WorldWideScience

Sample records for factor site dependencies

  1. Real-time correction of tsunami site effect by frequency-dependent tsunami-amplification factor

    Science.gov (United States)

    Tsushima, H.

    2017-12-01

    For tsunami early warning, I developed frequency-dependent tsunami-amplification factor and used it to design a recursive digital filter that can be applicable for real-time correction of tsunami site response. In this study, I assumed that a tsunami waveform at an observing point could be modeled by convolution of source, path and site effects in time domain. Under this assumption, spectral ratio between offshore and the nearby coast can be regarded as site response (i.e. frequency-dependent amplification factor). If the amplification factor can be prepared before tsunamigenic earthquakes, its temporal convolution to offshore tsunami waveform provides tsunami prediction at coast in real time. In this study, tsunami waveforms calculated by tsunami numerical simulations were used to develop frequency-dependent tsunami-amplification factor. Firstly, I performed numerical tsunami simulations based on nonlinear shallow-water theory from many tsuanmigenic earthquake scenarios by varying the seismic magnitudes and locations. The resultant tsunami waveforms at offshore and the nearby coastal observing points were then used in spectral-ratio analysis. An average of the resulted spectral ratios from the tsunamigenic-earthquake scenarios is regarded as frequency-dependent amplification factor. Finally, the estimated amplification factor is used in design of a recursive digital filter that can be applicable in time domain. The above procedure is applied to Miyako bay at the Pacific coast of northeastern Japan. The averaged tsunami-height spectral ratio (i.e. amplification factor) between the location at the center of the bay and the outside show a peak at wave-period of 20 min. A recursive digital filter based on the estimated amplification factor shows good performance in real-time correction of tsunami-height amplification due to the site effect. This study is supported by Japan Society for the Promotion of Science (JSPS) KAKENHI grant 15K16309.

  2. Effect of positional dependence and alignment strategy on modeling transcription factor binding sites

    Directory of Open Access Journals (Sweden)

    Quader Saad

    2012-07-01

    Full Text Available Abstract Background Many consensus-based and Position Weight Matrix-based methods for recognizing transcription factor binding sites (TFBS are not well suited to the variability in the lengths of binding sites. Besides, many methods discard known binding sites while building the model. Moreover, the impact of Information Content (IC and the positional dependence of nucleotides within an aligned set of TFBS has not been well researched for modeling variable-length binding sites. In this paper, we propose ML-Consensus (Mixed-Length Consensus: a consensus model for variable-length TFBS which does not exclude any reported binding sites. Methods We consider Pairwise Score (PS as a measure of positional dependence of nucleotides within an alignment of TFBS. We investigate how the prediction accuracy of ML-Consensus is affected by the incorporation of IC and PS with a particular binding site alignment strategy. We perform cross-validations for datasets of six species from the TRANSFAC public database, and analyze the results using ROC curves and the Wilcoxon matched-pair signed-ranks test. Results We observe that the incorporation of IC and PS in ML-Consensus results in statistically significant improvement in the prediction accuracy of the model. Moreover, the existence of a core region among the known binding sites (of any length is witnessed by the pairwise coexistence of nucleotides within the core length. Conclusions These observations suggest the possibility of an efficient multiple sequence alignment algorithm for aligning TFBS, accommodating known binding sites of any length, for optimal (or near-optimal TFBS prediction. However, designing such an algorithm is a matter of further investigation.

  3. Survival of Manure-borne and Fecal Coliforms in Soil: Temperature Dependence as Affected by Site-Specific Factors.

    Science.gov (United States)

    Park, Yongeun; Pachepsky, Yakov; Shelton, Daniel; Jeong, Jaehak; Whelan, Gene

    2016-05-01

    Understanding pathogenic and indicator bacteria survival in soils is essential for assessing the potential of microbial contamination of water and produce. The objective of this work was to evaluate the effects of soil properties, animal source, experimental conditions, and the application method on temperature dependencies of manure-borne generic , O157:H7, and fecal coliforms survival in soils. A literature search yielded 151 survival datasets from 70 publications. Either one-stage or two-stage kinetics was observed in the survival datasets. We used duration and rate of the logarithm of concentration change as parameters of the first stage in the two-stage kinetics data. The second stage of the two-stage kinetics and the one-stage kinetics were simulated with the model to find the dependence of the inactivation rate on temperature. Classification and regression trees and linear regressions were applied to parameterize the kinetics. Presence or absence of two-stage kinetics was controlled by temperature, soil texture, soil water content, and for fine-textured soils by setting experiments in the field or in the laboratory. The duration of the first stage was predominantly affected by soil water content and temperature. In the model dependencies of inactivation rates on temperature, parameter estimates were significantly affected by the laboratory versus field conditions and by the application method, whereas inactivation rates at 20°C were significantly affected by all survival and management factors. Results of this work can provide estimates of coliform survival parameters for models of microbial water quality. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

  4. Comparison of Transcription Factor Binding Site Models

    KAUST Repository

    Bhuyan, Sharifulislam

    2012-05-01

    Modeling of transcription factor binding sites (TFBSs) and TFBS prediction on genomic sequences are important steps to elucidate transcription regulatory mechanism. Dependency of transcription regulation on a great number of factors such as chemical specificity, molecular structure, genomic and epigenetic characteristics, long distance interaction, makes this a challenging problem. Different experimental procedures generate evidence that DNA-binding domains of transcription factors show considerable DNA sequence specificity. Probabilistic modeling of TFBSs has been moderately successful in identifying patterns from a family of sequences. In this study, we compare performances of different probabilistic models and try to estimate their efficacy over experimental TFBSs data. We build a pipeline to calculate sensitivity and specificity from aligned TFBS sequences for several probabilistic models, such as Markov chains, hidden Markov models, Bayesian networks. Our work, containing relevant statistics and evaluation for the models, can help researchers to choose the most appropriate model for the problem at hand.

  5. The use of English in job advertisments on the Dutch job site Monsterboard.nl and factors on which it depends

    NARCIS (Netherlands)

    Meurs, F. van; Korzilius, H.P.L.M.; Hollander, Adriënne den

    2006-01-01

    Previous studies on the factors that determine the use of English in product advertising and print-medium job advertisements in non-English-speaking countries have overwhelmingly analysed English in product advertising. Drawing on the reasons suggested in such studies, the present contribution

  6. Systemic administration of kainic acid induces selective time dependent decrease in [125I]insulin-like growth factor I, [125I]insulin-like growth factor II and [125I]insulin receptor binding sites in adult rat hippocampal formation

    International Nuclear Information System (INIS)

    Quirion, R.; Chabot, J.-G.; Dore, S.; Seto, D.; Kar, S.

    1997-01-01

    Administration of kainic acid evokes acute seizure in hippocampal pathways that results in a complex sequence of functional and structural alterations resembling human temporal lobe epilepsy. The structural alterations induced by kainic acid include selective loss of neurones in CA1-CA3 subfields and the hilar region of the dentate gyrus followed by sprouting and permanent reorganization of the synaptic connections of the mossy fibre pathways. Although the neuronal degeneration and process of reactive synaptogenesis have been extensively studied, at present little is known about means to prevent pathological conditions leading to kainate-induced cell death. In the present study, to address the role of insulin-like growth factors I and II, and insulin in neuronal survival as well as synaptic reorganization following kainate-induced seizure, the time course alterations of the corresponding receptors were evaluated. Additionally, using histological preparations, the temporal profile of neuronal degeneration and hypertrophy of resident astroglial cells were also studied. [ 125 I]Insulin-like growth factor I binding was found to be decreased transiently in almost all regions of the hippocampal formation at 12 h following treatment with kainic acid. The dentate hilar region however, exhibited protracted decreases in [ 125 I]insulin-like growth factor I receptor sites throughout (i.e. 30 days) the study. [ 125 I]Insulin-like growth factor II receptor binding sites in the hippocampal formation were found to be differentially altered following systemic administration of kainic acid. A significant decrease in [ 125 I]insulin-like growth factor II receptor sites was observed in CA1 subfield and the pyramidal cell layer of the Ammon's horn at all time points studied whereas the hilar region and the stratum radiatum did not exhibit alteration at any time. A kainate-induced decrease in [ 125 I]insulin receptor binding was noted at all time points in the molecular layer of the

  7. Dependence among sites in RNA evolution

    DEFF Research Database (Denmark)

    Yu, Jiaye; Thorne, Jeffrey L

    2006-01-01

    this gap. In the model, RNA secondary structure links genotype and phenotype by treating the approximate free energy of a sequence folded into a secondary structure as a surrogate for fitness. The underlying idea is that a nucleotide substitution resulting in a more stable secondary structure should have...... a higher rate than a substitution that yields a less stable secondary structure. This free energy approach incorporates evolutionary dependencies among sequence positions beyond those that are reflected simply by jointly modeling change at paired positions in an RNA helix. Although there is not a formal...... a known phylogenetic tree topology. Analyses of 5S ribosomal RNA sequences are presented to illustrate and quantify the strong impact that RNA secondary structure has on substitution rates. Analyses on simulated sequences show that the new inference procedure has reasonable statistical properties...

  8. Properties of the manganese(II) binding site in ternary complexes of Mnter dot ADP and Mnter dot ATP with chloroplast coupling factor 1: Magnetic field dependence of solvent sup 1 H and sup 2 H NMR relaxation rates

    Energy Technology Data Exchange (ETDEWEB)

    Haddy, A.E.; Frasch, W.D.; Sharp, R.R. (Univ. of Michigan, Ann Arbor (USA))

    1989-05-02

    The influence of the binding of ADP and ATP on the high-affinity Mn(II) binding site of chloroplast coupling factor 1 (CF{sub 1}) was studied by analysis of field-dependent solvent proton and deuteron spin-lattice relaxation data. In order to characterize metal-nucleotide complexes of CF{sub 1} under conditions similar to those of the NMR experiments, the enzyme was analyzed for bound nucleotides and Mn(II) after incubation with AdN and MnCl{sub 2} and removal of labile ligands by extensive gel filtration chromatography. In the field-dependent NMR experiments, the Mn(II) binding site of CF{sub 1} was studied for three mole ratios of added Mn(II) to CF{sub 1}, 0.5, 1.0, and 1.5, in the presence of an excess of either ADP or ATP. The results were extrapolated to zero Mn(II) concentration to characterize the environment of the first Mn(II) binding site of Cf{sub 1}. In the presence of both adenine nucleotides, pronounced changes in the Mn(II) environment relative to that in Mn(II)-CF{sub 1} were evident; the local relaxation rate maxima were more pronounced and shifted to higher field strengths, and the relaxation rate per bound Mn(II) increased at all field strengths. Analysis of the data revealed that the number of exchangeable water molecules liganded to bound Mn(II) increased from one in the binary Mn(II)-CF{sub 1} complex to three and two in the ternary Mn(II)-ADP-CF{sub 1} and Mn(II)-ATP-CF{sub 1} complexes, respectively; these results suggest that a water ligand to bound Mn(II) in the Mn(II)-ADP-CF{sub 1} complex is replaced by the {gamma}-phosphate of ATP in the Mn(II)-ATP-CF{sub 1} complex. A binding model is presented to account for these observations.

  9. Socio-emotional factors in alcohol dependence

    OpenAIRE

    Deyashini Lahiri Tikka; Daya Ram; Indu Dubey; Sai Krishna Tikka

    2014-01-01

    Background: Alcohol-dependent patients are traditionally believed to have insecure attachment styles, higher anger expression, and lower self-esteem. There is a need to study them together. Aim: To understand the relationships amongst various of the socio-emotional factors. Materials and Methods: Forty male patients with Alcohol dependence syndrome and 40 matched healthy controls (General Health Questionnaire-12 score

  10. Willow yield is highly dependent on clone and site

    DEFF Research Database (Denmark)

    Ugilt Larsen, Søren; Jørgensen, Uffe; Lærke, Poul Erik

    2014-01-01

    Use of high-yielding genotypes is one of the means to achieve high yield and profitability in willow (Salix spp.) short rotation coppice. This study investigated the performance of eight willow clones (Inger, Klara, Linnea, Resolution, Stina, Terra Nova, Tora, Tordis) on five Danish sites......, differing considerably in soil type, climatic conditions and management. Compared to the best clone, the yield was up to 36 % lower for other clones across sites and up to 51 % lower within sites. Tordis was superior to other clones with dry matter yields between 5.2 and 10.2 Mg ha−1 year−1 during the first...... 3-year harvest rotation, and it consistently ranked as the highest yielding clone on four of the five sites and not significantly lower than the highest yielding clone on the fifth site. The ranking of the other clones was more dependent on site with significant interaction between clone and site...

  11. The metal-ion-dependent adhesion site in the Von Willebrand factor-A domain of α2δ subunits is key to trafficking voltage-gated Ca2+ channels

    Science.gov (United States)

    Cantí, C.; Nieto-Rostro, M.; Foucault, I.; Heblich, F.; Wratten, J.; Richards, M. W.; Hendrich, J.; Douglas, L.; Page, K. M.; Davies, A.; Dolphin, A. C.

    2005-01-01

    All auxiliary α2δ subunits of voltage-gated Ca2+ (CaV) channels contain an extracellular Von Willebrand factor-A (VWA) domain that, in α2δ-1 and -2, has a perfect metal-ion-dependent adhesion site (MIDAS). Modeling of the α2δ-2 VWA domain shows it to be highly likely to bind a divalent cation. Mutating the three key MIDAS residues responsible for divalent cation binding resulted in a MIDAS mutant α2δ-2 subunit that was still processed and trafficked normally when it was expressed alone. However, unlike WT α2δ-2, the MIDAS mutant α2δ-2 subunit did not enhance and, in some cases, further diminished CaV1.2, -2.1, and -2.2 currents coexpressed with β1b by using either Ba2+ or Na+ as a permeant ion. Furthermore, expression of the MIDAS mutant α2δ-2 reduced surface expression and strongly increased the perinuclear retention of CaVα1 subunits at the earliest time at which expression was observed in both Cos-7 and NG108–15 cells. Despite the presence of endogenous α2δ subunits, heterologous expression of α2δ-2 in differentiated NG108–15 cells further enhanced the endogenous high-threshold Ca2+ currents, whereas this enhancement was prevented by the MIDAS mutations. Our results indicate that α2δ subunits normally interact with the CaVα1 subunit early in their maturation, before the appearance of functional plasma membrane channels, and an intact MIDAS motif in the α2δ subunit is required to promote trafficking of the α1 subunit to the plasma membrane by an integrin-like switch. This finding provides evidence for a primary role of a VWA domain in intracellular trafficking of a multimeric complex, in contrast to the more usual roles in binding extracellular ligands in other exofacial VWA domains. PMID:16061813

  12. Socio-emotional factors in alcohol dependence.

    Science.gov (United States)

    Tikka, Deyashini Lahiri; Ram, Daya; Dubey, Indu; Tikka, Sai Krishna

    2014-04-01

    Alcohol-dependent patients are traditionally believed to have insecure attachment styles, higher anger expression, and lower self-esteem. There is a need to study them together. To understand the relationships amongst various of the socio-emotional factors. Forty male patients with Alcohol dependence syndrome and 40 matched healthy controls (General Health Questionnaire-12 score Relationship Scale Questionnaire), anger domains (on State Trait Anger Expression Inventory), and self-esteem (on Rosenberg Self-esteem Scale). Comparison using independent samples t test and chi square test; correlation using Pearson's correlation coefficient. Patients had significantly higher anger expression, 'anger in' and 'anger out,' and lower self-esteem than healthy controls. Severity of alcohol dependence had significant correlation with 'anger out,' and self-esteem had significant negative correlation with anger expression. The present study suggests that the socio-emotional factors studied are developmentally linked to each other.

  13. Site-dependent life-cycle impact assessment of acidification

    DEFF Research Database (Denmark)

    Potting, Josepha Maria Barbara; Schöpp, W.; Blok, Kornelis

    1998-01-01

    The lack of spatial differentiation in current life-cycle impact assessment (LCIA) affects the relevance of the assessed impact. This article first describes a framework for constructing factors relating the region of emission to the acidifying impact on its deposition areas. Next, these factors...... for acidification, eutrophication via air; and tropospheric ozone formation. The application of the acidification factors in LCIA is very straightforward. The only additional data required, the geographical site of the emission, is generally provided by current life-cycle inventory analysis. The acidification...... factors add resolving power of a factor of 1,000 difference between the highest and lowest ratings, while the combined uncertainties in the RAINS model are canceled out to a large extent in the acidification factors as a result of the large number of ecosystems they cover The framework presented is also...

  14. Smartphone dependence classification using tensor factorization

    Science.gov (United States)

    Kim, Yejin; Yook, In Hye; Yu, Hwanjo; Kim, Dai-Jin

    2017-01-01

    Excessive smartphone use causes personal and social problems. To address this issue, we sought to derive usage patterns that were directly correlated with smartphone dependence based on usage data. This study attempted to classify smartphone dependence using a data-driven prediction algorithm. We developed a mobile application to collect smartphone usage data. A total of 41,683 logs of 48 smartphone users were collected from March 8, 2015, to January 8, 2016. The participants were classified into the control group (SUC) or the addiction group (SUD) using the Korean Smartphone Addiction Proneness Scale for Adults (S-Scale) and a face-to-face offline interview by a psychiatrist and a clinical psychologist (SUC = 23 and SUD = 25). We derived usage patterns using tensor factorization and found the following six optimal usage patterns: 1) social networking services (SNS) during daytime, 2) web surfing, 3) SNS at night, 4) mobile shopping, 5) entertainment, and 6) gaming at night. The membership vectors of the six patterns obtained a significantly better prediction performance than the raw data. For all patterns, the usage times of the SUD were much longer than those of the SUC. From our findings, we concluded that usage patterns and membership vectors were effective tools to assess and predict smartphone dependence and could provide an intervention guideline to predict and treat smartphone dependence based on usage data. PMID:28636614

  15. Smartphone dependence classification using tensor factorization.

    Directory of Open Access Journals (Sweden)

    Jingyun Choi

    Full Text Available Excessive smartphone use causes personal and social problems. To address this issue, we sought to derive usage patterns that were directly correlated with smartphone dependence based on usage data. This study attempted to classify smartphone dependence using a data-driven prediction algorithm. We developed a mobile application to collect smartphone usage data. A total of 41,683 logs of 48 smartphone users were collected from March 8, 2015, to January 8, 2016. The participants were classified into the control group (SUC or the addiction group (SUD using the Korean Smartphone Addiction Proneness Scale for Adults (S-Scale and a face-to-face offline interview by a psychiatrist and a clinical psychologist (SUC = 23 and SUD = 25. We derived usage patterns using tensor factorization and found the following six optimal usage patterns: 1 social networking services (SNS during daytime, 2 web surfing, 3 SNS at night, 4 mobile shopping, 5 entertainment, and 6 gaming at night. The membership vectors of the six patterns obtained a significantly better prediction performance than the raw data. For all patterns, the usage times of the SUD were much longer than those of the SUC. From our findings, we concluded that usage patterns and membership vectors were effective tools to assess and predict smartphone dependence and could provide an intervention guideline to predict and treat smartphone dependence based on usage data.

  16. Smartphone dependence classification using tensor factorization.

    Science.gov (United States)

    Choi, Jingyun; Rho, Mi Jung; Kim, Yejin; Yook, In Hye; Yu, Hwanjo; Kim, Dai-Jin; Choi, In Young

    2017-01-01

    Excessive smartphone use causes personal and social problems. To address this issue, we sought to derive usage patterns that were directly correlated with smartphone dependence based on usage data. This study attempted to classify smartphone dependence using a data-driven prediction algorithm. We developed a mobile application to collect smartphone usage data. A total of 41,683 logs of 48 smartphone users were collected from March 8, 2015, to January 8, 2016. The participants were classified into the control group (SUC) or the addiction group (SUD) using the Korean Smartphone Addiction Proneness Scale for Adults (S-Scale) and a face-to-face offline interview by a psychiatrist and a clinical psychologist (SUC = 23 and SUD = 25). We derived usage patterns using tensor factorization and found the following six optimal usage patterns: 1) social networking services (SNS) during daytime, 2) web surfing, 3) SNS at night, 4) mobile shopping, 5) entertainment, and 6) gaming at night. The membership vectors of the six patterns obtained a significantly better prediction performance than the raw data. For all patterns, the usage times of the SUD were much longer than those of the SUC. From our findings, we concluded that usage patterns and membership vectors were effective tools to assess and predict smartphone dependence and could provide an intervention guideline to predict and treat smartphone dependence based on usage data.

  17. Biophysical fitness landscapes for transcription factor binding sites.

    Directory of Open Access Journals (Sweden)

    Allan Haldane

    2014-07-01

    Full Text Available Phenotypic states and evolutionary trajectories available to cell populations are ultimately dictated by complex interactions among DNA, RNA, proteins, and other molecular species. Here we study how evolution of gene regulation in a single-cell eukaryote S. cerevisiae is affected by interactions between transcription factors (TFs and their cognate DNA sites. Our study is informed by a comprehensive collection of genomic binding sites and high-throughput in vitro measurements of TF-DNA binding interactions. Using an evolutionary model for monomorphic populations evolving on a fitness landscape, we infer fitness as a function of TF-DNA binding to show that the shape of the inferred fitness functions is in broad agreement with a simple functional form inspired by a thermodynamic model of two-state TF-DNA binding. However, the effective parameters of the model are not always consistent with physical values, indicating selection pressures beyond the biophysical constraints imposed by TF-DNA interactions. We find little statistical support for the fitness landscape in which each position in the binding site evolves independently, indicating that epistasis is common in the evolution of gene regulation. Finally, by correlating TF-DNA binding energies with biological properties of the sites or the genes they regulate, we are able to rule out several scenarios of site-specific selection, under which binding sites of the same TF would experience different selection pressures depending on their position in the genome. These findings support the existence of universal fitness landscapes which shape evolution of all sites for a given TF, and whose properties are determined in part by the physics of protein-DNA interactions.

  18. Biophysical fitness landscapes for transcription factor binding sites.

    Science.gov (United States)

    Haldane, Allan; Manhart, Michael; Morozov, Alexandre V

    2014-07-01

    Phenotypic states and evolutionary trajectories available to cell populations are ultimately dictated by complex interactions among DNA, RNA, proteins, and other molecular species. Here we study how evolution of gene regulation in a single-cell eukaryote S. cerevisiae is affected by interactions between transcription factors (TFs) and their cognate DNA sites. Our study is informed by a comprehensive collection of genomic binding sites and high-throughput in vitro measurements of TF-DNA binding interactions. Using an evolutionary model for monomorphic populations evolving on a fitness landscape, we infer fitness as a function of TF-DNA binding to show that the shape of the inferred fitness functions is in broad agreement with a simple functional form inspired by a thermodynamic model of two-state TF-DNA binding. However, the effective parameters of the model are not always consistent with physical values, indicating selection pressures beyond the biophysical constraints imposed by TF-DNA interactions. We find little statistical support for the fitness landscape in which each position in the binding site evolves independently, indicating that epistasis is common in the evolution of gene regulation. Finally, by correlating TF-DNA binding energies with biological properties of the sites or the genes they regulate, we are able to rule out several scenarios of site-specific selection, under which binding sites of the same TF would experience different selection pressures depending on their position in the genome. These findings support the existence of universal fitness landscapes which shape evolution of all sites for a given TF, and whose properties are determined in part by the physics of protein-DNA interactions.

  19. Smartphone dependence classification using tensor factorization

    OpenAIRE

    Choi, Jingyun; Rho, Mi Jung; Kim, Yejin; Yook, In Hye; Yu, Hwanjo; Kim, Dai-Jin; Choi, In Young

    2017-01-01

    Excessive smartphone use causes personal and social problems. To address this issue, we sought to derive usage patterns that were directly correlated with smartphone dependence based on usage data. This study attempted to classify smartphone dependence using a data-driven prediction algorithm. We developed a mobile application to collect smartphone usage data. A total of 41,683 logs of 48 smartphone users were collected from March 8, 2015, to January 8, 2016. The participants were classified ...

  20. Incorporating evolution of transcription factor binding sites into ...

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    Incorporating evolution of transcription factor binding sites into annotated alignments. 841. J. Biosci. 32(5), August 2007. 1. Introduction. A majority of computational approaches that aim to predict transcription factor binding sites employ cross- species comparison to focus on conserved locations. Such a comparison helps in ...

  1. Rank-dependant factorization of entanglement evolution

    International Nuclear Information System (INIS)

    Siomau, Michael

    2016-01-01

    Highlights: • In some cases the complex entanglement evolution can be factorized on simple terms. • We suggest factorization equations for multiqubit entanglement evolution. • The factorization is solely defined by the rank of the final state density matrices. • The factorization is independent on the local noisy channels and initial pure states. - Abstract: The description of the entanglement evolution of a complex quantum system can be significantly simplified due to the symmetries of the initial state and the quantum channels, which simultaneously affect parts of the system. Using concurrence as the entanglement measure, we study the entanglement evolution of few qubit systems, when each of the qubits is affected by a local unital channel independently on the others. We found that for low-rank density matrices of the final quantum state, such complex entanglement dynamics can be completely described by a combination of independent factors representing the evolution of entanglement of the initial state, when just one of the qubits is affected by a local channel. We suggest necessary conditions for the rank of the density matrices to represent the entanglement evolution through the factors. Our finding is supported with analytical examples and numerical simulations.

  2. Validity and factor structure of the bodybuilding dependence scale

    OpenAIRE

    Smith, D; Hale, B

    2004-01-01

    Objectives: To investigate the factor structure, validity, and reliability of the bodybuilding dependence scale and to investigate differences in bodybuilding dependence between men and women and competitive and non-competitive bodybuilders.

  3. Risk factors in prevention of drug dependences

    NARCIS (Netherlands)

    Orosova, Ol'ga; Gajdosova, Beata; Madarasova-Geckova, Andrea; Van Dijk, Jitse P.

    2007-01-01

    The study presents the state-of-art of knowledge of risk factors of drug use as a form of risk behaviour in adolescents in individual, interpersonal, and environmental domain (family, school, society). The attention is paid to general deviation syndrome and to the construct of general tendency to

  4. Social Network Sites as Educational Factors.

    Science.gov (United States)

    Ebrahimpour, Alireza; Rajabali, Farnaz; Yazdanfar, Fatemeh; Azarbad, Reza; Nodeh, Majid Rezaei; Siamian, Hasan; Vahedi, Mohammad

    2016-04-01

    in this present era, the technology development has established certain type of communication. Nowadays education as the fundamental principle in transferring cognition to the learners has found various methods. Recently the concept that social networks could be effective tool in easing the achievement to the educational goals has been under attention. Therefore, this investigation is trying to find out whether, the social networks could play role on the process of education among students? This cross sectional descriptive study was performed on 1000 students from 7 medical universities in 2015. The data collection tool was questionnaire that was approved Cronbach's alpha: was 0.85. Meanwhile its validity was confirmed too. The obtained data were analyzed by the descriptive statistic, ANOVA, Turkey and used X(2) SPSS-19. In this investigation, 940 subjects were under study. 85% used daily the social network. The highest usage was attributed to the Telegram. 52% preferred image suitable for transferring of information. Even though, 73% believed that these networks have significant effects on coordinating of students with in university charges. Considering the findings of the present study, it is proposed that the universities integrate the social networks in the education programs and recognize it as the awareness factor, therefore benefit it in the educational affairs.

  5. Siting factors for the Swedish deep repository for spent fuel

    International Nuclear Information System (INIS)

    Stroem, A.; Ericsson, Lars O.; Svemar, C.; Almen, K.E.; Andersson, Johan

    1998-01-01

    A project entitled Siting factors and criteria for site evaluation was initiated at the SKB in 1997. The project comprises an important part of the work of siting and site selection that is being pursued within SKB. The purpose of the project is to create a logical structure for the continued siting work, and its results should also be able to be used to assist in evaluating sites. The project will thereby also provide a means - in accordance with the Government's decision regarding Research Programme 95 - to obtain more detailed and quantified siting factors and criteria than those previously presented in the supplement to Research Programme 92. The overall goals of the project are to identify and quantify requirements and preferences regarding the properties of the rock and the soil from the perspectives of long-term safety, performance and planning and design of the rock works, and to identify siting factors and criteria. The latter should be able to be used to determine whether requirements and preferences are satisfied, both when screening sites for site investigation and after completed site investigation. Presented requirements, preferences, factors and criteria must be acceptable to national and municipal authorities or others with influence over the siting work. To start with, requirements and preferences regarding the performance of the rock in a deep repository have been clarified. These requirements and preferences are based on many years of experience of safety assessments and construction analyses within SKB. What is new here is the structuring that has been done, where a classification is made into different geoscientific disciplines, and the formalism that has been developed for the concepts requirements, preferences and performance. This is a prerequisite for a consistent and hopefully comprehensive set of requirements from a functional perspective. Work has continued on siting factors with reference to a coming site investigation programme. A

  6. Factors influencing dependence on mobile phone

    Directory of Open Access Journals (Sweden)

    Mohammad-Hossein Biglu

    2016-08-01

    Full Text Available Introduction: The purpose of current study was to investigate the relationship between the problematic use of mobile phone and Big Five personality traits among students of Tabriz University of Medical Sciences in Tabriz, Iran. Methods: A total number of 120 students (80 females and 40 males were selected by applying proportional randomized classification sampling method from Tabriz University of Medical Sciences. The Mobile Phone Problematic Use Scale (MPPUS and demographic questionnaire were used to gather data. Data were analyzed using SPSS software. Results: Analysis of gathered data showed that gender, neuroticism, extraversion, and openness to experience had positive correlation with the problematic use of mobile phone, whereas conscientiousness and agreeableness were not correlated with the problematic use of mobile phone. Conclusion: The evaluation of Big Five personality traits would be a reliable factor for predicting the problematic use of mobile phone among students.

  7. Reductant-dependent electron distribution among redox sites of laccase

    DEFF Research Database (Denmark)

    Farver, O; Goldberg, M; Wherland, S

    1978-01-01

    Rhus laccase (monophenol monooxygenase, monophenol,dihydroxyphenylalanine:oxygen oxidoreductase, EC 1.14.18.1) an O2/H2O oxidoreductase containing four copper ions bound to three redox sites (type 1, type 2, and type 3 Cu pair), was titrated anaerobically with several reductants having various...

  8. Reductant-dependent electron distribution among redox sites of laccase

    DEFF Research Database (Denmark)

    Farver, O; Goldberg, M; Wherland, S

    1978-01-01

    Rhus laccase (monophenol monooxygenase, monophenol,dihydroxyphenylalanine:oxygen oxidoreductase, EC 1.14.18.1) an O2/H2O oxidoreductase containing four copper ions bound to three redox sites (type 1, type 2, and type 3 Cu pair), was titrated anaerobically with several reductants having various ch...

  9. Validity and factor structure of the bodybuilding dependence scale.

    Science.gov (United States)

    Smith, D; Hale, B

    2004-04-01

    To investigate the factor structure, validity, and reliability of the bodybuilding dependence scale and to investigate differences in bodybuilding dependence between men and women and competitive and non-competitive bodybuilders. Seventy two male competitive bodybuilders, 63 female competitive bodybuilders, 87 male non-competitive bodybuilders, and 63 non-competitive female bodybuilders completed the bodybuilding dependence scale (BDS), the exercise dependence questionnaire (EDQ), and the muscle dysmorphia inventory (MDI). Confirmatory factor analysis of the BDS supported a three factor model of bodybuilding dependence, consisting of social dependence, training dependence, and mastery dependence (Q = 3.16, CFI = 0.98, SRMR = 0.04). Internal reliability of all three subscales was high (Cronbach's alpha = 0.92, 0.92, and 0.93 respectively). Significant (pbodybuilders scored significantly (pbodybuilders. However, there were no significant sex differences on any of the BDS subscales (p>0.05). The three factor BDS appears to be a reliable and valid measure of bodybuilding dependence. Symptoms of bodybuilding dependence are more prevalent in competitive bodybuilders than non-competitive ones, but there are no significant sex differences in bodybuilding dependence.

  10. A Systematic Analysis of Factors Localized to Damaged Chromatin Reveals PARP-Dependent Recruitment of Transcription Factors

    Directory of Open Access Journals (Sweden)

    Lior Izhar

    2015-06-01

    Full Text Available Localization to sites of DNA damage is a hallmark of DNA damage response (DDR proteins. To identify DDR factors, we screened epitope-tagged proteins for localization to sites of chromatin damaged by UV laser microirradiation and found >120 proteins that localize to damaged chromatin. These include the BAF tumor suppressor complex and the amyotrophic lateral sclerosis (ALS candidate protein TAF15. TAF15 contains multiple domains that bind damaged chromatin in a poly-(ADP-ribose polymerase (PARP-dependent manner, suggesting a possible role as glue that tethers multiple PAR chains together. Many positives were transcription factors; > 70% of randomly tested transcription factors localized to sites of DNA damage, and of these, ∼90% were PARP dependent for localization. Mutational analyses showed that localization to damaged chromatin is DNA-binding-domain dependent. By examining Hoechst staining patterns at damage sites, we see evidence of chromatin decompaction that is PARP dependent. We propose that PARP-regulated chromatin remodeling at sites of damage allows transient accessibility of DNA-binding proteins.

  11. Delivery Site Preferences and Associated Factors among Married ...

    African Journals Online (AJOL)

    BACKGROUND: Efforts to reduce maternal mortality and morbidity must address societal and cultural factors that affect women's health and their access to services. There was no research conducted previously on delivery site preferences and associated factors among married women of child bearing age in the study area.

  12. Magnitude and factors associated with post-cesarean surgical site ...

    African Journals Online (AJOL)

    Background: Surgical site infection (SSI) after cesarean section (CS) increases maternal morbidity, hospital stay and medical cost. However, in Ethiopia, limited evidence exists regarding the magnitude and risk factors of post-CS wound infection. The purpose of this study was to determine the prevalence of – and factors ...

  13. RISK FACTORS IN SUICIDE AMONG MALE ALCOHOL DEPENDENTS

    OpenAIRE

    Arun Prasanna; Gandhibabu; Asok Kumar

    2014-01-01

    BACKGROUND: Alcohol dependence is a potent risk factor for completed suicide but data are limited on factors that distinguish risk within this high risk population. AIM: To study the risk factors for suicide attempts among male alcohol dependents. METHODS: This was a case control study conducted from January to July in the Year 2014. Cases and controls were recruited from Department of Psychiatry, Rajah Muthiah Medical College, using various tools such as semi structured p...

  14. Protective actions as a factor in power reactor siting

    Energy Technology Data Exchange (ETDEWEB)

    Gant, K.S.; Schweitzer, M.

    1984-06-01

    This report examines the relationship between a power reactor site and the ease of implementing protective actions (emergency measures a serious accident). Limiting populating density around a reactor lowers the number of people at risk but cannot assure that all protective actions are possible for those who reside near the reactor. While some protective measures can always be taken (i.e., expedient respiratory protection, sheltering) the ability to evacuate the area or find adequate shelter may depend on the characteristics of the area near the reactor site. Generic siting restrictions designed to identify and eliminate these site-specific constraints would be difficult to formulate. The authors suggest identifying possible impediments to protective actions at a proposed reactor site and addressing these problems in the emergency plans. 66 references, 6 figures, 8 tables.

  15. Protective actions as a factor in power reactor siting

    International Nuclear Information System (INIS)

    Gant, K.S.; Schweitzer, M.

    1984-06-01

    This report examines the relationship between a power reactor site and the ease of implementing protective actions (emergency measures a serious accident). Limiting populating density around a reactor lowers the number of people at risk but cannot assure that all protective actions are possible for those who reside near the reactor. While some protective measures can always be taken (i.e., expedient respiratory protection, sheltering) the ability to evacuate the area or find adequate shelter may depend on the characteristics of the area near the reactor site. Generic siting restrictions designed to identify and eliminate these site-specific constraints would be difficult to formulate. The authors suggest identifying possible impediments to protective actions at a proposed reactor site and addressing these problems in the emergency plans. 66 references, 6 figures, 8 tables

  16. Accident Causal Factors on the Building Construction Sites: A Review

    Directory of Open Access Journals (Sweden)

    Opeyemi Samuel Williams

    2018-01-01

    Full Text Available The concerns for cost, quality and timely delivery of projects have been in existence from time immemorial, whereas the passion for these should be extended to safe execution of site works by the construction participants, as safety of life is very paramount. However, high level of commitment that is essential for the safe execution of site works has become a taboo. Hence, a plethora of accidents takes place on the site ranging from falls from height, contact with working tools, vehicle-related, slip and trip, collapse, exposure to harmful substances, to lifting and handling object accidents. It is pertinent to know that, responsibility for accidents on site cuts across all project participants (clients, consultants, contractors, workers, as well as the construction site environment. Recognition of the construction participants and site environmental factors as agents of accident is the focus of this research. Through extensive review of literature, a copious number of factors were identified and subsequently grouped under five factors as client-related, consultant-related, contractor-related, construction workers-related, and construction site-related. However, there has been a dearth of research in the grouping of accident contributing factors. The identification and understanding of these factors will go a long way in mitigating construction accidents, coupled with proven measures taken in positively addressing them. Efforts to prevent these causative factors include inter alia elimination of hazards from design, effective safety management, adequate planning of activities and employment of seasoned professionals by the client. The contractors are to embark on staff safety auditing, set up safety committees, conduct regular training for staff, use innovative technology, uphold housekeeping and report accident occurrence, while strict adherence to safety regulations must be adopted by all construction operatives.

  17. Multiple criteria landfill site selection method incorporating the NIMBY factors

    Science.gov (United States)

    Salleh, Abdul Hakim; Ahamad, Mohd Sanusi S.; Yusoff, Mohd Suffian; Aziz, Hamidi Abdul

    2017-10-01

    Waste management and disposal issues one way or another need to be resolved correctly. Today, every developing country is facing the very common question of finding the best suitable site for a landfill. Relying on the technical factors alone would not solve the problem, but the best suitable sites for landfill need to consider the Not-In-My-Backyard (NIMBY) policy in resisting the pressure from unwanted development within the neighborhood or town. Therefore, the main objective of this paper is to propose a sustainable approach in finding and determining the best landfill site using GIS. A spatial analytical study is presented by applying various criteria derived from several types of spatial data available in the search for the most suitable landfill site in three (3) districts of Kuala Muda, Kulim and Baling, in Kedah. The results of the analysis have not only satisfied the technical factors but have also put into consideration the public opposition to the NIMBY issues.

  18. Feasibility of applying site-dependent impact assessment of acidification in LCA

    NARCIS (Netherlands)

    Bellekom, A.A.; Potting, J; Benders, R.M.J.

    2006-01-01

    Goal, Scope and Background. Taking into account the location of emissions and its subsequent, site-dependent impacts improves the accuracy of LCIA. Opponents of site-dependent impact assessment argue that it is too time-consuming to collect the required additional inventory data. In this paper we

  19. DIAGNOSIS OF RISK FACTORS FOR BEER DEPENDENCE IN YOUNG PEOPLE

    Directory of Open Access Journals (Sweden)

    G. A. Novikova

    2017-10-01

    Full Text Available In the article the approach to identification of factors influencing beer consumption by young people. Describes the author’s methodology, identifying biological, social, psychological, pedagogical and economic risk factors of development of beer dependence in young people. The data obtained using the proposed methodology can be used to identify risk groups according to the dependent behavior and planning of preventive measures.

  20. Five-factor model personality traits in opioid dependence

    OpenAIRE

    Kornør, Hege; Nordvik, Hilmar

    2007-01-01

    Background: Personality traits may form a part of the aetiology of opioid dependence. For instance, opioid dependence may result from self-medication in emotionally unstable individuals, or from experimenting with drugs in sensation seekers. The five factor model (FFM) has obtained a central position in contemporary personality trait theory. The five factors are: Neuroticism, Extraversion, Openness to Experience, Agreeableness and Conscientiousness. Few studies have examined whether the...

  1. [Risk factors related to surgical site infection in elective surgery].

    Science.gov (United States)

    Angeles-Garay, Ulises; Morales-Márquez, Lucy Isabel; Sandoval-Balanzarios, Miguel Antonio; Velázquez-García, José Arturo; Maldonado-Torres, Lulia; Méndez-Cano, Andrea Fernanda

    2014-01-01

    The risk factors for surgical site infections in surgery should be measured and monitored from admission to 30 days after the surgical procedure, because 30% of Surgical Site Infection is detected when the patient was discharged. Calculate the Relative Risk of associated factors to surgical site infections in adult with elective surgery. Patients were classified according to the surgery contamination degree; patient with surgery clean was defined as no exposed and patient with clean-contaminated or contaminated surgery was defined exposed. Risk factors for infection were classified as: inherent to the patient, pre-operative, intra-operative and post-operative. Statistical analysis; we realized Student t or Mann-Whitney U, chi square for Relative Risk (RR) and multivariate analysis by Cox proportional hazards. Were monitored up to 30 days after surgery 403 patients (59.8% women), 35 (8.7%) developed surgical site infections. The factors associated in multivariate analysis were: smoking, RR of 3.21, underweight 3.4 hand washing unsuitable techniques 4.61, transfusion during the procedure 3.22, contaminated surgery 60, and intensive care stay 8 to 14 days 11.64, permanence of 1 to 3 days 2.4 and use of catheter 1 to 3 days 2.27. To avoid all risk factors is almost impossible; therefore close monitoring of elective surgery patients can prevent infectious complications.

  2. Blood donor show behaviour after an invitation to donate: The influence of collection site factors.

    Science.gov (United States)

    Merz, E-M; Zijlstra, B J H; de Kort, W L A M

    2017-10-01

    Show behaviour after invitation to donate varies considerably across donors. More insight into this variation is important for blood banks in achieving stable stocks. This study examined individual factors determining intended show behaviour. Most importantly, however, this study is the first study to account for variation in donor behaviour across different collection sites. We applied a multilevel approach to data from Donor InSight, including 11 889 donors from 257 fixed and mobile collection sites in the Netherlands. The aim of the multilevel models was to account for variance at two levels, that is donors and collection sites. We estimated the likelihood of showing after invitation based on individual predictors, including demographics, donation history and attitude. At the collection site level, we included satisfaction with the blood bank aggregated from individual responses by donors who donate at this site, opening hours and collection site type, that is fixed/mobile. Most importantly, show behaviour varied considerably across collection sites and depended on characteristics of these sites. Moreover, women, older and more experienced donors had higher odds of showing after invitation than men, younger and less experienced donors. Donors higher on warm glow, self-efficacy and donor identity more likely showed after an invitation. Higher aggregate satisfaction and donating at fixed collection sites increased the odds of show. In addition to individual factors, collection site characteristics are important in explaining variation in donor show behaviour, thus presenting clues for blood bank policies and interventions to improve donor show. © 2017 International Society of Blood Transfusion.

  3. Characterization of the protein Z-dependent protease inhibitor interactive-sites of protein Z.

    Science.gov (United States)

    Qureshi, Shabir H; Lu, Qiuya; Manithody, Chandrashekhara; Yang, Likui; Rezaie, Alireza R

    2014-09-01

    Protein Z (PZ) has been reported to promote the inactivation of factor Xa (FXa) by PZ-dependent protease inhibitor (ZPI) by about three orders of magnitude. Previously, we prepared a chimeric PZ in which its C-terminal pseudo-catalytic domain was grafted on FX light-chain (Gla and EGF-like domains) (PZ/FX-LC). Characterization of PZ/FX-LC revealed that the ZPI interactive-site is primarily located within PZ pseudo-catalytic domain. Nevertheless, the cofactor function and apparent Kd of PZ/FX-LC for interaction with ZPI remained impaired ~6-7-fold, suggesting that PZ contains a ZPI interactive-site outside pseudo-catalytic domain. X-ray structural data indicates that Tyr-240 of ZPI interacts with EGF2-domain of PZ. Structural data further suggests that 3 other ZPI surface loops make salt-bridge interactions with PZ pseudo-catalytic domain. To identify ZPI interactive-sites on PZ, we grafted the N-terminal EGF2 subdomain of PZ onto PZ/FX-LC chimera (PZ-EGF2/FX-LC) and also generated two compensatory charge reversal mutants of PZ pseudo-catalytic domain (Glu-244 and Arg-212) and ZPI surface loops (Lys-239 and Asp-293). PZ chimeras were expressed in mammalian cells and ZPI derivatives were expressed in Escherichia coli. The PZ EGF2 subdomain fusion restored the defective cofactor function of PZ/FX-LC. The activities of PZ and ZPI mutants were all impaired if assayed individually, but partially restored if the compensatory charge reversal mutants were used in the assay. PZ EGF2 subdomain constitutes an interactive-site for ZPI. Data with compensatory charge reversal mutants validates structural data that the identified residues are part of interactive-sites. Insight is provided into mechanisms through which specificity of ZPI-PZ-FXa complex formation is determined. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Risk Factors of Surgical Site Infection at Muhimbili National Hospital ...

    African Journals Online (AJOL)

    Superficial SSI was the most commonly observed type, 54.8%. Overall HIV prevalence in this study was 16.9% with a 5 times risk of developing SSI. Conclusions: Surgical site infection has remained a major Nosocomial infection in developing countries. Factors shown to be associated with increased risk are wound class, ...

  5. Risk factors for surgical site infections following clean orthopaedic ...

    African Journals Online (AJOL)

    It is recommended that preoperative hospital stay should be as short as possible and extra care/precautions taken when working on the elderly, using implants or requiring drainage. Keywords: Clean orthopaedic operations, risk factors, surgical site infection. Nigerian Journal of Clinical Practice • Oct-Dec 2013 • Vol 16 ...

  6. Geoscientific evaluation factors and criteria for siting and site evaluation. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Stroem, A.; Ericsson, Lars O.; Svemar, C. [Swedish Nuclear Fuel and Waste Management Co., Stockholm (Sweden); Almen, K.E. [KEA GEO-konsult AB (Sweden); Andersson, Johan [Golder Grundteknik KB (Sweden)

    1999-03-01

    The purposes of the present report are to: present the work that has been done to identify the parameters that need to be determined in a geoscientific site investigation and that serve as the basis for the work with geoscientific evaluation factors; give a progress report from the project that was initiated in 1997 named Siting Factors and Criteria for Site Evaluation, with an emphasis on definitions, outline and structure for the execution of the work; present geoscientific requirements on function both general and in detail in the form of an example for the discipline rock mechanics; present geoscientific evaluation factors associated with different stages in the siting work in the form of an example for the discipline hydrogeochemical composition; present plans for further work as regards criteria for site evaluation in different siting stages. The project is under way, and this is to be regarded as a progress report since e.g. criteria for site evaluation will be presented at a later date. The long-term performance and safety of the deep repository must always be evaluated by means of an integrated safety assessment. The work with factors and criteria can never take the place of such an assessment, but can provide guidance regarding its outcome. Requirements and preferences regarding the function of the rock in the deep repository have been clarified in this progress report. What is new here is the structuring that has been carried out, with a classification into different geoscientific disciplines, and the formalism that has been given to the terms requirement, preference and function. Based on fundamental safety and construction functions, requirements on function have been specified for the disciplines geology, thermal properties, hydro-geology, rock mechanics, chemistry and transport properties. Furthermore, function analyses have been identified by means of which it is possible to concretize requirements on function and which geoscientific parameters are

  7. Structural Fingerprints of Transcription Factor Binding Site Regions

    Directory of Open Access Journals (Sweden)

    Peter Willett

    2009-03-01

    Full Text Available Fourier transforms are a powerful tool in the prediction of DNA sequence properties, such as the presence/absence of codons. We have previously compiled a database of the structural properties of all 32,896 unique DNA octamers. In this work we apply Fourier techniques to the analysis of the structural properties of human chromosomes 21 and 22 and also to three sets of transcription factor binding sites within these chromosomes. We find that, for a given structural property, the structural property power spectra of chromosomes 21 and 22 are strikingly similar. We find common peaks in their power spectra for both Sp1 and p53 transcription factor binding sites. We use the power spectra as a structural fingerprint and perform similarity searching in order to find transcription factor binding site regions. This approach provides a new strategy for searching the genome data for information. Although it is difficult to understand the relationship between specific functional properties and the set of structural parameters in our database, our structural fingerprints nevertheless provide a useful tool for searching for function information in sequence data. The power spectrum fingerprints provide a simple, fast method for comparing a set of functional sequences, in this case transcription factor binding site regions, with the sequences of whole chromosomes. On its own, the power spectrum fingerprint does not find all transcription factor binding sites in a chromosome, but the results presented here show that in combination with other approaches, this technique will improve the chances of identifying functional sequences hidden in genomic data.

  8. Transcription factor binding sites prediction based on modified nucleosomes.

    Directory of Open Access Journals (Sweden)

    Mohammad Talebzadeh

    Full Text Available In computational methods, position weight matrices (PWMs are commonly applied for transcription factor binding site (TFBS prediction. Although these matrices are more accurate than simple consensus sequences to predict actual binding sites, they usually produce a large number of false positive (FP predictions and so are impoverished sources of information. Several studies have employed additional sources of information such as sequence conservation or the vicinity to transcription start sites to distinguish true binding regions from random ones. Recently, the spatial distribution of modified nucleosomes has been shown to be associated with different promoter architectures. These aligned patterns can facilitate DNA accessibility for transcription factors. We hypothesize that using data from these aligned and periodic patterns can improve the performance of binding region prediction. In this study, we propose two effective features, "modified nucleosomes neighboring" and "modified nucleosomes occupancy", to decrease FP in binding site discovery. Based on these features, we designed a logistic regression classifier which estimates the probability of a region as a TFBS. Our model learned each feature based on Sp1 binding sites on Chromosome 1 and was tested on the other chromosomes in human CD4+T cells. In this work, we investigated 21 histone modifications and found that only 8 out of 21 marks are strongly correlated with transcription factor binding regions. To prove that these features are not specific to Sp1, we combined the logistic regression classifier with the PWM, and created a new model to search TFBSs on the genome. We tested the model using transcription factors MAZ, PU.1 and ELF1 and compared the results to those using only the PWM. The results show that our model can predict Transcription factor binding regions more successfully. The relative simplicity of the model and capability of integrating other features make it a superior method

  9. SNOSite: exploiting maximal dependence decomposition to identify cysteine S-nitrosylation with substrate site specificity.

    Directory of Open Access Journals (Sweden)

    Tzong-Yi Lee

    Full Text Available S-nitrosylation, the covalent attachment of a nitric oxide to (NO the sulfur atom of cysteine, is a selective and reversible protein post-translational modification (PTM that regulates protein activity, localization, and stability. Despite its implication in the regulation of protein functions and cell signaling, the substrate specificity of cysteine S-nitrosylation remains unknown. Based on a total of 586 experimentally identified S-nitrosylation sites from SNAP/L-cysteine-stimulated mouse endothelial cells, this work presents an informatics investigation on S-nitrosylation sites including structural factors such as the flanking amino acids composition, the accessible surface area (ASA and physicochemical properties, i.e. positive charge and side chain interaction parameter. Due to the difficulty to obtain the conserved motifs by conventional motif analysis, maximal dependence decomposition (MDD has been applied to obtain statistically significant conserved motifs. Support vector machine (SVM is applied to generate predictive model for each MDD-clustered motif. According to five-fold cross-validation, the MDD-clustered SVMs could achieve an accuracy of 0.902, and provides a promising performance in an independent test set. The effectiveness of the model was demonstrated on the correct identification of previously reported S-nitrosylation sites of Bos taurus dimethylarginine dimethylaminohydrolase 1 (DDAH1 and human hemoglobin subunit beta (HBB. Finally, the MDD-clustered model was adopted to construct an effective web-based tool, named SNOSite (http://csb.cse.yzu.edu.tw/SNOSite/, for identifying S-nitrosylation sites on the uncharacterized protein sequences.

  10. Five-factor model personality traits in opioid dependence.

    Science.gov (United States)

    Kornør, Hege; Nordvik, Hilmar

    2007-08-06

    Personality traits may form a part of the aetiology of opioid dependence. For instance, opioid dependence may result from self-medication in emotionally unstable individuals, or from experimenting with drugs in sensation seekers. The five factor model (FFM) has obtained a central position in contemporary personality trait theory. The five factors are: Neuroticism, Extraversion, Openness to Experience, Agreeableness and Conscientiousness. Few studies have examined whether there is a distinct personality pattern associated with opioid dependence. We compared FFM personality traits in 65 opioid dependent persons (mean age 27 years, 34% females) in outpatient counselling after a minimum of 5 weeks in buprenorphine replacement therapy, with those in a non-clinical, age- and sex-matched sample selected from a national database. Personality traits were assessed by a Norwegian version of the Revised NEO Personality Inventory (NEO PI-R), a 240-item self-report questionnaire. Cohen's d effect sizes were calculated for the differences in personality trait scores. The opioid-dependent sample scored higher on Neuroticism, lower on Extraversion and lower on Conscientiousness (d = -1.7, 1.2 and 1.7, respectively) than the controls. Effects sizes were small for the difference between the groups in Openness to experience scores and Agreeableness scores. We found differences of medium and large effect sizes between the opioid dependent group and the matched comparison group, suggesting that the personality traits of people with opioid dependence are in fact different from those of non-clinical peers.

  11. A temperature dependent slip factor based thermal model for friction ...

    Indian Academy of Sciences (India)

    This paper proposes a new slip factor based three-dimensional thermal model to predict the temperature distribution during friction stir welding of 304L stainless steel plates. The proposed model employs temperature and radius dependent heat source to study the thermal cycle, temperature distribution, power required, the ...

  12. A temperature dependent slip factor based thermal model for friction

    Indian Academy of Sciences (India)

    This paper proposes a new slip factor based three-dimensional thermal model to predict the temperature distribution during friction stir welding of 304L stainless steel plates. The proposed model employs temperature and radius dependent heat source to study the thermal cycle, temperature distribution, power required, the ...

  13. Approximate factorization for time-dependent partial differential equations

    NARCIS (Netherlands)

    P.J. van der Houwen; B.P. Sommeijer (Ben)

    1999-01-01

    textabstractThe first application of approximate factorization in the numerical solution of time-dependent partial differential equations (PDEs) can be traced back to the celebrated papers of Peaceman and Rachford and of Douglas in 1955. For linear problems, the Peaceman-Rachford- Douglas method can

  14. Inhibition of factor-dependent transcription termination in ...

    Indian Academy of Sciences (India)

    2014-01-27

    Jan 27, 2014 ... H-NS might help reinforce xenogene silencing. [Chandraprakash D and Seshasayee ASN 2014 Inhibition of factor-dependent transcription termination in Escherichia coli might relieve xenogene silencing by abrogating H-NS-DNA interactions in vivo. J. Biosci. 39 53–61] DOI10.1007/s12038-014-9413-4. 1.

  15. A systems biology approach to transcription factor binding site prediction.

    Directory of Open Access Journals (Sweden)

    Xiang Zhou

    2010-03-01

    Full Text Available The elucidation of mammalian transcriptional regulatory networks holds great promise for both basic and translational research and remains one the greatest challenges to systems biology. Recent reverse engineering methods deduce regulatory interactions from large-scale mRNA expression profiles and cross-species conserved regulatory regions in DNA. Technical challenges faced by these methods include distinguishing between direct and indirect interactions, associating transcription regulators with predicted transcription factor binding sites (TFBSs, identifying non-linearly conserved binding sites across species, and providing realistic accuracy estimates.We address these challenges by closely integrating proven methods for regulatory network reverse engineering from mRNA expression data, linearly and non-linearly conserved regulatory region discovery, and TFBS evaluation and discovery. Using an extensive test set of high-likelihood interactions, which we collected in order to provide realistic prediction-accuracy estimates, we show that a careful integration of these methods leads to significant improvements in prediction accuracy. To verify our methods, we biochemically validated TFBS predictions made for both transcription factors (TFs and co-factors; we validated binding site predictions made using a known E2F1 DNA-binding motif on E2F1 predicted promoter targets, known E2F1 and JUND motifs on JUND predicted promoter targets, and a de novo discovered motif for BCL6 on BCL6 predicted promoter targets. Finally, to demonstrate accuracy of prediction using an external dataset, we showed that sites matching predicted motifs for ZNF263 are significantly enriched in recent ZNF263 ChIP-seq data.Using an integrative framework, we were able to address technical challenges faced by state of the art network reverse engineering methods, leading to significant improvement in direct-interaction detection and TFBS-discovery accuracy. We estimated the accuracy

  16. Scoring functions for transcription factor binding site prediction

    Directory of Open Access Journals (Sweden)

    Friberg Markus

    2005-04-01

    Full Text Available Abstract Background Transcription factor binding site (TFBS prediction is a difficult problem, which requires a good scoring function to discriminate between real binding sites and background noise. Many scoring functions have been proposed in the literature, but it is difficult to assess their relative performance, because they are implemented in different software tools using different search methods and different TFBS representations. Results Here we compare how several scoring functions perform on both real and semi-simulated data sets in a common test environment. We have also developed two new scoring functions and included them in the comparison. The data sets are from the yeast (S. cerevisiae genome. Our new scoring function LLBG (least likely under the background model performs best in this study. It achieves the best average rank for the correct motifs. Scoring functions based on positional bias performed quite poorly in this study. Conclusion LLBG may provide an interesting alternative to current scoring functions for TFBS prediction.

  17. A method for site-dependent planning and its application to the preselection of sites for thermal power plants

    International Nuclear Information System (INIS)

    Friedrich, R.

    1979-01-01

    In the first part of the paper a computer-aided method for dealing with the problems of site-dependent planning is described. By means of the modular program system COPLAN complex conjunction between locally varying data can be performed rapidly and accurately with respect to spatial orientation. The system consists of data input, numerous ways of processing, and graphical representation of the results. The second part shows the application of the system to preselection of sites for thermal power plants. By means of a method analyzing its usefulness, the suitability of each point in (the German Federal State of) Baden-Wuerttemberg as a power plant site is determined. Compared with the currently used methods of preliminary site selection the present method is distinguished by area-covering calculation, the possibility of balancing up advantages and disadvantages, as well as transparency and suitability for being checked up. The paper establishes and considers criteria from the fields of operational economy, safety, ecology, and district planning. The computations are performed for different orders of preference. It is shown that there are regions of sites which are acceptable with respect to a large spectrum of object systems. (orig.) [de

  18. Five-factor model personality traits in opioid dependence

    Directory of Open Access Journals (Sweden)

    Nordvik Hilmar

    2007-08-01

    Full Text Available Abstract Background Personality traits may form a part of the aetiology of opioid dependence. For instance, opioid dependence may result from self-medication in emotionally unstable individuals, or from experimenting with drugs in sensation seekers. The five factor model (FFM has obtained a central position in contemporary personality trait theory. The five factors are: Neuroticism, Extraversion, Openness to Experience, Agreeableness and Conscientiousness. Few studies have examined whether there is a distinct personality pattern associated with opioid dependence. Methods We compared FFM personality traits in 65 opioid dependent persons (mean age 27 years, 34% females in outpatient counselling after a minimum of 5 weeks in buprenorphine replacement therapy, with those in a non-clinical, age- and sex-matched sample selected from a national database. Personality traits were assessed by a Norwegian version of the Revised NEO Personality Inventory (NEO PI-R, a 240-item self-report questionnaire. Cohen's d effect sizes were calculated for the differences in personality trait scores. Results The opioid-dependent sample scored higher on Neuroticism, lower on Extraversion and lower on Conscientiousness (d = -1.7, 1.2 and 1.7, respectively than the controls. Effects sizes were small for the difference between the groups in Openness to experience scores and Agreeableness scores. Conclusion We found differences of medium and large effect sizes between the opioid dependent group and the matched comparison group, suggesting that the personality traits of people with opioid dependence are in fact different from those of non-clinical peers.

  19. Dynamics of a recovering Arctic bird population: the importance of climate, density dependence, and site quality

    Science.gov (United States)

    Bruggeman, Jason E.; Swem, Ted; Andersen, David E.; Kennedy, Patricia L.; Nigro, Debora A.

    2015-01-01

    Intrinsic and extrinsic factors affect vital rates and population-level processes, and understanding these factors is paramount to devising successful management plans for wildlife species. For example, birds time migration in response, in part, to local and broadscale climate fluctuations to initiate breeding upon arrival to nesting territories, and prolonged inclement weather early in the breeding season can inhibit egg-laying and reduce productivity. Also, density-dependent regulation occurs in raptor populations, as territory size is related to resource availability. Arctic Peregrine Falcons (Falco peregrinus tundrius; hereafter Arctic peregrine) have a limited and northern breeding distribution, including the Colville River Special Area (CRSA) in the National Petroleum Reserve–Alaska, USA. We quantified influences of climate, topography, nest productivity, prey habitat, density dependence, and interspecific competition affecting Arctic peregrines in the CRSA by applying the Dail-Madsen model to estimate abundance and vital rates of adults on nesting cliffs from 1981 through 2002. Arctic peregrine abundance increased throughout the 1980s, which spanned the population's recovery from DDT-induced reproductive failure, until exhibiting a stationary trend in the 1990s. Apparent survival rate (i.e., emigration; death) was negatively correlated with the number of adult Arctic peregrines on the cliff the previous year, suggesting effects of density-dependent population regulation. Apparent survival and arrival rates (i.e., immigration; recruitment) were higher during years with earlier snowmelt and milder winters, and apparent survival was positively correlated with nesting season maximum daily temperature. Arrival rate was positively correlated with average Arctic peregrine productivity along a cliff segment from the previous year and initial abundance was positively correlated with cliff height. Higher cliffs with documented higher productivity (presumably

  20. Evaluation of design safety factors for time-dependent buckling

    International Nuclear Information System (INIS)

    Stone, C.M.; Nickell, R.E.

    1977-02-01

    The ASME Boiler and Pressure Vessel Code rules concerning time-dependent (creep) buckling for Class 1 nuclear components have recently been changed. Previous requirements for a factor of ten on service life have been replaced with a factor of safety of 1.5 on loading for load-controlled buckling. This report examines the supposed equivalence of the two rules from the standpoint of materials behavior--specifically, the secondary creep strain rate exponent. The comparison is made using results obtained numerically for an axially-loaded, cylindrical shell with varying secondary creep exponents. A computationally efficient scheme for analyzing creep buckling problems is also presented

  1. Number of osteoporotic sites as a modifying factor for bone mineral density.

    Science.gov (United States)

    Lee, Jong Seok; Lee, Sungwha; Ryu, Ohk-Hyun; Choi, Moon-Gi; Kim, Youn Ji

    2015-11-01

    Discordance has been proposed as a new predictor of fracture risk that may affect fracture risk via bone mineral density (BMD). With an emphasis on better understanding the relationship between discordance and BMD, the aim of this study was to determine the effect of the number of osteoporotic sites, as an indicator of discordance, on BMD and to explore the clinical significance of BMD modification by this factor. This study was based on data obtained from the Korea National Health and Nutrition Examination Survey 2008-2011, which is a nationwide cross-sectional study. Among postmenopausal women aged 50 years or older, 3,849 women whose BMD was measured at three sites (lumbar spine, femoral neck, and total hip) were included in the study. The diagnosis was consistent across sites in only 39.2-59.0 % of cases. Lumbar spine T-score was reduced by 0.163 for two osteoporotic sites and by 0.462 for three osteoporotic sites, compared with having one osteoporotic site at the lumbar spine only. Femoral neck T-score was reduced by 0.609 for three osteoporotic sites compared with one or two osteoporotic sites. Using BMD adjusted for discordance, we found fracture risk probability changed significantly. Our results confirmed that BMD discordance was considerably high among Korean women in their 50s and older owing to site-dependent differences in the pattern of BMD reduction with age. Mean BMD decreased with increasing number of osteoporotic sites. Using a modified BMD adjusted for the number of osteoporotic sites may offer more accurate fracture risk assessment.

  2. Risk factors for surgical site infection after dermatological surgery.

    Science.gov (United States)

    Heal, Clare F; Buettner, Petra G; Drobetz, Herwig

    2012-07-01

      Surgical site infection (SSI) following minor surgery contributes to patient morbidity and compromises cosmetic outcomes. The purpose of this study was to determine the incidence of and risk factors for SSI after dermatological surgery in general practice.   A prospective, observational study which assessed infection among 972 patients was conducted in regional north Queensland, Australia. Consecutive patients presenting for minor skin excisions were invited to participate. Wounds were assessed for SSI at the time of removal of sutures. Infection occurred in 85 of the 972 excisions; thus, the overall incidence of infection was 8.7% (95% confidence interval 6.5-11.0). Excisions in the upper (Prisk factors for wound infection. The length of the excision (Prisk factors for infection. Diabetes was not found to be an independent risk factor for infection (P=0.891). Prophylactic antibiotics are probably prescribed excessively or inappropriately for dermatological surgery, and overall we wish to discourage their use. The results of this study may encourage the more judicial use of prophylactic antibiotics by defining high-risk procedures, such as excisions from the extremities, excision of BCC or SCC, and larger excisions, and patients who are at high risk for infection, such as ex-smokers. © 2012 The International Society of Dermatology.

  3. The sandwich estimator approach counting for inter-site dependence of extreme river flow in Sabah

    Science.gov (United States)

    Kahal Musakkal, N. F.; Gabda, D.

    2017-09-01

    Regional estimation method is often used for estimating parameters of a distribution when data are available at many sites in a region to capture inter-site dependence. In this paper, we fit generalized extreme value distribution independently to model data of river flows at each sites in Sabah to avoid extreme value complex modeling. Since our approach violated the condition of spatial analysis, we consider the adjusted standard error to correct the wrong assumption of our marginal approach. As a result, we have an appropriate corrected variance of the generalized extreme value parameters.

  4. Incidence of and risk factors for surgical site infections in women undergoing hysterectomy for endometrial carcinoma.

    Science.gov (United States)

    Tuomi, Taru; Pasanen, Annukka; Leminen, Arto; Bützow, Ralf; Loukovaara, Mikko

    2016-04-01

    The purpose of this study was to determine the incidence of, and risk factors for, surgical site infections in a contemporary cohort of women with endometrial carcinoma. We retrospectively studied 1164 women treated for endometrial carcinoma by hysterectomy at a single institution in 2007-2013. In all, 912 women (78.4%) had minimally invasive hysterectomy. Data on surgical site infections were collected from medical records. Univariate and multivariate analyses were used to identify risk factors for incisional and organ/space infections. Ninety-four women (8.1%) were diagnosed with a surgical site infection. Twenty women (1.7%) had an incisional infection and 74 (6.4%) had an organ/space infection. The associations of 17 clinico-pathologic and surgical variables were tested by univariate analyses. Those variables that were identified as potential risk factors in univariate analyses (p infections as dependent variables. Obesity (body mass index ≥ 30 kg/m(2)), diabetes, and long operative time (>80th centile) were independently associated with a higher risk of incisional infection, whereas minimally invasive surgery was associated with a smaller risk. Smoking, conversion to laparotomy, and lymphadenectomy were associated with a higher risk of organ/space infection. Organ/space infections comprised the majority of surgical site infections. Risk factors for incisional and organ/space infections differed. Minimally invasive hysterectomy was associated with a smaller risk of incisional infections but not of organ/space infections. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

  5. Leveraging cross-species transcription factor binding site patterns

    DEFF Research Database (Denmark)

    Claussnitzer, Melina; Dankel, Simon N; Klocke, Bernward

    2014-01-01

    Genome-wide association studies have revealed numerous risk loci associated with diverse diseases. However, identification of disease-causing variants within association loci remains a major challenge. Divergence in gene expression due to cis-regulatory variants in noncoding regions is central...... diabetes risk loci revealed a striking clustering of distinct homeobox TFBS. We identified the PRRX1 homeobox factor as a repressor of PPARG2 expression in adipose cells and demonstrate its adverse effect on lipid metabolism and systemic insulin sensitivity, dependent on the rs4684847 risk allele...

  6. Factors influencing clinical trial site selection in Europe: the Survey of Attitudes towards Trial sites in Europe (the SAT-EU Study).

    Science.gov (United States)

    Gehring, Marta; Taylor, Rod S; Mellody, Marie; Casteels, Brigitte; Piazzi, Angela; Gensini, Gianfranco; Ambrosio, Giuseppe

    2013-11-15

    Applications to run clinical trials in Europe fell 25% between 2007 and 2011. Costs, speed of approvals and shortcomings of European Clinical Trial Directive are commonly invoked to explain this unsatisfactory performance. However, no hard evidence is available on the actual weight of these factors or has it been previously investigated whether other criteria may also impact clinical trial site selection. The Survey of Attitudes towards Trial sites in Europe (SAT-EU Study) was an anonymous, cross-sectional web-based survey that systematically assessed factors impacting European clinical trial site selection. It explored 19 factors across investigator-driven, hospital-driven and environment-driven criteria, and costs. It also surveyed perceptions of the European trial environment. Clinical research organisations (CROs), academic clinical trial units (CTUs) and industry invited to respond. weight assigned to each factor hypothesised to impact trial site selection and trial incidence. Secondary outcome: desirability of European countries to run clinical trials. Responses were obtained from 485 professionals in 34 countries: 49% from BioPharma, 40% from CTUs or CROs. Investigator-dependent, environment-dependent and hospital-dependent factors were rated highly important, costs being less important (p<0.0001). Within environment-driven criteria, pool of eligible patients, speed of approvals and presence of disease-management networks were significantly more important than costs or government financial incentives (p<0.0001). The pattern of response was consistent across respondent groupings (CTU vs CRO vs industry). Considerable variability was demonstrated in the perceived receptivity of countries to undertake clinical trials, with Germany, the UK and the Netherlands rated the best trial markets (p<0.0001). Investigator-dependent factors and ease of approval dominate trial site selection, while costs appear less important. Fostering competitiveness of European clinical

  7. Surgical site infection following cesarean deliveries: trends and risk factors.

    Science.gov (United States)

    Krieger, Yuval; Walfisch, Asnat; Sheiner, Eyal

    2017-01-01

    To identify trends and risk factors for early surgical site infection (SSI) following cesarean delivery (CD). A population-based study comparing characteristics of women who have and have not developed post cesarean SSI was conducted. Deliveries occurred between the years 1988 and 2013 in a tertiary medical center. A multivariable logistic regression model, with backwards elimination, was used to control for confounders. Of the 41 375 cesarean deliveries performed during the study period, 1521 (3.7%) were complicated with SSI. SSI rates significantly deceased over the years, from 7.4% in 1988 to 1.5% in 2012. Using a multivariable regression model, the following independent risk factors for SSI were identified: obesity (OR 2.0; 95% CI, 1.6-2.5); previous CD (OR 1.8; 95% CI, 1.6-2.0); hypertensive disorders (OR 1.4; 95% CI, 1.2-1.6); premature rupture of membranes (OR 1.3; 95% CI, 1.1-1.6); gestational diabetes mellitus (GDM, OR 1.2; 95% CI, 1.1-1.4); and recurrent pregnancy losses (OR 1.2; 95% CI, 1.1-1.5). Independent risk factors for post-cesarean SSI include obesity, GDM, hypertensive disorders of pregnancy, premature rupture of membranes, and recurrent pregnancy losses. Information regarding higher rates of SSI and preventative measures should be provided to these high-risk women prior to surgery.

  8. Laryngotracheal Stenosis: Risk Factors for Tracheostomy Dependence and Dilation Interval

    Science.gov (United States)

    Gadkaree, Shekhar K; Pandian, Vinciya; Best, Simon; Motz, Kevin M; Allen, Clint; Kim, Young; Akst, Lee; Hillel, Alexander T

    2017-02-01

    Objective Laryngotracheal stenosis (LTS) is a fibrotic process that narrows the upper airway and has a significant impact on breathing and phonation. Iatrogenic injury from endotracheal and/or tracheostomy tubes is the most common etiology. This study investigates differences in LTS etiologies as they relate to tracheostomy dependence and dilation interval. Study Design Case series with chart review. Setting Single-center tertiary care facility. Subjects and Methods Review of adult patients with LTS was performed between 2004 and 2015. The association of patient demographics, comorbidities, disease etiology, and treatment modalities with patient outcomes was assessed. Multiple logistic regression analysis and Kaplan-Meier analysis were performed to determine factors associated with tracheostomy dependence and time to second procedure, respectively. Results A total of 262 patients met inclusion criteria. Iatrogenic patients presented with greater stenosis ( P = .023), greater length of stenosis ( P = .004), and stenosis farther from the vocal folds ( P tracheostomy dependence. Nonsmokers, patients without tracheostomy, and idiopathic LTS patients had a significantly longer time to second dilation procedure. Conclusion Iatrogenic LTS presents with a greater disease burden and higher risk of tracheostomy dependence when compared with other etiologies of LTS. Comorbid conditions promoting microvascular injury-including smoking, COPD, and diabetes-were prevalent in the iatrogenic cohort. Changes in hospital practice patterns to promote earlier tracheostomy in high-risk patients could reduce the incidence of LTS.

  9. Transport sensitivity studies for SITE-94: Time-dependent site-scale modelling of future glacial impact

    International Nuclear Information System (INIS)

    King-Clayton, L.; Smith, Paul

    1996-10-01

    The report details the methodology and preliminary results from the modelling of radionuclide transport from a hypothetical repository based at the Aespoe site in Sweden. The work complements and utilizes the results from regional-scale, variable density flow modelling by Provost, in which the groundwater flow field is time dependent, reflecting the impact of climate evolution over the next 130,000 years. The climate evolution include development of permafrost conditions and ice sheet advance and retreat. The results indicate that temporal changes in flow conditions owing to future climate changes have a significant effect on the transport of radionuclides from a repository. In all cases modelled with time-dependent boundary conditions, the greatest radionuclide fluxes occur towards the end of the main glacial periods, and correspond to periods of high groundwater discharge at the margin of the modelled ice sheets. Fluxes to the biosphere may, for limited periods (2000 years or less), be three times higher than those from the near field. The study provides a quantitative way of illustrating the possible effects of future glaciations on radionuclide transport from the repository. Such effects are likely to be significant in any potential siting area predicted to be affected by future periods of ice cover. 8 refs, 22 tabs, 119 figs

  10. Binding site graphs: a new graph theoretical framework for prediction of transcription factor binding sites.

    Directory of Open Access Journals (Sweden)

    Timothy E Reddy

    2007-05-01

    Full Text Available Computational prediction of nucleotide binding specificity for transcription factors remains a fundamental and largely unsolved problem. Determination of binding positions is a prerequisite for research in gene regulation, a major mechanism controlling phenotypic diversity. Furthermore, an accurate determination of binding specificities from high-throughput data sources is necessary to realize the full potential of systems biology. Unfortunately, recently performed independent evaluation showed that more than half the predictions from most widely used algorithms are false. We introduce a graph-theoretical framework to describe local sequence similarity as the pair-wise distances between nucleotides in promoter sequences, and hypothesize that densely connected subgraphs are indicative of transcription factor binding sites. Using a well-established sampling algorithm coupled with simple clustering and scoring schemes, we identify sets of closely related nucleotides and test those for known TF binding activity. Using an independent benchmark, we find our algorithm predicts yeast binding motifs considerably better than currently available techniques and without manual curation. Importantly, we reduce the number of false positive predictions in yeast to less than 30%. We also develop a framework to evaluate the statistical significance of our motif predictions. We show that our approach is robust to the choice of input promoters, and thus can be used in the context of predicting binding positions from noisy experimental data. We apply our method to identify binding sites using data from genome scale ChIP-chip experiments. Results from these experiments are publicly available at http://cagt10.bu.edu/BSG. The graphical framework developed here may be useful when combining predictions from numerous computational and experimental measures. Finally, we discuss how our algorithm can be used to improve the sensitivity of computational predictions of

  11. The calculation of site-dependent earthquake motions -3. The method of fast fourier transform

    International Nuclear Information System (INIS)

    Simpson, I.C.

    1976-10-01

    The method of Fast Fourier transform (FFT) is applied to the problem of the determination of site-dependent earthquake motions, which takes account of local geological effects. A program, VELAY 1, which uses the FFT method has been written and is described in this report. The assumptions of horizontally stratified, homogeneous, isotropic, linearly viscoelastic layers and a normally incident plane seismic wave are made. Several examples are given, using VELAY 1, of modified surface acceleration-time histories obtained using a selected input acceleration-time history and a representative system of soil layers. There is a discussion concerning the soil properties that need to be measured in order to use VELAY 1 (and similar programs described in previous reports) and hence generate site-dependent ground motions suitable for aseismic design of a nuclear power plant at a given site. (author)

  12. Factor copula models for data with spatio-temporal dependence

    KAUST Repository

    Krupskii, Pavel

    2017-10-13

    We propose a new copula model for spatial data that are observed repeatedly in time. The model is based on the assumption that there exists a common factor that affects the measurements of a process in space and in time. Unlike models based on multivariate normality, our model can handle data with tail dependence and asymmetry. The likelihood for the proposed model can be obtained in a simple form and therefore parameter estimation is quite fast. Simulation from this model is straightforward and data can be predicted at any spatial location and time point. We use simulation studies to show different types of dependencies, both in space and in time, that can be generated by this model. We apply the proposed copula model to hourly wind data and compare its performance with some classical models for spatio-temporal data.

  13. Effects of cytosine methylation on transcription factor binding sites

    KAUST Repository

    Medvedeva, Yulia A

    2014-03-26

    Background: DNA methylation in promoters is closely linked to downstream gene repression. However, whether DNA methylation is a cause or a consequence of gene repression remains an open question. If it is a cause, then DNA methylation may affect the affinity of transcription factors (TFs) for their binding sites (TFBSs). If it is a consequence, then gene repression caused by chromatin modification may be stabilized by DNA methylation. Until now, these two possibilities have been supported only by non-systematic evidence and they have not been tested on a wide range of TFs. An average promoter methylation is usually used in studies, whereas recent results suggested that methylation of individual cytosines can also be important.Results: We found that the methylation profiles of 16.6% of cytosines and the expression profiles of neighboring transcriptional start sites (TSSs) were significantly negatively correlated. We called the CpGs corresponding to such cytosines " traffic lights" We observed a strong selection against CpG " traffic lights" within TFBSs. The negative selection was stronger for transcriptional repressors as compared with transcriptional activators or multifunctional TFs as well as for core TFBS positions as compared with flanking TFBS positions.Conclusions: Our results indicate that direct and selective methylation of certain TFBS that prevents TF binding is restricted to special cases and cannot be considered as a general regulatory mechanism of transcription. 2013 Medvedeva et al.; licensee BioMed Central Ltd.

  14. Tissue factor-dependent activation of tritium-labeled factor IX and factor X in human plasma

    International Nuclear Information System (INIS)

    Morrison, S.A.; Jesty, J.

    1984-01-01

    A comparism was made of the tissue factor-dependent activation of tritium-labeled factor IX and factor X in a human plasma system and a study was made of the role of proteases known to stimulate factor VII activity. Plasma was defibrinated by heating and depleted of its factors IX and X by passing it through antibody columns. Addition of human brain thromboplastin, Ca2+, and purified 3H-labeled factor X to the plasma resulted, after a short lag, in burst-like activation of the factor X, measured as the release of radiolabeled activation peptide. The progress of activation was slowed by both heparin and a specific inhibitor of factor Xa but factor X activation could not be completely abolished by such inhibitors. In the case of 3H-factor IX activation, the rate also increased for approximately 3 min after addition of thromboplastin, but was not subsequently curtailed. A survey of proteases implicated as activators of factor VII in other settings showed that both factor Xa and factor IXa could accelerate the activation of factor IX. However, factor Xa was unique in obliterating activation when present at concentrations greater than approximately 1 nM. Heparin inhibited the tissue factor-dependent activation of factor IX almost completely, apparently through the effect of antithrombin on the feedback reactions of factors Xa and IXa on factor VII. These results suggest that a very tight, biphasic control of factor VII activity exists in human plasma, which is modulated mainly by factor Xa. At saturation of factor VIIa/tissue factor, factor IX activation was significantly more rapid than was previously found in bovine plasma under similar conditions. The activation of factor X at saturation was slightly more rapid than in bovine plasma, despite the presence of heparin

  15. Endogenously generated plasmin at the vascular wall injury site amplifies lysine binding site-dependent plasminogen accumulation in microthrombi.

    Directory of Open Access Journals (Sweden)

    Tomasz Brzoska

    Full Text Available The fibrinolytic system plays a pivotal role in the regulation of hemostasis; however, it remains unclear how and when the system is triggered to induce thrombolysis. Using intra-vital confocal fluorescence microscopy, we investigated the process of plasminogen binding to laser-induced platelet-rich microthrombi generated in the mesenteric vein of transgenic mice expressing green fluorescent protein (GFP. The accumulation of GFP-expressing platelets as well as exogenously infused Alexa Fluor 568-labeled Glu-plasminogen (Glu-plg on the injured vessel wall was assessed by measuring the increase in the corresponding fluorescence intensities. Glu-plg accumulated in a time-dependent manner in the center of the microthrombus, where phosphatidylserine is exposed on platelet surfaces and fibrin formation takes place. The rates of binding of Glu-plg in the presence of ε-aminocaproic acid and carboxypeptidase B, as well as the rates of binding of mini-plasminogen lacking kringle domains 1-4 and lysine binding sites, were significantly lower than that of Glu-plg alone, suggesting that the binding was dependent on lysine binding sites. Furthermore, aprotinin significantly suppressed the accumulation of Glu-plg, suggesting that endogenously generated plasmin activity is a prerequisite for the accumulation. In spite of the endogenous generation of plasmin and accumulation of Glu-plg in the center of microthrombi, the microthrombi did not change in size during the 2-hour observation period. When human tissue plasminogen activator was administered intravenously, Glu-plg further accumulated and the microthrombi were lysed. Glu-plg appeared to accumulate in the center of microthrombi in the early phase of microthrombus formation, and plasmin activity and lysine binding sites were required for this accumulation.

  16. InMoDe: tools for learning and visualizing intra-motif dependencies of DNA binding sites.

    Science.gov (United States)

    Eggeling, Ralf; Grosse, Ivo; Grau, Jan

    2017-02-15

    Recent studies have shown that the traditional position weight matrix model is often insufficient for modeling transcription factor binding sites, as intra-motif dependencies play a significant role for an accurate description of binding motifs. Here, we present the Java application InMoDe, a collection of tools for learning, leveraging and visualizing such dependencies of putative higher order. The distinguishing feature of InMoDe is a robust model selection from a class of parsimonious models, taking into account dependencies only if justified by the data while choosing for simplicity otherwise. InMoDe is implemented in Java and is available as command line application, as application with a graphical user-interface, and as an integration into Galaxy on the project website at http://www.jstacs.de/index.php/InMoDe . ralf.eggeling@cs.helsinki.fi. © The Author 2016. Published by Oxford University Press.

  17. Flow-induced elongation of von Willebrand factor precedes tension-dependent activation.

    Science.gov (United States)

    Fu, Hongxia; Jiang, Yan; Yang, Darren; Scheiflinger, Friedrich; Wong, Wesley P; Springer, Timothy A

    2017-08-23

    Von Willebrand factor, an ultralarge concatemeric blood protein, must bind to platelet GPIbα during bleeding to mediate hemostasis, but not in the normal circulation to avoid thrombosis. Von Willebrand factor is proposed to be mechanically activated by flow, but the mechanism remains unclear. Using microfluidics with single-molecule imaging, we simultaneously monitored reversible Von Willebrand factor extension and binding to GPIbα under flow. We show that Von Willebrand factor is activated through a two-step conformational transition: first, elongation from compact to linear form, and subsequently, a tension-dependent local transition to a state with high affinity for GPIbα. High-affinity sites develop only in upstream regions of VWF where tension exceeds ~21 pN and depend upon electrostatic interactions. Re-compaction of Von Willebrand factor is accelerated by intramolecular interactions and increases GPIbα dissociation rate. This mechanism enables VWF to be locally activated by hydrodynamic force in hemorrhage and rapidly deactivated downstream, providing a paradigm for hierarchical mechano-regulation of receptor-ligand binding.Von Willebrand factor (VWF) is a blood protein involved in clotting and is proposed to be activated by flow, but the mechanism is unknown. Here the authors show that VWF is first converted from a compact to linear form by flow, and is subsequently activated to bind GPIbα in a tension-dependent manner.

  18. Mutations and binding sites of human transcription factors

    KAUST Repository

    Kamanu, Frederick Kinyua

    2012-06-01

    Mutations in any genome may lead to phenotype characteristics that determine ability of an individual to cope with adaptation to environmental challenges. In studies of human biology, among the most interesting ones are phenotype characteristics that determine responses to drug treatments, response to infections, or predisposition to specific inherited diseases. Most of the research in this field has been focused on the studies of mutation effects on the final gene products, peptides, and their alterations. Considerably less attention was given to the mutations that may affect regulatory mechanism(s) of gene expression, although these may also affect the phenotype characteristics. In this study we make a pilot analysis of mutations observed in the regulatory regions of 24,667 human RefSeq genes. Our study reveals that out of eight studied mutation types, insertions are the only one that in a statistically significant manner alters predicted transcription factor binding sites (TFBSs). We also find that 25 families of TFBSs have been altered by mutations in a statistically significant manner in the promoter regions we considered. Moreover, we find that the related transcription factors are, for example, prominent in processes related to intracellular signaling; cell fate; morphogenesis of organs and epithelium; development of urogenital system, epithelium, and tube; neuron fate commitment. Our study highlights the significance of studying mutations within the genes regulatory regions and opens way for further detailed investigations on this topic, particularly on the downstream affected pathways. 2012 Kamanu, Medvedeva, Schaefer, Jankovic, Archer and Bajic.

  19. Random mutagenesis identifies factors involved in formate-dependent growth of the methanogenic archaeon Methanococcus maripaludis.

    Science.gov (United States)

    Sattler, Christian; Wolf, Sandro; Fersch, Julia; Goetz, Stefan; Rother, Michael

    2013-09-01

    Methane is a key intermediate in the carbon cycle and biologically produced by methanogenic archaea. Most methanogens are able to conserve energy by reducing CO2 to methane using molecular hydrogen as electron donor (hydrogenotrophic methanogenesis), but several hydrogenotrophic methanogens can also use formate as electron donor for methanogenesis. Formate dehydrogenase (Fdh) oxidizes formate to CO2 and is involved in funneling reducing equivalents into the methanogenic pathway, but details on other factors relevant for formate-dependent physiology of methanogens are not available. To learn more about the factors involved in formate-dependent growth of Methanococcus maripaludis strain JJ, we used a recently developed system for random in vitro mutagenesis, which is based on a modified insect transposable element to create 2,865 chromosomal transposon mutants and screened them for impaired growth on formate. Of 12 M. maripaludis transposon-induced mutants exhibiting this phenotype, the transposon insertion sites in the chromosome were mapped. Among the genes, apparently affecting formate-dependent growth were those encoding archaeal transcription factor S, a regulator of ion transport, and carbon monoxide dehydrogenase/acetyl-CoA synthase. Interestingly, in seven of the mutants, transposons were localized in a 10.2 kb region where Fdh1, one of two Fdh isoforms in the organism, is encoded. Two transcription start sites within the 10.2 kb region could be mapped, and quantification of transcripts revealed that transposon insertion in this region diminished fdhA1 expression due to polar effects.

  20. Factors associated with dry mouth in dependent Japanese elderly.

    Science.gov (United States)

    Kakudate, Naoki; Muramatsu, Tsukasa; Endoh, Mami; Satomura, Kazuhito; Koseki, Takeyoshi; Sato, Yuji; Ito, Kayoko; Ogasawara, Tadashi; Nakamura, Seiji; Kishimoto, Etsuo; Kashiwazaki, Haruhiko; Yamashita, Yoshihisa; Uchiyama, Kimio; Nishihara, Tatsuji; Kiyohara, Yutaka; Kakinoki, Yasuaki

    2014-03-01

    To identify factors associated with dry mouth. Dry mouth adversely affects oropharyngeal health, particularly in elderly, and can lead to pneumonia. A better understanding of the epidemiology of dry mouth is therefore important in improving treatment strategies and oral health in high-risk elderly patients. We conducted a cross-sectional study involving 383 dependent Japanese elderly individuals (65-84 [n = 167] and ≥85 [n = 216] years) at eight long-term care facilities and hospitals. Thirty-four potential factors associated with dry mouth were examined by multiple logistic regression analysis. The primary outcome was dry mouth, as diagnosed by tongue dorsum moisture. We identified that body mass index and severity of physical disability were identified as a potential factors associated with dry mouth in the super-elderly (≥85 years) group, whereas severity of physical disability, outcome measurement time, high daily water consumption, mouth breathing, use of antidepressants and diuretics, and high frequency of daily brushing (≥2 times per day; Odds ratio: 5.56; 95% Confidence Interval: 1.52-20.00) were associated with dry mouth in the 65- to 84-year-old group. To our knowledge, this is the first study to identify a link between frequency of daily brushing and dry mouth and suggests that tooth brushing should be encouraged in high-risk dependent Japanese elderly (65-84 years), particularly those taking antidepressants and/or diuretics. © 2012 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd.

  1. The next generation of transcription factor binding site prediction.

    Directory of Open Access Journals (Sweden)

    Anthony Mathelier

    Full Text Available Finding where transcription factors (TFs bind to the DNA is of key importance to decipher gene regulation at a transcriptional level. Classically, computational prediction of TF binding sites (TFBSs is based on basic position weight matrices (PWMs which quantitatively score binding motifs based on the observed nucleotide patterns in a set of TFBSs for the corresponding TF. Such models make the strong assumption that each nucleotide participates independently in the corresponding DNA-protein interaction and do not account for flexible length motifs. We introduce transcription factor flexible models (TFFMs to represent TF binding properties. Based on hidden Markov models, TFFMs are flexible, and can model both position interdependence within TFBSs and variable length motifs within a single dedicated framework. The availability of thousands of experimentally validated DNA-TF interaction sequences from ChIP-seq allows for the generation of models that perform as well as PWMs for stereotypical TFs and can improve performance for TFs with flexible binding characteristics. We present a new graphical representation of the motifs that convey properties of position interdependence. TFFMs have been assessed on ChIP-seq data sets coming from the ENCODE project, revealing that they can perform better than both PWMs and the dinucleotide weight matrix extension in discriminating ChIP-seq from background sequences. Under the assumption that ChIP-seq signal values are correlated with the affinity of the TF-DNA binding, we find that TFFM scores correlate with ChIP-seq peak signals. Moreover, using available TF-DNA affinity measurements for the Max TF, we demonstrate that TFFMs constructed from ChIP-seq data correlate with published experimentally measured DNA-binding affinities. Finally, TFFMs allow for the straightforward computation of an integrated TF occupancy score across a sequence. These results demonstrate the capacity of TFFMs to accurately model DNA

  2. Standard protocol for evaluation of environmental transfer factors around NPP sites

    International Nuclear Information System (INIS)

    Hegde, A.G.; Verma, P.C.; Rao, D.D.

    2009-01-01

    This document presents the standard procedures for evaluation of site specific environmental transfer factors around NPP sites. The scope of this document is to provide standard protocol to be followed for evaluation of environmental transfer factors around NPP sites. The studies on transfer factors are being carried out at various NPP sites under DAE-BRNS projects for evaluation of site specific transfer factors for radionuclides released from power plants. This document contains a common methodology in terms of sampling, processing, measurements and analysis of elemental/radionuclides, while keeping the site specific requirements also in place. (author)

  3. Risk Factors for Surgical Site Infections in Dermatological Surgery

    Directory of Open Access Journals (Sweden)

    Xiaomeng Liu

    2017-11-01

    Full Text Available Current literature on risk factors for surgical site infection (SSI in dermatological surgery in the absence of antibiotic prophylaxis is limited. The aim of this study was to retrospectively evaluate patients presenting for dermatological surgery. A total of 1,977 procedures were reviewed. SSI was clinically suspected in 79 (4.0% patients and confirmed by culture in 38 (1.9%. Using the strictest definition of SSI (clinical symptoms with positive culture significantly higher risk of SSI was found for location on the ear (odds ratio (OR 6.03, 95% confidence interval (95% CI 2.12–17.15, larger defects (OR 1.08 per cm2 increase, 95% CI 1.03–1.14, closure with flaps (OR 6.35, 95% CI 1.33–30.28 and secondary intention (OR 3.01, 95% CI 1.11–8.13. These characteristics were also associated with higher risk of clinically suspected SSI regardless of culture results with slightly lower ORs. In conclusion, the risk of acquiring a SSI is increased in surgeries performed on the ear, in larger wounds and in defects closed with flaps or healed by secondary intention.

  4. Totally asymmetric simple exclusion process with langmuir kinetics depending on the occupancy of the neighboring sites

    International Nuclear Information System (INIS)

    Ichiki, Shingo; Sato, Jun; Nishinari, Katsuhiro

    2016-01-01

    We generalize the totally asymmetric simple exclusion process with Langmuir kinetics (TASEP-LK). In the original TASEP-LK, when a site on the lattice is empty, a particle is attached at a certain rate, whereas the particle is detached at a certain rate when the site is occupied. In the extended TASEP-LK, the rates of attachment and detachment depend on the occupancy of the neighboring sites. In particular, we consider the case where the attachment rate and detachment rate are equal in each state of the neighboring sites. We analytically study a density profile using a mean-field approximation. Then, the results are compared with Monte Carlo simulations. We find in detail that the characteristic of the density profile is changed by manipulating each attachment and detachment parameter. It is showed that the position of a domain wall, which is fixed in the original model, changes depending on the inflow and outflow rates when the rates at the right and left boundaries are the same. (author)

  5. Surgical Site Infection Rate and Risk Factors among Obstetric Cases ...

    African Journals Online (AJOL)

    BACKGROUND: Surgical Site infections are the second most frequently reported infections of all nosocomial infections among hospital patients. Among surgical patients in obstetrics, Surgical Site Infections were the most common nosocomial infections and the rate is higher in sub-Saharan Africa. There has not been a ...

  6. Harvest time of Cryptomeria japonica seeds depending on climate factors

    Science.gov (United States)

    Son, Seog-Gu; Kim, Hyo-Jeong; Kim, Chang-Soo; Byun, Kwang-Ok

    2010-05-01

    Sound seeds should have good germination rates and seed germination can be influenced by several factors. Seed picking time is regarded as one of the necessary elements to obtain sound seeds. From a clonal seed orchard of Cryptomeria japonica located in southern part of Korean peninsular, cones were picked about every 10 days from 30th of July 2005 to 30th of October in both 2005 and 2006. We have also analyzed the effects of climatic factors about two consecutive years on seed productivity. From the picked cones, seeds were collected and these germination ability, seed size and embryo shapes were investigated according to cone picking time. The 1,000-seed weight picked on 18th of August was 3.3 g and 5.3 g on 30th of September 2005and 2006. The size of seeds picked from 18th of August to 30th of September increased from 19.3 mm to 21.3 mm in length and from 15.8 mm to 18.5 mm in width. Depending on picking time, various shapes of embryos, including embryos with liquid material, jellied material and fully matured ones were observed. Germination aspects also varied throughout the test days. About two weeks after seeding in a glass petri-dish, germinal apparatuses appeared from each test seed sets which had been picked from after 10 August 2005 and 10 August 2006. The germination rates started from 10.7% from seeds picked 20 August 2006. Average germination rate in 2005 was 18.3 and 19.6 in 2006. In 2005, the highest germination rate was 34.3% from seeds picked on the 30th of September. In 2006, the highest germination rate was 31.7% for seeds picked at the same date as the 2005 seeds. After September, the highest germination rate for picked seeds decreased in both 2005 and 2006. Among the climatic factors, monthly sum of temperature and of precipitation were the main factors for maturation of C. japonica seeds. The results implied that the best cone picking time for the Korean C. japonica seed orchard to be around the end of September.

  7. Hedging against service disruptions: an expected median location problem with site-dependent failure probabilities

    Science.gov (United States)

    Lei, Ting L.; Tong, Daoqin

    2013-10-01

    The vector assignment p-median problem (VAPMP) (Weaver and Church in Transp Sci 19(1):58-74, 1985) was one of the first location-allocation models developed to handle split assignment of a demand to multiple facilities. The underlying construct of the VAPMP has been subsequently used in a number of reliable facility location and backup location models. Although in many applications the chance that a facility fails may vary substantially with locations, many existing models have assumed a uniform failure probability across all sites. As an improvement, this paper proposes a new model, the expected p-median problem as a generalization of existing approaches by explicitly considering site-dependent failure probabilities. Multi-level closest assignment constraints and two efficient integer linear programming (ILP) formulations are introduced. While prior research generally concludes that similar problems are not integer-friendly and cannot be solved by ILP software, computational results show that our model can be used to solve medium-sized location problems optimally using existing ILP software. Moreover, the new model can be used to formulate other reliable or expected location problems with consideration of site-dependent failure probabilities.

  8. Geographic factors related to site suitability of low-level waste disposal

    International Nuclear Information System (INIS)

    Zittel, H.E.

    1981-01-01

    A number of factors related to the site suitability of low-level waste disposal sites are discussed. The factors are a combination of those which might be considered environmental and those dealing with site criteria. Among the factors covered are: possible population criteria, alternative site selection, transportation criteria and community involvement considerations. All these factors are discussed in a manner based on the premise that the technology exists to carry out low-level waste disposal in a manner such that public health and safety can be insured. The conclusion of the discussion is that problems encountered in siting low-level waste facilities will be largely societal and political in nature

  9. Cell-type specificity of ChIP-predicted transcription factor binding sites

    Directory of Open Access Journals (Sweden)

    Håndstad Tony

    2012-08-01

    Full Text Available Abstract Background Context-dependent transcription factor (TF binding is one reason for differences in gene expression patterns between different cellular states. Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq identifies genome-wide TF binding sites for one particular context—the cells used in the experiment. But can such ChIP-seq data predict TF binding in other cellular contexts and is it possible to distinguish context-dependent from ubiquitous TF binding? Results We compared ChIP-seq data on TF binding for multiple TFs in two different cell types and found that on average only a third of ChIP-seq peak regions are common to both cell types. Expectedly, common peaks occur more frequently in certain genomic contexts, such as CpG-rich promoters, whereas chromatin differences characterize cell-type specific TF binding. We also find, however, that genotype differences between the cell types can explain differences in binding. Moreover, ChIP-seq signal intensity and peak clustering are the strongest predictors of common peaks. Compared with strong peaks located in regions containing peaks for multiple transcription factors, weak and isolated peaks are less common between the cell types and are less associated with data that indicate regulatory activity. Conclusions Together, the results suggest that experimental noise is prevalent among weak peaks, whereas strong and clustered peaks represent high-confidence binding events that often occur in other cellular contexts. Nevertheless, 30-40% of the strongest and most clustered peaks show context-dependent regulation. We show that by combining signal intensity with additional data—ranging from context independent information such as binding site conservation and position weight matrix scores to context dependent chromatin structure—we can predict whether a ChIP-seq peak is likely to be present in other cellular contexts.

  10. Dressed Quark Mass Dependence of Pion and Kaon Form Factors

    Energy Technology Data Exchange (ETDEWEB)

    Ninomiya, Y.; Bentz, W.; Cloet, I. C.

    2015-02-04

    The structure of hadrons is described well by the Nambu-Jona-Lasinio (NJL) model, which is a chiral effective quark theory of QCD. In this work we explore the electromagnetic structure of the pion and kaon using the three-flavor NJL model in the proper-time regularization scheme, including effects of the pion cloud at the quark level. In the calculation there is only one free parameter, which we take as the dressed light quark (u and d) mass. In the regime where the dressed light quark mass is approximately 0.25 GeV we find that the calculated values of the kaon decay constant, current quark masses, and quark condensates are consistent with experiment- and QCD-based analyses. We also investigate the dressed light quark mass dependence of the pion and kaon electromagnetic form factors, where comparison with empirical data and QCD predictions also favors a dressed light quark mass near 0.25 GeV.

  11. Using TESS to predict transcription factor binding sites in DNA sequence.

    Science.gov (United States)

    Schug, Jonathan

    2008-03-01

    This unit describes how to use the Transcription Element Search System (TESS). This Web site predicts transcription factor binding sites (TFBS) in DNA sequence using two different kinds of models of sites, strings and positional weight matrices. The binding of transcription factors to DNA is a major part of the control of gene expression. Transcription factors exhibit sequence-specific binding; they form stronger bonds to some DNA sequences than to others. Identification of a good binding site in the promoter for a gene suggests the possibility that the corresponding factor may play a role in the regulation of that gene. However, the sequences transcription factors recognize are typically short and allow for some amount of mismatch. Because of this, binding sites for a factor can typically be found at random every few hundred to a thousand base pairs. TESS has features to help sort through and evaluate the significance of predicted sites.

  12. Identification of Site Selection Factors in the U.S. Franchise Restaurant Industry: An Exploratory Study

    OpenAIRE

    Park, Kunsoon

    2002-01-01

    The purpose of this study was to identify and rank the importance of the site selection factors that influence the U.S. franchise restaurant industry as well as rank the confidence level of the experts. To identify the site selection factors, this study sought assistance and support from restaurant professionals. The Delphi technique was used to elicit the opinions of a panel of experts regarding the site selection factors. The panel was composed of restaurant professionals of restaurant c...

  13. A reliable facility location design model with site-dependent disruption in the imperfect information context

    Science.gov (United States)

    Yun, Lifen; Wang, Xifu; Fan, Hongqiang; Li, Xiaopeng

    2017-01-01

    This paper proposes a reliable facility location design model under imperfect information with site-dependent disruptions; i.e., each facility is subject to a unique disruption probability that varies across the space. In the imperfect information contexts, customers adopt a realistic “trial-and-error” strategy to visit facilities; i.e., they visit a number of pre-assigned facilities sequentially until they arrive at the first operational facility or give up looking for the service. This proposed model aims to balance initial facility investment and expected long-term operational cost by finding the optimal facility locations. A nonlinear integer programming model is proposed to describe this problem. We apply a linearization technique to reduce the difficulty of solving the proposed model. A number of problem instances are studied to illustrate the performance of the proposed model. The results indicate that our proposed model can reveal a number of interesting insights into the facility location design with site-dependent disruptions, including the benefit of backup facilities and system robustness against variation of the loss-of-service penalty. PMID:28486564

  14. Incorporating evolution of transcription factor binding sites into ...

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    Most current methods in this field adopt a multi-step ap proach that segregates the two aspects. Again, it is widely accepted that the ... In a simulated setting, we provide a proof of concept that the approach works given the ... We study how alignments and binding site predictions interplay at varying evolutionary distances ...

  15. Macrophage migration inhibitory factor activates hypoxia-inducible factor in a p53-dependent manner.

    Directory of Open Access Journals (Sweden)

    Seiko Oda

    Full Text Available BACKGROUND: Macrophage migration inhibitory factor (MIF is not only a cytokine which has a critical role in several inflammatory conditions but also has endocrine and enzymatic functions. MIF is identified as an intracellular signaling molecule and is implicated in the process of tumor progression, and also strongly enhances neovascularization. Overexpression of MIF has been observed in tumors from various organs. MIF is one of the genes induced by hypoxia in an hypoxia-inducible factor 1 (HIF-1-dependent manner. METHODS/PRINCIPAL FINDINGS: The effect of MIF on HIF-1 activity was investigated in human breast cancer MCF-7 and MDA-MB-231 cells, and osteosarcoma Saos-2 cells. We demonstrate that intracellular overexpression or extracellular administration of MIF enhances activation of HIF-1 under hypoxic conditions in MCF-7 cells. Mutagenesis analysis of MIF and knockdown of 53 demonstrates that the activation is not dependent on redox activity of MIF but on wild-type p53. We also indicate that the MIF receptor CD74 is involved in HIF-1 activation by MIF at least when MIF is administrated extracellularly. CONCLUSION/SIGNIFICANCE: MIF regulates HIF-1 activity in a p53-dependent manner. In addition to MIF's potent effects on the immune system, MIF is linked to fundamental processes conferring cell proliferation, cell survival, angiogenesis, and tumor invasiveness. This functional interdependence between MIF and HIF-1alpha protein stabilization and transactivation activity provide a molecular mechanism for promotion of tumorigenesis by MIF.

  16. An assessment of different atmospheric stability methods for annual atmospheric dispersion factors at a coastal site

    International Nuclear Information System (INIS)

    Bagavathsingh, A.; Rakesh, P.T.; Srinivas, C.V.; Baskaran, R.; Venkatraman, B.

    2018-01-01

    The meteorological data is used for routine radiological release consequence analysis, real time consequence assessments of accidental releases of radiological effluents and design basis accidental analysis in a nuclear plant site. For dispersion estimate, it is often required to specify the type of stability and/or turbulence conditions in which diffusion of pollutants would occur. Stability indicates the degree of turbulence and thus the atmospheric mixing. Intensity of turbulence and dispersion of pollutant releases in to the lower atmosphere are strongly dependent on the local winds as well as resistance of atmosphere to vertical mixing which is called atmospheric stability. Three different methods of atmospheric stability based on Standard deviation of wind direction (σθ), temperature gradient and Bulk Richardson (Rib) number are used to compute stability over Kalpakkam site using hourly meteorological data. All the three methods of estimating atmospheric stability are compared with M-O similarity based method. Different atmospheric stability methods were analyzed to estimate the annual average atmospheric dispersion factors at Kalpakkam coastal site for the year 2016

  17. Transcription-dependent degradation controls the stability of the SREBP family of transcription factors.

    Science.gov (United States)

    Sundqvist, Anders; Ericsson, Johan

    2003-11-25

    Cholesterol metabolism is tightly controlled by members of the sterol regulatory element-binding protein (SREBP) family of transcription factors. Here we demonstrate that the ubiquitination and degradation of SREBPs depend on their transcriptional activity. Mutations in the transactivation or DNA-binding domains of SREBPs inhibit their transcriptional activity and stabilize the proteins. The transcriptional activity and degradation of these mutants are restored when fused to heterologous transactivation or DNA-binding domains. When SREBP1a was fused to the DBD of Gal4, the ubiquitination and degradation of the fusion protein depended on coexpression of a promoter-reporter gene containing Gal4-binding sites. In addition, disruption of the interaction between WT SREBP and endogenous p300/CBP resulted in inhibition of SREBP-dependent transcription and stabilization of SREBP. Chemical inhibitors of transcription reduced the degradation of transcriptionally active SREBP1a, whereas they had no effect on the stability of transcriptionally inactive mutants, demonstrating that transcriptional activation plays an important role in the degradation of SREBPs. Thus, transcription-dependent degradation of SREBP constitutes a feedback mechanism to regulate the expression of genes involved in cholesterol metabolism and may represent a general mechanism to regulate the duration of transcriptional responses.

  18. Climate and site dependence of the annual growth of silver fir (Abies alba Mill.) in the Northern Apennines, Italy

    Energy Technology Data Exchange (ETDEWEB)

    Gambetti, D.; Lo Vecchio, G.; Nanni, T. [Consiglio Nazionale delle Ricerche, Bologna (Italy). FISBAT; Schweingruber, F.H. [Federal Institute for Forest, Snow and Landscape Research, Birmensdorf (Switzerland)

    2000-04-01

    The study is focused on the relationship between ring width formation of the silver fir and the climatic factors. Therefore, material on two sites of the Northern Apennine has been collected at different altitudes, slope and soil characteristics and has been compared tree ring width with meteorological data from a neighbouring station. The results are that the ring growth depends mainly on the winter mean temperature of the current year, the summer precipitation and the mean summer temperature of the preceding year. The influence of winter mean temperature is more pronounced at high altitudes. The mean summer temperature and summer precipitation had a stronger effect on the growth year at lower altitudes and on the following year at higher altitudes.

  19. Impact of personality traits and demographic factors on relationship to deal sites

    DEFF Research Database (Denmark)

    Sudzina, Frantisek; Pavlicek, Antonin

    2017-01-01

    There is an increasing body of research about deal sites. But there is still exists a gap when it comes to factors influencing potential or existing users of deal sites. The aim of this paper is to investigate impact of gender, city of origin, and personality traits on relationship to deal sites....

  20. Geographic factors related to site suitability of low-level waste disposal

    Science.gov (United States)

    Zittel, H. E.

    Factors related to the site suitability of low level waste disposal sites are discussed including those which might be considered environmental and those dealing with site criteria. Possible population criteria, alternative site selection, transportation criteria, and community involvement are considered. All these factors are based on the premise that the technology exists to carry out low level waste disposal in a manner such that public health and safety can be insured. It is concluded that problems encountered in siting low level waste facilities are largely societal and political in nature.

  1. Probing the site-dependent Kondo response of nanostructured graphene with organic molecules.

    Science.gov (United States)

    Garnica, Manuela; Stradi, Daniele; Calleja, Fabián; Barja, Sara; Díaz, Cristina; Alcamí, Manuel; Arnau, Andrés; Vázquez de Parga, Amadeo L; Martín, Fernando; Miranda, Rodolfo

    2014-08-13

    TCNQ molecules are used as a sensitive probe for the Kondo response of the electron gas of a nanostructured graphene grown on Ru(0001) presenting a moiré pattern. All adsorbed molecules acquired an extra electron by charge transfer from the substrate, but only those adsorbed in the FCC-Top areas of the moiré show magnetic moment and Kondo resonance in the STS spectra. DFT calculations trace back this behavior to the existence of a surface resonance in the low areas of the graphene moiré, whose density distribution strongly depends on the stacking sequence of the moiré area and effectively quenches the magnetic moment for HCP-Top sites.

  2. The influence of site factors on nitrogen mineralization in forest soils ...

    African Journals Online (AJOL)

    This process of the N cycle can therefore be considered as the rate limiting step influencing tree growth. N mineralization is controlled by a complex interaction of various site factors, and numerous correlations and interactions between NH4 + mineralization (summer) and site factors are discussed. Statistical models were ...

  3. Toward a regional power plant siting method: AEC-Maryland regional siting factors study, FY 1974 progress report

    International Nuclear Information System (INIS)

    Yaffee, S.L.; Miller, C.A.

    1974-11-01

    The ''AEC-Maryland Regional Siting Factors Study'' examines the process of siting in a regional context. It is developing an analysis method to delineate candidate areas for siting of several power plant technology packages, including both fossil-fueled and nuclear options. Tools that are being used include simulation modeling, economic and demographic forecasting, spatial analysis, and computer graphics and numerical manipulation. The approach will describe the trade-offs incurred if a power plant is located in one candidate area rather than in another. In FY 1974, a suitability analysis method was developed which uses engineering and environmental parameters to define a level of environmental cost incurred if a segment of land is used to site a specific technology package. (U.S.)

  4. Effect of operating current dependent series resistance on the fill factor of a solar cell

    Energy Technology Data Exchange (ETDEWEB)

    Dadu, Meena; Kapoor, A.; Tripathi, K.N. [Department of Electronic Science, University of Delhi, South Campus, Benito Juarez road, -110 021 New Delhi (India)

    2002-02-01

    The fill factor of a solar cell depends upon the series resistance, reverse saturation current, diode quality factor, operating current and voltage. Since the series resistance itself depends upon the operating current (or voltage), it makes the evaluation of fill factor very complicated. In this paper, we have evaluated the fill factor of a solar cell, taking into account operating current dependence of the series resistance.

  5. Diet and density dependent competition affect larval performance and oviposition site selection in the mosquito species Aedes albopictus (Diptera: Culicidae

    Directory of Open Access Journals (Sweden)

    Yoshioka Miho

    2012-10-01

    Full Text Available Abstract Background Oviposition-site choice is an essential component of the life history of all mosquito species. According to the oviposition-preference offspring-performance (P-P hypothesis, if optimizing offspring performance and fitness ensures high overall reproductive fitness for a given species, the female should accurately assess details of the heterogeneous environment and lay her eggs preferentially in sites with conditions more suitable to offspring. Methods We empirically tested the P-P hypothesis using the mosquito species Aedes albopictus by artificially manipulating two habitat conditions: diet (measured as mg of food added to a container and conspecific density (CD; number of pre-existing larvae of the same species. Immature development (larval mortality, development time to pupation and time to emergence and fitness (measured as wing length were monitored from first instar through adult emergence using a factorial experimental design over two ascending gradients of diet (2.0, 3.6, 7.2 and 20 mg food/300 ml water and CD (0, 20, 40 and 80 larvae/300 ml water. Treatments that exerted the most contrasting values of larval performance were recreated in a second experiment consisting of single-female oviposition site selection assay. Results Development time decreased as food concentration increased, except from 7.2 mg to 20.0 mg (Two-Way CR ANOVA Post-Hoc test, P > 0.1. Development time decreased also as conspecific density increased from zero to 80 larvae (Two-Way CR ANOVA Post-Hoc test, P . Combined, these results support the role of density-dependent competition for resources as a limiting factor for mosquito larval performance. Oviposition assays indicated that female mosquitoes select for larval habitats with conspecifics and that larval density was more important than diet in driving selection for oviposition sites. Conclusions This study supports predictions of the P-P hypothesis and provides a mechanistic understanding

  6. Risk factors for surgical site infection and association with infliximab administration during surgery for Crohn's disease.

    Science.gov (United States)

    Uchino, Motoi; Ikeuchi, Hiroki; Matsuoka, Hiroki; Bando, Toshihiro; Ichiki, Kaoru; Nakajima, Kazuhiko; Tomita, Naohiro; Takesue, Yoshio

    2013-10-01

    Preoperative infliximab treatment may influence postoperative infectious complications in patients with Crohn's disease. The aim of this study was to identify predictors of surgical site infection after surgery for Crohn's disease and evaluate the effects of preoperative infliximab administration. We performed a prospective surveillance and review of surgical site infections. This study was conducted in the Surgical Department of Hyogo College of Medicine. A total of 405 consecutive patients with Crohn's disease who underwent abdominal surgery between January 2008 and December 2011 were included. Infection was diagnosed by the infection control team. The possible risk factors were analyzed by using logistic regression analyses to determine their predictive significance. Within the patient population, 20% of patients received infliximab, and 60% had penetrating disease. The median duration from the last infliximab infusion to surgery was 43 days (range, 4-80). The overall incidence of surgical site infection was 27%. The incidence of incisional surgical site infection was 18%, and the organ/space surgical site infection rate was 8%. In the multivariate analysis, proctectomy was the highest risk factor for all surgical site infection (OR, 3.4-11.8; p risk factor for surgical site infection. By contrast, there was a significantly reduced risk of incisional surgical site infection in patients with penetrating disease who received infliximab (OR, 0.1; p risk factor for surgical site infection in patients with Crohn's disease. The administration of preoperative infliximab was not a risk factor for surgical site infection.

  7. Site-Dependent Environmental Impacts of Industrial Hydrogen Production by Alkaline Water Electrolysis

    Directory of Open Access Journals (Sweden)

    Jan Christian Koj

    2017-06-01

    Full Text Available Industrial hydrogen production via alkaline water electrolysis (AEL is a mature hydrogen production method. One argument in favor of AEL when supplied with renewable energy is its environmental superiority against conventional fossil-based hydrogen production. However, today electricity from the national grid is widely utilized for industrial applications of AEL. Also, the ban on asbestos membranes led to a change in performance patterns, making a detailed assessment necessary. This study presents a comparative Life Cycle Assessment (LCA using the GaBi software (version 6.115, thinkstep, Leinfelden-Echterdingen, Germany, revealing inventory data and environmental impacts for industrial hydrogen production by latest AELs (6 MW, Zirfon membranes in three different countries (Austria, Germany and Spain with corresponding grid mixes. The results confirm the dependence of most environmental effects from the operation phase and specifically the site-dependent electricity mix. Construction of system components and the replacement of cell stacks make a minor contribution. At present, considering the three countries, AEL can be operated in the most environmentally friendly fashion in Austria. Concerning the construction of AEL plants the materials nickel and polytetrafluoroethylene in particular, used for cell manufacturing, revealed significant contributions to the environmental burden.

  8. Epigenetic switch involved in activation of pioneer factor FOXA1-dependent enhancers

    Science.gov (United States)

    Sérandour, Aurélien A.; Avner, Stéphane; Percevault, Frédéric; Demay, Florence; Bizot, Maud; Lucchetti-Miganeh, Céline; Barloy-Hubler, Frédérique; Brown, Myles; Lupien, Mathieu; Métivier, Raphaël; Salbert, Gilles; Eeckhoute, Jérôme

    2011-01-01

    Transcription factors (TFs) bind specifically to discrete regions of mammalian genomes called cis-regulatory elements. Among those are enhancers, which play key roles in regulation of gene expression during development and differentiation. Despite the recognized central regulatory role exerted by chromatin in control of TF functions, much remains to be learned regarding the chromatin structure of enhancers and how it is established. Here, we have analyzed on a genomic-scale enhancers that recruit FOXA1, a pioneer transcription factor that triggers transcriptional competency of these cis-regulatory sites. Importantly, we found that FOXA1 binds to genomic regions showing local DNA hypomethylation and that its cell-type-specific recruitment to chromatin is linked to differential DNA methylation levels of its binding sites. Using neural differentiation as a model, we showed that induction of FOXA1 expression and its subsequent recruitment to enhancers is associated with DNA demethylation. Concomitantly, histone H3 lysine 4 methylation is induced at these enhancers. These epigenetic changes may both stabilize FOXA1 binding and allow for subsequent recruitment of transcriptional regulatory effectors. Interestingly, when cloned into reporter constructs, FOXA1-dependent enhancers were able to recapitulate their cell type specificity. However, their activities were inhibited by DNA methylation. Hence, these enhancers are intrinsic cell-type-specific regulatory regions of which activities have to be potentiated by FOXA1 through induction of an epigenetic switch that includes notably DNA demethylation. PMID:21233399

  9. A temperature dependent slip factor based thermal model for friction ...

    Indian Academy of Sciences (India)

    the tool shoulder and pin to predict the thermal history of aluminium alloy was developed by. Rajamanickam et al .... where σy is the temperature dependent yield stress of the workpiece material as shown in table 2. ... greater than the material yield shear stress, hence the material accelerates to a velocity less than the tool ...

  10. Zooming in and out: Scale dependence of extrinsic and intrinsic factors affecting salt marsh erosion

    Science.gov (United States)

    Wang, Heng; van der Wal, Daphne; Li, Xiangyu; van Belzen, Jim; Herman, Peter M. J.; Hu, Zhan; Ge, Zhenming; Zhang, Liquan; Bouma, Tjeerd J.

    2017-07-01

    Salt marshes are valuable ecosystems that provide important ecosystem services. Given the global scale of marsh loss due to climate change and coastal squeeze, there is a pressing need to identify the critical extrinsic (wind exposure and foreshore morphology) and intrinsic factors (soil and vegetation properties) affecting the erosion of salt marsh edges. In this study, we quantified rates of cliff lateral retreat (i.e., the eroding edge of a salt marsh plateau) using a time series of aerial photographs taken over four salt marsh sites in the Westerschelde estuary, the Netherlands. In addition, we experimentally quantified the erodibility of sediment cores collected from the marsh edge of these four marshes using wave tanks. Our results revealed the following: (i) at the large scale, wind exposure and the presence of pioneer vegetation in front of the cliff were the key factors governing cliff retreat rates; (ii) at the intermediate scale, foreshore morphology was partially related to cliff retreat; (iii) at the local scale, the erodibility of the sediment itself at the marsh edge played a large role in determining the cliff retreat rate; and (iv) at the mesocosm scale, cliff erodibility was determined by soil properties and belowground root biomass. Thus, both extrinsic and intrinsic factors determined the fate of the salt marsh but at different scales. Our study highlights the importance of understanding the scale dependence of the factors driving the evolution of salt marsh landscapes.

  11. Actin-dependent activation of serum response factor in T cells by the viral oncoprotein tip

    Directory of Open Access Journals (Sweden)

    Katsch Kristin

    2012-03-01

    Full Text Available Abstract Serum response factor (SRF acts as a multifunctional transcription factor regulated by mutually exclusive interactions with ternary complex factors (TCFs or myocardin-related transcription factors (MRTFs. Binding of Rho- and actin-regulated MRTF:SRF complexes to target gene promoters requires an SRF-binding site only, whereas MAPK-regulated TCF:SRF complexes in addition rely on flanking sequences present in the serum response element (SRE. Here, we report on the activation of an SRE luciferase reporter by Tip, the viral oncoprotein essentially contributing to human T-cell transformation by Herpesvirus saimiri. SRE activation in Tip-expressing Jurkat T cells could not be attributed to triggering of the MAPK pathway. Therefore, we further analyzed the contribution of MRTF complexes. Indeed, Tip also activated a reporter construct responsive to MRTF:SRF. Activation of this reporter was abrogated by overexpression of a dominant negative mutant of the MRTF-family member MAL. Moreover, enrichment of monomeric actin suppressed the Tip-induced reporter activity. Further upstream, the Rho-family GTPase Rac, was found to be required for MRTF:SRF reporter activation by Tip. Initiation of this pathway was strictly dependent on Tip's ability to interact with Lck and on the activity of this Src-family kinase. Independent of Tip, T-cell stimulation orchestrates Src-family kinase, MAPK and actin pathways to induce SRF. These findings establish actin-regulated transcription in human T cells and suggest its role in viral oncogenesis.

  12. Transcription factor binding site positioning in yeast: proximal promoter motifs characterize TATA-less promoters.

    Science.gov (United States)

    Erb, Ionas; van Nimwegen, Erik

    2011-01-01

    The availability of sequence specificities for a substantial fraction of yeast's transcription factors and comparative genomic algorithms for binding site prediction has made it possible to comprehensively annotate transcription factor binding sites genome-wide. Here we use such a genome-wide annotation for comprehensively studying promoter architecture in yeast, focusing on the distribution of transcription factor binding sites relative to transcription start sites, and the architecture of TATA and TATA-less promoters. For most transcription factors, binding sites are positioned further upstream and vary over a wider range in TATA promoters than in TATA-less promoters. In contrast, a group of 6 'proximal promoter motifs' (GAT1/GLN3/DAL80, FKH1/2, PBF1/2, RPN4, NDT80, and ROX1) occur preferentially in TATA-less promoters and show a strong preference for binding close to the transcription start site in these promoters. We provide evidence that suggests that pre-initiation complexes are recruited at TATA sites in TATA promoters and at the sites of the other proximal promoter motifs in TATA-less promoters. TATA-less promoters can generally be classified by the proximal promoter motif they contain, with different classes of TATA-less promoters showing different patterns of transcription factor binding site positioning and nucleosome coverage. These observations suggest that different modes of regulation of transcription initiation may be operating in the different promoter classes. In addition we show that, across all promoter classes, there is a close match between nucleosome free regions and regions of highest transcription factor binding site density. This close agreement between transcription factor binding site density and nucleosome depletion suggests a direct and general competition between transcription factors and nucleosomes for binding to promoters.

  13. Rapidity dependence of strangeness enhancement factor at FAIR energies

    International Nuclear Information System (INIS)

    Dey, Kalyan; Bhattacharjee, B.

    2014-01-01

    Strange particles are produced only at the time of collisions and thus expected to carry important information of collision dynamics. Strangeness enhancement is considered to be one of the traditional signatures of formation of Quark Gluon Plasma (QGP). Due to the limitation of the detector acceptance, the past and ongoing heavy ion experiments could measure the strangeness enhancement at midrapidity only. But the future heavy ion experiment CBM at FAIR will have the access to the entire forward rapidity hemisphere and thus the experimental determination of rapidity dependent strangeness enhancement is a possibility. In this work, an attempt has therefore been made to study the rapidity dependent strangeness enhancement at FAIR energies with the help of a string based hadronic model (UrQMD). A sum of 93 million minimum biased UrQMD events have been used for the present analysis

  14. Coarse-grained molecular simulation of epidermal growth factor receptor protein tyrosine kinase multi-site self-phosphorylation.

    Directory of Open Access Journals (Sweden)

    John G Koland

    2014-01-01

    Full Text Available Upon the ligand-dependent dimerization of the epidermal growth factor receptor (EGFR, the intrinsic protein tyrosine kinase (PTK activity of one receptor monomer is activated, and the dimeric receptor undergoes self-phosphorylation at any of eight candidate phosphorylation sites (P-sites in either of the two C-terminal (CT domains. While the structures of the extracellular ligand binding and intracellular PTK domains are known, that of the ∼225-amino acid CT domain is not, presumably because it is disordered. Receptor phosphorylation on CT domain P-sites is critical in signaling because of the binding of specific signaling effector molecules to individual phosphorylated P-sites. To investigate how the combination of conventional substrate recognition and the unique topological factors involved in the CT domain self-phosphorylation reaction lead to selectivity in P-site phosphorylation, we performed coarse-grained molecular simulations of the P-site/catalytic site binding reactions that precede EGFR self-phosphorylation events. Our results indicate that self-phosphorylation of the dimeric EGFR, although generally believed to occur in trans, may well occur with a similar efficiency in cis, with the P-sites of both receptor monomers being phosphorylated to a similar extent. An exception was the case of the most kinase-proximal P-site-992, the catalytic site binding of which occurred exclusively in cis via an intramolecular reaction. We discovered that the in cis interaction of P-site-992 with the catalytic site was facilitated by a cleft between the N-terminal and C-terminal lobes of the PTK domain that allows the short CT domain sequence tethering P-site-992 to the PTK core to reach the catalytic site. Our work provides several new mechanistic insights into the EGFR self-phosphorylation reaction, and demonstrates the potential of coarse-grained molecular simulation approaches for investigating the complexities of self-phosphorylation in

  15. Factors for Successful Use of Social Networking Sites in Higher Education

    Directory of Open Access Journals (Sweden)

    L Schlenkrich

    2012-09-01

    Full Text Available Social networking sites are extremely popular online destinations that offer users easy ways to build and maintain relationships with each other, and to disseminate information in an activity referred to as social networking. Students, lecturers, teachers, parents and businesses, in increasing numbers, use tools available on social networking sites to communicate with each other in a fast and cost-effective manner. The use of social networking sites to support educational initiatives has received much attention. However, the full potential of social network sites has yet to be achieved as users continue to strive for optimal ways of using these sites, as well as battle to overcome the negative characteristics (for example, privacy, security, governance, user behaviour, information quality of these sites. This paper proposes factors for successful use of social networking sites in higher educational institutions. These success factors need to be adopted by users in order to develop the positive aspects of social networking, while at the same time mitigating the negative characteristics. An initial set of factors for successful use of social networking sites, as well as measures to test successful use of social networking sites were derived from the literature. These factors were tested by means of an online survey of students at a university, the results of which informed the final factors for successful use of social networking sites. The factors enable users to overcome the negative characteristics associated with social networking sites. If used successfully, social networking sites can offer lecturers and students a useful tool with which to develop their relationship and contribute to their learning experience.

  16. Dependence of wedge transmission factor on co-60 teletherapy ...

    African Journals Online (AJOL)

    Measuring the wedge factor (WF) for radiation field of 10 x 10 cm2 at a specified depth and Source to Surface Distance (SSD), and applying the value to all treatment depths and technique could introduce errors > ± 5 % of threshold stipulated for patient radiation dose delivery. Therefore, some Treatment Planning Systems ...

  17. Personality as a risk factor for illicit opioid use and a protective factor for illicit opioid dependence.

    Science.gov (United States)

    Zaaijer, Eline R; Bruijel, Jessica; Blanken, Peter; Hendriks, Vincent; Koeter, Maarten W J; Kreek, Mary Jeanne; Booij, Jan; Goudriaan, Anna E; van Ree, Jan M; van den Brink, Wim

    2014-12-01

    Most studies investigating the role of personality as a risk factor for the development of opioid dependence compare dependent opioid users with healthy controls who never used heroin. In order to understand the potential protective role of personality, it is crucial to compare illicit opioid users who never became dependent with dependent opioid users. This study aims to examine the role of personality as a risk factor for opioid use and as a protective factor for the development of opioid dependence. Comparing personality factors between three groups: (1) 161 never-dependent illicit opioid users who have been using illicit opioids but never became opioid dependent; (2) 402 dependent opioid users in methadone maintenance treatment or heroin-assisted treatment; and (3) 135 healthy controls who never used heroin. Personality was assessed with a short version of Cloninger's Temperament and Character Inventory. Never-dependent opioid users reported more Novelty Seeking and Harm Avoidance and less Self-Directedness and Cooperativeness than healthy controls and more Reward Dependence and Self-Directedness, and less Harm Avoidance than dependent opioid users. Furthermore, never-dependent opioid users reported more Self-Transcendence than both dependent opioid users and healthy controls. Never-dependent opioid users may have started to use opioids partly due to their tendency to seek novel and/or spiritual experiences (high Novelty Seeking, high Self-Transcendence) and their tendency to avoid aversive stimuli (high Harm Avoidance), whereas they may have been protected against the development of dependence by their need for social approval (high Reward Dependence) and their self-efficacy (high Self-Directedness). Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Kin, daytime associations, or preferred sleeping sites? Factors influencing sleep site selection in captive chimpanzees (Pan troglodytes).

    Science.gov (United States)

    Lock, Louise C; Anderson, James R

    2013-01-01

    Chimpanzee nesting behaviours and the factors that may influence these behaviours are rarely studied in captive settings. In the present study, the daytime associations, sleeping site selections and nesting groups of 11 zoo-housed chimpanzees over a 29-day period were analysed. Neither daytime associations nor presence of kin influenced sleeping site selection in females. Daytime associations did influence sleeping arrangements in males. Nighttime spatial arrangements and individual preferences for specific sleeping areas were broadly comparable to nesting patterns reported in free-living chimpanzee communities. In the interests of captive ape welfare, we conclude that exhibits should incorporate multilevel nesting areas and a choice of several potential sleeping sites. Copyright © 2013 S. Karger AG, Basel.

  19. ERAD-dependent control of the Wnt secretory factor Evi.

    Science.gov (United States)

    Glaeser, Kathrin; Urban, Manuela; Fenech, Emma; Voloshanenko, Oksana; Kranz, Dominique; Lari, Federica; Christianson, John C; Boutros, Michael

    2018-02-15

    Active regulation of protein abundance is an essential strategy to modulate cellular signaling pathways. Within the Wnt signaling cascade, regulated degradation of β-catenin by the ubiquitin-proteasome system (UPS) affects the outcome of canonical Wnt signaling. Here, we found that abundance of the Wnt cargo receptor Evi (Wls/GPR177), which is required for Wnt protein secretion, is also regulated by the UPS through endoplasmic reticulum (ER)-associated degradation (ERAD). In the absence of Wnt ligands, Evi is ubiquitinated and targeted for ERAD in a VCP-dependent manner. Ubiquitination of Evi involves the E2-conjugating enzyme UBE2J2 and the E3-ligase CGRRF1. Furthermore, we show that a triaging complex of Porcn and VCP determines whether Evi enters the secretory or the ERAD pathway. In this way, ERAD-dependent control of Evi availability impacts the scale of Wnt protein secretion by adjusting the amount of Evi to meet the requirement of Wnt protein export. As Wnt and Evi protein levels are often dysregulated in cancer, targeting regulatory ERAD components might be a useful approach for therapeutic interventions. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

  20. Preliminary geologic site selection factors for the National Waste Terminal Storage Program

    International Nuclear Information System (INIS)

    1977-06-01

    The geologic considerations and the associated factors that have to be addressed in the selection of repository sites in deep geologic formations are listed and described. In addition a description is given of the information necessary to assess the geologic factors. The methods of obtaining this information are described. An illustration is given of a general approach of how the geologic factors could be applied and integrated to assess the acceptability of candidate sites. No consideration is given to a detailed description of the application of integration of the geologic factors. The criteria associated with each factor that will be used are not defined

  1. DEPENDENCE RELATIONSHIP BETWEEN THE CRITICAL QUALITY FACTORS AND SOCIAL IMPACT

    Directory of Open Access Journals (Sweden)

    José Álvarez García

    2014-10-01

    Full Text Available This paper shows the results of the empirical study conducted in 186 tourist accommodation businesses in Spain certified under the “Q for Tourist Quality”, own System Quality Management. It was raised with the purpose of analyzing the structure of the relationship between critical quality factors and results-social impact, how they operate and the level of their influence on obtaining these results within the company. Starting from a deep theoretical revision we propose a theoretical model together with the hypotheses to be tested, and we proceed to validation using the technique of Structural Equation Models. The results obtained show that companies wishing to improve their social impact should take into account that leadership is the most important factor to achieve it. Leadership indirectly affects the social impact through its influence on alliances and resources, quality policy/planning, personnel management and learning.

  2. Surgical site infection and its associated factors following cesarean section: a cross sectional study from a public hospital in Ethiopia.

    Science.gov (United States)

    Gelaw, Kelemu Abebe; Aweke, Amlaku Mulat; Astawesegn, Feleke Hailemichael; Demissie, Birhanu Wondimeneh; Zeleke, Liknaw Bewket

    2017-01-01

    A cesarean section is a surgical procedure in which incisions are made through a woman's abdomen and uterus to deliver her baby. Surgical site infections are a common surgical complication among patients delivered with cesarean section. Further it caused to increase maternal morbidity, stay of hospital and the cost of treatment. Hospital based cross-sectional study was conducted to assess the magnitude of surgical site infection following cesarean Site Infections and its associated factors at Lemlem Karl hospital July 1, 2013 to June 30, 2016. Retrospective card review was done on 384 women who gave birth via cesarean section at Lemlem Karl hospital from July 1, 2013 to June 30, 2016. Systematic sampling technique was used to select patient medical cards. The data were entered by Epi info version 7.2 then analyzed using Statistical Package for Social Sciences windows version 20. Both bivariate and multivariate logistic regression was done to test association between predictors and dependent variables. P value of cesarean section, the magnitude of surgical site infection following cesarean section Infection was 6.8%. The identified independent risk factors for surgical site infections were the duration of labor AOR=3.48; 95%CI (1.25, 9.68), rupture of membrane prior to cesarean section AOR=3.678; 95%CI (1.13, 11.96) and the abdominal midline incision (AOR=5.733; 95%CI (2.05, 16.00). The magnitude of surgical site infection following cesarean section is low compare to other previous studies. The independent associated factors for surgical site infection after cesarean section in this study: Membranes rupture prior to cesarean section, duration of labor and sub umbilical abdominal incision. In addition to ensuring sterile environment and aseptic surgeries, use of WHO surgical safety checklist would appear to be a very important intervention to reduce surgical site infections.

  3. Risk factors for delayed healing at the free anterolateral thigh flap donor site

    Directory of Open Access Journals (Sweden)

    Yoshiro Abe

    2018-01-01

    Full Text Available Background The free anterolateral thigh (ALT flap has been widely used for various kinds of reconstructions. However, delayed healing at the donor site occasionally occurs due to wound dehiscence or the partial loss of grafted skin at the donor site. The aim of the present study was to identify reliable predictive factors for delayed healing at the donor site after the harvest of a free ALT flap. Methods This study included 52 patients who underwent reconstructive procedures using free ALT flaps. The delayed healing group included patients with wounds at the donor site that had not healed over 3 weeks after surgery, and the normal healing group included patients who showed wound healing within 3 weeks after surgery. Multivariate logistic regression models were created to identify the risk factors for delayed healing at the ALT flap donor site. Results Among the 52 patients, 24 (46.2% showed delayed healing at the donor site, and 6 patients required additional operative treatment. A high preoperative body mass index (BMI, smoking, and skin grafting were found to be significantly associated with delayed healing at the ALT donor site. Of the 37 patients who underwent skin grafting, 23 (62% experienced delayed healing at the donor site. Conclusions A high preoperative BMI, smoking, and skin grafting were risk factors for delayed healing at the free ALT donor site. Skin grafting at the ALT donor site should be avoided in patients with a high BMI or a habit of smoking.

  4. Influence of economic factor and site milestones on the salience of environmental issues at Department of Energy sites

    International Nuclear Information System (INIS)

    O'Connor, S.; Yin, J.

    1997-01-01

    The change in the US Department of Energy's (DOE) mission from nuclear weapons production to remediation and restoration of its installations, in 1989, challenged all citizens around the nation's weapons complex to get involved in DOE's environmental management decision-making process. The purpose of this study is to determine whether, and to what extent, economic factors and site milestones influence the rise and fall of environmental issues and participation. One might believe that citizen participation would be influenced by economic conditions, particularly with the down-sizing that occurred at many DOE sites. Another factor that might influence salience of environmental issues is the occurrence of crucial events, or site milestones. Important events occurring at DOE installations are well publicized by local and national media, and citizens' interest and opinions are influenced by media. In this study, the authors use the number of comments expressed by the public and Indian tribes as a measure of public involvement and salience of issues. Their study, using multiple regression analysis, examined the relationships between the number of comments expressed and the economic conditions as indicated by monthly unemployment rates, and the relationship between the number of comments expressed and the occurrence of crucial site events or milestones

  5. Site specific transfer factor studies for Kaiga region

    International Nuclear Information System (INIS)

    Karunakara, N.

    2012-01-01

    The Radioecology Laboratory of University Science Instrumentation Centre, Mangalore University is engaged in frontline research studies on different aspects of environmental radioactivity and radiation protection for the last 20 years. Extensive studies have been carried out on radiation levels, radionuclides distribution, and transfer of radionuclides through terrestrial, aquatic and atmospheric pathways in the environment of West Coast of India including the Kaiga nuclear power plant. The baseline studies on radioactivity levels around Kaiga region was carried out well before the nuclear power plant became operational and the data generated under these studies are considered to be highly valuable for future impact assessments. The nuclear power plant became operational in the year 1999 and since then this laboratory is involved in radiological impact assessment studies around the nuclear power plant. Detailed Kaiga specific studies are now ongoing to estimate the transfer factors and transfer coefficients for radionuclides for different pathways, such as, (i) soil to rice (ii) soil to different types of vegetables (iii) water/sediment to fish (iv) soil to grass (v) grass to cow milk and (vi) milk to child. For these studies, rice and vegetable fields were developed very close to the nuclear power plant in Kaiga to study the transfer of radionuclides. The water required for this field was drawn from coolant water discharge canal of the power plant. Rice and different types of vegetables were grown in the experimental fields in different seasons of the year and the uptake of radionuclides was studied. For a comparative study, rice and vegetables were also collected from the fields of farmers of nearby villages and analysed. The transfer of artificial radionuclides through pathway involving cow milk was also studied in detail. A grass field was developed and cows were adopted specifically for this study. The cows were allowed to graze freely in this grass field

  6. Immune mediated shaping of microflora community composition depends on barrier site.

    Directory of Open Access Journals (Sweden)

    Felix Scholz

    Full Text Available Barrier surfaces, such as the intestinal lining and the skin, are colonized by a diverse community of commensal microorganisms. Although commensal microorganisms clearly impact the host immune system, whether the immune system also shapes the commensal community is poorly understood. We used 16S rDNA deep sequencing to test whether mice with specific immune defects have an altered commensal microflora. Initially, skin swabs were obtained from wild-type and Langerhans Cell (LC deficient mice. Despite the intimate contacts that LC make with the upper epidermis, no significant differences were observed in microbial community composition. Similarly, the skin of MyD88/TRIF(-/-, Rag1(-/- and heterozygous littermate controls showed no alteration in their commensal communities. Next we examined mouth swabs and feces. We did not find a difference in the MyD88/TRIF(-/- mice. However, we did observe a significant shift in the microbial composition in the feces and mouths of Rag1(-/- mice. Thus, we conclude that the adaptive immune system modulates the microbial composition at mucosal surfaces in the steady-state but LC, adaptive immunity, and MyD88-dependent innate responses do not affect the skin microbiome revealing a major distinction between barrier sites.

  7. Ly49-dependent NK cell licensing and effector inhibition involve the same interaction site on MHC ligands1

    Science.gov (United States)

    Choi, Taewoong; Ferris, Stephen T.; Matsumoto, Naoki; Poursine-Laurent, Jennifer; Yokoyama, Wayne M.

    2011-01-01

    NK cells become functionally competent to be triggered by their activation receptors through the interaction of NK cell inhibitory receptors with their cognate self-MHC ligands, an MHC-dependent educational process termed “licensing.” For example, Ly49A+ NK cells become licensed by the interaction of the Ly49A inhibitory receptor with its MHC class I ligand, H2Dd while Ly49C+ NK cells are licensed by H2Kb. Structural studies indicate that the Ly49A inhibitory receptor may interact with two sites, termed site 1 and site 2, on its H2Dd ligand. Site 2 encompasses the α1/α2/α3 domains of the H2Dd heavy chain and β2-microglobulin (β2m), and is the functional binding site for the Ly49A in effector inhibition. Ly49C functionally interacts with a similar site in H2Kb. However, it is currently unknown whether this same site is involved in Ly49A or Ly49C-dependent licensing. Herein, we produced transgenic C57BL/6 mice expressing wild type or site 2 mutant H2Dd molecules and studied whether or not Ly49A+ NK cells are licensed. We also investigated Ly49A and Ly49C-dependent NK licensing in murine β2m-deficient mice which are transgenic for human β2m which has species-specific amino acid substitutions in β2m. Our data from these transgenic mice indicate that site 2 on self-MHC is critical for Ly49A and Ly49C-dependent NK cell licensing. Thus, NK cell licensing through Ly49 involves specific interactions with its MHC ligand that are similar to those involved in effector inhibition. PMID:21335486

  8. Measured and predicted aerosol light scattering enhancement factors at the high alpine site Jungfraujoch

    Directory of Open Access Journals (Sweden)

    R. Fierz-Schmidhauser

    2010-03-01

    Full Text Available Ambient relative humidity (RH determines the water content of atmospheric aerosol particles and thus has an important influence on the amount of visible light scattered by particles. The RH dependence of the particle light scattering coefficient (σsp is therefore an important variable for climate forcing calculations. We used a humidification system for a nephelometer which allows for the measurement of σsp at a defined RH in the range of 20–95%. In this paper we present measurements of light scattering enhancement factors f(RH=σsp(RH/σsp(dry from a 1-month campaign (May 2008 at the high alpine site Jungfraujoch (3580 m a.s.l., Switzerland. Measurements at the Jungfraujoch are representative for the lower free troposphere above Central Europe. For this aerosol type hardly any information about the f(RH is available so far. At this site, f(RH=85% varied between 1.2 and 3.3. Measured f(RH agreed well with f(RH calculated with Mie theory using measurements of the size distribution, chemical composition and hygroscopic diameter growth factors as input. Good f(RH predictions at RH<85% were also obtained with a simplified model, which uses the Ångström exponent of σsp(dry as input. RH influences further intensive optical aerosol properties. The backscatter fraction decreased by about 30% from 0.128 to 0.089, and the single scattering albedo increased on average by 0.05 at 85% RH compared to dry conditions. These changes in σsp, backscatter fraction and single scattering albedo have a distinct impact on the radiative forcing of the Jungfraujoch aerosol.

  9. Why Do You Adopt Social Networking Sites? Investigating the Driving Factors through Structural Equation Modelling

    Science.gov (United States)

    Jan, Muhammad Tahir

    2017-01-01

    Purpose: The purpose of this paper is to investigate those factors that are associated with the adoption of social networking sites from the perspective of Muslim users residing in Malaysia. Design/methodology/approach: A complete self-administered questionnaire was collected from 223 Muslim users of social networking sites in Malaysia. Both…

  10. Doping site dependent thermoelectric properties of epitaxial strontium titanate thin films

    KAUST Repository

    Abutaha, Anas I.

    2014-01-01

    We demonstrate that the thermoelectric properties of epitaxial strontium titanate (STO) thin films can be improved by additional B-site doping of A-site doped ABO3 type perovskite STO. The additional B-site doping of A-site doped STO results in increased electrical conductivity, but at the expense of Seebeck coefficient. However, doping on both sites of the STO lattice significantly reduces the lattice thermal conductivity of STO by adding more densely and strategically distributed phononic scattering centers that attack wider phonon spectra. The additional B-site doping limits the trade-off relationship between the electrical conductivity and total thermal conductivity of A-site doped STO, leading to an improvement in the room-temperature thermoelectric figure of merit, ZT. The 5% Pr3+ and 20% Nb5+ double-doped STO film exhibits the best ZT of 0.016 at room temperature. This journal is

  11. Radiological bioconcentration factors for aquatic, terrestrial, and wetland ecosystems at the Savannah River Site

    Energy Technology Data Exchange (ETDEWEB)

    Cummins, C.L.

    1994-09-01

    As a result of operations at the Savannah River Site (SRS), over 50 radionuclides have been released to the atmosphere and to onsite streams and seepage basins. Now, many of these radionuclides are available to aquatic and/or terrestrial organisms for uptake and cycling through the food chain. Knowledge about the uptake and cycling of these radionuclides is now crucial in evaluating waste management and clean-up alternatives for the site. Numerous studies have been conducted at the SRS over the past forty years to study the uptake and distribution of radionuclides in the Savannah River Site environment. In many instances, bioconcentration factors have been calculated to quantify the uptake of a radionuclide by an organism from the surrounding medium (i.e., soil or water). In the past, it has been common practice to use bioconcentration factors from the literature because site-specific data were not readily available. However, because of the variability of bioconcentration factors due to experimental or environmental conditions, site-specific data should be used when available. This report compiles and summarizes site-specific bioconcentration factors for selected radionuclides released at the Savannah River Site (SRS). An extensive literature search yielded site-specific bioconcentration factors for cesium, strontium, cobalt, plutonium, americium, curium, and tritium. These eight radionuclides have been the primary radionuclides studied at SRS because of their long half lives or because they are major contributors to radiological dose from exposure. For most radionuclides, it was determined that the site-specific bioconcentration factors were higher than those reported in literature. This report also summarizes some conditions that affect radionuclide bioavailability to and bioconcentration by aquatic and terrestrial organisms.

  12. Radiological bioconcentration factors for aquatic, terrestrial, and wetland ecosystems at the Savannah River Site

    International Nuclear Information System (INIS)

    Cummins, C.L.

    1994-09-01

    As a result of operations at the Savannah River Site (SRS), over 50 radionuclides have been released to the atmosphere and to onsite streams and seepage basins. Now, many of these radionuclides are available to aquatic and/or terrestrial organisms for uptake and cycling through the food chain. Knowledge about the uptake and cycling of these radionuclides is now crucial in evaluating waste management and clean-up alternatives for the site. Numerous studies have been conducted at the SRS over the past forty years to study the uptake and distribution of radionuclides in the Savannah River Site environment. In many instances, bioconcentration factors have been calculated to quantify the uptake of a radionuclide by an organism from the surrounding medium (i.e., soil or water). In the past, it has been common practice to use bioconcentration factors from the literature because site-specific data were not readily available. However, because of the variability of bioconcentration factors due to experimental or environmental conditions, site-specific data should be used when available. This report compiles and summarizes site-specific bioconcentration factors for selected radionuclides released at the Savannah River Site (SRS). An extensive literature search yielded site-specific bioconcentration factors for cesium, strontium, cobalt, plutonium, americium, curium, and tritium. These eight radionuclides have been the primary radionuclides studied at SRS because of their long half lives or because they are major contributors to radiological dose from exposure. For most radionuclides, it was determined that the site-specific bioconcentration factors were higher than those reported in literature. This report also summarizes some conditions that affect radionuclide bioavailability to and bioconcentration by aquatic and terrestrial organisms

  13. Size Dependence of Atomically Precise Gold Nanoclusters in Chemoselective Hydrogenation and Active Site Structure

    Energy Technology Data Exchange (ETDEWEB)

    Li, Gao [Carnegie Mellon University (CMU); Jiang, Deen [ORNL; Kumar, Santosh [Carnegie Mellon University (CMU); Chen, Yuxiang [Carnegie Mellon University (CMU); Jin, Rongchao [Carnegie Mellon University (CMU)

    2014-01-01

    We here investigate the catalytic properties of water-soluble Aun(SG)m nanocluster catalysts (H-SG = glutathione) of different sizes, including Au15(SG)13, Au18(SG)14, Au25(SG)18, Au38(SG)24, and captopril-capped Au25(Capt)18 nanoclusters. These Aun(SR)m nanoclusters (-SR represents thiolate generally) are used as homogeneous catalysts (i.e., without supports) in the chemoselective hydrogenation of 4-nitrobenzaldehyde (4-NO2PhCHO) to 4-nitrobenzyl alcohol (4-NO2PhCH2OH) in water with H2 gas (20 bar) as the hydrogen source. These nanocluster catalysts, except Au18(SG)14, remain intact after the catalytic reaction, evidenced by UV-vis spectra which are characteristic of each sized nanoclusters and thus serve as spectroscopic fingerprints . We observe a drastic size-dependence and steric effect of protecting ligands on the gold nanocluster catalysts in the hydrogenation reaction. Density functional theory (DFT) modeling of the 4-nitrobenzaldehyde adsorption shows that both the CHO and NO2 groups are in close interact with the S-Au-S staples on the gold nanocluster surface; the adsorption of the 4-nitrobenzaldehyde molecule on the four different sized Aun(SR)m nanoclusters are moderately strong and similar in strength. The DFT results suggest that the catalytic activity of the Aun(SR)m nanoclusters is primarily determined by the surface area of the Au nanocluster, consistent with the observed trend of the conversion of 4-nitrobenzaldehyde versus the cluster size. Overall, this work offers the molecular insight into the hydrogenation of 4-nitrobenzaldehyde and the catalytically active site structure on gold nanocluster catalysts.

  14. Novel fundamental building blocks and site dependent isomorphism in the first actinide borophosphates.

    Science.gov (United States)

    Wu, Shijun; Polinski, Matthew J; Malcherek, Thomas; Bismayer, Ulrich; Klinkenberg, Martina; Modolo, Giuseppe; Bosbach, Dirk; Depmeier, Wulf; Albrecht-Schmitt, Thomas E; Alekseev, Evgeny V

    2013-07-15

    Three novel uranyl borophosphates, Ag2(NH4)3[(UO2)2{B3O(PO4)4(PO4H)2}]H2O (AgNBPU-1), Ag(2-x)(NH4)3[(UO2)2{B2P5O(20-x)(OH)x}] (x = 1.26) (AgNBPU-2), and Ag(2-x)(NH4)3[(UO2)2{B2P(5-y)AsyO(20-x)(OH)x}] (x = 1.43, y = 2.24) (AgNBPU-3), have been prepared by the H3BO3-NH4H2PO4/NH4H2AsO4 flux method. The structure of AgNBPU-1 has an unprecedented fundamental building block (FBB), composed of three BO4 and six PO4 tetrahedra which can be written as 9□:[Φ] □□|□□|□□|. Two Ag atoms are linearly coordinated; the coordination of a third one is T-shaped. AgNBPU-2 and AgNBPU-3 are isostructural and possess a FBB of two BO4 and five TO4 (T = P, As) tetrahedra (7□:□□|□). AgNBPU-3 is a solid solution with some PO4 tetrahedra of the AgNBPU-2 end-member being substituted by AsO4. Only two out of the three independent P positions are partially occupied by As, resulting in site dependent isomorphism. The three compounds represent the first actinide borophosphates.

  15. Blood coagulation factor XIa binds specifically to a site on activated human platelets distinct from that for factor XI

    International Nuclear Information System (INIS)

    Sinha, D.; Seaman, F.S.; Koshy, A.; Knight, L.C.; Walsh, P.N.

    1984-01-01

    Binding of 125 I-Factor XIa to platelets required the presence of high molecular weight kininogen, was enhanced when platelets were stimulated with thrombin, and reached a plateau after 4-6 min of incubation at 37 degrees C. Factor XIa binding was specific: 50- to 100-fold molar excesses of unlabeled Factor XIa prevented binding, whereas Factor XI, prekallikrein, Factor XIIa, and prothrombin did not. When washed erythrocytes, added at concentrations calculated to provide an equivalent surface area to platelets, were incubated with Factor XIa, only a low level of nonspecific, nonsaturable binding was detected. Factor XIa binding to platelets was partially reversible and was saturable at concentrations of added Factor XIa of 0.2-0.4 microgram/ml (1.25-2.5 microM). The number of Factor XIa binding sites on activated platelets was estimated to be 225 per platelet (range, 110-450). We conclude that specific, high affinity, saturable binding sites for Factor XIa are present on activated platelets, are distinct from those previously demonstrated for Factor XI, and require the presence of high molecular weight kininogen

  16. A deeper look into transcription regulatory code by preferred pair distance templates for transcription factor binding sites

    KAUST Repository

    Kulakovskiy, Ivan V.

    2011-08-18

    Motivation: Modern experimental methods provide substantial information on protein-DNA recognition. Studying arrangements of transcription factor binding sites (TFBSs) of interacting transcription factors (TFs) advances understanding of the transcription regulatory code. Results: We constructed binding motifs for TFs forming a complex with HIF-1α at the erythropoietin 3\\'-enhancer. Corresponding TFBSs were predicted in the segments around transcription start sites (TSSs) of all human genes. Using the genome-wide set of regulatory regions, we observed several strongly preferred distances between hypoxia-responsive element (HRE) and binding sites of a particular cofactor protein. The set of preferred distances was called as a preferred pair distance template (PPDT). PPDT dramatically depended on the TF and orientation of its binding sites relative to HRE. PPDT evaluated from the genome-wide set of regulatory sequences was used to detect significant PPDT-consistent binding site pairs in regulatory regions of hypoxia-responsive genes. We believe PPDT can help to reveal the layout of eukaryotic regulatory segments. © The Author 2011. Published by Oxford University Press. All rights reserved.

  17. Age-dependent changes in Porphyromonas gingivalis and Prevotella species/phylotypes in healthy gingiva and inflamed/diseased sub-gingival sites.

    Science.gov (United States)

    Nadkarni, Mangala A; Chhour, Kim-Ly; Browne, Gina V; Byun, Roy; Nguyen, Ky-Anh; Chapple, Cheryl C; Jacques, Nicholas A; Hunter, Neil

    2015-05-01

    Early colonisation of oral surfaces by periodontal pathogens presents a significant risk factor for subsequent development of destructive disease affecting tissues that support the dentition. The aims of the present study were to establish the age-dependent relationship between sub-gingival profiles of 22 Prevotella species/phylotypes in children, adolescents and adults from an isolated Aboriginal community and, further, to use this information to identify Prevotella species that could serve as microbial risk indicators. DNA isolated from sub-gingival plaque samples (three healthy sites and three inflamed/diseased sites) from adults, adolescents and children was screened for Porphyromonas gingivalis load and 22 Prevotella species/phylotypes by species-specific PCR. A noticeable feature in adolescents was the marked increase in colonisation by P. gingivalis across all test sites. The mean number of Prevotella species/phylotypes colonising inflamed/diseased sub-gingival sites increased with age. Progressive partitioning of selected Prevotella species/phylotypes to healthy or inflamed/diseased sites was evident. Prevalence of Prevotella intermedia, Prevotella oral clone P4PB_24 and Prevotella oris increased significantly with age in diseased sites. Similarly, significant age-dependent increase in colonisation of healthy as well as inflamed/diseased sub-gingival sites was apparent for Prevotella oralis, Prevotella multiformis, Prevotella denticola, Prevotella strain P4P_53 and Prevotella oral clone BR014. Early colonisation of children by P. gingivalis, P. intermedia and Prevotella oral clone P4PB_24 provides indication of risk for subsequent development of periodontal disease. In the present study, the complexity of Prevotella species within gingival sites is explored as a basis for evaluating contribution of Prevotella species to disease.

  18. Risk factors for acute surgical site infections after lumbar surgery: a retrospective study.

    Science.gov (United States)

    Lai, Qi; Song, Quanwei; Guo, Runsheng; Bi, Haidi; Liu, Xuqiang; Yu, Xiaolong; Zhu, Jianghao; Dai, Min; Zhang, Bin

    2017-07-19

    Currently, many scholars are concerned about the treatment of postoperative infection; however, few have completed multivariate analyses to determine factors that contribute to the risk of infection. Therefore, we conducted a multivariate analysis of a retrospectively collected database to analyze the risk factors for acute surgical site infection following lumbar surgery, including fracture fixation, lumbar fusion, and minimally invasive lumbar surgery. We retrospectively reviewed data from patients who underwent lumbar surgery between 2014 and 2016, including lumbar fusion, internal fracture fixation, and minimally invasive surgery in our hospital's spinal surgery unit. Patient demographics, procedures, and wound infection rates were analyzed using descriptive statistics, and risk factors were analyzed using logistic regression analyses. Twenty-six patients (2.81%) experienced acute surgical site infection following lumbar surgery in our study. The patients' mean body mass index, smoking history, operative time, blood loss, draining time, and drainage volume in the acute surgical site infection group were significantly different from those in the non-acute surgical site infection group (p operative type in the acute surgical site infection group were significantly different than those in the non-acute surgical site infection group (p operative type, operative time, blood loss, and drainage time were independent predictors of acute surgical site infection following lumbar surgery. In order to reduce the risk of infection following lumbar surgery, patients should be evaluated for the risk factors noted above.

  19. Personality as a risk factor for illicit opioid use and a protective factor for illicit opioid dependence

    NARCIS (Netherlands)

    Zaaijer, Eline R.; Bruijel, Jessica; Blanken, Peter; Hendriks, Vincent; Koeter, Maarten W. J.; Kreek, Mary Jeanne; Booij, Jan; Goudriaan, Anna E.; van Ree, Jan M.; van den Brink, Wim

    2014-01-01

    Most studies investigating the role of personality as a risk factor for the development of opioid dependence compare dependent opioid users with healthy controls who never used heroin. In order to understand the potential protective role of personality, it is crucial to compare illicit opioid users

  20. Position specific variation in the rate of evolution intranscription factor binding sites

    Energy Technology Data Exchange (ETDEWEB)

    Moses, Alan M.; Chiang, Derek Y.; Kellis, Manolis; Lander, EricS.; Eisen, Michael B.

    2003-08-28

    The binding sites of sequence specific transcription factors are an important and relatively well-understood class of functional non-coding DNAs. Although a wide variety of experimental and computational methods have been developed to characterize transcription factor binding sites, they remain difficult to identify. Comparison of non-coding DNA from related species has shown considerable promise in identifying these functional non-coding sequences, even though relatively little is known about their evolution. Here we analyze the genome sequences of the budding yeasts Saccharomyces cerevisiae, S. bayanus, S. paradoxus and S. mikataeto study the evolution of transcription factor binding sites. As expected, we find that both experimentally characterized and computationally predicted binding sites evolve slower than surrounding sequence, consistent with the hypothesis that they are under purifying selection. We also observe position-specific variation in the rate of evolution within binding sites. We find that the position-specific rate of evolution is positively correlated with degeneracy among binding sites within S. cerevisiae. We test theoretical predictions for the rate of evolution at positions where the base frequencies deviate from background due to purifying selection and find reasonable agreement with the observed rates of evolution. Finally, we show how the evolutionary characteristics of real binding motifs can be used to distinguish them from artifacts of computational motif finding algorithms. As has been observed for protein sequences, the rate of evolution in transcription factor binding sites varies with position, suggesting that some regions are under stronger functional constraint than others. This variation likely reflects the varying importance of different positions in the formation of the protein-DNA complex. The characterization of the pattern of evolution in known binding sites will likely contribute to the effective use of comparative

  1. Theory of site-specific interactions of the combinatorial transcription factors with DNA

    International Nuclear Information System (INIS)

    Murugan, R

    2010-01-01

    We derive a functional relationship between the mean first passage time associated with the concurrent binding of multiple transcription factors (TFs) at their respective combinatorial cis-regulatory module sites (CRMs) and the number n of TFs involved in the regulation of the initiation of transcription of a gene of interest. Our results suggest that the overall search time τ s that is required by the n TFs to locate their CRMs which are all located on the same DNA chain scales with n as τ s ∼n α where α ∼ (2/5). When the jump size k that is associated with the dynamics of all the n TFs along DNA is higher than that of the critical jump size k c that scales with the size of DNA N as k c ∼ N 2/3 , we observe a similar power law scaling relationship and also the exponent α. When k c , α shows a strong dependence on both n and k. Apparently there is a critical number of combinatorial TFs n c ∼ 20 that is required to efficiently regulate the initiation of transcription of a given gene below which (2/5) 1. These results seem to be independent of the initial distances between the TFs and their corresponding CRMs and also suggest that the maximum number of TFs involved in a given combinatorial regulation of the initiation of transcription of a gene of interest seems to be restricted by the degree of condensation of the genomic DNA. The optimum number m opt of roadblock protein molecules per genome at which the search time associated with these n TFs to locate their binding sites is a minimum seems to scale as m opt ∼Ln α/2 where L is the sliding length of TFs whose maximum value seems to be such that L ≤ 10 4 bps for the E. coli bacterial genome.

  2. Spectral dependence of the linewidth enhancement factor in quantum dot lasers

    Energy Technology Data Exchange (ETDEWEB)

    Zubov, F. I., E-mail: fedyazu@mail.ru [Russian Academy of Sciences, St. Petersburg Academic University-Nanotechnology Research and Education Center (Russian Federation); Shernyakov, Yu. M.; Maximov, M. V. [Russian Academy of Sciences, Ioffe Physical-Technical Institute (Russian Federation); Zhukov, A. E. [Russian Academy of Sciences, St. Petersburg Academic University-Nanotechnology Research and Education Center (Russian Federation); Livshits, D. A. [Innolume GmbH (Germany); Payusov, A. S.; Nadtochiy, A. M. [Russian Academy of Sciences, Ioffe Physical-Technical Institute (Russian Federation); Savelyev, A. V.; Kryzhanovskaya, N. V. [Russian Academy of Sciences, St. Petersburg Academic University-Nanotechnology Research and Education Center (Russian Federation); Gordeev, N. Yu. [Russian Academy of Sciences, Ioffe Physical-Technical Institute (Russian Federation)

    2013-12-15

    The spectral analysis of amplified spontaneous emission is used to determine the linewidth enhancement factor (α-factor) in lasers based on InAs/InGaAs quantum dots (QDs) in a wide spectral range near the ground-state optical transition energy. The effect of the pump current and number of QDs on the spectral dependences of the α-factor is examined. The temperature dependence of the spectra of the α-factor is experimentally determined for the first time for lasers with InAs/InGaAs QDs. An explanation is suggested for the observed anomalous decrease in the α-factor with increasing temperature.

  3. Embracing the emerging precision agriculture technologies for site-specific management of yield-limiting factors.

    Science.gov (United States)

    Melakeberhan, H

    2002-09-01

    Precision agriculture (PA) is providing an information revolution using Global Positioning (GPS) and Geographic Information (GIS) systems and Remote Sensing (RS). These technologies allow better decision making in the management of crop yield-limiting biotic and abiotic factors and their interactions on a site-specific (SSM) basis in a wide range of production systems. Characterizing the nature of the problem(s) and public education are among the challenges that scientists, producers, and industry face when adapting PA technologies. To apply SSM, spatio-temporal characteristics of the problem(s) need to be determined and variations within a field demonstrated. Spatio-temporal characteristics of a given pathogen or pest problem may be known but may not be the only or primary cause of the problem. Hence, exact cause-and-effect relationships need to be established by incorporating GIS, GPS, and RS-generated data as well as possible interactions. Exploiting the potential of PA technologies in sustainable ways depends on whether or not we first ask ''Are we doing the right thing?'' (strategic) as opposed to ''Are we doing it right?'' (tactical).

  4. Description of Some Ecological Factors in Three Forest Sites in Lorestan Province and Their Impact on Myrtle (Myrtus communis L. Essential Oil Yield and Chemical Components

    Directory of Open Access Journals (Sweden)

    Z. Mir-Azadi

    2013-03-01

    Full Text Available Due to the side effects of chemical drugs, special attention is given recently to pharmaceutical plants. Myrtle (Myrtus communis L. is one of the valuable pharmaceutical plants, which is distributed over the vast areas of Iran. Yield and components of essential oil of this plant is dependent on ecological and genetic factors. In order to describe some ecological factors that affect myrtle in Lorestan province, three forest sites (Sepiddasht, Chame-moord, and Hamzeh Camp were selected. Some effective ecological factors on type of essential oil were measured and compared among the sites. To compare the yield and components of essential oil, myrtle leaves were collected during flowering stage in each site. Leaves were dried in open air conditions and the oil was extracted by distillation. Yield of essential oil was calculated and its components were identified by GC and GC/MS. Results showed that maximum yield belongs to Sepiddasht site. The altitude and soil Na, P, and organic carbon content of this site is quite different from other two sites. The main components of essential oils of these three sites had considerable differences. The amount of 9,10 anthracenedione was 29.1% in Sepiddasht site, while it was not found in the oil of Chame-moord site. It seems that differences in ecological and soil properties of the tree sites could have major effect on essential oil yield and its composition.

  5. Attachment Site Cysteine Thiol pKa Is a Key Driver for Site-Dependent Stability of THIOMAB Antibody-Drug Conjugates.

    Science.gov (United States)

    Vollmar, Breanna S; Wei, Binqing; Ohri, Rachana; Zhou, Jianhui; He, Jintang; Yu, Shang-Fan; Leipold, Douglas; Cosino, Ely; Yee, Sharon; Fourie-O'Donohue, Aimee; Li, Guangmin; Phillips, Gail L; Kozak, Katherine R; Kamath, Amrita; Xu, Keyang; Lee, Genee; Lazar, Greg A; Erickson, Hans K

    2017-10-18

    The incorporation of cysteines into antibodies by mutagenesis allows for the direct conjugation of small molecules to specific sites on the antibody via disulfide bonds. The stability of the disulfide bond linkage between the small molecule and the antibody is highly dependent on the location of the engineered cysteine in either the heavy chain (HC) or the light chain (LC) of the antibody. Here, we explore the basis for this site-dependent stability. We evaluated the in vivo efficacy and pharmacokinetics of five different cysteine mutants of trastuzumab conjugated to a pyrrolobenzodiazepine (PBD) via disulfide bonds. A significant correlation was observed between disulfide stability and efficacy for the conjugates. We hypothesized that the observed site-dependent stability of the disulfide-linked conjugates could be due to differences in the attachment site cysteine thiol pK a . We measured the cysteine thiol pK a using isothermal titration calorimetry (ITC) and found that the variants with the highest thiol pK a (LC K149C and HC A140C) were found to yield the conjugates with the greatest in vivo stability. Guided by homology modeling, we identified several mutations adjacent to LC K149C that reduced the cysteine thiol pK a and, thus, decreased the in vivo stability of the disulfide-linked PBD conjugated to LC K149C. We also present results suggesting that the high thiol pK a of LC K149C is responsible for the sustained circulation stability of LC K149C TDCs utilizing a maleimide-based linker. Taken together, our results provide evidence that the site-dependent stability of cys-engineered antibody-drug conjugates may be explained by interactions between the engineered cysteine and the local protein environment that serves to modulate the side-chain thiol pK a . The influence of cysteine thiol pK a on stability and efficacy offers a new parameter for the optimization of ADCs that utilize cysteine engineering.

  6. Psychological risk factors of social maladjustment and protective factors in alcohol-dependent women

    Directory of Open Access Journals (Sweden)

    Pleshakova E.A.

    2015-08-01

    Full Text Available The paper analyzes the psychological characteristics of alcohol-dependent women, including the particularities of subjective psychological symptomatic status, psychological well-being, motivation, social desirability and self-esteem. We tested the hypothesis that: 1 alcohol-dependent women expressed less motivation of social desirability and expressed more subjectively perceived symptoms in comparison with normal; 2 alcohol-dependent women have lower levels of well-being, self-esteem and level of aspiration in comparison with the conventional norm. The experimental group consisted of 46 women (mean age 45 years who are dependent on alcohol. The comparison group included 33 women with normal behavior who are not dependent on alcohol (the average age 33 years. We have found that a statistically significant contribution to the classification of women in a group of alcohol-dependent is made by low self-esteem, high levels of anxiety, low real self-evaluation of their success in business, willpower and mental health, low ideal self-evaluation in terms of the happiness and mind, achievable self-evaluation in terms of the happiness and visual attractiveness, the average level of the personal growth as basic component of well-being.

  7. Workers’ Age and the Impact of Psychological Factors on the Perception of Safety at Construction Sites

    Directory of Open Access Journals (Sweden)

    Muhammad Dawood Idrees

    2017-05-01

    Full Text Available The safety of construction workers is always a major concern at construction sites as the construction industry is inherently dangerous with many factors influencing worker safety. Several studies concluded that psychological factors such as workload, organizational relationships, mental stress, job security, and job satisfaction have significant effects on workers’ safety. However, research on psychological factors that are characteristic of different age groups have been limited. The aim of this study was to examine the impact of psychological factors on the perception of worker safety for two different age groups. After an extensive literature review, different psychological factors were identified, and a hypothetical research model was developed based on psychological factors that could affect workers’ perception of safety. A survey instrument was developed, and data were collected from seven different construction sites in Pakistan. Structural equation modeling (SEM was employed to test the hypothetical model for both age groups. The results revealed that workload and job satisfaction are significantly dominant factors on workers’ perception of safety in older workers, whereas organizational relationships, mental stress, and job security are dominant factors for younger workers at construction sites.

  8. Asap: a framework for over-representation statistics for transcription factor binding sites

    DEFF Research Database (Denmark)

    Marstrand, Troels T; Frellsen, Jes; Moltke, Ida

    2008-01-01

    -founded choice. METHODOLOGY: We introduce a software package, Asap, for fast searching with position weight matrices that include several standard methods for assessing over-representation. We have compared the ability of these methods to detect over-represented transcription factor binding sites in artificial......BACKGROUND: In studies of gene regulation the efficient computational detection of over-represented transcription factor binding sites is an increasingly important aspect. Several published methods can be used for testing whether a set of hypothesised co-regulated genes share a common regulatory...... regime based on the occurrence of the modelled transcription factor binding sites. However there is little or no information available for guiding the end users choice of method. Furthermore it would be necessary to obtain several different software programs from various sources to make a well...

  9. Evaluation factors for verification and validation of low-level waste disposal site models

    International Nuclear Information System (INIS)

    Moran, M.S.; Mezga, L.J.

    1982-01-01

    The purpose of this paper is to identify general evaluation factors to be used to verify and validate LLW disposal site performance models in order to assess their site-specific applicability and to determine their accuracy and sensitivity. It is intended that the information contained in this paper be employed by model users involved with LLW site performance model verification and validation. It should not be construed as providing protocols, but rather as providing a framework for the preparation of specific protocols or procedures. A brief description of each evaluation factor is provided. The factors have been categorized according to recommended use during either the model verification or the model validation process. The general responsibilities of the developer and user are provided. In many cases it is difficult to separate the responsibilities of the developer and user, but the user is ultimately accountable for both verification and validation processes. 4 refs

  10. Analysis of usability factors affecting purchase intention in online e-commerce sites

    Science.gov (United States)

    Perdana, R. A.; Suzianti, A.

    2017-03-01

    The growing number of internet users plays a significant role in the emergence of a variety of online e-commerce sites to meet the needs of Indonesians. However, there are still some problems faced by the users in using e-commerce sites. Therefore, a research related to user experience on their purchase intention to foster e-commerce sites is required. This study is conducted to find out the relationship between usability factors on e-commerce users’ purchase intention using a case study by using SEM to analyse the usability of the website. The result of this study shows that credibility, readability and telepresence are usability factors that directly affect purchase intention, while simplicity, consistency and interactivity are usability factors that indirectly affect purchase intention. Therefore, we can conclude that Indonesian consumers are on the Early Majority phase in adopting Company A.

  11. Site-SpecificCu Labeling of the Serine Protease, Active Site Inhibited Factor Seven Azide (FVIIai-N), Using Copper Free Click Chemistry

    DEFF Research Database (Denmark)

    Jeppesen, Troels E; Kristensen, Lotte K; Nielsen, Carsten H

    2018-01-01

    A method for site-specific radiolabeling of the serine protease active site inhibited factor seven (FVIIai) with64Cu has been applied using a biorthogonal click reaction. FVIIai binds to tissue factor (TF), a trans-membrane protein involved in hemostasis, angiogenesis, proliferation, cell migrati...

  12. ATP-Dependent Chromatin Remodeling Factors and Their Roles in Affecting Nucleosome Fiber Composition

    Directory of Open Access Journals (Sweden)

    Alexandra Lusser

    2011-10-01

    Full Text Available ATP-dependent chromatin remodeling factors of the SNF2 family are key components of the cellular machineries that shape and regulate chromatin structure and function. Members of this group of proteins have broad and heterogeneous functions ranging from controlling gene activity, facilitating DNA damage repair, promoting homologous recombination to maintaining genomic stability. Several chromatin remodeling factors are critical components of nucleosome assembly processes, and recent reports have identified specific functions of distinct chromatin remodeling factors in the assembly of variant histones into chromatin. In this review we will discuss the specific roles of ATP-dependent chromatin remodeling factors in determining nucleosome composition and, thus, chromatin fiber properties.

  13. Phosphorylation-dependent Regulation of Connecdenn/DENND1 Guanine Nucleotide Exchange Factors.

    Science.gov (United States)

    Kulasekaran, Gopinath; Nossova, Nadya; Marat, Andrea L; Lund, Ingrid; Cremer, Christopher; Ioannou, Maria S; McPherson, Peter S

    2015-07-17

    Connecdenn 1/2 are DENN (differentially expressed in normal and neoplastic cells) domain-bearing proteins that function as GEFs (guanine nucleotide exchange factors) for the small GTPase Rab35. Disruption of connecdenn/Rab35 function leads to defects in the recycling of multiple cargo proteins from endosomes with altered cell function, yet the regulation of connecdenn GEF activity is unexplored. We now demonstrate that connecdenn 1/2 are autoinhibited such that the purified, full-length proteins have significantly less Rab35 binding and GEF activity than the isolated DENN domain. Both proteins are phosphorylated with prominent phosphorylation sites between residues 500 and 600 of connecdenn 1. A large scale proteomics screen revealed that connecdenn 1 is phosphorylated at residues Ser-536 and Ser-538 in an Akt-dependent manner in response to insulin stimulation of adipocytes. Interestingly, we find that an Akt inhibitor reduces connecdenn 1 interaction with Rab35 after insulin treatment of adipocytes. Remarkably, a peptide flanking Ser-536/Ser-538 binds the DENN domain of connecdenn 1, whereas a phosphomimetic peptide does not. Moreover, connecdenn 1 interacts with 14-3-3 proteins, and this interaction is also disrupted by Akt inhibition and by mutation of Ser-536/Ser-538. We propose that Akt phosphorylation of connecdenn 1 downstream of insulin activation regulates connecdenn 1 function through an intramolecular interaction. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Phosphorylation-dependent Regulation of Connecdenn/DENND1 Guanine Nucleotide Exchange Factors*

    Science.gov (United States)

    Kulasekaran, Gopinath; Nossova, Nadya; Marat, Andrea L.; Lund, Ingrid; Cremer, Christopher; Ioannou, Maria S.; McPherson, Peter S.

    2015-01-01

    Connecdenn 1/2 are DENN (differentially expressed in normal and neoplastic cells) domain-bearing proteins that function as GEFs (guanine nucleotide exchange factors) for the small GTPase Rab35. Disruption of connecdenn/Rab35 function leads to defects in the recycling of multiple cargo proteins from endosomes with altered cell function, yet the regulation of connecdenn GEF activity is unexplored. We now demonstrate that connecdenn 1/2 are autoinhibited such that the purified, full-length proteins have significantly less Rab35 binding and GEF activity than the isolated DENN domain. Both proteins are phosphorylated with prominent phosphorylation sites between residues 500 and 600 of connecdenn 1. A large scale proteomics screen revealed that connecdenn 1 is phosphorylated at residues Ser-536 and Ser-538 in an Akt-dependent manner in response to insulin stimulation of adipocytes. Interestingly, we find that an Akt inhibitor reduces connecdenn 1 interaction with Rab35 after insulin treatment of adipocytes. Remarkably, a peptide flanking Ser-536/Ser-538 binds the DENN domain of connecdenn 1, whereas a phosphomimetic peptide does not. Moreover, connecdenn 1 interacts with 14-3-3 proteins, and this interaction is also disrupted by Akt inhibition and by mutation of Ser-536/Ser-538. We propose that Akt phosphorylation of connecdenn 1 downstream of insulin activation regulates connecdenn 1 function through an intramolecular interaction. PMID:26055712

  15. Morbidity and risk factors for surgical site infection following cesarean section in Guangdong Province, China.

    Science.gov (United States)

    Gong, Shi-Peng; Guo, Hong-Xia; Zhou, Hong-Zhen; Chen, Li; Yu, Yan-Hong

    2012-03-01

    To estimate the incidence of and identify the risk factors for a surgical site infection after a cesarean section. A survey of women who underwent a cesarean section was conducted in eight hospitals in Guangdong Province, China. The rate of surgical site infection was estimated and a nested case control study was then carried out to identify the risk factors. Among 13 798 women surveyed, 96 (0.7%) developed a surgical site infection after a cesarean section. Multivariate logistic regression analysis identified six factors independently associated with an increased risk of surgical site infection, which included obesity, premature rupture of membranes, lower preoperative hemoglobin, prolonged surgery, lack of prophylactic antibiotics and excessive anal examinations performed during hospitalization. Surgical site infection occurs in approximately 0.7% of cesarean section cases in the general obstetric population in China. Obesity, premature rupture of membranes, lower preoperative hemoglobin, prolonged surgery, lack of prophylactic antibiotics and excessive anal examinations during hospitalization are considered to be independent risk factors. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

  16. Conserved epitope on several human vitamin K-dependent proteins: location of the antigenic site and influence of metal ions on antibody binding

    International Nuclear Information System (INIS)

    Church, W.R.; Messier, T.; Howard, P.R.; Amiral, J.; Meyer, D.; Mann, K.G.

    1988-01-01

    A murine monoclonal antibody (designated H-11) produced by injecting mice with purified human protein C was found to bind several human vitamin K-dependent proteins. Using a solid-phase competitive radioimmunoassay with antibody immobilized onto microtiter plates, binding of 125 I-labeled protein C to the antibody was inhibited by increasing amounts of protein C, prothrombin, and Factors X and VII over a concentration range of 1 x 10 -8 to 1 x 10 -6 M. Chemical treatment of prothrombin with a variety of agents did not destroy the antigenic site recognized by the antibody as measured by immunoblotting of prothrombin or prothrombin derivative immobilized onto nitrocellulose. Immunoblotting of purified vitamin K-dependent polypeptides with the monoclonal antibody following sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrophoretic transfer to nitrocellulose indicated that the antigenic site was found on the light chains of protein C and Factor X. The exact location of the antigenic determinant for antibody H-11 was established using synthetic peptides. Comparison of protein sequences of bovine and human vitamin K-dependent proteins suggests that the sequence Phe-Leu-Glu-Glu-Xaa-Arg/Lys is required for antibody binding. Increasing concentrations of Ca 2+ , Mg 2+ , or Mn 2+ partially inhibited binding of 125 I-protein C to the antibody in a solid-phase assay system with half-maximal binding observed at divalent metal ion concentrations of 2, 4, and 0.6 mM, respectively. The antigenic site thus recognized by monoclonal antibody H-11 is located at the amino-terminal region in the highly conserved γ-carboxyglutamic acid-containing domains of several, but not all, vitamin K-dependent proteins

  17. Measurement of the energy dependence of the form factor $f_{+}$ in $K^{0}_{e3}$ decay

    CERN Document Server

    Apostolakis, Alcibiades J; Backenstoss, Gerhard; Bargassa, P; Behnke, O; Benelli, A; Bertin, V; Blanc, F; Bloch, P; Carlson, P J; Carroll, M; Cawley, E; Chertok, M B; Danielsson, M; Dejardin, M; Derré, J; Ealet, A; Eleftheriadis, C; Fetscher, W; Fidecaro, Maria; Filipcic, A; Francis, D; Fry, J; Gabathuler, Erwin; Gamet, R; Gerber, H J; Go, A; Haselden, A; Hayman, P J; Henry-Coüannier, F; Hollander, R W; Jon-And, K; Kettle, P R; Kokkas, P; Kreuger, R; Le Gac, R; Leimgruber, F; Mandic, I; Manthos, N; Marel, Gérard; Mikuz, M; Miller, J; Montanet, François; Müller, A; Nakada, Tatsuya; Pagels, B; Papadopoulos, I M; Pavlopoulos, P; Polivka, G; Rickenbach, R; Roberts, B L; Ruf, T; Schäfer, M; Schaller, L A; Schietinger, T; Schopper, A; Tauscher, Ludwig; Thibault, C; Touchard, F; Touramanis, C; van Eijk, C W E; Vlachos, S; Weber, P; Wigger, O; Wolter, M; Zavrtanik, D; Zimmerman, D

    2000-01-01

    Neutral-kaon decays to \\pielnu\\ % recorded by the CPLEAR experimentwere analysed to determine the $q^2$ dependence of the \\Kzet\\ electroweak form factor $f_+$. Based on $365\\,612$ events,this form factor was found to have a linear dependence on $q^2$with a slope $\\lambda_+ = 0.0245 \\pm 0.0012_{\\text{stat}} \\pm 0.0022_{\\text{syst}}$.

  18. Association analysis between polymorphisms in the conserved dopamine neurotrophic factor (CDNF) gene and cocaine dependence

    OpenAIRE

    Lohoff, Falk W.; Bloch, Paul J.; Ferraro, Thomas N.; Berrettini, Wade H.; Pettinati, Helen M.; Dackis, Charles A.; O’Brien, Charles P.; Kampman, Kyle M.; Oslin, David W.

    2009-01-01

    Cocaine induced neuroplasticity changes in the mesocorticolimbic dopamine systems are thought to be involved in the pathophysiology of cocaine dependence. Since neurotrophic factors have been observed to prevent/reverse and mimic cocaine-induced neurobiological changes in the brain, related genes are plausible candidates for susceptibility to cocaine dependence. The novel conserved dopamine neurotrophic factor protein (CDNF) promotes the survival, growth, and function of dopamine-specific neu...

  19. The role of the endothelial dependent relaxing factor in the regulation of cerebral circulation

    OpenAIRE

    Salles, Antonio A. F. de

    1988-01-01

    It has recently been demonstrated that vessel dilation induced by several physiological agents is dependent on an intact vascular endothelium. In order to explain this endothelium dependence, it has been hypothesized that a still unknown chemical substance, generically named Endothelium Dependent Relaxing Factor (EDRF) is necessary for physiological vasodilation. The role of this EDRF in the cerebrovascular physiology is not yet well understood. In this article the cerebrovascular physiologic...

  20. The influence of occupational stress factors on the nicotine dependence: a cross sectional study

    Directory of Open Access Journals (Sweden)

    Wolf Jürgen

    2010-04-01

    Full Text Available Abstract Objective This study analyses the association between occupational stress factors and nicotine dependence. Our hypothesis is that occupational stress factors increase nicotine dependence. Methods Data were taken from the Cologne Smoking Study, a case-control study that examines which genetic/psychosocial factors lead to a higher risk for smokers to suffer from cardiac infarction, lung cancer and/or to become addicted to nicotine. Our sample consisted of N = 197 currently smoking and employed participants. Nicotine dependence was measured using the Fagerström Test for Nicotine Dependence (FTND. The extent of the stress factors experienced at work was assessed using the Effort-Reward Imbalance scale (ERI. Logistic regression was used for the statistical analysis. Results Contrary to our hypothesis, the results show that occupational stress factors are actually associated with lower levels of nicotine dependence (N = 197; adjusted OR = 0.439; p = .059. Conclusions One possible explanation for the study's findings is that the participants have a heavy workload and can only smoke in their spare time. Another reason may be workplace smoking bans. Furthermore, the Fagerström Test for Nicotine Dependence is unable to examine nicotine dependence during working hours.

  1. Does work-site physical activity improve self-reported psychosocial workplace factors and job satisfaction?

    DEFF Research Database (Denmark)

    Roessler, K K; Rugulies, R; Bilberg, R

    2013-01-01

    PURPOSE: To investigate whether a work-site strength-training program has a positive effect on self-reported psychosocial workplace factors and job satisfaction. METHODS: We conducted a randomized controlled trial among laboratory technicians implementing neck and shoulder exercises for pain relief......, with 199 participants in the training group and 228 in the control group. Influence at work, sense of community, time pressure, and job satisfaction were measured with the Copenhagen Psychosocial Questionnaire at baseline and post-intervention after 20 weeks. RESULTS: There was no statistically significant...... of a work-site strength-training program on self-reported psychosocial workplace factors and job satisfaction....

  2. No generalized transverse momentum dependent factorization in the hadroproduction of high transverse momentum hadrons

    NARCIS (Netherlands)

    Rogers, T.C.; Mulders, P.J.G.

    2010-01-01

    It has by now been established that standard QCD factorization using transverse momentum dependent parton distribution functions fails in hadroproduction of nearly back-to-back hadrons with high transverse momentum. The essential problem is that gauge-invariant transverse momentum dependent parton

  3. IRF8 Transcription-Factor-Dependent Classical Dendritic Cells Are Essential for Intestinal T Cell Homeostasis

    DEFF Research Database (Denmark)

    Luda, Katarzyna M.; Joeris, Thorsten; Persson, Emma K.

    2016-01-01

    The role of dendritic cells (DCs) in intestinal immune homeostasis remains incompletely defined. Here we show that mice lacking IRF8 transcription-factor-dependent DCs had reduced numbers of T cells in the small intestine (SI), but not large intestine (LI), including an almost complete absence...... dependent DCs in the maintenance of intestinal T cell homeostasis....

  4. Oral health care behavior and frailty-related factors in a care-dependent older population.

    NARCIS (Netherlands)

    Niesten, D.J.M.; Witter, D.J.; Bronkhorst, E.M.; Creugers, N.H.J.

    2017-01-01

    OBJECTIVES: To assess, in older people with different levels of care-dependency 1) which frailty- and non-frailty related predisposing, enabling and need factors are associated with a) dental service use (DSU) frequency, b) changed DSU after the onset of care-dependency, c) brushing frequency, and

  5. Transcription factor control of growth rate dependent genes in Saccharomyces cerevisiae: A three factor design

    DEFF Research Database (Denmark)

    Fazio, Alessandro; Jewett, Michael Christopher; Daran-Lapujade, Pascale

    2008-01-01

    transcription factor target sets, transcription factors that coordinate balanced growth were also identified. Our analysis shows that FhII, Rap1, and Sfp1, regulating protein biosynthesis, have significantly enriched target sets for genes up-regulated with increasing growth rate. Cell cycle regulators...

  6. Mefloquine inhibits voltage dependent Nav1.4 channel by overlapping the local anaesthetic binding site.

    Science.gov (United States)

    Paiz-Candia, Bertin; Islas, Angel A; Sánchez-Solano, Alfredo; Mancilla-Simbro, Claudia; Scior, Thomas; Millan-PerezPeña, Lourdes; Salinas-Stefanon, Eduardo M

    2017-02-05

    Mefloquine constitutes a multitarget antimalaric that inhibits cation currents. However, the effect and the binding site of this compound on Na + channels is unknown. To address the mechanism of action of mefloquine, we employed two-electrode voltage clamp recordings on Xenopus laevis oocytes, site-directed mutagenesis of the rat Na + channel, and a combined in silico approach using Molecular Dynamics and docking protocols. We found that mefloquine: i) inhibited Na v 1.4 currents (IC 50 =60μM), ii) significantly delayed fast inactivation but did not affect recovery from inactivation, iii) markedly the shifted steady-state inactivation curve to more hyperpolarized potentials. The presence of the β1 subunit significantly reduced mefloquine potency, but the drug induced a significant frequency-independent rundown upon repetitive depolarisations. Computational and experimental results indicate that mefloquine overlaps the local anaesthetic binding site by docking at a hydrophobic cavity between domains DIII and DIV that communicates the local anaesthetic binding site with the selectivity filter. This is supported by the fact that mefloquine potency significantly decreased on mutant Na v 1.4 channel F1579A and significantly increased on K1237S channels. In silico this compound docked above F1579 forming stable π-π interactions with this residue. We provide structure-activity insights into how cationic amphiphilic compounds may exert inhibitory effects by docking between the local anaesthetic binding site and the selectivity filter of a mammalian Na + channel. Our proposed synergistic cycle of experimental and computational studies may be useful for elucidating binding sites of other drugs, thereby saving in vitro and in silico resources. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. A screening system to identify transcription factors that induce binding site-directed DNA demethylation.

    Science.gov (United States)

    Suzuki, Takahiro; Maeda, Shiori; Furuhata, Erina; Shimizu, Yuri; Nishimura, Hajime; Kishima, Mami; Suzuki, Harukazu

    2017-12-08

    DNA methylation is a fundamental epigenetic modification that is involved in many biological systems such as differentiation and disease. We and others recently showed that some transcription factors (TFs) are involved in the site-specific determination of DNA demethylation in a binding site-directed manner, although the reports of such TFs are limited. Here, we develop a screening system to identify TFs that induce binding site-directed DNA methylation changes. The system involves the ectopic expression of target TFs in model cells followed by DNA methylome analysis and overrepresentation analysis of the corresponding TF binding motif at differentially methylated regions. It successfully identified binding site-directed demethylation of SPI1, which is known to promote DNA demethylation in a binding site-directed manner. We extended our screening system to 15 master TFs involved in cellular differentiation and identified eight novel binding site-directed DNA demethylation-inducing TFs (RUNX3, GATA2, CEBPB, MAFB, NR4A2, MYOD1, CEBPA, and TBX5). Gene ontology and tissue enrichment analysis revealed that these TFs demethylate genomic regions associated with corresponding biological roles. We also describe the characteristics of binding site-directed DNA demethylation induced by these TFs, including the targeting of highly methylated CpGs, local DNA demethylation, and the overlap of demethylated regions between TFs of the same family. Our results show the usefulness of the developed screening system for the identification of TFs that induce DNA demethylation in a site-directed manner.

  8. Site-dependent distribution of macrophages in normal human extraocular muscles

    NARCIS (Netherlands)

    Schmidt, E. D.; van der Gaag, R.; Mourits, M. P.; Koornneef, L.

    1993-01-01

    PURPOSE: Clinical data indicate that extraocular muscles have different susceptibilities for some orbital immune disorders depending on their anatomic location. The resident immunocompetent cells may be important mediators in the local pathogenesis of such disorders so the distribution of these

  9. Risk factors for surgical site infection following cesarean delivery: a retrospective cohort study.

    Science.gov (United States)

    Ketcheson, Felicia; Woolcott, Christy; Allen, Victoria; Langley, Joanne M

    2017-07-11

    The rate of cesarean delivery is increasing in North America. Surgical site infection following this operation can make it difficult to recover, care for a baby and return home. We aimed to determine the incidence of surgical site infection to 30 days following cesarean delivery, associated risk factors and whether risk factors differed for predischarge versus postdischarge infection. We identified a retrospective cohort in Nova Scotia by linking the provincial perinatal database to hospital admissions and physician billings databases to follow women for 30 days after they had given birth by cesarean delivery between Jan. 1, 1997 and Dec. 31, 2012. Logistic regression with generalized estimating equations was used to determine risk factors for infection. A total of 25 123 women had 33 991 cesarean deliveries over the study period. Of the 25 123, 923 had surgical site infections, giving an incidence rate of 2.7% (95% CI 2.54%-2.89%); the incidence decreased over time. Risk factors for infection (adjusted odds ratios ≥ 1.5) were prepregnancy weight 87.0 kg or more, gaining 30.0 kg or more during pregnancy, chorioamnionitis, maternal blood transfusion, anticoagulation therapy, alcohol or drug abuse, second stage of labour before surgery, delivery in 1997-2000 and delivery in a hospital performing 130-1249 cesarean deliveries annually. Women who gave birth earlier in the study period, those who gave birth in a hospital with 130-949 cesarean deliveries per year and those with more than 1 fetus were at a significantly higher risk for surgical site infection before discharge; women who smoked were at significantly higher risk for surgical site infection after discharge. Most risk factors are known before delivery, and some are potentially modifiable. Although the incidence of surgical site infection decreased over time, targeted clinical and infection prevention and control interventions could further reduce the burden of illness associated with this health

  10. Effects of contraceptive steroids on cardiovascular risk factors in women with insulin-dependent diabetes mellitus

    DEFF Research Database (Denmark)

    Petersen, K R; Skouby, S O; Sidelmann, Johannes Jakobsen

    1994-01-01

    plasminogen activator and plasminogen activator inhibitor. The concentration of von Willebrand factor increased, but no change in albumin excretion rates were found. In the control group no changes in any of the variables were observed. CONCLUSION: Intake of modern oral contraceptives does not deteriorate......OBJECTIVE: We evaluated established cardiovascular risk factors within lipoprotein metabolism, hemostasis, and endothelial function in women with insulin-dependent diabetes mellitus who were using oral contraceptives. STUDY DESIGN: Twenty-five women with uncomplicated insulin-dependent diabetes...... the cardiovascular risk profile in women with insulin-dependent diabetes mellitus, but our study indicates a risk of disturbances of the endothelial integrity, which needs further investigation....

  11. AN ASSESSMENT OF FACTORS AFFECTING MATERIAL STOCK CONTROL PRACTICE ON SELECTED CONSTRUCTION SITES IN NIGERIA

    OpenAIRE

    Adafin, Johnson Kayode; Ayodele, Elijah Olusegun; Daramola, Olufemi

    2011-01-01

    This research examines the stock control methods utilized by construction firms on construction sites with a view to assessing the factors affecting material stock control practice by construction firms as well as determining the impact of factors affecting material stock control on building project performance. Data were collected with the aid of well-structured questionnaire administered on a number of construction professionals and technicians in some randomly selected building constructio...

  12. Risk Factors for Puncture Site Complications After Endovascular Procedures in Patients With Peripheral Arterial Disease.

    Science.gov (United States)

    Hackl, Gerald; Gary, Thomas; Belaj, Klara; Hafner, Franz; Eller, Philipp; Brodmann, Marianne

    2015-10-01

    To compare femoral access site closure techniques and to highlight risk factors for puncture site complications after lower extremity endovascular procedures. This retrospective study included 787 patients. Procedures were performed according to a standardized protocol. Puncture site complications within 24 hours were regarded as study end points. Ninety (11.5%) puncture site complications were registered. Conventional manual compression (n = 87, 11.1%) was significantly associated with puncture site complications (odds ratio [OR] 2.08, P = .03). Body mass index > 25 kg/m(2) (OR 0.54, P = .01) and prothrombin time > 70% (OR 0.38, P = .04) were protective. All bleeding occurred in procedures >45 minutes. Blood pressure >200 mm Hg and below the knee (BTK) procedures were strong predictors for access site complications (OR 4.21, P = .01 and OR 3.33, P = .02). We observed an inferiority of conventional manual compression. Age, procedure duration > 45 minutes, BTK procedures, uncontrolled hypertension, and impaired coagulation were risk factors. © The Author(s) 2015.

  13. Unit root tests for cross-sectionally dependent panels : The influence of observed factors

    NARCIS (Netherlands)

    Becheri, I.G.; Drost, F.C.; van den Akker, R.

    This paper considers a heterogeneous panel unit root model with cross-sectional dependence generated by a factor structure—the factor common to all units being an observed covariate. The model is shown to be Locally Asymptotically Mixed Normal (LAMN), with the random part of the limiting Fisher

  14. Time-dependent recovery of in vivo binding sites after drug dosing: A method for radiotracer evaluation

    International Nuclear Information System (INIS)

    Kilbourn, Michael R.

    1997-01-01

    The recovery of in vivo binding sites for (±)-α-[ 11 C]methoxytetrabenazine, a radioligand for the monoamine vesicular transporter (VMAT2), was determined in mouse brain at various times following a pharmacological dose of tetrabenazine. Concentrations of in vivo radioligand binding sites progressively increased and had reached control values by 8.5 h, and this recovery was consistent with the pharmacokinetics of the competing drug tetrabenazine and its active metabolite, dihydrotetrabenazine. This study demonstrates a simple experimental protocol of using a single dose of a reversible competing drug and time-dependent measurements of in vivo binding of a radioligand. This protocol is suitable for testing the sensitivity of an in vivo radiotracer for measurement of varying concentrations of in vivo binding sites

  15. Global analysis of ion dependence unveils hidden steps in DNA binding and bending by integration host factor

    Science.gov (United States)

    Vivas, Paula; Velmurugu, Yogambigai; Kuznetsov, Serguei V.; Rice, Phoebe A.; Ansari, Anjum

    2013-09-01

    Proteins that recognize and bind to specific sites on DNA often distort the DNA at these sites. The rates at which these DNA distortions occur are considered to be important in the ability of these proteins to discriminate between specific and nonspecific sites. These rates have proven difficult to measure for most protein-DNA complexes in part because of the difficulty in separating the kinetics of unimolecular conformational rearrangements (DNA bending and kinking) from the kinetics of bimolecular complex association and dissociation. A notable exception is the Integration Host Factor (IHF), a eubacterial architectural protein involved in chromosomal compaction and DNA recombination, which binds with subnanomolar affinity to specific DNA sites and bends them into sharp U-turns. The unimolecular DNA bending kinetics has been resolved using both stopped-flow and laser temperature-jump perturbation. Here we expand our investigation by presenting a global analysis of the ionic strength dependence of specific binding affinity and relaxation kinetics of an IHF-DNA complex. This analysis enables us to obtain each of the underlying elementary rates (DNA bending/unbending and protein-DNA association/dissociation), and their ionic strength dependence, even under conditions where the two processes are coupled. Our analysis indicates interesting differences in the ionic strength dependence of the bi- versus unimolecular steps. At moderate [KCl] (100-500 mM), nearly all the ionic strength dependence to the overall equilibrium binding affinity appears in the bimolecular association/dissociation of an initial, presumably weakly bent, encounter complex, with a slope SKbi ≈ 8 describing the loglog-dependence of the equilibrium constant to form this complex on [KCl]. In contrast, the unimolecular equilibrium constant to form the fully wrapped specific complex from the initial complex is nearly independent of [KCl], with SKuni protein-DNA contacts in the fully wrapped complex

  16. Risk factors of dependency of Chilean older adults and consequences on informal caregiving

    Directory of Open Access Journals (Sweden)

    María Consuelo CHEIX DIEGUEZ

    2015-12-01

    Full Text Available  Based on the 2009 National Survey of Elderly Dependency we characterize older people who are dependent in Chile, and we compute multivariate logistic regression models to assess the factors associated with dependency. In addition to age and the presence of diseases, there are other factors that are associated with increased prevalence of dependence, such as educational level, quality of family relationships and conducting activities such as physical exercise and reading. We also characterize and describe the level of well-being of the informal caregivers of the dependent persons. Stress informal caregiver is expressed both by an increase in depressive feelings and overload, as well as by a deterioration of physical health, who also tend to be women, older, low educational levels, intensifying further vulnerability context of this group.

  17. Nucleotide sequence of the gene coding for human factor VII, a vitamin K-dependent protein participating in blood coagulation

    International Nuclear Information System (INIS)

    O'Hara, P.J.; Grant, F.J.; Haldeman, B.A.; Gray, C.L.; Insley, M.Y.; Hagen, F.S.; Murray, M.J.

    1987-01-01

    Activated factor VII (factor VIIa) is a vitamin K-dependent plasma serine protease that participates in a cascade of reactions leading to the coagulation of blood. Two overlapping genomic clones containing sequences encoding human factor VII were isolated and characterized. The complete sequence of the gene was determined and found to span about 12.8 kilobases. The mRNA for factor VII as demonstrated by cDNA cloning is polyadenylylated at multiple sites but contains only one AAUAAA poly(A) signal sequence. The mRNA can undergo alternative splicing, forming one transcript containing eight segments as exons and another with an additional exon that encodes a larger prepro leader sequence. The latter transcript has no known counterpart in the other vitamin K-dependent proteins. The positions of the introns with respect to the amino acid sequence encoded by the eight essential exons of factor VII are the same as those present in factor IX, factor X, protein C, and the first three exons of prothrombin. These exons code for domains generally conserved among members of this gene family. The comparable introns in these genes, however, are dissimilar with respect to size and sequence, with the exception of intron C in factor VII and protein C. The gene for factor VII also contains five regions made up of tandem repeats of oligonucleotide monomer elements. More than a quarter of the intron sequences and more than a third of the 3' untranslated portion of the mRNA transcript consist of these minisatellite tandem repeats

  18. The effect of utilising age and sex dependent factors for calculating detriment from medical irradiation

    International Nuclear Information System (INIS)

    Mettler, F.A.; Davis, M.; Moseley, R.D.; Kelsey, C.A.

    1986-01-01

    Proposals have been made for a quantity that can be used to estimate possible detriment from medical radiology better than the ICRP's collective effective dose equivalent. One such approach utilises age and sex dependent 'weighting' factors. The magnitude of the effect obtained by utilising such factors when applied to an actual population has not been previously assessed. When age and sex dependent weighting factors are applied to diagnostic medical radiology for all hospital examinations conducted in the United States in 1980, estimates of detriment are reduced by one-third. (author)

  19. Understanding the factors that limit restoration success on a recreation-impacted subalpine site

    Science.gov (United States)

    Catherine Zabinski; David Cole

    2000-01-01

    Factors that limit successful revegetation of a subalpine site were studied through a combination of soil assays, greenhouse studies, and field manipulations. Campsite soils had higher available nitrogen, lower microbial community diversity, and lower seed bank density than undisturbed soils. In the greenhouse, there was no significant difference in plant growth on...

  20. AthaMap: from in silico data to real transcription factor binding sites.

    Science.gov (United States)

    Bülow, Lorenz; Steffens, Nils Ole; Galuschka, Claudia; Schindler, Martin; Hehl, Reinhard

    2006-01-01

    AthaMap generates a map for cis-regulatory sequences for the whole Arabidopsis thaliana genome. AthaMap was initially developed by matrix-based detection of putative transcription factor binding sites (TFBS) mostly determined from random binding site selection experiments. Now, also experimentally verified TFBS have been included for 48 different Arabidopsis thaliana transcription factors (TF). Based on these sequences, 89,416 very similar putative TFBS were determined within the genome of A. thaliana and annotated to AthaMap. Matrix- and single sequence-based binding sites can be included in colocalization analysis for the identification of combinatorial cis-regulatory elements. As an example, putative target genes of the WRKY18 transcription factor that is involved in plant-pathogen interaction were determined. New functions of AthaMap include descriptions for all annotated Arabidopsis thaliana genes and direct links to TAIR, TIGR and MIPS. Transcription factors used in the binding site determination are linked to TAIR and TRANSFAC databases. AthaMap is freely available at http://www.athamap.de.

  1. Soil-Site Factors Affecting Southern Upland Oak Managment and Growth

    Science.gov (United States)

    John K. Francis

    1980-01-01

    Soil supplies trees with physical support, moisture, oxygen, and nutrients. Amount of moisture most limits tree growth; and soil and topographic factors such as texture and aspect, which influence available soil moisture. are most useful in predicting growth. Equations that include soil and topographic variables can be used to predict site index. Foresters can also...

  2. Secretory Phospholipase A2 Hydrolysis Phospholipid Analogs is Dependent on Water Accessibility to the Active Site

    DEFF Research Database (Denmark)

    Peters, Günther H.J.; Møller, Martin S.; Jørgensen, Kent

    2007-01-01

    A new and unnatural type of phospholipids with the head group attached to the 2-position of the glycerol backbone has been synthesized and shown to be a good substrate for secretory phospholipase A2 (sPLA2). To investigate the unexpected sPLA2 activity, we have compared three different phospholip...... the correct position such that hydrolysis can occur is reduced for the unnatural lipids. The relative water count follows 1R > 2R > 3S. This is in good agreement with experimental data that indicate the same trend for sPLA2 activity:  1R > 2R > 3S....... observed experimentally in sPLA2 activity might be caused by reduced access of water molecules to the active site. We have monitored the number of water molecules that enter the active site region for the different sPLA2−phospholipid complexes and found that the probability of a water molecule reaching...

  3. Neighborhood geographical factors and the presence of advanced community pharmacy practice sites in Greater Chicago.

    Science.gov (United States)

    Johnson, Charisse L; Crawford, Stephanie Y; Lin, Swu-Jane; Salmon, J Warren; Smith, Miriam Mobley

    2009-02-19

    To determine the availability of experiential learning opportunities in culturally diverse areas and to identify opportunities and barriers to attract and sustain sites for the University of Illinois at Chicago College of Pharmacy. Utilizing variables of census tract income, racial/ethnicity composition and crime index, data analyses included descriptive statistics and multivariate logistic regression. Faculty members involved in experiential education were interviewed to identify other factors influencing site placement and selection for community-based advanced pharmacy practice experiences (APPEs). Median family income and Asian population were significantly higher and black population was significantly lower in census tracts with community APPE sites than in census tracts without APPE sites (p managers, and strategic initiatives were critical considerations in site establishment and overall sustainability. Advanced community pharmacy practice sites were fairly well distributed across metropolitan Chicago, indicating that exposure to diverse populations during the advanced community practice experiences parallels with strategic College objectives of expanding and diversifying experiential sites to enhance pharmacy students' abilities to meet emerging patient care challenges and opportunities.

  4. Field size dependence of wedge factor: miniphantom vs full phantom measurements

    International Nuclear Information System (INIS)

    Allen Li, X.; Szanto, J.; Soubra, M.; Gerig, L. H.

    1995-01-01

    It is empirically known that the transmission factor for wedge in a high-energy photon beam is dependent upon field size and depth of measurement. The field-size dependence of wedge factors may be attributed to changes in (i) head scatter, (ii) phantom scatter, and (iii) backscatter from the wedge into the linac monitor chamber. In this work we present the results of studies designed to examine each of these factors in isolation. The wedge factors for wedges with nominal wedge angles of 15 deg. , 30 deg. , 45 deg. and 60 deg. were measured with a 3-g/cm 2 -diameter narrow cylindrical phantom (miniphantom), a brass cap with 1.5-g/cm 2 side-wall thickness and a full water phantom for 6-, 10- and 18-MV photon beams. The measurements were performed with and without flattening filter in place. The wedge factors measured with the miniphantom and the brass cap exclude the phantom scatter contribution. It has been found that the field-size behaviour of wedge factor measured with full water phantom is similar to that measured with the miniphantom and cap. This indicates that the head scatter radiation is the major contributor to the field size dependence of wedge factors. Wedge factors measured with water phantom are up to 5.0% smaller than those measured with miniphantom. This difference increases with wedge angle. When Measured with the flattening filter removed, the field size dependence of the wedge factor is reduced. This justify that the flattening filter is one of the major contributors to head scatters. The measurement results made with the brass cap agree well with those made by using the miniphantom. By measuring the monitor chamber output, it is found that the backscatters from the wedge into the linac ion chamber have little effect on the field size dependence of the wedge factor

  5. Incidence and risk factors of surgical site infection and septic arthritis after elective arthroscopy in horses.

    Science.gov (United States)

    Brunsting, Julie Y; Pille, Frederik J; Oosterlinck, Maarten; Haspeslagh, Maarten; Wilderjans, Hans C

    2018-01-01

    To determine the incidence of infection and associated risk factors, after elective arthroscopy. Retrospective case study. Horses (n=1079) undergoing elective arthroscopy. Medical records of all horses that underwent elective arthroscopy between 2006 and 2013 were reviewed. Age, gender, breed, surgeon, number of joints operated, total anesthetic time, perioperative antimicrobial administration, and the presence and size of osteochondral fragments/subchondral lesions were recorded. For each operated joint, the development of postoperative infection (surgical site infection [SSI] and/or septic arthritis) and long-term outcome (>6 months) were recorded. Multivariate logistic regression was used to test for association between the independent variables and the dependent outcomes. A total of 1741 joints in 1079 horses underwent arthroscopy. SSI without septic arthritis occurred in 1 fetlock joint (0.14%), 1 tibiotarsal joint (0.19%), and 6 femoropatellar joints (1.67%). Thirteen joints (0.75%) were diagnosed with septic arthritis, including 1 fetlock joint (0.14%), 4 tibiotarsal joints (0.74%), and 8 femoropatellar joints (2.23%). The probability of postoperative SSI was higher when large lesions (>40 mm long) were treated, compared to medium (20-40 mm, P = .005) and small (septic arthritis (P septic arthritis rate (P = .028). Septic arthritis after elective arthroscopy was more likely in the presence of SSI and younger age. Horses with large lesions were at risk for SSI, which translated into a higher incidence of postoperative septic arthritis after femoropatellar arthroscopy. © 2017 The American College of Veterinary Surgeons.

  6. Pipeline for Efficient Mapping of Transcription Factor Binding Sites and Comparison of Their Models

    KAUST Repository

    Ba alawi, Wail

    2011-06-01

    The control of genes in every living organism is based on activities of transcription factor (TF) proteins. These TFs interact with DNA by binding to the TF binding sites (TFBSs) and in that way create conditions for the genes to activate. Of the approximately 1500 TFs in human, TFBSs are experimentally derived only for less than 300 TFs and only in generally limited portions of the genome. To be able to associate TF to genes they control we need to know if TFs will have a potential to interact with the control region of the gene. For this we need to have models of TFBS families. The existing models are not sufficiently accurate or they are too complex for use by ordinary biologists. To remove some of the deficiencies of these models, in this study we developed a pipeline through which we achieved the following: 1. Through a comparison analysis of the performance we identified the best models with optimized thresholds among the four different types of models of TFBS families. 2. Using the best models we mapped TFBSs to the human genome in an efficient way. The study shows that a new scoring function used with TFBS models based on the position weight matrix of dinucleotides with remote dependency results in better accuracy than the other three types of the TFBS models. The speed of mapping has been improved by developing a parallelized code and shows a significant speed up of 4x when going from 1 CPU to 8 CPUs. To verify if the predicted TFBSs are more accurate than what can be expected with the conventional models, we identified the most frequent pairs of TFBSs (for TFs E4F1 and ATF6) that appeared close to each other (within the distance of 200 nucleotides) over the human genome. We show unexpectedly that the genes that are most close to the multiple pairs of E4F1/ATF6 binding sites have a co-expression of over 90%. This indirectly supports our hypothesis that the TFBS models we use are more accurate and also suggests that the E4F1/ATF6 pair is exerting the

  7. Assessing frequency-dependent site polarisabilities in linear response polarisable embedding

    DEFF Research Database (Denmark)

    Nørby, Morten S.; Vahtras, Olav; Norman, Patrick

    2017-01-01

    equations defining specific molecular properties. On the other hand, we also show from a numerical point of view that the consequences of using such a frequency-dependent embedding potential is almost negligible. Thus, for the kind of systems and processes studied in this paper the general recommendation...

  8. Sodium-dependent reorganization of the sugar-binding site of SGLT1

    DEFF Research Database (Denmark)

    Hirayama, Bruce A; Loo, Donald D F; Díez-Sampedro, Ana

    2007-01-01

    The sodium-dependent glucose cotransporter SGLT1 undergoes a series of voltage- and ligand-induced conformational changes that underlie the cotransport mechanism. In this study we describe how the binding of external Na changes the conformation of the sugar-binding domain, exposing residues that ...

  9. Transcription-factor-dependent enhancer transcription defines a gene regulatory network for cardiac rhythm.

    Science.gov (United States)

    Yang, Xinan H; Nadadur, Rangarajan D; Hilvering, Catharina Re; Bianchi, Valerio; Werner, Michael; Mazurek, Stefan R; Gadek, Margaret; Shen, Kaitlyn M; Goldman, Joseph Aaron; Tyan, Leonid; Bekeny, Jenna; Hall, Johnathon M; Lee, Nutishia; Perez-Cervantes, Carlos; Burnicka-Turek, Ozanna; Poss, Kenneth D; Weber, Christopher R; de Laat, Wouter; Ruthenburg, Alexander J; Moskowitz, Ivan P

    2017-12-27

    The noncoding genome is pervasively transcribed. Noncoding RNAs (ncRNAs) generated from enhancers have been proposed as a general facet of enhancer function and some have been shown to be required for enhancer activity. Here we examine the transcription-factor-(TF)-dependence of ncRNA expression to define enhancers and enhancer-associated ncRNAs that are involved in a TF-dependent regulatory network. TBX5, a cardiac TF, regulates a network of cardiac channel genes to maintain cardiac rhythm. We deep sequenced wildtype and Tbx5 -mutant mouse atria, identifying ~2600 novel Tbx5 -dependent ncRNAs. Tbx5-dependent ncRNAs were enriched for tissue-specific marks of active enhancers genome-wide. Tbx5-dependent ncRNAs emanated from regions that are enriched for TBX5-binding and that demonstrated Tbx5-dependent enhancer activity. Tbx5 -dependent ncRNA transcription provided a quantitative metric of Tbx5 -dependent enhancer activity, correlating with target gene expression. We identified RACER , a novel Tbx5 -dependent long noncoding RNA (lncRNA) required for the expression of the calcium-handling gene Ryr2 . We illustrate that TF-dependent enhancer transcription can illuminate components of TF-dependent gene regulatory networks.

  10. Infirmity and injury complexity are risk factors for surgical-site infection after operative fracture care.

    Science.gov (United States)

    Bachoura, Abdo; Guitton, Thierry G; Smith, R Malcolm; Vrahas, Mark S; Zurakowski, David; Ring, David

    2011-09-01

    Orthopaedic surgical-site infections prolong hospital stays, double rehospitalization rates, and increase healthcare costs. Additionally, patients with orthopaedic surgical-site infections (SSI) have substantially greater physical limitations and reductions in their health-related quality of life. However, the risk factors for SSI after operative fracture care are unclear. We determined the incidence and quantified modifiable and nonmodifiable risk factors for SSIs in patients with orthopaedic trauma undergoing surgery. We retrospectively indentified, from our prospective trauma database and billing records, 1611 patients who underwent 1783 trauma-related procedures between 2006 and 2008. Medical records were reviewed and demographics, surgery-specific data, and whether the patients had an SSI were recorded. We determined which if any variables predicted SSI. Six factors independently predicted SSI: (1) the use of a drain, OR 2.3, 95% CI (1.3-3.8); (2) number of operations OR 3.4, 95% CI (2.0-6.0); (3) diabetes, OR 2.1, 95% CI (1.2-3.8); (4) congestive heart failure (CHF), OR 2.8, 95% CI (1.3-6.5); (5) site of injury tibial shaft/plateau, OR 2.3, 95% CI (1.3-4.2); and (6) site of injury, elbow, OR 2.2, 95% CI (1.1-4.7). The risk factors for SSIs after skeletal trauma are most strongly determined by nonmodifiable factors: patient infirmity (diabetes and heart failure) and injury complexity (site of injury, number of operations, use of a drain). Level II, prognostic study. See the Guideline for Authors for a complete description of levels of evidence.

  11. Factors Affecting Intention to Use in Social Networking Sites: An Empirical Study on Thai Society

    Science.gov (United States)

    Jairak, Rath; Sahakhunchai, Napath; Jairak, Kallaya; Praneetpolgrang, Prasong

    This research aims to explore the factors that affect the intention to use in Social Networking Sites (SNS). We apply the theory of Technology Acceptance Model (TAM), intrinsic motivation, and trust properties to develop the theoretical framework for SNS users' intention. The results show that the important factors influencing SNS users' intention for general purpose and collaborative learning are task-oriented, pleasure-oriented, and familiarity-based trust. In marketing usage, dispositional trust and pleasure-oriented are two main factors that reflect intention to use in SNS.

  12. Occupancy classification of position weight matrix-inferred transcription factor binding sites.

    Directory of Open Access Journals (Sweden)

    Hollis Wright

    Full Text Available BACKGROUND: Computational prediction of Transcription Factor Binding Sites (TFBS from sequence data alone is difficult and error-prone. Machine learning techniques utilizing additional environmental information about a predicted binding site (such as distances from the site to particular chromatin features to determine its occupancy/functionality class show promise as methods to achieve more accurate prediction of true TFBS in silico. We evaluate the Bayesian Network (BN and Support Vector Machine (SVM machine learning techniques on four distinct TFBS data sets and analyze their performance. We describe the features that are most useful for classification and contrast and compare these feature sets between the factors. RESULTS: Our results demonstrate good performance of classifiers both on TFBS for transcription factors used for initial training and for TFBS for other factors in cross-classification experiments. We find that distances to chromatin modifications (specifically, histone modification islands as well as distances between such modifications to be effective predictors of TFBS occupancy, though the impact of individual predictors is largely TF specific. In our experiments, Bayesian network classifiers outperform SVM classifiers. CONCLUSIONS: Our results demonstrate good performance of machine learning techniques on the problem of occupancy classification, and demonstrate that effective classification can be achieved using distances to chromatin features. We additionally demonstrate that cross-classification of TFBS is possible, suggesting the possibility of constructing a generalizable occupancy classifier capable of handling TFBS for many different transcription factors.

  13. Risk factors for surgical site infection following operative ankle fracture fixation.

    Science.gov (United States)

    Kelly, E G; Cashman, J P; Groarke, P J; Morris, S F

    2013-09-01

    Ankle fracture is a common injury and there is an increasingly greater emphasis on operative fixation. The purpose of the study was to determine the complication rate in this cohort of patients and, in doing so, determine risk factors which predispose to surgical site infection. A prospective cohort study was performed at a tertiary referral trauma center examining risk factors for surgical site infection in operatively treated ankle fractures. Univariate and multivariate analysis was performed. Female gender and advancing age were determined to be the risk factors in univariate analysis. Drain usage and peri-operative pyrexia were found to be significant for infection in multivariate analysis. This study allows surgeons to identify those at increased risk of infection and counsel them appropriately. It also allows for a high level of vigilance with regard to soft tissue handling intra-operatively in this higher risk group.

  14. Reserpine: interactions with batrachotoxin and brevetoxin sites on voltage-dependent sodium channels.

    Science.gov (United States)

    Flowers, Andrew; Onwueme, Kenolisa; Creveling, Cyrus R; Daly, John W

    2002-02-01

    Reserpine inhibited batrachotoxin-elicited sodium influx in guinea pig brain synaptoneurosomes with an IC50 of about 1 microM. In the presence of brevetoxin the IC50 increased to about 80 microM. Reserpine inhibited binding of batrachotoxinin-A [3H]benzoate ([3H]BTX-B) binding in a complex manner causing a partial inhibition from 0.001 to 0.08 microM, then a rebound stimulation from 0.1 to 0.8 microM, followed by complete inhibition by 80 microM. The stimulation was prevented by the presence of brevetoxin; reserpine then smoothly inhibited binding with an IC50 of about 1 microM. Reserpine at 1 microM slightly reduced the off-rate of [3H]BTX-B binding measured in the presence of veratridine, while at a concentration of 50 microM it enhanced the off-rate, presumably by an allosteric mechanism. Reserpine at 0.3-10 microM elicited a partial inhibition of the binding of [3H]brevetoxin-3. The local anesthetic dibucaine had effects similar to reserpine: It partially inhibited binding of [3H]brevetoxin. The presence of brevetoxin reduced the potency of dibucaine as an inhibitor of batrachotoxin-elicited sodium influx from an IC50 of about 2 microM to an IC50 of about 50 microM. The results suggest that reserpine binds at both a local anesthetic site to cause allosteric inhibition of batrachotoxin-binding and action, but that it also binds to another site causing, like brevetoxin, an enhancement of batrachotoxin-binding and action. Local anesthetics also may bind to the brevetoxin site.

  15. Photoaffinity labeling with cholesterol analogues precisely maps a cholesterol-binding site in voltage-dependent anion channel-1.

    Science.gov (United States)

    Budelier, Melissa M; Cheng, Wayland W L; Bergdoll, Lucie; Chen, Zi-Wei; Janetka, James W; Abramson, Jeff; Krishnan, Kathiresan; Mydock-McGrane, Laurel; Covey, Douglas F; Whitelegge, Julian P; Evers, Alex S

    2017-06-02

    Voltage-dependent anion channel-1 (VDAC1) is a highly regulated β-barrel membrane protein that mediates transport of ions and metabolites between the mitochondria and cytosol of the cell. VDAC1 co-purifies with cholesterol and is functionally regulated by cholesterol, among other endogenous lipids. Molecular modeling studies based on NMR observations have suggested five cholesterol-binding sites in VDAC1, but direct experimental evidence for these sites is lacking. Here, to determine the sites of cholesterol binding, we photolabeled purified mouse VDAC1 (mVDAC1) with photoactivatable cholesterol analogues and analyzed the photolabeled sites with both top-down mass spectrometry (MS), and bottom-up MS paired with a clickable, stable isotope-labeled tag, FLI -tag. Using cholesterol analogues with a diazirine in either the 7 position of the steroid ring (LKM38) or the aliphatic tail (KK174), we mapped a binding pocket in mVDAC1 localized to Thr 83 and Glu 73 , respectively. When Glu 73 was mutated to a glutamine, KK174 no longer photolabeled this residue, but instead labeled the nearby Tyr 62 within this same binding pocket. The combination of analytical strategies employed in this work permits detailed molecular mapping of a cholesterol-binding site in a protein, including an orientation of the sterol within the site. Our work raises the interesting possibility that cholesterol-mediated regulation of VDAC1 may be facilitated through a specific binding site at the functionally important Glu 73 residue. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Concentrations of Chemical Elements in Willow Biomass Depend on Clone, Site and Management in the Field

    DEFF Research Database (Denmark)

    Liu, Na; Jørgensen, Uffe; Lærke, Poul Erik

    2016-01-01

    Eight willow (Salix) clones (Inger, Klara, Linnea, Resolution, Stina, Terra Nova, Tora, Tordis) were planted on two soil types in Denmark. The biomass quality was evaluated after 3 years of growth by measuring differences in concentrations of 14 elements associated with ash behavior during...... plant densities (8000 and 12,000 trees ha−1) of the clones Inger and Tora after the first 3-year rotation when grown at the site with a coarse sandy soil. The study indicates considerable diversity in concentration of elements within commercially available willow cultivars and suggests breeders...

  17. What Factors are Associated With a Surgical Site Infection After Operative Treatment of an Elbow Fracture?

    Science.gov (United States)

    Claessen, Femke M A P; Braun, Yvonne; van Leeuwen, Wouter F; Dyer, George S; van den Bekerom, Michel P J; Ring, David

    2016-02-01

    Surgical site infections are one of the more common major complications of elbow fracture surgery and can contribute to other adverse outcomes, prolonged hospital stays, and increased healthcare costs. We asked: (1) What are the factors associated with a surgical site infection after elbow fracture surgery? (2) When taking the subset of closed elbow fractures only, what are the factors associated with a surgical site infection? (3) What are the common organisms isolated from an elbow infection after open treatment? One thousand three hundred twenty adult patients underwent surgery for an elbow fracture between January 2002 and July 2014 and were included in our study. Forty-eight of 1320 patients (4%) had a surgical site infection develop. Thirty-four of 1113 patients with a closed fracture (3%) had a surgical site infection develop. For all elbow fractures, use of plate and screw fixation (adjusted odds ratio [OR]= 2.2; 95% CI, 1.0-4.5; p = 0.041) and use of external fixation before surgery (adjusted OR = 4.7; 95% CI, 1.1-21; p = 0.035) were associated with higher infection rates. When subset analysis was performed for closed fractures, only smoking (adjusted OR = 2.2; 95% CI, 1.1-4.5; p = 0.023) was associated with higher infection rates. Staphylococcus aureus was the most common bacteria cultured (59%). The only modifiable risk factor for a surgical site infection after open reduction and internal fixation was cigarette smoking. Plate fixation and temporary external fixation are likely surrogates for more complex injuries, therefore no recommendations should be inferred from this association. Surgeons should counsel patients who smoke. Level IV, prognostic study.

  18. MONKEY: Identifying conserved transcription-factor binding sitesin multiple alignments using a binding site-specific evolutionarymodel

    Energy Technology Data Exchange (ETDEWEB)

    Moses, Alan M.; Chiang, Derek Y.; Pollard, Daniel A.; Iyer, VenkyN.; Eisen, Michael B.

    2004-10-28

    We introduce a method (MONKEY) to identify conserved transcription-factor binding sites in multispecies alignments. MONKEY employs probabilistic models of factor specificity and binding site evolution, on which basis we compute the likelihood that putative sites are conserved and assign statistical significance to each hit. Using genomes from the genus Saccharomyces, we illustrate how the significance of real sites increases with evolutionary distance and explore the relationship between conservation and function.

  19. SPECIFIC SITES OF BONE EXPANSION DEPEND ON THE LEVEL OF VOLLEYBALL PRACTICE IN PREPUBESCENT BOYS

    Directory of Open Access Journals (Sweden)

    Hamada Chaari

    2013-06-01

    Full Text Available The purpose of this study was to investigate the effect of 18 months of high and low levels of volleyball practice on bone acquisition. 130 prepubescent boys (mean age 11.4 ± 0.7 were divided into a high-level training group (HLG, low-level training group (LLG, and controls. Bone mineral content (BMC and bone area at the whole body, lumbar spine L2-L4, femoral neck of the dominant leg, and right and left radius were measured using dual-photon X-ray absorptiometry. Enhanced BMC resulted from high-training volleyball activity in all measured sites except the third left and right distal radius, which is not modified by low-level training in prepubescent players but it was accompanied by a bone area expansion in radius and weight-bearing sites for the HLG, and in legs, whole right and left radius for the LLG. Significant improvement of skeletal tissues is associated with the intensity and duration of volleyball training.

  20. Time-dependent evolution of the excavation damaged zone in the argillaceous Tournemire site

    International Nuclear Information System (INIS)

    Rejeb, A.; Cabrera, J.

    2006-01-01

    The experimental Tournemire site enables the assessment of the Excavation Damaged Zones (EDZ) around three structures excavated in argilites: the century-old tunnel, the ten year-old east and west galleries, and the three year-old main gallery. This paper discusses the main experimental results concerning the EDZ characterisation and their interpretation. EDZ fracture analyses from the galleries (cartography) and the radial boreholes (core analyses) allow for accurate structural characterisation of the EDZs. The tunnel has an EDZ with dense, homogeneous fracturing parallel to the wall, resembling onion skins. However, the new galleries do not have an EDZ similar to that of the tunnel. Unsaturated micro-cracks, mainly parallel to the bedding planes are observed on the non covered walls of each gallery. The extent of the EDZ does not seem to be affected by the age of the structure. It is approximately 20 % of the mean radius of the structure. Based on the modelling and experimental characterisation work completed, it is considered that the EDZ in this argillaceous Tournemire site is due to a deferred failure. At first time, when the wall of the structures are not covered the desaturation/re-saturation phenomena induced a tensile failure around the new galleries. During the time, these desaturation/re-saturation phenomena cause a gradual weakening of the material. The EDZ tunnel fractures are explained by this possible hydric damage and a decreasing mechanical strength with the time. These assumptions remain to be confirmed through coupled numerical modelling in unsaturated medium. (authors)

  1. Radiological bioconcentration factors for aquatic, terrestrial, and wetland ecosystems at the Savannah River site

    International Nuclear Information System (INIS)

    Friday, G.P.; Cummins, C.L.; Schwartzman, A.L.

    1996-01-01

    Since the early 1950s, the Savannah River Site (SRS) released over 50 radionuclides into the environment while producing nuclear defense materials. These releases directly exposed aquatic and terrestrial biota to ionizing radiation from surface water, soil, and sediment, and also indirectly by the ingestion of items in the food chain. As part of new missions to develop waste management strategies and identify cost-effective environmental restoration options, knowledge concerning the uptake and distribution of these radionuclides is essential. This report compiles and summarizes site-specific bioconcentration factors for selected radionuclides released at SRS

  2. Radiological bioconcentration factors for aquatic, terrestrial, and wetland ecosystems at the Savannah River site

    Energy Technology Data Exchange (ETDEWEB)

    Friday, G.P.; Cummins, C.L.; Schwartzman, A.L.

    1996-12-31

    Since the early 1950s, the Savannah River Site (SRS) released over 50 radionuclides into the environment while producing nuclear defense materials. These releases directly exposed aquatic and terrestrial biota to ionizing radiation from surface water, soil, and sediment, and also indirectly by the ingestion of items in the food chain. As part of new missions to develop waste management strategies and identify cost-effective environmental restoration options, knowledge concerning the uptake and distribution of these radionuclides is essential. This report compiles and summarizes site-specific bioconcentration factors for selected radionuclides released at SRS.

  3. Biotic mortality factors affecting emerald ash borer (Agrilus planipennis) are highly dependent on life stage and host tree crown condition.

    Science.gov (United States)

    Jennings, D E; Duan, J J; Shrewsbury, P M

    2015-10-01

    Emerald ash borer (EAB), Agrilus planipennis, is a serious invasive forest pest in North America responsible for killing tens to hundreds of millions of ash trees since it was accidentally introduced in the 1990 s. Although host-plant resistance and natural enemies are known to be important sources of mortality for EAB in Asia, less is known about the importance of different sources of mortality at recently colonized sites in the invaded range of EAB, and how these relate to host tree crown condition. To further our understanding of EAB population dynamics, we used a large-scale field experiment and life-table analyses to quantify the fates of EAB larvae and the relative importance of different biotic mortality factors at 12 recently colonized sites in Maryland. We found that the fates of larvae were highly dependent on EAB life stage and host tree crown condition. In relatively healthy trees (i.e., with a low EAB infestation) and for early instars, host tree resistance was the most important mortality factor. Conversely, in more unhealthy trees (i.e., with a moderate to high EAB infestation) and for later instars, parasitism and predation were the major sources of mortality. Life-table analyses also indicated how the lack of sufficient levels of host tree resistance and natural enemies contribute to rapid population growth of EAB at recently colonized sites. Our findings provide further evidence of the mechanisms by which EAB has been able to successfully establish and spread in North America.

  4. Structural and Kinetic Analyses of Macrophage Migration Inhibitory Factor Active Site Interactions

    Energy Technology Data Exchange (ETDEWEB)

    Crichlow, G.; Lubetsky, J; Leng, L; Bucala, R; Lolis, E

    2009-01-01

    Macrophage migration inhibitory factor (MIF) is a secreted protein expressed in numerous cell types that counters the antiinflammatory effects of glucocorticoids and has been implicated in sepsis, cancer, and certain autoimmune diseases. Interestingly, the structure of MIF contains a catalytic site resembling the tautomerase/isomerase sites of microbial enzymes. While bona fide physiological substrates remain unknown, model substrates have been identified. Selected compounds that bind in the tautomerase active site also inhibit biological functions of MIF. It had previously been shown that the acetaminophen metabolite, N-acetyl-p-benzoquinone imine (NAPQI), covalently binds to the active site of MIF. In this study, kinetic data indicate that NAPQI inhibits MIF both covalently and noncovalently. The structure of MIF cocrystallized with NAPQI reveals that the NAPQI has undergone a chemical alteration forming an acetaminophen dimer (bi-APAP) and binds noncovalently to MIF at the mouth of the active site. We also find that the commonly used protease inhibitor, phenylmethylsulfonyl fluoride (PMSF), forms a covalent complex with MIF and inhibits the tautomerase activity. Crystallographic analysis reveals the formation of a stable, novel covalent bond for PMSF between the catalytic nitrogen of the N-terminal proline and the sulfur of PMSF with complete, well-defined electron density in all three active sites of the MIF homotrimer. Conclusions are drawn from the structures of these two MIF-inhibitor complexes regarding the design of novel compounds that may provide more potent reversible and irreversible inhibition of MIF.

  5. Patient, Surgery, and Hospital Related Risk Factors for Surgical Site Infections following Total Hip Arthroplasty

    Directory of Open Access Journals (Sweden)

    Georgios Triantafyllopoulos

    2015-01-01

    Full Text Available Surgical site infections (SSI following total hip arthroplasty (THA have a significantly adverse impact on patient outcomes and pose a great challenge to the treating surgeon. Therefore, timely recognition of those patients at risk for this complication is very important, as it allows for adopting measures to reduce this risk. This review discusses literature reported risk factors for SSI after THA. These can be classified into patient-related factors (age, gender, obesity, comorbidities, history of infection, primary diagnosis, and socioeconomic profile, surgery-related factors (allogeneic blood transfusion, DVT prophylaxis and coagulopathy, duration of surgery, antibiotic prophylaxis, bearing surface and fixation, bilateral procedures, NNIS index score, and anesthesia type, and hospital-related factors (duration of hospitalization, institution and surgeon volume, and admission from a healthcare facility. All these factors are discussed with respect to potential measures that can be taken to reduce their effect and consequently the overall risk for infection.

  6. Abscisic-acid-dependent basic leucine zipper (bZIP) transcription factors in plant abiotic stress.

    Science.gov (United States)

    Banerjee, Aditya; Roychoudhury, Aryadeep

    2017-01-01

    One of the major causes of significant crop loss throughout the world is the myriad of environmental stresses including drought, salinity, cold, heavy metal toxicity, and ultraviolet-B (UV-B) rays. Plants as sessile organisms have evolved various effective mechanism which enable them to withstand this plethora of stresses. Most of such regulatory mechanisms usually follow the abscisic-acid (ABA)-dependent pathway. In this review, we have primarily focussed on the basic leucine zipper (bZIP) transcription factors (TFs) activated by the ABA-mediated signalosome. Upon perception of ABA by specialized receptors, the signal is transduced via various groups of Ser/Thr kinases, which phosphorylate the bZIP TFs. Following such post-translational modification of TFs, they are activated so that they bind to specific cis-acting sequences called abscisic-acid-responsive elements (ABREs) or GC-rich coupling elements (CE), thereby influencing the expression of their target downstream genes. Several in silico techniques have been adopted so far to predict the structural features, recognize the regulatory modification sites, undergo phylogenetic analyses, and facilitate genome-wide survey of TF under multiple stresses. Current investigations on the epigenetic regulation that controls greater accessibility of the inducible regions of DNA of the target gene to the bZIP TFs exclusively under stress situations, along with the evolved stress memory responses via genomic imprinting mechanism, have been highlighted. The potentiality of overexpression of bZIP TFs, either in a homologous or in a heterologous background, in generating transgenic plants tolerant to various abiotic stressors have also been addressed by various groups. The present review will provide a coherent documentation on the functional characterization and regulation of bZIP TFs under multiple environmental stresses, with the major goal of generating multiple-stress-tolerant plant cultivars in near future.

  7. Estrogen induced concentration dependent differential gene expression in human breast cancer (MCF7) cells: Role of transcription factors

    Energy Technology Data Exchange (ETDEWEB)

    Chandrasekharan, Sabarinath, E-mail: csab@bio.psgtech.ac.in [Department of Biotechnology, PSG College of Technology, Coimbatore 641004 (India); Kandasamy, Krishna Kumar [Max Planck Institute for Biology of Ageing, Cologne (Germany); Dayalan, Pavithra; Ramamurthy, Viraragavan [Department of Biotechnology, PSG College of Technology, Coimbatore 641004 (India)

    2013-08-02

    Highlights: •Estradiol (E2) at low dose induced cell proliferation in breast cancer cells. •E2 at high concentration induced cell stress in breast cancer cells. •Estrogen receptor physically interacts only with a few transcription factors. •Differential expression of genes with Oct-1 binding sites increased under stress. •Transcription factor binding sites showed distinct spatial distribution on genes. -- Abstract: Background: Breast cancer cells respond to estrogen in a concentration dependent fashion, resulting in proliferation or apoptosis. The mechanism of this concentration dependent differential outcome is not well understood yet. Methodology: Meta-analysis of the expression data of MCF7 cells treated with low (1 nM) or high (100 nM) dose of estradiol (E2) was performed. We identified genes differentially expressed at the low or the high dose, and examined the nature of regulatory elements in the vicinity of these genes. Specifically, we looked for the difference in the presence, abundance and spatial distribution of binding sites for estrogen receptor (ER) and selected transcription factors (TFs) in the genomic region up to 25 kb upstream and downstream from the transcription start site (TSS) of these genes. Results: It was observed that at high dose E2 induced the expression of stress responsive genes, while at low dose, genes involved in cell cycle were induced. We found that the occurrence of transcription factor binding regions (TFBRs) for certain factors such as Sp1 and SREBP1 were higher on regulatory regions of genes expressed at low dose. At high concentration of E2, genes with a higher frequency of Oct-1 binding regions were predominantly involved. In addition, there were differences in the spatial distribution pattern of the TFBRs in the genomic regions among the two sets of genes. Discussion: E2 induced predominantly proliferative/metabolic response at low concentrations; but at high concentration, stress–rescue responses were induced

  8. Estrogen induced concentration dependent differential gene expression in human breast cancer (MCF7) cells: Role of transcription factors

    International Nuclear Information System (INIS)

    Chandrasekharan, Sabarinath; Kandasamy, Krishna Kumar; Dayalan, Pavithra; Ramamurthy, Viraragavan

    2013-01-01

    Highlights: •Estradiol (E2) at low dose induced cell proliferation in breast cancer cells. •E2 at high concentration induced cell stress in breast cancer cells. •Estrogen receptor physically interacts only with a few transcription factors. •Differential expression of genes with Oct-1 binding sites increased under stress. •Transcription factor binding sites showed distinct spatial distribution on genes. -- Abstract: Background: Breast cancer cells respond to estrogen in a concentration dependent fashion, resulting in proliferation or apoptosis. The mechanism of this concentration dependent differential outcome is not well understood yet. Methodology: Meta-analysis of the expression data of MCF7 cells treated with low (1 nM) or high (100 nM) dose of estradiol (E2) was performed. We identified genes differentially expressed at the low or the high dose, and examined the nature of regulatory elements in the vicinity of these genes. Specifically, we looked for the difference in the presence, abundance and spatial distribution of binding sites for estrogen receptor (ER) and selected transcription factors (TFs) in the genomic region up to 25 kb upstream and downstream from the transcription start site (TSS) of these genes. Results: It was observed that at high dose E2 induced the expression of stress responsive genes, while at low dose, genes involved in cell cycle were induced. We found that the occurrence of transcription factor binding regions (TFBRs) for certain factors such as Sp1 and SREBP1 were higher on regulatory regions of genes expressed at low dose. At high concentration of E2, genes with a higher frequency of Oct-1 binding regions were predominantly involved. In addition, there were differences in the spatial distribution pattern of the TFBRs in the genomic regions among the two sets of genes. Discussion: E2 induced predominantly proliferative/metabolic response at low concentrations; but at high concentration, stress–rescue responses were induced

  9. Cleavage site selection within a folded substrate by the ATP-dependent lon protease

    Czech Academy of Sciences Publication Activity Database

    Ondrovičová, G.; Liu, T.; Singh, K.; Tian, B.; Li, H.; Gakh, Alexander; Perečko, D.; Janata, Jiří; Granot, Z.; Orly, J.; Kutejová, E.; Suzuki, C. K.

    2005-01-01

    Roč. 280, č. 26 (2005), s. 25103-25110 ISSN 0021-9258 Institutional research plan: CEZ:AV0Z50200510 Keywords : lon protease * peptidase * proteolysis Subject RIV: EE - Microbiology, Virology Impact factor: 5.854, year: 2005

  10. Factors influencing unsafe behaviors and accidents on construction sites: a review.

    Science.gov (United States)

    Khosravi, Yahya; Asilian-Mahabadi, Hassan; Hajizadeh, Ebrahim; Hassanzadeh-Rangi, Narmin; Bastani, Hamid; Behzadan, Amir H

    2014-01-01

    Construction is a hazardous occupation due to the unique nature of activities involved and the repetitiveness of several field behaviors. The aim of this methodological and theoretical review is to explore the empirical factors influencing unsafe behaviors and accidents on construction sites. In this work, results and findings from 56 related previous studies were investigated. These studies were categorized based on their design, type, methods of data collection, analytical methods, variables, and key findings. A qualitative content analysis procedure was used to extract variables, themes, and factors. In addition, all studies were reviewed to determine the quality rating and to evaluate the strength of provided evidence. The content analysis identified 8 main categories: (a) society, (b) organization, (c) project management, (d) supervision, (e) contractor, (f) site condition, (g) work group, and (h) individual characteristics. The review highlighted the importance of more distal factors, e.g., society and organization, and project management, that may contribute to reducing the likelihood of unsafe behaviors and accidents through the promotion of site condition and individual features (as proximal factors). Further research is necessary to provide a better understanding of the links between unsafe behavior theories and empirical findings, challenge theoretical assumptions, develop new applied theories, and make stronger recommendations.

  11. Shorebird roost-site selection at two temporal scales: Is human disturbance a factor?

    Science.gov (United States)

    Peters, K.A.; Otis, D.L.

    2007-01-01

    1. Roost-site selection in shorebirds is governed by ambient factors, including environmental conditions and human disturbance. Determination of the extent to which these factors affect roost use and the associated implications for shorebird habitat protection is important for conservation strategies and informed management of human recreational use of these habitats. Shorebird conservation as a whole is a high priority world-wide because a large proportion of shorebird species is in decline. However, little is understood about the consistency of roost use by different species, what conditions affect species-specific roost-site selection, and at what spatial and temporal scales conditions influence selection. 2. We studied high-tide roost-site selection by eight species of non-breeding shorebirds on a critically important stopover and wintering refuge. We calculated spatial and temporal variability in roost use for each species based on counts and consistency of incidence. We then examined roost-site selection in relation to structural, environmental and human disturbance factors, and how this varied across spatial and temporal scales. 3. Most roosts were used less than 50% of the time, although larger roosts were used more consistently. This varied among species, with red knot Calidris canutus tending to concentrate at a few roosts and American oystercatcher Haematopus palliatus, dowitcher Limnodromus griseus and Limnodromus scolopaceus and ruddy turnstone Arenaria interpres more diffusely distributed among roosts. 4. At an annual scale, the principal factors affecting shorebird presence at roosts were roost length (size), local region, substrate and aspect. The extent and direction of these effects varied among species. Among years, red knots avoided roosts that had high average boat activity within 1000 m, but disturbance did not appear to be a factor for other species. 5. Daily roost use was influenced primarily by wind speed and the ability of roosts to

  12. Alternative pathways of thromboplastin-dependent activation of human factor X in plasma

    International Nuclear Information System (INIS)

    Marlar, R.A.; Griffin, J.H.

    1981-01-01

    To determine the interrelationships of the major coagulation pathways, the activation of 3H-labeled factor X in normal and various deficient human plasmas was evaluated when clotting was triggered by dilute rabbit or human thromboplastin. Various dilutions of thromboplastin and calcium were added to plasma samples containing 3H-factor X, and the time course of factor X activation was determined. At a 1/250 dilution of rabbit brain thromboplastin, the rate of factor X activation in plasmas deficient in factor VIII or factor IX was 10% of the activation rate of normal plasma or of factor XI deficient plasma. Reconstitution of the deficient plasmas with factors VIII or IX, respectively, reconstituted normal factor X activation. Similar results were obtained when various dilutions of human thromboplastin replaced the rabbit thromboplastin. From these plasma experiments, it is inferred that the dilute thromboplastin-dependent activation of factor X requires factors VII, IX, and VIII. An alternative extrinsic pathway that involves factors IX and VIII may be the physiologic extrinsic pathway and hence help to explain the consistent clinical observations of bleeding diatheses in patients deficient in factors IX or VIII

  13. First positive reactions to cannabis constitute a priority risk factor for cannabis dependence.

    Science.gov (United States)

    Le Strat, Yann; Ramoz, Nicolas; Horwood, John; Falissard, Bruno; Hassler, Christine; Romo, Lucia; Choquet, Marie; Fergusson, David; Gorwood, Philip

    2009-10-01

    To assess the association between first reactions to cannabis and the risk of cannabis dependence. A cross-sectional population-based assessment in 2007. A campus in a French region (Champagne-Ardennes). A total of 1472 participants aged 18-21 years who reported at least one life-time cannabis consumption, of 3056 students who were screened initially [the Susceptibility Addiction Gene Environment (SAGE) study]. Positive and negative effects of first cannabis consumptions, present cannabis dependence and related risk factors were assessed through questionnaires.   The effects of first cannabis consumptions were associated dose-dependently with cannabis dependence at age 18-21 years, both according to the transversal approach of the SAGE study and to the prospective cohort of the Christchurch Health and Development Study (CHDS) assessed at the age of 25 years. Participants of the SAGE study who reported five positive effects of their first cannabis consumption had odds of life-time cannabis dependence that were 28.7 (95% confidence interval: 14.6-56.5) higher than those who reported no positive effects. This association remains significant after controlling for potentially confounding factors, including individual and familial variables. This study suggests an association between positive reactions to first cannabis uses and risk of life-time cannabis dependence, this variable having a central role among, and through, other risk factors. © 2009 The Authors. Journal compilation © 2009 Society for the Study of Addiction.

  14. Identifying the principal driving factors of water ecosystem dependence and the corresponding indicator species in a pilot City, China

    Science.gov (United States)

    Zhao, C. S.; Shao, N. F.; Yang, S. T.; Xiang, H.; Lou, H. Z.; Sun, Y.; Yang, Z. Y.; Zhang, Y.; Yu, X. Y.; Zhang, C. B.; Yu, Q.

    2018-01-01

    The world's aquatic ecosystems yield numerous vital services, which are essential to human existence but have deteriorated seriously in recent years. By studying the mechanisms of interaction between ecosystems and habitat processes, the constraining factors can be identified, and this knowledge can be used to improve the success rate of ecological restoration initiatives. At present, there is insufficient data on the link between hydrological, water quality factors and the changes in the structure of aquatic communities to allow any meaningful study of driving factors of aquatic ecosystems. In this study, the typical monitoring stations were selected by fuzzy clustering analysis based on the spatial and temporal distribution characteristics of water ecology in Jinan City, the first pilot city for the construction of civilized aquatic ecosystems in China. The dominant species identification model was used to identify the dominant species of the aquatic community. The driving effect of hydrological and water quality factors on dominant species was analyzed by Canonical Correspondence Analysis. Then, the principal factors of aquatic ecosystem dependence were selected. The results showed that there were 10 typical monitoring stations out of 59 monitoring sites, which were representative of aquatic ecosystems, 9 dominant fish species, and 20 dominant invertebrate species. The selection of factors for aquatic ecosystem dependence in Jinan were highly influenced by its regional conditions. Chemical environmental parameters influence the temporal and spatial variation of invertebrate much more than that of fish in Jinan City. However, the methodologies coupling typical monitoring stations selection, dominant species determination and driving factors identification were certified to be a cost-effective way, which can provide in-deep theoretical and technical directions for the restoration of aquatic ecosystems elsewhere.

  15. The Temperature Dependence of the Debye-Waller Factor of Magnesium

    DEFF Research Database (Denmark)

    Sledziewska-Blocka, D.; Lebech, Bente

    1976-01-01

    The temperature dependence of the average Debye-Waller factor for magnesium was measured by means of neutron diffraction spectrometry. The experimental results obtained in the temperature range from 5 to 256 K are compared with theoretical calculations, using the harmonic and quasi-harmonic appro......The temperature dependence of the average Debye-Waller factor for magnesium was measured by means of neutron diffraction spectrometry. The experimental results obtained in the temperature range from 5 to 256 K are compared with theoretical calculations, using the harmonic and quasi...

  16. A temperature-dependent theory for HeII: Application to the liquid structure factor

    International Nuclear Information System (INIS)

    Chela-Flores, J.; Ghassib, H.B.

    1981-08-01

    A temperature-dependent theory is presented for HeII, which is based on both a gauge-theoretic formulation as well as a mean-field (Hartree) approach. A simple model calculation is then performed within this framework for the liquid structure factor of the system. In particular, explicit expressions are obtained for the low-momentum-transfer and low-temperature limits, which seem to conform with the available experimental data. Further, the curvature of the structure factor is predicted, under these circumstances, to be only mildly dependent on temperature. Throughout, we compare and contrast with other theoretical attempts, including Feynman's. (author)

  17. Effects of contraceptive steroids on cardiovascular risk factors in women with insulin-dependent diabetes mellitus

    DEFF Research Database (Denmark)

    Petersen, K R; Skouby, S O; Sidelmann, Johannes Jakobsen

    1994-01-01

    OBJECTIVE: We evaluated established cardiovascular risk factors within lipoprotein metabolism, hemostasis, and endothelial function in women with insulin-dependent diabetes mellitus who were using oral contraceptives. STUDY DESIGN: Twenty-five women with uncomplicated insulin-dependent diabetes...... mellitus, allocated to treatment with a monophasic combination of 30 micrograms ethinyl estradiol and 75 micrograms gestodene (treatment group, n = 12) or with nonhormonal contraception (control group, n = 13), were prospectively followed up for 12 months. Nonparametric methods were used for statistical...... the cardiovascular risk profile in women with insulin-dependent diabetes mellitus, but our study indicates a risk of disturbances of the endothelial integrity, which needs further investigation....

  18. Feather content of porphyrins in Eurasian eagle owl (Bubo bubo) fledglings depends on body condition and breeding site quality.

    Science.gov (United States)

    Galván, Ismael; Del Mar Delgado, María; Camarero, Pablo R; Mateo, Rafael; Lourenço, Rui; Penteriani, Vincenzo

    2018-02-13

    Porphyrins are pigments produced in most animal cells during the synthesis of heme, but their importance for external coloration is unclear. Owls (Order Strigiformes) are among the few animals that accumulate porphyrins in the integument, where it could serve as a means of signaling. Here we hypothesized that the porphyrin content of feathers may depend on body condition and breeding site quality in Eurasian eagle owl (Bubo bubo) fledglings and thus constitute amplifiers of the quality of the area where they are born. Using high-performance liquid chromatography (HPLC), we found two porphyrins (protoporphyrin IX and coproporphyrin III) in the body feathers of 19 eagle owl fledglings from seven breeding territories. Coproporphyrin III, but not protoporphyrin IX feather concentration, was positively associated with the body mass of fledglings and with the quality of the breeding sites where they were reared with respect to food quality and availability. As coproporphyrin III is produced under oxidative stress, we suggest that good breeding sites may lead to fledglings in good condition. This in turn may make fledglings induce certain level of free radical and coproporphyrin III production to signal to conspecifics their site-mediated capacity to cope with oxidative stress. This is the first time that porphyrin content in the integument has been found to be related to individual quality, opening a new scenario for studying evolution of animal coloration. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  19. Incidence and risk factors of surgical site infection following cesarean section at Dhulikhel Hospital.

    Science.gov (United States)

    Shrestha, S; Shrestha, R; Shrestha, B; Dongol, A

    2014-01-01

    Cesarean Section (CS) is one of the most commonly performed surgical procedures in obstetrical and gynecological department. Surgical site infection (SSI) after a cesarean section increases maternal morbidity prolongs hospital stay and medical costs. The aim of this study was to find out the incidence and associated risk factors of surgical site infection among cesarean section cases. A prospective, descriptive study was conducted at Dhulikhel Hospital, department of Obstetrics and Gynaecology from July 2013 to June 2014. Total of 648 women who underwent surgical procedure for delivery during study period were included in the study. Data was collected from patient using structred pro forma and examination of wound till discharge was done. Data was compared in terms of presence of surgical site infection and study variables. Wound was evaluated for the development of SSI on third day, and fifth post-operative day, and on the day of discharge. Total of 648 cases were studied. The mean age was 24±4.18. Among the studied cases 92% were literate and 8% were illiterate. Antenatal clinic was attended by 97.7%. The incidence rate of surgical site infection was 82 (12.6%). SSI was found to be common in women who had rupture of membrane before surgery (p=0.020), who underwent emergency surgery (p=0.0004), and the women who had vertical skin incision (p=0.0001) and interrupted skin suturing (p=0.0001) during surgery. Surgical site infection following caesarean section is common. Various modifiable risk factors were observed in this study. Development of SSI is related to multifactorial rather than one factor. Development and strict implementation of protocol by all the health care professionals could be effective to minimize and prevent the infection rate after caesarean section.

  20. Biophysical Models of Evolution: Application to Transcription Factor Binding Sites in Yeast

    Science.gov (United States)

    Manhart, Michael; Haldane, Allan; Morozov, Alexandre

    2012-02-01

    There has been growing interest in understanding the physical driving forces of evolution at the molecular scale, in particular how biophysics determines the fitness landscapes that shape the evolution of DNA and proteins. To that end we study a model of molecular evolution that explicitly incorporates the underlying biophysics. Using population genetics, we derive a steady-state distribution of monomorphic populations evolving on an arbitrary fitness landscape. Compared to previous studies, we find this result is universal for a large class of population models and fully incorporates both stochastic effects and strong natural selection. This distribution can then be used to infer the underlying fitness landscape from genomic data. This model can be applied to a variety of systems, but we focus on transcription factor binding sites, which play a crucial role in gene regulatory networks. Since these sites must be bound for successful gene regulation, we consider a simple thermodynamic model of fitness as a function of the free energy for binding a transcription factor at the site. Using empirical energy matrices and genome-wide sets of binding sites from the yeast Saccharomyces cerevisiae, we use this model to infer the role of DNA-protein interaction physics in evolution.

  1. An Empirical Examination of Factors Affecting Continuance Intention Towards Social Networking Sites

    OpenAIRE

    Abed, Salma,

    2016-01-01

    Part 3: Adoption and Diffusion; International audience; This study examines the factors that affect consumer continuance intention to use social networking sites as a business tool. Using the Technology Acceptance Model (TAM) as the theoretical framework, the researcher tested the research model and related hypotheses using structural equation modelling. The results from a survey of 304 Facebook users in Saudi Arabia indicate that trust, perceived usefulness, and perceived enjoyment had signi...

  2. Diet and density dependent competition affect larval performance and oviposition site selection in the mosquito species Aedes albopictus (Diptera: Culicidae).

    Science.gov (United States)

    Yoshioka, Miho; Couret, Jannelle; Kim, Frances; McMillan, Joseph; Burkot, Thomas R; Dotson, Ellen M; Kitron, Uriel; Vazquez-Prokopec, Gonzalo M

    2012-10-08

    Oviposition-site choice is an essential component of the life history of all mosquito species. According to the oviposition-preference offspring-performance (P-P) hypothesis, if optimizing offspring performance and fitness ensures high overall reproductive fitness for a given species, the female should accurately assess details of the heterogeneous environment and lay her eggs preferentially in sites with conditions more suitable to offspring. We empirically tested the P-P hypothesis using the mosquito species Aedes albopictus by artificially manipulating two habitat conditions: diet (measured as mg of food added to a container) and conspecific density (CD; number of pre-existing larvae of the same species). Immature development (larval mortality, development time to pupation and time to emergence) and fitness (measured as wing length) were monitored from first instar through adult emergence using a factorial experimental design over two ascending gradients of diet (2.0, 3.6, 7.2 and 20 mg food/300 ml water) and CD (0, 20, 40 and 80 larvae/300 ml water). Treatments that exerted the most contrasting values of larval performance were recreated in a second experiment consisting of single-female oviposition site selection assay. Development time decreased as food concentration increased, except from 7.2 mg to 20.0 mg (Two-Way CR ANOVA Post-Hoc test, P > 0.1). Development time decreased also as conspecific density increased from zero to 80 larvae (Two-Way CR ANOVA Post-Hoc test, P factor for mosquito larval performance. Oviposition assays indicated that female mosquitoes select for larval habitats with conspecifics and that larval density was more important than diet in driving selection for oviposition sites. This study supports predictions of the P-P hypothesis and provides a mechanistic understanding of the underlying factors driving mosquito oviposition site selection.

  3. Postdischarge surveillance following cesarean section: the incidence of surgical site infection and associated factors.

    Science.gov (United States)

    Cardoso Del Monte, Meire Celeste; Pinto Neto, Aarão Mendes

    2010-08-01

    The rate of surgical site infections (SSI) and their associated risk factors was identified by performing postdischarge surveillance following cesarean section at a public university teaching hospital in Brazil. The study was conducted at the Center for Women's Integrated Health Care in Brazil between May 2008 and March 2009. Women were contacted by telephone 15 and 30 days after cesarean section. During hospitalization, a form was completed on factors associated with post-cesarean SSI. The chi(2) test and Fisher exact test were used to analyze categorical variables and the Mann-Whitney test for numerical variables. Relative risks (RR) and their respective 95% confidence intervals (95% CI) were calculated for factors associated with SSI. P values cesarean section SSI. A 15-day postdischarge follow-up was shown to be sufficient. Hypertension was a factor associated with SSI. Copyright 2010 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

  4. Generation of a synthetic mammalian promoter library by modification of sequences spacing transcription factor binding sites

    DEFF Research Database (Denmark)

    Tornøe, Jens; Kusk, P.; Johansen, T.E.

    2002-01-01

    promoters. The JeT promoter was made by separating the included consensus boxes by the same distances in base pairs as found in the wild-type promoters, thus preserving transcription factor interaction. The resulting promoter was shown to drive reporter expression to high levels in enhanced green...... fluorescent protein and secreted alkaline phosphatase reporter assays. By replacing sequences separating the transcription factor binding sites with randomized sequences of the same length, sets of new promoters with different strengths, spanning a 10-fold range of transcriptional activity in cell culture...

  5. Site-directed enzymatic PEGylation of the human granulocyte colony-stimulating factor.

    Science.gov (United States)

    Maullu, Carlo; Raimondo, Domenico; Caboi, Francesca; Giorgetti, Alejandro; Sergi, Mauro; Valentini, Maria; Tonon, Giancarlo; Tramontano, Anna

    2009-11-01

    Poly(ethylene glycol) (PEG) is a widely used polymer employed to increase the circulating half-life of proteins in blood and to decrease their immunogenicity and antigenicity. PEG attaches to free amines, typically at lysine residues or at the N-terminal amino acid. This lack of selectivity can present problems when a PEGylated protein therapeutic is being developed, because predictability of activity and manufacturing reproducibility are needed for regulatory approval. Enzymatic modification of proteins is one route to overcome this limitation. Bacterial transglutaminases are enzyme candidates for site-specific modification, but they also have rather broad specificity. The need arises to be able to predict a priori potential PEGylation sites on the protein of interest and, especially, to be able to design mutants where unique PEGylation sites can be introduced when needed. We investigated the feasibility of a computational approach to the problem, using human granulocyte colony-stimulating factor as a test case. The selected protein is therapeutically relevant and represents a challenging problem, as it contains 17 potential PEGylation sites. Our results show that a combination of computational methods allows the identification of the specific glutamines that are substrates for enzymatic PEGylation by a microbial transglutaminase, and that it is possible to rationally modify the protein and introduce PEG moieties at desired sites, thus allowing the selection of regions that are unlikely to interfere with the biological activity of a therapeutic protein.

  6. A Parzen window-based approach for the detection of locally enriched transcription factor binding sites.

    Science.gov (United States)

    Vandenbon, Alexis; Kumagai, Yutaro; Teraguchi, Shunsuke; Amada, Karlou Mar; Akira, Shizuo; Standley, Daron M

    2013-01-21

    Identification of cis- and trans-acting factors regulating gene expression remains an important problem in biology. Bioinformatics analyses of regulatory regions are hampered by several difficulties. One is that binding sites for regulatory proteins are often not significantly over-represented in the set of DNA sequences of interest, because of high levels of false positive predictions, and because of positional restrictions on functional binding sites with regard to the transcription start site. We have developed a novel method for the detection of regulatory motifs based on their local over-representation in sets of regulatory regions. The method makes use of a Parzen window-based approach for scoring local enrichment, and during evaluation of significance it takes into account GC content of sequences. We show that the accuracy of our method compares favourably to that of other methods, and that our method is capable of detecting not only generally over-represented regulatory motifs, but also locally over-represented motifs that are often missed by standard motif detection approaches. Using a number of examples we illustrate the validity of our approach and suggest applications, such as the analysis of weaker binding sites. Our approach can be used to suggest testable hypotheses for wet-lab experiments. It has potential for future analyses, such as the prediction of weaker binding sites. An online application of our approach, called LocaMo Finder (Local Motif Finder), is available at http://sysimm.ifrec.osaka-u.ac.jp/tfbs/locamo/.

  7. Risk factors for surgical site infection and urinary tract infection after spine surgery.

    Science.gov (United States)

    Tominaga, Hiroyuki; Setoguchi, Takao; Ishidou, Yasuhiro; Nagano, Satoshi; Yamamoto, Takuya; Komiya, Setsuro

    2016-12-01

    This study aimed to identify and compare risk factors for surgical site infection (SSI) and non-surgical site infections (non-SSIs), particularly urinary tract infection (UTI), after spine surgery. We retrospectively reviewed 825 patients (median age 59.0 years (range 33-70 years); 442 males) who underwent spine surgery at Kagoshima University Hospital from January 2009 to December 2014. Patient parameters were compared using the Mann-Whitney U and Fisher's exact tests. Risk factors associated with SSI and UTI were analyzed via the multiple logistic regression analysis. P operation time (P = 0.0019 and 0.0162, respectively) and ASA classification 3 (P = 0.0132 and 0.0356, respectively). The 1 week post-operative C-reactive protein (CRP) level was a risk factor for UTI (P = 0.0299), but not for SSI (P = 0.4996). There was no relationship between SSI and symptomatic UTI after spine surgery. Risk factors for post-operative SSI and UTI were operative time and ASA classification 3; 1 week post-operative CRP was a risk factor for UTI only.

  8. Contributing factors in restaurant-associated foodborne disease outbreaks, FoodNet sites, 2006 and 2007.

    Science.gov (United States)

    Gould, L Hannah; Rosenblum, Ida; Nicholas, David; Phan, Quyen; Jones, Timothy F

    2013-11-01

    An estimated 48 million cases of foodborne illness occur each year in the United States, resulting in approximately 128,000 hospitalizations and 3,000 deaths. Over half of all foodborne disease outbreaks reported to the Centers for Disease Control and Prevention are associated with eating in restaurants or delicatessens. We reviewed data from restaurant-associated foodborne disease outbreaks to better understand the factors that contribute to these outbreaks. Data on restaurant-associated foodborne disease outbreaks reported by sites participating in the Foodborne Diseases Active Surveillance Network (FoodNet) were analyzed to characterize contributing factors reported in foodborne disease outbreaks and the levels of evidence used to identify these factors. Of 457 foodborne disease outbreaks reported in 2006 and 2007 by FoodNet sites, 300 (66%) were restaurant associated, and of these 295 (98%) had at least one reported contributing factor. One to nine (with a median of two) contributing factors were reported per outbreak. Of the 257 outbreaks with a single etiology reported, contributing factors associated with food worker health and hygiene were reported for 165 outbreaks (64%), factors associated with food preparation practices within the establishment were reported for 88 outbreaks (34%), and factors associated with contamination introduced before reaching the restaurant were reported for 56 outbreaks (22%). The pronounced role of food workers in propagating outbreaks makes it clear that more work is needed to address prevention at the local level. Food workers should be instructed not to prepare food while ill to prevent the risk of transmitting pathogens.

  9. Size and shape dependence of CO adsorption sites on sapphire supported Fe microcrystals

    Science.gov (United States)

    Papageorgopoulos, C.; Heinemann, K.

    1985-01-01

    The surface structure and stoichiometry of alumina substrates, as well as the size, growth characteristics, and shape of Fe deposits on sapphire substrates have been investigated by low energy electron diffraction (LEED), Auger electron spectroscopy, electron energy loss spectroscopy, and X-ray photoemission spectroscopy (XPS), as well as work function measurements, in conjunction with transition electron microscopy observations. The substrates used in this work were the following: (1) new, clean Al2O3; (2) same surface amorphized by Ar ion bombardment; (3) same surface regenerated by 650 C annealing; (4) amorphous alumina films on Ta slab; and (5) polycrystal alumina films, obtained by heating amorphous films to 600 C. Substrate cleaning was found to be most effective in producing a reproducible surface upon oxygen RF plasma treatment. The Fe nucleation and growth process was found to depend strongly on the type of substrate surface and deposition conditions. Ar ion bombardment under beam flooding, and subsequent annealing at 650 C was found an effective means to restore the original Al2O3 (1102) surface for renewed Fe deposition.

  10. Prevalence and Risk Factors of Caregiver Dependence among Older Adults in a Southeast Asian Population.

    Science.gov (United States)

    Picco, Louisa; Abdin, Edimansyah; Vaingankar, Janhavi A; Pang, Shirlene; Shafie, Saleha; Sambasivam, Rajeswari; Chong, Siow Ann; Subramaniam, Mythily

    2016-11-01

    Currently very little is known about the prevalence or magnitude of caregiver dependence in Singapore and thus, there is a need to fill this gap in this multiethnic ageing population. This study aims to determine the prevalence and risk factors of caregiver dependence among older adults in Singapore. Data were used from the Well-being of the Singapore Elderly (WiSE) study, a nationally representative, cross-sectional survey among Singapore residents aged 60 years and above. Caregiver dependence was ascertained by asking the informant (the person who knows the older person best) a series of open-ended questions about the older person's care needs. The older adult sample comprised 57.1% females and the majority were aged 60 to 74 years (74.8%), while 19.5% were 75 to 84 years, and 5.7% were 85 years and above. The prevalence of caregiver dependence was 17.2% among older adults. Significant sociodemographic risk factors of caregiver dependence included older age (75 to 84 years, and 85 years and above, P dementia ( P cough ( P = 0.016), paralysis ( P <0.001), asthma ( P = 0.016) and cancer ( P = 0.026) were significantly associated with caregiver dependence. Various sociodemographic and health-related conditions were significantly associated with caregiver dependence. Dependent older adults will put greater demands on health and social services, resulting in greater healthcare expenditures. Hence, effective planning, services and support are crucial to meet the needs of dependent older adults and their caregivers.

  11. Vascular risk factor burden, atherosclerosis, and functional dependence in old age: a population-based study.

    Science.gov (United States)

    Welmer, Anna-Karin; Liang, Yajun; Angleman, Sara; Santoni, Giola; Yan, Zhongrui; Cai, Chuanzhu; Qiu, Chengxuan

    2014-08-01

    Vascular risk factors such as hypertension and obesity have been associated with physical limitations among older adults. The purpose of this study is to examine whether individual and aggregated vascular risk factors (VRFs) are associated with functional dependence and to what extent carotid atherosclerosis (CAS) or peripheral artery disease (PAD) may mediate the possible associations of aggregated VRFs with functional dependence. This cross-sectional study included 1,451 community-living participants aged ≥60 years in the Confucius Hometown Aging Project of China. Data on demographic features, hypertension, high total cholesterol, obesity, smoking, physical inactivity, diabetes, CAS, PAD, and cardiovascular diseases (CVDs) were collected through an interview, a clinical examination, and laboratory tests. Functional dependence was defined as being dependent in at least one activity in the personal or instrumental activities of daily living. Data were analyzed using multiple logistic models controlling for potential confounders. We used the mediation model to explore the potential mediating effect of CAS and PAD on the associations of aggregated VRFs with functional dependence. Of the 1,451 participants, 222 (15.3%) had functional dependence. The likelihood of functional dependence increased linearly with increasing number of VRFs (hypertension, high total cholesterol, abdominal obesity, and physical inactivity) (p for trend <0.002). Mediation analysis showed that controlling for demographics and CVDs up to 11% of the total association of functional dependence with clustering VRFs was mediated by CAS and PAD. Aggregation of multiple VRFs is associated with an increased likelihood of functional dependence among Chinese older adults; the association is partially mediated by carotid and peripheral artery atherosclerosis independently of CVDs.

  12. Streptococcal phosphoenolpyruvate-sugar phosphotransferase system: amino acid sequence and site of ATP-dependent phosphorylation of HPr

    International Nuclear Information System (INIS)

    Deutscher, J.; Pevec, B.; Beyreuther, K.; Kiltz, H.H.; Hengstenberg, W.

    1986-01-01

    The amino acid sequence of histidine-containing protein (HPr) from Streptococcus faecalis has been determined by direct Edman degradation of intact HPr and by amino acid sequence analysis of tryptic peptides, V8 proteolyptic peptides, thermolytic peptides, and cyanogen bromide cleavage products. HPr from S. faecalis was found to contain 89 amino acid residues, corresponding to a molecular weight of 9438. The amino acid sequence of HPr from S. faecalis shows extended homology to the primary structure of HPr proteins from other bacteria. Besides the phosphoenolpyruvate-dependent phosphorylation of a histidyl residue in HPr, catalyzed by enzyme I of the bacterial phosphotransferase system, HPr was also found to be phosphorylated at a seryl residue in an ATP-dependent protein kinase catalyzed reaction. The site of ATP-dependent phosphorylation in HPr of S faecalis has now been determined. [ 32 P]P-Ser-HPr was digested with three different proteases, and in each case, a single labeled peptide was isolated. Following digestion with subtilisin, they obtained a peptide with the sequence -(P)Ser-Ile-Met-. Using chymotrypsin, they isolated a peptide with the sequence -Ser-Val-Asn-Leu-Lys-(P)Ser-Ile-Met-Gly-Val-Met-. The longest labeled peptide was obtained with V8 staphylococcal protease. According to amino acid analysis, this peptide contained 36 out of the 89 amino acid residues of HPr. The following sequence of 12 amino acid residues of the V8 peptide was determined: -Tyr-Lys-Gly-Lys-Ser-Val-Asn-Leu-Lys-(P)Ser-Ile-Met-. Thus, the site of ATP-dependent phosphorylation was determined to be Ser-46 within the primary structure of HPr

  13. Streptococcal phosphoenolpyruvate-sugar phosphotransferase system: amino acid sequence and site of ATP-dependent phosphorylation of HPr

    Energy Technology Data Exchange (ETDEWEB)

    Deutscher, J.; Pevec, B.; Beyreuther, K.; Kiltz, H.H.; Hengstenberg, W.

    1986-10-21

    The amino acid sequence of histidine-containing protein (HPr) from Streptococcus faecalis has been determined by direct Edman degradation of intact HPr and by amino acid sequence analysis of tryptic peptides, V8 proteolyptic peptides, thermolytic peptides, and cyanogen bromide cleavage products. HPr from S. faecalis was found to contain 89 amino acid residues, corresponding to a molecular weight of 9438. The amino acid sequence of HPr from S. faecalis shows extended homology to the primary structure of HPr proteins from other bacteria. Besides the phosphoenolpyruvate-dependent phosphorylation of a histidyl residue in HPr, catalyzed by enzyme I of the bacterial phosphotransferase system, HPr was also found to be phosphorylated at a seryl residue in an ATP-dependent protein kinase catalyzed reaction. The site of ATP-dependent phosphorylation in HPr of S faecalis has now been determined. (/sup 32/P)P-Ser-HPr was digested with three different proteases, and in each case, a single labeled peptide was isolated. Following digestion with subtilisin, they obtained a peptide with the sequence -(P)Ser-Ile-Met-. Using chymotrypsin, they isolated a peptide with the sequence -Ser-Val-Asn-Leu-Lys-(P)Ser-Ile-Met-Gly-Val-Met-. The longest labeled peptide was obtained with V8 staphylococcal protease. According to amino acid analysis, this peptide contained 36 out of the 89 amino acid residues of HPr. The following sequence of 12 amino acid residues of the V8 peptide was determined: -Tyr-Lys-Gly-Lys-Ser-Val-Asn-Leu-Lys-(P)Ser-Ile-Met-. Thus, the site of ATP-dependent phosphorylation was determined to be Ser-46 within the primary structure of HPr.

  14. Response to Comment on "Tissue Factor-Dependent Chemokine Production Aggravates Experimental Colitis"

    NARCIS (Netherlands)

    Queiroz, Karla C.; Spek, C. Arnold

    2011-01-01

    In our recent work we utilized genetically modified mice to investigate the role of tissue factor (TF) in experimental colitis. We present evidence suggesting TF plays a detrimental role in this disease via signal transduction dependent KC production in colon epithelial cells, which provokes

  15. Country-dependent characterisation factors for acidification in Europe - A critical evaluation

    NARCIS (Netherlands)

    Hettelingh, JP; Posch, M; Potting, J

    2005-01-01

    Goal, Scope and Background. Country-dependent characterisation factors for acidification have been derived for use in life cycle assessments to describe the effect on ecosystem protection of a change in national emissions. They have recently also been used in support of European air pollution

  16. Transcription-factor-dependent enhancer transcription defines a gene regulatory network for cardiac rhythm

    NARCIS (Netherlands)

    Yang, Xinan H; Nadadur, Rangarajan D; Hilvering, Catharina Re; Bianchi, Valerio; Werner, Michael; Mazurek, Stefan R; Gadek, Margaret; Shen, Kaitlyn M; Goldman, Joseph Aaron; Tyan, Leonid; Bekeny, Jenna; Hall, Johnathan M; Lee, Nutishia; Perez-Cervantes, Carlos; Burnicka-Turek, Ozanna; Poss, Kenneth D; Weber, Christopher R; de Laat, Wouter; Ruthenburg, Alexander J; Moskowitz, Ivan P

    2017-01-01

    The noncoding genome is pervasively transcribed. Noncoding RNAs (ncRNAs) generated from enhancers have been proposed as a general facet of enhancer function and some have been shown to be required for enhancer activity. Here we examine the transcription-factor-(TF)-dependence of ncRNA expression to

  17. Noise-intolerance and state-dependent factors in patients with whiplash associated disorder

    NARCIS (Netherlands)

    Blokhorst, M.G.B.G.; Meeldijk, S.J.; Luijtelaar, E.L.J.M. van; Toor, T. van; Lousberg, R.; Ganzevles, P.

    2005-01-01

    An experiment was carried out in which the level of noise-intolerance in patients with a Whiplash Associated Disorder (WAD) was compared to healthy matched control subjects. In addition, the relationship between state-dependent factors (as headache, neck pain, fatigue and tension) and

  18. Time horizon dependent characterization factors for acidification in life-cycle assessment based on forest plant species occurrence in Europe

    NARCIS (Netherlands)

    Zelm, van R.; Huijbregts, M.J.A.; Jaarsveld, van H.A.; Reinds, G.J.; Zwart, de D.; Struijs, J.; Meent, van de D.

    2007-01-01

    This paper describes a new approach in life-cycle impact assessment to derive characterization factors for acidification in European forests. Time horizon dependent characterization factors for acidification were calculated, whereas before only steady-state factors were available. The

  19. [Socio-demographic and health factors associated with the institutionalization of dependent people].

    Science.gov (United States)

    Ayuso Gutiérrez, Mercedes; Pozo Rubio, Raúl Del; Escribano Sotos, Francisco

    2010-01-01

    The analysis of the effect that different variables have in the probability that dependent people are institutionalized is a topic scantily studied in Spain. The aim of the work is to analyze as certain socio-demographic and health factors can influence probability of dependent person living in a residence. A cross-section study has been conducted from a representative sample of the dependent population in Cuenca (Spain) in February, 2009. We have obtained information for people with level II and III of dependence. A binary logit regression model has been estimated to identify those factors related to the institutionalization of dependent people. People with ages between 65-74 years old are six times more likely to be institutionalized than younger people (institutionalization of people who live in an urban area is three times the probability of people who live in a rural area. People who need pharmacological, psychotherapy or rehabilitation treatments have between two and four times more probability of being institutionalized that those who do not need those. Age, marital status, place of residence, cardiovascular and musculoskeletal diseases and four times of medical treatment are the principal variables associated with the institutionalization of dependent people.

  20. Panel Data with Cross-Sectional Dependence Characterized by a Multi-Level Factor Structure

    DEFF Research Database (Denmark)

    Rodríguez-Caballero, Carlos Vladimir

    A panel data model with a multi-level cross-sectional dependence is proposed. The factor structure is driven by top-level common factors as well as non-pervasive factors. I propose a simple method to filter out the full factor structure that overcomes limitations in standard procedures which may...... mix up both levels of unobservable factors and may hamper the identification of the model. The model covers both stationary and non-stationary cases and takes into account other relevant features that make the model well suited to the analysis of many types of time series frequently addressed...... in macroeconomics and finance. The model makes it possible to examine the time series and cross-sectional dynamics of variables allowing for a rich fractional cointegration analysis. A Monte Carlo simulation is conducted to examine the finite sample features of the suggested procedure. Findings indicate...

  1. Prediction models for assessing anthocyanins in grape berries by fluorescence sensors: Dependence on cultivar, site and growing season.

    Science.gov (United States)

    Pinelli, Patrizia; Romani, Annalisa; Fierini, Elisa; Agati, Giovanni

    2018-04-01

    Fluorescence sensors are useful tools for the non-destructive assessment of grape berry anthocyanins. The Multiplex (Mx) sensor here studied provides two anthocyanin indices: ANTH R  = log(1/Chl-fluorescence_R) and ANTH RG  = log(Chl-fluorescence_R/Chl-fluorescence_G), based on the chlorophyll (Chl) fluorescence excited with red (R) and green (G) light. These indices were calibrated against wet chemistry. The dependence of anthocyanin prediction models on cultivar, season and site was studied on four cultivars in two Italian regions during three consecutive years. The 2010 global model (all cultivars at both growing sites) gave relative prediction errors on anthocyanin content less than 14.1% (ANTH R ) and 19.0% (ANTH RG ). The ANTH RG was independent of season, maintaining a relative error of about 20% in both 2011 and 2012. In field applications of the calibrated Mx, it showed its ability to detect inter-plot and inter-season differences on both growing sites. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Identification of functional sites in the catalytic subunit of cAMP-dependent protein kinase by differential modification and site-directed mutagenesis

    International Nuclear Information System (INIS)

    Buechler, J.A.

    1989-01-01

    In order to characterize substrate-induced conformational changes in the catalytic (C) subunit of cAMP-dependent protein kinase, the reactivity of the lysine residues towards [ 3 H]-acetic anhydride was determined in the absence of substrates, with MgATP bound to the enzyme, and when MgATP and an inhibitor peptide were present. A model for a portion of the ATP binding site in the C subunit was proposed based in part on the changes in lysine reactivity induced by MgATP binding to the C subunit. An intramolecular cross-link between a carboxyl group activated by dicyclohexylcarbodiimide (DCCD) and a lysine residue was circumvented by first modifying the lysine residues in the C subunit with acetic anhydride, and then labeling the modified C subunit with DCCD and [ 14 C]-glycine ethyl ester. Two carboxyl groups, Asp 184 and Glu 91, were labeled in the apoenzyme, but protected from modification in the presence of MgATP. The two residues accounting for the intramolecular cross-link mediated by DCCD were identified by first labeling the apoenzyme with DCCD, followed by modification of the lysine residues with [ 3 H]-acetic anhydride. The two residues involved in the cross-link, Asp 184 and Lys 72, are both invariant amino acids in the protein kinase family, and a potential orientation of the active site was proposed. The C subunit was modified with a water soluble carbodiimide, 1-ethyl-3-(3-dimethyl-amino-propyl) carbodiimide (EDC) and [ 14 C]glycine ethyl ester in order to identify carboxyl groups that may interact with the basic residues of the protein substrates. Either MgATP or peptide inhibitor alone did not protect the C subunit from inhibition, but together they blocked the inactivation by EDC

  3. Using an ensemble of statistical metrics to quantify large sets of plant transcription factor binding sites.

    Science.gov (United States)

    Hosseini, Parsa; Ovcharenko, Ivan; Matthews, Benjamin F

    2013-04-11

    From initial seed germination through reproduction, plants continuously reprogram their transcriptional repertoire to facilitate growth and development. This dynamic is mediated by a diverse but inextricably-linked catalog of regulatory proteins called transcription factors (TFs). Statistically quantifying TF binding site (TFBS) abundance in promoters of differentially expressed genes can be used to identify binding site patterns in promoters that are closely related to stress-response. Output from today's transcriptomic assays necessitates statistically-oriented software to handle large promoter-sequence sets in a computationally tractable fashion. We present Marina, an open-source software for identifying over-represented TFBSs from amongst large sets of promoter sequences, using an ensemble of 7 statistical metrics and binding-site profiles. Through software comparison, we show that Marina can identify considerably more over-represented plant TFBSs compared to a popular software alternative. Marina was used to identify over-represented TFBSs in a two time-point RNA-Seq study exploring the transcriptomic interplay between soybean (Glycine max) and soybean rust (Phakopsora pachyrhizi). Marina identified numerous abundant TFBSs recognized by transcription factors that are associated with defense-response such as WRKY, HY5 and MYB2. Comparing results from Marina to that of a popular software alternative suggests that regardless of the number of promoter-sequences, Marina is able to identify significantly more over-represented TFBSs.

  4. [Factors associated with involuntary hospital admissions in technology-dependent children].

    Science.gov (United States)

    Okido, Aline Cristiane Cavicchioli; Pina, Juliana Coelho; Lima, Regina Aparecida Garcia

    2016-02-01

    To identify the factors associated with involuntary hospital admissions of technology-dependent children, in the municipality of Ribeirão Preto, São Paulo State, Brazil. A cross-sectional study, with a quantitative approach. After an active search, 124 children who qualified under the inclusion criteria, that is to say, children from birth to age 12, were identified. Data was collected in home visits to mothers or the people responsible for the children, through the application of a questionnaire. Analysis of the data followed the assumptions of the Generalized Linear Models technique. 102 technology-dependent children aged between 6 months and 12 years participated in the study, of whom 57% were male. The average number of involuntary hospital admissions in the previous year among the children studied was 0.71 (±1.29). In the final model the following variables were significantly associated with the outcome: age (OR=0.991; CI95%=0.985-0.997), and the number of devices (OR=0.387; CI95%=0.219-0.684), which were characterized as factors of protection and quantity of medications (OR=1.532; CI95%=1.297-1.810), representing a risk factor for involuntary hospital admissions in technology-dependent children. The results constitute input data for consideration of the process of care for technology-dependent children by supplying an explanatory model for involuntary hospital admissions for this client group.

  5. Specificity of social anxiety disorder as a risk factor for alcohol and cannabis dependence.

    Science.gov (United States)

    Buckner, Julia D; Schmidt, Norman B; Lang, Alan R; Small, Jason W; Schlauch, Robert C; Lewinsohn, Peter M

    2008-02-01

    Social anxiety disorder (SAD) is highly comorbid with alcohol use disorders (AUDs) and cannabis dependence. However, the temporal sequencing of these disorders has not been extensively studied to determine whether SAD serves as a specific risk factor for problematic substance use. The present study examined these relationships after controlling for theoretically-relevant variables (e.g., gender, other Axis I pathology) in a longitudinal cohort over approximately 14 years. The sample was drawn from participants in the Oregon Adolescent Depression Project. After excluding those with substance use disorders at baseline, SAD at study entry was associated with 6.5 greater odds of cannabis dependence (but not abuse) and 4.5 greater odds of alcohol dependence (but not abuse) at follow-up after controlling for relevant variables (e.g., gender, depression, conduct disorder). The relationship between SAD and alcohol and cannabis dependence remained even after controlling for other anxiety disorders. Other anxiety disorders and mood disorders were not associated with subsequent cannabis or alcohol use disorder after controlling for relevant variables. Among the internalizing disorders, SAD appears to serve as a unique risk factor for the subsequent onset of cannabis and alcohol dependence.

  6. Specificity of Social Anxiety Disorder as a Risk Factor for Alcohol and Cannabis Dependence

    Science.gov (United States)

    Buckner, Julia D.; Schmidt, Norman B.; Lang, Alan R.; Small, Jason W.; Schlauch, Robert C.; Lewinsohn, Peter M.

    2008-01-01

    Social anxiety disorder (SAD) is highly comorbid with alcohol use disorders (AUDs) and cannabis dependence. However, the temporal sequencing of these disorders has not been extensively studied to determine whether SAD serves as a specific risk factor for problematic substance use. The present study examined these relationships after controlling for theoretically-relevant variables (e.g., gender, other Axis I pathology) in a longitudinal cohort over approximately 14 years. The sample was drawn from participants in the Oregon Adolescent Depression Project. After excluding those with substance use disorders at baseline, SAD at study entry was associated with 6.5 greater odds of cannabis dependence (but not abuse) and 4.5 greater odds of alcohol dependence (but not abuse) at follow-up after controlling for relevant variables (e.g., gender, depression, conduct disorder). The relationship between SAD and alcohol and cannabis dependence remained even after controlling for other anxiety disorders. Other anxiety disorders and mood disorders were not associated with subsequent cannabis or alcohol use disorder after controlling for relevant variables. Among the internalizing disorders, SAD appears to serve as a unique risk factor for the subsequent onset of cannabis and alcohol dependence. PMID:17320907

  7. Commonalities in the psychological factors associated with problem gambling and Internet dependence.

    Science.gov (United States)

    Dowling, N A; Brown, M

    2010-08-01

    The most commonly applied conceptual approach for excessive Internet use has been as a behavioral addiction, similar to pathological or problem gambling. In order to contribute to the understanding of Internet dependence as a disorder resembling problem gambling, the current study aimed to examine the relationship between problem gambling and Internet dependence and the degree to which psychological factors associated with problem gambling are relevant to the study of Internet dependence. The factors of depression, anxiety, student stressors, loneliness, and social support were examined in a sample of university students from several Australian universities. The findings revealed that there is no overlap between the populations reporting problem gambling and Internet dependence, but that individuals with these disorders report similar psychological profiles. Although requiring replication with larger community samples and longitudinal designs, these preliminary findings suggest that problem gambling and Internet dependence may be separate disorders with common underlying etiologies or consequences. The implications of the findings in relation to the conceptualization and management of these disorders are briefly discussed.

  8. Preclinical characterization of a recombinant adeno-associated virus type 1-pseudotyped vector demonstrates dose-dependent injection site inflammation and dissemination of vector genomes to distant sites.

    Science.gov (United States)

    Flotte, Terence R; Conlon, Thomas J; Poirier, Amy; Campbell-Thompson, Martha; Byrne, Barry J

    2007-03-01

    To translate the potential advantages of recombinant adeno-associated virus type 1 (rAAV1) vectors into a clinical application for muscle-directed gene therapy for alpha1 -antitrypsin (AAT) deficiency, we performed safety studies in 170 C57BL/6 mice and 26 New Zealand White rabbits. A mouse toxicology study included 8 cohorts of 10 mice each (5 per sex). Mice were killed either 21 or 90 days after intramuscular injection of doses ranging up to 1x10(13)vector genomes (VG), equivalent to 4 x 10(14)VG/kg. A mouse biodistribution study was performed in 5 cohorts of 10 mice, receiving intramuscular injections at the same doses; as well as in a lower dose cohort (3 x 10(8) VG; equivalent to 1.2 x 10(10)VG/kg); and in 4 other cohorts (excluding the vehicle control) injected with identical doses intravenously. Finally, biodistribution was examined in rabbits, with serial collection of blood and semen, as well as terminal tissue collection. Two significant findings were present, both of which were dose dependent. First, inflammatory cell infiltrates were detected at the site of injection 21, 60, or 90 days after intramuscular injection of 1 x 10(13)VG. This was not associated with loss of transgene expression. Second, vector DNA sequences were detected in most animals, levels being highest with the highest doses and earliest time points. Vector DNA was also present in liver, spleen, kidneys, and a number of other organs, including the gonads of animals receiving the highest dose. Likewise, vector DNA was present in the semen of male rabbits at higher doses. The copy number of vector DNA in the blood and semen declined over time throughout the study. These two dose-dependent findings have served to guide to the design of a phase 1 human trial of rAAV1-AAT.

  9. The amino acid exchange R28E in ciliary neurotrophic factor (CNTF) abrogates interleukin-6 receptor-dependent but retains CNTF receptor-dependent signaling via glycoprotein 130 (gp130)/leukemia inhibitory factor receptor (LIFR).

    Science.gov (United States)

    Wagener, Eva-Maria; Aurich, Matthias; Aparicio-Siegmund, Samadhi; Floss, Doreen M; Garbers, Christoph; Breusing, Kati; Rabe, Björn; Schwanbeck, Ralf; Grötzinger, Joachim; Rose-John, Stefan; Scheller, Jürgen

    2014-06-27

    Ciliary neurotrophic factor (CNTF) is a neurotrophic factor with therapeutic potential for neurodegenerative diseases. Moreover, therapeutic application of CNTF reduced body weight in mice and humans. CNTF binds to high or low affinity receptor complexes consisting of CNTFR·gp130·LIFR or IL-6R·gp130·LIFR, respectively. Clinical studies of the CNTF derivative Axokine revealed intolerance at higher concentrations, which may rely on the low-affinity binding of CNTF to the IL-6R. Here, we aimed to generate a CNTFR-selective CNTF variant (CV). CV-1 contained the single amino acid exchange R28E. Arg(28) is in close proximity to the CNTFR binding site. Using molecular modeling, we hypothesized that Arg(28) might contribute to IL-6R/CNTFR plasticity of CNTF. CV-2 to CV-5 were generated by transferring parts of the CNTFR-binding site from cardiotrophin-like cytokine to CNTF. Cardiotrophin-like cytokine selectively signals via the CNTFR·gp130·LIFR complex, albeit with a much lower affinity compared with CNTF. As shown by immunoprecipitation, all CNTF variants retained the ability to bind to CNTFR. CV-1, CV-2, and CV-5, however, lost the ability to bind to IL-6R. Although all variants induced cytokine-dependent cellular proliferation and STAT3 phosphorylation via CNTFR·gp130·LIFR, only CV-3 induced STAT3 phosphorylation via IL-6R·gp130·LIFR. Quantification of CNTF-dependent proliferation of CNTFR·gp130·LIFR expressing cells indicated that only CV-1 was as biologically active as CNTF. Thus, the CNTFR-selective CV-1 will allow discriminating between CNTFR- and IL-6R-mediated effects in vivo. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. The Amino Acid Exchange R28E in Ciliary Neurotrophic Factor (CNTF) Abrogates Interleukin-6 Receptor-dependent but Retains CNTF Receptor-dependent Signaling via Glycoprotein 130 (gp130)/Leukemia Inhibitory Factor Receptor (LIFR)*

    Science.gov (United States)

    Wagener, Eva-Maria; Aurich, Matthias; Aparicio-Siegmund, Samadhi; Floss, Doreen M.; Garbers, Christoph; Breusing, Kati; Rabe, Björn; Schwanbeck, Ralf; Grötzinger, Joachim; Rose-John, Stefan; Scheller, Jürgen

    2014-01-01

    Ciliary neurotrophic factor (CNTF) is a neurotrophic factor with therapeutic potential for neurodegenerative diseases. Moreover, therapeutic application of CNTF reduced body weight in mice and humans. CNTF binds to high or low affinity receptor complexes consisting of CNTFR·gp130·LIFR or IL-6R·gp130·LIFR, respectively. Clinical studies of the CNTF derivative Axokine revealed intolerance at higher concentrations, which may rely on the low-affinity binding of CNTF to the IL-6R. Here, we aimed to generate a CNTFR-selective CNTF variant (CV). CV-1 contained the single amino acid exchange R28E. Arg28 is in close proximity to the CNTFR binding site. Using molecular modeling, we hypothesized that Arg28 might contribute to IL-6R/CNTFR plasticity of CNTF. CV-2 to CV-5 were generated by transferring parts of the CNTFR-binding site from cardiotrophin-like cytokine to CNTF. Cardiotrophin-like cytokine selectively signals via the CNTFR·gp130·LIFR complex, albeit with a much lower affinity compared with CNTF. As shown by immunoprecipitation, all CNTF variants retained the ability to bind to CNTFR. CV-1, CV-2, and CV-5, however, lost the ability to bind to IL-6R. Although all variants induced cytokine-dependent cellular proliferation and STAT3 phosphorylation via CNTFR·gp130·LIFR, only CV-3 induced STAT3 phosphorylation via IL-6R·gp130·LIFR. Quantification of CNTF-dependent proliferation of CNTFR·gp130·LIFR expressing cells indicated that only CV-1 was as biologically active as CNTF. Thus, the CNTFR-selective CV-1 will allow discriminating between CNTFR- and IL-6R-mediated effects in vivo. PMID:24802752

  11. Active site of Zn2+-dependent sn-glycerol-1-phosphate dehydrogenase from Aeropyrum pernix K1

    Directory of Open Access Journals (Sweden)

    Jin-Suk Han

    2005-01-01

    Full Text Available The enzyme sn-glycerol-1-phosphate dehydrogenase (Gro1PDH, EC 1.1.1.261 is key to the formation of the enantiomeric configuration of the glycerophosphate backbone (sn-glycerol-1-phosphate of archaeal ether lipids. This enzyme catalyzes the reversible conversion between dihydroxyacetone phosphate and glycerol-1-phosphate. To date, no information about the active site and catalytic mechanism of this enzyme has been reported. Using the sequence and structural information for glycerol dehydrogenase, we constructed six mutants (D144N, D144A, D191N, H271A, H287A and D191N/H271A of Gro1PDH from Aeropyrum pernix K1 and examined their characteristics to clarify the active site of this enzyme. The enzyme was found to be a zinc-dependent metalloenzyme, containing one zinc ion for every monomer protein that was essential for activity. Site-directed mutagenesis of D144 increased the activity of the enzyme. Mutants D144N and D144A exhibited low affinity for the substrates and higher activity than the wild type, but their affinity for the zinc ion was the same as that of the wild type. Mutants D191N, H271A and H287A had a low affinity for the zinc ion and a low activity compared with the wild type. The double mutation, D191N/ H271A, had no enzyme activity and bound no zinc. From these results, it was clarified that residues D191, H271 and H287 participate in the catalytic activity of the enzyme by binding the zinc ion, and that D144 has an effect on substrate binding. The structure of the active site of Gro1PDH from A. pernix K1 seems to be similar to that of glycerol dehydrogenase, despite the differences in substrate specificity and biological role.

  12. Risk factors for deep surgical site infection following operative treatment of ankle fractures.

    Science.gov (United States)

    Ovaska, Mikko T; Mäkinen, Tatu J; Madanat, Rami; Huotari, Kaisa; Vahlberg, Tero; Hirvensalo, Eero; Lindahl, Jan

    2013-02-20

    Surgical site infection is one of the most common complications following ankle fracture surgery. These infections are associated with substantial morbidity and lead to increased resource utilization. Identification of risk factors is crucial for developing strategies to prevent these complications. We performed an age and sex-matched case-control study to identify patient and surgery-related risk factors for deep surgical site infection following operative ankle fracture treatment. We identified 1923 ankle fracture operations performed in 1915 patients from 2006 through 2009. A total of 131 patients with deep infection were identified and compared with an equal number of uninfected control patients. Risk factors for infection were determined with use of conditional logistic regression analysis. The incidence of deep infection was 6.8%. Univariate analysis showed diabetes (odds ratio [OR] = 2.2, 95% confidence interval [CI] = 1.0, 4.9), alcohol abuse (OR = 3.8, 95% CI = 1.6, 9.4), fracture-dislocation (OR = 2.0, 95% CI = 1.2, 3.5), and soft-tissue injury (a Tscherne grade of ≥1) (OR = 2.6, 95% CI = 1.3, 5.3) to be significant patient-related risk factors for infection. Surgery-related risk factors were suboptimal timing of prophylactic antibiotics (OR = 1.9, 95% CI = 1.0, 3.4), difficulties encountered during surgery, (OR = 2.1, 95% CI = 1.1, 4.0), wound complications (OR = 4.8, 95% CI = 1.6, 14.0), and fracture malreduction (OR = 3.4, 95% CI = 1.3, 9.2). Independent risk factors for infection identified by multivariable analyses were tobacco use (OR = 3.7, 95% CI = 1.6, 8.5) and a duration of surgery of more than ninety minutes (OR = 2.5, 95% CI = 1.1, 5.7). Cast application in the operating room was independently associated with a decreased infection rate (OR = 0.4, 95% CI = 0.2, 0.8). We identified several modifiable risk factors for deep surgical site infection following operative treatment of ankle fractures.

  13. Evolution and distribution of RNA polymerase II regulatory sites from RNA polymerase III dependant mobile Alu elements

    Directory of Open Access Journals (Sweden)

    Brahmachari Samir K

    2004-10-01

    Full Text Available Abstract Background The primate-specific Alu elements, which originated 65 million years ago, exist in over a million copies in the human genome. These elements have been involved in genome shuffling and various diseases not only through retrotransposition but also through large scale Alu-Alu mediated recombination. Only a few subfamilies of Alus are currently retropositionally active and show insertion/deletion polymorphisms with associated phenotypes. Retroposition occurs by means of RNA intermediates synthesised by a RNA polymerase III promoter residing in the A-Box and B-Box in these elements. Alus have also been shown to harbour a number of transcription factor binding sites, as well as hormone responsive elements. The distribution of Alus has been shown to be non-random in the human genome and these elements are increasingly being implicated in diverse functions such as transcription, translation, response to stress, nucleosome positioning and imprinting. Results We conducted a retrospective analysis of putative functional sites, such as the RNA pol III promoter elements, pol II regulatory elements like hormone responsive elements and ligand-activated receptor binding sites, in Alus of various evolutionary ages. We observe a progressive loss of the RNA pol III transcriptional potential with concomitant accumulation of RNA pol II regulatory sites. We also observe a significant over-representation of Alus harboring these sites in promoter regions of signaling and metabolism genes of chromosome 22, when compared to genes of information pathway components, structural and transport proteins. This difference is not so significant between functional categories in the intronic regions of the same genes. Conclusions Our study clearly suggests that Alu elements, through retrotransposition, could distribute functional and regulatable promoter elements, which in the course of subsequent selection might be stabilized in the genome. Exaptation of

  14. The importance of scale-dependent ravine characteristics on breeding-site selection by the Burrowing Parrot, Cyanoliseus patagonus

    Directory of Open Access Journals (Sweden)

    Myriam Ramirez-Herranz

    2017-04-01

    Full Text Available In birds, the environmental variables and intrinsic characteristics of the nest have important fitness consequences through its influence on the selection of nesting sites. However, the extent to which these variables interact with variables that operate at the landscape scale, and whether there is a hierarchy among the different scales that influences nest-site selection, is unknown. This interaction could be crucial in burrowing birds, which depend heavily on the availability of suitable nesting locations. One representative of this group is the burrowing parrot, Cyanoliseus patagonus that breeds on specific ravines and forms large breeding colonies. At a particular site, breeding aggregations require the concentration of adequate environmental elements for cavity nesting, which are provided by within ravine characteristics. Therefore, intrinsic ravine characteristics should be more important in determining nest site selection compared to landscape level characteristics. Here, we assess this hypothesis by comparing the importance of ravine characteristics operating at different scales on nest-site selection and their interrelation with reproductive success. We quantified 12 characteristics of 105 ravines in their reproductive habitat. For each ravine we quantified morphological variables, distance to resources and disturbance as well as nest number and egg production in order to compare selected and non-selected ravines and determine the interrelationship among variables in explaining ravine differences. In addition, the number of nests and egg production for each reproductive ravine was related to ravine characteristics to assess their relation to reproductive success. We found significant differences between non-reproductive and reproductive ravines in both intrinsic and extrinsic characteristics. The multidimensional environmental gradient of variation between ravines, however, shows that differences are mainly related to intrinsic

  15. The X-factor in Galaxies: I. Dependence on Environment and Scale

    Energy Technology Data Exchange (ETDEWEB)

    Feldmann, Robert; /Fermilab /Chicago U., EFI; Gnedin, Nickolay Y.; /Fermilab /Chicago U., EFI /Chicago U.; Kravtsov, Andrey V.; /Chicago U., EFI /Chicago U.

    2011-12-01

    Characterizing the conversion factor between CO emission and column density of molecular hydrogen, X{sub CO}, is crucial in studying the gaseous content of galaxies, its evolution, and relation to star formation. In most cases the conversion factor is assumed to be close to that of giant molecular clouds (GMCs) in the Milky Way, except possibly for mergers and star-bursting galaxies. However, there are physical grounds to expect that it should also depend on the gas metallicity, surface density, and strength of the interstellar radiation field. The X{sub CO} factor may also depend on the scale on which CO emission is averaged due to effects of limited resolution. We study the dependence of X{sub CO} on gas properties and averaging scale using a model that is based on a combination of results of sub-pc scale magneto-hydrodynamic simulations and on the gas distribution from self-consistent cosmological simulations of galaxy formation. Our model predicts X{sub CO} {approx} 2 - 4 x 10{sup 20} K{sup -1} cm{sup -2} km{sup -1} s, consistent with the Galactic value, for interstellar medium conditions typical for the Milky Way. For such conditions the predicted X{sub CO} varies by only a factor of two for gas surfaced densities in the range {Sigma}{sub H{sub 2}} {approx} 50-500 M{sub {circle_dot}} pc{sup -2}. However, the model also predicts that more generally on the scale of GMCs, X{sub CO} is a strong function of metallicity, and depends on the column density and the interstellar UV flux. We show explicitly that neglecting these dependencies in observational estimates can strongly bias the inferred distribution of H2 column densities of molecular clouds to have a narrower and offset range compared to the true distribution. We find that when averaged on {approx} kpc scales the X-factor depends only weakly on radiation field and column density, but is still a strong function of metallicity. The predicted metallicity dependence can be approximated as X{sub CO} {proportional

  16. Temperature dependent electron Lande g-factor and interband matrix element in GaAs

    Energy Technology Data Exchange (ETDEWEB)

    Huebner, Jens; Doehrmann, Stefanie; Haegele, Daniel; Oestreich, Michael [Institute for Solid State Physics, Gottfried Wilhelm Leibniz University Hannover (Germany)

    2007-07-01

    High precision measurements of the electron Lande g-factor in GaAs are presented using spin quantum beat spectroscopy at low excitation densities and temperatures ranging from 2.6 to 300 K. Influences of nuclear spin polarization at low temperatures have been fully compensated. Comparing these measurements with available data for the temperature dependent effective mass reveals an unexpected strong temperature dependence of the interband matrix element and resolves a long lasting discrepancy between experiment and kp - theory. The strong decrease of the interband matrix element with increasing temperature is explained by phonon induced fluctuations of the interatomic spacing and adiabatic following of the electrons.

  17. Factors affecting Malaysian university students’ purchase intention in social networking sites

    Directory of Open Access Journals (Sweden)

    Saeideh Sharifi fard

    2016-12-01

    Full Text Available This study applied the unified theory of acceptance and use of technology 2 to examine acceptance and use of social networking sites in a marketing setting. This study uses 370 regular higher education students in Malaysia as respondents. Quantitative method is used. The findings revealed that performance expectancy (PE and hedonic motivation were the main factors that influence users’ online purchase intention (PI through social networking sites (SNSs in Malaysia. As for moderating influences of gender and age, the results showed that gender significantly moderated purposed association between these four elements and the online PI, while the moderating effect of age was only recognized in PE. Findings of this research offer practitioners with better insights that would aid them in developing effective online marketing strategies to attract online purchasing users through SNSs.

  18. Estimation of site-specific deposition velocities and mass interception factor using 7Be and the prediction of deposition pattern of radionuclides at Kaiga site (India)

    International Nuclear Information System (INIS)

    James, J. P.; Ravi, P. M.; Joshi, R. M.; Hegde, A. G.; Sarkar, P. K.

    2010-01-01

    Site-specific wet, dry deposition velocities and mass interception factors at Kaiga site, where three PHWR type power plants are operational, using 7 Be as a tracer are presented. Mean wet and dry deposition velocities for Kaiga site were found to be 7.4x10 -2 m s -1 and 3.0x10 -4 m s -1 , respectively. Mass interception factors for vegetation were found to be 0.7-5.6 m 2 kg -1 dry weight with a mean of 2.4 m 2 kg -1 dry weight. The site-specific data were used for the prediction of radionuclide distribution pattern in soil and vegetation in the case of a hypothetical air contamination. (authors)

  19. GTRD: a database of transcription factor binding sites identified by ChIP-seq experiments.

    Science.gov (United States)

    Yevshin, Ivan; Sharipov, Ruslan; Valeev, Tagir; Kel, Alexander; Kolpakov, Fedor

    2017-01-04

    GTRD-Gene Transcription Regulation Database (http://gtrd.biouml.org)-is a database of transcription factor binding sites (TFBSs) identified by ChIP-seq experiments for human and mouse. Raw ChIP-seq data were obtained from ENCODE and SRA and uniformly processed: (i) reads were aligned using Bowtie2; (ii) ChIP-seq peaks were called using peak callers MACS, SISSRs, GEM and PICS; (iii) peaks for the same factor and peak callers, but different experiment conditions (cell line, treatment, etc.), were merged into clusters; (iv) such clusters for different peak callers were merged into metaclusters that were considered as non-redundant sets of TFBSs. In addition to information on location in genome, the sets contain structured information about cell lines and experimental conditions extracted from descriptions of corresponding ChIP-seq experiments. A web interface to access GTRD was developed using the BioUML platform. It provides: (i) browsing and displaying information; (ii) advanced search possibilities, e.g. search of TFBSs near the specified gene or search of all genes potentially regulated by a specified transcription factor; (iii) integrated genome browser that provides visualization of the GTRD data: read alignments, peaks, clusters, metaclusters and information about gene structures from the Ensembl database and binding sites predicted using position weight matrices from the HOCOMOCO database. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  20. Allelic variants of ADH, ALDH and the five factor model of personality in alcohol dependence syndrome.

    Science.gov (United States)

    Salujha, S K; Chaudhury, S; Menon, P K; Srivastava, K; Gupta, A

    2014-01-01

    The etiology of alcohol dependence is a complex interplay of biopsychosocial factors. The genes for alcohol-metabolizing enzymes: Alcohol dehydrogenase (ADH2 and ADH3) and aldehyde dehydrogenase (ALDH2) exhibit functional polymorphisms. Vulnerability of alcohol dependence may also be in part due to heritable personality traits. To determine whether any association exists between polymorphisms of ADH2, ADH3 and ALDH2 and alcohol dependence syndrome in a group of Asian Indians. In addition, the personality of these patients was assessed to identify traits predisposing to alcoholism. In this study, 100 consecutive males with alcohol dependence syndrome attending the psychiatric outpatient department of a tertiary care service hospital and an equal number of matched healthy controls were included with their consent. Blood samples of all the study cases and controls were collected and genotyped for the ADH2, ADH3 and ALDH2 loci. Personality was evaluated using the neuroticism, extraversion, openness (NEO) personality inventory and sensation seeking scale. Allele frequencies of ADH2*2 (0.50), ADH3*1 (0.67) and ALSH2*2 (0.09) were significantly low in the alcohol dependent subjects. Personality traits of NEO personality inventory and sensation seeking were significantly higher when compared to controls. The functional polymorphisms of genes coding for alcohol metabolizing enzymes and personality traits of NEO and sensation seeking may affect the propensity to develop dependence.

  1. Allelic variants of ADH, ALDH and the five factor model of personality in alcohol dependence syndrome

    Directory of Open Access Journals (Sweden)

    S K Salujha

    2014-01-01

    Full Text Available Background: The etiology of alcohol dependence is a complex interplay of biopsychosocial factors. The genes for alcohol-metabolizing enzymes: Alcohol dehydrogenase (ADH2 and ADH3 and aldehyde dehydrogenase (ALDH2 exhibit functional polymorphisms. Vulnerability of alcohol dependence may also be in part due to heritable personality traits. Aim: To determine whether any association exists between polymorphisms of ADH2, ADH3 and ALDH2 and alcohol dependence syndrome in a group of Asian Indians. In addition, the personality of these patients was assessed to identify traits predisposing to alcoholism. Materials and Methods: In this study, 100 consecutive males with alcohol dependence syndrome attending the psychiatric outpatient department of a tertiary care service hospital and an equal number of matched healthy controls were included with their consent. Blood samples of all the study cases and controls were collected and genotyped for the ADH2, ADH3 and ALDH2 loci. Personality was evaluated using the neuroticism, extraversion, openness (NEO personality inventory and sensation seeking scale. Results: Allele frequencies of ADH2FNx012 (0.50, ADH3FNx011 (0.67 and ALSH2FNx012 (0.09 were significantly low in the alcohol dependent subjects. Personality traits of NEO personality inventory and sensation seeking were significantly higher when compared to controls. Conclusions: The functional polymorphisms of genes coding for alcohol metabolizing enzymes and personality traits of NEO and sensation seeking may affect the propensity to develop dependence.

  2. Modelling and assessment of dependent performance shaping factors through Analytic Network Process

    International Nuclear Information System (INIS)

    De Ambroggi, Massimiliano; Trucco, Paolo

    2011-01-01

    Despite continuous progresses in research and applications, one of the major weaknesses of current HRA methods dwells in their limited capability of modelling the mutual influences between performance shaping factors (PSFs). Indeed at least two types of dependencies between PSFs can be defined: (i) dependency between the states of the PSFs; (ii) dependency between the influences (impacts) of the PSFs on the human performance. This paper introduces a method, based on Analytic Network Process (ANP), for the quantification of the latter, where the overall contribution of each PSF (weight) to the human error probability (HEP) is eventually returned. The core of the method is the modelling process, articulated into two steps: firstly, a qualitative network of dependencies between PSFs is identified, then, the importance of each PSF is quantitatively assessed using ANP. The model allows to distinguish two components of the PSF influence: direct influence that is the influence that the considered PSF is able to express by itself, notwithstanding the presence of other PSFs and indirect influence that is the incremental influence of the considered PSF through its influence on other PSFs. A case study in Air Traffic Control is presented where the proposed approach is integrated into the cognitive simulator PROCOS. The results demonstrated a significant modification of the influence of PSFs over the operator performance when dependencies are taken into account, underlining the importance of considering not only the possible correlation between the states of PSFs but also their mutual dependency in affecting human performance in complex systems.

  3. Dependence of Ideality Factor in Lateral PNP Transistors on Surface Carrier Concentration

    Science.gov (United States)

    Li, Xingji; Yang, Jianqun; Barnaby, Hugh J.; Galloway, Kenneth F.; Schrimpf, Ronald D.; Fleetwood, Daniel M.; Liu, Chaoming

    2017-06-01

    The influence of surface carrier concentration on the ideality factor of excess base current (ΔIB) in gated lateral PNP (GLPNP) bipolar junction transistors (BJTs) induced by 1-MeV electrons is investigated. ΔIB in LPNP BJTs is impacted by the surface carrier density and radiation-induced interface traps. In GLPNP BJTs, the surface carrier concentration can be controlled by the voltage applied to a gate over the base region. The ideality factor changes after irradiation, and its dependence on emitter-base voltage (VEB) is a function of gate voltage. For the irradiated devices, as the gate voltage decreases from +20 to -5 V, the ideality factor for excess base current changes from a single slope to two-slope behavior. The majority carrier concentration at the surface of the base, controlled by the gate voltage, impacts the excess base current and its ideality factor.

  4. Stratification of surgical site infection by operative factors and comparison of infection rates after hernia repair.

    Science.gov (United States)

    Olsen, Margaret A; Nickel, Katelin B; Wallace, Anna E; Mines, Daniel; Fraser, Victoria J; Warren, David K

    2015-03-01

    To investigate whether operative factors are associated with risk of surgical site infection (SSI) after hernia repair. Retrospective cohort study. Patients Commercially insured enrollees aged 6 months-64 years with International Classification of Diseases, Ninth Revision, Clinical Modification procedure or Current Procedural Terminology, fourth edition, codes for inguinal/femoral, umbilical, and incisional/ventral hernia repair procedures from January 1, 2004, through December 31, 2010. SSIs within 90 days after hernia repair were identified by diagnosis codes. The χ2 and Fisher exact tests were used to compare SSI incidence by operative factors. A total of 119,973 hernia repair procedures were analyzed. The incidence of SSI differed significantly by anatomic site, with rates of 0.45% (352/77,666) for inguinal/femoral, 1.16% (288/24,917) for umbilical, and 4.11% (715/17,390) for incisional/ventral hernia repair. Within anatomic sites, the incidence of SSI was significantly higher for open versus laparoscopic inguinal/femoral (0.48% [295/61,142] vs 0.34% [57/16,524], P=.020) and incisional/ventral (4.20% [701/16,699] vs 2.03% [14/691], P=.005) hernia repairs. The rate of SSI was higher following procedures with bowel obstruction/necrosis than procedures without obstruction/necrosis for open inguinal/femoral (0.89% [48/5,422] vs 0.44% [247/55,720], Poperative factors may facilitate accurate comparison of SSI rates between facilities.

  5. Human factors in environmental management: New directions from the Hanford Site

    Energy Technology Data Exchange (ETDEWEB)

    Wise, J.A.; Savage, S.F.

    1992-10-01

    Environmental management is the general term given to modern attempts to seek technological solutions to certain constrained environmental problems. it involves developing and applying new technologies that respond to changes in environmental policy. It does not eliminate the need for environmental ethics'' in society. Nor does it substitute for the fundamental changes in political and social structures that are needed for dealing with large-scale environmental issues. The scope of these issues can be illustrated by looking at the Hanford Site. Since 1943, the 560-square-mile Hanford Site in southeastern Washington state has been the production source of much of the nuclear weapons-grade radioactive materials for the United States. The legacy of 50 years of producing fissile materials has been an environmental cleanup problem of impressive proportions. In 1989, with the Cold War winding down, Secretary of Energy James Watkins established a new vision for Hanford as the flagship for waste management research.'' As plans and preparations for cleanup work proceed at the Hanford Site and around the world, the need for well-orchestrated environmental management methodologies has become increasingly apparent. In 1990, a Human Factors Engineering Group was established in the Technology Planning and Analysis Center at PNL to provide appropriate support for the Laboratory's research efforts. At an ever-increasing rate, these research efforts require integrating human performance into complex environmental technology systems. The endeavor of responding to the Laboratory's research needs has provided innovative opportunities for the application of the concept of Human Factors. Discussed are some of the major applications of Human Factors to environmental management.

  6. PET Imaging of Tissue Factor in Pancreatic Cancer Using 64Cu-Labeled Active Site-Inhibited Factor VII

    DEFF Research Database (Denmark)

    Nielsen, Carsten H; Jeppesen, Troels E; Kristensen, Lotte K

    2016-01-01

    with advanced stage, increased microvessel density, metastasis, and poor overall survival. Imaging of TF expression is of clinical relevance as a prognostic biomarker and as a companion diagnostic for TF-directed therapies currently under clinical development. Factor VII (FVII) is the natural ligand to TF....... The purpose of this study was to investigate the possibility of using active site-inhibited FVII (FVIIai) labeled with (64)Cu for PET imaging of TF expression. METHODS: FVIIai was conjugated to 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) and labeled with (64)Cu...... ((64)Cu-NOTA-FVIIai). Longitudinal in vivo PET imaging was performed at 1, 4, 15, and 36 h after injection of (64)Cu-NOTA-FVIIai in mice with pancreatic adenocarcinomas (BxPC-3). The specificity of TF imaging with (64)Cu-NOTA-FVIIai was investigated in subcutaneous pancreatic tumor models...

  7. Number of active transcription factor binding sites is essential for the Hes7 oscillator

    Directory of Open Access Journals (Sweden)

    de Angelis Martin

    2006-02-01

    Full Text Available Abstract Background It is commonly accepted that embryonic segmentation of vertebrates is regulated by a segmentation clock, which is induced by the cycling genes Hes1 and Hes7. Their products form dimers that bind to the regulatory regions and thereby repress the transcription of their own encoding genes. An increase of the half-life of Hes7 protein causes irregular somite formation. This was shown in recent experiments by Hirata et al. In the same work, numerical simulations from a delay differential equations model, originally invented by Lewis, gave additional support. For a longer half-life of the Hes7 protein, these simulations exhibited strongly damped oscillations with, after few periods, severely attenuated the amplitudes. In these simulations, the Hill coefficient, a crucial model parameter, was set to 2 indicating that Hes7 has only one binding site in its promoter. On the other hand, Bessho et al. established three regulatory elements in the promoter region. Results We show that – with the same half life – the delay system is highly sensitive to changes in the Hill coefficient. A small increase changes the qualitative behaviour of the solutions drastically. There is sustained oscillation and hence the model can no longer explain the disruption of the segmentation clock. On the other hand, the Hill coefficient is correlated with the number of active binding sites, and with the way in which dimers bind to them. In this paper, we adopt response functions in order to estimate Hill coefficients for a variable number of active binding sites. It turns out that three active transcription factor binding sites increase the Hill coefficient by at least 20% as compared to one single active site. Conclusion Our findings lead to the following crucial dichotomy: either Hirata's model is correct for the Hes7 oscillator, in which case at most two binding sites are active in its promoter region; or at least three binding sites are active, in which

  8. Factors associated with poor mental health status among homeless women with and without dependent children.

    Science.gov (United States)

    Chambers, Catharine; Chiu, Shirley; Scott, Allison N; Tolomiczenko, George; Redelmeier, Donald A; Levinson, Wendy; Hwang, Stephen W

    2014-07-01

    The purpose of this study was to estimate the prevalence of mental health problems among a representative sample of homeless women with and without dependent children and determine if the effects of risk factors for mental health are modified by the presence of dependent children. Homeless women (n = 522) were recruited in 2004-2005 from shelters and meal programs in Toronto, Canada. Linear and logistic regression was performed to identify factors associated with mental health status. Poor mental health was associated with low perceived access to social support, physical/sexual assault in the past 12 months, presence of a chronic health condition, and presence of a drug use problem in the past month. Efforts to improve mental health in this population will need to address the associated problems of victimization, substance abuse, and lack of social supports.

  9. Extrinsic skin ageing in German, Chinese and Japanese women manifests differently in all three groups depending on ethnic background, age and anatomical site.

    Science.gov (United States)

    Vierkötter, Andrea; Hüls, Anke; Yamamoto, Ai; Stolz, Sabine; Krämer, Ursula; Matsui, Mary S; Morita, Akimichi; Wang, Sijia; Li, Zhiwen; Jin, Li; Krutmann, Jean; Schikowski, Tamara

    2016-09-01

    It has been suggested that extrinsic skin ageing manifests differently in Caucasians versus East Asians. In particular, from previous studies it was concluded that Caucasians are more prone to develop wrinkles, whereas pigment spot formation is the hallmark of extrinsic skin ageing in East Asians. However, these assumptions are based on a very limited number of studies which did not include different East Asian populations. We here compare the manifestation of extrinsic skin ageing signs in German, Japanese and Chinese women by specifically elucidating the age and anatomical site dependence of any potential ethnic difference. In the present study, we assessed skin ageing in N=902 German, N=165 Japanese and N=1260 Chinese women ranging from 30 to 90 years by means of SCINEXA™. Linear regression analysis was used to test for ethnic differences and their age and site dependence adjusted for educational level, sun exposure, smoking and sun protection behaviours. Pigment spots and wrinkles on the face were present among all three ethnic groups and differences were influenced by age and anatomical sites independently of further influencing factors. Pigment spots on the forehead were most pronounced over the whole age range in Chinese and German women and least developed in Japanese. Pigment spots on cheeks were a typical extrinsic skin an ageing sign in the two East Asian populations in all age groups. However, in older German women they reach the same level as observed in the two East Asian populations. In contrast, pigment spots on arms and hands were significantly more pronounced in German women ≥45years of age. Wrinkles were not exclusively a skin an ageing sign of German women, but were also very pronounced in Chinese women on forehead, between the eyebrows and in the crow's feet area. These results corroborate the previous notion that the occurrence of pigments spots and wrinkles is different between Caucasians and East Asians. In addition, this study shows

  10. Activity-dependent brain-derived neurotrophic factor expression regulates cortistatin-interneurons and sleep behavior

    Directory of Open Access Journals (Sweden)

    Martinowich Keri

    2011-03-01

    Full Text Available Abstract Background Sleep homeostasis is characterized by a positive correlation between sleep length and intensity with the duration of the prior waking period. A causal role for brain-derived neurotrophic factor (BDNF in sleep homeostasis has been suggested, but the underlying mechanisms remain unclear. Cortistatin, a neuropeptide expressed primarily in a subset of cortical GABAergic interneurons, is another molecule implicated in sleep homeostasis. Results We confirmed that sleep deprivation leads to an increase in cortical cortistatin mRNA expression. Disruption of activity-dependent BDNF expression in a genetically modified mouse line impairs both baseline levels of cortistatin mRNA as well as its levels following sleep deprivation. Disruption of activity-dependent BDNF also leads to a decrease in sleep time during the active (dark phase. Conclusion Our studies suggest that regulation of cortistatin-expressing interneurons by activity-dependent BDNF expression may contribute to regulation of sleep behavior.

  11. Development of variable LRFD \\0x03C6 factors for deep foundation design due to site variability [summary].

    Science.gov (United States)

    2012-01-01

    Both the Florida Department of Transportation : (FDOT) and the Federal Highway Administration : (FHWA) specify use of fixed resistance factors () : for Load and Resistance Factored Design (LRFD) of : deep foundations, depending on design approach :...

  12. Specificity of Social Anxiety Disorder as a Risk Factor for Alcohol and Cannabis Dependence

    OpenAIRE

    Buckner, Julia D.; Schmidt, Norman B.; Lang, Alan R.; Small, Jason W.; Schlauch, Robert C.; Lewinsohn, Peter M.

    2007-01-01

    Social anxiety disorder (SAD) is highly comorbid with alcohol use disorders (AUDs) and cannabis dependence. However, the temporal sequencing of these disorders has not been extensively studied to determine whether SAD serves as a specific risk factor for problematic substance use. The present study examined these relationships after controlling for theoretically-relevant variables (e.g., gender, other Axis I pathology) in a longitudinal cohort over approximately 14 years. The sample was drawn...

  13. Factors that Determine the Non-Linear Amygdala Influence on Hippocampus-Dependent Memory

    OpenAIRE

    Akirav, Irit; Richter-Levin, Gal

    2006-01-01

    Stressful experiences are known to either improve or impair hippocampal-dependent memory tasks and synaptic plasticity. These positive and negative effects of stress on the hippocampus have been largely documented, however little is known about the mechanism involved in the twofold influence of stress on hippocampal functioning and about what factors define an enhancing or inhibitory outcome. We have recently demonstrated that activation of the basolateral amygdala can produce a biphasic effe...

  14. Role of Dicer1-Dependent Factors in the Paracrine Regulation of Epididymal Gene Expression.

    Directory of Open Access Journals (Sweden)

    Olivia Jerczynski

    Full Text Available Dicer1 is an endoribonuclease involved in the biogenesis of functional molecules such as microRNAs (miRNAs and endogenous small interfering RNAs (endo-siRNAs. These small non-coding RNAs are important regulators of post-transcriptional gene expression and participate in the control of male fertility. With the knowledge that 1 Dicer1-dependent factors are required for proper sperm maturation in the epididymis, and that 2 miRNAs are potent mediators of intercellular communication in most biological systems, we investigated the role of Dicer1-dependent factors produced by the proximal epididymis (initial segment/caput- including miRNAs- on the regulation of epididymal gene expression in the distal epididymis regions (i.e. corpus and cauda. To this end, we performed comparative microarray and ANOVA analyses on control vs. Defb41iCre/wt;Dicer1fl/fl mice in which functional Dicer1 is absent from the principal cells of the proximal epididymis. We identified 35 and 33 transcripts that displayed significant expression level changes in the corpus and cauda regions (Fold change > 2 or 2 or < -2; p < 0.01. These miRNAs are secreted via extracellular vesicles (EVs derived from the DC2 epididymal principal cell line, and their expression correlates with target transcripts involved in distinct biological pathways, as evidenced by in silico analysis. Albeit correlative and based on in silico approach, our study proposes that Dicer1-dependent factors trigger- directly or not-significant genes expression changes in distinct regions of this organ. The paracrine control of functions important to post-testicular sperm maturation by Dicer1-dependent factors may open new avenues for the identification of molecular targets important to male fertility control.

  15. Factors associated with involuntary hospital admissions in technology-dependent children

    OpenAIRE

    Okido,Aline Cristiane Cavicchioli; Pina,Juliana Coelho; Lima,Regina Aparecida Garcia

    2016-01-01

    Abstract OBJECTIVE To identify the factors associated with involuntary hospital admissions of technology-dependent children, in the municipality of Ribeirão Preto, São Paulo State, Brazil. METHOD A cross-sectional study, with a quantitative approach. After an active search, 124 children who qualified under the inclusion criteria, that is to say, children from birth to age 12, were identified. Data was collected in home visits to mothers or the people responsible for the children, through th...

  16. Factors Predicting Ventilator Dependence in Patients with Ventilator-Associated Pneumonia

    Directory of Open Access Journals (Sweden)

    Chia-Cheng Tseng

    2012-01-01

    Full Text Available Objectives. To determine risk factors associated with ventilator dependence in patients with ventilator-associated pneumonia (VAP. Study Design. A retrospective study was conducted at Chang Gung Memorial Hospital, Kaohsiung, from January 1, 2007 to January 31, 2008. Methods. This study evaluated 163 adult patients (aged ≥18 years. Eligibility was evaluated according to the criterion for VAP, Sequential Organ Failure Assessment (SOFA score, Acute Physiological Assessment and Chronic Health Evaluation II (APACHE II score. Oxygenation index, underlying comorbidities, septic shock status, previous tracheostomy status, and factors related to pneumonia were collected for analysis. Results. Of the 163 VAP patients in the study, 90 patients survived, yielding a mortality rate of 44.8%. Among the 90 surviving patients, only 36 (40% had been weaned off ventilators at the time of discharge. Multivariate logistic regression analysis was used to identify underlying factors such as congestive cardiac failure (P=0.009, initial high oxygenation index value (P=0.04, increased SOFA scores (P=0.01, and increased APACHE II scores (P=0.02 as independent predictors of ventilator dependence. Results from the Kaplan-Meier method indicate that initial therapy with antibiotics could increase the ventilator weaning rate (log Rank test, P<0.001. Conclusions. Preexisting cardiopulmonary function, high APACHE II and SOFA scores, and high oxygenation index were the strongest predictors of ventilator dependence. Initial empiric antibiotic treatment can improve ventilator weaning rates at the time of discharge.

  17. Surgical site infection after cesarean delivery: incidence and risk factors at a US academic institution.

    Science.gov (United States)

    Moulton, Laura J; Munoz, Jessian L; Lachiewicz, Mark; Liu, Xiaobo; Goje, Oluwatosin

    2017-06-08

    To identify the rate of surgical site infection (SSI) after Cesarean delivery (CD) and determine risk factors predictive for infection at a large academic institution. This was a retrospective cohort study in women undergoing CD during 2013. SSIs were defined by Centers for Disease Control (CDC) criteria. Chi square and t-tests were used for bivariate analysis and multivariate logistic regression was used to identify SSI risk factors. In 2419 patients, the rate of SSI was 5.5% (n = 133) with cellulitis in 4.9% (n = 118), deep incisional infection in 0.6% (n = 15) and intra-abdominal infection in 0.3% (n = 7). On multivariate analysis, SSI was higher among CD for labor arrest (OR 2.4; 95%CI 1.6-3.5; p infection control interventions.

  18. Epigenetic control of hypoxia inducible factor-1α-dependent expression of placental growth factor in hypoxic conditions.

    Science.gov (United States)

    Tudisco, Laura; Della Ragione, Floriana; Tarallo, Valeria; Apicella, Ivana; D'Esposito, Maurizio; Matarazzo, Maria Rosaria; De Falco, Sandro

    2014-04-01

    Hypoxia plays a crucial role in the angiogenic switch, modulating a large set of genes mainly through the activation of hypoxia-inducible factor (HIF) transcriptional complex. Endothelial cells play a central role in new vessels formation and express placental growth factor (PlGF), a member of vascular endothelial growth factor (VEGF) family, mainly involved in pathological angiogenesis. Despite several observations suggest a hypoxia-mediated positive modulation of PlGF, the molecular mechanism governing this regulation has not been fully elucidated. We decided to investigate if epigenetic modifications are involved in hypoxia-induced PlGF expression. We report that PlGF expression was induced in cultured human and mouse endothelial cells exposed to hypoxia (1% O 2), although DNA methylation at the Plgf CpG-island remains unchanged. Remarkably, robust hyperacetylation of histones H3 and H4 was observed in the second intron of Plgf, where hypoxia responsive elements (HREs), never described before, are located. HIF-1α, but not HIF-2α, binds to identified HREs. Noteworthy, only HIF-1α silencing fully inhibited PlGF upregulation. These results formally demonstrate a direct involvement of HIF-1α in the upregulation of PlGF expression in hypoxia through chromatin remodeling of HREs sites. Therefore, PlGF may be considered one of the putative targets of anti-HIF therapeutic applications.

  19. The DMI1 and DMI2 Early Symbiotic Genes of Medicago truncatula Are Required for a High-Affinity Nodulation Factor-Binding Site Associated to a Particulate Fraction of Roots1

    Science.gov (United States)

    Hogg, Bridget V.; Cullimore, Julie V.; Ranjeva, Raoul; Bono, Jean-Jacques

    2006-01-01

    The establishment of the legume-rhizobia symbiosis between Medicago spp. and Sinorhizobium meliloti is dependent on the production of sulfated lipo-chitooligosaccharidic nodulation (Nod) factors by the bacterial partner. In this article, using a biochemical approach to characterize putative Nod factor receptors in the plant host, we describe a high-affinity binding site (Kd = 0.45 nm) for the major Nod factor produced by S. meliloti. This site is termed Nod factor-binding site 3 (NFBS3). NFBS3 is associated to a high-density fraction prepared from roots of Medicago truncatula and shows binding specificity for lipo-chitooligosaccharidic structures. As for the previously characterized binding sites (NFBS1 and NFBS2), NFBS3 does not recognize the sulfate group on the S. meliloti Nod factor. Studies of Nod factor binding in root extracts of early symbiotic mutants of M. truncatula reveals that the new site is present in Nod factor perception and does not make infections 3 (dmi3) mutants but is absent in dmi1 and dmi2 mutants. Roots and cell cultures of all these mutants still contain sites similar to NFBS1 and NFBS2, respectively. These results suggest that NFBS3 is different from NFBS2 and NFBS1 and is dependent on the common symbiotic genes DMI1 and DMI2 required for establishment of symbioses with both rhizobia and arbuscular mycorrhizal fungi. The potential role of this site in the establishment of root endosymbioses is discussed. PMID:16377749

  20. Application of classification algorithms for analysis of road safety risk factor dependencies.

    Science.gov (United States)

    Kwon, Oh Hoon; Rhee, Wonjong; Yoon, Yoonjin

    2015-02-01

    Transportation continues to be an integral part of modern life, and the importance of road traffic safety cannot be overstated. Consequently, recent road traffic safety studies have focused on analysis of risk factors that impact fatality and injury level (severity) of traffic accidents. While some of the risk factors, such as drug use and drinking, are widely known to affect severity, an accurate modeling of their influences is still an open research topic. Furthermore, there are innumerable risk factors that are waiting to be discovered or analyzed. A promising approach is to investigate historical traffic accident data that have been collected in the past decades. This study inspects traffic accident reports that have been accumulated by the California Highway Patrol (CHP) since 1973 for which each accident report contains around 100 data fields. Among them, we investigate 25 fields between 2004 and 2010 that are most relevant to car accidents. Using two classification methods, the Naive Bayes classifier and the decision tree classifier, the relative importance of the data fields, i.e., risk factors, is revealed with respect to the resulting severity level. Performances of the classifiers are compared to each other and a binary logistic regression model is used as the basis for the comparisons. Some of the high-ranking risk factors are found to be strongly dependent on each other, and their incremental gains on estimating or modeling severity level are evaluated quantitatively. The analysis shows that only a handful of the risk factors in the data dominate the severity level and that dependency among the top risk factors is an imperative trait to consider for an accurate analysis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Isospin asymmetry dependence of the α spectroscopic factor for heavy nuclei

    International Nuclear Information System (INIS)

    Seif, W. M.; Shalaby, M.; Alrakshy, M. F.

    2011-01-01

    Both the valence nucleons (holes) and the isospin asymmetry dependencies of the preformation probability of an α-cluster inside parents radioactive nuclei are investigated. The calculations are employed in the framework of the density-dependent cluster model of an α-decay process for the even-even spherical parents nuclei with protons number around the closed shell Z 0 = 82 and neutrons number around the closed shells Z 0 = 82 and Z 0 = 126. The microscopic α-daughter nuclear interaction potential is calculated in the framework of the Hamiltonian energy density approach based on the SLy4 Skyrme-like effective interaction. Also, the calculations based on the realistic effective M3Y-Paris nucleon-nucleon force have been used to confirm the results. The calculations then proceed to find the assault frequency and the α penetration probability within the WKB approximation. The half-lives of the different mentioned α decays are then determined and have been used in turn to find the α spectroscopic factor. We found that the spectroscopic factor increases with increasing the isospin asymmetry of the parent nuclei if they have valence protons and neutrons. When the parent nuclei have neutron or proton holes in addition to the valence protons or neutrons, then the spectroscopic factor is found to decrease with increasing isospin asymmetry. The obtained results show also that the deduced spectroscopic factors follow individual linear behaviors as a function of the multiplication of the valence proton (N p ) and neutron (N n ) numbers. These linear dependencies are correlated with the closed shells core (Z 0 ,N 0 ). The same individual linear behaviors are obtained as a function of the multiplication of N p N n and the isospin asymmetry parameter, N p N n I. Moreover, the whole deduced spectroscopic factors are found to exhibit a nearly general linear trend with the function N p N n /(Z 0 +N 0 ).

  2. Frequency-dependent alternating-current scanning electrochemical microscopy (4D AC-SECM) for local visualisation of corrosion sites.

    Science.gov (United States)

    Eckhard, Kathrin; Erichsen, Thomas; Stratmann, Martin; Schuhmann, Wolfgang

    2008-01-01

    For a better understanding of the initiation of localised corrosion, there is a need for analytical tools that are capable of imaging corrosion pits and precursor sites with high spatial resolution and sensitivity. The lateral electrochemical contrast in alternating-current scanning electrochemical microscopy (AC-SECM) has been found to be highly dependent on the frequency of the applied alternating voltage. In order to be able to obtain data with optimum contrast and high resolution, the AC frequency is swept in a full spectrum at each point in space instead of performing spatially resolved measurements at one fixed perturbation frequency. In doing so, four-dimensional data sets are acquired (4D AC-SECM). Here, we describe the instrument set-up and modus operandi, along with the first results from the imaging of corroding surfaces. Corrosion precursor sites and local defects in protective organic coatings, as well as an actively corroding pit on 304 stainless steel, have been successfully visualised. Since the lateral electrochemical contrast in these images varies with the perturbation frequency, the proposed approach constitutes an indispensable tool for obtaining optimum electrochemical contrast.

  3. Dopant-site-dependent scattering by dislocations in epitaxial films of perovskite semiconductor BaSnO3

    Directory of Open Access Journals (Sweden)

    Useong Kim

    2014-05-01

    Full Text Available We studied the conduction mechanism in Sb-doped BaSnO3 epitaxial films, and compared its behavior with that of the mechanism of its counterpart, La-doped BaSnO3. We found that the electron mobility in BaSnO3 films was reduced by almost 7 times when the dopant was changed from La to Sb, despite little change in the effective mass of the carriers. This indicates that the scattering rate of conduction electrons in the BaSnO3 system is strongly affected by the site at which the dopants are located. More importantly, we found that electron scattering by threading dislocations also depends critically on the dopant site. We propose that the large enhancement of scattering by the threading dislocations in Sb-doped BaSnO3 films is caused by the combination effect of the change in the distribution of Sb impurities in the films, the formation of the Sb impurity clusters near the threading dislocations, and the conduction electron clustering near the Sb impurities.

  4. Body Site Is a More Determinant Factor than Human Population Diversity in the Healthy Skin Microbiome.

    Directory of Open Access Journals (Sweden)

    Guillermo I Perez Perez

    Full Text Available We studied skin microbiota present in three skin sites (forearm, axilla, scalp in men from six ethnic groups living in New York City.Samples were obtained at baseline and after four days following use of neutral soap and stopping regular hygiene products, including shampoos and deodorants. DNA was extracted using the MoBio Power Lyzer kit and 16S rRNA gene sequences determined on the IIlumina MiSeq platform, using QIIME for analysis.Our analysis confirmed skin swabbing as a useful method for sampling different areas of the skin because DNA concentrations and number of sequences obtained across subject libraries were similar. We confirmed that skin location was the main factor determining the composition of bacterial communities. Alpha diversity, expressed as number of species observed, was greater in arm than on scalp or axilla in all studied groups. We observed an unexpected increase in α-diversity on arm, with similar tendency on scalp, in the South Asian group after subjects stopped using their regular shampoos and deodorants. Significant differences at phylum and genus levels were observed between subjects of the different ethnic origins at all skin sites.We conclude that ethnicity and particular soap and shampoo practices are secondary factors compared to the ecological zone of the human body in determining cutaneous microbiota composition.

  5. Psychological risk factors of addiction to social networking sites among Chinese smartphone users.

    Science.gov (United States)

    Wu, Anise M S; Cheung, Vivi I; Ku, Lisbeth; Hung, Eva P W

    2013-09-01

    Smartphones allow users to access social networking sites (SNSs) whenever and wherever they want. Such easy availability and accessibility may increase their vulnerability to addiction. Based on the social cognitive theory (SCT), we examined the impacts of outcome expectancies, self-efficacy, and impulsivity on young Chinese smartphone users' addictive tendencies toward SNSs. Two hundred seventy-seven Macau young smartphone users (116 males and 161 females; mean age = 26.62) filled out an online Chinese questionnaire concerning their usage of social networking sites via smartphones, addiction tendencies toward SNSs, impulsivity trait, outcome expectancies toward the use, and Internet self-efficacy. The findings revealed that those who spent more time on SNSs also reported higher addictive tendencies. Addictive tendencies were positively correlated with both outcome expectancies and impulsivity, but negatively associated with Internet self-efficacy. These three psychological variables explained 23% of the variance in addictive tendencies. The findings of this study suggest that, compared to demographics, psychological factors provide a better account for addictive tendencies towards SNSs among Chinese smartphone users in Macau. The three psychological risk factors were low Internet self-efficacy, favorable outcome expectancies, and high impulsivity trait. Educational campaigns with screening procedures for high-risk groups are recommended for effective prevention and treatment.

  6. HOCOMOCO: expansion and enhancement of the collection of transcription factor binding sites models

    KAUST Repository

    Kulakovskiy, Ivan V.

    2015-11-19

    Models of transcription factor (TF) binding sites provide a basis for a wide spectrum of studies in regulatory genomics, from reconstruction of regulatory networks to functional annotation of transcripts and sequence variants. While TFs may recognize different sequence patterns in different conditions, it is pragmatic to have a single generic model for each particular TF as a baseline for practical applications. Here we present the expanded and enhanced version of HOCOMOCO (http://hocomoco.autosome.ru and http://www.cbrc.kaust.edu.sa/hocomoco10), the collection of models of DNA patterns, recognized by transcription factors. HOCOMOCO now provides position weight matrix (PWM) models for binding sites of 601 human TFs and, in addition, PWMs for 396 mouse TFs. Furthermore, we introduce the largest up to date collection of dinucleotide PWM models for 86 (52) human (mouse) TFs. The update is based on the analysis of massive ChIP-Seq and HT-SELEX datasets, with the validation of the resulting models on in vivo data. To facilitate a practical application, all HOCOMOCO models are linked to gene and protein databases (Entrez Gene, HGNC, UniProt) and accompanied by precomputed score thresholds. Finally, we provide command-line tools for PWM and diPWM threshold estimation and motif finding in nucleotide sequences.

  7. Activation of factor IX zymogen results in exposure of a binding site for low-density lipoprotein receptor-related protein.

    Science.gov (United States)

    Neels, J G; van Den Berg, B M; Mertens, K; ter Maat, H; Pannekoek, H; van Zonneveld, A J; Lenting, P J

    2000-11-15

    The interaction between the endocytic receptor low density lipoprotein receptor-related protein (LRP) and either coagulation factor IX or its active derivative factor IXa was studied. Purified factor IX was unable to associate with LRP when analyzed by surface plasmon resonance. By contrast, factor XIa-mediated conversion of factor IX into factor IXa resulted in reversible dose- and calcium-dependent binding to LRP. Active-site blocking of factor IXa did not affect binding to LRP, whereas LRP binding was efficiently inhibited in the presence of heparin or antibodies against factor IX or LRP. The factor IXa-LRP interaction could be described by a 2-site binding model with equilibrium dissociation constants of 27 nmol/L and 69 nmol/L. Consistent with this model, it was observed that factor IXa binds to 2 different recombinant receptor fragments of LRP (denoted cluster II and cluster IV) with equilibrium dissociation constants of 227 nmol/L and 53 nmol/L, respectively. The amount of factor IXa degraded by LRP-deficient cells was 35% lower than by LRP-expressing cells, demonstrating that LRP contributes to the transport of factor IXa to the intracellular degradation pathway. Because ligand binding to LRP is often preceded by binding to proteoglycans, the contribution of proteoglycans to the catabolism of factor IXa was addressed by employing proteoglycan-deficient cells. Degradation of factor IXa by proteoglycan-deficient cells proceeded at a 83% lower rate than wild-type cells. In conclusion, the data presented here indicate that both LRP and proteoglycans have the potential to contribute to the catabolism of factor IXa.

  8. A three-site Langmuir adsorption model to elucidate the temperature, pressure, and support dependence of the hydrogen coverage on supported Pt particles

    NARCIS (Netherlands)

    Ji, Y.; Koot, V.; van der Eerden, A.M.J.; Weckhuysen, B.M.; Koningsberger, D.C.; Ramaker, D.E.

    2007-01-01

    The three-site adsorption model, previously developed to describe H adsorption on small Pt particles, was used to gain insight into dependence of hydrogen coverage on temperature, pressure, and support ionicity. The three sites, in order of decreasing PtH bond strength, involve H in an atop, a

  9. Ab initio identification of putative human transcription factor binding sites by comparative genomics

    Directory of Open Access Journals (Sweden)

    Provero P

    2005-05-01

    Full Text Available Abstract Background Understanding transcriptional regulation of gene expression is one of the greatest challenges of modern molecular biology. A central role in this mechanism is played by transcription factors, which typically bind to specific, short DNA sequence motifs usually located in the upstream region of the regulated genes. We discuss here a simple and powerful approach for the ab initio identification of these cis-regulatory motifs. The method we present integrates several elements: human-mouse comparison, statistical analysis of genomic sequences and the concept of coregulation. We apply it to a complete scan of the human genome. Results By using the catalogue of conserved upstream sequences collected in the CORG database we construct sets of genes sharing the same overrepresented motif (short DNA sequence in their upstream regions both in human and in mouse. We perform this construction for all possible motifs from 5 to 8 nucleotides in length and then filter the resulting sets looking for two types of evidence of coregulation: first, we analyze the Gene Ontology annotation of the genes in the set, searching for statistically significant common annotations; second, we analyze the expression profiles of the genes in the set as measured by microarray experiments, searching for evidence of coexpression. The sets which pass one or both filters are conjectured to contain a significant fraction of coregulated genes, and the upstream motifs characterizing the sets are thus good candidates to be the binding sites of the TF's involved in such regulation. In this way we find various known motifs and also some new candidate binding sites. Conclusion We have discussed a new integrated algorithm for the "ab initio" identification of transcription factor binding sites in the human genome. The method is based on three ingredients: comparative genomics, overrepresentation, different types of coregulation. The method is applied to a full-scan of the

  10. Stem cell-dependent formation of a functional anterior regeneration pole in planarians requires Zic and Forkhead transcription factors.

    Science.gov (United States)

    Vogg, Matthias C; Owlarn, Suthira; Pérez Rico, Yuvia A; Xie, Jianlei; Suzuki, Yoko; Gentile, Luca; Wu, Wei; Bartscherer, Kerstin

    2014-06-15

    Planarians can regenerate their head within days. This process depends on the direction of adult stem cells to wound sites and the orchestration of their progenitors to commit to appropriate lineages and to arrange into patterned tissues. We identified a zinc finger transcription factor, Smed-ZicA, as a downstream target of Smed-FoxD, a Forkhead transcription factor required for head regeneration. Smed-zicA and Smed-FoxD are co-expressed with the Wnt inhibitor notum and the Activin inhibitor follistatin in a cluster of cells at the anterior-most tip of the regenerating head - the anterior regeneration pole - and in surrounding stem cell progeny. Depletion of Smed-zicA and Smed-FoxD by RNAi abolishes notum and follistatin expression at the pole and inhibits head formation downstream of initial polarity decisions. We suggest a model in which ZicA and FoxD transcription factors synergize to control the formation of Notum- and Follistatin-producing anterior pole cells. Pole formation might constitute an early step in regeneration, resulting in a signaling center that orchestrates cellular events in the growing tissue. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Assessing the model transferability for prediction of transcription factor binding sites based on chromatin accessibility.

    Science.gov (United States)

    Liu, Sheng; Zibetti, Cristina; Wan, Jun; Wang, Guohua; Blackshaw, Seth; Qian, Jiang

    2017-07-27

    Computational prediction of transcription factor (TF) binding sites in different cell types is challenging. Recent technology development allows us to determine the genome-wide chromatin accessibility in various cellular and developmental contexts. The chromatin accessibility profiles provide useful information in prediction of TF binding events in various physiological conditions. Furthermore, ChIP-Seq analysis was used to determine genome-wide binding sites for a range of different TFs in multiple cell types. Integration of these two types of genomic information can improve the prediction of TF binding events. We assessed to what extent a model built upon on other TFs and/or other cell types could be used to predict the binding sites of TFs of interest. A random forest model was built using a set of cell type-independent features such as specific sequences recognized by the TFs and evolutionary conservation, as well as cell type-specific features derived from chromatin accessibility data. Our analysis suggested that the models learned from other TFs and/or cell lines performed almost as well as the model learned from the target TF in the cell type of interest. Interestingly, models based on multiple TFs performed better than single-TF models. Finally, we proposed a universal model, BPAC, which was generated using ChIP-Seq data from multiple TFs in various cell types. Integrating chromatin accessibility information with sequence information improves prediction of TF binding.The prediction of TF binding is transferable across TFs and/or cell lines suggesting there are a set of universal "rules". A computational tool was developed to predict TF binding sites based on the universal "rules".

  12. Landscape dose conversion factors used in the safety assessment SR-Site

    International Nuclear Information System (INIS)

    Avila, Rodolfo; Ekstroem, Per-Anders; Aastrand, Per-Gustav

    2010-12-01

    In this report two types of Dose Conversion Factors have been derived: i) a Landscape Dose Conversion Factor (LDF) that is applicable to continuous long-term releases to the biosphere at a constant rate, and ii) a Landscape Dose Conversion Factor for pulse releases (LDF pulse) that is applicable to a radionuclide release that reaches the biosphere in a pulse within years to hundreds of years. In SR-Site these Dose Factors are multiplied with modelled release rates or pulse releases from the geosphere to obtain dose estimates used in assessment of compliance with the regulatory risk criterion. The LDFs were calculated for three different periods of the reference glacial cycle; a period of submerged conditions following the deglaciation, the temperate period, and a prolonged period of periglacial conditions. Additionally, LDFs were calculated for the global warming climate case. The LDF pulse was calculated only for temperate climate conditions. The LDF and LDF pulse can be considered as Best Estimate values, which can be used in calculations of Best Estimate values of doses to a representative individual of the most exposed group from potential releases from a future repository. A systematic analysis of the effects of system, model and parameter uncertainties on the LDFs has been carried out. This analysis has shown that the use of the derived LDF would lead to cautious or realistic dose estimates. The models and methods that were used for derivation of the LDFs and LDF pulse are also described in this report

  13. Landscape dose conversion factors used in the safety assessment SR-Site

    Energy Technology Data Exchange (ETDEWEB)

    Avila, Rodolfo; Ekstroem, Per-Anders; Aastrand, Per-Gustav (Facilia AB (Sweden))

    2010-12-15

    In this report two types of Dose Conversion Factors have been derived: i) a Landscape Dose Conversion Factor (LDF) that is applicable to continuous long-term releases to the biosphere at a constant rate, and ii) a Landscape Dose Conversion Factor for pulse releases (LDF pulse) that is applicable to a radionuclide release that reaches the biosphere in a pulse within years to hundreds of years. In SR-Site these Dose Factors are multiplied with modelled release rates or pulse releases from the geosphere to obtain dose estimates used in assessment of compliance with the regulatory risk criterion. The LDFs were calculated for three different periods of the reference glacial cycle; a period of submerged conditions following the deglaciation, the temperate period, and a prolonged period of periglacial conditions. Additionally, LDFs were calculated for the global warming climate case. The LDF pulse was calculated only for temperate climate conditions. The LDF and LDF pulse can be considered as Best Estimate values, which can be used in calculations of Best Estimate values of doses to a representative individual of the most exposed group from potential releases from a future repository. A systematic analysis of the effects of system, model and parameter uncertainties on the LDFs has been carried out. This analysis has shown that the use of the derived LDF would lead to cautious or realistic dose estimates. The models and methods that were used for derivation of the LDFs and LDF pulse are also described in this report

  14. A Humidity-Dependent Lifetime Derating Factor for DC Film Capacitors

    DEFF Research Database (Denmark)

    Wang, Huai; Reigosa, Paula Diaz; Blaabjerg, Frede

    2015-01-01

    accelerated testing of film capacitors under different humidity conditions, enabling a more justified lifetime prediction of film capacitors for DC-link applications under specific climatic environments. The analysis of the testing results and the detailed discussion on the derating factor with different......Film capacitors are widely assumed to have superior reliability performance than Aluminum electrolytic capacitors in DC-link design of power electronic converters. However, the assumption needs to be critically judged especially for applications under high humidity environments. This paper proposes...... a humidity-dependent lifetime derating factor for a type of plastic-boxed metallized DC film capacitors. It overcomes the limitation that the humidity impact is not considered in the state-of-the-art DC film capacitor lifetime models. The lifetime derating factor is obtained based on a total of 8,700 hours...

  15. Vif is an auxiliary factor of the HIV-1 reverse transcriptase and facilitates abasic site bypass.

    Science.gov (United States)

    Cancio, Reynel; Spadari, Silvio; Maga, Giovanni

    2004-11-01

    The HIV-1 accessory protein Vif was found to modulate the RNA- and DNA-dependent DNA synthesis activity of the viral RT (reverse transcriptase) in two ways: (i) it stimulated the binding of the viral RT to the primer by increasing the association rate kcat/K(m) and by decreasing the thermodynamic barrier DeltaH([ES]) for complex formation, and (ii) it increased the polymerization rate of HIV-1 RT. A Vif mutant lacking the final 56 amino acids at the C-terminus failed to stimulate the viral RT. On the other hand, another Vif mutant lacking the first 43 amino acids at the N-terminus, which are involved in RNA binding and interaction with the viral protease, was able to stimulate RT activity. In addition, Vif was found to promote the bypass of an abasic site by HIV-1 RT.

  16. Study on alcohol dependence and factors related to erectile dysfunction among aborigines in Taiwan.

    Science.gov (United States)

    Chao, Jian-Kang; Ma, Mi-Chia; Lin, Yen-Chin; Chiang, Han-Sun; Hwang, Thomas I-Sheng

    2015-05-01

    Relatively few studies have addressed the risk factors of erectile dysfunction (ED) in Taiwanese- most have described ED and medical problems in the general population. In this study, the cardiovascular risk factors of ED among aborigines in Taiwan were investigated. However, alcohol dependence (AD) was prevalent in Taiwan's aborigine population. So this study also focused on the relationship among AD, the cardiovascular risk factors and ED. A cross-sectional study was conducted, and data was obtained from a baseline survey of 192 aboriginal adults (35-75 years of age). The participants' demographic data, AD, markers of endothelial function, serum testosterone, and ED status were assessed. Ninety-four (49%) of the 192 participants had a history of alcoholism and 79 (84%) of those with alcoholism had ED. The study reported that AD and hyperlipidemia, metabolic syndrome (MetS), ED, abnormality of testosterone, and high-sensitivity C-reactive protein are highly prevalent among the aborigines. Factors that may affect ED included age, AD, central obesity, diabetes mellitus, hyperlipidemia, hypertension, MetS, and testosterone. ED is highly prevalent among aborigines with the risk factors of AD, MetS, old age, and abnormal testosterone serum level. MetS, atherosclerosis, and ED are risk factors for cardiovascular diseases. Hence, an increased focus on Taiwanese aborigines with ED is necessary. © The Author(s) 2014.

  17. Site-Specific Hydrogen Isotope Composition of Propane: Mass spectrometric methods, equilibrium temperature dependence, and kinetics of exchange

    Science.gov (United States)

    Xie, H.; Ponton, C.; Kitchen, N.; Lloyd, M. K.; Lawson, M.; Formolo, M. J.; Eiler, J. M.

    2016-12-01

    Intramolecular isotope ordering can constrain temperatures of synthesis, mechanisms of formation, and/or source substrates of organic compounds. Here we explore site-specific hydrogen isotope variations of propane. Statistical thermodynamic models predict that at equilibrium methylene hydrogen (-CH2-) in propane will be 10's of per mil higher in D/H ratio than methyl hydrogen (-CH3) at geologically relevant temperatures, and that this difference is highly temperature dependent ( 0.5-1 ‰/°C). Chemical-kinetic controls on site-specific D/H in propane could constrain the mechanisms, conditions and extents of propane synthesis or destruction. We have developed a method for measuring the difference in D/H ratio between methylene and methyl hydrogen in propane by gas source mass spectrometry. The data were measured using the Thermo Fisher Double Focusing Sector high resolution mass spectrometer (DFS), and involve comparison of the D/H ratios of molecular ion (C3H8+) and the ethyl fragmental ion (C2H5+). We demonstrate the accuracy and precision of this method through analysis of D-labeled and independently analyzed propanes. In the exchange experiments, propane was heated (100-200 oC) either alone or in the presence of D-enriched water (δD=1,1419 ‰ SMOW), with or without one of several potentially catalytic substrates for hours to weeks. Propane was found to exchange hydrogen with water vigorously at 200 °C in the presence of metal catalysts. In the presence of Ni catalyst, methylene hydrogen exchanges 2.5 times faster than methyl hydrogen. Hydrogen exchange in the presence of Pd catalyst is more effective and can equilibrate hydrogen isotope distribution on propane on the order of 7 days. Isotopic exchange in the presence of natural materials have also been tested, but is only measurable in the methylene group at 200 °C. High catalytic activity of Pd permits attainment of a bracketed, time-invariant equilibrium state that we use to calibrate the site

  18. The association between fracture and obesity is site-dependent: a population-based study in postmenopausal women.

    Science.gov (United States)

    Prieto-Alhambra, Daniel; Premaor, Melissa O; Fina Avilés, Francesc; Hermosilla, Eduard; Martinez-Laguna, Daniel; Carbonell-Abella, Cristina; Nogués, Xavier; Compston, Juliet E; Díez-Pérez, Adolfo

    2012-02-01

    The association between obesity and fracture is controversial. We investigated the relationship between body mass index (BMI) and fracture at different skeletal sites in women aged ≥50 years using data from the Sistema d' Informació per al Desenvolupament de la Investigació en Atenció Primària (SIDIAP) database. SIDIAP contains the computerized medical records of >3400 general practitioners in Catalonia (northeastern Spain), with information on a representative 80% of the population (>5 million people). In 2009, 1,039,878 women aged ≥50 years were eligible, of whom 832,775 (80.1%) had a BMI measurement. These were categorized into underweight/normal (302,414 women), overweight (266,798), and obese (263,563). Fractures were ascertained using the International Classification of Diseases, 10th revision (ICD-10) codes. Multivariate Poisson regression models were fitted to adjust for age, smoking, high alcohol intake, type 2 diabetes, and oral corticosteroid use. Hip fractures were significantly less common in overweight and obese women than in normal/underweight women (rate ratio [RR] 0.77 [95% confidence interval (CI) 0.68 to 0.88], RR 0.63 [95% CI 0.64 to 0.79], p obese (RR 0.58 [95% CI 0.47 to 0.73], p obese women were at significantly higher risk of proximal humerus fracture than the normal/underweight group (RR 1.28 [95% CI 1.04 to 1.58], p = 0.018). Clinical spine, wrist, tibial, and multiple rib fracture rates were not significantly different between groups. An age-related increase in incidence was seen for all BMI groups at all fracture sites; obese women with hip, clinical spine, and pelvis fracture were significantly younger at the time of fracture than normal/underweight women, whereas those with wrist fracture were significantly older. The association between obesity and fracture in postmenopausal women is site-dependent, obesity being protective against hip and pelvis fractures but associated with an almost 30% increase in risk for proximal humerus

  19. Comprehensive human transcription factor binding site map for combinatory binding motifs discovery.

    Directory of Open Access Journals (Sweden)

    Arnoldo J Müller-Molina

    Full Text Available To know the map between transcription factors (TFs and their binding sites is essential to reverse engineer the regulation process. Only about 10%-20% of the transcription factor binding motifs (TFBMs have been reported. This lack of data hinders understanding gene regulation. To address this drawback, we propose a computational method that exploits never used TF properties to discover the missing TFBMs and their sites in all human gene promoters. The method starts by predicting a dictionary of regulatory "DNA words." From this dictionary, it distills 4098 novel predictions. To disclose the crosstalk between motifs, an additional algorithm extracts TF combinatorial binding patterns creating a collection of TF regulatory syntactic rules. Using these rules, we narrowed down a list of 504 novel motifs that appear frequently in syntax patterns. We tested the predictions against 509 known motifs confirming that our system can reliably predict ab initio motifs with an accuracy of 81%-far higher than previous approaches. We found that on average, 90% of the discovered combinatorial binding patterns target at least 10 genes, suggesting that to control in an independent manner smaller gene sets, supplementary regulatory mechanisms are required. Additionally, we discovered that the new TFBMs and their combinatorial patterns convey biological meaning, targeting TFs and genes related to developmental functions. Thus, among all the possible available targets in the genome, the TFs tend to regulate other TFs and genes involved in developmental functions. We provide a comprehensive resource for regulation analysis that includes a dictionary of "DNA words," newly predicted motifs and their corresponding combinatorial patterns. Combinatorial patterns are a useful filter to discover TFBMs that play a major role in orchestrating other factors and thus, are likely to lock/unlock cellular functional clusters.

  20. Coactivator-dependent acetylation stabilizes members of the SREBP family of transcription factors.

    Science.gov (United States)

    Giandomenico, Valeria; Simonsson, Maria; Grönroos, Eva; Ericsson, Johan

    2003-04-01

    Members of the SREBP family of transcription factors control cholesterol and lipid homeostasis and play important roles during adipocyte differentiation. The transcriptional activity of SREBPs is dependent on the coactivators p300 and CBP. We now present evidence that SREBPs are acetylated by the intrinsic acetyltransferase activity of p300 and CBP. In SREBP1a, the acetylated lysine residue resides in the DNA-binding domain of the protein. Coexpression with p300 dramatically increases the expression of both SREBP1a and SREBP2, and this effect is dependent on the acetyltransferase activity of p300, indicating that acetylation of SREBPs regulates their stability. Indeed, acetylation or mutation of the acetylated lysine residue in SREBP1a stabilizes the protein. We demonstrate that the acetylated residue in SREBP1a is also targeted by ubiquitination and that acetylation inhibits this process. Thus, our studies define acetylation-dependent stabilization of transcription factors as a novel mechanism for coactivators to regulate gene expression.

  1. Temperature dependence of the calibration factor of radon and radium determination in water samples by SSNTD

    CERN Document Server

    Hunyadi, I; Hakl, J; Baradacs, E; Dezso, Z

    1999-01-01

    The sensitivity of a sup 2 sup 2 sup 6 Ra determination method of water samples by SSNTD was measured as a function of storage temperature during exposure. The method is based on an etched track type radon monitor, which is closed into a gas permeable foil and is immersed in the water sample. The sample is sealed in a glass vessel and stored for an exposure time of 10-30 days. The sensitivity increased more than a factor of two when the storage temperature was raised from 2 deg. C to 30 deg. C. Temperature dependence of the partition coefficient of radon between water and air provides explanation for this dependence. For practical radio- analytical application the temperature dependence of the calibration factor is given by fitting the sensitivity data obtained by measuring sup 2 sup 2 sup 6 Ra standard solutions (in the activity concentration range of 0.1-48.5 kBq m sup - sup 3) at different storage temperatures.

  2. Different papillomaviruses have different repertoires of transcription factor binding sites: convergence and divergence in the upstream regulatory region

    Directory of Open Access Journals (Sweden)

    Alonso Ángel

    2006-03-01

    Full Text Available Abstract Background Papillomaviruses (PVs infect stratified squamous epithelia in warm-blooded vertebrates and have undergone a complex evolutionary process. The control of the expression of the early ORFs in PVs depends on the binding of cellular and viral transcription factors to the upstream regulatory region (URR of the virus. It is believed that there is a core of transcription factor binding sites (TFBS common to all PVs, with additional individual differences, although most of the available information focuses only on a handful of viruses. Results We have studied the URR of sixty-one PVs, covering twenty different hosts. We have predicted the TFBS present in the URR and analysed these results by principal component analysis and genetic algorithms. The number and nature of TFBS in the URR might be much broader than thus far described, and different PVs have different repertoires of TFBS. Conclusion There are common fingerprints in the URR in PVs that infect primates, although the ancestors of these viruses diverged a long time ago. Additionally, there are obvious differences between the URR of alpha and beta PVs, despite these PVs infect similar histological cell types in the same host, i.e. human. A thorough analysis of the TFBS in the URR might provide crucial information about the differential biology of cancer-associated PVs.

  3. Ovarian metastases resection from extragenital primary sites: outcome and prognostic factor analysis of 147 patients

    International Nuclear Information System (INIS)

    Li, Wenhua; Wang, Huaying; Wang, Jian; LV, Fangfang; Zhu, Xiaodong; Wang, Zhonghua

    2012-01-01

    To explore the outcomes and prognostic factors of ovarian metastasectomy intervention on overall survival from extragenital primary cancer. Patients with ovarian metastases from extragenital primary cancer confirmed by laparotomy surgery and ovarian metastases resection were retrospectively collected in a single institution during an 8-year period. A total of 147 cases were identified and primary tumor sites were colorectal region (49.0%), gastric (40.8%), breast (8.2%), biliary duct (1.4%) and liver (0.7%). The pathological and clinical features were evaluated. Patients’ outcome with different primary tumor sites and predictive factors for overall survival were also investigated by univariate and multivariate analysis. Metachronous ovarian metastasis occurred in 92 (62.6%) and synchronous in 55 (37.4%) patients. Combined metastases occurred in 40 (27.2%). Bilateral metastasis was found in 97 (66%) patients. The median ovarian metastasis tumor size was 9 cm. There were 39 (26.5%) patients with massive ascites ≥ 1000 mL on intraoperative evaluation. With a median follow-up of 48 months, the median OS after ovarian metastasectomy for all patients was 8.2 months (95% CI 7.2-9.3 months). In univariate analyses, there is significant (8.0 months vs. 41.0 months, P = 0.000) difference in OS between patients with gastrointestinal cancer origin from breast origin, and between patients with gastric origin from colorectal origin (7.4 months vs. 8.8 months, P = 0.036). In univariate analyses, synchronous metastases, locally invasion, massive intraoperative ascites (≥ 1000 mL), and combined metastasis, were identified as significant poor prognostic factors. In multivariate analyses combined metastasis (RR, 1.72; 95% CI, 1.09-2.69, P = 0.018), locally invasion (RR, 1.62; 95% CI, 1.03-2.54, P = 0.038) and massive intraoperative ascites (RR, 1.58; 95% CI, 1.02-2.49, P = 0.04) were independent factors for predicting unfavorable overall survival. Ovarian metastases are more

  4. Ovarian metastases resection from extragenital primary sites: outcome and prognostic factor analysis of 147 patients

    Directory of Open Access Journals (Sweden)

    Li Wenhua

    2012-07-01

    Full Text Available Abstract Background To explore the outcomes and prognostic factors of ovarian metastasectomy intervention on overall survival from extragenital primary cancer. Methods Patients with ovarian metastases from extragenital primary cancer confirmed by laparotomy surgery and ovarian metastases resection were retrospectively collected in a single institution during an 8-year period. A total of 147 cases were identified and primary tumor sites were colorectal region (49.0%, gastric (40.8%, breast (8.2%, biliary duct (1.4% and liver (0.7%. The pathological and clinical features were evaluated. Patients’ outcome with different primary tumor sites and predictive factors for overall survival were also investigated by univariate and multivariate analysis. Results Metachronous ovarian metastasis occurred in 92 (62.6% and synchronous in 55 (37.4% patients. Combined metastases occurred in 40 (27.2%. Bilateral metastasis was found in 97 (66% patients. The median ovarian metastasis tumor size was 9 cm. There were 39 (26.5% patients with massive ascites ≥ 1000 mL on intraoperative evaluation. With a median follow-up of 48 months, the median OS after ovarian metastasectomy for all patients was 8.2 months (95% CI 7.2-9.3 months. In univariate analyses, there is significant (8.0 months vs. 41.0 months, P = 0.000 difference in OS between patients with gastrointestinal cancer origin from breast origin, and between patients with gastric origin from colorectal origin (7.4 months vs. 8.8 months, P = 0.036. In univariate analyses, synchronous metastases, locally invasion, massive intraoperative ascites (≥ 1000 mL, and combined metastasis, were identified as significant poor prognostic factors. In multivariate analyses combined metastasis (RR, 1.72; 95% CI, 1.09-2.69, P = 0.018, locally invasion (RR, 1.62; 95% CI, 1.03-2.54, P = 0.038 and massive intraoperative ascites (RR, 1.58; 95% CI, 1.02-2.49, P = 0.04 were independent factors for predicting

  5. Development of variable LRFD \\0x03C6 factors for deep foundation design due to site variability.

    Science.gov (United States)

    2012-04-01

    The current design guidelines of Load and Resistance Factor Design (LRFD) specifies constant values : for deep foundation design, based on analytical method selected and degree of redundancy of the pier. : However, investigation of multiple sites in ...

  6. Risk factors for cesarean surgical site infections at a Thai-Myanmar border hospital.

    Science.gov (United States)

    Assawapalanggool, Srisuda; Kasatpibal, Nongyao; Sirichotiyakul, Supatra; Arora, Rajin; Suntornlimsiri, Watcharin

    2016-09-01

    Cesarean surgical site infections (SSIs) are a major challenge in Thai-Myanmar border hospital settings. This study aimed to examine risk factors for SSIs after cesarean section. This was a prospective cohort study conducted in a Thai-Myanmar border hospital between January 2007 and December 2012. Data were collected from the medical record database by trained infection control nurses. Stepwise multivariable logistic regression was used for risk factor analysis and expressed as a risk ratio (RR). The cesarean SSI rate was 5.9% (293 SSIs in 4,988 cases). Of these, 17.1% were incisional SSIs (10.9% superficial and 6.2% deep incisional SSIs), and 82.9% were organ or space SSIs. Risk factors for cesarean organ-space SSIs included a wound class ≥3 (RR, 4.82; 95% confidence interval [CI], 3.41-6.83), ethnic minority (RR, 2.51; 95% CI, 1.61-3.92), hemoglobin Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  7. Surgical Site Infection following Cesarean Delivery: Patient, Provider, and Procedure-Specific Risk Factors.

    Science.gov (United States)

    Shree, Raj; Park, Seo Young; Beigi, Richard H; Dunn, Shannon L; Krans, Elizabeth E

    2016-01-01

    This study aims to identify risk factors for cesarean delivery (CD) surgical site infection (SSI). study design: Retrospective analysis of 2,739 CDs performed at the University of Pittsburgh in 2011. CD SSIs were defined using National Healthcare Safety Network (NHSN) criteria. Chi-square test and t-test were used for bivariate analyses and multivariate logistic regression was used to identify SSI risk factors. Of 2,739 CDs, 178 (6.5%) were complicated by SSI. Patients with a SSI were more likely to have Medicaid, have resident physicians perform the CD, an American Society of Anesthesiologists (ASA) class of ≥ 3, chorioamnionitis, tobacco use, and labor before CD. In multivariable analysis, labor (odds ratio [OR], 2.35; 95% confidence interval [95% CI], 1.65-3.38), chorioamnionitis (OR, 2.24; 95% CI, 1.25-3.83), resident teaching service (OR, 2.15; 95% CI, 1.54-3.00), tobacco use (OR, 1.70; 95% CI, 1.04-2.70), ASA class ≥ 3 (OR, 1.61; 95% CI, 1.06-2.39), and CDs performed for nonreassuring fetal status (OR, 0.43; 95% CI, 0.26-0.67) were significantly associated with CD SSI. Multiple patient, provider, and procedure-specific risk factors contribute to CD SSI risk which may be targeted in infection-control efforts. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  8. Extraction of depth-dependent perturbation factors for silicon diodes using a plastic scintillation detector

    International Nuclear Information System (INIS)

    Lacroix, Frederic; Guillot, Mathieu; McEwen, Malcolm; Gingras, Luc; Beaulieu, Luc

    2011-01-01

    Purpose: This work presents the experimental extraction of the perturbation factor in megavoltage electron beams for three models of silicon diodes (IBA Dosimetry, EFD and SFD, and the PTW 60012 unshielded) using a plastic scintillation detector (PSD). Methods: The authors used a single scanning PSD mounted on a high-precision scanning tank to measure depth-dose curves in 6-, 12-, and 18-MeV clinical electron beams. They also measured depth-dose curves using the IBA Dosimetry, EFD and SFD, and the PTW 60012 unshielded diodes. The authors used the depth-dose curves measured with the PSD as a perturbation-free reference to extract the perturbation factors of the diodes. Results: The authors found that the perturbation factors for the diodes increased substantially with depth, especially for low-energy electron beams. The experimental results show the same trend as published Monte Carlo simulation results for the EFD diode; however, the perturbations measured experimentally were greater. They found that using an effective point of measurement (EPOM) placed slightly away from the source reduced the variation of perturbation factors with depth and that the optimal EPOM appears to be energy dependent. Conclusions: The manufacturer recommended EPOM appears to be incorrect at low electron energy (6 MeV). In addition, the perturbation factors for diodes may be greater than predicted by Monte Carlo simulations.

  9. Extraction of depth-dependent perturbation factors for silicon diodes using a plastic scintillation detector.

    Science.gov (United States)

    Lacroix, Frederic; Guillot, Mathieu; McEwen, Malcolm; Gingras, Luc; Beaulieu, Luc

    2011-10-01

    This work presents the experimental extraction of the perturbation factor in megavoltage electron beams for three models of silicon diodes (IBA Dosimetry, EFD and SFD, and the PTW 60012 unshielded) using a plastic scintillation detector (PSD). The authors used a single scanning PSD mounted on a high-precision scanning tank to measure depth-dose curves in 6-, 12-, and 18-MeV clinical electron beams. They also measured depth-dose curves using the IBA Dosimetry, EFD and SFD, and the PTW 60012 unshielded diodes. The authors used the depth-dose curves measured with the PSD as a perturbation-free reference to extract the perturbation factors of the diodes. The authors found that the perturbation factors for the diodes increased substantially with depth, especially for low-energy electron beams. The experimental results show the same trend as published Monte Carlo simulation results for the EFD diode; however, the perturbations measured experimentally were greater. They found that using an effective point of measurement (EPOM) placed slightly away from the source reduced the variation of perturbation factors with depth and that the optimal EPOM appears to be energy dependent. The manufacturer recommended EPOM appears to be incorrect at low electron energy (6 MeV). In addition, the perturbation factors for diodes may be greater than predicted by Monte Carlo simulations.

  10. Neuromodulated Spike-Timing-Dependent Plasticity, and Theory of Three-Factor Learning Rules

    Science.gov (United States)

    Frémaux, Nicolas; Gerstner, Wulfram

    2016-01-01

    Classical Hebbian learning puts the emphasis on joint pre- and postsynaptic activity, but neglects the potential role of neuromodulators. Since neuromodulators convey information about novelty or reward, the influence of neuromodulators on synaptic plasticity is useful not just for action learning in classical conditioning, but also to decide “when” to create new memories in response to a flow of sensory stimuli. In this review, we focus on timing requirements for pre- and postsynaptic activity in conjunction with one or several phasic neuromodulatory signals. While the emphasis of the text is on conceptual models and mathematical theories, we also discuss some experimental evidence for neuromodulation of Spike-Timing-Dependent Plasticity. We highlight the importance of synaptic mechanisms in bridging the temporal gap between sensory stimulation and neuromodulatory signals, and develop a framework for a class of neo-Hebbian three-factor learning rules that depend on presynaptic activity, postsynaptic variables as well as the influence of neuromodulators. PMID:26834568

  11. Influence of time-dependent factors in the evaluation of critical infrastructure protection measures.

    Energy Technology Data Exchange (ETDEWEB)

    Buehring, W. A.; Samsa, M. E.; Decision and Information Sciences

    2008-03-28

    The examination of which protective measures are the most appropriate to be implemented in order to prevent, protect against, respond to, and recover from attacks on critical infrastructures and key resources typically involves a comparison of the consequences that could occur when the protective measure is implemented to those that could occur when it is not. This report describes a framework for evaluation that provides some additional capabilities for comparing optional protective measures. It illustrates some potentially important time-dependent factors, such as the implementation rate, that affect the relative pros and cons associated with widespread implementation of protective measures. It presents example results from the use of protective measures, such as detectors and pretrained responders, for an illustrative biological incident. Results show that the choice of an alternative measure can depend on whether or not policy and financial support can be maintained for extended periods of time. Choice of a time horizon greatly influences the comparison of alternatives.

  12. Neuromodulated Spike-Timing-Dependent Plasticity and Theory of Three-Factor Learning Rules

    Directory of Open Access Journals (Sweden)

    Wulfram eGerstner

    2016-01-01

    Full Text Available Classical Hebbian learning puts the emphasis on joint pre- and postsynaptic activity, but neglects the potential role of neuromodulators. Since neuromodulators convey information about novelty or reward, the influence of neuromodulatorson synaptic plasticity is useful not just for action learning in classical conditioning, but also to decide 'when' to create new memories in response to a flow of sensory stimuli.In this review, we focus on timing requirements for pre- and postsynaptic activity in conjunction with one or several phasic neuromodulatory signals. While the emphasis of the text is on conceptual models and mathematical theories, we also discusssome experimental evidence for neuromodulation of Spike-Timing-Dependent Plasticity.We highlight the importance of synaptic mechanisms in bridging the temporal gap between sensory stimulation and neuromodulatory signals, and develop a framework for a class of neo-Hebbian three-factor learning rules that depend on presynaptic activity, postsynaptic variables as well as the influence of neuromodulators.

  13. Neuromodulated Spike-Timing-Dependent Plasticity, and Theory of Three-Factor Learning Rules.

    Science.gov (United States)

    Frémaux, Nicolas; Gerstner, Wulfram

    2015-01-01

    Classical Hebbian learning puts the emphasis on joint pre- and postsynaptic activity, but neglects the potential role of neuromodulators. Since neuromodulators convey information about novelty or reward, the influence of neuromodulators on synaptic plasticity is useful not just for action learning in classical conditioning, but also to decide "when" to create new memories in response to a flow of sensory stimuli. In this review, we focus on timing requirements for pre- and postsynaptic activity in conjunction with one or several phasic neuromodulatory signals. While the emphasis of the text is on conceptual models and mathematical theories, we also discuss some experimental evidence for neuromodulation of Spike-Timing-Dependent Plasticity. We highlight the importance of synaptic mechanisms in bridging the temporal gap between sensory stimulation and neuromodulatory signals, and develop a framework for a class of neo-Hebbian three-factor learning rules that depend on presynaptic activity, postsynaptic variables as well as the influence of neuromodulators.

  14. Regulation of human papillomavirus transcription by the differentiation-dependent epithelial factor Epoc-1/skn-1a.

    Science.gov (United States)

    Yukawa, K; Butz, K; Yasui, T; Kikutani, H; Hoppe-Seyler, F

    1996-01-01

    Human papillomavirus (HPV) early gene expression is closely linked to the differentiation status of infected epithelial cells. Typically, HPV type 16 (HPV16) or HPV18 E6 and E7 transcripts are only barely detectable within the undifferentiated basal cell layer, but their levels increase concomitantly with higher degrees of epithelial cell differentiation in suprabasal cells. A similar differentiation-dependent distribution of expression has been reported for the recently cloned epithelial cell specific transcription factor Epoc-1/skn-1a. We therefore examined whether Epoc-1/skn-1a may be directly involved in the activation of HPV E6/E7 transcription. Transient transfection studies showed that Epoc-1/skn-1a specifically stimulated the HPV16 and HPV18 E6/E7 promoters. Moreover, ectopically expressed Epoc-1/skn-1a was sufficient to stimulate HPV transcription also in nonepithelial cells. By deletion analyses, the Epoc-1/skn-1a-responsive element was mapped to the promoter-proximal portion of the HPV18 transcriptional control region. Footprint analyses and gel retardation assays demonstrated direct binding of Epoc-1/skn-1a to a hitherto uncharacterized site within this region. Mutation of the Epoc-1/skn-1a recognition site within the context of the complete HPV18 upstream regulatory region inhibited Epoc-1/skn-1a-mediated transactivation. These results show that Epoc-1/skn-1a can directly activate the E6/E7 promoter by binding to the viral transcriptional control region. Thus, Epoc-1/skn-1a may be involved in the differentiation-dependent regulation of HPV transcription.

  15. Nucleic Acid-Dependent Conformational Changes in CRISPR-Cas9 Revealed by Site-Directed Spin Labeling.

    Science.gov (United States)

    Vazquez Reyes, Carolina; Tangprasertchai, Narin S; Yogesha, S D; Nguyen, Richard H; Zhang, Xiaojun; Rajan, Rakhi; Qin, Peter Z

    2017-06-01

    In a type II clustered regularly interspaced short palindromic repeats (CRISPR) system, RNAs that are encoded at the CRISPR locus complex with the CRISPR-associated (Cas) protein Cas9 to form an RNA-guided nuclease that cleaves double-stranded DNAs at specific sites. In recent years, the CRISPR-Cas9 system has been successfully adapted for genome engineering in a wide range of organisms. Studies have indicated that a series of conformational changes in Cas9, coordinated by the RNA and the target DNA, direct the protein into its active conformation, yet details on these conformational changes, as well as their roles in the mechanism of function of Cas9, remain to be elucidated. Here, nucleic acid-dependent conformational changes in Streptococcus pyogenes Cas9 (SpyCas9) were investigated using the method of site-directed spin labeling (SDSL). Single nitroxide spin labels were attached, one at a time, at one of the two native cysteine residues (Cys80 and Cys574) of SpyCas9, and the spin-labeled proteins were shown to maintain their function. X-band continuous-wave electron paramagnetic resonance spectra of the nitroxide attached at Cys80 revealed conformational changes of SpyCas9 that are consistent with a large-scale domain re-arrangement upon binding to its RNA partner. The results demonstrate the use of SDSL to monitor conformational changes in CRISPR-Cas9, which will provide key information for understanding the mechanism of CRISPR function.

  16. Early survival factor deprivation in the olfactory epithelium enhances activity-dependent survival

    Directory of Open Access Journals (Sweden)

    Adrien eFrançois

    2013-12-01

    Full Text Available The neuronal olfactory epithelium undergoes permanent renewal because of environmental aggression. This renewal is partly regulated by factors modulating the level of neuronal apoptosis. Among them, we had previously characterized endothelin as neuroprotective. In this study, we explored the effect of cell survival factor deprivation in the olfactory epithelium by intranasal delivery of endothelin receptors antagonists to rat pups. This treatment induced an overall increase of apoptosis in the olfactory epithelium. The responses to odorants recorded by electroolfactogram were decreased in treated animal, a result consistent with a loss of olfactory sensory neurons (OSNs. However, the treated animal performed better in an olfactory orientation test based on maternal odor compared to non-treated littermates. This improved performance could be due to activity-dependent neuronal survival of OSNs in the context of increased apoptosis level. In order to demonstrate it, we odorized pups with octanal, a known ligand for the rI7 olfactory receptor (Olr226. We quantified the number of OSN expressing rI7 by RT-qPCR and whole mount in situ hybridization. While this number was reduced by the survival factor removal treatment, this reduction was abolished by the presence of its ligand. This improved survival was optimal for low concentration of odorant and was specific for rI7-expressing OSNs. Meanwhile, the number of rI7-expressing OSNs was not affected by the odorization in non-treated littermates; showing that the activity-dependant survival of OSNs did not affect the OSN population during the 10 days of odorization in control conditions. Overall, our study shows that when apoptosis is promoted in the olfactory mucosa, the activity-dependent neuronal plasticity allows faster tuning of the olfactory sensory neuron population towards detection of environmental odorants.

  17. Coupled factors influencing concentration-dependent colloid transport and retention in saturated porous media.

    Science.gov (United States)

    Bradford, Scott A; Kim, Hyunjiung N; Haznedaroglu, Berat Z; Torkzaban, Saeed; Walker, Sharon L

    2009-09-15

    The coupled influence of input suspension concentration (Ci), ionic strength (IS), and hydrodynamics on the transport and retention of 1.1 microm carboxyl-modified latex colloids in saturated quartz sand (150 microm) under unfavorable attachment conditions (pH 10) was investigated. The percentage of retained colloids in column experiments decreased with Ci at intermediate IS conditions (31 or 56 mM) when colloids were weakly associated with the solid phase by a shallow secondary energy minima. In contrast, the effects of Ci on colloid retention were absent when IS was too low (6 mM) or too high (106 mM). The concentration effects under intermediate IS conditions were dependent on the system hydrodynamics, magnitude of Ci, and injection order of Ci, but they were largely independent of the input colloid mass. These observations were explained in part by time- and concentration-dependent filling of retention sites. Only a small fraction of the solid surface area was found to contribute to retention when IS was 31 mM, and micromodel observations indicated that colloid retention was enhanced in lower velocity regions of the pore space that occurred near grain-grain contacts. Consequently, retention profiles for IS = 31 mM conditions were increasingly nonexponential at lower values of Ci (during filling), whereas the observed concentration effect was largely eliminated as retention locations became filled. In addition, micromodel observations indicated that liquid and solid phase mass transfer of colloids to retention locations was influenced by Ci under intermediate IS conditions. Higher values of Ci are expected to produce less relative mass transfer to retention locations due to increased numbers of collisions that knock weakly associated colloids off the solid phase. Hence, the concentration effects were found to be largely independent of input colloid mass during filling of retention sites.

  18. An Elk transcription factor is required for Runx-dependent survival signaling in the sea urchin embryo.

    Science.gov (United States)

    Rizzo, Francesca; Coffman, James A; Arnone, Maria Ina

    2016-08-01

    Elk proteins are Ets family transcription factors that regulate cell proliferation, survival, and differentiation in response to ERK (extracellular-signal regulated kinase)-mediated phosphorylation. Here we report the embryonic expression and function of Sp-Elk, the single Elk gene of the sea urchin Strongylocentrotus purpuratus. Sp-Elk is zygotically expressed throughout the embryo beginning at late cleavage stage, with peak expression occurring at blastula stage. Morpholino antisense-mediated knockdown of Sp-Elk causes blastula-stage developmental arrest and embryo disintegration due to apoptosis, a phenotype that is rescued by wild-type Elk mRNA. Development is also rescued by Elk mRNA encoding a serine to aspartic acid substitution (S402D) that mimics ERK-mediated phosphorylation of a conserved site that enhances DNA binding, but not by Elk mRNA encoding an alanine substitution at the same site (S402A). This demonstrates both that the apoptotic phenotype of the morphants is specifically caused by Elk depletion, and that phosphorylation of serine 402 of Sp-Elk is critical for its anti-apoptotic function. Knockdown of Sp-Elk results in under-expression of several regulatory genes involved in cell fate specification, cell cycle control, and survival signaling, including the transcriptional regulator Sp-Runt-1 and its target Sp-PKC1, both of which were shown previously to be required for cell survival during embryogenesis. Both Sp-Runt-1 and Sp-PKC1 have sequences upstream of their transcription start sites that specifically bind Sp-Elk. These results indicate that Sp-Elk is the signal-dependent activator of a feed-forward gene regulatory circuit, consisting also of Sp-Runt-1 and Sp-PKC1, which actively suppresses apoptosis in the early embryo. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Genome-wide identification of transcription factors and transcription-factor binding sites in oleaginous microalgae Nannochloropsis.

    Science.gov (United States)

    Hu, Jianqiang; Wang, Dongmei; Li, Jing; Jing, Gongchao; Ning, Kang; Xu, Jian

    2014-06-26

    Nannochloropsis spp. are a group of oleaginous microalgae that harbor an expanded array of lipid-synthesis related genes, yet how they are transcriptionally regulated remains unknown. Here a phylogenomic approach was employed to identify and functionally annotate the transcriptional factors (TFs) and TF binding-sites (TFBSs) in N. oceanica IMET1. Among 36 microalgae and higher plants genomes, a two-fold reduction in the number of TF families plus a seven-fold decrease of average family-size in Nannochloropsis, Rhodophyta and Chlorophyta were observed. The degree of similarity in TF-family profiles is indicative of the phylogenetic relationship among the species, suggesting co-evolution of TF-family profiles and species. Furthermore, comparative analysis of six Nannochloropsis genomes revealed 68 "most-conserved" TFBS motifs, with 11 of which predicted to be related to lipid accumulation or photosynthesis. Mapping the IMET1 TFs and TFBS motifs to the reference plant TF-"TFBS motif" relationships in TRANSFAC enabled the prediction of 78 TF-"TFBS motif" interaction pairs, which consisted of 34 TFs (with 11 TFs potentially involved in the TAG biosynthesis pathway), 30 TFBS motifs and 2,368 regulatory connections between TFs and target genes. Our results form the basis of further experiments to validate and engineer the regulatory network of Nannochloropsis spp. for enhanced biofuel production.

  20. Risk factors for cardiovascular diseases among male workers of building construction site in Delhi

    Directory of Open Access Journals (Sweden)

    Mamta Parashar

    2017-01-01

    Full Text Available Background: Cardiovascular disease (CVD is mainly attributable to a combination of risk factors (RFs: tobacco use, alcohol use, high blood pressure, diabetes, unhealthy diet, and obesity which are amenable to interventions. Building construction workers are poor and vulnerable. They are also the victims of adverse working environmental conditions and subjected to health hazards of occupational origin. Objective: The aim was to study the RFs and associated sociodemographics for CVD among construction site workers. Materials and Methods: This cross-sectional study was conducted among construction site workers. A total of 172 male workers over the age of 18 years were included in the study. Modified World Health Organization Step-wise approach to chronic disease RF surveillance was used to collect data. The data were analyzed in SPSS version 17 and the Chi-square test was applied to analyze the qualitative data. Results: At least one RF for CVD was present in all the subjects, with majority (93.6% of them having at least two RFs. The presence of the RFs (moderate to high, 3–11 was found to be significantly associated with lower income group, unskilled workers, migration year <1, alcoholics, personal tobacco use, family history of tobacco use, and the low knowledge score regarding tobacco use (0–2. Conclusions: Community-based comprehensive behavioral and life style communication package should be established for workers to reduce the modifiable RFs of CVD.

  1. Alcohol dependence: analysis of factors associated with retention of patients in outpatient treatment.

    Science.gov (United States)

    Fonsi Elbreder, Márcia; de Souza e Silva, Rebeca; Pillon, Sandra Cristina; Laranjeira, Ronaldo

    2011-01-01

    To identify factors associated with retention in treatment of alcohol-dependent individuals and to compare treatment retention between men and women. Analysis of the treatment attendance records and baseline characteristics of 833 men and 218 women who undertook to attend follow-up treatment in an alcoholism treatment centre. Retention after 4 weeks of treatment is more likely to occur among those using adjuvant medication (the most frequent of which was disulfiram), those presenting severe alcoholism and those who are older and tend to be frequent drinkers. There was no gender difference regarding treatment retention. Such results suggest possibilities for developing specific strategies to reduce the risk of early dropout from treatment.

  2. Runx transcription factors repress human and murine c-Myc expression in a DNA-binding and C-terminally dependent manner.

    Directory of Open Access Journals (Sweden)

    Paejonette T Jacobs

    Full Text Available The transcription factors Runx1 and c-Myc have individually been shown to regulate important gene targets as well as to collaborate in oncogenesis. However, it is unknown whether there is a regulatory relationship between the two genes. In this study, we investigated the transcriptional regulation of endogenous c-Myc by Runx1 in the human T cell line Jurkat and murine primary hematopoietic cells. Endogenous Runx1 binds to multiple sites in the c-Myc locus upstream of the c-Myc transcriptional start site. Cells transduced with a C-terminally truncated Runx1 (Runx1.d190, which lacks important cofactor interaction sites and can block C-terminal-dependent functions of all Runx transcription factors, showed increased transcription of c-Myc. In order to monitor c-Myc expression in response to early and transiently-acting Runx1.d190, we generated a cell membrane-permeable TAT-Runx1.d190 fusion protein. Murine splenocytes treated with TAT-Runx1.d190 showed an increase in the transcription of c-Myc within 2 hours, peaking at 4 hours post-treatment and declining thereafter. This effect is dependent on the ability of Runx1.d190 to bind to DNA. The increase in c-Myc transcripts is correlated with increased c-Myc protein levels. Collectively, these data show that Runx1 directly regulates c-Myc transcription in a C-terminal- and DNA-binding-dependent manner.

  3. E1A-dependent trans-activation of the human MYC promoter is mediated by the E2F factor

    International Nuclear Information System (INIS)

    Hiebert, S.W.; Lipp, M.; Nevins, J.R.

    1989-01-01

    E2F is a cellular transcription factor that binds to two sites in the adenovirus E2 promoter. Previous experiments have implicated E2F in the E1A-dependent transactivation of the E2 gene since levels of active E2F increase markedly during adenovirus infection in parallel with the increase in E2 transcription, and an E2F binding site can confer E1A inducibility to a heterologous promoter. Here the authors show that E2F binds to two sequence elements within the P2 promoter of the human MYC gene which are within a region that is critical for promoter activity. The MYC promoter can be trans-activated in an E1A-dependent manner and site-directed mutagenesis demonstrates that these E2F elements are essential for trans-activation. Finally, they also find that adenovirus infection of quiescent cells results in a stimulation of the endogenous MYC gene. They conclude that the activation of the E2F factor, which is likely responsible for the activation of viral E2 transcription, is also responsible for the E1A-dependent induction of MYC transcription

  4. Prevalence of disability and associated factors in Dabat Health and Demographic Surveillance System site, northwest Ethiopia

    Directory of Open Access Journals (Sweden)

    Mulugeta Bayisa Chala

    2017-10-01

    Full Text Available Abstract Background Despite the high burden of disability in Ethiopia, little is known about it, particularly in the study area. Hence, this study aimed to investigate the prevalence and factors associated with disability at Dabat Health and Demographic Surveillance System (HDSS site, northwest Ethiopia. Method A population-based study was conducted from October to December 2014 at Dabat HDSS site. A total of 67,395 people were included in the study. The multivariable binary logistic regression analysis was employed to identify factors associated with disability. The Adjusted Odds Ratio (AOR with a 95% Confidence Interval (CI was estimated to show the strength of association. A p-value of <0.05 was used to declare statistical significance. Results One thousand two hundred twenty-eight individuals were reported to have a disability giving a prevalence rate of 1.82%, of which, about 39% was related to a vision disability. The high odds of disability were observed among the elderly (≥50 years [AOR: 4.49; 95% CI: 1.95, 10.33], severely food in-secured [AOR: 2.11; 95% CI: 1.59, 2.80], and separated marital status [AOR: 7.52; 95% CI: 1.18, 47.84]. While having a paid job [AOR: 0.46; 95% CI: 0.28, 0.77], being in the richest quintile [AOR: 0.55; 95% CI: 0.41, 0.75], and high engagement in work-related physical activities [AOR: 0.36; 95% CI: 0.27, 0.49] were inversely associated with the disability. Conclusion Disability is a major public health problem, and the burden is noticeable in the study area. Vision disability is the highest of all disabilities. Thus, efforts must be made on educating the public about disability and injury prevention. Measures that reduce disability should target the elderly, the poorer and the unemployed segment of the population.

  5. Prevalence of disability and associated factors in Dabat Health and Demographic Surveillance System site, northwest Ethiopia.

    Science.gov (United States)

    Chala, Mulugeta Bayisa; Mekonnen, Solomon; Andargie, Gashaw; Kebede, Yigzaw; Yitayal, Mezgebu; Alemu, Kassahun; Awoke, Tadesse; Wubeshet, Mamo; Azmeraw, Temesgen; Birku, Melkamu; Tariku, Amare; Gebeyehu, Abebaw; Shimeka, Alemayehu; Gizaw, Zemichael

    2017-10-02

    Despite the high burden of disability in Ethiopia, little is known about it, particularly in the study area. Hence, this study aimed to investigate the prevalence and factors associated with disability at Dabat Health and Demographic Surveillance System (HDSS) site, northwest Ethiopia. A population-based study was conducted from October to December 2014 at Dabat HDSS site. A total of 67,395 people were included in the study. The multivariable binary logistic regression analysis was employed to identify factors associated with disability. The Adjusted Odds Ratio (AOR) with a 95% Confidence Interval (CI) was estimated to show the strength of association. A p-value of <0.05 was used to declare statistical significance. One thousand two hundred twenty-eight individuals were reported to have a disability giving a prevalence rate of 1.82%, of which, about 39% was related to a vision disability. The high odds of disability were observed among the elderly (≥50 years) [AOR: 4.49; 95% CI: 1.95, 10.33], severely food in-secured [AOR: 2.11; 95% CI: 1.59, 2.80], and separated marital status [AOR: 7.52; 95% CI: 1.18, 47.84]. While having a paid job [AOR: 0.46; 95% CI: 0.28, 0.77], being in the richest quintile [AOR: 0.55; 95% CI: 0.41, 0.75], and high engagement in work-related physical activities [AOR: 0.36; 95% CI: 0.27, 0.49] were inversely associated with the disability. Disability is a major public health problem, and the burden is noticeable in the study area. Vision disability is the highest of all disabilities. Thus, efforts must be made on educating the public about disability and injury prevention. Measures that reduce disability should target the elderly, the poorer and the unemployed segment of the population.

  6. Homelessness during pregnancy: a unique, time-dependent risk factor of birth outcomes.

    Science.gov (United States)

    Cutts, Diana B; Coleman, Sharon; Black, Maureen M; Chilton, Mariana M; Cook, John T; de Cuba, Stephanie Ettinger; Heeren, Timothy C; Meyers, Alan; Sandel, Megan; Casey, Patrick H; Frank, Deborah A

    2015-06-01

    Evaluate homelessness during pregnancy as a unique, time-dependent risk factor for adverse birth outcomes. 9,995 mothers of children homeless during pregnancy with the index child, homeless only after the index child's birth, or consistently housed. Outcomes included birth weight as a continuous variable, as well as categorical outcomes of low birth weight (LBW; homelessness with the referent group of consistently housed mothers, controlling for maternal demographic characteristics, smoking, and child age at interview. Prenatal homelessness was associated with higher adjusted odds of LBW (AOR 1.43, 95 % CI 1.14, 1.80, p homelessness was not associated with these outcomes. Prenatal homelessness is an independent risk factor for LBW, rather than merely a marker of adverse maternal and social characteristics associated with homelessness. Targeted interventions to provide housing and health care to homeless women during pregnancy may result in improved birth outcomes.

  7. Antibody-Dependent Enhancement of Dengue Virus Growth in Human Monocytes as a Risk Factor for Dengue Hemorrhagic Fever

    Science.gov (United States)

    1989-01-01

    Clamfication) Antibody-Dependent Enhancement of Dengue Virus Growth in Human Monocytes as a Risk Factor for Dengue Hemorrhagic Fever 𔃼 PERSONAL AjTHOR(S...FELD GROUP SUBGROUP Antibody-Dependent Enhancement of Dengue Virus Growth in Human Monocytes as a Risk Factor for Dengue Hemorrhagic Fever . 19...clinically diagnosed as dengue hemorrhagic fever . Antibody-dependent enhancement of virus growth was quantitated by measurement of virus yields in

  8. Membrane-associated transcription factor peptidase, site-2 protease, antagonizes ABA signaling in Arabidopsis.

    Science.gov (United States)

    Zhou, Shun-Fan; Sun, Le; Valdés, Ana Elisa; Engström, Peter; Song, Ze-Ting; Lu, Sun-Jie; Liu, Jian-Xiang

    2015-10-01

    Abscisic acid plays important roles in maintaining seed dormancy while gibberellins (GA) and other phytohormones antagonize ABA to promote germination. However, how ABA signaling is desensitized during the transition from dormancy to germination is still poorly understood. We functionally characterized the role of membrane-associated transcription factor peptidase, site-2 protease (S2P), in ABA signaling during seed germination in Arabidopsis. Genetic analysis showed that loss-of-function of S2P conferred high ABA sensitivity during seed germination, and expression of the activated form of membrane-associated transcription factor bZIP17, in which the transmembrane domain and endoplasmic reticulum (ER) lumen-facing C-terminus were deleted, in the S2P mutant rescued its ABA-sensitive phenotype. MYC and green fluorescent protein (GFP)-tagged bZIP17 were processed and translocated from the ER to the nucleus in response to ABA treatment. Furthermore, genes encoding negative regulators of ABA signaling, such as the transcription factor ATHB7 and its target genes HAB1, HAB2, HAI1 and AHG3, were up-regulated in seeds of the wild-type upon ABA treatment; this up-regulation was impaired in seeds of S2P mutants. Our results suggest that S2P desensitizes ABA signaling during seed germination through regulating the activation of the membrane-associated transcription factor bZIP17 and therefore controlling the expression level of genes encoding negative regulators of ABA signaling. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  9. [Present situation and influencing factors on classroom mobile phone dependence syndrome in college students].

    Science.gov (United States)

    Hu, X B; Yang, Y N; Zhang, M Y; Miao, M; Bai, Y N; Zheng, S; Wang, M Z

    2017-10-10

    Objective: To explore the current situation and influencing factors on Classroom Mobile Phone Dependence Syndrome (CMPDS) among college students, and to provide scientific basis for guiding college students to use mobile phones reasonably and healthily. Methods: Stratified cluster sampling method was used. Students from different majors and different grades in Lanzhou University were included as the research objects. Classes were recognized as a unit in receiving basic field investigation in this questionnaire related study. Informed consent principles were followed and process of survey was anonymously carried out. Results: The overall rate of CMPDS in college students was 8.7 % , including 'mild rate' as 6.6 % and 'seriously mild rate' as 2.1 % . No significant differences were found on genders or grades. Factors as shopping in the classroom shopping ( OR =3.720), being bored on courses ( OR =1.740), WiFi coverage ( OR =1.787), time of practice in the classrooms ( OR =1.514), and the total time of daily mobile phone use ( OR =1.513) etc, appeared as risk factors related to CMPDS among the college students. However. shooting courseware ( OR =0.579) appeared as a protective factor. Conclusions: Rate of CMPDS was high in college students and we suggested to form a joint task force among the college authority, teachers and students to work on the related problems. Hopefully, the serious CMPDS condition will be minimized and both physical and mental health of the college students be improved.

  10. Cardiovascular risk factors in patients with rheumatoid arthritis in combination with hypertension depending on body weight

    Directory of Open Access Journals (Sweden)

    Sіrenko O.Yu.

    2014-11-01

    Full Text Available The objective was to evaluate the frequency of cardiovascular risk factors and hypertension in patients with rheumatoid arthritis depending on body weight. The study involved 100 patients with rheumatoid arthritis and stably selected therapy for more than 6 months at the age from 45 to 65 years (mean age 53,19 ± 5,40 years. Traditional cardiovascular risk was assessed, taking into account risk factors by SCORE scale and amended for patients with RA. The levels of total cholesterol, triglycerides, C-reactive protein, serum creatinine, body mass index, body area index were determined. Arterial hypertension was diagnosed in 41 (41% patients with rheuma¬toid arthritis and was associated with traditional risk factors (age, obesity, rheumatoid factor, hyperuricemia and the duration of glucocorticoid therapy. Obesity and excess body mass occurred in the majority of patients with rheumatoid arthritis, herewith the highest level of inflammation indicators and risk of cardiovascular events was in overweight patients. Obesity was associated with duration of rheumatoid arthritis, the activity of the inflammatory process, the duration of glucocorticoids taking. It is found that the traditional SCORE scale does not fully reflect the risk of cardiovascular events in rheumatoid arthritis. Identification of hypertension and obesity increases the information content of the risk assessment of cardiovascular events in rheumatoid arthritis.

  11. Secretory pathway-dependent localization of the Saccharomyces cerevisiae Rho GTPase-activating protein Rgd1p at growth sites.

    Science.gov (United States)

    Lefèbvre, Fabien; Prouzet-Mauléon, Valérie; Hugues, Michel; Crouzet, Marc; Vieillemard, Aurélie; McCusker, Derek; Thoraval, Didier; Doignon, François

    2012-05-01

    Establishment and maintenance of cell polarity in eukaryotes depends upon the regulation of Rho GTPases. In Saccharomyces cerevisiae, the Rho GTPase activating protein (RhoGAP) Rgd1p stimulates the GTPase activities of Rho3p and Rho4p, which are involved in bud growth and cytokinesis, respectively. Consistent with the distribution of Rho3p and Rho4p, Rgd1p is found mostly in areas of polarized growth during cell cycle progression. Rgd1p was mislocalized in mutants specifically altered for Golgi apparatus-based phosphatidylinositol 4-P [PtdIns(4)P] synthesis and for PtdIns(4,5)P(2) production at the plasma membrane. Analysis of Rgd1p distribution in different membrane-trafficking mutants suggested that Rgd1p was delivered to growth sites via the secretory pathway. Rgd1p may associate with post-Golgi vesicles by binding to PtdIns(4)P and then be transported by secretory vesicles to the plasma membrane. In agreement, we show that Rgd1p coimmunoprecipitated and localized with markers specific to secretory vesicles and cofractionated with a plasma membrane marker. Moreover, in vivo imaging revealed that Rgd1p was transported in an anterograde manner from the mother cell to the daughter cell in a vectoral manner. Our data indicate that secretory vesicles are involved in the delivery of RhoGAP Rgd1p to the bud tip and bud neck.

  12. Effects of hepatocyte growth factor on glutathione synthesis, growth, and apoptosis is cell density-dependent

    International Nuclear Information System (INIS)

    Yang Heping; Magilnick, Nathaniel; Xia Meng; Lu, Shelly C.

    2008-01-01

    Hepatocyte growth factor (HGF) is a potent hepatocyte mitogen that exerts opposing effects depending on cell density. Glutathione (GSH) is the main non-protein thiol in mammalian cells that modulates growth and apoptosis. We previously showed that GSH level is inversely related to cell density of hepatocytes and is positively related to growth. Our current work examined whether HGF can modulate GSH synthesis in a cell density-dependent manner and how GSH in turn influence HGF's effects. We found HGF treatment of H4IIE cells increased cell GSH levels only under subconfluent density. The increase in cell GSH under low density was due to increased transcription of GSH synthetic enzymes. This correlated with increased protein levels and nuclear binding activities of c-Jun, c-Fos, p65, p50, Nrf1 and Nrf2 to the promoter region of these genes. HGF acts as a mitogen in H4IIE cells under low cell density and protects against tumor necrosis factor α (TNFα)-induced apoptosis by limiting JNK activation. However, HGF is pro-apoptotic under high cell density and exacerbates TNFα-induced apoptosis by potentiating JNK activation. The increase in cell GSH under low cell density allows HGF to exert its full mitogenic effect but is not necessary for its anti-apoptotic effect

  13. p35 regulates the CRM1-dependent nucleocytoplasmic shuttling of nuclear hormone receptor coregulator-interacting factor 1 (NIF-1.

    Directory of Open Access Journals (Sweden)

    Xiao-Su Zhao

    Full Text Available Cyclin-dependent kinase 5 (Cdk5 is a proline-directed serine/threonine kinase, which plays critical roles in a wide spectrum of neuronal functions including neuronal survival, neurite outgrowth, and synapse development and plasticity. Cdk5 activity is controlled by its specific activators: p35 or p39. While knockout studies reveal that Cdk5/p35 is critical for neuronal migration during early brain development, functions of Cdk5/p35 have been unraveled through the identification of the interacting proteins of p35, most of which are Cdk5/p35 substrates. However, it remains unclear whether p35 can regulate neuronal functions independent of Cdk5 activity. Here, we report that a nuclear protein, nuclear hormone receptor coregulator (NRC-interacting factor 1 (NIF-1, is a new interacting partner of p35. Interestingly, p35 regulates the functions of NIF-1 independent of Cdk5 activity. NIF-1 was initially discovered as a transcriptional regulator that enhances the transcriptional activity of nuclear hormone receptors. Our results show that p35 interacts with NIF-1 and regulates its nucleocytoplasmic trafficking via the nuclear export pathway. Furthermore, we identified a nuclear export signal on p35; mutation of this site or blockade of the CRM1/exportin-dependent nuclear export pathway resulted in the nuclear accumulation of p35. Intriguingly, blocking the nuclear export of p35 attenuated the nuclear accumulation of NIF-1. These findings reveal a new p35-dependent mechanism in transcriptional regulation that involves the nucleocytoplasmic shuttling of transcription regulators.

  14. p35 regulates the CRM1-dependent nucleocytoplasmic shuttling of nuclear hormone receptor coregulator-interacting factor 1 (NIF-1).

    Science.gov (United States)

    Zhao, Xiao-Su; Fu, Wing-Yu; Chien, Winnie W Y; Li, Zhen; Fu, Amy K Y; Ip, Nancy Y

    2014-01-01

    Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase, which plays critical roles in a wide spectrum of neuronal functions including neuronal survival, neurite outgrowth, and synapse development and plasticity. Cdk5 activity is controlled by its specific activators: p35 or p39. While knockout studies reveal that Cdk5/p35 is critical for neuronal migration during early brain development, functions of Cdk5/p35 have been unraveled through the identification of the interacting proteins of p35, most of which are Cdk5/p35 substrates. However, it remains unclear whether p35 can regulate neuronal functions independent of Cdk5 activity. Here, we report that a nuclear protein, nuclear hormone receptor coregulator (NRC)-interacting factor 1 (NIF-1), is a new interacting partner of p35. Interestingly, p35 regulates the functions of NIF-1 independent of Cdk5 activity. NIF-1 was initially discovered as a transcriptional regulator that enhances the transcriptional activity of nuclear hormone receptors. Our results show that p35 interacts with NIF-1 and regulates its nucleocytoplasmic trafficking via the nuclear export pathway. Furthermore, we identified a nuclear export signal on p35; mutation of this site or blockade of the CRM1/exportin-dependent nuclear export pathway resulted in the nuclear accumulation of p35. Intriguingly, blocking the nuclear export of p35 attenuated the nuclear accumulation of NIF-1. These findings reveal a new p35-dependent mechanism in transcriptional regulation that involves the nucleocytoplasmic shuttling of transcription regulators.

  15. Risk Factors for Social Networking Site Scam Victimization Among Malaysian Students.

    Science.gov (United States)

    Kirwan, Gráinne H; Fullwood, Chris; Rooney, Brendan

    2018-02-01

    Social networking sites (SNSs) can provide cybercriminals with various opportunities, including gathering of user data and login credentials to enable fraud, and directing of users toward online locations that may install malware onto their devices. The techniques employed by such cybercriminals can include clickbait (text or video), advertisement of nonexistent but potentially desirable products, and hoax competitions/giveaways. This study aimed to identify risk factors associated with falling victim to these malicious techniques. An online survey was completed by 295 Malaysian undergraduate students, finding that more than one-third had fallen victim to SNS scams. Logistic regression analysis identified several victimization risk factors including having higher scores in impulsivity (specifically cognitive complexity), using fewer devices for SNSs, and having been on an SNS for a longer duration. No reliable model was found for vulnerability to hoax valuable gift giveaways and "friend view application" advertising specifically, but vulnerability to video clickbait was predicted by lower extraversion scores, higher levels of openness to experience, using fewer devices, and being on an SNS for a longer duration. Other personality traits were not associated with either overall victimization susceptibility or increased risk of falling victim to the specific techniques. However, age approached significance within both the video clickbait and overall victimization models. These findings suggest that routine activity theory may be particularly beneficial in understanding and preventing SNSs scam victimization.

  16. Harvest surgical site infection following coronary artery bypass grafting: risk factors, microbiology, and outcomes.

    Science.gov (United States)

    Sharma, Mamta; Fakih, Mohamad G; Berriel-Cass, Dorine; Meisner, Susan; Saravolatz, Louis; Khatib, Riad

    2009-10-01

    Our goals were to evaluate the risk factors predisposing to saphenous vein harvest surgical site infection (HSSI), the microbiology implicated, associated outcomes including 30-day mortality, and identify opportunities for prevention of infection. All patients undergoing coronary artery bypass grafting (CABG) procedures from January 2000 through September 2004 were included. Data were collected on preoperative, intraoperative, and postoperative factors, in addition to microbiology and outcomes. Eighty-six of 3578 (2.4%) patients developed HSSI; 28 (32.6%) of them were classified as deep. The median time to detection was 17 (range, 4-51) days. An organism was identified in 64 (74.4%) cases; of them, a single pathogen was implicated in 50 (78%) cases. Staphylococcus aureus was the most frequently isolated pathogen: 19 (38% [methicillin-susceptible S aureus (MSSA) = 12, methicillin-resistant S aureus (MRSA) = 7]). Gram-negative organisms were recovered in 50% of cases, with Pseudomonas aeruginosa predominating in 11 (22%) because of a single pathogen. Multiple pathogens were identified in 14 (22%) cases. The 30-day mortality was not significantly different in patients with or without HSSI. Multivariate analysis showed age, diabetes mellitus, obesity, congestive heart failure, renal insufficiency, and duration of surgery to be associated with increased risk. Diabetes mellitus, obesity, congestive heart failure, renal insufficiency, and duration of surgery were associated with increased risk for HSSI. S aureus was the most frequently isolated pathogen.

  17. IRF8 Transcription-Factor-Dependent Classical Dendritic Cells Are Essential for Intestinal T Cell Homeostasis.

    Science.gov (United States)

    Luda, Katarzyna M; Joeris, Thorsten; Persson, Emma K; Rivollier, Aymeric; Demiri, Mimoza; Sitnik, Katarzyna M; Pool, Lieneke; Holm, Jacob B; Melo-Gonzalez, Felipe; Richter, Lisa; Lambrecht, Bart N; Kristiansen, Karsten; Travis, Mark A; Svensson-Frej, Marcus; Kotarsky, Knut; Agace, William W

    2016-04-19

    The role of dendritic cells (DCs) in intestinal immune homeostasis remains incompletely defined. Here we show that mice lacking IRF8 transcription-factor-dependent DCs had reduced numbers of T cells in the small intestine (SI), but not large intestine (LI), including an almost complete absence of SI CD8αβ(+) and CD4(+)CD8αα(+) T cells; the latter requiring β8 integrin expression by migratory IRF8 dependent CD103(+)CD11b(-) DCs. SI homing receptor induction was impaired during T cell priming in mesenteric lymph nodes (MLN), which correlated with a reduction in aldehyde dehydrogenase activity by SI-derived MLN DCs, and inefficient T cell localization to the SI. These mice also lacked intestinal T helper 1 (Th1) cells, and failed to support Th1 cell differentiation in MLN and mount Th1 cell responses to Trichuris muris infection. Collectively these results highlight multiple non-redundant roles for IRF8 dependent DCs in the maintenance of intestinal T cell homeostasis. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Endocrine disrupting chemicals as potential risk factor for estrogen-dependent cancers.

    Science.gov (United States)

    Rutkowska, Aleksandra Z; Szybiak, Aleksandra; Serkies, Krystyna; Rachoń, Dominik

    2016-08-09

    Civilization, industrialization, and urbanization create an environment where humans are continuously exposed to endocrine disrupting chemicals (EDCs). Some of breast cancers and endometrial cancer, which are the most common female malignant neoplasms, are estrogen-dependent tumors. Prolonged exposure to estrogens or substances with estrogenic properties may be a risk factor for their development. This paper aimed to discuss the potential adverse effect of EDCs on human health, including the role of EDCs in hormone-dependent carcinogenesis. A review of literature regarding the sources of environmental exposure to EDCs and molecular mechanisms of their action was performed. We analyzed the possible mechanisms of how these substances alter the function of the endocrine system, resulting in adverse health effects. Hundreds of substances with endocrine disrupting potential have been identified in our environment. There is accumulating evidence linking exposure to EDCs with the development of mammary and endometrial cancer. By interacting with steroid receptors, EDCs can impact the cellular processes potentially leading to carcinogenesis. There are also data showing the effect of EDCs on immune dysfunction. During lifespan, people are usually exposed to a mixture of various EDCs, which complicates the assessment of individual substances or compounds implicated in cancer development. As the prevalence of hormone-dependent tumors among women continues to increase, their successful prevention is of human benefit. Institutions representing medicine, science, industry, and governments should develop joint strategies to decrease exposure to EDC, and thus to reduce the risk of hormonedependent tumors in women.

  19. GATA Factor-Dependent Positive-Feedback Circuit in Acute Myeloid Leukemia Cells

    Directory of Open Access Journals (Sweden)

    Koichi R. Katsumura

    2016-08-01

    Full Text Available The master regulatory transcription factor GATA-2 triggers hematopoietic stem and progenitor cell generation. GATA2 haploinsufficiency is implicated in myelodysplastic syndrome (MDS and acute myeloid leukemia (AML, and GATA2 overexpression portends a poor prognosis for AML. However, the constituents of the GATA-2-dependent genetic network mediating pathogenesis are unknown. We described a p38-dependent mechanism that phosphorylates GATA-2 and increases GATA-2 target gene activation. We demonstrate that this mechanism establishes a growth-promoting chemokine/cytokine circuit in AML cells. p38/ERK-dependent GATA-2 phosphorylation facilitated positive autoregulation of GATA2 transcription and expression of target genes, including IL1B and CXCL2. IL-1β and CXCL2 enhanced GATA-2 phosphorylation, which increased GATA-2-mediated transcriptional activation. p38/ERK-GATA-2 stimulated AML cell proliferation via CXCL2 induction. As GATA2 mRNA correlated with IL1B and CXCL2 mRNAs in AML-M5 and high expression of these genes predicted poor prognosis of cytogenetically normal AML, we propose that the circuit is functionally important in specific AML contexts.

  20. On Strong Positive Frequency Dependencies of Quality Factors in Local-Earthquake Seismic Studies

    Science.gov (United States)

    Morozov, Igor B.; Jhajhria, Atul; Deng, Wubing

    2018-03-01

    Many observations of seismic waves from local earthquakes are interpreted in terms of the frequency-dependent quality factor Q( f ) = Q0 f^{η } , where η is often close to or exceeds one. However, such steep positive frequency dependencies of Q require careful analysis with regard to their physical consistency. In particular, the case of η = 1 corresponds to frequency-independent (elastic) amplitude decays with time and consequently requires no Q-type attenuation mechanisms. For η > 1, several problems with physical meanings of such Q-factors occur. First, contrary to the key premise of seismic attenuation, high-frequency parts of the wavefield are enhanced with increasing propagation times relative to the low-frequency ones. Second, such attenuation cannot be implemented by mechanical models of wave-propagating media. Third, with η > 1, the velocity dispersion associated with such Q(f) occurs over unrealistically short frequency range and has an unexpected oscillatory shape. Cases η = 1 and η > 1 are usually attributed to scattering; however, this scattering must exhibit fortuitous tuning into the observation frequency band, which appears unlikely. The reason for the above problems is that the inferred Q values are affected by the conventional single-station measurement procedure. Both parameters Q 0 and are apparent, i.e., dependent on the selected parameterization and inversion method, and they should not be directly attributed to the subsurface. For η ≈ 1, parameter Q 0 actually describes the frequency-independent amplitude decay in access of some assumed geometric spreading t -α , where α is usually taken equal one. The case η > 1 is not allowed physically and could serve as an indicator of problematic interpretations. Although the case 0 < η < 1 is possible, its parameters Q 0 and may also be biased by the measurement procedure. To avoid such difficulties of Q-based approaches, we recommend measuring and interpreting the amplitude-decay rates

  1. The risk and associated factors of methamphetamine psychosis in methamphetamine-dependent patients in Malaysia.

    Science.gov (United States)

    Sulaiman, Ahmad Hatim; Said, Mas Ayu; Habil, Mohd Hussain; Rashid, Rusdi; Siddiq, Amer; Guan, Ng Chong; Midin, Marhani; Nik Jaafar, Nik Ruzyanei; Sidi, Hatta; Das, Srijit

    2014-01-01

    The objective of this study was to determine the risk of lifetime and current methamphetamine-induced psychosis in patients with methamphetamine dependence. The association between psychiatric co-morbidity and methamphetamine-induced psychosis was also studied. This was a cross-sectional study conducted concurrently at a teaching hospital and a drug rehabilitation center in Malaysia. Patients with the diagnosis of methamphetamine based on DSM-IV were interviewed using the Mini International Neuropsychiatric Interview (M.I.N.I.) for methamphetamine-induced psychosis and other Axis I psychiatric disorders. The information on sociodemographic background and drug use history was obtained from interview or medical records. Of 292 subjects, 47.9% of the subjects had a past history of psychotic symptoms and 13.0% of the patients were having current psychotic symptoms. Co-morbid major depressive disorder (OR=7.18, 95 CI=2.612-19.708), bipolar disorder (OR=13.807, 95 CI=5.194-36.706), antisocial personality disorder (OR=12.619, 95 CI=6.702-23.759) and heavy methamphetamine uses were significantly associated with lifetime methamphetamine-induced psychosis after adjusted for other factors. Major depressive disorder (OR=2.870, CI=1.154-7.142) and antisocial personality disorder (OR=3.299, 95 CI=1.375-7.914) were the only factors associated with current psychosis. There was a high risk of psychosis in patients with methamphetamine dependence. It was associated with co-morbid affective disorder, antisocial personality, and heavy methamphetamine use. It is recommended that all cases of methamphetamine dependence should be screened for psychotic symptoms. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Four-year long-path monitoring of ambient aerosol extinction at a central European urban site: dependence on relative humidity

    Directory of Open Access Journals (Sweden)

    A. Skupin

    2016-02-01

    Full Text Available The ambient aerosol particle extinction coefficient is measured with the Spectral Aerosol Extinction Monitoring System (SÆMS along a 2.84 km horizontal path at 30–50 m height above ground in the urban environment of Leipzig (51.3° N, 12.4° E, Germany, since 2009. The dependence of the particle extinction coefficient (wavelength range from 300 to 1000 nm on relative humidity up to almost 100 % was investigated. The main results are presented. For the wavelength of 550 nm, the mean extinction enhancement factor was found to be 1.75 ± 0.4 for an increase of relative humidity from 40 to 80 %. The respective 4-year mean extinction enhancement factor is 2.8 ± 0.6 for a relative-humidity increase from 40 to 95 %. A parameterization of the dependency of the urban particle extinction coefficient on relative humidity is presented. A mean hygroscopic exponent of 0.46 for the 2009–2012 period was determined. Based on a backward trajectory cluster analysis, the dependence of several aerosol optical properties for eight air flow regimes was investigated. Large differences were not found, indicating that local pollution sources widely control the aerosol conditions over the urban site. The comparison of the SÆMS extinction coefficient statistics with respective statistics from ambient AERONET sun photometer observations yields good agreement. Also, time series of the particle extinction coefficient computed from in situ-measured dry particle size distributions and humidity-corrected SÆMS extinction values (for 40 % relative humidity were found in good overall consistency, which verifies the applicability of the developed humidity parameterization scheme. The analysis of the spectral dependence of particle extinction (Ångström exponent revealed an increase of the 390–881 nm Ångström exponent from, on average, 0.3 (at 30 % relative humidity to 1.3 (at 95 % relative humidity for the 4-year period.

  3. Characterization of a highly conserved binding site of Mlh1 required for exonuclease I-dependent mismatch repair

    DEFF Research Database (Denmark)

    Dherin, Claudine; Gueneau, Emeric; Francin, Mathilde

    2009-01-01

    , and Sgs1 proteins, designated as site S2 by reference to the Mlh1/Pms1 heterodimerization site S1. We show that site S2 is also involved in the interaction between human MLH1 and EXO1 or BLM. Binding at this site involves a common motif on Mlh1 partners that we called the MIP-box for the Mlh1 interacting...

  4. Surgical site infection after liver transplantation: risk factors and association with graft loss or death.

    Science.gov (United States)

    Hellinger, Walter C; Crook, Julia E; Heckman, Michael G; Diehl, Nancy N; Shalev, Jefree A; Zubair, Abba C; Willingham, Darrin L; Hewitt, Winston R; Grewal, Hani P; Nguyen, Justin H; Hughes, Christopher B

    2009-05-15

    Risk factors for surgical site infection (SSI) after liver transplantation and outcomes associated with these infections have not been assessed using consensus surveillance and optimal analytic methods. A cohort study was performed of patients undergoing first liver transplantation at Mayo Clinic, Jacksonville, Florida, in 2003 and 2004. SSIs were identified by definitions and methods of the National Nosocomial Infections Surveillance System. Measures of known or suspected risk factors for SSI, graft loss, or death were collected on all patients. Associations of SSI with these factors and also with the primary composite endpoint of graft loss or death within 1 year of liver transplantation were examined using Cox proportional hazards models; relative risks (RRs) were estimated along with 95% confidence intervals (CIs). Of 370 patients, 66 (18%) had SSI and 57 (15%) died or sustained graft loss within 1 year after liver transplantation. Donor liver mass-to-recipient body mass ratio of less than 0.01 (RR 2.56; 95% CI 1.17-5.62; P=0.019) and increased operative time (RR 1.19 [1-hr increase]; 95% CI 1.03-1.37; P=0.018) were associated with increased SSI risk. SSI was associated with increased risk of death or graft loss within the first year after liver transplantation (RR 3.06; 95% CI 1.66-5.64; P<0.001). SSI is associated with increased risk of death or graft loss during the first year after liver transplantation. Increased operative time and decreased donor liver-to-recipient body mass ratio showed evidence of association with SSI.

  5. Surgical site infection rates and risk factors in orthopedic pediatric patients in Madrid, Spain.

    Science.gov (United States)

    Viqueira, Almudena Quintás; Caravaca, Gil Rodríguez; Quesada Rubio, José Antonio; Francés, Victoria Soler

    2014-07-01

    The objective of the study is to study surgical site infection (SSI) rates and risk factors in a pediatric population. We conducted a prospective cohort study to estimate the SSI rate at a national pediatric referral center, covering all patients managed at the Orthopedic Surgery Department of the Niño Jesús Children's University Teaching Hospital from January 2010 through December 2012. Risk factors and antibiotic prophylaxis were monitored. A comparison between Spanish and US data was performed, with a breakdown by National Nosocomial Infection Surveillance risk indices. We also conducted a comparative study of SSI rates from 2010 to 2012 to assess the impact of the epidemiologic surveillance system. The study population of 1079 patients had a SSI rate of 2.8%. SSI rates were calculated for spinal fusion and other musculoskeletal procedures according to the National Nosocomial Infection Surveillance risk index. In the case of other musculoskeletal procedures, our SSI rates were 0.8 times lower than the overall Spanish rate, but higher than US rates for all risk categories. For spinal fusion procedures, our SSI rates were 1.2 times higher than the Spanish rates and 3.5 times higher than National Nosocomial Infection Surveillance rates. This latter finding should be interpreted with caution because it was based on a small sample. The multivariate analysis indicated that the only predictive factors of SSI were American Society of Anesthesiologists score and age. The surveillance program showed that for clean procedures, SSI incidence decreased from 4% in 2010 to 3.2% in 2011 and to 2.4% in 2012.

  6. Temperature Dependency of the Correlation between Secondary Organic Aerosol and Monoterpenes Concentrations at a Boreal Forest Site in Finland

    Science.gov (United States)

    Zhou, Y.; Zhang, W.; Rinne, J.

    2016-12-01

    Climate feedbacks represent the large uncertainty in the climate projection partly due to the difficulties to quantify the feedback mechanisms in the biosphere-atmosphere interaction. Recently, a negative climate feedback mechanism whereby higher temperatures and CO2-levels boost continental biomass production, leading to increased biogenic secondary organic aerosol (SOA) and cloud condensation nuclei concentrations, tending to cause cooling, has been attached much attention. To quantify the relationship between biogenic organic compounds (BVOCs) and SOA, a five-year data set (2008, 2010-2011,2013-2014) for SOA and monoterpenes concentrations (the dominant fraction of BVOCs) measured at the SMEAR II station in Hyytiälä, Finland, is analyzed. Our results show that there is a moderate linear correlation between SOA and monoterpenes concentration with the correlation coefficient (R) as 0.66. To rule out the influence of anthropogenic aerosols, the dataset is further filtered by selecting the data at the wind direction of cleaner air mass, leading to an improved R as 0.68. As temperature is a critical factor for vegetation growth, BVOC emissions, and condensation rate, the correlation between SOA and monoterpenes concentration at different temperature windows are studied. The result shows a higher R and slope of linear regression as temperature increases. To identify the dominant oxidant responsible for the BVOC-SOA conversion, the correlations between SOA concentration and the monoterpenes oxidation rates by O3 and OH are compared, suggesting more SOA is contributed by O3 oxidation process. Finally, the possible processes and factors such as the atmospheric boundary layer depth, limiting factor in the monoterpenes oxidation process, as well as temperature sensitivity in the condensation process contributing to the temperature dependence of correlation between BVOA and SOA are investigated.

  7. Survival and medical utilization of children and adolescents with prolonged ventilator-dependent and associated factors.

    Directory of Open Access Journals (Sweden)

    Szu-Chi Pai

    Full Text Available Over the course of a year, more than 20,000 patients in Taiwan require prolonged mechanical ventilation (PMV. Data from the National Health Insurance Research Database for patients between 2005 and 2011 were used to conduct a retrospective analysis on ventilator dependence. The study subjects were PMV patients aged <17 years in Taiwan. A multiple regression model employing general estimating equations was applied to investigate the factors affecting the use of medical resources by children and adolescent PMV patients. A Cox proportional hazard model was incorporated to explore the factors affecting the survival of these patients. Data were collected for a total of 1,019 children and adolescent PMV patients in Taiwan. The results revealed that the average number of outpatient visits per subject was 32.1 times per year, whereas emergency treatments averaged 1.56 times per year per subject and hospitalizations averaged 160.8 days per year per subject. Regarding average annual medical costs, hospitalizations accounted for the largest portion at NT$821,703 per year per subject, followed by outpatient care at NT$123,136 per year per subject and emergency care at NT$3,806 per year per subject. The demographic results indicated that the patients were predominately male (61.24%, with those under 1 year of age accounting for the highest percentage (36.38%. According to the Kaplan-Meier curve, the 1-year and 5-year mortality rates of the patients were approximately 32% and 47%, respectively. The following factors affecting the survival rate were considered: age, the Charlson Comorbidity Index (CCI, diagnosis type necessitating ventilator use, and whether an invasive ventilator was used. This study investigated the use of medical resources and the survival rates of children and adolescent PMV patients. The findings of this study can serve as a reference for the National Health Insurance Administration in promoting its future integrated pilot projects on

  8. Surgical site infection after total en bloc spondylectomy: risk factors and the preventive new technology.

    Science.gov (United States)

    Hayashi, Hiroyuki; Murakami, Hideki; Demura, Satoru; Kato, Satoshi; Yoshioka, Katsuhito; Shinmura, Kazuya; Yokogawa, Noriaki; Ishii, Takayoshi; Fang, Xiang; Shirai, Toshiharu; Tsuchiya, Hiroyuki

    2015-01-01

    Surgical site infection (SSI) associated with instruments remains a serious and common complication in patients who undergo total en bloc spondylectomy (TES). It is very important that the risk factors for SSI are known to prevent it. The purpose of the study was to identify independent risk factors for SSI after TES and evaluate the positive effect of iodine-supported spinal instruments in the prevention of SSI after TES. This is a retrospective clinical study. One hundred twenty-five patients who underwent TES for vertebral tumor were evaluated. Incidence rate of SSI, risk factors for SSI after TES, and safety of iodine-supported spinal instruments were the outcome measures. Risk factors for SSI were analyzed using logistic regression. In recent 69 patients with iodine-supported spinal instruments, the thyroid hormone levels in the blood were examined to confirm if iodine from the implant influenced thyroid function. Postoperative radiological evaluations were performed regularly. The rate of SSI was 6.4% (8/125 patients). By multivariate logistic regression, combined anterior and posterior approach and nonuse of iodine-supported spinal instruments were associated with an increased risk of SSI. The rate of SSI without iodine-supported spinal instruments was 12.5%, whereas the rate with iodine-supported spinal instruments was 1.4%. This difference was statistically significant. There were no detected abnormalities of thyroid gland function with the use of iodine-supported instruments. Among the 69 patients with iodine-supported spinal instruments, 2 patients required additional surgery because of instrument failure. However, there were no obvious involvements with the use of iodine-supported spinal instruments. This study identified combined anterior and posterior approach and nonuse of iodine-supported spinal instruments to be independent risk factors for SSI after TES. Iodine-supported spinal instrument was extremely effective for prevention of SSI in patients

  9. Risk factors for surgical site infection after low transverse cesarean section.

    Science.gov (United States)

    Olsen, Margaret A; Butler, Anne M; Willers, Denise M; Devkota, Preetishma; Gross, Gilad A; Fraser, Victoria J

    2008-06-01

    Independent risk factors for surgical site infection (SSI) after cesarean section have not been well documented, despite the large number of cesarean sections performed and the relatively common occurrence of SSI. To determine independent risk factors for SSI after low transverse cesarean section. Retrospective case-control study. Barnes-Jewish Hospital, a 1,250-bed tertiary care hospital. A total of 1,605 women who underwent low transverse cesarean section during the period from July 1999 to June 2001. Using the International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes for SSI or wound complication and/or data on antibiotic use during the surgical hospitalization or at readmission to the hospital or emergency department, we identified potential cases of SSI in a cohort of patients who underwent a low transverse cesarean section. Cases of SSI were verified by chart review using the definitions from the Centers for Disease Control and Prevention's National Nosocomial Infections Surveillance System. Control patients without SSI or endomyometritis were randomly selected from the population of patients who underwent cesarean section. Independent risk factors for SSI were determined by logistic regression. SSIs were identified in 81 (5.0%) of 1,605 women who underwent low transverse cesarean section. Independent risk factors for SSI included development of subcutaneous hematoma after the procedure (adjusted odds ratio [aOR], 11.6 [95% confidence interval [CI], 4.1-33.2]), operation performed by the university teaching service (aOR, 2.7 [95% CI, 1.4-5.2]), and a higher body mass index at admission (aOR, 1.1 [95% CI, 1.0-1.1]). Cephalosporin therapy before or after the operation was associated with a significantly lower risk of SSI (aOR, 0.2 [95% CI, 0.1-0.5]). Use of staples for skin closure was associated with a marginally increased risk of SSI. These independent risk factors should be incorporated into approaches for the prevention

  10. Copper-dependent and -independent hypoxia-inducible factor-1 regulation of gene expression.

    Science.gov (United States)

    Zhang, Zhen; Qiu, Liying; Lin, Chen; Yang, Hong; Fu, Haiying; Li, Rui; Kang, Y James

    2014-10-01

    Hypoxia-inducible factor-1 (HIF-1) regulates the expression of the vascular endothelial growth factor (VEGF), a process requiring copper (Cu) participation. HIF-1 is also involved in the expression of more than a hundred of genes, but it is unknown how HIF-1 differentially controls the expression of these genes timely and spatially. The present study was undertaken to test the hypothesis that Cu is not required for the expression of all HIF-1-regulated genes, thus exploring mechanistic insights into the differential control of multiple gene expression by one transcription factor. Human umbilical vein endothelial cells (HUVECs) were treated with siRNA targeting HIF-1α to define the essential role of HIF-1 in the regulation of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3) and insulin-like growth factor 2 (IGF-2) expression. A Cu chelator, tetraethylenepentamine (TEPA), was used to reduce intracellular availability of Cu. In comparison, a zinc chelator, N,N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN), was used to reduce intracellular zinc concentration. The expression of both BNIP3 and IGF-2 was completely suppressed in the HIF-1α deficient cells. The removal of Cu suppressed the expression of BNIP3, but did not affect that of IGF-2. The reduction of intracellular zinc did not cause the same effect. Further screening identified a group of genes whose expression required Cu and the others did not need Cu. The present study thus demonstrates Cu-dependent and -independent HIF-1 regulation of gene expression, indicating a mechanism for differential control of multiple gene expression by one transcription factor.

  11. Factors contributing to intervention fidelity in a multi-site chronic disease self-management program

    Directory of Open Access Journals (Sweden)

    Pitt Seraphine

    2006-10-01

    Full Text Available Abstract Background and objectives Disease self-management programs have been a popular approach to reducing morbidity and mortality from chronic disease. Replicating an evidence-based disease management program successfully requires practitioners to ensure fidelity to the original program design. Methods The Florida Health Literacy Study (FHLS was conducted to investigate the implementation impact of the Pfizer, Inc. Diabetes Mellitus and Hypertension Disease Self-Management Program based on health literacy principles in 14 community health centers in Florida. The intervention components discussed include health educator recruitment and training, patient recruitment, class sessions, utilization of program materials, translation of program manuals, patient retention and follow-up, and technical assistance. Results This report describes challenges associated with achieving a balance between adaptation for cultural relevance and fidelity when implementing the health education program across clinic sites. This balance was necessary to achieve effectiveness of the disease self-management program. The FHLS program was implemented with a high degree of fidelity to the original design and used original program materials. Adaptations identified as advantageous to program participation are discussed, such as implementing alternate methods for recruiting patients and developing staff incentives for participation. Conclusion Effective program implementation depends on the talent, skill and willing participation of clinic staff. Program adaptations that conserve staff time and resources and recognize their contribution can increase program effectiveness without jeopardizing its fidelity.

  12. Interaction of hookworm 14-3-3 with the forkhead transcription factor DAF-16 requires intact Akt phosphorylation sites

    Directory of Open Access Journals (Sweden)

    Hawdon John M

    2009-04-01

    Full Text Available Abstract Background Third-stage infective larvae (L3 of hookworms are in an obligatory state of developmental arrest that ends upon entering the definitive host, where they receive a signal that re-activates development. Recovery from the developmentally arrested dauer stage of Caenorhabditis elegans is analogous to the resumption of development during hookworm infection. Insulin-like signaling (ILS mediates recovery from arrest in C. elegans and activation of hookworm dauer L3. In C. elegans, phosphorylation of the forkhead transcription factor DAF-16 in response to ILS creates binding cites for the 14-3-3 protein Ce-FTT-2, which translocates DAF-16 out of the nucleus, resulting in resumption of reproductive development. Results To determine if hookworm 14-3-3 proteins play a similar role in L3 activation, hookworm FTT-2 was identified and tested for its ability to interact with A. caninum DAF-16 in vitro. The Ac-FTT-2 amino acid sequence was 91% identical to the Ce-FTT-2, and was most closely related to FTT-2 from other nematodes. Ac-FTT-2 was expressed in HEK 293T cells, and was recognized by an antibody against human 14-3-3β isoform. Reciprocal co-immunoprecipitations using anti-epitope tag antibodies indicated that Ac-FTT-2 interacts with Ac-DAF-16 when co-expressed in serum-stimulated HEK 293T cells. This interaction requires intact Akt consensus phosphorylation sites at serine107 and threonine312, but not serine381. Ac-FTT-2 was undetectable by Western blot in excretory/secretory products from serum-stimulated (activated L3 or adult A. caninum. Conclusion The results indicate that Ac-FTT-2 interacts with DAF-16 in a phosphorylation-site dependent manner, and suggests that Ac-FTT-2 mediates activation of L3 by binding Ac-DAF-16 during hookworm infection.

  13. Identifying functional transcription factor binding sites in yeast by considering their positional preference in the promoters.

    Directory of Open Access Journals (Sweden)

    Fu-Jou Lai

    Full Text Available Transcription factor binding site (TFBS identification plays an important role in deciphering gene regulatory codes. With comprehensive knowledge of TFBSs, one can understand molecular mechanisms of gene regulation. In the recent decades, various computational approaches have been proposed to predict TFBSs in the genome. The TFBS dataset of a TF generated by each algorithm is a ranked list of predicted TFBSs of that TF, where top ranked TFBSs are statistically significant ones. However, whether these statistically significant TFBSs are functional (i.e. biologically relevant is still unknown. Here we develop a post-processor, called the functional propensity calculator (FPC, to assign a functional propensity to each TFBS in the existing computationally predicted TFBS datasets. It is known that functional TFBSs reveal strong positional preference towards the transcriptional start site (TSS. This motivates us to take TFBS position relative to the TSS as the key idea in building our FPC. Based on our calculated functional propensities, the TFBSs of a TF in the original TFBS dataset could be reordered, where top ranked TFBSs are now the ones with high functional propensities. To validate the biological significance of our results, we perform three published statistical tests to assess the enrichment of Gene Ontology (GO terms, the enrichment of physical protein-protein interactions, and the tendency of being co-expressed. The top ranked TFBSs in our reordered TFBS dataset outperform the top ranked TFBSs in the original TFBS dataset, justifying the effectiveness of our post-processor in extracting functional TFBSs from the original TFBS dataset. More importantly, assigning functional propensities to putative TFBSs enables biologists to easily identify which TFBSs in the promoter of interest are likely to be biologically relevant and are good candidates to do further detailed experimental investigation. The FPC is implemented as a web tool at http://santiago.ee.ncku.edu.tw/FPC/.

  14. Interesting pressure dependence of power factor in BiTeI

    International Nuclear Information System (INIS)

    Guo, San-Dong; Wang, Jian-Li

    2016-01-01

    We investigate pressure dependence of electronic structures and thermoelectric properties in BiTeI by using a modified Becke and Johnson exchange potential. Spin–orbit coupling (SOC) effects are also included due to giant Rashba splitting. Thermoelectric properties are illuminated through solving Boltzmann transport equations within the constant scattering time approximation. The calculated energy band gap of 0.36 eV agrees well with the experimental value of 0.38 eV. As the pressure increases, the energy band gap first decreases, and then increases. The Rashba energy has the opposite trend with the energy band gap. SOC has obvious detrimental influence on the power factor in both n-type and p-type doping. For low doping concentration, the power factor has the same trend with the energy band gap with increasing pressure, but shows a monotonic changing trend in high doping. It is found that the pressure can induce a significantly enhanced power factor in high n-type doping, which can be understood as pressure leading to two-dimensional-like density of states in the conduction bands. These results suggest that BiTeI may be a potential candidate for efficient thermoelectricity in n-type doping by pressure, turning an ordinary insulator into a topological insulator. (paper)

  15. Age-dependent risk factors for malnutrition in traumatology and orthopedic patients.

    Science.gov (United States)

    Lambert, Christine; Nüssler, Andreas; Biesalski, Hans Konrad; Freude, Thomas; Bahrs, Christian; Ochs, Gunnar; Flesch, Ingo; Stöckle, Ulrich; Ihle, Christoph

    2017-05-01

    The aim of this study was to investigate the prevalence of risk of malnutrition (RoM) in an orthopedic and traumatology patient cohort with a broad range of ages. In addition to the classical indicators for risk assessment (low body mass index, weight loss, and comorbidity), this study aimed to analyze the effects of lifestyle factors (eating pattern, smoking, physical activity) on RoM. The prospective cohort study included 1053 patients in a level 1 trauma center in Germany. RoM was assessed by Nutritional Risk Screening (NRS) 2002 and for the elderly additionally by Mini Nutritional Assessment (MNA). Age-dependent risk factors identified in univariate statistical analysis were used for multivariate logistic regression models. The prevalence of patients at RoM (NRS ≥3) was 22%. In the three age categories (Malnutrition in trauma and orthopedic patients is not only a problem related to age. Lifestyle-related factors also contribute significantly to malnutrition in geriatric patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Molecular imaging of nuclear factor-Y transcriptional activity maps proliferation sites in live animals.

    Science.gov (United States)

    Goeman, Frauke; Manni, Isabella; Artuso, Simona; Ramachandran, Balaji; Toietta, Gabriele; Bossi, Gianluca; Rando, Gianpaolo; Cencioni, Chiara; Germoni, Sabrina; Straino, Stefania; Capogrossi, Maurizio C; Bacchetti, Silvia; Maggi, Adriana; Sacchi, Ada; Ciana, Paolo; Piaggio, Giulia

    2012-04-01

    In vivo imaging involving the use of genetically engineered animals is an innovative powerful tool for the noninvasive assessment of the molecular and cellular events that are often targets of therapy. On the basis of the knowledge that the activity of the nuclear factor-Y (NF-Y) transcription factor is restricted in vitro to proliferating cells, we have generated a transgenic reporter mouse, called MITO-Luc (for mitosis-luciferase), in which an NF-Y-dependent promoter controls luciferase expression. In these mice, bioluminescence imaging of NF-Y activity visualizes areas of physiological cell proliferation and regeneration during response to injury. Using this tool, we highlight for the first time a role of NF-Y activity on hepatocyte proliferation during liver regeneration. MITO-Luc reporter mice should facilitate investigations into the involvement of genes in cell proliferation and provide a useful model for studying aberrant proliferation in disease pathogenesis. They should be also useful in the development of new anti/proproliferative drugs and assessment of their efficacy and side effects on nontarget tissues.

  17. Spatially dependent biotic and abiotic factors drive survivorship and physical structure of green roof vegetation.

    Science.gov (United States)

    Aloisio, Jason M; Palmer, Matthew I; Giampieri, Mario A; Tuininga, Amy R; Lewis, James D

    2017-01-01

    Plant survivorship depends on biotic and abiotic factors that vary at local and regional scales. This survivorship, in turn, has cascading effects on community composition and the physical structure of vegetation. Survivorship of native plant species is variable among populations planted in environmentally stressful habitats like urban roofs, but the degree to which factors at different spatial scales affect survivorship in urban systems is not well understood. We evaluated the effects of biotic and abiotic factors on survivorship, composition, and physical structure of two native perennial species assemblages, one characterized by a mixture of C 4 grasses and forbs (Hempstead Plains, HP) and one characterized by a mixture of C 3 grasses and forbs (Rocky Summit, RS), that were initially sown at equal ratios of growth forms (5:1:4; grass, N-fixing forb and non-N-fixing forb) in replicate 2-m 2 plots planted on 10 roofs in New York City (New York, USA). Of 24 000 installed plants, 40% survived 23 months after planting. Within-roof factors explained 71% of variation in survivorship, with biotic (species identity and assemblage) factors accounting for 54% of the overall variation, and abiotic (growing medium depth and plot location) factors explaining 17% of the variation. Among-roof factors explained 29% of variation in survivorship and increased solar radiation correlated with decreased survivorship. While growing medium properties (pH, nutrients, metals) differed among roofs there was no correlation with survivorship. Percent cover and sward height increased with increasing survivorship. At low survivorship, cover of the HP assemblage was greater compared to the RS assemblage. Sward height of the HP assemblage was about two times greater compared to the RS assemblage. These results highlight the effects of local biotic and regional abiotic drivers on community composition and physical structure of green roof vegetation. As a result, initial green roof plant

  18. Abdominal surgical site infections: incidence and risk factors at an Iranian teaching hospital

    Directory of Open Access Journals (Sweden)

    Sabouri Kashani Ahmad

    2005-02-01

    Full Text Available Abstract Background Abdominal surgical site infections are among the most common complications of inpatient admissions and have serious consequences for outcomes and costs. Different risk factors may be involved, including age, sex, nutrition and immunity, prophylactic antibiotics, operation type and duration, type of shaving, and secondary infections. This study aimed to determine the risk factors affecting abdominal surgical site infections and their incidence at Imam Khomeini, a major referral teaching hospital in Iran. Methods Patients (n = 802 who had undergone abdominal surgery were studied and the relationships among variables were analyzed by Student's t and Chi-square tests. The subjects were followed for 30 days and by a 20-item questionnaire. Data were collected through pre- and post-operative examinations and telephone follow-ups. Results Of the 802 patients, 139 suffered from SSI (17.4%. In 40.8% of the cases, the wound was dirty infected. The average age for the patients was 46.7 years. The operations were elective in 75.7% of the cases and 24.7% were urgent. The average duration of the operation was 2.24 hours, the average duration of pre-operative hospital stay 4.31 days and the average length of (pre- and post-operation hospital stay 11.2 days. Three quarters of the cases were shaved 12 hours before the operation. The increased operation time, increased bed stay, electivity of the operation, septicity of the wound, type of incision, the administration of prophylactic antibiotic, type of operation, background disease, and the increased time lapse between shaving and operation all significantly associated with SSI with a p-value less than 0.001. Conclusion In view of the high rate of SSI reported here (17.4% compared with the 14% quoted in literature, this study suggests that by reducing the average operation time to less than 2 hours, the average preoperative stay to 4 days and the overall stay to less than 11 days, and

  19. Axl Can Serve as Entry Factor for Lassa Virus Depending on the Functional Glycosylation of Dystroglycan.

    Science.gov (United States)

    Fedeli, Chiara; Torriani, Giulia; Galan-Navarro, Clara; Moraz, Marie-Laurence; Moreno, Hector; Gerold, Gisa; Kunz, Stefan

    2018-03-01

    Fatal infection with the highly pathogenic Lassa virus (LASV) is characterized by extensive viral dissemination, indicating broad tissue tropism. The major cellular receptor for LASV is the highly conserved extracellular matrix receptor dystroglycan (DG). Binding of LASV depends on DG's tissue-specific posttranslational modification with the unusual O-linked polysaccharide matriglycan. Interestingly, functional glycosylation of DG does not always correlate with viral tropism observed in vivo The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3 were recently identified as alternative LASV receptor candidates. However, their role in LASV entry is not entirely understood. Here, we examine LASV receptor candidates in primary human cells and found coexpression of Axl with differentially glycosylated DG. To study LASV receptor use in the context of productive arenavirus infection, we employed recombinant lymphocytic choriomeningitis virus expressing LASV glycoprotein (rLCMV-LASV GP) as a validated biosafety level 2 (BSL2) model. We confirm and extend previous work showing that Axl can contribute to LASV entry in the absence of functional DG using "apoptotic mimicry" in a way similar to that of other enveloped viruses. We further show that Axl-dependent LASV entry requires receptor activation and involves a pathway resembling macropinocytosis. Axl-mediated LASV entry is facilitated by heparan sulfate and critically depends on the late endosomal protein LAMP-1 as an intracellular entry factor. In endothelial cells expressing low levels of functional DG, both receptors are engaged by the virus and can contribute to productive entry. In sum, we characterize the role of Axl in LASV entry and provide a rationale for targeting Axl in antiviral therapy. IMPORTANCE The highly pathogenic arenavirus Lassa virus (LASV) represents a serious public health problem in Africa. Although the principal LASV receptor, dystroglycan (DG), is ubiquitously expressed, virus

  20. Factors affecting the occurrence of symptomatic intracerebral haemorrhage after intravenous thrombolysis depending on the haemorrhage definition.

    Science.gov (United States)

    Sledzińska-Dźwigał, M; Sobolewski, Piotr; Szczuchniak, W

    2013-01-01

    Symptomatic intracerebral haemorrhage (sICH) remains the most feared complication of systemic thrombolysis in patients with ischaemic stroke. The aim of the study was to analyze the impact of different factors on the occurrence of sICH, depending on definition used. We retrospectively evaluated the influence of several factors on the occurrence of sICH (according to definitions used in ECASS2, SITS-MOST and NINDS studies) in 200 patients treated with systemic thrombolysis from 2006 to 2011. Multivariate analysis of impact of individual variables on the occurrence of haemorrhagic transformation (HT) and parenchymal haemorrhage type 2 (PH2) were performed. Haemorrhagic transformation occurred in 35 cases (17.5%). SICH was found in 10 cases according to ECASS2, in 7 cases according to SITS and in 13 cases according to NINDS. Older age was related to higher risk of sICH, regardless which definition was used (ECASS2: p = 0.014, SITS-MOST: p = 0.048, NINDS: p = 0.008), and female sex was related to higher risk of sICH according to NINDS and ECASS2 definition (p = 0.002 and p = 0.04, respectively). Blood glucose level and high NIHSS score (> 14 pts) were found as risk factor of sICH in ECASS2 definition (p = 0.044 and p = 0.03, respectively). In multivariate logistic regression higher NIHSS scores were associated with HT independent of age, gender and glucose level (p = 0.012). Multivariate analysis showed no impact of age, gender, severity of stroke and glucose level on presence of PH2. Definition of sICH can determine variables that are related to a high risk of this complication. In our study most factors correlated with sICH using the ECASS2 definition.

  1. Twisting dependent properties of twisted carbon nanotube fibers: microstructure and strain transfer factors

    International Nuclear Information System (INIS)

    Zhou, Jinyuan; Xie, Erqing; Sun, Gengzhi; Zhan, Zhaoyao; Zheng, Lianxi

    2014-01-01

    The dependences of twisting parameters on the electric and mechanical properties of twisted CNT fibers were systematically studied. Results from electric and mechanical measurements showed that twisting intensity is very effective to improve the electric and mechanical properties of CNT fibers. Further calculations combined with Raman results indicate that the twisting treatments, to a certain extent, can greatly enhance the strain transfer factors of the samples, which dominates the mechanical properties of CNT fibers. In addition, studies on the effect of twisting speeds suggested that lower twisting speed can lead to higher uniformity but lower performances in the electric and mechanical properties, higher twisting speed to higher Young’s modulus and higher conductance but lower uniformities. Ultra-strong uniform CNT fibers need to be prepared with a suitable twisting speed. (paper)

  2. Epigenetic control of viral life-cycle by a DNA-methylation dependent transcription factor.

    Directory of Open Access Journals (Sweden)

    Kirsty Flower

    Full Text Available Epstein-Barr virus (EBV encoded transcription factor Zta (BZLF1, ZEBRA, EB1 is the prototype of a class of transcription factor (including C/EBPalpha that interact with CpG-containing DNA response elements in a methylation-dependent manner. The EBV genome undergoes a biphasic methylation cycle; it is extensively methylated during viral latency but is reset to an unmethylated state following viral lytic replication. Zta is expressed transiently following infection and again during the switch between latency and lytic replication. The requirement for CpG-methylation at critical Zta response elements (ZREs has been proposed to regulate EBV replication, specifically it could aid the activation of viral lytic gene expression from silenced promoters on the methylated genome during latency in addition to preventing full lytic reactivation from the non-methylated EBV genome immediately following infection. We developed a computational approach to predict the location of ZREs which we experimentally assessed using in vitro and in vivo DNA association assays. A remarkably different binding motif is apparent for the CpG and non-CpG ZREs. Computational prediction of the location of these binding motifs in EBV revealed that the majority of lytic cycle genes have at least one and many have multiple copies of methylation-dependent CpG ZREs within their promoters. This suggests that the abundance of Zta protein coupled with the methylation status of the EBV genome act together to co-ordinate the expression of lytic cycle genes at the majority of EBV promoters.

  3. Identification of a phosphorylation-dependent nuclear localization motif in interferon regulatory factor 2 binding protein 2.

    Directory of Open Access Journals (Sweden)

    Allen C T Teng

    Full Text Available Interferon regulatory factor 2 binding protein 2 (IRF2BP2 is a muscle-enriched transcription factor required to activate vascular endothelial growth factor-A (VEGFA expression in muscle. IRF2BP2 is found in the nucleus of cardiac and skeletal muscle cells. During the process of skeletal muscle differentiation, some IRF2BP2 becomes relocated to the cytoplasm, although the functional significance of this relocation and the mechanisms that control nucleocytoplasmic localization of IRF2BP2 are not yet known.Here, by fusing IRF2BP2 to green fluorescent protein and testing a series of deletion and site-directed mutagenesis constructs, we mapped the nuclear localization signal (NLS to an evolutionarily conserved sequence (354ARKRKPSP(361 in IRF2BP2. This sequence corresponds to a classical nuclear localization motif bearing positively charged arginine and lysine residues. Substitution of arginine and lysine with negatively charged aspartic acid residues blocked nuclear localization. However, these residues were not sufficient because nuclear targeting of IRF2BP2 also required phosphorylation of serine 360 (S360. Many large-scale phosphopeptide proteomic studies had reported previously that serine 360 of IRF2BP2 is phosphorylated in numerous human cell types. Alanine substitution at this site abolished IRF2BP2 nuclear localization in C(2C(12 myoblasts and CV1 cells. In contrast, substituting serine 360 with aspartic acid forced nuclear retention and prevented cytoplasmic redistribution in differentiated C(2C(12 muscle cells. As for the effects of these mutations on VEGFA promoter activity, the S360A mutation interfered with VEGFA activation, as expected. Surprisingly, the S360D mutation also interfered with VEGFA activation, suggesting that this mutation, while enforcing nuclear entry, may disrupt an essential activation function of IRF2BP2.Nuclear localization of IRF2BP2 depends on phosphorylation near a conserved NLS. Changes in phosphorylation status

  4. IGF2/H19 hypomethylation is tissue, cell, and CpG site dependent and not correlated with body asymmetry in adolescents with Silver-Russell syndrome

    Directory of Open Access Journals (Sweden)

    Kannenberg Kai

    2012-09-01

    Full Text Available Abstract Background Silver-Russell syndrome (SRS is characterized by severe intrauterine and postnatal growth failure and frequent body asymmetry. Half of the patients with SRS carry a DNA hypomethylation of the imprinting center region 1 (ICR1 of the insulin-like growth factor 2 (IGF2/H19 locus, and the clinical phenotype is most severe in these patients. We aimed to elucidate the epigenetic basis of asymmetry in SRS and the cellular consequences of the ICR1 hypomethylation. Results The ICR1 methylation status was analyzed in blood and in addition in buccal smear probes and cultured fibroblasts obtained from punch biopsies taken from the two body halves of 5 SRS patients and 3 controls. We found that the ICR1 hypomethylation in SRS patients was stronger in blood leukocytes and oral mucosa cells than in fibroblasts. ICR1 CpG sites were affected differently. The severity of hypomethylation was not correlated to body asymmetry. IGF2 expression and IGF-II secretion of fibroblasts were not correlated to the degree of ICR1 hypomethylation. SRS fibroblasts responded well to stimulation by recombinant human IGF-I or IGF-II, with proliferation rates comparable with controls. Clonal expansion of primary fibroblasts confirmed the complexity of the cellular mosaicism. Conclusions We conclude that the ICR1 hypomethylation SRS is tissue, cell, and CpG site specific. The correlation of the ICR1 hypomethylation to IGF2 and H19 expression is not strict, may depend on the investigated tissue, and may become evident only in case of more severe methylation defects. The body asymmetry in juvenile SRS patients is not related to a corresponding ICR1 hypomethylation gradient, rendering more likely an intrauterine origin of asymmetry. Overall, it may be instrumental to consider not only the ICR1 methylation status as decisive for IGF2/H19 expression regulation.

  5. HOCOMOCO: A comprehensive collection of human transcription factor binding sites models

    KAUST Repository

    Kulakovskiy, Ivan V.

    2012-11-21

    Transcription factor (TF) binding site (TFBS) models are crucial for computational reconstruction of transcription regulatory networks. In existing repositories, a TF often has several models (also called binding profiles or motifs), obtained from different experimental data. Having a single TFBS model for a TF is more pragmatic for practical applications. We show that integration of TFBS data from various types of experiments into a single model typically results in the improved model quality probably due to partial correction of source specific technique bias. We present the Homo sapiens comprehensive model collection (HOCOMOCO, http://autosome.ru/HOCOMOCO/, http://cbrc.kaust.edu.sa/ hocomoco/) containing carefully hand-curated TFBS models constructed by integration of binding sequences obtained by both low- and high-throughput methods. To construct position weight matrices to represent these TFBS models, we used ChIPMunk software in four computational modes, including newly developed periodic positional prior mode associated with DNA helix pitch. We selected only one TFBS model per TF, unless there was a clear experimental evidence for two rather distinct TFBS models. We assigned a quality rating to each model. HOCOMOCO contains 426 systematically curated TFBS models for 401 human TFs, where 172 models are based on more than one data source. The Author(s) 2012.

  6. HOCOMOCO: a comprehensive collection of human transcription factor binding sites models

    Science.gov (United States)

    Kulakovskiy, Ivan V.; Medvedeva, Yulia A.; Schaefer, Ulf; Kasianov, Artem S.; Vorontsov, Ilya E.; Bajic, Vladimir B.; Makeev, Vsevolod J.

    2013-01-01

    Transcription factor (TF) binding site (TFBS) models are crucial for computational reconstruction of transcription regulatory networks. In existing repositories, a TF often has several models (also called binding profiles or motifs), obtained from different experimental data. Having a single TFBS model for a TF is more pragmatic for practical applications. We show that integration of TFBS data from various types of experiments into a single model typically results in the improved model quality probably due to partial correction of source specific technique bias. We present the Homo sapiens comprehensive model collection (HOCOMOCO, http://autosome.ru/HOCOMOCO/, http://cbrc.kaust.edu.sa/hocomoco/) containing carefully hand-curated TFBS models constructed by integration of binding sequences obtained by both low- and high-throughput methods. To construct position weight matrices to represent these TFBS models, we used ChIPMunk software in four computational modes, including newly developed periodic positional prior mode associated with DNA helix pitch. We selected only one TFBS model per TF, unless there was a clear experimental evidence for two rather distinct TFBS models. We assigned a quality rating to each model. HOCOMOCO contains 426 systematically curated TFBS models for 401 human TFs, where 172 models are based on more than one data source. PMID:23175603

  7. Crohn's disease but not diverticulitis is an independent risk factor for surgical site infections in colectomy.

    Science.gov (United States)

    Wideroff, Matthew; Xing, Yunfan; Liao, Junlin; Byrn, John C

    2014-10-01

    Surgical site infections (SSIs) after colectomy for colon cancer (CC), Crohn's disease (CD), and diverticulitis (DD) significantly impact both the immediate postoperative course and long-term disease-specific outcomes. We aim to profile the effect of diagnosis on SSI after segmental colectomy using the National Surgical Quality Improvement Program (NSQIP) data set. NSQIP data from 2006 to 2011 were investigated, and segmental colectomy procedures performed for the diagnoses of Crohn's disease, DD, and colon malignancy were included. SSI complications were compared by diagnosis using univariate and multivariate analysis. We included 35,557 colectomy cases in the analysis. CD had the highest rate of postoperative SSI (17 vs. 13% DD vs. 10% CC; p risk for acquiring at least one SSI (odds ratio (OR) = 1.38, p ≤ 0.001), deep incisional SSI (OR = 1.85, p = 0.03), and organ space SSI (OR = 1.51, p = 0.02). For patients undergoing segmental colectomy in the NSQIP data set, statistically significant increases in SSI are seen in CD, but not DD, when compared to CC, thus confirming CD as an independent risk factor for SSI.

  8. A novel method for improved accuracy of transcription factor binding site prediction

    KAUST Repository

    Khamis, Abdullah M.

    2018-03-20

    Identifying transcription factor (TF) binding sites (TFBSs) is important in the computational inference of gene regulation. Widely used computational methods of TFBS prediction based on position weight matrices (PWMs) usually have high false positive rates. Moreover, computational studies of transcription regulation in eukaryotes frequently require numerous PWM models of TFBSs due to a large number of TFs involved. To overcome these problems we developed DRAF, a novel method for TFBS prediction that requires only 14 prediction models for 232 human TFs, while at the same time significantly improves prediction accuracy. DRAF models use more features than PWM models, as they combine information from TFBS sequences and physicochemical properties of TF DNA-binding domains into machine learning models. Evaluation of DRAF on 98 human ChIP-seq datasets shows on average 1.54-, 1.96- and 5.19-fold reduction of false positives at the same sensitivities compared to models from HOCOMOCO, TRANSFAC and DeepBind, respectively. This observation suggests that one can efficiently replace the PWM models for TFBS prediction by a small number of DRAF models that significantly improve prediction accuracy. The DRAF method is implemented in a web tool and in a stand-alone software freely available at http://cbrc.kaust.edu.sa/DRAF.

  9. Rotation of nucleotide sites is not required for the enzymatic activity of chloroplast coupling factor

    Energy Technology Data Exchange (ETDEWEB)

    Musier, K.M.; Hammes, G.G.

    1987-09-22

    New heterobifunctional photoaffinity cross-linking reagents, 6-maleimido-N-(4-benzoylphenyl)hexanamide, 12-maleimido-N-(4-benzoylphenyl)dodecanamide, and 12-(/sup 14/C)maleimido-N-(4-benzoylphenyo)dodecanamide, were synthesized to investigate the mechanism of ATP hydrolysis by chloroplast coupling factor 1. These reagents react with sulfhydryl groups on the ..gamma..-polypeptide. Subsequent photolysis cross-links the ..gamma..-polypeptide covalently to ..cap alpha..- and ..beta..-polypeptides. The cross-linkers prevent major movements of the ..gamma..-polypeptide with respect to the ..cap alpha..- and ..beta..-polypeptides but are sufficiently long to permit some flexibility in the enzyme structure. When approx. 50% of the ..gamma..-polypeptide was cross-linked to a ..cap alpha..- and ..beta..-polypeptides, a 7% loss in ATPase activity was observed for the longer cross-linker and a 12% loss for the shorter. These results indicate that large movements of ..cap alpha..- and ..beta..-polypeptides with respect to the ..gamma..-polypeptide are not essential for catalysis. In particular, rotation of the polypeptide chains to crease structurally equivalent sites during catalysis is not a required feature of the enzyme mechanism.

  10. Demonstration of epidermal growth factor binding sites in the adult rat pancreas by light microscopic autoradiography

    International Nuclear Information System (INIS)

    Chabot, J.G.; Walker, P.; Pelletier, G.

    1987-01-01

    The distribution of epidermal growth factor (EGF) receptors was studied in the pancreas using light microscopic autoradiography, which was performed at different time intervals (2-60 min) after injecting 125 I-labeled EGF intravenously into the adult rat. In the exocrine pancreas, a labeling was found to occur over the pyramidal cells of the acini and cells lining the intercalated ducts. Moreover, substantial binding of EGF to cells of the islets of Langerhans was also revealed. At the 2-min time interval, most silver grains were found at the periphery of the target cells. The localization, as well as the diminution of silver grains over the cytoplasm of these cells, between 7 and 60 min, suggested the internalization and degradation of 125 I-labeled EGF. Control experiments indicated that the autoradiography reaction was due to specific interaction of 125 I-labeled EGF with its receptor. These results clearly indicate that EGF receptors are present in the acinar cells and the cells of intercalated ducts of the exocrine pancreas, as well as the cells of the endocrine pancreas. Finding that there are EGF binding sites in pancreatic acinar cells supports the physiological role of EGF in the regulation of pancreatic exocrine function. The presence of EGF receptors in cells of the islets of Langerhans suggests that EGF may play a role in the regulation of the endocrine pancreas

  11. Rotation of nucleotide sites is not required for the enzymatic activity of chloroplast coupling factor

    International Nuclear Information System (INIS)

    Musier, K.M.; Hammes, G.G.

    1987-01-01

    New heterobifunctional photoaffinity cross-linking reagents, 6-maleimido-N-(4-benzoylphenyl)hexanamide, 12-maleimido-N-(4-benzoylphenyl)dodecanamide, and 12-[ 14 C]maleimido-N-(4-benzoylphenyo)dodecanamide, were synthesized to investigate the mechanism of ATP hydrolysis by chloroplast coupling factor 1. These reagents react with sulfhydryl groups on the γ-polypeptide. Subsequent photolysis cross-links the γ-polypeptide covalently to α- and β-polypeptides. The cross-linkers prevent major movements of the γ-polypeptide with respect to the α- and β-polypeptides but are sufficiently long to permit some flexibility in the enzyme structure. When ∼ 50% of the γ-polypeptide was cross-linked to a α- and β-polypeptides, a 7% loss in ATPase activity was observed for the longer cross-linker and a 12% loss for the shorter. These results indicate that large movements of α- and β-polypeptides with respect to the γ-polypeptide are not essential for catalysis. In particular, rotation of the polypeptide chains to crease structurally equivalent sites during catalysis is not a required feature of the enzyme mechanism

  12. The role of anthropic, ecological, and social factors in sleeping site choice by long-tailed macaques (Macaca fascicularis).

    Science.gov (United States)

    Brotcorne, Fany; Maslarov, Cindy; Wandia, I Nengah; Fuentes, Agustin; Beudels-Jamar, Roseline C; Huynen, Marie-Claude

    2014-12-01

    When choosing their sleeping sites, primates make adaptive trade-offs between various biotic and abiotic constraints. In human-modified environments, anthropic factors may play a role. We assessed the influence of ecological (predation), social (intergroup competition), and anthropic (proximity to human settlements) factors in sleeping site choice by long-tailed macaques (Macaca fascicularis) occupying a habitat at the interface of natural forests and human-modified zones in Bali Barat National Park, Indonesia. Over the course of 56 nights, we collected data relating to physical features of sleeping trees, patterns of the use of sleeping sites within the home range, pre-sleep behavior, diurnal ranging patterns and availability of natural and human food. Overall, the macaques used 17 sleeping sites with 37 sleeping trees. When the monkeys slept in forest zones, they selected sleeping trees that had larger trunks but were not significantly taller than surrounding trees. Though the macaques rarely re-used sleeping sites on consecutive nights, they frequently re-used four sites over the study period. The group favored sleeping within the core area of its home range, despite the occurrence of frequent agonistic intergroup encounters there. Macaques preferentially selected sleeping trees located within or near human-modified zones, especially when human food was abundant and natural food was scarce. These results partially support the hypothesis that long-tailed macaques choose their sleeping sites to avoid predation; proximity to human settlements appears to be the primary factor influencing sleeping site choice in this primate species. Our results reflect the strong influence that anthropic factors have on primates, which subsist in increasingly human-dominated landscapes. © 2014 Wiley Periodicals, Inc.

  13. Dependence of the surf zone aerosol on wind direction and wind speed at a coastal site on the Baltic Sea

    Directory of Open Access Journals (Sweden)

    Tymon Zieliński

    2003-09-01

    Full Text Available Since 1992 lidar-based measurements have been carried out under various meteorological conditions and at various times of the year. The aerosol optical properties were determined in the marine boundary layer as a function of altitude using such factors as wind direction, duration and velocity and aerosol size distribution and concentration. It was confirmed that in all cases, the total aerosol concentration, size distribution and aerosol extinction increase with wind speed but decrease with altitude. In the range of wind velocities from 1 to 15 m s-1 the mean aerosol optical thickness of the atmosphere (VIS obtained from the lidar varied from 0.1 to 0.38 for offshore winds and from 0.01 to about 0.1 for onshore winds, while the Ångström parameter for VIS oscillated around 0.65 for onshore winds and around 1 for offshore winds. Both parameters depended strongly on the history of the air mass above the Baltic Sea. Such aerosol optical thicknesses are in agreement with those obtained by other researchers in the Baltic Sea area.

  14. Identification and Analysis of Significant Factors Influencing Visitor Satisfaction at Heritage Sites – The Case of Serbian Medieval Fortresses

    Directory of Open Access Journals (Sweden)

    Ivana Blešić

    2013-01-01

    Full Text Available With increased appreciation of general public, heritage sites gained more attention regarding contemporary tourism and management studies. Accordingly, the assessment of visitors’ satisfaction on these sites is important tool for both financial and organization management. The aim of this research is to identify the main (statistically significant factors that influence visitors’ satisfaction. Data was obtained by survey conducted during the visit of three medieval fortresses in Serbia, with aim to capture tourist’s expectations and perceptions on ten given attributes. The results of factor and descriptive statistical analysis indicate three factors: “regional settings”, “marketing”, “aesthetic appeal” significant for visitors’ satisfaction of the investigated heritage sites.

  15. Differentiation-dependent secretion of proangiogenic factors by mesenchymal stem cells.

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    Allison I Hoch

    Full Text Available Mesenchymal stem cells (MSCs are a promising cell population for cell-based bone repair due to their proliferative potential, ability to differentiate into bone-forming osteoblasts, and their secretion of potent trophic factors that stimulate angiogenesis and neovascularization. To promote bone healing, autogenous or allogeneic MSCs are transplanted into bone defects after differentiation to varying degrees down the osteogenic lineage. However, the contribution of the stage of osteogenic differentiation upon angiogenic factor secretion is unclear. We hypothesized that the proangiogenic potential of MSCs was dependent upon their stage of osteogenic differentiation. After 7 days of culture, we observed the greatest osteogenic differentiation of MSCs when cells were cultured with dexamethasone (OM+. Conversely, VEGF protein secretion and upregulation of angiogenic genes were greatest in MSCs cultured in growth media (GM. Using conditioned media from MSCs in each culture condition, GM-conditioned media maximized proliferation and enhanced chemotactic migration and tubule formation of endothelial colony forming cells (ECFCs. The addition of a neutralizing VEGF(165/121 antibody to conditioned media attenuated ECFC proliferation and chemotactic migration. ECFCs seeded on microcarrier beads and co-cultured with MSCs previously cultured in GM in a fibrin gel exhibited superior sprouting compared to MSCs previously cultured in OM+. These results confirm that MSCs induced farther down the osteogenic lineage possess reduced proangiogenic potential, thereby providing important findings for consideration when using MSCs for bone repair.

  16. The Neuro Imaging Description of Giant Pituitary Adenomas Depending on Mechanical Factor

    Directory of Open Access Journals (Sweden)

    Yu.M. Urmanova

    2016-05-01

    Full Text Available The research aim is to analyze of magnetically-resonance tomography data depending on the mechanical factor of giant pituitary adenomas. Materials and methods. Twenty-two adult patients with giant pituitary adenomas were observed during the period from 2015 to 2016 (men 50 %, aged 48.5 years old. The duration of disease varied from 2 months to 25 years. Results. Patients with endo-suprasellar growth of pituitary tumour had signs of chiasmal syndrome with bitemporal hemianopsia, initial or complete homonym hemianopsia, scotomas and others. Such variant of pituitary tumour growth was observed in 7 cases (31.8 %. 4.5 % patients with retro-sellar growth of pituitary tumour typically had violations caused by the growth of tumour into brainstem, that stipulated both the lesion of craniocerebral nerves and vegetative disorders, and also pyramid symptomatology (pathological reflexes, symptoms of oral automatism. Patients with the endo-laterosellar growth of tumour suffered from decline of sharpness of sight on one eye, one-sided headaches, lesion of oculomotorius. For 4.5 % patients with the endo-infrasellar growth of tumour violations of the nasal breathing and swallowing (odynophagia were typical. Conclusions. The most expressed neuroendocrine, ophthalmology and pillar disorders were observed in patients with the total growth of tumor. The giant pituitary adenomas are often accompanied by an invasion growth into surrounding anatomic structures (69.2 % that is a basic factor limiting radical operative intervention and increasing the number of relapses.

  17. Common elements in interleukin 4 and insulin signaling pathways in factor-dependent hematopoietic cells.

    Science.gov (United States)

    Wang, L M; Keegan, A D; Li, W; Lienhard, G E; Pacini, S; Gutkind, J S; Myers, M G; Sun, X J; White, M F; Aaronson, S A

    1993-05-01

    Interleukin 4 (IL-4), insulin, and insulin-like growth factor I (IGF-I) efficiently induced DNA synthesis in the IL-3-dependent murine myeloid cell lines FDC-P1 and FDC-P2. Although these factors could not individually sustain long-term growth of these lines, a combination of IL-4 with either insulin or IGF-I did support continuous growth. The principal tyrosine-phosphorylated substrate observed in FDC cells stimulated with IL-4, previously designated 4PS, was of the same size (170 kDa) as the major substrate phosphorylated in response to insulin or IGF-I. These substrates had phosphopeptides of the same size when analyzed by digestion with Staphylococcus aureus V8 protease, and each tightly associated with the 85-kDa component of phosphatidylinositol 3-kinase after factor stimulation. IRS-1, the principal substrate phosphorylated in response to insulin or IGF-I stimulation in nonhematopoietic cells, is similar in size to 4PS. However, anti-IRS-1 antibodies failed to efficiently precipitate 4PS, and some phosphopeptides generated by V8 protease digestion of IRS-1 were distinct in size from the phosphopeptides of 4PS. Nevertheless, IL-4, insulin, and IGF-I were capable of stimulating tyrosine phosphorylation of IRS-1 in FDC cells that expressed this substrate as a result of transfection. These findings indicate that (i) IL-4, insulin, and IGF-I use signal transduction pathways in FDC lines that have at least one major feature in common, the rapid tyrosine phosphorylation of 4PS, and (ii) insulin and IGF-I stimulation of hematopoietic cell lines leads to the phosphorylation of a substrate that may be related to but is not identical to IRS-1.

  18. Site of deposition and factors affecting clearance of aerosolized solute from canine lungs

    International Nuclear Information System (INIS)

    Rizk, N.W.; Luce, J.M.; Hoeffel, J.M.; Price, D.C.; Murray, J.F.

    1984-01-01

    The influence of several factors on lung solute clearance using aerosolized /sup 99m/Tc-diethylenetriaminepentaacetate was determined. The authors used a jet nebulizer-plate separator-balloon system to generate particles with an activity median aerodynamic diameter of 1.1 μm, administered the aerosol in a standard fashion, and determined clearance half times (t/sub 1/2/) with a gamma-scintillation camera. The following serial studies were performed in five anesthetized, paralyzed, intubated, mechanically ventilated dogs: (1) control, with ventilatory frequency (f) = 15 breaths/min and tidal volume (V/sub T/) = 15 ml/kg during solute clearance; (2) repeat control, for reproducibility; (3) increased frequency, with f = 25 breaths/min and V/sub T/ = 10 ml/kg; (4) positive end-expiratory pressure (PEEP) of 10 cmH 2 O; (5) unilateral pulmonary arterial occlusion (PAO); and (6) bronchial arterial occlusion (BAO). Control t/sub 1/2/ was 25 +/- 5 min and did not change in the repeat control, increased frequency, or BAO experiments. PEEP markedly decreased t/sub 1/2/ to 13 +/- 3 min (P < 0.01), and PAO increased it to 37 +/- 6 min (P < 0.05). We conclude that clearance from the lungs by our method is uninfluenced by increased frequency, increases markedly with PEEP, and depends on pulmonary, not bronchial, blood flow

  19. Instrumental neutron activation analysis of site-dependent uptake and distribution of trace elements in the saltmarsh plant Aster tripolium from marsh fields in the Schelde estuary, Netherlands

    International Nuclear Information System (INIS)

    Rossbach, M.

    1986-07-01

    As part of an environmental chemical investigation the uptake of heavy metals by a saltmarsh plant Aster tripolium from two differently polluted salt marsh sites of the North Sea between 20 to 30 trace elements were determined in soil and plant organs. A sensitive gamma ray counting system was installed and tested for instrumental activation analyses (INAA). Installations to improve sensitivity as well as conditions necessary for reliable trace element analysis with the aid of Anticompton spectrometers (ACS) are described. The accuracy and reproducibility of the method was determined by the analysis of reference- and control materials of the german environmental specimen bank. In order to characterise the state of pollution of the salt marsh soils pollution-factors for single elements as well as interelemental correlations were evaluated. In addition, uptake and translocation factors of the biological samples were calculated. The many highly significant correlations between elements within the plant organs indicated that uptake appears to be physiologicaly controlled and not dependent on soil concentration. In order to detect further consequences of differing pollution influences within these plants biochemical separation techniques were applied and trace element levels in selected extracts were determined. For the specification of heavy metals gelpermeation chromatography of ethanolic extracts proved to be the most promising method. Furthermore, propositions for the use of trace elements as a fingerprint for pollution status and characterisation of species for referenz- and specimenbank materials have been developed. Aster tripolium as a cadmium accumulating plant can probably be used as an indicator in the monitoring of cadmium polluted salt marsh areas. (orig.) [de

  20. Analysis of Patient-Dependent and Trauma-Dependent Risk Factors for Persistent Brachial Plexus Injury after Shoulder Dislocation

    Directory of Open Access Journals (Sweden)

    Olga Gutkowska

    2018-01-01

    Full Text Available Brachial plexus injuries (BPIs caused by shoulder dislocation usually have a transient character and tend to resolve spontaneously. However, in some patients the symptoms can persist and require operative intervention. This work aims to determine the risk factors for persistent BPIs resulting from shoulder dislocation. The study comprised 73 patients (58 men, 15 women; mean age: 50 years treated operatively between the years 2000 and 2016 for persistent BPIs resulting from shoulder dislocation. Patient age, gender, type of initial trauma, number of affected nerves, presence of accompanying injuries, and time interval from dislocation to its reduction were analysed. Elderly patients more often sustained multiple-nerve injuries, while single nerve injuries were more often observed in younger patients. Injury to a single nerve was diagnosed in 30% of the patients. Axillary nerve was most commonly affected. Fracture of the greater tuberosity of humerus coincided with total BPI in 50% of the cases. Longer unreduced period caused injury to multiple nerves. Analysis of our patient group against relevant literature revealed that persistent BPI after shoulder dislocation is more common in older patients. Injuries to ulnar and median nerves more often require operative intervention due to low potential for spontaneous recovery of these nerves.

  1. Identification of transcription factor AML-1 binding site upstream of human cytomegalovirus UL111A gene.

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    Xiaoqun Zheng

    Full Text Available Human cytomegalovirus (HCMV interleukin-10 (hcmvIL-10, encoded by HCMV UL111A gene, is a homolog of human IL-10. It exerts immunomodulatory effects that allow HCMV to evade host defense mechanisms. However, the exact mechanism underlying the regulation of hcmvIL-10 expression is not well understood. The transcription factor acute myeloid leukemia 1 (AML-1 plays an important role in the regulation of various genes involved in the differentiation of hematopoietic lineages. A putative AML-1 binding site is present within the upstream regulatory region (URR of UL111A gene. To provide evidence that AML-1 is involved in regulating UL111A gene expression, we examined the interaction of AML-1 with the URR of UL111A in HCMV-infected human monocytic THP-1 cells using a chromatin immunoprecipitation assay. HcmvIL-10 transcription was detected in differentiated THP-1 cells, but not in undifferentiated ones. Furthermore, the URR of UL111A showed a higher intensity of AML-1 binding, a higher level of histone H3 acetyl-K9, but a lower level of histone H3 dimethyl-K9 in differentiated THP-1 cells than undifferentiated cells. Down-regulation of AML1 by RNA interference decreased the expression of the UL111A gene. Our results suggest that AML-1 may contribute to the epigenetic regulation of UL111A gene via histone modification in HCMV-infected differentiated THP-1 cells. This finding could be useful for the development of new anti-viral therapies.

  2. Interaction between nucleotide binding sites on chloroplast coupling factor 1 during ATP hydrolysis

    Energy Technology Data Exchange (ETDEWEB)

    Leckband, D.; Hammes, G.G.

    1987-04-21

    The initial hydrolysis of radioactively-labelled CaATP by chloroplast coupling factor 1 was studied with the quenched-flow method. The time course of hydrolysis can be described as a first-order conversion of the enzyme to an active form followed by steady-state formation of product. The rate constant for the first-order process is independent of substrate concentration but increased hyperbolically to a limiting value of 0.43 s/sup -1/ with increasing concentrations of free Ca/sup 2 +/. A mechanism involving a Ca/sup 2 +/-triggered conversion to an active form of the enzyme is consistent with the data. The steady-state rate varied sigmoidally with the CaATP concentration. Initial exchange of tightly bound ADP is complex: approx. 50% of the bound nucleotide is lost within 30 s, with complete exchange requiring several minutes. The first-order rate constant characterizing the rapid phase of the reaction increases hyperbolically to a limiting value of 0.26 s/sup -1/ as the concentration of CaATP is increased, indicating that the binding of CaATP to the enzyme promotes the exchange process. Modification of the quenched-flow apparatus permitted measurement of the rate of nucleotide exchange during steady-state catalysis. The value of the first-order rate constant characterizing this process is similar to the catalytic rate constant determined under identical conditions. When MgATP is tightly bound to the enzyme, none of the kinetic properties of the enzyme described above were significantly changes. The results obtained suggest a mechanism in which two sites on the enzyme participate in catalysis. Several possible mechanisms consistent with the data are discussed.

  3. Sterol regulation of human fatty acid synthase promoter I requires nuclear factor-Y- and Sp-1-binding sites.

    Science.gov (United States)

    Xiong, S; Chirala, S S; Wakil, S J

    2000-04-11

    To understand cholesterol-mediated regulation of human fatty acid synthase promoter I, we tested various 5'-deletion constructs of promoter I-luciferase reporter gene constructs in HepG2 cells. The reporter gene constructs that contained only the Sp-1-binding site (nucleotides -82 to -74) and the two tandem sterol regulatory elements (SREs; nucleotides -63 to -46) did not respond to cholesterol. Only the reporter gene constructs containing a nuclear factor-Y (NF-Y) sequence, the CCAAT sequence (nucleotides -90 to -86), an Sp-1 sequence, and the two tandem SREs responded to cholesterol. The NF-Y-binding site, therefore, is essential for cholesterol response. Mutating the SREs or the NF-Y site and inserting 4 bp between the Sp-1- and NF-Y-binding sites both resulted in a minimal cholesterol response of the reporter genes. Electrophoretic mobility-shift assays using anti-SRE-binding protein (SREBP) and anti-NF-Ya antibodies confirmed that these SREs and the NF-Y site bind the respective factors. We also identified a second Sp-1 site located between nucleotides -40 and -30 that can substitute for the mutated Sp-1 site located between nucleotides -82 and -74. The reporter gene expression of the wild-type promoter and the Sp-1 site (nucleotides -82 to -74) mutant promoter was similar when SREBP1a [the N-terminal domain of SREBP (amino acids 1-520)] was constitutively overexpressed, suggesting that Sp-1 recruits SREBP to the SREs. Under the same conditions, an NF-Y site mutation resulted in significant loss of reporter gene expression, suggesting that NF-Y is required to activate the cholesterol response.

  4. Problem list completeness in electronic health records: A multi-site study and assessment of success factors.

    Science.gov (United States)

    Wright, Adam; McCoy, Allison B; Hickman, Thu-Trang T; Hilaire, Daniel St; Borbolla, Damian; Bowes, Watson A; Dixon, William G; Dorr, David A; Krall, Michael; Malholtra, Sameer; Bates, David W; Sittig, Dean F

    2015-10-01

    To assess problem list completeness using an objective measure across a range of sites, and to identify success factors for problem list completeness. We conducted a retrospective analysis of electronic health record data and interviews at ten healthcare organizations within the United States, United Kingdom, and Argentina who use a variety of electronic health record systems: four self-developed and six commercial. At each site, we assessed the proportion of patients who have diabetes recorded on their problem list out of all patients with a hemoglobin A1c elevation>=7.0%, which is diagnostic of diabetes. We then conducted interviews with informatics leaders at the four highest performing sites to determine factors associated with success. Finally, we surveyed all the sites about common practices implemented at the top performing sites to determine whether there was an association between problem list management practices and problem list completeness. Problem list completeness across the ten sites ranged from 60.2% to 99.4%, with a mean of 78.2%. Financial incentives, problem-oriented charting, gap reporting, shared responsibility, links to billing codes, and organizational culture were identified as success factors at the four hospitals with problem list completeness at or near 90.0%. Incomplete problem lists represent a global data integrity problem that could compromise quality of care and put patients at risk. There was a wide range of problem list completeness across the healthcare facilities. Nevertheless, some facilities have achieved high levels of problem list completeness, and it is important to better understand the factors that contribute to success to improve patient safety. Problem list completeness varies substantially across healthcare facilities. In our review of EHR systems at ten healthcare facilities, we identified six success factors which may be useful for healthcare organizations seeking to improve the quality of their problem list

  5. Can diet-dependent factors help explain fish-to-fish variation in thiamine-dependent early mortality syndrome?

    Science.gov (United States)

    Brown, S.B.; Arts, M.T.; Brown, L.R.; Brown, M.; Moore, K.; Villella, M.; Fitzsimons, J.D.; Honeyfield, D.C.; Tillitt, D.E.; Zajicek, J.L.; Wolgamood, M.; Hnath, J.G.

    2005-01-01

    To provide insight into the reasons why offspring of certain salmonine females exhibit early mortality syndrome (EMS) in the Great Lakes whereas others do not, we measured the egg concentrations of potential biochemical markers (stable isotopes of nitrogen and carbon, fatty acid signatures, and lipid-soluble carotenoids and vitamins) that are indicative of differing food web and trophic structure. To corroborate the presence of EMS, we also measured the egg content of thiamine vitamers. For all the stocks of coho salmon Oncorhynchus kisutch and Chinook salmon O. tshawytscha we studied, there was a very high correspondence between EMS and low concentrations of unphosphorylated thiamine in unfertilized eggs. For salmonine stocks in the Platte River, Thompson Creek, and the Swan River, Michigan, small but significant shifts occurred in measures of egg carotenoids, retinoids, ??15N depletion, and fatty acid profiles of fish producing normal offspring relative to those exhibiting EMS. Egg thiamine concentrations in Chinook salmon from the Little Manistee River, Michigan, in the low-EMS group were only marginally above the threshold for EMS induction. Along with this small thiamine differential, there was no evidence of differing food web or dietary factors between EMS-positive and normal Chinook salmon from the Little Manistee River. Further investigations are required to determine the potential dietary sources for the observed differences in biochemical markers between EMS-positive and normal fish. These findings are generally consistent with the hypothesis that a more diverse forage base may help to limit overall dietary content of species that contain thiaminase, such as alewives Alosa pseudoharengus, and may lead to improved embryonic survival for feral salmonids. ?? Copyright by the American Fisheries Society 2005.

  6. Factors for assessment of human health risk associated with remedial action at hazardous waste sites

    International Nuclear Information System (INIS)

    Stephenson, D.E.; King, C.M.; Looney, B.B.; Holmes, W.G.; Gordon, D.E.

    1985-01-01

    A risk assessment strategy that is cost effective and minimized human health risks was developed for closure of hazardous waste sites at the Savannah River Plant. The strategy consists of (1) site characterization, (2) contaminant transport modeling, and (3) determination of relative merits of alternative remedial actions according to the degree of health protection they provide

  7. Ash dust co-centration in the vicinity of the ash disposal site depending on the size of the pond (“Water Mirror”

    Directory of Open Access Journals (Sweden)

    Zoran Gršić

    2010-09-01

    Full Text Available Thermal power plants Nikola Tesla “A” and “B” are large sources of ash from their ashes/slag deposit sites. Total sizes of ashes/slag depots are 600ha and 382ha, with active cassettes having dimensions ∼200 ha and ∼130 ha. The active cassettes of the disposal sites are covered by rather large waste ponds, the sizes of vary depending on the working condition of a sluice system and on meteorological conditions. Modeling of ash lifting was attempted using results from the dust lifting research. The relation between sizes of ponds and air dust concentration in the vicinity of ash disposal sites was analyzed. As expected, greater sizes of dried disposal site surfaces in combination with stronger winds gave greater dust emission and greater air dust concentration.

  8. Hypoxia inducible factor signaling modulates susceptibility to mycobacterial infection via a nitric oxide dependent mechanism.

    Science.gov (United States)

    Elks, Philip M; Brizee, Sabrina; van der Vaart, Michiel; Walmsley, Sarah R; van Eeden, Fredericus J; Renshaw, Stephen A; Meijer, Annemarie H

    2013-01-01

    Tuberculosis is a current major world-health problem, exacerbated by the causative pathogen, Mycobacterium tuberculosis (Mtb), becoming increasingly resistant to conventional antibiotic treatment. Mtb is able to counteract the bactericidal mechanisms of leukocytes to survive intracellularly and develop a niche permissive for proliferation and dissemination. Understanding of the pathogenesis of mycobacterial infections such as tuberculosis (TB) remains limited, especially for early infection and for reactivation of latent infection. Signaling via hypoxia inducible factor α (HIF-α) transcription factors has previously been implicated in leukocyte activation and host defence. We have previously shown that hypoxic signaling via stabilization of Hif-1α prolongs the functionality of leukocytes in the innate immune response to injury. We sought to manipulate Hif-α signaling in a well-established Mycobacterium marinum (Mm) zebrafish model of TB to investigate effects on the host's ability to combat mycobacterial infection. Stabilization of host Hif-1α, both pharmacologically and genetically, at early stages of Mm infection was able to reduce the bacterial burden of infected larvae. Increasing Hif-1α signaling enhanced levels of reactive nitrogen species (RNS) in neutrophils prior to infection and was able to reduce larval mycobacterial burden. Conversely, decreasing Hif-2α signaling enhanced RNS levels and reduced bacterial burden, demonstrating that Hif-1α and Hif-2α have opposing effects on host susceptibility to mycobacterial infection. The antimicrobial effect of Hif-1α stabilization, and Hif-2α reduction, were demonstrated to be dependent on inducible nitric oxide synthase (iNOS) signaling at early stages of infection. Our findings indicate that induction of leukocyte iNOS by stabilizing Hif-1α, or reducing Hif-2α, aids the host during early stages of Mm infection. Stabilization of Hif-1α therefore represents a potential target for therapeutic

  9. Hypoxia inducible factor signaling modulates susceptibility to mycobacterial infection via a nitric oxide dependent mechanism.

    Directory of Open Access Journals (Sweden)

    Philip M Elks

    Full Text Available Tuberculosis is a current major world-health problem, exacerbated by the causative pathogen, Mycobacterium tuberculosis (Mtb, becoming increasingly resistant to conventional antibiotic treatment. Mtb is able to counteract the bactericidal mechanisms of leukocytes to survive intracellularly and develop a niche permissive for proliferation and dissemination. Understanding of the pathogenesis of mycobacterial infections such as tuberculosis (TB remains limited, especially for early infection and for reactivation of latent infection. Signaling via hypoxia inducible factor α (HIF-α transcription factors has previously been implicated in leukocyte activation and host defence. We have previously shown that hypoxic signaling via stabilization of Hif-1α prolongs the functionality of leukocytes in the innate immune response to injury. We sought to manipulate Hif-α signaling in a well-established Mycobacterium marinum (Mm zebrafish model of TB to investigate effects on the host's ability to combat mycobacterial infection. Stabilization of host Hif-1α, both pharmacologically and genetically, at early stages of Mm infection was able to reduce the bacterial burden of infected larvae. Increasing Hif-1α signaling enhanced levels of reactive nitrogen species (RNS in neutrophils prior to infection and was able to reduce larval mycobacterial burden. Conversely, decreasing Hif-2α signaling enhanced RNS levels and reduced bacterial burden, demonstrating that Hif-1α and Hif-2α have opposing effects on host susceptibility to mycobacterial infection. The antimicrobial effect of Hif-1α stabilization, and Hif-2α reduction, were demonstrated to be dependent on inducible nitric oxide synthase (iNOS signaling at early stages of infection. Our findings indicate that induction of leukocyte iNOS by stabilizing Hif-1α, or reducing Hif-2α, aids the host during early stages of Mm infection. Stabilization of Hif-1α therefore represents a potential target for

  10. Matriptase activation connects tissue factor-dependent coagulation initiation to epithelial proteolysis and signaling.

    Science.gov (United States)

    Le Gall, Sylvain M; Szabo, Roman; Lee, Melody; Kirchhofer, Daniel; Craik, Charles S; Bugge, Thomas H; Camerer, Eric

    2016-06-23

    The coagulation cascade is designed to sense tissue injury by physical separation of the membrane-anchored cofactor tissue factor (TF) from inactive precursors of coagulation proteases circulating in plasma. Once TF on epithelial and other extravascular cells is exposed to plasma, sequential activation of coagulation proteases coordinates hemostasis and contributes to host defense and tissue repair. Membrane-anchored serine proteases (MASPs) play critical roles in the development and homeostasis of epithelial barrier tissues; how MASPs are activated in mature epithelia is unknown. We here report that proteases of the extrinsic pathway of blood coagulation transactivate the MASP matriptase, thus connecting coagulation initiation to epithelial proteolysis and signaling. Exposure of TF-expressing cells to factors (F) VIIa and Xa triggered the conversion of latent pro-matriptase to an active protease, which in turn cleaved the pericellular substrates protease-activated receptor-2 (PAR2) and pro-urokinase. An activation pathway-selective PAR2 mutant resistant to direct cleavage by TF:FVIIa and FXa was activated by these proteases when cells co-expressed pro-matriptase, and matriptase transactivation was necessary for efficient cleavage and activation of wild-type PAR2 by physiological concentrations of TF:FVIIa and FXa. The coagulation initiation complex induced rapid and prolonged enhancement of the barrier function of epithelial monolayers that was dependent on matriptase transactivation and PAR2 signaling. These observations suggest that the coagulation cascade engages matriptase to help coordinate epithelial defense and repair programs after injury or infection, and that matriptase may contribute to TF-driven pathogenesis in cancer and inflammation.

  11. Is Growth Differentiation Factor 11 a Realistic Therapeutic for Aging-Dependent Muscle Defects?

    Science.gov (United States)

    Harper, Shavonn C; Brack, Andrew; MacDonnell, Scott; Franti, Michael; Olwin, Bradley B; Bailey, Beth A; Rudnicki, Michael A; Houser, Steven R

    2016-04-01

    This "Controversies in Cardiovascular Research" article evaluates the evidence for and against the hypothesis that the circulating blood level of growth differentiation factor 11 (GDF11) decreases in old age and that restoring normal GDF11 levels in old animals rejuvenates their skeletal muscle and reverses pathological cardiac hypertrophy and cardiac dysfunction. Studies supporting the original GDF11 hypothesis in skeletal and cardiac muscle have not been validated by several independent groups. These new studies have either found no effects of restoring normal GDF11 levels on cardiac structure and function or have shown that increasing GDF11 or its closely related family member growth differentiation factor 8 actually impairs skeletal muscle repair in old animals. One possible explanation for what seems to be mutually exclusive findings is that the original reagent used to measure GDF11 levels also detected many other molecules so that age-dependent changes in GDF11 are still not well known. The more important issue is whether increasing blood [GDF11] repairs old skeletal muscle and reverses age-related cardiac pathologies. There are substantial new and existing data showing that GDF8/11 can exacerbate rather than rejuvenate skeletal muscle injury in old animals. There is also new evidence disputing the idea that there is pathological hypertrophy in old C57bl6 mice and that GDF11 therapy can reverse cardiac pathologies. Finally, high [GDF11] causes reductions in body and heart weight in both young and old animals, suggestive of a cachexia effect. Our conclusion is that elevating blood levels of GDF11 in the aged might cause more harm than good. © 2016 American Heart Association, Inc.

  12. Functional role of fumarate site Glu59 involved in allosteric regulation and subunit-subunit interaction of human mitochondrial NAD(P)+-dependent malic enzyme.

    Science.gov (United States)

    Hsieh, Ju-Yi; Chiang, Yu-Hsiu; Chang, Kuan-Yu; Hung, Hui-Chih

    2009-02-01

    Here we report on the role of Glu59 in the fumarate-mediated allosteric regulation of the human mitochondrial NAD(P)+-dependent malic enzyme (m-NAD-ME). In the present study, Glu59 was substituted by Asp, Gln or Leu. Our kinetic data strongly indicated that the charge properties of this residue significantly affect the allosteric activation of the enzyme. The E59L enzyme shows nonallosteric kinetics and the E59Q enzyme displays a much higher threshold in enzyme activation with elevated activation constants, K(A,Fum) and alphaK(A,Fum). The E59D enzyme, although retaining the allosteric property, is quite different from the wild-type in enzyme activation. The K(A,Fum) and alphaK(A,Fum) of E59D are also much greater than those of the wild-type, indicating that not only the negative charge of this residue but also the group specificity and side chain interactions are important for fumarate binding. Analytical ultracentrifugation analysis shows that both the wild-type and E59Q enzymes exist as a dimer-tetramer equilibrium. In contrast to the E59Q mutant, the E59D mutant displays predominantly a dimer form, indicating that the quaternary stability in the dimer interface is changed by shortening one carbon side chain of Glu59 to Asp59. The E59L enzyme also shows a dimer-tetramer model similar to that of the wild-type, but it displays more dimers as well as monomers and polymers. Malate cooperativity is not significantly notable in the E59 mutant enzymes, suggesting that the cooperativity might be related to the molecular geometry of the fumarate-binding site. Glu59 can precisely maintain the geometric specificity for the substrate cooperativity. According to the sequence alignment analysis and our experimental data, we suggest that charge effect and geometric specificity are both critical factors in enzyme regulation. Glu59 discriminates human m-NAD-ME from mitochondrial NADP+-dependent malic enzyme and cytosolic NADP+-dependent malic enzyme in fumarate activation and

  13. Site-response Estimation by 1D Heterogeneous Velocity Model using Borehole Log and its Relationship to Damping Factor

    International Nuclear Information System (INIS)

    Sato, Hiroaki

    2014-01-01

    In the Niigata area, which suffered from several large earthquakes such as the 2007 Chuetsu-oki earthquake, geographical observation that elucidates the S-wave structure of the underground is advancing. Modeling of S-wave velocity structure in the subsurface is underway to enable simulation of long-period ground motion. The one-dimensional velocity model by inverse analysis of micro-tremors is sufficiently appropriate for long-period site response but not for short-period, which is important for ground motion evaluation at NPP sites. The high-frequency site responses may be controlled by the strength of heterogeneity of underground structure because the heterogeneity of the 1D model plays an important role in estimating high-frequency site responses and is strongly related to the damping factor of the 1D layered velocity model. (author)

  14. Inhibition of human immunodeficiency virus type 1 replication with artificial transcription factors targeting the highly conserved primer-binding site

    NARCIS (Netherlands)

    Eberhardy, Scott R.; Goncalves, Joao; Coelho, Sofia; Segal, David J.; Berkhout, Ben; Barbas, Carlos F.

    2006-01-01

    The human immunodeficiency virus type 1 (HIV-1) primer-binding site (PBS) is a highly conserved region in the HIV genome and represents an attractive target for the development of new anti-HIV therapies. In this study, we designed four artificial zinc finger transcription factors to bind at or

  15. CONREAL: conserved regulatory elements anchored alignment algorithm for identification of transcription factor binding sites by phylogenetic footprinting

    NARCIS (Netherlands)

    Berezikov, E.; Guryev, V.; Plasterk, R.; Cuppen, E.

    2004-01-01

    Prediction of transcription-factor target sites in promoters remains difficult due to the short length and degeneracy of the target sequences. Although the use of orthologous sequences and phylogenetic footprinting approaches may help in the recognition of conserved and potentially functional

  16. NAGRA - Sites for geological repositories - Technical safety factors: Suggestions for stage 3

    International Nuclear Information System (INIS)

    2015-01-01

    This comprehensive brochure published by the Swiss National Cooperative for the Disposal of Radioactive Waste (NAGRA) examines the six sites for repositories for nuclear wastes in Switzerland which have been proposed in Stage 1 of the program concerning nuclear waste repositories. Three of these sites are proposed for both highly radioactive wastes as well as for low and medium-active wastes, the other three for low and medium-active wastes only. The evaluation of the sites is discussed. The sites are to be further evaluated in Stage 2 of the program. The work to be done in the further stages involved in the selection of the final site (or sites) is described. Along with definition of the regions where deep repositories could possibly be built, suggestions for the placing of the facilities required on the surface are discussed. Geological requirements on the repositories and safety-relevant characteristics of the various site options are discussed. The results of the assessments made are presented in tabular form. Maps and geological cross-sections of all the suggested areas are included

  17. Some interactive factors affecting trench-cover integrity on low-level waste sites

    International Nuclear Information System (INIS)

    Hakonson, T.E.; Lane, L.J.; Steger, J.G.; DePoorter, G.L.

    1982-01-01

    This paper describes important mechanisms by which radionuclide can be transported from low-level waste disposal sites into biological pathways, discuss interactions of abiotic and biotic processes, and recommends environmental characteristics that should be measured to design sites that minimize this transport. Past experience at shallow land burial sites for low-level radioactive wastes suggest that occurrences of waste exposure and radionuclide transport are often related to inadequate trench cover designs. Meeting performance standards at low-level waste sites can only be achieved by recognizing that physical, chemical, and biological processes operating on and in a trench cover profile are highly interactive. Failure to do so can lead to improper design criteria and subsequent remedial action procedures that can adversely affect site stability. Based upon field experiments and computer modeling, recommendations are made on site characteristics that require measurement in order to design systems that reduce surface runoff and erosion, manage soil moisture and biota in the cover profile to maximize evapotranspiration and minimize percolation, and place bounds on the intrusion potential of plants and animals into the waste material. Major unresolved problems include developing probabilistic approaches that include climatic variability, improved knowledge of soil-water-plant-erosion relationships, development of practical vegetation establishment and maintenance procedures, prediction and quantification of site potential and plant succession, and understanding the interaction of processes occurring on and in the cover profile with deeper subsurface processes

  18. Frank-ter Haar syndrome protein Tks4 regulates epidermal growth factor-dependent cell migration.

    Science.gov (United States)

    Bögel, Gábor; Gujdár, Annamária; Geiszt, Miklós; Lányi, Árpád; Fekete, Anna; Sipeki, Szabolcs; Downward, Julian; Buday, László

    2012-09-07

    Mutations in the SH3PXD2B gene coding for the Tks4 protein are responsible for the autosomal recessive Frank-ter Haar syndrome. Tks4, a substrate of Src tyrosine kinase, is implicated in the regulation of podosome formation. Here, we report a novel role for Tks4 in the EGF signaling pathway. In EGF-treated cells, Tks4 is tyrosine-phosphorylated and associated with the activated EGF receptor. This association is not direct but requires the presence of Src tyrosine kinase. In addition, treatment of cells with LY294002, an inhibitor of PI 3-kinase, or mutations of the PX domain reduces tyrosine phosphorylation and membrane translocation of Tks4. Furthermore, a PX domain mutant (R43W) Tks4 carrying a reported point mutation in a Frank-ter Haar syndrome patient showed aberrant intracellular expression and reduced phosphoinositide binding. Finally, silencing of Tks4 was shown to markedly inhibit HeLa cell migration in a Boyden chamber assay in response to EGF or serum. Our results therefore reveal a new function for Tks4 in the regulation of growth factor-dependent cell migration.

  19. Assessment of radioactivity for 24 hours urine sample depending on correction factor by using creatinine

    International Nuclear Information System (INIS)

    Kharita, M. H.; Maghrabi, M.

    2006-09-01

    Assessment of intake and internal does requires knowing the amount of radioactivity in 24 hours urine sample, sometimes it is difficult to get 24 hour sample because this method is not comfortable and in most cases the workers refuse to collect this amount of urine. This work focuses on finding correction factor of 24 hour sample depending on knowing the amount of creatinine in the sample whatever the size of this sample. Then the 24 hours excretion of radionuclide is calculated assuming the average creatinine excretion rate is 1.7 g per 24 hours, based on the amount of activity and creatinine in the urine sample. Several urine sample were collected from occupationally exposed workers the amount and ratios of creatinine and activity in these samples were determined, then normalized to 24 excretion of radionuclide. The average chemical recovery was 77%. It should be emphasized that this method should only be used if a 24 hours sample was not possible to collect. (author)

  20. Leucemia inhibitory factor; investigating the time-dependent effect on viability of vitrified bovine embryos.

    Science.gov (United States)

    Kocyigit, A; Cevik, M

    2017-12-01

    Leucemia inhibitory factor (LIF) is involved in various reproductive processes, including sperm development, regulation of ovulation, as well as blastocyst formation, hatching and implantation in embryos. Moreover, LIF has also been shown significantly to enhance the blastocyst formation rates of bovine embryos, a finding that remains controversial. Our purpose was to investigate time-dependent effect of LIF on bovine embryo culture, especially in terms of addition timing. Presumptive zygotes were cultured in five different groups. In this study, 100 ng/ml LIF was added to the culture medium were as follows; control: SOF alone, group A: at day 0 (fertilization day), group B: at day 4 post-insemination (p.i.), group C: at day 4 to 7 (p.i. before vitrification) and group D: at day 8 (p.i. after thawing). Addition of LIF to the culture medium at day 4 significantly increased the percentage of blastocyst rate when compared day 0, day 4 at 6/7 and control group (41.8% versus 24.3%, 19.7%, 34.6%). In conclusion, the addition of LIF only on day 4 (p.i.) to the culture medium was found to be beneficial for bovine embryonic development based on several measures, including blastocysts rate, re-expansion rate and cellular cryotolerance after vitrification. © 2017 Blackwell Verlag GmbH.

  1. Characterization of a human coagulation factor Xa-binding site on Viperidae snake venom phospholipases A2 by affinity binding studies and molecular bioinformatics

    Directory of Open Access Journals (Sweden)

    Gowda Veerabasappa T

    2007-12-01

    Full Text Available Abstract Background The snake venom group IIA secreted phospholipases A2 (SVPLA2, present in the Viperidae snake family exhibit a wide range of toxic and pharmacological effects. They exert their different functions by catalyzing the hydrolysis of phospholipids (PL at the membrane/water interface and by highly specific direct binding to: (i presynaptic membrane-bound or intracellular receptors; (ii natural PLA2-inhibitors from snake serum; and (iii coagulation factors present in human blood. Results Using surface plasmon resonance (SPR protein-protein interaction measurements and an in vitro biological test of inhibition of prothrombinase activity, we identify a number of Viperidae venom SVPLA2s that inhibit blood coagulation through direct binding to human blood coagulation factor Xa (FXa via a non-catalytic, PL-independent mechanism. We classify the SVPLA2s in four groups, depending on the strength of their binding. Molecular electrostatic potentials calculated at the surface of 3D homology-modeling models show a correlation with inhibition of prothrombinase activity. In addition, molecular docking simulations between SVPLA2 and FXa guided by the experimental data identify the potential FXa binding site on the SVPLA2s. This site is composed of the following regions: helices A and B, the Ca2+ loop, the helix C-β-wing loop, and the C-terminal fragment. Some of the SVPLA2 binding site residues belong also to the interfacial binding site (IBS. The interface in FXa involves both, the light and heavy chains. Conclusion We have experimentally identified several strong FXa-binding SVPLA2s that disrupt the function of the coagulation cascade by interacting with FXa by the non-catalytic PL-independent mechanism. By theoretical methods we mapped the interaction sites on both, the SVPLA2s and FXa. Our findings may lead to the design of novel, non-competitive FXa inhibitors.

  2. Effective transcription factor binding site prediction using a combination of optimization, a genetic algorithm and discriminant analysis to capture distant interactions.

    Science.gov (United States)

    Levitsky, Victor G; Ignatieva, Elena V; Ananko, Elena A; Turnaev, Igor I; Merkulova, Tatyana I; Kolchanov, Nikolay A; Hodgman, T C

    2007-12-19

    Reliable transcription factor binding site (TFBS) prediction methods are essential for computer annotation of large amount of genome sequence data. However, current methods to predict TFBSs are hampered by the high false-positive rates that occur when only sequence conservation at the core binding-sites is considered. To improve this situation, we have quantified the performance of several Position Weight Matrix (PWM) algorithms, using exhaustive approaches to find their optimal length and position. We applied these approaches to bio-medically important TFBSs involved in the regulation of cell growth and proliferation as well as in inflammatory, immune, and antiviral responses (NF-kappaB, ISGF3, IRF1, STAT1), obesity and lipid metabolism (PPAR, SREBP, HNF4), regulation of the steroidogenic (SF-1) and cell cycle (E2F) genes expression. We have also gained extra specificity using a method, entitled SiteGA, which takes into account structural interactions within TFBS core and flanking regions, using a genetic algorithm (GA) with a discriminant function of locally positioned dinucleotide (LPD) frequencies. To ensure a higher confidence in our approach, we applied resampling-jackknife and bootstrap tests for the comparison, it appears that, optimized PWM and SiteGA have shown similar recognition performances. Then we applied SiteGA and optimized PWMs (both separately and together) to sequences in the Eukaryotic Promoter Database (EPD). The resulting SiteGA recognition models can now be used to search sequences for BSs using the web tool, SiteGA. Analysis of dependencies between close and distant LPDs revealed by SiteGA models has shown that the most significant correlations are between close LPDs, and are generally located in the core (footprint) region. A greater number of less significant correlations are mainly between distant LPDs, which spanned both core and flanking regions. When SiteGA and optimized PWM models were applied together, this substantially reduced

  3. Site-dependent bone mineral density response to oral pamidronate and calcium in postmenopausal osteoporosis: a preliminary report.

    Science.gov (United States)

    Barreira, J C; Messina, O D; Maldonado-Cocco, J A; Roldan, E J

    1997-06-01

    Radiologically diagnosed postmenopausal osteoporotic patients with at least one nontraumatic vertebral flattening were treated for one year with either oral pamidronate (APD), 300 mg/day plus calcium 1 g/day (n=39) or with calcium alone (n=21). Bone mineral density (BMD) was assessed in lumbar spine, femoral neck, trochanter and Ward's triangle by dual X-ray absorptiometry in order to determine the number of responders at each site. As no densitometric inclusion criteria were stipulated, wide inter- and intra-individual variations in both regional basal BMD and response to therapy were found. However, the APD-treated group showed significant mean BMD increases in spine (+3.1%; p cases, 9 (24%) on APD and 6 (32%) on calcium alone responded in all 4 areas evaluated, while a single case on the latter treatment failed to show BMD response at any site. Overall, the mean number of responsive sites was 2.7. Odds ratios were calculated considering treatment modality and high or low basal BMD as parameters, but no significant differences were found in the number of responders. It may be concluded that APD induces moderate lumbar and femoral neck bone mass gain in severe postmenopausal osteoporosis, whereas calcium alone leads to non significant variations, both findings being in agreement with reported data. Therefore, evaluated APD doses enhance mineralization in responsive sites alone, but fail to increase the total number of responders. Interestingly, responsive sites seem to be those relitively spared by the course of the disease.

  4. Decomposition of the factors that govern binding site preference in a multiple rotaxane.

    Science.gov (United States)

    Angelo, Joseph P; Sohlberg, Karl

    2009-06-18

    A particularly interesting class of multiple rotaxanes consists of complexes where one long shaft threads two rings. If the shaft contains three or more potential binding sites for the rings, multiple co-conformations are possible. Such a complex is a molecular topological analogue to an abacus. Here we address the question, how does strength of ring binding to the shaft vary with respect to position on the shaft? Previous studies have found that a shaft with three binding sites exhibits strongest ring binding at the center site. Here a five-binding-site shaft is studied. We employ a novel method to partition the total energy of the system into contributions from intercomponent binding and intracomponent distortion. The method uses the output of quantum mechanical electronic structure calculations to determine fitting parameters in a set of coupled equations. The solution of the equations yields the energy partitioning and reveals the influence of long-range intercomponent interactions.

  5. The seasonal factor at the prehistoric site of Shag River Mouth, New Zealand

    International Nuclear Information System (INIS)

    Higham, T.F.G.

    1997-01-01

    This paper addresses moa hunters' seasonality at the Shag River Mouth site. A two meters section in layer 4 of the SM/C: Dune site was left as a baulk in 1988 to enable the stratigraphic profile (∼2m) to be more carefully investigated. Within the baulk, detailed lensing and microstrata could be identified. Claassen (1991) has suggested that one of the most important variables in determining seasonal and prehistoric shell-bearing site formation more accurately is emphasizing finer stratigraphic resolution and more rigorous attention to retrieving midden components. At Shag River Mouth, seven sub-layers, or spits, were excavated within the 2m baulk to refine the precision of subsequent seasonal analyses and enable a detailed assessment of the components of each and their season of deposition. A variety of seasonal methods were utilised including 18 O analysis of blue mussel shell carbonate and growth ring analysis of estuarine bivalves. In addition, sagital otoliths of red cod excavated from the site were sectioned and the annual and seasonal growth rings formed during the fishes' life were analysed for seasonal information. This has enabled a detailed analysis of the seasonality of this discrete area of the Shag River Mouth site. The significance of the results for understanding the prehistoric seasonal round of activities within the site and its wider orbit is presented

  6. A ChIP-Seq benchmark shows that sequence conservation mainly improves detection of strong transcription factor binding sites.

    Directory of Open Access Journals (Sweden)

    Tony Håndstad

    Full Text Available BACKGROUND: Transcription factors are important controllers of gene expression and mapping transcription factor binding sites (TFBS is key to inferring transcription factor regulatory networks. Several methods for predicting TFBS exist, but there are no standard genome-wide datasets on which to assess the performance of these prediction methods. Also, it is believed that information about sequence conservation across different genomes can generally improve accuracy of motif-based predictors, but it is not clear under what circumstances use of conservation is most beneficial. RESULTS: Here we use published ChIP-seq data and an improved peak detection method to create comprehensive benchmark datasets for prediction methods which use known descriptors or binding motifs to detect TFBS in genomic sequences. We use this benchmark to assess the performance of five different prediction methods and find that the methods that use information about sequence conservation generally perform better than simpler motif-scanning methods. The difference is greater on high-affinity peaks and when using short and information-poor motifs. However, if the motifs are specific and information-rich, we find that simple motif-scanning methods can perform better than conservation-based methods. CONCLUSIONS: Our benchmark provides a comprehensive test that can be used to rank the relative performance of transcription factor binding site prediction methods. Moreover, our results show that, contrary to previous reports, sequence conservation is better suited for predicting strong than weak transcription factor binding sites.

  7. Nicotine stimulates nerve growth factor in lung fibroblasts through an NFκB-dependent mechanism.

    Directory of Open Access Journals (Sweden)

    Cherry Wongtrakool

    Full Text Available Airway hyperresponsiveness (AHR is classically found in asthma, and persistent AHR is associated with poor asthma control. Although airway smooth muscle (ASM cells play a critical pathophysiologic role in AHR, the paracrine contributions of surrounding cells such as fibroblasts to the contractile phenotype of ASM cells have not been examined fully. This study addresses the hypothesis that nicotine promotes a contractile ASM cell phenotype by stimulating fibroblasts to increase nerve growth factor (NGF secretion into the environment.Primary lung fibroblasts isolated from wild type and α7 nicotinic acetylcholine receptor (α7 nAChR deficient mice were treated with nicotine (50 µg/ml in vitro for 72 hours. NGF levels were measured in culture media and in bronchoalveolar lavage (BAL fluid from asthmatic, smoking and non-smoking subjects by ELISA. The role of the NFκB pathway in nicotine-induced NGF expression was investigated by measuring NFκB nuclear translocation, transcriptional activity, chromatin immunoprecipitation assays, and si-p65 NFκB knockdown. The ability of nicotine to stimulate a fibroblast-mediated, contractile ASM cell phenotype was confirmed by examining expression of contractile proteins in ASM cells cultured with fibroblast-conditioned media or BAL fluid.NGF levels were elevated in the bronchoalveolar lavage fluid of nicotine-exposed mice, current smokers, and asthmatic children. Nicotine increased NGF secretion in lung fibroblasts in vitro in a dose-dependent manner and stimulated NFκB nuclear translocation, p65 binding to the NGF promoter, and NFκB transcriptional activity. These responses were attenuated in α7 nAChR deficient fibroblasts and in wild type fibroblasts following NFκB inhibition. Nicotine-treated, fibroblast-conditioned media increased expression of contractile proteins in ASM cells.Nicotine stimulates NGF release by lung fibroblasts through α7 nAChR and NFκB dependent pathways. These novel findings

  8. Transcription factor binding site enrichment analysis predicts drivers of altered gene expression in nonalcoholic steatohepatitis

    Czech Academy of Sciences Publication Activity Database

    Lake, A.D.; Chaput, A.L.; Novák, Petr; Cherrington, N.J.; Smith, C.L.

    2016-01-01

    Roč. 122, December 15 (2016), s. 62-71 ISSN 0006-2952 Institutional support: RVO:60077344 Keywords : Transcription factor * Liver * Gene expression * Bioinformatics Subject RIV: CE - Biochemistry Impact factor: 4.581, year: 2016

  9. A case-control study of risk factors for surgical site infection after cesarean delivery in eastern Burkina Faso.

    Science.gov (United States)

    Kaboré, Boezemwendé; Soudouem, Georges; Seck, Ibrahima; Millogo, Tieba; Evariste Yaméogo, Wambi Maurice; Kouanda, Seni

    2016-11-01

    To identify the risk factors for surgical site infection after cesarean delivery in a rural area in eastern Burkina Faso. A matched case-control study was conducted in Fada N'Gourma Regional Hospital Center and the Diapaga Medical Center with Surgical Antenna using data from 2011-2014. A total of 99 cases of surgical site infection after cesarean delivery were included in the study. Each case was matched with a control patient similar for age, admission date, and facility where the cesarean took place. Risk factors were identified using conditional logistic regression. Multivariate analysis identified hyperthermia at admission (OR 2.37; P=0.035), the presence of caput succedaneum in newborns (OR 7.07; P=0.001), and difficult delivery (OR 3.69; P=0. 019) as risk factors for surgical site infection. Provision of quality prenatal care, use of the partograph during labor, and the responsiveness of health workers during labor can reduce surgical site infection after cesarean delivery. Copyright © 2016. Published by Elsevier Ireland Ltd.

  10. Prognostic factors for tube feeding dependence after curative (chemo-) radiation in head and neck cancer: A systematic review of literature.

    Science.gov (United States)

    Wopken, Kim; Bijl, Hendrik P; Langendijk, Johannes A

    2018-01-01

    Tube feeding dependence is a commonly observed debilitating side-effect of curative (chemo-) radiation in head and neck cancer patients that severely affects quality of life. Prevention of this side-effect can be obtained using advanced radiation techniques, such as IMRT. For radiotherapy treatment plan optimization, it has become increasingly important to develop prediction models that enable clinicians to predict the risk of tube feeding dependence for individual patients. To develop such a tool, information regarding the most relevant prognostic factors for tube feeding dependence is necessary. The primary aim of this systematic review, conducted according to PRISMA guidelines, was to identify prognostic factors that are consistently found to be associated with tube feeding dependence at ≥6months after treatment. The secondary aim was to identify prognostic factors found to be associated with tube feeding placement and use at factors for tube feeding dependence at ≥6months. The studies reported on patient and disease variables, treatment variables and DVH parameters. Two of these studies reported on a model for tube feeding dependence, one including DVH parameters. Additionally, 18 studies were identified that reported on prognostic factors for tube feeding placement and use at factors that were consistently associated with the risk of tube feeding dependence at ≥6months for head and neck cancer patients treated with (chemo-) radiotherapy were DVH parameters, including dose to the larynx, the pharyngeal constrictor muscle inferior and superior, and the dose to the contralateral parotid gland. Furthermore, advanced tumor and nodal stage, pretreatment weight loss, (concomitant) chemotherapy and prophylactic gastrostomy policy were prognostic for tube feeding dependence ≥6months. For tube feeding use at less than 6months, prognostic DVH parameters included dose and volume to the oral mucosa, dose to the contralateral submandibular gland, and also dose to

  11. The transcription factor ABI4 Is required for the ascorbic acid-dependent regulation of growth and regulation of jasmonate-dependent defense signaling pathways in Arabidopsis.

    Science.gov (United States)

    Kerchev, Pavel I; Pellny, Till K; Vivancos, Pedro Diaz; Kiddle, Guy; Hedden, Peter; Driscoll, Simon; Vanacker, Hélène; Verrier, Paul; Hancock, Robert D; Foyer, Christine H

    2011-09-01

    Cellular redox homeostasis is a hub for signal integration. Interactions between redox metabolism and the ABSCISIC ACID-INSENSITIVE-4 (ABI4) transcription factor were characterized in the Arabidopsis thaliana vitamin c defective1 (vtc1) and vtc2 mutants, which are defective in ascorbic acid synthesis and show a slow growth phenotype together with enhanced abscisic acid (ABA) levels relative to the wild type (Columbia-0). The 75% decrease in the leaf ascorbate pool in the vtc2 mutants was not sufficient to adversely affect GA metabolism. The transcriptome signatures of the abi4, vtc1, and vtc2 mutants showed significant overlap, with a large number of transcription factors or signaling components similarly repressed or induced. Moreover, lincomycin-dependent changes in LIGHT HARVESTING CHLOROPHYLL A/B BINDING PROTEIN 1.1 expression were comparable in these mutants, suggesting overlapping participation in chloroplast to nucleus signaling. The slow growth phenotype of vtc2 was absent in the abi4 vtc2 double mutant, as was the sugar-insensitive phenotype of the abi4 mutant. Octadecanoid derivative-responsive AP2/ERF-domain transcription factor 47 (ORA47) and AP3 (an ABI5 binding factor) transcripts were enhanced in vtc2 but repressed in abi4 vtc2, suggesting that ABI4 and ascorbate modulate growth and defense gene expression through jasmonate signaling. We conclude that low ascorbate triggers ABA- and jasmonate-dependent signaling pathways that together regulate growth through ABI4. Moreover, cellular redox homeostasis exerts a strong influence on sugar-dependent growth regulation.

  12. Networks of enzymatically oxidized membrane lipids support calcium-dependent coagulation factor binding to maintain hemostasis.

    Science.gov (United States)

    Lauder, Sarah N; Allen-Redpath, Keith; Slatter, David A; Aldrovandi, Maceler; O'Connor, Anne; Farewell, Daniel; Percy, Charles L; Molhoek, Jessica E; Rannikko, Sirpa; Tyrrell, Victoria J; Ferla, Salvatore; Milne, Ginger L; Poole, Alastair W; Thomas, Christopher P; Obaji, Samya; Taylor, Philip R; Jones, Simon A; de Groot, Phillip G; Urbanus, Rolf T; Hörkkö, Sohvi; Uderhardt, Stefan; Ackermann, Jochen; Vince Jenkins, P; Brancale, Andrea; Krönke, Gerhard; Collins, Peter W; O'Donnell, Valerie B

    2017-11-28

    Blood coagulation functions as part of the innate immune system by preventing bacterial invasion, and it is critical to stopping blood loss (hemostasis). Coagulation involves the external membrane surface of activated platelets and leukocytes. Using lipidomic, genetic, biochemical, and mathematical modeling approaches, we found that enzymatically oxidized phospholipids (eoxPLs) generated by the activity of leukocyte or platelet lipoxygenases (LOXs) were required for normal hemostasis and promoted coagulation factor activities in a Ca 2+ - and phosphatidylserine (PS)-dependent manner. In wild-type mice, hydroxyeicosatetraenoic acid-phospholipids (HETE-PLs) enhanced coagulation and restored normal hemostasis in clotting-deficient animals genetically lacking p12-LOX or 12/15-LOX activity. Murine platelets generated 22 eoxPL species, all of which were missing in the absence of p12-LOX. Humans with the thrombotic disorder antiphospholipid syndrome (APS) had statistically significantly increased HETE-PLs in platelets and leukocytes, as well as greater HETE-PL immunoreactivity, than healthy controls. HETE-PLs enhanced membrane binding of the serum protein β2GP1 (β2-glycoprotein 1), an event considered central to the autoimmune reactivity responsible for APS symptoms. Correlation network analysis of 47 platelet eoxPL species in platelets from APS and control subjects identified their enzymatic origin and revealed a complex network of regulation, with the abundance of 31 p12-LOX-derived eoxPL molecules substantially increased in APS. In summary, circulating blood cells generate networks of eoxPL molecules, including HETE-PLs, which change membrane properties to enhance blood coagulation and contribute to the excessive clotting and immunoreactivity of patients with APS. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  13. Alcohol impairment of saccadic and smooth pursuit eye movements: impact of risk factors for alcohol dependence.

    Science.gov (United States)

    Roche, Daniel J O; King, Andrea C

    2010-09-01

    While persons at risk for alcohol dependence by virtue of heavy drinking patterns or family history (FH) of alcohol use disorders have exhibited differential alcohol responses on a variety of measures, few studies have examined alcohol's effects on eye movements in these subgroups. The purpose of this study was to (1) conduct a placebo-controlled, dose-ranging study of alcohol's effects on eye movements and (2) examine the impact of these risk factors on oculomotor response to alcohol. A within-subject, double-blind laboratory study was conducted in N = 138 heavy (HD; n = 78) and light social drinkers (LD; n = 60) with self-reported positive (FH+) or negative (FH-) family history. Subjects participated in three laboratory sessions in which they consumed a beverage containing a high (0.8 g/kg) or low (0.4 g/kg) dose of alcohol or placebo. Smooth pursuit, pro-saccadic, and anti-saccadic eye movements were recorded before and at two intervals after alcohol consumption. Alcohol significantly impaired smooth pursuit gain and pro- and anti-saccade latency, velocity, and accuracy in a dose and time specific matter. HD and LD showed similar impairment on smooth pursuit gain and anti-saccade measures, but HD were less impaired in pro-saccade latency, velocity, and accuracy. FH+ and FH- subjects were equally impaired in nearly all pro- and anti-saccade measures, but FH+ were less impaired in smooth pursuit gain. In sum, alcohol produced systematic impairment on oculomotor functioning, even at a non-intoxicating dose. Furthermore, high- and low-risk drinkers may be vulnerable to select performance deficits relative to eye movement task.

  14. Spectral dependence of aerosol light absorption at an urban and a remote site over the Tibetan Plateau.

    Science.gov (United States)

    Zhu, Chong-Shu; Cao, Jun-Ji; Hu, Ta-Feng; Shen, Zhen-Xing; Tie, Xue-Xi; Huang, Hong; Wang, Qi-Yuan; Huang, Ru-Jin; Zhao, Zhu-Zi; Močnik, Griša; Hansen, Anthony D A

    2017-07-15

    We present a study of aerosol light absorption by using a 7-wavelength Aethalometer model AE33 at an urban site (Lhasa) and a remote site (Lulang) in the Tibetan Plateau. Approximately 5 times greater aerosol absorption values were observed at Lhasa (53±46Mm -1 at 370nm and 20±18Mm -1 at 950nm, respectively) in comparison to Lulang (15±19Mm -1 at 370nm and 4±5Mm -1 at 950nm, respectively). Black carbon (BC) was the dominant light absorbing aerosol component at all wavelengths. The brown carbon (BrC) absorption at 370nm is 32±15% of the total aerosol absorption at Lulang, whereas it is 8±6% at Lhasa. Higher value of absorption Ångström exponent (AAE, 370-950nm) was obtained for Lulang (1.18) than that for Lhasa (1.04) due to the presence of BrC. The AAEs (370-950nm) of BrC were directly extracted at Lulang (3.8) and Lhasa (3.3). The loading compensation parameters (k) increased with wavelengths for both sites, and lower values were obtained at Lulang than those observed at Lhasa for all wavelengths. This study underlines the relatively high percentage of BrC absorption contribution in remote area compared to urban site over the Tibetan Plateau. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Reduction of stem growth and site dependency of leaf injury in Massachusetts black cherries exhibiting ozone symptoms

    International Nuclear Information System (INIS)

    Vollenweider, P.; Woodcock, H.; Kelty, M.J.; Hofer, R.-M.

    2003-01-01

    Ozone symptomatic trees had a reduced stem growth and symptom expression was enhanced on moister and better growing stands. - Leaf ozone symptoms in natural ecosystems are increasingly reported but ozone effects on tree growth and the mediation of site conditions are still little documented. This study tests two hypotheses: (1) leaf injury in black cherry is associated with decline in radial growth, (2) symptoms are more prevalent on mesic sites. On sites supporting black cherry across Massachusetts, tree growth and leaf ozone injury were surveyed in 1996 using a randomized plot network established in the 1960s. Forty-seven percent of 120 trees sampled for ozone symptoms were symptomatic with generally low levels of injury. Over a 31-year period symptomatic trees had 28% lower stem growth rates than asymptomatic trees. Ozone symptom expression was enhanced in well growing stands on moister, cooler and more elevated sites. Ozone appeared to increase environmental stress and had a more pronounced effect on growth in better growing black cherry stands. This complicates management decisions as thinning increases growth and moisture availability

  16. Temperature-dependent thermal conductivities of one-dimensional nonlinear Klein-Gordon lattices with a soft on-site potential.

    Science.gov (United States)

    Yang, Linlin; Li, Nianbei; Li, Baowen

    2014-12-01

    The temperature-dependent thermal conductivities of one-dimensional nonlinear Klein-Gordon lattices with soft on-site potential (soft-KG) are investigated systematically. Similarly to the previously studied hard-KG lattices, the existence of renormalized phonons is also confirmed in soft-KG lattices. In particular, the temperature dependence of the renormalized phonon frequency predicted by a classical field theory is verified by detailed numerical simulations. However, the thermal conductivities of soft-KG lattices exhibit the opposite trend in temperature dependence in comparison with those of hard-KG lattices. The interesting thing is that the temperature-dependent thermal conductivities of both soft- and hard-KG lattices can be interpreted in the same framework of effective phonon theory. According to the effective phonon theory, the exponents of the power-law dependence of the thermal conductivities as a function of temperature are only determined by the exponents of the soft or hard on-site potentials. These theoretical predictions are consistently verified very well by extensive numerical simulations.

  17. Quantitative in vivo Analyses Reveal Calcium-dependent Phosphorylation Sites and Identifies a Novel Component of the Toxoplasma Invasion Motor Complex

    Science.gov (United States)

    Nebl, Thomas; Prieto, Judith Helena; Kapp, Eugene; Smith, Brian J.; Williams, Melanie J.; Yates, John R.; Cowman, Alan F.; Tonkin, Christopher J.

    2011-01-01

    Apicomplexan parasites depend on the invasion of host cells for survival and proliferation. Calcium-dependent signaling pathways appear to be essential for micronemal release and gliding motility, yet the target of activated kinases remains largely unknown. We have characterized calcium-dependent phosphorylation events during Toxoplasma host cell invasion. Stimulation of live tachyzoites with Ca2+-mobilizing drugs leads to phosphorylation of numerous parasite proteins, as shown by differential 2-DE display of 32[P]-labeled protein extracts. Multi-dimensional Protein Identification Technology (MudPIT) identified ∼546 phosphorylation sites on over 300 Toxoplasma proteins, including 10 sites on the actomyosin invasion motor. Using a Stable Isotope of Amino Acids in Culture (SILAC)-based quantitative LC-MS/MS analyses we monitored changes in the abundance and phosphorylation of the invasion motor complex and defined Ca2+-dependent phosphorylation patterns on three of its components - GAP45, MLC1 and MyoA. Furthermore, calcium-dependent phosphorylation of six residues across GAP45, MLC1 and MyoA is correlated with invasion motor activity. By analyzing proteins that appear to associate more strongly with the invasion motor upon calcium stimulation we have also identified a novel 15-kDa Calmodulin-like protein that likely represents the MyoA Essential Light Chain of the Toxoplasma invasion motor. This suggests that invasion motor activity could be regulated not only by phosphorylation but also by the direct binding of calcium ions to this new component. PMID:21980283

  18. Sources identification of the atmospheric aerosol at urban and suburban sites in Indonesia by positive matrix factorization

    International Nuclear Information System (INIS)

    Santoso, Muhayatun; Hopke, Philip K.; Hidayat, Achmad; Diah Dwiana L

    2008-01-01

    Samples of fine and coarse fractions of airborne particulate matter were collected in Indonesia (west central Java) at an urban site in Bandung and in suburban Lembang from January 2002 to December 2004. The samples were collected using a Gent stacked filter sampler in two size fractions of 2.5-10 mass at both sites comes from soil dust and road dust. The biomass burning factor contributes about 40% of the PM 2.5 mass in case of suburban Lembang and about 20% in urban Bandung

  19. Evaluation of risk factors in patients with vitamin K-dependent coagulopathy presumed to be caused by exposure to brodifacoum

    OpenAIRE

    Lee, Hee-Jeong; You, Mi-Ra; Moon, Woo-Ram; Sul, Hyoung; Chung, Choon-Hae; Park, Chi-Young; Park, Sang-Gon

    2014-01-01

    Background/Aims Recently, many cases of vitamin K-dependent coagulopathy of unknown origin have been reported. Such patients lack any relevant family history and have no systemic disease, raising suspicion of superwarfarin intoxication. We evaluated individual risk factors causing coagulopathy and hemorrhagic symptoms in patients with suspected superwarfarin intoxication. In addition, we determined how to effectively treat vitamin K-dependent coagulopathy caused by suspected superwarfarin int...

  20. Protein oxidation mediated by heme-induced active site conversion specific for heme-regulated transcription factor, iron response regulator.

    Science.gov (United States)

    Kitatsuji, Chihiro; Izumi, Kozue; Nambu, Shusuke; Kurogochi, Masaki; Uchida, Takeshi; Nishimura, Shin-ichiro; Iwai, Kazuhiro; O'Brian, Mark R; Ikeda-Saito, Masao; Ishimori, Koichiro

    2016-01-05

    The Bradyrhizobium japonicum transcriptional regulator Irr (iron response regulator) is a key regulator of the iron homeostasis, which is degraded in response to heme binding via a mechanism that involves oxidative modification of the protein. Here, we show that heme-bound Irr activates O2 to form highly reactive oxygen species (ROS) with the "active site conversion" from heme iron to non-heme iron to degrade itself. In the presence of heme and reductant, the ROS scavenging experiments show that Irr generates H2O2 from O2 as found for other hemoproteins, but H2O2 is less effective in oxidizing the peptide, and further activation of H2O2 is suggested. Interestingly, we find a time-dependent decrease of the intensity of the Soret band and appearance of the characteristic EPR signal at g = 4.3 during the oxidation, showing the heme degradation and the successive formation of a non-heme iron site. Together with the mutational studies, we here propose a novel "two-step self-oxidative modification" mechanism, during which O2 is activated to form H2O2 at the heme regulatory motif (HRM) site and the generated H2O2 is further converted into more reactive species such as ·OH at the non-heme iron site in the His-cluster region formed by the active site conversion.

  1. Factors of site selection for nuclear power plants in selected industrial states

    International Nuclear Information System (INIS)

    Hoffmann, L.; Obermair, G.; Ringler, W.; Romahn, B.; Sanders, H.

    1978-01-01

    The range of the tasks within the project consists of working out an optimal catalogue of criteria for the site selection for nuclear power plants; establishing a structured documentation system for the criteria and licensing procedures used by selected industrial countries when selecting sites for nuclear power plants; analyzing and evaluating the documented material with the aim of supplying the basis for decisions concerning land use. The tasks are being realized within a technological ring of data (for the period until 1990, reactor types, cooling, power-heat coupling, special sites, block sizes, local concentration) and a set politico-economical ring of data for the following countries: F.R. Germany, Belgium, Switzerland, Great Britain, Sweden, Denmark, Austria, France, Netherlands, USA, Japan, Yougoslavia. (HP) [de

  2. Site of ADP-ribosylation and the RNA-binding site are situated in different domains of the elongation factor EF-2

    International Nuclear Information System (INIS)

    Davydova, E.K.

    1987-01-01

    One of the proteins participating in the process of elongation of polypeptide chains - elongation factor 2 (EF-2) - can be ADP-ribosylated at a unique amino acid residue - diphthamide. Since the ADP-ribosylation of EF-2 at dipthamide leads to a loss of affinity of the factor for RNA while the presence of RNA inhibits the ADP-ribosylation reaction, it seemed probable to the authors that diphthamide participated directly in the binding of EF-2 to DNA. The experiments presented in this article showed that this was not the case: diphthamide and the RNA-binding site are situated on different domains of EF-2. Thus, ADP-ribosylation of factor EF-2 in one domain leads to a loss of the ability to bind to RNA in the other. The authors investigated the mutual arrangement of diphthamide and the RNA-binding site on the EF-2 molecule by preparing a factor from rabbit reticulocytes and subjecting it to proteolytic digestion with elastase. The factor was incubated with elastase for 15 min at 37 0 C at an enzyme:substrate ratio of 1:100 in buffer solution containing 20 mM Tris-HCl, pH 7.6, 10 mM KCl, 1 mM MgCl 2 , and 2 mM dithiothreitol. The reaction was stopped by adding para-methylsulfonyl fluoride to 50 micro-M. The authors obtained a preparation as a result of proteolysis and applied it on a column with RNA-Sepharose and separated into two fractions: RNA-binding and without affinity for RNA. The initial preparation and its fractions were subjected to exhaustive ADP-ribosylation in the presence of diphtheria toxin and [U- 14 C] nicotinaide adenine dinucleotide ([ 14 C]NAD) (296 mCi/mmole). The samples were analyzed electrophoretically in a polyacrylamide gel gradient in the presence of sodium dodecyl sulfate. For the detection of [ 14 C] ADP-ribosylated components, the gels were dried and exposed with RM-V x-ray film

  3. Identification of a functional hepatocyte nuclear factor 4 binding site in the neutral ceramidase promoter

    DEFF Research Database (Denmark)

    Maltesen, Henrik R; Troelsen, Jesper T; Olsen, Jørgen

    2010-01-01

    in ceramide digestion. It was the purpose of the present work to experimentally verify the functional importance of a HNF-4a binding site predicted by bioinformatic analysis to be present in the Asah2 promoter. Using supershift analysis, HNF-4a overexpression, and HNF-4a knockdown experiments it was confirmed...... that the predicted HNF-4a binding site identified in the Asah2 promoter is functional. The results support the hypothesis that HNF-4a might be important for intestinal glycolipid metabolism....

  4. Investigating the factor structure of the Illness Perception Questionnaire-revised for substance dependence among injecting drug users in China.

    Science.gov (United States)

    Mo, Phoenix K H; Lau, Joseph T F; Cheng, Kit Man; Mak, Winnie W S; Gu, Jing; Wu, Anise M S; Li, Jinghua

    2015-03-01

    The Illness Perception Questionnaire-Revised (IPQ-R) has commonly been used to measure illness representations of various diseases. The present study examined whether the original factor structure of the IPQ-R could be confirmed or a new structure could be established on substance dependence among injecting drug users (IDU) in China. A total of 257 IDU completed the 38-item IPQ-R on substance dependence. Results of confirmatory factor analysis (CFA) showed that the 7-factor structure as proposed by the original IPQ-R reported poor goodness-of-fit statistics. Although removal of 12 items improved the model fit, the goodness-of-fit statistics were still below acceptable standards. Furthermore, factors obtained from the exploratory factor analysis (EFA) of the IPQ-R were not interpretable. The CFA found that the original IPQ-R factor structure fit the data poorly. Factors derived from EFA were also not interpretable. Use of the IPQ-R for assessment of illness representations of substance dependence among IDU in China is cautioned until further validation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. 9p21.3 Coronary Artery Disease Risk Variants Disrupt TEAD Transcription Factor-Dependent Transforming Growth Factor β Regulation of p16 Expression in Human Aortic Smooth Muscle Cells.

    Science.gov (United States)

    Almontashiri, Naif A M; Antoine, Darlène; Zhou, Xun; Vilmundarson, Ragnar O; Zhang, Sean X; Hao, Kennedy N; Chen, Hsiao-Huei; Stewart, Alexandre F R

    2015-11-24

    The mechanism whereby the 9p21.3 locus confers risk for coronary artery disease remains incompletely understood. Risk alleles are associated with reduced expression of the cell cycle suppressor genes CDKN2A (p16 and p14) and CDKN2B (p15) and increased vascular smooth muscle cell proliferation. We asked whether risk alleles disrupt transcription factor binding to account for this effect. A bioinformatic screen was used to predict which of 59 single nucleotide polymorphisms at the 9p21.3 locus disrupt (or create) transcription factor binding sites. Electrophoretic mobility shift and luciferase reporter assays examined the binding and functionality of the predicted regulatory sequences. Primary human aortic smooth muscle cells (HAoSMCs) were genotyped for 9p21.3, and HAoSMCs homozygous for the risk allele showed reduced p15 and p16 levels and increased proliferation. rs10811656 and rs4977757 disrupted functional TEF-1 TEC1 AbaA domain (TEAD) transcription factor binding sites. TEAD3 and TEAD4 overexpression induced p16 in HAoSMCs homozygous for the nonrisk allele, but not for the risk allele. Transforming growth factor β, known to activate p16 and also to interact with TEAD factors, failed to induce p16 or to inhibit proliferation of HAoSMCs homozygous for the risk allele. Knockdown of TEAD3 blocked transforming growth factor β-induced p16 mRNA and protein expression, and dual knockdown of TEAD3 and TEAD4 markedly reduced p16 expression in heterozygous HAoSMCs. Here, we identify a novel mechanism whereby sequences at the 9p21.3 risk locus disrupt TEAD factor binding and TEAD3-dependent transforming growth factor β induction of p16 in HAoSMCs. This mechanism accounts, in part, for the 9p21.3 coronary artery disease risk. © 2015 American Heart Association, Inc.

  6. Fibroblast growth factor-mediated proliferation of central nervous system precursors depends on endogenous production of insulin-like growth factor I

    International Nuclear Information System (INIS)

    Drago, J.; Murphy, M.; Carroll, S.M.; Harvey, R.P.; Bartlett, P.F.

    1991-01-01

    Fibroblast growth factor stimulates proliferation and subsequent differentiation of precursor cells isolated from the neuroepithelium of embryonic day 10 mice in vitro. Here we show that fibroblast growth factor-induced proliferation is dependent on the presence of insulin-like growth factors (IGFs) and that IGF-I is endogenously produced by the neuroepithelial cells. Blocking of endogenous IGF-I activity with anti-IGF-I antibodies results in complete inhibition of fibroblast growth factor-mediated proliferation and in cell death. IGF-I alone acts as a survival agent. These observations correlate with the detection of transcripts for IGF-I and basic fibroblast growth factor in freshly isolated neuroepithelium and are consistent with an autocrine action of these factors in early brain development in vivo

  7. Modulators of drug dependence phenomena : factors affecting morphine withdrawal syndrome and cocaine-intake in rodents

    NARCIS (Netherlands)

    S.L.T. Cappendijk (Susanne)

    1995-01-01

    textabstractThis thesis compiles the experimental studies on several drugs, which modulate drug dependence phenomena in rodents. The main part of the studies is related to the morphine withdrawal (chapters 3-7), while a minor part is dealing with cocaine psychic dependence (chapter 9).

  8. Supervision on Site: A Critical Factor in the Online Facilitated Internship

    Science.gov (United States)

    Dotson, Kaye B.; Bian, Hui

    2013-01-01

    Online education is increasingly prevalent in graduate schools of teacher education. Questions arise, however, as to the effectiveness of the online facilitated graduate internship. This article examines perspectives of librarian site supervisors within online supported internships. Perspectives in regard to program support and self-perceived…

  9. Impact of personality traits and demographic factors on relationship to deal sites

    DEFF Research Database (Denmark)

    Sudzina, Frantisek; Pavlicek, Antonin

    2017-01-01

    . Big Five Inventory framework is used for personality traits. The research was conducted in the Czech Republic. With regards to the findings, city of origin has a significant effect, and openness to experience a borderline significant effect on the relationship to deal sites....

  10. Two behavioural indicators of dependency and the Five-Factor Model of personality.

    Science.gov (United States)

    Rubinstein, Gidi

    2007-09-01

    Residence with parents and unemployment during studies were chosen as the two behavioural indicators of dependency among 601 undergraduate students. Students completed a demographic questionnaire, Costa and McCrae's (1992) NEO-FFI and Beck, Davis, and Freeman's (1990) Typical Beliefs of DPD. Unemployed students, living with their parents, were found to be significantly more dependent, neurotic and agreeable and less extraverted, conscientious and open than employed students who did not reside with their parents. Residing with parents during one's studies was the strongest predictor of dependency and neuroticism, followed by unemployment. Unemployed male students, who resided with their parents, were the most dependent, neurotic and agreeable and the least open, extraverted and conscientious group. The relationship between dependency and the Big Five is also discussed.

  11. Activation of the Arabidopsis membrane-bound transcription factor bZIP28 is mediated by site-2 protease, but not site-1 protease.

    Science.gov (United States)

    Iwata, Yuji; Ashida, Makoto; Hasegawa, Chisa; Tabara, Kazuki; Mishiba, Kei-Ichiro; Koizumi, Nozomu

    2017-08-01

    The unfolded protein response (UPR) is a homeostatic cellular response conserved in eukaryotic cells to alleviate the accumulation of unfolded proteins in the endoplasmic reticulum (ER). Arabidopsis bZIP28 is a membrane-bound transcription factor activated by proteolytic cleavage in response to ER stress, thereby releasing its cytosolic portion containing the bZIP domain from the membrane to translocate into the nucleus where it induces the transcription of genes encoding ER-resident molecular chaperones and folding enzymes. It has been widely recognized that the proteolytic activation of bZIP28 is mediated by the sequential cleavage of site-1 protease (S1P) and site-2 protease (S2P). In the present study we provide evidence that bZIP28 protein is cleaved by S2P, but not by S1P. We demonstrated that wild-type and s1p mutant plants produce the active, nuclear form of bZIP28 in response to the ER stress inducer tunicamycin. In contrast, tunicamycin-treated s2p mutants do not accumulate the active, nuclear form of bZIP28. Consistent with these observations, s2p mutants, but not s1p mutants, exhibited a defective transcriptional response of ER stress-responsive genes and significantly higher sensitivity to tunicamycin. Interestingly, s2p mutants accumulate two membrane-bound bZIP28 fragments with a shorter ER lumen-facing C-terminal domain. Importantly, the predicted cleavage sites are located far from the canonical S1P recognition motif previously described. We propose that ER stress-induced proteolytic activation of bZIP28 is mediated by the sequential actions of as-yet-unidentified protease(s) and S2P, and does not require S1P. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  12. Spatial Dependence and Heterogeneity in Bayesian Factor Analysis : A Cross-National Investigation of Schwartz Values

    NARCIS (Netherlands)

    Stakhovych, Stanislav; Bijmolt, Tammo H. A.; Wedel, Michel

    2012-01-01

    In this article, we present a Bayesian spatial factor analysis model. We extend previous work on confirmatory factor analysis by including geographically distributed latent variables and accounting for heterogeneity and spatial autocorrelation. The simulation study shows excellent recovery of the

  13. Structure of an N276-Dependent HIV-1 Neutralizing Antibody Targeting a Rare V5 Glycan Hole Adjacent to the CD4 Binding Site

    Energy Technology Data Exchange (ETDEWEB)

    Wibmer, Constantinos Kurt; Gorman, Jason; Anthony, Colin S.; Mkhize, Nonhlanhla N.; Druz, Aliaksandr; York, Talita; Schmidt, Stephen D.; Labuschagne, Phillip; Louder, Mark K.; Bailer, Robert T.; Karim, Salim S. Abdool; Mascola, John R.; Williamson, Carolyn; Moore, Penny L.; Kwong, Peter D.; Morris, Lynn (NHLS-South Africa); (NIH); (Witwatersrand); (KwaZulu-Natal)

    2016-08-31

    ABSTRACT

    All HIV-1-infected individuals develop strain-specific neutralizing antibodies to their infecting virus, which in some cases mature into broadly neutralizing antibodies. Defining the epitopes of strain-specific antibodies that overlap conserved sites of vulnerability might provide mechanistic insights into how broadly neutralizing antibodies arise. We previously described an HIV-1 clade C-infected donor, CAP257, who developed broadly neutralizing plasma antibodies targeting an N276 glycan-dependent epitope in the CD4 binding site. The initial CD4 binding site response potently neutralized the heterologous tier 2 clade B viral strain RHPA, which was used to design resurfaced gp120 antigens for single-B-cell sorting. Here we report the isolation and structural characterization of CAP257-RH1, an N276 glycan-dependent CD4 binding site antibody representative of the early CD4 binding site plasma response in donor CAP257. The cocrystal structure of CAP257-RH1 bound to RHPA gp120 revealed critical interactions with the N276 glycan, loop D, and V5, but not with aspartic acid 368, similarly to HJ16 and 179NC75. The CAP257-RH1 monoclonal antibody was derived from the immunoglobulin-variable IGHV3-33 and IGLV3-10 genes and neutralized RHPA but not the transmitted/founder virus from donor CAP257. Its narrow neutralization breadth was attributed to a binding angle that was incompatible with glycosylated V5 loops present in almost all HIV-1 strains, including the CAP257 transmitted/founder virus. Deep sequencing of autologous CAP257 viruses, however, revealed minority variants early in infection that lacked V5 glycans. These glycan-free V5 loops are unusual holes in the glycan shield that may have been necessary for initiating this N276 glycan-dependent CD4 binding site B-cell lineage.

    IMPORTANCEThe conserved CD4 binding site on gp120 is a major target for HIV-1 vaccine design, but key events in the elicitation and maturation of

  14. Structure of an N276-Dependent HIV-1 Neutralizing Antibody Targeting a Rare V5 Glycan Hole Adjacent to the CD4 Binding Site.

    Science.gov (United States)

    Wibmer, Constantinos Kurt; Gorman, Jason; Anthony, Colin S; Mkhize, Nonhlanhla N; Druz, Aliaksandr; York, Talita; Schmidt, Stephen D; Labuschagne, Phillip; Louder, Mark K; Bailer, Robert T; Abdool Karim, Salim S; Mascola, John R; Williamson, Carolyn; Moore, Penny L; Kwong, Peter D; Morris, Lynn

    2016-11-15

    All HIV-1-infected individuals develop strain-specific neutralizing antibodies to their infecting virus, which in some cases mature into broadly neutralizing antibodies. Defining the epitopes of strain-specific antibodies that overlap conserved sites of vulnerability might provide mechanistic insights into how broadly neutralizing antibodies arise. We previously described an HIV-1 clade C-infected donor, CAP257, who developed broadly neutralizing plasma antibodies targeting an N276 glycan-dependent epitope in the CD4 binding site. The initial CD4 binding site response potently neutralized the heterologous tier 2 clade B viral strain RHPA, which was used to design resurfaced gp120 antigens for single-B-cell sorting. Here we report the isolation and structural characterization of CAP257-RH1, an N276 glycan-dependent CD4 binding site antibody representative of the early CD4 binding site plasma response in donor CAP257. The cocrystal structure of CAP257-RH1 bound to RHPA gp120 revealed critical interactions with the N276 glycan, loop D, and V5, but not with aspartic acid 368, similarly to HJ16 and 179NC75. The CAP257-RH1 monoclonal antibody was derived from the immunoglobulin-variable IGHV3-33 and IGLV3-10 genes and neutralized RHPA but not the transmitted/founder virus from donor CAP257. Its narrow neutralization breadth was attributed to a binding angle that was incompatible with glycosylated V5 loops present in almost all HIV-1 strains, including the CAP257 transmitted/founder virus. Deep sequencing of autologous CAP257 viruses, however, revealed minority variants early in infection that lacked V5 glycans. These glycan-free V5 loops are unusual holes in the glycan shield that may have been necessary for initiating this N276 glycan-dependent CD4 binding site B-cell lineage. The conserved CD4 binding site on gp120 is a major target for HIV-1 vaccine design, but key events in the elicitation and maturation of different antibody lineages to this site remain elusive

  15. Growth factor-induced contraction of human bronchial smooth muscle is Rho-kinase-dependent

    NARCIS (Netherlands)

    Gosens, Reinout; Schaafsma, D.; Grootte Bromhaar, M.M; Vrugt, B.; Zaagsma, Hans; Meurs, Herman; Nelemans, Herman

    2004-01-01

    Growth factors have been implicated in the pathophysiology of asthma. However, the putative effects of these growth factors on human airway smooth muscle tone are still largely unknown. We performed contraction experiments using human bronchial smooth muscle ring preparations. The growth factor

  16. Monitoring human factor risk characteristics at nuclear legacy sites in northwest Russia in support of radiation safety regulation.

    Science.gov (United States)

    Scheblanov, V Y; Sneve, M K; Bobrov, A F

    2012-12-01

    This paper describes research aimed at improving regulatory supervision of radiation safety during work associated with the management of spent nuclear fuel and radioactive waste at legacy sites in northwest Russia through timely identification of employees presenting unfavourable human factor risk characteristics. The legacy sites of interest include sites of temporary storage now operated by SevRAO on behalf of Rosatom. The sites were previously operational bases for servicing nuclear powered submarines and are now subject to major remediation activities. These activities include hazardous operations for recovery of spent nuclear fuel and radioactive waste from sub-optimal storage conditions. The paper describes the results of analysis of methods, procedures, techniques and informational issues leading to the development of an expert-diagnostic information system for monitoring of workers involved in carrying out the most hazardous operations. The system serves as a tool for human factor and professional reliability risk monitoring and has been tested in practical working environments and implemented as part of regulatory supervision. The work has been carried out by the Burnasyan Federal Medical Biophysical Center, within the framework of the regulatory cooperation programme between the Federal Medical-Biological Agency of Russia and the Norwegian Radiation Protection Authority.

  17. Monitoring human factor risk characteristics at nuclear legacy sites in northwest Russia in support of radiation safety regulation

    International Nuclear Information System (INIS)

    Scheblanov, V Y; Bobrov, A F; Sneve, M K

    2012-01-01

    This paper describes research aimed at improving regulatory supervision of radiation safety during work associated with the management of spent nuclear fuel and radioactive waste at legacy sites in northwest Russia through timely identification of employees presenting unfavourable human factor risk characteristics. The legacy sites of interest include sites of temporary storage now operated by SevRAO on behalf of Rosatom. The sites were previously operational bases for servicing nuclear powered submarines and are now subject to major remediation activities. These activities include hazardous operations for recovery of spent nuclear fuel and radioactive waste from sub-optimal storage conditions. The paper describes the results of analysis of methods, procedures, techniques and informational issues leading to the development of an expert-diagnostic information system for monitoring of workers involved in carrying out the most hazardous operations. The system serves as a tool for human factor and professional reliability risk monitoring and has been tested in practical working environments and implemented as part of regulatory supervision. The work has been carried out by the Burnasyan Federal Medical Biophysical Center, within the framework of the regulatory cooperation programme between the Federal Medical–Biological Agency of Russia and the Norwegian Radiation Protection Authority. (paper)

  18. Factors Related to Initiating Interpersonal Contacts on Internet Dating Sites: A View From the Social Exchange Theory

    Directory of Open Access Journals (Sweden)

    Rivka Shtatfeld

    2009-12-01

    Full Text Available The purpose of this study was to identify factors that influence dating-site users to initiate contact with potential romantic partners. The study was carried out by observing online behaviors and analyzing the profiles and authentic messages of these users (N = 106 over seven months. Contacts made by and with the research participants were analyzed in terms of the relationships between initiators‘ and receivers‘ demographic variables (marital status, age, level of education, income, writing skills, and stated physical appearance. In addition, the relationship between contacting partners and site accessibility was examined. The findings revealed that dating-site users initiated contact primarily with those having a similar marital status or slightly better characteristics (income, education, writing skills. In regard to writing skills, it was found that skilled writers attracted more contacts than did less skilled writers. However, the factor that was found to be most significantly related to initiating contact was the length of time that elapsed from last connection to the site, which implies the perceived accessibility of potential romantic partners. The findings were explained in terms of the Social Exchange Theory: people are attracted to those who grant them rewards.

  19. Obstacle factors and overcoming plans of public communication: With an emphasis on radioactive waste disposal facility siting

    International Nuclear Information System (INIS)

    Yoo, Hae-Woon; Oh, Chang-Taeg

    1996-01-01

    Korea is confronting a serious social conflict, which is phenomenon of local residents reaction to radioactive waste disposal facility. This phenomenon is traced back to the reason that the project sponsors and local residents do not communicate sufficiently each other. Accordingly, in order to overcome local residents' reaction to radioactive waste disposal facility siting effectively, it is absolutely necessary to consider the way of solutions and strategies with regard to obstacle factors for public communication. In this content, this study will review three cases (An-myon Island, Gul-up Island, Yang-yang) on local residents reaction to facility siting. As a result of analysis, authoritarian behavior of project sponsors, local stigma, risk, antinuclear activities of environmental group, failures in siting the radioactive waste disposal facility, etc. has negative impact on public communication of the radioactive waste disposal facility siting. In this study, 5 strategies (reform of project sponsor's authoritarianism, incentive offer, strengthening PA activities, more active talks with environmental groups, promoting credibility of project sponsors) arc suggested to cope with obstacle factors of public communication

  20. Fluorescence resonance energy transfer on the voltage-dependent sodium channel. Spatial relationship and site coupling between the batrachotoxin and Leiurus quinquestriatus quinquestriatus alpha-scorpion toxin receptors.

    Science.gov (United States)

    Angelides, K J; Brown, G B

    1984-05-25

    A fluorescent N- methylanthraniloyl derivative of the potent depolarizing agent batrachotoxin has been used to probe the structural and conformational properties of the neurotoxin receptor site on the voltage-dependent sodium channel. Batrachotoxin A 20-alpha-N- methylanthranilate (BTX-NMA) retains high affinity for its receptor site on the synaptosomal sodium channel with a Kd between 78 and 91 nM and an average site capacity of 2 pmol/mg of synaptosomal protein in the presence of Leiurus quinquestriatus quinquestriatus alpha-scorpion toxin. The fluorescence emission of BTX-NMA upon binding to synaptosomes indicates a hydrophobic environment. Toxin V from L. quinquestriatus, an allosteric activator, effects a 20-nm red shift in the spectrum of bound BTX-NMA and a 4-fold enhancement in the fluorescence quantum yield disclosing a conformational change into a hydrophilic environment. Fluorescence resonance energy transfer measurements show that the distance separating the receptor sites is 37 +/- 10 A. Thus, the binding of alpha-scorpion toxin must involve conformational changes that extend over large distances from the batrachotoxin-binding locus. This information together with the distance measurements between the tetrodotoxin and alpha-scorpion toxin receptors and the conformational transition associated with this distance upon batrachotoxin addition indicate a conformationally flexible channel with coupling of sites through the polyatomic framework of individual subunits or through extensive alterations in subunit/subunit interactions.

  1. Statistical tests for natural selection on regulatory regions based on the strength of transcription factor binding sites

    Directory of Open Access Journals (Sweden)

    Moses Alan M

    2009-12-01

    Full Text Available Abstract Background Although cis-regulatory changes play an important role in evolution, it remains difficult to establish the contribution of natural selection to regulatory differences between species. For protein coding regions, powerful tests of natural selection have been developed based on comparisons of synonymous and non-synonymous substitutions, and analogous tests for regulatory regions would be of great utility. Results Here, tests for natural selection on regulatory regions are proposed based on nucleotide substitutions that occur in characterized transcription factor binding sites (an important type functional element within regulatory regions. In the absence of selection, these substitutions will tend to reduce the strength of existing binding sites. On the other hand, purifying selection will act to preserve the binding sites in regulatory regions, while positive selection can act to create or destroy binding sites, as well as change their strength. Using standard models of binding site strength and molecular evolution in the absence of selection, this intuition can be used to develop statistical tests for natural selection. Application of these tests to two well-characterized regulatory regions in Drosophila provides evidence for purifying selection. Conclusion This demonstrates that it is possible to develop tests for selection on regulatory regions based on the specific functional constrains on these sequences.

  2. The full oncogenic activity of Ret/ptc2 depends on tyrosine 539, a docking site for phospholipase Cgamma.

    Science.gov (United States)

    Borrello, M G; Alberti, L; Arighi, E; Bongarzone, I; Battistini, C; Bardelli, A; Pasini, B; Piutti, C; Rizzetti, M G; Mondellini, P; Radice, M T; Pierotti, M A

    1996-01-01

    RET/PTC oncogenes, generated by chromosomal rearrangements in papillary thyroid carcinomas, are constitutively activated versions of proto-RET, a gene coding for a receptor-type tyrosine kinase (TK) whose ligand is still unknown. RET/PTCs encode fusion proteins in which proto-RET TK and C-terminal domains are fused to different donor genes. The respective Ret/ptc oncoproteins display constitutive TK activity and tyrosine phosphorylation. We found that Ret/ptcs associate with and phosphorylate the SH2-containing transducer phospholipase Cgamma (PLCgamma). Two putative PLCgamma docking sites, Tyr-505 and Tyr-539, have been identified on Ret/ptc2 by competition experiments using phosphorylated peptides modelled on Ret sequence. Transfection experiments and biochemical analysis using Tyr-->Phe mutants of Ret/ptc2 allowed us to rule out Tyr-505 and to identify Tyr-539 as a functional PLCgamma docking site in vivo. Moreover, kinetic measurements showed that Tyr-539 is able to mediate high-affinity interaction with PLCgamma. Mutation of Tyr-539 resulted in a drastically reduced oncogenic activity of Ret/ptc2 on NIH 3T3 cells (75 to 90% reduction) both in vitro and in vivo, which correlates with impaired ability of Ret/ptc2 to activate PLCgamma. In conclusion, this paper demonstrates that Tyr-539 of Ret/ptc2 (Tyr-761 on the proto-RET product) is an essential docking site for the full transforming potential of the oncogene. In addition, the present data identify PLCgamma as a downstream effector of Ret/ptcs and suggest that this transducing molecule could play a crucial role in neoplastic signalling triggered by Ret/ptc oncoproteins. PMID:8628282

  3. Site selection factors for repositories of solid high-level and alpha-bearing wastes in geological formations

    International Nuclear Information System (INIS)

    1977-01-01

    The purpose of this report is to provide guidelines for the selection and evaluation of suitable areas and sites for the disposal of solid high-level and alpha-bearing wastes into geological formations. This report is also intended to provide summary information on many types of geological formations underlying the land masses that might be considered as well as guidance on the geological and hydrological factors that should be investigated to demonstrate the suitability of the formations. In addition, other factors that should be considered in selecting a site for a radioactive waste repository are discussed briefly. The information, as presented, was developed to the extent of current technology for application to the evaluation of deep (greater than about 300 metres below ground level) geological formations in the selection of suitable areas for the disposal of solid or solidified high-level and alpha-bearing wastes. The extreme complexity of many geological environments and of the rock features that govern the presence and circulation of groundwater does not make it feasible to derive strict criteria for the selection of a site for a radioactive waste repository in a geological formation. Each potential repository location must be evaluated according to its own unique geological and hydrological setting. Therefore, only general guidance is offered, and this is done through discussion of the many factors that need to be considered in order to obtain the necessary assurances that the radionuclides will be confined in the geological repository over the required period of time

  4. Contributing Factors in Restaurant-Associated Foodborne Disease Outbreaks, FoodNet Sites, 2006 and 2007†

    Science.gov (United States)

    GOULD, L. HANNAH; ROSENBLUM, IDA; NICHOLAS, DAVID; PHAN, QUYEN; JONES, TIMOTHY F.

    2015-01-01

    An estimated 48 million cases of foodborne illness occur each year in the United States, resulting in approximately 128,000 hospitalizations and 3,000 deaths. Over half of all foodborne disease outbreaks reported to the Centers for Disease Control and Prevention are associated with eating in restaurants or delicatessens. We reviewed data from restaurant-associated foodborne disease outbreaks to better understand the factors that contribute to these outbreaks. Data on restaurant-associated foodborne disease outbreaks reported by sites participating in the Foodborne Diseases Active Surveillance Network (FoodNet) were analyzed to characterize contributing factors reported in foodborne disease outbreaks and the levels of evidence used to identify these factors. Of 457 foodborne disease outbreaks reported in 2006 and 2007 by FoodNet sites, 300 (66%) were restaurant associated, and of these 295 (98%) had at least one reported contributing factor. One to nine (with a median of two) contributing factors were reported per outbreak. Of the 257 outbreaks with a single etiology reported, contributing factors associated with food worker health and hygiene were reported for 165 outbreaks (64%), factors associated with food preparation practices within the establishment were reported for 88 outbreaks (34%), and factors associated with contamination introduced before reaching the restaurant were reported for 56 outbreaks (22%). The pronounced role of food workers in propagating outbreaks makes it clear that more work is needed to address prevention at the local level. Food workers should be instructed not to prepare food while ill to prevent the risk of transmitting pathogens. PMID:24215683

  5. Tat-dependent repression of human immunodeficiency virus type 1 long terminal repeat promoter activity by fusion of cellular transcription factors

    International Nuclear Information System (INIS)

    Zhao Cunyou; Chen Yali; Park, Jiyoung; Kim, Jae Bum; Tang Hong

    2004-01-01

    Transcription initiation from HIV-1 long terminal repeat (LTR) promoter requires the virally encoded transactivator, Tat, and several cellular co-factors to accomplish the Tat-dependent processive transcription elongation. Individual cellular transcription activators, LBP-1b and Oct-1, on the other hand, have been shown to inhibit LTR promoter activities probably via competitive binding against TFIID to the TATA-box in LTR promoter. To explore the genetic interference strategies against the viral replication, we took advantage of the existence of the bipartite DNA binding domains and the repression domains of LBP-1b and Oct-1 factors to generate a chimeric transcription repressor. Our results indicated that the fusion protein of LBP-1b and Oct-1 exhibited higher DNA binding affinity to the viral promoter than the individual factors, and little interference with the host cell gene expression due to its anticipated rare cognate DNA sites in the host cell genome. Moreover, the chimera exerted increased Tat-dependent repression of transcription initiation at the LTR promoter both in vitro and in vivo compared to LBP-1b, Oct-1 or combination of LBP-1b and Oct-1. These results might provide the lead in generating a therapeutic reagent useful to suppress HIV-1 replication

  6. Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein

    Directory of Open Access Journals (Sweden)

    Berkhout Ben

    2006-11-01

    Full Text Available Abstract Background We previously described the selection of a T20-dependent human immunodeficiency virus type-1 (HIV-1 variant in a patient on T20 therapy. The fusion inhibitor T20 targets the viral envelope (Env protein by blocking a conformational switch that is critical for viral entry into the host cell. T20-dependent viral entry is the result of 2 mutations in Env (GIA-SKY, creating a protein that undergoes a premature conformational switch, and the presence of T20 prevents this premature switch and rescues viral entry. In the present study, we performed 6 independent evolution experiments with the T20-dependent HIV-1 variant in the absence of T20, with the aim to identify second site compensatory changes, which may provide new mechanistic insights into Env function and the T20-dependence mechanism. Results Escape variants with improved replication capacity appeared within 42 days in 5 evolution cultures. Strikingly, 3 cultures revealed the same single amino acid change in the CD4 binding region of Env (glycine at position 431 substituted for arginine: G431R. This mutation was sufficient to abolish the T20-dependence phenotype and restore viral replication in the absence of T20. The GIA-SKY-G431R escape variant produces an Env protein that exhibits reduced syncytia formation and reduced cell-cell fusion activity. The escape variant was more sensitive to an antibody acting on an early gp41 intermediate, suggesting that the G431R mutation helps preserve a pre-fusion Env conformation, similar to T20 action. The escape variant was also less sensitive to soluble CD4, suggesting a reduced CD4 receptor affinity. Conclusion The forced evolution experiments indicate that the premature conformational switch of the T20-dependent HIV-1 Env variant (GIA-SKY can be corrected by a second site mutation in Env (GIA-SKY-G431R that affects the interaction with the CD4 receptor.

  7. Injectable multiple sclerosis medications: a patient survey of factors associated with injection-site reactions.

    Science.gov (United States)

    Stewart, Thomas M; Tran, Zung Vu

    2012-01-01

    Although injection-site reactions (ISRs) occur with US Food and Drug Administration-approved injectable disease-modifying therapies (DMTs) for multiple sclerosis, there are currently few reports of real-world data on ISR management strategies or possible correlations between ISRs and patient demographics, disease characteristics, and missed injections. Patient-reported data on the use of DMTs, patient demographic and disease characteristics, missed injections, and ISR reduction strategies were collected via e-mail, a patient registry (www.ms-cam.org), and a Web-based survey. Of the 1380 respondents, 1201 (87%) indicated that they had used injectable DMTs, of whom 377 (31%) had used intramuscular (IM) interferon beta-1a (IFNβ-1a), 172 (14%) had used subcutaneous (SC) IFNβ-1a, 183 (15%) had used SC IFNβ-1b, and 469 (39%) had used glatiramer acetate (GA). The majority of respondents were older (73% were ≥40 years), female (79%), married or living with a partner (72%), white (94%), and nonsmoking (82%). Injection-site reaction incidence, grouped according to severity, varied among DMTs, with IM IFNβ-1a causing significantly (P ISRs than the other therapies. Female sex and younger age were significantly (P ISRs among users of IM IFNβ-1a, SC IFNβ-1b, and GA. Nonwhites reported severe ISRs more often than whites. For all DMTs injection-site massage and avoidance of sensitive sites were the most frequently used strategies to minimize ISRs. These data may help identify patients with characteristics associated with a higher risk for ISRs, allowing health-care professionals to provide anticipatory guidance to patients at risk for decreased adherence or discontinuation.

  8. Preoperative skin preparation with 2% chlorhexidine as a factor in the prevention of surgical site infection

    OpenAIRE

    Evelyn Solano Castro

    2014-01-01

    The results of secondary research that refers to preoperative skin preparation with antiseptic chlorhexidine 2% are presented. Surgical Site Infections are one of the most common complications in surgical procedures are associated with significant morbidity and mortality in the user and are the third -associated infection more frequent in the health care . Steps of clinical practice based on evidence were applied, considering in the first instance a question in PICO format, then a search for ...

  9. Factors associated with resilience in wives of individuals with alcohol dependence syndrome

    Directory of Open Access Journals (Sweden)

    Sreeja Sreekumar

    2016-01-01

    Conclusion: Assessment of resilience in wives of individuals with alcohol dependence and identification and management of those with poor resilience should go hand in hand with their husband's treatment program.

  10. Distribution of epidermal growth factor binding sites in the adult rat anterior pituitary gland

    Energy Technology Data Exchange (ETDEWEB)

    Chabot, J.G.; Walker, P.; Pelletier, G.

    1986-01-01

    The distribution of epidermal growth (EGF) binding sites was studied in the pituitary gland using light and electron microscope autoradiography which was performed at different time intervals (2 to 60 min) after intravenous (IV) injection of (/sup 125/I)EGF into adult rats. At the light microscopic level, the labeling was found over cells of the anterior pituitary gland. The time-course study performed by light microscope autoradiography showed that the maximal values were reached at the 2 min time interval. At this time interval, most silver grains were found at the periphery of the target cells. After, the number of silver grains decreased progressively and the localization of silver grains in the cytoplasm indicated the internalization of (/sup 125/I)EGF. Electron microscope autoradiography showed that labeling was mostly restricted to mammotrophs and somatotrophs. Control experiments indicated that the autoradiographic labeling was due specific interaction of (/sup 125/I)EGF with its binding site. These results indicate that EGF binding sites are present in at least two anterior pituitary cell types and suggest that EGF can exert a physiological role in the pituitary gland.

  11. A 5' splice site enhances the recruitment of basal transcription initiation factors in vivo

    DEFF Research Database (Denmark)

    Damgaard, Christian Kroun; Kahns, Søren; Lykke-Andersen, Søren

    2008-01-01

    Transcription and pre-mRNA splicing are interdependent events. Although mechanisms governing the effects of transcription on splicing are becoming increasingly clear, the means by which splicing affects transcription remain elusive. Using cell lines stably expressing HIV-1 or β-globin mRNAs, harb...... a promoter-proximal 5′ splice site via its U1 snRNA interaction can feed back to stimulate transcription initiation by enhancing preinitiation complex assembly.......Transcription and pre-mRNA splicing are interdependent events. Although mechanisms governing the effects of transcription on splicing are becoming increasingly clear, the means by which splicing affects transcription remain elusive. Using cell lines stably expressing HIV-1 or β-globin mRNAs......, harboring wild-type or various 5′ splice site mutations, we demonstrate a strong positive correlation between splicing efficiency and transcription activity. Interestingly, a 5′ splice site can stimulate transcription even in the absence of splicing. Chromatin immunoprecipitation experiments show enhanced...

  12. SU-E-T-98: Dependence of Radiotherapy Couch Transmission Factors On Field Size and Couch-Isocenter Distance

    International Nuclear Information System (INIS)

    Benhabib, S; Duan, J; Wu, X; Cardan, R; Shen, S; Huang, M; Popple, R; Brezovich, I

    2014-01-01

    Purpose: The dosimetric effect of the treatment couch is non-negligible in today's radiotherapy treatment. To accurately include couch in dose calculation, we investigated the dependence of couch transmission factors on field size and couch-isocenter distance. Methods: Couch transmission factors for Varian Exact Couch were determined by taking the ratios of ionization of a posterior-anterior beam with and without the couch in the beam path. Measurements were performed at the isocenter using a PTW cylindrical ionization chamber (Model 31030) with an Aluminum buildup cap of 1.1 cm thick for the 6 MV photon beam. Ionization readings for beam sizes ranging from 2 × 2 cm2 to 40 × 40 cm2 were taken. Transmission factors for couch-isocenter distances ranging from 3 cm to 20 cm were also investigated. Results: The couch transmission factors increased with the field size approximately in an exponential manner. For the field sizes that we tested, the transmission factor ranged from 0.976 to 0.992 for couch-isocenter distance of 3 cm. The transmission factor was also monotonically dependent on couch-isocenter separation distance, but in a lighter magnitude. For the tested couch heights, the transmission factor ranged from 0.974 – 0.972 for 2 × 2 cm2 field size and 0.992 – 0.986 for 40 × 40 cm2 field size. The dependence on couch-isocenter distance is stronger for larger field size. Conclusions: The transmission factor of a radiotherapy treatment couch increases with field size of the radiation beam and its distance from the isocenter. Such characterization of the couch transmission factor helps improve the accuracy of couch modeling for radiotherapy treatment planning

  13. Siroheme- and [Fe4-S4]-dependent NirA from Mycobacterium tuberculosis is a sulfite reductase with a covalent Cys-Tyr bond in the active site.

    Science.gov (United States)

    Schnell, Robert; Sandalova, Tatyana; Hellman, Ulf; Lindqvist, Ylva; Schneider, Gunter

    2005-07-22

    The nirA gene of Mycobacterium tuberculosis is up-regulated in the persistent state of the bacteria, suggesting that it is a potential target for the development of antituberculosis agents particularly active against the pathogen in its dormant phase. This gene encodes a ferredoxin-dependent sulfite reductase, and the structure of the enzyme has been determined using x-ray crystallography. The enzyme is a monomer comprising 555 amino acids and contains a [Fe4-S4] cluster and a siroheme cofactor. The molecule is built up of three domains with an alpha/beta fold. The first domain consists of two ferredoxin-like subdomains, related by a pseudo-2-fold symmetry axis passing through the whole molecule. The other two domains, which provide much of the binding interactions with the cofactors, have a common fold that is unique to the sulfite/nitrite reductase family. The domains form a trilobal structure, with the cofactors and the active site located at the interface of all three domains in the center of the molecule. NirA contains an unusual covalent bond between the side chains of Tyr69 and Cys161 in the active site, in close proximity to the siroheme cofactor. Removal of this covalent bond by site-directed mutagenesis impairs catalytic activity, suggesting that it is important for the enzymatic reaction. These residues are part of a sequence fingerprint, able to distinguish between ferredoxin-dependent sulfite and nitrite reductases. Comparison of NirA with the structure of the truncated NADPH-dependent sulfite reductase from Escherichia coli suggests a binding site for the external electron donor ferredoxin close to the [Fe4-S4] cluster.

  14. Factor VIIa response to a fat-rich meal does not depend on fatty acid composition: A randomized controlled trial

    NARCIS (Netherlands)

    Mennen, L.; Maat, M. de; Meijer, G.; Zock, P.; Grobbee, D.; Kok, F.; Kluft, C.; Schouten, E.

    1998-01-01

    A fat-rich meal increases activated factor VII (FVIIa), but it is not clear whether this increase depends on the fatty acid composition of the meal. Therefore, we studied the FVIIa response to fat-rich meals with different fatty acid composition in a randomized controlled crossover trial and

  15. Studies on the association between immunoglobulin E autoreactivity and immunoglobulin E-dependent histamine-releasing factors

    NARCIS (Netherlands)

    Budde, Ilona Kleine; de Heer, Pleuni G.; Natter, Susanne; Mahler, Vera; van der Zee, Jaring S.; Valenta, Rudolf; Aalberse, Rob C.

    2002-01-01

    It has been reported that serum immunoglobulin E (IgE) from certain atopic patients can sensitize basophils to release histamine in response to IgE-dependent histamine-releasing factors (HRFs). It has also been shown that patients suffering from severe forms of atopy may contain IgE autoantibodies.

  16. Reactivity to IgE-dependent histamine-releasing factor is due to monomeric IgE

    NARCIS (Netherlands)

    Budde, I. K.; Aalbers, M.; Aalberse, R. C.; van der Zee, J. S.; Knol, E. F.

    2000-01-01

    IgE-dependent histamine-releasing factor (HRF) can distinguish between IgE+ and IgE-. In contrast to IgE-, IgE+ sensitizes basophils to release histamine in response to HRF. But we do not know what particular feature distinguishes IgE+ from IgE-. The objective was to investigate the hypothesis that

  17. Dynamic subnuclear relocalization of WRKY40, a potential new mechanism of ABA-dependent transcription factor regulation.

    Science.gov (United States)

    Geilen, Katja; Böhmer, Maik

    2015-01-01

    The phytohormone ABA plays a major role during plant development, e.g. seed maturation and seed germination, and during adaptation to abiotic stresses like stomatal aperture regulation. The three closely related WRKY transcription factors WRKY18, WRKY40 and WRKY60 function in ABA signal transduction. We recently demonstrated that WRKY18 and WRKY40 but not WRKY60 localize to nuclear bodies in A. thaliana mesophyll protoplasts. WRKY40, a negative regulator of ABA-dependent inhibition of seed germination, relocalizes from PNBs to the nucleoplasm in the presence of ABA in a dynamic and phosphorylation-dependent manner. We propose that subnuclear relocalization of WRKY40 might constitute a new regulatory mechanism of ABA-dependent modulation of transcription factor activity.

  18. Grain size-dependent strength of phyllosilicate-rich gouges in the shallow crust: Insights from the SAFOD site

    Science.gov (United States)

    Phillips, Noah John; White, Joseph Clancy

    2017-07-01

    The San Andreas Fault Observatory at Depth (SAFOD) drilling project directly sampled a transitional (between creeping and locked) segment of the San Andreas Fault at 2.7 km depth. At the site, changes in strain rate occur between periods of coseismic slip (>10-7 s-1) and interseismic creep (10-10 s-1) over decadal scales ( 30 years). Microstructural observations of core retrieved from the SAFOD site show throughgoing fractures and gouge-rich cores within the fractures, evidence of predominantly brittle deformation mechanisms. Within the gouge-rich cores, strong phases show evidence of deformation by pressure solution once the grain size is reduced to a critical effective grain size. Models of pressure solution-accommodated creep for quartz-phyllosilicate mixtures indicate that viscous weakening of quartz occurs during the interseismic period once a critical effective grain size of 1 μm is achieved, consistent with microstructural observations. This causes pronounced weakening, as the strength of the mixture is then controlled by the frictional properties of the phyllosilicate phases. These results have pronounced implications for the internal deformation of fault zones in the shallow crust, where at low strain rates, deformation is accommodated by both viscous and brittle deformation mechanisms. As strain rates increase, the critical effective grain size for weakening decreases, localizing deformation into the finest-grained gouges until deformation can no longer be accommodated by viscous processes and purely brittle failure occurs.

  19. Evaluation of site-specific factors influencing heavy metal contents in the topsoil of vegetated infiltration swales

    International Nuclear Information System (INIS)

    Horstmeyer, Nils; Huber, Maximilian; Drewes, Jörg E.; Helmreich, Brigitte

    2016-01-01

    Stormwater runoff of traffic areas is usually polluted by organic and inorganic substances and must be treated prior to discharge into groundwater. One widely used treatment method is infiltrating the runoff over the topsoil of vegetated swales. The aim of this study was to evaluate the factors influencing the heavy metal contents in such topsoil layers of vegetated infiltration swales near highways, roads, and parking lots. In total, 262 topsoil samples were taken from 35 sampling sites, which varied in age, traffic volume, road design, driving style, and site-specific conditions. In the evaluation of all soil samples, the median heavy metal values of cadmium, chromium, copper, lead, and zinc were yielding 0.36 (mean: 1.21) mg/kg DM, 37.0 (mean: 44.5) mg/kg DM, 28.0 (mean: 61.5) mg/kg DM, 27.0 (mean: 71.9) mg/kg DM, and 120 (mean: 257) mg/kg DM, respectively. The main purpose was to evaluate the site-specific data (i.e., surrounding land use characteristics, traffic area site data, and operational characteristics). In general, heavy metal contents increased with increasing traffic volumes. However, other factors also had a notable impact. Factors such as road design (e.g., curves, crossings, and roundabouts) and grade of congestion significantly influenced the heavy metal contents. High heavy metal contents were detected for stop-and-go areas, roundabouts, crossings, and sites with traffic lights, signs, and guardrails. Findings of this study can be used to identify highly polluted traffic areas and to verify or improve standards regarding the treatment of runoff from traffic areas. - Highlights: • Correlation of contents with traffic volume, road design, and stop-and-go traffic • Increased heavy metal contents at stop-and-go sites, roundabouts, and crossings • Different soil contents and behavior of cadmium, chromium, copper, lead, and zinc • Identification of factors influencing the variability of zinc in topsoil samples

  20. Site-Dependent Degradation of a Non-Cleavable Auristatin-Based Linker-Payload in Rodent Plasma and Its Effect on ADC Efficacy.

    Directory of Open Access Journals (Sweden)

    Magdalena Dorywalska

    Full Text Available The efficacy of an antibody-drug conjugate (ADC is dependent on the properties of its linker-payload which must remain stable while in systemic circulation but undergo efficient processing upon internalization into target cells. Here, we examine the stability of a non-cleavable Amino-PEG6-based linker bearing the monomethyl auristatin D (MMAD payload site-specifically conjugated at multiple positions on an antibody. Enzymatic conjugation with transglutaminase allows us to create a stable amide linkage that remains intact across all tested conjugation sites on the antibody, and provides us with an opportunity to examine the stability of the auristatin payload itself. We report a position-dependent degradation of the C terminus of MMAD in rodent plasma that has a detrimental effect on its potency. The MMAD cleavage can be eliminated by either modifying the C terminus of the toxin, or by selection of conjugation site. Both approaches result in improved stability and potency in vitro and in vivo. Furthermore, we show that the MMAD metabolism in mouse plasma is likely mediated by a serine-based hydrolase, appears much less pronounced in rat, and was not detected in cynomolgus monkey or human plasma. Clarifying these species differences and controlling toxin degradation to optimize ADC stability in rodents is essential to make the best ADC selection from preclinical models. The data presented here demonstrate that site selection and toxin susceptibility to mouse plasma degradation are important considerations in the design of non-cleavable ADCs, and further highlight the benefits of site-specific conjugation methods.

  1. Blood donor show behavior after an invitation to donate: The influence of collection site factors

    NARCIS (Netherlands)

    Merz, E.M.; Zijlstra, Bonne; De Kort, Wim L.A.M.

    2017-01-01

    Background and Objectives Show behaviour after invitation to donate varies considerably across donors. More insight into this variation is important for blood banks in achieving stable stocks. This study examined individual factors determining intended show behaviour. Most importantly, however, this

  2. A High-Throughput Technique Reveals the Load- and Site Density-Dependent Kinetics of E-Selectin

    Science.gov (United States)

    Snook, Jeremy H.; Guilford, William H.

    2013-01-01

    The kinetics of bond rupture between receptors and ligand are critically dependent on applied mechanical force. Force spectroscopy of single receptor-ligand pairs to measure kinetics is a laborious and time-consuming process that is generally performed using individual force probes and making one measurement at a time when typically hundreds of measurements are needed. A high-throughput approach is thus desirable. We report here a magnetic bond puller that provides high-throughput measurements of single receptor-ligand bond kinetics. Electromagnets are used to apply pN tensile and compressive forces to receptor-coated magnetic microspheres while monitoring their contact with a ligand-coated surface. Bond lifetimes and the probability of forming a bond are measured via videomicroscopy, and the data are used to determine the load dependent rates of bond rupture and bond formation. The approach is simple, customizable, relatively inexpensive, and can make dozens of kinetic measurements simultaneously. We used the device to investigate how compressive and tensile forces affect the rates of formation and rupture, respectively, of bonds between E-selectin and sialyl Lewisa (sLea), a sugar on P-selectin glycoprotein ligand-1 to which selectins bind. We confirmed earlier findings of a load-dependent rate of bond formation between these two molecules, and that they form a catch-slip bond like other selectin family members. We also make the novel observation of an “ideal” bond in a highly multivalent system of this receptor-ligand pair. PMID:24511329

  3. Romantic Partner Monitoring After Breakups: Attachment, Dependence, Distress, and Post-Dissolution Online Surveillance via Social Networking Sites.

    Science.gov (United States)

    Fox, Jesse; Tokunaga, Robert S

    2015-09-01

    Romantic relationship dissolution can be stressful, and social networking sites make it difficult to separate from a romantic partner online as well as offline. An online survey (N = 431) tested a model synthesizing attachment, investment model variables, and post-dissolution emotional distress as predictors of interpersonal surveillance (i.e., "Facebook stalking") of one's ex-partner on Facebook after a breakup. Results indicated that anxious attachment predicted relational investment but also seeking relationship alternatives; avoidant attachment was negatively related to investment but positively related to seeking alternatives. Investment predicted commitment, whereas seeking alternatives was negatively related to commitment. Commitment predicted emotional distress after the breakup. Distress predicted partner monitoring immediately following the breakup, particularly for those who did not initiate the breakup, as well as current partner monitoring. Given their affordances, social media are discussed as potentially unhealthy enablers for online surveillance after relationship termination.

  4. Elimination of Endogenous Toxin, Creatinine from Blood Plasma Depends on Albumin Conformation: Site Specific Uremic Toxicity & Impaired Drug Binding

    Science.gov (United States)

    Varshney, Ankita; Rehan, Mohd; Subbarao, Naidu; Rabbani, Gulam; Khan, Rizwan Hasan

    2011-01-01

    Uremic syndrome results from malfunctioning of various organ systems due to the retention of uremic toxins which, under normal conditions, would be excreted into the urine and/or metabolized by the kidneys. The aim of this study was to elucidate the mechanisms underlying the renal elimination of uremic toxin creatinine that accumulate in chronic renal failure. Quantitative investigation of the plausible correlations was performed by spectroscopy, calorimetry, molecular docking and accessibility of surface area. Alkalinization of normal plasma from pH 7.0 to 9.0 modifies the distribution of toxin in the body and therefore may affect both the accumulation and the rate of toxin elimination. The ligand loading of HSA with uremic toxin predicts several key side chain interactions of site I that presumably have the potential to impact the specificity and impaired drug binding. These findings provide useful information for elucidating the complicated mechanism of toxin disposition in renal disease state. PMID:21386972

  5. Sites of recurrent disease and prognostic factors in SCLC patients treated with radiochemotherapy

    Directory of Open Access Journals (Sweden)

    Rebecca Bütof

    2017-12-01

    Full Text Available Objectives: Concurrent radiochemotherapy (RCHT is standard treatment in locally advanced small cell lung cancer (SCLC patients. Due to conflicting results on elective nodal irradiation (ENI or selective node irradiation (SNI there is no clear evidence on optimal target volumes. Therefore, the purposes of this study were to assess the sites of recurrent disease in SCLC and to evaluate the feasibility of SNI versus ENI. Methods: A retrospective single-institution study of 43 consecutive patients treated with RCHT was performed. After state-of-the-art staging including FDG-PET/CT, all patients underwent three-dimensional conformal radiotherapy to a total dose of 45 Gy in twice-daily fractions of 1.5 Gy starting concurrently with the first or second chemotherapy cycle. All sites of loco-regional recurrences were correlated to the initial tumor and dose delivered. The impact of potential prognostic variables on outcome was evaluated using the Cox-regression model. Results: 13 patients (30% relapsed locally or regionally: six within the initial primary tumor volume, five within the initially affected lymph nodes, one metachronously within primary tumor and initially affected lymph nodes, and one both inside and outside of the initial nodal disease. All sites of loco-regional recurrence had received 92–106% of the prescribed dose. Conclusion: In our study most recurrences occurred within the primary tumor or initially affected lymph nodes, or distantly. We did not register any case of isolated nodal failure, supporting the use of selective nodal irradiation, possibly with the addition of supraclavicular irradiation in patients with nodal disease in the upper mediastinum. Keywords: Small cell lung cancer, Recurrence, Radiotherapy, Selective node irradiation

  6. Risk factors for cocaine-induced psychosis in cocaine-dependent patients.

    Science.gov (United States)

    Roncero, C; Daigre, C; Gonzalvo, B; Valero, S; Castells, X; Grau-López, L; Eiroa-Orosa, F J; Casas, M

    2013-03-01

    Cocaine consumption can induce transient psychotic symptoms, expressed as paranoia or hallucinations. Cocaine induced psychosis (CIP) is common but not developed in all cases. This is the first European study on the relationship between CIP, consumption pattern variables and personality disorders. We evaluated 173 cocaine-dependent patients over 18 years; mostly males, whose average age was 33.6 years (SD=7.8). Patients attending an outpatient addictions department were enrolled in the study and subsequently systematically evaluated using SCID I and SCID II interviews for comorbid disorders, a clinical interview for psychotic symptoms and EuropASI for severity of addiction. A high proportion of cocaine dependent patients reported psychotic symptoms under the influence of cocaine (53.8%), the most frequently reported being paranoid beliefs and suspiciousness (43.9%). A logistic regression analysis was performed, finding that a model consisting of amount of cocaine consumption, presence of an antisocial personality disorder and cannabis dependence history had 66.2% sensitivity 75.8% specificity predicting the presence of CIP. In our conclusions, we discuss the relevance of evaluating CIP in all cocaine dependent-patients, and particularly in those fulfilling the clinical profile derived from our results. These findings could be useful for a clinical approach to the risks of psychotic states in cocaine-dependent patients. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  7. Dependence of twinned volume fraction on loading mode and Schmid factor in randomly textured magnesium

    Czech Academy of Sciences Publication Activity Database

    Čapek, Jan; Máthis, K.; Clausen, B.; Barnett, M.R.

    2017-01-01

    Roč. 130, MAY (2017), s. 319-328 ISSN 1359-6454 R&D Projects: GA ČR GB14-36566G Institutional support: RVO:61389005 Keywords : twinning * magnesium * neutron diffraction * Schmid factor Subject RIV: BM - Solid Matter Physics ; Magnetism OBOR OECD: Condensed matter physics (including formerly solid state physics, supercond.) Impact factor: 5.301, year: 2016

  8. Investigation of the factorization scheme dependence of finite order perturbative QCD calculations

    Czech Academy of Sciences Publication Activity Database

    Kolář, Karel

    -, č. 11 (2011), 005/1-005/44 ISSN 1126-6708 R&D Projects: GA MŠk LC527 Institutional research plan: CEZ:AV0Z10100502 Keywords : QCD * parton distribution functions * factorization schemes * NLO Monte Carlo event generators Subject RIV: BF - Elementary Particles and High Energy Physics Impact factor: 5.831, year: 2011

  9. Self-Derogation, Peer Factors, and Drug Dependence among a Multiethnic Sample of Young Adults

    Science.gov (United States)

    Taylor, John; Lloyd, Donald A.; Warheit, George J.

    2006-01-01

    Previous research suggests that self-derogation/rejection and peer factors are strongly related to adolescent substance use. However, much less is known about the role and significance of these risk factors in the escalation of drug use over time. In the current study, we examined whether early reports of self-derogation and peer approval…

  10. A Dynamic Multi-Level Factor Model with Long-Range Dependence

    DEFF Research Database (Denmark)

    Ergemen, Yunus Emre; Rodríguez-Caballero, Carlos Vladimir

    common factors is performed in two steps employing canonical correlation analysis and a sequential least-squares algorithm. Selection of the number of global and regional factors is discussed. The small sample properties of our methodology are investigated by some Monte Carlo simulations. The method...

  11. Spatial Dependence and Heterogeneity in Bayesian Factor Analysis: A Cross-National Investigation of Schwartz Values

    Science.gov (United States)

    Stakhovych, Stanislav; Bijmolt, Tammo H. A.; Wedel, Michel

    2012-01-01

    In this article, we present a Bayesian spatial factor analysis model. We extend previous work on confirmatory factor analysis by including geographically distributed latent variables and accounting for heterogeneity and spatial autocorrelation. The simulation study shows excellent recovery of the model parameters and demonstrates the consequences…

  12. Sex dependent risk factors for mortality after myocardial infarction : Individual patient data meta-analysis

    NARCIS (Netherlands)

    van Loo, H.M.; van den Heuvel, E.R.; Schroevers, R.A.; Anselmino, M.; Carney, R.M.; Denollet, J.; Doyle, F.; Freedland, K.E.; Hosseini, S.H.; Pilote, L.; Rafanelli, C.; Roest, A.M.; Sato, H.; Steeds, R.P.; Kessler, R.C.; de Jonge, P.

    2014-01-01

    Background Although a number of risk factors are known to predict mortality within the first years after myocardial infarction, little is known about interactions between risk factors, whereas these could contribute to accurate differentiation of patients with higher and lower risk for mortality.

  13. Cyclin T1-dependent genes in activated CD4 T and macrophage cell lines appear enriched in HIV-1 co-factors.

    Directory of Open Access Journals (Sweden)

    Wendong Yu

    2008-09-01

    Full Text Available HIV-1 is dependent upon cellular co-factors to mediate its replication cycle in CD4(+ T cells and macrophages, the two major cell types infected by the virus in vivo. One critical co-factor is Cyclin T1, a subunit of a general RNA polymerase II elongation factor known as P-TEFb. Cyclin T1 is targeted directly by the viral Tat protein to activate proviral transcription. Cyclin T1 is up-regulated when resting CD4(+ T cells are activated and during macrophage differentiation or activation, conditions that are also necessary for high levels of HIV-1 replication. Because Cyclin T1 is a subunit of a transcription factor, the up-regulation of Cyclin T1 in these cells results in the induction of cellular genes, some of which might be HIV-1 co-factors. Using shRNA depletions of Cyclin T1 and transcriptional profiling, we identified 54 cellular mRNAs that appear to be Cyclin T1-dependent for their induction in activated CD4(+ T Jurkat T cells and during differentiation and activation of MM6 cells, a human monocytic cell line. The promoters for these Cyclin T1-dependent genes (CTDGs are over-represented in two transcription factor binding sites, SREBP1 and ARP1. Notably, 10 of these CTDGs have been reported to be involved in HIV-1 replication, a significant over-representation of such genes when compared to randomly generated lists of 54 genes (p value<0.00021. The results of siRNA depletion and dominant-negative protein experiments with two CTDGs identified here, CDK11 and Casein kinase 1 gamma 1, suggest that these genes are involved either directly or indirectly in HIV-1 replication. It is likely that the 54 CTDGs identified here include novel HIV-1 co-factors. The presence of CTDGs in the protein space that was available for HIV-1 to sample during its evolution and acquisition of Tat function may provide an explanation for why CTDGs are enriched in viral co-factors.

  14. Risk factors for surgical site infection following cesarean section in a Brazilian Women's Hospital: a case-control study.

    Science.gov (United States)

    Farret, Túlio Cícero Franco; Dallé, Jessica; Monteiro, Vinícius da Silva; Riche, Cezar Vinícius Würdig; Antonello, Vicente Sperb

    2015-01-01

    The present study evaluated patients with diagnosis of surgical site infection (SSI) following cesarean section and their controls to det