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Sample records for clr8 directionality factors

  1. External Factors, Internal Factors and Self-Directed Learning Readiness

    Ramli, Nurjannah; Muljono, Pudji; Afendi, Farit M.

    2018-01-01

    There are many factors which affect the level of self-directed learning readiness. This study aims to investigate the relationship between external factors, internal factors and self-directed learning readiness. This study was carried out by using a census method for fourth year students of medical program of Tadulako University. Data were…

  2. Direct measurement of aerosol shape factors

    Zeller, W.

    1983-12-01

    The dynamic shape factor whereas the coagulation shape factor is an average over the total examined size range. The experiments have shown that the results of experiments with a certain aerosol system cannot be transferred to other aerosol systems without further consideration. The outer shape of particles of a certain size depends on the specific properties of the material as well as on the experimental conditions during the aerosol generation. For both aerosol systems examined the mean dynamic shape factor, averaged over the total examined size range, agrees roughly with the coagulation shape factor. (Description of aerosol centrifuge and of differential mobility analyzer). (orig./HP) [de

  3. 523 factors influencing direct costs dynamics of building projects

    Osondu

    2013-08-16

    Aug 16, 2013 ... effect of the direct cost variation factors (p-values between 0.365 and 0.930). Construction, resources, and performance factors are the most significant of the groups (MS range = 3.66 to 4.33), though no .... financial control on site ranked first and second ... order according to the consultants were, inflation.

  4. Directional reflectance factor distributions of a cotton row crop

    Kimes, D. S.; Newcomb, W. W.; Schutt, J. B.; Pinter, P. J., Jr.; Jackson, R. D.

    1984-01-01

    The directional reflectance factor distribution spanning the entire exitance hemisphere was measured for a cotton row crop (Gossypium barbadense L.) with 39 percent ground cover. Spectral directional radiances were taken in NOAA satellite 7 AVHRR bands 1 and 2 using a three-band radiometer with restricted 12 deg full angle field of view at half peak power points. Polar co-ordinate system plots of directional reflectance factor distributions and three-dimensional computer graphic plots of scattered flux were used to study the dynamics of the directional reflectance factor distribution as a function of spectral band, geometric structure of the scene, solar zenith and azimuth angles, and optical properties of the leaves and soil. The factor distribution of the incomplete row crops was highly polymodal relative to that for complete vegetation canopies. Besides the enhanced reflectance for the antisolar point, a reflectance minimum was observed towards the forwardscatter direction in the principle plane of the sun. Knowledge of the mechanics of the observed dynamics of the data may be used to provide rigorous validation for two- or three-dimensional radiative transfer models, and is important in interpreting aircraft and satellite data where the solar angle varies widely.

  5. A comparative analysis of foreign direct investment factors

    Miškinis, Algirdas; Juozėnaitė, Ilma

    2015-01-01

    The paper identifies factors affecting the foreign direct investment (FDI) inflow. It analyzes the determinants of FDI in recent empirical evidence as well as determines differences among FDI factors in Greece, Ireland, and the Netherlands. The determinants being examined are the gross domestic product (GDP) per capita, exchange rate, unit labor costs, trade openness as well as inflation. The analyzed period is 1974–2012. Data were collected from the World Bank and the Organization for Econom...

  6. Factors influencing individual variation in perceptual directional microphone benefit.

    Keidser, Gitte; Dillon, Harvey; Convery, Elizabeth; Mejia, Jorge

    2013-01-01

    Large variations in perceptual directional microphone benefit, which far exceed the variation expected from physical performance measures of directional microphones, have been reported in the literature. The cause for the individual variation has not been systematically investigated. To determine the factors that are responsible for the individual variation in reported perceptual directional benefit. A correlational study. Physical performance measures of the directional microphones obtained after they had been fitted to individuals, cognitive abilities of individuals, and measurement errors were related to perceptual directional benefit scores. Fifty-nine hearing-impaired adults with varied degrees of hearing loss participated in the study. All participants were bilaterally fitted with a Motion behind-the-ear device (500 M, 501 SX, or 501 P) from Siemens according to the National Acoustic Laboratories' non-linear prescription, version two (NAL-NL2). Using the Bamford-Kowal-Bench (BKB) sentences, the perceptual directional benefit was obtained as the difference in speech reception threshold measured in babble noise (SRTn) with the devices in directional (fixed hypercardioid) and in omnidirectional mode. The SRTn measurements were repeated three times with each microphone mode. Physical performance measures of the directional microphone included the angle of the microphone ports to loudspeaker axis, the frequency range dominated by amplified sound, the in situ signal-to-noise ratio (SNR), and the in situ three-dimensional, articulation-index weighted directivity index (3D AI-DI). The cognitive tests included auditory selective attention, speed of processing, and working memory. Intraparticipant variation on the repeated SRTn's and the interparticipant variation on the average SRTn were used to determine the effect of measurement error. A multiple regression analysis was used to determine the effect of other factors. Measurement errors explained 52% of the variation

  7. Form factors in (HI,HI') direct reactions

    Chu, Y.H.

    1981-01-01

    Using the semiclassical theory, the inelastic transition form factors are analyzed. For the first order form factors, we find that: (i) In the strong absorption limit, the Austern-Blair theory is a good approximation to the inelastic form factor--even in highly mismatched reactions. (ii) In weak to moderate absorption, the amplitude of the inelastic form factor oscillates due to overlapping potential resonances. The internal part of the form factor can be expressed in a simple form, which may easily be used to analyze heavy-ion inelastic scattering. (iii) In the presence of an isolated resonance, the inelastic form factor is enhanced greatly at the resonance due to multiple reflections inside the potential well. The second order form factors contain two terms, i.e. the one-step direct process (OSD) term and the two-step process (TS) term. It is found that: (i) In the strong absorption limit, OSD and TS form factors are equally important and interfere destructively near the grazing angular momentum. The Austern-Blair theory gives satisfactory results for well-matched reactions. The angular distributions of the mutual and double excitations are out of phase compared with that of the single excitation. (ii) For the weak absorption case, the internal part of the TS form factor is so enhanced that the OSD form factor can simply be neglected. The internal TS form factor can be parameterized in a form proportional to the internal-wave elastic Smatrix, where the angular distribution shows characteristically refractive phenomenon

  8. Foreign Direct Investment, Host Country Factors and Economic Growth

    Edna Maeyen Solomon

    2011-01-01

    This paper analyses how the levels of economic development, human capital, financial development and the qualities of the economic and political environments in host countries simultaneously affects the impact of aggregate inflows of Foreign Direct Investment (FDI) on economic growth. Multiple interaction terms are employed between inward FDI and each of the host country factors mentioned above. The System GMM estimator is applied to a panel of 111 countries from 1981 to 2005. The results sho...

  9. Insights into the Functions of a Prophage Recombination Directionality Factor

    Mireille Ansaldi

    2012-10-01

    Full Text Available Recombination directionality factors (RDFs, or excisionases, are essential players of prophage excisive recombination. Despite the essentially catalytic role of the integrase in both integrative and excisive recombination, RDFs are required to direct the reaction towards excision and to prevent re-integration of the prophage genome when entering a lytic cycle. KplE1, HK620 and numerous (prophages that integrate at the same site in enterobacteria genomes (such as the argW tRNA gene all share a highly conserved recombination module. This module comprises the attL and attR recombination sites and the RDF and integrase genes. The KplE1 RDF was named TorI after its initial identification as a negative regulator of the tor operon. However, it was characterized as an essential factor of excisive recombination. In this study, we designed an extensive random mutagenesis protocol of the torI gene and identified key residues involved in both functions of the TorI protein. We show that, in addition to TorI-TorR protein-protein interaction, TorI interacts in solution with the IntS integrase. Moreover, in vitro, TorR and IntS appear to compete for TorI binding. Finally, our mutagenesis results suggest that the C-terminal part of the TorI protein is dedicated to protein-protein interactions with both proteins TorR and IntS.

  10. Foreign Direct Investments Expansion – Essential Globalization Factor

    Cătălin Emilian HUIDUMAC PETRESCU

    2011-01-01

    Full Text Available We live in a time when the world economy is constantly changing. Foreign direct investments is one of the most dynamic part of the world economy and in a continuous globalization, those international financial flows determining the traders to know their defining elements and to adopt a specific management in the international affairs field. We are viewers of an unprecedented expansion of foreign direct investments, essential factor of the globalization development process. The paper analyzes the evolution of FDI so far, along with a brief illustration as the main trends of international financial flows for 2010 and 2011. In the context of economic globalization, it is absolutely necessary to clear out a study on the various economic activities, especially on the differences between countries. The analysis of these differences is particularly important as it helps improve and optimize the strategies adopted by foreign transnational companies. In the past 15 years, one observes that most companies in emerging countries, characterized by a great expansion, have adopted in the first phase of their existence, corporate strategies that gave them the opportunity to become global companies. According to surveys, after reaching the first goal, becoming a multinational or a transnational company, they have developed new business models beyond the classical principles and strategies. It is anticipated that in the coming decades, the strategies of emerging companies will be influenced by functional specialization, which, according to experts, influence the process of globalization. The analysis of strategies adopted by companies in emerging countries is absolutely necessary because the results cannot be overlooked. For example, until 2004, only five Asian companies were part of the top 100 transnational companies. The study was carried out by UNCTAD and the identification criterion was the size of foreign assets. In 2006, 14% of world total FDI came from

  11. Sequential induction of three recombination directionality factors directs assembly of tripartite integrative and conjugative elements.

    Timothy L Haskett

    2018-03-01

    Full Text Available Tripartite integrative and conjugative elements (ICE3 are a novel form of ICE that exist as three separate DNA regions integrated within the genomes of Mesorhizobium spp. Prior to conjugative transfer the three ICE3 regions of M. ciceri WSM1271 ICEMcSym1271 combine and excise to form a single circular element. This assembly requires three coordinated recombination events involving three site-specific recombinases IntS, IntG and IntM. Here, we demonstrate that three excisionases-or recombination directionality factors-RdfS, RdfG and RdfM are required for ICE3 excision. Transcriptome sequencing revealed that expression of ICE3 transfer and conjugation genes was induced by quorum sensing. Quorum sensing activated expression of rdfS, and in turn RdfS stimulated transcription of both rdfG and rdfM. Therefore, RdfS acts as a "master controller" of ICE3 assembly and excision. The dependence of all three excisive reactions on RdfS ensures that ICE3 excision occurs via a stepwise sequence of recombination events that avoids splitting the chromosome into a non-viable configuration. These discoveries expose a surprisingly simple control system guiding molecular assembly of these novel and complex mobile genetic elements and highlight the diverse and critical functions of excisionase proteins in control of horizontal gene transfer.

  12. Sequential induction of three recombination directionality factors directs assembly of tripartite integrative and conjugative elements.

    Haskett, Timothy L; Terpolilli, Jason J; Ramachandran, Vinoy K; Verdonk, Callum J; Poole, Phillip S; O'Hara, Graham W; Ramsay, Joshua P

    2018-03-01

    Tripartite integrative and conjugative elements (ICE3) are a novel form of ICE that exist as three separate DNA regions integrated within the genomes of Mesorhizobium spp. Prior to conjugative transfer the three ICE3 regions of M. ciceri WSM1271 ICEMcSym1271 combine and excise to form a single circular element. This assembly requires three coordinated recombination events involving three site-specific recombinases IntS, IntG and IntM. Here, we demonstrate that three excisionases-or recombination directionality factors-RdfS, RdfG and RdfM are required for ICE3 excision. Transcriptome sequencing revealed that expression of ICE3 transfer and conjugation genes was induced by quorum sensing. Quorum sensing activated expression of rdfS, and in turn RdfS stimulated transcription of both rdfG and rdfM. Therefore, RdfS acts as a "master controller" of ICE3 assembly and excision. The dependence of all three excisive reactions on RdfS ensures that ICE3 excision occurs via a stepwise sequence of recombination events that avoids splitting the chromosome into a non-viable configuration. These discoveries expose a surprisingly simple control system guiding molecular assembly of these novel and complex mobile genetic elements and highlight the diverse and critical functions of excisionase proteins in control of horizontal gene transfer.

  13. [Factors associated with self-directed learning among medical students].

    Spormann R, Camila; Pérez V, Cristhian; Fasce H, Eduardo; Ortega B, Javiera; Bastías V, Nancy; Bustamante D, Carolina; Ibáñez G, Pilar

    2015-03-01

    Self-directed learning is a skill that must be taught and evaluated in future physicians. To analyze the association between self-directed learning, self-esteem, self-efficacy, time management and academic commitment among medical students. The self-directed learning, Rosemberg self-esteem, general self- efficacy, time management and Utrecht work engagement scales were applied to 297 first year medical students. A multiple regression analysis showed a significant association between self-efficacy, time management and academic commitment with self-directed learning. Self-esteem and satisfaction with studies did not enter in the model. self-esteem, academic commitment and a good time management were associated with self-directed learning in these students.

  14. Directions of improvement of account of factoring operations

    V.I. Kuz

    2015-06-01

    Full Text Available With the height of competition on commodity markets the suppliers of commodities and services for bringing in of new and maintenance of present clients are forced to give certain privileges to them, including postponement or arranging on the installment system of payment. In these terms one of perspective instruments of financing of enterprises of the real sector is factoring. Factoring plays an important role in a market economy. He provides to the enterprises and organizations of height of volume of turnover means and acceleration of circulating of capital; assists more rapid redemption a debtor and creditor debts and as a result, height of rates of production and circulating of commodities, works or services; assists expansion of production. How a process of development of factoring operations is intensive enough, a necessity grows for the detailed consideration of methodology of record-keeping of factoring operations. Methodology of record-keeping of factoring operations offered in the article for a supplier, at a factor and debtor, on the basis of operating card of accounts can be used in practice of commercial organizations-participants of agreement of factoring.

  15. Comparison of the Economic Factors that Influence Foreign Direct ...

    The study determined the compound growth rate of FDI and the factors ... India attracted more FDI than Nigeria due to its large GDP, higher real interest rate and trade openness; it is suggested that a further depreciated currency would ...

  16. Soluble Factors on Stage to Direct Mesenchymal Stem Cells Fate

    Cristina Sobacchi

    2017-05-01

    Full Text Available Mesenchymal stem cells (MSCs are multipotent stromal cells that are identified by in vitro plastic adherence, colony-forming capacity, expression of a panel of surface molecules, and ability to differentiate at least toward osteogenic, adipogenic, and chondrogenic lineages. They also produce trophic factors with immunomodulatory, proangiogenic, and antiapoptotic functions influencing the behavior of neighboring cells. On the other hand, a reciprocal regulation takes place; in fact, MSCs can be isolated from several tissues, and depending on the original microenvironment and the range of stimuli received from there, they can display differences in their essential characteristics. Here, we focus mainly on the bone tissue and how soluble factors, such as growth factors, cytokines, and hormones, present in this microenvironment can orchestrate bone marrow-derived MSCs fate. We also briefly describe the alteration of MSCs behavior in pathological settings such as hematological cancer, bone metastasis, and bone marrow failure syndromes. Overall, the possibility to modulate MSCs plasticity makes them an attractive tool for diverse applications of tissue regeneration in cell therapy. Therefore, the comprehensive understanding of the microenvironment characteristics and components better suited to obtain a specific MSCs response can be extremely useful for clinical use.

  17. Direct foreign investment: a migration push-factor?

    Sassen-koob, S

    1984-01-01

    Policymakers and analysts now recognize that US military activities abroad contribute to the creation of refugee flows into the US. Previously, immigration into the US was viewed as a result of inept and failed domestic policies in the countries of origin. Results show that recent immigrants to the US come from countries with neither the poorest nor the largest population growth rate in the less developed world. However, the sending countries received US direct foreign investment (DFI) in the 1970s, particularly labor intensive investment in export manufacturing. Significant levels and concentrations of DFI promote emigration through: 1) the incorporation of new segments of the population into wage labor and the associated disruption of traditional work structures, 2) the feminization of the new industrial work force and its impact on the work opportunities of men, and 3) the consolidation of objective and ideological links with the highly industrialized countries where most foreign capital originates. The data suggest an examination of the causes of emigration on a much more specific level than that of underdevelopment, poverty, and population growth. These facts carry immediate policy implications for US immigration organizations: 1) if US firms in export processing zones recruited workers from the pool of unemployed--mostly prime-age males--rather than expanding the labor supply by recruiting young women, thereby disrupting unwaged work structures, and 2) if these firms would desist from having high turnover rates among workers, then the migration impact of this type of development would be minimized.

  18. First Steps in the Direction of Synthetic, Allosteric, Direct Inhibitors of Thrombin and Factor Xa

    Verghese, Jenson; Liang, Aiye; Sidhu, Preet Pal Singh; Hindle, Michael; Zhou, Qibing; Desai, Umesh R.

    2009-01-01

    Designing non-saccharide functional mimics of heparin is a major challenge. In this work, a library of small, aromatic molecules based on the sulfated DHP scaffold was synthesized and screened against thrombin and factor Xa. The results reveal that i) selected monomeric benzofuran derivatives inhibit the two enzymes, albeit weakly; ii) the two enzymes recognize different structural features in the benzofurans studied suggesting significant selectivity of recognition; and iii) the mechanism of...

  19. The factor structure of the self-directed learning readiness scale | de ...

    The factor structure of the Self-Directed Learning Readiness Scale (SDLRS) was investigated for Afrikaans and English-speaking first-year university students. Five factors were extracted and rotated to oblique simple structure for both groups. Four of the five factors were satisfactorily replicated. The fifth factor appeared to ...

  20. First steps in the direction of synthetic, allosteric, direct inhibitors of thrombin and factor Xa.

    Verghese, Jenson; Liang, Aiye; Sidhu, Preet Pal Singh; Hindle, Michael; Zhou, Qibing; Desai, Umesh R

    2009-08-01

    Designing non-saccharide functional mimics of heparin is a major challenge. In this work, a library of small, aromatic molecules based on the sulfated DHP scaffold was synthesized and screened against thrombin and factor Xa. The results reveal that (i) selected monomeric benzofuran derivatives inhibit the two enzymes, albeit weakly; (ii) the two enzymes recognize different structural features in the benzofurans studied suggesting significant selectivity of recognition; and (iii) the mechanism of inhibition is allosteric. The molecules represent the first allosteric small molecule inhibitors of the two enzymes.

  1. First Steps in the Direction of Synthetic, Allosteric, Direct Inhibitors of Thrombin and Factor Xa

    Verghese, Jenson; Liang, Aiye; Sidhu, Preet Pal Singh; Hindle, Michael; Zhou, Qibing; Desai, Umesh R.

    2009-01-01

    Designing non-saccharide functional mimics of heparin is a major challenge. In this work, a library of small, aromatic molecules based on the sulfated DHP scaffold was synthesized and screened against thrombin and factor Xa. The results reveal that i) selected monomeric benzofuran derivatives inhibit the two enzymes, albeit weakly; ii) the two enzymes recognize different structural features in the benzofurans studied suggesting significant selectivity of recognition; and iii) the mechanism of inhibition is allosteric. The molecules represent the first allosteric small molecule inhibitors of the two enzymes. PMID:19540113

  2. Human projected area factors for detailed direct and diffuse solar radiation analysis

    Kubaha, K.; Fiala, D.; Toftum, Jørn

    2004-01-01

    Projected area factors for individual segments of the standing and sedentary human body were modelled for both direct and diffuse solar radiation using detailed 3D geometry and radiation models. The local projected area factors with respect to direct short-wave radiation are a function of the solar...

  3. Discovery of non-directional and directional pioneer transcription factors by modeling DNase profile magnitude and shape

    Lewis, Sophia; Barkal, Amira A; van Hoff, John Peter; Karun, Vivek; Jaakkola, Tommi; Gifford, David K

    2014-01-01

    Here we describe Protein Interaction Quantitation (PIQ), a computational method that models the magnitude and shape of genome-wide DNase profiles to facilitate the identification of transcription factor (TF) binding sites. Through the use of machine learning techniques, PIQ identified binding sites for >700 TFs from one DNase-seq experiment with accuracy comparable to ChIP-seq for motif-associated TFs (median AUC=0.93 across 303 TFs). We applied PIQ to analyze DNase-seq data from mouse embryonic stem cells differentiating into pre-pancreatic and intestinal endoderm. We identified (n=120) and experimentally validated eight ‘pioneer’ TF families that dynamically open chromatin, enabling other TFs to bind to adjacent DNA. Four pioneer TF families only open chromatin in one direction from their motifs. Furthermore, we identified a class of ‘settler’ TFs whose genomic binding is principally governed by proximity to open chromatin. Our results support a model of hierarchical TF binding in which directional and non-directional pioneer activity shapes the chromatin landscape for population by settler TFs. PMID:24441470

  4. Defining the Minimal Factors Required for Erythropoiesis through Direct Lineage Conversion

    Sandra Capellera-Garcia

    2016-06-01

    Full Text Available Erythroid cell commitment and differentiation proceed through activation of a lineage-restricted transcriptional network orchestrated by a group of well characterized genes. However, the minimal set of factors necessary for instructing red blood cell (RBC development remains undefined. We employed a screen for transcription factors allowing direct lineage reprograming from fibroblasts to induced erythroid progenitors/precursors (iEPs. We show that Gata1, Tal1, Lmo2, and c-Myc (GTLM can rapidly convert murine and human fibroblasts directly to iEPs. The transcriptional signature of murine iEPs resembled mainly that of primitive erythroid progenitors in the yolk sac, whereas addition of Klf1 or Myb to the GTLM cocktail resulted in iEPs with a more adult-type globin expression pattern. Our results demonstrate that direct lineage conversion is a suitable platform for defining and studying the core factors inducing the different waves of erythroid development.

  5. The Measure of Human Error: Direct and Indirect Performance Shaping Factors

    Ronald L. Boring; Candice D. Griffith; Jeffrey C. Joe

    2007-08-01

    The goal of performance shaping factors (PSFs) is to provide measures to account for human performance. PSFs fall into two categories—direct and indirect measures of human performance. While some PSFs such as “time to complete a task” are directly measurable, other PSFs, such as “fitness for duty,” can only be measured indirectly through other measures and PSFs, such as through fatigue measures. This paper explores the role of direct and indirect measures in human reliability analysis (HRA) and the implications that measurement theory has on analyses and applications using PSFs. The paper concludes with suggestions for maximizing the reliability and validity of PSFs.

  6. Factor structure of suggestibility revisited: new evidence for direct and indirect suggestibility

    Romuald Polczyk

    2016-05-01

    Full Text Available Background Yielding to suggestions can be viewed as a relatively stable individual trait, called suggestibility. It has been long proposed that there are two kinds of suggestible influence, and two kinds of suggestibility corresponding to them: direct and indirect. Direct suggestion involves overt unhidden influence, while indirect suggestion concerns influence that is hidden, and the participant does not know that the suggestibility is being measured. So far however, empirical evidence for the existence of the two factors has been scarce. In the present study, more sophisticated and reliable tools for measuring suggestibility were applied than in the previous research, in the hope that better measurement would reveal the factor structure of suggestibility. Two tests of direct suggestibility were used: the Harvard Group Scale of Hypnotic Susceptibility, Form A, measuring hypnotic susceptibility, and the Barber Suggestibility Scale, measuring non-hypnotic direct imaginative suggestibility. Three tests served to measure indirect suggestibility: the Sensory Suggestibility Scale, measuring indirect suggestibility relating to perception; the Gudjonsson Suggestibility Scale, measuring the tendency to yield to suggestive questions and changing answers after negative feedback; and the Emotional Dialogs Tests, measuring the tendency to perceive nonexistent aggression. Participants and procedure In sum, 115 participants were tested, 69 women, 49 men, mean age 22.20 years, SD = 2.20. Participants were tested in two sessions, lasting for a total of four hours. Results Confirmatory factor analyses confirmed the existence of two uncorrelated factors of suggestibility: direct and indirect. Conclusions Suggestibility may indeed involve two factors, direct and indirect, and failure to discover them in previous research may be due to methodological problems.

  7. Risk versus direct protective factors and youth violence: Seattle social development project.

    Herrenkohl, Todd I; Lee, Jungeun; Hawkins, J David

    2012-08-01

    Numerous studies have examined predictors of youth violence associated with the individual child, the family, school, and the surrounding neighborhood or community. However, few studies have examined predictors using a systematic approach to differentiate and compare risk and direct protective factors. This study examines risk and protective factors associated with youth violence in an ongoing longitudinal panel study of 808 students from 18 Seattle public elementary schools followed since 1985 when they were in 5th grade. Predictors span the individual, family, school, peer, and neighborhood domains. Data were collected annually, beginning in 1985, to age 16 years, and then again at age 18 years. This paper provides findings of analyses in which continuous predictor variables, measured at ages 10-12 years, were trichotomized to reflect a risk end of the variable, a direct protective end, and a middle category of scores. Youth violence was measured at ages 13-14 years and 15-18 years. Bivariate analyses of risk and direct protective factors identified the following predictors of violence at ages 13-14 years and 15-18 years. Risk for violence was increased by earlier antisocial behavior (e.g., prior violence, truancy, nonviolent delinquency), attention problems, family conflict, low school commitment, and living in a neighborhood where young people were in trouble. Direct protective factors at ages 10-12 years include a low level of attention problems, low risk-taking, refusal skills, school attachment, and low access and exposure to marijuana at ages 10-12 years. Multivariate regressions showed neighborhood risk factors to be among the most salient and consistent predictors of violence after accounting for all other variables in the tested models. Relatively few direct protective factors were identified in these statistical tests, suggesting the need for further review and possible refinement of the measures and methods that were applied. Implications provide

  8. Lifestyle factors, direct and indirect costs for a Brazilian airline company

    Rabacow, Fabiana Maluf; Luiz, Olinda do Carmo; Malik, Ana Maria; Burdorf, Alex

    2014-01-01

    OBJECTIVE To analyze lifestyle risk factors related to direct healthcare costs and the indirect costs due to sick leave among workers of an airline company in Brazil. METHODS In this longitudinal 12-month study of 2,201 employees of a Brazilian airline company, the costs of sick leave and healthcare were the primary outcomes of interest. Information on the independent variables, such as gender, age, educational level, type of work, stress, and lifestyle-related factors (body mass index, physical activity, and smoking), was collected using a questionnaire on enrolment in the study. Data on sick leave days were available from the company register, and data on healthcare costs were obtained from insurance records. Multivariate linear regression analysis was used to investigate the association between direct and indirect healthcare costs with sociodemographic, work, and lifestyle-related factors. RESULTS Over the 12-month study period, the average direct healthcare expenditure per worker was US$505.00 and the average indirect cost because of sick leave was US$249.00 per worker. Direct costs were more than twice the indirect costs and both were higher in women. Body mass index was a determinant of direct costs and smoking was a determinant of indirect costs. CONCLUSIONS Obesity and smoking among workers in a Brazilian airline company were associated with increased health costs. Therefore, promoting a healthy diet, physical activity, and anti-tobacco campaigns are important targets for health promotion in this study population. PMID:26039398

  9. Risk factors for human-directed canine aggression in a referral level clinical population.

    Lord, M; Casey, R A; Loftus, B A; Blackwell, E J

    2017-07-07

    Risk factors for human-directed aggression were investigated using retrospective analysis of data from a referral-level clinical behaviour population in the UK. A sample of 200 cases involving human-directed canine aggression and 200 control cases involving no instance of human-directed aggression were selected at random from a population of 746 cases. The final model suggested that clinical cases with human-directed aggression were significantly younger than those presenting with other undesired behaviours (P=0.008) and that male dogs were 1.4 times more likely to be aggressive towards human beings than female dogs (P=0.019). Dogs were 1.7 times more likely to be aggressive towards people if they had attended more than five puppy classes than if they had never attended puppy class (P=0.015) and that dogs were 2.8 times more likely to be aggressive towards human beings if there was another dog between 0 months and 24 months of age in the home (P=0.004). These factors only account for 7 per cent to 10 per cent of the variance between the human-directed aggression population and the control population, but factors such as attendance at puppy classes and numbers of dogs in the household suggest the need for longitudinal studies to investigate temporal relationships.

  10. Lifestyle factors, direct and indirect costs for a Brazilian airline company.

    Rabacow, Fabiana Maluf; Luiz, Olinda do Carmo; Malik, Ana Maria; Burdorf, Alex

    2014-12-01

    OBJECTIVE To analyze lifestyle risk factors related to direct healthcare costs and the indirect costs due to sick leave among workers of an airline company in Brazil. METHODS In this longitudinal 12-month study of 2,201 employees of a Brazilian airline company, the costs of sick leave and healthcare were the primary outcomes of interest. Information on the independent variables, such as gender, age, educational level, type of work, stress, and lifestyle-related factors (body mass index, physical activity, and smoking), was collected using a questionnaire on enrolment in the study. Data on sick leave days were available from the company register, and data on healthcare costs were obtained from insurance records. Multivariate linear regression analysis was used to investigate the association between direct and indirect healthcare costs with sociodemographic, work, and lifestyle-related factors. RESULTS Over the 12-month study period, the average direct healthcare expenditure per worker was US$505.00 and the average indirect cost because of sick leave was US$249.00 per worker. Direct costs were more than twice the indirect costs and both were higher in women. Body mass index was a determinant of direct costs and smoking was a determinant of indirect costs. CONCLUSIONS Obesity and smoking among workers in a Brazilian airline company were associated with increased health costs. Therefore, promoting a healthy diet, physical activity, and anti-tobacco campaigns are important targets for health promotion in this study population.

  11. Lifestyle factors, direct and indirect costs for a Brazilian airline company

    Fabiana Maluf Rabacow

    2014-12-01

    Full Text Available OBJECTIVE To analyze lifestyle risk factors related to direct healthcare costs and the indirect costs due to sick leave among workers of an airline company in Brazil. METHODS In this longitudinal 12-month study of 2,201 employees of a Brazilian airline company, the costs of sick leave and healthcare were the primary outcomes of interest. Information on the independent variables, such as gender, age, educational level, type of work, stress, and lifestyle-related factors (body mass index, physical activity, and smoking, was collected using a questionnaire on enrolment in the study. Data on sick leave days were available from the company register, and data on healthcare costs were obtained from insurance records. Multivariate linear regression analysis was used to investigate the association between direct and indirect healthcare costs with sociodemographic, work, and lifestyle-related factors. RESULTS Over the 12-month study period, the average direct healthcare expenditure per worker was US$505.00 and the average indirect cost because of sick leave was US$249.00 per worker. Direct costs were more than twice the indirect costs and both were higher in women. Body mass index was a determinant of direct costs and smoking was a determinant of indirect costs. CONCLUSIONS Obesity and smoking among workers in a Brazilian airline company were associated with increased health costs. Therefore, promoting a healthy diet, physical activity, and anti-tobacco campaigns are important targets for health promotion in this study population.

  12. Determining eyeball surface area directly exposed to the effects of external factors.

    Juliszewski, Tadeusz; Kadłuczka, Filip; Kiełbasa, Paweł

    2016-01-01

    This article discusses determining the surface area of eyeballs of men and women exposed to the direct effects of external factors in the working environment. For one eye, the mean surface is 172-182 mm(2). The determined surface area can be used in formulas for calculating the exposure of eyeballs to harmful chemical substances in workplace air.

  13. High Dietary Fructose: Direct or Indirect Dangerous Factors Disturbing Tissue and Organ Functions.

    Zhang, Dong-Mei; Jiao, Rui-Qing; Kong, Ling-Dong

    2017-03-29

    High dietary fructose is a major contributor to insulin resistance and metabolic syndrome, disturbing tissue and organ functions. Fructose is mainly absorbed into systemic circulation by glucose transporter 2 (GLUT2) and GLUT5, and metabolized in liver to produce glucose, lactate, triglyceride (TG), free fatty acid (FFA), uric acid (UA) and methylglyoxal (MG). Its extrahepatic absorption and metabolism also take place. High levels of these metabolites are the direct dangerous factors. During fructose metabolism, ATP depletion occurs and induces oxidative stress and inflammatory response, disturbing functions of local tissues and organs to overproduce inflammatory cytokine, adiponectin, leptin and endotoxin, which act as indirect dangerous factors. Fructose and its metabolites directly and/or indirectly cause oxidative stress, chronic inflammation, endothelial dysfunction, autophagy and increased intestinal permeability, and then further aggravate the metabolic syndrome with tissue and organ dysfunctions. Therefore, this review addresses fructose-induced metabolic syndrome, and the disturbance effects of direct and/or indirect dangerous factors on the functions of liver, adipose, pancreas islet, skeletal muscle, kidney, heart, brain and small intestine. It is important to find the potential correlations between direct and/or indirect risk factors and healthy problems under excess dietary fructose consumption.

  14. High Dietary Fructose: Direct or Indirect Dangerous Factors Disturbing Tissue and Organ Functions

    Dong-Mei Zhang

    2017-03-01

    Full Text Available High dietary fructose is a major contributor to insulin resistance and metabolic syndrome, disturbing tissue and organ functions. Fructose is mainly absorbed into systemic circulation by glucose transporter 2 (GLUT2 and GLUT5, and metabolized in liver to produce glucose, lactate, triglyceride (TG, free fatty acid (FFA, uric acid (UA and methylglyoxal (MG. Its extrahepatic absorption and metabolism also take place. High levels of these metabolites are the direct dangerous factors. During fructose metabolism, ATP depletion occurs and induces oxidative stress and inflammatory response, disturbing functions of local tissues and organs to overproduce inflammatory cytokine, adiponectin, leptin and endotoxin, which act as indirect dangerous factors. Fructose and its metabolites directly and/or indirectly cause oxidative stress, chronic inflammation, endothelial dysfunction, autophagy and increased intestinal permeability, and then further aggravate the metabolic syndrome with tissue and organ dysfunctions. Therefore, this review addresses fructose-induced metabolic syndrome, and the disturbance effects of direct and/or indirect dangerous factors on the functions of liver, adipose, pancreas islet, skeletal muscle, kidney, heart, brain and small intestine. It is important to find the potential correlations between direct and/or indirect risk factors and healthy problems under excess dietary fructose consumption.

  15. Lifestyle factors, direct and indirect costs for a Brazilian airline company

    F.M. Rabacow (Fabiana Maluf); O. Do Carmo Luiz (Olinda); A.M. Malik (Ana Maria); A. Burdorf (Alex)

    2014-01-01

    textabstractObjective: To analyze lifestyle risk factors related to direct healthcare costs and the indirect costs due to sick leave among workers of an airline company in Brazil. Methods: In this longitudinal 12-month study of 2,201 employees of a Brazilian airline company, the costs of sick leave

  16. Practical Consideration Factors to Design Array Configuration of Direction Finding System for Airborne Signal Intelligence

    Jong-Hwan Lee

    2018-01-01

    Full Text Available Airborne signal intelligence (SIGINT systems must be capable of locating radio signal sources. Direction finding (DF to support this capability is an important factor. There are some practical considerations to be taken when designing the array configuration of a DF system for airborne SIGINT systems. This paper summarizes the practical factors when designing the array configuration of the DF system for airborne SIGINT. In particular, it focuses on four areas: antenna consideration factors when installing the DF system for airborne SIGINT from a practical point of view, array configuration methods for airborne communications intelligence and electronic intelligence, and a numerical analysis to select the optimum antenna position for airborne SIGINT.

  17. Characteristics of the socio-geographical factors in the Drina-Velika Morava strategic direction zone

    Dejan Radivoj Inđić

    2013-06-01

    Full Text Available This paper presents the assessment of the operational – geographic features of the Drina–Velikamorava strategic direction. Due to the scope of the article, a variant of the assessment of the strategic direction is presented through its socio–geographic factors, while the mathematical–geographical and physical–geographic factors, as well as the operating lines of action are not discussed. Within the socio–geographic factors, the characteristics of the population, economy and communication networks are considered. The geographic area of the direction is nationally compact and provides war mobilization of units with no particular strain. The transportation network is not fully developed which makes combat operations difficult to attackers and facilitates them for the deffenders.. There are significant technical and technological potentials in the direction of the zone, but they are not evenly distributed. After the consideration of the complex socio – geographical factors, it is  concluded that the shown strategic direction enables, without any special restrictions, a successful execution of combat operations in the long run.   Introduction The Drina–Velikamorava strategic direction of action consists of two operational lines: Semberija–Šumadija and Glasinac–Zapadnamorava. This paper presents a variant of a complex evaluation of the socio–geographic factors in the area of strategic direction. Within the socio–geographic factors in the strategic direction, the characteristics of the population, economy and communication networks are discussed.   Characteristics of the population and settlements In the geographic strategic direction, there is about 30% of the population of the Republic of Serbia. The highest population density is in major cities (Belgrade, Novi Sad, Šabac, Čačak, etc.. The space is nationally compact, and over 95% of the population are Serbs. In terms of building methods,there are the following types of

  18. Effects on coagulation factor production following primary hepatomitogen-induced direct hyperplasia.

    Tatsumi, Kohei; Ohashi, Kazuo; Taminishi, Sanae; Takagi, Soichi; Utoh, Rie; Yoshioka, Akira; Shima, Midori; Okano, Teruo

    2009-11-14

    To investigate the molecular mechanisms involved in coagulation factor expression and/or function during direct hyperplasia (DH)-mediated liver regeneration. Direct hyperplasia-mediated liver regeneration was induced in female C57BL/6 mice by administering 1,4-bis[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP), a representative hepatomitogen. Mice were weighed and sacrificed at various time points [Day 0 (D0: prior to injection), 3 h, D1, D2, D3, and D10] after TCPOBOP administration to obtain liver and blood samples. Using the RNA samples extracted from the liver, a comprehensive analysis was performed on the hepatic gene expression profiling of coagulation-related factors by real-time RT-PCR (fibrinogen, prothrombin, factors V, VII, VIII, IX, X, XI, XII, XIIIbeta, plasminogen, antithrombin, protein C, protein S, ADAMTS13, and VWF). The corresponding plasma levels of coagulation factors (fibrinogen, prothrombin, factors V, VII, VIII, IX, X, XI, XII, XIII, and VWF) were also analyzed and compared with their mRNA levels. Gavage administration of TCPOBOP (3 mg/kg body weight) resulted in a marked and gradual increase in the weight of the mouse livers relative to the total body weight to 220% by D10 relative to the D0 (control) ratios. At the peak of liver regeneration (D1 and D2), the gene expression levels for most of the coagulation-related factors (fibrinogen, prothrombin, factors V, VII, VIII, IX, XI, XII, XIIIbeta, plasminogen, antithrombin, protein C, ADAMTS13, VWF) were found to be down-regulated in a time-dependent manner, and gradually recovered by D10 to the basal levels. Only mRNA levels of factor X and protein S failed to show any decrease during the regenerative phase. As for the plasma levels, 5 clotting factors (prothrombin, factors VIII, IX, XI, and XII) demonstrated a significant decrease (Pfactors, factor IX and factor XI showed the most dramatic decline in their activities by about 50% at D2 compared to the basal levels, and these reductions in

  19. [Self-directed learning in nursing students with different background factors].

    Kao, Yu-Hsiu; Yu, Chu-Wei; Kuo, Shu-Yi; Kuang, I-Hsiu

    2013-08-01

    Fostering self-directed learning skills in nursing students may provide a foundation for improving the specialty knowledge of these nurses. This study examines the current status of nursing student self-directed learning behavior and explores how different background factors impact self-directed learning. This research design used a cross-sectional survey and convenience sampling. A total of 550 questionnaires were distributed to participants in enrolled in nursing programs at a 2-year nursing program at an institute of technology in northern Taiwan and a 4-year nursing program at an institute of technology in southern Taiwan. A convenience sampling was used to collect data, with 537 valid questionnaires used in data analysis. Results indicated that the self-directed learning and self-management of nursing students between 20-21 years old was significantly higher than those of students between 18-19 years old. Self-directed learning, desire of learning and self-control in 2-year nursing students were significantly higher than in 4-year and extension education department nursing student participants. Two-year nursing students had the highest self-management scores, followed by extension education department participants and 4-year nursing students. Finally, participants who associated highly with the nursing profession earned the highest self-directed total score, followed by those participants who associated generally and those who associated mildly. The results recommend that teachers at nursing institutes help students develop self-directed learning. Results also recommend teachers increase their students' association with the nursing specialty through understanding the impact of different background factors on self-directed learning.

  20. Direct observation of a single proton in a Penning trap. Towards a direct measurement of the proton g-factor

    Kreim, Susanne Waltraud

    2009-08-25

    This PhD thesis presents experiments performed on a single proton stored in a Penning trap. The eigenmotion of an isolated, free proton could be detected electronically via a coupling to a resonance circuit. This represents a non-destructive measurement, i.e. the particle is not lost during the measurement. The free cyclotron frequency emerging from the measured eigenfrequencies is one of the two frequencies required for the determination of the magnetic moment. This enables a direct determination of the g-factor contrary to already existing works. Design, developing, and commissioning of the experimental setup have been accomplished within the scope of this work leading to a measuring accuracy of 10{sup -7}. The technical challenges for the determination of the second frequency (the Larmor frequency) arising from the smallness of the magnetic moment were mastered. Since the spin state required for this measurement is an internal degree of freedom, it can only be accessed through a coupling of the magnetic moment to the eigenmotion. A novel, hybrid penning trap is presented in this work, which imprints the spin information onto the eigenmotion, thus, realizing a quantum jump spectrometer. Therewith, the frequency shift of the two spin states resulting from the magnetic coupling reaches for the first time an electronically detectable range. (orig.)

  1. Direct observation of a single proton in a Penning trap. Towards a direct measurement of the proton g-factor

    Kreim, Susanne Waltraud

    2009-01-01

    This PhD thesis presents experiments performed on a single proton stored in a Penning trap. The eigenmotion of an isolated, free proton could be detected electronically via a coupling to a resonance circuit. This represents a non-destructive measurement, i.e. the particle is not lost during the measurement. The free cyclotron frequency emerging from the measured eigenfrequencies is one of the two frequencies required for the determination of the magnetic moment. This enables a direct determination of the g-factor contrary to already existing works. Design, developing, and commissioning of the experimental setup have been accomplished within the scope of this work leading to a measuring accuracy of 10 -7 . The technical challenges for the determination of the second frequency (the Larmor frequency) arising from the smallness of the magnetic moment were mastered. Since the spin state required for this measurement is an internal degree of freedom, it can only be accessed through a coupling of the magnetic moment to the eigenmotion. A novel, hybrid penning trap is presented in this work, which imprints the spin information onto the eigenmotion, thus, realizing a quantum jump spectrometer. Therewith, the frequency shift of the two spin states resulting from the magnetic coupling reaches for the first time an electronically detectable range. (orig.)

  2. Direct conversion of human fibroblasts into functional osteoblasts by defined factors.

    Yamamoto, Kenta; Kishida, Tsunao; Sato, Yoshiki; Nishioka, Keisuke; Ejima, Akika; Fujiwara, Hiroyoshi; Kubo, Toshikazu; Yamamoto, Toshiro; Kanamura, Narisato; Mazda, Osam

    2015-05-12

    Osteoblasts produce calcified bone matrix and contribute to bone formation and remodeling. In this study, we established a procedure to directly convert human fibroblasts into osteoblasts by transducing some defined factors and culturing in osteogenic medium. Osteoblast-specific transcription factors, Runt-related transcription factor 2 (Runx2), and Osterix, in combination with Octamer-binding transcription factor 3/4 (Oct4) and L-Myc (RXOL) transduction, converted ∼ 80% of the fibroblasts into osteocalcin-producing cells. The directly converted osteoblasts (dOBs) induced by RXOL displayed a similar gene expression profile as normal human osteoblasts and contributed to bone repair after transplantation into immunodeficient mice at artificial bone defect lesions. The dOBs expressed endogenous Runx2 and Osterix, and did not require continuous expression of the exogenous genes to maintain their phenotype. Another combination, Oct4 plus L-Myc (OL), also induced fibroblasts to produce bone matrix, but the OL-transduced cells did not express Osterix and exhibited a more distant gene expression profile to osteoblasts compared with RXOL-transduced cells. These findings strongly suggest successful direct reprogramming of fibroblasts into functional osteoblasts by RXOL, a technology that may provide bone regeneration therapy against bone disorders.

  3. Factor structure of overall autobiographical memory usage: the directive, self and social functions revisited.

    Rasmussen, Anne S; Habermas, Tilmann

    2011-08-01

    According to theory, autobiographical memory serves three broad functions of overall usage: directive, self, and social. However, there is evidence to suggest that the tripartite model may be better conceptualised in terms of a four-factor model with two social functions. In the present study we examined the two models in Danish and German samples, using the Thinking About Life Experiences Questionnaire (TALE; Bluck, Alea, Habermas, & Rubin, 2005), which measures the overall usage of the three functions generalised across concrete memories. Confirmatory factor analysis supported the four-factor model and rejected the theoretical three-factor model in both samples. The results are discussed in relation to cultural differences in overall autobiographical memory usage as well as sharing versus non-sharing aspects of social remembering.

  4. Environmental determinants of cardiovascular diseases risk factors: a qualitative directed content analysis.

    Sabzmakan, Leila; Mohammadi, Eesa; Morowatisharifabad, Mohammad Ali; Afaghi, Ahmad; Naseri, Mohammad Hassan; Mirzaei, Masoud

    2014-05-01

    Cardiovascular diseases (CVDs) are the number one cause of death in the world. In most analyses of health problems, environment plays a significant and modifiable role in causing the problem either directly or indirectly through behavior. This study aims to understand the patients and healthcare providers' experiences about the environmental determinants of CVD risk factors based on the Precede Model. This qualitative study conducted over six months in 2012 at Diabetes Units of Health Centers associated with Alborz University of Medical Sciences and Health Services which is located in Karaj, Iran. The data were collected based on individual semi-structured interviews with 50 patients and 12 healthcare providers. Data analysis was performed simultaneous with data collection using the content analysis directed method. Lack of behaviors like stress control, healthy eating and physical activity were the roots of the risk factors for CVD. The environmental factor is one of the barriers for conducting these behaviors. The environmental barriers included of structural environment including "availability and accessibility of health resources", "new skills", and "law and policies" which are located in enabling category and social environment including "social support", "motivation to comply" and "consequences of behavior" which are located in reinforcing category. The most barriers to performing health behaviors were often structural. The environmental factors were barriers for doing healthy behaviors. These factors need to be considered to design health promotion interventions. Policymakers should not only focus on patients' education but also should provide specific facilities to enhance economic, social and cultural status.

  5. Factors affecting long-term-care residents' decision-making processes as they formulate advance directives.

    Lambert, Heather C; McColl, Mary Ann; Gilbert, Julie; Wong, Jiahui; Murray, Gale; Shortt, Samuel E D

    2005-10-01

    The purpose of this study was to describe factors contributing to the decision-making processes of elderly persons as they formulate advance directives in long-term care. This study was qualitative, based on grounded theory. Recruitment was purposive and continued until saturation was reached. Nine residents of a long-term-care facility were interviewed by use of a semistructured format. Open and axial coding of interview transcripts were carried out and the factors contributing to the decision process were defined. Elders based their decisions primarily on information gathered from personal experiences with death and illness. They obtained very little information from professionals or the media. Major factors considered by elders as they weighed information included spiritual, emotional, and social considerations. The factors considered during the decision-making process were oriented more toward the individual's experiences and less on contributions from objective sources than anticipated. Decision making for advance directives is a highly personalized process. The approach of health professionals when assisting with end-of-life decision making should be planned with these contributing factors in mind, so that the services offered to the individuals in this population best meet their needs.

  6. Calculation of the Cholesky factor directly from the stiffness matrix of the structural element

    Prates, C.L.M.; Soriano, H.L.

    1978-01-01

    The analysis of the structures of nuclear power plants requires the evaluation of the internal forces. This is attained by the solution of a system of equations. This solution takes most of the computing time and memory. One of the ways it can be achieved is based on the Cholesky factor. The structural matrix of the coeficients is transformed into an upper triangular matrix by the Cholesky decomposition. Cholesky factor can be obtained directly from the stiffness matrix of the structural element. The result can thus be obtained in a more precise and quick way. (Author)

  7. Factors affecting the development of sprays produced by multihole injectors for direct-injection engine applications

    Van Romunde, R. Z.

    2011-01-01

    The spray form development from a state of the art multi-hole injector for gasoline direct injection internal combustion engines is examined to attempt to determine the thermo-fluid dynamics affecting the spray development. The current state of knowledge regarding spray break-up and the interactivity of the factors on spray form are detailed. The spray under investigation was injected into purposely designed quiescent chambers to decouple the effects of the fluid mechanics on s...

  8. Study on direct determination of uranium and efficient equilibrium factor by gamma-ray spectrometer

    Liu Chunkui

    1990-01-01

    The test principle, test set and surveying methods for conducting gamma-ray spectrometry on conveyer are presented. The conversion coefficient of the spectrometer has been found by using duallinear regression analysis of uranium and radon and their higher and lower bands of gamma-ray spectra. The efficient equilibrium factor can be quickly determined, and the direct determination of uranium in the non-equilibrium condition of uranium and radium can be made

  9. Identification of direct regulatory targets of the transcription factor Sox10 based on function and conservation

    Lee Sanghyuk

    2008-09-01

    Full Text Available Abstract Background Sox10, a member of the Sry-related HMG-Box gene family, is a critical transcription factor for several important cell lineages, most notably the neural crest stem cells and the derivative peripheral glial cells and melanocytes. Thus far, only a handful of direct target genes are known for this transcription factor limiting our understanding of the biological network it governs. Results We describe identification of multiple direct regulatory target genes of Sox10 through a procedure based on function and conservation. By combining RNA interference technique and DNA microarray technology, we have identified a set of genes that show significant down-regulation upon introduction of Sox10 specific siRNA into Schwannoma cells. Subsequent comparative genomics analyses led to potential binding sites for Sox10 protein conserved across several mammalian species within the genomic region proximal to these genes. Multiple sites belonging to 4 different genes (proteolipid protein, Sox10, extracellular superoxide dismutase, and pleiotrophin were shown to directly interact with Sox10 by chromatin immunoprecipitation assay. We further confirmed the direct regulation through the identified cis-element for one of the genes, extracellular superoxide dismutase, using electrophoretic mobility shift assay and reporter assay. Conclusion In sum, the process of combining differential expression profiling and comparative genomics successfully led to further defining the role of Sox10, a critical transcription factor for the development of peripheral glia. Our strategy utilizing relatively accessible techniques and tools should be applicable to studying the function of other transcription factors.

  10. Subjective cognitive complaints, psychosocial factors and nursing work function in nurses providing direct patient care.

    Barbe, Tammy; Kimble, Laura P; Rubenstein, Cynthia

    2018-04-01

    The aim of this study was to examine relationships among subjective cognitive complaints, psychosocial factors and nursing work function in nurses providing direct patient care. Cognitive functioning is a critical component for nurses in the assurance of error prevention, identification and correction when caring for patients. Negative changes in nurses' cognitive and psychosocial functioning can adversely affect nursing care and patient outcomes. A descriptive correlational design with stratified random sampling. The sample included 96 nurses from the major geographic regions of the United States. Over 9 months in 2016-2017, data were collected using a web-based survey. Stepwise multiple linear regression analyses were used to examine relationships among subjective cognitive complaints, psychosocial factors and nursing work function. Overall, participants reported minimal work function impairment and low levels of subjective cognitive complaints, depression and stress. In multivariate analyses, depression was not associated with nurses' work function. However, perceived stress and subjective concerns about cognitive function were associated with greater impairment of work function. Nurses experiencing subjective cognitive complaints should be encouraged to address personal and environmental factors that are associated with their cognitive status. Additionally, stress reduction in nurses should be a high priority as a potential intervention to promote optimal functioning of nurses providing direct patient care. Healthcare institutions should integrate individual and institutional strategies to reduce factors contributing to workplace stress. © 2017 John Wiley & Sons Ltd.

  11. FOREIGN DIRECT INVESTMENTS IN SOUTH-EASTERN EUROPE COUNTRIES ANALYSIS OF INFLUENCE FACTORS

    Nenad POPOVIĆ

    2010-01-01

    Full Text Available That influences the inflow of foreign direct investments (FDIs into South-Eastern Europe (SEE, whereby main emphasis will be put on republics of Former Yugoslavia, but also with some references to Romania’s case.Choice of the countries for comparison is made upon assumption that they were characterized by relatively the same industrial, market and social development before they entered the process of transition, so comparisons from the aspect of achieved results is of scientific importance. Special attention will be directed to the result made by the Republic of Serbia in the process of attracting FDIs. First of all, main terms of foreign direct investments will be defined in this paper and we will give general review of literature related to allocation of foreign direct investments. Then, recent trends of foreign direct investments in south-astern Europe will be described. Finally, the factors that influence allocation of FDIs,as well as relationship between index of global competitiveness of observed countries and accumulated FDIs during period of transition will be analyzed.

  12. Direct induction of chondrogenic cells from human dermal fibroblast culture by defined factors.

    Hidetatsu Outani

    Full Text Available The repair of large cartilage defects with hyaline cartilage continues to be a challenging clinical issue. We recently reported that the forced expression of two reprogramming factors (c-Myc and Klf4 and one chondrogenic factor (SOX9 can induce chondrogenic cells from mouse dermal fibroblast culture without going through a pluripotent state. We here generated induced chondrogenic (iChon cells from human dermal fibroblast (HDF culture with the same factors. We developed a chondrocyte-specific COL11A2 promoter/enhancer lentiviral reporter vector to select iChon cells. The human iChon cells expressed marker genes for chondrocytes but not fibroblasts, and were derived from non-chondrogenic COL11A2-negative cells. The human iChon cells formed cartilage but not tumors in nude mice. This approach could lead to the preparation of cartilage directly from skin in human, without going through pluripotent stem cells.

  13. Identification of factors contributing to successful self-directed weight loss: a qualitative study.

    Rafiei, N; Gill, T

    2017-11-21

    Despite the number of weight management programmes and their wide promotion, most overweight and obese individuals tend to lose weight on their own. The present study aimed to understand the characteristics and strategies of those who successfully engage in self-directed weight loss, which could empower other overweight and obese individuals with information and strategies to manage their weight on their own. Men and women who had lost at least 5% of their body weight without direct interaction with professionals or weight management programmes were recruited. Demographic data were collected by questionnaire and participants' weight-loss experiences were explored using semi- structured interviews to elicit in-depth individual experiences and perspectives. Iterative thematic method data analysis was used to generate themes describing contributing factors to the success of self-directed weight loss identified by participants. Most characteristics of those who successfully self-managed their weight loss were in line with those reported by successful weight losers participating in professional-led projects. However, strategies such as early embedding of new lifestyle behaviours into daily routine, the ability to learn from previous weight-loss experiences, and not requiring social support were identified as distinctive factors that contributed to the success of self-directed weight loss by participants of the present study. Overweight or obese individuals with strong internal motivation, problem-solving skills and self-reliance are more likely to be successful at achieving self-directed weight loss. The patients identified with these characteristics could be encouraged to self-manage their weight-loss process, leaving the places available in more resource-intensive professional-led programmes to those individuals unlikely to succeed on their own. © 2017 The British Dietetic Association Ltd.

  14. A structured elicitation method to identify key direct risk factors for the management of natural resources

    Michael Smith

    2015-11-01

    Full Text Available The high level of uncertainty inherent in natural resource management requires planners to apply comprehensive risk analyses, often in situations where there are few resources. In this paper, we demonstrate a broadly applicable, novel and structured elicitation approach to identify important direct risk factors. This new approach combines expert calibration and fuzzy based mathematics to capture and aggregate subjective expert estimates of the likelihood that a set of direct risk factors will cause management failure. A specific case study is used to demonstrate the approach; however, the described methods are widely applicable in risk analysis. For the case study, the management target was to retain all species that characterise a set of natural biological elements. The analysis was bounded by the spatial distribution of the biological elements under consideration and a 20-year time frame. Fourteen biological elements were expected to be at risk. Eleven important direct risk factors were identified that related to surrounding land use practices, climate change, problem species (e.g., feral predators, fire and hydrological change. In terms of their overall influence, the two most important risk factors were salinisation and a lack of water which together pose a considerable threat to the survival of nine biological elements. The described approach successfully overcame two concerns arising from previous risk analysis work: (1 the lack of an intuitive, yet comprehensive scoring method enabling the detection and clarification of expert agreement and associated levels of uncertainty; and (2 the ease with which results can be interpreted and communicated while preserving a rich level of detail essential for informed decision making.

  15. Pipe elbow stiffness coefficients including shear and bend flexibility factors for use in direct stiffness codes

    Perry, R.F.

    1977-01-01

    Historically, developments of computer codes used for piping analysis were based upon the flexibility method of structural analysis. Because of the specialized techniques employed in this method, the codes handled systems composed of only piping elements. Over the past ten years, the direct stiffness method has gained great popularity because of its systematic solution procedure regardless of the type of structural elements composing the system. A great advantage is realized with a direct stiffness code that combines piping elements along with other structural elements such as beams, plates, and shells, in a single model. One common problem, however, has been the lack of an accurate pipe elbow element that would adequately represent the effects of transverse shear and bend flexibility factors. The purpose of the present paper is to present a systematic derivation of the required 12x12 stiffness matrix and load vectors for a three dimensional pipe elbow element which includes the effects of transverse shear and pipe bend flexibility according to the ASME Boiler and Pressure Vessel Code, Section III. The results are presented analytically and as FORTRAN subroutines to be directly incorporated into existing direct stiffness codes. (Auth.)

  16. Direct and Indirect Factors Influencing Selection of Birthing Attendants in Gunungsari, West Lombok (NTB

    Ni Nyoman Aryaniti

    2015-04-01

    Full Text Available Background and purpose: This study aims to determine the direct and indirect factors influencing the selection of birth attendants in Gunungsari subdistrict, West Lombok.Methods: This study was cross-sectional with a purposively selected sample of 27 mothers giving birth assisted by non-health professionals. Samples of those assisted by health professionals were taken by means of proportional systematic random sampling in Gunungsari and Penimbung health centers, respectively 29 of 916 and 14 of 437. Exogenous factors were maternal education levels, attendance to ANC classes, knowledge levels regarding to birthing attendants, maternal attitude, family support, and access to facilities. Birth attendant selection was the endogenousfactor. Data were collected by means of interviews. Data analysis includes descriptive and inferential analysis with path analysis by linear regression.Results: The majority of respondents were 21-25 years old (87.4% , housewives (47.14% had educat ion under high school (65.72% and were married (88.57%. Family support had a direct influence in decision making with a coefficient of 0.534 and 35.54% influence overall. Attendance to ANC classes in addition to family support had anindirect influence with a coefficient of 0.520 and 34.78% influence overall. Family support had a direct influence and the factor of attendance to ANC classes and family support has an indirect effect with the overall effect of 70.32%.Conclusion: The presence of the husband/family was needed in ANC class, through an implementation of schedule agreement.Keywords: family support, ANC class, birth attendants, path analysis, West Lombok

  17. Rice homeobox transcription factor HOX1a positively regulates gibberellin responses by directly suppressing EL1.

    Wen, Bi-Qing; Xing, Mei-Qing; Zhang, Hua; Dai, Cheng; Xue, Hong-Wei

    2011-11-01

    Homeobox transcription factors are involved in various aspects of plant development, including maintenance of the biosynthesis and signaling pathways of different hormones. However, few direct targets of homeobox proteins have been identified. We here show that overexpression of rice homeobox gene HOX1a resulted in enhanced gibberellin (GA) response, indicating a positive effect of HOX1a in GA signaling. HOX1a is induced by GA and encodes a homeobox transcription factor with transcription repression activity. In addition, HOX1a suppresses the transcription of early flowering1 (EL1), a negative regulator of GA signaling, and further electrophoretic mobility shift assay and chromatin immunoprecipitation analysis revealed that HOX1a directly bound to the promoter region of EL1 to suppress its expression and stimulate GA signaling. These results demonstrate that HOX1a functions as a positive regulator of GA signaling by suppressing EL1, providing informative hints on the study of GA signaling. © 2011 Institute of Botany, Chinese Academy of Sciences.

  18. Hypoxia-inducible factor directs POMC gene to mediate hypothalamic glucose sensing and energy balance regulation.

    Hai Zhang

    2011-07-01

    Full Text Available Hypoxia-inducible factor (HIF is a nuclear transcription factor that responds to environmental and pathological hypoxia to induce metabolic adaptation, vascular growth, and cell survival. Here we found that HIF subunits and HIF2α in particular were normally expressed in the mediobasal hypothalamus of mice. Hypothalamic HIF was up-regulated by glucose to mediate the feeding control of hypothalamic glucose sensing. Two underlying molecular pathways were identified, including suppression of PHDs by glucose metabolites to prevent HIF2α degradation and the recruitment of AMPK and mTOR/S6K to regulate HIF2α protein synthesis. HIF activation was found to directly control the transcription of POMC gene. Genetic approach was then employed to develop conditional knockout mice with HIF inhibition in POMC neurons, revealing that HIF loss-of-function in POMC neurons impaired hypothalamic glucose sensing and caused energy imbalance to promote obesity development. The metabolic effects of HIF in hypothalamic POMC neurons were independent of leptin signaling or pituitary ACTH pathway. Hypothalamic gene delivery of HIF counteracted overeating and obesity under conditions of nutritional excess. In conclusion, HIF controls hypothalamic POMC gene to direct the central nutrient sensing in regulation of energy and body weight balance.

  19. Hypoxia-Inducible Factor Directs POMC Gene to Mediate Hypothalamic Glucose Sensing and Energy Balance Regulation

    Zhang, Hai; Zhang, Guo; Gonzalez, Frank J.; Park, Sung-min; Cai, Dongsheng

    2011-01-01

    Hypoxia-inducible factor (HIF) is a nuclear transcription factor that responds to environmental and pathological hypoxia to induce metabolic adaptation, vascular growth, and cell survival. Here we found that HIF subunits and HIF2α in particular were normally expressed in the mediobasal hypothalamus of mice. Hypothalamic HIF was up-regulated by glucose to mediate the feeding control of hypothalamic glucose sensing. Two underlying molecular pathways were identified, including suppression of PHDs by glucose metabolites to prevent HIF2α degradation and the recruitment of AMPK and mTOR/S6K to regulate HIF2α protein synthesis. HIF activation was found to directly control the transcription of POMC gene. Genetic approach was then employed to develop conditional knockout mice with HIF inhibition in POMC neurons, revealing that HIF loss-of-function in POMC neurons impaired hypothalamic glucose sensing and caused energy imbalance to promote obesity development. The metabolic effects of HIF in hypothalamic POMC neurons were independent of leptin signaling or pituitary ACTH pathway. Hypothalamic gene delivery of HIF counteracted overeating and obesity under conditions of nutritional excess. In conclusion, HIF controls hypothalamic POMC gene to direct the central nutrient sensing in regulation of energy and body weight balance. PMID:21814490

  20. Imitative and Direct Learning as Interacting Factors in Life History Evolution.

    Bullinaria, John A

    2017-01-01

    The idea that lifetime learning can have a significant effect on life history evolution has recently been explored using a series of artificial life simulations. These involved populations of competing individuals evolving by natural selection to learn to perform well on simplified abstract tasks, with the learning consisting of identifying regularities in their environment. In reality, there is more to learning than that type of direct individual experience, because it often includes a substantial degree of social learning that involves various forms of imitation of what other individuals have learned before them. This article rectifies that omission by incorporating memes and imitative learning into revised versions of the previous approach. To do this reliably requires formulating and testing a general framework for meme-based simulations that will enable more complete investigations of learning as a factor in any life history evolution scenarios. It does that by simulating imitative information transfer in terms of memes being passed between individuals, and developing a process for merging that information with the (possibly inconsistent) information acquired by direct experience, leading to a consistent overall body of learning. The proposed framework is tested on a range of learning variations and a representative set of life history factors to confirm the robustness of the approach. The simulations presented illustrate the types of interactions and tradeoffs that can emerge, and indicate the kinds of species-specific models that could be developed with this approach in the future.

  1. Fibroblast growth factor 21 has no direct role in regulating fertility in female mice

    Garima Singhal

    2016-08-01

    Full Text Available Objective: Reproduction is an energetically expensive process. Insufficient calorie reserves, signaled to the brain through peripheral signals such as leptin, suppress fertility. Recently, fibroblast growth factor 21 (FGF21 was implicated as a signal from the liver to the hypothalamus that directly inhibits the hypothalamic–gonadotropin axis during fasting and starvation. However, FGF21 itself increases metabolic rate and can induce weight loss, which suggests that the effects of FGF21 on fertility may not be direct and may reflect changes in energy balance. Methods: To address this important question, we evaluated fertility in several mouse models with elevated FGF21 levels including ketogenic diet fed mice, fasted mice, mice treated with exogenous FGF21 and transgenic mice over-expressing FGF21. Results: We find that ketogenic diet fed mice remain fertile despite significant elevation in serum FGF21 levels. Absence of FGF21 does not alter transient infertility induced by fasting. Centrally infused FGF21 does not suppress fertility despite its efficacy in inducing browning of inguinal white adipose tissue. Furthermore, a high fat diet (HFD can restore fertility of female FGF21-overexpressing mice, a model of growth restriction, even in the presence of supraphysiological serum FGF21 levels. Conclusions: We conclude that FGF21 is not a direct physiological regulator of fertility in mice. The infertility observed in FGF21 overexpressing mice is likely driven by the increased energy expenditure and consequent excess calorie requirements resulting from high FGF21 levels. Keywords: FGF21, Fertility, Leptin, Hypothalamic action

  2. Social and behavioural factors associated with condom use among direct sex workers in Siem Reap, Cambodia.

    Wong, M L; Lubek, I; Dy, B C; Pen, S; Kros, S; Chhit, M

    2003-04-01

    To determine the social and behavioural factors associated with condom use among direct sex workers in Siem Reap, Cambodia. Using a structured behavioural questionnaire, interviews were conducted with 140 direct sex workers attending a health centre in Siem Reap for HIV screening. Consistent condom use with their clients was reported by 78% of sex workers compared to only 20% with their non-paying partners. Consistent condom use with clients was significantly higher among higher income than lower income sex workers (adjusted prevalence ratio: 1.91, 95% CI: 1.15 to 3.18) and those with good rather than poor negotiation skills (adjusted prevalence ratio: 1.51, 95% CI: 1.01 to 2.26), after adjustment for age, educational level, marital status, number of sexual encounters per week, and knowledge of AIDS/HIV and sexually transmitted infections. The most frequently reported reason for not using condoms with clients was not being able to persuade them (66.7%), while for non-paying partners, the reason was that they loved them (60.0%). To complement the government's current programme of client education, 100% condom policy and brothel administrative measures, additional strategies to increase condom use among clients and non-paying partners should be directed at (i) the social policy and community levels to address sex workers' economic and cultural barriers to condom use, and (ii) personal level empowerment through developing sex workers' condom negotiation skills.

  3. Transcription factor HBP1 is a direct anti-cancer target of transcription factor FOXO1 in invasive oral cancer.

    Chan, Chien-Yi; Huang, Shih-Yi; Sheu, Jim Jinn-Chyuan; Roth, Mendel M; Chou, I-Tai; Lien, Chia-Hsien; Lee, Ming-Fen; Huang, Chun-Yin

    2017-02-28

    Either FOXO1 or HBP1 transcription factor is a downstream effector of the PI3K/Akt pathway and associated with tumorigenesis. However, the relationship between FOXO1 and HBP1 in oral cancer remains unclear. Analysis of 30 oral tumor specimens revealed that mean mRNA levels of both FOXO1 and HBP1 in non-invasive and invasive oral tumors were found to be significantly lower than that of the control tissues, and the status of low FOXO1 and HBP1 (oral tumors. To investigate if HBP1 is a direct transcription target of FOXO1, we searched potential FOXO1 binding sites in the HBP1 promoter using the MAPPER Search Engine, and two putative FOXO1 binding sites located in the HBP1 promoter -132 to -125 bp and -343 to -336 bp were predicted. These binding sites were then confirmed by both reporter gene assays and the in cellulo ChIP assay. In addition, Akt activity manipulated by PI3K inhibitor LY294002 or Akt mutants was shown to negatively affect FOXO1-mediated HBP1 promoter activation and gene expression. Last, the biological significance of the FOXO1-HBP1 axis in oral cancer malignancy was evaluated in cell growth, colony formation, and invasiveness. The results indicated that HBP1 knockdown potently promoted malignant phenotypes of oral cancer and the suppressive effect of FOXO1 on cell growth, colony formation, and invasion was alleviated upon HBP1 knockdown in invasive oral cancer cells. Taken together, our data provide evidence for HBP1 as a direct downstream target of FOXO1 in oral cancer malignancy.

  4. Biomechanical factors associated with time to complete a change of direction cutting maneuver.

    Marshall, Brendan M; Franklyn-Miller, Andrew D; King, Enda A; Moran, Kieran A; Strike, Siobhán C; Falvey, Éanna C

    2014-10-01

    Cutting ability is an important aspect of many team sports, however, the biomechanical determinants of cutting performance are not well understood. This study aimed to address this issue by identifying the kinetic and kinematic factors correlated with the time to complete a cutting maneuver. In addition, an analysis of the test-retest reliability of all biomechanical measures was performed. Fifteen (n = 15) elite multidirectional sports players (Gaelic hurling) were recruited, and a 3-dimensional motion capture analysis of a 75° cut was undertaken. The factors associated with cutting time were determined using bivariate Pearson's correlations. Intraclass correlation coefficients (ICCs) were used to examine the test-retest reliability of biomechanical measures. Five biomechanical factors were associated with cutting time (2.28 ± 0.11 seconds): peak ankle power (r = 0.77), peak ankle plantar flexor moment (r = 0.65), range of pelvis lateral tilt (r = -0.54), maximum thorax lateral rotation angle (r = 0.51), and total ground contact time (r = -0.48). Intraclass correlation coefficient scores for these 5 factors, and indeed for the majority of the other biomechanical measures, ranged from good to excellent (ICC >0.60). Explosive force production about the ankle, pelvic control during single-limb support, and torso rotation toward the desired direction of travel were all key factors associated with cutting time. These findings should assist in the development of more effective training programs aimed at improving similar cutting performances. In addition, test-retest reliability scores were generally strong, therefore, motion capture techniques seem well placed to further investigate the determinants of cutting ability.

  5. Direct measurement of electron beam quality conversion factors using water calorimetry

    Renaud, James, E-mail: james.renaud@mail.mcgill.ca; Seuntjens, Jan [Medical Physics Unit, McGill University, Montréal, Québec H3G 1A4 (Canada); Sarfehnia, Arman [Medical Physics Unit, McGill University, Montréal, Québec H3G 1A4, Canada and Department of Radiation Oncology, University of Toronto, Toronto, Ontario M5S 3E2 (Canada); Marchant, Kristin [Allan Blair Cancer Centre, Saskatchewan Cancer Agency, Regina, Saskatchewan S4T 7T1, Canada and Department of Oncology, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5A1 (Canada); McEwen, Malcolm; Ross, Carl [Ionizing Radiation Standards, National Research Council of Canada, Ottawa, Ontario K1A 0R6 (Canada)

    2015-11-15

    Purpose: In this work, the authors describe an electron sealed water calorimeter (ESWcal) designed to directly measure absorbed dose to water in clinical electron beams and its use to derive electron beam quality conversion factors for two ionization chamber types. Methods: A functioning calorimeter prototype was constructed in-house and used to obtain reproducible measurements in clinical accelerator-based 6, 9, 12, 16, and 20 MeV electron beams. Corrections for the radiation field perturbation due to the presence of the glass calorimeter vessel were calculated using Monte Carlo (MC) simulations. The conductive heat transfer due to dose gradients and nonwater materials was also accounted for using a commercial finite element method software package. Results: The relative combined standard uncertainty on the ESWcal dose was estimated to be 0.50% for the 9–20 MeV beams and 1.00% for the 6 MeV beam, demonstrating that the development of a water calorimeter-based standard for electron beams over such a wide range of clinically relevant energies is feasible. The largest contributor to the uncertainty was the positioning (Type A, 0.10%–0.40%) and its influence on the perturbation correction (Type B, 0.10%–0.60%). As a preliminary validation, measurements performed with the ESWcal in a 6 MV photon beam were directly compared to results derived from the National Research Council of Canada (NRC) photon beam standard water calorimeter. These two independent devices were shown to agree well within the 0.43% combined relative uncertainty of the ESWcal for this beam type and quality. Absorbed dose electron beam quality conversion factors were measured using the ESWcal for the Exradin A12 and PTW Roos ionization chambers. The photon-electron conversion factor, k{sub ecal}, for the A12 was also experimentally determined. Nonstatistically significant differences of up to 0.7% were found when compared to the calculation-based factors listed in the AAPM’s TG-51 protocol

  6. Direct measurement of electron beam quality conversion factors using water calorimetry.

    Renaud, James; Sarfehnia, Arman; Marchant, Kristin; McEwen, Malcolm; Ross, Carl; Seuntjens, Jan

    2015-11-01

    In this work, the authors describe an electron sealed water calorimeter (ESWcal) designed to directly measure absorbed dose to water in clinical electron beams and its use to derive electron beam quality conversion factors for two ionization chamber types. A functioning calorimeter prototype was constructed in-house and used to obtain reproducible measurements in clinical accelerator-based 6, 9, 12, 16, and 20 MeV electron beams. Corrections for the radiation field perturbation due to the presence of the glass calorimeter vessel were calculated using Monte Carlo (MC) simulations. The conductive heat transfer due to dose gradients and nonwater materials was also accounted for using a commercial finite element method software package. The relative combined standard uncertainty on the ESWcal dose was estimated to be 0.50% for the 9-20 MeV beams and 1.00% for the 6 MeV beam, demonstrating that the development of a water calorimeter-based standard for electron beams over such a wide range of clinically relevant energies is feasible. The largest contributor to the uncertainty was the positioning (Type A, 0.10%-0.40%) and its influence on the perturbation correction (Type B, 0.10%-0.60%). As a preliminary validation, measurements performed with the ESWcal in a 6 MV photon beam were directly compared to results derived from the National Research Council of Canada (NRC) photon beam standard water calorimeter. These two independent devices were shown to agree well within the 0.43% combined relative uncertainty of the ESWcal for this beam type and quality. Absorbed dose electron beam quality conversion factors were measured using the ESWcal for the Exradin A12 and PTW Roos ionization chambers. The photon-electron conversion factor, kecal, for the A12 was also experimentally determined. Nonstatistically significant differences of up to 0.7% were found when compared to the calculation-based factors listed in the AAPM's TG-51 protocol. General agreement between the relative

  7. Factors Influencing Nursing Students' Clinical Judgment: A Qualitative Directed Content Analysis in an Iranian Context.

    Pouralizadeh, Moluk; Khankeh, Hamidreza; Ebadi, Abbas; Dalvandi, Asghar

    2017-05-01

    Clinical judgment is necessary for clinical decision making and enhancing it in nursing students improves health care quality. Since clinical judgment is an interactive phenomenon and dependent on context and culture, it can be affected by many different factors. To understand the experiences of Iranian nursing students and teachers about the factors influencing nursing students' clinical judgment. A qualitative study was conducted using a directed content analysis approach. In this study, purposive sampling and semi-structured interviews were applied with seven nursing students, six faculty member teachers and four clinical instructors from Guilan University of Medical Sciences, Gilan, Iran. The factors influencing nursing students' clinical judgment consisted of five main categories including thoughtful behaviour, professional ethics, use of evidence based care, the context of learning environment and individual and professional features of clinical teachers. Relying on the results of this research, teachers can create an appropriate educational condition and a safe psychological atmosphere, use instructional strategies strengthening deep thought processes, applying professional ethics and scientific evidence and principles to establish clinical judgment in nursing students.

  8. Average value of the shape and direction factor in the equation of refractive index

    Zhang, Tao

    2017-10-01

    The theoretical calculation of the refractive indices is of great significance for the developments of new optical materials. The calculation method of refractive index, which was deduced from the electron-cloud-conductor model, contains the shape and direction factor 〈g〉. 〈g〉 affects the electromagnetic-induction energy absorbed by the electron clouds, thereby influencing the refractive indices. It is not yet known how to calculate 〈g〉 value of non-spherical electron clouds. In this paper, 〈g〉 value is derived by imaginatively dividing the electron cloud into numerous little volume elements and then regrouping them. This paper proves that 〈g〉 = 2/3 when molecules’ spatial orientations distribute randomly. The calculations of the refractive indices of several substances validate this equation. This result will help to promote the application of the calculation method of refractive index.

  9. miR-27 regulates mitochondrial networks by directly targeting the mitochondrial fission factor.

    Tak, Hyosun; Kim, Jihye; Jayabalan, Aravinth Kumar; Lee, Heejin; Kang, Hoin; Cho, Dong-Hyung; Ohn, Takbum; Nam, Suk Woo; Kim, Wook; Lee, Eun Kyung

    2014-11-28

    Mitochondrial morphology is dynamically regulated by forming small, fragmented units or interconnected networks, and this is a pivotal process that is used to maintain mitochondrial homeostasis. Although dysregulation of mitochondrial dynamics is related to the pathogenesis of several human diseases, its molecular mechanism is not fully elucidated. In this study, we demonstrate the potential role of miR-27 in the regulation of mitochondrial dynamics. Mitochondrial fission factor (MFF) mRNA is a direct target of miR-27, whose ectopic expression decreases MFF expression through binding to its 3'-untranslated region. Expression of miR-27 results in the elongation of mitochondria as well as an increased mitochondrial membrane potential and mitochondrial ATP level. Our results suggest that miR-27 is a novel regulator affecting morphological mitochondrial changes by targeting MFF.

  10. Reg IV is a direct target of intestinal transcriptional factor CDX2 in gastric cancer.

    Yutaka Naito

    Full Text Available REG4, which encodes Reg IV protein, is a member of the calcium-dependent lectin superfamily and potent activator of the epidermal growth factor receptor/Akt/activator protein-1 signaling pathway. Several human cancers overexpress Reg IV, and Reg IV expression is associated with intestinal phenotype differentiation. However, regulation of REG4 transcription remains unclear. In the present study, we investigated whether CDX2 regulates Reg IV expression in gastric cancer (GC cells. Expression of Reg IV and CDX2 was analyzed by Western blot and quantitative reverse transcription-polymerase chain reaction in 9 GC cell lines and 2 colon cancer cell lines. The function of the 5'-flanking region of the REG4 gene was characterized by luciferase assay. In 9 GC cell lines, endogenous Reg IV and CDX2 expression were well correlated. Using an estrogen receptor-regulated form of CDX2, rapid induction of Reg IV expression was observed in HT-29 cells. Reporter gene assays revealed an important role in transcription for consensus CDX2 DNA binding elements in the 5'-flanking region of the REG4 gene. Chromatin immunoprecipitation assays showed that CDX2 binds directly to the 5'-flanking region of REG4. These results indicate that CDX2 protein directly regulates Reg IV expression.

  11. Peptidyl Prolyl Isomerase PIN1 Directly Binds to and Stabilizes Hypoxia-Inducible Factor-1α.

    Hyeong-Jun Han

    Full Text Available Peptidyl prolyl isomerase (PIN1 regulates the functional activity of a subset of phosphoproteins through binding to phosphorylated Ser/Thr-Pro motifs and subsequently isomerization of the phosphorylated bonds. Interestingly, PIN1 is overexpressed in many types of malignancies including breast, prostate, lung and colon cancers. However, its oncogenic functions have not been fully elucidated. Here, we report that PIN1 directly interacts with hypoxia-inducible factor (HIF-1α in human colon cancer (HCT116 cells. PIN1 binding to HIF-1α occurred in a phosphorylation-dependent manner. We also found that PIN1 interacted with HIF-1α at both exogenous and endogenous levels. Notably, PIN1 binding stabilized the HIF-1α protein, given that their levels were significantly increased under hypoxic conditions. The stabilization of HIF-1α resulted in increased transcriptional activity, consequently upregulating expression of vascular endothelial growth factor, a major contributor to angiogenesis. Silencing of PIN1 or pharmacologic inhibition of its activity abrogated the angiogenesis. By utilizing a bioluminescence imaging technique, we were able to demonstrate that PIN1 inhibition dramatically reduced the tumor volume in a subcutaneous mouse xenograft model and angiogenesis as well as hypoxia-induced transcriptional activity of HIF-1α. These results suggest that PIN1 interacting with HIF-1α is a potential cancer chemopreventive and therapeutic target.

  12. Behavioral determinants of cardiovascular diseases risk factors: A qualitative directed content analysis.

    Sabzmakan, Leila; Morowatisharifabad, Mohammad Ali; Mohammadi, Eesa; Mazloomy-Mahmoodabad, Seid Saied; Rabiei, Katayoun; Naseri, Mohammad Hassan; Shakibazadeh, Elham; Mirzaei, Masoud

    2014-03-01

    The PRECEDE model is a useful tool for planers to assess health problems, the behavioral and environmental causes of the problems, and their determinants. This study aims to understand the experiences of patients and health care providers about the behavioral causes of cardiovascular diseases (CVDs) risk factors and their determinants. This qualitative study utilized content analysis approach based on the PRECEDE model. The study was conducted for over 6 months in 2012 at the diabetes units of health centers associated with Alborz University of Medical Sciences, which is located in Karaj, Iran. Data were collected using individual semi-structured interviews with 50 patients and 12 health care providers. Data analysis was performed simultaneously with data collection using the content analysis directed method. Stress, unhealthy eating, and physical inactivity were the behaviors, which predict the risk factors for CVD. Most of the patients considered stress as the most important underlying cause of their illness. In this study, 110 of the primary codes were categorized into seven subcategories, including knowledge, attitude, perceived susceptibility, severity, perceived benefits, barriers, and self-efficacy, which were located in the predisposing category of the PRECEDE model. Among these determinants, perceived barriers and self-efficacy for the mentioned behaviors seemed to be of great importance. Identifying behavioral determinants will help the planners design future programs and select the most appropriate methods and applications to address these determinants in order to reduce risky behaviors.

  13. Evolved α-factor prepro-leaders for directed laccase evolution in Saccharomyces cerevisiae.

    Mateljak, Ivan; Tron, Thierry; Alcalde, Miguel

    2017-11-01

    Although the functional expression of fungal laccases in Saccharomyces cerevisiae has proven to be complicated, the replacement of signal peptides appears to be a suitable approach to enhance secretion in directed evolution experiments. In this study, twelve constructs were prepared by fusing native and evolved α-factor prepro-leaders from S. cerevisiae to four different laccases with low-, medium- and high-redox potential (PM1L from basidiomycete PM1; PcL from Pycnoporus cinnabarinus; TspC30L from Trametes sp. strain C30; and MtL from Myceliophthora thermophila). Microcultures of the prepro-leader:laccase fusions were grown in selective expression medium that used galactose as both the sole carbon source and as the inducer of expression so that the secretion and activity were assessed with low- and high-redox potential mediators in a high-throughput screening context. With total activity improvements as high as sevenfold over those obtained with the native α-factor prepro-leader, the evolved prepro-leader from PcL (α PcL ) most strongly enhanced secretion of the high- and medium-redox potential laccases PcL, PM1L and TspC30L in the microtiter format with an expression pattern driven by prepro-leaders in the order α PcL  > α PM 1L  ~ α native . By contrast, the pattern of the low-redox potential MtL was α native  > α PcL  > α PM 1L . When produced in flask with rich medium, the evolved prepro-leaders outperformed the α native signal peptide irrespective of the laccase attached, enhancing secretion over 50-fold. Together, these results highlight the importance of using evolved α-factor prepro-leaders for functional expression of fungal laccases in directed evolution campaigns. © 2017 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

  14. The pluripotency factor Nanog is directly upregulated by the androgen receptor in prostate cancer cells.

    Kregel, Steven; Szmulewitz, Russell Z; Vander Griend, Donald J

    2014-11-01

    The Androgen Receptor (AR) is a nuclear hormone receptor that functions as a critical oncogene in all stages of prostate cancer progression, including progression to castration-resistance following androgen-deprivation therapy. Thus, identifying and targeting critical AR-regulated genes is one potential method to block castration-resistant cancer proliferation. Of particular importance are transcription factors that regulate stem cell pluripotency; many of these genes are emerging as critical oncogenes in numerous tumor cell types. Of these, Nanog has been previously shown to increase the self-renewal and stem-like properties of prostate cancer cells. Thus, we hypothesized that Nanog is a candidate AR target gene that may impart castration-resistance. We modulated AR signaling in LNCaP prostate cancer cells and assayed for Nanog expression. Direct AR binding to the NANOG promoter was tested using AR Chromatin Immunoprecipation (ChIP) and analyses of publically available AR ChIP-sequencing data-sets. Nanog over-expressing cells were analyzed for cell growth and cytotoxicity in response to the AR antagonist enzalutamide and the microtubule stabilizing agent docetaxel. AR signaling upregulates Nanog mRNA and protein. AR binds directly to the NANOG promoter, and was not identified within 75 kb of the NANOGP8 pseudogene, suggesting the NANOG gene locus was preferentially activated. Nanog overexpression in LNCaP cells increases overall growth, but does not increase resistance to enzalutamide or docetaxel. Nanog is a novel oncogenic AR target gene in prostate cancer cells, and stable expression of Nanog increases proliferation and growth of prostate cancer cells, but not resistance to enzalutamide or docetaxel. © 2014 Wiley Periodicals, Inc.

  15. The Quality of Entrepreneurial Environment as a Factor of Foreign Direct Investments Inflows

    Peter Kuzmisin

    2013-12-01

    Full Text Available The content of this paper is built on the fact that foreign direct investments have the potential to influence the structure and quality of economic development and competitiveness that many scientific researches and studies have already confirmed. The paper presents entrepreneurial environment as a significant factor for increasing country’s competitiveness. It clarifies and proves relationship between entrepreneurial environment, or more precisely its barriers, and foreign direct investment inflows. The starting point is identification of the barriers of the Slovak entrepreneurial environment according to Doing Business 2012 by comparing Slovakia with the Visegrad Four Countries. Subsequently relationship of barriers (paying taxes, trading across borders, enforcing contracts, protecting investors and FDI inflows on the sample of 25 leading countries for foreign investors according to FDI Confidence Index (Brazil, China, Germany, India, USA etc. is tested by Spearman's rank correlation test. The paper specifies barriers of EE, which removal would have a real impact on increasing FDI inflows into economy of Slovakia with relevant effects on its competitiveness.Research limitations were determined by the availability of statistical data, relatively large sample of surveyed economies in the world and comparison with other assessments (indices of FDI and competitiveness of countries. Given the limits on the scope of a magazine article, we will continue in our research in more detail in the future. Specific attention in this context will be devoted to the impact of investment incentives on FDI inflows. Methodology and selection of applied testing tool in synergy with selected statistical set of datas can bring new approach to the studied field and can stimulate extension of possibilities reached in this paper. The value of this paper lays in the specification of weak points of the Slovak entrepreneurial environment in the context of  its location

  16. MiRNA-directed regulation of VEGF and other angiogenic factors under hypoxia.

    Zhong Hua

    Full Text Available MicroRNAs (miRNAs are a class of 20-24 nt non-coding RNAs that regulate gene expression primarily through post-transcriptional repression or mRNA degradation in a sequence-specific manner. The roles of miRNAs are just beginning to be understood, but the study of miRNA function has been limited by poor understanding of the general principles of gene regulation by miRNAs. Here we used CNE cells from a human nasopharyngeal carcinoma cell line as a cellular system to investigate miRNA-directed regulation of VEGF and other angiogenic factors under hypoxia, and to explore the principles of gene regulation by miRNAs. Through computational analysis, 96 miRNAs were predicted as putative regulators of VEGF. But when we analyzed the miRNA expression profile of CNE and four other VEGF-expressing cell lines, we found that only some of these miRNAs could be involved in VEGF regulation, and that VEGF may be regulated by different miRNAs that were differentially chosen from 96 putative regulatory miRNAs of VEGF in different cells. Some of these miRNAs also co-regulate other angiogenic factors (differential regulation and co-regulation principle. We also found that VEGF was regulated by multiple miRNAs using different combinations, including both coordinate and competitive interactions. The coordinate principle states that miRNAs with independent binding sites in a gene can produce coordinate action to increase the repressive effect of miRNAs on this gene. By contrast, the competitive principle states when multiple miRNAs compete with each other for a common binding site, or when a functional miRNA competes with a false positive miRNA for the same binding site, the repressive effects of miRNAs may be decreased. Through the competitive principle, false positive miRNAs, which cannot directly repress gene expression, can sometimes play a role in miRNA-mediated gene regulation. The competitive principle, differential regulation, multi-miRNA binding sites, and false

  17. Oral direct thrombin inhibitors or oral factor Xa inhibitors for the treatment of deep vein thrombosis.

    Robertson, Lindsay; Kesteven, Patrick; McCaslin, James E

    2015-06-30

    Deep vein thrombosis (DVT) is a condition in which a clot forms in the deep veins, most commonly of the leg. It occurs in approximately 1 in 1,000 people. If left untreated, the clot can travel up to the lungs and cause a potentially life-threatening pulmonary embolism (PE). Previously, a DVT was treated with the anticoagulants heparin and vitamin K antagonists. However, two forms of novel oral anticoagulants (NOACs) have been developed: oral direct thrombin inhibitors (DTI) and oral factor Xa inhibitors. The new drugs have characteristics that may be favourable over conventional treatment, including oral administration, a predictable effect, lack of frequent monitoring or re-dosing and few known drug interactions. To date, no Cochrane review has measured the effectiveness and safety of these drugs in the treatment of DVT. To assess the effectiveness of oral DTIs and oral factor Xa inhibitors for the treatment of DVT. The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched January 2015) and the Cochrane Register of Studies (last searched January 2015). We searched clinical trials databases for details of ongoing or unpublished studies and the reference lists of relevant articles retrieved by electronic searches for additional citations. We included randomised controlled trials in which people with a DVT confirmed by standard imaging techniques, were allocated to receive an oral DTI or an oral factor Xa inhibitor for the treatment of DVT. Two review authors (LR, JM) independently extracted the data and assessed the risk of bias in the trials. Any disagreements were resolved by discussion with the third review author (PK). We performed meta-analyses when we considered heterogeneity low. The two primary outcomes were recurrent VTE and PE. Other outcomes included all-cause mortality and major bleeding. We calculated all outcomes using an odds ratio (OR) with a 95% confidence interval (CI). We included

  18. Bioassay-directed fractionation of a blood coagulation factor Xa inhibitor, betulinic acid from Lycopus lucidus

    Tan Yin-Feng

    2018-03-01

    Full Text Available Thrombosis is a major cause of morbidity and mortality worldwide and plays a pivotal role in the pathogenesis of several cardiovascular disorders, including acute coronary syndrome, unstable angina, myocardial infarction, sudden cardiac death, peripheral arterial occlusion, ischemic stroke, deep-vein thrombosis, and pulmonary embolism. Anticoagulants, antiplatelet agents, and fibrinolytics can reduce the risks of these clinical events. Especially, the blood coagulation factor Xa (FXa inhibitor is a proven anticoagulant. Promoting blood circulation, using traditional Chinese medicine (TCM, for the treatment of these diseases has been safely used for thousands of years in clinical practice. Therefore, highly safe and effective anticoagulant ingredients, including FXa inhibitors, could be found in TCM for activating the blood circulation. One FXa inhibitor, a pentacyclic triterpene (compound 1, betulinic acid characterized by IR, MS and NMR analyses, was isolated from the ethyl acetate fraction of Lycopus lucidus by bioassay-directed fractionation. Compound 1 exhibited an inhibitory effect on FXa with IC50 25.05 μmol/L and reduced the thrombus weight in an animal model at 25-100 mg/kg. These results indicate that betulinic acid could be the potential for anticoagulant therapy.

  19. Parallel Factor-Based Model for Two-Dimensional Direction Estimation

    Nizar Tayem

    2017-01-01

    Full Text Available Two-dimensional (2D Direction-of-Arrivals (DOA estimation for elevation and azimuth angles assuming noncoherent, mixture of coherent and noncoherent, and coherent sources using extended three parallel uniform linear arrays (ULAs is proposed. Most of the existing schemes have drawbacks in estimating 2D DOA for multiple narrowband incident sources as follows: use of large number of snapshots, estimation failure problem for elevation and azimuth angles in the range of typical mobile communication, and estimation of coherent sources. Moreover, the DOA estimation for multiple sources requires complex pair-matching methods. The algorithm proposed in this paper is based on first-order data matrix to overcome these problems. The main contributions of the proposed method are as follows: (1 it avoids estimation failure problem using a new antenna configuration and estimates elevation and azimuth angles for coherent sources; (2 it reduces the estimation complexity by constructing Toeplitz data matrices, which are based on a single or few snapshots; (3 it derives parallel factor (PARAFAC model to avoid pair-matching problems between multiple sources. Simulation results demonstrate the effectiveness of the proposed algorithm.

  20. Nurse-Administered, Gut-Directed Hypnotherapy in IBS: Efficacy and Factors Predicting a Positive Response.

    Lövdahl, Jenny; Ringström, Gisela; Agerforz, Pia; Törnblom, Hans; Simrén, Magnus

    2015-07-01

    Hypnotherapy is an effective treatment in irritable bowel syndrome (IBS). It is often delivered by a psychotherapist and is costly and time consuming. Nurse-administered hypnotherapy could increase availability and reduce costs. In this study the authors evaluate the effectiveness of nurse-administered, gut-directed hypnotherapy and identify factors predicting treatment outcome. Eighty-five patients were included in the study. Participants received hypnotherapy by a nurse once/week for 12 weeks. Patients reported marked improvement in gastrointestinal (GI) and extra-colonic symptoms after treatment, as well as a reduction in GI-specific anxiety, general anxiety, and depression. Fifty-eight percent were responders after the 12 weeks treatment period, and of these 82% had a favorable clinical response already at week 6. Women were more likely than men to respond favorably to the treatment. Nurse-administered hypnotherapy is an effective treatment for IBS. Being female and reporting a favorable response to treatment by week 6 predicted a positive treatment response at the end of the 12 weeks treatment period.

  1. Factors associated with compliance with community directed treatment with ivermectin for onchocerciasis control in Southwestern Ethiopia

    Wondafrash Mekite

    2010-06-01

    Full Text Available Abstract Background Although ivermectin is distributed free of charge through the African Programme for Onchocerciasis Control (APOC, not all eligible individuals within communities receive the annual treatment. This poses a serious threat to efforts aimed to control onchocerciasis. This study attempts to determine factors associated with compliance to Community Directed Treatment with Ivermectin (CDTI and provides a basis for trying to understand how best to sustain long-term compliance in order to achieve success in the control of onchocerciasis. Methods An unmatched case-control study was conducted in Bebeka coffee plantation southwest Ethiopia. Cases were, compliant i.e., those individuals who had been registered on the relevant treatment registers and had taken all the five annual doses of Ivermectin. Controls were non-compliant, i.e. those individuals who had been recorded in the relevant treatment registers during the first treatment round(2003, and did not take at least two doses of which one being in the last treatment round (2007. Data were collected using a pre-tested interviewer administered structured questionnaire. Data were edited, cleaned, coded and analyzed using SPSS version 12.0.1 for Microsoft Windows. Multiple logistic regression models was used to identify factors associated with compliance to ivermectin. Results From the total of 456 individuals selected for administration of the survey questionnaire, 450(225 cases and 225 controls were contacted and completed the study 2 refused and 4 were unavailable. Five factors associated with compliance were identified: high risk perception [Adjusted Odds Ratio(AOR = 1.98, 95% Confidence Interval (CI, 1.32-2.95], one's family support [AOR = 1.86, 95% CI, 1.22-2.84], perceiving that the Community Drug Distributors (CDDs are doing their work well [AOR = 2.84, 95% CI, 1.50-5.37] and perceiving measuring height is the best way to determine a person's treatment dose [AOR = 6.37, 95% CI, 2

  2. Pathogenicity Island Cross Talk Mediated by Recombination Directionality Factors Facilitates Excision from the Chromosome.

    Carpenter, Megan R; Rozovsky, Sharon; Boyd, E Fidelma

    2015-12-14

    Pathogenicity islands (PAIs) are mobile integrated genetic elements (MIGEs) that contain a diverse range of virulence factors and are essential in the evolution of pathogenic bacteria. PAIs are widespread among bacteria and integrate into the host genome, commonly at a tRNA locus, via integrase-mediated site-specific recombination. The excision of PAIs is the first step in the horizontal transfer of these elements and is not well understood. In this study, we examined the role of recombination directionality factors (RDFs) and their relationship with integrases in the excision of two PAIs essential for Vibrio cholerae host colonization: Vibrio pathogenicity island 1 (VPI-1) and VPI-2. VPI-1 does not contain an RDF, which allowed us to answer the question of whether RDFs are an absolute requirement for excision. We found that an RDF was required for efficient excision of VPI-2 but not VPI-1 and that RDFs can induce excision of both islands. Expression data revealed that the RDFs act as transcriptional repressors to both VPI-1- and VPI-2-encoded integrases. We demonstrated that the RDFs Vibrio excision factor A (VefA) and VefB bind at the attachment sites (overlapping the int promoter region) of VPI-1 and VPI-2, thus supporting this mode of integrase repression. In addition, V. cholerae RDFs are promiscuous due to their dual functions of promoting excision of both VPI-1 and VPI-2 and acting as negative transcriptional regulators of the integrases. This is the first demonstration of cross talk between PAIs mediated via RDFs which reveals the complex interactions that occur between separately acquired MIGEs. Deciphering the mechanisms of pathogenicity island excision is necessary for understanding the evolution and spread of these elements to their nonpathogenic counterparts. Such mechanistic insight would assist in predicting the mobility of uncharacterized genetic elements. This study identified extensive RDF-mediated cross talk between two nonhomologous VPIs and

  3. Oral direct thrombin inhibitors or oral factor Xa inhibitors for the treatment of pulmonary embolism.

    Robertson, Lindsay; Kesteven, Patrick; McCaslin, James E

    2015-12-04

    Pulmonary embolism is a potentially life-threatening condition in which a clot can travel from the deep veins, most commonly in the leg, up to the lungs. Previously, a pulmonary embolism was treated with the anticoagulants heparin and vitamin K antagonists. Recently, however, two forms of direct oral anticoagulants (DOACs) have been developed: oral direct thrombin inhibitors (DTI) and oral factor Xa inhibitors. The new drugs have characteristics that may be favourable over conventional treatment, including oral administration, a predictable effect, lack of frequent monitoring or re-dosing and few known drug interactions. To date, no Cochrane review has measured the effectiveness and safety of these drugs in the long-term treatment (minimum duration of three months) of pulmonary embolism. To assess the effectiveness of oral DTIs and oral factor Xa inhibitors for the long-term treatment of pulmonary embolism. The Cochrane Vascular Trials Search Co-ordinator searched the Specialised Register (last searched January 2015) and the Cochrane Register of Studies (last searched January 2015). Clinical trials databases were also searched for details of ongoing or unpublished studies. We searched the reference lists of relevant articles retrieved by electronic searches for additional citations. We included randomised controlled trials in which patients with a pulmonary embolism confirmed by standard imaging techniques were allocated to receive an oral DTI or an oral factor Xa inhibitor for the long-term (minimum duration three months) treatment of pulmonary embolism. Two review authors (LR, JM) independently extracted the data and assessed the risk of bias in the trials. Any disagreements were resolved by discussion with the third author (PK). We used meta-analyses when we considered heterogeneity low. The two primary outcomes were recurrent venous thromboembolism and pulmonary embolism. Other outcomes included all-cause mortality and major bleeding. We calculated all outcomes

  4. Vascular endothelial growth factor receptor-3 directly interacts with phosphatidylinositol 3-kinase to regulate lymphangiogenesis.

    Sanja Coso

    Full Text Available BACKGROUND: Dysfunctional lymphatic vessel formation has been implicated in a number of pathological conditions including cancer metastasis, lymphedema, and impaired wound healing. The vascular endothelial growth factor (VEGF family is a major regulator of lymphatic endothelial cell (LEC function and lymphangiogenesis. Indeed, dissemination of malignant cells into the regional lymph nodes, a common occurrence in many cancers, is stimulated by VEGF family members. This effect is generally considered to be mediated via VEGFR-2 and VEGFR-3. However, the role of specific receptors and their downstream signaling pathways is not well understood. METHODS AND RESULTS: Here we delineate the VEGF-C/VEGF receptor (VEGFR-3 signaling pathway in LECs and show that VEGF-C induces activation of PI3K/Akt and MEK/Erk. Furthermore, activation of PI3K/Akt by VEGF-C/VEGFR-3 resulted in phosphorylation of P70S6K, eNOS, PLCγ1, and Erk1/2. Importantly, a direct interaction between PI3K and VEGFR-3 in LECs was demonstrated both in vitro and in clinical cancer specimens. This interaction was strongly associated with the presence of lymph node metastases in primary small cell carcinoma of the lung in clinical specimens. Blocking PI3K activity abolished VEGF-C-stimulated LEC tube formation and migration. CONCLUSIONS: Our findings demonstrate that specific VEGFR-3 signaling pathways are activated in LECs by VEGF-C. The importance of PI3K in VEGF-C/VEGFR-3-mediated lymphangiogenesis provides a potential therapeutic target for the inhibition of lymphatic metastasis.

  5. FOREIGN DIRECT INVESTMENTS – AN ESSENTIAL FACTOR FOR ECONOMIC GROWTH IN TRANSITION ECONOMIES

    Carmen BOGHEAN

    2015-06-01

    Full Text Available The purpose of this analysis is to analyse the connection between foreign direct investments and economic growth in transition economies during a period of increased integration of financial systems in the global financial system. The research focuses on the relationship between foreign direct investments and economic growth during 1970-2013, by means of methods such as the graphic, the regression and the correlation ones. The research findings show that there is a direct and strong connection between the inward financial flows of foreign direct investments and the GDP during the period under analysis in transition economies. In transition economies, a high inward flow of foreign direct investments leads to an increase of the Gross Domestic Product per capita, while a positive development of the standard of living will attract new inward FDI flows, since transition economies are seen as attractive recipients/hosts for foreign direct investments.

  6. No evidence for a direct effect of von Willebrand factor's ABH blood group antigens on von Willebrand factor clearance

    Groeneveld, D J; van Bekkum, T; Cheung, K L; Dirven, R J; Castaman, G; Reitsma, P H; van Vlijmen, B; Eikenboom, J

    BACKGROUND: One of the major determinants of von Willebrand factor (VWF) plasma levels is ABO blood group status, and individuals with blood group O have ~ 25% lower plasma levels. The exact mechanism behind this relationship remains unknown, although effects on clearance have been postulated.

  7. Motivational Factors in Self-Directed Informal Learning from Online Learning Resources

    Song, Donggil; Bonk, Curtis J.

    2016-01-01

    Learning is becoming more self-directed and informal with the support of emerging technologies. A variety of online resources have promoted informal learning by allowing people to learn on demand and just when needed. It is significant to understand self-directed informal learners' motivational aspects, their learning goals, obstacles, and…

  8. Bivariate Gaussian bridges: directional factorization of diffusion in Brownian bridge models.

    Kranstauber, Bart; Safi, Kamran; Bartumeus, Frederic

    2014-01-01

    In recent years high resolution animal tracking data has become the standard in movement ecology. The Brownian Bridge Movement Model (BBMM) is a widely adopted approach to describe animal space use from such high resolution tracks. One of the underlying assumptions of the BBMM is isotropic diffusive motion between consecutive locations, i.e. invariant with respect to the direction. Here we propose to relax this often unrealistic assumption by separating the Brownian motion variance into two directional components, one parallel and one orthogonal to the direction of the motion. Our new model, the Bivariate Gaussian bridge (BGB), tracks movement heterogeneity across time. Using the BGB and identifying directed and non-directed movement within a trajectory resulted in more accurate utilisation distributions compared to dynamic Brownian bridges, especially for trajectories with a non-isotropic diffusion, such as directed movement or Lévy like movements. We evaluated our model with simulated trajectories and observed tracks, demonstrating that the improvement of our model scales with the directional correlation of a correlated random walk. We find that many of the animal trajectories do not adhere to the assumptions of the BBMM. The proposed model improves accuracy when describing the space use both in simulated correlated random walks as well as observed animal tracks. Our novel approach is implemented and available within the "move" package for R.

  9. Factor structure of suggestibility revisited: new evidence for direct and indirect suggestibility

    Romuald Polczyk

    2016-01-01

    Background Yielding to suggestions can be viewed as a relatively stable individual trait, called suggestibility. It has been long proposed that there are two kinds of suggestible influence, and two kinds of suggestibility corresponding to them: direct and indirect. Direct suggestion involves overt unhidden influence, while indirect suggestion concerns influence that is hidden, and the participant does not know that the suggestibility is being measured. So far however, empirical evidence ...

  10. (Reinforcing) Factors Influencing a Physical Education Teacher's Use of the Direct Instruction Model Teaching Games

    Jayantilal, Kumar; O'Leary, Nick

    2017-01-01

    The purpose of this study was to explore how a physical education (PE) teacher employed the direct instruction model (DIM) teaching games in a United Kingdom secondary school. The research sought to identify how the teacher utilised the DIM and those factors that influenced his use of the model. Occupational socialization was used to identify the…

  11. A validation of direct grey Dancoff factors results for cylindrical cells in cluster geometry by the Monte Carlo method

    Rodrigues, Leticia Jenisch; Bogado, Sergio; Vilhena, Marco T.

    2008-01-01

    The WIMS code is a well known and one of the most used codes to handle nuclear core physics calculations. Recently, the PIJM module of the WIMS code was modified in order to allow the calculation of Grey Dancoff factors, for partially absorbing materials, using the alternative definition in terms of escape and collision probabilities. Grey Dancoff factors for the Canadian CANDU-37 and CANFLEX assemblies were calculated with PIJM at five symmetrically distinct fuel pin positions. The results, obtained via Direct Method, i.e., by direct calculation of escape and collision probabilities, were satisfactory when compared with the ones of literature. On the other hand, the PIJMC module was developed to calculate escape and collision probabilities using Monte Carlo method. Modifications in this module were performed to determine Black Dancoff factors, considering perfectly absorbing fuel rods. In this work, we proceed further in the task of validating the Direct Method by the Monte Carlo approach. To this end, the PIJMC routine is modified to compute Grey Dancoff factors using the cited alternative definition. Results are reported for the mentioned CANDU-37 and CANFLEX assemblies obtained with PIJMC, at the same fuel pin positions as with PIJM. A good agreement is observed between the results from the Monte Carlo and Direct methods

  12. Expression of DDX3 is directly modulated by hypoxia inducible factor-1 alpha in breast epithelial cells.

    Mahendran Botlagunta

    2011-03-01

    Full Text Available DEAD box protein, DDX3, is aberrantly expressed in breast cancer cells ranging from weakly invasive to aggressive phenotypes and functions as an important regulator of cancer cell growth and survival. Here, we demonstrate that hypoxia inducible factor-1α is a transcriptional activator of DDX3 in breast cancer cells. Within the promoter region of the human DDX3 gene, we identified three putative hypoxia inducible factor-1 responsive elements. By luciferase reporter assays in combination with mutated hypoxia inducible factor-1 responsive elements, we determined that the hypoxia inducible factor-1 responsive element at position -153 relative to the translation start site is essential for transcriptional activation of DDX3 under hypoxic conditions. We also demonstrated that hypoxia inducible factor-1 binds to the DDX3 promoter and that the binding is specific, as revealed by siRNA against hypoxia inducible factor-1 and chromatin immunoprecipitation assays. Thus, the activation of DDX3 expression during hypoxia is due to the direct binding of hypoxia inducible factor-1 to hypoxia responsive elements in the DDX3 promoter. In addition, we observed a significant overlap in the protein expression pattern of hypoxia inducible factor-1α and DDX3 in MDA-MB-231 xenograft tumors. Taken together, our results demonstrate, for the first time, the role of DDX3 as a hypoxia-inducible gene that exhibits enhanced expression through the interaction of hypoxia inducible factor-1 with hypoxia inducible factor-1 responsive elements in its promoter region.

  13. Directing traffic on DNA-How transcription factors relieve or induce transcriptional interference.

    Hao, Nan; Palmer, Adam C; Dodd, Ian B; Shearwin, Keith E

    2017-03-15

    Transcriptional interference (TI) is increasingly recognized as a widespread mechanism of gene control, particularly given the pervasive nature of transcription, both sense and antisense, across all kingdoms of life. Here, we discuss how transcription factor binding kinetics strongly influence the ability of a transcription factor to relieve or induce TI.

  14. A direct measurement of g-factors in II-VI and III-V core-shell nanocrystals

    Fradkin, L.; Langof, L.; Lifshitz, E.; Gaponik, N.; Rogach, A.; Eychmüller, A.; Weller, H.; Micic, O. I.; Nozik, A. J.

    2005-02-01

    This study describes a direct measurement of spectroscopic g-factors of photo-generated carriers in InP/ZnS and HgTe/Hg xCd 1-xTe(S) core-shell nanocrystals. The g-factor of trapped electrons and their spin-lattice versus radiative relaxation ratio ( T1/ τ) were measured by the use of continuous-wave and time-resolved optically detected magnetic resonance (ODMR) spectroscopy. The g-factors of excitons and donor-hole pairs were derived by the use of field-induced circular-polarized photoluminescence (CP-PL) spectroscopy. The combined information enabled to determine the g-factors of the individual band-edge electrons and holes. The results suggested an increase of the g-factor of the exciton and conduction electron with a decrease of the nanocrystal size.

  15. Structure of Political Success Factors as an Indicator of Political Direction in Electoral System Development

    Panina, Nataliia

    2005-01-01

    The article presents a conceptual model of democratic electoral system development and analysis of empirical data on factors of political success in the electoral situation. Various participants of the electoral process (population, politicians, journalists, government employees, analysts-politologists) evaluated the political success factors; and comparative analysis of these evaluations made it possible to determine the main vectors (“reverse” and “manipulative-mystifying”) affecting deviat...

  16. Psychosocial factors in the development of heart disease in women: current research and future directions.

    Low, Carissa A; Thurston, Rebecca C; Matthews, Karen A

    2010-11-01

    To review the recent (1995-2009) literature on psychosocial risk and protective factors for coronary heart disease (CHD) among women, including negative emotions, stress, social relationships, and positive psychological factors. Articles for the review were identified using PubMed and bibliographies of relevant articles. Eligible studies included at least 100 women and either focused on a) exclusively female participants or b) both men and women, conducting either gender-stratified analyses or examining interactions with gender. Sixty-seven published reports were identified that examined prospective associations with incident or recurrent CHD. In general, evidence suggests that depression, anxiety disorders, anger suppression, and stress associated with relationships or family responsibilities are associated with elevated CHD risk among women, that supportive social relationships and positive psychological factors may be associated with reduced risk, and that general anxiety, hostility, and work-related stress are less consistently associated with CHD among women relative to men. A growing literature supports the significance of psychosocial factors for the development of CHD among women. Consideration of both traditional psychosocial factors (e.g., depression) and factors that may be especially important for women (e.g., stress associated with responsibilities at home or multiple roles) may improve identification of women at elevated risk as well as the development of effective psychological interventions for women with or at risk for CHD.

  17. e-Portfolios Enhancing Students' Self-Directed Learning: A Systematic Review of Influencing Factors

    Beckers, Jorrick; Dolmans, Diana; Van Merriënboer, Jeroen

    2016-01-01

    e-Portfolios have become increasingly popular among educators as learning tools. Some research even shows that e-portfolios can be utilised to facilitate the development of skills for self-directed learning. Such skills include self-assessment of performance, formulation of learning goals, and selection of future tasks. However, it is not yet…

  18. Direct economic burden and influencing factors in patients with hepatitis B virus related diseases in Jiangsu, China.

    Zhang, Hua; Chao, Jianqian; Zhu, Liguo; Song, Long; Li, Xiyan; Liu, Pei

    2015-03-01

    The purpose of this study was to explore direct economic burden and its influencing factors in patients with hepatitis B virus (HBV) related diseases. Time phasing continuous sampling was used to select patients from August 1, 2012, to December 31, 2012, in 3 county hospitals of 3 model regions in Jiangsu Province, China. A total of 436 outpatients and 196 inpatients were observed. The average direct economic burden of HBV-associated admission was US$107.11 for outpatients, and drug fees accounted for 74%; the burden was US$3193.47 for inpatients, and the direct medical costs accounted for 96%. Multivariate linear regression analysis showed that drug fee, examination fee, and antiviral therapy were influencing factors for outpatients, while hospitalization stay, drug ratio, and patient's age were influencing factors for inpatients. It can be concluded that the direct economic burden of patients with HBV-related diseases was high compared to their household income. Measures should be taken to reduce the economic burden of patients. © 2014 APJPH.

  19. Risk factors associated with domestic abuse directed at adults with disabilities in South Korea.

    Kim, Kyung Mee; Lee, Byung Hwa

    2016-07-01

    Most research on domestic abuse and disability has focused on women with disabilities, while research on abuse against men with disabilities and their risk factors is virtually non-existent. The purpose of this research is to understand domestic abuse experienced by people with disabilities by investigating its prevalence and risk factors. This research used the National Survey on Persons with Disabilities (2011). Using a stratified sampling method, 5259 respondents were identified to make up the final sample. Ordered logistic regression was used to verify risk factors for abuse. Risk factors for women with disabilities are age, educational attainment level, ADL, experiences of discrimination, awareness of disability discrimination, external support, and satisfaction with number of friends. Risk factors for men with disabilities are region, experiences of discrimination, awareness of disability discrimination, external support, and satisfaction with number of friends. For both women and men with disabilities, more experience of discrimination, greater awareness of disability discrimination, less external support, and less satisfaction with number of friends are associated with a higher likelihood of having experiences of abuse. Men with disabilities living in rural areas have a higher risk of abuse than those living in cities. Younger women, women with lower educational attainment, and those with lower physical functioning are more likely to have experienced abuse. Based on these findings, the authors make recommendations designed to protect people with disabilities from domestic abuse. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Dancoff factors with partial absorption in cluster geometry by the direct method

    Rodrigues, Leticia Jenisch; Leite, Sergio de Queiroz Bogado; Vilhena, Marco Tullio de; Bodmann, Bardo Ernest Josef

    2007-01-01

    Accurate analysis of resonance absorption in heterogeneous systems is essential in problems like criticality, breeding ratios and fuel depletion calculations. In compact arrays of fuel rods, resonance absorption is strongly affected by the Dancoff factor, defined in this study as the probability that a neutron emitted from the surface of a fuel element, enters another fuel element without any collision in the moderator or cladding. In the original WIMS code, Black Dancoff factors were computed in cluster geometry by the collision probability method, for each one of the symmetrically distinct fuel pin positions in the cell. Recent improvements to the code include a new routine (PIJM) that was created to incorporate a more efficient scheme for computing the collision matrices. In that routine, each system region is considered individually, minimizing convergence problems and reducing the number of neutron track lines required in the in-plane integrations of the Bickley functions for any given accuracy. In the present work, PIJM is extended to compute Grey Dancoff factors for two-dimensional cylindrical cells in cluster geometry. The effectiveness of the method is accessed by comparing Grey Dancoff factors as calculated by PIJM, with those available in the literature by the Monte Carlo method, for the irregular geometry of the Canadian CANDU37 assembly. Dancoff factors at five symmetrically distinct fuel pin positions are found in very good agreement with the literature results (author)

  1. The Direct and Indirect Effects of Environmental Factors on Nurturing Intellectual Giftedness

    Al-Shabatat, Ahmad Mohammad; Abbas, Merza; Ismail, Hairul Nizam

    2011-01-01

    Many people believe that environmental factors promote giftedness and invest in many programs to adopt gifted students providing them with challenging activities. Intellectual giftedness is founded on fluid intelligence and extends to more specific abilities through the growth and inputs from the environment. Acknowledging the roles played by the…

  2. Asymptotic normalization coefficients from direct transfer reactions and astrophysical S factors

    Gagliardi, C. A.; Azhari, A.; Bém, Pavel; Burjan, Václav; Carstoiu, F.; Cejpek, Jan; Clark, H. L.; Kroha, Václav; Lui, Z. W.; Mukhamedzhanov, A. M.; Novák, Jan; Piskoř, Štěpán; Sattarov, A.; Šimečková, Eva; Tang, X.; Trache, L.; Tribble, R. E.; Vincour, Jiří

    2001-01-01

    Roč. 682, - (2001), s. 369C-374C ISSN 0375-9474 R&D Projects: GA ČR GA202/01/0709; GA AV ČR KSK1048102 Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders Impact factor: 2.074, year: 2001

  3. Factors Associated with Choice of Web or Print Intervention Materials in the Healthy Directions 2 Study

    Greaney, Mary L.; Puleo, Elaine; Bennett, Gary G.; Haines, Jess; Viswanath, K.; Gillman, Matthew W.; Sprunck-Harrild, Kim; Coeling, Molly; Rusinak, Donna; Emmons, Karen M.

    2014-01-01

    Background: Many U.S. adults have multiple behavioral risk factors, and effective, scalable interventions are needed to promote population-level health. In the health care setting, interventions are often provided in print, although accessible to nearly everyone, are brief (e.g., pamphlets), are not interactive, and can require some logistics…

  4. Influence of Parenting Factors on Childhood Social Anxiety: Direct Observation of Parental Warmth and Control

    Rork, Kristine E.; Morris, Tracy L.

    2009-01-01

    The purpose of the present study is to determine the association of parenting behaviors and social anxiety in children. Three parental factors--including parental socialization, control, and warmth--were investigated in a sample of 31 two-parent families. Rather than solely relying upon retrospective questionnaires, this study incorporated direct…

  5. Functional studies of elongation factor Tu from Escherichia coli : Site-directed mutagenesis and antibiotic action

    Krab, Ivo Maarten

    2001-01-01

    This PhD thesis describes several studies into the structure and function of Escherichia coli Elongation Factor Tu (EF-Tu). EF-Tu plays a central role in the bacterial protein synthesis machinery as the carrier of "coded building blocks" for protein synthesis, aminoacylated tRNA (aa-tRNA). Without

  6. Mipu1, a novel direct target gene, is involved in hypoxia inducible factor 1-mediated cytoprotection.

    Kangkai Wang

    Full Text Available Mipu1 (myocardial ischemic preconditioning up-regulated protein 1, recently identified in our lab, is a novel zinc-finger transcription factor which is up-regulated during ischemic preconditioning. However, it is not clear what transcription factor contributes to its inducible expression. In the present study, we reported that HIF-1 regulates the inducible expression of Mipu1 which is involved in the cytoprotection of HIF-1α against oxidative stress by inhibiting Bax expression. Our results showed that the inducible expression of Mipu1 was associated with the expression and activation of transcription factor HIF-1 as indicated by cobalt chloride (CoCl2 treatment, HIF-1α overexpression and knockdown assays. EMSA and luciferase reporter gene assays showed that HIF-1α bound to the hypoxia response element (HRE within Mipu1 promoter region and promoted its transcription. Moreover, our results revealed that Mipu1 inhibited the expression of Bax, an important pro-apoptosis protein associated with the intrinsic pathway of apoptosis, elevating the cytoprotection of HIF-1 against hydrogen peroxide (H2O2-mediated injury in H9C2 cells. Our findings implied that Bax may be a potential target gene of transcription factor Mipu1, and provided a novel insight for understanding the cytoprotection of HIF-1 and new clues for further elucidating the mechanisms by which Mipu1 protects cell against pathological stress.

  7. Monoclonal antibodies directed to human insulin-like growth factor I (IGF I)

    Laubli, U.K.; Baier, W.; Celio, M.R.; Binz, H.; Humbel, R.E.

    1982-01-01

    Mouse hybridomas secreting antibodies to human insulin-like growth factor I (IGF I) were produced by fusion of spleen cells of hyperimmunised mice with FO mouse-myeloma cells. Eight clones producing antibodies against human IGF I have been isolated, two of which have been characterised. One was used in a radioimmunoassay, the other for immunopurification of IGF. (Auth.)

  8. Dancoff factors with partial neutrons absorption in cluster geometry by the direct method

    Rodrigues, Leticia Jenisch

    2007-01-01

    Accurate analysis of resonance absorption in heterogeneous systems is essential in problems like criticality, breeding ratios and fuel depletion calculations. In compact arrays of fuel rods, resonance absorption is strongly affected by the Dancoff factor, defined in mis study as the probability that a neutron emitted from the surface of a fuel element, enters another fuel element without any collusion in the moderator or cladding. In fact, in the most practical cases of irregular cells, it is observed that inaccuracies in computing both Grey and Black Dancoff factors, i.e. for partially and perfectly absorbing fuel rods, can lead to considerable errors in the calculated values of such integral quantities. For this reason, much effort has been made in the past decades to further improve the models for calculating Dancoff factors, a task that has been accomplished in connection with the development of faster computers. In the WIMS code, Black Dancoff factors based on the above mentioned collusion probability definition are computed in cluster geometry, for each one of the symmetrically distinct fuel pin positions in the cell. Sets of equally-spaced parallel lines are drawn in subroutine PIJ, at a number of discrete equally-incremented azimuthal angles, covering the whole system and forming a mesh over which the in-plane integrations of the Bickley functions are carried out by simple trapezoidal rule, leading to the first-flight collusion matrices. Although fast, the method in PIJ is inefficient, since the constructed mesh does not depended on the system details, so that regions of small relative volumes are crossed out by relatively few lines, which affects the convergence of the calculated probabilities. A new routine (PIJM) was then created to incorporate a more efficient integration scheme considering each system region individually, minimizing convergence problems and reducing the number of neutron track lines required in the in-plane integrations for any given

  9. A comparison of policy and direct practice stakeholder perceptions of factors affecting evidence-based practice implementation using concept mapping.

    Green, Amy E; Aarons, Gregory A

    2011-09-07

    The goal of this study was to assess potential differences between administrators/policymakers and those involved in direct practice regarding factors believed to be barriers or facilitating factors to evidence-based practice (EBP) implementation in a large public mental health service system in the United States. Participants included mental health system county officials, agency directors, program managers, clinical staff, administrative staff, and consumers. As part of concept mapping procedures, brainstorming groups were conducted with each target group to identify specific factors believed to be barriers or facilitating factors to EBP implementation in a large public mental health system. Statements were sorted by similarity and rated by each participant in regard to their perceived importance and changeability. Multidimensional scaling, cluster analysis, descriptive statistics and t-tests were used to analyze the data. A total of 105 statements were distilled into 14 clusters using concept-mapping procedures. Perceptions of importance of factors affecting EBP implementation varied between the two groups, with those involved in direct practice assigning significantly higher ratings to the importance of Clinical Perceptions and the impact of EBP implementation on clinical practice. Consistent with previous studies, financial concerns (costs, funding) were rated among the most important and least likely to change by both groups. EBP implementation is a complex process, and different stakeholders may hold different opinions regarding the relative importance of the impact of EBP implementation. Implementation efforts must include input from stakeholders at multiple levels to bring divergent and convergent perspectives to light.

  10. External and internal factors influencing self-directed online learning of physiotherapy undergraduate students in Sweden: a qualitative study.

    Hammarlund, Catharina Sjödahl; Nilsson, Maria H; Gummesson, Christina

    2015-01-01

    Online courses have become common in health sciences education. This learning environment can be designed using different approaches to support student learning. To further develop online environment, it is important to understand how students perceive working and learning online. The aim of this study is to identify aspects influencing students' learning processes and their adaptation to self-directed learning online. Thirty-four physiotherapy students with a mean age of 25 years (range, 21 to 34 years) participated. Qualitative content analysis and triangulation was used when investigating the students' self-reflections, written during a five week self-directed, problem-oriented online course. Two categories emerged: 'the influence of the structured framework' and 'communication and interaction with teachers and peers.' The learning processes were influenced by external factors, e.g., a clear structure including a transparent alignment of assignments and assessment. Important challenges to over-come were primarily internal factors, e.g., low self-efficacy, difficulties to plan the work effectively and adapting to a new environment. The analyses reflected important perspectives targeting areas which enable further course development. The influences of external and internal factors on learning strategies and self-efficacy are important aspects to consider when designing online courses. Factors such as pedagogical design, clarity of purpose, goals, and guidelines were important as well as continuous opportunities for communication and collaboration. Further studies are needed to understand and scaffold the motivational factors among students with low self-efficacy.

  11. Directional variance adjustment: bias reduction in covariance matrices based on factor analysis with an application to portfolio optimization.

    Daniel Bartz

    Full Text Available Robust and reliable covariance estimates play a decisive role in financial and many other applications. An important class of estimators is based on factor models. Here, we show by extensive Monte Carlo simulations that covariance matrices derived from the statistical Factor Analysis model exhibit a systematic error, which is similar to the well-known systematic error of the spectrum of the sample covariance matrix. Moreover, we introduce the Directional Variance Adjustment (DVA algorithm, which diminishes the systematic error. In a thorough empirical study for the US, European, and Hong Kong stock market we show that our proposed method leads to improved portfolio allocation.

  12. Directional variance adjustment: bias reduction in covariance matrices based on factor analysis with an application to portfolio optimization.

    Bartz, Daniel; Hatrick, Kerr; Hesse, Christian W; Müller, Klaus-Robert; Lemm, Steven

    2013-01-01

    Robust and reliable covariance estimates play a decisive role in financial and many other applications. An important class of estimators is based on factor models. Here, we show by extensive Monte Carlo simulations that covariance matrices derived from the statistical Factor Analysis model exhibit a systematic error, which is similar to the well-known systematic error of the spectrum of the sample covariance matrix. Moreover, we introduce the Directional Variance Adjustment (DVA) algorithm, which diminishes the systematic error. In a thorough empirical study for the US, European, and Hong Kong stock market we show that our proposed method leads to improved portfolio allocation.

  13. Directional Variance Adjustment: Bias Reduction in Covariance Matrices Based on Factor Analysis with an Application to Portfolio Optimization

    Bartz, Daniel; Hatrick, Kerr; Hesse, Christian W.; Müller, Klaus-Robert; Lemm, Steven

    2013-01-01

    Robust and reliable covariance estimates play a decisive role in financial and many other applications. An important class of estimators is based on factor models. Here, we show by extensive Monte Carlo simulations that covariance matrices derived from the statistical Factor Analysis model exhibit a systematic error, which is similar to the well-known systematic error of the spectrum of the sample covariance matrix. Moreover, we introduce the Directional Variance Adjustment (DVA) algorithm, which diminishes the systematic error. In a thorough empirical study for the US, European, and Hong Kong stock market we show that our proposed method leads to improved portfolio allocation. PMID:23844016

  14. EZH2 regulates dental pulp inflammation by direct effect on inflammatory factors.

    Hui, Tianqian; A, Peng; Zhao, Yuan; Yang, Jing; Ye, Ling; Wang, Chenglin

    2018-01-01

    Pulpitis is a multi-factorial disease that could be caused by complex interactions between genetics, epigenetics and environmental factors. We aimed to evaluate the role of Enhancer of Zeste Homolog 2 (EZH2) in the inflammatory response of human dental pulp cells (HDPCs) and dental pulp tissues. The expressions of inflammatory cytokines in HDPCs treated by EZH2 complex or EZH2 siRNA with or without rhTNF-α were examined by quantitative real-time polymerase chain reaction (q-PCR). The levels of secreted inflammatory cytokines including IL-6, IL-8, IL-15, CCL2 and CXCL12 in culture supernatants were measured by Luminex assay. In rat pulpitis model, the effects of EZH2 on dental pulp tissues were verified by histology. We invested the mechanisms of the effect of EZH2 on the inflammatory factors by ChIP assay. EZH2 down-regulation inhibited the expression of inflammatory factors, including IL-6, IL-8, IL-15, CCL2 and CXCL12 in HDPCs. EZH2 complex promoted the expression and secretion of these inflammatory factors in HDPCs, while EZH2 silencing could attenuate the promotion of inflammatory factors that were induced by rhTNF-α. In pulpitis models of rats, EZH2 down-regulation inhibited the inflammatory process of dental pulp while EZH2 complex showed no significant facilitation of pulpal inflammation. In addition, EZH2 could bind on the promoters of IL-6, IL-8 and CCL2, but not IL-15 and CXCL12, to affect the transcription of these proinflammatory cytokines. In HDPCs, EZH2 could induce inflammation, while EZH2 down-regulation could attenuate the inflammatory responses. EZH2 plays an important role in this inflammatory process of dental pulp. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Imaging analysis of nuclear antiviral factors through direct detection of incoming adenovirus genome complexes

    Komatsu, Tetsuro [Microbiologie Fondamentale et Pathogénicité, MFP CNRS UMR 5234, Université de Bordeaux, Bordeaux 33076 (France); Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575 (Japan); Will, Hans [Department of Tumor Biology, University Hospital Hamburg-Eppendorf, 20246 Hamburg (Germany); Nagata, Kyosuke [Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575 (Japan); Wodrich, Harald, E-mail: harald.wodrich@u-bordeaux.fr [Microbiologie Fondamentale et Pathogénicité, MFP CNRS UMR 5234, Université de Bordeaux, Bordeaux 33076 (France)

    2016-04-22

    Recent studies involving several viral systems have highlighted the importance of cellular intrinsic defense mechanisms through nuclear antiviral proteins that restrict viral propagation. These factors include among others components of PML nuclear bodies, the nuclear DNA sensor IFI16, and a potential restriction factor PHF13/SPOC1. For several nuclear replicating DNA viruses, it was shown that these factors sense and target viral genomes immediately upon nuclear import. In contrast to the anticipated view, we recently found that incoming adenoviral genomes are not targeted by PML nuclear bodies. Here we further explored cellular responses against adenoviral infection by focusing on specific conditions as well as additional nuclear antiviral factors. In line with our previous findings, we show that neither interferon treatment nor the use of specific isoforms of PML nuclear body components results in co-localization between incoming adenoviral genomes and the subnuclear domains. Furthermore, our imaging analyses indicated that neither IFI16 nor PHF13/SPOC1 are likely to target incoming adenoviral genomes. Thus our findings suggest that incoming adenoviral genomes may be able to escape from a large repertoire of nuclear antiviral mechanisms, providing a rationale for the efficient initiation of lytic replication cycle. - Highlights: • Host nuclear antiviral factors were analyzed upon adenovirus genome delivery. • Interferon treatments fail to permit PML nuclear bodies to target adenoviral genomes. • Neither Sp100A nor B targets adenoviral genomes despite potentially opposite roles. • The nuclear DNA sensor IFI16 does not target incoming adenoviral genomes. • PHF13/SPOC1 targets neither incoming adenoviral genomes nor genome-bound protein VII.

  16. Imaging analysis of nuclear antiviral factors through direct detection of incoming adenovirus genome complexes

    Komatsu, Tetsuro; Will, Hans; Nagata, Kyosuke; Wodrich, Harald

    2016-01-01

    Recent studies involving several viral systems have highlighted the importance of cellular intrinsic defense mechanisms through nuclear antiviral proteins that restrict viral propagation. These factors include among others components of PML nuclear bodies, the nuclear DNA sensor IFI16, and a potential restriction factor PHF13/SPOC1. For several nuclear replicating DNA viruses, it was shown that these factors sense and target viral genomes immediately upon nuclear import. In contrast to the anticipated view, we recently found that incoming adenoviral genomes are not targeted by PML nuclear bodies. Here we further explored cellular responses against adenoviral infection by focusing on specific conditions as well as additional nuclear antiviral factors. In line with our previous findings, we show that neither interferon treatment nor the use of specific isoforms of PML nuclear body components results in co-localization between incoming adenoviral genomes and the subnuclear domains. Furthermore, our imaging analyses indicated that neither IFI16 nor PHF13/SPOC1 are likely to target incoming adenoviral genomes. Thus our findings suggest that incoming adenoviral genomes may be able to escape from a large repertoire of nuclear antiviral mechanisms, providing a rationale for the efficient initiation of lytic replication cycle. - Highlights: • Host nuclear antiviral factors were analyzed upon adenovirus genome delivery. • Interferon treatments fail to permit PML nuclear bodies to target adenoviral genomes. • Neither Sp100A nor B targets adenoviral genomes despite potentially opposite roles. • The nuclear DNA sensor IFI16 does not target incoming adenoviral genomes. • PHF13/SPOC1 targets neither incoming adenoviral genomes nor genome-bound protein VII.

  17. The Transcription Factor STAT6 Mediates Direct Repression of Inflammatory Enhancers and Limits Activation of Alternatively Polarized Macrophages

    Czimmerer, Zsolt; Daniel, Bence; Horvath, Attila; Rückerl, Dominik; Nagy, Gergely; Kiss, Mate; Peloquin, Matthew; Budai, Marietta M.; Cuaranta-Monroy, Ixchelt; Simandi, Zoltan; Steiner, Laszlo; Nagy, Bela; Poliska, Szilard; Banko, Csaba; Bacso, Zsolt

    2018-01-01

    Summary The molecular basis of signal-dependent transcriptional activation has been extensively studied in macrophage polarization, but our understanding remains limited regarding the molecular determinants of repression. Here we show that IL-4-activated STAT6 transcription factor is required for the direct transcriptional repression of a large number of genes during in vitro and in vivo alternative macrophage polarization. Repression results in decreased lineage-determining transcription fac...

  18. The Research of Self-Management Team and Superior-Direction Team in Team Learning Influential Factors

    Zhang Wei

    2013-01-01

    Team learning is a cure for bureaucracy; it facilitates team innovation and team performance. But team learning occurs only when necessary conditions were met. This research focused on differences of team learning influential factors between self-management team and superior-direction team. Four variables were chosen as predictors of team learning though literature review and pilot interview. The 4 variables are team motivation, team trust, team conflict and team leadership. Selected 54 self ...

  19. The Self-Rating Scale of Self-Directed Learning (SRSSDL): a factor analysis of the Italian version.

    Cadorin, Lucia; Bortoluzzi, Guido; Palese, Alvisa

    2013-12-01

    The development of self-directed learning (SDL) is a growing priority among nurses and other health care workers: they need to be prepared in order for their university education to be effective and relevant to their lifelong learning. To learn in a self-directed manner, it is necessary to develop an awareness of one's ability to self-learn and then to implement appropriate and effective strategies; progress must be assessed using validated measurement tools. The aim of this study was to examine the factor structure of the Italian version of the Self-Rating Scale of Self-directed Learning (SRSSDL(Ita)), and to provide evidence of its validity. A cross-sectional design was undertaken. Given that the instrument is composed of 60 items, a total of 600 to 900 participants were targeted. In addition, according to the theoretical assumption that self-directed learning - as a crucial component of lifelong learning - is a measurable skill that is developed across the individual's professional life, a maximum variation sample was examined. Therefore, 847 participants were involved, including 453 nurses, 141 radiology technicians, 182 nursing students and 68 radiology technician students. Principal component analysis and factor analysis were performed. The Italian version of the SRSSDL Scale consists of 40 items composed of eight factors: Awareness (α=0.805), Attitudes (α=0.778), Motivation (α=0.789), Learning Strategies (α=0.789), Learning Methods (α=0.781), Learning Activities (α=0.676), Interpersonal Skills (α=0.684), and Constructing Knowledge (α=0.732). The SRSSDLIta consists of 40 items across eight factors. The shorter Italian version might reduce the time needed to complete, thereby making the tool faster and easier to use. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Directing factors affecting the synthesis of a MFI-type zeolite

    Vinaches, P.; Pergher, S.B.C. [Universidade Federal de Rio Grande do Norte (UFRN), RN (Brazil); Lopes, C.W. [Institute of Chemical Technology, Mumbai (India); Gomez-Hortiguela, L. [Instituto de Catalisis y Petroleoquimica, Madrid (Spain); Finger, P.H.; Silva, B.A. da; Dallago, R.M.; Mignoni, M.L. [Universidade Regional Integrada do Alto Uruguai e das Missoes (URI), Erechim, RS (Brazil)

    2016-07-01

    Full text: Zeolites are crystalline tectosilicates constituted by (TO4) tetrahedra connected through the oxygens of their vertices. The importance of these materials is that their properties differ, due to their variable compositions and structures, leading to the possibility of applying them into different industries, for example, as catalyst in petroleum industry or sensors in quality control. One of the big questions in this area is about the understanding of the chemistry that directs to one or another type of zeolite. Another important question is the search of new zeolitic structures for new applications. One approach to answer both is the study of the structure-directing agents, which are inorganic or organic molecules used in the synthesis of zeolites. New and already-used molecules have been studied within different synthesis conditions and different techniques, as characterization or computational studies. And several attempts of rationalization were and, still, will be performed. In this research, an imidazolium-based compound was studied in hydrothermal zeolite synthesis as organic structure-directing agent (OSDA). The products were obtained with Si/Al or Si/(Al+Zn) compositions, proved by ICP data. X-ray diffractograms showed two different zeolitic types: MFI and TON. It was observed that when Zn was present in the synthesis gel, pure MFI phases were able to appear. But in his absence, the products were all mixtures of MFI and TON zeolites. It was also possible to distinguish both phases by SEM micrographs, as MFI had brick-like shape and TON appeared as needles. The obtained zeolites were stable until 900°C minimum, as tested by a TG/DTG/DSC experiment. To prove that the chosen OSDA directed these structures, a CHN analysis was performed, resulting in integrity of the molecules inside the zeolitic pores and cavities. Finally, a rationale about the location and conformation of the OSDA was needed to understand these experimental results. So, it was

  1. International Trade and Foreign Direct Investment as Innovation Factors of the U.S. Economy

    Napiórkowski1 Tomasz M.

    2014-10-01

    Full Text Available The aim of this research is to asses the hypothesis that foreign direct investment (FDI and international trade have had a positive impact on innovation in one of the most significant economies in the world, the United States (U.S.. To do so, the author used annual data from 1995 to 2010 to build a set of econometric models. In each model, 11 in total the number of patent applications by U.S. residents is regressed on inward FDI stock, exports and imports of the economy as a collective, and in each of the 10 SITC groups separately.

  2. Directing factors affecting the synthesis of a MFI-type zeolite

    Vinaches, P.; Pergher, S.B.C.; Lopes, C.W.; Gomez-Hortiguela, L.; Finger, P.H.; Silva, B.A. da; Dallago, R.M.; Mignoni, M.L.

    2016-01-01

    Full text: Zeolites are crystalline tectosilicates constituted by (TO4) tetrahedra connected through the oxygens of their vertices. The importance of these materials is that their properties differ, due to their variable compositions and structures, leading to the possibility of applying them into different industries, for example, as catalyst in petroleum industry or sensors in quality control. One of the big questions in this area is about the understanding of the chemistry that directs to one or another type of zeolite. Another important question is the search of new zeolitic structures for new applications. One approach to answer both is the study of the structure-directing agents, which are inorganic or organic molecules used in the synthesis of zeolites. New and already-used molecules have been studied within different synthesis conditions and different techniques, as characterization or computational studies. And several attempts of rationalization were and, still, will be performed. In this research, an imidazolium-based compound was studied in hydrothermal zeolite synthesis as organic structure-directing agent (OSDA). The products were obtained with Si/Al or Si/(Al+Zn) compositions, proved by ICP data. X-ray diffractograms showed two different zeolitic types: MFI and TON. It was observed that when Zn was present in the synthesis gel, pure MFI phases were able to appear. But in his absence, the products were all mixtures of MFI and TON zeolites. It was also possible to distinguish both phases by SEM micrographs, as MFI had brick-like shape and TON appeared as needles. The obtained zeolites were stable until 900°C minimum, as tested by a TG/DTG/DSC experiment. To prove that the chosen OSDA directed these structures, a CHN analysis was performed, resulting in integrity of the molecules inside the zeolitic pores and cavities. Finally, a rationale about the location and conformation of the OSDA was needed to understand these experimental results. So, it was

  3. Elongation factor Ts directly facilitates the formation and disassembly of the Escherichia coli elongation factor Tu·GTP·aminoacyl-tRNA ternary complex.

    Burnett, Benjamin J; Altman, Roger B; Ferrao, Ryan; Alejo, Jose L; Kaur, Navdep; Kanji, Joshua; Blanchard, Scott C

    2013-05-10

    Aminoacyl-tRNA (aa-tRNA) enters the ribosome in a ternary complex with the G-protein elongation factor Tu (EF-Tu) and GTP. EF-Tu·GTP·aa-tRNA ternary complex formation and decay rates are accelerated in the presence of the nucleotide exchange factor elongation factor Ts (EF-Ts). EF-Ts directly facilitates the formation and disassociation of ternary complex. This system demonstrates a novel function of EF-Ts. Aminoacyl-tRNA enters the translating ribosome in a ternary complex with elongation factor Tu (EF-Tu) and GTP. Here, we describe bulk steady state and pre-steady state fluorescence methods that enabled us to quantitatively explore the kinetic features of Escherichia coli ternary complex formation and decay. The data obtained suggest that both processes are controlled by a nucleotide-dependent, rate-determining conformational change in EF-Tu. Unexpectedly, we found that this conformational change is accelerated by elongation factor Ts (EF-Ts), the guanosine nucleotide exchange factor for EF-Tu. Notably, EF-Ts attenuates the affinity of EF-Tu for GTP and destabilizes ternary complex in the presence of non-hydrolyzable GTP analogs. These results suggest that EF-Ts serves an unanticipated role in the cell of actively regulating the abundance and stability of ternary complex in a manner that contributes to rapid and faithful protein synthesis.

  4. Direct linkage of mitochondrial genome variation to risk factors for type 2 diabetes in conplastic strains

    Pravenec, Michal; Hyakukoku, M.; Houštěk, Josef; Zídek, Václav; Landa, Vladimír; Mlejnek, Petr; Mikšík, Ivan; Mothejzíková-Dudová, Kristýna; Pecina, Petr; Vrbacký, Marek; Drahota, Zdeněk; Vojtíšková, Alena; Mráček, Tomáš; Kazdová, L.; Oliyarnyk, O.; Wang, Ji.; Ho, Ch.; Qi, N.; Sugimoto, K.; Kurtz, T.

    2007-01-01

    Roč. 17, č. 9 (2007), s. 1319-1326 ISSN 1088-9051 R&D Projects: GA MŠk(CZ) 1M0520; GA ČR(CZ) GA301/06/0028; GA ČR GA303/07/0781 Grant - others:GA UK(CZ) 24/2005; GA UK(CZ) 26/2005; National Institutes of Health(US) HL35018; National Institutes of Health(US) HL56028; National Institutes of Health(US) HL63709; EURATOOLS(XE) LSHG-CT-2005-019015 Institutional research plan: CEZ:AV0Z50110509 Source of funding: R - rámcový projekt EK Keywords : mitochondrial genome * conplastic strains * risk factors for type 2 diabetes Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 11.224, year: 2007

  5. Qualitative ergonomics/human factors research in health care: Current state and future directions.

    Valdez, Rupa Sheth; McGuire, Kerry Margaret; Rivera, A Joy

    2017-07-01

    The objective of this systematic review was to understand the current state of Ergonomics/Human Factors (E/HF) qualitative research in health care and to draw implications for future efforts. This systematic review identified 98 qualitative research papers published between January 2005 and August 2015 in the seven journals endorsed by the International Ergonomics Association with an impact factor over 1.0. The majority of the studies were conducted in hospitals and outpatient clinics, were focused on the work of formal health care professionals, and were classified as cognitive or organizational ergonomics. Interviews, focus groups, and observations were the most prevalent forms of data collection. Triangulation and data archiving were the dominant approaches to ensuring rigor. Few studies employed a formal approach to qualitative inquiry. Significant opportunities remain to enhance the use of qualitative research to advance systems thinking within health care. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Increased mitochondrial mass in cells with functionally compromised mitochondria after exposure to both direct gamma radiation and bystander factors.

    Nugent, Sharon M E

    2007-07-01

    The bystander effect describes radiation-like damage in unirradiated cells either in the vicinity of irradiated cells or exposed to medium from irradiated cells. This study aimed to further characterize the poorly understood mitochondrial response to both direct irradiation and bystander factor(s) in human keratinocytes (HPV-G) and Chinese hamster ovarian cells (CHO-K1). Oxygen consumption rates were determined during periods of state 4, state 3 and uncoupled respiration. Mitochondrial mass was determined using MitoTracker FM. CHO-K1 cells showed significantly reduced oxygen consumption rates 4 h after exposure to 5 Gy direct radiation and irradiated cell conditioned medium (ICCM) and an apparent recovery 12-24 h later. The apparent recovery was likely due to the substantial increase in mitochondrial mass observed in these cells as soon as 4 h after exposure. HPV-G cells, on the other hand, showed a sustained increase in oxygen consumption rates after ICCM exposure and a transient increase 4 h after exposure to 5 Gy direct radiation. A significant increase in mitochondrial mass per HPV-G cell was observed after exposure to both direct radiation and ICCM. These findings are indicative of a stress response to mitochondrial dysfunction that increases the number of mitochondria per cell.

  7. Direct compression of chitosan: process and formulation factors to improve powder flow and tablet performance.

    Buys, Gerhard M; du Plessis, Lissinda H; Marais, Andries F; Kotze, Awie F; Hamman, Josias H

    2013-06-01

    Chitosan is a polymer derived from chitin that is widely available at relatively low cost, but due to compression challenges it has limited application for the production of direct compression tablets. The aim of this study was to use certain process and formulation variables to improve manufacturing of tablets containing chitosan as bulking agent. Chitosan particle size and flow properties were determined, which included bulk density, tapped density, compressibility and moisture uptake. The effect of process variables (i.e. compression force, punch depth, percentage compaction in a novel double fill compression process) and formulation variables (i.e. type of glidant, citric acid, pectin, coating with Eudragit S®) on chitosan tablet performance (i.e. mass variation, tensile strength, dissolution) was investigated. Moisture content of the chitosan powder, particle size and the inclusion of glidants had a pronounced effect on its flow ability. Varying the percentage compaction during the first cycle of a double fill compression process produced chitosan tablets with more acceptable tensile strength and dissolution rate properties. The inclusion of citric acid and pectin into the formulation significantly decreased the dissolution rate of isoniazid from the tablets due to gel formation. Direct compression of chitosan powder into tablets can be significantly improved by the investigated process and formulation variables as well as applying a double fill compression process.

  8. Foreign Direct Investment as a Determining Factor in Turkey’s Export Performance

    İ. Yaşar VURAL

    2011-05-01

    Full Text Available Export growth in Turkey has been much faster than GDP growth over the past few decades. Although in the last several years Turkey has been experiencing a constant growth of both exports and foreign direct investments as a result of marketoriented reform process, often associated with European Union (EU accession, the export performance as well as the inflow of foreign direct investment (FDI to Turkey is not satisfactory. Despite increasing inflows of FDI especially in recent years there has not been any attempt to assess its contribution to Turkey’s export performance—one of the channels through which FDI influences growth. Using annual data for 1982–2009 this paper investigates the determinants of Turkey’s export performance in a simultaneous equation framework (3SLS. Results suggest that the real appreciation of the Turkish Lira adversely affects Turkey’s export performance. Export supply is positively related to the domestic relative price of exports while the higher domestic demand reduces export supply. Foreign investment appears to have statistically significant impact on export performance as well as its coefficient has a positive sign. Also, the statistical adequacy of the models used is supported by the following diagnostic tests.

  9. ATAF1 transcription factor directly regulates abscisic acid biosynthetic gene NCED3 in Arabidopsis thaliana

    Jensen, Michael Krogh; Lindemose, Søren; De Masi, Federico

    2013-01-01

    ATAF1, an Arabidopsis thaliana NAC transcription factor, plays important roles in plant adaptation to environmental stress and development. To search for ATAF1 target genes, we used protein binding microarrays and chromatin-immunoprecipitation (ChIP). This identified T[A,C,G]CGT[A,G] and TT[A,C,G...... abscisic acid (ABA) phytohormone biosynthetic gene NCED3. ChIP-qPCR and expression analysis showed that ATAF1 binding to the NCED3 promoter correlated with increased NCED3 expression and ABA hormone levels. These results indicate that ATAF1 regulates ABA biosynthesis....

  10. Adipose Expression of Tumor Necrosis Factor-α: Direct Role in Obesity-Linked Insulin Resistance

    Hotamisligil, Gokhan S.; Shargill, Narinder S.; Spiegelman, Bruce M.

    1993-01-01

    Tumor necrosis factor-α (TNF-α) has been shown to have certain catabolic effects on fat cells and whole animals. An induction of TNF-α messenger RNA expression was observed in adipose tissue from four different rodent models of obesity and diabetes. TNF-α protein was also elevated locally and systemically. Neutralization of TNF-α in obese fa/fa rats caused a significant increase in the peripheral uptake of glucose in response to insulin. These results indicate a role for TNF-α in obesity and particularly in the insulin resistance and diabetes that often accompany obesity.

  11. Covalent growth factor tethering to direct neural stem cell differentiation and self-organization.

    Ham, Trevor R; Farrag, Mahmoud; Leipzig, Nic D

    2017-04-15

    Tethered growth factors offer exciting new possibilities for guiding stem cell behavior. However, many of the current methods present substantial drawbacks which can limit their application and confound results. In this work, we developed a new method for the site-specific covalent immobilization of azide-tagged growth factors and investigated its utility in a model system for guiding neural stem cell (NSC) behavior. An engineered interferon-γ (IFN-γ) fusion protein was tagged with an N-terminal azide group, and immobilized to two different dibenzocyclooctyne-functionalized biomimetic polysaccharides (chitosan and hyaluronan). We successfully immobilized azide-tagged IFN-γ under a wide variety of reaction conditions, both in solution and to bulk hydrogels. To understand the interplay between surface chemistry and protein immobilization, we cultured primary rat NSCs on both materials and showed pronounced biological effects. Expectedly, immobilized IFN-γ increased neuronal differentiation on both materials. Expression of other lineage markers varied depending on the material, suggesting that the interplay of surface chemistry and protein immobilization plays a large role in nuanced cell behavior. We also investigated the bioactivity of immobilized IFN-γ in a 3D environment in vivo and found that it sparked the robust formation of neural tube-like structures from encapsulated NSCs. These findings support a wide range of potential uses for this approach and provide further evidence that adult NSCs are capable of self-organization when exposed to the proper microenvironment. For stem cells to be used effectively in regenerative medicine applications, they must be provided with the appropriate cues and microenvironment so that they integrate with existing tissue. This study explores a new method for guiding stem cell behavior: covalent growth factor tethering. We found that adding an N-terminal azide-tag to interferon-γ enabled stable and robust Cu-free 'click

  12. Factors that affect micro-tooling features created by direct printing approach

    Kumbhani, Mayur N.

    Current market required faster pace production of smaller, better, and improved products in shorter amount of time. Traditional high-rate manufacturing process such as hot embossing, injection molding, compression molding, etc. use tooling to replicate feature on a products. Miniaturization of many product in the field of biomedical, electronics, optical, and microfluidic is occurring on a daily bases. There is a constant need to produce cheaper, and faster tooling, which can be utilize by existing manufacturing processes. Traditionally, in order to manufacture micron size tooling features processes such as micro-machining, Electrical Discharge Machining (EDM), etc. are utilized. Due to a higher difficulty to produce smaller size features, and longer production cycle time, various additive manufacturing approaches are proposed, e.g. selective laser sintering (SLS), inkjet printing (3DP), fused deposition modeling (FDM), etc. were proposed. Most of these approaches can produce net shaped products from different materials such as metal, ceramic, or polymers. Several attempts were made to produce tooling features using additive manufacturing approaches. Most of these produced tooling were not cost effective, and the life cycle of these tooling was reported short. In this research, a method to produce tooling features using direct printing approach, where highly filled feedstock was dispensed on a substrate. This research evaluated different natural binders, such as guar gum, xanthan gum, and sodium carboxymethyl cellulose (NaCMC) and their combinations were evaluated. The best binder combination was then use to evaluate effect of different metal (316L stainless steel (3 mum), 316 stainless steel (45 mum), and 304 stainless steel (45 mum)) particle size on feature quality. Finally, the effect of direct printing process variables such as dispensing tip internal diameter (500 mum, and 333 mum) at different printing speeds were evaluated.

  13. Factors affecting direction and strength of patient preferences for treatment of molar teeth with nonvital pulps.

    Vernazza, C R; Steele, J G; Whitworth, J M; Wildman, J R; Donaldson, C

    2015-12-01

    To elicit the factors affecting willingness to pay (WTP) values for the preferred options of participants for dealing with a molar tooth with a nonvital pulp, a common but difficult problem. A total of 503 patients were recruited from dental practices in the North East of England and interviewed. Their preferred treatment option for a molar tooth with a nonvital pulp (endodontics, extraction and various prosthetic restorative options) and WTP for this preferred option were elicited. Factors affecting preferred option and WTP were analysed using econometric modelling. Overall, 53% of the sample wished to save the tooth with a mean WTP of £373. The variance in WTP was high. Of those opting for extraction, the majority chose to leave a gap or have an implant. The preferred option was influenced by previous treatment experience. WTP was only influenced by having a low income. The high level of variance in WTP and its relatively unpredictable nature pose difficult questions for policy makers trying to ensure the delivery of an equitable service. For dentists, it is important not to make assumptions about patient preference and strength of preference when making decisions. Ideally, WTP values should be considered alongside effectiveness data, and those on costs, in policy making. © 2014 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  14. The need and direction of a human factors research program for the nuclear power industry

    Blackman, H.S.; Meyer, O.R.; Nelson, W.R.

    1986-01-01

    It is axiomatic that the need for a human factors program in the nuclear power industry must be based upon an examination of the process of nuclear energy production and the role that the human plays in this process. It has been pointed out by others that a large number of incidents in technology based industries can be attributed to human error, thereby demonstrating the need to understand the human in interacting with complex processes. But an emphasis upon human ''error'' is a negative approach and can be non-productive, particularly when the ''correct'' human action has not been clearly defined prior to the incident. Some industries have expended great resources in a positive attempt to maximize the performance of the human in critical roles, e.g., the man-in-space program, the commercial airlines industry, deep-sea exploration. Central to this issue of human factors in nuclear power is the question of the role that the human plays in reducing the risk of the total system. If, as in other areas of application, the nuclear industry can make substantial improvements in the performance of humans, one needs to know how much risk is really reduced

  15. Amperometric magnetoimmunoassay for the direct detection of tumor necrosis factor alpha biomarker in human serum

    Eletxigerra, U. [Micro-NanoFabrication Unit, IK4-Tekniker, Eibar (Spain); CIC microGUNE, Arrasate-Mondragón (Spain); Martinez-Perdiguero, J. [CIC microGUNE, Arrasate-Mondragón (Spain); Merino, S. [Micro-NanoFabrication Unit, IK4-Tekniker, Eibar (Spain); CIC microGUNE, Arrasate-Mondragón (Spain); Villalonga, R.; Pingarrón, J.M. [Departamento de Química Analítica, Facultad de CC. Químicas, Universidad Complutense de Madrid, Madrid (Spain); Campuzano, S., E-mail: susanacr@quim.ucm.es [Departamento de Química Analítica, Facultad de CC. Químicas, Universidad Complutense de Madrid, Madrid (Spain)

    2014-08-01

    Highlights: • Electrochemical magnetoimmunosensor for tumor necrosis factor alpha (TNFα) biomarker. • Sensitive and selective detection of TNFα in undiluted serum. • LOD achieved lower than the cut-off value established for relevant illnesses. • Useful and affordable alternative to ELISAs for TNFα determination in serum. - Abstract: An amperometric immunoassay for the determination of tumor necrosis factor alpha (TNFα) protein biomarker in human serum based on the use of magnetic microbeads (MBs) and disposable screen-printed carbon electrodes (SPCEs) has been developed. The specifically modified microbeads were magnetically captured on the working electrode surface and the amperometric responses were measured at −0.20 V (vs. Ag pseudo-reference electrode), upon addition of hydroquinone (HQ) as electron transfer mediator and H{sub 2}O{sub 2} as the enzyme substrate. After a thorough optimization of the assay, extremely low limits of detection were achieved: 2.0 pg mL{sup −1} (36 fM) and 5.8 pg mL{sup −1} (105 fM) for standard solutions and spiked human serum, respectively. The simplicity, robustness and this clinically interesting LOD proved the developed TNFα immunoassay as a good contender for real clinical application.

  16. Amperometric magnetoimmunoassay for the direct detection of tumor necrosis factor alpha biomarker in human serum

    Eletxigerra, U.; Martinez-Perdiguero, J.; Merino, S.; Villalonga, R.; Pingarrón, J.M.; Campuzano, S.

    2014-01-01

    Highlights: • Electrochemical magnetoimmunosensor for tumor necrosis factor alpha (TNFα) biomarker. • Sensitive and selective detection of TNFα in undiluted serum. • LOD achieved lower than the cut-off value established for relevant illnesses. • Useful and affordable alternative to ELISAs for TNFα determination in serum. - Abstract: An amperometric immunoassay for the determination of tumor necrosis factor alpha (TNFα) protein biomarker in human serum based on the use of magnetic microbeads (MBs) and disposable screen-printed carbon electrodes (SPCEs) has been developed. The specifically modified microbeads were magnetically captured on the working electrode surface and the amperometric responses were measured at −0.20 V (vs. Ag pseudo-reference electrode), upon addition of hydroquinone (HQ) as electron transfer mediator and H 2 O 2 as the enzyme substrate. After a thorough optimization of the assay, extremely low limits of detection were achieved: 2.0 pg mL −1 (36 fM) and 5.8 pg mL −1 (105 fM) for standard solutions and spiked human serum, respectively. The simplicity, robustness and this clinically interesting LOD proved the developed TNFα immunoassay as a good contender for real clinical application

  17. Factors related to self-directed learning readiness of students in health professional programs: A scoping review.

    Slater, Craig E; Cusick, Anne

    2017-05-01

    Academic and professional drivers have stimulated interest in self-directed learning of students in pre-certification health professional programs. Particular attention has focussed on factors which may influence a students' readiness for self-directed learning. A five stage structured scoping review of published literature was conducted to identify measures of self-directed learning readiness used with students in pre-certification health professional programs and those factors that have been investigated as potential determinants. Relevant articles were identified in six databases using key search terms and a search strategy. Two independent reviewers used criteria to cull irrelevant sources. Articles which met eligibility criteria were charted. The final analysis included 49 articles conducted in nursing, medicine, physiotherapy, pharmacy, occupational therapy and dentistry cohorts. Twenty-one potential determinants had been investigated with gender, year level, age program delivery and previous education level the most common. Self-directed learning readiness has been of interest globally, mostly in medicine and nursing, and studies have nearly exclusively used one of two instruments. There is nascent evidence that age, year level and previous education level may have positive influence. These factors have in common the passing of time and may in fact be proxy for more encompassing developmental or social constructs. Further research is needed particularly in the allied health professions where there is limited research in very few disciplines. Studies in interprofessional contexts may be an efficient approach to increasing the knowledge base. Further work is also warranted to determine appropriate use of the two instruments across the range of health disciplines. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Validation of cosmogenic nuclide production rate scaling factors through direct measurement

    Graham, I.J. E-mail: i.graham@gns.cri.nz; Barry, B.J.; Ditchburn, R.G.; Whitehead, N.E

    2000-10-01

    {sup 7}Be produced in water targets by nuclear interactions of cosmic rays has been measured to determine cosmogenic nuclide production rates as a function of altitude (sea level to 2 km) and geomagnetic latitude (20-79 deg. S). Relative intensities of low energy cosmic ray neutrons have at the same time been measured using neutron monitors based on IGY/NM-64 designed to efficiently thermalise ca. 2-30 MeV neutrons. The research is on-going and we present here preliminary data from the past two years. Water target and neutron flux results are in general agreement, and are consistent with the altitude-dependent scaling factors of Lal [Earth Planet. Sci. Lett. 104 (1991) 4241]. Significant differences between the sea level, latitude-dependent neutron flux data and Lal's predictions are possibly related to the response function of the detector.

  19. Validation of cosmogenic nuclide production rate scaling factors through direct measurement

    Graham, I J; Ditchburn, R G; Whitehead, N E

    2000-01-01

    sup 7 Be produced in water targets by nuclear interactions of cosmic rays has been measured to determine cosmogenic nuclide production rates as a function of altitude (sea level to 2 km) and geomagnetic latitude (20-79 deg. S). Relative intensities of low energy cosmic ray neutrons have at the same time been measured using neutron monitors based on IGY/NM-64 designed to efficiently thermalise ca. 2-30 MeV neutrons. The research is on-going and we present here preliminary data from the past two years. Water target and neutron flux results are in general agreement, and are consistent with the altitude-dependent scaling factors of Lal [Earth Planet. Sci. Lett. 104 (1991) 4241]. Significant differences between the sea level, latitude-dependent neutron flux data and Lal's predictions are possibly related to the response function of the detector.

  20. Transcription Factor Networks Directing the Development, Function, and Evolution of Innate Lymphoid Effectors

    Kang, Joonsoo; Malhotra, Nidhi

    2015-01-01

    Mammalian lymphoid immunity is mediated by fast and slow responders to pathogens. Fast innate lymphocytes are active within hours after infections in mucosal tissues. Slow adaptive lymphocytes are conventional T and B cells with clonal antigen receptors that function days after pathogen exposure. A transcription factor (TF) regulatory network guiding early T cell development is at the core of effector function diversification in all innate lymphocytes, and the kinetics of immune responses is set by developmental programming. Operational units within the innate lymphoid system are not classified by the types of pathogen-sensing machineries but rather by discrete effector functions programmed by regulatory TF networks. Based on the evolutionary history of TFs of the regulatory networks, fast effectors likely arose earlier in the evolution of animals to fortify body barriers, and in mammals they often develop in fetal ontogeny prior to the establishment of fully competent adaptive immunity. PMID:25650177

  1. Directed random walks and constraint programming reveal active pathways in hepatocyte growth factor signaling.

    Kittas, Aristotelis; Delobelle, Aurélien; Schmitt, Sabrina; Breuhahn, Kai; Guziolowski, Carito; Grabe, Niels

    2016-01-01

    An effective means to analyze mRNA expression data is to take advantage of established knowledge from pathway databases, using methods such as pathway-enrichment analyses. However, pathway databases are not case-specific and expression data could be used to infer gene-regulation patterns in the context of specific pathways. In addition, canonical pathways may not always describe the signaling mechanisms properly, because interactions can frequently occur between genes in different pathways. Relatively few methods have been proposed to date for generating and analyzing such networks, preserving the causality between gene interactions and reasoning over the qualitative logic of regulatory effects. We present an algorithm (MCWalk) integrated with a logic programming approach, to discover subgraphs in large-scale signaling networks by random walks in a fully automated pipeline. As an exemplary application, we uncover the signal transduction mechanisms in a gene interaction network describing hepatocyte growth factor-stimulated cell migration and proliferation from gene-expression measured with microarray and RT-qPCR using in-house perturbation experiments in a keratinocyte-fibroblast co-culture. The resulting subgraphs illustrate possible associations of hepatocyte growth factor receptor c-Met nodes, differentially expressed genes and cellular states. Using perturbation experiments and Answer Set programming, we are able to select those which are more consistent with the experimental data. We discover key regulator nodes by measuring the frequency with which they are traversed when connecting signaling between receptors and significantly regulated genes and predict their expression-shift consistently with the measured data. The Java implementation of MCWalk is publicly available under the MIT license at: https://bitbucket.org/akittas/biosubg. © 2015 FEBS.

  2. Long-term trends in direct and indirect household energy intensities: a factor in dematerialisation?

    Vringer, K.; Blok, K.

    2000-01-01

    Dematerialisation is assumed to contribute significantly to the alleviation of environmental problems. One of the possible causes of dematerialisation is a change in the consumption patterns of households. The aim of this article is to analyse changes in consumption patterns of Dutch households in the period between 1948 to 1996 in order to discover whether these changes have influenced the energy intensity of society. Due to the rise in consumption, the total household energy requirement per capita grew on average by 2.4 per cent per year over a period of 48 years (this figure ignores efficiency changes in the supplying sectors). In the same period the total energy intensity of households fluctuated but on average changed from 5.6 to 6.3 MJ/NLG, an increase of 0.25 per cent per year. If we exclude the direct energy consumption we find a slight decline in the indirect energy intensity, namely from 3.8 to 3.6 MJ/NLG ( - 0.14 per cent per year). No significant trends to a lower energy intensity are found and there is no indication of dematerialisation of the consumption patterns. If governments pursue a policy of sustainable development they have to take into account the fact that dematerialisation of the consumption pattern does not seem to be an autonomous process. (author)

  3. The Composition Effect of Macroeconomic Factors on Foreign Direct Investment in Selected SAARC Countries

    Mehwish MALIK

    2014-06-01

    Full Text Available The objective of the study is to investigate the most promising economic variables i.e., foreign direct investment (FDI, exports and financial development on economic growth in selected South Asian Association of Regional Co-corporation (SAARC countries. In addition, this study argued that whether FDI, Exports and financial development fosters or hinder economic growth in SAARC countries, for this purpose, panel data set of selected five SAARC countries namely, Bangladesh, India, Nepal, Pakistan and Srilanka considered for empirical consideration over a period of 1975 to 2011. By using two-stage least square (2SLSL technique, empirical evidence on the effects of FDI, exports and financial development on economic growth is mix in terms of apriori expectations. In case of Bangladesh, exports and broad money supply (M2 is the positive and significant contributor to increase economic growth, whereas, M2 increases India’s GDP. FDI is the only significant contributor to increase Pakistan’s economic growth. In case of Nepal and Srilanka, broad money supply increases economic growth, whereas, due to high dependency on imports, exports could not considerably increases economic growth in those regions.

  4. Sarcopenia and its relationship with osteoarthritis: risk factor or direct consequence?

    Papalia, R; Zampogna, B; Torre, G; Lanotte, A; Vasta, S; Albo, E; Tecame, A; Denaro, V

    2014-06-01

    The aim of this review is to evaluate the clinical role of sarcopenia in patients affected by osteoarthritis (OA) of major joints. An online database research was performed, in order to retrieve all articles investigating the relationship between sarcopenia and OA. No peer-reviewed journal was excluded. Papers in English, French, Spanish and Italian language were considered. After consulting the full-text article, five studies have been included in the review. Of the five studies included, four are prospective studies and only one is a cross-sectional study which retrieved data retrospectively. A total of 4,231 patients, presenting a mean age of 62.0 years, were studied. Three studies evaluated only female subjects. Weight, height and body mass index were reported in all the articles. Knee OA has been assessed using the Kellgren-Lawrence grading system and the American college of rheumatology criteria. Alterations of the lean body mass on body weight ratio have been reported to be as a significant predictive parameter in two studies. Relationship between radiographic OA and an increase in the leg lean mass has been observed in one study. We cannot support neither the thesis of a direct effect of sarcopenia on OA development nor the opposite relation, because the up-to-date literature lacks basic science studies concerning these topics. The absence of clinical studies regarding measurements and tools to compare sarcopenia and OA do not allow to definitely clarify this relationship.

  5. Validation of an instrument to measure tutor performance in promoting self-directed learning by using confirmatory factor analysis

    Genoveva Amador Fierros

    Full Text Available Objective.This work sought to validate and propose an instrument to measure the performance of tutors in promoting self-directed learning in students involved in processes of problem-based learning. Methods. Confirmatory factor analysis (CFA was applied to validate the instrument composed of 60 items and six factors (self-assessment of learning gaps within the United Nations specific context: self-assessment, reflexion, critical thinking, administration of information, group skills, using a sample of 207 students from a total of 279, which comprise the student population of the Faculty of Nursing at Universidad de Colima in Mexico. (2007. Results. The CFA results demonstrated that the instrument is acceptable to measure performance of tutors in promoting self-directed learning, given that all the indicators, variances, covariances, and thresholds are statistically significant. Conclusion. The instrument permits obtaining students' opinions on how much professors contribute for them to develop each of the 60 skills described in the scale. Lastly, the results could report if professors are placing more emphasis in some areas than in other areas they should address during the problem-based learning (PBL process, or if definitely their actions are removed from the premises of PBL, information that will be useful for school management in decision making on the direction of teaching as a whole.

  6. Novel direct factor Xa inhibitory compounds from Tenebrio molitor with anti-platelet aggregation activity.

    Lee, Wonhwa; Kim, Mi-Ae; Park, InWha; Hwang, Jae Sam; Na, MinKyun; Bae, Jong-Sup

    2017-11-01

    Tenebrio molitor is an edible insect that has antimicrobial, anticancer, and antihypertensive effects. The aim of this study was to identify the unreported bioactive compounds from T. molitor larvae with inhibitory activities against factor Xa (FXa) and platelet aggregation. Isolated compounds were evaluated for their anti-FXa and anti-platelet aggregation properties by monitoring clotting time, platelet aggregation, FXa activity, and thrombus formation. A diketopiperazine (1, cyclo( L -Pro- L -Tyr)) and a phenylethanoid (2, N-acetyltyramine) were isolated and inhibited the catalytic activity of FXa in a mixed inhibition model and inhibited platelet aggregation induced by adenosine diphosphate (ADP) and U46619. They inhibited ADP- and U46619-induced phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) and the expression of P-selectin and PAC-1 in platelets. They also improved the production of nitric oxide and inhibited the oversecretion of endothelin-1 compared to that of the ADP- or U46619-treated group. In an animal model of arterial and pulmonary thrombosis, the isolated compounds showed enhanced antithrombotic effects. They also elicited anticoagulant effects in mice. Compounds 1-2 inhibited ADP-, collagen-, or U46619-induced platelet aggregation and showed similar anti-thrombotic efficacy to rivaroxaban, a positive control. Therefore, 1-2 could serve as candidates and provide scaffolds for the development of new anti-FXa and anti-platelet drugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Transcription factors and plant response to drought stress: Current understanding and future directions

    Rohit Joshi

    2016-07-01

    Full Text Available Increasing vulnerability of plants to a variety of stresses such as drought, salt and extreme temperatures poses a global threat to sustained growth and productivity of major crops. Of these stresses, drought represents a considerable threat to plant growth and development. In view of this, developing staple food cultivars with improved drought tolerance emerges as the most sustainable solution towards improving crop productivity in a scenario of climate change. In parallel, unraveling the genetic architecture and the targeted identification of molecular networks using modern OMICS analyses, that can underpin drought tolerance mechanisms, is urgently required. Importantly, integrated studies intending to elucidate complex mechanisms can bridge the gap existing in our current knowledge about drought stress tolerance in plants. It is now well established that drought tolerance is regulated by several genes, including transcription factors (TFs that enable plants to withstand unfavorable conditions, and these remain potential genomic candidates for their wide application in crop breeding. These TFs represent the key molecular switches orchestrating the regulation of plant developmental processes in response to a variety of stresses. The current review aims to offer a deeper understanding of TFs engaged in regulating plant’s response under drought stress and to devise potential strategies to improve plant tolerance against drought.

  8. Efficient Direct Reprogramming of Mature Amniotic Cells into Endothelial Cells by ETS Factors and TGFβ Suppression

    Ginsberg, Michael; James, Daylon; Ding, Bi-Sen; Nolan, Daniel; Geng, Fuqiang; Butler, Jason M; Schachterle, William; Pulijaal, Venkat R; Mathew, Susan; Chasen, Stephen T; Xiang, Jenny; Rosenwaks, Zev; Shido, Koji; Elemento, Olivier; Rabbany, Sina Y; Rafii, Shahin

    2012-01-01

    ETS transcription factors ETV2, FLI1 and ERG1 specify pluripotent stem cells into endothelial cells (ECs). However, these ECs are unstable and drift towards non-vascular cell fates. We show that human mid-gestation c-Kit− lineage-committed amniotic cells (ACs) can be readily reprogrammed into induced vascular endothelial cells (iVECs). Transient ETV2 expression in ACs generated proliferative but immature iVECs, while co-expression with FLI1/ERG1 endowed iVECs with a vascular repertoire and morphology matching mature stable ECs. Brief TGFβ-inhibition functionalized VEGFR2 signaling, augmenting specification of ACs to iVECs. Genome-wide transcriptional analyses showed that iVECs are similar to adult ECs in which vascular-specific genes are turned on and non-vascular genes are silenced. Functionally, iVECs form long-lasting patent vasculature in Matrigel plugs and regenerating livers. Thus, short-term ETV2 expression and TGFβ-inhibition along with constitutive ERG1/FLI1 co-expression reprogram mature ACs into durable and functional iVECs with clinical-scale expansion potential. Public banking of HLA-typed iVECs would establish a vascular inventory for treatment of genetically diverse disorders. PMID:23084400

  9. Neuropeptide delivery to the brain: a von Willebrand factor signal peptide to direct neuropeptide secretion

    de Backer Marijke WA

    2010-08-01

    Full Text Available Abstract Background Multiple neuropeptides, sometimes with opposing functions, can be produced from one precursor gene. To study the roles of the different neuropeptides encoded by one large precursor we developed a method to overexpress minigenes and establish local secretion. Results We fused the signal peptide from the Von Willebrand Factor (VWF to a furin site followed by a processed form of the Agouti related protein (AgRP, AgRP83-132 or α-melanocyte stimulating hormone. In vitro, these minigenes were secreted and biologically active. Additionally, the proteins of the minigenes were not transported into projections of primary neurons, thereby ensuring local release. In vivo administration of VWF-AgRP83-132 , using an adeno-associated viral vector as a delivery vehicle, into the paraventricular hypothalamus increased body weight and food intake of these rats compared to rats which received a control vector. Conclusions This study demonstrated that removal of the N-terminal part of full length AgRP and addition of a VWF signal peptide is a successful strategy to deliver neuropeptide minigenes to the brain and establish local neuropeptide secretion.

  10. External and internal factors influencing self-directed online learning of physiotherapy undergraduate students in Sweden: a qualitative study

    Catharina Sjödahl Hammarlund

    2015-06-01

    Full Text Available Purpose: Online courses have become common in health sciences education. This learning environment can be designed using different approaches to support student learning. To further develop online environment, it is important to understand how students perceive working and learning online. The aim of this study is to identify aspects influencing students’ learning processes and their adaptation to self-directed learning online. Methods: Thirty-four physiotherapy students with a mean age of 25 years (range, 21 to 34 years participated. Qualitative content analysis and triangulation was used when investigating the students’ self-reflections, written during a five week self-directed, problem-oriented online course. Results: Two categories emerged: ‘the influence of the structured framework’ and ‘communication and interaction with teachers and peers.’ The learning processes were influenced by external factors, e.g., a clear structure including a transparent alignment of assignments and assessment. Important challenges to over-come were primarily internal factors, e.g., low self-efficacy, difficulties to plan the work effectively and adapting to a new environment. Conclusion: The analyses reflected important perspectives targeting areas which enable further course development. The influences of external and internal factors on learning strategies and self-efficacy are important aspects to consider when designing online courses. Factors such as pedagogical design, clarity of purpose, goals, and guidelines were important as well as continuous opportunities for communication and collaboration. Further studies are needed to understand and scaffold the motivational factors among students with low self-efficacy.

  11. Direct and Indirect Effects of Five Factor Personality and Gender on Depressive Symptoms Mediated by Perceived Stress.

    Kim, Song E; Kim, Han-Na; Cho, Juhee; Kwon, Min-Jung; Chang, Yoosoo; Ryu, Seungho; Shin, Hocheol; Kim, Hyung-Lae

    2016-01-01

    This study was designed to investigate associations among five factor personality traits, perceived stress, and depressive symptoms and to examine the roles of personality and perceived stress in the relationship between gender and depressive symptoms. The participants (N = 3,950) were part of a cohort study for health screening and examination at the Kangbuk Samsung Hospital. Personality was measured with the Revised NEO Personality Inventory (NEO-PI-R). Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). Perceived stress level was evaluated with a self-reported stress questionnaire developed for the Korea National Health and Nutrition Examination Survey. A higher degree of neuroticism and lower degrees of extraversion, agreeableness, and conscientiousness were significantly associated with greater perceived stress and depressive symptoms. Neuroticism and extraversion had significant direct and indirect effects (via stress as a mediator) on depressive symptoms in both genders. Agreeableness and conscientiousness had indirect effects on depression symptoms in both genders. Multiple mediation models were used to examine the mediational roles of each personality factor and perceived stress in the link between gender and depressive symptoms. Four of the personality factors (except openness) were significant mediators, along with stress, on the relationship between gender and depressive symptoms. Our findings suggest that the links between personality factors and depressive symptoms are mediated by perceived stress. As such, personality is an important factor to consider when examining the link between gender and depression.

  12. Direct and Indirect Effects of Five Factor Personality and Gender on Depressive Symptoms Mediated by Perceived Stress

    Kim, Song E.; Cho, Juhee; Kwon, Min-Jung; Chang, Yoosoo; Ryu, Seungho; Shin, Hocheol

    2016-01-01

    This study was designed to investigate associations among five factor personality traits, perceived stress, and depressive symptoms and to examine the roles of personality and perceived stress in the relationship between gender and depressive symptoms. The participants (N = 3,950) were part of a cohort study for health screening and examination at the Kangbuk Samsung Hospital. Personality was measured with the Revised NEO Personality Inventory (NEO-PI-R). Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). Perceived stress level was evaluated with a self-reported stress questionnaire developed for the Korea National Health and Nutrition Examination Survey. A higher degree of neuroticism and lower degrees of extraversion, agreeableness, and conscientiousness were significantly associated with greater perceived stress and depressive symptoms. Neuroticism and extraversion had significant direct and indirect effects (via stress as a mediator) on depressive symptoms in both genders. Agreeableness and conscientiousness had indirect effects on depression symptoms in both genders. Multiple mediation models were used to examine the mediational roles of each personality factor and perceived stress in the link between gender and depressive symptoms. Four of the personality factors (except openness) were significant mediators, along with stress, on the relationship between gender and depressive symptoms. Our findings suggest that the links between personality factors and depressive symptoms are mediated by perceived stress. As such, personality is an important factor to consider when examining the link between gender and depression. PMID:27120051

  13. EMT transcription factors snail and slug directly contribute to cisplatin resistance in ovarian cancer

    Haslehurst, Alexandria M; Weberpals, Johanne; Davey, Scott; Squire, Jeremy; Park, Paul C; Feilotter, Harriet; Koti, Madhuri; Dharsee, Moyez; Nuin, Paulo; Evans, Ken; Geraci, Joseph; Childs, Timothy; Chen, Jian; Li, Jieran

    2012-01-01

    The epithelial to mesenchymal transition (EMT) is a molecular process through which an epithelial cell undergoes transdifferentiation into a mesenchymal phenotype. The role of EMT in embryogenesis is well-characterized and increasing evidence suggests that elements of the transition may be important in other processes, including metastasis and drug resistance in various different cancers. Agilent 4 × 44 K whole human genome arrays and selected reaction monitoring mass spectrometry were used to investigate mRNA and protein expression in A2780 cisplatin sensitive and resistant cell lines. Invasion and migration were assessed using Boyden chamber assays. Gene knockdown of snail and slug was done using targeted siRNA. Clinical relevance of the EMT pathway was assessed in a cohort of primary ovarian tumours using data from Affymetrix GeneChip Human Genome U133 plus 2.0 arrays. Morphological and phenotypic hallmarks of EMT were identified in the chemoresistant cells. Subsequent gene expression profiling revealed upregulation of EMT-related transcription factors including snail, slug, twist2 and zeb2. Proteomic analysis demonstrated up regulation of Snail and Slug as well as the mesenchymal marker Vimentin, and down regulation of E-cadherin, an epithelial marker. By reducing expression of snail and slug, the mesenchymal phenotype was largely reversed and cells were resensitized to cisplatin. Finally, gene expression data from primary tumours mirrored the finding that an EMT-like pathway is activated in resistant tumours relative to sensitive tumours, suggesting that the involvement of this transition may not be limited to in vitro drug effects. This work strongly suggests that genes associated with EMT may play a significant role in cisplatin resistance in ovarian cancer, therefore potentially leading to the development of predictive biomarkers of drug response or novel therapeutic strategies for overcoming drug resistance

  14. EMT transcription factors snail and slug directly contribute to cisplatin resistance in ovarian cancer

    Haslehurst Alexandria M

    2012-03-01

    Full Text Available Abstract Background The epithelial to mesenchymal transition (EMT is a molecular process through which an epithelial cell undergoes transdifferentiation into a mesenchymal phenotype. The role of EMT in embryogenesis is well-characterized and increasing evidence suggests that elements of the transition may be important in other processes, including metastasis and drug resistance in various different cancers. Methods Agilent 4 × 44 K whole human genome arrays and selected reaction monitoring mass spectrometry were used to investigate mRNA and protein expression in A2780 cisplatin sensitive and resistant cell lines. Invasion and migration were assessed using Boyden chamber assays. Gene knockdown of snail and slug was done using targeted siRNA. Clinical relevance of the EMT pathway was assessed in a cohort of primary ovarian tumours using data from Affymetrix GeneChip Human Genome U133 plus 2.0 arrays. Results Morphological and phenotypic hallmarks of EMT were identified in the chemoresistant cells. Subsequent gene expression profiling revealed upregulation of EMT-related transcription factors including snail, slug, twist2 and zeb2. Proteomic analysis demonstrated up regulation of Snail and Slug as well as the mesenchymal marker Vimentin, and down regulation of E-cadherin, an epithelial marker. By reducing expression of snail and slug, the mesenchymal phenotype was largely reversed and cells were resensitized to cisplatin. Finally, gene expression data from primary tumours mirrored the finding that an EMT-like pathway is activated in resistant tumours relative to sensitive tumours, suggesting that the involvement of this transition may not be limited to in vitro drug effects. Conclusions This work strongly suggests that genes associated with EMT may play a significant role in cisplatin resistance in ovarian cancer, therefore potentially leading to the development of predictive biomarkers of drug response or novel therapeutic strategies for

  15. Direct transcriptional activation of BT genes by NLP transcription factors is a key component of the nitrate response in Arabidopsis.

    Sato, Takeo; Maekawa, Shugo; Konishi, Mineko; Yoshioka, Nozomi; Sasaki, Yuki; Maeda, Haruna; Ishida, Tetsuya; Kato, Yuki; Yamaguchi, Junji; Yanagisawa, Shuichi

    2017-01-29

    Nitrate modulates growth and development, functioning as a nutrient signal in plants. Although many changes in physiological processes in response to nitrate have been well characterized as nitrate responses, the molecular mechanisms underlying the nitrate response are not yet fully understood. Here, we show that NLP transcription factors, which are key regulators of the nitrate response, directly activate the nitrate-inducible expression of BT1 and BT2 encoding putative scaffold proteins with a plant-specific domain structure in Arabidopsis. Interestingly, the 35S promoter-driven expression of BT2 partially rescued growth inhibition caused by reductions in NLP activity in Arabidopsis. Furthermore, simultaneous disruption of BT1 and BT2 affected nitrate-dependent lateral root development. These results suggest that direct activation of BT1 and BT2 by NLP transcriptional activators is a key component of the molecular mechanism underlying the nitrate response in Arabidopsis. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. EEG source space analysis of the supervised factor analytic approach for the classification of multi-directional arm movement

    Shenoy Handiru, Vikram; Vinod, A. P.; Guan, Cuntai

    2017-08-01

    Objective. In electroencephalography (EEG)-based brain-computer interface (BCI) systems for motor control tasks the conventional practice is to decode motor intentions by using scalp EEG. However, scalp EEG only reveals certain limited information about the complex tasks of movement with a higher degree of freedom. Therefore, our objective is to investigate the effectiveness of source-space EEG in extracting relevant features that discriminate arm movement in multiple directions. Approach. We have proposed a novel feature extraction algorithm based on supervised factor analysis that models the data from source-space EEG. To this end, we computed the features from the source dipoles confined to Brodmann areas of interest (BA4a, BA4p and BA6). Further, we embedded class-wise labels of multi-direction (multi-class) source-space EEG to an unsupervised factor analysis to make it into a supervised learning method. Main Results. Our approach provided an average decoding accuracy of 71% for the classification of hand movement in four orthogonal directions, that is significantly higher (>10%) than the classification accuracy obtained using state-of-the-art spatial pattern features in sensor space. Also, the group analysis on the spectral characteristics of source-space EEG indicates that the slow cortical potentials from a set of cortical source dipoles reveal discriminative information regarding the movement parameter, direction. Significance. This study presents evidence that low-frequency components in the source space play an important role in movement kinematics, and thus it may lead to new strategies for BCI-based neurorehabilitation.

  17. New estimates of direct N2O emissions from Chinese croplands from 1980 to 2007 using localized emission factors

    F. S. Zhang

    2011-10-01

    Full Text Available Nitrous oxide (N2O is a long-lived greenhouse gas with a large radiation intensity and it is emitted mainly from agricultural land. Accurate estimates of total direct N2O emissions from croplands on a country scale are important for global budgets of anthropogenic sources of N2O emissions and for the development of effective mitigation strategies. The objectives of this study were to re-estimate direct N2O emissions using localized emission factors and a database of measurements from Chinese croplands. We obtained N2O emission factors for paddy fields (0.41 ± 0.04% and uplands (1.05 ± 0.02% from a normalization process through cube root transformation of the original data. After comparing the results of normalization from the original values, Logarithmic and cube root transformations were used because the frequency of the original data was not normally distributed. Direct N2O emissions from Chinese croplands from 1980 to 2007 were estimated using IPCC (2006 guidelines combined with separate localized emission factors for paddy fields and upland areas. Direct N2O emissions from paddy fields showed little change, increasing by 10.5% with an annual rate of increase of 0.4% from 32.3 Gg N2O-N in 1980 to 35.7 Gg N2O-N in 2007. In contrast, emissions from uplands changed dramatically, increasing by 308% with an annual rate of 11% from 68.0 Gg N2O-N in 1980 to 278 Gg N2O-N in 2007. Total direct N2O emissions from Chinese croplands increased by 213% with an annual rate of 7.6% from 100 Gg N2O-N in 1980 to 313 Gg N2O-N in 2007, and were determined mainly by upland emissions (accounting for 67.8–88.6% of total emissions from 1980 to 2007. Synthetic N fertilizers played a major role in N2O emissions from agricultural land, and the magnitude of the contributions to total direct N2O emissions made by different amendments was synthetic N fertilizer > manure > straw, representing about 78, 15, and 6% of total direct N2O emissions, respectively, between

  18. Efficient small molecule bulk heterojunction solar cells with high fill factors via pyrene-directed molecular self-assembly

    Lee, Olivia P.; Yiu, Alan T.; Beaujuge, Pierre; Woo, Claire; Holcombe, Thomas W.; Millstone, Jill E.; Douglas, Jessica D.; Chen, Mark S.; Frechet, Jean

    2011-01-01

    Efficient organic photovoltaic (OPV) materials are constructed by attaching completely planar, symmetric end-groups to donor-acceptor electroactive small molecules. Appending C2-pyrene as the small molecule end-group to a diketopyrrolopyrrole core leads to materials with a tight, aligned crystal packing and favorable morphology dictated by π-π interactions, resulting in high power conversion efficiencies and high fill factors. The use of end-groups to direct molecular self-assembly is an effective strategy for designing high-performance small molecule OPV devices. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Efficient small molecule bulk heterojunction solar cells with high fill factors via pyrene-directed molecular self-assembly

    Lee, Olivia P.

    2011-10-21

    Efficient organic photovoltaic (OPV) materials are constructed by attaching completely planar, symmetric end-groups to donor-acceptor electroactive small molecules. Appending C2-pyrene as the small molecule end-group to a diketopyrrolopyrrole core leads to materials with a tight, aligned crystal packing and favorable morphology dictated by π-π interactions, resulting in high power conversion efficiencies and high fill factors. The use of end-groups to direct molecular self-assembly is an effective strategy for designing high-performance small molecule OPV devices. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Threshold stress intensity factor for delayed hydride cracking of a recrystallized N18 alloy plate along the rolling direction

    Sun Chao, E-mail: sunchaonpic@yahoo.com.c [National Key Laboratory for Nuclear Fuel and Materials, Nuclear Power Institute of China, P.O. Box 436, Chengdu 610041 (China); Tan Jun; Ying Shihao; Peng Qian [National Key Laboratory for Nuclear Fuel and Materials, Nuclear Power Institute of China, P.O. Box 436, Chengdu 610041 (China); Li Cong [Department of R and D, State Nuclear Power Technology Corporation Limited, Beijing (China)

    2010-11-15

    The objective of this study is to obtain the threshold stress intensity factor, K{sub IH}, for an initiation of delayed hydride cracking in a recrystallized N18 (Zr-Sn-Nb-Fe-Cr) alloy plate which was manufactured in China, gaseously charged with 60 ppm of hydrogen by weight. By using both the load increasing method and load drop method, the K{sub IH}'s along the rolling direction were investigated over a temperature range of 150-255 {sup o}C. The results showed that K{sub IH} along the rolling direction was found to be higher in the load increasing method than that in the load drop method. In the load increasing method, K{sub IH}'s of the N18 alloy plate appeared to be in the range of 31-32.5MPa{radical}(m), and K{sub IH} in the load drop method appeared to be in the range of 27.5-28.6MPa{radical}(m). This means that the N18 alloy plate has high tolerance for DHC initiation along the rolling direction. The texture of a N18 alloy plate was investigated using an X-ray diffraction and the K{sub IH} was discussed based on texture and analytically as a function of the tilting angle of hydride habit planes to the cracking plane.

  1. Threshold stress intensity factor for delayed hydride cracking of a recrystallized N18 alloy plate along the rolling direction

    Sun Chao; Tan Jun; Ying Shihao; Peng Qian; Li Cong

    2010-01-01

    The objective of this study is to obtain the threshold stress intensity factor, K IH , for an initiation of delayed hydride cracking in a recrystallized N18 (Zr-Sn-Nb-Fe-Cr) alloy plate which was manufactured in China, gaseously charged with 60 ppm of hydrogen by weight. By using both the load increasing method and load drop method, the K IH 's along the rolling direction were investigated over a temperature range of 150-255 o C. The results showed that K IH along the rolling direction was found to be higher in the load increasing method than that in the load drop method. In the load increasing method, K IH 's of the N18 alloy plate appeared to be in the range of 31-32.5MPa√(m), and K IH in the load drop method appeared to be in the range of 27.5-28.6MPa√(m). This means that the N18 alloy plate has high tolerance for DHC initiation along the rolling direction. The texture of a N18 alloy plate was investigated using an X-ray diffraction and the K IH was discussed based on texture and analytically as a function of the tilting angle of hydride habit planes to the cracking plane.

  2. Direct proteolytic cleavage of NLRP1B is necessary and sufficient for inflammasome activation by anthrax lethal factor.

    Joseph Chavarría-Smith

    Full Text Available Inflammasomes are multimeric protein complexes that respond to infection by recruitment and activation of the Caspase-1 (CASP1 protease. Activated CASP1 initiates immune defense by processing inflammatory cytokines and by causing a rapid and lytic cell death called pyroptosis. Inflammasome formation is orchestrated by members of the nucleotide-binding domain and leucine-rich repeat (NLR or AIM2-like receptor (ALR protein families. Certain NLRs and ALRs have been shown to function as direct receptors for specific microbial ligands, such as flagellin or DNA, but the molecular mechanism responsible for activation of most NLRs is still poorly understood. Here we determine the mechanism of activation of the NLRP1B inflammasome in mice. NLRP1B, and its ortholog in rats, is activated by the lethal factor (LF protease that is a key virulence factor secreted by Bacillus anthracis, the causative agent of anthrax. LF was recently shown to cleave mouse and rat NLRP1 directly. However, it is unclear if cleavage is sufficient for NLRP1 activation. Indeed, other LF-induced cellular events have been suggested to play a role in NLRP1B activation. Surprisingly, we show that direct cleavage of NLRP1B is sufficient to induce inflammasome activation in the absence of LF. Our results therefore rule out the need for other LF-dependent cellular effects in activation of NLRP1B. We therefore propose that NLRP1 functions primarily as a sensor of protease activity and thus could conceivably detect a broader spectrum of pathogens than just B. anthracis. By adding proteolytic cleavage to the previously established ligand-receptor mechanism of NLR activation, our results illustrate the remarkable flexibility with which the NLR architecture can be deployed for the purpose of pathogen-detection and host defense.

  3. Risk Factors for Falls in Older Adults with Lower Extremity Arthritis: A Conceptual Framework of Current Knowledge and Future Directions

    Gyurcsik, Nancy C.

    2012-01-01

    ABSTRACT Purpose: As the numbers of Canadians aged 65 years and over increases over the next 20 years, the prevalence of chronic conditions, including arthritis, will rise as will the number of falls. Although known fall-risk factors are associated with hip and knee osteoarthritis (OA), minimal research has evaluated fall and fracture risk and/or rates in this population. Thus, the purpose was to summarize research on fall and fracture risk in older adults with hip or knee OA and to develop a conceptual framework of fall-risk screening and assessment. Method: The International Classification of Functioning, Disability and Health, clinical practice guidelines for fall-risk screening, and a selected literature review were used. Results: Gaps exist in our knowledge of fall and fracture risk for this population. Muscle performance, balance, and mobility impairments have been identified, but little is known about whether personal and environmental contextual factors impact fall and fracture risk. Physical activity may help to prevent falls, but non-adherence is a problem. Conclusion: A need exists to assess fall risk in older adults with hip and knee OA. Promoting regular physical activity by focusing on disease- and activity-specific personal contextual factors may help direct treatment planning. PMID:23729967

  4. The factors impacted to local contractor from Foreign Direct Investment in advancing economic hub development in Iskandar Malaysia

    Syafiq Salim, Muhamad; Zakaria, Rozana; Aminuddin, Eeydzah; Hamid, Abdul Rahim Abdul; Abdullah, Redzuan; Shahzaib Khan, Jam

    2018-04-01

    Iskandar Malaysia is an advanced economic hub which is rapidly growing in the State of Johor. It has been an attractive place for Foreign Direct Investment (FDI) to invest. Many sectors are affected by the presence of FDI including the construction sector. This paper highlights the investigation on the effects of FDI to the local contractor in the Iskandar Malaysia Development. In this study, a questionnaire survey was carried out to gain the information on problems from internal factors and external factors that caused the limitation on involvement in FDI project by local contractors. 73 numbers of local contractor registered under CIDB in class G5, G6 and G7 are the respondents. Frequency analysis and Average Index Analysis are used for the results. This study provides the factors that impacted local construction players in Iskandar Malaysia Development. This study has portrayed that FDI plays a vital and significant role in spearheading the active involvement of local contractors in an urban sustainable development.

  5. Determination of dose correction factor for energy and directional dependence of the MOSFET dosimeter in an anthropomorphic phantom

    Cho, Sung Koo; Choi, Sang Hyoun; Kim, Chan Hyeong; Na, Seong Ho

    2006-01-01

    In recent years, the MOSFET dosimeter has been widely used in various medical applications such as dose verification in radiation therapeutic and diagnostic applications. The MOSFET dosimeter is, however, mainly made of silicon and shows some energy dependence for low energy photons. Therefore, the MOSFET dosimeter tends to overestimate the dose for low energy scattered photons in a phantom. This study determines the correction factors to compensate these dependences of the MOSFET dosimeter in ATOM phantom. For this, we first constructed a computational model of the ATOM phantom based on the 3D CT image data of the phantom. The voxel phantom was then implemented in a Monte Carlo simulation code and used to calculate the energy spectrum of the photon field at each of the MOSFET dosimeter locations in the phantom. Finally, the correction factors were calculated based on the energy spectrum of the photon field at the dosimeter locations and the pre-determined energy and directional dependence of the MOSFET dosimeter. Our result for 60 Co and 137 Cs photon fields shows that the correction factors are distributed within the range of 0.89 and 0.97 considering all the MOSFET dosimeter locations in the phantom

  6. A direct solver with reutilization of LU factorizations for h-adaptive finite element grids with point singularities

    Paszyński, Maciej R.

    2013-04-01

    This paper describes a direct solver algorithm for a sequence of finite element meshes that are h-refined towards one or several point singularities. For such a sequence of grids, the solver delivers linear computational cost O(N) in terms of CPU time and memory with respect to the number of unknowns N. The linear computational cost is achieved by utilizing the recursive structure provided by the sequence of h-adaptive grids with a special construction of the elimination tree that allows for reutilization of previously computed partial LU (or Cholesky) factorizations over the entire unrefined part of the computational mesh. The reutilization technique reduces the computational cost of the entire sequence of h-refined grids from O(N2) down to O(N). Theoretical estimates are illustrated with numerical results on two- and three-dimensional model problems exhibiting one or several point singularities. © 2013 Elsevier Ltd. All rights reserved.

  7. Tranexamic Acid Failed to Reverse the Anticoagulant Effect and Bleeding by an Oral Direct Factor Xa Inhibitor Edoxaban.

    Honda, Yuko; Furugohri, Taketoshi; Morishima, Yoshiyuki

    2018-01-01

    Agents to reverse the anticoagulant effect of edoxaban, an oral direct factor Xa inhibitor, would be desirable in emergency situations. The aim of this study is to determine the effect of tranexamic acid, an antifibrinolytic agent, on the anticoagulant activity and bleeding by edoxaban in rats. A supratherapeutic dose of edoxaban (3 mg/kg) was intravenously administered to rats. Three minutes after dosing, tranexamic acid (100 mg/kg) was given intravenously. Bleeding was induced by making an incision with a blade on the planta 8 min after edoxaban injection and bleeding time was measured. Prothrombin time (PT) and clot lysis were examined. A supratherapeutic dose of edoxaban significantly prolonged PT and bleeding time. Tranexamic acid did not affect PT or bleeding time prolonged by edoxaban, although tranexamic acid significantly inhibited clot lysis in rat plasma. An antifibrinolytic agent tranexamic acid failed to reverse the anticoagulant effect and bleeding by edoxaban in rats. © 2017 S. Karger AG, Basel.

  8. Direct astatination of a tumour-binding protein, human epidermal growth factor, using nido-carborane as a prosthetic group

    Sjoestroem, A.; Carlsson, J.; Lundqvist, H.; Koziorowski, J.

    2003-01-01

    A method for direct astatine labeling of proteins has been investigated. Binding sites for astatine were created by coupling of a nido-carborane derivative to a protein, the human epidermal growth factor (hEGF), using two different conjugation methods - by glutaraldehyde cross-linking or by introduction of sulfohydryl groups by Traut's reagent with subsequent linking of ANC-1 with m-maleimidobenzoyl-N-hydroxysulfosuccinimide ester. The conjugates were astatinated using the Chloramine-T method in high yield. The best labeling was obtained by the glutaraldehyde conjugate with an average yield of 68 ± 9%. In vitro stability tests indicated that the glutaraldehyde conjugated label was as stable as hEGF labeled with astatobenzoate. (author)

  9. A direct solver with reutilization of LU factorizations for h-adaptive finite element grids with point singularities

    Paszyński, Maciej R.; Calo, Victor M.; Pardo, David

    2013-01-01

    This paper describes a direct solver algorithm for a sequence of finite element meshes that are h-refined towards one or several point singularities. For such a sequence of grids, the solver delivers linear computational cost O(N) in terms of CPU time and memory with respect to the number of unknowns N. The linear computational cost is achieved by utilizing the recursive structure provided by the sequence of h-adaptive grids with a special construction of the elimination tree that allows for reutilization of previously computed partial LU (or Cholesky) factorizations over the entire unrefined part of the computational mesh. The reutilization technique reduces the computational cost of the entire sequence of h-refined grids from O(N2) down to O(N). Theoretical estimates are illustrated with numerical results on two- and three-dimensional model problems exhibiting one or several point singularities. © 2013 Elsevier Ltd. All rights reserved.

  10. AMP-Activated Protein Kinase Directly Phosphorylates and Destabilizes Hedgehog Pathway Transcription Factor GLI1 in Medulloblastoma

    Yen-Hsing Li

    2015-07-01

    Full Text Available The Hedgehog (Hh pathway regulates cell differentiation and proliferation during development by controlling the Gli transcription factors. Cell fate decisions and progression toward organ and tissue maturity must be coordinated, and how an energy sensor regulates the Hh pathway is not clear. AMP-activated protein kinase (AMPK is an important sensor of energy stores and controls protein synthesis and other energy-intensive processes. AMPK is directly responsive to intracellular AMP levels, inhibiting a wide range of cell activities if ATP is low and AMP is high. Thus, AMPK can affect development by influencing protein synthesis and other processes needed for growth and differentiation. Activation of AMPK reduces GLI1 protein levels and stability, thus blocking Sonic-hedgehog-induced transcriptional activity. AMPK phosphorylates GLI1 at serines 102 and 408 and threonine 1074. Mutation of these three sites into alanine prevents phosphorylation by AMPK. This leads to increased GLI1 protein stability, transcriptional activity, and oncogenic potency.

  11. A putative model of overeating and obesity based on brain-derived neurotrophic factor: direct and indirect effects.

    Ooi, Cara L; Kennedy, James L; Levitan, Robert D

    2012-08-01

    Increased food intake is a major contributor to the obesity epidemic in all age groups. Elucidating brain systems that drive overeating and that might serve as targets for novel prevention and treatment interventions is thus a high priority for obesity research. The authors consider 2 major pathways by which decreased activity of brain-derived neurotrophic factor (BDNF) may confer vulnerability to overeating and weight gain in an obesogenic environment. The first "direct" pathway focuses on the specific role of BDNF as a mediator of food intake control at brain areas rich in BDNF receptors, including the hypothalamus and hindbrain. It is proposed that low BDNF activity limited to this direct pathway may best explain overeating and obesity outside the context of major neuropsychiatric disturbance. A second "indirect" pathway considers the broad neurotrophic effects of BDNF on key monoamine systems that mediate mood dysregulation, impulsivity, and executive dysfunction as well as feeding behavior per se. Disruption in this pathway may best explain overeating and obesity in the context of various neuropsychiatric disturbances including mood disorders, attention-deficit disorder, and/or binge eating disorders. An integrative model that considers these potential roles of BDNF in promoting obesity is presented. The implications of this model for the early prevention and treatment of obesity are also considered.

  12. The astrophysical S-factor of the direct 18O(p, γ)19F capture by the ANC method

    Burjan, V.; Hons, Z.; Kroha, V.; Mrázek, J.; Piskoř, Š.; Mukhamedzhanov, A. M.; Trache, L.; Tribble, R. E.; La Cognata, M.; Lamia, L.; Pizzone, G. R.; Romano, S.; Spitaleri, C.; Tumino, A.

    2018-01-01

    We attempted to determine the astrophysical S-factor of the direct part of the 18O(p, γ)19F capture by the indirect method of asymptotic normalization coefficients (ANC). We measured the differential cross section of the transfer reaction 18O(3He, d)19F at a 3He energy of 24.6 MeV. The measurement was realized on the cyclotron of the NPI in Řež, Czech Republic, with the gas target consisting of the high purity 18O (99.9 %). The reaction products were measured by eight ΔE-E telescopes composed from thin and thick silicon surface-barrier detectors. The parameters of the optical model for the input channel were deduced by means of the code ECIS and the analysis of transfer reactions to 12 levels of the 19F nucleus up to 8.014 MeV was made by the code FRESCO. The deduced ANCs were then used to specify the direct contribution to the 18O(p, γ)19F capture process and were compared with the mutually different results of two works.

  13. A Nonnegative Latent Factor Model for Large-Scale Sparse Matrices in Recommender Systems via Alternating Direction Method.

    Luo, Xin; Zhou, MengChu; Li, Shuai; You, Zhuhong; Xia, Yunni; Zhu, Qingsheng

    2016-03-01

    Nonnegative matrix factorization (NMF)-based models possess fine representativeness of a target matrix, which is critically important in collaborative filtering (CF)-based recommender systems. However, current NMF-based CF recommenders suffer from the problem of high computational and storage complexity, as well as slow convergence rate, which prevents them from industrial usage in context of big data. To address these issues, this paper proposes an alternating direction method (ADM)-based nonnegative latent factor (ANLF) model. The main idea is to implement the ADM-based optimization with regard to each single feature, to obtain high convergence rate as well as low complexity. Both computational and storage costs of ANLF are linear with the size of given data in the target matrix, which ensures high efficiency when dealing with extremely sparse matrices usually seen in CF problems. As demonstrated by the experiments on large, real data sets, ANLF also ensures fast convergence and high prediction accuracy, as well as the maintenance of nonnegativity constraints. Moreover, it is simple and easy to implement for real applications of learning systems.

  14. Lack of Evidence for a Direct Interaction of Progranulin and Tumor Necrosis Factor Receptor-1 and Tumor Necrosis Factor Receptor-2 From Cellular Binding Studies

    Isabell Lang

    2018-04-01

    Full Text Available Progranulin (PGRN is a secreted anti-inflammatory protein which can be processed by neutrophil proteases to various granulins. It has been reported that at least a significant portion of the anti-inflammatory effects of PGRN is due to direct high affinity binding to tumor necrosis factor receptor-1 (TNFR1 and TNFR2 and inhibition of tumor necrosis factor (TNF-induced TNFR1/2 signaling. Two studies failed to reproduce the interaction of TNFR1 and TNFR2 with PGRN, but follow up reports speculated that this was due to varying experimental circumstances and/or the use of PGRN from different sources. However, even under consideration of these speculations, there is still a striking discrepancy in the literature between the concentrations of PGRN needed to inhibit TNF signaling and the concentrations required to block TNF binding to TNFR1 and TNFR2. While signaling events induced by 0.2–2 nM of TNF have been efficiently inhibited by low, near to equimolar concentrations (0.5–2.5 nM of PGRN in various studies, the reported inhibitory effects of PGRN on TNF-binding to TNFR1/2 required a huge excess of PGRN (100–1,000-fold. Therefore, we investigated the effect of PGRN on TNF binding to TNFR1 and TNFR2 in highly sensitive cellular binding studies. Unlabeled TNF inhibited >95% of the specific binding of a Gaussia princeps luciferase (GpL fusion protein of TNF to TNFR1 and TNFR2 and blocked binding of soluble GpL fusion proteins of TNFR1 and TNFR2 to membrane TNF expressing cells to >95%, too. Purified PGRN, however, showed in both assays no effect on TNF–TNFR1/2 interaction even when applied in huge excess. To rule out that tags and purification- or storage-related effects compromise the potential ability of PGRN to bind TNF receptors, we directly co-expressed PGRN, and as control TNF, in TNFR1- and TNFR2-expressing cells and looked for binding of GpL-TNF. While expression of TNF strongly inhibited binding of GpL-TNF to TNFR1/2, co

  15. Mapping the epitopes of a neutralizing antibody fragment directed against the lethal factor of Bacillus anthracis and cross-reacting with the homologous edema factor.

    Philippe Thullier

    Full Text Available The lethal toxin (LT of Bacillus anthracis, composed of the protective antigen (PA and the lethal factor (LF, plays an essential role in anthrax pathogenesis. PA also interacts with the edema factor (EF, 20% identity with LF to form the edema toxin (ET, which has a lesser role in anthrax pathogenesis. The first recombinant antibody fragment directed against LF was scFv 2LF; it neutralizes LT by blocking the interaction between PA and LF. Here, we report that scFv 2LF cross-reacts with EF and cross-neutralizes ET, and we present an in silico method taking advantage of this cross-reactivity to map the epitope of scFv 2LF on both LF and EF. This method identified five epitope candidates on LF, constituted of a total of 32 residues, which were tested experimentally by mutating the residues to alanine. This combined approach precisely identified the epitope of scFv 2LF on LF as five residues (H229, R230, Q234, L235 and Y236, of which three were missed by the consensus epitope candidate identified by pre-existing in silico methods. The homolog of this epitope on EF (H253, R254, E258, L259 and Y260 was experimentally confirmed to constitute the epitope of scFv 2LF on EF. Other inhibitors, including synthetic molecules, could be used to target these epitopes for therapeutic purposes. The in silico method presented here may be of more general interest.

  16. Sendai viroplexes for epidermal growth factor receptor-directed delivery of interleukin-12 and salmosin genes to cancer cells.

    Kim, Jung Seok; Kim, Min Woo; Jeong, Hwa Yeon; Kang, Seong Jae; Park, Sang Il; Lee, Yeon Kyung; Kim, Hong Sung; Kim, Keun Sik; Park, Yong Serk

    2016-07-01

    The effective delivery of therapeutic genes to target cells has been a fundamental goal in cancer gene therapy because of its advantages with respect to both safety and transfection efficiency. In the present, study we describe a tumor-directed gene delivery system that demonstrates remarkable efficacy in gene delivery and minimizes the off-target effects of gene transfection. The system consists of a well-verified cationic O,O'-dimyristyl-N-lysyl glutamate (DMKE), Sendai virus fusion (F) protein and hemagglutinin-neuraminidase (HN) protein, referred to as cationic Sendai F/HN virosomes. To achieve tumor-specific recognition, anti-epidermal growth factor (EGF) receptor antibody was coupled to the surface of the virosomes containing interleukin-12 (IL-12) and/or salmosin genes that have potent anti-angiogenetic functions. Among the virosomal formulations, the anti-EGF receptor (EGFR) viroplexes, prepared via complexation of plasmid DNA (pDNA) with cationic DMKE lipid, exhibited more efficient gene transfection to tumor cells over-expressing EGF receptors compared to the neutrally-charged anti-EGFR virosomes encapsulating pDNA. In addition, the anti-EGFR viroplexes with IL-12 and salmosin genes exhibited the most effective therapeutic efficacy in a mouse tumor model. Especially when combined with doxorubicin, transfection of the two genes via the anti-EGFR viroplexes exhibited an enhanced inhibitory effect on tumor growth and metastasis in lungs. The results of the present study suggest that anti-EGFR viroplexes can be utilized as an effective strategy for tumor-directed gene delivery. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  17. Soluble CD40 ligand directly alters glomerular permeability and may act as a circulating permeability factor in FSGS.

    Doublier, Sophie; Zennaro, Cristina; Musante, Luca; Spatola, Tiziana; Candiano, Giovanni; Bruschi, Maurizio; Besso, Luca; Cedrino, Massimo; Carraro, Michele; Ghiggeri, Gian Marco; Camussi, Giovanni; Lupia, Enrico

    2017-01-01

    CD40/CD40 ligand (CD40L) dyad, a co-stimulatory bi-molecular complex involved in the adaptive immune response, has also potent pro-inflammatory actions in haematopoietic and non-haematopoietic cells. We describe here a novel role for soluble CD40L (sCD40L) as modifier of glomerular permselectivity directly acting on glomerular epithelial cells (GECs). We found that stimulation of CD40, constitutively expressed on GEC cell membrane, by the sCD40L rapidly induced redistribution and loss of nephrin in GECs, and increased albumin permeability in isolated rat glomeruli. Pre-treatment with inhibitors of CD40-CD40L interaction completely prevented these effects. Furthermore, in vivo injection of sCD40L induced a significant reduction of nephrin and podocin expression in mouse glomeruli, although no significant increase of urine protein/creatinine ratio was observed after in vivo injection. The same effects were induced by plasma factors partially purified from post-transplant plasma exchange eluates of patients with focal segmental glomerulosclerosis (FSGS), and were blocked by CD40-CD40L inhibitors. Moreover, 17 and 34 kDa sCD40L isoforms were detected in the same plasmapheresis eluates by Western blotting. Finally, the levels of sCD40Lwere significantly increased in serum of children both with steroid-sensitive and steroid-resistant nephrotic syndrome (NS), and in adult patients with biopsy-proven FSGS, compared to healthy subjects, but neither in children with congenital NS nor in patients with membranous nephropathy. Our results demonstrate that sCD40L directly modifies nephrin and podocin distribution in GECs. Moreover, they suggest that sCD40L contained in plasmapheresis eluates from FSGS patients with post-transplant recurrence may contribute, presumably cooperating with other mediators, to FSGS pathogenesis by modulating glomerular permeability.

  18. Soluble CD40 ligand directly alters glomerular permeability and may act as a circulating permeability factor in FSGS.

    Sophie Doublier

    Full Text Available CD40/CD40 ligand (CD40L dyad, a co-stimulatory bi-molecular complex involved in the adaptive immune response, has also potent pro-inflammatory actions in haematopoietic and non-haematopoietic cells. We describe here a novel role for soluble CD40L (sCD40L as modifier of glomerular permselectivity directly acting on glomerular epithelial cells (GECs. We found that stimulation of CD40, constitutively expressed on GEC cell membrane, by the sCD40L rapidly induced redistribution and loss of nephrin in GECs, and increased albumin permeability in isolated rat glomeruli. Pre-treatment with inhibitors of CD40-CD40L interaction completely prevented these effects. Furthermore, in vivo injection of sCD40L induced a significant reduction of nephrin and podocin expression in mouse glomeruli, although no significant increase of urine protein/creatinine ratio was observed after in vivo injection. The same effects were induced by plasma factors partially purified from post-transplant plasma exchange eluates of patients with focal segmental glomerulosclerosis (FSGS, and were blocked by CD40-CD40L inhibitors. Moreover, 17 and 34 kDa sCD40L isoforms were detected in the same plasmapheresis eluates by Western blotting. Finally, the levels of sCD40Lwere significantly increased in serum of children both with steroid-sensitive and steroid-resistant nephrotic syndrome (NS, and in adult patients with biopsy-proven FSGS, compared to healthy subjects, but neither in children with congenital NS nor in patients with membranous nephropathy. Our results demonstrate that sCD40L directly modifies nephrin and podocin distribution in GECs. Moreover, they suggest that sCD40L contained in plasmapheresis eluates from FSGS patients with post-transplant recurrence may contribute, presumably cooperating with other mediators, to FSGS pathogenesis by modulating glomerular permeability.

  19. Factors affecting osteoarthritis patients' self-reported goal-directed drug information-seeking behaviors after exposure to direct-to-consumer advertising from physicians and the internet.

    Liu, Yifei; Farris, Karen B; Doucette, William R

    2011-10-01

    The objective of this study was to investigate appraisal of means (ie, self-efficacy, outcome expectancy, and affect) in predicting patients' goal-directed behaviors of direct-to-consumer advertising (DTCA)-prompted drug-information search from physicians and the internet. One thousand patients were randomly selected from a nationwide sample frame of 3000 osteoarthritis patients. A self-administered survey assessed exposure to DTCA, drug-information search as goal, self-efficacy, outcome expectancy, affect, and osteoarthritis pain. After 6 weeks, another survey measured the behavior of drug-information search for respondents to the first survey. Study subjects were those who were exposed to DTCA in the previous month, and who set drug-information search as their goal. For each information source, a multiple regression analysis was conducted in which drug-information search was the dependent variable, and self-efficacy, outcome expectancy, affect, and osteoarthritis pain were the independent variables. Among 454 patients who were exposed to DTCA, 174 patients set drug-information search as their goal and were the study subjects. The regression for physicians was not statistically significant. The regression for the internet was significant, accounting for 15% of behavior variance. Self-efficacy was a strong predictor of goal-directed drug-information search from the internet. Appraisal of means was useful to predict the goal-directed behavior of DTCA-prompted drug-information search from the internet. For patients who set drug-information search as a goal, actions to promote drug-information search from the internet need to focus on self-efficacy.

  20. Direct effect of plasma permeability factors from patients with idiopatic FSGS on nephrin and podocin expression in human podocytes.

    Doublier, Sophie; Musante, Luca; Lupia, Enrico; Candiano, Giovanni; Spatola, Tiziana; Caridi, Gianluca; Zennaro, Cristina; Carraro, Michele; Ghiggeri, Gian Marco; Camussi, Giovanni

    2005-07-01

    The presence of circulating plasma factors (PF) altering renal permeability to proteins has been previously described in patients with focal segmental glomerulosclerosis (FSGS). Since these patients show reduced nephrin and podocin expression at renal biopsy, we evaluated the effect of serum and PF from patients with FSGS on nephrin and podocin expression in human podocytes. We studied 7 sera from patients with steroid-resistant FSGS, 3 from patients with nephrotic syndrome caused by non-immune disease, and 6 from healthy subjects. PF was prepared from plasmapheresis eluates of 2 patients with post-transplant recurrence of FSGS. Purification procedure was based on protein A Sepharose chromatography and differential precipitation in ammonium sulphate. Nephrin and podocin expression was semi-quantitatively evaluated by immunofluorescence. We found that serum and PF from FSGS patients rapidly induced redistribution and loss of nephrin in podocytes. This effect was associated with cytoskeleton redistribution and inhibited by cytochalasin B and sodium azide. On the contrary, podocin expression was unchanged after incubation with serum and PF from FSGS patients for short periods, but markedly reduced at 24 h. Our results demonstrate that serum and PF from FSGS patients may directly affect nephrin and podocin in human podocytes, thus providing new insights into the mechanisms causing proteinuria in FSGS.

  1. Factors influencing consumers' attitudinal and behavioral responses to direct-to-consumer and over-the-counter drug advertising.

    Lee, Mina; Whitehill King, Karen; Reid, Leonard N

    2015-04-01

    Using a model developed from the research literature, the authors compared consumers' attitudinal and behavioral responses to direct-to-consumer prescription drug advertising (DCTA) and over-the-counter nonprescription drug advertising (OTCA) of drugs. Adults 18 years of age and older who had taken any prescription drugs in the past 6 months completed online survey questionnaires. Variables measured included demographics (age, gender, race, education, and income), health-related characteristics (health status, prescription and over-the-counter drug use, health consciousness, and involvement with prescription or over-the-counter drugs), perceived amount of attention and exposure to DTCA and OTCA, attitudinal outcomes (skepticism toward DTCA/OTCA and attitude toward DTCA/OTCA), and behavioral outcomes triggered by DTCA and OTCA. The findings indicate that exposure to drug advertising is one of the most significant predictors of attitudinal and behavioral outcomes. Some audience factors such as health status, involvement with drugs, health consciousness, drug use, income, and age also were differentially associated with consumer responses to drug advertising.

  2. Factors which influence directional coarsening of Gamma prime during creep in nickel-base superalloy single crystals

    Mackay, R.A.; Ebert, L.J.

    1984-01-01

    Changes in the morphology of the gamma prime precipitate were examined as a function of time during creep at 982 C in 001 oriented single crystals of a Ni-Al-Mo-Ta superalloy. In this alloy, which has a large negative misfit of -0.80 pct., the gamma prime particles link together during creep to form platelets, or rafts, which are aligned with their broad faces perpendicular to the applied tensile axis. The effects of initial microstructure and alloy composition of raft development and creep properties were investigated. Directional coarsening of gamma prime begins during primary creep and continues well after the onset of second state creep. The thickness of the rafts remains constant up through the onset of tertiary creep a clear indication of the stability of the finely-spaced gamma/gamma prime lamellar structure. The thickness of the rafts which formed was equal to the initial gamma prime size which was present prior to testing. The single crystals with the finest gamma prime size exhibited the longest creep lives, because the resultant rafted structure had a larger number of gamma/gamma prime interfaces per unit volume of material. Reducing the Mo content by only 0.73 wt. pct. increased the creep life by a factor of three, because the precipitation of a third phase was eliminated

  3. Selected Factors Determining Inward of Foreign Direct Investment in the Czech Regions in Years 2002 to 2012

    Ondřej Babuněk

    2017-09-01

    Full Text Available This study aims at the research of the influence of unemployment rate (Un, exchange rate of CZK/USD (Ex, inflation rate (Inf, expenditures on research and development (RaD, size of wages and environmental pollution on inward foreign direct investment (FDI into regions in the Czech Republic in the period 2002–2012. The study dealt with the whole period, then the pre-crisis and crisis period, altogether with the inclusion or elimination of Prague in or out of the group of Czech regions. Models without and with dynamic parameter were checked. For estimation of influence of the above mentioned parameters the fixed effects model, random effects model and pooled ordinary least squares (POLS were used. For dynamic model the generalized method of moments and POLS were applied. The results showed that Wage, appreciation of Ex and RaD positively determined the inflow of FDI to Czech regions and no negative determinant of inward FDI has been found. On the other hand, results of dynamic model imply that inward FDI in preceding year, appreciation of Ex, RaD have positive impact on inward FDI in current year. However, negative impact of Un and Inf on inward FDI were detected. Results of this research enable the policy makers or decision makers try to focus their attention on specific factors and eliminate to consume scarce funding.

  4. Epigenetic regulation of the transcription factor Foxa2 directs differential elafin expression in melanocytes and melanoma cells

    Yu, Kyung Sook [Therapeutic Antibody Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806 (Korea, Republic of); Jo, Ji Yoon; Kim, Su Jin [Therapeutic Antibody Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806 (Korea, Republic of); Department of Functional Genomics, University of Science and Technology, Daejeon 305-333 (Korea, Republic of); Lee, Yangsoon [Therapeutic Antibody Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806 (Korea, Republic of); Bae, Jong Hwan [NeoPharm Co. Ltd., Daejeon 305-510 (Korea, Republic of); Chung, Young-Hwa [Department of Cogno-Mechatronics Engineering, BK21 Nanofusion Technology Team, Pusan National University, Busan 609-736 (Korea, Republic of); Koh, Sang Seok, E-mail: sskoh@kribb.re.kr [Therapeutic Antibody Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806 (Korea, Republic of); Department of Functional Genomics, University of Science and Technology, Daejeon 305-333 (Korea, Republic of)

    2011-04-29

    Highlights: {yields} Elafin expression is epigenetically silenced in human melanoma cells. {yields} Foxa2 expression in melanoma cells is silenced by promoter hypermethylation. {yields} Foxa2 directs activation of the elafin promoter in vivo. {yields} Foxa2 expression induces apoptosis of melanoma cells via elafin re-expression. -- Abstract: Elafin, a serine protease inhibitor, induces the intrinsic apoptotic pathway in human melanoma cells, where its expression is transcriptionally silenced. However, it remains unknown how the elafin gene is repressed in melanoma cells. We here demonstrate that elafin expression is modulated via epigenetically regulated expression of the transcription factor Foxa2. Treatment of melanoma cells with a DNA methyltransferase inhibitor induced elafin expression, which was specifically responsible for reduced proliferation and increased apoptosis. Suppression of Foxa2 transcription, mediated by DNA hypermethylation in its promoter region, was released in melanoma cells upon treatment with the demethylating agent. Luciferase reporter assays indicated that the Foxa2 binding site in the elafin promoter was critical for the activation of the promoter. Chromatin immunoprecipitation assays further showed that Foxa2 bound to the elafin promoter in vivo. Analyses of melanoma cells with varied levels of Foxa2 revealed a correlated expression between Foxa2 and elafin and the ability of Foxa2 to induce apoptosis. Our results collectively suggest that, in melanoma cells, Foxa2 expression is silenced and therefore elafin is maintained unexpressed to facilitate cell proliferation in the disease melanoma.

  5. Factors associated with the persuasiveness of direct-to-consumer advertising on HPV vaccination among young women.

    Manika, Danae; Ball, Jennifer G; Stout, Patricia A

    2014-01-01

    This quantitative study explored young women's response to direct-to-consumer pharmaceutical advertising (DTCA) for a human papillomavirus (HPV) vaccine. In particular, the study examined (a) the association of factors stemming from consumer research with actual and intended behavioral responses to DTCA for HPV and (b) key elements drawn from commonly used health-related theories to determine the strongest associations with behavioral intentions regarding the HPV vaccine. Survey findings showed that vaccinated women indicated that DTCA played a role in their decision to get vaccinated against HPV more so than those who were not vaccinated. Trust in DTCA for an HPV vaccine brand was significantly related to intentions to seek more information about the vaccine. Also, perceived barriers had the only significant association with behavioral intentions when taking into account perceived threat and response efficacy. These results provide practical implications for key industry decision makers and health communication professionals on the design of effective theory-based health communication message content for an HPV vaccine brand with consequent social implications.

  6. Physician perspectives and compliance with patient advance directives: the role external factors play on physician decision making.

    Burkle, Christopher M; Mueller, Paul S; Swetz, Keith M; Hook, C Christopher; Keegan, Mark T

    2012-11-21

    Following passage of the Patient Self Determination Act in 1990, health care institutions that receive Medicare and Medicaid funding are required to inform patients of their right to make their health care preferences known through execution of a living will and/or to appoint a surrogate-decision maker. We evaluated the impact of external factors and perceived patient preferences on physicians' decisions to honor or forgo previously established advance directives (ADs). In addition, physician views regarding legal risk, patients' ability to comprehend complexities involved with their care, and impact of medical costs related to end-of-life care decisions were explored. Attendees of two Mayo Clinic continuing medical education courses were surveyed. Three scenarios based in part on previously court-litigated matters assessed impact of external factors and perceived patient preferences on physician compliance with patient-articulated wishes regarding resuscitation. General questions measured respondents' perception of legal risk, concerns over patient knowledge of idiosyncrasies involved with their care, and impact medical costs may have on compliance with patient preferences. Responses indicating strength of agreement or disagreement with statements were treated as ordinal data and analyzed using the Cochran Armitage trend test. Three hundred eighty-eight of 951 surveys were completed (41% response rate). Eighty percent reported they were likely to honor a patient's AD despite its 5 year age. Fewer than half (41%) would honor the AD of a patient in ventricular fibrillation who had expressed a desire to "pass away in peace." Few (17%) would forgo an AD following a family's request for continued resuscitative treatment. A majority (52%) considered risk of liability to be lower when maintaining someone alive against their wishes than mistakenly failing to provide resuscitative efforts. A large percentage (74%) disagreed that patients could not appreciate complexities

  7. Physician perspectives and compliance with patient advance directives: the role external factors play on physician decision making

    Burkle Christopher M

    2012-11-01

    Full Text Available Abstract Background Following passage of the Patient Self Determination Act in 1990, health care institutions that receive Medicare and Medicaid funding are required to inform patients of their right to make their health care preferences known through execution of a living will and/or to appoint a surrogate-decision maker. We evaluated the impact of external factors and perceived patient preferences on physicians’ decisions to honor or forgo previously established advance directives (ADs. In addition, physician views regarding legal risk, patients’ ability to comprehend complexities involved with their care, and impact of medical costs related to end-of-life care decisions were explored. Methods Attendees of two Mayo Clinic continuing medical education courses were surveyed. Three scenarios based in part on previously court-litigated matters assessed impact of external factors and perceived patient preferences on physician compliance with patient-articulated wishes regarding resuscitation. General questions measured respondents’ perception of legal risk, concerns over patient knowledge of idiosyncrasies involved with their care, and impact medical costs may have on compliance with patient preferences. Responses indicating strength of agreement or disagreement with statements were treated as ordinal data and analyzed using the Cochran Armitage trend test. Results Three hundred eighty-eight of 951 surveys were completed (41% response rate. Eighty percent reported they were likely to honor a patient’s AD despite its 5 year age. Fewer than half (41% would honor the AD of a patient in ventricular fibrillation who had expressed a desire to “pass away in peace.” Few (17% would forgo an AD following a family’s request for continued resuscitative treatment. A majority (52% considered risk of liability to be lower when maintaining someone alive against their wishes than mistakenly failing to provide resuscitative efforts. A large percentage

  8. Exploring the Factor Structure of the Job Demands-Resources Measure With Patient Violence on Direct Care Workers in the Home Setting.

    Byon, Ha Do; Harrington, Donna; Storr, Carla L; Lipscomb, Jane

    2017-08-01

    Workplace violence research in health care settings using the Job Demands-Resources (JD-R) framework is hindered by the lack of comprehensive examination of the factor structure of the JD-R measure when it includes patient violence. Is patient violence a component of job demands or its own factor as an occupational outcome? Exploratory factor analysis and confirmatory factor analysis were conducted using a sample of direct care workers in the home setting (n = 961). The overall 2-construct JD-R structure persisted. Patient violence was not identified as a separate factor from job demands; rather, two demand factors emerged: violence/emotional and workload/physical demands. Although the three-factor model fits the data, the two-factor model with patient violence being a component of job demands is a parsimonious and effective measurement framework.

  9. Analysis Of Supporting Factors On Foreign Direct Investment And Its Impact Toward Indonesian Employment And Export Performance Period 2005-2015

    Suharto

    2017-09-01

    Full Text Available This research analyzes effects of foreign direct investment and Its Impact toward employment and export performance in Indonesia 2005-2015. This research with secondary data focuses on the Supporting factors in which attract foreign direct investment into Indonesia. This research focused on the problem First the impact of labor export results economic growth rate exchange rate inflation rate interest rate and tax toward foreign direct investment second the impact of foreign direct investment on the expansion of employment and export performance in Indonesia during the period 2005-2015. The result of this research explains that variables of human resourceslabor and export performance give positive effect as significantly to attracting foreign direct investment in Indonesia. While foreign direct investment in Indonesia gives positive effect to employment creation and to export performance.

  10. Factors Associated With the Increasing Rates of Discharges Directly Home From Intensive Care Units-A Direct From ICU Sent Home Study.

    Lau, Vincent I; Priestap, Fran A; Lam, Joyce N H; Ball, Ian M

    2018-02-01

    To evaluate the relationship between rates of discharge directly to home (DDH) from the intensive care unit (ICU) and bed availability (ward and ICU). Also to identify patient characteristics that make them candidates for safe DDH and describe transfer delay impact on length of stay (LOS). Retrospective cohort study of all adult patients who survived their stay in our medical-surgical-trauma ICU between April 2003 and March 2015. Median age was 49 years (interquartile range [IQR]: 33.5-60.4), and the majority of the patients were males (54.8%). Median number of preexisting comorbidities was 5 (IQR: 2-7) diagnoses. Discharge directly to home increased from 28 (3.1% of all survivors) patients in 2003 to 120 (12.5%) patients in 2014. The mean annual rate of DDH was between 11% and 12% over the last 6 years. Approximately 62% (n = 397) of patients waited longer than 4 hours for a ward bed, with a median delay of 2.0 days (IQR: 0.5-4.7) before being DDH. There was an inverse correlation between ICU occupancy and DDH rates ( r P = -.55, P < .0001, 95% confidence interval [CI] = -0.36 to -0.69, R 2 = .29). There was no correlation with ward occupancy and DDH rates ( r s = -.055, P = .64, 95% CI = -0.25 to 0.21). The DDH rates have been increasing over time at our institution and were inversely correlated with ICU bed occupancy but were not associated with ward occupancy. The DDH patients are young, have few comorbidities on admission, and few discharge diagnoses, which are usually reversible single system problems with low disease burden. Transfers to the ward are delayed in a majority of cases, leading to increased ICU LOS and likely increased overall hospital LOS as well.

  11. Directed evolution induces tributyrin hydrolysis in a virulence factor of Xylella fastidiosa using a duplicated gene as a template.

    Gouran, Hossein; Chakraborty, Sandeep; Rao, Basuthkar J; Asgeirsson, Bjarni; Dandekar, Abhaya

    2014-01-01

    Duplication of genes is one of the preferred ways for natural selection to add advantageous functionality to the genome without having to reinvent the wheel with respect to catalytic efficiency and protein stability. The duplicated secretory virulence factors of Xylella fastidiosa (LesA, LesB and LesC), implicated in Pierce's disease of grape and citrus variegated chlorosis of citrus species, epitomizes the positive selection pressures exerted on advantageous genes in such pathogens. A deeper insight into the evolution of these lipases/esterases is essential to develop resistance mechanisms in transgenic plants. Directed evolution, an attempt to accelerate the evolutionary steps in the laboratory, is inherently simple when targeted for loss of function. A bigger challenge is to specify mutations that endow a new function, such as a lost functionality in a duplicated gene. Previously, we have proposed a method for enumerating candidates for mutations intended to transfer the functionality of one protein into another related protein based on the spatial and electrostatic properties of the active site residues (DECAAF). In the current work, we present in vivo validation of DECAAF by inducing tributyrin hydrolysis in LesB based on the active site similarity to LesA. The structures of these proteins have been modeled using RaptorX based on the closely related LipA protein from Xanthomonas oryzae. These mutations replicate the spatial and electrostatic conformation of LesA in the modeled structure of the mutant LesB as well, providing in silico validation before proceeding to the laborious in vivo work. Such focused mutations allows one to dissect the relevance of the duplicated genes in finer detail as compared to gene knockouts, since they do not interfere with other moonlighting functions, protein expression levels or protein-protein interaction.

  12. Factors affecting the precipitation of pure calcium carbonate during the direct aqueous carbonation of flue gas desulfurization gypsum

    Song, Kyungsun; Jang, Young-Nam; Kim, Wonbaek; Lee, Myung Gyu; Shin, Dongbok; Bang, Jun-Hwan; Jeon, Chi Wan; Chae, Soo Chun

    2014-01-01

    The mineral carbonation of FGD (flue gas desulfurization) gypsum was carried out through CO 2 sorption into ammonia solution containing FGD gypsum. High-purity calcium carbonate was precipitated from DCC (dissolved calcium carbonate) solution which was extracted during the induction period. The factors affecting the preparation of pure calcium carbonate were examined under the following conditions: CO 2 flow rate (1–3 L/min), ammonia content (4–12%), and S/L (solid-to-liquid) ratio (5–300 g/L). X-Ray diffraction study revealed that the PCC (precipitated calcium carbonate) was round-shaped vaterite. The induction time for PCC decreased as the CO 2 flow rate increased. The maximum formation efficiency for pure PCC was seen to increase linearly with the ammonia content. The formation efficiency for pure PCC was the highest (90%) for S/L ratio of 5 g/L but it decreased as S/L ratio increased. On the other hand, S/L ratio didn't affect the maximum solubility limit of DCC. It is believed that the pure PCC would add an economic value to the FGD gypsum carbonation for industrial CO 2 sequestration. - Highlights: • Pure and white CaCO 3 was synthesized using induction period during direct carbonation of FGD gypsum. • Its formation efficiency was increased with ammonia content but decreased with solid-to-liquid ratio. • This method is expected to extend to other industrial CO 2 sequestration for the enhanced economic value of precipitated CaCO 3

  13. Risk and direct protective factors for youth violence: results from the Centers for Disease Control and Prevention's Multisite Violence Prevention Project.

    Henry, David B; Tolan, Patrick H; Gorman-Smith, Deborah; Schoeny, Michael E

    2012-08-01

    This study was conducted as part of a multisite effort to examine risk and direct protective factors for youth violence. The goal was to identify those factors in the lives of young people that increase or decrease the risk of violence. These analyses fill an important gap in the literature, as few studies have examined risk and direct protective factors for youth violence across multiple studies. Data on 4432 middle-school youth, from the CDC Multisite Violence Prevention Project were used. Evaluations were made of effects of variables coded as risk and direct protective factors in the fall of 6th grade on violence measured in spring of 7th and 8th grades. Factors tested included depression, delinquency, alcohol and drug involvement, involvement in family activities, academic achievement, attitudes toward school, truancy, and peer deviance. Most variables were coded with two sets of dummy variables indicating risk and protective directions of effects. Results showed that higher teacher-rated study skills were associated with lower subsequent violence across genders and ethnic groups. Affiliation with deviant peers was significantly associated with increased subsequent violence among youth reporting their race/ethnicity as white or other, marginally associated with increased violence among African-American youth, and unrelated among Latino youth. This study identified some factors than should be areas of interest for effective prevention programs. Some ethnic differences also should be considered in planning of prevention. The CDC Multisite Violence Prevention Project completed enrollment prior to July 2005. Copyright © 2012. Published by Elsevier Inc.

  14. Gene array analysis of neural crest cells identifies transcription factors necessary for direct conversion of embryonic fibroblasts into neural crest cells

    Tsutomu Motohashi

    2016-03-01

    Full Text Available Neural crest cells (NC cells are multipotent cells that emerge from the edge of the neural folds and migrate throughout the developing embryo. Although the gene regulatory network for generation of NC cells has been elucidated in detail, it has not been revealed which of the factors in the network are pivotal to directing NC identity. In this study we analyzed the gene expression profile of a pure NC subpopulation isolated from Sox10-IRES-Venus mice and investigated whether these genes played a key role in the direct conversion of Sox10-IRES-Venus mouse embryonic fibroblasts (MEFs into NC cells. The comparative molecular profiles of NC cells and neural tube cells in 9.5-day embryos revealed genes including transcription factors selectively expressed in developing trunk NC cells. Among 25 NC cell-specific transcription factor genes tested, SOX10 and SOX9 were capable of converting MEFs into SOX10-positive (SOX10+ cells. The SOX10+ cells were then shown to differentiate into neurons, glial cells, smooth muscle cells, adipocytes and osteoblasts. These SOX10+ cells also showed limited self-renewal ability, suggesting that SOX10 and SOX9 directly converted MEFs into NC cells. Conversely, the remaining transcription factors, including well-known NC cell specifiers, were unable to convert MEFs into SOX10+ NC cells. These results suggest that SOX10 and SOX9 are the key factors necessary for the direct conversion of MEFs into NC cells.

  15. Understanding the 'four directions of travel': qualitative research into the factors affecting recruitment and retention of doctors in rural Vietnam.

    Witter, Sophie; Thi Thu Ha, Bui; Shengalia, Bakhuti; Vujicic, Marko

    2011-08-17

    Motivation and retention of health workers, particularly in rural areas, is a question of considerable interest to policy-makers internationally. Many countries, including Vietnam, are debating the right mix of interventions to motivate doctors in particular to work in remote areas. The objective of this study was to understand the dynamics of the health labour market in Vietnam, and what might encourage doctors to accept posts and remain in-post in rural areas. This study forms part of a labour market survey which was conducted in Vietnam in November 2009 to February 2010. The study had three stages. This article describes the findings of the first stage - the qualitative research and literature review, which fed into the design of a structured survey (second stage) and contingent valuation (third stage). For the qualitative research, three tools were used - key informant interviews at national and provincial level (6 respondents); in-depth interviews of doctors at district and commune levels (11 respondents); and focus group discussions with medical students (15 participants). The study reports on the perception of the problem by national level stakeholders; the motivation for joining the profession by doctors; their views on the different factors affecting their willingness to work in rural areas (including different income streams, working conditions, workload, equipment, support and supervision, relationships with colleagues, career development, training, and living conditions). It presents findings on their overall satisfaction, their ranking of different attributes, and willingness to accept different kinds of work. Finally, it discusses recent and possible policy interventions to address the distribution problem. Four typical 'directions of travel' are identified for Vietnamese doctors - from lower to higher levels of the system, from rural to urban areas, from preventive to curative health and from public to private practice. Substantial differences in

  16. Understanding the 'four directions of travel': qualitative research into the factors affecting recruitment and retention of doctors in rural Vietnam

    Witter Sophie

    2011-08-01

    Full Text Available Abstract Background Motivation and retention of health workers, particularly in rural areas, is a question of considerable interest to policy-makers internationally. Many countries, including Vietnam, are debating the right mix of interventions to motivate doctors in particular to work in remote areas. The objective of this study was to understand the dynamics of the health labour market in Vietnam, and what might encourage doctors to accept posts and remain in-post in rural areas. Methods This study forms part of a labour market survey which was conducted in Vietnam in November 2009 to February 2010. The study had three stages. This article describes the findings of the first stage - the qualitative research and literature review, which fed into the design of a structured survey (second stage and contingent valuation (third stage. For the qualitative research, three tools were used - key informant interviews at national and provincial level (6 respondents; in-depth interviews of doctors at district and commune levels (11 respondents; and focus group discussions with medical students (15 participants. Results The study reports on the perception of the problem by national level stakeholders; the motivation for joining the profession by doctors; their views on the different factors affecting their willingness to work in rural areas (including different income streams, working conditions, workload, equipment, support and supervision, relationships with colleagues, career development, training, and living conditions. It presents findings on their overall satisfaction, their ranking of different attributes, and willingness to accept different kinds of work. Finally, it discusses recent and possible policy interventions to address the distribution problem. Conclusions Four typical 'directions of travel' are identified for Vietnamese doctors - from lower to higher levels of the system, from rural to urban areas, from preventive to curative health and

  17. Calculation of gamma ray dose buildup factors in water for isotropic point, plane mono directional and line sources using MCNP code

    Atak, H.; Celikten, O. S.; Tombakoglu, M.

    2009-01-01

    Gamma ray dose buildup factors in water for isotropic point, plane mono directional and infinite/finite line sources were calculated using the MCNP code. The buildup factors are determined for gamma ray energies of 1, 2, 3 and 4 Mev and for shield thicknesses of 1, 2, 4 and 7 mean free paths. The calculated buildup factors were then fitted in the Taylor and Berger forms. For the line sources a buildup factor table was also constructed using the Sievert function and the constants in Taylor form derived in this study to compare with the Monte Carlo results. All buildup factors were compared with the tabulated data given in literature. In order to reduce the statistical errors on buildup factors, 'forced collision' option was used in the MCNP calculations.

  18. Factors Affecting the Self-directed Learning of Students at Clinical Practice Course for Advanced Practice Nurse

    Miyoung Kim, RN, PhD, MBA, GNP

    2011-03-01

    Conclusions: This study demonstrated the hierarchical relationship among belongingness, self-esteem, and self-directed learning based on the conceptual framework developed by Levett-Jones and Lathlean, thus proving the usefulness of this framework for application in the field. Therefore, this study found that there are needs of high self-esteem and belongingness in order to improve self-directed learning for APN students in clinical practice.

  19. Who exhibits more energy-saving behavior in direct and indirect ways in china? The role of psychological factors and socio-demographics

    Yang, Shu; Zhang, Yanbing; Zhao, Dingtao

    2016-01-01

    This research explores the possibilities for further energy saving in households in the Chinese context by conducting of a survey on energy curtailment behaviors. We examine how people's demographic characteristics and psychological factors affect their direct and indirect energy curtailment behaviors at home, as well as the different effects of these antecedents. Results suggest that people with high sense of environmental responsibility and curtailment attitude are more likely to engage in both direct and indirect energy curtailment actions. Generally, indirect energy curtailment behavior is more strongly related to psychological and socio-demographic factors than direct behavior, and these socio-demographic factors vary for direct and indirect behaviors. Interesting patterns emerged with respect to gender, age, family structure, family income, and level of education. Results indicate that strengthening publicity and education to increase environmental awareness among Chinese urban residents would be effective in reducing household energy consumption, especially when the said measures target a specific population and specific behaviors. - Highlights: •A survey is used to explore Chinese urban residents' energy curtailment behaviors. •Make a distinction between direct and indirect energy curtailment behaviors. •Effects of demographic and psychological variables are different on two behaviors. •Policy should target at specific behaviors and specific population.

  20. Evolutionary dynamics of DNA-binding sites and direct target genes of a floral master regulatory transcription factor [ChIP-Seq

    Muiño, J.M.; Bruijn, de S.A.; Vingron, Martin; Angenent, G.C.; Kaufmann, K.

    2015-01-01

    Plant development is controlled by transcription factors (TFs) which form complex gene-regulatory networks. Genome-wide TF DNA-binding studies revealed that these TFs have several thousands of binding sites in the Arabidopsis genome, and may regulate the expression of many genes directly. Given the

  1. Fibronectin type III (FN3) modules of the neuronal cell adhesion molecule L1 interact directly with the fibroblast growth factor (FGF) receptor

    Kulahin, Nikolaj; Li, Shizhong; Hinsby, Anders Mørkeberg

    2008-01-01

    The neuronal cell adhesion molecule (CAM) L1 promotes axonal outgrowth, presumably through an interaction with the fibroblast growth factor receptor (FGFR). The present study demonstrates a direct interaction between L1 fibronectin type III (FN3) modules I-V and FGFR1 immunoglobulin (Ig) modules II...

  2. Evolutionary dynamics of DNA-binding sites and direct target genes of a floral master regulatory transcription factor [RNA-Seq

    Muiño, J.M.; Bruijn, de S.A.; Vingron, Martin; Angenent, G.C.; Kaufmann, Kerstin

    2015-01-01

    Plant development is controlled by transcription factors (TFs) which form complex gene-regulatory networks. Genome-wide TF DNA-binding studies revealed that these TFs have several thousands of binding sites in the Arabidopsis genome, and may regulate the expression of many genes directly. Given the

  3. Steroidogenic factor 1 directs programs regulating diet-induced thermogenesis and leptin action in the ventral medial hypothalamic nucleus

    The transcription factor steroidogenic factor 1 (SF-1) is exclusively expressed in the brain in the ventral medial hypothalamic nucleus (VMH) and is required for the development of this nucleus. However, the physiological importance of transcriptional programs regulated by SF-1 in the VMH is not wel...

  4. The Relationship between Bullying Victimization and School Avoidance: An Examination of Direct Associations, Protective Influences, and Aggravating Factors

    Hutzell, Kirsten L.; Payne, Allison Ann

    2018-01-01

    This study examines the impact of bullying victimization on school avoidance by proposing the following hypotheses: (1) Net of other factors, students who have experienced bullying victimization are more likely to engage in school avoidance behaviors; (2) There are protective factors that will decrease this relationship between bullying…

  5. The positive transcription factor of the 5S RNA gene proteolyses during direct exchange between 5S DNA sites

    1986-01-01

    We have examined the association, dissociation, and exchange of the 5S specific transcription factor (TFIIIA) with somatic- and oocyte-type 5S DNA. The factor associates faster with somatic than with oocyte 5S DNA, and the rate of complex formation is accelerated by vector DNA. Once formed, the TFIIIA-5S DNA complex is stable for greater than 4 h in the absence of free 5S DNA, and its dissociation is identical for somatic and for oocyte 5S DNA. In the presence of free 5S DNA, the factor trans...

  6. Elongation Factor Ts Directly Facilitates the Formation and Disassembly of the Escherichia coli Elongation Factor Tu·GTP·Aminoacyl-tRNA Ternary Complex*

    Burnett, Benjamin J.; Altman, Roger B.; Ferrao, Ryan; Alejo, Jose L.; Kaur, Navdep; Kanji, Joshua; Blanchard, Scott C.

    2013-01-01

    Aminoacyl-tRNA enters the translating ribosome in a ternary complex with elongation factor Tu (EF-Tu) and GTP. Here, we describe bulk steady state and pre-steady state fluorescence methods that enabled us to quantitatively explore the kinetic features of Escherichia coli ternary complex formation and decay. The data obtained suggest that both processes are controlled by a nucleotide-dependent, rate-determining conformational change in EF-Tu. Unexpectedly, we found that this conformational change is accelerated by elongation factor Ts (EF-Ts), the guanosine nucleotide exchange factor for EF-Tu. Notably, EF-Ts attenuates the affinity of EF-Tu for GTP and destabilizes ternary complex in the presence of non-hydrolyzable GTP analogs. These results suggest that EF-Ts serves an unanticipated role in the cell of actively regulating the abundance and stability of ternary complex in a manner that contributes to rapid and faithful protein synthesis. PMID:23539628

  7. Direct compatibility check of the CEA and Cornell electroproduction pion form factor data with e+e- ones

    Dubnicka, S.; Martinovic, L.

    1988-01-01

    Using precise experimental information on the imaginary part of the pion form factor from e + e - → π + π - up to the inelastic threshold and QCD constraints for it in the range of momenta (m π 0 +m ω ) 2 < t < infinity, was investigated by means of a dispersion integral the reliability of individual electroproduction CEA and Cornell model-dependent pion form factor data points

  8. Linking Contextual Factors with Rhetorical Pattern Shift: Direct and Indirect Strategies Recommended in English Business Communication Textbooks in China

    Wang, Junhua; Zhu, Pinfan

    2011-01-01

    Scholars have consistently claimed that rhetorical patterns are culturally bound, and indirectness is a defining characteristic of Chinese writing. Through examining how the rhetorical mechanism of directness and indirectness is presented in 29 English business communication textbooks published in China, we explore how English business…

  9. How do socio-demographic and psychological factors relate to households' direct and indirect energy use and savings?

    Abrahamse, Wokje; Steg, Linda

    2009-01-01

    Households constitute an important target group for energy conservation. They not only use energy in a direct way (gas, electricity and fuel) but also in an indirect way (embedded in the production, consumption and disposal of goods). During a period of five months (viz., October 2002-March 2003),

  10. Adolescent Sibling Relationship Quality and Adjustment: Sibling Trustworthiness and Modeling, as Factors Directly and Indirectly Influencing These Associations

    Gamble, Wendy C.; Yu, Jeong Jin; Kuehn, Emily D.

    2011-01-01

    The main goal of this study was to examine the direct and moderating effects of trustworthiness and modeling on adolescent siblings' adjustment. Data were collected from 438 families including a mother, a younger sibling in fifth, sixth, or seventh grade (M = 11.6 years), and an older sibling (M = 14.3 years). Respondents completed Web-based…

  11. Direct and Interaction Effects of Co-Existing Familial Risk Factors and Protective Factors Associated with Internet Addiction among Chinese Students in Hong Kong

    Wu, Anise M. S.; Lau, Joseph T. F.; Cheng, Kit-man; Law, Rita W.; Tse, Vincent W. S.; Lau, Mason M. C.

    2018-01-01

    Internet addiction (IA) is prevalent among adolescents and imposes a serious public health threat. Familial risk and protective factors may co-exist and interact with each other to determine IA. We conducted a cross-sectional survey among 9,618 Secondary 1 to 4 students in Hong Kong, China. About 16% of the surveyed students were classified as…

  12. The Direct Binding of Insulin-like Growth Factor-1 (IGF-1) to Integrin αvβ3 Is Involved in IGF-1 Signaling*

    Saegusa, Jun; Yamaji, Satoshi; Ieguchi, Katsuaki; Wu, Chun-Yi; Lam, Kit S.; Liu, Fu-Tong; Takada, Yoko K.; Takada, Yoshikazu

    2009-01-01

    It has been proposed that ligand occupancy of integrin αvβ3 with extracellular matrix ligands (e.g. vitronectin) plays a critical role in insulin-like growth factor-1 (IGF-1) signaling. We found that expression of αvβ3 enhanced IGF-1-induced proliferation of Chinese hamster ovary cells in serum-free conditions (in the absence of vitronectin). We hypothesized that the direct integrin binding to IGF-1 may play a role in IGF-1 signaling. We demonstrated that αvβ3 specifically and directly bound ...

  13. FOREIGN DIRECT INVESTMENTS AND THEIR NON-TRADITIONAL QUALITY FACTORS. A VAR ANALYSIS IN ROMANIA AND BULGARIA

    Magdalena RADULESCU

    2016-05-01

    Full Text Available The aim of this paper is to present an econometric analysis using VAR techniques for emphasizing the political institutional factors, economic freedom factors and the quality of labor force factors impacting on FDIs attracted in Bulgaria and Romania. We used yearly data series between 2000 and 2014, provided by the World Bank. These two countries display a very friendly climate (law income corporate tax, but they attracted large amounts of FDIs only for a short period of time at mid-2000s’. The foreign investments sharply dropped during the crisis, and the perspectives are not so good. The foreign investors claim that high corruption and bureaucracy greatly diminish the advantages of an attractive fiscal environment in these two specific countries.

  14. Personality, Political Attitudes and Participation in Protests: The Direct and Mediated Effects of Psychological Factors on Political Activism

    Ednaldo Aparecido Ribeiro

    2016-12-01

    Full Text Available Studies combining psychology and political science have shown that personality traits such as extroversion and openness to experiences are conditioning factors of political activism. However, the mechanisms through which this effect occurs are still poorly understood. Aiming to advance this topic, this article presents the results of an investigation that looked to analyse the mediated effects of personality traits in the Brazilian context, taking as mediating conditioning factors various attitudes and subjective dispositions commonly found in the literature, such as interest in politics and subjective political efficacy. Using the Latin American Public Opinion Project data, the hypothesis was tested that personality influences behaviour, since it favours the development of a number of attitudes that function as basic factors conditioning civic engagement. The results indicate the significant mediated effects of extroversion and openness to experience, especially with regard to political knowledge.

  15. Evaluation of related factors, prediction and treatment drugs of no-reflow phenomenon in patients with acute ST-segment elevation myocardial infarction after direct PCI.

    Li, Hui; Fu, Du-Guan; Liu, Fu-Yuan; Zhou, Heng; Li, Xiao-Mei

    2018-04-01

    This study determined the related factors of no-reflow phenomenon in patients with acute ST-segment elevation myocardial infarction (STEMI) after direct percutaneous coronary intervention (PCI), and evaluated related factor scores in predicting the occurrence of no-reflow phenomenon and drug treatments. A total of 203 patients with acute STEMI receiving PCI who were admitted to the Department of Cardiovascularology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine (Xiangyang, China) from January 2015 to December 2016 were selected. The clinical and image data were analyzed to determine the related factors of no-reflow phenomenon after operation, and related factor scores were quantified to predict the occurrence of no-reflow phenomenon. Three drugs (diltiazem, nitroglycerin and tirofiban needles) were continuously injected in coronary arteries of patients with no-reflow phenomenon, and the effects of these drugs were analyzed. There were 38 patients (18.7%) with no-reflow phenomenon. The correlation analysis showed that 10 factors were associated with no-reflow phenomenon, in which five factors were identified as risk factors, including IRA open-up time ≥8 h, SBP 18 mg/l, thrombus loads, length of the culprit vessel ≥20 mm. The score analysis of related factors of 38 patients with no-reflow phenomenon was conducted. Three points were set for five risk factors each, and 1 point was set for the other five factors each. It was found that the score was approximately normally distributed. The average was 11.5±1.57 points and the lower limit of 95% confidence interval was >8.93 points. The effective rates of three drugs were different (P<0.05), and the pairwise comparison showed their effective rates were not fully identical (P<0.05). The results showed that: i) Τhere are 10 related factors, including five risk factors; ii) related factors with the score ≥9 points can be used for clinical prediction of STEMI after direct PCI; and iii) it is

  16. Diapause induction as an interplay between seasonal token stimuli, and modifying and directly limiting factors: hibernation in Chymomyza costata

    Košťál, Vladimír; Mollaei, M.; Schöttner, Konrad

    2016-01-01

    Roč. 41, č. 4 (2016), s. 344-357 ISSN 0307-6962 R&D Projects: GA ČR GA13-01057S Institutional support: RVO:60077344 Keywords : environmental signals * overcrowding * photoperiodism Subject RIV: ED - Physiology Impact factor: 1.364, year: 2016 http://onlinelibrary.wiley.com/doi/10.1111/phen.12159/abstract

  17. Direct astatination of a tumour-binding protein, human epidermal growth factor, using nido-carborane as a prosthetic group

    Sjostrom, A.; Tolmachev, V.; Lebeda, Ondřej; Koziorowski, J.; Carlsson, J.; Lundqvist, H.

    2003-01-01

    Roč. 256, č. 7 (2003), s. 191-197 ISSN 0236-5731 R&D Projects: GA AV ČR KSK4055109 Keywords : neutron-capture therapy * astatine-211 Subject RIV: CH - Nuclear ; Quantum Chemistry Impact factor: 0.472, year: 2003

  18. Genome-wide identification of genes directly regulated by the pleiotropic transcription factor Spx in Bacillus subtilis

    Rochat, T.; Nicolas, P.; Delumeau, O.; Rabatinová, Alžběta; Korelusová, Jana; Leduc, A.; Bessieres, P.; Dervyn, E.; Krásný, Libor; Noirot, P.

    2012-01-01

    Roč. 40, č. 19 (2012), s. 9571-9583 ISSN 0305-1048 R&D Projects: GA ČR GAP302/11/0855 Institutional support: RVO:61388971 Key words : C-TERMINAL DOMAIN * RNA-POLYMERASE * DISULFIDE STRESS Subject RIV: CE - Biochemistry Impact factor: 8.278, year: 2012

  19. Risk factors and direct medical cost of early versus late unplanned readmissions among diabetes patients at a tertiary hospital in Singapore.

    Png, May Ee; Yoong, Joanne; Chen, Cynthia; Tan, Chuen Seng; Tai, E Shyong; Khoo, Eric Y H; Wee, Hwee Lin

    2018-02-20

    To examine the risk factors and direct medical costs associated with early (≤30 days) versus late (31-180 days) unplanned readmissions among patients with type 2 diabetes in Singapore. Risk factors and associated costs among diabetes patients were investigated using electronic medical records from a local tertiary care hospital from 2010 to 2012. Multivariable logistic regression was used to identify risk factors associated with early and late unplanned readmissions while a generalized linear model was used to estimate the direct medical cost. Sensitivity analysis was also performed. A total of 1729 diabetes patients had unplanned readmissions within 180 days of an index discharge. Length of index stay (a marker of acute illness burden) was one of the risk factors associated with early unplanned readmission while patient behavior-related factors, like diabetes-related medication adherence, were associated with late unplanned readmission. Adjusted mean cost of index admission was higher among patients with unplanned readmission. Sensitivity analysis yielded similar results. Existing routinely captured data can be used to develop prediction models that flag high risk patients during their index admission, potentially helping to support clinical decisions and prevent such readmissions.

  20. Understanding the relative contributions of direct environmental effects and passive genotype-environment correlations in the association between familial risk factors and child disruptive behavior disorders.

    Bornovalova, M A; Cummings, J R; Hunt, E; Blazei, R; Malone, S; Iacono, W G

    2014-03-01

    Previous work reports an association between familial risk factors stemming from parental characteristics and offspring disruptive behavior disorders (DBDs). This association may reflect (a) the direct effects of familial environment and (b) a passive gene-environment correlation (r(GE)), wherein the parents provide both the genes and the environment. The current study examined the contributions of direct environmental influences and passive r(GE) by comparing the effects of familial risk factors on child DBDs in genetically related (biological) and non-related (adoptive) families. Participants were 402 adoptive and 204 biological families. Familial environment was defined as maternal and paternal maladaptive parenting and antisociality, marital conflict and divorce; offspring DBDs included attention deficit hyperactivity disorder (ADHD), conduct disorder (CD) and oppositional defiant disorder (ODD). Mixed-level regressions estimated the main effects of familial environment, adoption status and the familial environment by adoption status interaction term, which tested for the presence of passive r(GE). There was a main effect of maternal and paternal maladaptive parenting and marital discord on child DBDs, indicating a direct environmental effect. There was no direct environmental effect of maternal or paternal antisociality, but maternal and paternal antisociality had stronger associations with child DBDs in biological families than adoptive families, indicating the presence of a passive r(GE). Many familial risk factors affected children equally across genetically related and non-related families, providing evidence for direct environmental effects. The relationship of parental antisociality and offspring DBDs was best explained by a passive r(GE), where a general vulnerability toward externalizing psychopathology is passed down by the parents to the children.

  1. Factors that affect implementation of a nurse staffing directive: results from a qualitative multi-case evaluation.

    Robinson, Claire H; Annis, Ann M; Forman, Jane; Krein, Sarah L; Yankey, Nicholas; Duffy, Sonia A; Taylor, Beth; Sales, Anne E

    2016-08-01

    To assess implementation of the Veterans Health Administration staffing methodology directive. In 2010 the Veterans Health Administration promulgated a staffing methodology directive for inpatient nursing units to address staffing and budget forecasting. A qualitative multi-case evaluation approach assessed staffing methodology implementation. Semi-structured telephone interviews were conducted from March - June 2014 with Nurse Executives and their teams at 21 facilities. Interviews focused on the budgeting process, implementation experiences, use of data, leadership support, and training. An implementation score was created for each facility using a 4-point rating scale. The scores were used to select three facilities (low, medium and high implementation) for more detailed case studies. After analysing interview summaries, the evaluation team developed a four domain scoring structure: (1) integration of staffing methodology into budget development; (2) implementation of the Directive elements; (3) engagement of leadership and staff; and (4) use of data to support the staffing methodology process. The high implementation facility had leadership understanding and endorsement of staffing methodology, confidence in and ability to work with data, and integration of staffing methodology results into the budgeting process. The low implementation facility reported poor leadership engagement and little understanding of data sources and interpretation. Implementation varies widely across facilities. Implementing staffing methodology in facilities with complex and changing staffing needs requires substantial commitment at all organizational levels especially for facilities that have traditionally relied on historical levels to budget for staffing. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  2. Assessing the relationship between total factor productivity and foreign direct investment in an economy with a skills shortage: the case of South Africa

    Bonga-Bonga, Lumengo; Phume, Maphelane

    2017-01-01

    This paper assesses the relationship between total factor productivity (TFP) and foreign direct investment (FDI) in a country with skills shortage. South Africa is used as a case study. Literature is inconclusive on how FDI should affect TFP. This paper shows that it is important to account for the interactivity between FDI and human capital when assessing the effects of FDI on TFP. Moreover, the empirical results show that, contrary to countries with abundance of skills, in countries with sk...

  3. Racial and Ethnic Differences in Advance Directive Possession: Role of Demographic Factors, Religious Affiliation, and Personal Health Values in a National Survey of Older Adults.

    Huang, Ivy A; Neuhaus, John M; Chiong, Winston

    2016-02-01

    Black and Hispanic older Americans are less likely than white older Americans to possess advance directives. Understanding the reasons for this racial and ethnic difference is necessary to identify targets for future interventions to improve advance care planning in these populations. The aim of the study was to evaluate whether racial and ethnic differences in advance directive possession are explained by other demographic factors, religious characteristics, and personal health values. A general population survey was conducted in a nationally representative sample using a web-enabled survey panel of American adults aged 50 and older (n = 2154). In a sample of older Americans, white participants are significantly more likely to possess advance directives (44.0%) than black older Americans (24.0%, p personal health values. These findings support targeted efforts to mitigate racial disparities in access to advance care planning.

  4. Direct Heat

    Lienau, P J

    1990-01-01

    Potential resources and applications of earth heat in the form of geothermal energy are large. United States direct uses amount to 2,100 MWt thermal and worldwide 8,850 MWt above a reference temperature of 35 degrees Celsius. Space and district heating are the major direct uses of geothermal energy. Equipment employed in direct use projects is of standard manufacture and includes downhole and circulation pumps, transmission and distribution pipelines, heat exchangers and convectors, heat pumps and chillers. Direct uses of earth heat discussed are space and district heating, greenhouse heating and fish farming, process and industrial applications. The economic feasibility of direct use projects is governed by site specific factors such as location of user and resource, resource quality, system load factor and load density, as well as financing. Examples are presented of district heating in Klamath Falls, and Elko. Further developments of direct uses of geothermal energy will depend on matching user needs to the resource, and improving load factors and load density.

  5. Post traumatic stress disorder in the wake of heart disease: Prevalence, risk factors, and future research directions

    Spindler, Helle; Pedersen, Susanne Schmidt

    2005-01-01

    0-38% across studies. Studies thatincluded control groups showed that cardiac patients were at a significantly increased risk of developingPTSD. Risk factors included gender, personality, and low social support. Possible mechanisms comprisedelevations in heart rate and blood pressure, and lack......Background There is increasing recognition that patients following a cardiac event may be at riskof developing PTSD. The present article reviews studies looking at PTSD as a sequel of heart disease witha particular focus on prevalence and risk factors. Potential pathogenic pathways that may link...... of adherence with lifestyle changes and medication.Conclusions Subgroups of patients with established heart disease are at risk of developing PTSD following acardiac event. Although few studies have looked at the impact of PTSD on prognosis, preliminary evidencesuggests that PTSD may increase the risk of major...

  6. Future Directions in Research on Racism-Related Stress and Racial-Ethnic Protective Factors for Black Youth.

    Jones, Shawn C T; Neblett, Enrique W

    2017-01-01

    Research on racism-related stress and racial-ethnic protective factors represents an important enterprise for optimizing the mental health of African American and other racial and ethnic minority youth. However, there has been a relative dearth of work on these factors in the clinical psychology research literature, and more work is needed in outlets such as these. To this end, the current article adopts a developmental psychopathology framework and uses recent empirical findings to outline our current understanding of racism-related stress and racial-ethnic protective factors (i.e., racial identity, racial socialization, Africentric worldview) for African American youth. We then provide nine recommendations-across basic, applied, and broader/cross-cutting research lines-that we prioritize as essential to advancing the future scientific investigation of this crucial research agenda. Within and across these recommendations, we issue a charge to researchers and clinicians alike, with the ultimate goal of alleviating the negative mental health impact that racism-related stress can have on the well-being and mental health of African American and other racial and ethnic minority youth.

  7. Home food environment factors associated with the presence of fruit and vegetables at dinner: A direct observational study.

    Trofholz, Amanda C; Tate, Allan D; Draxten, Michelle L; Neumark-Sztainer, Dianne; Berge, Jerica M

    2016-01-01

    Little research exists about the factors influencing the foods available at family meals. This study examines the home food environment factors contributing to the presence of fruit and vegetables at family meals. Home food inventory (HFI) and survey data were collected from low-income, minority families (n = 120) with children 6-12 years old. Observations from video-recorded family dinner meals, totaling 800 videos, were used to measure the frequency at which fruit and vegetables were served. Multiple regression was used to investigate how the fruit and vegetables in the HFI and other home food environment factors were related to the number of days fruit and vegetables were served at dinner during the observation period. Availability and accessibility of fruit and vegetables in the home were each found to be significantly associated with the presence of fruits and vegetables at family dinners. Of the fruit and vegetable categories (i.e., fresh, canned, or frozen), having fresh fruit and vegetables available in the home was found to be most strongly associated with serving fruit and vegetables at dinner, respectively. Higher parent intake of vegetables was associated with the presence of vegetables at dinners, and parent meal planning was associated with the presence of fruit at dinners. Increasing the availability and accessibility of fresh fruit and vegetables in the home may be an effective approach to increasing the presence of fruits and vegetables at family dinners, especially among low-income, minority households. It is also essential to understand why families are not using all fruits and vegetables (e.g., canned and frozen) available in the home for family meals. Family meals are a place to promote the increased presence of both fruit and vegetables. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Factors Attributing to Outwards Direct Investments from Developing Countries to Developed Countries: Evidence from China and India

    Diyah Ayu Amalia Avina

    2016-12-01

    Full Text Available The purpose of this research is to explore the growing trend of outward foreign direct investments (OFDIs from developing countries to developed countries. Market-seeking and strategic asset explorations are the main motivations for conducting OFDIs in developed countries. Meanwhile, cross-border greenfield investments and cross-border mergers and acquisitions are the main entry strategies used by developing countries when penetrating the developed markets. Finally, this paper reveals mixed results about the explaining ability of John Dunning’s International Development Path (IDP theory on the patterns of selected developing markets' OFDIs to developed countries. On the one hand, China’s OFDIs follow the paths in the IDP theory. On the other hand, those of India do not confirm so.

  9. Direct measurements of safety factor profiles with motional Stark effect for KSTAR tokamak discharges with internal transport barriers

    Ko, J.; Chung, J.

    2017-06-01

    The safety factor profile evolutions have been measured from the plasma discharges with the external current drive mechanism such as the multi-ion-source neutral beam injection for the Korea Superconducting Tokamak Advanced Research (KSTAR) for the first time. This measurement has been possible by the newly installed motional Stark effect (MSE) diagnostic system that utilizes the polarized Balmer-alpha emission from the energetic neutral deuterium atoms induced by the Stark effect under the Lorentz electric field. The 25-channel KSTAR MSE diagnostic is based on the conventional photoelastic modulator approach with the spatial and temporal resolutions less than 2 cm (for the most of the channels except 2 to 3 channels inside the magnetic axis) and about 10 ms, respectively. The strong Faraday rotation imposed on the optical elements in the diagnostic system is calibrated out from a separate and well-designed polarization measurement procedure using an in-vessel reference polarizer during the toroidal-field ramp-up phase before the plasma experiment starts. The combination of the non-inductive current drive during the ramp-up and shape control enables the formation of the internal transport barrier where the pitch angle profiles indicate flat or slightly hollow profiles in the safety factor.

  10. Improved efficacy of soluble human receptor activator of nuclear factor kappa B (RANK) fusion protein by site-directed mutagenesis.

    Son, Young Jun; Han, Jihye; Lee, Jae Yeon; Kim, HaHyung; Chun, Taehoon

    2015-06-01

    Soluble human receptor activator of nuclear factor kappa B fusion immunoglobulin (hRANK-Ig) has been considered as one of the therapeutic agents to treat osteoporosis or diseases associated with bone destruction by blocking the interaction between RANK and the receptor activator of nuclear factor kappa B ligand (RANKL). However, no scientific record showing critical amino acid residues within the structural interface between the human RANKL and RANK complex is yet available. In this study, we produced several mutants of hRANK-Ig by replacement of amino acid residue(s) and tested whether the mutants had increased binding affinity to human RANKL. Based on the results from flow cytometry and surface plasmon resonance analyses, the replacement of E(125) with D(125), or E(125) and C(127) with D(125) and F(127) within loop 3 of cysteine-rich domain 3 of hRANK-Ig increases binding affinity to human RANKL over the wild-type hRANK-Ig. This result may provide the first example of improvement in the efficacy of hRANK-Ig by protein engineering and may give additional information to understand a more defined structural interface between hRANK and RANKL.

  11. Combination of interferon-alpha and 5-fluorouracil inhibits endothelial cell growth directly and by regulation of angiogenic factors released by tumor cells

    Wada, Hiroshi; Tanemura, Masahiro; Umeshita, Koji; Doki, Yuichiro; Mori, Masaki; Nagano, Hiroaki; Yamamoto, Hirofumi; Noda, Takehiro; Murakami, Masahiro; Kobayashi, Shogo; Marubashi, Shigeru; Eguchi, Hidetoshi; Takeda, Yutaka

    2009-01-01

    The combination therapy of interferon (IFN)-alpha and 5-fluorouracil (5-FU) improved the prognosis of the patients with hepatocellular carcinoma (HCC). To determine the molecular mechanisms of the anti-tumor and anti-angiogenic effects, we examined the direct anti-proliferative effects on human umbilical vein endothelial cells (HUVEC) and indirect effects by regulating secretion of angiogenic factors from HCC cells. The direct effects on HUVEC were examined by TUNEL, Annexin-V assays and cell cycles analysis. For analysis of the indirect effects, the apoptosis induced by the conditioned medium from HCC cell treated by IFN-alpha/5-FU and expression of angiogenic factors was examined. IFN-alpha and 5-FU alone had anti-proliferative properties on HUVEC and their combination significantly inhibited the growth (compared with control, 5-FU or IFN alone). TUNEL and Annexin-V assays showed no apoptosis. Cell cycle analysis revealed that IFN-alpha and 5-FU delayed cell cycle progression in HUVEC with S-phase accumulation. The conditioned medium from HuH-7 cells after treatment with IFN/5-FU significantly inhibited HUVEC growth and induced apoptosis, and contained high levels of angiopoietin (Ang)-1 and low levels of vascular endothelial growth factor (VEGF) and Ang-2. Knockdown of Ang-1 in HuH-7 cells abrogated the anti-proliferative effects on HUVEC while knockdown of Ang-2 partially rescue the cells. These results suggested that IFN-alpha and 5-FU had direct growth inhibitory effects on endothelial cells, as well as anti-angiogenic effects through regulation of angiogenic factors released from HCC cells. Modulation of VEGF and Angs secretion by IFN-alpha and 5-FU may contribute to their anti-angiogenic and anti-tumor effects on HCC

  12. The PDZ domain of the guanine nucleotide exchange factor PDZGEF directs binding to phosphatidic acid during brush border formation.

    Sarah V Consonni

    Full Text Available PDZGEF is a guanine nucleotide exchange factor for the small G protein Rap. It was recently found that PDZGEF contributes to establishment of intestinal epithelial polarity downstream of the kinase Lkb1. By binding to phosphatidic acid enriched at the apical membrane, PDZGEF locally activates Rap2a resulting in induction of brush border formation via a pathway that includes the polarity players TNIK, Mst4 and Ezrin. Here we show that the PDZ domain of PDZGEF is essential and sufficient for targeting PDZGEF to the apical membrane of polarized intestinal epithelial cells. Inhibition of PLD and consequently production of phosphatidic acid inhibitis targeting of PDZGEF to the plasma membrane. Furthermore, localization requires specific positively charged residues within the PDZ domain. We conclude that local accumulation of PDZGEF at the apical membrane during establishment of epithelial polarity is mediated by electrostatic interactions between positively charged side chains in the PDZ domain and negatively charged phosphatidic acid.

  13. Cardiovascular disease risk factors among children of different socioeconomic status in Istanbul, Turkey: Directions for public health and nutrition policy

    Keskin Yasar

    2004-06-01

    Full Text Available Abstract Objectives The aim of the current study was to examine the influence of socioeconomic status (SES on physiological (lipid profile, obesity indices and behavioral (dietary habits, physical activity cardiovascular disease (CVD risk factors among primary schoolchildren in Istanbul. Design Cross sectional study. Setting One private school and two public schools from different SES districts in Istanbul. Participants 510 randomly selected children aged 12 and 13 years old (257 boys, 253 girls. Results The prevalence of overweight (15.2% and the energy intake (p Conclusion The findings of the current study revealed a coexistence of both overweight and higher energy intake in middle/ high SES children, as well as a coexistence of underweight and lower physical activity levels in low SES children. These observations should guide the public health policy in developing appropriate intervention strategies to efficiently tackle these health and social issues early in life.

  14. Principal component analysis of the main factors of line intensity enhancements observed in oscillating direct current plasma

    Stoiljkovic, Milovan M.; Pasti, Igor A.; Momcilovic, Milos D.; Savovic, Jelena J.; Pavlovic, Mirjana S.

    2010-01-01

    Enhancement of emission line intensities by induced oscillations of direct current (DC) arc plasma with continuous aerosol sample supply was investigated using multivariate statistics. Principal component analysis (PCA) was employed to evaluate enhancements of 34 atomic spectral lines belonging to 33 elements and 35 ionic spectral lines belonging to 23 elements. Correlation and classification of the elements were done not only by a single property such as the first ionization energy, but also by considering other relevant parameters. Special attention was paid to the influence of the oxide bond strength in an attempt to clarify/predict the enhancement effect. Energies of vaporization, atomization, and excitation were also considered in the analysis. In the case of atomic lines, the best correlation between the enhancements and first ionization energies was obtained as a negative correlation, with weak consistency in grouping of elements in score plots. Conversely, in the case of ionic lines, the best correlation of the enhancements with the sum of the first ionization energies and oxide bond energies was obtained as a positive correlation, with four distinctive groups of elements. The role of the gas-phase atom-oxide bond energy in the entire enhancement effect is underlined.

  15. Potential impact of internet addiction and protective psychosocial factors onto depression among Hong Kong Chinese adolescents - direct, mediation and moderation effects.

    Wu, Anise M S; Li, Jibin; Lau, Joseph T F; Mo, Phoenix K H; Lau, Mason M C

    2016-10-01

    Internet addiction (IA) is a risk factor while some psychosocial factors can be protective against depression among adolescents. Mechanisms of IA onto depression in terms of mediations and moderations involving protective factors are unknown and were investigated in this study. A representative cross-sectional study was conducted among Hong Kong Chinese secondary school students (n=9518). Among males and females, prevalence of depression at moderate or severe level (CES-D≥21) was 38.36% and 46.13%, and that of IA (CIAS>63) was 17.64% and 14.01%, respectively. Adjusted for socio-demographics, depression was positively associated with IA [males: adjusted odds ratio (AOR)=4.22, 95% CI=3.61-4.94; females: AOR=4.79, 95% CI=3.91-5.87] and negatively associated with psychosocial factors including self-esteem, positive affect, family support, and self-efficacy (males: AOR=0.76-0.94; females: AOR=0.72-0.92, pmoderations, IA also reduced magnitude of protective effects of self-efficacy and family support among males and that of positive affect among both sexes against depression. The high IA prevalence contributes to increased risk of prevalent depression through its direct effect, mediation (reduced level of protective factors) and moderation (reduced magnitude of protective effects) effects. Understanding to mechanisms between IA and depression through protective factors is enhanced. Screening and interventions for IA and depression are warranted, and should cultivate protective factors, and unlink negative impact of IA onto levels and effects of protective factors. Copyright © 2016. Published by Elsevier Inc.

  16. An aptamer-based biosensing platform for highly sensitive detection of platelet-derived growth factor via enzyme-mediated direct electrochemistry

    Deng Kun; Xiang Yang; Zhang Liqun; Chen Qinghai [Laboratory of the Clinical Experimental Base of Biosensor and Microarray, Center of Molecule and Gene Diagnosis, Southwest Hospital, Third Military Medical University, Chongqing 400042 (China); Fu Weiling, E-mail: weilingfu@yahoo.com [Laboratory of the Clinical Experimental Base of Biosensor and Microarray, Center of Molecule and Gene Diagnosis, Southwest Hospital, Third Military Medical University, Chongqing 400042 (China)

    2013-01-08

    Highlights: Black-Right-Pointing-Pointer Direct electrochemistry of glucose oxidase used for signal generation in aptasensor. Black-Right-Pointing-Pointer Using novel nanocomposite for immobilization and signal amplification. Black-Right-Pointing-Pointer Sensitive electrochemical detection of platelet-derived growth factor. - Abstract: In this work, a new label-free electrochemical aptamer-based sensor (aptasensor) was constructed for detection of platelet-derived growth factor (PDGF) based on the direct electrochemistry of glucose oxidase (GOD). For this proposed aptasensor, poly(diallyldimethylammonium chloride) (PDDA)-protected graphene-gold nanoparticles (P-Gra-GNPs) composite was firstly coated on electrode surface to form the interface with biocompatibility and huge surface area for the adsorption of GOD layer. Subsequently, gold nanoclusters (GNCs) were deposited on the surface of GOD to capture PDGF binding aptamer (PBA). Finally, GOD as a blocking reagent was employed to block the remaining active sites of the GNCs and avoid the nonspecific adsorption. With the direct electron transfer of double layer GOD membranes, the aptasensor showed excellent electrochemical response and the peak current decreased linearly with increasing logarithm of PDGF concentration from 0.005 nM to 60 nM with a relatively low limit of detection of 1.7 pM. The proposed aptasensor exhibited high specificity, good reproducibility and long-term stability, which provided a new promising technique for aptamer-based protein detection.

  17. Major regulatory factors in the evolution of development: the roles of goosecoid and Msx in the evolution of the direct-developing sea urchin Heliocidaris erythrogramma.

    Wilson, Keen A; Andrews, Mary E; Rudolf Turner, F; Raff, Rudolf A

    2005-01-01

    The transcription factors Gsc and Msx are expressed in the oral ectoderm of the indirect-developing sea urchin Heliocidaris tuberculata. Their patterns of expression are highly modified in the direct developer Heliocidaris erythrogramma, which lacks an oral ectoderm. We here test the hypothesis that they are large effect genes responsible for the loss of the oral ectoderm module in the direct-developing larva of H. erythrogramma as well as for the restoration of an overt oral ectoderm in H.e. xH.t. hybrids. We undertook misexpression/overexpression and knockdown assays in the two species and in hybrids by mRNA injection. The results indicate that dramatic changes of function of these transcription factors has occurred. One of these genes, Gsc, has the ability when misexpressed to partially restore oral ectoderm in H. erythrogramma. On the other hand, Msx has lost any oral function and instead has a role in mesoderm proliferation and patterning. In addition, we found that the H. tuberculataGsc is up regulated in H.e. xH.t. hybrids, showing a preferential use of the indirect developing parental gene in the development of the hybrid. We suggest that Gsc qualifies as a gene of large evolutionary effect and is partially responsible for the evolution of direct development of H. erythrogramma. We discuss these results in light of modularity and genetic networks in development, as well as in their implications for the rapid evolution of large morphological changes in development.

  18. An aptamer-based biosensing platform for highly sensitive detection of platelet-derived growth factor via enzyme-mediated direct electrochemistry

    Deng Kun; Xiang Yang; Zhang Liqun; Chen Qinghai; Fu Weiling

    2013-01-01

    Highlights: ► Direct electrochemistry of glucose oxidase used for signal generation in aptasensor. ► Using novel nanocomposite for immobilization and signal amplification. ► Sensitive electrochemical detection of platelet-derived growth factor. - Abstract: In this work, a new label-free electrochemical aptamer-based sensor (aptasensor) was constructed for detection of platelet-derived growth factor (PDGF) based on the direct electrochemistry of glucose oxidase (GOD). For this proposed aptasensor, poly(diallyldimethylammonium chloride) (PDDA)-protected graphene-gold nanoparticles (P-Gra-GNPs) composite was firstly coated on electrode surface to form the interface with biocompatibility and huge surface area for the adsorption of GOD layer. Subsequently, gold nanoclusters (GNCs) were deposited on the surface of GOD to capture PDGF binding aptamer (PBA). Finally, GOD as a blocking reagent was employed to block the remaining active sites of the GNCs and avoid the nonspecific adsorption. With the direct electron transfer of double layer GOD membranes, the aptasensor showed excellent electrochemical response and the peak current decreased linearly with increasing logarithm of PDGF concentration from 0.005 nM to 60 nM with a relatively low limit of detection of 1.7 pM. The proposed aptasensor exhibited high specificity, good reproducibility and long-term stability, which provided a new promising technique for aptamer-based protein detection.

  19. Factors affecting the potential of direct load control for non-generating utilities. Final report. [Distribution and wholesale power supply interaction

    None

    1979-04-01

    Several alternatives are available for achieving load management, including direct or voluntary control of customer loads, customer or utility energy storage systems for diurnal load shifting, and expanded interconnection and operation of electric power systems. All of these alternatives are available to the fully integrated (generating, transmitting and distributing) electric utility and the analysis of their effects encompasses the power supply and delivery system. However, the costs and benefits of the alternatives to the fully integrated electric utility are perhaps not so obvious. Therefore, by considering a non-generating utility, this analysis focuses upon the distribution system and wholesale power supply interaction as a step toward an analysis including the power supply and delivery system. This report develops an analysis procedure and discusses some of the relevant factors to be consdered in the application of direct load control for a non-generating utility system. The analysis concentrates on the distribution system only to determine the effect of rates and payback as a result of direct load control. Thus, the study is responsive to the specific needs of the non-generating utility. This analysis of direct load control encompasses the determination of those loads amenable to control, the selection of a suitable one-way communications system to rend control and the estimation of expected benefits and costs. The complementary functions to the application of direct load control such as automatic meter reading via the addition of a bi-directional communications system and voltage control are not included in the analysis but are detailed for future consideration.

  20. The regulatory mechanism of fruit ripening revealed by analyses of direct targets of the tomato MADS-box transcription factor RIPENING INHIBITOR

    Fujisawa, Masaki; Ito, Yasuhiro

    2013-01-01

    The developmental process of ripening is unique to fleshy fruits and a key factor in fruit quality. The tomato (Solanum lycopersicum) MADS-box transcription factor RIPENING INHIBITOR (RIN), one of the earliest-acting ripening regulators, is required for broad aspects of ripening, including ethylene-dependent and -independent pathways. However, our knowledge of direct RIN target genes has been limited, considering the broad effects of RIN on ripening. In a recent work published in The Plant Cell, we identified 241 direct RIN target genes by chromatin immunoprecipitation coupled with DNA microarray (ChIP-chip) and transcriptome analysis. Functional classification of the targets revealed that RIN participates in the regulation of many biological processes including well-known ripening processes such as climacteric ethylene production and lycopene accumulation. In addition, we found that ethylene is required for the full expression of RIN and several RIN-targeting transcription factor genes at the ripening stage. Here, based on our recently published findings and additional data, we discuss the ripening processes regulated by RIN and the interplay between RIN and ethylene. PMID:23518588

  1. Climatic factors directly impact the volatile organic compound fingerprint in green Arabica coffee bean as well as coffee beverage quality.

    Bertrand, B; Boulanger, R; Dussert, S; Ribeyre, F; Berthiot, L; Descroix, F; Joët, T

    2012-12-15

    Coffee grown at high elevations fetches a better price than that grown in lowland regions. This study was aimed at determining whether climatic conditions during bean development affected sensory perception of the coffee beverage and combinations of volatile compounds in green coffee. Green coffee samples from 16 plots representative of the broad range of climatic variations in Réunion Island were compared by sensory analysis. Volatiles were extracted by solid phase micro-extraction and the volatile compounds were analysed by GC-MS. The results revealed that, among the climatic factors, the mean air temperature during seed development greatly influenced the sensory profile. Positive quality attributes such as acidity, fruity character and flavour quality were correlated and typical of coffees produced at cool climates. Two volatile compounds (ethanal and acetone) were identified as indicators of these cool temperatures. Among detected volatiles, most of the alcohols, aldehydes, hydrocarbons and ketones appeared to be positively linked to elevated temperatures and high solar radiation, while the sensory profiles displayed major defects (i.e. green, earthy flavour). Two alcohols (butan-1,3-diol and butan-2,3-diol) were closely correlated with a reduction in aromatic quality, acidity and an increase in earthy and green flavours. We assumed that high temperatures induce accumulation of these compounds in green coffee, and would be detected as off-flavours, even after roasting. Climate change, which generally involves a substantial increase in average temperatures in mountainous tropical regions, could be expected to have a negative impact on coffee quality. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Direct activation of human and mouse Oct4 genes using engineered TALE and Cas9 transcription factors.

    Hu, Jiabiao; Lei, Yong; Wong, Wing-Ki; Liu, Senquan; Lee, Kai-Chuen; He, Xiangjun; You, Wenxing; Zhou, Rui; Guo, Jun-Tao; Chen, Xiongfong; Peng, Xianlu; Sun, Hao; Huang, He; Zhao, Hui; Feng, Bo

    2014-04-01

    The newly developed transcription activator-like effector protein (TALE) and clustered regularly interspaced short palindromic repeats/Cas9 transcription factors (TF) offered a powerful and precise approach for modulating gene expression. In this article, we systematically investigated the potential of these new tools in activating the stringently silenced pluripotency gene Oct4 (Pou5f1) in mouse and human somatic cells. First, with a number of TALEs and sgRNAs targeting various regions in the mouse and human Oct4 promoters, we found that the most efficient TALE-VP64s bound around -120 to -80 bp, while highly effective sgRNAs targeted from -147 to -89-bp upstream of the transcription start sites to induce high activity of luciferase reporters. In addition, we observed significant transcriptional synergy when multiple TFs were applied simultaneously. Although individual TFs exhibited marginal activity to up-regulate endogenous gene expression, optimized combinations of TALE-VP64s could enhance endogenous Oct4 transcription up to 30-fold in mouse NIH3T3 cells and 20-fold in human HEK293T cells. More importantly, the enhancement of OCT4 transcription ultimately generated OCT4 proteins. Furthermore, examination of different epigenetic modifiers showed that histone acetyltransferase p300 could enhance both TALE-VP64 and sgRNA/dCas9-VP64 induced transcription of endogenous OCT4. Taken together, our study suggested that engineered TALE-TF and dCas9-TF are useful tools for modulating gene expression in mammalian cells.

  3. Brown carbon aerosols from burning of boreal peatlands: microphysical properties, emission factors, and implications for direct radiative forcing

    R. K. Chakrabarty

    2016-03-01

    Full Text Available The surface air warming over the Arctic has been almost twice as much as the global average in recent decades. In this region, unprecedented amounts of smoldering peat fires have been identified as a major emission source of climate-warming agents. While much is known about greenhouse gas emissions from these fires, there is a knowledge gap on the nature of particulate emissions and their potential role in atmospheric warming. Here, we show that aerosols emitted from burning of Alaskan and Siberian peatlands are predominantly brown carbon (BrC – a class of visible light-absorbing organic carbon (OC – with a negligible amount of black carbon content. The mean fuel-based emission factors for OC aerosols ranged from 3.8 to 16.6 g kg−1. Their mass absorption efficiencies were in the range of 0.2–0.8 m2 g−1 at 405 nm (violet and dropped sharply to 0.03–0.07 m2 g−1 at 532 nm (green, characterized by a mean Ångström exponent of  ≈  9. Electron microscopy images of the particles revealed their morphologies to be either single sphere or agglomerated “tar balls”. The shortwave top-of-atmosphere aerosol radiative forcing per unit optical depth under clear-sky conditions was estimated as a function of surface albedo. Only over bright surfaces with albedo greater than 0.6, such as snow cover and low-level clouds, the emitted aerosols could result in a net warming (positive forcing of the atmosphere.

  4. The POU Factor Ventral Veins Lacking/Drifter Directs the Timing of Metamorphosis through Ecdysteroid and Juvenile Hormone Signaling

    Chaieb, Leila; Koyama, Takashi; Sarwar, Prioty; Mirth, Christen K.; Smith, Wendy A.; Suzuki, Yuichiro

    2014-01-01

    Although endocrine changes are known to modulate the timing of major developmental transitions, the genetic mechanisms underlying these changes remain poorly understood. In insects, two developmental hormones, juvenile hormone (JH) and ecdysteroids, are coordinated with each other to induce developmental changes associated with metamorphosis. However, the regulation underlying the coordination of JH and ecdysteroid synthesis remains elusive. Here, we examined the function of a homolog of the vertebrate POU domain protein, Ventral veins lacking (Vvl)/Drifter, in regulating both of these hormonal pathways in the red flour beetle, Tribolium castaneum (Tenebrionidae). RNA interference-mediated silencing of vvl expression led to both precocious metamorphosis and inhibition of molting in the larva. Ectopic application of a JH analog on vvl knockdown larvae delayed the onset of metamorphosis and led to a prolonged larval stage, indicating that Vvl acts upstream of JH signaling. Accordingly, vvl knockdown also reduced the expression of a JH biosynthesis gene, JH acid methyltransferase 3 (jhamt3). In addition, ecdysone titer and the expression of the ecdysone response gene, hormone receptor 3 (HR3), were reduced in vvl knockdown larvae. The expression of the ecdysone biosynthesis gene phantom (phm) and spook (spo) were reduced in vvl knockdown larvae in the anterior and posterior halves, respectively, indicating that Vvl might influence ecdysone biosynthesis in both the prothoracic gland and additional endocrine sources. Injection of 20-hydroxyecdysone (20E) into vvl knockdown larvae could restore the expression of HR3 although molting was never restored. These findings suggest that Vvl coordinates both JH and ecdysteroid biosynthesis as well as molting behavior to influence molting and the timing of metamorphosis. Thus, in both vertebrates and insects, POU factors modulate the production of major neuroendocrine regulators during sexual maturation. PMID:24945490

  5. Model independent spectroscopic information from an analysis of peripheral direct radiative capture reaction and its application for an extrapolation of an astrophysical S-factor to stellar energies

    Igamov, S.B.; Tursunmuratov, T.M.; Yarmukhamedov, R.

    2003-01-01

    In this work, within the framework of the cluster potential approach we develop a method which can be used an independent source of getting information on the value of the nuclear vertex constant (NVC) (or respective asymptotical normalization coefficient (ANC)) from the analysis of the direct radiative capture cross section σ(E)(or the astrophysical S-factor S(E)) at extremely low energies by a model independent way as possible. The main idea of the proposed method is that at stellar energies peripheral direct radiative capture reaction of astrophysical interest proceeds mainly through the tail of the overlap integral, which is completely determined by the binding energy and the respective ANC (or NVC). The main advantage of the proposed method is that it allows us to determine both the absolute value of NVC (or ANC) and the astrophysical S-factor S(E) at solar energies (0-50 keV) by means of the analysis of the same experimental astrophysical S-factor S exp (E) in a correct self consistent way using the same potential both for the bound state and for scattering state. The method has been applied for an investigation of the direct radiative capture t(α, γ) 7 Li and 3 He(α, γ) 7 Be reactions at extremely low energies. At first, this method was used for analysis of the S exp (E) to determine values of the modulus squared of the NVC's (or the respective ANC's). The values of NVC's are presented. Then, the obtained NVC's are used by us for extrapolation of the S(E) of the reactions considered to stellar energies (E=0-50 keV) for the 3 He(α, γ) 7 Be reaction and for the t(α, γ) 7 Li reaction. The obtained results are compared with those other authors

  6. Chemical and physical factors which control the substitution reactions of direct fission-produced iodine with gaseous methane and the methyl halides

    Kikuchi, M.; Church, L.B.

    1976-01-01

    The factors controlling the hydrogen and halogen substitution reactions resulting from direct fission-produced iodine isotopes (*I) with gaseous methane and methyl halides were investigated. The chemical reaction probabilities, corrected for any secondary decomposition, were compared as a function of various chemical and physical parameters. These include carbon-halogen bond strength, halogen electronegativity, volume and cross sectional area of the substituted and neighboring atoms. On the basis of this analysis, it is concluded that *I-for-X (where X = H, F, Cl, Br and I) substitution reactions are controlled by the cross sectional area of the X atom. The *I-for-H substitution probability is reduced in proportion to the volume of X, suggesting that steric interference is the dominant factor influencing the reaction probability. (orig.) [de

  7. AN ANALYSIS OF THE ECONOMIC DETERMINANTS AND THE QUALITY OF THE INSTITUTIONAL FRAMEWORK AS FACTORS TO ATTRACT FOREIGN DIRECT INVESTMENT IN SOUTHEASTERN EUROPE: THE CASE OF GREECE

    Constantinos CHOROMIDES

    2015-06-01

    Full Text Available Foreign Direct Investment (FDI is considered by researchers as a critical factor for economic growth and development since they have shown a positive relationship between FDI and economic growth. The recent economic crisis in the European Union (EU has brought up again the discussion of the key drivers specific to the attraction of FDI. In addition to strict economic factors the literature emphasizes the role of institutions in a country as determinants in attracting FDI inflows. An analysis of the role that the quality of institutions in attracting FDI has in Greece is attempted using an econometric model on institutional, regulatory, country specific and firm level data. For the purpose of giving a regional dimension in the analysis, and for attempting a comparison of the findings, the analysis focuses besides Greece, in two other Southeastern European countries (SEE, Bulgaria and Romania, being two new member states of the EU.

  8. Gata4 expression in lateral mesoderm is downstream of BMP4 and isactivated directly by Forkhead and GATA transcription factors through adistal enhancer element

    Rojas, Anabel; De Val, Sarah; Heidt, Analeah B.; Xu, Shan-Mei; Bristow, James; Black, Brian L.

    2005-05-20

    The GATA family of zinc-finger transcription factors plays key roles in the specification and differentiation of multiple cell types during development. GATA4 is an early regulator of gene expression during the development of endoderm and mesoderm, and genetic studies in mice have demonstrated that GATA4 is required for embryonic development.Despite the importance of GATA4 in tissue specification and differentiation, the mechanisms by which Gata4 expression is activated and the transcription factor pathways upstream of GATA4 remain largely undefined. To identify transcriptional regulators of Gata4 in the mouse,we screened conserved noncoding sequences from the mouse Gata4 gene for enhancer activity in transgenic embryos. Here, we define the regulation of a distal enhancer element from Gata4 that is sufficient to direct expression throughout the lateral mesoderm, beginning at 7.5 days of mouse embryonic development. The activity of this enhancer is initially broad but eventually becomes restricted to the mesenchyme surrounding the liver. We demonstrate that the function of this enhancer in transgenic embryos is dependent upon highly conserved Forkhead and GATA transcription factor binding sites, which are bound by FOXF1 and GATA4,respectively. Furthermore, the activity of the Gata4 lateral mesoderm enhancer is attenuated by the BMP antagonist Noggin, and the enhancer is not activated in Bmp4-null embryos. Thus, these studies establish that Gata4 is a direct transcriptional target of Forkhead and GATA transcription factors in the lateral mesoderm, and demonstrate that Gata4lateral mesoderm enhancer activation requires BMP4, supporting a model in which GATA4 serves as a downstream effector of BMP signaling in the lateral mesoderm.

  9. Safety and risk factors for difficult endoscopist-directed ERCP sedation in daily practice: a hospital-based case-control study

    Enrique Pérez-Cuadrado-Robles

    Full Text Available Background: There are limited data concerning endoscopist-directed endoscopic retrograde cholangiopancreatography deep sedation. The aim of this study was to establish the safety and risk factors for difficult sedation in daily practice. Patients and methods: Hospital-based, frequency matched case-control study. All patients were identified from a database of 1,008 patients between 2014 and 2015. The cases were those with difficult sedations. This concept was defined based on the combination of the receipt of high-doses of midazolam or propofol, poor tolerance, use of reversal agents or sedation-related adverse events. The presence of different factors was evaluated to determine whether they predicted difficult sedation. Results: One-hundred and eighty-nine patients (63 cases, 126 controls were included. Cases were classified in terms of high-dose requirements (n = 35, 55.56%, sedation-related adverse events (n = 14, 22.22%, the use of reversal agents (n = 13, 20.63% and agitation/discomfort (n = 8, 12.7%. Concerning adverse events, the total rate was 1.39%, including clinically relevant hypoxemia (n = 11, severe hypotension (n = 2 and paradoxical reactions to midazolam (n = 1. The rate of hypoxemia was higher in patients under propofol combined with midazolam than in patients with propofol alone (2.56% vs. 0.8%, p < 0.001. Alcohol consumption (OR: 2.674 [CI 95%: 1.098-6.515], p = 0.030, opioid consumption (OR: 2.713 [CI 95%: 1.096-6.716], p = 0.031 and the consumption of other psychoactive drugs (OR: 2.015 [CI 95%: 1.017-3.991], p = 0.045 were confirmed to be independent risk factors for difficult sedation. Conclusions: Endoscopist-directed deep sedation during endoscopic retrograde cholangiopancreatography is safe. The presence of certain factors should be assessed before the procedure to identify patients who are high-risk for difficult sedation.

  10. Different Effects of Human Umbilical Cord Mesenchymal Stem Cells on Glioblastoma Stem Cells by Direct Cell Interaction or Via Released Soluble Factors

    Adriana Bajetto

    2017-10-01

    Full Text Available Glioblastoma (GBM, the most common primary brain tumor in adults, is an aggressive, fast-growing and highly vascularized tumor, characterized by extensive invasiveness and local recurrence. In GBM and other malignancies, cancer stem cells (CSCs are believed to drive invasive tumor growth and recurrence, being responsible for radio- and chemo-therapy resistance. Mesenchymal stem cells (MSCs are multipotent progenitors that exhibit tropism for tumor microenvironment mediated by cytokines, chemokines and growth factors. Initial studies proposed that MSCs might exert inhibitory effects on tumor development, although, to date, contrasting evidence has been provided. Different studies reported either MSC anti-tumor activity or their support to tumor growth. Here, we examined the effects of umbilical cord (UC-MSCs on in vitro GBM-derived CSC growth, by direct cell-to-cell interaction or indirect modulation, via the release of soluble factors. We demonstrate that UC-MSCs and CSCs exhibit reciprocal tropism when co-cultured as 3D spheroids and their direct cell interaction reduces the proliferation of both cell types. Contrasting effects were obtained by UC-MSC released factors: CSCs, cultured in the presence of conditioned medium (CM collected from UC-MSCs, increased proliferation rate through transient ERK1/2 and Akt phosphorylation/activation. Analysis of the profile of the cytokines released by UC-MSCs in the CM revealed a strong production of molecules involved in inflammation, angiogenesis, cell migration and proliferation, such as IL-8, GRO, ENA-78 and IL-6. Since CXC chemokine receptor 2 (CXCR2, a receptor shared by several of these ligands, is expressed in GBM CSCs, we evaluated its involvement in CSC proliferation induced by UC-MSC-CM. Using the CXCR2 antagonist SB225002, we observed a partial but statistically significant inhibition of CSC proliferation and migration induced by the UC-MSC-released cytokines. Conversely, CXCR2 blockade did not

  11. Different Effects of Human Umbilical Cord Mesenchymal Stem Cells on Glioblastoma Stem Cells by Direct Cell Interaction or Via Released Soluble Factors

    Bajetto, Adriana; Pattarozzi, Alessandra; Corsaro, Alessandro; Barbieri, Federica; Daga, Antonio; Bosio, Alessia; Gatti, Monica; Pisaturo, Valerio; Sirito, Rodolfo; Florio, Tullio

    2017-01-01

    Glioblastoma (GBM), the most common primary brain tumor in adults, is an aggressive, fast-growing and highly vascularized tumor, characterized by extensive invasiveness and local recurrence. In GBM and other malignancies, cancer stem cells (CSCs) are believed to drive invasive tumor growth and recurrence, being responsible for radio- and chemo-therapy resistance. Mesenchymal stem cells (MSCs) are multipotent progenitors that exhibit tropism for tumor microenvironment mediated by cytokines, chemokines and growth factors. Initial studies proposed that MSCs might exert inhibitory effects on tumor development, although, to date, contrasting evidence has been provided. Different studies reported either MSC anti-tumor activity or their support to tumor growth. Here, we examined the effects of umbilical cord (UC)-MSCs on in vitro GBM-derived CSC growth, by direct cell-to-cell interaction or indirect modulation, via the release of soluble factors. We demonstrate that UC-MSCs and CSCs exhibit reciprocal tropism when co-cultured as 3D spheroids and their direct cell interaction reduces the proliferation of both cell types. Contrasting effects were obtained by UC-MSC released factors: CSCs, cultured in the presence of conditioned medium (CM) collected from UC-MSCs, increased proliferation rate through transient ERK1/2 and Akt phosphorylation/activation. Analysis of the profile of the cytokines released by UC-MSCs in the CM revealed a strong production of molecules involved in inflammation, angiogenesis, cell migration and proliferation, such as IL-8, GRO, ENA-78 and IL-6. Since CXC chemokine receptor 2 (CXCR2), a receptor shared by several of these ligands, is expressed in GBM CSCs, we evaluated its involvement in CSC proliferation induced by UC-MSC-CM. Using the CXCR2 antagonist SB225002, we observed a partial but statistically significant inhibition of CSC proliferation and migration induced by the UC-MSC-released cytokines. Conversely, CXCR2 blockade did not reduce the

  12. ChIP-on-chip analysis identifies IL-22 as direct target gene of ectopically expressed FOXP3 transcription factor in human T cells

    Jeron Andreas

    2012-12-01

    Full Text Available Abstract Background The transcription factor (TF forkhead box P3 (FOXP3 is constitutively expressed at high levels in naturally occurring CD4+CD25+ regulatory T cells (nTregs. It is not only the most accepted marker for that cell population but is also considered lineage determinative. Chromatin immunoprecipitation (ChIP of TFs in combination with genomic tiling microarray analysis (ChIP-on-chip has been shown to be an appropriate tool for identifying FOXP3 transcription factor binding sites (TFBSs on a genome-wide scale. In combination with microarray expression analysis, the ChIP-on-chip technique allows identification of direct FOXP3 target genes. Results ChIP-on-chip analysis of the human FOXP3 expressed in resting and PMA/ionomycin–stimulated Jurkat T cells revealed several thousand putative FOXP3 binding sites and demonstrated the importance of intronic regions for FOXP3 binding. The analysis of expression data showed that the stimulation-dependent down-regulation of IL-22 was correlated with direct FOXP3 binding in the IL-22 promoter region. This association was confirmed by real-time PCR analysis of ChIP-DNA. The corresponding ChIP-region also contained a matching FOXP3 consensus sequence. Conclusions Knowledge of the general distribution patterns of FOXP3 TFBSs in the human genome under resting and activated conditions will contribute to a better understanding of this TF and its influence on direct target genes, as well as its importance for the phenotype and function of Tregs. Moreover, FOXP3-dependent repression of Th17-related IL-22 may be relevant to an understanding of the phenomenon of Treg/Th17 cell plasticity.

  13. A STUDY OF CHINESE YUAN (RMB APPRECIATION ACCOMPANYING WITH OTHERS FACTORS INCLUDING FOREIGN DIRECT INVESTMENT (FDI AND THEIR EFFECT ON CHINA ECONOMY

    Ping-fu (Brian LAI

    2014-07-01

    Full Text Available The Chinese Yuan (RMB has been on the trend of appreciation over the last decade, and such a trend will likely be continuing for some years over the next decade. According to some scholars in their published literatures, the appreciation of RMB, the influx of Foreign Direct Investment (FDI has been ongoing accompanying the sustained growing economy in mainland China over the past decade. It is believed that the China economy has an implication from some significant factors including appreciation of RMB, interest rate of RMB, inflation and continuous increase of FDI for the next several years. The present study aims to provide an emphasis on investigation into effect on China economy as a result of appreciation of RMB and FDI together with some other factors, and to provide an outlook on the economy in China for the coming decades. First, a review was carried on relevant background information and development history of RMB and FDI. There are many reasons and factors behind leading to the sustained growth in the economy in China in the last decade and such effects were in coverage in the literature review. An overview of the development of RMB exchange mechanism, and other variables including (1 RMB exchange rate, (2 China interest rate, (3 Foreign Direct Investment (FDI, (4 Trade Balance of China, (5 Annual Inflation rate in China, (6 Energy Consumption in China, (7 Foreign Exchange Reserve in China, (8 China wages, (9 China External Debt and (10 China Consumer Price Index, which may have effect on the growth of the economy in China is covered in the literature review conducted in Chapter 2.

  14. Tyrosine phosphorylation of platelet derived growth factor β receptors in coronary artery lesions: implications for vascular remodelling after directional coronary atherectomy and unstable angina pectoris

    Abe, J; Deguchi, J; Takuwa, Y; Hara, K; Ikari, Y; Tamura, T; Ohno, M; Kurokawa, K

    1998-01-01

    Background—Growth factors such as platelet derived growth factor (PDGF) have been postulated to be important mediators of neointimal proliferation observed in atherosclerotic plaques and restenotic lesions following coronary interventions. Binding of PDGF to its receptor results in intrinsic receptor tyrosine kinase activation and subsequent cellular migration, proliferation, and vascular contraction.
Aims—To investigate whether the concentration of PDGF β receptor tyrosine phosphorylation obtained from directional coronary atherectomy (DCA) samples correlate with atherosclerotic plaque burden, the ability of diseased vessels to remodel, coronary risk factors, and clinical events.
Methods—DCA samples from 59 patients and 15 non-atherosclerotic left internal thoracic arteries (LITA) were analysed for PDGF β receptor tyrosine phosphorylation content by receptor immunoprecipitation and antiphosphotyrosine western blot. The amount of PDGF β receptor phosphorylation was analysed in relation to angiographic follow up data and clinical variables.
Results—PDGF β receptor tyrosine phosphorylation in the 59 DCA samples was greater than in the 15 non-atherosclerotic LITA (mean (SD) 0.84 (0.67) v 0.17 (0.08) over a control standard, p atherectomy;  restenosis PMID:9616351

  15. Extracellular matrix protein 1, a direct targeting molecule of parathyroid hormone–related peptide, negatively regulates chondrogenesis and endochondral ossification via associating with progranulin growth factor

    Kong, Li; Zhao, Yun-Peng; Tian, Qing-Yun; Feng, Jian-Quan; Kobayashi, Tatsuya; Merregaert, Joseph; Liu, Chuan-Ju

    2016-01-01

    Chondrogenesis and endochondral ossification are precisely controlled by cellular interactions with surrounding matrix proteins and growth factors that mediate cellular signaling pathways. Here, we report that extracellular matrix protein 1 (ECM1) is a previously unrecognized regulator of chondrogenesis. ECM1 is induced in the course of chondrogenesis and its expression in chondrocytes strictly depends on parathyroid hormone–related peptide (PTHrP) signaling pathway. Overexpression of ECM1 suppresses, whereas suppression of ECM1 enhances, chondrocyte differentiation and hypertrophy in vitro and ex vivo. In addition, target transgene of ECM1 in chondrocytes or osteoblasts in mice leads to striking defects in cartilage development and endochondral bone formation. Of importance, ECM1 seems to be critical for PTHrP action in chondrogenesis, as blockage of ECM1 nearly abolishes PTHrP regulation of chondrocyte hypertrophy, and overexpression of ECM1 rescues disorganized growth plates of PTHrP-null mice. Furthermore, ECM1 and progranulin chondrogenic growth factor constitute an interaction network and act in concert in the regulation of chondrogenesis.—Kong, L., Zhao, Y.-P., Tian, Q.-Y., Feng, J.-Q., Kobayashi, T., Merregaert, J., Liu, C.-J. Extracellular matrix protein 1, a direct targeting molecule of parathyroid hormone–related peptide, negatively regulates chondrogenesis and endochondral ossification via associating with progranulin growth factor. PMID:27075243

  16. Modeling state-level soil carbon emission factors under various scenarios for direct land use change associated with United States biofuel feedstock production

    Kwon, Ho-Young; Mueller, Steffen; Dunn, Jennifer B.; Wander, Michelle M.

    2013-01-01

    Current estimates of life cycle greenhouse gas emissions of biofuels produced in the US can be improved by refining soil C emission factors (EF; C emissions per land area per year) for direct land use change associated with different biofuel feedstock scenarios. We developed a modeling framework to estimate these EFs at the state-level by utilizing remote sensing data, national statistics databases, and a surrogate model for CENTURY's soil organic C dynamics submodel (SCSOC). We estimated the forward change in soil C concentration within the 0–30 cm depth and computed the associated EFs for the 2011 to 2040 period for croplands, grasslands or pasture/hay, croplands/conservation reserve, and forests that were suited to produce any of four possible biofuel feedstock systems [corn (Zea Mays L)-corn, corn–corn with stover harvest, switchgrass (Panicum virgatum L), and miscanthus (Miscanthus × giganteus Greef et Deuter)]. Our results predict smaller losses or even modest gains in sequestration for corn based systems, particularly on existing croplands, than previous efforts and support assertions that production of perennial grasses will lead to negative emissions in most situations and that conversion of forest or established grasslands to biofuel production would likely produce net emissions. The proposed framework and use of the SCSOC provide transparency and relative simplicity that permit users to easily modify model inputs to inform biofuel feedstock production targets set forth by policy. -- Highlights: ► We model regionalized feedstock-specific United States soil C emission factors. ► We simulate soil C changes from direct land use change associated with biofuel feedstock production. ► Corn, corn-stover, and perennial grass biofuel feedstocks grown in croplands maintain soil C levels. ► Converting grasslands to bioenergy crops risks soil C loss. ► This modeling framework yields more refined soil C emissions than national-level emissions

  17. De novo transcriptome sequence assembly from coconut leaves and seeds with a focus on factors involved in RNA-directed DNA methylation.

    Huang, Ya-Yi; Lee, Chueh-Pai; Fu, Jason L; Chang, Bill Chia-Han; Matzke, Antonius J M; Matzke, Marjori

    2014-09-04

    Coconut palm (Cocos nucifera) is a symbol of the tropics and a source of numerous edible and nonedible products of economic value. Despite its nutritional and industrial significance, coconut remains under-represented in public repositories for genomic and transcriptomic data. We report de novo transcript assembly from RNA-seq data and analysis of gene expression in seed tissues (embryo and endosperm) and leaves of a dwarf coconut variety. Assembly of 10 GB sequencing data for each tissue resulted in 58,211 total unigenes in embryo, 61,152 in endosperm, and 33,446 in leaf. Within each unigene pool, 24,857 could be annotated in embryo, 29,731 could be annotated in endosperm, and 26,064 could be annotated in leaf. A KEGG analysis identified 138, 138, and 139 pathways, respectively, in transcriptomes of embryo, endosperm, and leaf tissues. Given the extraordinarily large size of coconut seeds and the importance of small RNA-mediated epigenetic regulation during seed development in model plants, we used homology searches to identify putative homologs of factors required for RNA-directed DNA methylation in coconut. The findings suggest that RNA-directed DNA methylation is important during coconut seed development, particularly in maturing endosperm. This dataset will expand the genomics resources available for coconut and provide a foundation for more detailed analyses that may assist molecular breeding strategies aimed at improving this major tropical crop. Copyright © 2014 Huang et al.

  18. An aptamer-based biosensing platform for highly sensitive detection of platelet-derived growth factor via enzyme-mediated direct electrochemistry.

    Deng, Kun; Xiang, Yang; Zhang, Liqun; Chen, Qinghai; Fu, Weiling

    2013-01-08

    In this work, a new label-free electrochemical aptamer-based sensor (aptasensor) was constructed for detection of platelet-derived growth factor (PDGF) based on the direct electrochemistry of glucose oxidase (GOD). For this proposed aptasensor, poly(diallyldimethylammonium chloride) (PDDA)-protected graphene-gold nanoparticles (P-Gra-GNPs) composite was firstly coated on electrode surface to form the interface with biocompatibility and huge surface area for the adsorption of GOD layer. Subsequently, gold nanoclusters (GNCs) were deposited on the surface of GOD to capture PDGF binding aptamer (PBA). Finally, GOD as a blocking reagent was employed to block the remaining active sites of the GNCs and avoid the nonspecific adsorption. With the direct electron transfer of double layer GOD membranes, the aptasensor showed excellent electrochemical response and the peak current decreased linearly with increasing logarithm of PDGF concentration from 0.005 nM to 60 nM with a relatively low limit of detection of 1.7 pM. The proposed aptasensor exhibited high specificity, good reproducibility and long-term stability, which provided a new promising technique for aptamer-based protein detection. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. ETHYLENE RESPONSE FACTOR 96 positively regulates Arabidopsis resistance to necrotrophic pathogens by direct binding to GCC elements of jasmonate - and ethylene-responsive defence genes.

    Catinot, Jérémy; Huang, Jing-Bo; Huang, Pin-Yao; Tseng, Min-Yuan; Chen, Ying-Lan; Gu, Shin-Yuan; Lo, Wan-Sheng; Wang, Long-Chi; Chen, Yet-Ran; Zimmerli, Laurent

    2015-12-01

    The ERF (ethylene responsive factor) family is composed of transcription factors (TFs) that are critical for appropriate Arabidopsis thaliana responses to biotic and abiotic stresses. Here we identified and characterized a member of the ERF TF group IX, namely ERF96, that when overexpressed enhances Arabidopsis resistance to necrotrophic pathogens such as the fungus Botrytis cinerea and the bacterium Pectobacterium carotovorum. ERF96 is jasmonate (JA) and ethylene (ET) responsive and ERF96 transcripts accumulation was abolished in JA-insensitive coi1-16 and in ET-insensitive ein2-1 mutants. Protoplast transactivation and electrophoresis mobility shift analyses revealed that ERF96 is an activator of transcription that binds to GCC elements. In addition, ERF96 mainly localized to the nucleus. Microarray analysis coupled to chromatin immunoprecipitation-PCR of Arabidopsis overexpressing ERF96 revealed that ERF96 enhances the expression of the JA/ET defence genes PDF1.2a, PR-3 and PR-4 as well as the TF ORA59 by direct binding to GCC elements present in their promoters. While ERF96-RNAi plants demonstrated wild-type resistance to necrotrophic pathogens, basal PDF1.2 expression levels were reduced in ERF96-silenced plants. This work revealed ERF96 as a key player of the ERF network that positively regulates the Arabidopsis resistance response to necrotrophic pathogens. © 2015 John Wiley & Sons Ltd.

  20. Measuring the Total-Factor Carbon Emission Performance of Industrial Land Use in China Based on the Global Directional Distance Function and Non-Radial Luenberger Productivity Index

    Wei Wang

    2016-04-01

    Full Text Available Industry is a major contributor to carbon emissions in China, and industrial land is an important input to industrial production. Therefore, a detailed analysis of the carbon emission performance of industrial land use is necessary for making reasonable carbon reduction policies that promote the sustainable use of industrial land. This paper aims to analyze the dynamic changes in the total-factor carbon emission performance of industrial land use (TCPIL in China by applying a global directional distance function (DDF and non-radial Luenberger productivity index. The empirical results show that the eastern region enjoys better TCPIL than the central and western regions, but the regional gaps in TCPIL are narrowing. The growth in NLCPILs (non-radial Luenberger carbon emission performance of industrial land use in the eastern and central regions is mainly driven by technological progress, whereas efficiency improvements contribute more to the growth of NLCPIL in the western region. The provinces in the eastern region have the most innovative and environmentally-friendly production technologies. The results of the analysis of the influencing factors show implications for improving the NLCPIL, including more investment in industrial research and development (R&D, the implementation of carbon emission reduction policies, reduction in the use of fossil energy, especially coal, in the process of industrial production, actively learning about foreign advanced technology, properly solving the problem of surplus labor in industry and the expansion of industrial development.

  1. Transcranial direct current stimulation (tDCS) facilitates overall visual search response times but does not interact with visual search task factors.

    Sung, Kyongje; Gordon, Barry

    2018-01-01

    Whether transcranial direct current stimulation (tDCS) affects mental functions, and how any such effects arise from its neural effects, continue to be debated. We investigated whether tDCS applied over the visual cortex (Oz) with a vertex (Cz) reference might affect response times (RTs) in a visual search task. We also examined whether any significant tDCS effects would interact with task factors (target presence, discrimination difficulty, and stimulus brightness) that are known to selectively influence one or the other of the two information processing stages posited by current models of visual search. Based on additive factor logic, we expected that the pattern of interactions involving a significant tDCS effect could help us colocalize the tDCS effect to one (or both) of the processing stages. In Experiment 1 (n = 12), anodal tDCS improved RTs significantly; cathodal tDCS produced a nonsignificant trend toward improvement. However, there were no interactions between the anodal tDCS effect and target presence or discrimination difficulty. In Experiment 2 (n = 18), we manipulated stimulus brightness along with target presence and discrimination difficulty. Anodal and cathodal tDCS both produced significant improvements in RTs. Again, the tDCS effects did not interact with any of the task factors. In Experiment 3 (n = 16), electrodes were placed at Cz and on the upper arm, to test for a possible effect of incidental stimulation of the motor regions under Cz. No effect of tDCS on RTs was found. These findings strengthen the case for tDCS having real effects on cerebral information processing. However, these effects did not clearly arise from either of the two processing stages of the visual search process. We suggest that this is because tDCS has a DIFFUSE, pervasive action across the task-relevant neuroanatomical region(s), not a discrete effect in terms of information processing stages.

  2. Short-term salivary acetaldehyde increase due to direct exposure to alcoholic beverages as an additional cancer risk factor beyond ethanol metabolism

    Monakhova Yulia B

    2011-01-01

    Full Text Available Abstract Background An increasing body of evidence now implicates acetaldehyde as a major underlying factor for the carcinogenicity of alcoholic beverages and especially for oesophageal and oral cancer. Acetaldehyde associated with alcohol consumption is regarded as 'carcinogenic to humans' (IARC Group 1, with sufficient evidence available for the oesophagus, head and neck as sites of carcinogenicity. At present, research into the mechanistic aspects of acetaldehyde-related oral cancer has been focused on salivary acetaldehyde that is formed either from ethanol metabolism in the epithelia or from microbial oxidation of ethanol by the oral microflora. This study was conducted to evaluate the role of the acetaldehyde that is found as a component of alcoholic beverages as an additional factor in the aetiology of oral cancer. Methods Salivary acetaldehyde levels were determined in the context of sensory analysis of different alcoholic beverages (beer, cider, wine, sherry, vodka, calvados, grape marc spirit, tequila, cherry spirit, without swallowing, to exclude systemic ethanol metabolism. Results The rinsing of the mouth for 30 seconds with an alcoholic beverage is able to increase salivary acetaldehyde above levels previously judged to be carcinogenic in vitro, with levels up to 1000 μM in cases of beverages with extreme acetaldehyde content. In general, the highest salivary acetaldehyde concentration was found in all cases in the saliva 30 sec after using the beverages (average 353 μM. The average concentration then decreased at the 2-min (156 μM, 5-min (76 μM and 10-min (40 μM sampling points. The salivary acetaldehyde concentration depends primarily on the direct ingestion of acetaldehyde contained in the beverages at the 30-sec sampling, while the influence of the metabolic formation from ethanol becomes the major factor at the 2-min sampling point. Conclusions This study offers a plausible mechanism to explain the increased risk for oral

  3. Effect of MCM09, an active site-directed inhibitor of factor Xa, on B16-BL6 melanoma lung colonies in mice.

    Rossi, C; Hess, S; Eckl, R W; di Lena, A; Bruno, A; Thomas, O; Poggi, A

    2006-03-01

    Treatment with anticoagulant drugs has shown potential inhibitory effect on tumor invasion, although the relationship with clotting inhibition was not clear. The aim of our study was to evaluate the potential antitumor activity of MCM09, a newly developed, active site-directed, small molecule inhibitor of factor Xa (FXa) [WO0216312], and to relate the findings to anticlotting potency. MCM09 (0.1-10 mg kg(-1)) or heparin (H; 10 mg kg(-1)) was injected intravenously (i.v.), with 5 x 10(4) B16-BL6 melanoma cells, in C57BL/6 mice. Mice were killed after 18 days, to count lung colonies. Ex vivo anticoagulant activity was measured by activated partial thromboplastin time (APTT) on mouse plasma. MCM09, a selective inhibitor of FXa (IC-50 = 2.4 nm against human FXa), inhibited in a dose-dependent manner B16-BL6 melanoma lung colonies in mice. Mean lung metastasis number was 20.9 +/- 4.8 in controls (n = 10), 1.2 +/- 0.4 in mice treated with H, 10 mg kg(-1) i.v. (P < 0.01), 0.9 +/- 0.3, 9.2 +/- 2.2 and 15.5 +/- 2.6 in mice treated with MCM09, at 10 (P < 0.01), 1 (P < 0.05) and 0.1 mg kg(-1) i.v. (ns), respectively. MCM09 (10 mg kg(-1) i.v.) significantly prolonged APTT (57.1 +/- 10.2 s) 30 min after i.v. injection when compared with controls (25.3 +/- 1.6 s; P < 0.05). Lung colonies were 74.2-72.6% reduced by MCM09 (10 mg kg(-1)) given 60 or 120 min before cells, but not by MCM09 given 60 min thereafter, suggesting a direct cell interaction as a mechanism underlying antitumor activity.

  4. Factors influencing the shift of patients from one proton pump inhibitor to another: the effect of direct-to-consumer advertising.

    Hansen, Richard A; Shaheen, Nicholas J; Schommer, Jon C

    2005-09-01

    Switching from one proton pump inhibitor (PPI) to another is common, and may be related to factors other than efficacy and tolerability. The purposes of this study were to describe the incidence of therapeutic switching among PPI users, quantify direct ambulatory medical costs of switching, and characterize the relationship between product switching and variables hypothesized to influence a switch (eg, direct-to-consumer [DTC] advertising, structure of insurance coverage, disease diagnosis). This was a retrospective cohort study of health plans using 1998 data. The subjects were employees and dependents with employer-sponsored health insurance contributing to the Medstat Market-Scan administrative dataset. Using a commercially available database to quantify DTC advertising by marketing area, market-specific expenditures were matched to eligible subjects. Among PPI users, we identified those who switched from one product to another (switchers) and compared their utilization and spending with nonswitchers. We then evaluated the relationship between drug use and variables hypothesized to affect switching: DTC advertising, insurance characteristics, patient diagnosis, diagnostic procedures, comorbidities, age, and sex. The analysis used data for 396,500 individuals from 47 unique markets that were geographically well distributed, with population density similar to that of the United States overall. The sample was also comparable with US census estimates for age and sex among working adults and their dependents. Only 620 (6.3%) of PPI users switched products during the 1998 calendar year. Annual diagnostic and drug costs were >US $400 higher for switchers than nonswitchers. Subjects in areas with high levels of DTC advertising were 43% more likely to switch from lansoprazole to omeprazole than those in the low-expenditure areas. Additionally, patients paying prescription drug copayments >US $5 were 12% less likely to switch from lansoprazole to omeprazole than patients

  5. A direct thrombin inhibitor suppresses protein C activation and factor Va degradation in human plasma: Possible mechanisms of paradoxical enhancement of thrombin generation.

    Kamisato, Chikako; Furugohri, Taketoshi; Morishima, Yoshiyuki

    2016-05-01

    We have demonstrated that antithrombin (AT)-independent thrombin inhibitors paradoxically increase thrombin generation (TG) in human plasma in a thrombomodulin (TM)- and protein C (PC)-dependent manner. We determined the effects of AT-independent thrombin inhibitors on the negative-feedback system, activation of PC and production and degradation of factor Va (FVa), as possible mechanisms underlying the paradoxical enhancement of TG. TG in human plasma containing 10nM TM was assayed by means of the calibrated automated thrombography. As an index of PC activation, plasma concentration of activated PC-PC inhibitor complex (aPC-PCI) was measured. The amounts of FVa heavy chain and its degradation product (FVa(307-506)) were examined by western blotting. AT-independent thrombin inhibitors, melagatran and dabigatran (both at 25-600nM) and 3-30μg/ml active site-blocked thrombin (IIai), increased peak levels of TG. Melagatran, dabigatran and IIai significantly decreased plasma concentration of aPC-PCI complex at 25nM or more, 75nM or more, and 10 and 30μg/ml, respectively. Melagatran (300nM) significantly increased FVa and decreased FVa(307-506). In contrast, a direct factor Xa inhibitor edoxaban preferentially inhibited thrombin generation (≥25nM), and higher concentrations were required to inhibit PC activation (≥150nM) and FVa degradation (300nM). The present study suggests that the inhibitions of protein C activation and subsequent degradation of FVa and increase in FVa by antithrombin-independent thrombin inhibitors may contribute to the paradoxical TG enhancement, and edoxaban may inhibit PC activation and FVa degradation as a result of TG suppression. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. The Drosophila melanogaster Eip74EF-PA transcription factor directly binds the sciarid BhC4-1 promoter.

    Frank, Henrique Oliveira; Sanchez, Danilo Garcia; de Freitas Oliveira, Lucas; Kobarg, Jörg; Monesi, Nadia

    2017-11-01

    The DNA puff BhC4-1 gene of Bradysia hygida (Diptera, Sciaridae) is amplified and expressed in the salivary glands at the end of the last larval instar. Even though there are no BhC4-1 orthologs in Drosophila melanogaster, the mechanisms that regulate BhC4-1 gene expression in B. hygida are for the most part conserved in D. melanogaster. The BhC4-1 promoter contains a 129bp (-186/-58) cis-regulatory module (CRM) that drives developmentally regulated expression in transgenic salivary glands at the onset of metamorphosis. Both in the sciarid and in transgenic D. melanogaster, BhC4-1 gene expression is induced by the increase in ecdysone titers that triggers metamorphosis. Genetic interaction experiments revealed that in the absence of the Eip74EF-PA early gene isoform BhC4-1-lacZ levels of expression in the salivary gland are severely reduced. Here we show that the overexpression of the Eip74EF-PA transcription factor is sufficient to anticipate BhC4-1-lacZ expression in transgenic D. melanogaster. Through yeast one-hybrid assays we confirm that the Eip74EF-PA transcription factor directly binds to the 129 bp sciarid CRM. Together, these results contribute to the characterization of an insect CRM and indicate that the ecdysone gene regulatory network that promotes metamorphosis is conserved between D. melanogaster and the sciarid B. hygida. © 2017 Wiley Periodicals, Inc.

  7. The direct costs of intensive care management and risk factors for financial burden of patients with severe sepsis and septic shock.

    Khwannimit, Bodin; Bhurayanontachai, Rungsun

    2015-10-01

    The costs of severe sepsis care from middle-income countries are lacking. This study investigated direct intensive care unit (ICU) costs and factors that could affect the financial outcomes. A prospective cohort study was conducted in the medical ICU of a tertiary referral university teaching hospital in Thailand. A total of 897 patients were enrolled in the study, with 683 (76.1%) having septic shock. Community-, nosocomial, and ICU-acquired infections were documented in 574, 282, and 41 patients, respectively. The median ICU costs per patient were $2716.5 ($1296.1-$5367.6) and $599.9 ($414.3-$948.6) per day. The ICU costs accounted for 64.7% of the hospital costs. In 2008 to 2011, the ICU costs significantly decreased by 40% from $3542.5 to $2124.9, whereas, the daily ICU costs decreased only 3.3% from $609.7 to $589.7. By multivariate logistic regression analysis, age, nosocomial or ICU infection, admission from the emergency department, number of organ failures, ICU length of stay, and fluid balance the first 72 hours were independently associated with ICU costs. The ICU costs of severe sepsis management significantly declined in our study. However, the ICU costs were a financial burden accounting for two thirds of the hospital costs. It is essential for intensivists to contribute a high standard of care within a restricted budget. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Scratch that itch: revisiting links between self-directed behaviour and parasitological, social and environmental factors in a free-ranging primate.

    Duboscq, Julie; Romano, Valéria; Sueur, Cédric; MacIntosh, Andrew J J

    2016-11-01

    Different hypotheses explain variation in the occurrence of self-directed behaviour such as scratching and self-grooming: a parasite hypothesis linked with ectoparasite load, an environmental hypothesis linked with seasonal conditions and a social hypothesis linked with social factors. These hypotheses are not mutually exclusive but are often considered separately. Here, we revisited these hypotheses together in female Japanese macaques ( Macaca fuscata fuscata ) of Kōjima islet, Japan. We input occurrences of scratching and self-grooming during focal observations in models combining parasitological (lice load), social (dominance rank, social grooming, aggression received and proximity), and environmental (rainfall, temperature and season) variables. Using an information-theory approach, we simultaneously compared the explanatory value of models against each other using variation in Akaike's information criterion and Akaike's weights. We found that evidence for models with lice load, with or without environmental-social parameters, was stronger than that for other models. In these models, scratching was positively associated with lice load and social grooming whereas self-grooming was negatively associated with lice load and positively associated with social grooming, dominance rank and number of female neighbours. This study indicates that the study animals scratch primarily because of an immune/stimulus itch, possibly triggered by ectoparasite bites/movements. It also confirms that self-grooming could act as a displacement activity in the case of social uncertainty. We advocate that biological hypotheses be more broadly considered even when investigating social processes, as one does not exclude the other.

  9. Universal factorization of 3n-j(j > 2) symbols of the first and second kinds for SU(2) group and their direct and exact calculation and tabulation

    Wei Liqiang; Dalgarno, Alexander

    2004-01-01

    We show that general 3n-j(n > 2) symbols of the first and second kinds for the group SU(2) can be reformulated in terms of binomial coefficients. The proof is based on the graphical technique established by Yutsis et al and through a definition of a reduced 6-j symbol. The resulting 3n-j symbols thereby take a combinatorial form which is simply the product of two factors. The one is an integer or polynomial which is the single sum over the products of reduced 6-j symbols. They are in the form of summing over the products of binomial coefficients. The other is a multiplication of all the triangle relations appearing in the symbols, which can also be rewritten using binomial coefficients. The new formulation indicates that the intrinsic structure for the general recoupling coefficients is much nicer and simpler, which might serve as a bridge for study with other fields. Along with our newly developed algorithms, this also provides a basis for a direct, exact and efficient calculation or tabulation of all the 3n-j symbols of the SU(2) group for all the range of quantum angular momentum arguments. As an illustration, we present the results for the 12-j symbols of the first kind

  10. Computational investigation of potential dosing schedules for a switch of medication from warfarin to rivaroxaban-an oral, direct Factor Xa inhibitor.

    Burghaus, Rolf; Coboeken, Katrin; Gaub, Thomas; Niederalt, Christoph; Sensse, Anke; Siegmund, Hans-Ulrich; Weiss, Wolfgang; Mueck, Wolfgang; Tanigawa, Takahiko; Lippert, Jörg

    2014-01-01

    The long-lasting anticoagulant effect of vitamin K antagonists can be problematic in cases of adverse drug reactions or when patients are switched to another anticoagulant therapy. The objective of this study was to examine in silico the anticoagulant effect of rivaroxaban, an oral, direct Factor Xa inhibitor, combined with the residual effect of discontinued warfarin. Our simulations were based on the recommended anticoagulant dosing regimen for stroke prevention in patients with atrial fibrillation. The effects of the combination of discontinued warfarin plus rivaroxaban were simulated using an extended version of a previously validated blood coagulation computer model. A strong synergistic effect of the two distinct mechanisms of action was observed in the first 2-3 days after warfarin discontinuation; thereafter, the effect was close to additive. Nomograms for the introduction of rivaroxaban therapy after warfarin discontinuation were derived for Caucasian and Japanese patients using safety and efficacy criteria described previously, together with the coagulation model. The findings of our study provide a mechanistic pharmacologic rationale for dosing schedules during the therapy switch from warfarin to rivaroxaban and support the switching strategies as outlined in the Summary of Product Characteristics and Prescribing Information for rivaroxaban.

  11. Computational investigation of potential dosing schedules for a switch of medication from warfarin to rivaroxaban—an oral, direct Factor Xa inhibitor

    Burghaus, Rolf; Coboeken, Katrin; Gaub, Thomas; Niederalt, Christoph; Sensse, Anke; Siegmund, Hans-Ulrich; Weiss, Wolfgang; Mueck, Wolfgang; Tanigawa, Takahiko; Lippert, Jörg

    2014-01-01

    The long-lasting anticoagulant effect of vitamin K antagonists can be problematic in cases of adverse drug reactions or when patients are switched to another anticoagulant therapy. The objective of this study was to examine in silico the anticoagulant effect of rivaroxaban, an oral, direct Factor Xa inhibitor, combined with the residual effect of discontinued warfarin. Our simulations were based on the recommended anticoagulant dosing regimen for stroke prevention in patients with atrial fibrillation. The effects of the combination of discontinued warfarin plus rivaroxaban were simulated using an extended version of a previously validated blood coagulation computer model. A strong synergistic effect of the two distinct mechanisms of action was observed in the first 2–3 days after warfarin discontinuation; thereafter, the effect was close to additive. Nomograms for the introduction of rivaroxaban therapy after warfarin discontinuation were derived for Caucasian and Japanese patients using safety and efficacy criteria described previously, together with the coagulation model. The findings of our study provide a mechanistic pharmacologic rationale for dosing schedules during the therapy switch from warfarin to rivaroxaban and support the switching strategies as outlined in the Summary of Product Characteristics and Prescribing Information for rivaroxaban. PMID:25426077

  12. Analysis of transcription factors, microRNAs and cytokines involved in T lymphocyte differentiation in patients with tuberculosis after directly observed treatment short-course.

    Corral-Fernández, Nancy Elizabeth; Cortes-García, Juan Diego; Bruno, Rivas-Santiago; Romano-Moreno, Silvia; Medellín-Garibay, Susanna E; Magaña-Aquino, Martín; Salazar-González, Raúl A; González-Amaro, Roberto; Portales-Pérez, Diana Patricia

    2017-07-01

    Tuberculosis (Tb) is an infectious disease in which the immune system plays an important role. MicroRNAs are involved in the development and maintenance of CD4 + T lymphocyte subpopulations. miR-326 regulates the differentiation to Th17 cells and miR-29 correlates with the Th1 response. The aim of this study was to determine the role of microRNAs, Transcription Factors, and cytokines in Th differentiation before and after the directly observed treatment short-course (DOTS). Peripheral blood mononuclear cells and serum from Tb patients were collected at times 0 (before therapy), 2 (after the intensive phase), and 6 months (after the holding phase). The cells were cultivated in presence or absence of ESAT-6 (10 μg/ml) and CFP-10 (10 μg/ml). Transcription Factor and microRNA expressions were analyzed by qPCR and cytokine production in both serum and culture supernatant using ELISA. A decrease in Th1 response with a diminishing in the relative expression of TBET and miR-29a at 2 and 6 months after the anti-Tb therapy (p < 0.01) were found. The miR-326 levels decreased after the intensive phase of the DOTS scheme. However, subdivision of the Tb patients according to gender, showed increased levels of miR-29a and miR-155 in females after the intensive phase of the therapeutic treatment when compared to time 0 and similar increased levels of miR-326 at time 6 versus time 0. In contrast, we observed a decrease in miR-326 levels in males at 6 months when compared to before therapy (time 0). In addition, high production of IL-17 in the culture supernatant was found at 2 and 6 months (p < 0.05) while in serum IL-17 was decreased. A positive correlation between IL-17 and RORC2 at time 6 was detected (p = 0.0202, r = 0.7880). In conclusion, these data suggest a reduction in Th1 and an induction of Th17 response after the anti-Tb therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Treatment Outcome of Tuberculosis Patients under Directly Observed Treatment Short Course and Factors Affecting Outcome in Southern Ethiopia: A Five-Year Retrospective Study.

    Gebremedhin Gebrezgabiher

    Full Text Available Tuberculosis (TB is one of the major public health and socio-economic issues in the 21st century globally. Assessment of TB treatment outcomes, and monitoring and evaluation of its risk factors in Directly Observed Treatment Short Course (DOTS are among the major indicators of the performance of a national TB control program. Hence, this institution-based retrospective study was conducted to determine the treatment outcome of TB patients and investigate factors associated with unsuccessful outcome at Dilla University Referral Hospital, southern Ethiopia. Five years (2008 to 2013 TB record of TB clinic of the hospital was reviewed. A total 1537 registered TB patients with complete information were included. Of these, 942 (61.3% were male, 1015 (66% were from rural areas, 544 (35.4% were smear positive pulmonary TB (PTB+, 816 (53.1% were smear negative pulmonary TB (PTB- and 177(11.5% were extra pulmonary TB (EPTB patients. Records of the 1537 TB patients showed that 181 (11.8% were cured, 1129(73.5% completed treatment, 171 (11.1% defaulted, 52 (3.4% died and 4 (0.3% had treatment failure. The overall mean treatment success rate of the TB patients was 85.2%. The treatment success rate of the TB patients increased from 80.5% in September 2008-August 2009 to 84.8% in September 2012-May 2013. Tuberculosis type, age, residence and year of treatment were significantly associated with unsuccessful treatment outcome. The risk of unsuccessful outcome was significantly higher among TB patients from rural areas (AOR = 1.63, 95% CI: 1.21-2.20 compared to their urban counterparts. Unsuccessful treatment outcome was also observed in PTB- patients (AOR = 1.77, 95% CI: 1.26-2.50 and EPTB (AOR = 2.07, 95% CI: 1.28-3.37 compared to the PTB+ patients. In conclusion, it appears that DOTS have improved treatment success in the hospital during five years. Regular follow-up of patients with poor treatment outcome and provision of health information on TB treatment to

  14. Direct anti-inflammatory effects of granulocyte colony-stimulating factor (G-CSF) on activation and functional properties of human T cell subpopulations in vitro.

    Malashchenko, Vladimir Vladimirovich; Meniailo, Maxsim Evgenievich; Shmarov, Viacheslav Anatolievich; Gazatova, Natalia Dinislamovna; Melashchenko, Olga Borisovna; Goncharov, Andrei Gennadievich; Seledtsova, Galina Victorovna; Seledtsov, Victor Ivanovich

    2018-03-01

    We investigated the direct effects of human granulocyte colony-stimulating factor (G-CSF) on functionality of human T-cell subsets. CD3 + T-lymphocytes were isolated from blood of healthy donors by positive magnetic separation. T cell activation with particles conjugated with antibodies (Abs) to human CD3, CD28 and CD2 molecules increased the proportion of cells expressing G-CSF receptor (G-CSFR, CD114) in all T cell subpopulations studied (CD45RA + /CD197 + naive T cells, CD45RA - /CD197 + central memory T cells, CD45RA - /CD197 - effector memory T cells and CD45RA + /CD197 - terminally differentiated effector T cells). Upon T-cell activation in vitro, G-CSF (10.0 ng/ml) significantly and specifically enhanced the proportion of CD114 + T cells in central memory CD4 + T cell compartment. A dilution series of G-CSF (range, 0.1-10.0 ng/ml) was tested, with no effect on the expression of CD25 (interleukin-2 receptor α-chain) on activated T cells. Meanwhile, G-CSF treatment enhanced the proportion of CD38 + T cells in CD4 + naïve T cell, effector memory T cell and terminally differentiated effector T cell subsets, as well as in CD4 - central memory T cells and terminally differentiated effector T cells. G-CSF did not affect IL-2 production by T cells; relatively low concentrations of G-CSF down-regulated INF-γ production, while high concentrations of this cytokine up-regulated IL-4 production in activated T cells. The data obtained suggests that G-CSF could play a significant role both in preventing the development of excessive and potentially damaging inflammatory reactivity, and in constraining the expansion of potentially cytodestructive T cells. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Synthesis, purification, and characterization of an Arg152 → Glu site-directed mutant of recombinant human blood clotting factor VII

    Wildgoose, P.; Kisiel, W.; Berkner, K.L.

    1990-01-01

    Coagulation factor VII circulates in blood as a single-chain zymogen of a serine protease and is converted to its activated two-chain form, factor VIIa, by cleavage of an internal peptide bond located at Arg 152 -Ile 153 . Previous studies using serine protease active-site inhibitors suggest that zymogen factor VII may possess sufficient proteolytic activity to initiate the extrinsic pathway of blood coagulation. In order to assess the putative intrinsic proteolytic activity of single-chain factor VII, the authors have constructed a site-specific mutant of recombinant human factor VII in which arginine-152 has been replaced with a glutamic acid residue. Mutant factor VII was purified in a single step from culture supernatants of baby hamster kidney cells transfected with a plasmid containing the sequence for Arg 152 → Glu factor VII using a calcium-dependent, murine anti-factor VII monoclonal antibody column. The clotting activity of mutant factor VII was completely inhibited following incubation with dansyl-Glu-Gly-Arg chloromethyl ketone, suggesting that the apparent clotting activity of mutant factor VII was due to a contaminating serine protease. Immunoblots of mutant factor VII with human factor IXa revealed no cleavage, whereas incubation of mutant factor VII with human factor Xa resulted in cleavage of mutant factor VII and the formation of a lower molecular weight degradation product migrating at M r ∼40 000. The results are consistent with the proposal that zymogen factor VII possesses no intrinsic proteolytic activity toward factor X or factor IX

  16. Synthesis, purification, and characterization of an Arg sub 152 yields Glu site-directed mutant of recombinant human blood clotting factor VII

    Wildgoose, P.; Kisiel, W. (Univ. of New Mexico, Albuquerque (USA)); Berkner, K.L. (ZymoGenetics, Inc., Seattle, WA (USA))

    1990-04-03

    Coagulation factor VII circulates in blood as a single-chain zymogen of a serine protease and is converted to its activated two-chain form, factor VIIa, by cleavage of an internal peptide bond located at Arg{sub 152}-Ile{sub 153}. Previous studies using serine protease active-site inhibitors suggest that zymogen factor VII may possess sufficient proteolytic activity to initiate the extrinsic pathway of blood coagulation. In order to assess the putative intrinsic proteolytic activity of single-chain factor VII, the authors have constructed a site-specific mutant of recombinant human factor VII in which arginine-152 has been replaced with a glutamic acid residue. Mutant factor VII was purified in a single step from culture supernatants of baby hamster kidney cells transfected with a plasmid containing the sequence for Arg{sub 152} {yields} Glu factor VII using a calcium-dependent, murine anti-factor VII monoclonal antibody column. The clotting activity of mutant factor VII was completely inhibited following incubation with dansyl-Glu-Gly-Arg chloromethyl ketone, suggesting that the apparent clotting activity of mutant factor VII was due to a contaminating serine protease. Immunoblots of mutant factor VII with human factor IXa revealed no cleavage, whereas incubation of mutant factor VII with human factor Xa resulted in cleavage of mutant factor VII and the formation of a lower molecular weight degradation product migrating at M{sup r}{approx}40 000. The results are consistent with the proposal that zymogen factor VII possesses no intrinsic proteolytic activity toward factor X or factor IX.

  17. Direct projection from the suprachiasmatic nucleus to hypophysiotrophic corticotropin-releasing factor immunoreactive cells in the paraventricular nucleus of the hypothalamus demonstrated...

    Vrang, N.; Larsen, P.J.; Mikkelsen, J.D.

    1995-01-01

    Suprachiasmatic nucleus, paraventricular nucleus, circadian rhythms, phaseolus vulgaris-leucoagglutinin, corticotropin-releasing factor, dual immunocytochemistry......Suprachiasmatic nucleus, paraventricular nucleus, circadian rhythms, phaseolus vulgaris-leucoagglutinin, corticotropin-releasing factor, dual immunocytochemistry...

  18. Future direction of direct writing

    Kim, Nam-Soo; Han, Kenneth N.

    2010-11-01

    Direct write technology using special inks consisting of finely dispersed metal nanoparticles in liquid is receiving an undivided attention in recent years for its wide range of applicability in modern electronic industry. The application of this technology covers radio frequency identification-tag (RFID-tag), flexible-electronics, organic light emitting diodes (OLED) display, e-paper, antenna, bumpers used in flip-chip, underfilling, frit, miniresistance applications and biological uses, artificial dental applications and many more. In this paper, the authors have reviewed various direct write technologies on the market and discussed their advantages and shortfalls. Emphasis has given on microdispensing deposition write (MDDW), maskless mesoscale materials deposition (M3D), and ink-jet technologies. All of these technologies allow printing various patterns without employing a mask or a resist with an enhanced speed with the aid of computer. MDDW and M3D are capable of drawing patterns in three-dimension and MDDW, in particular, is capable of writing nanoinks with high viscosity. However, it is still far away for direct write to be fully implemented in the commercial arena. One of the hurdles to overcome is in manufacturing conductive inks which are chemically and physically stable, capable of drawing patterns with acceptable conductivity, and also capable of drawing patterns with acceptable adhesiveness with the substrates. The authors have briefly discussed problems involved in manufacturing nanometal inks to be used in various writing devices. There are numerous factors to be considered in manufacturing such inks. They are reducing agents, concentrations, oxidation, compact ability allowing good conductivity, and stability in suspension.

  19. Risk factors for differential outcome following directly observed treatment (DOT) of slum and non-slum tuberculosis patients: a retrospective cohort study.

    Snyder, Robert E; Marlow, Mariel A; Phuphanich, Melissa E; Riley, Lee W; Maciel, Ethel Leonor Noia

    2016-09-20

    Brazil's National Tuberculosis Control Program seeks to improve tuberculosis (TB) treatment in vulnerable populations. Slum residents are more vulnerable to TB due to a variety of factors, including their overcrowded living conditions, substandard infrastructure, and limited access to healthcare compared to their non-slum dwelling counterparts. Directly observed treatment (DOT) has been suggested to improve TB treatment outcomes among vulnerable populations, but the program's differential effectiveness among urban slum and non-slum residents is not known. We retrospectively compared the impact of DOT on TB treatment outcome in residents of slum and non-slum census tracts in Rio de Janeiro reported to the Brazilian Notifiable Disease Database in 2010. Patient residential addresses were geocoded to census tracts from the 2010 Brazilian Census, which were identified as slum (aglomerados subnormais -AGSN) and non-slum (non-AGSN) by the Census Bureau. Homeless and incarcerated cases as well as those geocoded outside the city's limits were excluded from analysis. In 2010, 6,601 TB cases were geocoded within Rio de Janeiro; 1,874 (27.4 %) were residents of AGSN, and 4,794 (72.6 %) did not reside in an AGSN area. DOT coverage among AGSN cases was 35.2 % (n = 638), while the coverage in non-AGSN cases was 26.2 % (n = 1,234). Clinical characteristics, treatment, follow-up, cure, death and abandonment were similar in both AGSN and non-AGSN TB patients. After adjusting for covariates, AGSN TB cases on DOT had 1.67 (95 % CI: 1.17, 2.4) times the risk of cure, 0.61 (95 % CI: 0.41, 0.90) times the risk of abandonment, and 0.1 (95 % CI: 0.01, 0.77) times the risk of death from TB compared to non-AGSN TB cases not on DOT. While DOT coverage was low among TB cases in both AGSN and non-AGSN communities, it had a greater impact on TB cure rate in AGSN than in non-AGSN populations in the city of Rio de Janeiro.

  20. Psychometric data concerning the Positive and Negative Affect Schedule – Direction (PANAS-D in athletes in Arabic-Tunisian language supporting a 2-factor structure of its short modified version

    Sofiane Mnadla

    2017-04-01

    Full Text Available The Positive and Negative Affect Schedule – Direction (PANAS-D questionnaire was translated from the French version developed by Nicolas and coworkers into Arabic-Tunisian language and administered to a sample of 519 athletes (mean age 19.43±3.78 years; 230 male, 229 female; 75 competing at international level, 287 at national level, 130 at regional level, and 27 at local level. A semi-confirmatory factor analysis was carried out in order to shed light on the factor structure of the questionnaire. Different models were tested, including the 1-factor, the 2-factor and the 3-factor structure models, and compared in terms of fitting indexes. Data support a 2-factor solution of the modified short version of the PANAS-D questionnaire.

  1. The Impact of Direct Involvement I and Direct Involvement II Experiences on Secondary School Students' Social Capital, as Measured by Co-Cognitive Factors of the Operation Houndstooth Intervention Theory

    Sands, Michelle M.; Heilbronner, Nancy N.

    2014-01-01

    A mixed-methods study grounded in Renzulli's Operation Houndstooth Intervention Theory examined the impact of different types of volunteer experiences on the six co-cognitive factors (Optimism, Courage, Romance With a Topic/Discipline, Sensitivity to Human Concerns, Physical/Mental Energy, and Vision/Sense of Destiny) associated with the…

  2. Rivaroxaban-once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation: rationale and design of the ROCKET AF study

    NN, NN

    2010-01-01

    BACKGROUND: Atrial fibrillation (AF), the most common significant cardiac arrhythmia, increases the risk of stroke, particularly in the elderly. Warfarin is effective in reducing stroke risk but is burdensome to patients and is difficult to control. Rivaroxaban is an oral direct factor Xa inhibit...

  3. Design Guidelines and Criteria for User/Operator Transactions with Battlefield Automated Systems. Volume III-A. Human Factors Analyses of User/ Operator Transactions with TACFIRE - The Tactical Fire Direction System

    1981-02-01

    7. Reseaarch Product 81-26 - DESIGN GUIDELINES AND CRITERIA FOR USER/ I;. I’OPERATOR TRANSACTIONS WITH BATTLEFIELD AUTOMIATED SYSTEMS I’ /HVtAN...FACTORS XWLYSES :’F K~R/ OPERATOR TRANSACTIONS WTHT TACFIRE - THE TACTICAL FIRE DiRECTION SY2T3EM A HUMAN FACTORS TECHNICAL AREA L~h~h K L-J 1’ U~~i~ ll...Battlefield Auto- Inter : Oct 1979-Feb 1981 mated Systems Volume III-A: Human Factors 4t C/ Analyses of User/Operator Transactions with 6. PERFORMING

  4. Site-directed mutagenesis of Arg58 and Asp86 of elongation factor Tu from Escherichia coli: effects on the GTPase reaction and aminoacyl-tRNA binding

    Knudsen, Charlotte Rohde; Clark, Brian F. C.

    1996-01-01

    Elongation factor Tu from Escherichia coli was mutated separately at positions Asp86 and Arg58, in order to shed light both on the GTPase mechanism of elongation factor Tu and on the binding of aminoacyl-tRNA. In addition, the binding of guanine nucleotides was investigated by determination...

  5. On the importance of adjusting for distorting factors in benchmarking analysis, as illustrated by a cost comparison of the different forms of implementation of the EU Packaging Directive.

    Baum, Heinz-Georg; Schuch, Dieter

    2017-12-01

    Benchmarking is a proven and widely used business tool for identifying best practice. To produce robust results, the objects of comparison used in benchmarking analysis need to be structurally comparable and distorting factors need to be eliminated. We focus on a specific example - a benchmark study commissioned by the European Commission's Directorate-General for Environment on the implementation of Extended Producer Responsibility (EPR) for packaging at the national level - to discuss potential distorting factors and take them into account in the calculation. The cost of compliance per inhabitant and year, which is used as the key cost efficiency indicator in the study, is adjusted to take account of seven factors. The results clearly show that differences in performance may play a role, but the (legal) implementation of EPR - which is highly heterogeneous across countries - is the single most important cost determinant and must be taken into account to avoid misinterpretation and false conclusions.

  6. Leukocyte- and platelet-rich fibrin (L-PRF) for long-term delivery of growth factor in rotator cuff repair: review, preliminary results and future directions.

    Zumstein, Matthias A; Berger, Simon; Schober, Martin; Boileau, Pascal; Nyffeler, Richard W; Horn, Michael; Dahinden, Clemens A

    2012-06-01

    Surgical repair of the rotator cuff repair is one of the most common procedures in orthopedic surgery. Despite it being the focus of much research, the physiological tendon-bone insertion is not recreated following repair and there is an anatomic non-healing rate of up to 94%. During the healing phase, several growth factors are upregulated that induce cellular proliferation and matrix deposition. Subsequently, this provisional matrix is replaced by the definitive matrix. Leukocyte- and platelet-rich fibrin (L-PRF) contain growth factors and has a stable dense fibrin matrix. Therefore, use of LPRF in rotator cuff repair is theoretically attractive. The aim of the present study was to determine 1) the optimal protocol to achieve the highest leukocyte content; 2) whether L-PRF releases growth factors in a sustained manner over 28 days; 3) whether standard/gelatinous or dry/compressed matrix preparation methods result in higher growth factor concentrations. 1) The standard L-PRF centrifugation protocol with 400 x g showed the highest concentration of platelets and leukocytes. 2) The L-PRF clots cultured in medium showed a continuous slow release with an increase in the absolute release of growth factors TGF-β1, VEGF and MPO in the first 7 days, and for IGF1, PDGF-AB and platelet activity (PF4=CXCL4) in the first 8 hours, followed by a decrease to close to zero at 28 days. Significantly higher levels of growth factor were expressed relative to the control values of normal blood at each culture time point. 3) Except for MPO and the TGFβ-1, there was always a tendency towards higher release of growth factors (i.e., CXCL4, IGF-1, PDGF-AB, and VEGF) in the standard/gelatinous- compared to the dry/compressed group. L-PRF in its optimal standard/gelatinous-type matrix can store and deliver locally specific healing growth factors for up to 28 days and may be a useful adjunct in rotator cuff repair.

  7. Direct nitrous oxide emissions in Mediterranean climate cropping systems : Emission factors based on a meta-analysis of available measurement data

    Cayuela, Maria L.; Aguilera, Eduardo; Sanz-Cobena, Alberto; Adams, Dean C.; Abalos, Diego; Barton, Louise; Ryals, Rebecca; Silver, Whendee L.; Alfaro, Marta A.; Pappa, Valentini A.; Smith, Pete; Garnier, Josette; Billen, Gilles; Bouwman, Lex; Bondeau, Alberte; Lassaletta, Luis

    2017-01-01

    Many recent reviews and meta-analyses of N2O emissions do not include data from Mediterranean studies. In this paper we present a meta-analysis of the N2O emissions from Mediterranean cropping systems, and propose a more robust and reliable regional emission factor (EF) for N2O, distinguishing the

  8. Mechanism of Diphtheria Toxin Catalytic Domain Delivery to the Eukaryotic Cell Cytosol and the Cellular Factors that Directly Participate in the Process

    Murphy, John R.

    2011-01-01

    Research on diphtheria and anthrax toxins over the past three decades has culminated in a detailed understanding of their structure function relationships (e.g., catalytic (C), transmembrane (T), and receptor binding (R) domains), as well as the identification of their eukaryotic cell surface receptor, an understanding of the molecular events leading to the receptor-mediated internalization of the toxin into an endosomal compartment, and the pH triggered conformational changes required for pore formation in the vesicle membrane. Recently, a major research effort has been focused on the development of a detailed understanding of the molecular interactions between each of these toxins and eukaryotic cell factors that play an essential role in the efficient translocation of their respective catalytic domains through the trans-endosomal vesicle membrane pore and delivery into the cell cytosol. In this review, I shall focus on recent findings that have led to a more detailed understanding of the mechanism by which the diphtheria toxin catalytic domain is delivered to the eukaryotic cell cytosol. While much work remains, it is becoming increasingly clear that the entry process is facilitated by specific interactions with a number of cellular factors in an ordered sequential fashion. In addition, since diphtheria, anthrax lethal factor and anthrax edema factor all carry multiple coatomer I complex binding motifs and COPI complex has been shown to play an essential role in entry process, it is likely that the initial steps in catalytic domain entry of these divergent toxins follow a common mechanism. PMID:22069710

  9. Direct Democracy

    Beramendi, Virginia; Ellis, Andrew; Kaufman, Bruno

    While many books on direct democracy have a regional or national approach, or simply focus on one of the many mechanisms associated with direct democracy, this Handbook delves into a global comparison of direct democracy mechanisms, including referendums, citizens' initiatives, agenda initiatives...... learned. In addition, the uniquely comprehensive world survey outlines direct democracy provisions in 214 countries and territories and indicates which, if any, of these provisions are used by each country or territory at both the national and sub-national levels. Furthermore, the world survey includes...

  10. Directing 101.

    Pintoff, Ernest

    Providing an introduction to anyone considering directing as a field of study or career, this book takes a broad look at the process of directing and encourages students and professionals alike to look outside of the movie industry for inspiration. Chapters in the book discuss selecting and acquiring material; budgeting and financing; casting and…

  11. Atrial Fibrillation in Hematologic Malignancies, Especially After Autologous Hematopoietic Stem Cell Transplantation: Review of Risk Factors, Current Management, and Future Directions.

    Mathur, Pankaj; Paydak, Hakan; Thanendrarajan, Sharmilan; van Rhee, Frits

    2016-02-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with significant morbidity and mortality worldwide. In addition to well-established risk factors, cancer has been increasingly associated with the development of AF. Its increased occurrence in those with hematologic malignancies has been attributed to chemotherapeutic agents and autologous hematopoietic stem cell transplantation (AHSCT). Recently, a few studies have attempted to define the etiopathogenesis of AF in hematologic malignancies. The management of AF in these patients is challenging because of the concurrent complicating factors, such as thrombocytopenia, orthostatic hypotension, and cardiac amyloidosis. More studies are needed to define the management of AF, especially rate versus rhythm control and anticoagulation. Arrhythmias, in particular, AF, have been associated with an increased length of stay, increased intensive care unit admissions, and greater cardiovascular mortality. In the present review, we describe AF in patients with hematologic malignancies, the risk factors, especially after AHSCT, and the current management of AF. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Direct visualization of epidermal growth factor receptors (EGFR) in A431 and placental cell membrane by western blot with 125I-EGF

    Lin, P.H.; Selinfreund, R.; Wharton, W.

    1986-01-01

    Using the western blot technique, they have devised a new procedure that allowed the direct visualization of both the 150KD and the 170KD forms of EGFR by its natural ligand, 125 I-EGF. A431, and placental plasmalemma were purified and solubilized in either SDS-PAGE buffer (without DTT, EDTA) or Triton X-100 (0.5%), resolved on PAGE and electrophoretically transferred onto nitrocellulose (NC) paper. In the absence of boiling, SDS did not denature the EGFR. Although EGER band can be detected after hybridization with 125 I-EGF, the receptor signal was considerably improved with the addition of 0.1% Tween-20. The binding of 125 I-EGF to the both the 150KD and the 170KD bands of the EGFR was specific, reversible and increased with the amount of membrane protein present. The direct visualization of the EGFR using its natural ligand eliminated the necessity for the time consuming antibody preparation. Presently, they are using this technique to identify specific receptors for other ligands

  13. Factors affecting the attrition of community-directed distributors of ivermectin, in an onchocerciasis-control programme in the Imo and Abia states of south-eastern Nigeria.

    Emukah, E C; Enyinnaya, U; Olaniran, N S; Akpan, E A; Hopkins, D R; Miri, E S; Amazigo, U; Okoronkwo, C; Stanley, A; Rakers, L; Richards, F O; Katabarwa, M N

    2008-01-01

    In areas of Nigeria where onchocerciasis is endemic, community-directed distributors (CDD) distribute ivermectin annually, as part of the effort to control the disease. Unfortunately, it has been reported that at least 35% of the distributors who have been trained in Nigeria are unwilling to participate further as CDD. The selection and training of new CDD, to replace those unwilling to continue, leads to annual expense that the national onchocerciasis-programme is finding difficult to meet, given other programme priorities and the limited resources. If the reported levels of attrition are true, they seriously threaten the sustainability of community-directed treatment with ivermectin (CDTI) in Nigeria. In 2002, interviews were held with 101 people who had been trained as CDD, including those who had stopped serving their communities, from 12 communities in south-eastern Nigeria that had high rates of CDD attrition. The results showed that, although the overall reported CDD attrition was 40.6%, the actual rate was only 10.9%. The CDD who had ceased participating in the annual rounds of ivermectin blamed a lack of incentives (65.9%), the demands of other employment (14.6%), the long distances involved in the house-to-house distribution (12.2%) or marital duties (7.3%). Analysis of the data obtained from all the interviewed CDD showed that inadequate supplies of ivermectin (P<0.01), lack of supervision (P<0.05) and a lack of monetary incentives (P<0.001) led to significant increases in attrition. Conversely, CDD retention was significantly enhanced when the distributors were selected by their community members (P<0.001), supervised (P<0.001), supplied with adequate ivermectin tablets (P<0.05), involved in educating their community members (P<0.05), and/or involved in other health programmes (P<0.001). Although CDD who were involved in other health programmes were relatively unlikely to cease participating in the distributions, they were more likely to take longer

  14. Childhood trauma and complex posttraumatic stress disorder symptoms in older adults: A study of direct effects and social-interpersonal factors as potential mediators.

    Krammer, Sandy; Kleim, Birgit; Simmen-Janevska, Keti; Maercker, Andreas

    2016-01-01

    Childhood traumatic events may lead to long-lasting psychological effects and contribute to the development of complex posttraumatic sequelae. These might be captured by the diagnostic concept of complex posttraumatic stress disorder (CPTSD) as an alternative to classic posttraumatic stress disorder (PTSD). CPTSD comprises a further set of symptoms in addition to those of PTSD, namely, changes in affect, self, and interpersonal relationships. Previous empirical research on CPTSD has focused on middle-aged adults but not on older adults. Moreover, predictor models of CPTSD are still rare. The current study investigated the association between traumatic events in childhood and complex posttraumatic stress symptoms in older adults. The mediation of this association by 2 social-interpersonal factors (social acknowledgment as a survivor and dysfunctional disclosure) was investigated. These 2 factors focus on the perception of acknowledgment by others and either the inability to disclose traumatic experiences or the ability to do so only with negative emotional reactions. A total of 116 older individuals (age range = 59-98 years) who had experienced childhood traumatic events completed standardized self-report questionnaires indexing childhood trauma, complex trauma sequelae, social acknowledgment, and dysfunctional disclosure of trauma. The results showed that traumatic events during childhood were associated with later posttraumatic stress symptoms but with classic rather than complex symptoms. Social acknowledgment and dysfunctional disclosure partially mediated this relationship. These findings suggest that childhood traumatic stress impacts individuals across the life span and may be associated with particular adverse psychopathological consequences.

  15. Endoplasmic reticulum stress-responsive transcription factor ATF6α directs recruitment of the Mediator of RNA polymerase II transcription and multiple histone acetyltransferase complexes.

    Sela, Dotan; Chen, Lu; Martin-Brown, Skylar; Washburn, Michael P; Florens, Laurence; Conaway, Joan Weliky; Conaway, Ronald C

    2012-06-29

    The basic leucine zipper transcription factor ATF6α functions as a master regulator of endoplasmic reticulum (ER) stress response genes. Previous studies have established that, in response to ER stress, ATF6α translocates to the nucleus and activates transcription of ER stress response genes upon binding sequence specifically to ER stress response enhancer elements in their promoters. In this study, we investigate the biochemical mechanism by which ATF6α activates transcription. By exploiting a combination of biochemical and multidimensional protein identification technology-based mass spectrometry approaches, we have obtained evidence that ATF6α functions at least in part by recruiting to the ER stress response enhancer elements of ER stress response genes a collection of RNA polymerase II coregulatory complexes, including the Mediator and multiple histone acetyltransferase complexes, among which are the Spt-Ada-Gcn5 acetyltransferase (SAGA) and Ada-Two-A-containing (ATAC) complexes. Our findings shed new light on the mechanism of action of ATF6α, and they outline a straightforward strategy for applying multidimensional protein identification technology mass spectrometry to determine which RNA polymerase II transcription factors and coregulators are recruited to promoters and other regulatory elements to control transcription.

  16. Directing Creativity

    Darsø, Lotte; Ibbotson, Piers

    2008-01-01

    In this article we argue that leaders facing complex challenges can learn from the arts, specifically that leaders can learn by examining how theatre directors direct creativity through creative constraints. We suggest that perceiving creativity as a boundary phenomenon is helpful for directing it....... Like leaders, who are caught in paradoxical situations where they have to manage production and logistics simultaneously with making space for creativity and innovation, theatre directors need to find the delicate balance between on one hand renewal of perceptions, acting and interaction...... and on the other hand getting ready for the opening night. We conclude that the art of directing creativity is linked to developing competencies of conscious presence, attention and vigilance, whereas the craft of directing creativity concerns communication, framing and choice....

  17. The impact of system level factors on treatment timeliness: utilizing the Toyota Production System to implement direct intake scheduling in a semi-rural community mental health clinic.

    Weaver, Addie; Greeno, Catherine G; Goughler, Donald H; Yarzebinski, Kathleen; Zimmerman, Tina; Anderson, Carol

    2013-07-01

    This study examined the effect of using the Toyota Production System (TPS) to change intake procedures on treatment timeliness within a semi-rural community mental health clinic. One hundred randomly selected cases opened the year before the change and 100 randomly selected cases opened the year after the change were reviewed. An analysis of covariance demonstrated that changing intake procedures significantly decreased the number of days consumers waited for appointments (F(1,160) = 4.9; p = .03) from an average of 11 to 8 days. The pattern of difference on treatment timeliness was significantly different between adult and child programs (F(1,160) = 4.2; p = .04), with children waiting an average of 4 days longer than adults for appointments. Findings suggest that small system level changes may elicit important changes and that TPS offers a valuable model to improve processes within community mental health settings. Results also indicate that different factors drive adult and children's treatment timeliness.

  18. The effect of a new direct Factor Xa inhibitor on human osteoblasts: an in-vitro study comparing the effect of rivaroxaban with enoxaparin

    Solayar, Gandhi N

    2011-10-28

    Abstract Background Current treatments for the prevention of thromboembolism include heparin and low-molecular weight heparins (LMWHs). A number of studies have suggested that long term administration of these drugs may adversely affect osteoblasts and therefore, bone metabolism. Xarelto™ (Rivaroxaban) is a new anti-thrombotic drug for the prevention of venous thromboembolism in adult patients undergoing elective hip and knee replacement surgery. The aim of this in vitro study was to investigate the possible effects of rivaroxaban on osteoblast viability, function and gene expression compared to enoxaparin, a commonly used LMWH. Methods Primary human osteoblast cultures were treated with varying concentrations of rivaroxaban (0.013, 0.13, 1.3 and 13 μg\\/ml) or enoxaparin (1, 10 and 100 μg\\/ml). The effect of each drug on osteoblast function was evaluated by measuring alkaline phosphatase activity. The MTS assay was used to assess the effect of drug treatments on cell proliferation. Changes in osteocalcin, Runx2 and BMP-2 messenger RNA (mRNA) expression following drug treatments were measured by real-time polymerase chain reaction (PCR). Results Rivaroxaban and enoxaparin treatment did not adversely affect osteoblast viability. However, both drugs caused a significant reduction in osteoblast function, as measured by alkaline phosphatase activity. This reduction in osteoblast function was associated with a reduction in the mRNA expression of the bone marker, osteocalcin, the transcription factor, Runx2, and the osteogenic factor, BMP-2. Conclusions These data show that rivaroxaban treatment may negatively affect bone through a reduction in osteoblast function.

  19. Parental educational level and cardiovascular disease risk factors in schoolchildren in large urban areas of Turkey: Directions for public health policy

    Hayran Osman

    2005-02-01

    Full Text Available Abstract Background It is widely accepted that the development of atherosclerosis starts at an early age. However, there are very few studies evaluating the prevalence of the common clinical and behavioral cardiovascular disease (CVD risk factors among children, especially in developing countries. The aim of the present cross-sectional survey was to evaluate the distribution of blood lipid profile and various behavioral (i.e. dietary habits, physical activity status factors related to CVD risk and its relationships to paternal (PEL and maternal educational level (MEL among primary schoolchildren in Turkey. Methods In three major metropolises in Turkey (Istanbul, Ankara and Izmir, a random sample of 1044 children aged 12 and 13 years old was examined. ANOVA was applied to evaluate the tested hypothesis, after correcting for multiple comparisons (Tukey correction. Results After controlling for energy and fat intake, physical activity status and Body Mass Index (BMI, it was found that mostly PEL had a significant positive effect for most of the subgroups examined (Lower vs. Higher and Medium vs. Higher on TC and HDL-cholesterol and a negative effect on TC/HDL ratio for both genders. Furthermore, both boys and girls with higher PEL and MEL were found to have higher energy intake derived from fat and protein than their counterparts with Medium and Lower PEL and MEL, while the opposite was observed for the percentage of energy derived from carbohydrates. Conclusions Our study provides indications for a possible association between an adverse lipid profile, certain dietary patterns and Higher PEL and MEL among schoolchildren in Turkey. These findings underline the possible role of social status, indicated by the degree of education of both parents, in developing certain health behaviors and health indices among Turkish children and provide some guidance for Public Health Policy.

  20. Computing and Learning Year-Round Daily Patterns of Hourly Wind Speed and Direction and Their Global Associations with Meteorological Factors

    Hsing-Ti Wu

    2015-08-01

    Full Text Available Daily wind patterns and their relational associations with other metocean (oceanographic and meteorological variables were algorithmically computed and extracted from a year-long wind and weather dataset, which was collected hourly from an ocean buoy located in the Penghu archipelago of Taiwan. The computational algorithm is called data cloud geometry (DCG. This DCG algorithm is a clustering-based nonparametric learning approach that was constructed and developed implicitly based on various entropy concepts. Regarding the bivariate aspect of wind speed and wind direction, the resulting multiscale clustering hierarchy revealed well-known wind characteristics of year-round pattern cycles pertaining to the particular geographic location of the buoy. A wind pattern due to a set of extreme weather days was also identified. Moreover, in terms of the relational aspect of wind and other weather variables, causal patterns were revealed through applying the DCG algorithm alternatively on the row and column axes of a data matrix by iteratively adapting distance measures to computed DCG tree structures. This adaptation technically constructed and integrated a multiscale, two-sample testing into the distance measure. These computed wind patterns and pattern-based causal relationships are useful for both general sailing and competition planning.

  1. Directed polymers versus directed percolation

    Halpin-Healy, Timothy

    1998-10-01

    Universality plays a central role within the rubric of modern statistical mechanics, wherein an insightful continuum formulation rises above irrelevant microscopic details, capturing essential scaling behaviors. Nevertheless, occasions do arise where the lattice or another discrete aspect can constitute a formidable legacy. Directed polymers in random media, along with its close sibling, directed percolation, provide an intriguing case in point. Indeed, the deep blood relation between these two models may have sabotaged past efforts to fully characterize the Kardar-Parisi-Zhang universality class, to which the directed polymer belongs.

  2. Multiple transcription factors directly regulate Hox gene lin-39 expression in ventral hypodermal cells of the C. elegans embryo and larva, including the hypodermal fate regulators LIN-26 and ELT-6.

    Liu, Wan-Ju; Reece-Hoyes, John S; Walhout, Albertha J M; Eisenmann, David M

    2014-05-13

    Hox genes encode master regulators of regional fate specification during early metazoan development. Much is known about the initiation and regulation of Hox gene expression in Drosophila and vertebrates, but less is known in the non-arthropod invertebrate model system, C. elegans. The C. elegans Hox gene lin-39 is required for correct fate specification in the midbody region, including the Vulval Precursor Cells (VPCs). To better understand lin-39 regulation and function, we aimed to identify transcription factors necessary for lin-39 expression in the VPCs, and in particular sought factors that initiate lin-39 expression in the embryo. We used the yeast one-hybrid (Y1H) method to screen for factors that bound to 13 fragments from the lin-39 region: twelve fragments contained sequences conserved between C. elegans and two other nematode species, while one fragment was known to drive reporter gene expression in the early embryo in cells that generate the VPCs. Sixteen transcription factors that bind to eight lin-39 genomic fragments were identified in yeast, and we characterized several factors by verifying their physical interactions in vitro, and showing that reduction of their function leads to alterations in lin-39 levels and lin-39::GFP reporter expression in vivo. Three factors, the orphan nuclear hormone receptor NHR-43, the hypodermal fate regulator LIN-26, and the GATA factor ELT-6 positively regulate lin-39 expression in the embryonic precursors to the VPCs. In particular, ELT-6 interacts with an enhancer that drives GFP expression in the early embryo, and the ELT-6 site we identified is necessary for proper embryonic expression. These three factors, along with the factors ZTF-17, BED-3 and TBX-9, also positively regulate lin-39 expression in the larval VPCs. These results significantly expand the number of factors known to directly bind and regulate lin-39 expression, identify the first factors required for lin-39 expression in the embryo, and hint at a

  3. Programmatic factors associated with the limited impact of Community-Directed Treatment with Ivermectin to control Onchocerciasis in three drainage basins of South West Cameroon.

    Christian Tetteh Duamor

    2017-11-01

    Full Text Available The CDTI model is known to have enhanced community participation in planning and resource mobilization toward the control of onchocerciasis. These effects were expected to translate into better individual acceptance of the intervention and hence high Treatment Coverage, leading to a sustainable community-led strategy and reduction in the disease burden. A survey revealed that after 10-12 rounds of treatment, prevalence of onchocerciasis was still high in three drainage basins of South West Cameroon and transmission was going on.We designed a three (3-year retrospective (2012, 2013 and 2014, descriptive cross-sectional study to explore the roles of operational challenges in the failure of CDTI to control the disease as expected. We administered 83 semi-structured questionnaires and conducted 12 in-depth interviews with Chiefs of Bureau Health, Chiefs of Centers, CDDs and Community Heads. Descriptive statistics was used to explore indicators of performance which were supported with views from in-depth interviews.We found that community participation was weak; communities were not deciding time and mode of distributions. Only 6 (15.0% of 40 Community Drug Distributors reported they were selected at general community meetings as required. The health service was not able to meet and discuss Community-Directed Treatment with Ivermectin activities with individual communities partly due to transportation challenges; this was mostly done through letters. Funding was reported to be inadequate and not timely. Funds were not available to conduct Community-Self Monitoring after the 2014 Mass Drug Administration. There was inadequate health staff at the frontline health facility levels, and some Chiefs of Center reported that Community-Directed Treatment with Ivermectin work was too much for them. The mean operational Community Drug Distributor-population ratio was 1 Community Drug Distributor per 317 populations (range: 194-464, expected is 1:250. Community

  4. Tyrosine kinase inhibitors directed against the vascular endothelial growth factor receptor (VEGFR) have distinct cutaneous toxicity profiles: a meta-analysis and review of the literature.

    Massey, Paul R; Okman, Jonathan S; Wilkerson, Julia; Cowen, Edward W

    2015-06-01

    Inhibition of the vascular endothelial growth factor receptor (VEGFR) with tyrosine kinase inhibitors (TKIs) is associated with cutaneous adverse effects that increase patient morbidity. Our objective was to examine the skin toxicity profile of anti-VEGFR TKIs and determine the changing incidence in clinical trials. PubMed was queried for phase II or III trials of anti-VEGFR TKIs between 2000 and 2013 involving ≥50 patients. Adverse events were abstracted, with results presented in both fixed and random effects models. Odds ratios (OR) and 95 % confidence intervals (CIs) were estimated for studies with at least two arms. Across 82 included studies, all grades rash (OR, 2.68; 95 % CI, 2.45-2.94), hand-foot skin reaction (HFSR) (OR, 2.70; 95 % CI, 2.43-3.00), and pruritus (OR, 1.25; 95 % CI, 1.12-1.39) were associated with anti-VEGFR TKIs. Vandetanib had the highest incidence of rash (41 %), while sorafenib was most commonly associated with HFSR (37 %) and pruritus (14 %). The incidence of HFSR from 2000 to 2013 showed an upward trend (r (2) = 0.042, p = 0.10) and in sunitinib therapy increased significantly (r (2) = 0.237, p = 0.04). The incidence of HFSR, rash, and pruritus varies considerably by drug. Our data suggest a continued need to address skin toxicities and improve reporting strategies.

  5. The Impact of System Level Factors on Treatment Timeliness: Utilizing the Toyota Production System to Implement Direct Intake Scheduling in a Semi-Rural Community Mental Health Clinic

    Weaver, A.; Greeno, C.G.; Goughler, D.H.; Yarzebinski, K.; Zimmerman, T.; Anderson, C.

    2013-01-01

    This study examined the effect of using the Toyota Production System (TPS) to change intake procedures on treatment timeliness within a semi-rural community mental health clinic. One hundred randomly selected cases opened the year before the change and one hundred randomly selected cases opened the year after the change were reviewed. An analysis of covariance (ANCOVA) demonstrated that changing intake procedures significantly decreased the number of days consumers waited for appointments (F(1,160)=4.9; p=.03) from an average of 11 days to 8 days. The pattern of difference on treatment timeliness was significantly different between adult and child programs (F(1,160)=4.2; p=.04), with children waiting an average of 4 days longer than adults for appointments. Findings suggest that small system level changes may elicit important changes and that TPS offers a valuable model to improve processes within community mental health settings. Results also indicate that different factors drive adult and children’s treatment timeliness. PMID:23576137

  6. Direct association of thioredoxin-1 (TRX) with macrophage migration inhibitory factor (MIF): regulatory role of TRX on MIF internalization and signaling.

    Son, Aoi; Kato, Noriko; Horibe, Tomohisa; Matsuo, Yoshiyuki; Mochizuki, Michika; Mitsui, Akira; Kawakami, Koji; Nakamura, Hajime; Yodoi, Junji

    2009-10-01

    Thioredoxin-1 (TRX) is a small (14 kDa) multifunctional protein with the redox-active site Cys-Gly-Pro-Cys. Macrophage migration inhibitory factor (MIF) is a 12 kDa cytokine belonging to the TRX family. Historically, when we purified TRX from the supernatant of ATL-2 cells, a 12 kDa protein was identified along with TRX, which was later proved to be MIF. Here, we show that TRX and MIF form a complex in the cell and the culture supernatant of ATL-2 cells. Using a BIAcore assay, we confirmed that TRX has a specific affinity with MIF. We also found that extracellular MIF was more effectively internalized into the ATL-2 cells expressing TRX on the cell surface, than the Jurkat T cells which do not express surface TRX. Moreover, anti-TRX antibody blocked the MIF internalization, suggesting that the cell surface TRX is involved in MIF internalization into the cells. Furthermore, anti-TRX antibody inhibited MIF-mediated enhancement of TNF-alpha production from macrophage RAW264.7 cells. These results suggest that the cell surface TRX serves as one of the MIF binding molecules or MIF receptor component and inhibits MIF-mediated inflammatory signals.

  7. Hypoxia-inducible factor-1α regulates chemotactic migration of pancreatic ductal adenocarcinoma cells through directly transactivating the CX3CR1 gene.

    Tiansuo Zhao

    Full Text Available CX3CR1 is an important chemokine receptor and regulates the chemotactic migration of pancreatic ductal adenocarcinoma (PDAC cells. Up to now, its regulatory mechanism remains largely undefined. Here, we report that hypoxia upregulates the expression of CX3CR1 in pancreatic cancer cells. When hypoxia-inducible factor (HIF-1α expression was knocked down in vitro and in vivo, the expression of CX3CR1 was significantly decreased. Chromatin immunoprecipitation assay demonstrated that HIF-1α bound to the hypoxia-response element (HRE; 5'-A/GCGTG-3' of CX3CR1 promoter under normoxia, and this binding was significantly enhanced under hypoxia. Overexpression of HIF-1α significantly upregulated the expression of luciferase reporter gene under the control of the CX3CR1 promoter in pancreatic cancer cells. Importantly, we demonstrated that HIF-1α may regulate cancer cell migration through CX3CR1. The HIF-1α/CX3CR1 pathway might represent a valuable therapeutic target to prevent invasion and distant metastasis in PDAC.

  8. Comparative evaluation of direct thrombin and factor Xa inhibitors with antiplatelet agents under flow and static conditions: an in vitro flow chamber model.

    Kazuya Hosokawa

    Full Text Available Dabigatran and rivaroxaban are novel oral anticoagulants that specifically inhibit thrombin and factor Xa, respectively. The aim of this study is to elucidate antithrombotic properties of these anticoagulant agents under arterial and venous shear conditions. Whole blood samples treated with dabigatran or rivaroxaban at 250, 500, and 1000 nM, with/without aspirin and AR-C66096, a P2Y12 antagonist, were perfused over a microchip coated with collagen and tissue thromboplastin at shear rates of 240 and 600 s(-1. Fibrin-rich platelet thrombus formation was quantified by monitoring flow pressure changes. Dabigatran at higher concentrations (500 and 1000 nM potently inhibited thrombus formation at both shear rates, whereas 1000 nM of rivaroxaban delayed, but did not completely inhibit, thrombus formation. Dual antiplatelet agents weakly suppressed thrombus formation at both shear rates, but intensified the anticoagulant effects of dabigatran and rivaroxaban. The anticoagulant effects of dabigatran and rivaroxaban were also evaluated under static conditions using thrombin generation (TG assay. In platelet-poor plasma, dabigatran at 250 and 500 nM efficiently prolonged the lag time (LT and moderately reduce peak height (PH of TG, whereas rivaroxaban at 250 nM efficiently prolonged LT and reduced PH of TG. In platelet-rich plasma, however, both anticoagulants efficiently delayed LT and reduced PH of TG. Our results suggest that dabigatran and rivaroxaban may exert distinct antithrombotic effects under flow conditions, particularly in combination with dual antiplatelet therapy.

  9. Direct and indirect effects of climate on demography and early growth of Pinus sylvestris at the rear edge: changing roles of biotic and abiotic factors.

    Raquel Benavides

    Full Text Available Global change triggers shifts in forest composition, with warming and aridification being particularly threatening for the populations located at the rear edge of the species distributions. This is the case of Scots pine (Pinus sylvestris in the Mediterranean Basin where uncertainties in relation to its dynamics under these changing scenarios are still high. We analysed the relative effect of climate on the recruitment patterns of Scots pine and its interactions with local biotic and abiotic variables at different spatial scales. Number of seedlings and saplings was surveyed, and their annual shoot growth measured in 96 plots located across altitudinal gradients in three different regions in the Iberian Peninsula. We found a significant influence of climate on demography and performance of recruits, with a non-linear effect of temperature on the presence of juveniles, and a positive effect of precipitation on their survival. Abundance of juveniles of P. sylvestris that underwent their first summer drought was skewed towards higher altitudes than the altitudinal mean range of the conspecific adults and the optimum elevation for seedlings' emergence. At local level, light availability did not influence juveniles' density, but it enhanced their growth. Biotic interactions were found between juveniles and the herb cover (competition and between the number of newly emerged seedlings and shrubs (facilitation. Results also highlighted the indirect effect that climate exerts over the local factors, modulating the interactions with the pre-existing vegetation that were more evident at more stressful sites. This multiscale approach improves our understanding of the dynamics of these marginal populations and some management criteria can be inferred to boost their conservation under the current global warming.

  10. Direct and indirect effects of climate on demography and early growth of Pinus sylvestris at the rear edge: changing roles of biotic and abiotic factors.

    Benavides, Raquel; Rabasa, Sonia G; Granda, Elena; Escudero, Adrián; Hódar, José A; Martínez-Vilalta, Jordi; Rincón, Ana M; Zamora, Regino; Valladares, Fernando

    2013-01-01

    Global change triggers shifts in forest composition, with warming and aridification being particularly threatening for the populations located at the rear edge of the species distributions. This is the case of Scots pine (Pinus sylvestris) in the Mediterranean Basin where uncertainties in relation to its dynamics under these changing scenarios are still high. We analysed the relative effect of climate on the recruitment patterns of Scots pine and its interactions with local biotic and abiotic variables at different spatial scales. Number of seedlings and saplings was surveyed, and their annual shoot growth measured in 96 plots located across altitudinal gradients in three different regions in the Iberian Peninsula. We found a significant influence of climate on demography and performance of recruits, with a non-linear effect of temperature on the presence of juveniles, and a positive effect of precipitation on their survival. Abundance of juveniles of P. sylvestris that underwent their first summer drought was skewed towards higher altitudes than the altitudinal mean range of the conspecific adults and the optimum elevation for seedlings' emergence. At local level, light availability did not influence juveniles' density, but it enhanced their growth. Biotic interactions were found between juveniles and the herb cover (competition) and between the number of newly emerged seedlings and shrubs (facilitation). Results also highlighted the indirect effect that climate exerts over the local factors, modulating the interactions with the pre-existing vegetation that were more evident at more stressful sites. This multiscale approach improves our understanding of the dynamics of these marginal populations and some management criteria can be inferred to boost their conservation under the current global warming.

  11. Direct marketing

    Čičić Muris

    2002-01-01

    Full Text Available Direct Marketing (DM is usually treated as unworthy activity, with actions at the edge of legality and activities minded cheating. Despite obvious problems regarding ethics and privacy threat, DM with its size, importance and role in a concept of integrated marketing communication deserves respect and sufficient analysis and review

  12. TH-CD-BRA-05: First Water Calorimetric Dw Measurement and Direct Measurement of Magnetic Field Correction Factors, KQ,B, in a 1.5 T B-Field of An MRI Linac

    Prez, L de; Pooter, J de; Jansen, B [VSL, Delft (Netherlands); Wolthaus, J; Asselen, B van; Woodings, S; Soest, T; Kok, J; Raaymakers, B [University Medical Center Utrecht, Utrecht (Netherlands)

    2016-06-15

    Purpose: Reference dosimetry in MR-guided radiotherapy is performed in the presence of a B-field. As a consequence the response of ionization chambers changes considerably and depends on parameters not considered in traditional reference dosimetry. Therefore future Codes of Practices need ionization chamber correction factors to correct for both the change in beam quality and the presence of a B-field. The objective was to study the feasibility of water calorimetric absorbed-dose measurements in a 1.5 T B-field of an MRLinac and the direct measurement of kQ,B calibration of ionization chambers. Methods: Calorimetric absorbed dose to water Dw was measured with a new water calorimeter in the bore of an MRLinac (TPR20,10 of 0.702). Two waterproof ionization chambers (PTW 30013, IBA FC-65G) were calibrated inside the calorimeter phantom (ND,w,Q,B). Both measurements were normalized to a monitor ionization chamber. Ionization chamber measurements were corrected for conventional influence parameter. Based on the chambers’ Co-60 calibrations (ND,w,Q0), measured directly against the calorimeter. In this study the correction factors kQ,B was determined as the ratio of the calibration coefficients in the MRLinac and in Co-60. Additionally, kB was determined based on kQ values obtained with the IAEA TRS-398 Code of Practice. Results: The kQ,B factors of the ionization chambers mentioned above were respectively 0.9488(8) and 0.9445(8) with resulting kB factors of 0.961(13) and 0.952(13) with standard uncertainties on the least significant digit(s) between brackets. Conclusion: Calorimetric Dw measurements and calibration of waterproof ionization chambers were successfully carried out in the 1.5 T B-field of an MRLinac with a standard uncertainty of 0.7%. Preliminary kQ,B and kB factors were determined with standard uncertainties of respectively 0.8% and 1.3%. The kQ,B agrees with an alternative method within 0.4%. The feasibility of water calorimetry in the presence of B

  13. Direct demonstration of rapid insulin-like growth factor II receptor internalization and recycling in rat adipocytes. Insulin stimulates 125I-insulin-like growth factor II degradation by modulating the IGF-II receptor recycling process

    Oka, Y.; Rozek, L.M.; Czech, M.P.

    1985-01-01

    The photoactive insulin-like growth factor (IGF)-II analogue 4-azidobenzoyl- 125 I-IGF-II was synthesized and used to label specifically and covalently the Mr = 250,000 Type II IGF receptor. When rat adipocytes are irradiated after a 10-min incubation with 4-azidobenzoyl- 125 I-IGF-II at 10 degrees C and immediately homogenized, most of the labeled IGF-II receptors are associated with the plasma membrane fraction, indicating that receptors accessible to the labeling reagent at low temperature are on the cell surface. However, when the photolabeled cells are incubated at 37 degrees C for various times before homogenization, labeled IGF-II receptors are rapidly internalized with a half-time of 3.5 min as evidenced by a loss from the plasma membrane fraction and a concomitant appearance in the low density microsome fraction. The steady state level of cell surface IGF-II receptors in the presence or absence of IGF-II remains constant under these conditions, demonstrating that IGF-II receptors rapidly recycle back to the cell surface at the same rate as receptor internalization. Using the above methodology, it is shown that acute insulin action: 1) increases the steady state number of cell surface IGF-II receptors; 2) increases the number of ligand-bound IGF-II receptors that are internalized per unit of time; and 3) increases the rate of cellular 125 I-IGF-II degradation by a process that is blocked by anti-IGF-II receptor antibody

  14. Direct Reactions

    Austern, N. [University of Pittsburgh, Pittsburgh, PA (United States)

    1963-01-15

    In order to give a unified presentation of one point of view, these lectures are devoted only to a detailed development of the standard theories of direct reactions, starting from basic principles. Discussion is given of the present status of the theories, of the techniques used for practical calculation, and of possible future developments. The direct interaction (DI) aspects of a reaction are those which involve only a few of the many degrees of freedom of a nucleus. In fact the minimum number of degrees of freedom which must be involved in a reaction are those required to describe the initial and final channels, and DI studies typically consider these degrees of freedom and no others. Because of this simplicity DI theories may be worked out in painstaking detail. DI processes concern only part of the wave function for a problem. The other part involves complicated excitations of many degrees of freedom, and gives the compound nucleus (CN) effects. While it is extremely interesting to learn how to separate DI and CN effects in an orderly manner, if they are both present in a reaction, no suitable method has yet been found. Instead, current work stresses the kinds of reactions and the kinds of final states in which DI effects dominate and in which CN effects may almost be forgotten. The DI cross-sections which are studied are often extremely large, comparable to elastic scattering cross-sections. (author)

  15. The search for a main cause of uncertainty of the calculated astrophysical S factor for the direct radiative capture d(α, γ)6Li reaction at stellar energies

    Blokhintsev, L.D.; Igamov, S.B.; Nishonov, M.M.; Yarmukhamedov, R.

    2004-01-01

    Full text: It is well known that the d( α,γ ) 6 Li reaction is one of the sources of the 6 Li production in the Big Bang nucleosynthesis. At the present time rather large uncertainties exist in the prediction of the rate of this reaction, which are mainly due to the absence both of the reliable experimental cross section (or the astrophysical S factor, S(E)) and of the theoretical calculations at extremely low energies E (E ≤ 600 keV) (see [1] and references therein). The aim of our work is to find out the principal cause of the existing large spread of the calculated values of S(E) at extremely low energies obtained by different authors, including the results of the present work. The basic idea of our consideration is that the d( α, γ) 6 Li reaction at such energies is predominantly peripheral [2]-[4]. Therefore the values of S(E) at extremely low energies are mainly determined by the nuclear vertex constant (NVC) (or by the asymptotic normalization constant (ANC)) for the virtual decay 6 Li→α+ d. Taking this circumstance into account, we calculated the NVC for the virtual decay 6 Li→α + d in the framework of three- body ( np) Faddeev equations in the momentum space. The Malfliet-Tjon and Graz potentials for NN interaction and the Sack-Biedenharn-Breit and Yamaguchi type potentials for αN interaction were used. The results of our calculations show that the obtained values of the NVC (or the ANC) are sensitive to the form of NN and αN potentials. This result is also corroborated by the values of the NVC calculated within the microscopic model using the Minnesota and Volkov potentials for NN- interaction [5]. The values of the NVC obtained in the present work were used to determine the values of the astrophysical S factor for the direct radiative capture d( α,γ ) 6 Li reaction at extremely low energies. It is shown that the values of the NVC corresponding to the different forms of NN and αN potentials lead to the different values of the

  16. Hypoxia-inducible factor-1α plays roles in Epstein-Barr virus's natural life cycle and tumorigenesis by inducing lytic infection through direct binding to the immediate-early BZLF1 gene promoter.

    Richard J Kraus

    2017-06-01

    Full Text Available When confronted with poor oxygenation, cells adapt by activating survival signaling pathways, including the oxygen-sensitive transcriptional regulators called hypoxia-inducible factor alphas (HIF-αs. We report here that HIF-1α also regulates the life cycle of Epstein-Barr virus (EBV. Incubation of EBV-positive gastric carcinoma AGS-Akata and SNU-719 and Burkitt lymphoma Sal and KemIII cell lines with a prolyl hydroxylase inhibitor, L-mimosine or deferoxamine, or the NEDDylation inhibitor MLN4924 promoted rapid and sustained accumulation of both HIF-1α and lytic EBV antigens. ShRNA knockdown of HIF-1α significantly reduced deferoxamine-mediated lytic reactivation. HIF-1α directly bound the promoter of the EBV primary latent-lytic switch BZLF1 gene, Zp, activating transcription via a consensus hypoxia-response element (HRE located at nt -83 through -76 relative to the transcription initiation site. HIF-1α did not activate transcription from the other EBV immediate-early gene, BRLF1. Importantly, expression of HIF-1α induced EBV lytic-gene expression in cells harboring wild-type EBV, but not in cells infected with variants containing base-pair substitution mutations within this HRE. Human oral keratinocyte (NOK and gingival epithelial (hGET cells induced to differentiate by incubation with either methyl cellulose or growth in organotypic culture accumulated both HIF-1α and Blimp-1α, another cellular factor implicated in lytic reactivation. HIF-1α activity also accumulated along with Blimp-1α during B-cell differentiation into plasma cells. Furthermore, most BZLF1-expressing cells observed in lymphomas induced by EBV in NSG mice with a humanized immune system were located distal to blood vessels in hypoxic regions of the tumors. Thus, we conclude that HIF-1α plays central roles in both EBV's natural life cycle and EBV-associated tumorigenesis. We propose that drugs that induce HIF-1α protein accumulation are good candidates for

  17. A TetR family transcriptional factor directly regulates the expression of a 3-methyladenine DNA glycosylase and physically interacts with the enzyme to stimulate its base excision activity in Mycobacterium bovis BCG.

    Liu, Lei; Huang, Cheng; He, Zheng-Guo

    2014-03-28

    3-Methyladenine DNA glycosylase recognizes and excises a wide range of damaged bases and thus plays a critical role in base excision repair. However, knowledge on the regulation of DNA glycosylase in prokaryotes and eukaryotes is limited. In this study, we successfully characterized a TetR family transcriptional factor from Mycobacterium bovis bacillus Calmette-Guerin (BCG), namely BCG0878c, which directly regulates the expression of 3-methyladenine DNA glycosylase (designated as MbAAG) and influences the base excision activity of this glycosylase at the post-translational level. Using electrophoretic mobility shift assay and DNase I footprinting experiments, we identified two conserved motifs within the upstream region of mbaag specifically recognized by BCG0878c. Significant down-regulation of mbaag was observed in BCG0878c-overexpressed M. bovis BCG strains. By contrast, about 12-fold up-regulation of mbaag expression was found in bcg0878c-deleted mutant M. bovis BCG strains. β-Galactosidase activity assays also confirmed these results. Thus, BCG0878c can function as a negative regulator of mbaag expression. In addition, the regulator was shown to physically interact with MbAAG to enhance the ability of the glycosylase to bind damaged DNA. Interaction between the two proteins was further found to facilitate AAG-catalyzed removal of hypoxanthine from DNA. These results indicate that a TetR family protein can dually regulate the function of 3-methyladenine DNA glycosylase in M. bovis BCG both at the transcriptional and post-translational levels. These findings enhance our understanding of the expression and regulation of AAG in mycobacteria.

  18. Directed evolution induces tributyrin hydrolysis in a virulence factor of Xylella fastidiosa using a duplicated gene as a template [v1; ref status: indexed, http://f1000r.es/48i

    Hossein Gouran

    2014-09-01

    Full Text Available Duplication of genes is one of the preferred ways for natural selection to add advantageous functionality to the genome without having to reinvent the wheel with respect to catalytic efficiency and protein stability. The duplicated secretory virulence factors of Xylella fastidiosa (LesA, LesB and LesC, implicated in Pierce's disease of grape and citrus variegated chlorosis of citrus species, epitomizes the positive selection pressures exerted on advantageous genes in such pathogens. A deeper insight into the evolution of these lipases/esterases is essential to develop resistance mechanisms in transgenic plants. Directed evolution, an attempt to accelerate the evolutionary steps in the laboratory, is inherently simple when targeted for loss of function. A bigger challenge is to specify mutations that endow a new function, such as a lost functionality in a duplicated gene. Previously, we have proposed a method for enumerating candidates for mutations intended to transfer the functionality of one protein into another related protein based on the spatial and electrostatic properties of the active site residues (DECAAF. In the current work, we present in vivo validation of DECAAF by inducing tributyrin hydrolysis in LesB based on the active site similarity to LesA. The structures of these proteins have been modeled using RaptorX based on the closely related LipA protein from Xanthomonas oryzae. These mutations replicate the spatial and electrostatic conformation of LesA in the modeled structure of the mutant LesB as well, providing in silico validation before proceeding to the laborious in vivo work. Such focused mutations allows one to dissect the relevance of the duplicated genes in finer detail as compared to gene knockouts, since they do not interfere with other moonlighting functions, protein expression levels or protein-protein interaction.

  19. Human factors in training

    Dutton, J.W.; Brown, W.R.

    1981-01-01

    The Human Factors concept is a focused effort directed at those activities which require human involvement. Training is, by its nature, an activity totally dependent on the Human Factor. This paper identifies several concerns significant to training situations and discusses how Human Factor awareness can increase the quality of learning. Psychology in the training arena is applied Human Factors. Training is a method of communication represented by sender, medium, and receiver. Two-thirds of this communications model involves the human element directly

  20. Direct oral anticoagulants: An update.

    Franco Moreno, Ana Isabel; Martín Díaz, Rosa María; García Navarro, María José

    2017-12-30

    Vitamin K antagonists were the only choice for chronic oral anticoagulation for more than half a century. Over the past few years, direct oral anticoagulants have emerged, including one direct thrombin inhibitor (dabigatran etexilate) and three factor Xa inhibitors (apixaban, edoxaban and rivaroxaban). In randomised controlled trials comparing direct oral anticoagulants with traditional vitamin K antagonists, the direct oral anticoagulants all showed a favourable benefit-risk balance in their safety and efficacy profile, in prevention of thromboembolic events in patients with atrial fibrillation and in the prevention and treatment of venous thromboembolism and acute coronary syndrome. In 2008, dabigatran was the first direct oral anticoagulant approved by the European Medicine Agency. Subsequently, rivaroxaban, apixaban and edoxaban were also authorised. This article reviews the evidence related to the use of these drugs. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  1. Renal Cell Carcinoma Programmed Death-ligand 1, a New Direct Target of Hypoxia-inducible Factor-2 Alpha, is Regulated by von Hippel-Lindau Gene Mutation Status.

    Messai, Yosra; Gad, Sophie; Noman, Muhammad Zaeem; Le Teuff, Gwenael; Couve, Sophie; Janji, Bassam; Kammerer, Solenne Florence; Rioux-Leclerc, Nathalie; Hasmim, Meriem; Ferlicot, Sophie; Baud, Véronique; Mejean, Arnaud; Mole, David Robert; Richard, Stéphane; Eggermont, Alexander M M; Albiges, Laurence; Mami-Chouaib, Fathia; Escudier, Bernard; Chouaib, Salem

    2016-10-01

    Clear cell renal cell carcinomas (ccRCC) frequently display a loss of function of the von Hippel-Lindau (VHL) gene. To elucidate the putative relationship between VHL mutation status and immune checkpoint ligand programmed death-ligand 1 (PD-L1) expression. A series of 32 renal tumors composed of 11 VHL tumor-associated and 21 sporadic RCCs were used to evaluate PD-L1 expression levels after sequencing of the three exons and exon-intron junctions of the VHL gene. The 786-O, A498, and RCC4 cell lines were used to investigate the mechanisms of PD-L1 regulation. Fisher's exact test was used for VHL mutation and Kruskal-Wallis test for PD-L1 expression. If no covariate accounted for the association of VHL and PD-L1, then a Kruskal-Wallis test was used; otherwise Cochran-Mantel-Haenzsel test was used. We also used the Fligner-Policello test to compare two medians when the distributions had different dispersions. We demonstrated that tumors from ccRCC patients with VHL biallelic inactivation (ie, loss of function) display a significant increase in PD-L1 expression compared with ccRCC tumors carrying one VHL wild-type allele. Using the inducible VHL 786-O-derived cell lines with varying hypoxia-inducible factor-2 alpha (HIF-2α) stabilization levels, we showed that PD-L1 expression levels positively correlate with VHL mutation and HIF-2α expression. Targeting HIF-2α decreased PD-L1, while HIF-2α overexpression increased PD-L1 mRNA and protein levels in ccRCC cells. Interestingly, chromatin immunoprecipitation and luciferase assays revealed a direct binding of HIF-2α to a transcriptionally active hypoxia-response element in the human PD-L1 proximal promoter in 786-O cells. Our work provides the first evidence that VHL mutations positively correlate with PD-L1 expression in ccRCC and may influence the response to ccRCC anti-PD-L1/PD-1 immunotherapy. We investigated the relationship between von Hippel-Lindau mutations and programmed death-ligand 1 expression. We

  2. Physical activity in 3-6 year old children measured by SenseWear Pro®: direct accelerometry in the course of the week and relation to weight status, media consumption, and socioeconomic factors.

    Yvonne Vorwerg

    Full Text Available BACKGROUND: Data on objectively measured physical activity (PA in preschoolers are controversial. Direct accelerometry was performed in children aged 3-6 years, and differences in PA patterns over the course of the week were evaluated. Data were analyzed with gender, BMI, lifestyle, and socioeconomic parameters as covariates. METHODS: PA was measured in 119 children by the SensewearPro® accelerometer and analyzed in the 92 (40 girls that wore it for at least 4 days including one day of the weekend. Median measuring time in this group was 7 consecutive days (median/mean daily measuring time: 23.5 h/d and 21.8 h/d, respectively, corresponding to 834,000 analyzed minutes. PA questionnaires were completed by 103 parents and 87 preschool teachers to collect anthropometric, lifestyle, and socioeconomic data. RESULTS: Median daily PA (MET>3 was 4.3 hours (mean: 4.4 hours. Boys spent an estimated 52 min/week more being very active (MET>6 than girls (95% CI [6, 96] min/week, p = 0.02. PA was lower during the weekend (3.7 h/d compared to weekdays (4.5 h/d, p = 3 × 10(-6, where a 95% CI for the difference is [0.5, 1.0] h/d. PA levels did not differ between overweight/obese children (median 4.7 h/d and normal-weight peers (median 4.2 h/d. Daily media consumption increased with decreasing social class on weekdays (p = 0.05 and during the weekend (p = 0.01, but was not related to the amount of daily PA. A multivariate regression with BMI-SDS as independent variable and gender, age, amount of PA>6 MET, parental BMI, media time and socioeconomic status as explanatory variables revealed that only SES had a significant contribution. CONCLUSION: The negative impact of obesity-promoting factors in older children is rather low for preschoolers, but there is evidently a gradient in PA between weekdays and weekends already in this age group. Weight status of preschoolers is already considerably influenced by SES, but not physical activity levels.

  3. Physical activity in 3-6 year old children measured by SenseWear Pro®: direct accelerometry in the course of the week and relation to weight status, media consumption, and socioeconomic factors.

    Vorwerg, Yvonne; Petroff, David; Kiess, Wieland; Blüher, Susann

    2013-01-01

    Data on objectively measured physical activity (PA) in preschoolers are controversial. Direct accelerometry was performed in children aged 3-6 years, and differences in PA patterns over the course of the week were evaluated. Data were analyzed with gender, BMI, lifestyle, and socioeconomic parameters as covariates. PA was measured in 119 children by the SensewearPro® accelerometer and analyzed in the 92 (40 girls) that wore it for at least 4 days including one day of the weekend. Median measuring time in this group was 7 consecutive days (median/mean daily measuring time: 23.5 h/d and 21.8 h/d, respectively), corresponding to 834,000 analyzed minutes. PA questionnaires were completed by 103 parents and 87 preschool teachers to collect anthropometric, lifestyle, and socioeconomic data. Median daily PA (MET>3) was 4.3 hours (mean: 4.4 hours). Boys spent an estimated 52 min/week more being very active (MET>6) than girls (95% CI [6, 96] min/week, p = 0.02). PA was lower during the weekend (3.7 h/d) compared to weekdays (4.5 h/d), p = 3 × 10(-6)), where a 95% CI for the difference is [0.5, 1.0] h/d. PA levels did not differ between overweight/obese children (median 4.7 h/d) and normal-weight peers (median 4.2 h/d). Daily media consumption increased with decreasing social class on weekdays (p = 0.05) and during the weekend (p = 0.01), but was not related to the amount of daily PA. A multivariate regression with BMI-SDS as independent variable and gender, age, amount of PA>6 MET, parental BMI, media time and socioeconomic status as explanatory variables revealed that only SES had a significant contribution. The negative impact of obesity-promoting factors in older children is rather low for preschoolers, but there is evidently a gradient in PA between weekdays and weekends already in this age group. Weight status of preschoolers is already considerably influenced by SES, but not physical activity levels.

  4. Nanoparticles and direct immunosuppression

    Ngobili, Terrika A

    2016-01-01

    Targeting the immune system with nanomaterials is an intensely active area of research. Specifically, the capability to induce immunosuppression is a promising complement for drug delivery and regenerative medicine therapies. Many novel strategies for immunosuppression rely on nanoparticles as delivery vehicles for small-molecule immunosuppressive compounds. As a consequence, efforts in understanding the mechanisms in which nanoparticles directly interact with the immune system have been overshadowed. The immunological activity of nanoparticles is dependent on the physiochemical properties of the nanoparticles and its subsequent cellular internalization. As the underlying factors for these reactions are elucidated, more nanoparticles may be engineered and evaluated for inducing immunosuppression and complementing immunosuppressive drugs. This review will briefly summarize the state-of-the-art and developments in understanding how nanoparticles induce immunosuppressive responses, compare the inherent properties of nanomaterials which induce these immunological reactions, and comment on the potential for using nanomaterials to modulate and control the immune system. PMID:27229901

  5. Is direct marketing a risk factor? Inaccurate forecasting of power generation from renewables raises the demand for balancing power; Risikofaktor Direktvermarktung? Durch ungenaue Prognosen bei der Einspeisung von gruenem Strom steigt der Bedarf an Regelleistung

    Korn, Stefan

    2012-05-15

    Since the amendment of the EEG in January 2012, enormous amounts of electric power from renewable energy sources are marketed directly, i.e. outside the control of power supply grid owners and operators that formerly sold the electric power in the stock exchange. Inaccurate prognoses made by the direct marketers as well as their marketing strategies have increased the demand for balancing power and made critical situations in the power grid even more difficult.

  6. Multi-directional productivity change

    Asmild, Mette; Balezentis, Tomas; Hougaard, Jens Leth

    2016-01-01

    In this paper we introduce an extension of the Malmquist total factor productivity index, which utilizes the Multi-directional Efficiency Analysis approach. This enables variable-specific analysis of productivity change as well as its components (efficiency change and technical change). The new...

  7. Direction-dependent exponential biassing

    Bending, R.C.

    1974-01-01

    When Monte Carlo methods are applied to penetration problems, the use of variance reduction techniques is essential if realistic computing times are to be achieved. A technique known as direction-dependent exponential biassing is described which is simple to apply and therefore suitable for problems with difficult geometry. The material cross section in any region is multiplied by a factor which depends on the particle direction, so that particles travelling in a preferred direction ''see'' a smaller cross section than those travelling in the opposite direction. A theoretical study shows that substantial gains may be obtained, and that the choice of biassing parameter is not critical. The method has been implemented alongside other importance sampling techniques in the general Monte Carlo code SPARTAN, and results obtained for simple problems using this code are included. 4 references. (U.S.)

  8. Potential theory for directed networks.

    Qian-Ming Zhang

    Full Text Available Uncovering factors underlying the network formation is a long-standing challenge for data mining and network analysis. In particular, the microscopic organizing principles of directed networks are less understood than those of undirected networks. This article proposes a hypothesis named potential theory, which assumes that every directed link corresponds to a decrease of a unit potential and subgraphs with definable potential values for all nodes are preferred. Combining the potential theory with the clustering and homophily mechanisms, it is deduced that the Bi-fan structure consisting of 4 nodes and 4 directed links is the most favored local structure in directed networks. Our hypothesis receives strongly positive supports from extensive experiments on 15 directed networks drawn from disparate fields, as indicated by the most accurate and robust performance of Bi-fan predictor within the link prediction framework. In summary, our main contribution is twofold: (i We propose a new mechanism for the local organization of directed networks; (ii We design the corresponding link prediction algorithm, which can not only testify our hypothesis, but also find out direct applications in missing link prediction and friendship recommendation.

  9. Potential Theory for Directed Networks

    Zhang, Qian-Ming; Lü, Linyuan; Wang, Wen-Qiang; Zhou, Tao

    2013-01-01

    Uncovering factors underlying the network formation is a long-standing challenge for data mining and network analysis. In particular, the microscopic organizing principles of directed networks are less understood than those of undirected networks. This article proposes a hypothesis named potential theory, which assumes that every directed link corresponds to a decrease of a unit potential and subgraphs with definable potential values for all nodes are preferred. Combining the potential theory with the clustering and homophily mechanisms, it is deduced that the Bi-fan structure consisting of 4 nodes and 4 directed links is the most favored local structure in directed networks. Our hypothesis receives strongly positive supports from extensive experiments on 15 directed networks drawn from disparate fields, as indicated by the most accurate and robust performance of Bi-fan predictor within the link prediction framework. In summary, our main contribution is twofold: (i) We propose a new mechanism for the local organization of directed networks; (ii) We design the corresponding link prediction algorithm, which can not only testify our hypothesis, but also find out direct applications in missing link prediction and friendship recommendation. PMID:23408979

  10. Direct determination of k Q factors for cylindrical and plane-parallel ionization chambers in high-energy electron beams from 6 MeV to 20 MeV

    Krauss, A.; Kapsch, R.-P.

    2018-02-01

    For the ionometric determination of the absorbed dose to water, D w, in high-energy electron beams from a clinical accelerator, beam quality dependent correction factors, k Q, are required. By using a water calorimeter, these factors can be determined experimentally and potentially with lower standard uncertainties than those of the calculated k Q factors, which are tabulated in various dosimetry protocols. However, one of the challenges of water calorimetry in electron beams is the small measurement depths in water, together with the steep dose gradients present especially at lower energies. In this investigation, water calorimetry was implemented in electron beams to determine k Q factors for different types of cylindrical and plane-parallel ionization chambers (NE2561, NE2571, FC65-G, TM34001) in 10 cm  ×  10 cm electron beams from 6 MeV to 20 MeV (corresponding beam quality index R 50 ranging from 1.9 cm to 7.5 cm). The measurements were carried out using the linear accelerator facility of the Physikalisch-Technische Bundesanstalt. Relative standard uncertainties for the k Q factors between 0.50% for the 20 MeV beam and 0.75% for the 6 MeV beam were achieved. For electron energies above 8 MeV, general agreement was found between the relative electron energy dependencies of the k Q factors measured and those derived from the AAPM TG-51 protocol and recent Monte Carlo-based studies, as well as those from other experimental investigations. However, towards lower energies, discrepancies of up to 2.0% occurred for the k Q factors of the TM34001 and the NE2571 chamber.

  11. Direct determination of k Q factors for cylindrical and plane-parallel ionization chambers in high-energy electron beams from 6 MeV to 20 MeV.

    Krauss, A; Kapsch, R-P

    2018-02-06

    For the ionometric determination of the absorbed dose to water, D w , in high-energy electron beams from a clinical accelerator, beam quality dependent correction factors, k Q , are required. By using a water calorimeter, these factors can be determined experimentally and potentially with lower standard uncertainties than those of the calculated k Q factors, which are tabulated in various dosimetry protocols. However, one of the challenges of water calorimetry in electron beams is the small measurement depths in water, together with the steep dose gradients present especially at lower energies. In this investigation, water calorimetry was implemented in electron beams to determine k Q factors for different types of cylindrical and plane-parallel ionization chambers (NE2561, NE2571, FC65-G, TM34001) in 10 cm  ×  10 cm electron beams from 6 MeV to 20 MeV (corresponding beam quality index R 50 ranging from 1.9 cm to 7.5 cm). The measurements were carried out using the linear accelerator facility of the Physikalisch-Technische Bundesanstalt. Relative standard uncertainties for the k Q factors between 0.50% for the 20 MeV beam and 0.75% for the 6 MeV beam were achieved. For electron energies above 8 MeV, general agreement was found between the relative electron energy dependencies of the k Q factors measured and those derived from the AAPM TG-51 protocol and recent Monte Carlo-based studies, as well as those from other experimental investigations. However, towards lower energies, discrepancies of up to 2.0% occurred for the k Q factors of the TM34001 and the NE2571 chamber.

  12. FORMS AND MOTIVATIONS OF FOREIGN DIRECT INVESTMENT

    Maria-Ramona SÂRBU

    2014-04-01

    Full Text Available This study proposes the identification of forms of Foreign Direct Investment (FDI and analyzes factors influencing FDI motivation. Designing a coherent program to encourage foreign direct investment is based on knowledge of the factors that determine international companies to resort to this type of development: these companies resort to foreign direct investment if they have ownership advantages and internationalization, while another country has locational advantages to the company's home country. Thus, identifying the factors that influence the motivation of FDI is important both at the microeconomic level, local, local authorities and macroeconomic, national, government to develop measures for multiplying FDI .

  13. Plerocercoid growth factor (PGF), a human growth hormone (hGH) analogue produced by the tapeworm Spirometra mansonoides, has direct insulin-like action in adipose tissue of normal rats in vitro

    Salem, M.A.M.; Phares, C.K.

    1986-01-01

    The metabolic actions of GH can be divided into acute (insulin-like) and chronic (lipolytic/anti-insulin). The insulin-like actions of GH are most readily elicited in GH-deficient animals as GH induces resistance to its own insulin-like action. Like GH, PGF stimulates growth and cross-reacts with anti-hGH antibodies. Independent experiments were conducted comparing the direct actions of PGF to insulin or hGH in vitro. Insulin-like effects were determined by the ability of PGF, insulin or hGH to stimulate [U- 14 C]glucose metabolism in epidydimal fat pads from normal rats and by inhibition of epinephrine-stimulated lipolysis. Direct stimulation of lipolysis was used as anti-insulin activity. To determine if PGF competes for insulin or GH receptors, adipocytes (3 x 10 5 cells/ml) were incubated with either [ 125 I]insulin or [ 125 I]hGH +/- PGF, +/- insulin or +/- hGH. PGF stimulated glucose oxidation and 14 C-incorporation into lipids. Insulin, hGH and PGF inhibited lipolysis (33%, 29% and 34%, respectively). Adipose tissue was very sensitive to the lipolytic effect of hGH but PGF was neither lipolytic nor did it confer refractoriness to its insulin-like action. PGF bound to GH but not to insulin receptors. Therefore, PGF had direct insulin-like effects but did not stimulate lipolysis in tissue from normal rats in vitro

  14. Dancoff factors with partial neutrons absorption in cluster geometry by the direct method; Calculo dos fatores de Dancoff com absorcao parcial de neutrons em geometria cluster pelo metodo direto

    Rodrigues, Leticia Jenisch

    2007-07-01

    Accurate analysis of resonance absorption in heterogeneous systems is essential in problems like criticality, breeding ratios and fuel depletion calculations. In compact arrays of fuel rods, resonance absorption is strongly affected by the Dancoff factor, defined in mis study as the probability that a neutron emitted from the surface of a fuel element, enters another fuel element without any collusion in the moderator or cladding. In fact, in the most practical cases of irregular cells, it is observed that inaccuracies in computing both Grey and Black Dancoff factors, i.e. for partially and perfectly absorbing fuel rods, can lead to considerable errors in the calculated values of such integral quantities. For this reason, much effort has been made in the past decades to further improve the models for calculating Dancoff factors, a task that has been accomplished in connection with the development of faster computers. In the WIMS code, Black Dancoff factors based on the above mentioned collusion probability definition are computed in cluster geometry, for each one of the symmetrically distinct fuel pin positions in the cell. Sets of equally-spaced parallel lines are drawn in subroutine PIJ, at a number of discrete equally-incremented azimuthal angles, covering the whole system and forming a mesh over which the in-plane integrations of the Bickley functions are carried out by simple trapezoidal rule, leading to the first-flight collusion matrices. Although fast, the method in PIJ is inefficient, since the constructed mesh does not depended on the system details, so that regions of small relative volumes are crossed out by relatively few lines, which affects the convergence of the calculated probabilities. A new routine (PIJM) was then created to incorporate a more efficient integration scheme considering each system region individually, minimizing convergence problems and reducing the number of neutron track lines required in the in-plane integrations for any given

  15. Validation of cosmogenic nuclide production rate scaling factors through direct measurement. Part 2, Production of 7Be and 10Be in water targets deployed in the Southern Hemisphere, 1997-2001

    Graham, I.J.; Barry, B.J.; Ditchburn, R.G.; Zondervan, A.

    2005-01-01

    Sealed containers of de-ionised water were exposed to cosmic-rays at seven sites in Australia, New Zealand and Antarctica, covering a range of altitudes and geomagnetic latitudes, over time periods of six months to three years (1997-2001). After isotopic analysis by gamma counting (for 7 Be) and accelerator mass spectrometry (for 10 Be), the data obtained were corrected to obtain relative production factors (i.e., 'k' values). This report presents a full description of the target design, isotope extraction, and measurement procedures employed. It thus provides the raw data from which cosmogenic nuclide production rates for the Southern Hemisphere can be calculated, and scaling factors used in surface exposure dating can be independently validated. (author). 35 refs., 7 figs., 5 tabs

  16. Direct selling particularities

    Greifová, Daniela

    2009-01-01

    Bachelor thesis is focused on the parcularities of direct selling, self regulation of this industry, multi-level marketing which is the most used sales method in the field of direct selling. The part of the thesis is dedicated to the issue of customer psychology that is very important for achieving success in direct selling. Main goals are to provide readers with the general view of direct selling and analysis of growing possibilities of the industry in the future.

  17. Directed Energy Weapons

    2007-12-01

    future business . In defense systems, the key to future business is the existence of funded programs. Military commanders understand the lethality and...directed energp capabilities that can provide visibiliy into the likey futur business case for sustaining directed energy industry capabilities...the USD (I) staff to be afocalpointfor advocating improvement in all dimensions of directed energy intelligence. - The Director, Defense Inteligence

  18. Modeling switching behaviour of direct selling customers

    P Msweli-Mbanga

    2004-04-01

    Full Text Available The direct selling industry suffers a high turnover rate of salespeople, resulting in high costs of training new salespeople. Further costs are incurred when broken relationships with customers cause them to switch from one product supplier to another. This study identifies twelve factors that drive the switching behaviour of direct sales customers and examines the extent to which these factors influence switching. Exploratory factor analysis was used to assess the validity of these factors. The factors were represented in a model that posits that an interpersonal relationship between a direct sales person and a customer moderates the relationship between switching behaviour and loyalty. Structural equation modeling was used to test the proposed model. The author then discusses the empirical findings and their managerial implications, providing further avenues for research.

  19. Natural History and Factors Associated with Early and Delayed Mortality in HIV-Infected Patients Treated of Tuberculosis under Directly Observed Treatment Short-Course Strategy: A Prospective Cohort Study in India

    Gerardo Alvarez-Uria

    2012-01-01

    Full Text Available Despite the impressive global results of DOTS in India, the effectiveness of DOTS for the treatment of tuberculosis in HIV-infected patients is not well known. This is an observational prospective cohort study performed in Anantapur District, Andhra Pradesh, India. The study included 1000 DOTS antituberculosis treatment (ATT episodes and 840 person-years. CD4 lymphocyte count was below 200 cells/mm3 in 77% of the cases, and 21% were retreatments. Two thirds were presented with extrapulmonary tuberculosis, and the most common form of extrapulmonary tuberculosis was tuberculous meningitis followed by pleuritis, abdominal tuberculosis, and lymphadenitis. Cumulative incidence of mortality was 16%, 26%, 39%, and 46% at 1, 3, 12, and 24 months, respectively. Factors associated with three-month (early mortality were being homeless, having low CD4+ lymphocyte count, having tuberculous meningitis, belonging to a socially disadvantaged community, having more than 35 years, and being on an antiretroviral therapy at the moment of initiating the ATT. Factors associated with delayed mortality were having low CD4+ lymphocyte count, belonging to a socially disadvantaged community, receiving a category II ATT because of a previous episode of ATT and having acid fast bacilli in sputum before the ATT initiation. These findings indicate that there is an urgent need to improve the treatment of tuberculosis in HIV-infected patients in India.

  20. Directed Energy Anechoic Chamber

    Federal Laboratory Consortium — The Directed Energy Anechoic Chamber comprises a power anechoic chamber and one transverse electromagnetic cell for characterizing radiofrequency (RF) responses of...

  1. Records Management Directive

    Office of Personnel Management — The Office of Personnel Management (OPM) Records Management Directive provides guidelines for the management of OPM records, and identifies the records management...

  2. Direct Conversion of Energy.

    Corliss, William R.

    This publication is one of a series of information booklets for the general public published by the United States Atomic Energy Commission. Direct energy conversion involves energy transformation without moving parts. The concepts of direct and dynamic energy conversion plus the laws governing energy conversion are investigated. Among the topics…

  3. Decisions Concerning Directional Dependence

    von Eye, Alexander; DeShon, Richard P.

    2012-01-01

    In this rejoinder, von Eye and DeShon discuss the decision strategies proposed in their original article ("Directional Dependence in Developmental Research," this issue), as well as the ones proposed by the authors of the commentary (Pornprasertmanit and Little, "Determining Directional Dependency in Causal Associations," this issue). In addition,…

  4. Theory of direct interparticle action

    Vladimirov, Yu.S.; Turygin, A.Yu.

    1986-01-01

    Unusual point of view on the physical picture of the Universe and ratio between main physical categories is considered. Principal moments and theory peculiarities based on the conception of direct interparticle action are underlined. The direct interparticle action theory (DIAT) is considered from the position of choosing one or another axiomatics. At first the Fokker action principle is postulated there and then identical satisfiability of field equations is proved. All that relates to vacuum DIAT ignores and actions of matter formations are used as the basis. DIAT bears up against a global factor-account of absrbers of all surroundings (the Mach principle). The DIAT pretended to relativistic description of only additional concepts with the previously asigned space-time ratios. Concept for construction of the physical picture of the Universe, where classical space-time ratios being of secondary character, is suggested

  5. Directionality of dog vocalizations

    Frommolt, Karl-Heinz; Gebler, Alban

    2004-07-01

    The directionality patterns of sound emission in domestic dogs were measured in an anechoic environment using a microphone array. Mainly long-distance signals from four dogs were investigated. The radiation pattern of the signals differed clearly from an omnidirectional one with average differences in sound-pressure level between the frontal and rear position of 3-7 dB depending from the individual. Frequency dependence of directionality was shown for the range from 250 to 3200 Hz. The results indicate that when studying acoustic communication in mammals, more attention should be paid to the directionality pattern of sound emission.

  6. FAA Directives System

    1992-08-26

    Consistent with the Federal Aviation Administration's mission to foster a safe, : secure, and efficient aviation system is the need for an effective and efficient : process for communitcating policy and procedures. The FAA Directives System : provide...

  7. Assessing directionality in context

    Kate H

    In support of first-language interpreting as the exclusive interpreting direction, ... some light on the possible interaction between two independent variables, .... the “local context” refers to the setting, genre, participants, and aims of the event.

  8. Directed line liquids

    Kamien, R.D.

    1992-01-01

    This thesis is devoted to the study of ensembles of dense directed lines. These lines are principally to be thought of as polymers, though they also have the morphology of flux lines in high temperature superconductors, strings of colloidal spheres in electrorheological fluids and the world lines of quantum mechanical bosons. The authors discuss how directed polymer melts, string-like formations in electrorheological and ferro-fluids, flux lines in high temperature superconductors and the world lines of quantum mechanical bosons all share similar descriptions. They study a continuous transition in all of these systems, and then study the critical mixing properties of binary mixtures of directed polymers through the renormalization group. They predict the exponents for a directed polymer blend consolute point and a novel two-phase superfluid liquid-gas critical point

  9. The ''energy tax'' directive

    Anon.

    2003-01-01

    As Austria dropped its reservation, U.E. Economics and Finance Ministers gave, on 20 March at Brussels, their political agreement to the proposed Directive on a Community framework for the taxation of energy products. (author)

  10. Directed GF-spaces

    F.G. Arenas

    2001-10-01

    Full Text Available In this paper we introduce the concept of directed fractal structure, which is a generalization of the concept of fractal structure (introduced by the authors. We study the relation with transitive quasiuniformities and inverse limits of posets. We define the concept of GF-compactification and apply it to prove that the Stone-Cech compactification can be obtained as the GF-compactification of the directed fractal structure associated to the Pervin quasi-uniformity.

  11. Boosters and barriers for direct cardiac reprogramming.

    Talkhabi, Mahmood; Zonooz, Elmira Rezaei; Baharvand, Hossein

    2017-06-01

    Heart disease is currently the most significant cause of morbidity and mortality worldwide, which accounts for approximately 33% of all deaths. Recently, a promising and alchemy-like strategy has been developed called direct cardiac reprogramming, which directly converts somatic cells such as fibroblasts to cardiac lineage cells such as cardiomyocytes (CMs), termed induced CMs or iCMs. The first in vitro cardiac reprogramming study, mediated by cardiac transcription factors (TFs)-Gata4, Tbx5 and Mef2C-, was not enough efficient to produce an adequate number of fully reprogrammed, functional iCMs. As a result, numerous combinations of cardiac TFs exist for direct cardiac reprogramming of mouse and human fibroblasts. However, the efficiency of direct cardiac reprogramming remains low. Recently, a number of cellular and molecular mechanisms have been identified to increase the efficiency of direct cardiac reprogramming and the quality of iCMs. For example, microgrooved substrate, cardiogenic growth factors [VEGF, FGF, BMP4 and Activin A], and an appropriate stoichiometry of TFs boost the direct cardiac reprogramming. On the other hand, serum, TGFβ signaling, activators of epithelial to mesenchymal transition, and some epigenetic factors (Bmi1 and Ezh2) are barriers for direct cardiac reprogramming. Manipulating these mechanisms by the application of boosters and removing barriers can increase the efficiency of direct cardiac reprogramming and possibly make iCMs reliable for cell-based therapy or other potential applications. In this review, we summarize the latest trends in cardiac TF- or miRNA-based direct cardiac reprogramming and comprehensively discuses all molecular and cellular boosters and barriers affecting direct cardiac reprogramming. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Directed network modules

    Palla, Gergely; Farkas, Illes J; Pollner, Peter; Derenyi, Imre; Vicsek, Tamas

    2007-01-01

    A search technique locating network modules, i.e. internally densely connected groups of nodes in directed networks is introduced by extending the clique percolation method originally proposed for undirected networks. After giving a suitable definition for directed modules we investigate their percolation transition in the Erdos-Renyi graph both analytically and numerically. We also analyse four real-world directed networks, including Google's own web-pages, an email network, a word association graph and the transcriptional regulatory network of the yeast Saccharomyces cerevisiae. The obtained directed modules are validated by additional information available for the nodes. We find that directed modules of real-world graphs inherently overlap and the investigated networks can be classified into two major groups in terms of the overlaps between the modules. Accordingly, in the word-association network and Google's web-pages, overlaps are likely to contain in-hubs, whereas the modules in the email and transcriptional regulatory network tend to overlap via out-hubs

  13. Directivity of singers

    Jers, Harald

    2005-09-01

    Studies of acoustical balance between singers within a choir by means of room acoustical measurements have shown that the directional sound propagation of the source is important. For this reason the directivity of female and male singers for different vowels has been measured in this investigation. Measurements of a pilot study and some first measurements in 1998 have been supplemented with new measurements and an enhanced setup. A special measurement setup with reference and recording microphones was used to collect the directivity data. A resolution of 10 deg for azimuth and elevation angle was obtained. The results will be shown in 3D spherical plots with frequency adjustments in semitones from 80 to 8000 Hz. The measurements are compared to an artificial singer's directivity, and the influence of a sheet music binder in front of a singer will be shown. The results give information on the directivity of singers and are relevant for the prediction of self-to-other-ratios that result from placement and formation aspects within a choir.

  14. Estimating directional epistasis

    Le Rouzic, Arnaud

    2014-01-01

    Epistasis, i.e., the fact that gene effects depend on the genetic background, is a direct consequence of the complexity of genetic architectures. Despite this, most of the models used in evolutionary and quantitative genetics pay scant attention to genetic interactions. For instance, the traditional decomposition of genetic effects models epistasis as noise around the evolutionarily-relevant additive effects. Such an approach is only valid if it is assumed that there is no general pattern among interactions—a highly speculative scenario. Systematic interactions generate directional epistasis, which has major evolutionary consequences. In spite of its importance, directional epistasis is rarely measured or reported by quantitative geneticists, not only because its relevance is generally ignored, but also due to the lack of simple, operational, and accessible methods for its estimation. This paper describes conceptual and statistical tools that can be used to estimate directional epistasis from various kinds of data, including QTL mapping results, phenotype measurements in mutants, and artificial selection responses. As an illustration, I measured directional epistasis from a real-life example. I then discuss the interpretation of the estimates, showing how they can be used to draw meaningful biological inferences. PMID:25071828

  15. Direct reading dosimeter

    Thomson, I.

    1985-01-01

    This invention is a direct reading dosimeter which is light, small enough to be worn on a person, and measures both dose rates and total dose. It is based on a semiconductor sensor. The gate threshold voltage change rather than absolute value is measured and displayed as a direct reading of the dose rate. This is effected by continuously switching the gate of an MOS transistor from positive to negative bias. The output can directly drive a digital readout or trigger an audible alarm. The sensor device can be a MOSFET, bipolar transistor, or MOSFET capacitor which has its electrical characteristics change due to the trapped charge in the insulating layer of the device

  16. Risk Factors

    ... cells do not invade nearby tissues or spread. Risk Factors Key Points Factors That are Known to ... chemicals . Factors That are Known to Increase the Risk of Cancer Cigarette Smoking and Tobacco Use Tobacco ...

  17. The direction of time

    Reichenbach, Hans

    1999-01-01

    Ever a source of philosophical conjecture and debate, the concept of time represents the beating heart of physics. This final work by the distinguished physicist Hans Reichenbach represents the culmination and integration of a lifetime's philosophical contributions and inquiries into the analysis of time. The result is an outstanding overview of such qualitative, or topological, attributes of time as order and direction.Beginning with a discussion of the emotive significance of time, Reichenbach turns to an examination of the time order of mechanics, the time direction of thermodynamics and m

  18. Incretin secretion: direct mechanisms

    Balk-Møller, Emilie; Holst, Jens Juul; Kuhre, Rune Ehrenreich

    2014-01-01

    The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are secreted from gastro-intestinal K- and L-cells, respectively, and play an important role in post-prandial blood glucose regulation. They do this by direct stimulation of the pancreatic β...... enzyme responsible for incretin degradation (dipeptidyl peptidase-4) is inhibited (drugs are already on the market) while the secretion of endogenous GLP-1 secretion is stimulated at the same time may prove particularly rewarding. In this section we review current knowledge on the mechanisms for direct...

  19. Enhancing Scalability of Sparse Direct Methods

    Li, Xiaoye S.; Demmel, James; Grigori, Laura; Gu, Ming; Xia, Jianlin; Jardin, Steve; Sovinec, Carl; Lee, Lie-Quan

    2007-01-01

    TOPS is providing high-performance, scalable sparse direct solvers, which have had significant impacts on the SciDAC applications, including fusion simulation (CEMM), accelerator modeling (COMPASS), as well as many other mission-critical applications in DOE and elsewhere. Our recent developments have been focusing on new techniques to overcome scalability bottleneck of direct methods, in both time and memory. These include parallelizing symbolic analysis phase and developing linear-complexity sparse factorization methods. The new techniques will make sparse direct methods more widely usable in large 3D simulations on highly-parallel petascale computers

  20. Direct and retrospective assessment of factors contributing to compulsive buying.

    Miltenberger, Raymond G; Redlin, Jennifer; Crosby, Ross; Stickney, Marcella; Mitchell, Jim; Wonderlich, Stephen; Faber, Ronald; Smyth, Joshua

    2003-03-01

    Compulsive buying is a disorder that has begun to receive attention from researchers in recent years. The results of a handful of studies suggest that compulsive buying occurs in response to negative emotions and results in a decrease in the intensity of the negative emotions. In this investigation, we used interview and self-monitoring methods to evaluate the antecedents and consequences of compulsive buying in a sample of women who met criteria for compulsive buying on the compulsive buying scale (J. Consumer Res. 19 (1992) 459). As a group, the participants reported negative emotions as the most common antecedents to compulsive buying, and euphoria or relief from the negative emotions as the most common consequence of compulsive buying. These findings were consistent across the interview and self-monitoring assessment methods. The implications for assessment and treatment are discussed.

  1. Nuclear transport factor directs localization of protein synthesis during mitosis

    Bogaart, Geert van den; Meinema, Anne C.; Krasnikov, Viktor; Veenhoff, Liesbeth M.; Poolman, Bert

    Export of messenger RNA from the transcription site in the nucleus and mRNA targeting to the translation site in the cytoplasm are key regulatory processes in protein synthesis. In yeast, the mRNA-binding proteins Nab2p and Nab4p/Hrp1p accompany transcripts to their translation site, where the

  2. Factors influencing direct costs dynamics of building projects - team ...

    Ethiopian Journal of Environmental Studies and Management. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 6, No 5 (2013) >. Log in or Register to get access to full text downloads.

  3. Direct Sulfation of Limestone

    Hu, Guilin; Dam-Johansen, Kim; Wedel, Stig

    2007-01-01

    The direct sulfation of limestone was studied in a laboratory fixed-bed reactor. It is found that the direct sulfation of limestone involves nucleation and crystal grain growth of the solid product (anhydrite). At 823 K and at low-conversions (less than about 0.5 %), the influences of SO2, O-2...... and CO2 on the direct sulfation of limestone corresponds to apparent reaction orders of about 0.2, 0.2 and -0.5, respectively. Water is observed to promote the sulfation reaction and increase the apparent reaction orders of SO2 and O-2. The influence of O-2 at high O-2 concentrations (> about 15...... %) becomes negligible. In the temperature interval from 723 K to 973 K, an apparent activation energy of about 104 kJ/mol is observed for the direct sulfation of limestone. At low temperatures and low conversions, the sulfation process is most likely under mixed control by chemical reaction and solid...

  4. Danish directional adverbs:

    Hovmark, Henrik

    2013-01-01

    Danish directional adverbs (DDA) (for instance op ’up’, ned ’down’, and ud ’out’) are characterized by an important special feature as satellites – they have different forms: a zero-form (ud-Ø), a form with a derivative e-suffix (ud-e), and a third form with a prepositional ad-suffix (‘ wards’). ...

  5. Directional loudness perception

    Sivonen, Ville Pekka

    developed. The research and modeling of loudness have mainly been concerned with the temporal and spectral aspects of sounds, while the spatial aspects have mostly been overlooked. This PhD thesis investigates the spatial aspects of loudness perception, namely, how does the direction from which a sound...

  6. Direct contamination - seasonality

    Aarkrog, A.

    1994-01-01

    Direct contamination is the primary pathway to terrestrial vegetation in the first period after an activity release to the atmosphere. All radionuclides are able to be transferred via this pathway. Deposition, interception and retention are the three processes involved in direct contamination of crops. Wet deposition is more important than dry deposition in temperature regions. Resuspension and rainsplash both belong to secondary direct deposition and became evident for e.g. radiocaesium after the Chernobyl accident. Seasonality is the varying response to radioactive contamination of crops according to the time of the year when the contamination occurs. Shortlived radionuclides (as 131 I) and those that mainly enter the foodchain by direct contamination (e.g. 137 Cs) are especially important in this connection. In particular, the contamination of cereal crops is influenced by seasonality. As a result of seasonality the impact of the Chernobyl accident on the radioactive contamination of human diet was for the same deposition density higher in southern than in northern Europe. (orig.)

  7. Direct vision internal urethrotomy

    Jakobsen, H; Willumsen, H; Søndergaard Jensen, L

    1984-01-01

    During a five-year period, direct vision internal urethrotomy was used for the treatment of urethral strictures in 34 men. After the primary operation the patients were followed for an average period of 29 months (range 3-73 months). During this period 53% of the patients were found to have one...

  8. Direct photon experiments

    Boeggild, H.

    1986-11-01

    The author reviews the experiments on direct photon production in hadronic collisions. After a description of the experimental methods for the study of such processes he presents some results on differential cross sections and the γ/π 0 ratio in π - p, π + p, pp, and anti pp processes as well as in reactions of π - , π + , and p on carbon. (HSI)

  9. Polymer Directed Protein Assemblies

    Patrick van Rijn

    2013-05-01

    Full Text Available Protein aggregation and protein self-assembly is an important occurrence in natural systems, and is in some form or other dictated by biopolymers. Very obvious influences of biopolymers on protein assemblies are, e.g., virus particles. Viruses are a multi-protein assembly of which the morphology is dictated by poly-nucleotides namely RNA or DNA. This “biopolymer” directs the proteins and imposes limitations on the structure like the length or diameter of the particle. Not only do these bionanoparticles use polymer-directed self-assembly, also processes like amyloid formation are in a way a result of directed protein assembly by partial unfolded/misfolded biopolymers namely, polypeptides. The combination of proteins and synthetic polymers, inspired by the natural processes, are therefore regarded as a highly promising area of research. Directed protein assembly is versatile with respect to the possible interactions which brings together the protein and polymer, e.g., electrostatic, v.d. Waals forces or covalent conjugation, and possible combinations are numerous due to the large amounts of different polymers and proteins available. The protein-polymer interacting behavior and overall morphology is envisioned to aid in clarifying protein-protein interactions and are thought to entail some interesting new functions and properties which will ultimately lead to novel bio-hybrid materials.

  10. Direct Lending Works.

    Riley, Richard W.

    1997-01-01

    In its third year, direct lending is working well for college students and administration. It is a simpler, faster, more efficient way of getting loan funds to students that cuts out financial middlemen. It helps students manage their finances better when repaying loans, promotes competition, stimulates program innovation, leads to greater…

  11. Advanced directives: open issues

    Gabriella Negrini

    2013-05-01

    Full Text Available BACKGROUND In Italy Advanced directives have not been regulated by law yet. Moreover, there is a confusion of concepts: advanced directives, refusal of treatment, medical futility and euthanasia are not synonymous.DISCUSSION The following aspects are then discussed: object of directives; elapse of time between their expression and their application; knowledge of the directives and their obligatory nature. The refusal of a treatment that can save a person’s life is a critical subject. There are different ethical points of view: according to lay ethics, the patient’s self-determination prevails; the religious viewpoint, instead, says that life is a gift which we cannot dispose of. In any case, the patient will be confronted with the professional autonomy of the doctor. Should the doctor save a patient’s life in any case or should he achieve best clinical practice, in respect of his will? The doctor should interpret the patient’s will but with caution and judgment. An exemption from responsibility should be provided by law for doctors who respect patient’s living will.

  12. Photometric estimation of defect size in radiation direction

    Zuev, V.M.

    1993-01-01

    Factors, affecting accuracy of photometric estimation of defect size in radiation transmission direction, are analyzed. Experimentally obtained dependences of contrast of defect image on its size in radiation transmission direction are presented. Practical recommendations on improving accuracy of photometric estimation of defect size in radiation transmission direction, are developed

  13. On the Directionality Test of Peer Effects in Social Networks

    An, Weihua

    2016-01-01

    One interesting idea in social network analysis is the directionality test that utilizes the directions of social ties to help identify peer effects. The null hypothesis of the test is that if contextual factors are the only force that affects peer outcomes, the estimated peer effects should not differ, if the directions of social ties are…

  14. Analysis of Lithuanian Direct Investment into European Union Countries

    Evelina Zigmantavičiūtė

    2015-05-01

    Full Text Available In this paper the valuation of macroeconomic factors influencing the Lithuanian direct investment into European Union was conducted. The problem of this paper is the different chosen macroeconomic factors influencing foreign direct investment. The object of this paper is Lithuanian direct investment. The methods of this paper include: comparative literature analysis, correlation regression analysis, paired regression analysis. After conducting a research of dependency of Lithuanian direct investment to EU countries from price changes, government sector income, gross domestic product, inflation, jobless rate results, it is found that gross domestic product and government sector income have the most influence on the changes of Lithuanian direct investment.

  15. Direct utilization of geothermal energy

    Lund, J. W.

    2010-01-01

    The worldwide application of geothermal energy for direct utilization is reviewed. This paper is based on the world update for direct-use presented at the World Geothermal Congress 2010 in Bali, Indonesia (WGC2010) which also includes material presented at three world geothermal congresses in Italy, Japan and Turkey (WGC95, WGC2000 and WGC2005). This report is based on country update papers prepared for WGC2010 and data from other sources. Final update papers were received from 70 countries of which 66 reported some direct utilization of geothermal energy for WGC2010. Twelve additional countries were added to the list based on other sources of information. The 78 countries having direct utilization of geothermal energy, is a significant increase from the 72 reported in 2005, the 58 reported in 2000, and the 28 reported in 1995. An estimate of the installed thermal power for direct utilization at the end of 2009, reported from WGC2010 is 48,493 MW th , almost a 72 % increased over the 2005 data, growing at a compound rate of 11.4% annually with a capacity factor of 0.28. The thermal energy used is 423,830 TJ/year (117,740 GWh/yr), about a 55% increase over 2005, growing at a compound rate of 9.2% annually. The distribution of thermal energy used by category is approximately 47.2% for ground-source heat pumps, 25.8% for bathing and swimming (including balneology), 14.9% for space heating (of which 85% is for district heating), 5.5% for greenhouses and open ground heating, 2.8% for industrial process heating, 2.7% for aquaculture pond and raceway heating, 0.4% for agricultural drying, 0.5% for snow melting and cooling, and 0.2% for other uses. Energy savings amounted to 250 million barrels (38 million tonnes) of equivalent oil annually, preventing 33 million tonnes of carbon and 107 million tonnes of CO 2 being released to the atmosphere which includes savings in geothermal heat pump cooling (compared to using fuel oil to generate electricity). (author)

  16. Direct Utilization of Geothermal Energy

    John W. Lund

    2010-08-01

    Full Text Available The worldwide application of geothermal energy for direct utilization is reviewed. This paper is based on the world update for direct-use presented at the World Geothermal Congress 2010 in Bali, Indonesia (WGC2010 [1] which also includes material presented at three world geothermal congresses in Italy, Japan and Turkey (WGC95, WGC2000 and WGC2005. This report is based on country update papers prepared for WGC2010 and data from other sources. Final update papers were received from 70 countries of which 66 reported some direct utilization of geothermal energy for WGC2010. Twelve additional countries were added to the list based on other sources of information. The 78 countries having direct utilization of geothermal energy, is a significant increase from the 72 reported in 2005, the 58 reported in 2000, and the 28 reported in 1995. An estimate of the installed thermal power for direct utilization at the end of 2009, reported from WGC2010 is 48,493 MWt, almost a 72 % increased over the 2005 data, growing at a compound rate of 11.4% annually with a capacity factor of 0.28. The thermal energy used is 423,830 TJ/year (117,740 GWh/yr, about a 55% increase over 2005, growing at a compound rate of 9.2% annually. The distribution of thermal energy used by category is approximately 47.2% for ground-source heat pumps, 25.8% for bathing and swimming (including balneology, 14.9% for space heating (of which 85% is for district heating, 5.5% for greenhouses and open ground heating, 2.8% for industrial process heating, 2.7% for aquaculture pond and raceway heating, 0.4% for agricultural drying, 0.5% for snow melting and cooling, and 0.2% for other uses. Energy savings amounted to 250 million barrels (38 million tonnes of equivalent oil annually, preventing 33 million tonnes of carbon and 107 million tonnes of CO2 being release to the atmosphere which includes savings in geothermal heat pump cooling (compared to using fuel oil to generate electricity.

  17. Direct oxide reducing method

    Tokiwai, Moriyasu.

    1995-01-01

    Calcium oxides and magnetic oxides as wastes generated upon direct reduction are subjected to molten salt electrolysis, and reduced metallic calcium and magnesium are separated and recovered. Then calcium and magnesium are used recyclically as the reducing agent upon conducting direct oxide reduction. Even calcium oxides and magnesium oxides, which have high melting points and difficult to be melted usually, can be melted in molten salts of mixed fluorides or chlorides by molten-salt electrolysis. Oxides are decomposed by electrolysis, and oxygen is removed in the form of carbon monoxide, while the reduced metallic calcium and magnesium rise above the molten salts on the side of a cathode, and then separated. Since only carbon monoxide is generated as radioactive wastes upon molten salt electrolysis, the amount of radioactive wastes can be greatly reduced, and the amount of the reducing agent used can also be decreased remarkably. (N.H.)

  18. Direct use in Hawaii

    Beck, A.G.

    1990-01-01

    This paper reports on a public laboratory, Noi'i O Puna, that was established in Hawaii to support direct use research in 1985, tapping the previously unutilized heat in brines from the HGP-A well. Two rounds of small grants were offered to entrepreneurs. With the closure of the HGP-A power plant in late 1989, Noi'i O Puna is expanding its facilities. When the HGP-A well is back in service, Noi'i O Puna will be able to support additional research and development projects, as well as pre-commercial ventures. Direct use industries, which support existing agricultural activities in the region have good potential

  19. Direct Communication Systems

    Krajačić, Ivan

    2016-01-01

    Today we use numerous methods of direct communications, for which we use a technical term Unified Communications. It is almost impossible to imagine the business world today without Unified Communications, which are improving productivity and reducing costs. The goal of using Unified Communications is to ensure a consistent user experience at any location and any device. Skype for Business, a Microsoft product, is one of the solutions for Unified Communications and is described in this thesis...

  20. Directional borehole antenna - Theory

    Falk, L.

    1992-02-01

    A directional antenna has been developed for the borehole radar constructed during phase 2 of the Stripa project. The new antenna can determine the azimuth of a strong reflector with an accuracy of about 3 degrees as confirmed during experiments in Stripa, although the ratio of borehole diameter to wavelength is small, about 0.03. The antenna synthesizes the effect of a loop antenna rotating in the borehole from four signals measured in turn by a stationary antenna. These signals are also used to calculate an electric dipole signal and a check sum which is used to examine the function of the system. The theory of directional antennas is reviewed and used to design an antenna consisting of four parallel wires. The radiation pattern of this antenna is calculated using transmission line theory with due regard to polarization, which is of fundamental importance for the analysis of directional data. In particular the multipole expansion of the field is calculated to describe the antenna radiation pattern. Various sources of error, e.g. the effect of the borehole, are discussed and the methods of calibrating the antenna are reviewed. The ambiguity inherent in a loop antenna can be removed by taking the phase of the signal into account. Typical reflectors in rock, e.g. fracture zones an tunnels, may be modelled as simple geometrical structures. The corresponding analysis is described and exemplified on measurements from Stripa. Radar data is nowadays usually analyzed directly on the computer screen using the program RADINTER developed within the Stripa project. An algorithm for automatic estimation of the parameters of a reflector have been tested with some success. The relation between measured radar data and external coordinates as determined by rotational indicators is finally expressed in terms of Euler angles. (au)

  1. Direct hydrocarbon fuel cells

    Barnett, Scott A.; Lai, Tammy; Liu, Jiang

    2010-05-04

    The direct electrochemical oxidation of hydrocarbons in solid oxide fuel cells, to generate greater power densities at lower temperatures without carbon deposition. The performance obtained is comparable to that of fuel cells used for hydrogen, and is achieved by using novel anode composites at low operating temperatures. Such solid oxide fuel cells, regardless of fuel source or operation, can be configured advantageously using the structural geometries of this invention.

  2. Future directions for QCD

    Bjorken, J.D.

    1996-10-01

    New directions for exploring QCD at future high-energy colliders are sketched. These include jets within jets. BFKL dynamics, soft and hard diffraction, searches for disoriented chiral condensate, and doing a better job on minimum bias physics. The new experimental opportunities include electron-ion collisions at HERA, a new collider detector at the C0 region of the TeVatron, and the FELIX initiative at the LHC

  3. Perspective on direct conversion

    Lewis, W B

    1963-10-15

    The objective of direct conversion is high electrical output for minimum total cost, and not always high conversion efficiency. The wide range of techniques embracing cryogenics and hot plasma derives from the special requirements of source, environment, and application. Sources include solar and other radiation, nuclear fission and fusion, chemical energy, and heat. Environments and applications range from space vehicles to submarines and from giant power networks to isolated buoys and pocket devices. (auth)

  4. Farm Management: rethinking directions?

    Kemp, David R.; Girdwood, John; Parton, Kevin A.; Charry, Al A.

    2004-01-01

    Farms and farming are major contributors to the world economy, directly responsible for a large part of GDP. These achievements are not trivial and imply that farms are being managed in reasonably effective ways, else agricultural industries would not be sustained. However has the study of Farm Management within Australia made significant contributions to agriculture or lagged in the background. Is it contributing to better Farm Management or merely cataloguing what has happened? Is it leadin...

  5. An algorithmic metatheorem for directed treewidth

    de Oliveira Oliveira, Mateus

    2016-01-01

    Roč. 204, May (2016), s. 49-76 ISSN 0166-218X EU Projects: European Commission(XE) 339691 - FEALORA Institutional support: RVO:67985840 Keywords : combinatorial slice theory * directed treewidth * tree-zig-zag number Subject RIV: BA - General Mathematics Impact factor: 0.956, year: 2016 http://www.sciencedirect.com/science/article/pii/S0166218X15005077

  6. Apparent directional selection by biased pleiotropic mutation.

    Tanaka, Yoshinari

    2010-07-01

    Pleiotropic effects of deleterious mutations are considered to be among the factors responsible for genetic constraints on evolution by long-term directional selection acting on a quantitative trait. If pleiotropic phenotypic effects are biased in a particular direction, mutations generate apparent directional selection, which refers to the covariance between fitness and the trait owing to a linear association between the number of mutations possessed by individuals and the genotypic values of the trait. The present analysis has shown how the equilibrium mean value of the trait is determined by a balance between directional selection and biased pleiotropic mutations. Assuming that genes act additively both on the trait and on fitness, the total variance-standardized directional selection gradient was decomposed into apparent and true components. Experimental data on mutation bias from the bristle traits of Drosophila and life history traits of Daphnia suggest that apparent selection explains a small but significant fraction of directional selection pressure that is observed in nature; the data suggest that changes induced in a trait by biased pleiotropic mutation (i.e., by apparent directional selection) are easily compensated for by (true) directional selection.

  7. The ascorbate peroxidase APX1 is a direct target of a zinc finger transcription factor ZFP36 and a late embryogenesis abundant protein OsLEA5 interacts with ZFP36 to co-regulate OsAPX1 in seed germination in rice.

    Huang, Liping; Jia, Jing; Zhao, Xixi; Zhang, MengYao; Huang, Xingxiu; E Ji; Ni, Lan; Jiang, Mingyi

    2018-01-01

    Seed germination is a vital developmental process. Abscisic acid (ABA) is an essential repressor of seed germination, while ROS (reactive oxygen species) also plays a vital role in regulating seed germination. ABA could inhibit the production of ROS in seed germination, but the mechanism of ABA reduced ROS production in seed germination was hitherto unknown. Here, by ChIP (chromatin immunoprecipitation)-seq, we found that ZFP36, a rice zinc finger transcription factor, could directly bind to the promoter of OsAPX1, coding an ascorbate peroxidase (APX) which has the most affinity for H 2 O 2 (substrate; a type of ROS), and act as a transcriptional activator of OsAPX1 promoter. Moreover, ZFP36 could interact with a late embryogenesis abundant protein OsLEA5 to co-regulate the promoter activity of OsAPX1. The seed germination is highly inhibited in ZFP36 overexpression plants under ABA treatment, while an RNA interference (RNAi) mutant of OsLEA5 rice seeds were less sensitive to ABA, and exogenous ASC (ascorbate acid) could alleviate the inhibition induced by ABA. Thus, our conclusion is that OsAPX1 is a direct target of ZFP36 and OsLEA5 could interact with ZFP36 to co-regulate ABA-inhibited seed germination by controlling the expression of OsAPX1. Copyright © 2017. Published by Elsevier Inc.

  8. AngularJS directives

    Vanston, Alex

    2013-01-01

    This book uses a practical, step-by-step approach, starting with how to build directives from the ground up before moving on to creating web applications comprised of multiple modules all working together to provide the best user experience possible.This book is intended for intermediate JavaScript developers who are looking to enhance their understanding of single-page web application development with a focus on AngularJS and the JavaScript MVC frameworks.It is expected that readers will understand basic JavaScript patterns and idioms and can recognize JSON formatted data.

  9. Direct olive oil analysis

    Peña, F.

    2002-03-01

    Full Text Available The practical impact of “direct analysis” is undeniable as it strong contributes to enhance the so-called productive analytical features such as expeditiousness, reduction of costs and minimisation of risks for the analysts and environment. The main objective is to establish a reliable bypass to the conventional preliminary operations of the analytical process. This paper offers a systematic approach in this context and emphasises the great field of action of direct methodologies in the routine analysis of olive oil. Two main types of methodologies are considered. On the one hand, the direct determination of volatile components is systematically considered. On the other hand, simple procedures to automatically implement the preliminary operations of the oil analysis using simple devices in which the sample is directly introduced with/without a simple dilution are present and discussed.El impacto práctico del análisis directo es tan innegable como que el contribuye decisivamente a mejorar las denominadas características analíticas relacionadas con la productividad como la rapidez, la reducción de costes y la minimización de riesgos para los analistas y el ambiente. El principal objetivo es establecer un adecuado "bypass" a las operaciones convencionales preliminares del proceso analítico. Este artículo ofrece una propuesta sistemática en este contexto y resalta el gran campo de acción de las metodologías directas en los análisis de rutina del aceite de oliva. Se analizan los dos tipos principales de metodologías. Por una lado, se analiza la determinación directa de los compuestos volátiles. Por el otro, se presentan y discuten los procedimientos simples para implementar automáticamente las operaciones preliminares del análisis del aceite usando sistemas simples en los que la muestra se introduce directamente con/sin un dilución simple.

  10. The direct manipulation shell

    Allen, M.E.; Christiansen, M.

    1992-01-01

    Accelerator controls systems provide parameter display pages which allow the operator to monitor and manipulate selected control points in the system. Display pages are generally implemented as either hand-crafted, purpose-built programs; or by using a specialized display page layout tool. These two methods of display page development exhibit the classic trade-off between functionality vs. ease of implementation. In the Direct Manipulation Shell we approach the process of developing a display page in a manifestly object-oriented manner. This is done by providing a general framework for interactively instantiating and manipulating display objects. (author)

  11. Does direct experience matter?

    Miralles, Francesc; Giones, Ferran; Gozun, Brian

    2017-01-01

    of being engaged in entrepreneurial behavior on entrepreneurial intention. We aim to shed light on whether the direct experience reinforces an individual’s entrepreneurial intention or reduces it. Building on an extended version of the planned behavior theory, we use the behavioral reasoning theory...... and an individual’s intention by introducing behavioral reasoning theory. These results provide support to initiatives to adapt entrepreneurship promotion efforts to the specific characteristics of the participants.......Entrepreneurial behavior research has used intention models to explain how an individual’s beliefs shape the attitudes and motivations that influence entrepreneurial intention. Nevertheless, as entrepreneurship promotion initiatives become global, it becomes relevant to explore the consequences...

  12. Directions for further research

    Minsaas, Atle; Psaraftis, Harilaos N.

    2015-01-01

    Green transportation logistics is an area that combines the following: (a) it is relatively new in terms of research carried out thus far, (b) it has become increasingly important for both industry and society, and (c) it is rich in topics for further research, both basic and applied. In this final...... chapter of this book we discuss directions for further research in this area. We do so by taking stock of (1) related recommendations of project SuperGreen, and (2) related activities mainly in European research. Links between research and policy-making as two activities that should go hand in hand...

  13. Directionally Solidified Multifunctional Ceramics

    2006-12-01

    Vidrio , Vol. 44 [5] (2005) pp 347 - 352. 9. F. W. Dynys and A. Sayir, "Self Assemble Silicide Architectures by Directional Solidification," Journal...Sociedad Espanola de Ceramica y Vidrio , Vol. 43 [4] (2004) pp 753 - 758. 21. A. Sayir and F. S. Lowery, "Combustion-Resistance of Silicon-Based Ceramics...Espafiola de Cerdmica y Vidrio , Vol. 43 [3], 2004. ISSN-0366-3175-BSCVB9. 14 37. P. Berger, A. Sayir and M. H. Berger, "Nuclear Microprobe using Elastic

  14. DNA cytosine methylation in the bovine leukemia virus promoter is associated with latency in a lymphoma-derived B-cell line: potential involvement of direct inhibition of cAMP-responsive element (CRE)-binding protein/CRE modulator/activation transcription factor binding.

    Pierard, Valérie; Guiguen, Allan; Colin, Laurence; Wijmeersch, Gaëlle; Vanhulle, Caroline; Van Driessche, Benoît; Dekoninck, Ann; Blazkova, Jana; Cardona, Christelle; Merimi, Makram; Vierendeel, Valérie; Calomme, Claire; Nguyên, Thi Liên-Anh; Nuttinck, Michèle; Twizere, Jean-Claude; Kettmann, Richard; Portetelle, Daniel; Burny, Arsène; Hirsch, Ivan; Rohr, Olivier; Van Lint, Carine

    2010-06-18

    Bovine leukemia virus (BLV) proviral latency represents a viral strategy to escape the host immune system and allow tumor development. Besides the previously demonstrated role of histone deacetylation in the epigenetic repression of BLV expression, we showed here that BLV promoter activity was induced by several DNA methylation inhibitors (such as 5-aza-2'-deoxycytidine) and that overexpressed DNMT1 and DNMT3A, but not DNMT3B, down-regulated BLV promoter activity. Importantly, cytosine hypermethylation in the 5'-long terminal repeat (LTR) U3 and R regions was associated with true latency in the lymphoma-derived B-cell line L267 but not with defective latency in YR2 cells. Moreover, the virus-encoded transactivator Tax(BLV) decreased DNA methyltransferase expression levels, which could explain the lower level of cytosine methylation observed in the L267(LTaxSN) 5'-LTR compared with the L267 5'-LTR. Interestingly, DNA methylation inhibitors and Tax(BLV) synergistically activated BLV promoter transcriptional activity in a cAMP-responsive element (CRE)-dependent manner. Mechanistically, methylation at the -154 or -129 CpG position (relative to the transcription start site) impaired in vitro binding of CRE-binding protein (CREB) transcription factors to their respective CRE sites. Methylation at -129 CpG alone was sufficient to decrease BLV promoter-driven reporter gene expression by 2-fold. We demonstrated in vivo the recruitment of CREB/CRE modulator (CREM) and to a lesser extent activating transcription factor-1 (ATF-1) to the hypomethylated CRE region of the YR2 5'-LTR, whereas we detected no CREB/CREM/ATF recruitment to the hypermethylated corresponding region in the L267 cells. Altogether, these findings suggest that site-specific DNA methylation of the BLV promoter represses viral transcription by directly inhibiting transcription factor binding, thereby contributing to true proviral latency.

  15. Direct access to INIS

    Zheludev, I.S.; Romanenko, A.G.

    1981-01-01

    Librarians, researchers, and information specialists throughout the world now have the opportunity for direct access to coverage of almost 95% of the world's literature dealing with the peaceful uses of atomic energy and nuclear science. This opportunity has been provided by the International Nuclear Information System (INIS) of the IAEA. INIS, with the voluntary collaboration of more than 60 of the Agency's Member States, maintains a comprehensive, computer-resident data-base, containing the bibliographic details plus informative abstracts of the bulk of the world's literature on nuclear science and technology. Since this data-base is growing at a rate of 75,000 items per year, and already contains more than 500,000 items, it is obviously important to be able to search this collection conveniently and efficiently. The usefulness of this ability is enhanced when other data-bases on related subjects are made available on an information network. During the early 1970s, on-line interrogation of large bibliographic data-bases became the accepted method for searching this type of information resource. Direct interaction between the searcher and the data-base provides quick feed-back resulting in improved literature listings for launching research and development projects. On-line access enables organizations which cannot store a large data-base on their own computer to expand the information resources at their command. Because of these advantages, INIS undertook to extend to interested Member States on-line access to its data-base in Vienna

  16. Direct thermal dyes

    Ehlinger, Edward

    1990-07-01

    Direct thermal dyes are members of a class of compounds referred to in the imaging industry as color formers or leuco dyes. The oldest members of that class have simple triarylmethane structures, and have been employed for years in various dyeing applications. More complex triarylmethane compounds, such as phthalides and fluorans, are now used in various imaging systems to produce color. Color is derived from all of these compounds via the same mechanism, on a molecular level. That is, an event of activation produces a highly resonating cationic system whose interaction with incident light produces reflected light of a specific color. The activation event in the case of a direct thermal system is the creation of a melt on the paper involving dye and an acidic developer. The three major performance parameters in a thermal system are background color, image density, and image stability. The three major dye physical parameters affecting thermal performance are chemical constituency, purity, and particle size. Those dyes having the best combination of characteristics which can also be manufactured economically dominate the marketplace. Manufacturing high performance dyes for the thermal market involves multi-step, convergent reaction sequences performed on large scale. Intermediates must be manufactured at the right time, and at the right quality to be useful.

  17. Remote direct memory access

    Archer, Charles J.; Blocksome, Michael A.

    2012-12-11

    Methods, parallel computers, and computer program products are disclosed for remote direct memory access. Embodiments include transmitting, from an origin DMA engine on an origin compute node to a plurality target DMA engines on target compute nodes, a request to send message, the request to send message specifying a data to be transferred from the origin DMA engine to data storage on each target compute node; receiving, by each target DMA engine on each target compute node, the request to send message; preparing, by each target DMA engine, to store data according to the data storage reference and the data length, including assigning a base storage address for the data storage reference; sending, by one or more of the target DMA engines, an acknowledgment message acknowledging that all the target DMA engines are prepared to receive a data transmission from the origin DMA engine; receiving, by the origin DMA engine, the acknowledgement message from the one or more of the target DMA engines; and transferring, by the origin DMA engine, data to data storage on each of the target compute nodes according to the data storage reference using a single direct put operation.

  18. Direct neutrino mass measurements

    Weinheimer, Christian, E-mail: weinheimer@uni-muenster.de [Westfaelische Wilhelms-Universitaet, Institut fuer Kernphysik (Germany)

    2013-03-15

    Direct neutrino mass experiments are complementary to searches for neutrinoless double {beta}-decay and to analyses of cosmological data. The previous tritium beta decay experiments at Mainz and at Troitsk have achieved upper limits on the neutrino mass of about 2 eV/c{sup 2} . The KATRIN experiment under construction will improve the neutrino mass sensitivity down to 200 meV/c{sup 2} by increasing strongly the statistics and-at the same time-reducing the systematic uncertainties. Huge improvements have been made to operate the system extremely stably and at very low background rate. The latter comprises new methods to reject secondary electrons from the walls as well as to avoid and to eject electrons stored in traps. As an alternative to tritium {beta}-decay experiments cryo-bolometers investigating the endpoint region of {sup 187}Re {beta}-decay or the electron capture of {sup 163}Ho are being developed. This article briefly reviews the current status of the direct neutrino mass measurements.

  19. Factor XII (Hageman factor) deficiency

    ... this page: //medlineplus.gov/ency/article/000545.htm Factor XII (Hageman factor) deficiency To use the sharing features on this ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  20. Direct saccharification of milo

    1981-10-28

    Crude or unrefined milo grain is pulverized to less than 100 mesh, suspended in water, and directly saccharified with enzymes. Thus, 10 kg of pulverized milo (100 mesh) was suspended in 20 liters water, liquified in the presence of bacterial amylase at 90/sup 0/ for 30 minutes and autoclaved for 10 minutes at 120/sup 0/, the liquifaction autoclave procedures were then repeated. The liquified preparation was saccharified in the presence of bacterial glucoamylase at 55/sup 0/ for 72 hours. The percentage saccharification of unrefined milo was 92-97%, which was comparable to that obtained with refined milo or a milo starch preparation. The saccharified milo preparation, when used as a sugar source in glutamic acid, lysine, or inosine fermentation, also showed similar efficiency to that of saccharified milo starch.

  1. Site directed recombination

    Jurka, Jerzy W.

    1997-01-01

    Enhanced homologous recombination is obtained by employing a consensus sequence which has been found to be associated with integration of repeat sequences, such as Alu and ID. The consensus sequence or sequence having a single transition mutation determines one site of a double break which allows for high efficiency of integration at the site. By introducing single or double stranded DNA having the consensus sequence flanking region joined to a sequence of interest, one can reproducibly direct integration of the sequence of interest at one or a limited number of sites. In this way, specific sites can be identified and homologous recombination achieved at the site by employing a second flanking sequence associated with a sequence proximal to the 3'-nick.

  2. Directionally positionable neutron beam

    Dance, W.E.; Bumgardner, H.M.

    1981-01-01

    Disclosed is apparatus for forming and directionally positioning a neutron beam. The apparatus includes an enclosed housing rotatable about a first axis with a neutron source axially positioned on the axis of rotation of the enclosed housing but not rotating with the housing. The rotatable housing is carried by a vertically positionable arm carried on a mobile transport. A collimator is supported by the rotatable housing and projects into the housing to orientationally position its inlet window at an adjustably fixed axial and radial spacing from the neutron source so that rotation of the enclosed housing causes the inlet window to rotate about a circle which is a fixed axial distance from the neutron source and has the axis of rotation of the housing as its center. (author)

  3. Directional epithermal neutron detector

    Givens, W.W.; Mills, W.R. Jr.

    1986-01-01

    A borehole tool for epithermal neutron die-away logging of subterranean formations surrounding a borehole is described which consists of: (a) a pulsed source of fast neutrons for irradiating the formations surrounding a borehole, (b) at least one neutron counter for counting epithermal neutrons returning to the borehole from the irradiated formations, (c) a neutron moderating material, (d) an outer thermal neutron shield providing a housing for the counter and the moderating material, (e) an inner thermal neutron shield dividing the housing so as to provide a first compartment bounded by the inner thermal neutron shield and a first portion of the outer thermal neutron shield and a second compartment bounded by the inner thermal neutron shield and a second portion of the outer thermal neutron shield, the counter being positioned within the first compartment and the moderating material being positioned within the second compartment, and (f) means for positioning the borehole tool against one side of the borehole wall and azimuthally orienting the borehole tool such that the first chamber is in juxtaposition with the borehole wall, the formation epithermal neutrons penetrating into the first chamber through the first portion of the outer thermal neutron shield are detected by the neutron counter for die-away measurement, thereby maximizing the directional sensitivty of the neutron counter to formation epithermal neutrons, the borehole fluid epithermal neutrons penetrating into the second chamber through the second chamber through the second portion of the outer thermal neutron shield are largely slowed down and lowered in energy by the moderating material and absorbed by the inner thermal neutron shield before penetrating into the first chamber, thereby minimizing the directional sensitivity of the neutron counter to borehole fluid epithermal neutrons

  4. Discovery and progress of direct cardiac reprogramming.

    Kojima, Hidenori; Ieda, Masaki

    2017-06-01

    Cardiac disease remains a major cause of death worldwide. Direct cardiac reprogramming has emerged as a promising approach for cardiac regenerative therapy. After the discovery of MyoD, a master regulator for skeletal muscle, other single cardiac reprogramming factors (master regulators) have been sought. Discovery of cardiac reprogramming factors was inspired by the finding that multiple, but not single, transcription factors were needed to generate induced pluripotent stem cells (iPSCs) from fibroblasts. We first reported a combination of cardiac-specific transcription factors, Gata4, Mef2c, and Tbx5 (GMT), that could convert mouse fibroblasts into cardiomyocyte-like cells, which were designated as induced cardiomyocyte-like cells (iCMs). Following our first report of cardiac reprogramming, many researchers, including ourselves, demonstrated an improvement in cardiac reprogramming efficiency, in vivo direct cardiac reprogramming for heart regeneration, and cardiac reprogramming in human cells. However, cardiac reprogramming in human cells and adult fibroblasts remains inefficient, and further efforts are needed. We believe that future research elucidating epigenetic barriers and molecular mechanisms of direct cardiac reprogramming will improve the reprogramming efficiency, and that this new technology has great potential for clinical applications.

  5. Direct oral anticoagulants and venous thromboembolism

    Massimo Franchini

    2016-09-01

    Full Text Available Venous thromboembolism (VTE, consisting of deep vein thrombosis and pulmonary embolism, is a major clinical concern associated with significant morbidity and mortality. The cornerstone of management of VTE is anticoagulation, and traditional anticoagulants include parenteral heparins and oral vitamin K antagonists. Recently, new oral anticoagulant drugs have been developed and licensed, including direct factor Xa inhibitors (e.g. rivaroxaban, apixaban and edoxaban and thrombin inhibitors (e.g. dabigatran etexilate. This narrative review focusses on the characteristics of these direct anticoagulants and the main results of published clinical studies on their use in the prevention and treatment of VTE.

  6. Future directions in research

    Hall, J.G.; Lopez-Rangel, E.

    1996-01-01

    New studies of the effects of ionizing radiation on the human genome must include not only its effect on the sequence of a particular gene, but must also consider the possible location, complete structure, regulation, and function of the gene as well. Historically, genetic disorders have been characterized as single gene disorders, chromosomal aberrations, and multifactorial disorders. Now, however, the following have to be considered: mosaicism, genomic imprinting, uniparental disomy, cytoplasmic inheritance, allelic expansion. Molecular techniques that may be useful in analyzing radiation damage include Fluorescent In Situ Hybridization and the Polymerase Chain Reaction. The effect of radiation on the fibroblast growth factor receptor 3, damage to which is associated with the development of achondroplasia, is recommended as a fruitful, if complicated, research topic

  7. Coatings for directional eutectics

    Rairden, J. R.; Jackson, M. R.

    1976-01-01

    Coatings developed to provide oxidation protection for the directionally-solidified eutectic alloy NiTaC-B (4.4 weight percent Cr) were evaluated. Of seven Co-, Fe- and Ni-base coatings that were initially investigated, best resistance to cyclic oxidation was demonstrated by duplex coatings fabricated by depositing a layer of NiCrAl(Y) by vacuum evaporation from an electron beam source followed by deposition of an Al overlayer using the pack cementation process. It was found that addition of carbon to the coating alloy substantially eliminated the problem of fiber denudation in TaC-type eutectic alloys. Burner rig cycled NiTaC-B samples coated with Ni-20Cr-5Al-0.1C-0.1Y+Al and rupture-tested at 1100 deg C performed as well as or better than uncoated, vacuum cycled and air-tested NiTaC-13; however, a slight degradation with respect to uncoated material was noted in air-stress rupture tests at 870 deg C for both cycled and uncycled samples.

  8. New directions in Guatemala.

    1997-02-01

    This news brief relates some new directions, since its inception in 1988, which the Family Welfare Association of Guatemala (APROFAM) will be undertaking during 1996-97. In December 1997, APROFAM restructured its program to include reproductive health services with family planning services. The program will target rural Mayan communities. The program will be working toward service sustainability, due to reduced external support. In October 1996 a new board was established that will focus on marketing, IEC, finance and administration, rural development, and clinical services. Meetings between the new board of directors of APROFAM and JOICFP focused on the use of integrated programs as a model for widespread programming among the rural Mayan population. The integrated program that was implemented by JOICFP was successful in reaching Mayan communities of Solola. This population was difficult to reach with conventional family planning approaches. The integrated program was successful in establishing trust with and participation of the rural Mayans. Activities such as parasite control, skills training, and income generation for women were useful in establishing trust and promoting self-reliance. Integrated programs will refocus on family planning and developing self-reliance. The UNFPA will be conducting an annual internal evaluation as a means of sharing information and deepening understanding of project implementation.

  9. A direct Newton-Raphson economic dispatch

    Lin, C.E.; Chen, S.T.; Huang, C.L.

    1992-01-01

    This paper presents a new method to solve the real-time economic dispatch problem using an alternative Jacobian matrix considering system constraints. The transition loss is approximately expressed in terms of generating powers and the generalized generation shift distribution factor. Based on this expression, a set of simultaneous equations of Jacobian matrix is formulated and solved by the Newton-Raphson method. The proposed method eliminates the penalty factor calculation, and solves the economic dispatch directly. The proposed method obtains very fast solution speed and maintains good accuracy from test examples. It is good approach to solve the economic dispatch problem

  10. DETERMINANTS OF FOREIGN DIRECT INVESTMENT DEVELOPMENT

    Elena Chirila - Donciu

    2013-12-01

    Full Text Available FDI had a strong impact in the last three decades on economic growth, foreign trade and production structures in almost all countries. The purpose of this paper is to analyze the main factors that contribute to attracting foreign direct investment flows and also the competitiveness of the business environment in Romania and its implications on investment decisions and economic growth. Research results show that the presence of FDI goes to those areas that can provide efficiencies investment factors: skilled and qualified labor, educational and research institutions etc..

  11. Robust factorization

    Aanæs, Henrik; Fisker, Rune; Åström, Kalle

    2002-01-01

    Factorization algorithms for recovering structure and motion from an image stream have many advantages, but they usually require a set of well-tracked features. Such a set is in generally not available in practical applications. There is thus a need for making factorization algorithms deal effect...

  12. Organizational factors

    Holy, J.

    1999-12-01

    The following organizational factors are considered with respect to the human factor and operating safety of nuclear power plants: external influences; objectives and strategy; positions and ways of management; allocation of resources; working with human resources; operators' training; coordination of work; knowledge of organization and management; proceduralization of the topic; labour organizing culture; self-improvement system; and communication. (P.A.)

  13. El factoring

    Alberto Rosenthal

    1988-04-01

    Full Text Available RESUMEN El artículo  presenta, una conceptualización general de lo que es el factoring, el origen del mismo, su evolución y hace una clasificación de los distintos tipos de factoring.

  14. Direct UV-written broadband directional broadband planar waveguide couplers

    Olivero, Massimo; Svalgaard, Mikael

    2005-01-01

    We report the fabrication of broadband directional couplers by direct UV-writing. The fabrication process is shown to be beneficial, robust and flexible. The components are compact and show superior performance in terms of loss and broadband operation.......We report the fabrication of broadband directional couplers by direct UV-writing. The fabrication process is shown to be beneficial, robust and flexible. The components are compact and show superior performance in terms of loss and broadband operation....

  15. MULTINATIONAL COMPANIES AND FOREIGN DIRECT INVESTMENT

    Lucia P. BLĂJUȚ

    2014-01-01

    This paper highlights the significant share of multinational companies in international trade that are a factor of developing global economies. In the context of economic globalization the activity of multinational companies and their foreign direct investment have a strong impact on the host country which presents advantages and disadvantages for them. The main objective of this article is the review of the important role played by multinationals in economic development, especially in develo...

  16. Application of the Seveso Directive in France

    Pineau, J.-P.

    1999-01-01

    First, the paper presents a brief summary of the French actual regulation on installations registered for the protection of the environment and covered by the Seveso I Directive. Then the paper discusses research and development needs for a sound implementation of the Directive, and for the new requirements on safety reports established by the Seveso II Directive. Further, it discusses issues connected with coverage of hazardous activities, learning from accidents, technical and organisational measures (safety management systems and emergency response) and human factors. The conclusions stress the need for networking and dissemination of accident investigations, development of safety management systems, and research on cognitive ergonomics and psychology related to the decision making and interventions of the operator. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

  17. Laboratory Directed Research ampersand Development Program

    Ogeka, G.J.; Romano, A.J.

    1993-12-01

    At Brookhaven National Laboratory the Laboratory Directed Research and Development (LDRD) Program is a discretionary research and development tool critical in maintaining the scientific excellence and vitality of the laboratory. It is also a means to stimulate the scientific community, fostering new science and technology ideas, which is the major factor in achieving and maintaining staff excellence, and a means to address national needs, within the overall mission of the Department of Energy and Brookhaven National Laboratory. This report summarizes research which was funded by this program during fiscal year 1993. The research fell in a number of broad technical and scientific categories: new directions for energy technologies; global change; radiation therapies and imaging; genetic studies; new directions for the development and utilization of BNL facilities; miscellaneous projects. Two million dollars in funding supported 28 projects which were spread throughout all BNL scientific departments

  18. Direct or indirect - that is the question!

    Pallesen, Ulla

    2016-01-01

    Time has passed since the prevention of caries was performed by extending cavity preparations wide in the tooth and below the gingiva. In the same period adhesive techniques have improved and nowadays made it possible to extend the indications for direct composite resin restorations, also when...... rather destroyed teeth need to be restored. Although much can be solved by direct fillings and thereby make treatments less invasive for the tooth and less expensive for the patient, there still will be teeth, where the prognosis is improved, if an indirect restoration in terms of an inlay, onlay...... or crown is made. Factors as remaining tooth structure, endodontic treatment, number of teeth, caries risk, para-functional habits, material properties, economy etc. will all have an influence, when the dentist guides the patient to choose the best solution. What is best for the tooth – direct or indirect...

  19. Directional Etching of Silicon by Silver Nanostructures

    Sharma, Pradeep; Wang, Yuh-Lin

    2011-02-01

    We report directional etching of nanostructures (nanochannels and nanotrenches) into the Si(100) substrates in aqueous HF and H2O2 solution by lithographically defined Ag patterns (nanoparticles, nanorods, and nanorings). The Effect of Ag/Si interface oxide on the directional etching has been studied by etching Ag/SiOx/Si samples of known interface oxide thickness. Based on high resolution transmission electron microscopy (HRTEM) imaging and TEM-energy dispersive X-ray (EDX) spectra of the Ag/Si interfaces, we propose that maintenance of the sub-nanometer oxide at the Ag/Si interfaces and Ag-Si interaction are the key factors which regulate the directional etching of Si.

  20. RISK AND FOREIGN DIRECT INVESTMENT IN ROMANIA

    Catalin Drob

    2014-07-01

    Full Text Available This paper tries to present the main categories (types of risks that affect the inflows of foreign direct investment (FDI in Romania, such as: country risk, political risk, economic risks, sovereign risks and so on. FDI is an important factor contributing to the economic development and to the economic growth of a country. In order to recuperate its economic handicap as compared to the other countries in the EU, Romania needs a massive inflow of foreign capital, especially in the form of direct investment. The paper also presents the evolution of FDI inflows in Romania and how they were influenced by the main factors affecting the FDI. In principle, between risk and the level of FDI inflows there is a direct dependency relationship: the higher the risk is in a country, the lower the level of FDI inflows is in that country. This is demonstrated by the empirical studies regarding FDI. These studies show that countries with high risk have major difficulties in attracting foreign investment. Therefore, it is important to identify very precisely the main risks that may affect the level of FDI inflows in Romania, in order to propose and implement strategies to mitigate these risks and to attract more foreign direct investment in Romania.

  1. Estimation of directional wave spreading

    Mandal, S.; Bhat, S.S.; Anand, N.M.; Nayak, B.U.

    Directional properties of ocean waves are of great economic interest. The knowledge of wave directionality is important for the design of maritime structures and offshore operations. Two main aspects are considered for this study for the data...

  2. Estimation of wave directional spreading

    Deo, M.C.; Gondane, D.S.; SanilKumar, V.

    One of the useful measures of waves directional spreading at a given location is the directional spreading parameter. This paper presents a new approach to arrive at its characteristic value using the computational technique of Artificial Neural...

  3. Geothermal Technologies Program: Direct Use

    2004-08-01

    This general publication describes geothermal direct use systems, and how they have been effectively used throughout the country. It also describes the DOE program R&D efforts in this area, and summarizes several projects using direct use technology.

  4. Innovative tool of direct marketing

    T.S. Maksymova

    2010-01-01

    The aspects of direct marketing activation on the basis of interactive applications introduction are examined. Basic advantages, linked with the use of the integrated marketing communications during formation of direct marketing strategies are open up.

  5. Direct channel problems and phenomena

    Cutkosky, R.E.

    1975-01-01

    Direct channel problems and phenomena are considered covering the need for precision hadron spectroscopy, the data base for precision hadron spectroscopy, some relations between direct-channel and cross-channel effects, and spin rotation phenomena

  6. Directional wave measurements and modelling

    Anand, N.M.; Nayak, B.U.; Bhat, S.S.; SanilKumar, V.

    Some of the results obtained from analysis of the monsoon directional wave data measured over 4 years in shallow waters off the west coast of India are presented. The directional spectrum computed from the time series data seems to indicate...

  7. Psychiatric Advance Directives: Getting Started

    ... News Legal Issues Search for: About PADs A psychiatric advance directive (PAD) is a legal document that ... decisions during a mental health crisis. Getting Started Psychiatric advance directives (PADs) are relatively new legal instruments ...

  8. El factoring

    Alberto Rosenthal

    2015-04-01

    Full Text Available RESUMEN Se presenta la segunda parte del artículo aparecido en  el número 6 de la revista EAN. Su contenido es complementario a lo expuesto en dicho número, en está aparecen las ventajas del factoring, conveniencias, limitaciones así como la forma  de efectuar un factor en Colombia,  su necesidad, incidencia económica, etc.

  9. Filmless radiography - present possibilities and direction of future developing

    Wocial, A.; Wojciechowski, Z.A.; Rozenblicki, Z.

    2008-01-01

    The paper presents introduction for new filmless radiography like CR Computed Radiography and DR Digital Radiography direct and non direct. The main factors are considered, which determine classification to different type of radiography. For each technique authors describe advantages and disadvantages supporting by practice examples. Paper contains a lot of practical information about a most of existing radiographic equipment at the NDT market. (author)

  10. Direction: happiness : improving well-being of vulnerable groups

    Weiss, Laura Anne

    2016-01-01

    In the PhD-thesis ‘Direction: Happiness. Improving well-being of vulnerable groups’, the effects of the Happiness Route, a positive psychology intervention, were examined. The intervention is directed at a vulnerable group with an accumulation of risk factors for a low well-being; lonely people with

  11. Determinants Of Consumers’ Satisfaction and Acceptance of Direct Selling

    Alturas, Bráulio; Santos, Maria da Conceição; Pereira, Ivo

    2005-01-01

    This paper studies the factors that influence the consumers’ satisfaction and acceptance of direct selling. Direct selling has been exhibiting in the last decade substantial growth in sales revenues and number of salespeople involved. Also the acceptance on the part of the consumers has been increasing; in spite of they show more and more demanding and informed. The literature reveals that the relationship between customer satisfaction and direct selling has not been sufficiently studied, yet...

  12. Seveso directive: the leading innovations

    Cozzani, V.; Zanelli, S.

    1998-01-01

    Directive 96/82/EC on the control of major accident hazards caused by dangerous substances, also known as 'Seveso-II' Directive, was adopted by the European Council on December 1996. The member states of the European Community shall bring into force the Directive not later than February 1999. Some innovative aspects of the Directive are discussed. In particular, this paper focuses on the effects of the new criteria for the identification of establishments to which the Directive obligations will apply and for land use planning in the vicinity of the establishments [it

  13. Quality factors

    Kerr, G.D.

    1986-01-01

    The quality factor, Q, is a dimensionless modifier used in converting absorbed dose, expressed in rads (or grays), to dose equivalent, expressed in rems (or seiverts). The dose equivalent is used in radiation protection to account for the biological effectiveness of different kinds of radiation. The quality factor is related to both the linear energy transfer (LET) and relative biological effectiveness (RBE). The RBE's obtained from biological experiments depend in a complex way on the observed biological effect, the specific test organism, and the experimental conditions. Judgement is involved, therefore, in the choice of the quality factor. Questions regarding the adequacy of current Q values for neutrons were raised first in a 1980 statement by the National Council on Radiation Protection (NCRP) and later in a 1985 statement by the International Commission on Radiological Protection (ICRP). In 1980, the NCRP alerted the technical community to possible future increases between a factor of three and ten in the Q for neutrons, and in 1985, the ICRP suggested an increase by a factor of two in Q for neutrons. Both the ICRP and NRCP are now recommending essentially the same guidance with regard to Q for neutrons: an increase by a factor of two. The Q for neutrons is based on a large, albeit unfocused, body of experimental data. In spite of the lack of focus, the data supporting a change in the neutron quality factor are substantial. However, the proposed doubling of Q for neutrons is clouded by other issues regarding its application. 33 refs., 4 figs., 6 tabs

  14. Gradient angle estimation by uniform directional simulation on a cone

    Ditlevsen, Ove Dalager

    1997-01-01

    approximation to a locally most central limit state point. Moreover, the estimated angle can be used to correct the geometric reliability index.\\bfseries Keywords: Directional simulation, effectivity factor, gradient angle estimation, maximum likelihood, model-correction-factor method, Monte Carlo simulation...

  15. Dynamic behaviors in directed networks

    Park, Sung Min; Kim, Beom Jun

    2006-01-01

    Motivated by the abundance of directed synaptic couplings in a real biological neuronal network, we investigate the synchronization behavior of the Hodgkin-Huxley model in a directed network. We start from the standard model of the Watts-Strogatz undirected network and then change undirected edges to directed arcs with a given probability, still preserving the connectivity of the network. A generalized clustering coefficient for directed networks is defined and used to investigate the interplay between the synchronization behavior and underlying structural properties of directed networks. We observe that the directedness of complex networks plays an important role in emerging dynamical behaviors, which is also confirmed by a numerical study of the sociological game theoretic voter model on directed networks

  16. Direct photons in WA98

    Aggarwal, M M; Ahammed, Z; Angelis, Aris L S; Antonenko, V G; Arefev, V; Astakhov, V A; Avdeichikov, V; Awes, T C; Baba, P V K S; Badyal, S K; Barlag, C; Bathe, S; Batyunya, B; Bernier, T; Bhalla, K B; Bhatia, V S; Blume, C; Bock, R; Bohne, E M; Böröcz, Z K; Bucher, D; Buijs, A; Büsching, H; Carlén, L; Chalyshev, V; Chattopadhyay, S; Cherbachev, R; Chujo, T; Claussen, A; Das, A C; Decowski, M P; Delagrange, H; Dzhordzhadze, V; Dönni, P; Dubovik, I; Dutt, S; Dutta-Majumdar, M R; El-Chenawi, K F; Eliseev, S; Enosawa, K; Foka, P Y; Fokin, S L; Ganti, M S; Garpman, S; Gavrishchuk, O P; Geurts, F J M; Ghosh, T K; Glasow, R; Gupta, S K; Guskov, B; Gustafsson, Hans Åke; Gutbrod, H H; Higuchi, R; Hrivnacova, I; Ippolitov, M S; Kalechofsky, H; Kamermans, R; Kampert, K H; Karadzhev, K; Karpio, K; Kato, S; Kees, S; Klein-Bösing, C; Knoche, S; Kolb, B W; Kosarev, I G; Kucheryaev, I; Krümpel, T; Kugler, A; Kulinich, P A; Kurata, M; Kurita, K; Kuzmin, N A; Langbein, I; Lee, Y Y; Löhner, H; Luquin, Lionel; Mahapatra, D P; Man'ko, V I; Martin, M; Martínez, G; Maksimov, A; Mgebrishvili, G; Miake, Y; Mir, M F; Mishra, G C; Miyamoto, Y; Mohanty, B; Morrison, D; Mukhopadhyay, D S; Naef, H; Nandi, B K; Nayak, S K; Nayak, T K; Neumaier, S; Nyanin, A; Nikitin, V A; Nikolaev, S; Nilsson, P O; Nishimura, S; Nomokonov, V P; Nystrand, J; Obenshain, F E; Oskarsson, A; Otterlund, I; Pachr, M; Pavlyuk, S; Peitzmann, Thomas; Petracek, V; Pinganaud, W; Plasil, F; Von Poblotzki, U; Purschke, M L; Rak, J; Raniwala, R; Raniwala, S; Ramamurthy, V S; Rao, N K; Retière, F; Reygers, K; Roland, G; Rosselet, L; Rufanov, I A; Roy, C; Rubio, J M; Sako, H; Sambyal, S S; Santo, R; Sato, S; Schlagheck, H; Schmidt, H R; Schutz, Y; Shabratova, G; Shah, T H; Sibiryak, Yu; Siemiarczuk, T; Silvermyr, D; Sinha, B C; Slavin, N V; Söderström, K; Solomey, Nickolas; Sood, G; Sørensen, S P; Stankus, P; Stefanek, G; Steinberg, P; Stenlund, E; Stüken, D; Sumbera, M; Svensson, S; Trivedi, M D; Tsvetkov, A A; Tykarski, L; Urbahn, J; Van den Pijll, E C; van Eijndhoven, N; van Nieuwenhuizen, G J; Vinogradov, A; Viyogi, Y P; Vodopyanov, A S; Vörös, S; Wyslouch, B; Yagi, K; Yokota, Y; Young, G R

    2002-01-01

    A measurement of direct photon production in /sup 208/Pb+/sup 208/Pb collisions at 158 A GeV has been carried out in the CERN WA98 experiment. The invariant yield of direct photons was extracted as a function of transverse momentum in the interval 0.51.5 GeV/c. the result constitutes the first observation of direct photons in ultrarelativistic heavy-ion collisions. (19 refs).

  17. Patients direct costs to undergo TB diagnosis.

    de Cuevas, Rachel M Anderson; Lawson, Lovett; Al-Sonboli, Najla; Al-Aghbari, Nasher; Arbide, Isabel; Sherchand, Jeevan B; Nnamdi, Emenyonu E; Aseffa, Abraham; Yassin, Mohammed A; Abdurrahman, Saddiq T; Obasanya, Joshua; Olanrewaju, Oladimeji; Datiko, Daniel; Theobald, Sally J; Ramsay, Andrew; Squire, S Bertel; Cuevas, Luis E

    2016-03-24

    A major impediment to the treatment of TB is a diagnostic process that requires multiple visits. Descriptions of patient costs associated with diagnosis use different protocols and are not comparable. We aimed to describe the direct costs incurred by adults attending TB diagnostic centres in four countries and factors associated with expenditure for diagnosis. Surveys of 2225 adults attending smear-microscopy centres in Nigeria, Nepal, Ethiopia and Yemen. Adults >18 years with cough >2 weeks were enrolled prospectively. Direct costs were quantified using structured questionnaires. Patients with costs >75(th) quartile were considered to have high expenditure (cases) and compared with patients with costs <75(th) quartile to identify factors associated with high expenditure. The most significant expenses were due to clinic fees and transport. Most participants attended the centres with companions. High expenditure was associated with attending with company, residing in rural areas/other towns and illiteracy. The costs incurred by patients are substantial and share common patterns across countries. Removing user fees, transparent charging policies and reimbursing clinic expenses would reduce the poverty-inducing effects of direct diagnostic costs. In locations with limited resources, support could be prioritised for those most at risk of high expenditure; those who are illiterate, attend the service with company and rural residents.

  18. Direct cooled power electronics substrate

    Wiles, Randy H [Powell, TN; Wereszczak, Andrew A [Oak Ridge, TN; Ayers, Curtis W [Kingston, TN; Lowe, Kirk T [Knoxville, TN

    2010-09-14

    The disclosure describes directly cooling a three-dimensional, direct metallization (DM) layer in a power electronics device. To enable sufficient cooling, coolant flow channels are formed within the ceramic substrate. The direct metallization layer (typically copper) may be bonded to the ceramic substrate, and semiconductor chips (such as IGBT and diodes) may be soldered or sintered onto the direct metallization layer to form a power electronics module. Multiple modules may be attached to cooling headers that provide in-flow and out-flow of coolant through the channels in the ceramic substrate. The modules and cooling header assembly are preferably sized to fit inside the core of a toroidal shaped capacitor.

  19. Epidemic threshold in directed networks

    Li, Cong; Wang, Huijuan; Van Mieghem, Piet

    2013-12-01

    Epidemics have so far been mostly studied in undirected networks. However, many real-world networks, such as the online social network Twitter and the world wide web, on which information, emotion, or malware spreads, are directed networks, composed of both unidirectional links and bidirectional links. We define the directionality ξ as the percentage of unidirectional links. The epidemic threshold τc for the susceptible-infected-susceptible (SIS) epidemic is lower bounded by 1/λ1 in directed networks, where λ1, also called the spectral radius, is the largest eigenvalue of the adjacency matrix. In this work, we propose two algorithms to generate directed networks with a given directionality ξ. The effect of ξ on the spectral radius λ1, principal eigenvector x1, spectral gap (λ1-λ2), and algebraic connectivity μN-1 is studied. Important findings are that the spectral radius λ1 decreases with the directionality ξ, whereas the spectral gap and the algebraic connectivity increase with the directionality ξ. The extent of the decrease of the spectral radius depends on both the degree distribution and the degree-degree correlation ρD. Hence, in directed networks, the epidemic threshold is larger and a random walk converges to its steady state faster than that in undirected networks with the same degree distribution.

  20. Seeking coherence among environmental directives

    Beijen, Barbara

    2014-01-01

    European environmental law consists of a large number of directives and regulations dealing with environmental domains such as air, water, or waste, or with issues such as greenhouse gases, chemicals or industrial emissions. These directives and regulations do not form a comprehensive system of

  1. Direct activation of microcrystalline zeolites

    Ortiz-Iniesta, Maria Jesus; Heeres, Hero Jan; Melian-Cabrera, Ignacio

    2013-01-01

    In this work a direct activation route of zeolites is assessed. It consists of NH4-exchanging the as-synthesized solids before removing the organic template. Calcination afterwards serves to combust the organic template and creates the Bronsted sites directly; thus applying merely a single thermal

  2. Type-Directed Partial Evaluation

    Danvy, Olivier

    1998-01-01

    Type-directed partial evaluation uses a normalization function to achieve partial evaluation. These lecture notes review its background, foundations, practice, and applications. Of specific interest is the modular technique of offline and online type-directed partial evaluation in Standard ML...

  3. Exchange effects in direct reactions

    LeMere, M.; Kanellopoulos, E.J.; Suenkel, W.; Tang, Y.C.

    1979-01-01

    The effect of antisymmetrization in direct reactions is examined by studying the properties of the coupling-normalization kernel function occurring in a resonating-group formulation. From this study, one obtains useful information concerning the general behavior of direct-reactiion processes and some justification for the use of three-body models in phenomenological analyses

  4. Type-Directed Partial Evaluation

    Danvy, Olivier

    1998-01-01

    Type-directed partial evaluation uses a normalization function to achieve partial evaluation. These lecture notes review its background, foundations, practice, and applications. Of specific interest is the modular technique of offline and online type-directed partial evaluation in Standard ML of ...

  5. Eldercare at Home: Advanced Directives

    ... permanently? Helping the person fill out a living will (advance directive) A living will states a person's wishes about medical care if ... never be in a situation where another person will have to make decisions ... it is to have an advance directive. However, don't assume that your loved ...

  6. New directions in information organization

    Park, Jung-ran; Spink, Amanda

    2013-01-01

    New Directions in Information Organization, co-edited by Dr. Jung-ran Park and Dr. Lynne Howarth seeks to provide an overview and understanding of the future directions, leading edge theories and models for research and practice in information organization.

  7. Target selection for direct marketing.

    Bult, Jan Roelf

    1993-01-01

    In this thesis we concentrated on the use ol direct mail for targeting potential buyers. The major characteristics that influences the success of a plomotional direct mail campaign are the of-fbr,the communication elements, the timing or sequence of these communication elements, and the list of

  8. Risk factors

    Dennery, M.; Dupont, M.A.

    2007-01-01

    This article deals with the development of risk management in the gas sector business: why a risk factor legal mention must precede any published financial information? Do gas companies have to face new risks? Is there specific risks bound to gas activities? Why companies want to master their risks? Is it mandatory or just a new habit? Do they expect a real benefit in return? These are the risk management questions that are analyzed in this article which is based on the public communication of 15 gas companies randomly selected over the world. The information comes from their annual reports or from documents available on their web sites. The intention of this document is not to be exhaustive or to make statistics but only to shade light on the risk factors of the gas sector. (J.S.)

  9. Organizational factors

    Wahlstroem, B.; Kettunen, J.

    2005-01-01

    The goal of this lecture is to give an overview of important concepts connected to organisational factors and to provide an understanding of mechanisms by which they can contribute to safe or unsafe behaviour of people. The lecture gives examples of ways to organise work, organisational deficiencies and good practices applied in safety oriented organisations. The lecture also gives an introduction to international work and Finnish national regulation connected to organisation and management. (orig.)

  10. Factor analysis

    Gorsuch, Richard L

    2013-01-01

    Comprehensive and comprehensible, this classic covers the basic and advanced topics essential for using factor analysis as a scientific tool in psychology, education, sociology, and related areas. Emphasizing the usefulness of the techniques, it presents sufficient mathematical background for understanding and sufficient discussion of applications for effective use. This includes not only theory but also the empirical evaluations of the importance of mathematical distinctions for applied scientific analysis.

  11. Efficient Placement of Directional Antennas

    Pan, Feng [Los Alamos National Laboratory; Kasiviswanathan, Shiva [Los Alamos National Laboratory

    2010-09-20

    Directional antenna is an technology for the proliferation of wireless networks. In centralized wireless network, wireless devices communicate through base stations. Directed antennas are placed on base stations and form a backbone of communication. The communication between base stations and wireless devices can be interfered due to a large number of wireless device. Methodically positioning and orienting directed antennas can help to reduce the interference while saving energy. An integer linear programming is developed for siting and directing antennas on multiple base stations, and this formulation can be extended to model non-overlapping channels. Through the integer programming formulation, optimal antenna positions can be used to analyze the performance of directed antennas with different parameters like the number base stations and the number of non-overlapping channels.

  12. Direct catastrophic injury in sports.

    Boden, Barry P

    2005-11-01

    Catastrophic sports injuries are rare but tragic events. Direct (traumatic) catastrophic injury results from participating in the skills of a sport, such as a collision in football. Football is associated with the greatest number of direct catastrophic injuries for all major team sports in the United States. Pole vaulting, gymnastics, ice hockey, and football have the highest incidence of direct catastrophic injuries for sports in which males participate. In most sports, the rate of catastrophic injury is higher at the collegiate than at the high school level. Cheerleading is associated with the highest number of direct catastrophic injuries for all sports in which females participate. Indirect (nontraumatic) injury is caused by systemic failure as a result of exertion while participating in a sport. Cardiovascular conditions, heat illness, exertional hyponatremia, and dehydration can cause indirect catastrophic injury. Understanding the common mechanisms of injury and prevention strategies for direct catastrophic injuries is critical in caring for athletes.

  13. Factorization and pion form factor in QCD

    Efremov, A.V.; Radyushkin, A.V.

    1979-01-01

    The behaviour of the pion electromagnetic form factor (EMFF) in the framework of quantum chromodynamics (QCD) is discussed. Pion is considered to be a quark-antiquark bound state. It is proposed to use an OPE description of the bound state structure by matrix elements of certain local gauge-invariant operators. Short-distance quark interactions is proved using a direct analysis of perturbation theory in the α-parametric representation of the Feynman diagrams. It is shown that the short-distance parton picture privides a self-consistent description of the large Q 2 momentum behaviour of the pion EMFF in QCD. Pion EMFF asymptotics is expressed in terms of fu fundamental constants of the theory

  14. Direct calculation of wind turbine tip loss

    Wood, D.H.; Okulov, Valery; Bhattacharjee, D.

    2016-01-01

    . We develop three methods for the direct calculation of the tip loss. The first is the computationally expensive calculation of the velocities induced by the helicoidal wake which requires the evaluation of infinite sums of products of Bessel functions. The second uses the asymptotic evaluation......The usual method to account for a finite number of blades in blade element calculations of wind turbine performance is through a tip loss factor. Most analyses use the tip loss approximation due to Prandtl which is easily and cheaply calculated but is known to be inaccurate at low tip speed ratio...

  15. Direct reading spectrochemical analysis of sodium uranate

    Roca, M.; Capdevila, C.

    1966-01-01

    We describe the application of the quantometer to the analysis of sodium uranate. To determine boron, cadmium, phosphorus and molybdenum contents, the samples are mixed with graphite powder (1:30) and excited in a 10 amperes direct current arc with 4x4,,5 mm cup graphite rods, using silver as internal standard. A not se deep cup and a dilution factor of 90 are more suitable for calcium, copper, iron, silicon and vanadium determination; cobalt and chromium are the internal standards. (Author) 6 refs

  16. Direct electromechanical driving systems: diversity, constraints and solutions; Les entrainements electromecaniques directs: diversite, contraintes et solutions

    Multon, B. [Ecole Normale Superieure, 94 - Cachan (France); Bonal, J. [Promethee Groupe Schneider Electric S.A., 92 - Boulogne-Billancourt (France)

    1999-11-01

    Direct electromechanical drives are the simplest possible transmission systems requiring no additional mechanical components such as gearboxes or rotary to linear converters. This simplicity leads a number of advantages including greater reliability, less maintenance, improved dynamic characteristics and reduced weight and volume. However, the performance specification of direct drives is usually high, with a correspondingly high cost, and often this cannot be justified in complete systems where the other components limit the overall performance. This factor alone has been sufficient to restrict the market penetration of direct drives. The majority of applications are in linear actuators, and in motors operating at very high or very low speeds. New developments are constantly being introduced, especially in relation to structures.

  17. Direct Manipulation in Virtual Reality

    Bryson, Steve

    2003-01-01

    Virtual Reality interfaces offer several advantages for scientific visualization such as the ability to perceive three-dimensional data structures in a natural way. The focus of this chapter is direct manipulation, the ability for a user in virtual reality to control objects in the virtual environment in a direct and natural way, much as objects are manipulated in the real world. Direct manipulation provides many advantages for the exploration of complex, multi-dimensional data sets, by allowing the investigator the ability to intuitively explore the data environment. Because direct manipulation is essentially a control interface, it is better suited for the exploration and analysis of a data set than for the publishing or communication of features found in that data set. Thus direct manipulation is most relevant to the analysis of complex data that fills a volume of three-dimensional space, such as a fluid flow data set. Direct manipulation allows the intuitive exploration of that data, which facilitates the discovery of data features that would be difficult to find using more conventional visualization methods. Using a direct manipulation interface in virtual reality, an investigator can, for example, move a data probe about in space, watching the results and getting a sense of how the data varies within its spatial volume.

  18. Future directions for positive body image research.

    Halliwell, Emma

    2015-06-01

    The emergence of positive body image research during the last 10 years represents an important shift in the body image literature. The existing evidence provides a strong empirical basis for the study of positive body image and research has begun to address issues of age, gender, ethnicity, culture, development, and intervention in relation to positive body image. This article briefly reviews the existing evidence before outlining directions for future research. Specifically, six areas for future positive body image research are outlined: (a) conceptualization, (b) models, (c) developmental factors, (d) social interactions, (e) cognitive processing style, and (f) interventions. Finally, the potential role of positive body image as a protective factor within the broader body image literature is discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Plastic apron wear during direct patient care.

    Candlin, Josie; Stark, Sheila

    To identify factors that influence nurses' practice in apron use during direct patient care. A small-scale documentary analysis of a purposive sample of 15 journal articles relating to nurses' apron use during patient care was undertaken. The analysis sought to address what factors affect nurses' decisions in relation to apron use. Nurses' decisions regarding apron use during patient care tend to be ritualistic rather than evidence-based. Their knowledge of infection control is limited. Although there is current literature available on infection control, as well as health and safety regulations, if local policy regarding apron use in nursing care is scant this can result in inconsistent and, perhaps, less desirable practices.

  20. Direct megavoltage photon calibration service in Australia

    Butler, D.J.; Ramanthan, G.; Oliver, C.; Cole, A.; Harty, P.D.; Wright, T.; Webb, D.V.; Lye, J.; Followill, D.S.

    2014-01-01

    The Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) maintains the Australian primary standard of absorbed dose. Until recently, the standard was used to calibrate ionisation chambers only in 60 Co gamma rays. These chambers are then used by radiotherapy clinics to determine linac output, using a correction factor (k Q ) to take into account the different spectra of 60 Co and the linac. Over the period 2010–2013, ARPANSA adapted the primary standard to work in megavoltage linac beams, and has developed a calibration service at three photon beams (6, 10 and 18 MV) from an Elekta Synergy linac. We describe the details of the new calibration service, the method validation and the use of the new calibration factors with the International Atomic Energy Agency’s TRS-398 dosimetry Code of Practice. The expected changes in absorbed dose measurements in the clinic when shifting from 60 Co to the direct calibration are determined. For a Farmer chamber (model 2571), the measured chamber calibration coefficient is expected to be reduced by 0.4, 1.0 and 1.1 % respectively for these three beams when compared to the factor derived from 60 Co. These results are in overall agreement with international absorbed dose standards and calculations by Muir and Rogers in 2010 of k Q factors using Monte Carlo techniques. The reasons for and against moving to the new service are discussed in the light of the requirements of clinical dosimetry.

  1. Proximinality in generalized direct sums

    Darapaneni Narayana

    2004-01-01

    Full Text Available We consider proximinality and transitivity of proximinality for subspaces of finite codimension in generalized direct sums of Banach spaces. We give several examples of Banach spaces where proximinality is transitive among subspaces of finite codimension.

  2. EOP Current Magnitude and Direction

    National Oceanic and Atmospheric Administration, Department of Commerce — These data contain shipboard current magnitudes and directions collected in the Pacific, both pelagic and near shore environments. Data is collected using an RD...

  3. Law, autonomy and advance directives.

    Willmott, Lindy; White, Ben; Mathews, Ben

    2010-12-01

    The principle of autonomy underpins legal regulation of advance directives that refuse life-sustaining medical treatment. The primacy of autonomy in this domain is recognised expressly in the case law, through judicial pronouncement, and implicitly in most Australian jurisdictions, through enactment into statute of the right to make an advance directive. This article seeks to justify autonomy as an appropriate principle for regulating advance directives and relies on three arguments: the necessity of autonomy in a liberal democracy; the primacy of autonomy in medical ethics discourse; and the uncontested importance of autonomy in the law on contemporaneous refusal of medical treatment. This article also responds to key criticisms that autonomy is not an appropriate organising principle to underpin legal regulation of advance directives.

  4. Directed Energy for Interstellar Study

    National Aeronautics and Space Administration — We propose to expand our investigations started in our NIAC Phase I of using directed energy to allow the achievement of relativistic flight to pave the way to the...

  5. Foreign direct investment in China

    Bredero, Q.S.

    2007-01-01

    Foreign Direct Investment in China is one of the most comprehensive studies of FDI in China and provides a remarkable background of information on the evolution of China’s FDI policies over the last 30 years.

  6. New directions in tokamak reactors

    Baker, C.C.

    1985-01-01

    New directions for tokamak research are briefly mentioned. Some of the areas for new considerations are the following: reactor size, beta ratio, current drivers, blankets, impurity control, and modular designs

  7. Directional spectrum of ocean waves

    Fernandes, A.A; Gouveia, A; Nagarajan, R.

    This paper describes a methodology for obtaining the directional spectrum of ocean waves from time series measurement of wave elevation at several gauges arranged in linear or polygonal arrays. Results of simulated studies using sinusoidal wave...

  8. Directed Innovation of Business Models

    Stelian Brad

    2016-06-01

    Full Text Available Business model innovation is an important issue to keep business competitive and increase company’s profits. Due to many market attractors, identification of appropriate paths of business model evolution is a painful and risky process. To improve decision’s effectiveness in this process, an architectural construct of analysis and conceptualization for business model innovation that combines directed evolution and blue ocean concepts is proposed in this paper under the name of directed innovation. It displays the key points where innovations would happen to direct adaptation of the business model towards sustainable competitiveness. Formulation of mature solutions is supported by inventive problem solving tools. The significance of the directed innovation approach is demonstrated in a case study dealing with business model innovation of a software company.

  9. Multi-Directional Experimental Facility

    Federal Laboratory Consortium — The ATLSS Multi-directional Experimental Laboratory was constructed in 1987 under funding from the National Science Foundation to be a major facility for large-scale...

  10. Threshold factorization redux

    Chay, Junegone; Kim, Chul

    2018-05-01

    We reanalyze the factorization theorems for the Drell-Yan process and for deep inelastic scattering near threshold, as constructed in the framework of the soft-collinear effective theory (SCET), from a new, consistent perspective. In order to formulate the factorization near threshold in SCET, we should include an additional degree of freedom with small energy, collinear to the beam direction. The corresponding collinear-soft mode is included to describe the parton distribution function (PDF) near threshold. The soft function is modified by subtracting the contribution of the collinear-soft modes in order to avoid double counting on the overlap region. As a result, the proper soft function becomes infrared finite, and all the factorized parts are free of rapidity divergence. Furthermore, the separation of the relevant scales in each factorized part becomes manifest. We apply the same idea to the dihadron production in e+e- annihilation near threshold, and show that the resultant soft function is also free of infrared and rapidity divergences.

  11. Spontaneous direct and reverse osmosis

    Valitov, N.Kh.

    1996-01-01

    It has been ascertained experimentally that in the course of separation of CsCl, KCl, NaCl aqueous solutions by semi-permeable membrane from distilled water the direct and then reverse osmosis are observed. The same sequence is observed in case of separation of CsCl aqueous solutions from NaCl of different concentrations. The reason for the direct and reverse osmosis has been explained. 5 refs.; 3 figs. 1 tab

  12. Spillovers from Foreign Direct Investment

    Meyer, Klaus E.; Sinani, Evis

    2005-01-01

    The extensive empirical literature analyzing productivity spillovers from foreign direct investment to local firms provides inconclusive results. Some studies find that foreign presence has a positive impact on the productivity of domestic firms, while others find no evidence or a negative effect...... for industrialized countries in the 1990s. Transition economies may experience spillovers, but these have been declining in recent years. Keywords: developing countries, transition economies, spillovers, foreign direct investment, technology transfer, meta-analysis...

  13. Quantum direct communication with authentication

    Lee, Hwayean; Lim, Jongin; Yang, HyungJin

    2006-01-01

    We propose two quantum direct communication (QDC) protocols with user authentication. Users can identify each other by checking the correlation of Greenberger-Horne-Zeilinger (GHZ) states. Alice can directly send a secret message to Bob without any previously shared secret using the remaining GHZ states after authentication. Our second QDC protocol can be used even though there is no quantum link between Alice and Bob. The security of the transmitted message is guaranteed by properties of entanglement of GHZ states

  14. Direct Bandgap Group IV Materials

    2016-01-21

    AFRL-AFOSR-JP-TR-2017-0049 Direct Bandgap group IV Materials Hung Hsiang Cheng NATIONAL TAIWAN UNIVERSITY Final Report 01/21/2016 DISTRIBUTION A...NAME(S) AND ADDRESS(ES) NATIONAL TAIWAN UNIVERSITY 1 ROOSEVELT RD. SEC. 4 TAIPEI CITY, 10617 TW 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING...14. ABSTRACT Direct bandgap group IV materials have been long sought for in both academia and industry for the implementation of photonic devices

  15. Geothermal Direct Heat Application Potential

    Lienau, Paul J

    1989-01-01

    The geothermal direct-use industry growth trends, potential, needs, and how they can be met, are addressed. Recent investigations about the current status of the industry and the identification of institutional and technical needs provide the basis on which this paper is presented. Initial drilling risk is the major obstacle to direct-use development. The applications presented include space and district heating projects, heat pumps (heating and cooling), industrial processes, resorts and pools, aquaculture and agriculture.

  16. Human factors

    Brown, G.J.

    1991-01-01

    Recent reactor accidents have spurred the major review, described here, of the contribution of operator personnel to safety in Scottish Nuclear Power Stations. The review aims to identify factors leading to the Chernobyl accident and take preventative measures to avoid possible recurrence. Scottish Nuclear power stations aim to remove the operator from a position where failure to take correct action could lead to a safety hazard. Instead operators concentrate on routine and breakdown maintenance and measures are taken to minimize the probability of operator error. The review concluded that most safety procedures were satisfactory but safety analysis supported by good design practices may offer a significant reduction in the risk of operator error. (UK)

  17. Direct block scheduling technology: Analysis of Avidity

    Felipe Ribeiro Souza

    Full Text Available Abstract This study is focused on Direct Block Scheduling testing (Direct Multi-Period Scheduling methodology which schedules mine production considering the correct discount factor of each mining block, resulting in the final pit. Each block is analyzed individually in order to define the best target period. This methodology presents an improvement of the classical methodology derived from Lerchs-Grossmann's initial proposition improved by Whittle. This paper presents the differences between these methodologies, specially focused on the algorithms' avidity. Avidity is classically defined by the voracious search algorithms, whereupon some of the most famous greedy algorithms are Branch and Bound, Brutal Force and Randomized. Strategies based on heuristics can accentuate the voracity of the optimizer system. The applied algorithm use simulated annealing combined with Tabu Search. The most avid algorithm can select the most profitable blocks in early periods, leading to higher present value in the first periods of mine operation. The application of discount factors to blocks on the Lerchs-Grossmann's final pit has an accentuated effect with time, and this effect may make blocks scheduled for the end of the mine life unfeasible, representing a trend to a decrease in reported reserves.

  18. 75 FR 76630 - Direct Investment Surveys: BE-577, Quarterly Survey of U.S. Direct Investment Abroad-Direct...

    2010-12-09

    ....S. Direct Investment Abroad--Direct Transactions of U.S. Reporter With Foreign Affiliate.'' The..., Quarterly Survey of U.S. Direct Investment Abroad--Direct Transactions of U.S. Reporter With Foreign...] RIN 0691--AA75 Direct Investment Surveys: BE-577, Quarterly Survey of U.S. Direct Investment Abroad...

  19. The level of insulin growth factor-1 receptor expression is directly correlated with the tumor uptake of {sup 111}In-IGF-1(E3R) in vivo and the clonogenic survival of breast cancer cells exposed in vitro to trastuzumab (Herceptin)

    Cornelissen, Bart; McLarty, Kristin; Kersemans, Veerle [Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Reilly, Raymond M. [Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Department of Medical Imaging, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Toronto General Research Institute, University Health Network Toronto, Toronto, ON, M5S 3M2 (Canada)], E-mail: raymond.reilly@utoronto.ca

    2008-08-15

    Introduction: Our objective was to define the relationships between tumor uptake of [{sup 111}In]-IGF-1 and [{sup 111}In]-IGF-1(E3R), an analogue which does not bind insulin growth factor-1 (IGF-1) binding proteins (i.e., IGFBP-3), and the level of IGF-1 receptor (IGF-1R) expression on human breast cancer (BC) xenografts in athymic mice, as well as the feasibility for tumor imaging. A second objective was to correlate IGF-1R (and HER2 density) with the cytotoxicity of trastuzumab in the absence/presence of IGFBP-3 or the IGF-1R tyrosine kinase inhibitor, AG1024. Methods: The tumor and normal tissue uptake of [{sup 111}In]-IGF-1 and [{sup 111}In]-IGF-1(E3R) were determined at 4 h postinjection in mice implanted subcutaneously with MDA-MB-231, H2N, HR2 or MCF-7/HER2-18 human BC xenografts (8.5x10{sup 4}, 1.4x10{sup 4}, 4.0x10{sup 4} and 1.0x10{sup 5} IGF-1R/cell, respectively). The effect of co-injection of IGF-1 (50 {mu}g) or IGFBP-3 (2 or 25 {mu}g) was studied. The relationship between tumor uptake of [{sup 111}In]-IGF-1(E3R) and IGF-1R density was examined. MicroSPECT/CT imaging was performed on mice with MCF-7/HER2-18 tumors injected with [{sup 111}In]-IGF-1(E3R). The surviving fraction of BC cells exposed to trastuzumab (67.5 {mu}g/ml) in the absence/presence of IGFBP-3 (1 {mu}g/ml) or the IGF-1R kinase inhibitor, AG1024 (1 or 5 {mu}g/ml), was determined. Results: [{sup 111}In]-IGF-1 was specifically taken up by MCF-7/HER2-18 xenografts; tumor uptake was decreased twofold when co-injected with IGF-1 (1.9{+-}0.1 vs. 1.0{+-}0.1 %ID/g). Co-injection of IGBP-3 decreased kidney uptake of [{sup 111}In]-IGF-1 up to twofold and increased circulating radioactivity threefold. There was a strong linear correlation (r{sup 2}=0.99) between the tumor uptake of {sup 111}In-IGF-1(E3R) and IGF-1R density. Tumor uptake ranged from 0.4{+-}0.05 %ID/g for H2N to 2.5{+-}0.5 %ID/g for MCF-7/HER2-18 xenografts. MCF-7/HER2-18 tumors were visualized by microSPECT/CT. Resistance of BC

  20. The level of insulin growth factor-1 receptor expression is directly correlated with the tumor uptake of 111In-IGF-1(E3R) in vivo and the clonogenic survival of breast cancer cells exposed in vitro to trastuzumab (Herceptin)

    Cornelissen, Bart; McLarty, Kristin; Kersemans, Veerle; Reilly, Raymond M.

    2008-01-01

    Introduction: Our objective was to define the relationships between tumor uptake of [ 111 In]-IGF-1 and [ 111 In]-IGF-1(E3R), an analogue which does not bind insulin growth factor-1 (IGF-1) binding proteins (i.e., IGFBP-3), and the level of IGF-1 receptor (IGF-1R) expression on human breast cancer (BC) xenografts in athymic mice, as well as the feasibility for tumor imaging. A second objective was to correlate IGF-1R (and HER2 density) with the cytotoxicity of trastuzumab in the absence/presence of IGFBP-3 or the IGF-1R tyrosine kinase inhibitor, AG1024. Methods: The tumor and normal tissue uptake of [ 111 In]-IGF-1 and [ 111 In]-IGF-1(E3R) were determined at 4 h postinjection in mice implanted subcutaneously with MDA-MB-231, H2N, HR2 or MCF-7/HER2-18 human BC xenografts (8.5x10 4 , 1.4x10 4 , 4.0x10 4 and 1.0x10 5 IGF-1R/cell, respectively). The effect of co-injection of IGF-1 (50 μg) or IGFBP-3 (2 or 25 μg) was studied. The relationship between tumor uptake of [ 111 In]-IGF-1(E3R) and IGF-1R density was examined. MicroSPECT/CT imaging was performed on mice with MCF-7/HER2-18 tumors injected with [ 111 In]-IGF-1(E3R). The surviving fraction of BC cells exposed to trastuzumab (67.5 μg/ml) in the absence/presence of IGFBP-3 (1 μg/ml) or the IGF-1R kinase inhibitor, AG1024 (1 or 5 μg/ml), was determined. Results: [ 111 In]-IGF-1 was specifically taken up by MCF-7/HER2-18 xenografts; tumor uptake was decreased twofold when co-injected with IGF-1 (1.9±0.1 vs. 1.0±0.1 %ID/g). Co-injection of IGBP-3 decreased kidney uptake of [ 111 In]-IGF-1 up to twofold and increased circulating radioactivity threefold. There was a strong linear correlation (r 2 =0.99) between the tumor uptake of 111 In-IGF-1(E3R) and IGF-1R density. Tumor uptake ranged from 0.4±0.05 %ID/g for H2N to 2.5±0.5 %ID/g for MCF-7/HER2-18 xenografts. MCF-7/HER2-18 tumors were visualized by microSPECT/CT. Resistance of BC cells to trastuzumab was directly associated with IGF-1R expression, despite co

  1. Customer Satisfaction in Farmer-to-consumer Direct Marketing

    Lulfs-Baden, Frederike; Spiller, Achim; Zuhlsdorf, Anke; Mellin, Matthias

    2008-01-01

    The importance of direct marketing for high quality farm products has increased during the past few years. This paper analyzes the impact of customer satisfaction and its driving forces for farmer-to-consumer direct marketing and is based on a customer survey among 1,537 customers in 33 organic and conventional on-farm stores in Germany. The results emphasize the role of store atmosphere, customer service and product quality as the main factors which influence customer satisfaction.

  2. Analysis of primary cilia in directional cell migration in fibroblasts

    Christensen, Søren Tvorup; Veland, Iben; Schwab, Albrecht

    2013-01-01

    summarize selected methods in analyzing ciliary function in directional cell migration, including immunofluorescence microscopy, scratch assay, and chemotaxis assay by micropipette addition of PDGFRα ligands to cultures of fibroblasts. These methods should be useful not only in studying cell migration....... In particular, platelet-derived growth factor receptor alpha (PDGFRα) is compartmentalized to the primary cilium to activate signaling pathways that regulate reorganization of the cytoskeleton required for lamellipodium formation and directional migration in the presence of a specific ligand gradient. We...

  3. Direct conversion of fusion energy

    Johansson, Markus

    2003-03-01

    Deuterium and tritium are expected to be used as fuel in the first fusion reactors. Energy is released as kinetic energy of ions and neutrons, when deuterium reacts with tritium. One way to convert the kinetic energy to electrical energy, is to let the ions and neutrons hit the reactor wall and convert the heat that is caused by the particle bombardment to electrical energy with ordinary thermal conversion. If the kinetic energy of the ions instead is converted directly to electrical energy, a higher efficiency of the energy conversion is possible. The majority of the fusion energy is released as kinetic energy of neutrons, when deuterium reacts with tritium. Fusion reactions such as the D-D reactions, the D- 3 He reaction and the p- 11 B reaction, where a larger part of the fusion energy becomes kinetic energy of charged particles, appears therefore more suitable for direct conversion. Since they have lower reactivity than the D-T reaction, they need a larger βB 2 0 to give sufficiently high fusion power density. Because of this, the fusion configurations spherical torus (ST) and field-reversed configuration (FRC), where high β values are possible, appear interesting. Rosenbluth and Hinton come to the conclusion that efficient direct conversion isn't possible in closed field line systems and that open geometries, which facilitate direct conversion, provide inadequate confinement for D- 3 He. It is confirmed in this study that it doesn't seem possible to achieve as high direct conversion efficiency in closed systems as in open systems. ST and FRC fusion power plants that utilize direct conversion seem however interesting. Calculations with the help of Maple indicate that the reactor parameters needed for a D-D ST and a D 3 He ST hopefully are possible to achieve. The best energy conversion option for a D-D or D 3 He ST appears to be direct electrodynamic conversion (DEC) together with ordinary thermal conversion or liquid metal MHD conversion (LMMHD). For a D

  4. Direct conversion of fusion energy

    Johansson, Markus

    2003-03-01

    Deuterium and tritium are expected to be used as fuel in the first fusion reactors. Energy is released as kinetic energy of ions and neutrons, when deuterium reacts with tritium. One way to convert the kinetic energy to electrical energy, is to let the ions and neutrons hit the reactor wall and convert the heat that is caused by the particle bombardment to electrical energy with ordinary thermal conversion. If the kinetic energy of the ions instead is converted directly to electrical energy, a higher efficiency of the energy conversion is possible. The majority of the fusion energy is released as kinetic energy of neutrons, when deuterium reacts with tritium. Fusion reactions such as the D-D reactions, the D-{sup 3}He reaction and the p-{sup 11}B reaction, where a larger part of the fusion energy becomes kinetic energy of charged particles, appears therefore more suitable for direct conversion. Since they have lower reactivity than the D-T reaction, they need a larger {beta}B{sup 2}{sub 0} to give sufficiently high fusion power density. Because of this, the fusion configurations spherical torus (ST) and field-reversed configuration (FRC), where high {beta} values are possible, appear interesting. Rosenbluth and Hinton come to the conclusion that efficient direct conversion isn't possible in closed field line systems and that open geometries, which facilitate direct conversion, provide inadequate confinement for D-{sup 3}He. It is confirmed in this study that it doesn't seem possible to achieve as high direct conversion efficiency in closed systems as in open systems. ST and FRC fusion power plants that utilize direct conversion seem however interesting. Calculations with the help of Maple indicate that the reactor parameters needed for a D-D ST and a D{sub 3} He ST hopefully are possible to achieve. The best energy conversion option for a D-D or D{sub 3} He ST appears to be direct electrodynamic conversion (DEC) together with ordinary thermal conversion

  5. Directive and Non-Directive Movement in Child Therapy.

    Krason, Katarzyna; Szafraniec, Grazyna

    1999-01-01

    Presents a new authorship method of child therapy based on visualization through motion. Maintains that this method stimulates motor development and musical receptiveness, and promotes personality development. Suggests that improvised movement to music facilitates the projection mechanism and that directed movement starts the channeling phase.…

  6. Proinflammatory mediators stimulate neutrophil-directed angiogenesis.

    McCourt, M

    2012-02-03

    BACKGROUND: Vascular endothelial growth factor (VEGF; vascular permeability factor) is one of the most potent proangiogenic cytokines, and it plays a central role in mediating the process of angiogenesis or new blood vessel formation. Neutrophils (PMNs) recently have been shown to produce VEGF. HYPOTHESIS: The acute inflammatory response is a potent stimulus for PMN-directed angiogenesis. METHODS: Neutrophils were isolated from healthy volunteers and stimulated with lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and anti-human Fas monoclonal antibody. Culture supernatants were assayed for VEGF using enzyme-linked immunosorbent assays. Culture supernatants from LPS- and TNF-alpha-stimulated PMNs were then added to human umbilical vein endothelial cells and human microvessel endothelial cells and assessed for endothelial cell proliferation using 5-bromodeoxyuridine labeling. Tubule formation was also assessed on MATRIGEL basement membrane matrix. Neutrophils were lysed to measure total VEGF release, and VEGF expression was detected using Western blot analysis. RESULTS: Lipopolysaccharide and TNF-alpha stimulation resulted in significantly increased release of PMN VEGF (532+\\/-49 and 484+\\/-80 pg\\/mL, respectively; for all, presented as mean +\\/- SEM) compared with control experiments (32+\\/-4 pg\\/mL). Interleukin 6 and Fas had no effect. Culture supernatants from LPS- and TNF-alpha-stimulated PMNs also resulted in significant increases (P<.005) in macrovascular and microvascular endothelial cell proliferation and tubule formation. Adding anti-human VEGF-neutralizing polyclonal antibody to stimulated PMN supernatant inhibited these effects. Total VEGF release following cell lysis and Western blot analysis suggests that the VEGF is released from an intracellular store. CONCLUSION: Activated human PMNs are directly angiogenic by releasing VEGF, and this has important implications for inflammation, capillary leak syndrome

  7. Multi-Directional Environmental Sensors

    Manohara, Harish (Inventor); Del Castillo, Linda Y. (Inventor); Mojarradi, Mohammed M. (Inventor)

    2016-01-01

    Systems and methods in accordance with embodiments of the invention implement multi-directional environmental sensors. In one embodiment, a multi-directional environmental sensor includes: an inner conductive element that is substantially symmetrical about three orthogonal planes; an outer conductive element that is substantially symmetrical about three orthogonal planes; and a device that measures the electrical characteristics of the multi-directional environmental sensor, the device having a first terminal and a second terminal; where the inner conductive element is substantially enclosed within the outer conductive element; where the inner conductive element is electrically coupled to the first terminal of the device; and where the outer conductive element is electrically coupled to the second terminal of the device.

  8. Physician Self-directed Learning and Education

    Masami Tagawa

    2008-07-01

    Full Text Available Physicians are expected to be life-long learners because updated and effective patient care should be provided while medical and clinical knowledge and skills and social requirements for patient care are rapidly changing. Also, qualified clinical competence needs long periods of training and each physician has to continually learn as long as he/she works as a professional. Self-directed learning is an important factor in adult learning. Medical students' readiness for self-directed learning is not high, and should be improved by medical school and postgraduate training curricula. Garrison proposed a comprehensive model of self-directed learning, and it has dimensions of motivation (entering and task, self-monitoring (responsibility, and self-management (responsibility. To teach individual self-directed learning competencies, the following are important: (1 situate learners to experience “real” problems; (2 encourage learners to reflect on their own performance; (3 create an educational atmosphere in clinical training situations. In 2005, a 2-year mandatory residency program was implemented in Japan, and fewer medical school graduates took residency programs in medical school hospitals and advanced specialty programs provided by medical school departments. Medical school departments provide traditional, but life-long clinical training opportunities. Under the new residency program, an additional postgraduate and continuing medical training system has to be built up to maintain and confirm a physician's competencies. If physicians do clinical work using a scholarly way of thinking with critical analysis of their own competencies and improvement by reflection, they will become an excellent life-long learner.

  9. SOCIO-ECONOMIC FACTORS AFFECTING APPLE PRODUCTION ...

    ACSS

    Research Organisation scientists working directly with apple farmers ... be productive up to 40 years, it was more realistic to consider .... to determine the factors that affect apple production. ..... profit maximising model using flexible production ...

  10. Direct Methanol Fuel Cell, DMFC

    Amornpitoksuk, P.

    2003-09-01

    Full Text Available Direct Methanol Fuel Cell, DMFC is a kind of fuel cell using methanol as a fuel for electric producing. Methanol is low cost chemical substance and it is less harmful than that of hydrogen fuel. From these reasons it can be commercial product. The electrocatalytic reaction of methanol fuel uses Pt-Ru metals as the most efficient catalyst. In addition, the property of membrane and system designation are also effect to the fuel cell efficient. Because of low power of methanol fuel cell therefore, direct methanol fuel cell is proper to use for the energy source of small electrical devices and vehicles etc.

  11. Directional Validation of Wave Predictions

    2007-03-01

    motivators: I) the desire to make the problem more solution is simply to use only variables directly Cx- manageable via frequency-wise integration of direc...ViaW()2 + bi(f), where . = j F(f) d. The calculation in reverse is a, = in, cosO , and b, = ni, sinf0 . Note that if we choose f, andf2 as values close...34). The use of a broader band of frequencies makes the metric more stable, but CALCULATION OF MEAN WAVE DIRECTION AND increases the risk that two

  12. Directions for improved fusion reactors

    Krakowski, R.A.; Miller, R.L.; Delene, J.G.

    1986-01-01

    Conceptual fusion reactor studies over the past 10 to 15 years have projected systems that may be too large, complex, and costly to be of commercial interest. One main direction for improved fusion reactors points towards smaller, higher-power-density approaches. First-order economic issues (i.e., unit direct cost and cost of electricity) are used to support the need for more compact fusion reactors. A generic fusion physics/engineering/costing model is used to provide a quantiative basis for these arguments for specific fusion concepts

  13. Restraining Sodium Volatilization in the Ferric Bauxite Direct Reduction System

    Wentao Hu

    2016-03-01

    Full Text Available Direct reduction is an emerging utilization technology of ferric bauxite. However, it requires much more sodium carbonate than ordinary bauxite does. The volatilization is one of the most significant parts of sodium carbonate consumption, as reported in previous studies. Based on the new direct reduction method for utilization of ferric bauxite, this paper has systematically investigated factors including heating temperature, heating time, and sodium carbonate dosage influencing sodium volatilization. For the purpose of reducing sodium volatilization, the Box–Benhken design was employed, and the possibility of separating iron and sodium after direct reduction was also investigated.

  14. Directional dual-tree rational-dilation complex wavelet transform.

    Serbes, Gorkem; Gulcur, Halil Ozcan; Aydin, Nizamettin

    2014-01-01

    Dyadic discrete wavelet transform (DWT) has been used successfully in processing signals having non-oscillatory transient behaviour. However, due to the low Q-factor property of their wavelet atoms, the dyadic DWT is less effective in processing oscillatory signals such as embolic signals (ESs). ESs are extracted from quadrature Doppler signals, which are the output of Doppler ultrasound systems. In order to process ESs, firstly, a pre-processing operation known as phase filtering for obtaining directional signals from quadrature Doppler signals must be employed. Only then, wavelet based methods can be applied to these directional signals for further analysis. In this study, a directional dual-tree rational-dilation complex wavelet transform, which can be applied directly to quadrature signals and has the ability of extracting directional information during analysis, is introduced.

  15. Analysis of foreign direct investment in the Czech Republic

    Marcela Domesová

    2011-01-01

    Full Text Available The foreign direct investments are joined with the process of world globalisation. Foreign direct investments are carried out especially by multinational companies. The basic forms of the foreign direct investments are “greenfield” investments and “brownfield“ investments in the form of the privatization. The Czech Republic has shown mass inflow of foreign direct investments since 1998. The aim of the paper is to evaluate the inflow of foreign direct investments in the context of the balance of payments and the evaluation their impact on the outside economic equilibrium and gross value added in the Czech Republic. The subject of the analysis is the identification of the most important factors of foreign direct investments inflow and the classification of foreign direct investments inflow from the point of view of branches and technological intensity of production as well. The aim is fulfilled by analysis of selected indicators of the balance of payments, analysis of gross value added and international comparison of foreign direct investments inflow in countries of Visegrad Group. The results show the part of privatization in foreign capital inflow, increasing import intensity and export efficiency linked with foreign direct investments. The results are subject of research focused on the process of world globalisation and regional development.

  16. Risk factors for cancer

    Lyman, G.H.

    1992-01-01

    It is no longer reasonable to divide cancers into those that are genetic in origin and those that are environmental in origin. With rare exception, carcinogenesis involves environmental factors that directly or indirectly exert a change in the cell's genome. Virtually all causes of cancer are multifactorial, sometimes involving an inherited predisposition to the carcinogenic effects of environmental factors, which include chemicals, ionizing radiation, and oncogenic virus. Carcinogenesis is a multistep process including induction, promotion, and progression. Initiation requires an irreversible change in the cellular genome, whereas promotion is commonly associated with prolonged and reversible exposure. Tumor progression results in genotypic and phenotypic changes associated with tumor growth, invasion, and metastasis. Most information on human cancer risk is based on epidemiologic studies involving both exposed and unexposed individuals. The quality of such studies depends on their ability to assess the strength of any association of exposure and disease and careful attention to any potential bias. Few cancers are inherited in a Mendelian fashion. Several preneoplastic conditions, however, are clearly inherited and several malignancies demonstrate weak familial patterns. Environmental factors may exert their effect on DNA in a random fashion, but certain consistent changes, including specific translocations of genetic information, are often found. Currently, there is great interest in the close proximity of certain oncogenes governing growth control to the consistent chromosomal changes observed. Such changes may represent a final common pathway of action for environmental carcinogens. Sufficient laboratory and epidemiologic evidence exists to establish a causal association of several chemical agents with cancer

  17. Advance Directives in Hospice Healthcare Providers: A Clinical Challenge.

    Luck, George R; Eggenberger, Terry; Newman, David; Cortizo, Jacqueline; Blankenship, Derek C; Hennekens, Charles H

    2017-11-01

    On a daily basis, healthcare providers, especially those dealing with terminally ill patients, such as hospice workers, witness how advance directives help ensure the wishes of patients. They also witness the deleterious consequences when patients fail to document the care they desire at their end of life. To the best of our knowledge there are no data concerning the prevalence of advance directives among hospice healthcare providers. We therefore explored the prevalence and factors influencing completion rates in a survey of hospice healthcare providers. Surveys that included 32 items to explore completion rates, as well as barriers, knowledge, and demographics, were e-mailed to 2097 healthcare providers, including employees and volunteers, at a nonprofit hospice. Of 890 respondents, 44% reported having completed an advance directive. Ethnicity, age, relationship status, and perceived knowledge were all significant factors influencing the completion rates, whereas years of experience or working directly with patients had no effect. Procrastination, fear of the subject, and costs were common reasons reported as barriers. Upon completion of the survey, 43% said they will now complete an advance directive, and 45% will talk to patients and families about their wishes. The majority of hospice healthcare providers have not completed an advance directive. These results are very similar to those for other healthcare providers treating patients with terminal diseases, specifically oncologists. Because, at completion, 43% said that they would now complete an advance directive, such a survey of healthcare providers may help increase completion rates. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. PROTOTIPE VIDEO EDITOR DENGAN MENGGUNAKAN DIRECT X DAN DIRECT SHOW

    Djoni Haryadi Setiabudi

    2004-01-01

    Full Text Available Technology development had given people the chance to capture their memorable moments in video format. A high quality digital video is a result of a good editing process. Which in turn, arise the new need of an editor application. In accordance to the problem, here the process of making a simple application for video editing needs. The application development use the programming techniques often applied in multimedia applications, especially video. First part of the application will begin with the video file compression and decompression, then we'll step into the editing part of the digital video file. Furthermore, the application also equipped with the facilities needed for the editing processes. The application made with Microsoft Visual C++ with DirectX technology, particularly DirectShow. The application provides basic facilities that will help the editing process of a digital video file. The application will produce an AVI format file after the editing process is finished. Through the testing process of this application shows the ability of this application to do the 'cut' and 'insert' of video files in AVI, MPEG, MPG and DAT formats. The 'cut' and 'insert' process only can be done in static order. Further, the aplication also provide the effects facility for transition process in each clip. Lastly, the process of saving the new edited video file in AVI format from the application. Abstract in Bahasa Indonesia : Perkembangan teknologi memberi kesempatan masyarakat untuk mengabadikan saat - saat yang penting menggunakan video. Pembentukan video digital yang baik membutuhkan proses editing yang baik pula. Untuk melakukan proses editing video digital dibutuhkan program editor. Berdasarkan permasalahan diatas maka pada penelitian ini dibuat prototipe editor sederhana untuk video digital. Pembuatan aplikasi memakai teknik pemrograman di bidang multimedia, khususnya video. Perencanaan dalam pembuatan aplikasi tersebut dimulai dengan pembentukan

  19. Verification of the directivity index and other measures of directivity in predicting directional benefit

    Dittberner, Andrew; Bentler, Ruth

    2005-09-01

    The relationship between various directivity measures and subject performance with directional microphone hearing aids was determined. Test devices included first- and second-order directional microphones. Recordings of sentences and noise (Hearing in Noise Test, HINT) were made through each test device in simple, complex, and anisotropic background noise conditions. Twenty-six subjects, with normal hearing, were administered the HINT test recordings, and directional benefit was computed. These measures were correlated to theoretical, free-field, and KEMAR DI values, as well as front-to-back ratios, in situ SNRs, and a newly proposed Db-SNR, wherein a predictive value of the SNR improvement is calculated as a function of the noise source incidence. The different predictive scores showed high correlation to the measured directional benefit scores in the complex (diffuse-like) background noise condition (r=0.89-0.97, pThe Db-SNR approach and the in situ SNR measures provided excellent prediction of subject performance in all background noise conditions (0.85-0.97, pthe predictive measures could account for the effects of reverberation on the speech signal (r=0.35-0.40, p<0.05).

  20. Direct-semidirect (DSD) codes

    Cvelbar, F.

    1999-01-01

    Recent codes for direct-semidirect (DSD) model calculations in the form of answers to a detailed questionnaire are reviewed. These codes include those embodying the classical DSD approach covering only the transitions to the bound states (RAF, HIKARI, and those of the Bologna group), as well as the code CUPIDO++ that also treats transitions to unbound states. (author)