide ranging, including the generation of fuels, chemicals, foods, feeds...... of metabolic engineering and will discuss how new technologies can enable metabolic engineering to be scaled up to the industrial level, either by cutting off the lines of control for endogenous metabolism or by infiltrating the system with disruptive, heterologous pathways that overcome cellular regulation....

  10. Feynman perturbation expansion for the price of coupon bond options and swaptions in quantum finance. II. Empirical.

    Science.gov (United States)

    Baaquie, Belal E; Liang, Cui

    2007-01-01

    The quantum finance pricing formulas for coupon bond options and swaptions derived by Baaquie [Phys. Rev. E 75, 016703 (2006)] are reviewed. We empirically study the swaption market and propose an efficient computational procedure for analyzing the data. Empirical results of the swaption price, volatility, and swaption correlation are compared with the predictions of quantum finance. The quantum finance model generates the market swaption price to over 90% accuracy.

  11. Plant-derived modulators of inflammation and cartilage metabolism

    NARCIS (Netherlands)

    Hougee, S.

    2008-01-01

    Currently the treatment of chronic inflammatory diseases is aimed at inhibiting the symptoms of the disease since there are no curative or preventive treatments available. Rheumatoid arthritis (RA) is a painful chronic inflammatory disease of the joints. Osteoarthritis (OA) is a disease in which

  12. Fibroblast growth factor signaling in metabolic regulation

    Directory of Open Access Journals (Sweden)

    Vera eNies

    2016-01-01

    Full Text Available The prevalence of obesity is a growing health problem. Obesity is strongly associated with several comorbidities, such as non-alcoholic fatty liver disease, certain cancers, insulin resistance and type 2 diabetes, which all reduce life expectancy and life quality. Several drugs have been put forward in order to treat these diseases, but many of them have detrimental side effects. The unexpected role of the family of fibroblast growth factors in the regulation of energy metabolism provides new approaches to the treatment of metabolic diseases, and offers a valuable tool to gain more insight into metabolic regulation. The known beneficial effects of FGF19 and FGF21 on metabolism, together with recently discovered similar effects of FGF1 suggest that FGFs and their derivatives carry great potential as novel therapeutics to treat metabolic conditions. To facilitate the development of new therapies with improved targeting and minimal side effects, a better understanding of the molecular mechanism of action of FGFs is needed.In this review we will discuss what is currently known about the physiological roles of FGF signaling in tissues important for metabolic homeostasis. In addition, we will discuss current concepts regarding their pharmacological properties and effector tissues in the context of metabolic disease. Also the recent progress in the development of FGF variants will be reviewed. Our goal is to provide a comprehensive overview of the current concepts and consensuses regarding FGF signaling in metabolic health and disease, and to provide starting points for the development of FGF-based therapies against metabolic conditions.

  13. Symbiotic empirical ethics: a practical methodology.

    Science.gov (United States)

    Frith, Lucy

    2012-05-01

    Like any discipline, bioethics is a developing field of academic inquiry; and recent trends in scholarship have been towards more engagement with empirical research. This 'empirical turn' has provoked extensive debate over how such 'descriptive' research carried out in the social sciences contributes to the distinctively normative aspect of bioethics. This paper will address this issue by developing a practical research methodology for the inclusion of data from social science studies into ethical deliberation. This methodology will be based on a naturalistic conception of ethical theory that sees practice as informing theory just as theory informs practice - the two are symbiotically related. From this engagement with practice, the ways that such theories need to be extended and developed can be determined. This is a practical methodology for integrating theory and practice that can be used in empirical studies, one that uses ethical theory both to explore the data and to draw normative conclusions. © 2010 Blackwell Publishing Ltd.

  14. Reframing Serial Murder Within Empirical Research.

    Science.gov (United States)

    Gurian, Elizabeth A

    2017-04-01

    Empirical research on serial murder is limited due to the lack of consensus on a definition, the continued use of primarily descriptive statistics, and linkage to popular culture depictions. These limitations also inhibit our understanding of these offenders and affect credibility in the field of research. Therefore, this comprehensive overview of a sample of 508 cases (738 total offenders, including partnered groups of two or more offenders) provides analyses of solo male, solo female, and partnered serial killers to elucidate statistical differences and similarities in offending and adjudication patterns among the three groups. This analysis of serial homicide offenders not only supports previous research on offending patterns present in the serial homicide literature but also reveals that empirically based analyses can enhance our understanding beyond traditional case studies and descriptive statistics. Further research based on these empirical analyses can aid in the development of more accurate classifications and definitions of serial murderers.

  15. Wireless and empire geopolitics radio industry and ionosphere in the British Empire 1918-1939

    CERN Document Server

    Anduaga, Aitor

    2009-01-01

    Although the product of consensus politics, the British Empire was based on communications supremacy and the knowledge of the atmosphere. Focusing on science, industry, government, the military, and education, this book studies the relationship between wireless and Empire throughout the interwar period.

  16. Empirical psychology, common sense, and Kant's empirical markers for moral responsibility.

    Science.gov (United States)

    Frierson, Patrick

    2008-12-01

    This paper explains the empirical markers by which Kant thinks that one can identify moral responsibility. After explaining the problem of discerning such markers within a Kantian framework I briefly explain Kant's empirical psychology. I then argue that Kant's empirical markers for moral responsibility--linked to higher faculties of cognition--are not sufficient conditions for moral responsibility, primarily because they are empirical characteristics subject to natural laws. Next. I argue that these markers are not necessary conditions of moral responsibility. Given Kant's transcendental idealism, even an entity that lacks these markers could be free and morally responsible, although as a matter of fact Kant thinks that none are. Given that they are neither necessary nor sufficient conditions, I discuss the status of Kant's claim that higher faculties are empirical markers of moral responsibility. Drawing on connections between Kant's ethical theory and 'common rational cognition' (4:393), I suggest that Kant's theory of empirical markers can be traced to ordinary common sense beliefs about responsibility. This suggestion helps explain both why empirical markers are important and what the limits of empirical psychology are within Kant's account of moral responsibility.

  17. A statistical test of the stability assumption inherent in empirical estimates of economic depreciation.

    Science.gov (United States)

    Shriver, K A

    1986-01-01

    Realistic estimates of economic depreciation are required for analyses of tax policy, economic growth and production, and national income and wealth. THe purpose of this paper is to examine the stability assumption underlying the econometric derivation of empirical estimates of economic depreciation for industrial machinery and and equipment. The results suggest that a reasonable stability of economic depreciation rates of decline may exist over time. Thus, the assumption of a constant rate of economic depreciation may be a reasonable approximation for further empirical economic analyses.

  18. Countertransference when working with narcissistic personality disorder: An empirical investigation.

    Science.gov (United States)

    Tanzilli, Annalisa; Muzi, Laura; Ronningstam, Elsa; Lingiardi, Vittorio

    2017-06-01

    Narcissistic personality disorder (NPD) is one of the most challenging clinical syndromes to treat in psychotherapy, especially due to the difficulties of establishing a good enough therapist-patient relationship. Countertransference responses to NPD can be particularly intense, frustrating, and difficult to manage, as is often reported in the clinical literature though not clearly supported empirically. The aims of this study were to (a) investigate the relationship between patients' NPD and therapists' responses; (b) examine the associations between patient, clinician, therapy variables and clinicians' reactions during treatment of NPD patients; and (c) provide an empirically derived portrait of countertransference with NPD. A sample of psychiatrists and clinical psychologists (N = 67) completed the Therapist Response Questionnaire to identify patterns of countertransference, the Shedler-Westen Assessment Procedure-200, and the Global Assessment of Functioning Scale to assess the personality pathology and psychosocial functioning of a patient in their care. The results showed that NPD was positively associated with hostile/angry, criticized/devalued, helpless/inadequate, and disengaged countertransference and negatively associated with therapists' positive response, regardless of patients' personality and psychosocial functioning. NPD patients with stronger traits of cluster B personality pathology tended to elicit more negative and heterogeneous countertransference reactions than NPD patients without these features. The countertransference patterns with NPD patients were not strongly influenced by the variables of clinicians and therapy, with the exception of clinical experience. Overall, the portrait of therapists' reactions to NPD provided a clinically nuanced and empirically founded description strongly resembling theoretical-clinical accounts. The therapeutic implications of these findings were discussed. (PsycINFO Database Record (c) 2017 APA, all rights

  19. Empirical evaluation methods in computer vision

    CERN Document Server

    Christensen, Henrik I

    2002-01-01

    This book provides comprehensive coverage of methods for the empirical evaluation of computer vision techniques. The practical use of computer vision requires empirical evaluation to ensure that the overall system has a guaranteed performance. The book contains articles that cover the design of experiments for evaluation, range image segmentation, the evaluation of face recognition and diffusion methods, image matching using correlation methods, and the performance of medical image processing algorithms. Sample Chapter(s). Foreword (228 KB). Chapter 1: Introduction (505 KB). Contents: Automate

  20. Evaluation of empirical atmospheric diffusion data

    International Nuclear Information System (INIS)

    Horst, T.W.; Doran, J.C.; Nickola, P.W.

    1979-10-01

    A study has been made of atmospheric diffusion over level, homogeneous terrain of contaminants released from non-buoyant point sources up to 100 m in height. Current theories of diffusion are compared to empirical diffusion data, and specific dispersion estimation techniques are recommended which can be implemented with the on-site meteorological instrumentation required by the Nuclear Regulatory Commission. A comparison of both the recommended diffusion model and the NRC diffusion model with the empirical data demonstrates that the predictions of the recommended model have both smaller scatter and less bias, particularly for groundlevel sources

  1. Evaluation of empirical atmospheric diffusion data

    Energy Technology Data Exchange (ETDEWEB)

    Horst, T.W.; Doran, J.C.; Nickola, P.W.

    1979-10-01

    A study has been made of atmospheric diffusion over level, homogeneous terrain of contaminants released from non-buoyant point sources up to 100 m in height. Current theories of diffusion are compared to empirical diffusion data, and specific dispersion estimation techniques are recommended which can be implemented with the on-site meteorological instrumentation required by the Nuclear Regulatory Commission. A comparison of both the recommended diffusion model and the NRC diffusion model with the empirical data demonstrates that the predictions of the recommended model have both smaller scatter and less bias, particularly for ground-level sources.

  2. Empirical Model Building Data, Models, and Reality

    CERN Document Server

    Thompson, James R

    2011-01-01

    Praise for the First Edition "This...novel and highly stimulating book, which emphasizes solving real problems...should be widely read. It will have a positive and lasting effect on the teaching of modeling and statistics in general." - Short Book Reviews This new edition features developments and real-world examples that showcase essential empirical modeling techniques Successful empirical model building is founded on the relationship between data and approximate representations of the real systems that generated that data. As a result, it is essential for researchers who construct these m

  3. Matrix effect studies with empirical formulations in maize saplings

    International Nuclear Information System (INIS)

    Bansal, Meenakshi; Deep, Kanan; Mittal, Raj

    2012-01-01

    In X-ray fluorescence, the earlier derived matrix effects from fundamental relations of intensities of analyte/matrix elements with basic atomic and experimental setup parameters and tested on synthetic known samples were found empirically related to analyte/matrix elemental amounts. The present study involves the application of these relations on potassium and calcium macronutrients of maize saplings treated with different fertilizers. The novelty of work involves a determination of an element in the presence of its secondary excitation rather than avoiding the secondary fluorescence. Therefore, the possible utility of this process is in studying the absorption for some intermediate samples in a lot of a category of samples with close Z interfering constituents (just like Ca and K). Once the absorption and enhancement terms are fitted to elemental amounts and fitted coefficients are determined, with the absorption terms from the fit and an enhancer element amount known from its selective excitation, the next iterative elemental amount can be directly evaluated from the relations. - Highlights: ► Empirical formulation for matrix corrections in terms of amounts of analyte and matrix element. ► The study applied on K and Ca nutrients of maize, rice and potato organic materials. ► The formulation provides matrix terms from amounts of analyte/matrix elements and vice versa.

  4. A Behaviorally Specific, Empirical Alternative to Bullying: Aggravated Peer Victimization.

    Science.gov (United States)

    Finkelhor, David; Shattuck, Anne; Turner, Heather; Hamby, Sherry

    2016-11-01

    To test a behaviorally specific measure of serious peer victimization, called aggravated peer victimization (APV), using empirically derived aggravating elements of episodes (injury, weapon, bias content, sexual content, multiple perpetrators, and multiple contexts) and compare this measure with the conventional Olweus bullying (OB) measure, which uses repetition and power imbalance as its seriousness criteria. The data for this study come from The National Survey of Children's Exposure to Violence 2014, a study conducted via telephone interviews with a nationally representative sample. This analysis uses the 1,949 youth ages 10-17 from that survey. The APV measure identified twice as many youth with serious episodes involving injury, weapons, sexual assaults, and bias content as the OB measure. In terms of demographic and social characteristics, the groups were very similar. However, the APV explained significantly more of the variation in distress than the OB (R 2  = .19 vs. .12). An empirical approach to identifying the most serious incidents of peer victimization has advantages in identifying more of the youth suffering the effects of peer victimization. Moreover, its behaviorally specific criteria also bypass the difficult challenge of trying to reliably assess what is truly bullying with its ambiguous definitional element of power imbalance. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  5. Renal Ammonia Metabolism and Transport

    Science.gov (United States)

    Weiner, I. David; Verlander, Jill W.

    2015-01-01

    Renal ammonia metabolism and transport mediates a central role in acid-base homeostasis. In contrast to most renal solutes, the majority of renal ammonia excretion derives from intrarenal production, not from glomerular filtration. Renal ammoniagenesis predominantly results from glutamine metabolism, which produces 2 NH4+ and 2 HCO3− for each glutamine metabolized. The proximal tubule is the primary site for ammoniagenesis, but there is evidence for ammoniagenesis by most renal epithelial cells. Ammonia produced in the kidney is either excreted into the urine or returned to the systemic circulation through the renal veins. Ammonia excreted in the urine promotes acid excretion; ammonia returned to the systemic circulation is metabolized in the liver in a HCO3−-consuming process, resulting in no net benefit to acid-base homeostasis. Highly regulated ammonia transport by renal epithelial cells determines the proportion of ammonia excreted in the urine versus returned to the systemic circulation. The traditional paradigm of ammonia transport involving passive NH3 diffusion, protonation in the lumen and NH4+ trapping due to an inability to cross plasma membranes is being replaced by the recognition of limited plasma membrane NH3 permeability in combination with the presence of specific NH3-transporting and NH4+-transporting proteins in specific renal epithelial cells. Ammonia production and transport are regulated by a variety of factors, including extracellular pH and K+, and by several hormones, such as mineralocorticoids, glucocorticoids and angiotensin II. This coordinated process of regulated ammonia production and transport is critical for the effective maintenance of acid-base homeostasis. PMID:23720285

  6. PROBLEMS WITH WIREDU'S EMPIRICALISM Martin Odei Ajei1 ...

    African Journals Online (AJOL)

    In his “Empiricalism: The Empirical Character of an African Philosophy”,. Kwasi Wiredu sets out ... others, that an empirical metaphysical system contains both empirical ..... realms which multiple categories of existents inhabit and conduct their being in .... to a mode of reasoning that conceives categories polarized by formal.

  7. [Menopause and metabolic syndrome].

    Science.gov (United States)

    Meirelles, Ricardo M R

    2014-03-01

    The incidence of cardiovascular disease increases considerably after the menopause. One reason for the increased cardiovascular risk seems to be determined by metabolic syndrome, in which all components (visceral obesity, dyslipidemia, hypertension, and glucose metabolism disorder) are associated with higher incidence of coronary artery disease. After menopause, metabolic syndrome is more prevalent than in premenopausal women, and may plays an important role in the occurrence of myocardial infarction and other atherosclerotic and cardiovascular morbidities. Obesity, an essential component of the metabolic syndrome, is also associated with increased incidence of breast, endometrial, bowel, esophagus, and kidney cancer. The treatment of metabolic syndrome is based on the change in lifestyle and, when necessary, the use of medication directed to its components. In the presence of symptoms of the climacteric syndrome, hormonal therapy, when indicated, will also contribute to the improvement of the metabolic syndrome.

  8. New peptides players in metabolic disorders

    Directory of Open Access Journals (Sweden)

    Agata Mierzwicka

    2016-08-01

    Full Text Available Among new peptides responsible for the pathogenesis of metabolic disorders and carbohydrate metabolism, adipokines are of great importance. Adipokines are substances of hormonal character, secreted by adipose tissue. Apart from the well-known adipokines, adropin and preptin are relatively newly discovered, hence their function is not fully understood. They are peptides not secreted by adipose tissue but their role in the metabolic regulations seems to be significant. Preptin is a 34-amino acid peptide, a derivative of proinsulin growth factor II (pro-IGF-II, secreted by pancreatic β cells, considered to be a physiological enhancer of insulin secretion. Additionally, preptin has a stimulating effect on osteoblasts, inducing their proliferation, differentiation and survival. Adropin is a 76-amino acid peptide, encoded by the energy homeostasis associated gene (Enho, mainly in liver and brain, and its expression is dependent on a diet. Adropin is believed to play an important role in metabolic homeostasis, fatty acids metabolism control, insulin resistance prevention, dyslipidemia, and impaired glucose tolerance. The results of studies conducted so far show that the diseases resulting from metabolic syndrome, such as obesity, type 2 diabetes mellitus, polycystic ovary syndrome, non-alcoholic fatty liver disease, or cardiovascular disease are accompanied by significant changes in the concentration of these peptides. It is also important to note that preptin has an anabolic effect on bone tissue, which might be preventive in osteoporosis.

  9. Computational Modeling of Lipid Metabolism in Yeast

    Directory of Open Access Journals (Sweden)

    Vera Schützhold

    2016-09-01

    Full Text Available Lipid metabolism is essential for all major cell functions and has recently gained increasing attention in research and health studies. However, mathematical modeling by means of classical approaches such as stoichiometric networks and ordinary differential equation systems has not yet provided satisfactory insights, due to the complexity of lipid metabolism characterized by many different species with only slight differences and by promiscuous multifunctional enzymes.Here, we present a object-oriented stochastic model approach as a way to cope with the complex lipid metabolic network. While all lipid species are treated objects in the model, they can be modified by the respective converting reactions based on reaction rules, a hybrid method that integrates benefits of agent-based and classical stochastic simulation. This approach allows to follow the dynamics of all lipid species with different fatty acids, different degrees of saturation and different headgroups over time and to analyze the effect of parameter changes, potential mutations in the catalyzing enzymes or provision of different precursors. Applied to yeast metabolism during one cell cycle period, we could analyze the distribution of all lipids to the various membranes in time-dependent manner.The presented approach allows to efficiently treat the complexity of cellular lipid metabolism and to derive conclusions on the time- and location-dependent distributions of lipid species and their properties such as saturation. It is widely applicable, easily extendable and will provide further insights in healthy and diseased states of cell metabolism.

  10. Lipoprotein metabolism indicators improve cardiovascular risk prediction.

    Directory of Open Access Journals (Sweden)

    Daniël B van Schalkwijk

    Full Text Available BACKGROUND: Cardiovascular disease risk increases when lipoprotein metabolism is dysfunctional. We have developed a computational model able to derive indicators of lipoprotein production, lipolysis, and uptake processes from a single lipoprotein profile measurement. This is the first study to investigate whether lipoprotein metabolism indicators can improve cardiovascular risk prediction and therapy management. METHODS AND RESULTS: We calculated lipoprotein metabolism indicators for 1981 subjects (145 cases, 1836 controls from the Framingham Heart Study offspring cohort in which NMR lipoprotein profiles were measured. We applied a statistical learning algorithm using a support vector machine to select conventional risk factors and lipoprotein metabolism indicators that contributed to predicting risk for general cardiovascular disease. Risk prediction was quantified by the change in the Area-Under-the-ROC-Curve (ΔAUC and by risk reclassification (Net Reclassification Improvement (NRI and Integrated Discrimination Improvement (IDI. Two VLDL lipoprotein metabolism indicators (VLDLE and VLDLH improved cardiovascular risk prediction. We added these indicators to a multivariate model with the best performing conventional risk markers. Our method significantly improved both CVD prediction and risk reclassification. CONCLUSIONS: Two calculated VLDL metabolism indicators significantly improved cardiovascular risk prediction. These indicators may help to reduce prescription of unnecessary cholesterol-lowering medication, reducing costs and possible side-effects. For clinical application, further validation is required.

  11. Metabolic syndrome and menopause

    OpenAIRE

    Jouyandeh, Zahra; Nayebzadeh, Farnaz; Qorbani, Mostafa; Asadi, Mojgan

    2013-01-01

    Abstract Background The metabolic syndrome is defined as an assemblage of risk factors for cardiovascular diseases, and menopause is associated with an increase in metabolic syndrome prevalence. The aim of this study was to assess the prevalence of metabolic syndrome and its components among postmenopausal women in Tehran, Iran. Methods In this cross-sectional study in menopause clinic in Tehran, 118 postmenopausal women were investigated. We used the adult treatment panel 3 (ATP3) criteria t...

  12. Downside Risk And Empirical Asset Pricing

    NARCIS (Netherlands)

    P. van Vliet (Pim)

    2004-01-01

    textabstractCurrently, the Nobel prize winning Capital Asset Pricing Model (CAPM) celebrates its 40th birthday. Although widely applied in financial management, this model does not fully capture the empirical riskreturn relation of stocks; witness the beta, size, value and momentum effects. These

  13. Empirical analysis of uranium spot prices

    International Nuclear Information System (INIS)

    Morman, M.R.

    1988-01-01

    The objective is to empirically test a market model of the uranium industry that incorporates the notion that, if the resource is viewed as an asset by economic agents, then its own rate of return along with the own rate of return of a competing asset would be a major factor in formulating the price of the resource. The model tested is based on a market model of supply and demand. The supply model incorporates the notion that the decision criteria used by uranium mine owners is to select that extraction rate that maximizes the net present value of their extraction receipts. The demand model uses a concept that allows for explicit recognition of the prospect of arbitrage between a natural-resource market and the market for other capital goods. The empirical approach used for estimation was a recursive or causal model. The empirical results were consistent with the theoretical models. The coefficients of the demand and supply equations had the appropriate signs. Tests for causality were conducted to validate the use of the causal model. The results obtained were favorable. The implication of the findings as related to future studies of exhaustible resources are: (1) in some cases causal models are the appropriate specification for empirical analysis; (2) supply models should incorporate a measure to capture depletion effects

  14. Trade costs in empirical New Economic Geography

    NARCIS (Netherlands)

    Bosker, E.M.; Garretsen, J.H.

    Trade costs are a crucial element of New Economic Geography (NEG) models. Without trade costs there is no role for geography. In empirical NEG studies the unavailability of direct trade cost data calls for the need to approximate these trade costs by introducing a trade cost function. In doing so,

  15. Methods for Calculating Empires in Quasicrystals

    Directory of Open Access Journals (Sweden)

    Fang Fang

    2017-10-01

    Full Text Available This paper reviews the empire problem for quasiperiodic tilings and the existing methods for generating the empires of the vertex configurations in quasicrystals, while introducing a new and more efficient method based on the cut-and-project technique. Using Penrose tiling as an example, this method finds the forced tiles with the restrictions in the high dimensional lattice (the mother lattice that can be cut-and-projected into the lower dimensional quasicrystal. We compare our method to the two existing methods, namely one method that uses the algorithm of the Fibonacci chain to force the Ammann bars in order to find the forced tiles of an empire and the method that follows the work of N.G. de Bruijn on constructing a Penrose tiling as the dual to a pentagrid. This new method is not only conceptually simple and clear, but it also allows us to calculate the empires of the vertex configurations in a defected quasicrystal by reversing the configuration of the quasicrystal to its higher dimensional lattice, where we then apply the restrictions. These advantages may provide a key guiding principle for phason dynamics and an important tool for self error-correction in quasicrystal growth.

  16. Alternative Approaches to Evaluation in Empirical Microeconomics

    Science.gov (United States)

    Blundell, Richard; Dias, Monica Costa

    2009-01-01

    This paper reviews some of the most popular policy evaluation methods in empirical microeconomics: social experiments, natural experiments, matching, instrumental variables, discontinuity design, and control functions. It discusses identification of traditionally used average parameters and more complex distributional parameters. The adequacy,…

  17. Characterizing Student Expectations: A Small Empirical Study

    Science.gov (United States)

    Warwick, Jonathan

    2016-01-01

    This paper describes the results of a small empirical study (n = 130), in which undergraduate students in the Business Faculty of a UK university were asked to express views and expectations relating to the study of a mathematics. Factor analysis is used to identify latent variables emerging from clusters of the measured variables and these are…

  18. EVOLVING AN EMPIRICAL METHODOLOGY DOR DETERMINING ...

    African Journals Online (AJOL)

    The uniqueness of this approach, is that it can be applied to any forest or dynamic feature on the earth, and can enjoy universal application as well. KEY WORDS: Evolving empirical methodology, innovative mathematical model, appropriate interval, remote sensing, forest environment planning and management. Global Jnl ...

  19. Caught between Empires: Ambivalence in Australian Films ...

    African Journals Online (AJOL)

    Caught between Empires: Ambivalence in Australian Films. Greg McCarthy. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL · AJOL's Partners · Terms and Conditions of Use · Contact AJOL · News. OTHER RESOURCES... for Researchers · for ...

  20. Spitsbergen - Imperialists beyond the British Empire

    NARCIS (Netherlands)

    Kruse, Frigga; Hacquebord, Louwrens

    2012-01-01

    This paper looks at the relationship between Spitsbergen in the European High Arctic and the global British Empire in the first quarter of the twentieth century. Spitsbergen was an uninhabited no man's land and comprised an unknown quantity of natural resources. The concepts of geopolitics and New

  1. An Empirical Investigation into Nigerian ESL Learners ...

    African Journals Online (AJOL)

    General observations indicate that ESL learners in Nigeria tend to manifest fear and anxiety in grammar classes, which could influence their performance negatively or positively. This study examines empirically some of the reasons for some ESL learners' apprehension of grammar classes. The data for the study were ...

  2. Air pollutant taxation: an empirical survey

    International Nuclear Information System (INIS)

    Cansier, D.; Krumm, R.

    1997-01-01

    An empirical analysis of the current taxation of the air pollutants sulphur dioxide, nitrogen oxides and carbon dioxide in the Scandinavian countries, the Netherlands, France and Japan is presented. Political motivation and technical factors such as tax base, rate structure and revenue use are compared. The general concepts of the current polices are characterised

  3. Empirical research on constructing Taiwan's ecoenvironmental ...

    African Journals Online (AJOL)

    In this paper, the material flow indicators and ecological footprint approach structured are adopted to construct eco-environmental stress indicators. We use relevant data to proceed with the empirical analyses on environmental stress and ecological impacts in Taiwan between the years of 1998 and 2007. Analysis of ...

  4. Empirical Bayes Approaches to Multivariate Fuzzy Partitions.

    Science.gov (United States)

    Woodbury, Max A.; Manton, Kenneth G.

    1991-01-01

    An empirical Bayes-maximum likelihood estimation procedure is presented for the application of fuzzy partition models in describing high dimensional discrete response data. The model describes individuals in terms of partial membership in multiple latent categories that represent bounded discrete spaces. (SLD)

  5. Empirically Exploring Higher Education Cultures of Assessment

    Science.gov (United States)

    Fuller, Matthew B.; Skidmore, Susan T.; Bustamante, Rebecca M.; Holzweiss, Peggy C.

    2016-01-01

    Although touted as beneficial to student learning, cultures of assessment have not been examined adequately using validated instruments. Using data collected from a stratified, random sample (N = 370) of U.S. institutional research and assessment directors, the models tested in this study provide empirical support for the value of using the…

  6. Empirically Based Myths: Astrology, Biorhythms, and ATIs.

    Science.gov (United States)

    Ragsdale, Ronald G.

    1980-01-01

    A myth may have an empirical basis through chance occurrence; perhaps Aptitude Treatment Interactions (ATIs) are in this category. While ATIs have great utility in describing, planning, and implementing instruction, few disordinal interactions have been found. Article suggests narrowing of ATI research with replications and estimates of effect…

  7. Transition States from Empirical Force Fields

    DEFF Research Database (Denmark)

    Jensen, Frank; Norrby, Per-Ola

    2003-01-01

    This is an overview of the use of empirical force fields in the study of reaction mechanisms. EVB-type methods (including RFF and MCMM) produce full reaction surfaces by mixing, in the simplest case, known force fields describing reactants and products. The SEAM method instead locates approximate...

  8. Empirical scaling for present ohmic heated tokamaks

    International Nuclear Information System (INIS)

    Daughney, C.

    1975-06-01

    Empirical scaling laws are given for the average electron temperature and electron energy confinement time as functions of plasma current, average electron density, effective ion charge, toroidal magnetic field, and major and minor plasma radius. The ohmic heating is classical, and the electron energy transport is anomalous. The present scaling indicates that ohmic-heating becomes ineffective with larger experiments. (U.S.)

  9. Developing empirical relationship between interrill erosion, rainfall ...

    African Journals Online (AJOL)

    In order to develop an empirical relationship for interrill erosion based on rainfall intensity, slope steepness and soil types, an interrill erosion experiment was conducted using laboratory rainfall simulator on three soil types (Vertisols, Cambisols and Leptosols) for the highlands of North Shewa Zone of Oromia Region.

  10. Governance and Human Development: Empirical Evidence from ...

    African Journals Online (AJOL)

    This study empirically investigates the effects of governance on human development in Nigeria. Using annual time series data covering the period 1998 to 2010, obtained from various sources, and employing the classical least squares estimation technique, the study finds that corruption, foreign aid and government ...

  11. Software Development Management: Empirical and Analytical Perspectives

    Science.gov (United States)

    Kang, Keumseok

    2011-01-01

    Managing software development is a very complex activity because it must deal with people, organizations, technologies, and business processes. My dissertation consists of three studies that examine software development management from various perspectives. The first study empirically investigates the impacts of prior experience with similar…

  12. The Italian Footwear Industry: an Empirical Analysis

    OpenAIRE

    Pirolo, Luca; Giustiniano, Luca; Nenni, Maria Elena

    2013-01-01

    This paper aims to provide readers with a deep empirical analysis on the Italian footwear industry in order to investigate the evolution of its structure (trends in sales and production, number of firms and employees, main markets, etc.), together with the identification of the main drivers of competitiveness in order to explain the strategies implemented by local actors.

  13. Multiscale empirical interpolation for solving nonlinear PDEs

    KAUST Repository

    Calo, Victor M.; Efendiev, Yalchin R.; Galvis, Juan; Ghommem, Mehdi

    2014-01-01

    residuals and Jacobians on the fine grid. We use empirical interpolation concepts to evaluate these residuals and Jacobians of the multiscale system with a computational cost which is proportional to the size of the coarse-scale problem rather than the fully

  14. Quantitative analyses of empirical fitness landscapes

    International Nuclear Information System (INIS)

    Szendro, Ivan G; Franke, Jasper; Krug, Joachim; Schenk, Martijn F; De Visser, J Arjan G M

    2013-01-01

    The concept of a fitness landscape is a powerful metaphor that offers insight into various aspects of evolutionary processes and guidance for the study of evolution. Until recently, empirical evidence on the ruggedness of these landscapes was lacking, but since it became feasible to construct all possible genotypes containing combinations of a limited set of mutations, the number of studies has grown to a point where a classification of landscapes becomes possible. The aim of this review is to identify measures of epistasis that allow a meaningful comparison of fitness landscapes and then apply them to the empirical landscapes in order to discern factors that affect ruggedness. The various measures of epistasis that have been proposed in the literature appear to be equivalent. Our comparison shows that the ruggedness of the empirical landscape is affected by whether the included mutations are beneficial or deleterious and by whether intragenic or intergenic epistasis is involved. Finally, the empirical landscapes are compared to landscapes generated with the rough Mt Fuji model. Despite the simplicity of this model, it captures the features of the experimental landscapes remarkably well. (paper)

  15. Qualitative Case Study Research as Empirical Inquiry

    Science.gov (United States)

    Ellinger, Andrea D.; McWhorter, Rochell

    2016-01-01

    This article introduces the concept of qualitative case study research as empirical inquiry. It defines and distinguishes what a case study is, the purposes, intentions, and types of case studies. It then describes how to determine if a qualitative case study is the preferred approach for conducting research. It overviews the essential steps in…

  16. The problem analysis for empirical studies

    NARCIS (Netherlands)

    Groenland, E.A.G.

    2014-01-01

    This article proposes a systematic methodology for the development of a problem analysis for cross-sectional, empirical research. This methodology is referred to as the 'Annabel approach'. It is suitable both for academic studies and applied (business) studies. In addition it can be used for both

  17. Empirical questions for collective-behaviour modelling

    Indian Academy of Sciences (India)

    The collective behaviour of groups of social animals has been an active topic of study ... Models have been successful at reproducing qualitative features of ... quantitative and detailed empirical results for a range of animal systems. ... standard method [23], the redundant information recorded by the cameras can be used to.

  18. Synthetic and Empirical Capsicum Annuum Image Dataset

    NARCIS (Netherlands)

    Barth, R.

    2016-01-01

    This dataset consists of per-pixel annotated synthetic (10500) and empirical images (50) of Capsicum annuum, also known as sweet or bell pepper, situated in a commercial greenhouse. Furthermore, the source models to generate the synthetic images are included. The aim of the datasets are to

  19. An Empirical Investigation into Programming Language Syntax

    Science.gov (United States)

    Stefik, Andreas; Siebert, Susanna

    2013-01-01

    Recent studies in the literature have shown that syntax remains a significant barrier to novice computer science students in the field. While this syntax barrier is known to exist, whether and how it varies across programming languages has not been carefully investigated. For this article, we conducted four empirical studies on programming…

  20. Self-Published Books: An Empirical "Snapshot"

    Science.gov (United States)

    Bradley, Jana; Fulton, Bruce; Helm, Marlene

    2012-01-01

    The number of books published by authors using fee-based publication services, such as Lulu and AuthorHouse, is overtaking the number of books published by mainstream publishers, according to Bowker's 2009 annual data. Little empirical research exists on self-published books. This article presents the results of an investigation of a random sample…

  1. Empirical Differential Balancing for Nonlinear Systems

    NARCIS (Netherlands)

    Kawano, Yu; Scherpen, Jacquelien M.A.; Dochain, Denis; Henrion, Didier; Peaucelle, Dimitri

    In this paper, we consider empirical balancing of nonlinear systems by using its prolonged system, which consists of the original nonlinear system and its variational system. For the prolonged system, we define differential reachability and observability Gramians, which are matrix valued functions

  2. [Metabolic functions and sport].

    Science.gov (United States)

    Riviere, Daniel

    2004-01-01

    Current epidemiological studies emphasize the increased of metabolic diseases of the adults, such as obesity, type-2 diabetes and metabolic syndromes. Even more worrying is the rising prevalence of obesity in children. It is due more to sedentariness, caused more by inactivity (television, video, games, etc.) than by overeating. Many studies have shown that regular physical activities benefit various bodily functions including metabolism. After dealing with the major benefits of physical exercise on some adult metabolic disorders, we focus on the prime role played by physical activity in combating the public health problem of childhood obesity.

  3. Multiscale empirical interpolation for solving nonlinear PDEs

    KAUST Repository

    Calo, Victor M.

    2014-12-01

    In this paper, we propose a multiscale empirical interpolation method for solving nonlinear multiscale partial differential equations. The proposed method combines empirical interpolation techniques and local multiscale methods, such as the Generalized Multiscale Finite Element Method (GMsFEM). To solve nonlinear equations, the GMsFEM is used to represent the solution on a coarse grid with multiscale basis functions computed offline. Computing the GMsFEM solution involves calculating the system residuals and Jacobians on the fine grid. We use empirical interpolation concepts to evaluate these residuals and Jacobians of the multiscale system with a computational cost which is proportional to the size of the coarse-scale problem rather than the fully-resolved fine scale one. The empirical interpolation method uses basis functions which are built by sampling the nonlinear function we want to approximate a limited number of times. The coefficients needed for this approximation are computed in the offline stage by inverting an inexpensive linear system. The proposed multiscale empirical interpolation techniques: (1) divide computing the nonlinear function into coarse regions; (2) evaluate contributions of nonlinear functions in each coarse region taking advantage of a reduced-order representation of the solution; and (3) introduce multiscale proper-orthogonal-decomposition techniques to find appropriate interpolation vectors. We demonstrate the effectiveness of the proposed methods on several nonlinear multiscale PDEs that are solved with Newton\\'s methods and fully-implicit time marching schemes. Our numerical results show that the proposed methods provide a robust framework for solving nonlinear multiscale PDEs on a coarse grid with bounded error and significant computational cost reduction.

  4. Pay-What-You-Want pricing: An integrative review of the empirical research literature

    Directory of Open Access Journals (Sweden)

    Torsten J.

    2017-01-01

    Full Text Available In a Pay What You Want (PWYW setting companies empower their customers to fix the prices buyers voluntarily pay for a delivered product or service. The seller agrees to any price (includ-ing zero customers are paying. For about ten years researchers empirically investigate customer reactions to and economic outcomes of this pricing method. The present paper distinguishes PWYW from other voluntary payment mechanisms and reviews 72 English- or German-speaking PWYW publications, which appeared between January 2006 and September 2016 and contain 97 independent empirical data sets. Prior PWYW research is structured with the help of a conceptual framework which incorporates payment procedure design, buyer, seller, focal sales object and market context characteristics as factors potentially influencing customer perceptions of the PWYW scheme and their behavioral reactions to PWYW offers. The review discusses both consistent key findings as well as contradictory results and derives recommendations for future empirical PWYW research efforts.

  5. A review of the empirical literature on Pay-What-You-Want price setting

    Directory of Open Access Journals (Sweden)

    Gerpott Torsten J.

    2016-12-01

    Full Text Available In a Pay What You Want (PWYW setting companies empower their customers to fix the prices buyers voluntarily pay for a delivered product or service. The seller agrees to any price (including zero customers are paying. For about ten years researchers empirically investigate customer reactions to and economic outcomes of this pricing method. The present paper distinguishes PWYW from other voluntary payment mechanisms and reviews 72 English- or German-speaking PWYW publications, which appeared between January 2006 and September 2016 and contain 97 independent empirical data sets. Prior PWYW research is structured with the help of a conceptual framework which incorporates payment procedure design, buyer, seller, focal sales object and market context characteristics as factors potentially influencing customer perceptions of the PWYW scheme and their behavioral reactions to PWYW offers. The review discusses both consistent key findings as well as contradictory results and derives recommendations for future empirical PWYW research efforts.

  6. Fluoroacetylcarnitine: metabolism and metabolic effects in mitochondria

    Energy Technology Data Exchange (ETDEWEB)

    Bremer, J; Davis, E J

    1973-01-01

    The metabolism and metabolic effects of fluoroacetylcarnitine have been investigated. Carnitineacetyltransferase transfers the fluoro-acetyl group of fluoroacetylcarnitine nearly as rapidly to CoA as the acetyl group of acetylcarnitine. Fluorocitrate is then formed by citrate synthase, but this second reaction is relatively slow. The fluorocitrate formed intramitochondrially inhibits the metabolism of citrate. In heart and skeletal muscle mitochondria the accumulated citrate inhibits citrate synthesis and the ..beta..-oxidation of fatty acids. Free acetate is formed, presumably because accumulated acetyl-CoA is hydrolyzed. In liver mitochondria the accumulation of citrate leads to a relatively increased rate of ketogenesis. Increased ketogenesis is obtained also upon the addition of citrate to the reaction mixture.

  7. Fatty acid metabolism: target for metabolic syndrome

    OpenAIRE

    Wakil, Salih J.; Abu-Elheiga, Lutfi A.

    2009-01-01

    Fatty acids are a major energy source and important constituents of membrane lipids, and they serve as cellular signaling molecules that play an important role in the etiology of the metabolic syndrome. Acetyl-CoA carboxylases 1 and 2 (ACC1 and ACC2) catalyze the synthesis of malonyl-CoA, the substrate for fatty acid synthesis and the regulator of fatty acid oxidation. They are highly regulated and play important roles in the energy metabolism of fatty acids in animals, including humans. They...

  8. Metabolic disturbances connecting obesity and depression

    Directory of Open Access Journals (Sweden)

    Cecile eHryhorczuk

    2013-10-01

    Full Text Available Obesity markedly increases the odds of developing depression. Depressed mood not only impairs motivation, quality of life and overall functioning but also increases the risks of obesity complications. Abdominal obesity is a better predictor of depression and anxiety risk than overall adipose mass. A growing amount of research suggests that metabolic abnormalities stemming from central obesity that lead to metabolic disease may also responsible for the increased incidence of depression in obesity. As reviewed here, a higher mass of dysfunctional adipose tissue is associated with several metabolic disturbances that are either directly or indirectly implicated in the control of emotions and mood. To better comprehend the development of depression in obesity, this review pulls together select findings addressing the link between adiposity, diet and negative emotional states and discusses the evidence that alterations in glucocorticoids, adipose-derived hormones and inflammatory signalling that are characteristic of central obesity may be involved.

  9. Synthetic cannabimimetic agents metabolized by carboxylesterases

    DEFF Research Database (Denmark)

    Thomsen, Ragnar; Nielsen, Line M; Holm, Niels B

    2015-01-01

    Synthetic cannabimimetic agents are a large group of diverse compounds which act as agonists at cannabinoid receptors. Since 2004, synthetic cannabinoids have been used recreationally, although several of the compounds have been shown to cause severe toxicity in humans. In this study......, the metabolism of two indazole carboxamide derivatives, AB-PINACA and AB-FUBINACA, was investigated by using human liver microsomes (HLM). For both compounds, a major metabolic pathway was the enzymatic hydrolysis of the primary amide, resulting in the major metabolites AB-PINACA-COOH and AB-FUBINACA-COOH. Other...... major metabolic pathways were mono-hydroxylation of the N-pentyl chain in AB-PINACA and mono-hydroxylation of the 1-amino-3-methyl-1-oxobutane moiety in AB-FUBINACA. To identify the enzyme(s) responsible for the amide hydrolysis, incubations with recombinant carboxylesterases and human serum, as well...

  10. Investigation of metabolic encephalopathy

    African Journals Online (AJOL)

    cycle defects is the X-linked recessive disorder, ornithine ... life, or if the child is fed the compounds that they are unable .... as learning difficulties, drowsiness and avoidance of ... Table 2. Laboratory investigation of suspected metabolic encephalopathy. Laboratory .... Clinical approach to treatable inborn metabolic diseases:.

  11. Metabolic regulation of inflammation.

    Science.gov (United States)

    Gaber, Timo; Strehl, Cindy; Buttgereit, Frank

    2017-05-01

    Immune cells constantly patrol the body via the bloodstream and migrate into multiple tissues where they face variable and sometimes demanding environmental conditions. Nutrient and oxygen availability can vary during homeostasis, and especially during the course of an immune response, creating a demand for immune cells that are highly metabolically dynamic. As an evolutionary response, immune cells have developed different metabolic programmes to supply them with cellular energy and biomolecules, enabling them to cope with changing and challenging metabolic conditions. In the past 5 years, it has become clear that cellular metabolism affects immune cell function and differentiation, and that disease-specific metabolic configurations might provide an explanation for the dysfunctional immune responses seen in rheumatic diseases. This Review outlines the metabolic challenges faced by immune cells in states of homeostasis and inflammation, as well as the variety of metabolic configurations utilized by immune cells during differentiation and activation. Changes in cellular metabolism that contribute towards the dysfunctional immune responses seen in rheumatic diseases are also briefly discussed.

  12. Metabolic syndrome and menopause

    Directory of Open Access Journals (Sweden)

    Jouyandeh Zahra

    2013-01-01

    Full Text Available Abstract Background The metabolic syndrome is defined as an assemblage of risk factors for cardiovascular diseases, and menopause is associated with an increase in metabolic syndrome prevalence. The aim of this study was to assess the prevalence of metabolic syndrome and its components among postmenopausal women in Tehran, Iran. Methods In this cross-sectional study in menopause clinic in Tehran, 118 postmenopausal women were investigated. We used the adult treatment panel 3 (ATP3 criteria to classify subjects as having metabolic syndrome. Results Total prevalence of metabolic syndrome among our subjects was 30.1%. Waist circumference, HDL-cholesterol, fasting blood glucose, diastolic blood pressure ,Systolic blood pressure, and triglyceride were significantly higher among women with metabolic syndrome (P-value Conclusions Our study shows that postmenopausal status is associated with an increased risk of metabolic syndrome. Therefore, to prevent cardiovascular disease there is a need to evaluate metabolic syndrome and its components from the time of the menopause.

  13. Melphalan metabolism in cultured cells

    International Nuclear Information System (INIS)

    Seagrave, J.C.; Valdez, J.G.; Tobey, R.A.; Gurley, L.R.

    1985-06-01

    Procedures are presented for the adaptation of reversed-phase-HPLC methods to accomplish separation and isolation of the cancer therapeutic drug melphalan (L-phenylalanine mustard) and its metabolic products from whole cells. Five major degradation products of melphalan were observed following its hydrolysis in phosphate buffer in vitro. The two most polar of these products (or modifications of them) were also found in the cytosol of Chinese hamster CHO cells. The amounts of these two polar products (shown not to be mono- or dihydroxymelphalan) were significantly changed by the pretreatment of cells with ZnC1 2 , one being increased in amount while the other was reduced to an insignificant level. In ZnC1 2 -treated cells, there was also an increased binding of melphalan (or its derivatives) to one protein fraction resolved by gel filtration-HPLC. These observations suggest that changes in polar melphalan products, and perhaps their interaction with a protein, may by involved in the reduction of melphalan cytotoxicity observed in ZnC1 2 -treated cells. While ZnC1 2 is also known to increase the level of glutathione in cells, no significant amounts of glutathione-melphalan derivatives of the type formed non-enzymatically in vitro could be detected in ZnC1 2 -treated or untreated cells. Formation of derivatives of melphalan with glutathione catabolic products in ZnC1 2 -treated cells has not yet been eliminated, however. 17 refs., 5 figs., 1 tab

  14. Perspectives on empirical approaches for ocean color remote sensing of chlorophyll in a changing climate.

    Science.gov (United States)

    Dierssen, Heidi M

    2010-10-05

    Phytoplankton biomass and productivity have been continuously monitored from ocean color satellites for over a decade. Yet, the most widely used empirical approach for estimating chlorophyll a (Chl) from satellites can be in error by a factor of 5 or more. Such variability is due to differences in absorption and backscattering properties of phytoplankton and related concentrations of colored-dissolved organic matter (CDOM) and minerals. The empirical algorithms have built-in assumptions that follow the basic precept of biological oceanography--namely, oligotrophic regions with low phytoplankton biomass are populated with small phytoplankton, whereas more productive regions contain larger bloom-forming phytoplankton. With a changing world ocean, phytoplankton composition may shift in response to altered environmental forcing, and CDOM and mineral concentrations may become uncoupled from phytoplankton stocks, creating further uncertainty and error in the empirical approaches. Hence, caution is warranted when using empirically derived Chl to infer climate-related changes in ocean biology. The Southern Ocean is already experiencing climatic shifts and shows substantial errors in satellite-derived Chl for different phytoplankton assemblages. Accurate global assessments of phytoplankton will require improved technology and modeling, enhanced field observations, and ongoing validation of our "eyes in space."

  15. Drug metabolism in birds

    Science.gov (United States)

    Pan, Huo Ping; Fouts, James R.

    1979-01-01

    Papers published over 100 years since the beginning of the scientific study of drug metabolism in birds were reviewed. Birds were found to be able to accomplish more than 20 general biotransformation reactions in both functionalization and conjugation. Chickens were the primary subject of study but over 30 species of birds were used. Large species differences in drug metabolism exist between birds and mammals as well as between various birds, these differences were mostly quantitative. Qualitative differences were rare. On the whole, drug metabolism studies in birds have been neglected as compared with similar studies on insects and mammals. The uniqueness of birds and the advantages of using birds in drug metabolism studies are discussed. Possible future studies of drug metabolism in birds are recommended.

  16. Metabolic imaging using SPECT

    International Nuclear Information System (INIS)

    Taki, Junichi; Matsunari, Ichiro

    2007-01-01

    In normal condition, the heart obtains more than two-thirds of its energy from the oxidative metabolism of long chain fatty acids, although a wide variety of substrates such as glucose, lactate, ketone bodies and amino acids are also utilised. In ischaemic myocardium, on the other hand, oxidative metabolism of free fatty acid is suppressed and anaerobic glucose metabolism plays a major role in residual oxidative metabolism. Therefore, metabolic imaging can be an important technique for the assessment of various cardiac diseases and conditions. In SPECT, several iodinated fatty acid traces have been introduced and studied. Of these, 123 I-labelled 15-(p-iodophenyl)3-R, S-methylpentadecanoic acid (BMIPP) has been the most commonly used tracer in clinical studies, especially in some of the European countries and Japan. In this review article, several fatty acid tracers for SPECT are characterised, and the mechanism of uptake and clinical utility of BMIPP are discussed in detail. (orig.)

  17. Mycobacterium tuberculosis Metabolism

    Science.gov (United States)

    Warner, Digby F.

    2015-01-01

    Metabolism underpins the physiology and pathogenesis of Mycobacterium tuberculosis. However, although experimental mycobacteriology has provided key insights into the metabolic pathways that are essential for survival and pathogenesis, determining the metabolic status of bacilli during different stages of infection and in different cellular compartments remains challenging. Recent advances—in particular, the development of systems biology tools such as metabolomics—have enabled key insights into the biochemical state of M. tuberculosis in experimental models of infection. In addition, their use to elucidate mechanisms of action of new and existing antituberculosis drugs is critical for the development of improved interventions to counter tuberculosis. This review provides a broad summary of mycobacterial metabolism, highlighting the adaptation of M. tuberculosis as specialist human pathogen, and discusses recent insights into the strategies used by the host and infecting bacillus to influence the outcomes of the host–pathogen interaction through modulation of metabolic functions. PMID:25502746

  18. Metabolic Engineering VII Conference

    Energy Technology Data Exchange (ETDEWEB)

    Kevin Korpics

    2012-12-04

    The aims of this Metabolic Engineering conference are to provide a forum for academic and industrial researchers in the field; to bring together the different scientific disciplines that contribute to the design, analysis and optimization of metabolic pathways; and to explore the role of Metabolic Engineering in the areas of health and sustainability. Presentations, both written and oral, panel discussions, and workshops will focus on both applications and techniques used for pathway engineering. Various applications including bioenergy, industrial chemicals and materials, drug targets, health, agriculture, and nutrition will be discussed. Workshops focused on technology development for mathematical and experimental techniques important for metabolic engineering applications will be held for more in depth discussion. This 2008 meeting will celebrate our conference tradition of high quality and relevance to both industrial and academic participants, with topics ranging from the frontiers of fundamental science to the practical aspects of metabolic engineering.

  19. Metabolic imaging using PET

    International Nuclear Information System (INIS)

    Kudo, Takashi

    2007-01-01

    There is growing evidence that myocardial metabolism plays a key role not only in ischaemic heart disease but also in a variety of diseases which involve myocardium globally, such as heart failure and diabetes mellitus. Understanding myocardial metabolism in such diseases helps to elucidate the pathophysiology and assists in making therapeutic decisions. As well as providing information on regional changes, PET can deliver quantitative information about both regional and global changes in metabolism. This capability of quantitative measurement is one of the major advantages of PET along with physiological positron tracers, especially relevant in evaluating diseases which involve the whole myocardium. This review discusses major PET tracers for metabolic imaging and their clinical applications and contributions to research regarding ischaemic heart disease and other diseases such as heart failure and diabetic heart disease. Future applications of positron metabolic tracers for the detection of vulnerable plaque are also highlighted briefly. (orig.)

  20. Astrocytes and energy metabolism.

    Science.gov (United States)

    Prebil, Mateja; Jensen, Jørgen; Zorec, Robert; Kreft, Marko

    2011-05-01

    Astrocytes are glial cells, which play a significant role in a number of processes, including the brain energy metabolism. Their anatomical position between blood vessels and neurons make them an interface for effective glucose uptake from blood. After entering astrocytes, glucose can be involved in different metabolic pathways, e.g. in glycogen production. Glycogen in the brain is localized mainly in astrocytes and is an important energy source in hypoxic conditions and normal brain functioning. The portion of glucose metabolized into glycogen molecules in astrocytes is as high as 40%. It is thought that the release of gliotransmitters (such as glutamate, neuroactive peptides and ATP) into the extracellular space by regulated exocytosis supports a significant part of communication between astrocytes and neurons. On the other hand, neurotransmitter action on astrocytes has a significant role in brain energy metabolism. Therefore, understanding the astrocytes energy metabolism may help understanding neuron-astrocyte interactions.

  1. Interest rate derivatives

    DEFF Research Database (Denmark)

    Svenstrup, Mikkel

    This Ph.D. thesis consists of four self-contained essays on valuation of interest rate derivatives. In particular derivatives related to management of interest rate risk care are considered.......This Ph.D. thesis consists of four self-contained essays on valuation of interest rate derivatives. In particular derivatives related to management of interest rate risk care are considered....

  2. Intrinsic fluorescence of protein in turbid media using empirical relation based on Monte Carlo lookup table

    Science.gov (United States)

    Einstein, Gnanatheepam; Udayakumar, Kanniyappan; Aruna, Prakasarao; Ganesan, Singaravelu

    2017-03-01

    Fluorescence of Protein has been widely used in diagnostic oncology for characterizing cellular metabolism. However, the intensity of fluorescence emission is affected due to the absorbers and scatterers in tissue, which may lead to error in estimating exact protein content in tissue. Extraction of intrinsic fluorescence from measured fluorescence has been achieved by different methods. Among them, Monte Carlo based method yields the highest accuracy for extracting intrinsic fluorescence. In this work, we have attempted to generate a lookup table for Monte Carlo simulation of fluorescence emission by protein. Furthermore, we fitted the generated lookup table using an empirical relation. The empirical relation between measured and intrinsic fluorescence is validated using tissue phantom experiments. The proposed relation can be used for estimating intrinsic fluorescence of protein for real-time diagnostic applications and thereby improving the clinical interpretation of fluorescence spectroscopic data.

  3. Empirical Bayesian inference and model uncertainty

    International Nuclear Information System (INIS)

    Poern, K.

    1994-01-01

    This paper presents a hierarchical or multistage empirical Bayesian approach for the estimation of uncertainty concerning the intensity of a homogeneous Poisson process. A class of contaminated gamma distributions is considered to describe the uncertainty concerning the intensity. These distributions in turn are defined through a set of secondary parameters, the knowledge of which is also described and updated via Bayes formula. This two-stage Bayesian approach is an example where the modeling uncertainty is treated in a comprehensive way. Each contaminated gamma distributions, represented by a point in the 3D space of secondary parameters, can be considered as a specific model of the uncertainty about the Poisson intensity. Then, by the empirical Bayesian method each individual model is assigned a posterior probability

  4. Porphyry of Russian Empires in Paris

    Science.gov (United States)

    Bulakh, Andrey

    2014-05-01

    Porphyry of Russian Empires in Paris A. G. Bulakh (St Petersburg State University, Russia) So called "Schokhan porphyry" from Lake Onega, Russia, belongs surely to stones of World cultural heritage. One can see this "porphyry" at facades of a lovely palace of Pavel I and in pedestal of the monument after Nicolas I in St Petersburg. There are many other cases of using this stone in Russia. In Paris, sarcophagus of Napoleon I Bonaparte is constructed of blocks of this stone. Really, it is Proterozoic quartzite. Geology situation, petrography and mineralogical characteristic will be reported too. Comparison with antique porphyre from the Egyptian Province of the Roma Empire is given. References: 1) A.G.Bulakh, N.B.Abakumova, J.V.Romanovsky. St Petersburg: a History in Stone. 2010. Print House of St Petersburg State University. 173 p.

  5. Hybrid empirical--theoretical approach to modeling uranium adsorption

    International Nuclear Information System (INIS)

    Hull, Larry C.; Grossman, Christopher; Fjeld, Robert A.; Coates, John T.; Elzerman, Alan W.

    2004-01-01

    An estimated 330 metric tons of U are buried in the radioactive waste Subsurface Disposal Area (SDA) at the Idaho National Engineering and Environmental Laboratory (INEEL). An assessment of U transport parameters is being performed to decrease the uncertainty in risk and dose predictions derived from computer simulations of U fate and transport to the underlying Snake River Plain Aquifer. Uranium adsorption isotherms were measured for 14 sediment samples collected from sedimentary interbeds underlying the SDA. The adsorption data were fit with a Freundlich isotherm. The Freundlich n parameter is statistically identical for all 14 sediment samples and the Freundlich K f parameter is correlated to sediment surface area (r 2 =0.80). These findings suggest an efficient approach to material characterization and implementation of a spatially variable reactive transport model that requires only the measurement of sediment surface area. To expand the potential applicability of the measured isotherms, a model is derived from the empirical observations by incorporating concepts from surface complexation theory to account for the effects of solution chemistry. The resulting model is then used to predict the range of adsorption conditions to be expected in the vadose zone at the SDA based on the range in measured pore water chemistry. Adsorption in the deep vadose zone is predicted to be stronger than in near-surface sediments because the total dissolved carbonate decreases with depth

  6. Whole-body cryotherapy: empirical evidence and theoretical perspectives.

    Science.gov (United States)

    Bleakley, Chris M; Bieuzen, François; Davison, Gareth W; Costello, Joseph T

    2014-01-01

    Whole-body cryotherapy (WBC) involves short exposures to air temperatures below -100°C. WBC is increasingly accessible to athletes, and is purported to enhance recovery after exercise and facilitate rehabilitation postinjury. Our objective was to review the efficacy and effectiveness of WBC using empirical evidence from controlled trials. We found ten relevant reports; the majority were based on small numbers of active athletes aged less than 35 years. Although WBC produces a large temperature gradient for tissue cooling, the relatively poor thermal conductivity of air prevents significant subcutaneous and core body cooling. There is weak evidence from controlled studies that WBC enhances antioxidant capacity and parasympathetic reactivation, and alters inflammatory pathways relevant to sports recovery. A series of small randomized studies found WBC offers improvements in subjective recovery and muscle soreness following metabolic or mechanical overload, but little benefit towards functional recovery. There is evidence from one study only that WBC may assist rehabilitation for adhesive capsulitis of the shoulder. There were no adverse events associated with WBC; however, studies did not seem to undertake active surveillance of predefined adverse events. Until further research is available, athletes should remain cognizant that less expensive modes of cryotherapy, such as local ice-pack application or cold-water immersion, offer comparable physiological and clinical effects to WBC.

  7. Surface Passivation in Empirical Tight Binding

    OpenAIRE

    He, Yu; Tan, Yaohua; Jiang, Zhengping; Povolotskyi, Michael; Klimeck, Gerhard; Kubis, Tillmann

    2015-01-01

    Empirical Tight Binding (TB) methods are widely used in atomistic device simulations. Existing TB methods to passivate dangling bonds fall into two categories: 1) Method that explicitly includes passivation atoms is limited to passivation with atoms and small molecules only. 2) Method that implicitly incorporates passivation does not distinguish passivation atom types. This work introduces an implicit passivation method that is applicable to any passivation scenario with appropriate parameter...

  8. Empirically Examining Prostitution through a Feminist Perspective

    OpenAIRE

    Child, Shyann

    2009-01-01

    The purpose of this thesis is to empirically explore prostitution through a feminist perspective. Several background factors are explored on a small sample of women in the northeastern United States. Some of these women have been involved in an act of prostitution in their lifetime; some have not. This research will add to the body of knowledge on prostitution, as well as highlight the unique experiences of women. The goal is to understand whether or not these life experiences have had a h...

  9. Theoretical and Empirical Descriptions of Thermospheric Density

    Science.gov (United States)

    Solomon, S. C.; Qian, L.

    2004-12-01

    The longest-term and most accurate overall description the density of the upper thermosphere is provided by analysis of change in the ephemeris of Earth-orbiting satellites. Empirical models of the thermosphere developed in part from these measurements can do a reasonable job of describing thermospheric properties on a climatological basis, but the promise of first-principles global general circulation models of the coupled thermosphere/ionosphere system is that a true high-resolution, predictive capability may ultimately be developed for thermospheric density. However, several issues are encountered when attempting to tune such models so that they accurately represent absolute densities as a function of altitude, and their changes on solar-rotational and solar-cycle time scales. Among these are the crucial ones of getting the heating rates (from both solar and auroral sources) right, getting the cooling rates right, and establishing the appropriate boundary conditions. However, there are several ancillary issues as well, such as the problem of registering a pressure-coordinate model onto an altitude scale, and dealing with possible departures from hydrostatic equilibrium in empirical models. Thus, tuning a theoretical model to match empirical climatology may be difficult, even in the absence of high temporal or spatial variation of the energy sources. We will discuss some of the challenges involved, and show comparisons of simulations using the NCAR Thermosphere-Ionosphere-Electrodynamics General Circulation Model (TIE-GCM) to empirical model estimates of neutral thermosphere density and temperature. We will also show some recent simulations using measured solar irradiance from the TIMED/SEE instrument as input to the TIE-GCM.

  10. Insurability of Cyber Risk: An Empirical Analysis

    OpenAIRE

    Biener, Christian; Eling, Martin; Wirfs, Jan Hendrik

    2015-01-01

    This paper discusses the adequacy of insurance for managing cyber risk. To this end, we extract 994 cases of cyber losses from an operational risk database and analyse their statistical properties. Based on the empirical results and recent literature, we investigate the insurability of cyber risk by systematically reviewing the set of criteria introduced by Berliner (1982). Our findings emphasise the distinct characteristics of cyber risks compared with other operational risks and bring to li...

  11. Conducting empirical research in virtual worlds

    OpenAIRE

    Minocha, Shailey

    2011-01-01

    We will focus on the following aspects of conducting empirical research in virtual worlds: the toolbox of techniques for data collection; selection of technique(s) for the research questions; tips on how the techniques need to be adapted for conducting research in virtual worlds; guidance for developing research materials such as the consent form, project summary sheet, and how to address the possible concerns of an institution’s ethics committee who may not be familiar with the avatar-based ...

  12. Empirical solar/stellar cycle simulations

    Directory of Open Access Journals (Sweden)

    Santos Ângela R. G.

    2015-01-01

    Full Text Available As a result of the magnetic cycle, the properties of the solar oscillations vary periodically. With the recent discovery of manifestations of activity cycles in the seismic data of other stars, the understanding of the different contributions to such variations becomes even more important. With this in mind, we built an empirical parameterised model able to reproduce the properties of the sunspot cycle. The resulting simulations can be used to estimate the magnetic-induced frequency shifts.

  13. The empirical turn in international legal scholarship

    Directory of Open Access Journals (Sweden)

    Gregory Shaffer

    2015-07-01

    Full Text Available This article presents and assesses a new wave of em- pirical research on international law. Recent scholar- ship has moved away from theoretical debates over whether international law “matters,” and focuses in- stead on exploring the conditions under which inter- national law is created and produces effects. As this empirical research program has matured, it has al- lowed for new, midlevel theorizing that we call “conditional international law theory”. 

  14. Compassion: An Evolutionary Analysis and Empirical Review

    OpenAIRE

    Goetz, Jennifer L.; Keltner, Dacher; Simon-Thomas, Emiliana

    2010-01-01

    What is compassion? And how did it evolve? In this review, we integrate three evolutionary arguments that converge on the hypothesis that compassion evolved as a distinct affective experience whose primary function is to facilitate cooperation and protection of the weak and those who suffer. Our empirical review reveals compassion to have distinct appraisal processes attuned to undeserved suffering, distinct signaling behavior related to caregiving patterns of touch, posture, and vocalization...

  15. Services outsourcing and innovation: an empirical investigation

    OpenAIRE

    Görg, Holger; Hanley, Aoife

    2009-01-01

    We provide a comprehensive empirical analysis of the links between international services outsourcing, domestic outsourcing, profits and innovation using plant level data. We find a positive effect of international outsourcing of services on innovative activity at the plant level. Such a positive effect can also be observed for domestic outsourcing of services, but the magnitude is smaller. This makes intuitive sense, as international outsourcing allows more scope for exploiting international...

  16. Semi-empirical proton binding constants for natural organic matter

    Science.gov (United States)

    Matynia, Anthony; Lenoir, Thomas; Causse, Benjamin; Spadini, Lorenzo; Jacquet, Thierry; Manceau, Alain

    2010-03-01

    Average proton binding constants ( KH,i) for structure models of humic (HA) and fulvic (FA) acids were estimated semi-empirically by breaking down the macromolecules into reactive structural units (RSUs), and calculating KH,i values of the RSUs using linear free energy relationships (LFER) of Hammett. Predicted log KH,COOH and log KH,Ph-OH are 3.73 ± 0.13 and 9.83 ± 0.23 for HA, and 3.80 ± 0.20 and 9.87 ± 0.31 for FA. The predicted constants for phenolic-type sites (Ph-OH) are generally higher than those derived from potentiometric titrations, but the difference may not be significant in view of the considerable uncertainty of the acidity constants determined from acid-base measurements at high pH. The predicted constants for carboxylic-type sites agree well with titration data analyzed with Model VI (4.10 ± 0.16 for HA, 3.20 ± 0.13 for FA; Tipping, 1998), the Impermeable Sphere model (3.50-4.50 for HA; Avena et al., 1999), and the Stockholm Humic Model (4.10 ± 0.20 for HA, 3.50 ± 0.40 for FA; Gustafsson, 2001), but differ by about one log unit from those obtained by Milne et al. (2001) with the NICA-Donnan model (3.09 ± 0.51 for HA, 2.65 ± 0.43 for FA), and used to derive recommended generic values. To clarify this ambiguity, 10 high-quality titration data from Milne et al. (2001) were re-analyzed with the new predicted equilibrium constants. The data are described equally well with the previous and new sets of values ( R2 ⩾ 0.98), not necessarily because the NICA-Donnan model is overparametrized, but because titration lacks the sensitivity needed to quantify the full binding properties of humic substances. Correlations between NICA-Donnan parameters are discussed, but general progress is impeded by the unknown number of independent parameters that can be varied during regression of a model fit to titration data. The high consistency between predicted and experimental KH,COOH values, excluding those of Milne et al. (2001), gives faith in the proposed

  17. Semi-empirical atom-atom interaction models and X-ray crystallography

    International Nuclear Information System (INIS)

    Braam, A.W.M.

    1981-01-01

    Several aspects of semi-empirical energy calculations in crystallography are considered. Solid modifications of ethane have been studied using energy calculations and a fast summation technique has been evaluated. The structure of tetramethylpyrazine has been determined at room temperature and at 100K and accurate structure factors have been derived from measured Bragg intensities. Finally electrostatic properties have been deduced from X-ray structure factors. (C.F.)

  18. Influencing Factors on Earnings Management, Empirical Evidence from Listed German and Austrian Companies

    OpenAIRE

    Thomas Dilger; Sabine Graschitz

    2015-01-01

    Purpose – Since the 1960s earnings management has been a widely researched area and became presumably known by the current accounting scandals. This paper aims at empirically showing which factors affect earnings management. Design/methodology/approach – According to former research literature factors are derived, which might influence the companies' earnings management behavior. These factors are the applied accounting standard, the industry sector and the country of official quotation. ...

  19. Principles of Work Sample Testing. 1. A Non-Empirical Taxonomy of Test Uses

    Science.gov (United States)

    1979-04-01

    UNIVERSITY % ’ Bowling Green , Ohio 43403 e April 1979 Contract DAHC 19-77-C-0007 Cj Prepared for U.S. ARMY RESEARCH INSTITUTEfor the BEHAVIORAL and...inferring changes in enotionality, and GSR is said to be a measure of emotion . Much of psychological measurement is derived measurement, but it is...ARI TECHNICAL REPORT TR-79-A8 Principles of Work Sample Testingi I. A Non-Empirical Taxonomy of Test Uses b y Robert M. Guion BOWLING GREEN STATE

  20. Engineering strategy of yeast metabolism for higher alcohol production

    Directory of Open Access Journals (Sweden)

    Shimizu Hiroshi

    2011-09-01

    Full Text Available Abstract Background While Saccharomyces cerevisiae is a promising host for cost-effective biorefinary processes due to its tolerance to various stresses during fermentation, the metabolically engineered S. cerevisiae strains exhibited rather limited production of higher alcohols than that of Escherichia coli. Since the structure of the central metabolism of S. cerevisiae is distinct from that of E. coli, there might be a problem in the structure of the central metabolism of S. cerevisiae. In this study, the potential production of higher alcohols by S. cerevisiae is compared to that of E. coli by employing metabolic simulation techniques. Based on the simulation results, novel metabolic engineering strategies for improving higher alcohol production by S. cerevisiae were investigated by in silico modifications of the metabolic models of S. cerevisiae. Results The metabolic simulations confirmed that the high production of butanols and propanols by the metabolically engineered E. coli strains is derived from the flexible behavior of their central metabolism. Reducing this flexibility by gene deletion is an effective strategy to restrict the metabolic states for producing target alcohols. In contrast, the lower yield using S. cerevisiae originates from the structurally limited flexibility of its central metabolism in which gene deletions severely reduced cell growth. Conclusions The metabolic simulation demonstrated that the poor productivity of S. cerevisiae was improved by the introduction of E. coli genes to compensate the structural difference. This suggested that gene supplementation is a promising strategy for the metabolic engineering of S. cerevisiae to produce higher alcohols which should be the next challenge for the synthetic bioengineering of S. cerevisiae for the efficient production of higher alcohols.