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. Adaptive evolution of transcription factor binding sites

    Directory of Open Access Journals (Sweden)

    Berg Johannes

    2004-10-01

    Full Text Available Abstract Background The regulation of a gene depends on the binding of transcription factors to specific sites located in the regulatory region of the gene. The generation of these binding sites and of cooperativity between them are essential building blocks in the evolution of complex regulatory networks. We study a theoretical model for the sequence evolution of binding sites by point mutations. The approach is based on biophysical models for the binding of transcription factors to DNA. Hence we derive empirically grounded fitness landscapes, which enter a population genetics model including mutations, genetic drift, and selection. Results We show that the selection for factor binding generically leads to specific correlations between nucleotide frequencies at different positions of a binding site. We demonstrate the possibility of rapid adaptive evolution generating a new binding site for a given transcription factor by point mutations. The evolutionary time required is estimated in terms of the neutral (background mutation rate, the selection coefficient, and the effective population size. Conclusions The efficiency of binding site formation is seen to depend on two joint conditions: the binding site motif must be short enough and the promoter region must be long enough. These constraints on promoter architecture are indeed seen in eukaryotic systems. Furthermore, we analyse the adaptive evolution of genetic switches and of signal integration through binding cooperativity between different sites. Experimental tests of this picture involving the statistics of polymorphisms and phylogenies of sites are discussed.

  3. Manipulation of the membrane binding site of vitamin K-dependent proteins: Enhanced biological function of human factor VII

    OpenAIRE

    Shah, Amit M.; Kisiel, Walter; Foster, Donald C.; Nelsestuen, Gary L.

    1998-01-01

    Recent studies suggested that modification of the membrane contact site of vitamin K-dependent proteins may enhance the membrane affinity and function of members of this protein family. The properties of a factor VII mutant, factor VII-Q10E32, relative to wild-type factor VII (VII, containing P10K32), have been compared. Membrane affinity of VII-Q10E32 was about 20-fold higher than that of wild-type factor VII. The rate of autoactivation VII-Q10E32 with soluble tissue factor was 100-fold fast...

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

    Science.gov (United States)

    Izhar, Lior; Adamson, Britt; Ciccia, Alberto; Lewis, Jedd; Pontano-Vaites, Laura; Leng, Yumei; Liang, Anthony C; Westbrook, Thomas F; Harper, J Wade; Elledge, Stephen J

    2015-06-09

    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. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  5. 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.

  6. Deriving amplification factors from simple site parameters using generalized regression neural networks: implications for relevant site proxies

    Science.gov (United States)

    Boudghene Stambouli, Ahmed; Zendagui, Djawad; Bard, Pierre-Yves; Derras, Boumédiène

    2017-07-01

    Most modern seismic codes account for site effects using an amplification factor (AF) that modifies the rock acceleration response spectra in relation to a "site condition proxy," i.e., a parameter related to the velocity profile at the site under consideration. Therefore, for practical purposes, it is interesting to identify the site parameters that best control the frequency-dependent shape of the AF. The goal of the present study is to provide a quantitative assessment of the performance of various site condition proxies to predict the main AF features, including the often used short- and mid-period amplification factors, Fa and Fv, proposed by Borcherdt (in Earthq Spectra 10:617-653, 1994). In this context, the linear, viscoelastic responses of a set of 858 actual soil columns from Japan, the USA, and Europe are computed for a set of 14 real accelerograms with varying frequency contents. The correlation between the corresponding site-specific average amplification factors and several site proxies (considered alone or as multiple combinations) is analyzed using the generalized regression neural network (GRNN). The performance of each site proxy combination is assessed through the variance reduction with respect to the initial amplification factor variability of the 858 profiles. Both the whole period range and specific short- and mid-period ranges associated with the Borcherdt factors Fa and Fv are considered. The actual amplification factor of an arbitrary soil profile is found to be satisfactorily approximated with a limited number of site proxies (4-6). As the usual code practice implies a lower number of site proxies (generally one, sometimes two), a sensitivity analysis is conducted to identify the "best performing" site parameters. The best one is the overall velocity contrast between underlying bedrock and minimum velocity in the soil column. Because these are the most difficult and expensive parameters to measure, especially for thick deposits, other

  7. Nuclear power plant site evaluation using site population-meterology factor

    International Nuclear Information System (INIS)

    Rho, B.H.; Kang, C.H.

    1982-01-01

    In this paper, as a site evaluation technique, SPNF(Site Population Neteorology Factor) which is modified from SPF(Site Population Factor) of the USNRC model, is defined from site population and meteorology data in order to consider the radiological impacts to the population at large from the atmospheric dispersion of the radioactive effluents released during routine plant operation as well as accidental conditions. The SPMF model proved its propriety from the comparison of SPMF and SPF for Kori site. The relative suitability of Korean sites to the U.S. sites have been also examined using SPF. (Author)

  8. Discovery and information-theoretic characterization of transcription factor binding sites that act cooperatively.

    Science.gov (United States)

    Clifford, Jacob; Adami, Christoph

    2015-09-02

    Transcription factor binding to the surface of DNA regulatory regions is one of the primary causes of regulating gene expression levels. A probabilistic approach to model protein-DNA interactions at the sequence level is through position weight matrices (PWMs) that estimate the joint probability of a DNA binding site sequence by assuming positional independence within the DNA sequence. Here we construct conditional PWMs that depend on the motif signatures in the flanking DNA sequence, by conditioning known binding site loci on the presence or absence of additional binding sites in the flanking sequence of each site's locus. Pooling known sites with similar flanking sequence patterns allows for the estimation of the conditional distribution function over the binding site sequences. We apply our model to the Dorsal transcription factor binding sites active in patterning the Dorsal-Ventral axis of Drosophila development. We find that those binding sites that cooperate with nearby Twist sites on average contain about 0.5 bits of information about the presence of Twist transcription factor binding sites in the flanking sequence. We also find that Dorsal binding site detectors conditioned on flanking sequence information make better predictions about what is a Dorsal site relative to background DNA than detection without information about flanking sequence features.

  9. 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.

  10. Nucleotide Interdependency in Transcription Factor Binding Sites in the Drosophila Genome.

    Science.gov (United States)

    Dresch, Jacqueline M; Zellers, Rowan G; Bork, Daniel K; Drewell, Robert A

    2016-01-01

    A long-standing objective in modern biology is to characterize the molecular components that drive the development of an organism. At the heart of eukaryotic development lies gene regulation. On the molecular level, much of the research in this field has focused on the binding of transcription factors (TFs) to regulatory regions in the genome known as cis-regulatory modules (CRMs). However, relatively little is known about the sequence-specific binding preferences of many TFs, especially with respect to the possible interdependencies between the nucleotides that make up binding sites. A particular limitation of many existing algorithms that aim to predict binding site sequences is that they do not allow for dependencies between nonadjacent nucleotides. In this study, we use a recently developed computational algorithm, MARZ, to compare binding site sequences using 32 distinct models in a systematic and unbiased approach to explore nucleotide dependencies within binding sites for 15 distinct TFs known to be critical to Drosophila development. Our results indicate that many of these proteins have varying levels of nucleotide interdependencies within their DNA recognition sequences, and that, in some cases, models that account for these dependencies greatly outperform traditional models that are used to predict binding sites. We also directly compare the ability of different models to identify the known KRUPPEL TF binding sites in CRMs and demonstrate that a more complex model that accounts for nucleotide interdependencies performs better when compared with simple models. This ability to identify TFs with critical nucleotide interdependencies in their binding sites will lead to a deeper understanding of how these molecular characteristics contribute to the architecture of CRMs and the precise regulation of transcription during organismal development.

  11. 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

  12. Prevalence and correlates of nicotine dependence among construction site workers: A cross-sectional study in Delhi

    Directory of Open Access Journals (Sweden)

    Mamta Parashar

    2016-01-01

    Full Text Available Introduction: Workers represent half the world′s population and are major contributors to economic and social development. Tobacco consumption in construction site workers has been considered a big challenge. Objectives: (1 To assess the prevalence of nicotine dependence among tobacco users. (2 To study the correlates of nicotine dependence among the construction site workers. Methodology: A cross sectional study was conducted using a predesigned and pretested structured proforma. The study was conducted among all construction site workers aged 18yrs and above in campus of Hamdard Institute of Medical Sciences and Research and associated HAH centenary hospital, New Delhi.Karl Fagerstrom Nicotine Dependence Questionnaire was used to assess dependence on nicotine. Results: The mean age of construction site workers was 32.04±11.6 years. Among the workers, majority (91% were tobacco user. Among the users, 60% found it difficult to refrain from smoking/chewing in places where use of tobacco is not allowed (e.g. hospitals, government offices, cinemas, Libraries etc. 55% of the users smoked or chewed tobacco during the first hours after waking than during the rest of the day. On multivariate analysis, the factors which were found to be significantly associated with nicotine dependence were lower income group (OR 2.57, CI:1.66-3.99, smokeless tobacco use (OR 2.36,CI:1.30-4.27 and lower education (OR = 2.86 (95% CI 1.97-4.16 for illiterate. Discussion: The prevalence of tobacco use (91% among construction workers is very high compared to that in the general population. Recognition of construction sites as work places and proper implementation of law is needed.

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

    International Nuclear Information System (INIS)

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

    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

  14. 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

  15. Unbiased proteomics analysis demonstrates significant variability in mucosal immune factor expression depending on the site and method of collection.

    Directory of Open Access Journals (Sweden)

    Kenzie M Birse

    Full Text Available Female genital tract secretions are commonly sampled by lavage of the ectocervix and vaginal vault or via a sponge inserted into the endocervix for evaluating inflammation status and immune factors critical for HIV microbicide and vaccine studies. This study uses a proteomics approach to comprehensively compare the efficacy of these methods, which sample from different compartments of the female genital tract, for the collection of immune factors. Matching sponge and lavage samples were collected from 10 healthy women and were analyzed by tandem mass spectrometry. Data was analyzed by a combination of differential protein expression analysis, hierarchical clustering and pathway analysis. Of the 385 proteins identified, endocervical sponge samples collected nearly twice as many unique proteins as cervicovaginal lavage (111 vs. 61 with 55% of proteins common to both (213. Each method/site identified 73 unique proteins that have roles in host immunity according to their gene ontology. Sponge samples enriched for specific inflammation pathways including acute phase response proteins (p = 3.37×10(-24 and LXR/RXR immune activation pathways (p = 8.82×10(-22 while the role IL-17A in psoriasis pathway (p = 5.98×10(-4 and the complement system pathway (p = 3.91×10(-3 were enriched in lavage samples. Many host defense factors were differentially enriched (p<0.05 between sites including known/potential antimicrobial factors (n = 21, S100 proteins (n = 9, and immune regulatory factors such as serpins (n = 7. Immunoglobulins (n = 6 were collected at comparable levels in abundance in each site although 25% of those identified were unique to sponge samples. This study demonstrates significant differences in types and quantities of immune factors and inflammation pathways collected by each sampling technique. Therefore, clinical studies that measure mucosal immune activation or factors assessing HIV transmission should utilize

  16. Exercise identity as a risk factor for exercise dependence.

    Science.gov (United States)

    Murray, Aja L; McKenzie, Karen; Newman, Emily; Brown, Erin

    2013-05-01

    The aim of the study was to explore the relationship between exercise identity and exercise dependence. We hypothesized that stronger exercise identities would be associated with greater odds of experiencing exercise dependence symptoms. Logistic regression was used to assess the extent of association between exercise identity and the risk of experiencing exercise dependence symptoms. Participants (101) were recruited online via sports clubs and social networking sites and were asked to complete online measures of exercise identity and exercise dependence. The overall model fit was a significant improvement on the baseline model, but only the exercise beliefs factor was significantly associated with the odds of dependence symptoms, with higher scores on the belief scale predicting greater odds of experiencing dependence symptoms. Exercise role identity, in contrast, was not significantly associated with odds of experiencing dependence symptoms. Per cent correct classification was 55.9% for asymptomatic and 88.2% for symptomatic individuals and the overall per cent correct classification was 77.5%. The relation between identity and dependence could represent both a fruitful research avenue and a potential therapeutic target for those experiencing dependence symptoms; although our findings only showed a relationship between one of the two factors of the exercise identity measure and dependence. Longitudinal research is required to examine the relationship between identity and dependence in the context of other variables to better understand why some individuals become exercise dependent whereas others do not. What is already known on this subject? Exercise identity has been identified as an important determinant of exercise behaviour and studies within the exercise identity framework have proven elucidative with respect to the psychological processes that may underpin commitment to exercise. It has separately been established that some individuals may become

  17. 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.

  18. Effective stochastic generator with site-dependent interactions

    Science.gov (United States)

    Khamehchi, Masoumeh; Jafarpour, Farhad H.

    2017-11-01

    It is known that the stochastic generators of effective processes associated with the unconditioned dynamics of rare events might consist of non-local interactions; however, it can be shown that there are special cases for which these generators can include local interactions. In this paper, we investigate this possibility by considering systems of classical particles moving on a one-dimensional lattice with open boundaries. The particles might have hard-core interactions similar to the particles in an exclusion process, or there can be many arbitrary particles at a single site in a zero-range process. Assuming that the interactions in the original process are local and site-independent, we will show that under certain constraints on the microscopic reaction rules, the stochastic generator of an unconditioned process can be local but site-dependent. As two examples, the asymmetric zero-temperature Glauber model and the A-model with diffusion are presented and studied under the above-mentioned constraints.

  19. 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...

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

    African Journals Online (AJOL)

    Risk factors for surgical site infections following clean orthopaedic operations. ... the host and environmental risk factors for surgical site infections following clean ... Materials and Methods: Consecutive patients who satisfied the inclusion ...

  1. 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)

  2. Two DNA sites for MelR in the same orientation are sufficient for optimal MelR-dependent

    OpenAIRE

    Elrobh, M.; Webster, C.; Samarasinghe, S.; Durose, D.; Busby, S.

    2012-01-01

    The Escherichia coli melR gene encodes the MelR transcription factor that controls melibiose utilization. Expression of melR is autoregulated by MelR, which represses the melR promoter by binding to a target that overlaps the transcript start. Here, we show that MelR-dependent repression of the melR promoter can be enhanced by the presence of a second single DNA site for MelR located up to 250 base pairs upstream. Parallels with AraC-dependent repression at the araC–araBAD regulatory region a...

  3. 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.

  4. 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

  5. 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.

  6. Tissue factor-dependent vascular endothelial growth factor production by human fibroblasts in response to activated factor VII.

    Science.gov (United States)

    Ollivier, V; Bentolila, S; Chabbat, J; Hakim, J; de Prost, D

    1998-04-15

    The transmembrane protein tissue factor (TF) is the cell surface receptor for coagulation factor VII (FVII) and activated factor VII (FVIIa). Recently, TF has been identified as a regulator of angiogenesis, tumor growth, and metastasis. This study was designed to link the binding of FVII(a) to its receptor, TF, with the subsequent triggering of angiogenesis through vascular endothelial growth factor (VEGF) production by human lung fibroblasts. We report that incubation of fibroblasts, which express constitutive surface TF, with FVII(a) induces VEGF synthesis. FVII(a)-induced VEGF secretion, assessed by a specific enzyme-linked immunosorbent assay, was time- and concentration-dependent. VEGF secretion was maximal after 24 hours of incubation of the cells with 100 nmol/L FVII(a) and represented a threefold induction of the basal VEGF level. Reverse transcriptase-polymerase chain reaction analysis of VEGF detected three mRNA species of 180, 312, and 384 bp corresponding, respectively, to VEGF121, VEGF165, and VEGF189. A 2.5- to 3.5-fold increase was observed for the 180- and 312-bp transcripts at 12 and 24 hours, respectively. FVII(a)-dependent VEGF production was inhibited by a pool of antibodies against TF, pointing to the involvement of this receptor. On specific active-site inhibition with dansyl-glutamyl-glycinyl-arginyl chloromethyl ketone, FVIIa lost 70% of its capacity to elicit VEGF production. Consistent with this, the native form (zymogen) of FVII only had a 1.8-fold stimulating effect. Protein tyrosine kinase and protein kinase C are involved in signal transduction leading to VEGF production, as shown by the inhibitory effects of genistein and GF 109203X. The results of this study indicate that TF is essential for VIIa-induced VEGF production by human fibroblasts and that its role is mainly linked to the proteolytic activity of the TF-VIIa complex.

  7. 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

  8. 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

  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. 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.

  11. 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.

  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. 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.

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. msCentipede: Modeling Heterogeneity across Genomic Sites and Replicates Improves Accuracy in the Inference of Transcription Factor Binding.

    Directory of Open Access Journals (Sweden)

    Anil Raj

    Full Text Available Understanding global gene regulation depends critically on accurate annotation of regulatory elements that are functional in a given cell type. CENTIPEDE, a powerful, probabilistic framework for identifying transcription factor binding sites from tissue-specific DNase I cleavage patterns and genomic sequence content, leverages the hypersensitivity of factor-bound chromatin and the information in the DNase I spatial cleavage profile characteristic of each DNA binding protein to accurately infer functional factor binding sites. However, the model for the spatial profile in this framework fails to account for the substantial variation in the DNase I cleavage profiles across different binding sites. Neither does it account for variation in the profiles at the same binding site across multiple replicate DNase I experiments, which are increasingly available. In this work, we introduce new methods, based on multi-scale models for inhomogeneous Poisson processes, to account for such variation in DNase I cleavage patterns both within and across binding sites. These models account for the spatial structure in the heterogeneity in DNase I cleavage patterns for each factor. Using DNase-seq measurements assayed in a lymphoblastoid cell line, we demonstrate the improved performance of this model for several transcription factors by comparing against the Chip-seq peaks for those factors. Finally, we explore the effects of DNase I sequence bias on inference of factor binding using a simple extension to our framework that allows for a more flexible background model. The proposed model can also be easily applied to paired-end ATAC-seq and DNase-seq data. msCentipede, a Python implementation of our algorithm, is available at http://rajanil.github.io/msCentipede.

  19. msCentipede: Modeling Heterogeneity across Genomic Sites and Replicates Improves Accuracy in the Inference of Transcription Factor Binding.

    Science.gov (United States)

    Raj, Anil; Shim, Heejung; Gilad, Yoav; Pritchard, Jonathan K; Stephens, Matthew

    2015-01-01

    Understanding global gene regulation depends critically on accurate annotation of regulatory elements that are functional in a given cell type. CENTIPEDE, a powerful, probabilistic framework for identifying transcription factor binding sites from tissue-specific DNase I cleavage patterns and genomic sequence content, leverages the hypersensitivity of factor-bound chromatin and the information in the DNase I spatial cleavage profile characteristic of each DNA binding protein to accurately infer functional factor binding sites. However, the model for the spatial profile in this framework fails to account for the substantial variation in the DNase I cleavage profiles across different binding sites. Neither does it account for variation in the profiles at the same binding site across multiple replicate DNase I experiments, which are increasingly available. In this work, we introduce new methods, based on multi-scale models for inhomogeneous Poisson processes, to account for such variation in DNase I cleavage patterns both within and across binding sites. These models account for the spatial structure in the heterogeneity in DNase I cleavage patterns for each factor. Using DNase-seq measurements assayed in a lymphoblastoid cell line, we demonstrate the improved performance of this model for several transcription factors by comparing against the Chip-seq peaks for those factors. Finally, we explore the effects of DNase I sequence bias on inference of factor binding using a simple extension to our framework that allows for a more flexible background model. The proposed model can also be easily applied to paired-end ATAC-seq and DNase-seq data. msCentipede, a Python implementation of our algorithm, is available at http://rajanil.github.io/msCentipede.

  20. 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

  1. 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.

  2. Predictors of Mobile Phone and Social Networking Site Dependency in Adulthood.

    Science.gov (United States)

    Burnell, Kaitlyn; Kuther, Tara L

    2016-10-01

    The present study explored social and psychological predictors of social networking site (SNS) and mobile phone dependency in a sample of emerging adults (ages 18-25, n = 159, M = 21.87, SD = 2.08) and young adults (ages 26-40, n = 97, M = 31.21, SD = 4.11). Path analysis revealed that SNS dependency mediated the relationship of social comparison, SNS support, and impulsivity on mobile phone dependency. Impulsivity also showed direct links to mobile phone dependency. The present findings suggest that individuals with a strong orientation toward social comparison, who perceive a strong sense of support through SNS networks, or who show difficulty with self-regulation may be at risk for SNS and mobile phone dependency.

  3. Dispersion factors - tables and diagrams for the Karlsruhe site

    International Nuclear Information System (INIS)

    Papadopoulos, D.; Baer, M.; Honcu, S.

    1984-02-01

    Dispersion experiments were performed at the Nuclear Research Center for the Karlsruhe site. The evaluation of these experiments allowed to determine the parameters of lateral or vertical atmospheric dispersions. This report is a compilation of tables and diagrams showing the dispersion factors calculated with the help of the dispersion parameters. These dispersion factors are valid for the Karlsruhe site. They have been normalized to 1 m/s wind speed and to 1 g/s (or 1 Bq/s) source strength. (orig.) [de

  4. Empirical Site Amplification Factors Incorporating Soil Nonlinearity in Taiwan

    Science.gov (United States)

    Kuo, C. H.; Chung, C. H.; Che-Min, L.; Huang, J. Y.; Wen, K. L.

    2017-12-01

    Characteristics of site amplifications caused by both crustal and subduction earthquakes are important in Taiwan. For example, seismic waves were amplified and led to significant building damages in the Taipei Basin by the 1986 Hualien offshore (subduction interface) and the 1999 Chi-Chi earthquakes (crustal), for which the epicentral distances were about 100 km. To understand local site amplifications in Taiwan, empirical site amplification factors for horizontal ground motions are studied using recently constructed strong motion and site databases for the free-field TSMIP stations in Taiwan. Records of large magnitude earthquakes of ML larger than six from 1994 to 2014 were selected for this study. Site amplification factors at site conditions with Vs30 of 120 m/s to 1500 m/s and base accelerations up to 0.7g were inferred from intensity ratios of station pairs within specific distances. The reference site condition is assumed as Vs30 of 760 m/s (B/C boundary). Preliminary results indicate: 1. Soil nonlinearity is more obviously at short periods (PGA, Sa0.3) than long periods (PGV, Sa1.0). 2. Soil nonlinearity is significant for stations belong to site classes of B, C, D, and E in Taiwan. 3. Effect of station-pair distance is seen at short periods (PGA and Sa0.3). 4. No significant different is found in site amplifications of crustal and subduction earthquakes. The result could be a reference for the Fa and Fv in Taiwan's building code.

  5. 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.

  6. 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

  7. Examination of the site amplification factor of OBS and their application to magnitude estimation and ground-motion prediction for EEW

    Science.gov (United States)

    Hayashimoto, N.; Hoshiba, M.

    2013-12-01

    1. Introduction Ocean bottom seismograph (OBS) is useful for making Earthquake Early Warning (EEW) earlier. However, careful handling of these data is required because the installation environment of OBSs may be different from that of land stations. Site amplification factor is an important factor to estimate the magnitudes, and to predict ground motions (e.g. seismic intensity) in EEW. In this presentation, we discuss the site amplification factor of OBS in the Tonankai area of Japan from these two points of view. 2. Examination of magnitude correction of OBS In the EEW of JMA, the magnitude is estimated from the maximum amplitude of the displacement in real time. To provide the fast magnitude estimation, the magnitude-estimation algorithm switches from the P to S formula (Meew(P) to Meew(S)) depending on the expected S-phase arrival (Kamigaichi,2004). To estimate the magnitude correction for OBS, we determine Meew(P) and Meew(S) at OBSs and compare them with JMA magnitude (Mjma). We find Meew(S) at OBS is generally larger than Mjma by approximately 0.6. The slight differences of spatial distribution of Meew(S) amplification are also found among other OBSs. From the numerical simulations, Nakamura et al. (MGR,submitted) pointed out that the oceanic layer and the low-velocity sediment layers causes the large amplifications in low frequency range (0.1-0.2Hz) at OBSs. We conclude that the site effect of OBS characterized by such a low velocity sediment layers causes those amplification of Magnitude. 3. The frequency-dependent site factor of OBS estimated from Fourier spectrum ratio and their application for prediction of seismic intensity of land station We compare Fourier spectra of S-wave portion on OBSs with those on adjacent land stations. Station pair whose distance is smaller than 50 km is analyzed, and we obtain that spectral ratio of land station (MIEH05 of the KiK-net/NIED) to OBS (KMA01 of the DONET/JAMSTEC) is 5-20 for frequencies 10-20Hz for both

  8. Time dependent view factor methods

    International Nuclear Information System (INIS)

    Kirkpatrick, R.C.

    1998-03-01

    View factors have been used for treating radiation transport between opaque surfaces bounding a transparent medium for several decades. However, in recent years they have been applied to problems involving intense bursts of radiation in enclosed volumes such as in the laser fusion hohlraums. In these problems, several aspects require treatment of time dependence

  9. 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

  10. [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.

  11. 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.

  12. Identifying influential factors of business process performance using dependency analysis

    Science.gov (United States)

    Wetzstein, Branimir; Leitner, Philipp; Rosenberg, Florian; Dustdar, Schahram; Leymann, Frank

    2011-02-01

    We present a comprehensive framework for identifying influential factors of business process performance. In particular, our approach combines monitoring of process events and Quality of Service (QoS) measurements with dependency analysis to effectively identify influential factors. The framework uses data mining techniques to construct tree structures to represent dependencies of a key performance indicator (KPI) on process and QoS metrics. These dependency trees allow business analysts to determine how process KPIs depend on lower-level process metrics and QoS characteristics of the IT infrastructure. The structure of the dependencies enables a drill-down analysis of single factors of influence to gain a deeper knowledge why certain KPI targets are not met.

  13. 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

  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. Identification of a mammalian nuclear factor and human cDNA-encoded proteins that recognize DNA containing apurinic sites

    International Nuclear Information System (INIS)

    Lenz, J.; Okenquist, S.A.; LoSardo, J.E.; Hamilton, K.K.; Doetsch, P.W.

    1990-01-01

    Damage to DNA can have lethal or mutagenic consequences for cells unless it is detected and repaired by cellular proteins. Repair depends on the ability of cellular factors to distinguish the damaged sites. Electrophoretic binding assays were used to identify a factor from the nuclei of mammalian cells that bound to DNA containing apurinic sites. A binding assay based on the use of β-galactosidase fusion proteins was subsequently used to isolate recombinant clones of human cDNAs that encoded apurinic DNA-binding proteins. Two distinct human cDNAs were identified that encoded proteins that bound apurinic DNA preferentially over undamaged, methylated, or UV-irradiated DNA. These approaches may offer a general method for the detection of proteins that recognize various types of DNA damage and for the cloning of genes encoding such proteins

  16. Time dependence of the 137Cs resuspension factor on the Romanian territory after the Chernobyl accident

    International Nuclear Information System (INIS)

    Mihaila, B.; Cuculeanu, V.

    1994-01-01

    On the basis of the radioactivity levels in aerosol and atmospheric deposition samples due to the Chernobyl accident, the resuspension factor of 137 Cs as a four-parameter function has been inferred. The standard procedure to derive the dependence of resuspension on time assumes that the initial deposit is instantaneous. A simple method assuming a constant deposition rate over a fixed period has been proposed. Also, based on existing experimental data, an attempt was made to consider a realistic time dependence of the deposition rate to cope with the particular case of the Chernobyl accident. The differences between the two models are outlined. The Chernobyl direct deposit has been assumed to be the deposit measured between 30 April and 30 June 1986. The calculated values of the resuspension factor are consistent with the IAEA's recommended model and depend on the rainfall that occurred in June 1986 and the site-specific disturbance conditions during the first 100 d following 1 July 1986 and only on artificial disturbance by humans and vehicles after that. 16 refs., 5 figs., 3 tabs

  17. 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

  18. 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

  19. 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

  20. Scale-dependent associations of Band-tailed Pigeon counts at mineral sites

    Science.gov (United States)

    Overton, Cory T.; Casazza, Michael L.; Coates, Peter S.

    2010-01-01

    The abundance of Band-tailed Pigeons (Patagioenas fasciata monilis) has declined substantially from historic numbers along the Pacific Coast. Identification of patterns and causative factors of this decline are hampered because habitat use data are limited, and temporal and spatial variability patterns associated with population indices are not known. Furthermore, counts are influenced not only by pigeon abundance but also by rate of visitation to mineral sites, which may not be consistent. To address these issues, we conducted mineral site counts during 2001 and 2002 at 20 locations from 4 regions in the Pacific Northwest, including central Oregon and western Washington, USA, and British Columbia, Canada. We developed inference models that consisted of environmental factors and spatial characteristics at multiple spatial scales. Based on information theory, we compared models within a final set that included variables measured at 3 spatial scales (0.03 ha, 3.14 ha, and 7850 ha). Pigeon counts increased from central Oregon through northern Oregon and decreased into British Columbia. After accounting for this spatial pattern, we found that pigeon counts increased 12% ± 2.7 with a 10% increase in the amount of deciduous forested area within 100 m from a mineral site. Also, distance from the mineral site of interest to the nearest known mineral site was positively related to pigeon counts. These findings provide direction for future research focusing on understanding the relationships between indices of relative abundance and complete counts (censuses) of pigeon populations by identifying habitat characteristics that might influence visitation rates. Furthermore, our results suggest that spatial arrangement of mineral sites influences Band-tailed Pigeon counts and the populations which those counts represent.

  1. 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.

  2. 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)

  3. New Site Coefficients and Site Classification System Used in Recent Building Seismic Code Provisions

    Science.gov (United States)

    Dobry, R.; Borcherdt, R.D.; Crouse, C.B.; Idriss, I.M.; Joyner, W.B.; Martin, G.R.; Power, M.S.; Rinne, E.E.; Seed, R.B.

    2000-01-01

    Recent code provisions for buildings and other structures (1994 and 1997 NEHRP Provisions, 1997 UBC) have adopted new site amplification factors and a new procedure for site classification. Two amplitude-dependent site amplification factors are specified: Fa for short periods and Fv for longer periods. Previous codes included only a long period factor S and did not provide for a short period amplification factor. The new site classification system is based on definitions of five site classes in terms of a representative average shear wave velocity to a depth of 30 m (V?? s). This definition permits sites to be classified unambiguously. When the shear wave velocity is not available, other soil properties such as standard penetration resistance or undrained shear strength can be used. The new site classes denoted by letters A - E, replace site classes in previous codes denoted by S1 - S4. Site classes A and B correspond to hard rock and rock, Site Class C corresponds to soft rock and very stiff / very dense soil, and Site Classes D and E correspond to stiff soil and soft soil. A sixth site class, F, is defined for soils requiring site-specific evaluations. Both Fa and Fv are functions of the site class, and also of the level of seismic hazard on rock, defined by parameters such as Aa and Av (1994 NEHRP Provisions), Ss and S1 (1997 NEHRP Provisions) or Z (1997 UBC). The values of Fa and Fv decrease as the seismic hazard on rock increases due to soil nonlinearity. The greatest impact of the new factors Fa and Fv as compared with the old S factors occurs in areas of low-to-medium seismic hazard. This paper summarizes the new site provisions, explains the basis for them, and discusses ongoing studies of site amplification in recent earthquakes that may influence future code developments.

  4. 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

  5. Position dependence of the rous sarcoma virus negative regulator of splicing element reflects proximity to a 5' splice site

    International Nuclear Information System (INIS)

    Wang Yuedi; McNally, Mark T.

    2003-01-01

    Rous sarcoma virus (RSV) requires incomplete splicing of its viral transcripts to maintain efficient replication. A splicing inhibitor element, the negative regulator of splicing (NRS), is located near the 5' end of the RNA but the significance of this positioning is not known. In a heterologous intron the NRS functions optimally when positioned close to the authentic 5' splice site. This observation led us to investigate the basis of the position dependence. Four explanations were put forth and stressed the role of three major elements involved in splicing, the 3' splice site, the 5' splice site, and the 5' end cap structure. NRS function was unrelated to its position relative to the 3' splice site or the cap structure and appeared to depend on its position relative to the authentic 5' splice site. We conclude that position dependence may reflect distance constraints necessary for competition of the NRS with the authentic 5' splice site for pairing with the 3' splice sites

  6. 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

  7. 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

  8. Rate of progression from first use to dependence on cocaine or opioids: a cross-substance examination of associated demographic, psychiatric, and childhood risk factors.

    Science.gov (United States)

    Sartor, Carolyn E; Kranzler, Henry R; Gelernter, Joel

    2014-02-01

    A number of demographic factors, psychiatric disorders, and childhood risk factors have been associated with cocaine dependence (CD) and opioid dependence (OD), but little is known about their relevance to the rate at which dependence develops. Identification of the subpopulations at elevated risk for rapid development of dependence and the risk factors that accelerate the course of dependence is an important public health goal. Data were derived from cocaine dependent (n=6333) and opioid dependent (n=3513) participants in a multi-site study of substance dependence. Mean age was approximately 40 and 40% of participants were women; 51.9% of cocaine dependent participants and 29.5% of opioid dependent participants self-identified as Black/African-American. The time from first use to dependence was calculated for each substance and a range of demographic, psychiatric, and childhood risk factors were entered into ordinal logistic regression models to predict the (categorical) transition time to CD and OD. In both the cocaine and opioid models, conduct disorder and childhood physical abuse predicted rapid development of dependence and alcohol and nicotine dependence diagnoses were associated with slower progression to CD or OD. Blacks/African Americans were at greater risk than European Americans to progress rapidly to OD. Only a subset of factors known to be associated with CD and OD predicted the rate at which dependence developed. Nearly all were common to cocaine and opioids, suggesting that sources of influence on the timing of transitions to dependence are shared across the two substances. © 2013.

  9. 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...

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

    African Journals Online (AJOL)

    Magnitude and factors associated with post-cesarean surgical site infection at Hawassa University Teaching and referral hospital, southern Ethiopia: a ... the hospital. Thus, it should be averted by implementing infection prevention techniques.

  11. 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

  12. 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.

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

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    Identifying transcription factor binding sites (TFBSs) is essential to elucidate ... alignments with parts annotated as gap lessly aligned TFBSs (pair-profile hits) are generated. Moreover, the pair- profile related parameters are derived in a sound statistical framework. ... Much research has gone into the study of the evolution of.

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

    Indian Academy of Sciences (India)

    Inhibition of factor-dependent transcription termination in Escherichia coli might relieve xenogene silencing by abrogating. H-NS-DNA interactions in vivo. DEEPTI CHANDRAPRAKASH and ASWIN SAI NARAIN SESHASAYEE. Chromatin immunoprecipitation. MG1655 hns::3xFLAG cells were grown in liquid LB me-.

  15. 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

  16. 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.

  17. 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...

  18. 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.

  19. 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.

  20. Synthesis and characterization of 18F-labeled active site inhibited factor VII (ASIS)

    DEFF Research Database (Denmark)

    Erlandsson, Maria; Nielsen, Carsten Haagen; Jeppesen, Troels Elmer

    2015-01-01

    Activated factor VII blocked in the active site with Phe-Phe-Arg-chloromethyl ketone (active site inhibited factor VII (ASIS)) is a 50-kDa protein that binds with high affinity to its receptor, tissue factor (TF). TF is a transmembrane glycoprotein that plays an important role in, for example......, thrombosis, metastasis, tumor growth, and tumor angiogenesis. The aim of this study was to develop an 18F-labeled ASIS derivative to assess TF expression in tumors. Active site inhibited factor VII was labeled using N-succinimidyl-4-[18F]fluorobenzoate, and the [18F]ASIS was purified on a PD-10 desalting...... column. The radiochemical yield was 25 ± 6%, the radiochemical purity was >97%, and the pseudospecific radioactivity was 35 ± 9 GBq/µmol. The binding efficacy was evaluated in pull-down experiments, which monitored the binding of unlabeled ASIS and [18F]ASIS to TF and to a specific anti-factor VII...

  1. 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.

  2. The spin-dependent neutralino-nucleus form factor for 127I

    International Nuclear Information System (INIS)

    Ressell, M.T.

    1996-01-01

    We present the results of detailed shell model calculations of the spin-dependent elastic form factor for the nucleus 127 I. the calculations were performed in extremely large model spaces which adequately describe the configuration mixing in this nucleus. Good agreement between the calculated and experimental values of the magnetic moment are found. Other nuclear observables are also compared to experiment. The dependence of the form factor upon the model space and effective interaction is discussed

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

    International Nuclear Information System (INIS)

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

    1990-01-01

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

  4. Temperature Dependence of Factors Controlling Isoprene Emissions

    Science.gov (United States)

    Duncan, Bryan N.; Yoshida, Yasuko; Damon, Megan R.; Douglass, Anne R.; Witte, Jacquelyn C.

    2009-01-01

    We investigated the relationship of variability in the formaldehyde (HCHO) columns measured by the Aura Ozone Monitoring Instrument (OMI) to isoprene emissions in the southeastern United States for 2005-2007. The data show that the inferred, regional-average isoprene emissions varied by about 22% during summer and are well correlated with temperature, which is known to influence emissions. Part of the correlation with temperature is likely associated with other causal factors that are temperature-dependent. We show that the variations in HCHO are convolved with the temperature dependence of surface ozone, which influences isoprene emissions, and the dependence of the HCHO column to mixed layer height as OMI's sensitivity to HCHO increases with altitude. Furthermore, we show that while there is an association of drought with the variation in HCHO, drought in the southeastern U.S. is convolved with temperature.

  5. 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...

  6. FACTORS PREDICTING CONSUMERS' ASSESSMENT OF ADVERTISEMENTS ON SOCIAL NETWORKING SITES

    OpenAIRE

    Hossam Deraz; Gabriel Baffour Awuah; Desalegn Abraha Gebrekidan

    2015-01-01

    Marketers act on social networking sites (SNSs) in order to be more efficient in merchandising their products and/or services. Even so, the scope of the published studies regarding the assessment of advertisements on social networking sites (SNAs) is limited. Consequently, the present study aimed to consider credibility and interactivity, in addition to information, entertainment and irritation values, as main factors for consumers’ assessment of SNAs, as perceived by SNSs’ users. An analysis...

  7. 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.

  8. 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.)

  9. Prediction of nucleosome positioning based on transcription factor binding sites.

    Directory of Open Access Journals (Sweden)

    Xianfu Yi

    Full Text Available BACKGROUND: The DNA of all eukaryotic organisms is packaged into nucleosomes, the basic repeating units of chromatin. The nucleosome consists of a histone octamer around which a DNA core is wrapped and the linker histone H1, which is associated with linker DNA. By altering the accessibility of DNA sequences, the nucleosome has profound effects on all DNA-dependent processes. Understanding the factors that influence nucleosome positioning is of great importance for the study of genomic control mechanisms. Transcription factors (TFs have been suggested to play a role in nucleosome positioning in vivo. PRINCIPAL FINDINGS: Here, the minimum redundancy maximum relevance (mRMR feature selection algorithm, the nearest neighbor algorithm (NNA, and the incremental feature selection (IFS method were used to identify the most important TFs that either favor or inhibit nucleosome positioning by analyzing the numbers of transcription factor binding sites (TFBSs in 53,021 nucleosomal DNA sequences and 50,299 linker DNA sequences. A total of nine important families of TFs were extracted from 35 families, and the overall prediction accuracy was 87.4% as evaluated by the jackknife cross-validation test. CONCLUSIONS: Our results are consistent with the notion that TFs are more likely to bind linker DNA sequences than the sequences in the nucleosomes. In addition, our results imply that there may be some TFs that are important for nucleosome positioning but that play an insignificant role in discriminating nucleosome-forming DNA sequences from nucleosome-inhibiting DNA sequences. The hypothesis that TFs play a role in nucleosome positioning is, thus, confirmed by the results of this study.

  10. 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.

  11. Positional dependence of the SNPP VIIRS SD BRDF degradation factor

    Science.gov (United States)

    Lei, Ning; Chen, Xuexia; Chang, Tiejun; Xiong, Xiaoxiong

    2017-09-01

    The Visible Infrared Imaging Radiometer Suite (VIIRS) aboard the Suomi National Polar-orbiting Partnership (SNPP) satellite is a passive scanning radiometer and an imager. The VIIRS regularly performs on-orbit radiometric calibration of its reflective solar bands (RSBs) through observing an onboard sunlit solar diffuser (SD). The reflectance of the SD changes over time and the change is denoted as the SD bidirectional reflectance distribution function degradation factor. The degradation factor, measured by an onboard solar diffuser stability monitor, has been shown to be both incident sunlight and outgoing direction dependent. In this Proceeding, we investigate the factor's dependence on SD position. We develop a model to relate the SD degradation factor with the amount of solar exposure. We use Earth measurements to evaluate the effectiveness of the model.

  12. 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

  13. 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.

  14. 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.

  15. Self-absorption alpha particle factor in water: interest in the monitoring of specific military sites

    International Nuclear Information System (INIS)

    Cazoulat, A.; Lecompte, Y.; Bohand, S.; Gerasimo, P.

    2007-01-01

    Self-absorption alpha particle factor validation in water: Interest in the monitoring of specific military sites. The population internal intake prevention by radionuclides present in water needs to monitor the radioactive Level of this water. The French public health legislation introduces four radiological parameters for monitoring water, such as the gross alpha radioactivity. Regarding the alpha particle characteristics, a self-absorption factor has to be established beforehand, not to underestimate the real alpha radioactivity in water samples. The aim of this paper is to describe the procedure used by the laboratory of the French army radioprotection service to determine this f factor, which depends on the water residue mass m after evaporation. The relation is f = 0.0253 m + 1.2813. This formula can be employed for such waters used in this experiment and for masses between 0 and 100 mg. The uncertainty associated is about 11% (k = 2). Some water monitoring examples are given. It is specially the case of depleted uranium shells experiment centres, localized in Gramat and Bourges. (authors)

  16. When Factorization Meets Heterogeneous Latent Topics:An Interpretable Cross-Site Recommendation Framework

    Institute of Scientific and Technical Information of China (English)

    辛欣; 林钦佑; 魏骁驰; 黄河燕

    2015-01-01

    Data sparsity is a well-known challenge in recommender systems. Previous studies alleviate this problem by incorporating the information within the corresponding social media site. In this paper, we solve this challenge by exploring cross-site information. Specifically, we examine: 1) how to effectively and efficiently utilize cross-site ratings and content features to improve recommendation performance and 2) how to make the recommendation interpretable by utilizing content features. We propose a joint model of matrix factorization and latent topic analysis. Heterogeneous content features are modeled by multiple kinds of latent topics. In addition, the combination of matrix factorization and latent topics makes the recommendation result interpretable. Therefore, the above two issues are simultaneously solved. Through a real-world dataset, where user behaviors in three social media sites are collected, we demonstrate that the proposed model is effective in improving recommendation performance and interpreting the rationale of ratings.

  17. Proliferating Cell Nuclear Antigen-dependent Rapid Recruitment of Cdt1 and CRL4Cdt2 at DNA-damaged Sites after UV Irradiation in HeLa Cells*

    Science.gov (United States)

    Ishii, Takashi; Shiomi, Yasushi; Takami, Toshihiro; Murakami, Yusuke; Ohnishi, Naho; Nishitani, Hideo

    2010-01-01

    The licensing factor Cdt1 is degraded by CRL4Cdt2 ubiquitin ligase dependent on proliferating cell nuclear antigen (PCNA) during S phase and when DNA damage is induced in G1 phase. Association of both Cdt2 and PCNA with chromatin was observed in S phase and after UV irradiation. Here we used a micropore UV irradiation assay to examine Cdt2 accumulation at cyclobutane pyrimidine dimer-containing DNA-damaged sites in the process of Cdt1 degradation in HeLa cells. Cdt2, present in the nucleus throughout the cell cycle, accumulated rapidly at damaged DNA sites during G1 phase. The recruitment of Cdt2 is dependent on prior PCNA chromatin binding because Cdt2 association was prevented when PCNA was silenced. Cdt1 was also recruited to damaged sites soon after UV irradiation through its PIP-box. As Cdt1 was degraded, the Cdt2 signal at damaged sites was reduced, but PCNA, cyclobutane pyrimidine dimer, and XPA (xeroderma pigmentosum, complementation group A) signals remained at the same levels. These findings suggest that Cdt1 degradation following UV irradiation occurs rapidly at damaged sites due to PCNA chromatin loading and the recruitment of Cdt1 and CRL4Cdt2, before DNA damage repair is completed. PMID:20929861

  18. 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.

  19. 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.

  20. A Study of Factors Influencing Consumer Adoption of Group-Buying Sites in Malaysia

    OpenAIRE

    Bohara, Shilpa

    2011-01-01

    Group-buying sites have been the biggest internet phenomena in the recent B2C ecommerce industry. This new development has led to this research’s main objective of identifying factors that influence consumers’ intention to purchase from groupbuying sites, particularly in Malaysia. Using the extended Technology Acceptance Model, the five factors measured against consumers’ behavioral intent to transact are perceived knowledge, perceived benefits of price promotion, personal innovativeness, soc...

  1. 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.

  2. 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......-harmonic approximations and results of previous experiments....

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1990-04-03

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

  4. 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

  5. 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....... 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....

  6. Factors Enabling Information Propagation in a Social Network Site

    DEFF Research Database (Denmark)

    Magnani, Matteo; Montesi, Danilo; Rossi, Luca

    2013-01-01

    A relevant feature of Social Network Sites is their ability to propagate units of information and create large distributed conversations. This phenomenon is particularly relevant because of the speed of information propagation, which is known to be much faster than within traditional media......, and because of the very large amount of people that can potentially be exposed to information items. While many general formal models of network propagation have been developed in different research fields, in this chapter we present the result of an empirical study on a Large Social Database (LSD) aimed...... at measuring specific socio-technical factors enabling information spreading in Social Network Sites....

  7. Path dependence in social and psychological risk factors for dementia

    Directory of Open Access Journals (Sweden)

    Hiroko Matsuoka

    Full Text Available Abstract This article focuses on social and psychological risk factors for Alzheimer's disease, dementia, and cognitive impairment and presents some key points for prevention in developing countries based on previous studies, a social science theory, and our preliminary survey. Previous population-based studies found that educational and occupational attainment, income, participation in social and mental activities, and psychological distress were associated with dementia risk. According to the theory of path dependence, earlier factors largely determine successive ones, where education is one of these early experiences in life. Our preliminary survey suggested that education sets a path that several psychosocial risk factors are dependent on. The expansion of basic education is indispensable. Resources for prevention should be concentrated on individuals with a low level of education. In order to break from a path creating self-reinforcement of risk factors, it is necessary to implement early and active interventions.

  8. 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.

  9. 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

  10. 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

  11. [Interaction of human factor X with thromboplastin].

    Science.gov (United States)

    Kiselev, S V; Zubairov, D M; Timarbaev, V N

    2003-01-01

    The binding of 125I-labeled human factor X to native and papaine-treated tissue tromboplastin in the presence of CaCl2 or EDTA was studied. The Scatchard analysis suggests the existence of high (Kd=l,8 x10(-9) M) and low affinity binding sites on the thromboplastin surface. The removal of Ca2+ reduced affinity of factor X to the high affinity sites. This was accompanied by some increase of their number. Proteolysis by papaine decreased affinity of high affinity sites and caused the increase of their number in the presence of Ca2+. In the absence of Ca2+ the affinity remained unchanged, but the number of sites decreased. At low concentrations of factor X positive cooperativity for high affinity binding sites was observed. It did not depend on the presence of Ca2+. The results indirectly confirm the role of hydrophobic interactons in Ca2+ dependent binding of factor X to thromboplastin and the fact that heterogeneity of this binding is determined by mesophase structure of the thromboplastin phospholipids.

  12. Determination of antenna factors using a three-antenna method at open-field test site

    Science.gov (United States)

    Masuzawa, Hiroshi; Tejima, Teruo; Harima, Katsushige; Morikawa, Takao

    1992-09-01

    Recently NIST has used the three-antenna method for calibration of the antenna factor of an antenna used for EMI measurements. This method does not require the specially designed standard antennas which are necessary in the standard field method or the standard antenna method, and can be used at an open-field test site. This paper theoretically and experimentally examines the measurement errors of this method and evaluates the precision of the antenna-factor calibration. It is found that the main source of the error is the non-ideal propagation characteristics of the test site, which should therefore be measured before the calibration. The precision of the antenna-factor calibration at the test site used in these experiments, is estimated to be 0.5 dB.

  13. 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

  14. [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.

  15. An analytical evaluation for spatial-dependent intra-pebble Dancoff factor and escape probability

    International Nuclear Information System (INIS)

    Kim, Songhyun; Kim, Hong-Chul; Kim, Jong Kyung; Kim, Soon Young; Noh, Jae Man

    2009-01-01

    The analytical evaluation of spatial-dependent intra-pebble Dancoff factors and their escape probabilities is pursued by the model developed in this study. Intra-pebble Dancoff factors and their escape probabilities are calculated as a function of fuel kernel radius, number of fuel kernels, and fuel region radius. The method in this study can be easily utilized to analyze the tendency of spatial-dependent intra-pebble Dancoff factor and spatial-dependent fuel region escape probability for the various geometries because it is faster than the MCNP method as well as good accuracy. (author)

  16. 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

  17. Risk of alcohol dependence: prevalence, related problems and socioeconomic factors

    Directory of Open Access Journals (Sweden)

    Juliana Gabrielle Martins-Oliveira

    2016-01-01

    Full Text Available Abstract The present study evaluated the possible alcohol dependence and related problems among adolescents and determined possible associations with socioeconomic factors and gender. A cross-sectional study was conducted with a representative sample of 936 adolescents aged 15 to 19 years enrolled at public and private schools in the city of Belo Horizonte, Brazil. Data related to alcohol consumption and associated problems were collected using the Alcohol Use Disorder Identification Test (AUDIT. The Social Vulnerability Index (SVI, mother's schooling and type of school were used to assess socioeconomic factors. Statistical analysis involved the chi-square test (p < 0.05 and Poisson regression. The prevalence of possible dependence was 16.4%, 52.1% reported concern of a family member regarding the adolescent's alcohol consumption. Female adolescents were less likely to exhibit possible dependence in comparison to males. Participants with living in a low vulnerability area were more likely to consume alcohol in comparison to those living in underprivileged areas. The results of the present study demonstrate that possible dependence was significantly associated with the male gender and low social vulnerability.

  18. Generalized Efficient Inference on Factor Models with Long-Range Dependence

    DEFF Research Database (Denmark)

    Ergemen, Yunus Emre

    . Short-memory dynamics are allowed in the common factor structure and possibly heteroskedastic error term. In the estimation, a generalized version of the principal components (PC) approach is proposed to achieve efficiency. Asymptotics for efficient common factor and factor loading as well as long......A dynamic factor model is considered that contains stochastic time trends allowing for stationary and nonstationary long-range dependence. The model nests standard I(0) and I(1) behaviour smoothly in common factors and residuals, removing the necessity of a priori unit-root and stationarity testing...

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

    OpenAIRE

    Saeideh Sharifi fard; Ezhar Tamam; Md Salleh Hj Hassan; Moniza Waheed; Zeinab Zaremohzzabieh

    2016-01-01

    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 influe...

  20. Effects of Velocity-Dependent Force on the Magnetic Form Factors of Odd-Z Nuclei

    International Nuclear Information System (INIS)

    Tie-Kuang, Dong; Zhong-Zhou, Ren

    2008-01-01

    We investigate the effects of the velocity-dependent force on the magnetic form factors and magnetic moments of odd-Z nuclei. The form factors are calculated with the harmonic-oscillator wavefunctions. It is found that the contributions of the velocity-dependent force manifest themselves in the very large momentum transfer region (q ≥ 4fm- 1 ). In the low and medium q region the contributions of the velocity-dependent force are very small compared with those without this force. However, in the high-q region the contributions of the velocity-dependent force are larger than the normal form factors. The diffraction structures beyond the existing experimental data are found after the contributions of the velocity-dependent force are included. The formula of the correction to the single particle magnetic moment due to the velocity-dependent force is reproduced exactly in the long-wavelength limit (q = 0) of the M1 form factor

  1. Social factors and readmission after inpatient detoxification in older alcohol-dependent patients

    NARCIS (Netherlands)

    van den Berg, Julia F.; van den Brink, Wim; Kist, Nicolien; Hermes, Jolanda S. J.; Kok, Rob M.

    2015-01-01

    Alcohol dependence is often a chronic relapsing disorder with frequent admissions to inpatient facilities. This study in older alcohol-dependent inpatients investigates the role of social factors in readmissions after inpatient detoxification. In a prospective study, 132 older alcohol-dependent

  2. Health behaviors of victims and related factors in Wenchuan earthquake resettlement sites.

    Science.gov (United States)

    Liu, Qiaolan; Zhou, Hongyu; Zhou, Huan; Yang, Yang; Yang, Xiaoyan; Yu, Lingyun; Qiu, Peiyuan; Ma, Xiao

    2011-03-01

    The purpose of this study was to describe the health behaviors of earthquake victims related to gastrointestinal and respiratory infectious diseases in the centralized transitional earthquake resettlement sites in Wenchuan, China; and to identify key factors related to health behaviors that may inform local infectious diseases prevention and control strategies. Data were collected using a questionnaire that included questions about socio-demographic characteristics and health beliefs and behaviors. In total, 1411 participants were included through a two-stage random sampling strategy. A bivariate multilevel model was used to explore the related factors. Approximately 67% of the participants wash their hands after going to lavatories every time, and 87% felt uncomfortable spitting on the ground. The more the participants perceived their susceptibility to and the severity of infectious diseases, the better their health-related behaviors (P resettlement sites (P resettlement sites. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Statistical discovery of site inter-dependencies in sub-molecular hierarchical protein structuring.

    Science.gov (United States)

    Durston, Kirk K; Chiu, David Ky; Wong, Andrew Kc; Li, Gary Cl

    2012-07-13

    Much progress has been made in understanding the 3D structure of proteins using methods such as NMR and X-ray crystallography. The resulting 3D structures are extremely informative, but do not always reveal which sites and residues within the structure are of special importance. Recently, there are indications that multiple-residue, sub-domain structural relationships within the larger 3D consensus structure of a protein can be inferred from the analysis of the multiple sequence alignment data of a protein family. These intra-dependent clusters of associated sites are used to indicate hierarchical inter-residue relationships within the 3D structure. To reveal the patterns of associations among individual amino acids or sub-domain components within the structure, we apply a k-modes attribute (aligned site) clustering algorithm to the ubiquitin and transthyretin families in order to discover associations among groups of sites within the multiple sequence alignment. We then observe what these associations imply within the 3D structure of these two protein families. The k-modes site clustering algorithm we developed maximizes the intra-group interdependencies based on a normalized mutual information measure. The clusters formed correspond to sub-structural components or binding and interface locations. Applying this data-directed method to the ubiquitin and transthyretin protein family multiple sequence alignments as a test bed, we located numerous interesting associations of interdependent sites. These clusters were then arranged into cluster tree diagrams which revealed four structural sub-domains within the single domain structure of ubiquitin and a single large sub-domain within transthyretin associated with the interface among transthyretin monomers. In addition, several clusters of mutually interdependent sites were discovered for each protein family, each of which appear to play an important role in the molecular structure and/or function. Our results

  4. Retroviral restriction and dependency factors in primates and carnivores

    Science.gov (United States)

    Fadel, Hind J.; Poeschla, Eric M.

    2014-01-01

    Recent studies have extended the rapidly developing retroviral restriction factor field to cells of carnivore species. Carnivoran genomes, and the domestic cat genome in particular, are revealing intriguing properties vis-à;-vis the primate and feline lentiviruses, not only with respect to their repertoires of virus-blocking restriction factors but also replication-enabling dependency factors. Therapeutic application of restriction factors is envisioned for human immunodeficiency virus (HIV) disease and the feline immunodeficiency virus (FIV) model has promise for testing important hypotheses at the basic and translational level. Feline cell-tropic HIV-1 clones have also been generated by a strategy of restriction factor evasion. We review progress in this area in the context of what is known about retroviral restriction factors such as TRIM5alpha, TRIMCyp, APOBEC3 proteins and BST-2/Tetherin. PMID:21715018

  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. Normalization of energy-dependent gamma survey data.

    Science.gov (United States)

    Whicker, Randy; Chambers, Douglas

    2015-05-01

    Instruments and methods for normalization of energy-dependent gamma radiation survey data to a less energy-dependent basis of measurement are evaluated based on relevant field data collected at 15 different sites across the western United States along with a site in Mongolia. Normalization performance is assessed relative to measurements with a high-pressure ionization chamber (HPIC) due to its "flat" energy response and accurate measurement of the true exposure rate from both cosmic and terrestrial radiation. While analytically ideal for normalization applications, cost and practicality disadvantages have increased demand for alternatives to the HPIC. Regression analysis on paired measurements between energy-dependent sodium iodide (NaI) scintillation detectors (5-cm by 5-cm crystal dimensions) and the HPIC revealed highly consistent relationships among sites not previously impacted by radiological contamination (natural sites). A resulting generalized data normalization factor based on the average sensitivity of NaI detectors to naturally occurring terrestrial radiation (0.56 nGy hHPIC per nGy hNaI), combined with the calculated site-specific estimate of cosmic radiation, produced reasonably accurate predictions of HPIC readings at natural sites. Normalization against two to potential alternative instruments (a tissue-equivalent plastic scintillator and energy-compensated NaI detector) did not perform better than the sensitivity adjustment approach at natural sites. Each approach produced unreliable estimates of HPIC readings at radiologically impacted sites, though normalization against the plastic scintillator or energy-compensated NaI detector can address incompatibilities between different energy-dependent instruments with respect to estimation of soil radionuclide levels. The appropriate data normalization method depends on the nature of the site, expected duration of the project, survey objectives, and considerations of cost and practicality.

  7. Structure-dependent inhibition of the ETS-family transcription factor PU.1 by novel heterocyclic diamidines

    Science.gov (United States)

    Munde, Manoj; Wang, Shuo; Kumar, Arvind; Stephens, Chad E.; Farahat, Abdelbasset A.; Boykin, David W.; Wilson, W. David; Poon, Gregory M. K.

    2014-01-01

    ETS transcription factors mediate a wide array of cellular functions and are attractive targets for pharmacological control of gene regulation. We report the inhibition of the ETS-family member PU.1 with a panel of novel heterocyclic diamidines. These diamidines are derivatives of furamidine (DB75) in which the central furan has been replaced with selenophene and/or one or both of the bridging phenyl has been replaced with benzimidazole. Like all ETS proteins, PU.1 binds sequence specifically to 10-bp sites by inserting a recognition helix into the major groove of a 5′-GGAA-3′ consensus, accompanied by contacts with the flanking minor groove. We showed that diamidines target the minor groove of AT-rich sequences on one or both sides of the consensus and disrupt PU.1 binding. Although all of the diamidines bind to one or both of the expected sequences within the binding site, considerable heterogeneity exists in terms of stoichiometry, site–site interactions and induced DNA conformation. We also showed that these compounds accumulate in live cell nuclei and inhibit PU.1-dependent gene transactivation. This study demonstrates that heterocyclic diamidines are capable of inhibiting PU.1 by targeting the flanking sequences and supports future efforts to develop agents for inhibiting specific members of the ETS family. PMID:24157839

  8. Cell cycle-dependent transcription factors control the expression of yeast telomerase RNA.

    Science.gov (United States)

    Dionne, Isabelle; Larose, Stéphanie; Dandjinou, Alain T; Abou Elela, Sherif; Wellinger, Raymund J

    2013-07-01

    Telomerase is a specialized ribonucleoprotein that adds repeated DNA sequences to the ends of eukaryotic chromosomes to preserve genome integrity. Some secondary structure features of the telomerase RNA are very well conserved, and it serves as a central scaffold for the binding of associated proteins. The Saccharomyces cerevisiae telomerase RNA, TLC1, is found in very low copy number in the cell and is the limiting component of the known telomerase holoenzyme constituents. The reasons for this low abundance are unclear, but given that the RNA is very stable, transcriptional control mechanisms must be extremely important. Here we define the sequences forming the TLC1 promoter and identify the elements required for its low expression level, including enhancer and repressor elements. Within an enhancer element, we found consensus sites for Mbp1/Swi4 association, and chromatin immunoprecipitation (ChIP) assays confirmed the binding of Mbp1 and Swi4 to these sites of the TLC1 promoter. Furthermore, the enhancer element conferred cell cycle-dependent regulation to a reporter gene, and mutations in the Mbp1/Swi4 binding sites affected the levels of telomerase RNA and telomere length. Finally, ChIP experiments using a TLC1 RNA-binding protein as target showed cell cycle-dependent transcription of the TLC1 gene. These results indicate that the budding yeast TLC1 RNA is transcribed in a cell cycle-dependent fashion late in G1 and may be part of the S phase-regulated group of genes involved in DNA replication.

  9. Site dependent factors affecting the economic feasibility of solar powered absorption cooling

    Science.gov (United States)

    Bartlett, J. C.

    1978-01-01

    A procedure was developed to evaluate the cost effectiveness of combining an absorption cycle chiller with a solar energy system. A basic assumption of the procedure is that a solar energy system exists for meeting the heating load of the building, and that the building must be cooled. The decision to be made is to either cool the building with a conventional vapor compression cycle chiller or to use the existing solar energy system to provide a heat input to the absorption chiller. Two methods of meeting the cooling load not supplied by solar energy were considered. In the first method, heat is supplied to the absorption chiller by a boiler using fossil fuel. In the second method, the load not met by solar energy is net by a conventional vapor compression chiller. In addition, the procedure can consider waste heat as another form of auxiliary energy. Commercial applications of solar cooling with an absorption chiller were found to be more cost effective than the residential applications. In general, it was found that the larger the chiller, the more economically feasible it would be. Also, it was found that a conventional vapor compression chiller is a viable alternative for the auxiliary cooling source, especially for the larger chillers. The results of the analysis gives a relative rating of the sites considered as to their economic feasibility of solar cooling.

  10. A method to identify dependencies between organizational factors using statistical independence test

    International Nuclear Information System (INIS)

    Kim, Y.; Chung, C.H.; Kim, C.; Jae, M.; Jung, J.H.

    2004-01-01

    A considerable number of studies on organizational factors in nuclear power plants have been made especially in recent years, most of which have assumed organizational factors to be independent. However, since organizational factors characterize the organization in terms of safety and efficiency etc. and there would be some factors that have close relations between them. Therefore, from whatever point of view, if we want to identify the characteristics of an organization, the dependence relationships should be considered to get an accurate result. In this study the organization of a reference nuclear power plant in Korea was analyzed for the trip cases of that plant using 20 organizational factors that Jacobs and Haber had suggested: 1) coordination of work, 2) formalization, 3) organizational knowledge, 4) roles and responsibilities, 5) external communication, 6) inter-department communications, 7) intra-departmental communications, 8) organizational culture, 9) ownership, 10) safety culture, 11) time urgency, 12) centralization, 13) goal prioritization, 14) organizational learning, 15) problem identification, 16) resource allocation, 17) performance evaluation, 18) personnel selection, 19) technical knowledge, and 20) training. By utilizing the results of the analysis, a method to identify the dependence relationships between organizational factors is presented. The statistical independence test for the analysis result of the trip cases is adopted to reveal dependencies. This method is geared to the needs to utilize many kinds of data that has been obtained as the operating years of nuclear power plants increase, and more reliable dependence relations may be obtained by using these abundant data

  11. Magnetization Reversal through Soliton in a Site-Dependent Weak Ferromagnet

    International Nuclear Information System (INIS)

    Kavitha, L.; Sathishkumar, P.; Saravanan, M.; Gopi, D.

    2010-06-01

    Switching the magnetization of a magnetic bit through flipping of soliton offers the possibility of developing a new innovative approach for data storage technologies. The spin dynamics of a site-dependent ferromagnet with antisymmetric Dzyaloshinskii-Moriya interaction is governed by a generalized inhomogeneous higher order nonlinear Schroedinger equation. We demonstrate the magnetization reversal through flipping of soliton in the ferromagnetic medium by solving the two coupled evolution equations for the velocity and amplitude of the soliton using the fourth order Runge-Kutta method numerically. We propose a new approach to induce the flipping behaviour of soliton in the presence of inhomogeneity by tuning the parameter associated with Dzyaloshinskii-Moriya interaction which causes the soliton to move with constant velocity and amplitude along the spin lattice. (author)

  12. Low nucleosome occupancy is encoded around functional human transcription factor binding sites

    Directory of Open Access Journals (Sweden)

    Daenen Floris

    2008-07-01

    Full Text Available Abstract Background Transcriptional regulation of genes in eukaryotes is achieved by the interactions of multiple transcription factors with arrays of transcription factor binding sites (TFBSs on DNA and with each other. Identification of these TFBSs is an essential step in our understanding of gene regulatory networks, but computational prediction of TFBSs with either consensus or commonly used stochastic models such as Position-Specific Scoring Matrices (PSSMs results in an unacceptably high number of hits consisting of a few true functional binding sites and numerous false non-functional binding sites. This is due to the inability of the models to incorporate higher order properties of sequences including sequences surrounding TFBSs and influencing the positioning of nucleosomes and/or the interactions that might occur between transcription factors. Results Significant improvement can be expected through the development of a new framework for the modeling and prediction of TFBSs that considers explicitly these higher order sequence properties. It would be particularly interesting to include in the new modeling framework the information present in the nucleosome positioning sequences (NPSs surrounding TFBSs, as it can be hypothesized that genomes use this information to encode the formation of stable nucleosomes over non-functional sites, while functional sites have a more open chromatin configuration. In this report we evaluate the usefulness of the latter feature by comparing the nucleosome occupancy probabilities around experimentally verified human TFBSs with the nucleosome occupancy probabilities around false positive TFBSs and in random sequences. Conclusion We present evidence that nucleosome occupancy is remarkably lower around true functional human TFBSs as compared to non-functional human TFBSs, which supports the use of this feature to improve current TFBS prediction approaches in higher eukaryotes.

  13. State-dependent factors and attention in Whiplash Associated Disorder

    NARCIS (Netherlands)

    Blokhorst, Mariëtte G.B.G.

    2005-01-01

    The main aim of this thesis is to investigate the relationship between state- dependent factors (headache, neck pain, fatigue, distress) and attention in WAD patients. Furthermore, the focus is on ‘noise-distractibility’ and ‘noise- intolerance’, which are symptoms related to attention and often

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

    African Journals Online (AJOL)

    The influence of site factors on nitrogen mineralization in forest soils of the ... on N mineralization, as well as the effect of N mineralization on forest productivity. ... of the natural log of mean annual temperature, geological substrate and total N ...

  15. Specificity of genetic and environmental risk factors for symptoms of cannabis, cocaine, alcohol, caffeine, and nicotine dependence.

    Science.gov (United States)

    Kendler, Kenneth S; Myers, John; Prescott, Carol A

    2007-11-01

    Although genetic risk factors have been found to contribute to dependence on both licit and illicit psychoactive substances, we know little of how these risk factors interrelate. To clarify the structure of genetic and environmental risk factors for symptoms of dependence on cannabis, cocaine, alcohol, caffeine, and nicotine in males and females. Lifetime history by structured clinical interview. General community. Four thousand eight hundred sixty-five members of male-male and female-female pairs from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. Main Outcome Measure Lifetime symptoms of abuse of and dependence on cannabis, cocaine, alcohol, caffeine, and nicotine. Controlling for greater symptom prevalence in males, genetic and environmental parameters could be equated across sexes. Two models explained the data well. The best-fit exploratory model contained 2 genetic factors and 1 individual environmental factor contributing to all substances. The first genetic factor loaded strongly on cocaine and cannabis dependence; the second, on alcohol and nicotine dependence. Nicotine and caffeine had high substance-specific genetic effects. A confirmatory model, which also fit well, contained 1 illicit drug genetic factor--loading only on cannabis and cocaine--and 1 licit drug genetic factor loading on alcohol, caffeine, and nicotine. However, these factors were highly intercorrelated (r = + 0.82). Large substance-specific genetic effects remained for nicotine and caffeine. The pattern of genetic and environmental risk factors for psychoactive substance dependence was similar in males and females. Genetic risk factors for dependence on common psychoactive substances cannot be explained by a single factor. Rather, 2 genetic factors-one predisposing largely to illicit drug dependence, the other primarily to licit drug dependence-are needed. Furthermore, a large proportion of the genetic influences on nicotine and particularly caffeine dependence

  16. 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.

  17. Synthesis and characterization of (18)F-labeled active site inhibited factor VII (ASIS).

    Science.gov (United States)

    Erlandsson, Maria; Nielsen, Carsten H; Jeppesen, Troels E; Kristensen, Jesper B; Petersen, Lars C; Madsen, Jacob; Kjaer, Andreas

    2015-05-15

    Activated factor VII blocked in the active site with Phe-Phe-Arg-chloromethyl ketone (active site inhibited factor VII (ASIS)) is a 50-kDa protein that binds with high affinity to its receptor, tissue factor (TF). TF is a transmembrane glycoprotein that plays an important role in, for example, thrombosis, metastasis, tumor growth, and tumor angiogenesis. The aim of this study was to develop an (18)F-labeled ASIS derivative to assess TF expression in tumors. Active site inhibited factor VII was labeled using N-succinimidyl-4-[(18)F]fluorobenzoate, and the [(18)F]ASIS was purified on a PD-10 desalting column. The radiochemical yield was 25 ± 6%, the radiochemical purity was >97%, and the pseudospecific radioactivity was 35 ± 9 GBq/µmol. The binding efficacy was evaluated in pull-down experiments, which monitored the binding of unlabeled ASIS and [(18)F]ASIS to TF and to a specific anti-factor VII antibody (F1A2-mAb). No significant difference in binding efficacy between [(18)F]ASIS and ASIS could be detected. Furthermore, [(18)F]ASIS was relatively stable in vitro and in vivo in mice. In conclusion, [(18)F]ASIS has for the first time been successfully synthesized as a possible positron emission tomography tracer to image TF expression levels. In vivo positron emission tomography studies to evaluate the full potential of [(18)F]ASIS are in progress. Copyright © 2015 John Wiley & Sons, Ltd.

  18. Distinct roles of beta1 metal ion-dependent adhesion site (MIDAS), adjacent to MIDAS (ADMIDAS), and ligand-associated metal-binding site (LIMBS) cation-binding sites in ligand recognition by integrin alpha2beta1.

    Science.gov (United States)

    Valdramidou, Dimitra; Humphries, Martin J; Mould, A Paul

    2008-11-21

    Integrin-ligand interactions are regulated in a complex manner by divalent cations, and previous studies have identified ligand-competent, stimulatory, and inhibitory cation-binding sites. In collagen-binding integrins, such as alpha2beta1, ligand recognition takes place exclusively at the alpha subunit I domain. However, activation of the alphaI domain depends on its interaction with a structurally similar domain in the beta subunit known as the I-like or betaI domain. The top face of the betaI domain contains three cation-binding sites: the metal-ion dependent adhesion site (MIDAS), the ADMIDAS (adjacent to MIDAS), and LIMBS (ligand-associated metal-binding site). The role of these sites in controlling ligand binding to the alphaI domain has yet to be elucidated. Mutation of the MIDAS or LIMBS completely blocked collagen binding to alpha2beta1; in contrast mutation of the ADMIDAS reduced ligand recognition but this effect could be overcome by the activating monoclonal antibody TS2/16. Hence, the MIDAS and LIMBS appear to be essential for the interaction between alphaI and betaI, whereas occupancy of the ADMIDAS has an allosteric effect on the conformation of betaI. An activating mutation in the alpha2 I domain partially restored ligand binding to the MIDAS and LIMBS mutants. Analysis of the effects of Ca(2+), Mg(2+), and Mn(2+) on ligand binding to these mutants showed that the MIDAS is a ligand-competent site through which Mn(2+) stimulates ligand binding, whereas the LIMBS is a stimulatory Ca(2+)-binding site, occupancy of which increases the affinity of Mg(2+) for the MIDAS.

  19. Transfer and concentration factors in laboratory and environmental conditions

    International Nuclear Information System (INIS)

    Paschoa, A.S.; Amaral, E.C.S.

    1993-01-01

    Environmental transfer factors, as well as concentration and accumulation factors, have been increasingly used in environmental dosimetric models. These models are often the basis for decision-making processes concerning radiological protection. However, the uncertainties associated with measured and default values of transfer and concentration factors are usually not taken into account in the decision making processes. In addition, laboratory-based values for these factors do not necessarily agree with site-specific and species-specific transfer and concentration factors. Soil-to-plant transfer factors and water-to-aquatic-organisms concentration factors are not only time and concentration-dependent, but also species-and site-specific environment-dependent. These uncertainties and dependencies may make the decision-making process, based on models, quite a difficult exercise. The current work examines, as an example, the time-dependent variations in the accumulation of 226 Ra in zooplankton in a laboratory experiment as compared with the concentration factor measured in a natural environment. In addition, the work reviews differences in 228 Ra and 226 Ra concentration factors for several plant families measured in a highly radioactive environment. (author). 9 refs, 3 figs, 3 tabs

  20. 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.

  1. 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.

  2. 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.

  3. Deep subsurface structure modeling and site amplification factor estimation in Niigata plain for broadband strong motion prediction

    International Nuclear Information System (INIS)

    Sato, Hiroaki

    2009-01-01

    This report addresses a methodology of deep subsurface structure modeling in Niigata plain, Japan to estimate site amplification factor in the broadband frequency range for broadband strong motion prediction. In order to investigate deep S-wave velocity structures, we conduct microtremor array measurements at nine sites in Niigata plain, which are important to estimate both long- and short-period ground motion. The estimated depths of the top of the basement layer agree well with those of the Green tuff formation as well as the Bouguer anomaly distribution. Dispersion characteristics derived from the observed long-period ground motion records are well explained by the theoretical dispersion curves of Love wave group velocities calculated from the estimated subsurface structures. These results demonstrate the deep subsurface structures from microtremor array measurements make it possible to estimate long-period ground motions in Niigata plain. Moreover an applicability of microtremor array exploration for inclined basement structure like a folding structure is shown from the two dimensional finite difference numerical simulations. The short-period site amplification factors in Niigata plain are empirically estimated by the spectral inversion analysis from S-wave parts of strong motion data. The resultant characteristics of site amplification are relative large in the frequency range of about 1.5-5 Hz, and decay significantly with the frequency increasing over about 5 Hz. However, these features can't be explained by the calculations from the deep subsurface structures. The estimation of site amplification factors in the frequency range of about 1.5-5 Hz are improved by introducing a shallow detailed structure down to GL-20m depth at a site. We also propose to consider random fluctuation in a modeling of deep S-wave velocity structure for broadband site amplification factor estimation. The Site amplification in the frequency range higher than about 5 Hz are filtered

  4. 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.

  5. SP Transcription Factor Paralogs and DNA-Binding Sites Coevolve and Adaptively Converge in Mammals and Birds

    Science.gov (United States)

    Yokoyama, Ken Daigoro; Pollock, David D.

    2012-01-01

    Functional modification of regulatory proteins can affect hundreds of genes throughout the genome, and is therefore thought to be almost universally deleterious. This belief, however, has recently been challenged. A potential example comes from transcription factor SP1, for which statistical evidence indicates that motif preferences were altered in eutherian mammals. Here, we set out to discover possible structural and theoretical explanations, evaluate the role of selection in SP1 evolution, and discover effects on coregulatory proteins. We show that SP1 motif preferences were convergently altered in birds as well as mammals, inducing coevolutionary changes in over 800 regulatory regions. Structural and phylogenic evidence implicates a single causative amino acid replacement at the same SP1 position along both lineages. Furthermore, paralogs SP3 and SP4, which coregulate SP1 target genes through competitive binding to the same sites, have accumulated convergent replacements at the homologous position multiple times during eutherian and bird evolution, presumably to preserve competitive binding. To determine plausibility, we developed and implemented a simple model of transcription factor and binding site coevolution. This model predicts that, in contrast to prevailing beliefs, even small selective benefits per locus can drive concurrent fixation of transcription factor and binding site mutants under a broad range of conditions. Novel binding sites tend to arise de novo, rather than by mutation from ancestral sites, a prediction substantiated by SP1-binding site alignments. Thus, multiple lines of evidence indicate that selection has driven convergent evolution of transcription factors along with their binding sites and coregulatory proteins. PMID:23019068

  6. 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.

  7. Fibroblast growth factor-2-induced host stroma reaction during initial tumor growth promotes progression of mouse melanoma via vascular endothelial growth factor A-dependent neovascularization.

    Science.gov (United States)

    Tsunoda, Satoshi; Nakamura, Toshiyuki; Sakurai, Hiroaki; Saiki, Ikuo

    2007-04-01

    Fibroblast growth factor (FGF)-2 has been considered to play a critical role in neovascularization in several tumors; however, its precise role in tumor progression is not fully understood. In the present study, we have characterized the role of FGF-2 in B16-BL6 mouse melanoma cells, focusing on effects during the initial phase of tumor growth. FGF-2 was injected at the tumor inoculation site of dorsal skin during the initial phase. FGF-2 induced marked tumor growth and lymph node metastasis. This was well correlated with an increase in neovascularization in the host stroma. FGF-2 also recruited inflammatory and mesenchymal cells in host stroma. Marked tumor growth, pulmonary metastasis and intensive neovascularization in tumor parenchyma were also observed after a single injection of FGF-2 into the footpad inoculation site. In contrast, repeated injections of FGF-2 at a site remote from the footpad tumor were ineffective in promoting tumor growth and metastasis. These promoting activities of FGF-2 were blocked by local injections of a glucocorticoid hormone, suggesting that host inflammatory responses induced by FGF-2 are associated with FGF-2-induced tumor progression. In addition, although FGF-2 did not promote cellular proliferation and vascular endothelial growth factor A (VEGFA) mRNA expression in B16-BL6 cells in vitro, FGF-2 induced VEGFA expression in host stroma rather than tumor tissue, and local injections of a neutralizing antibody against VEGFA inhibited these activities of FGF-2 in vivo. These results indicate that abundant FGF-2 during the initial phase of tumor growth induces VEGFA-dependent intensive neovascularization in host stroma, and supports marked tumor growth and metastasis.

  8. The Human Splicing Factor ASF/SF2 can Specifically Recognize Pre-mRNA 5' Splice Sites

    Science.gov (United States)

    Zuo, Ping; Manley, James L.

    1994-04-01

    ASF/SF2 is a human protein previously shown to function in in vitro pre-mRNA splicing as an essential factor necessary for all splices and also as an alternative splicing factor, capable of switching selection of 5' splice sites. To begin to study the protein's mechanism of action, we have investigated the RNA binding properties of purified recombinant ASF/SF2. Using UV crosslinking and gel shift assays, we demonstrate that the RNA binding region of ASF/SF2 can interact with RNA in a sequence-specific manner, recognizing the 5' splice site in each of two different pre-mRNAs. Point mutations in the 5' splice site consensus can reduce binding by as much as a factor of 100, with the largest effects observed in competition assays. These findings support a model in which ASF/SF2 aids in the recognition of pre-mRNA 5' splice sites.

  9. Risk and Protective Factors for Nicotine Dependence in Adolescence

    Science.gov (United States)

    Hu, Mei-Chen; Griesler, Pamela; Schaffran, Christine; Kandel, Denise

    2011-01-01

    Background: We investigated the role of psychosocial and proximal contextual factors on nicotine dependence in adolescence. Methods: Data on a multiethnic cohort of 6th to 10th graders from the Chicago public schools were obtained from four household interviews conducted with adolescents over two years and one interview with mothers. Structural…

  10. 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.

  11. 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

  12. De-novo discovery of differentially abundant transcription factor binding sites including their positional preference.

    Science.gov (United States)

    Keilwagen, Jens; Grau, Jan; Paponov, Ivan A; Posch, Stefan; Strickert, Marc; Grosse, Ivo

    2011-02-10

    Transcription factors are a main component of gene regulation as they activate or repress gene expression by binding to specific binding sites in promoters. The de-novo discovery of transcription factor binding sites in target regions obtained by wet-lab experiments is a challenging problem in computational biology, which has not been fully solved yet. Here, we present a de-novo motif discovery tool called Dispom for finding differentially abundant transcription factor binding sites that models existing positional preferences of binding sites and adjusts the length of the motif in the learning process. Evaluating Dispom, we find that its prediction performance is superior to existing tools for de-novo motif discovery for 18 benchmark data sets with planted binding sites, and for a metazoan compendium based on experimental data from micro-array, ChIP-chip, ChIP-DSL, and DamID as well as Gene Ontology data. Finally, we apply Dispom to find binding sites differentially abundant in promoters of auxin-responsive genes extracted from Arabidopsis thaliana microarray data, and we find a motif that can be interpreted as a refined auxin responsive element predominately positioned in the 250-bp region upstream of the transcription start site. Using an independent data set of auxin-responsive genes, we find in genome-wide predictions that the refined motif is more specific for auxin-responsive genes than the canonical auxin-responsive element. In general, Dispom can be used to find differentially abundant motifs in sequences of any origin. However, the positional distribution learned by Dispom is especially beneficial if all sequences are aligned to some anchor point like the transcription start site in case of promoter sequences. We demonstrate that the combination of searching for differentially abundant motifs and inferring a position distribution from the data is beneficial for de-novo motif discovery. Hence, we make the tool freely available as a component of the open

  13. 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.

  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. Hydrogeologic factors in the selection of shallow land burial sites for the disposal of low-level radioactive waste

    Science.gov (United States)

    Fischer, John N.

    1986-01-01

    In the United States, low-level radioactive waste is disposed of by shallow land burial. Commercial low-level radioactive waste has been buried at six sites, and low-level radioactive waste generated by the Federal Government has been buried at nine major and several minor sites. Several existing low-level radioactive waste sites have not provided expected protection of the environment. These shortcomings are related, at least in part, to an inadequate understanding of site hydrogeology at the time the sites were selected. To better understand the natural systems and the effect of hydrogeologic factors on long-term site performance, the U.S. Geological Survey has conducted investigations at five of the six commercial low-level radioactive waste sites and at three Federal sites. These studies, combined with those of other Federal and State agencies, have identified and confirmed important hydrogeologic factors in the effective disposal of low-level radioactive waste by shallow land burial. These factors include precipitation, surface drainage, topography, site stability, geology, thickness of the host soil-rock horizon, soil and sediment permeability, soil and water chemistry, and depth to the water table.

  16. 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.

  17. 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

  18. 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.

  19. Simultaneous analysis in renormalization and factorization scheme dependences in perturbative QCD

    International Nuclear Information System (INIS)

    Nakkagawa, Hisao; Niegawa, Akira.

    1983-01-01

    Combined and thorough investigations of both the factorization and the renormalization scheme dependences of perturbative QCD calculations are given. Our findings are that (i) by introducing a multiscale-dependent coupling the simultaneous parametrization of both scheme-dependences can be accomplished, (ii) Stevenson's optimization method works quite well so that it gives a remarkable prediction which forces us to exponentiate ''everything'' with uncorrected subprocess cross sections, and (iii) the perturbation series in QCD may converge when Stevenson's principle of minimal sensitivity is taken into account at each order of perturbative approximation. (author)

  20. 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

  1. Barriers and enabling factors for work-site physical activity programs: a qualitative examination.

    Science.gov (United States)

    Fletcher, Gena M; Behrens, Timothyh K; Domina, Lorie

    2008-05-01

    Work sites offer a productive setting for physical activity (PA) promoting interventions. Still, PA participation remains low. Thus, the purpose of this study was to examine the reasoning behind commonly reported barriers and enabling factors to participation in PA programs in a work-site setting. Employees from a large city government were recruited to participate in focus groups, stratified by white- and blue-collar occupations. Responses from open-ended questions about factors influencing participation in PA programs were audio recorded and transcribed verbatim. Resulting data were analyzed with open and axial coding. The sample consisted of 60 employees composing 9 focus groups. Although time was the most common barrier between both groups, white-collars workers responded that scheduling and work conflicts were the most common barrier concerning time. Blue-collar workers indicated shift work as their most common barrier. In addition, health was a significant enabling factor for both occupational categories. White-collar workers were much more concerned with appearances and were more highly motivated by weight loss and the hopefulness of quick results than were blue-collar workers. These findings are important in the understanding of PA as it relates to the reasoning behind participation in work-site programs in regard to occupational status.

  2. CONREAL web server: identification and visualization of conserved transcription factor binding sites

    NARCIS (Netherlands)

    Berezikov, E.; Guryev, V.; Cuppen, E.

    2005-01-01

    The use of orthologous sequences and phylogenetic footprinting approaches have become popular for the recognition of conserved and potentially functional sequences. Several algorithms have been developed for the identification of conserved transcription factor binding sites (TFBSs), which are

  3. Large enhancement of functional activity of active site-inhibited factor VIIa due to protein dimerization: insights into mechanism of assembly/disassembly from tissue factor.

    Science.gov (United States)

    Stone, Matthew D; Harvey, Stephen B; Martinez, Michael B; Bach, Ronald R; Nelsestuen, Gary L

    2005-04-26

    Active site-inhibited blood clotting factor VIIa (fVIIai) binds to tissue factor (TF), a cell surface receptor that is exposed upon injury and initiates the blood clotting cascade. FVIIai blocks binding of the corresponding enzyme (fVIIa) or zymogen (fVII) forms of factor VII and inhibits coagulation. Although several studies have suggested that fVIIai may have superior anticoagulation effects in vivo, a challenge for use of fVIIai is cost of production. This study reports the properties of dimeric forms of fVIIai that are cross-linked through their active sites. Dimeric wild-type fVIIai was at least 75-fold more effective than monomeric fVIIai in blocking fVIIa association with TF. The dimer of a mutant fVIIai with higher membrane affinity was 1600-fold more effective. Anticoagulation by any form of fVIIai differed substantially from agents such as heparin and showed a delayed mode of action. Coagulation proceeded normally for the first minutes, and inhibition increased as equilibrium binding was established. It is suggested that association of fVIIa(i) with TF in a collision-dependent reaction gives equal access of inhibitor and enzyme to TF. Assembly was not influenced by the higher affinity and slower dissociation of the dimer. As a result, anticoagulation was delayed until the reaction reached equilibrium. Properties of different dissociation experiments suggested that dissociation of fVIIai from TF occurred by a two-step mechanism. The first step was separation of TF-fVIIa(i) while both proteins remained bound to the membrane, and the second step was dissociation of the fVIIa(i) from the membrane. These results suggest novel actions of fVIIai that distinguish it from most of the anticoagulants that block later steps of the coagulation cascade.

  4. 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....

  5. Fatores de risco para dependência de álcool em adolescentes Factores de riesgo en adolescentes con dependencia al alcohol Risk factors for alcohol dependence in adolescents

    Directory of Open Access Journals (Sweden)

    Leandro Rozin

    2012-01-01

    Full Text Available OBJETIVO: Identificar os fatores de risco para dependência do álcool na adolescência. MÉTODOS: Revisão integrativa com 21 artigos publicados entre 2000 e 2009, capturados nas bases de dados LILACS, BVS, MEDLINE, COCHRANE e IBECS com as palavras-chave: adolescência, risco para dependência e álcool. RESULTADOS: Há evidências de que o álcool é a droga mais consumida por adolescentes, com início entre 14 a 16 anos. Os fatores de risco para dependência estão relacionados ao início precoce do uso, influência da mídia, relacionamento conturbado com os pais, uso por membro da família, abuso sexual, violência doméstica, baixa autoestima, curiosidade, pressão de colegas, entre outros. Apontam a vulnerabilidade genética para a dependência do álcool e controvérsias em relação ao gênero e classe social. CONCLUSÃO: Os serviços de saúde devem incorporar estratégias preventivas de identificação de riscos para a dependência, controle e acompanhamento específicos ao grupo de adolescentes dependentes.OBJETIVO: Identificar los factores de riesgo en adolescentes con dependencia al alcohol. MÉTODOS: Revisión integrativa realizada con 21 artículos publicados entre 2000 y 2009, identificados en las bases de datos LILACS, BVS, MEDLINE, COCHRANE e IBECS con las palabras-clave: adolescencia, riesgo a dependencia y alcohol. RESULTADOS: Hay evidencias de que el alcohol es la droga más consumida por adolescentes, con inicio entre 14 a 16 años. Los factores de riesgo para la dependencia están relacionados al inicio precoz del uso, influencia de los medios de comunicación, relacionamiento conturbado con los padres, uso por un miembro de la familia, abuso sexual, violencia doméstica, baja autoestima, curiosidad, presión de colegas, entre otros. Apuntan la vulnerabilidad genética para la dependencia al alcohol y controversias en relación al género y clase social. CONCLUSIÓN: Los servicios de salud deben incorporar estrategias

  6. Geo-Proxy-Based Site Classification for Regional Zonation of Seismic Site Effects in South Korea

    Directory of Open Access Journals (Sweden)

    Chang-Guk Sun

    2018-02-01

    Full Text Available Seismic site effects and topographic effects related to ground motion occur during an earthquake due to site-specific geotechnical or geological characteristics, including the geological or geographical structure and the characteristics of near-surface sub-soil layers. Site-specific site effects due to geological conditions have been confirmed in recent earthquake events. Earthquake-induced damage has mainly occurred at accumulated soft soil layers under basins or along coasts and rivers. An alternative method has recently been proposed for evaluating regional seismic site effects and amplification factors using digital elevation models (DEM. High-quality DEMs at high resolutions may be employed to resolve finer-scale variations in topographic gradients and consequently, correlated site response parameters. Because there are many regions in South Korea lacking borehole datasets, which are insufficient for site classification only using borehole datasets, a DEM-based proxy for seismic zonation can be effective. Thus, in this study, geo-proxy-based site classification was proposed based on empirical correlations with site response parameters and conducted for regional zonation of seismic site effects to identify the amplification of characteristics in the western metropolitan areas of South Korea, depending on the site-specific geo-spatial conditions.

  7. DEPENDENCE ON SOCIAL NETWORKING SITES IN ADOLESCENTS

    OpenAIRE

    Ranjith; Santosh; Amita Rao; Ramgopal; Ashvij

    2016-01-01

    BACKGROUND Social Networking Sites (SNSs) are “web-based services” that allow individuals to: (1) Construct a public or semi-public profile within a bounded system, (2) Articulate a list of other users with whom they share a connection, and (3) View and traverse their list of connections and those made by others within the system.” Social networking sites like Facebook, WhatsApp, Snapchat, Twitter, etc. are virtual communities where users can create individual public profiles,...

  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. Identification of regulatory targets for the bacterial Nus factor complex.

    Science.gov (United States)

    Baniulyte, Gabriele; Singh, Navjot; Benoit, Courtney; Johnson, Richard; Ferguson, Robert; Paramo, Mauricio; Stringer, Anne M; Scott, Ashley; Lapierre, Pascal; Wade, Joseph T

    2017-12-11

    Nus factors are broadly conserved across bacterial species, and are often essential for viability. A complex of five Nus factors (NusB, NusE, NusA, NusG and SuhB) is considered to be a dedicated regulator of ribosomal RNA folding, and has been shown to prevent Rho-dependent transcription termination. Here, we identify an additional cellular function for the Nus factor complex in Escherichia coli: repression of the Nus factor-encoding gene, suhB. This repression occurs primarily by translation inhibition, followed by Rho-dependent transcription termination. Thus, the Nus factor complex can prevent or promote Rho activity depending on the gene context. Conservation of putative NusB/E binding sites upstream of Nus factor genes suggests that Nus factor autoregulation occurs in many bacterial species. Additionally, many putative NusB/E binding sites are also found upstream of other genes in diverse species, and we demonstrate Nus factor regulation of one such gene in Citrobacter koseri. We conclude that Nus factors have an evolutionarily widespread regulatory function beyond ribosomal RNA, and that they are often autoregulatory.

  10. 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.

  11. Conversion of MyoD to a Neurogenic Factor: Binding Site Specificity Determines Lineage

    Directory of Open Access Journals (Sweden)

    Abraham P. Fong

    2015-03-01

    Full Text Available MyoD and NeuroD2, master regulators of myogenesis and neurogenesis, bind to a “shared” E-box sequence (CAGCTG and a “private” sequence (CAGGTG or CAGATG, respectively. To determine whether private-site recognition is sufficient to confer lineage specification, we generated a MyoD mutant with the DNA-binding specificity of NeuroD2. This chimeric mutant gained binding to NeuroD2 private sites but maintained binding to a subset of MyoD-specific sites, activating part of both the muscle and neuronal programs. Sequence analysis revealed an enrichment for PBX/MEIS motifs at the subset of MyoD-specific sites bound by the chimera, and point mutations that prevent MyoD interaction with PBX/MEIS converted the chimera to a pure neurogenic factor. Therefore, redirecting MyoD binding from MyoD private sites to NeuroD2 private sites, despite preserved binding to the MyoD/NeuroD2 shared sites, is sufficient to change MyoD from a master regulator of myogenesis to a master regulator of neurogenesis.

  12. 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.

  13. Two signaling molecules share a phosphotyrosine-containing binding site in the platelet-derived growth factor receptor.

    Science.gov (United States)

    Nishimura, R; Li, W; Kashishian, A; Mondino, A; Zhou, M; Cooper, J; Schlessinger, J

    1993-11-01

    Autophosphorylation sites of growth factor receptors with tyrosine kinase activity function as specific binding sites for Src homology 2 (SH2) domains of signaling molecules. This interaction appears to be a crucial step in a mechanism by which receptor tyrosine kinases relay signals to downstream signaling pathways. Nck is a widely expressed protein consisting exclusively of SH2 and SH3 domains, the overexpression of which causes cell transformation. It has been shown that various growth factors stimulate the phosphorylation of Nck and its association with autophosphorylated growth factor receptors. A panel of platelet-derived growth factor (PDGF) receptor mutations at tyrosine residues has been used to identify the Nck binding site. Here we show that mutation at Tyr-751 of the PDGF beta-receptor eliminates Nck binding both in vitro and in living cells. Moreover, the Y751F PDGF receptor mutant failed to mediate PDGF-stimulated phosphorylation of Nck in intact cells. A phosphorylated Tyr-751 is also required for binding of phosphatidylinositol-3 kinase to the PDGF receptor. Hence, the SH2 domains of p85 and Nck share a binding site in the PDGF receptor. Competition experiments with different phosphopeptides derived from the PDGF receptor suggest that binding of Nck and p85 is influenced by different residues around Tyr-751. Thus, a single tyrosine autophosphorylation site is able to link the PDGF receptor to two distinct SH2 domain-containing signaling molecules.

  14. 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.

  15. Occult Radiographically Evident Port-Site Hernia After Robot-Assisted Urologic Surgery: Incidence and Risk Factors.

    Science.gov (United States)

    Christie, Matthew C; Manger, Jules P; Khiyami, Abdulaziz M; Ornan, Afshan A; Wheeler, Karen M; Schenkman, Noah S

    2016-01-01

    Laparoscopic trocar-site hernias (TSH) are rare, with a reported incidence of 1% or less. The incidence of occult radiographically evident hernias has not been described after robot-assisted urologic surgery. We evaluated the incidence and risk factors of this problem. A single-institution retrospective review of robot-assisted urologic surgery was performed from April 2009 to December 2012. Patients with preoperative and postoperative CT were included for analysis. Imaging was reviewed by two radiologists and one urologist. One hundred four cases were identified, including 60 partial nephrectomy, 38 prostatectomy, and 6 cystectomy. Mean age was 58 years and mean body mass index (BMI) was 29 kg/m(2). The cohort was 77% male. Ten total hernias were identified by CT in 8 patients, 2 of which were clinically evident hernias. Excluding these two hernias, occult port-site hernias were identified radiographically in seven patients. Per-patient incidence of occult TSH was 6.7% (7/104), and per-port incidence was 1.4% (8/564). All hernias were midline and 30% contained bowel. Eight of the 10 occurred at 12 mm sites (p = 0.0065) and 3 of the 10 occurred at extended incisions. Age, gender, BMI, smoking status, diabetes mellitus, immunosuppressive drug therapy, ASA score, procedure, blood loss, prior abdominal surgery, and history of hernia were not significant risk factors. Specimen size >40 g (p = 0.024) and wound infection (p = 0.0052) were significant risk factors. While the incidence of clinically evident port-site hernia remains low in robot-assisted urologic surgery, the incidence of CT-detected occult hernia was 6.7% in this series. These occurred most often in sites extended for specimen extraction and at larger port sites. This suggests more attention should be paid to fascial closure at these sites.

  16. Probabilistic site dependent design spectra for a NPP

    International Nuclear Information System (INIS)

    Chavez, M.; Arroyo, M.; Romo, M.P.

    1985-01-01

    A methodology is proposed to compute the design spectra for a NPP site. Near field earthquakes are included by using an appropriately scaled sample of response spectra. Site effects are considered through a probabilistic site response analysis in the frequency domain which considers nonlinear behaviour of soils. The uncertainties of the soil shear modulus, G, are introduced by using Rosenblueth's point estimates. Strong motion duration is treated by using sensitivity analysis. The procedure is applied to a NPP site and the results are: a) the USNCR R.G.1.60 underestimate the spectral amplitudes for frequencies of interest; b) the omission of the uncertainties on the G leads to under or over-estimate the spectral amplitudes at certain frequency bands; c) the effect of considering the actual strong motion duration instead of an average value is to reduce the peak spectral amplitudes by a ten per cent. (orig.)

  17. Energy-dependent dissociation of ATP from high affinity catalytic sites of beef heart mitochondrial adenosine triphosphatase

    International Nuclear Information System (INIS)

    Penefsky, H.S.

    1985-01-01

    Incubation of [gamma- 32 P]ATP with a molar excess of the membrane-bound form of mitochondrial ATPase (F1) results in binding of the bulk of the radioactive nucleotide in high affinity catalytic sites (Ka = 10(12) M-1). Subsequent initiation of respiration by addition of succinate or NADH is accompanied by a profound decrease in the affinity for ATP. About one-third of the bound radioactive ATP appears to dissociate, that is, the [gamma- 32 P]ATP becomes accessible to hexokinase. The NADH-stimulated dissociation of [gamma- 32 P]ATP is energy-dependent since the stimulation is inhibited by uncouplers of oxidative phosphorylation and is prevented by respiratory chain inhibitors. The rate of the energy-dependent dissociation of ATP that occurs in the presence of NADH, ADP, and Pi is commensurate with the measured initial rate of ATP synthesis in NADH-supported oxidative phosphorylation catalyzed by the same submitochondrial particles. Thus, the rate of dissociation of ATP from the high affinity catalytic site of submitochondrial particles meets the criterion of kinetic competency under the conditions of oxidative phosphorylation. These experiments provide evidence in support of the argument that energy conserved during the oxidation of substrates by the respiratory chain can be utilized to reduce the very tight binding of product ATP in high affinity catalytic sites and to promote dissociation of the nucleotide

  18. 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

  19. Functions for fission yeast splicing factors SpSlu7 and SpPrp18 in alternative splice-site choice and stress-specific regulated splicing.

    Directory of Open Access Journals (Sweden)

    Geetha Melangath

    Full Text Available Budding yeast spliceosomal factors ScSlu7 and ScPrp18 interact and mediate intron 3'ss choice during second step pre-mRNA splicing. The fission yeast genome with abundant multi-intronic transcripts, degenerate splice signals and SR proteins is an apt unicellular fungal model to deduce roles for core spliceosomal factors in alternative splice-site choice, intron retention and to study the cellular implications of regulated splicing. From our custom microarray data we deduce a stringent reproducible subset of S. pombe alternative events. We examined the role of factors SpSlu7 or SpPrp18 for these splice events and investigated the relationship to growth phase and stress. Wild-type log and stationary phase cells showed ats1+ exon 3 skipped and intron 3 retained transcripts. Interestingly the non-consensus 5'ss in ats1+ intron 3 caused SpSlu7 and SpPrp18 dependent intron retention. We validated the use of an alternative 5'ss in dtd1+ intron 1 and of an upstream alternative 3'ss in DUF3074 intron 1. The dtd1+ intron 1 non-canonical 5'ss yielded an alternative mRNA whose levels increased in stationary phase. Utilization of dtd1+ intron 1 sub-optimal 5' ss required functional SpPrp18 and SpSlu7 while compromise in SpSlu7 function alone hampered the selection of the DUF3074 intron 1 non canonical 3'ss. We analysed the relative abundance of these splice isoforms during mild thermal, oxidative and heavy metal stress and found stress-specific splice patterns for ats1+ and DUF3074 intron 1 some of which were SpSlu7 and SpPrp18 dependent. By studying ats1+ splice isoforms during compromised transcription elongation rates in wild-type, spslu7-2 and spprp18-5 mutant cells we found dynamic and intron context-specific effects in splice-site choice. Our work thus shows the combinatorial effects of splice site strength, core splicing factor functions and transcription elongation kinetics to dictate alternative splice patterns which in turn serve as an additional

  20. Transcriptional activation of transforming growth factor alpha by estradiol: requirement for both a GC-rich site and an estrogen response element half-site.

    Science.gov (United States)

    Vyhlidal, C; Samudio, I; Kladde, M P; Safe, S

    2000-06-01

    17beta-Estradiol (E2) induces transforming growth factor alpha (TGFalpha) gene expression in MCF-7 cells and previous studies have identified a 53 bp (-252 to -200) sequence containing two imperfect estrogen responsive elements (EREs) that contribute to E2 responsiveness. Deletion analysis of the TGFalpha gene promoter in this study identified a second upstream region of the promoter (-623 to -549) that is also E2 responsive. This sequence contains three GC-rich sites and an imperfect ERE half-site, and the specific cis-elements and trans-acting factors were determined by promoter analysis in transient transfection experiments, gel mobility shift assays and in vitro DNA footprinting. The results are consistent with an estrogen receptor alpha (ERalpha)/Sp1 complex interacting with an Sp1(N)(30) ERE half-site ((1/2)) motif in which both ERalpha and Sp1 bind promoter DNA. The ER/Sp1-DNA complex is formed using nuclear extracts from MCF-7 cells but not with recombinant human ERalpha or Sp1 proteins, suggesting that other nuclear factor(s) are required for complex stabilization. The E2-responsive Sp1(N)(x)ERE(1/2) motif identified in the TGFalpha gene promoter has also been characterized in the cathepsin D and heat shock protein 27 gene promoters; however, in the latter two promoters the numbers of intervening nucleotides are 23 and 10 respectively.

  1. 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 ...

  2. Study of site layout in the Rokkasho site

    International Nuclear Information System (INIS)

    Sato, Kazuyoshi; Tamura, Kousaku; Yagenji, Akira; Sekiya, Shigeki; Takahashi, Hideo; Neyatani, Yuzuru; Uehara, Masaharu; Motohashi, Keiichi; Hashimoto, Masayoshi; Ogino, Shunji; Nagamatsu, Nobuhide

    2006-03-01

    The Final Design Report (FDR) of the International Thermonuclear Experimental Reactor (ITER) was published on July 2001 as a summary of the Engineering Design Activity (EDA). After the EDA, site dependent design has been investigated for the invitation of ITER toward Rokkasho Site (Iyasakadai area) in Aomori prefecture. This report describes the results of site layout of major buildings and structures of ITER in the Rokkasho-Site. The data of the ground near the site and the results of site dependent design in Japan were applied to this study. Through this study, the most appropriate site layout has been constructed with satisfaction of following conditions. (1) Bedrock level at the tokamak complex building is relatively high and it can be reduced the cost of excavation and foundation work. (2) Total amount of excavation soil for site preparation is minimized and the flexibility of the layout is ensured with flat ground level. (3) Accessibility of human and equipments, reduction of noise and vibration to the environment can be obtained. Total length of ducts and piping between buildings in site is minimized. (author)

  3. Quantitative PET Imaging of Tissue Factor Expression Using 18F-labled Active Site Inhibited Factor VII

    DEFF Research Database (Denmark)

    Nielsen, Carsten H; Erlandsson, Maria; Jeppesen, Troels E

    2016-01-01

    Tissue factor (TF) is up regulated in many solid tumors and its expression is linked to tumor angiogenesis, invasion, metastasis and prognosis. A non-invasive assessment of tumor TF expression status is therefore of obvious clinical relevance. Factor VII (FVII) is the natural ligand to TF. Here we...... report the development of a new PET tracer for specific imaging of TF using an (18)F-labeled derivative of FVII. METHODS: Active site inhibited factor VIIa (FVIIai) was obtained by inactivation with phenylalanine-phenylalanine-arginine-chloromethyl ketone. FVIIai was radiolabeled with N-succinimidyl 4......-[(18)F]-fluorobenzoate ([(18)F]SFB) and purified. The corresponding product, [(18)F]FVIIai, was injected into nude mice with subcutaneous human pancreatic xenograft tumors (BxPC-3) and investigated using small animal PET/CT imaging 1, 2 and 4 hours after injection. Ex vivo biodistribution was performed...

  4. 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…

  5. Kernel parameter dependence in spatial factor analysis

    DEFF Research Database (Denmark)

    Nielsen, Allan Aasbjerg

    2010-01-01

    kernel PCA. Shawe-Taylor and Cristianini [4] is an excellent reference for kernel methods in general. Bishop [5] and Press et al. [6] describe kernel methods among many other subjects. The kernel version of PCA handles nonlinearities by implicitly transforming data into high (even infinite) dimensional...... feature space via the kernel function and then performing a linear analysis in that space. In this paper we shall apply a kernel version of maximum autocorrelation factor (MAF) [7, 8] analysis to irregularly sampled stream sediment geochemistry data from South Greenland and illustrate the dependence...... of the kernel width. The 2,097 samples each covering on average 5 km2 are analyzed chemically for the content of 41 elements....

  6. Evidence for site-specific occupancy of the mitochondrial genome by nuclear transcription factors.

    Directory of Open Access Journals (Sweden)

    Georgi K Marinov

    Full Text Available Mitochondria contain their own circular genome, with mitochondria-specific transcription and replication systems and corresponding regulatory proteins. All of these proteins are encoded in the nuclear genome and are post-translationally imported into mitochondria. In addition, several nuclear transcription factors have been reported to act in mitochondria, but there has been no comprehensive mapping of their occupancy patterns and it is not clear how many other factors may also be found in mitochondria. Here we address these questions by using ChIP-seq data from the ENCODE, mouseENCODE and modENCODE consortia for 151 human, 31 mouse and 35 C. elegans factors. We identified 8 human and 3 mouse transcription factors with strong localized enrichment over the mitochondrial genome that was usually associated with the corresponding recognition sequence motif. Notably, these sites of occupancy are often the sites with highest ChIP-seq signal intensity within both the nuclear and mitochondrial genomes and are thus best explained as true binding events to mitochondrial DNA, which exist in high copy number in each cell. We corroborated these findings by immunocytochemical staining evidence for mitochondrial localization. However, we were unable to find clear evidence for mitochondrial binding in ENCODE and other publicly available ChIP-seq data for most factors previously reported to localize there. As the first global analysis of nuclear transcription factors binding in mitochondria, this work opens the door to future studies that probe the functional significance of the phenomenon.

  7. Genome-wide profiling of H3K56 acetylation and transcription factor binding sites in human adipocytes.

    Directory of Open Access Journals (Sweden)

    Kinyui Alice Lo

    Full Text Available The growing epidemic of obesity and metabolic diseases calls for a better understanding of adipocyte biology. The regulation of transcription in adipocytes is particularly important, as it is a target for several therapeutic approaches. Transcriptional outcomes are influenced by both histone modifications and transcription factor binding. Although the epigenetic states and binding sites of several important transcription factors have been profiled in the mouse 3T3-L1 cell line, such data are lacking in human adipocytes. In this study, we identified H3K56 acetylation sites in human adipocytes derived from mesenchymal stem cells. H3K56 is acetylated by CBP and p300, and deacetylated by SIRT1, all are proteins with important roles in diabetes and insulin signaling. We found that while almost half of the genome shows signs of H3K56 acetylation, the highest level of H3K56 acetylation is associated with transcription factors and proteins in the adipokine signaling and Type II Diabetes pathways. In order to discover the transcription factors that recruit acetyltransferases and deacetylases to sites of H3K56 acetylation, we analyzed DNA sequences near H3K56 acetylated regions and found that the E2F recognition sequence was enriched. Using chromatin immunoprecipitation followed by high-throughput sequencing, we confirmed that genes bound by E2F4, as well as those by HSF-1 and C/EBPα, have higher than expected levels of H3K56 acetylation, and that the transcription factor binding sites and acetylation sites are often adjacent but rarely overlap. We also discovered a significant difference between bound targets of C/EBPα in 3T3-L1 and human adipocytes, highlighting the need to construct species-specific epigenetic and transcription factor binding site maps. This is the first genome-wide profile of H3K56 acetylation, E2F4, C/EBPα and HSF-1 binding in human adipocytes, and will serve as an important resource for better understanding adipocyte

  8. Applying total interpretive structural modeling to study factors affecting construction labour productivity

    Directory of Open Access Journals (Sweden)

    Sayali Shrikrishna Sandbhor

    2014-03-01

    Full Text Available Construction sector has always been dependent on manpower. Most of the activities carried out on any construction site are labour intensive. Since productivity of any project depends directly on productivity of labour, it is a prime responsibility of the employer to enhance labour productivity. Measures to improve the same depend on analysis of positive and negative factors affecting productivity. Major attention should be given to factors that decrease the productivity of labour. Factor analysis thus is an integral part of any study aiming to improve productivity.  Interpretive structural modeling is a methodology for identifying and summarizing relationships among factors which define an issue or problem. It provides a means to arrange the factors in an order as per their complexity. This study attempts to use the latest version of interpretive structural modeling i.e. total interpretive structural modeling to analyze factors negatively affecting construction labour productivity. It establishes interpretive relationship among these factors facilitating improvement in the overall productivity of construction site.

  9. Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay.

    Science.gov (United States)

    Cui, Heying; Loftus, Kyle M; Noell, Crystal R; Solmaz, Sozanne R

    2018-05-03

    Cyclin-dependent kinase 1 (Cdk1) is a master controller for the cell cycle in all eukaryotes and phosphorylates an estimated 8 - 13% of the proteome; however, the number of identified targets for Cdk1, particularly in human cells is still low. The identification of Cdk1-specific phosphorylation sites is important, as they provide mechanistic insights into how Cdk1 controls the cell cycle. Cell cycle regulation is critical for faithful chromosome segregation, and defects in this complicated process lead to chromosomal aberrations and cancer. Here, we describe an in vitro kinase assay that is used to identify Cdk1-specific phosphorylation sites. In this assay, a purified protein is phosphorylated in vitro by commercially available human Cdk1/cyclin B. Successful phosphorylation is confirmed by SDS-PAGE, and phosphorylation sites are subsequently identified by mass spectrometry. We also describe purification protocols that yield highly pure and homogeneous protein preparations suitable for the kinase assay, and a binding assay for the functional verification of the identified phosphorylation sites, which probes the interaction between a classical nuclear localization signal (cNLS) and its nuclear transport receptor karyopherin α. To aid with experimental design, we review approaches for the prediction of Cdk1-specific phosphorylation sites from protein sequences. Together these protocols present a very powerful approach that yields Cdk1-specific phosphorylation sites and enables mechanistic studies into how Cdk1 controls the cell cycle. Since this method relies on purified proteins, it can be applied to any model organism and yields reliable results, especially when combined with cell functional studies.

  10. Quantification of source impact to PM using three-dimensional weighted factor model analysis on multi-site data

    Science.gov (United States)

    Shi, Guoliang; Peng, Xing; Huangfu, Yanqi; Wang, Wei; Xu, Jiao; Tian, Yingze; Feng, Yinchang; Ivey, Cesunica E.; Russell, Armistead G.

    2017-07-01

    Source apportionment technologies are used to understand the impacts of important sources of particulate matter (PM) air quality, and are widely used for both scientific studies and air quality management. Generally, receptor models apportion speciated PM data from a single sampling site. With the development of large scale monitoring networks, PM speciation are observed at multiple sites in an urban area. For these situations, the models should account for three factors, or dimensions, of the PM, including the chemical species concentrations, sampling periods and sampling site information, suggesting the potential power of a three-dimensional source apportionment approach. However, the principle of three-dimensional Parallel Factor Analysis (Ordinary PARAFAC) model does not always work well in real environmental situations for multi-site receptor datasets. In this work, a new three-way receptor model, called "multi-site three way factor analysis" model is proposed to deal with the multi-site receptor datasets. Synthetic datasets were developed and introduced into the new model to test its performance. Average absolute error (AAE, between estimated and true contributions) for extracted sources were all less than 50%. Additionally, three-dimensional ambient datasets from a Chinese mega-city, Chengdu, were analyzed using this new model to assess the application. Four factors are extracted by the multi-site WFA3 model: secondary source have the highest contributions (64.73 and 56.24 μg/m3), followed by vehicular exhaust (30.13 and 33.60 μg/m3), crustal dust (26.12 and 29.99 μg/m3) and coal combustion (10.73 and 14.83 μg/m3). The model was also compared to PMF, with general agreement, though PMF suggested a lower crustal contribution.

  11. 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 ).

  12. Progressive failure site generation in AlGaN/GaN high electron mobility transistors under OFF-state stress: Weibull statistics and temperature dependence

    International Nuclear Information System (INIS)

    Sun, Huarui; Bajo, Miguel Montes; Uren, Michael J.; Kuball, Martin

    2015-01-01

    Gate leakage degradation of AlGaN/GaN high electron mobility transistors under OFF-state stress is investigated using a combination of electrical, optical, and surface morphology characterizations. The generation of leakage “hot spots” at the edge of the gate is found to be strongly temperature accelerated. The time for the formation of each failure site follows a Weibull distribution with a shape parameter in the range of 0.7–0.9 from room temperature up to 120 °C. The average leakage per failure site is only weakly temperature dependent. The stress-induced structural degradation at the leakage sites exhibits a temperature dependence in the surface morphology, which is consistent with a surface defect generation process involving temperature-associated changes in the breakdown sites

  13. 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.

  14. 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)

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

    KAUST Repository

    Kulakovskiy, Ivan V.; Belostotsky, A. A.; Kasianov, Artem S.; Esipova, Natalia G.; Medvedeva, Yulia; Eliseeva, Irina A.; Makeev, Vsevolod J.

    2011-01-01

    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

  16. Applying total interpretive structural modeling to study factors affecting construction labour productivity

    OpenAIRE

    Sayali Shrikrishna Sandbhor; Rohan P. Botre

    2014-01-01

    Construction sector has always been dependent on manpower. Most of the activities carried out on any construction site are labour intensive. Since productivity of any project depends directly on productivity of labour, it is a prime responsibility of the employer to enhance labour productivity. Measures to improve the same depend on analysis of positive and negative factors affecting productivity. Major attention should be given to factors that decrease the productivity of labour. Factor anal...

  17. 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

  18. Trust and Product/Sellers Reviews as Factors Influencing Online Product Comparison Sites Usage by Young Consumers

    OpenAIRE

    Radoslaw Macik; Dorota Macik

    2016-01-01

    Paper describes young consumers’ behaviour connected with online product comparison sites usage as an example of online decision shopping aids. Authors’ main goal is to check whether or not such factors as: previous experience in such sites usage, personal innovativeness in domain of information technology – PIIT, and particularly cognitive trust (in several subdimensions), as well as affective trust toward online product comparison site, influence purchase intention via men...

  19. miRNA-dependent translational repression in the Drosophila ovary.

    Directory of Open Access Journals (Sweden)

    John Reich

    Full Text Available The Drosophila ovary is a tissue rich in post-transcriptional regulation of gene expression. Many of the regulatory factors are proteins identified via genetic screens. The more recent discovery of microRNAs, which in other animals and tissues appear to regulate translation of a large fraction of all mRNAs, raised the possibility that they too might act during oogenesis. However, there has been no direct demonstration of microRNA-dependent translational repression in the ovary.Here, quantitative analyses of transcript and protein levels of transgenes with or without synthetic miR-312 binding sites show that the binding sites do confer translational repression. This effect is dependent on the ability of the cells to produce microRNAs. By comparison with microRNA-dependent translational repression in other cell types, the regulated mRNAs and the protein factors that mediate repression were expected to be enriched in sponge bodies, subcellular structures with extensive similarities to the P bodies found in other cells. However, no such enrichment was observed.Our results reveal the variety of post-transcriptional regulatory mechanisms that operate in the Drosophila ovary, and have implications for the mechanisms of miRNA-dependent translational control used in the ovary.

  20. Factores psicosociales en alcohólicos dependientes Psychological and social factors in dependent alcoholic patients

    Directory of Open Access Journals (Sweden)

    Aurora Revilla Cervantes

    2012-07-01

    Full Text Available Se presentan 4 casos clínicos de pacientes alcohólicos dependientes no complicados pertenecientes al Consultorio Médico de Familia No. 5 del Policlínico Docente "Frank País García", con vistas a identificar los factores psicosociales que influían en estos. Como principales condicionantes de la conducta adictiva en el grupo estudiado se observaron: la influencia del medio, las tradiciones culturales y la participación de eventos vitales de prevalencia negativa. Además, los afectados mostraron un fuerte arraigo a la conducta alcohólica y el deseo de continuarla.Four case reports of uncomplicated dependent alcoholic patients belonging to the Family Doctor's Office No. 5 from «Frank País García Teaching Polyclinic are presented with the aim of identifying the psychological and social factors influencing on them. As main conditions of the addictive behavior in the studied group there were: the influence of the environment, the cultural traditions and the participation in vital events of negative prevalence. Also, those affected showed a strong dependence on the alcoholic behavior and the desire of continuing it.

  1. Problematic Internet Use among Greek university students: an ordinal logistic regression with risk factors of negative psychological beliefs, pornographic sites, and online games.

    Science.gov (United States)

    Frangos, Christos C; Frangos, Constantinos C; Sotiropoulos, Ioannis

    2011-01-01

    The aim of this paper is to investigate the relationships between Problematic Internet Use (PIU) among university students in Greece and factors such as gender, age, family condition, academic performance in the last semester of their studies, enrollment in unemployment programs, amount of Internet use per week (in general and per application), additional personal habits or dependencies (number of coffees, alcoholic drinks drunk per day, taking substances, cigarettes smoked per day), and negative psychological beliefs. Data were gathered from 2,358 university students from across Greece. The prevalence of PIU was 34.7% in our sample, and PIU was significantly associated with gender, parental family status, grade of studies during the previous semester, staying or not with parents, enrollment of the student in an unemployment program, and whether the student paid a subscription to the Internet (p pornographic sites, chat rooms, advertisement sites, Google, Yahoo!, their e-mail, ftp, games, and blogs more than non-problematic Internet users. PIU was also associated with other potential addictive personal habits of smoking, drinking alcohol or coffee, and taking drugs. Significant risk factors for PIU were being male, enrolment in unemployment programs, presence of negative beliefs, visiting pornographic sites, and playing online games. Thus PIU is prevalent among Greek university students and attention should be given to it by health officials.

  2. 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...

  3. Friend me: which factors influence top global brands participation in social network sites

    NARCIS (Netherlands)

    Araujo, T.; Neijens, P.

    2012-01-01

    Purpose - This study focuses on how brands participate in social network sites (SNSs) and investigates both the different strategies they adopt and the factors that influence these strategies. Design/methodology/approach - The activities of top brands in SNSs were investigated through a content

  4. 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

  5. Site occupancy, composition and magnetic structure dependencies of martensitic transformation in Mn2Ni1+xSn1-x.

    Science.gov (United States)

    Kundu, Ashis; Ghosh, Subhradip

    2017-11-14

    A delicate balance between various factors such as site occupancy, composition and magnetic ordering seems to affect the stability of the martensitic phase in Mn2Ni1+xSn1-x. Using first-principles DFT calculations, we explore the impacts of each one of these factors on the martensitic stability of this system. Our results on total energies, magnetic moments and electronic structures upon changes in the composition, the magnetic configurations and the site occupancies show that the occupancies at the 4d sites in the Inverse Heusler crystal structure play the most crucial role. The presence of Mn at the 4d sites originally occupied by Sn and its interaction with the Mn atoms at other sites decide the stability of the martensitic phases. This explains the discrepancy between the experiments and earlier DFT calculations regarding phase stability in Mn2NiSn. Our results qualitatively explain the trends observed experimentally with regard to martensitic phase stability and the magnetisations in Ni-excess, Sn-deficient Mn2NiSn system. © 2017 IOP Publishing Ltd.

  6. 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

  7. 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)

  8. 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.

  9. 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.

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

    KAUST Repository

    Krupskii, Pavel; Genton, Marc G.

    2017-01-01

    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.

  11. Tumor Necrosis Factor Antagonism Normalizes Rapid Eye Movement Sleep in Alcohol Dependence

    Science.gov (United States)

    Irwin, Michael R.; Olmstead, Richard; Valladares, Edwin M.; Breen, Elizabeth Crabb; Ehlers, Cindy L.

    2009-01-01

    Background In alcohol dependence, markers of inflammation are associated with increases in rapid eye movement (REM) sleep, which is thought to be a prognostic indicator of alcohol relapse. This study was undertaken to test whether blockade of biologically active tumor necrosis factor-α (TNF-α) normalizes REM sleep in alcohol-dependent adults. Methods In a randomized, placebo-controlled, double-blind, crossover trial, 18 abstinent alcohol-dependent male adults received a single dose of etanercept (25 mg) versus placebo in a counterbalanced order. Polysomnographic sleep was measured at baseline and for 3 nights after the acute dose of etanercept or placebo. Results Compared with placebo, administration of etanercept produced significant decreases in the amount and percentage of REM sleep. Decreases in REM sleep were robust and approached low levels typically found in age-comparable control subjects. Individual differences in biologically active drug as indexed by circulating levels of soluble tumor necrosis factor receptor II negatively correlated with the percentage of REM sleep. Conclusions Pharmacologic neutralization of TNF-α activity is associated with significant reductions in REM sleep in abstinent alcohol-dependent patients. These data suggest that circulating levels of TNF-α may have a physiologic role in the regulation of REM sleep in humans. PMID:19185287

  12. 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

  13. Evaluation of site-specific factors influencing heavy metal contents in the topsoil of vegetated infiltration swales

    Energy Technology Data Exchange (ETDEWEB)

    Horstmeyer, Nils; Huber, Maximilian; Drewes, Jörg E.; Helmreich, Brigitte, E-mail: b.helmreich@tum.de

    2016-08-01

    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.

  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. 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.

  16. 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

  17. 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

    Mlh1 is an essential factor of mismatch repair (MMR) and meiotic recombination. It interacts through its C-terminal region with MutL homologs and proteins involved in DNA repair and replication. In this study, we identified the site of yeast Mlh1 critical for the interaction with Exo1, Ntg2......, 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...... protein box. Direct and specific interactions between yeast Mlh1 and peptides derived from Exo1, Ntg2, and Sgs1 and between human MLH1 and peptide derived from EXO1 and BLM were measured with K(d) values ranging from 8.1 to 17.4 microM. In Saccharomyces cerevisiae, a mutant of Mlh1 targeted at site S2...

  18. Study on the binding sites of radiosensitivity associated transcription factor in the promoter region of Ier5 gene

    International Nuclear Information System (INIS)

    Cui Wei; Yin Lingling; Dong Lingyue

    2012-01-01

    Objective: To clarify the mechanism of immediate early response gene 5 (Ier5) transcription induced by radiation. Methods: Deletant construction, site-specific mutagenesis,electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) were used to forecast the promoter region, binding sites and transcription factors of Ier5 gene in HeLa cells. Results: The promoter region of Ier5 gene might be in the region of Ier5 -8 deletant (-408 - -238 bp). The Ier5 gene had two transcription factors of GCF and NFI, and GCF had two binding sites located in the region of -388 - -382 bp and -274 - -270 bp of Ier5 promoter. The binding site of NFI was located in -362 - -357 bp of Ier5 promoter. GCF could inhibit the expression of Ier5 gene and this inhibition was diminished when the radiation dose increased. In contrast, NFI increased the expression of Ier5. Conclusions: The most possible region of Ier5 promoter is from -408 to -238 bp which has two binding sites for the radiosensitivity transcription factors of GCF and NFI that could negatively and positively regulate the expression of Ier5 respectively. (authors)

  19. Factors affecting the frequency and amount of social networking site use: Motivations, perceptions, and privacy concerns

    OpenAIRE

    Cha, Jiyoung

    2010-01-01

    The purpose of this study is to explore the factors that affect the use of social networking Web sites. In doing so, this investigation focuses on two dimensions of social networking site use frequency (i.e., how often people use social networking sites) and amount (i.e., how much time people spend on social networks). Integrating the technology acceptance model with uses and gratification and other consumer characteristics, this study found that interpersonal utility, perceived ease of use, ...

  20. Stochastic seasonality and nonlinear density-dependent factors regulate population size in an African rodent

    DEFF Research Database (Denmark)

    Leirs, Herwig; Steneth, Nils Chr.; Nichols, James D.

    1997-01-01

    , but clear examples of both processes acting in the same population are rare(7,8). Key-factor analysis (regression of population changes on possible causal factors) and time-series analysis are often used to investigate the presence of density dependence, but such approaches may be biased and provide...... no information on actual demographic rates(9,10). Here we report on both density-dependent and density-independent effects in a murid rodent pest species, the multimammute rat Mastomys natalensis (Smith, 1834), using statistical capture-recapture models, Both effects occur simultaneously, but we also demonstrate...

  1. 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 $\\lambda_+ = 0.0245 \\pm 0.0012_{\\text{stat}} \\pm 0.0022_{\\text{syst}}$.

  2. 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.

  3. 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

  4. 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...

  5. Simultaneous fluorescence light-up and selective multicolor nucleobase recognition based on sequence-dependent strong binding of berberine to DNA abasic site.

    Science.gov (United States)

    Wu, Fei; Shao, Yong; Ma, Kun; Cui, Qinghua; Liu, Guiying; Xu, Shujuan

    2012-04-28

    Label-free DNA nucleobase recognition by fluorescent small molecules has received much attention due to its simplicity in mutation identification and drug screening. However, sequence-dependent fluorescence light-up nucleobase recognition and multicolor emission with individual emission energy for individual nucleobases have been seldom realized. Herein, an abasic site (AP site) in a DNA duplex was employed as a binding field for berberine, one of isoquinoline alkaloids. Unlike weak binding of berberine to the fully matched DNAs without the AP site, strong binding of berberine to the AP site occurs and the berberine's fluorescence light-up behaviors are highly dependent on the target nucleobases opposite the AP site in which the targets thymine and cytosine produce dual emission bands, while the targets guanine and adenine only give a single emission band. Furthermore, more intense emissions are observed for the target pyrimidines than purines. The flanking bases of the AP site also produce some modifications of the berberine's emission behavior. The binding selectivity of berberine at the AP site is also confirmed by measurements of fluorescence resonance energy transfer, excited-state lifetime, DNA melting and fluorescence quenching by ferrocyanide and sodium chloride. It is expected that the target pyrimidines cause berberine to be stacked well within DNA base pairs near the AP site, which results in a strong resonance coupling of the electronic transitions to the particular vibration mode to produce the dual emissions. The fluorescent signal-on and emission energy-modulated sensing for nucleobases based on this fluorophore is substantially advantageous over the previously used fluorophores. We expect that this approach will be developed as a practical device for differentiating pyrimidines from purines by positioning an AP site toward a target that is available for readout by this alkaloid probe. This journal is © The Royal Society of Chemistry 2012

  6. Site Amplification in the Central U.S.: Towards and understanding of factors influencing the site effect

    Science.gov (United States)

    Yassminh, R.; Sandvol, E. A.

    2017-12-01

    We have mapped site amplification using a Reverse Two Station (RTS) approach across much of the Central United States. We have found several unexpected results including a lack of amplification in Paleozoic basins such as the Illinois and Michigan basins. In general, we found that the amplification of high frequency regional waves is related to the topography. We also suggest that the HVSR spectra are primarily a function of the shallow velocity structure. The Central United States Seismic Observatory (CUSSO) is a vertical seismic array located adjacent to the central segment of the NMSZ. CUSSO data gives us the opportunity to understand the amplification of the ground motion at different depths within the uppermost crust. Simulating ground motions throughout the CUSSO borehole and examining the factors affecting the ground amplification, such as the velocity and thicknesses of the model layers and the source sizes, is an effective way to understand the role different factors playing in modifying the ground motion for both the local and regional seismic phases. We have used the spectral-element method (SEMs) with a 1D crustal velocity structure derived from logging data taken from CUSSO borehole. This model is comprised of near surface sediment layers and a Paleozoic basement. Utilizing the software package SPECFEM2D with virtual seismometers located on the surface and in the bottom of the different sediment layers, we have computed the true synthetic site amplification for frequencies between 0.01-3 Hz. For the local model, we have tested the sensitivity of the ground motion amplification to the source magnitude. For frequencies>0.6, the ground motions have been amplified with decreasing the magnitudes while for HZ2Hz.

  7. 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.

  8. Multiple phosphorylation sites at the C-terminus regulate nuclear import of HCMV DNA polymerase processivity factor ppUL44

    International Nuclear Information System (INIS)

    Alvisi, Gualtiero; Marin, Oriano; Pari, Gregory; Mancini, Manuela; Avanzi, Simone; Loregian, Arianna; Jans, David A.; Ripalti, Alessandro

    2011-01-01

    The processivity factor of human cytomegalovirus DNA polymerase, phosphoprotein ppUL44, is essential for viral replication. During viral infection ppUL44 is phosphorylated by the viral kinase pUL97, but neither the target residues on ppUL44 nor the effect of phosphorylation on ppUL44's activity are known. We report here that ppUL44 is phosphorylated when transiently expressed in mammalian cells and coimmunoprecipitates with cellular kinases. Of three potential phosphorylation sites (S413, S415, S418) located upstream of ppUL44's nuclear localization signal (NLS) and one (T427) within the NLS itself, protein kinase CK2 (CK2) specifically phosphorylates S413, to trigger a cascade of phosphorylation of S418 and S415 by CK1 and CK2, respectively. Negative charge at the CK2/CK1 target serine residues facilitates optimal nuclear accumulation of ppUL44, whereas negative charge on T427, a potential cyclin-dependent 1 phosphorylation site, strongly decreases nuclear accumulation. Thus, nuclear transport of ppUL44 is finely tuned during viral infection through complex phosphorylation events.

  9. 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.

  10. 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.

  11. 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 m...

  12. Personality Assessment Inventory scale characteristics and factor structure in the assessment of alcohol dependency.

    Science.gov (United States)

    Schinka, J A

    1995-02-01

    Individual scale characteristics and the inventory structure of the Personality Assessment Inventory (PAI; Morey, 1991) were examined by conducting internal consistency and factor analyses of item and scale score data from a large group (N = 301) of alcohol-dependent patients. Alpha coefficients, mean inter-item correlations, and corrected item-total scale correlations for the sample paralleled values reported by Morey for a large clinical sample. Minor differences in the scale factor structure of the inventory from Morey's clinical sample were found. Overall, the findings support the use of the PAI in the assessment of personality and psychopathology of alcohol-dependent patients.

  13. Prospective multicenter surveillance and risk factor analysis of deep surgical site infection after posterior thoracic and/or lumbar spinal surgery in adults.

    Science.gov (United States)

    Ogihara, Satoshi; Yamazaki, Takashi; Maruyama, Toru; Oka, Hiroyuki; Miyoshi, Kota; Azuma, Seiichi; Yamada, Takashi; Murakami, Motoaki; Kawamura, Naohiro; Hara, Nobuhiro; Terayama, Sei; Morii, Jiro; Kato, So; Tanaka, Sakae

    2015-01-01

    Surgical site infection is a serious and significant complication after spinal surgery and is associated with high morbidity rates, high healthcare costs and poor patient outcomes. Accurate identification of risk factors is essential for developing strategies to prevent devastating infections. The purpose of this study was to identify independent risk factors for surgical site infection among posterior thoracic and/or lumbar spinal surgery in adult patients using a prospective multicenter surveillance research method. From July 2010 to June 2012, we performed a prospective surveillance study in adult patients who had developed surgical site infection after undergoing thoracic and/or lumbar posterior spinal surgery at 11 participating hospitals. Detailed preoperative and operative patient characteristics were prospectively recorded using a standardized data collection format. Surgical site infection was based on the definition established by the Centers for Disease Control and Prevention. A total of 2,736 consecutive adult patients were enrolled, of which 24 (0.9%) developed postoperative deep surgical site infection. Multivariate regression analysis indicated four independent risk factors. Preoperative steroid therapy (P = 0.001), spinal trauma (P = 0.048) and gender (male) (P = 0.02) were statistically significant independent patient-related risk factors, whereas an operating time ≥3 h (P operating time ≥3 h were independent risk factors for deep surgical site infection after thoracic and/or lumbar spinal surgery in adult patients. Identification of these risk factors can be used to develop protocols aimed at decreasing the risk of surgical site infection.

  14. Natural variability of biochemical biomarkers in the macro-zoobenthos: Dependence on life stage and environmental factors.

    Science.gov (United States)

    Scarduelli, Lucia; Giacchini, Roberto; Parenti, Paolo; Migliorati, Sonia; Di Brisco, Agnese Maria; Vighi, Marco

    2017-11-01

    Biomarkers are widely used in ecotoxicology as indicators of exposure to toxicants. However, their ability to provide ecologically relevant information remains controversial. One of the major problems is understanding whether the measured responses are determined by stress factors or lie within the natural variability range. In a previous work, the natural variability of enzymatic levels in invertebrates sampled in pristine rivers was proven to be relevant across both space and time. In the present study, the experimental design was improved by considering different life stages of the selected taxa and by measuring more environmental parameters. The experimental design considered sampling sites in 2 different rivers, 8 sampling dates covering the whole seasonal cycle, 4 species from 3 different taxonomic groups (Plecoptera, Perla grandis; Ephemeroptera, Baetis alpinus and Epeorus alpicula; Tricoptera, Hydropsyche pellucidula), different life stages for each species, and 4 enzymes (acetylcholinesterase, glutathione S-transferase, alkaline phosphatase, and catalase). Biomarker levels were related to environmental (physicochemical) parameters to verify any kind of dependence. Data were statistically elaborated using hierarchical multilevel Bayesian models. Natural variability was found to be relevant across both space and time. The results of the present study proved that care should be paid when interpreting biomarker results. Further research is needed to better understand the dependence of the natural variability on environmental parameters. Environ Toxicol Chem 2017;36:3158-3167. © 2017 SETAC. © 2017 SETAC.

  15. Identifying Key Factors Relevant for Base Camp Siting

    Science.gov (United States)

    2017-12-01

    centers. 3.2.6.3 Religious and historical sites Respecting sacred sites helps build rapport with the host nation. 3.2.6.4 Local infrastructure...churches, mosques, national libraries, hospitals, cemeteries, historical ruins, religious sites, cultural areas, and other protected sites...controlled and protected wells. • Electricity: town engineer • Academic: government and religious leaders • Trash: private business (local

  16. Hydrologic factors and 90Sr transport at a low-level waste disposal site

    International Nuclear Information System (INIS)

    Huff, D.D.

    1982-01-01

    There are several hydrologic factors that can affect contaminant migration at a waste disposal site. Many studies recognize surface water and groundwater controls as major factors. But what are the specific hydrologic processes most often associated with contaminant transport. Studies of solid waste storage areas (SWSAs) for low-level radioactive wastes at Oak Ridge National Laboratory, which is located in the humid environment of east Tennessee, have identified several mechanisms. Most of the processes are associated with groundwater movement, but in at least one case, surface runoff has played a dominant role. In all cases, consideration of localized hydrologic conditions has been the key to understanding the factors responsible for radionuclide migration

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. 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

  3. Site selection: Past and present

    International Nuclear Information System (INIS)

    Tilford, N.R.

    1994-01-01

    Site selection has been going on since the earliest times. The process has evolved through the Industrial Revolution to the present period of exploding population and environmental awareness. Now the work must be done both with increasing sophistication and greater transparency. Modern techniques for site selection have been developed during the last two decades or so, utilizing a teachable body of knowledge and a growing literature. Many firms and individuals have contributed to this growing field. The driving force has been the need for such a process in siting and licensing of critical facilities such as nuclear power plants. A list of crucial, documented steps for identifying social impacts and acceptability are provided. A recent innovation is the self-selection method developed by government. The Superconducting Supercollider serves as an example of this approach. Geological or geologically dependent factors often dominate the process. The role as engineering and environmental geoscientists is to provide responsible leadership, consultation, and communication to the effort

  4. Site occupancy, composition and magnetic structure dependencies of martensitic transformation in Mn2Ni1 + x Sn1-x.

    Science.gov (United States)

    Kundu, Ashis; Ghosh, Subhradip

    2017-11-29

    A delicate balance between various factors such as site occupancy, composition and magnetic ordering seems to affect the stability of the martensitic phase in [Formula: see text] [Formula: see text] [Formula: see text]. Using first-principles DFT calculations, we explore the impacts of each one of these factors on the martensitic stability of this system. Our results on total energies, magnetic moments and electronic structures upon changes in the composition, the magnetic configurations and the site occupancies show that the occupancies at the 4d sites in the inverse Heusler crystal structure play the most crucial role. The presence of Mn at the 4d sites originally occupied by Sn and its interaction with the Mn atoms at other sites decide the stability of the martensitic phases. This explains the discrepancy between the experiments and earlier DFT calculations regarding phase stability in [Formula: see text]NiSn. Our results qualitatively explain the trends observed experimentally with regard to martensitic phase stability and the magnetisations in Ni-excess, Sn-deficient [Formula: see text]NiSn system.

  5. Lessons learned from international siting experiences of LLW Disposal facilities

    International Nuclear Information System (INIS)

    McCabe, G.H.

    1990-01-01

    This paper reports that the United States can gain insight into successfully siting low-level radioactive waste (LLW) disposal facilities by studying the process in other nations. Siting experiences in France and Sweden are compared to experiences in the United States. Three factors appear to making siting of LLW disposal facilities easier in France and Sweden than in the United States. First, the level of public trust in the government and the entities responsible for siting, developing, and operating a LLW disposal facility is much greater in France and Sweden than in the United States. Second, France and Sweden are much more dependent on nuclear power than is the United States. Third, French and Swedish citizens do not have the same access to the siting process (i.e., legal means to intervene) as do U.S. citizens. To compensate for these three factors, public officials responsible for siting a facility may need to better listen to the concerns of public interest groups and citizen advisory committees and amend their siting process accordingly and better share power and control with the public. If these two techniques are implemented earnestly by the states, siting efforts may be increasingly more successful in the United States

  6. 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

    , such as Ace2 and Swi6, and stress response regulators, such as Yap1, were also shown to have significantly enriched target sets. Conclusion: Our work, which is the first genome-wide gene expression study to investigate specific growth rate and consider the impact of oxygen availability, provides a more......Background: Characterization of cellular growth is central to understanding living systems. Here, we applied a three-factor design to study the relationship between specific growth rate and genome-wide gene expression in 36 steady-state chemostat cultures of Saccharomyces cerevisiae. The three...... factors we considered were specific growth rate, nutrient limitation, and oxygen availability. Results: We identified 268 growth rate dependent genes, independent of nutrient limitation and oxygen availability. The transcriptional response was used to identify key areas in metabolism around which m...

  7. Using sequence-specific chemical and structural properties of DNA to predict transcription factor binding sites.

    Directory of Open Access Journals (Sweden)

    Amy L Bauer

    2010-11-01

    Full Text Available An important step in understanding gene regulation is to identify the DNA binding sites recognized by each transcription factor (TF. Conventional approaches to prediction of TF binding sites involve the definition of consensus sequences or position-specific weight matrices and rely on statistical analysis of DNA sequences of known binding sites. Here, we present a method called SiteSleuth in which DNA structure prediction, computational chemistry, and machine learning are applied to develop models for TF binding sites. In this approach, binary classifiers are trained to discriminate between true and false binding sites based on the sequence-specific chemical and structural features of DNA. These features are determined via molecular dynamics calculations in which we consider each base in different local neighborhoods. For each of 54 TFs in Escherichia coli, for which at least five DNA binding sites are documented in RegulonDB, the TF binding sites and portions of the non-coding genome sequence are mapped to feature vectors and used in training. According to cross-validation analysis and a comparison of computational predictions against ChIP-chip data available for the TF Fis, SiteSleuth outperforms three conventional approaches: Match, MATRIX SEARCH, and the method of Berg and von Hippel. SiteSleuth also outperforms QPMEME, a method similar to SiteSleuth in that it involves a learning algorithm. The main advantage of SiteSleuth is a lower false positive rate.

  8. Size and Site Dependence of the Catalytic Activity of Iridium Clusters toward Ethane Dehydrogenation.

    Science.gov (United States)

    Ge, Yingbin; Jiang, Hao; Kato, Russell; Gummagatta, Prasuna

    2016-12-01

    This research focuses on optimizing transition metal nanocatalyst immobilization and activity to enhance ethane dehydrogenation. Ethane dehydrogenation, catalyzed by thermally stable Ir n (n = 8, 12, 18) atomic clusters that exhibit a cuboid structure, was studied using the B3LYP method with triple-ζ basis sets. Relativistic effects and dispersion corrections were included in the calculations. In the dehydrogenation reaction Ir n + C 2 H 6 → H-Ir n -C 2 H 5 → (H) 2 -Ir n -C 2 H 4 , the first H-elimination is the rate-limiting step, primarily because the reaction releases sufficient heat to facilitate the second H-elimination. The catalytic activity of the Ir clusters strongly depends on the Ir cluster size and the specific catalytic site. Cubic Ir 8 is the least reactive toward H-elimination in ethane: Ir 8 + C 2 H 6 → H-Ir 8 -C 2 H 5 has a large (65 kJ/mol) energy barrier, whereas Ir 12 (3 × 2 × 2 cuboid) and Ir 18 (3 × 3 × 2 cuboid) lower this energy barrier to 22 and 3 kJ/mol, respectively. The site dependence is as prominent as the size effect. For example, the energy barrier for the Ir 18 + C 2 H 6 → H-Ir 18 -C 2 H 5 reaction is 3, 48, and 71 kJ/mol at the corner, edge, or face-center sites of the Ir 18 cuboid, respectively. Energy release due to Ir cluster insertion into an ethane C-H bond facilitates hydrogen migration on the Ir cluster surface, and the second H-elimination of ethane. In an oxygen-rich environment, oxygen molecules may be absorbed on the Ir cluster surface. The oxygen atoms bonded to the Ir cluster surface may slightly increase the energy barrier for H-elimination in ethane. However, the adsorption of oxygen and its reaction with H atoms on the Ir cluster releases sufficient heat to yield an overall thermodynamically favored reaction: Ir n + C 2 H 6 + 1 / 2 O 2 → Ir n + C 2 H 4 + H 2 O. These results will be useful toward reducing the energy cost of ethane dehydrogenation in industry.

  9. Quantitative in vivo analyses reveal calcium-dependent phosphorylation sites and identifies a novel component of the Toxoplasma invasion motor complex.

    Directory of Open Access Journals (Sweden)

    Thomas Nebl

    2011-09-01

    Full Text Available 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.

  10. 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.

  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. Biosphere analysis - a complementary assessment of dose conversion factors for the Olkiluoto site

    International Nuclear Information System (INIS)

    Kylloenen, J.; Keto, V.

    2010-04-01

    The Olkiluoto site is currently the primary candidate for the final disposal site for spent nuclear fuel from the Olkiluoto and Loviisa NPPs. Safety analysis calculations must be performed to verify the compliance with the long-term safety requirements. The behaviour and distribution of radionuclides in the biosphere is of high importance in these calculations. The aim of this study was to perform a complementary assessment of dose conversion factors for the Olkiluoto site. Posiva has performed extensive analysis on the different ecosystems. In this work the biosphere analysis model of Fortum Nuclear Services (FNS) is used to give an independent estimate of biosphere dose conversion factors for the Olkiluoto site. The following nuclides are analysed: Cl-36, Ni-59, Se-79, Mo-93, Nb-94, Sn-126, I-129 and Cs-135. The FNS model is an equilibrium compartment model in which a steady annual release of 1 Bq of each radionuclide is distributed in different scenarios. The scenarios are the well scenario, which models a small agricultural ecosystem, the lake scenario which models a larger ecosystem with both agriculture and lake use, and sea and transition scenario, which models the behaviour of the radionuclides in marine environments. The scenarios are described and the transfer equations written for the lake scenario. The parameter values are taken from the FNS biosphere database, which has been used in the Finnish L/ILW waste repository safety analyses since mid 1990's. The results of the FNS analysis are compared to those presented in Posiva working report 2000-20 (POSIVA-WR-00-20). The results are of the same order of magnitude for all nuclides except I-129. Since the Posiva and FNS models were independently constructed, the results can be considered as convincing, and the compliance of the results give confidence to the modelling results. (orig.)

  13. Assessment of economic factors affecting the satellite power system. Volume 2: The systems implications of rectenna siting issues

    Science.gov (United States)

    Chapman, P. K.; Bugos, B. J.; Csigi, K. I.; Glaser, P. E.; Schimke, G. R.; Thomas, R. G.

    1979-01-01

    The feasibility was evaluated of finding potential sites for Solar Power Satellite (SPS) receiving antennas (rectennas) in the continental United States, in sufficient numbers to permit the SPS to make a major contribution to U.S. generating facilities, and to give statistical validity to an assessment of the characteristics of such sites and their implications for the design of the SPS system. It is found that the cost-optimum power output of the SPS does not depend on the particular value assigned to the cost per unit area of a rectenna and its site, as long as it is independent of rectenna area. Many characteristics of the sites chosen affect the optimum design of the rectenna itself.

  14. 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

  15. 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.

  16. 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 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.

  17. 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

  18. 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

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

    KAUST Repository

    Abutaha, Anas I.; Sarath Kumar, S. R.; Mehdizadeh Dehkordi, Arash; Tritt, Terry M.; Alshareef, Husam N.

    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

  20. 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...

  1. Practical Application of Site-Specific Earthquake Early Warning (EEW) System

    International Nuclear Information System (INIS)

    Kanda, Katsuhisa

    2014-01-01

    The development of an on-site warning system was reported. This system improves the timing of warnings and reduces the number of false alarms by improving the method of estimating the JMA seismic intensity using earthquake early warning system information based on site-specific data. Moreover, the development of an application for practical use in a construction company and an integrated system for realizing system shutdown was also reported. The concept of this system is based on the following. Seismic intensity is not distributed concentrically, and the attenuation relationship cannot explain the distribution of seismic intensity precisely. The standard method of seismic intensity prediction is construed as 'attenuation relationship + soil amplification factor', but this may be improved in the reformulation 'original attenuation relationship for each site + correction factors dependent on the epicenter location and depth' using a seismic intensity database that includes data on recent and historical earthquakes. (authors)

  2. Oviposition site selection by the grasshoppers Melanoplus borealis and M. sanguinipes (Orthoptera: Acrididae)

    Science.gov (United States)

    Female grasshoppers can affect the fitness of their offspring through their selection of oviposition sites. Successful embryological development depends on suitable temperature and moisture levels, factors which may vary considerably on a fine scale in natural environments where grasshoppers occur. ...

  3. Electric properties and carrier multiplication in breakdown sites in multi-crystalline silicon solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Schneemann, Matthias; Carius, Reinhard; Rau, Uwe [IEK5-Photovoltaics, Forschungszentrum Jülich, Jülich 52425 (Germany); Kirchartz, Thomas, E-mail: t.kirchartz@fz-juelich.de [IEK5-Photovoltaics, Forschungszentrum Jülich, Jülich 52425 (Germany); Faculty of Engineering and CENIDE, University of Duisburg-Essen, Carl-Benz-Str. 199, Duisburg 47057 (Germany)

    2015-05-28

    This paper studies the effective electrical size and carrier multiplication of breakdown sites in multi-crystalline silicon solar cells. The local series resistance limits the current of each breakdown site and is thereby linearizing the current-voltage characteristic. This fact allows the estimation of the effective electrical diameters to be as low as 100 nm. Using a laser beam induced current (LBIC) measurement with a high spatial resolution, we find carrier multiplication factors on the order of 30 (Zener-type breakdown) and 100 (avalanche breakdown) as new lower limits. Hence, we prove that also the so-called Zener-type breakdown is followed by avalanche multiplication. We explain that previous measurements of the carrier multiplication using thermography yield results higher than unity, only if the spatial defect density is high enough, and the illumination intensity is lower than what was used for the LBIC method. The individual series resistances of the breakdown sites limit the current through these breakdown sites. Therefore, the measured multiplication factors depend on the applied voltage as well as on the injected photocurrent. Both dependencies are successfully simulated using a series-resistance-limited diode model.

  4. 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.

  5. Bioremediation of contaminated sites

    International Nuclear Information System (INIS)

    Schneider, C.

    1996-01-01

    By volatilizing aromatic compounds through aeration, landfarming is a recognized approach to the bioremediation of hydrocarbon contaminated soil. With this method, the soil is cultivated and aided with fertilizer amendment to provide a nutrient source for the microbial population involved in the degradation of hydrocarbons. The effectiveness of bioremediation will depend on several factors, including topographic features, soil properties, and biochemistry. Since bioremediation is inhibited by anaerobic conditions, sites that are sloped or have trenches to collect runoff water are preferable. As for soil properties, the percentage of sand should not be too high, but aeration is essential to avoid anaerobic conditions. Addition of straw is generally beneficial, and fertilizers with nitrogen, phosphorous and potassium will help degrading hydrocarbons. Temperature, pH, and salt content are also important factors since they facilitate microbial activity. 3 refs

  6. Age-dependent regulation of ERF-VII transcription factor activity in Arabidopsis thaliana.

    Science.gov (United States)

    Giuntoli, Beatrice; Shukla, Vinay; Maggiorelli, Federica; Giorgi, Federico M; Lombardi, Lara; Perata, Pierdomenico; Licausi, Francesco

    2017-10-01

    The Group VII Ethylene Responsive Factors (ERFs-VII) RAP2.2 and RAP2.12 have been mainly characterized with regard to their contribution as activators of fermentation in plants. However, transcriptional changes measured in conditions that stabilize these transcription factors exceed the mere activation of this biochemical pathway, implying additional roles performed by the ERF-VIIs in other processes. We evaluated gene expression in transgenic Arabidopsis lines expressing a stabilized form of RAP2.12, or hampered in ERF-VII activity, and identified genes affected by this transcriptional regulator and its homologs, including some involved in oxidative stress response, which are not universally induced under anaerobic conditions. The contribution of the ERF-VIIs in regulating this set of genes in response to chemically induced or submergence-stimulated mitochondria malfunctioning was found to depend on the plant developmental stage. A similar age-dependent mechanism also restrained ERF-VII activity upon the core-hypoxic genes, independently of the N-end rule pathway, which is accounted for the control of the anaerobic response. To conclude, this study shed new light on a dual role of ERF-VII proteins under submergence: as positive regulators of the hypoxic response and as repressors of oxidative-stress related genes, depending on the developmental stage at which plants are challenged by stress conditions. © 2017 John Wiley & Sons Ltd.

  7. Activity-dependent shedding of the NMDA receptor glycine binding site by matrix metalloproteinase 3: a PUTATIVE mechanism of postsynaptic plasticity.

    Directory of Open Access Journals (Sweden)

    Thorsten Pauly

    Full Text Available Functional and structural alterations of clustered postsynaptic ligand gated ion channels in neuronal cells are thought to contribute to synaptic plasticity and memory formation in the human brain. Here, we describe a novel molecular mechanism for structural alterations of NR1 subunits of the NMDA receptor. In cultured rat spinal cord neurons, chronic NMDA receptor stimulation induces disappearance of extracellular epitopes of NMDA receptor NR1 subunits, which was prevented by inhibiting matrix metalloproteinases (MMPs. Immunoblotting revealed the digestion of solubilized NR1 subunits by MMP-3 and identified a fragment of about 60 kDa as MMPs-activity-dependent cleavage product of the NR1 subunit in cultured neurons. The expression of MMP-3 in the spinal cord culture was shown by immunoblotting and immunofluorescence microscopy. Recombinant NR1 glycine binding protein was used to identify MMP-3 cleavage sites within the extracellular S1 and S2-domains. N-terminal sequencing and site-directed mutagenesis revealed S542 and L790 as two putative major MMP-3 cleavage sites of the NR1 subunit. In conclusion, our data indicate that MMPs, and in particular MMP-3, are involved in the activity dependent alteration of NMDA receptor structure at postsynaptic membrane specializations in the CNS.

  8. Activity-dependent shedding of the NMDA receptor glycine binding site by matrix metalloproteinase 3: a PUTATIVE mechanism of postsynaptic plasticity.

    Science.gov (United States)

    Pauly, Thorsten; Ratliff, Miriam; Pietrowski, Eweline; Neugebauer, Rainer; Schlicksupp, Andrea; Kirsch, Joachim; Kuhse, Jochen

    2008-07-16

    Functional and structural alterations of clustered postsynaptic ligand gated ion channels in neuronal cells are thought to contribute to synaptic plasticity and memory formation in the human brain. Here, we describe a novel molecular mechanism for structural alterations of NR1 subunits of the NMDA receptor. In cultured rat spinal cord neurons, chronic NMDA receptor stimulation induces disappearance of extracellular epitopes of NMDA receptor NR1 subunits, which was prevented by inhibiting matrix metalloproteinases (MMPs). Immunoblotting revealed the digestion of solubilized NR1 subunits by MMP-3 and identified a fragment of about 60 kDa as MMPs-activity-dependent cleavage product of the NR1 subunit in cultured neurons. The expression of MMP-3 in the spinal cord culture was shown by immunoblotting and immunofluorescence microscopy. Recombinant NR1 glycine binding protein was used to identify MMP-3 cleavage sites within the extracellular S1 and S2-domains. N-terminal sequencing and site-directed mutagenesis revealed S542 and L790 as two putative major MMP-3 cleavage sites of the NR1 subunit. In conclusion, our data indicate that MMPs, and in particular MMP-3, are involved in the activity dependent alteration of NMDA receptor structure at postsynaptic membrane specializations in the CNS.

  9. 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.

  10. Oxygen dependency of epidermal growth factor receptor binding and DNA synthesis of rat hepatocytes

    International Nuclear Information System (INIS)

    Hirose, Tetsuro; Terajima, Hiroaki; Yamauchi, Akira

    1997-01-01

    Background/Aims: Changes in oxygen availability modulate replicative responses in several cell types, but the effects on hepatocyte replication remain unclear. We have studied the effects of transient nonlethal hypoxia on epidermal growth factor receptor binding and epidermal growth factor-induced DNA synthesis of rat hepatocytes. Methods: Lactate dehydrogenase activity in culture supernatant, intracellular adenosine triphosphate content, 125 I-epidermal growth factor specific binding, epidermal growth factor receptor protein expression, and 3 H-thymidine incorporation were compared between hepatocytes cultured in hypoxia and normoxia. Results: Hypoxia up to 3 h caused no significant increase in lactate dehydrogenase activity in the culture supernatant, while intracellular adenosine triphosphate content decreased time-dependently and was restored to normoxic levels by reoxygenation (nonlethal hypoxia). Concomitantly, 125 I-epidermal growth factor specific binding to hepatocytes decreased time-dependently (to 54.1% of normoxia) and was restored to control levels by reoxygenation, although 125 I-insulin specific binding was not affected. The decrease in 125 I-epidermal growth factor specific binding was explained by the decrease in the number or available epidermal growth factor receptors (21.37±3.08 to 12.16±1.42 fmol/10 5 cells), while the dissociation constant of the receptor was not affected. The change in the number of available receptors was not considered to be due to receptor degradation-resynthesis, since immuno-detection of the epidermal growth factor receptor revealed that the receptor protein expression did not change during hypoxia and reoxygenation, and since neither actinomycin D nor cycloheximide affected the recovery of 125 I-epidermal growth factor binding by reoxygenation. Inhibition of epidermal growth factor-induced DNA synthesis after hypoxia (to 75.4% of normoxia by 3 h hypoxia) paralleled the decrease in 125 I-epidermal growth factor binding

  11. Recharge at the Hanford Site: Status report

    International Nuclear Information System (INIS)

    Gee, G.W.

    1987-11-01

    A variety of field programs designed to evaluate recharge and other water balance components including precipitation, infiltration, evaporation, and water storage changes, have been carried out at the Hanford Site since 1970. Data from these programs have indicated that a wide range of recharge rates can occur depending upon specific site conditions. Present evidence suggests that minimum recharge occurs where soils are fine-textured and surfaces are vegetated with deep-rooted plants. Maximum recharge occurs where coarse soils or gravels exist at the surface and soils are kept bare. Recharge can occur in areas where shallow-rooted plants dominate the surface, particularly where soils are coarse-textured. Recharge estimates have been made for the site using simulation models. A US Geological Survey model that attempts to account for climate variability, soil storage parameters, and plant factors has calculated recharge values ranging from near zero to an average of about 1 cm/yr for the Hanford Site. UNSAT-H, a deterministic model developed for the site, appears to be the best code available for estimating recharge on a site-specific basis. Appendix I contains precipitation data from January 1979 to June 1987. 42 refs., 11 figs., 11 tabs

  12. 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.

  13. 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.

  14. 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.

  15. Design-dependent gauge factors of highly doped n-type 4H-SiC piezoresistors

    International Nuclear Information System (INIS)

    Akiyama, T; Briand, D; De Rooij, N F

    2012-01-01

    This paper presents the experimentally obtained gauge factor (GF) of 4H-SiC piezoresistors, fabricated out of the n-type epitaxial layer and characterized on millimeter-size SiC cantilever beams at room temperature. It was found that the GF is dependent on the piezoresistor's length and width. Piezoresistors narrower than approximately 30 µm showed a width-dependent GF. The highest GF of 20.8 was obtained with a single element piezoresistor in transverse orientation. In longitudinal orientation, the highest GF was −10, which was obtained with a clustered piezoresistor with plural identical elements. Essential factors to consider for the design of optimum 4H-SiC piezoresistors for a Wheatstone bridge configuration are presented. (paper)

  16. Recruitment of the cohesin loading factor NIPBL to DNA double-strand breaks depends on MDC1, RNF168 and HP1γ in human cells

    International Nuclear Information System (INIS)

    Oka, Yasuyoshi; Suzuki, Keiji; Yamauchi, Motohiro; Mitsutake, Norisato; Yamashita, Shunichi

    2011-01-01

    Highlights: → NIPBL is recruited to DSBs. → Localization of NIPBL to DSBs is regulated by MDC1 and RNF168. → HP1γ is required for NIPBL accumulation at DSBs. -- Abstract: The cohesin loading factor NIPBL is required for cohesin to associate with chromosomes and plays a role in DNA double-strand break (DSB) repair. Although the NIPBL homolog Scc2 is recruited to an enzymatically generated DSB and promotes cohesin-dependent DSB repair in yeast, the mechanism of the recruitment remains poorly understood. Here we show that the human NIPBL is recruited to the sites of DNA damage generated by micro-irradiation as well as to the sites of DSBs induced by homing endonuclease, I-PpoI. The recruitment of NIPBL was impaired by RNAi-mediated knockdown of MDC1 or RNF168, both of which also accumulate at DSBs. We also show that the recruitment of NIPBL to the sites of DNA damage is mediated by its C-terminal region containing HEAT repeats and Heterochromatin protein 1 (HP1) interacting motif. Furthermore, NIPBL accumulation at damaged sites was also compromised by HP1γ depletion. Taken together, our study reveals that human NIPBL is a novel protein recruited to DSB sites, and the recruitment is controlled by MDC1, RNF168 and HP1γ.

  17. Two signaling molecules share a phosphotyrosine-containing binding site in the platelet-derived growth factor receptor.

    OpenAIRE

    Nishimura, R; Li, W; Kashishian, A; Mondino, A; Zhou, M; Cooper, J; Schlessinger, J

    1993-01-01

    Autophosphorylation sites of growth factor receptors with tyrosine kinase activity function as specific binding sites for Src homology 2 (SH2) domains of signaling molecules. This interaction appears to be a crucial step in a mechanism by which receptor tyrosine kinases relay signals to downstream signaling pathways. Nck is a widely expressed protein consisting exclusively of SH2 and SH3 domains, the overexpression of which causes cell transformation. It has been shown that various growth fac...

  18. Frequency-dependent local field factors in dielectric liquids by a polarizable force field and molecular dynamics simulations

    International Nuclear Information System (INIS)

    Davari, Nazanin; Haghdani, Shokouh; Åstrand, Per-Olof

    2015-01-01

    A force field model for calculating local field factors, i.e. the linear response of the local electric field for example at a nucleus in a molecule with respect to an applied electric field, is discussed. It is based on a combined charge-transfer and point-dipole interaction model for the polarizability, and thereby it includes two physically distinct terms for describing electronic polarization: changes in atomic charges arising from transfer of charge between the atoms and atomic induced dipole moments. A time dependence is included both for the atomic charges and the atomic dipole moments and if they are assumed to oscillate with the same frequency as the applied electric field, a model for frequency-dependent properties are obtained. Furthermore, if a life-time of excited states are included, a model for the complex frequency-dependent polariability is obtained including also information about excited states and the absorption spectrum. We thus present a model for the frequency-dependent local field factors through the first molecular excitation energy. It is combined with molecular dynamics simulations of liquids where a large set of configurations are sampled and for which local field factors are calculated. We are normally not interested in the average of the local field factor but rather in configurations where it is as high as possible. In electrical insulation, we would like to avoid high local field factors to reduce the risk for electrical breakdown, whereas for example in surface-enhanced Raman spectroscopy, high local field factors are desired to give dramatically increased intensities

  19. Model calculating annual mean atmospheric dispersion factor for coastal site of nuclear power plant

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    This paper describes an atmospheric dispersion field experiment performed on the coastal site of nuclear power plant in the east part of China during 1995 to 1996. The three-dimension joint frequency are obtained by hourly observation of wind and temperature on a 100m high tower; the frequency of the “event day of land and sea breezes” are given by observation of surface wind and land and sea breezes; the diffusion parameters are got from measurements of turbulent and wind tunnel simulation test.A new model calculating the annual mean atmospheric dispersion factor for coastal site of nuclear power plant is developed and established.This model considers not only the effect from mixing release and mixed layer but also the effect from the internal boundary layer and variation of diffusion parameters due to the distance from coast.The comparison between results obtained by the new model and current model shows that the ratio of annual mean atmospheric dispersion factor gained by the new model and the current one is about 2.0.

  20. 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....

  1. Dependence of electromagnetic form factors of hadrons on light-cone frames

    International Nuclear Information System (INIS)

    Weber, H.J.; Xu Xiaoming; Chinese Acad. of Sci., Shanghai

    1996-01-01

    A constituent quark model is developed for an arbitrary light-cone direction so that the light-front time is x LF + =ω.x with a constant lightlike four-vector ω. Form factors are obtained from free one-body electromagnetic current matrix elements. They are found to be ω-independent for spin-0 mesons, nucleons and the Λ-hyperon, while there is an ω-dependence for spin-1 systems like the deuteron. (orig.)

  2. 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.

  3. 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.

  4. Diffusion of Sites versus Polymers in Polyelectrolyte Complexes and Multilayers.

    Science.gov (United States)

    Fares, Hadi M; Schlenoff, Joseph B

    2017-10-18

    It has long been assumed that the spontaneous formation of materials such as complexes and multilayers from charged polymers depends on (inter)diffusion of these polyelectrolytes. Here, we separately examine the mass transport of polymer molecules and extrinsic sites-charged polyelectrolyte repeat units balanced by counterions-within thin films of polyelectrolyte complex, PEC, using sensitive isotopic labeling techniques. The apparent diffusion coefficients of these sites within PEC films of poly(diallyldimethylammonium), PDADMA, and poly(styrenesulfonate), PSS, are at least 2 orders of magnitude faster than the diffusion of polyelectrolytes themselves. This is because site diffusion requires only local rearrangements of polyelectrolyte repeat units, placing far fewer kinetic limitations on the assembly of polyelectrolyte complexes in all of their forms. Site diffusion strongly depends on the salt concentration (ionic strength) of the environment, and diffusion of PDADMA sites is faster than that of PSS sites, accounting for the asymmetric nature of multilayer growth. Site diffusion is responsible for multilayer growth in the linear and into the exponential regimes, which explains how PDADMA can mysteriously "pass through" layers of PSS. Using quantitative relationships between site diffusion coefficient and salt concentration, conditions were identified that allowed the diffusion length to always exceed the film thickness, leading to full exponential growth over 3 orders of magnitude thickness. Both site and polymer diffusion were independent of molecular weight, suggesting that ion pairing density is a limiting factor. Polyelectrolyte complexes are examples of a broader class of dynamic bulk polymeric materials that (self-) assemble via the transport of cross-links or defects rather than actual molecules.

  5. Experimental determination of the angular dependence factor for the dose equivalent for photons in calibration phantoms of PMMA

    International Nuclear Information System (INIS)

    Lund, E.; Carlsson, C.A.; Pernicka, F.

    1994-01-01

    The conversion coefficients from air kerma to dose equivalent at a depth of 10 mm in both a spherical and a slab phantom of PMMA have been determined for the X ray qualities: 40, 80 and 295 kV, ISO 'narrow' spectra; and for 137 Cs γ rays. The angular dependence factors have been experimentally determined for the same qualities and for different angles between 0 o and 180 o . The absorbed doses have been measured with thermoluminescence LiF dosemeters. The conversion coefficients and the angular dependence factors are generally found to agree well with calculated ones. Some minor discrepancies are found for the angular dependence factors and the 30 x 30 x 15 cm 3 PMMA slab phantom. (Author)

  6. Active sites in char gasification: Final technical report

    Energy Technology Data Exchange (ETDEWEB)

    Wojtowicz, M.; Lilly, W.D.; Perkins, M.T.; Hradil, G.; Calo, J.M.; Suuberg, E.M.

    1987-09-01

    Among the key variables in the design of gasifiers and combustors is the reactivity of the chars which must be gasified or combusted. Significant loss of unburned char is unacceptable in virtually any process; the provision of sufficient residence time for complete conversion is essential. A very wide range of reactivities are observed, depending upon the nature of the char in a process. The current work focuses on furthering the understanding of gasification reactivities of chars. It has been well established that the reactivity of char to gasification generally depends upon three principal factors: (1) the concentration of ''active sites'' in the char; (2) mass transfer within the char; and (3) the type and concentration of catalytic impurities in the char. The present study primarily addresses the first factor. The subject of this research is the origin, nature, and fate of active sites in chars derived from parent hydrocarbons with coal-like structure. The nature and number of the active sites and their reactivity towards oxygen are examined in ''model'' chars derived from phenol-formaldehyde type resins. How the active sites are lost by the process of thermal annealing during heat treatment of chars are studied, and actual rate for the annealing process is derived. Since intrinsic char reactivities are of primary interest in the present study, a fair amount of attention was given to the model char synthesis and handling so that the effect of catalytic impurities and oxygen-containing functional groups in the chemical structure of the material were minimized, if not completely eliminated. The project would not be considered complete without comparing characteristic features of synthetic chars with kinetic behavior exhibited by natural chars, including coal chars.

  7. 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.

  8. 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.

  9. Correction of measured Gamma-Knife output factors for angular dependence of diode detectors and PinPoint ionization chamber.

    Science.gov (United States)

    Hršak, Hrvoje; Majer, Marija; Grego, Timor; Bibić, Juraj; Heinrich, Zdravko

    2014-12-01

    Dosimetry for Gamma-Knife requires detectors with high spatial resolution and minimal angular dependence of response. Angular dependence and end effect time for p-type silicon detectors (PTW Diode P and Diode E) and PTW PinPoint ionization chamber were measured with Gamma-Knife beams. Weighted angular dependence correction factors were calculated for each detector. The Gamma-Knife output factors were corrected for angular dependence and end effect time. For Gamma-Knife beams angle range of 84°-54°. Diode P shows considerable angular dependence of 9% and 8% for the 18 mm and 14, 8, 4 mm collimator, respectively. For Diode E this dependence is about 4% for all collimators. PinPoint ionization chamber shows angular dependence of less than 3% for 18, 14 and 8 mm helmet and 10% for 4 mm collimator due to volumetric averaging effect in a small photon beam. Corrected output factors for 14 mm helmet are in very good agreement (within ±0.3%) with published data and values recommended by vendor (Elekta AB, Stockholm, Sweden). For the 8 mm collimator diodes are still in good agreement with recommended values (within ±0.6%), while PinPoint gives 3% less value. For the 4 mm helmet Diodes P and E show over-response of 2.8% and 1.8%, respectively. For PinPoint chamber output factor of 4 mm collimator is 25% lower than Elekta value which is generally not consequence of angular dependence, but of volumetric averaging effect and lack of lateral electronic equilibrium. Diodes P and E represent good choice for Gamma-Knife dosimetry. Copyright © 2014 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  10. PolyaPeak: Detecting Transcription Factor Binding Sites from ChIP-seq Using Peak Shape Information

    Science.gov (United States)

    Wu, Hao; Ji, Hongkai

    2014-01-01

    ChIP-seq is a powerful technology for detecting genomic regions where a protein of interest interacts with DNA. ChIP-seq data for mapping transcription factor binding sites (TFBSs) have a characteristic pattern: around each binding site, sequence reads aligned to the forward and reverse strands of the reference genome form two separate peaks shifted away from each other, and the true binding site is located in between these two peaks. While it has been shown previously that the accuracy and resolution of binding site detection can be improved by modeling the pattern, efficient methods are unavailable to fully utilize that information in TFBS detection procedure. We present PolyaPeak, a new method to improve TFBS detection by incorporating the peak shape information. PolyaPeak describes peak shapes using a flexible Pólya model. The shapes are automatically learnt from the data using Minorization-Maximization (MM) algorithm, then integrated with the read count information via a hierarchical model to distinguish true binding sites from background noises. Extensive real data analyses show that PolyaPeak is capable of robustly improving TFBS detection compared with existing methods. An R package is freely available. PMID:24608116

  11. GIS and Multicriteria Decision Analysis for Landfill Site Selection in AL-HashimyahQadaa

    OpenAIRE

    Alanbari, Mohammad Ali; Al-Ansari, Nadhir; Jasim, Hadeel Kareem

    2014-01-01

    Waste management system is not well regulated in Iraq. Despite the fact that there are various techniques used for solid waste disposal, landfill is the most common mode for the disposal of solid waste in Iraq, landfill site selection criteria is quite complex process and it depends on several regulation and factors. In this study landfill site selection is performed by using Multicriteria Decision Analysis (MCDA) and Geographic Information System (GIS) for the Al-Hashimyahqadaa. Existing lan...

  12. Technical factors in the site selection for a radioactive wastes storage of low and intermediate level

    International Nuclear Information System (INIS)

    Badillo A, V. E.; Ramirez S, J. R.; Palacios H, J. C.

    2009-10-01

    The storage on surface or near surface it is viable for wastes of low and intermediate level which contain radio nuclides of short half life that would decay at insignificant levels of radioactivity in some decades and also radio nuclides of long half life but in very low concentrations. The sites selection, for the construction of radioactive waste storages, that present an appropriate stability at long term, a foreseeable behavior to future and a capacity to fulfill other operational requirements, is one of the great tasks that confront the waste disposal agencies. In the selection of potential sites for the construction of a radioactive wastes storage of low and intermediate level, several basic judgments should be satisfied that concern to physiography, climatology, geologic, geo-hydrology, tectonic and seismic aspects; as well as factors like the population density, socioeconomic develops and existent infrastructure. the necessary technician-scientific investigations for the selection of a site for the construction of radioactive waste storages are presented in this work and they are compared with the pre-selection factors realized in specify areas in previous studies in different regions of the Mexican Republic. (Author)

  13. Discovery and validation of information theory-based transcription factor and cofactor binding site motifs.

    Science.gov (United States)

    Lu, Ruipeng; Mucaki, Eliseos J; Rogan, Peter K

    2017-03-17

    Data from ChIP-seq experiments can derive the genome-wide binding specificities of transcription factors (TFs) and other regulatory proteins. We analyzed 765 ENCODE ChIP-seq peak datasets of 207 human TFs with a novel motif discovery pipeline based on recursive, thresholded entropy minimization. This approach, while obviating the need to compensate for skewed nucleotide composition, distinguishes true binding motifs from noise, quantifies the strengths of individual binding sites based on computed affinity and detects adjacent cofactor binding sites that coordinate with the targets of primary, immunoprecipitated TFs. We obtained contiguous and bipartite information theory-based position weight matrices (iPWMs) for 93 sequence-specific TFs, discovered 23 cofactor motifs for 127 TFs and revealed six high-confidence novel motifs. The reliability and accuracy of these iPWMs were determined via four independent validation methods, including the detection of experimentally proven binding sites, explanation of effects of characterized SNPs, comparison with previously published motifs and statistical analyses. We also predict previously unreported TF coregulatory interactions (e.g. TF complexes). These iPWMs constitute a powerful tool for predicting the effects of sequence variants in known binding sites, performing mutation analysis on regulatory SNPs and predicting previously unrecognized binding sites and target genes. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  14. 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.

  15. The origins of enhanced activity in factor VIIa analogs and the interplay between key allosteric sites revealed by hydrogen exchange mass spectrometry

    DEFF Research Database (Denmark)

    Rand, Kasper D; Andersen, Mette D; Olsen, Ole H

    2008-01-01

    Factor VIIa (FVIIa) circulates in the blood in a zymogen-like state. Only upon association with membrane-bound tissue factor (TF) at the site of vascular injury does FVIIa become active and able to initiate blood coagulation. Here we used hydrogen exchange monitored by mass spectrometry to invest......Factor VIIa (FVIIa) circulates in the blood in a zymogen-like state. Only upon association with membrane-bound tissue factor (TF) at the site of vascular injury does FVIIa become active and able to initiate blood coagulation. Here we used hydrogen exchange monitored by mass spectrometry...... to investigate the conformational effects of site-directed mutagenesis at key positions in FVIIa and the origins of enhanced intrinsic activity of FVIIa analogs. The differences in hydrogen exchange of two highly active variants, FVIIa(DVQ) and FVIIa(VEAY), imply that enhanced catalytic efficiency was attained...

  16. “Doing the Wrong Things Right” Site Investigations in Soft Soil

    Science.gov (United States)

    Jamilus, M. H.; Lim, A. J. M. S.; Azhar, A. T. S.; Azmi, M. A. M.

    2016-11-01

    Site investigation is a very important process by which geotechnical, geological and other relevant information which might affect the construction or performance of a civil engineering or building project is acquired. However, common practice in site investigations is not always in accordance to the standard that has been defined. Reliability on the information obtained depends upon several factors that involves correct procedures and competent workers and also supervision. Several examples on site investigation methods are discussed in this paper. Explanation on the difference between the site investigation methods used for real practices in the field and how it should be done are discussed in detail. Therefore, it is hoped that site investigation should always be uniquely planned and should be an interactive and flexible process of discovery and changes according to the condition of the soil.

  17. Relating Magnetic Parameters to Heavy Metal Concentrations and Environmental Factors at Formosa Mine Superfund Site, Douglas County, OR

    Science.gov (United States)

    Upton, T. L.

    2016-12-01

    Advances in the field of environmental magnetism have led to exciting new applications for this field. Magnetic minerals are ubiquitous in the environment and tend to have an affinity for heavy metals. Hence, it has been demonstrated that magnetic properties are often significantly related to concentrations of heavy metals and other pollutants. As a result, magnetic techniques have been used as proxy for determining hot spots of several types of pollution produced from a diversity of anthropogenic sources. Magnetic measurements are non-destructive and relatively inexpensive compared to geochemical analyses. The utility of environmental magnetic methods varies widely depending on biological, chemical and physical processes that create and transform soils and sediments. Applications in the direction of mapping heavy metals have been studied and shown to be quite useful in countries such as China and India but to date, little research has been done in the US. As such, there is need to expand the scope of research to a wider range of soil types and land uses, especially within the US. This study investigates the application of environmental magnetic techniques to mapping of heavy metal concentrations at the Formosa Mine Superfund Site, an abandoned mine about 25 miles southwest of Roseburg, OR. The soils and sediment at this site are derived from pyrite-rich bedrock which is weak in terms of magnetic susceptibility. Using hotspot analysis, correlation and cluster analyses, interactions between metals and magnetic parameters are investigated in relation to environmental factors such as proximity to seeps and adits. Preliminary results suggest significant correlation of magnetic susceptibility with certain heavy metals, signifying that magnetic methods may be useful in mapping heavy metal hotspots at this site. Further analysis examines the relation of various land use differences in magnetic signatures obtained throughout the Cow Creek watershed.

  18. 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.

  19. 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.

  20. Cooperative activation of cardiac transcription through myocardin bridging of paired MEF2 sites

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Courtney M. [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Hu, Jianxin [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Thomas, Reuben [Univ. of California, San Francisco, CA (United States). Gladstone Inst.; Gainous, T. Blair [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Celona, Barbara [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Sinha, Tanvi [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Dickel, Diane E. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Genomics Division; Heidt, Analeah B. [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Xu, Shan-Mei [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Bruneau, Benoit G. [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Univ. of California, San Francisco, CA (United States). Gladstone Inst.; Pollard, Katherine S. [Univ. of California, San Francisco, CA (United States). Gladstone Inst.; Pennacchio, Len A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Genomics Division; Black, Brian L. [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Univ. of California, San Francisco, CA (United States). Dept. of

    2017-03-28

    Enhancers frequently contain multiple binding sites for the same transcription factor. These homotypic binding sites often exhibit synergy, whereby the transcriptional output from two or more binding sites is greater than the sum of the contributions of the individual binding sites alone. Although this phenomenon is frequently observed, the mechanistic basis for homotypic binding site synergy is poorly understood. Here in this paper, we identify a bona fide cardiac-specific Prkaa2 enhancer that is synergistically activated by homotypic MEF2 binding sites. We show that two MEF2 sites in the enhancer function cooperatively due to bridging of the MEF2C-bound sites by the SAP domain-containing co-activator protein myocardin, and we show that paired sites buffer the enhancer from integration site-dependent effects on transcription in vivo. Paired MEF2 sites are prevalent in cardiac enhancers, suggesting that this might be a common mechanism underlying synergy in the control of cardiac gene expression in vivo.

  1. 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.

  2. 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

  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. Time-dependent analysis of incidence, risk factors and clinical significance of pneumothorax after percutaneous lung biopsy.

    Science.gov (United States)

    Lim, Woo Hyeon; Park, Chang Min; Yoon, Soon Ho; Lim, Hyun-Ju; Hwang, Eui Jin; Lee, Jong Hyuk; Goo, Jin Mo

    2018-03-01

    To evaluate the time-dependent incidence, risk factors and clinical significance of percutaneous lung biopsy (PLB)-related pneumothorax. From January 2012-November 2015, 3,251 patients underwent 3,354 cone-beam CT-guided PLBs for lung lesions. Cox, logistic and linear regression analyses were performed to identify time-dependent risk factors of PLB-related pneumothorax, risk factors of drainage catheter insertion and those of prolonged catheter placement, respectively. Pneumothorax occurred in 915/3,354 PLBs (27.3 %), with 230/915 (25.1 %) occurring during follow-ups. Risk factors for earlier occurrence of PLB-related pneumothorax include emphysema (HR=1.624), smaller target (HR=0.922), deeper location (HR=1.175) and longer puncture time (HR=1.036), while haemoptysis (HR=0.503) showed a protective effect against earlier development of pneumothorax. Seventy-five cases (8.2 %) underwent chest catheter placement. Mean duration of catheter placement was 3.2±2.0 days. Emphysema (odds ratio [OR]=2.400) and longer puncture time (OR=1.053) were assessed as significant risk factors for catheter insertion, and older age (parameter estimate=1.014) was a predictive factor for prolonged catheter placement. PLB-related pneumothorax occurred in 27.3 %, of which 25.1 % developed during follow-ups. Smaller target size, emphysema, deeply-located lesions were significant risk factors of PLB-related pneumothorax. Emphysema and older age were related to drainage catheter insertion and prolonged catheter placement, respectively. • One-fourth of percutaneous lung biopsy (PLB)-related pneumothorax occurs during follow-up. • Smaller, deeply-located target and emphysema lead to early occurrence of pneumothorax. • Emphysema is related to drainage catheter insertion for PLB-related pneumothorax. • Older age may lead to prolonged catheter placement for PLB-related pneumothorax. • Tailored management can be possible with time-dependent information of PLB-related pneumothorax.

  5. 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)

  6. 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.

  7. 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.

  8. 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

  9. Site selection factors for repositories of solid high-level and alpha-bearing wastes in geological formations

    Energy Technology Data Exchange (ETDEWEB)

    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 meters 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.

  10. Overweight/obesity and underweight are both risk factors for osteoporotic fractures at different sites in Japanese postmenopausal women.

    Science.gov (United States)

    Tanaka, S; Kuroda, T; Saito, M; Shiraki, M

    2013-01-01

    This cohort study of 1,614 postmenopausal Japanese women followed for 6.7 years showed that overweight/obesity and underweight are both risk factors for fractures at different sites. Fracture risk assessment may be improved if fracture sites are taken into account and BMI is categorized. The effect of body mass index (BMI) on fracture at a given level of bone mineral density (BMD) is controversial, since varying associations between BMI and fracture sites have been reported. A total of 1,614 postmenopausal Japanese women were followed for 6.7 years in a hospital-based cohort study. Endpoints included incident vertebral, femoral neck, and long-bone fractures. Rate ratios were estimated by Poisson regression models adjusted for age, diabetes mellitus, BMD, prior fracture, back pain, and treatment by estrogen. Over a mean follow-up period of 6.7 years, a total of 254 clinical and 335 morphometric vertebral fractures, 48 femoral neck fractures, and 159 long-bone fractures were observed. Incidence rates of vertebral fracture in underweight and normal weight women were significantly lower than overweight or obese women by 0.45 (95 % confidence interval: 0.32 to 0.63) and 0.61 (0.50 to 0.74), respectively, if BMD and other risk factors were adjusted, and by 0.66 (0.48 to 0.90) and 0.70 (0.58 to 0.84) if only BMD was not adjusted. Incidence rates of femoral neck and long-bone fractures in the underweight group were higher than the overweight/obese group by 2.15 (0.73 to 6.34) and 1.51 (0.82 to 2.77) and were similar between normal weight and overweight/obesity. Overweight/obesity and underweight are both risk factors for fractures at different sites. Fracture risk assessment may be improved if fracture sites are taken into account and BMI is categorized.

  11. Influence of region and site-specific factors on the degree of general validity of ecological and primary-energy-related assessments of biogas

    International Nuclear Information System (INIS)

    Dressler, Daniela

    2015-01-01

    As described in this publication, since the early 1990s numerous studies based on the life cycle assessment methodology have been dedicated to assessments of different kinds of bioenergy in comparison with fossil energy resources in terms of their energy balance and environmental impact. On reviewing the results of these studies one finds a strikingly wide range of variation. One major factor of influence on the results of life cycle assessments, besides methodological factors such as the choice of allocation method, is the representativeness of the data used. Thus, widely varying results are also obtained when balance calculations and assessments are performed on energy crops with due consideration to regional and site-specific factors. To address this problem the present study endeavoured to identify region and site-specific factors and assess them in terms of their influence on the life cycle assessment of the cultivation and conversion to biogas of different kinds of energy crops. For this purpose the following questions were explored: What influence do region, site and equipment-specific factors have on the results of ecological and primary-energy-related assessments; and how large are the differences in results between region and site-specific assessments on the one hand and assessments based on general assumptions on the other? It transpires that the results of region and site-specific assessments differ from one another in terms of both the assessment of energy cropping and the assessment of the entire process chain of biogas production and conversion to electricity.

  12. 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.

  13. Use of phytochrome-dependent reaction in evaluating the effect of space flight factors on the plant organism

    Science.gov (United States)

    Shteyne, B. A.; Nevzgodina, L. V.; Miller, A. T.

    1982-01-01

    The effects of space flight factors on lettuce seeds aboard the Kosmos-936 and Kosmos-1129 satellites for 20 days were studied. The phytochrome dependent (PD) reaction of light sensitive seeds was a sensitive criterion for evaluating the biological effects of space flight factors. The PD reaction of air dry lettuce seeds was suppressed after space flight, especially if the seeds were exposed to open space during the flight. Space flight affects the physiological activity of both phytochrome forms, and both the phi sub 730 dependent reactions of lettuce seeds were suppressed.

  14. Inhibition of fibroblast growth factor receptor 3-dependent lung adenocarcinoma with a human monoclonal antibody

    Directory of Open Access Journals (Sweden)

    Yongjun Yin

    2016-05-01

    Full Text Available Activating mutations in fibroblast growth factor receptor 3 (FGFR3 have been identified in multiple types of human cancer and in congenital birth defects. In human lung cancer, fibroblast growth factor 9 (FGF9, a high-affinity ligand for FGFR3, is overexpressed in 10% of primary resected non-small cell lung cancer (NSCLC specimens. Furthermore, in a mouse model where FGF9 can be induced in lung epithelial cells, epithelial proliferation and ensuing tumorigenesis is dependent on FGFR3. To develop new customized therapies for cancers that are dependent on FGFR3 activation, we have used this mouse model to evaluate a human monoclonal antibody (D11 with specificity for the extracellular ligand-binding domain of FGFR3, that recognizes both human and mouse forms of the receptor. Here, we show that D11 effectively inhibits signaling through FGFR3 in vitro, inhibits the growth of FGFR3-dependent FGF9-induced lung adenocarcinoma in mice, and reduces tumor-associated morbidity. Given the potency of FGF9 in this mouse model and the absolute requirement for signaling through FGFR3, this study validates the D11 antibody as a potentially useful and effective reagent for treating human cancers or other pathologies that are dependent on activation of FGFR3.

  15. The fitness landscapes of cis-acting binding sites in different promoter and environmental contexts.

    Directory of Open Access Journals (Sweden)

    Ryan K Shultzaberger

    2010-07-01

    Full Text Available The biophysical nature of the interaction between a transcription factor and its target sequences in vitro is sufficiently well understood to allow for the effects of DNA sequence alterations on affinity to be predicted. But even in relatively simple in vivo systems, the complexities of promoter organization and activity have made it difficult to predict how altering specific interactions between a transcription factor and DNA will affect promoter output. To better understand this, we measured the relative fitness of nearly all Escherichia coli sigma(70 -35 binding sites in different promoter and environmental contexts by competing four randomized -35 promoter libraries controlling the expression of the tetracycline resistance gene (tetagainst each other in increasing concentrations of drug. We sequenced populations after competition to determine the relative enrichment of each -35 sequence. We observed a consistent relationship between the frequency of recovery of each -35 binding site and its predicted affinity for sigma(70 that varied depending on the sequence context of the promoter and drug concentration. Overall the relative fitness of each promoter could be predicted by a simple thermodynamic model of transcriptional regulation, in which the rate of transcriptional initiation (and hence fitness is dependent upon the overall stability of the initiation complex, which in turn is dependent upon the energetic contributions of all sites within the complex. As implied by this model, a decrease in the free energy of association at one site could be compensated for by an increase in the binding energy at another to produce a similar output. Furthermore, these data show that a large and continuous range of transcriptional outputs can be accessed by merely changing the -35, suggesting that evolved or engineered mutations at this site could allow for subtle and precise control over gene expression.

  16. Síntomas depresivos como factor de riesgo de dependencia en adultos mayores Depressive symptoms as a risk factor for dependence in elderly people

    Directory of Open Access Journals (Sweden)

    José Alberto Ávila-Funes

    2007-10-01

    Full Text Available OBJETIVO: Determinar la relación entre síntomas depresivos y dependencia funcional. MATERIAL Y MÉTODOS: Estudio longitudinal con 1 880 adultos mayores evaluados en 2001 y 2003. Se determinaron los síntomas depresivos con una versión modificada de la Escala de Depresión del Centro de Estudios Epidemiológicos y la dependencia con las escalas de Lawton y Brody, y Katz. La dependencia implicó la asistencia y ayuda para realizar alguna de las actividades interrogadas. Los análisis multifactoriales probaron el nexo entre síntomas depresivos y desarrollo de dependencia. RESULTADOS: En 2001, 37.9% mostró síntomas depresivos. En 2003, 6.1 y 12.7% desarrollaron dependencia para al menos una de las actividades básicas (ABVD e instrumentales de la vida diaria (AIVD, respectivamente. En el análisis multivariado, los síntomas depresivos fueron factor de riesgo sólo para dependencia en las AIVD. CONCLUSIONES: Los síntomas depresivos favorecen el desarrollo de dependencia funcional. Es necesario su reconocimiento sistemático durante la evaluación clínica del adulto mayor.OBJECTIVE: To determine the relationship between depressive symptoms and dependence in activities of daily living. MATERIAL AND METHODS: Participants, aged 70 to 104 (n= 1 880, were evaluated twice (2001 and 2003. Depressive symptoms were established by a modified version of Center for Epidemiologic Studies Depression scale, whereas functional dependence was assessed with Lawton & Brody and Katz scales. Dependence implies the attendance and assistance of another person to accomplish the activity. Multivariate regression analyses were used to determine the effect of depressive symptoms on incident dependence. RESULTS: At baseline, 37.9% had depressive symptoms. After two years, 6.1 and 12.7% developed functional dependence for one or more ADL and IADL, respectively. Multivariate analyses showed that depressive symptoms were a risk factor to the development of functional

  17. 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

  18. 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

  19. Risk factor characteristics in carers who physically abuse or neglect their elderly dependants.

    Science.gov (United States)

    Reay, A M; Browne, K D

    2001-02-01

    This study investigates the prevalence of, and differences in, risk factor characteristics in a sample of two select populations of carers, one of which physically abused their elderly dependants and one of which neglected them. Nineteen carers (nine who had physically abused and 10 who had neglected their elderly relatives), who were referred to clinical psychology by either their general practitioner or their psychiatrist, were invited to take part in this study. A detailed history of risk factors was obtained, including history of alcohol dependency, type and history of mental ill health, history of maltreatment earlier in life, who they were caring for, how long they had been a carer and whether they felt isolated as a carer. Subjects were then given five assessments to determine whether there were any differences between the two groups. These were the Conflict Tactic Scale, Strain Scale, Beck Depression Inventory, Beck Anxiety Inventory and Cost of Care Index. An examination of the risk factors suggests that heavy alcohol consumption and past childhood abuse by fathers were likely to lead to physical abuse. Significantly higher conflict and depression scores were also present in the physical abuse group, while the neglect group had significantly higher anxiety scores. It is suggested that these findings should be incorporated into an assessment of future risk of abuse or neglect by the carer.

  20. [The contributing risk factors, prevention and treatment of functional dependence among the oldest-old and elderly subjects].

    Science.gov (United States)

    Liu, Dianrong; Tan, Jiping; Guo, Yuhe; Ye, Guanghua; Zhu, Linqi; Zhang, Jun; Li, Yinghao; Deng, Yucheng; Wang, Guichen; Wang, Luning

    2014-10-01

    To compare the risk factors on the functional dependence between the oldest-old and elderly veterans. A cross-sectional survey was conducted among veterans ( ≥ 60 years of age) lived in 44 veterans' communities in Beijing. The socio-demographic information and history of non-communicable chronic diseases were collected via face-to-face interviews, and the functional status was assessed by the 20-item version of the Activities of Daily Living Scale. The risk factors associated with increased hazard of the functional dependence in the oldest-old ( ≥ 80 years old) were cognitive impairment, extrapyramidal diseases, cerebral infarction, transient ischemic attack, sleep disorders, hypnotics, osteoarthrosis, hypertension and fall with the odds ratio (OR) of 1.241-2.962 (all P fall, cardiovascular diseases, osteoarthrosis and hearing loss were the risk factors for that in the elderly subjects (aged 60-79 years). The OR was 1.232-5.790 (all P risk of functional dependence in both the oldest-old and elderly people. Neuropsychiatric disorders are the leading causes contributed to the functional dependence among oldest-old and elderly population. Neurodegenerative diseases in the oldest-old, stroke and depression in elderly people should be the priorities in ameliorating disability. Healthy lifestyle and avocational activities could improve the functional status of the oldest-old and elderly population.

  1. Incidence and risk factors for surgical site infection after open reduction and internal fixation of tibial plateau fracture: A systematic review and meta-analysis.

    Science.gov (United States)

    Shao, Jiashen; Chang, Hengrui; Zhu, Yanbin; Chen, Wei; Zheng, Zhanle; Zhang, Huixin; Zhang, Yingze

    2017-05-01

    This study aimed to quantitatively summarize the risk factors associated with surgical site infection after open reduction and internal fixation of tibial plateau fracture. Medline, Embase, CNKI, Wanfang database and Cochrane central database were searched for relevant original studies from database inception to October 2016. Eligible studies had to meet quality assessment criteria according to the Newcastle-Ottawa Scale, and had to evaluate the risk factors for surgical site infection after open reduction and internal fixation of tibial plateau fracture. Stata 11.0 software was used for this meta-analysis. Eight studies involving 2214 cases of tibial plateau fracture treated by open reduction and internal fixation and 219 cases of surgical site infection were included in this meta-analysis. The following parameters were identified as significant risk factors for surgical site infection after open reduction and internal fixation of tibial plateau fracture (p operative time (OR 2.15; 95% CI 1.53-3.02), tobacco use (OR 2.13; 95% CI 1.13-3.99), and external fixation (OR 2.07; 95% CI 1.05-4.09). Other factors, including male sex, were not identified as risk factors for surgical site infection. Patients with the abovementioned medical conditions are at risk of surgical site infection after open reduction and internal fixation of tibial plateau fracture. Surgeons should be cognizant of these risks and give relevant preoperative advice. Copyright © 2017. Published by Elsevier Ltd.

  2. Doubly Nonparametric Sparse Nonnegative Matrix Factorization Based on Dependent Indian Buffet Processes.

    Science.gov (United States)

    Xuan, Junyu; Lu, Jie; Zhang, Guangquan; Xu, Richard Yi Da; Luo, Xiangfeng

    2018-05-01

    Sparse nonnegative matrix factorization (SNMF) aims to factorize a data matrix into two optimized nonnegative sparse factor matrices, which could benefit many tasks, such as document-word co-clustering. However, the traditional SNMF typically assumes the number of latent factors (i.e., dimensionality of the factor matrices) to be fixed. This assumption makes it inflexible in practice. In this paper, we propose a doubly sparse nonparametric NMF framework to mitigate this issue by using dependent Indian buffet processes (dIBP). We apply a correlation function for the generation of two stick weights associated with each column pair of factor matrices while still maintaining their respective marginal distribution specified by IBP. As a consequence, the generation of two factor matrices will be columnwise correlated. Under this framework, two classes of correlation function are proposed: 1) using bivariate Beta distribution and 2) using Copula function. Compared with the single IBP-based NMF, this paper jointly makes two factor matrices nonparametric and sparse, which could be applied to broader scenarios, such as co-clustering. This paper is seen to be much more flexible than Gaussian process-based and hierarchial Beta process-based dIBPs in terms of allowing the two corresponding binary matrix columns to have greater variations in their nonzero entries. Our experiments on synthetic data show the merits of this paper compared with the state-of-the-art models in respect of factorization efficiency, sparsity, and flexibility. Experiments on real-world data sets demonstrate the efficiency of this paper in document-word co-clustering tasks.

  3. Stimulation of Pol III-dependent 5S rRNA and U6 snRNA gene expression by AP-1 transcription factors.

    Science.gov (United States)

    Ahuja, Richa; Kumar, Vijay

    2017-07-01

    RNA polymerase III transcribes structurally diverse group of essential noncoding RNAs including 5S ribosomal RNA (5SrRNA) and U6 snRNA. These noncoding RNAs are involved in RNA processing and ribosome biogenesis, thus, coupling Pol III activity to the rate of protein synthesis, cell growth, and proliferation. Even though a few Pol II-associated transcription factors have been reported to participate in Pol III-dependent transcription, its activation by activator protein 1 (AP-1) factors, c-Fos and c-Jun, has remained unexplored. Here, we show that c-Fos and c-Jun bind to specific sites in the regulatory regions of 5S rRNA (type I) and U6 snRNA (type III) gene promoters and stimulate their transcription. Our chromatin immunoprecipitation studies suggested that endogenous AP-1 factors bind to their cognate promoter elements during the G1/S transition of cell cycle apparently synchronous with Pol III transcriptional activity. Furthermore, the interaction of c-Jun with histone acetyltransferase p300 promoted the recruitment of p300/CBP complex on the promoters and facilitated the occupancy of Pol III transcriptional machinery via histone acetylation and chromatin remodeling. The findings of our study, together, suggest that AP-1 factors are novel regulators of Pol III-driven 5S rRNA and U6 snRNA expression with a potential role in cell proliferation. © 2017 Federation of European Biochemical Societies.

  4. Oxygen-sensitive regulation and neuroprotective effects of growth hormone-dependent growth factors during early postnatal development.

    Science.gov (United States)

    Jung, Susan; Boie, Gudrun; Doerr, Helmuth-Guenther; Trollmann, Regina

    2017-04-01

    Perinatal hypoxia severely disrupts metabolic and somatotrophic development, as well as cerebral maturational programs. Hypoxia-inducible transcription factors (HIFs) represent the most important endogenous adaptive mechanisms to hypoxia, activating a broad spectrum of growth factors that contribute to cell survival and energy homeostasis. To analyze effects of systemic hypoxia and growth hormone (GH) therapy (rhGH) on HIF-dependent growth factors during early postnatal development, we compared protein (using ELISA) and mRNA (using quantitative RT PCR) levels of growth factors in plasma and brain between normoxic and hypoxic mice (8% O 2 , 6 h; postnatal day 7 , P7) at P14. Exposure to hypoxia led to reduced body weight ( P controls and was associated with significantly reduced plasma levels of mouse GH ( P controls. In addition, rhGH treatment increased cerebral IGF-1, IGF-2, IGFBP-2, and erythropoietin mRNA levels, resulting in significantly reduced apoptotic cell death in the hypoxic, developing mouse brain. These data indicate that rhGH may functionally restore hypoxia-induced systemic dysregulation of the GH/IGF-1 axis and induce upregulation of neuroprotective, HIF-dependent growth factors in the hypoxic developing brain. Copyright © 2017 the American Physiological Society.

  5. Atrial natriuretic factor binding sites in experimental congestive heart failure

    International Nuclear Information System (INIS)

    Bianchi, C.; Thibault, G.; Wrobel-Konrad, E.; De Lean, A.; Genest, J.; Cantin, M.

    1989-01-01

    A quantitative in vitro autoradiographic study was performed on the aorta, renal glomeruli, and adrenal cortex of cardiomyopathic hamsters in various stages of heart failure and correlated, in some instances, with in vivo autoradiography. The results indicate virtually no correlation between the degree of congestive heart failure and the density of 125I-labeled atrial natriuretic factor [(Ser99, Tyr126)ANF] binding sites (Bmax) in the tissues examined. Whereas the Bmax was increased in the thoracic aorta in moderate and severe heart failure, there were no significant changes in the zona glomerulosa. The renal glomeruli Bmax was lower in mild and moderate heart failure compared with control and severe heart failure. The proportion of ANF B- and C-receptors was also evaluated in sections of the aorta, adrenal, and kidney of control and cardiomyopathic hamsters with severe heart failure. (Arg102, Cys121)ANF [des-(Gln113, Ser114, Gly115, Leu116, Gly117) NH2] (C-ANF) at 10(-6) M displaced approximately 505 of (Ser99, Tyr126)125I-ANF bound in the aorta and renal glomeruli and approximately 20% in the adrenal zona glomerulosa in both series of animals. These results suggest that ANF may exert a buffering effect on the vasoconstriction of heart failure and to a certain extent may inhibit aldosterone secretion. The impairment of renal sodium excretion does not appear to be related to glomerular ANF binding sites at any stage of the disease

  6. Shaft siting decision

    International Nuclear Information System (INIS)

    1987-08-01

    This study identifies and establishes relative guidelines to be used for siting of repository shafts. Weights were determined for the significant factors that impact the selection of shaft locations for a nuclear waste repository in salt. The study identified a total of 45 factors. A panel of experienced mining people utilized the Kepner-Tregoe (K-T) Decision Analysis Process to perform a structured evaluation of each significant shaft siting factor. The evaluation determined that 22 of the factors were absolute constraints and that the other 23 factors were desirable characteristics. The group established the relative weights for each of the 23 desirable characteristics by using a paired comparison method. 8 refs., 2 figs., 5 tabs

  7. General equation for the differential pathlength factor of the frontal human head depending on wavelength and age.

    Science.gov (United States)

    Scholkmann, Felix; Wolf, Martin

    2013-10-01

    Continuous-wave near-infrared spectroscopy and near-infrared imaging enable the measurement of relative concentration changes in oxy- and deoxyhemoglobin and thus hemodynamics and oxygenation. The accuracy of determined changes depends mainly on the modeling of the light transport through the probed tissue. Due to the highly scattering nature of tissue, the light path is longer than the source-detector separation (d). This is incorporated in modeling by multiplying d by a differential pathlength factor (DPF) which depends on several factors such as wavelength, age of the subject, and type of tissue. In the present work, we derive a general DPF equation for the frontal human head, incorporating dependency on wavelength and age, based on published data. We validated the equation using different data sets of experimentally determined DPFs from six independent studies.

  8. 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)

  9. Observed and simulated temperature dependence of the liquid water path of low clouds

    Energy Technology Data Exchange (ETDEWEB)

    Del Genio, A.D.; Wolf, A.B. [NASA Goddard Institute for Space Studies, New York, NY (United States)

    1996-04-01

    Data being acquired at the Atmospheric Radiation Measurement (ARM) Southern great Plains (SGP) Cloud and Radiation Testbed (CART) site can be used to examine the factors determining the temperature dependence of cloud optical thickness. We focus on cloud liquid water and physical thickness variations which can be derived from existing ARM measurements.

  10. 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...

  11. Identification of Zika Virus and Dengue Virus Dependency Factors using Functional Genomics

    Directory of Open Access Journals (Sweden)

    George Savidis

    2016-06-01

    Full Text Available The flaviviruses dengue virus (DENV and Zika virus (ZIKV are severe health threats with rapidly expanding ranges. To identify the host cell dependencies of DENV and ZIKV, we completed orthologous functional genomic screens using RNAi and CRISPR/Cas9 approaches. The screens recovered the ZIKV entry factor AXL as well as multiple host factors involved in endocytosis (RAB5C and RABGEF, heparin sulfation (NDST1 and EXT1, and transmembrane protein processing and maturation, including the endoplasmic reticulum membrane complex (EMC. We find that both flaviviruses require the EMC for their early stages of infection. Together, these studies generate a high-confidence, systems-wide view of human-flavivirus interactions and provide insights into the role of the EMC in flavivirus replication.

  12. 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.

  13. 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

  14. Cytotoxic T lymphocyte-dependent tumor growth inhibition by a vascular endothelial growth factor-superantigen conjugate

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Qingwen [Shanghai Chest Hospital, Shanghai 200433 (China); State Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200433 (China); Jiang, Songmin [State Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200433 (China); Han, Baohui [Shanghai Chest Hospital, Shanghai 200433 (China); Sun, Tongwen [Wuhan Junyu Innovation Pharmaceuticals, Inc., Wuhan 430079 (China); Li, Zhengnan; Zhao, Lina; Gao, Qiang [College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457 (China); Sun, Jialin, E-mail: jialin_sun@126.com [Wuhan Junyu Innovation Pharmaceuticals, Inc., Wuhan 430079 (China)

    2012-11-02

    Highlights: Black-Right-Pointing-Pointer We construct and purify a fusion protein VEGF-SEA. Black-Right-Pointing-Pointer VEGF-SEA strongly repressed the growth of murine solid sarcoma 180 (S180) tumors. Black-Right-Pointing-Pointer T cells driven by VEGF-SEA were accumulated around tumor cells bearing VEGFR by mice image model. Black-Right-Pointing-Pointer VEGF-SEA can serve as a tumor targeting agent and sequester CTLs into the tumor site. Black-Right-Pointing-Pointer The induced CTLs could release the cytokines, perforins and granzyme B to kill the tumor cells. -- Abstract: T cells are major lymphocytes in the blood and passengers across the tumor vasculature. If these T cells are retained in the tumor site, a therapeutic potential will be gained by turning them into tumor-reactive cytotoxic T lymphocytes (CTLs). A fusion protein composed of human vascular endothelial growth factor (VEGF) and staphylococcal enterotoxin A (SEA) with a D227A mutation strongly repressed the growth of murine solid sarcoma 180 (S180) tumors (control versus VEGF-SEA treated with 15 {mu}g, mean tumor weight: 1.128 g versus 0.252 g, difference = 0.876 g). CD4{sup +} and CD8{sup +} T cells driven by VEGF-SEA were accumulated around VEGFR expressing tumor cells and the induced CTLs could release the tumoricidal cytokines, such as interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). Meanwhile, intratumoral CTLs secreted cytolytic pore-forming perforin and granzyme B proteins around tumor cells, leading to the death of tumor cells. The labeled fusion proteins were gradually targeted to the tumor site in an imaging mice model. These results show that VEGF-SEA can serve as a tumor targeting agent and sequester active infiltrating CTLs into the tumor site to kill tumor cells, and could therefore be a potential therapeutical drug for a variety of cancers.

  15. 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.

  16. The land use as a factor in the nuclear power plant site selection; Upotreba zemljista kao faktor u izboru lokacije za nuklearna postrojenja

    Energy Technology Data Exchange (ETDEWEB)

    Marsicanin, B [Institut za Nuklearne Nauke Boris Kidric, Belgrade (Yugoslavia)

    1981-07-01

    In this paper the methodology for the site comparison, taking into account the land use in the vicinity of a potential nuclear site is presented. Due to the established risk values and cost/benefit factors a quantitative comparison could be made. This, also makes possible a approach, common for the most of relevant factors, in order to make the optimization process practical. (author)

  17. Ebola virus RNA editing depends on the primary editing site sequence and an upstream secondary structure.

    Directory of Open Access Journals (Sweden)

    Masfique Mehedi

    Full Text Available Ebolavirus (EBOV, the causative agent of a severe hemorrhagic fever and a biosafety level 4 pathogen, increases its genome coding capacity by producing multiple transcripts encoding for structural and nonstructural glycoproteins from a single gene. This is achieved through RNA editing, during which non-template adenosine residues are incorporated into the EBOV mRNAs at an editing site encoding for 7 adenosine residues. However, the mechanism of EBOV RNA editing is currently not understood. In this study, we report for the first time that minigenomes containing the glycoprotein gene editing site can undergo RNA editing, thereby eliminating the requirement for a biosafety level 4 laboratory to study EBOV RNA editing. Using a newly developed dual-reporter minigenome, we have characterized the mechanism of EBOV RNA editing, and have identified cis-acting sequences that are required for editing, located between 9 nt upstream and 9 nt downstream of the editing site. Moreover, we show that a secondary structure in the upstream cis-acting sequence plays an important role in RNA editing. EBOV RNA editing is glycoprotein gene-specific, as a stretch encoding for 7 adenosine residues located in the viral polymerase gene did not serve as an editing site, most likely due to an absence of the necessary cis-acting sequences. Finally, the EBOV protein VP30 was identified as a trans-acting factor for RNA editing, constituting a novel function for this protein. Overall, our results provide novel insights into the RNA editing mechanism of EBOV, further understanding of which might result in novel intervention strategies against this viral pathogen.

  18. Ebola virus RNA editing depends on the primary editing site sequence and an upstream secondary structure.

    Science.gov (United States)

    Mehedi, Masfique; Hoenen, Thomas; Robertson, Shelly; Ricklefs, Stacy; Dolan, Michael A; Taylor, Travis; Falzarano, Darryl; Ebihara, Hideki; Porcella, Stephen F; Feldmann, Heinz

    2013-01-01

    Ebolavirus (EBOV), the causative agent of a severe hemorrhagic fever and a biosafety level 4 pathogen, increases its genome coding capacity by producing multiple transcripts encoding for structural and nonstructural glycoproteins from a single gene. This is achieved through RNA editing, during which non-template adenosine residues are incorporated into the EBOV mRNAs at an editing site encoding for 7 adenosine residues. However, the mechanism of EBOV RNA editing is currently not understood. In this study, we report for the first time that minigenomes containing the glycoprotein gene editing site can undergo RNA editing, thereby eliminating the requirement for a biosafety level 4 laboratory to study EBOV RNA editing. Using a newly developed dual-reporter minigenome, we have characterized the mechanism of EBOV RNA editing, and have identified cis-acting sequences that are required for editing, located between 9 nt upstream and 9 nt downstream of the editing site. Moreover, we show that a secondary structure in the upstream cis-acting sequence plays an important role in RNA editing. EBOV RNA editing is glycoprotein gene-specific, as a stretch encoding for 7 adenosine residues located in the viral polymerase gene did not serve as an editing site, most likely due to an absence of the necessary cis-acting sequences. Finally, the EBOV protein VP30 was identified as a trans-acting factor for RNA editing, constituting a novel function for this protein. Overall, our results provide novel insights into the RNA editing mechanism of EBOV, further understanding of which might result in novel intervention strategies against this viral pathogen.

  19. Site selection for nuclear power plants

    International Nuclear Information System (INIS)

    Ehjchkholz, D.

    1980-01-01

    Problem of NPP site selection in the USA including engineering factors, radiation and environmental protection factors is stated in detail. Floating and underground sites are considered especially. The attention in paid to waste storage and risk criterium in siting [ru

  20. 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.

  1. Targeted Deletion of a Plasmodium Site-2 Protease Impairs Life Cycle Progression in the Mammalian Host

    OpenAIRE

    Koussis, K.; Goulielmaki, E.; Chalari, A.; Withers-Martinez, C.; Siden-Kiamos, I.; Matuschewski, K.; Loukeris, T.

    2017-01-01

    Site-2 proteases (S2P) belong to the M50 family of metalloproteases, which typically perform essential roles by mediating activation of membrane?bound transcription factors through regulated intramembrane proteolysis (RIP). Protease-dependent liberation of dormant transcription factors triggers diverse cellular responses, such as sterol regulation, Notch signalling and the unfolded protein response. Plasmodium parasites rely on regulated proteolysis for controlling essential pathways througho...

  2. Development of site-specific soil cleanup criteria: New Brunswick Laboratory, New Jersey site

    Energy Technology Data Exchange (ETDEWEB)

    Veluri, V.R.; Moe, H.J.; Robinet, M.J.; Wynveen, R.A.

    1983-03-01

    The potential human exposure which results from the residual soil radioactivity at a decommissioned site is a prime concern during D and D projects. To estimate this exposure, a pathway analysis approach is often used to arrive at the residual soil radioactivity criteria. The development of such a criteria for the decommissioning of the New Brunswick Laboratory, New Jersey site is discussed. Contamination on this site was spotty and located in small soil pockets spread throughout the site area. Less than 1% of the relevant site area was contaminated. The major contaminants encountered at the site were /sup 239/Pu, /sup 241/Am, normal and natural uranium, and natural thorium. During the development of the pathway analysis to determine the site cleanup criteria, corrections for the inhomogeneity of the contamination were made. These correction factors and their effect upon the relevant pathway parameters are presented. Major pathways by which radioactive material may reach an individual are identified and patterns of use are specified (scenario). Each pathway is modeled to estimate the transfer parameters along the given pathway, such as soil to air to man, etc. The transfer parameters are then combined with dose rate conversion factors (ICRP 30 methodology) to obtain soil concentration to dose rate conversion factors (pCi/g/mrem/yr). For an appropriate choice of annual dose equivalent rate, one can then arrive at a value for the residual soil concentration. Pathway modeling, transfer parameters, and dose rate factors for the three major pathways; inhalation, ingestion and external exposure, which are important for the NBL site, are discussed.

  3. Distribution of basic fibroblast growth factor binding sites in various tissue membrane preparations from adult guinea pig

    International Nuclear Information System (INIS)

    Ledoux, D.; Mereau, A.; Dauchel, M.C.; Barritault, D.; Courty, J.

    1989-01-01

    In order to localize a rich source of basic FGF receptor, we examined the distribution of basic FGF binding sites in brain, stomach, lung, spleen, kidney, liver and intestine membrane preparations from adult guinea pig. Comparative binding studies using iodinated basic FGF showed that a specific binding was detected in all the membrane preparations tested. Scatchard plots from iodinated basic FGF competition experiment with native basic FGF in various membrane preparations, suggested the presence of one class of binding sites in some tissues such as liver, kidney, spleen, lung, stomach, and intestine with an apparent dissociation constant (appKD) value ranging from 4 to 7.5 nM and the existence of a second class of higher affinity sites in brain membranes with appKD value of 15 pM. Characterization of these basic FGF high affinity interaction sites was performed using a cross-linking reagent. These results show for the first time that specific interaction sites for basic FGF are widely distributed, suggesting that this growth factor might play a role in the physiological functions of a number of adult organs

  4. Trust and Product/Sellers Reviews as Factors Influencing Online Product Comparison Sites Usage by Young Consumers

    Directory of Open Access Journals (Sweden)

    Radoslaw Macik

    2016-06-01

    Full Text Available Paper describes young consumers’ behaviour connected with online product comparison sites usage as an example of online decision shopping aids. Authors’ main goal is to check whether or not such factors as: previous experience in such sites usage, personal innovativeness in domain of information technology – PIIT, and particularly cognitive trust (in several subdimensions, as well as affective trust toward online product comparison site, influence purchase intention via mentioned sites (acting as intermediaries in online sales channel, and anticipated satisfaction from choice made by consumer. Also indirect influence of users’ opinions about product and sellers on mentioned constructs has been researched. Study on effective sample of 456 young consumers with data collected through CAWI questionnaire confirmed reliability and validity of measurement scales. Path model estimated via PLS-SEM confirmed most hypotheses settled, particularly confirming strong positive relationships between cognitive trust (mostly in competence on affective trust, and later on purchase intention and choice satisfaction. Product and sellers reviews were partially mediating some of those relationships.

  5. [Family factors associated with co-dependency in nurses at a hospital in Cancun, Quintana Roo, México].

    Science.gov (United States)

    Ramírez-Amaro, Margarita; Martínez-Torres, Jorge; Ureña Bogarín, Enrique Leobardo

    2014-05-01

    Identifying family factors associated with the presence of co-dependency in nurses of a regional hospital in Cancún, Quintana Roo, Mexico. Cross-sectional, comparative study. City of Cancun (México). A random sample of 200nurses who met the inclusion criteria (having a partner for over a year, to be at work on the day of the interview), and who gave informed consent, completed three questionnaires during different shifts. Age, educational level, socioeconomic status, type of family structure, life cycle stage, co-dependency and family functioning. A total of 200nurses, with mean age of 36±8years, took part. The most common socioeconomic status was high (48%), and 47.5% had graduate studies. A co-dependency level of 20.5% (95%CI: 15-26.5) was found. Family factors associated with the presence of co-dependency were; family dysfunction, prevalence ratio (PR)=9.62 (95%CI: 3.47-27.3), stage of independence, PR=3.41 (95%CI: 1.44-7.86), single parent, PR=6.35 (95%CI: 2.41-16.68), and time with partner less than 5 years, PR=3.41 (95%CI: 1.54-7.85). It was found that family dysfunction and being a single parent were significantly associated with co-dependency in hospital nurses, therefore, on being able to identify these factors, family physicians can improve their dynamics and functioning by family study, and improving effective communication with nursing staff and their families. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  6. 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)

  7. General siting study 95. Siting of a deep repository for spent nuclear fuel

    International Nuclear Information System (INIS)

    1995-10-01

    General Siting Study 95 is a detailed description of the work carried out to put the siting of a deep repository in a national and regional context. The report is based on SKB's siting factors, which have been applied on a national scale. Different factors of importance or of possible importance for the long-term radiological safety, technology, land and environment as well as society are described and evaluated. This report is the overall description on general siting studies which the government considered that SKB should report in connection with the RD and D Programme 95. 121 refs, 40 figs

  8. General siting study 95. Siting of a deep repository for spent nuclear fuel

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-10-01

    General Siting Study 95 is a detailed description of the work carried out to put the siting of a deep repository in a national and regional context. The report is based on SKB`s siting factors, which have been applied on a national scale. Different factors of importance or of possible importance for the long-term radiological safety, technology, land and environment as well as society are described and evaluated. This report is the overall description on general siting studies which the government considered that SKB should report in connection with the RD and D Programme 95. 121 refs, 40 figs.

  9. Robust Replication Control Is Generated by Temporal Gaps between Licensing and Firing Phases and Depends on Degradation of Firing Factor Sld2

    Directory of Open Access Journals (Sweden)

    Karl-Uwe Reusswig

    2016-10-01

    Full Text Available Temporal separation of DNA replication initiation into licensing and firing phases ensures the precise duplication of the genome during each cell cycle. Cyclin-dependent kinase (CDK is known to generate this separation by activating firing factors and at the same time inhibiting licensing factors but may not be sufficient to ensure robust separation at transitions between both phases. Here, we show that a temporal gap separates the inactivation of firing factors from the re-activation of licensing factors during mitosis in budding yeast. We find that gap size critically depends on phosphorylation-dependent degradation of the firing factor Sld2 mediated by CDK, DDK, Mck1, and Cdc5 kinases and the ubiquitin-ligases Dma1/2. Stable mutants of Sld2 minimize the gap and cause increased genome instability in an origin-dependent manner when combined with deregulation of other replication regulators or checkpoint mechanisms. Robust separation of licensing and firing phases therefore appears indispensable to safeguard genome stability.

  10. DNA Binding Drugs Targeting the Regulatory DNA Binding Site of the ETS Domain Family Transcription Factor Associated With Human Breast Cancer

    National Research Council Canada - National Science Library

    Wang, Yong-Dong

    1999-01-01

    .... The key approach is to prevent the binding of two transcription factors, ESX and AP-2, to the consensus DNA binding sites contained within the Her2/neu promoter resulting in inhibition of transcription factor function...

  11. Dopant-site-dependent scattering by dislocations in epitaxial films of perovskite semiconductor BaSnO{sub 3}

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Useong; Park, Chulkwon; Kim, Rokyeon; Mun, Hyo Sik; Kim, Hoon Min; Kim, Namwook; Yu, Jaejun; Char, Kookrin, E-mail: kchar@phya.snu.ac.kr [Center for Strongly Correlated Materials Research, Department of Physics and Astronomy, Seoul National University, Seoul 151-747 (Korea, Republic of); Ha, Taewoo; Kim, Jae Hoon [Department of Physics, Yonsei University, Seoul 120-749 (Korea, Republic of); Kim, Hyung Joon; Kim, Tai Hoon; Kim, Kee Hoon [Center for Novel States of Complex Materials Research, Department of Physics and Astronomy, Seoul National University, Seoul 151-747 (Korea, Republic of)

    2014-05-01

    We studied the conduction mechanism in Sb-doped BaSnO{sub 3} epitaxial films, and compared its behavior with that of the mechanism of its counterpart, La-doped BaSnO{sub 3}. We found that the electron mobility in BaSnO{sub 3} 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 BaSnO{sub 3} 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 BaSnO{sub 3} 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.

  12. 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.

  13. Deep level observation in InP by temperature dependence of the van der Pauw`s symmetry factor

    Energy Technology Data Exchange (ETDEWEB)

    Somogyi, K. [Hungarian Academy of Sciences, Budapest (Hungary). Research Inst. for Technical Physics

    1996-12-31

    One of the most convenient methods of the basic characterization of the semiconductors is the Hall effect measurement by van der Pauw`s geometry. As a by-product, the symmetry factor and a function of the symmetry factor is calculated. It is supposed that temperature dependent changes in the value of the symmetry factor indicate inhomogeneities of the sample, since this factor describes an electrical symmetry of the sample, not simply a geometrical one. Otherwise this factor is not assumed as an important information. In this work the author wishes to demonstrate that this factor can indicate quite important properties of the sample.

  14. Factors Related to Depressive Symptoms in Mothers of Technology-Dependent Children.

    Science.gov (United States)

    Toly, Valerie Boebel; Musil, Carol M

    2015-07-01

    Mothers caring for technology-dependent children at home often suffer clinically significant and unrecognized depressive symptoms. The study aim was to determine factors related to elevated depressive symptoms and provide information to target interventions that assists mothers in self-management of their mental health. Secondary data analysis from a descriptive, correlational study of 75 mothers was performed. Hierarchical multiple regression analysis results indicate that younger, unpartnered mothers with lower normalization efforts and personal resourcefulness, and less care hours, had increased depressive symptoms. The importance of personal resourcefulness and the potential for a resourcefulness training intervention to reduce depressive symptoms are discussed.

  15. Time-dependent tumour repopulation factors in linear-quadratic equations

    International Nuclear Information System (INIS)

    Dale, R.G.

    1989-01-01

    Tumour proliferation effects can be tentatively quantified in the linear-quadratic (LQ) method by the incorporation of a time-dependent factor, the magnitude of which is related both to the value of α in the tumour α/β ratio, and to the tumour doubling time. The method, the principle of which has been suggested by a numbre of other workers for use in fractionated therapy, is here applied to both fractionated and protracted radiotherapy treatments, and examples of its uses are given. By assuming that repopulation of late-responding tissues is significant during normal treatment strategies in terms of the behaviour of the Extrapolated Response Dose (ERD). Although the numerical credibility of the analysis used here depends on the reliability of the LQ model, and on the assumption that the rate of repopulation is constant throughout treatment, the predictions are consistent with other lines of reasoning which point to the advantages of accelerated hyperfractionation. In particular, it is demonstrated that accelerated fractionation represents a relatively 'foregiving' treatment which enables tumours of a variety of sensitivities and clonogenic growth rates to be treated moderately successfully, even though the critical cellular parameters may not be known in individual cases. The analysis also suggests that tumours which combine low intrinsic sensitivity with a very short doubling time might be bettter controlled by low dose-rate continuous therapy than by almost any form of accelerated hyperfractionation. (author). 24 refs.; 5 figs

  16. Computational identification of developmental enhancers:conservation and function of transcription factor binding-site clustersin drosophila melanogaster and drosophila psedoobscura

    Energy Technology Data Exchange (ETDEWEB)

    Berman, Benjamin P.; Pfeiffer, Barret D.; Laverty, Todd R.; Salzberg, Steven L.; Rubin, Gerald M.; Eisen, Michael B.; Celniker, SusanE.

    2004-08-06

    The identification of sequences that control transcription in metazoans is a major goal of genome analysis. In a previous study, we demonstrated that searching for clusters of predicted transcription factor binding sites could discover active regulatory sequences, and identified 37 regions of the Drosophila melanogaster genome with high densities of predicted binding sites for five transcription factors involved in anterior-posterior embryonic patterning. Nine of these clusters overlapped known enhancers. Here, we report the results of in vivo functional analysis of 27 remaining clusters. We generated transgenic flies carrying each cluster attached to a basal promoter and reporter gene, and assayed embryos for reporter gene expression. Six clusters are enhancers of adjacent genes: giant, fushi tarazu, odd-skipped, nubbin, squeeze and pdm2; three drive expression in patterns unrelated to those of neighboring genes; the remaining 18 do not appear to have enhancer activity. We used the Drosophila pseudoobscura genome to compare patterns of evolution in and around the 15 positive and 18 false-positive predictions. Although conservation of primary sequence cannot distinguish true from false positives, conservation of binding-site clustering accurately discriminates functional binding-site clusters from those with no function. We incorporated conservation of binding-site clustering into a new genome-wide enhancer screen, and predict several hundred new regulatory sequences, including 85 adjacent to genes with embryonic patterns. Measuring conservation of sequence features closely linked to function--such as binding-site clustering--makes better use of comparative sequence data than commonly used methods that examine only sequence identity.

  17. Procedures for evaluation of vibratory ground motions of soil deposits at nuclear power plant sites

    International Nuclear Information System (INIS)

    1975-06-01

    According to USNRC requirements set forth in Appendix A, 10 CFR, Part 100, vibratory ground motion criteria for a nuclear plant must be based on local soil conditions, as well as on the seismicity, geology, and tectonics of the region. This report describes how such criteria can be developed by applying the latest technology associated with analytical predictions of site-dependent ground motions and with the use of composite spectra obtained from the current library of strong motion records. Recommended procedures for defining vibratory ground motion criteria contain the following steps: (1) geologic and seismologic studies; (2) site soils investigations; (3) site response sensitivity studies; (4) evaluation of local site response characteristics; (5) selection of site-matched records; and (6) appraisal and selection of seismic input criteria. An in-depth discussion of the engineering characteristics of earthquake ground motions including parameters used to characterize earthquakes and strong motion records, geologic factors that influence ground shaking, the current strong motion data base, and case histories of the effects of past earthquake events is presented. Next, geotechnical investigations of the seismologic, geologic, and site soil conditions required to develop vibratory motion criteria are briefly summarized. The current technology for establishing vibratory ground motion criteria at nuclear plant sites, including site-independent and site-dependent procedures that use data from strong motion records and from soil response analyses is described. (auth)

  18. [Affective dependency].

    Science.gov (United States)

    Scantamburlo, G; Pitchot, W; Ansseau, M

    2013-01-01

    Affective dependency is characterized by emotional distress (insecure attachment) and dependency to another person with a low self-esteem and reassurance need. The paper proposes a reflection on the definition of emotional dependency and the confusion caused by various denominations. Overprotective and authoritarian parenting, cultural and socio-environmental factors may contribute to the development of dependent personality. Psychological epigenetic factors, such as early socio-emotional trauma could on neuronal circuits in prefronto-limbic regions that are essential for emotional behaviour.We also focus on the interrelations between dependent personality, domestic violence and addictions. The objective for the clinician is to propose a restoration of self-esteem and therapeutic strategies focused on autonomy.

  19. 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 ...

  20. Risk Factors and Predictive Model Development of Thirty-Day Post-Operative Surgical Site Infection in the Veterans Administration Surgical Population.

    Science.gov (United States)

    Li, Xinli; Nylander, William; Smith, Tracy; Han, Soonhee; Gunnar, William

    2018-04-01

    Surgical site infection (SSI) complicates approximately 2% of surgeries in the Veterans Affairs (VA) hospitals. Surgical site infections are responsible for increased morbidity, length of hospital stay, cost, and mortality. Surgical site infection can be minimized by modifying risk factors. In this study, we identified risk factors and developed accurate predictive surgical specialty-specific SSI risk prediction models for the Veterans Health Administration (VHA) surgery population. In a retrospective observation study, surgical patients who underwent surgery from October 2013 to September 2016 from 136 VA hospitals were included. The Veteran Affairs Surgical Quality Improvement Program (VASQIP) database was used for the pre-operative demographic and clinical characteristics, intra-operative characteristics, and 30-day post-operative outcomes. The study population represents 11 surgical specialties: neurosurgery, urology, podiatry, otolaryngology, general, orthopedic, plastic, thoracic, vascular, cardiac coronary artery bypass graft (CABG), and cardiac valve/other surgery. Multivariable logistic regression models were developed for the 30-day post-operative SSIs. Among 354,528 surgical procedures, 6,538 (1.8%) had SSIs within 30 days. Surgical site infection rates varied among surgical specialty (0.7%-3.0%). Surgical site infection rates were higher in emergency procedures, procedures with long operative duration, greater complexity, and higher relative value units. Other factors associated with increased SSI risk were high level of American Society of Anesthesiologists (ASA) classification (level 4 and 5), dyspnea, open wound/infection, wound classification, ascites, bleeding disorder, chemotherapy, smoking, history of severe chronic obstructive pulmonary disease (COPD), radiotherapy, steroid use for chronic conditions, and weight loss. Each surgical specialty had a distinct combination of risk factors. Accurate SSI risk-predictive surgery specialty

  1. 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/.

  2. Effects of Place Identity, Place Dependence, and Experience-Use History on Perceptions of Recreation Impacts in a Natural Setting

    Science.gov (United States)

    White, Dave D.; Virden, Randy J.; van Riper, Carena J.

    2008-10-01

    It is generally accepted that recreation use in natural environments results in some degree of negative social and environmental impact. Environmental managers are tasked with mitigating the impact while providing beneficial recreation opportunities. Research on the factors that influence visitors’ perceptions of environmental and social conditions is necessary to inform sound environmental management of protected natural areas. This study examines the effect of prior experience with the setting and two dimensions of place attachment (i.e., place identity and place dependence) on visitors’ perceptions of three types of recreation impacts (i.e., depreciative behavior, environmental impacts, and recreation conflict). Principal components analysis, confirmatory factor analysis, and structural equation modeling were used to test the study hypotheses using data collected from 351 visitors through on-site questionnaires (response rate of 93 percent). The results show that prior experience exhibited a moderate and significant direct positive effect on place identity, place dependence, and visitors’ perceptions of recreation impacts. Contrary to study hypotheses and prior research, neither place dependence nor place identity exhibited a significant effect on the dependent variables. The results show that prior experience causes visitors to be more sensitive to depreciative behaviors, environmental impacts, and recreation conflict. These findings raise concerns over potential visitor displacement and deterioration of site conditions. Implications for resource managers are discussed, which include education, modifying visitor use patterns, and site design strategies.

  3. Effects of place identity, place dependence, and experience-use history on perceptions of recreation impacts in a natural setting.

    Science.gov (United States)

    White, Dave D; Virden, Randy J; van Riper, Carena J

    2008-10-01

    It is generally accepted that recreation use in natural environments results in some degree of negative social and environmental impact. Environmental managers are tasked with mitigating the impact while providing beneficial recreation opportunities. Research on the factors that influence visitors' perceptions of environmental and social conditions is necessary to inform sound environmental management of protected natural areas. This study examines the effect of prior experience with the setting and two dimensions of place attachment (i.e., place identity and place dependence) on visitors' perceptions of three types of recreation impacts (i.e., depreciative behavior, environmental impacts, and recreation conflict). Principal components analysis, confirmatory factor analysis, and structural equation modeling were used to test the study hypotheses using data collected from 351 visitors through on-site questionnaires (response rate of 93 percent). The results show that prior experience exhibited a moderate and significant direct positive effect on place identity, place dependence, and visitors' perceptions of recreation impacts. Contrary to study hypotheses and prior research, neither place dependence nor place identity exhibited a significant effect on the dependent variables. The results show that prior experience causes visitors to be more sensitive to depreciative behaviors, environmental impacts, and recreation conflict. These findings raise concerns over potential visitor displacement and deterioration of site conditions. Implications for resource managers are discussed, which include education, modifying visitor use patterns, and site design strategies.

  4. Plasma inflammatory factors are associated with anxiety, depression, and cognitive problems in adults with and without methamphetamine dependence: An exploratory protein array study

    Directory of Open Access Journals (Sweden)

    Marilyn eHuckans

    2015-12-01

    Full Text Available Objectives: It is hypothesized that immune factors influence addictive behaviors and contribute to relapse. The primary study objectives were to: 1 compare neuropsychiatric symptoms across adults with active methamphetamine dependence, in early remission from methamphetamine dependence, and with no history of substance dependence, 2 determine whether active or recent methamphetamine dependence affects the expression of immune factors, and 3 evaluate the association between immune factor levels and neuropsychiatric symptoms. Methods: A cross-sectional study was conducted using between group comparisons and regression analyses to investigate associations among variables. Eighty-four adults were recruited into control (n = 31, methamphetamine (MA-active (n = 17, or MA-remission (n = 36 groups. Participants completed self-report measures of anxiety, depression, and memory complaints and objective tests of attention and executive function. Blood samples were collected, and a panel of immune factors was measured using multiplex technology. Results: Relative to controls, MA dependent adults evidenced greater anxiety and depression during active use (p < 0.001 and remission (p < 0.007, and more attention, memory, and executive problems during remission (p < 0.01 but not active dependence. Regression analyses identified 10 immune factors (putatively associated with cytokine-cytokine receptor interactions associated with anxiety, depression, and memory problems. Conclusion: While psychiatric symptoms are present during active methamphetamine dependence and remission, at least some cognitive difficulties emerge only during remission. Altered expression of a network of immune factors contributes to neuropsychiatric symptom severity.

  5. 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...

  6. Bioinformatics Identification of Modules of Transcription Factor Binding Sites in Alzheimer's Disease-Related Genes by In Silico Promoter Analysis and Microarrays

    Directory of Open Access Journals (Sweden)

    Regina Augustin

    2011-01-01

    Full Text Available The molecular mechanisms and genetic risk factors underlying Alzheimer's disease (AD pathogenesis are only partly understood. To identify new factors, which may contribute to AD, different approaches are taken including proteomics, genetics, and functional genomics. Here, we used a bioinformatics approach and found that distinct AD-related genes share modules of transcription factor binding sites, suggesting a transcriptional coregulation. To detect additional coregulated genes, which may potentially contribute to AD, we established a new bioinformatics workflow with known multivariate methods like support vector machines, biclustering, and predicted transcription factor binding site modules by using in silico analysis and over 400 expression arrays from human and mouse. Two significant modules are composed of three transcription factor families: CTCF, SP1F, and EGRF/ZBPF, which are conserved between human and mouse APP promoter sequences. The specific combination of in silico promoter and multivariate analysis can identify regulation mechanisms of genes involved in multifactorial diseases.

  7. 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 :...

  8. Genetic factors may play a prominent role in the development of coronary heart disease dependent on important environmental factors

    Science.gov (United States)

    Song, C; Chang, Z; Magnusson, P K E; Ingelsson, E; Pedersen, N L

    2014-01-01

    Astract Song C, Chang Z, Magnusson PKE, Ingelsson E, Pedersen NL (Karolinska Institutet, Stockholm; Uppsala University, Uppsala; Sweden). Genetic factors may play a prominent role in the developmentofcoronary heart diseasedependenton important environmental factors. J InternMed2014; 275: 631–639. Objective The aim of the study was to examine whether various lifestyle factors modify genetic influences on coronary heart disease (CHD). Design The effect of lifestyle factors [including smoking, sedentary lifestyle, alcohol intake and body mass index (BMI)] on risk of CHD was evaluated via Cox regression models in a twin study of gene–environment interaction. Using structure equation modelling, we estimated genetic variance of CHD dependent on lifestyle factors. Subjects In total, 51 065 same-sex twins from 25 715 twin pairs born before 1958 and registered in the Swedish Twin Registry were eligible for this study. During the 40-year follow-up, 7264 incident CHD events were recorded. Results Smoking, sedentary lifestyle and above average BMI were significantly associated with increased CHD incidence. The heritability of CHD decreased with increasing age, as well as with increasing levels of BMI, in both men and women. Conclusions The difference in the genetic component of CHD as a function of BMI suggests that genetic factors may play a more prominent role for disease development in the absence of important environmental factors. Increased knowledge of gene–environment interactions will be important for a full understanding of the aetiology of CHD. PMID:24330166

  9. Extended synaptotagmins are Ca2+-dependent lipid transfer proteins at membrane contact sites.

    Science.gov (United States)

    Yu, Haijia; Liu, Yinghui; Gulbranson, Daniel R; Paine, Alex; Rathore, Shailendra S; Shen, Jingshi

    2016-04-19

    Organelles are in constant communication with each other through exchange of proteins (mediated by trafficking vesicles) and lipids [mediated by both trafficking vesicles and lipid transfer proteins (LTPs)]. It has long been known that vesicle trafficking can be tightly regulated by the second messenger Ca(2+), allowing membrane protein transport to be adjusted according to physiological demands. However, it remains unclear whether LTP-mediated lipid transport can also be regulated by Ca(2+) In this work, we show that extended synaptotagmins (E-Syts), poorly understood membrane proteins at endoplasmic reticulum-plasma membrane contact sites, are Ca(2+)-dependent LTPs. Using both recombinant and endogenous mammalian proteins, we discovered that E-Syts transfer glycerophospholipids between membrane bilayers in the presence of Ca(2+) E-Syts use their lipid-accommodating synaptotagmin-like mitochondrial lipid binding protein (SMP) domains to transfer lipids. However, the SMP domains themselves cannot transport lipids unless the two membranes are tightly tethered by Ca(2+)-bound C2 domains. Strikingly, the Ca(2+)-regulated lipid transfer activity of E-Syts was fully recapitulated when the SMP domain was fused to the cytosolic domain of synaptotagmin-1, the Ca(2+)sensor in synaptic vesicle fusion, indicating that a common mechanism of membrane tethering governs the Ca(2+)regulation of lipid transfer and vesicle fusion. Finally, we showed that microsomal vesicles isolated from mammalian cells contained robust Ca(2+)-dependent lipid transfer activities, which were mediated by E-Syts. These findings established E-Syts as a novel class of LTPs and showed that LTP-mediated lipid trafficking, like vesicular transport, can be subject to tight Ca(2+)regulation.

  10. 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

  11. Factors and Drivers Effecting the Decision of Using Off-Site Manufacturing (OSM Systems in House Building Industry

    Directory of Open Access Journals (Sweden)

    Hussein Elnaas

    2014-01-01

    Full Text Available Much has been written on Off-site Manufacturing (OSM in construction, particularly regarding the perceived benefits and barriers to implementation. However, there seems to be a wide misunderstanding of the state of OSM associated with the concept of decision by many of those involved in decision making process within the house building industry. This has led to a demand for guidance’s on decision making process for construction project leaders particularly at early project stages. Choosing a construction method for a project will require an optimum decision strategy which involves careful understanding, measurement and evaluation of a number of decision factors that can have the most influence on successful decision action. This paper, therefore, aims to identify the key decision factors to be considered at evaluation stage when choosing to use Off-Site Manufacturing (OSM as a construction strategy in house building projects. This will reveal the key drivers for change in the industry towards the use of OSM in house building.

  12. Safety factor profile dependence of turbulent structure formation in relevant to internal transport barrier relaxation

    International Nuclear Information System (INIS)

    Tokunaga, S.; Yagi, M.; Itoh, S.-I.; Itoh, K.

    2009-01-01

    Full text: It is widely understood that the improved confinement mode with transport barrier is necessary to achieve the self-ignition condition in ITER. The negative magnetic shear, mean ExB flow shear, and zonal flow are considered to play important roles for ITB formation. In our previous study, it is found that the non-linear interaction between the meso-scale modes produces non-local energy transfer to the off-resonant mode in the vicinity of q min surface and brings global relaxation of the temperature profile involving ITB collapse. Experimental studies indicate that a relationship exists between the ITB formation and safety factor q-profile, with a reversed magnetic shear (RS) configuration. Transitional ITB events occur on the low-order rational resonant surface. The ITB shape and location depend on the q-profile and q min position. These observations indicate that the q-profile might play an essential role in determining the turbulent structure. In this study, the effect of safety factor profile on the ion temperature gradient driven drift wave (ITG) turbulence is investigated using a global non-linear simulation code based on the gyro-fluid model. A heat source and toroidal momentum source are introduced. Dependence of safety factor profiles on ITB formation and its stability is examined to clarify the influence of the radial distribution of the rational surfaces and the q min value. It is found that the nonlinearly excited meso-scale mode in the vicinity of q min depends on the value of q min . A detailed analysis of the structure selection rule is in progress. (author)

  13. Molecular Stress-inducing Compounds Increase Osteoclast Formation in a Heat Shock Factor 1 Protein-dependent Manner*

    Science.gov (United States)

    Chai, Ryan C.; Kouspou, Michelle M.; Lang, Benjamin J.; Nguyen, Chau H.; van der Kraan, A. Gabrielle J.; Vieusseux, Jessica L.; Lim, Reece C.; Gillespie, Matthew T.; Benjamin, Ivor J.; Quinn, Julian M. W.; Price, John T.

    2014-01-01

    Many anticancer therapeutic agents cause bone loss, which increases the risk of fractures that severely reduce quality of life. Thus, in drug development, it is critical to identify and understand such effects. Anticancer therapeutic and HSP90 inhibitor 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) causes bone loss by increasing osteoclast formation, but the mechanism underlying this is not understood. 17-AAG activates heat shock factor 1 (Hsf1), the master transcriptional regulator of heat shock/cell stress responses, which may be involved in this negative action of 17-AAG upon bone. Using mouse bone marrow and RAW264.7 osteoclast differentiation models we found that HSP90 inhibitors that induced a heat shock response also enhanced osteoclast formation, whereas HSP90 inhibitors that did not (including coumermycin A1 and novobiocin) did not affect osteoclast formation. Pharmacological inhibition or shRNAmir knockdown of Hsf1 in RAW264.7 cells as well as the use of Hsf1 null mouse bone marrow cells demonstrated that 17-AAG-enhanced osteoclast formation was Hsf1-dependent. Moreover, ectopic overexpression of Hsf1 enhanced 17-AAG effects upon osteoclast formation. Consistent with these findings, protein levels of the essential osteoclast transcription factor microphthalmia-associated transcription factor were increased by 17-AAG in an Hsf1-dependent manner. In addition to HSP90 inhibitors, we also identified that other agents that induced cellular stress, such as ethanol, doxorubicin, and methotrexate, also directly increased osteoclast formation, potentially in an Hsf1-dependent manner. These results, therefore, indicate that cellular stress can enhance osteoclast differentiation via Hsf1-dependent mechanisms and may significantly contribute to pathological and therapeutic related bone loss. PMID:24692538

  14. Molecular stress-inducing compounds increase osteoclast formation in a heat shock factor 1 protein-dependent manner.

    Science.gov (United States)

    Chai, Ryan C; Kouspou, Michelle M; Lang, Benjamin J; Nguyen, Chau H; van der Kraan, A Gabrielle J; Vieusseux, Jessica L; Lim, Reece C; Gillespie, Matthew T; Benjamin, Ivor J; Quinn, Julian M W; Price, John T

    2014-05-09

    Many anticancer therapeutic agents cause bone loss, which increases the risk of fractures that severely reduce quality of life. Thus, in drug development, it is critical to identify and understand such effects. Anticancer therapeutic and HSP90 inhibitor 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) causes bone loss by increasing osteoclast formation, but the mechanism underlying this is not understood. 17-AAG activates heat shock factor 1 (Hsf1), the master transcriptional regulator of heat shock/cell stress responses, which may be involved in this negative action of 17-AAG upon bone. Using mouse bone marrow and RAW264.7 osteoclast differentiation models we found that HSP90 inhibitors that induced a heat shock response also enhanced osteoclast formation, whereas HSP90 inhibitors that did not (including coumermycin A1 and novobiocin) did not affect osteoclast formation. Pharmacological inhibition or shRNAmir knockdown of Hsf1 in RAW264.7 cells as well as the use of Hsf1 null mouse bone marrow cells demonstrated that 17-AAG-enhanced osteoclast formation was Hsf1-dependent. Moreover, ectopic overexpression of Hsf1 enhanced 17-AAG effects upon osteoclast formation. Consistent with these findings, protein levels of the essential osteoclast transcription factor microphthalmia-associated transcription factor were increased by 17-AAG in an Hsf1-dependent manner. In addition to HSP90 inhibitors, we also identified that other agents that induced cellular stress, such as ethanol, doxorubicin, and methotrexate, also directly increased osteoclast formation, potentially in an Hsf1-dependent manner. These results, therefore, indicate that cellular stress can enhance osteoclast differentiation via Hsf1-dependent mechanisms and may significantly contribute to pathological and therapeutic related bone loss.

  15. Radiation leukemia virus and x-irradiation induce in C57BL/6 mice two distinct T-cell neoplasms: a growth factor-dependent lymphoma and a growth factor-independent lymphoma

    International Nuclear Information System (INIS)

    Haas, Martin; Rothenberg, Ellen; Bogart, M.H.; Jones, O.W.

    1987-01-01

    Two different classes of neoplastic T cells were isolated from radiation leukemia virus (RadLV)-inoculated and from X-ray-treated C57BL/6 mice. One consisted of growth factor-dependent T-cell lymphoma (FD-TCL) lines which were established from the spleens and thymuses of treated mice within a day of lymphoma detection. Non-thymic, factor-dependent TCL cells produced interleukin-2 upon lectin stimulation, and were autostimulatory because they secreted growth factor(s) constitutively. In vivo, FD-TCL cells that were injected intraperitoneally or intravenously homed to the spleen, proliferated in it and killed the injected mice. The isolation and study of FD-TCL cells was facilitated by their cultivation on stromal hematopoietic monolayers in supplemented ''lymphocyte medium'', until an autostimulating, self-sustaining concentration of FD-TCL cells was obtained. FD-TCL cells could not be grown from lymphoid tissue of normal, control mice. In contrast, T-cell lymphoma (TCL) lines, which were established from virus-induced thymomas which had been kept in situ for 4-6 weeks after detection, consisted of factor-independent cells that possessed an aneuploid karyotype. The phenotypic markers of TCL cells differed from those of FD-TCL cells, suggesting heterogeneity in the stages of differentiation at which cells can give rise to growth factor-independent (TCL) and to growth factor-dependent (FD-TCL) lines. (author)

  16. pH-Dependent Binding of Chloride to a Marine Alkaline Phosphatase Affects the Catalysis, Active Site Stability, and Dimer Equilibrium.

    Science.gov (United States)

    Hjörleifsson, Jens G; Ásgeirsson, Bjarni

    2017-09-26

    The effect of ionic strength on enzyme activity and stability varies considerably between enzymes. Ionic strength is known to affect the catalytic activity of some alkaline phosphatases (APs), such as Escherichia coli AP, but how ions affect APs is debated. Here, we studied the effect of various ions on a cold-adapted AP from Vibrio splendidus (VAP). Previously, we have found that the active form of VAP is extremely unstable at low ionic strengths. Here we show that NaCl increased the activity and stability of VAP and that the effect was pH-dependent in the range of pH 7-10. The activity profile as a function of pH formed two maxima, indicating a possible conformational change. Bringing the pH from the neutral to the alkaline range was accompanied by a large increase in both the K i for inorganic phosphate (product inhibition) and the K M for p-nitrophenyl phosphate. The activity transitions observed as the pH was varied correlated with structural changes as monitored by tryptophan fluorescence. Thermal and urea-induced inactivation was shown to be accompanied by neither dissociation of the active site metal ions nor dimer dissociation. This would suggest that the inactivation involved subtle changes in active site conformation. Furthermore, the VAP dimer equilibrium was studied for the first time and shown to highly favor dimerization, which was dependent on pH and NaCl concentration. Taken together, the data support a model in which anions bind to some specific acceptor in the active site of VAP, resulting in great stabilization and catalytic rate enhancement, presumably through a different mechanism.

  17. Pre-treatment predictors and in-treatment factors associated with change in avoidant and dependent personality disorder traits among patients with social phobia.

    Science.gov (United States)

    Borge, Finn-Magnus; Hoffart, Asle; Sexton, Harold; Martinsen, Egil; Gude, Tore; Hedley, Liv Margaret; Abrahamsen, Gun

    2010-01-01

    We examined changes in avoidant and dependent personality disorder dimensions, and pre-treatment and in-treatment factors associated with such changes in 77 patients, randomized to medication-free residential cognitive (CT) or residential interpersonal therapy for social phobia. Personality disorders and personality dimensions according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) were assessed at pre-treatment and at one-year post-treatment. Both treatments were associated with a decrease in avoidant and dependent personality dimensions; dependent dimension decreased more in CT. Changes in cognitive factors predicted changes in both personality dimensions, whereas changes in symptoms or interpersonal factors did not. Change in the cognitive factor estimated cost was the most powerful predictor in the avoidant dimension, as it was the only predictor that remained significant in the forward regression analyses. Change in the cognitive factor estimated cost, and treatment were the most powerful predictors of change in the dependent dimension. Pre-treatment use of anxiolytics predicted larger changes in both PD dimensions.

  18. Platelet-activating factor increases platelet-dependent glycoconjugate secretion from tracheal submucosal gland

    International Nuclear Information System (INIS)

    Sasaki, T.; Shimura, S.; Ikeda, K.; Sasaki, H.; Takishima, T.

    1989-01-01

    Using isolated glands from feline trachea, we examined the effect of platelet-activating factor (PAF) on radiolabeled glycoconjugate release and glandular contraction by measuring induced tension in the absence or presence of platelets. PAF alone did not produce any significant glandular contraction nor any significant change in glycoconjugate release from isolated glands. In the presence of purified platelets containing no plasma, PAF (10(-8) to 10(-5) M) produced significant glycoconjugate secretion in a dose-dependent fashion, but it produced no significant glandular contraction. PAF-evoked glycoconjugate secretion was time dependent, reaching a peak response of 277% of control 15-30 min after the exposure of isolated glands to 10(-5) M PAF in the presence of platelets and returning to 135% of controls at 2 h. Platelets alone did not produce any significant stimulation in glycoconjugate release. CV-3988, a known PAF antagonist, inhibited the secretory response to PAF. Methysergide, a known antagonist to receptors for 5-hydroxytryptamine, did not alter PAF-evoked glycoconjugate secretion. Both indomethacin and SQ 29,548, a thromboxane receptor antagonist, abolished the PAF-evoked glycoconjugate secretion from isolated submucosal glands. Epithiomethanothromboxane A2, a stable thromboxane A2 analogue, produced a significant increase in glycoconjugate secretion in a dose-dependent fashion. These findings indicate that PAF increases glycoconjugate release in the presence of platelets and that the increase is dependent on some aspect of platelet function, namely thromboxane generation

  19. Siting guidelines and their role in repository site selection

    International Nuclear Information System (INIS)

    Hanlon, C.L.

    1985-01-01

    The first requirement of the Nuclear Waste Policy Act was for the Secretary of Energy to issue general guidelines for siting repositories. The guidelines were to specify detailed geologic considerations that would be the primary criteria for the selection of sites in various host rocks, as well as factors that would qualify or disqualify any site from development as a repository. These guidelines were clearly intended to provide not only the framework for the siting program but also the stimulus for establishing effective communication and consultation among the parties involved in the program. The Act further required that the guidelines be a factor in the development of all future decision documents of the Office of Civilian Radioactive Waste Management, including the environmental assessments that would accompany the nomination of sites for characterization, the site-characterization plans that are to be prepared before the sinking of exploratory shafts at any candidate site, and the environmental impact statement that is to support the recommendation of a site for development as a repository. More than two years after its passage, the intention of the Act for the guidelines has been realized. Concurred in by the Nuclear Regulatory Commission on June 22, 1984, and issued by the Department in November 1984, the guidelines include postclosure technical guidelines that apply to conditions governing the long-term performance of the repository system; preclosure technical guidelines that apply to conditions governing the siting, construction, operation, and closure of the repository; and system guidelines whose objective is to ensure that the regulatory requirements of the Environmental Protection Agency and the Nuclear Regulatory Commission are met

  20. 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.

  1. 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.

  2. Brain-Derived Neurotrophic Factor Elevates Activating Transcription Factor 4 (ATF4 in Neurons and Promotes ATF4-Dependent Induction of Sesn2

    Directory of Open Access Journals (Sweden)

    Jin Liu

    2018-03-01

    Full Text Available Activating transcription factor 4 (ATF4 plays important physiologic roles in the brain including regulation of learning and memory as well as neuronal survival and death. Yet, outside of translational regulation by the eIF2α-dependent stress response pathway, there is little information about how its levels are controlled in neurons. Here, we show that brain-derived neurotrophic factor (BDNF promotes a rapid and sustained increase in neuronal ATF4 transcripts and protein levels. This increase is dependent on tropomyosin receptor kinase (TrkB signaling, but independent of levels of phosphorylated eIF2α. The elevation in ATF4 protein occurs both in nuclei and processes. Transcriptome analysis revealed that ATF4 mediates BDNF-promoted induction of Sesn2 which encodes Sestrin2, a protector against oxidative and genotoxic stresses and a mTor complex 1 inhibitor. In contrast, BDNF-elevated ATF4 did not affect expression of a number of other known ATF4 targets including several with pro-apoptotic activity. The capacity of BDNF to elevate neuronal ATF4 may thus represent a means to maintain this transcription factor at levels that provide neuroprotection and optimal brain function without risk of triggering neurodegeneration.

  3. Dependence of the duration of geomagnetic polarity reversals on site latitude.

    Science.gov (United States)

    Clement, Bradford M

    2004-04-08

    An important constraint on the processes governing the geodynamo--the flow in the outer core responsible for generating Earth's magnetic field--is the duration of geomagnetic polarity reversals; that is, how long it takes for Earth's magnetic field to reverse. It is generally accepted that Earth's magnetic field strength drops to low levels during polarity reversals, and the field direction progresses through a 180 degrees change while the field is weak. The time it takes for this process to happen, however, remains uncertain, with estimates ranging from a few thousand up to 28,000 years. Here I present an analysis of the available sediment records of the four most recent polarity reversals. These records yield an average estimate of about 7,000 years for the time it takes for the directional change to occur. The variation about this mean duration is not random, but instead varies with site latitude, with shorter durations observed at low-latitude sites, and longer durations observed at mid- to high-latitude sites. Such variation of duration with site latitude is predicted by simple geometrical reversal models, in which non-dipole fields are allowed to persist while the axial dipole decays through zero and then builds in the opposite direction, and provides a constraint on numerical dynamo models.

  4. Testing the Scale Dependence of the Scale Factor $\\sigma_{eff}$ in Double Dijet Production at the LHC

    CERN Document Server

    Domdey, Svend; Wiedemann, Urs Achim

    2010-01-01

    The scale factor σ eff is the effective cross section used to characterize the measured rate of inclusive double dijet production in high energy hadron collisions. It is sensitive to the two-parton distributions in the hadronic projectile. In principle, the scale factor depends on the center of mass energy and on the minimal transverse energy of the jets contributing to the double dijet cross section. Here, we point out that proton-proton collisions at the LHC will provide for the first time experimental access to these scale dependences in a logarithmically wide, nominally perturbative kinematic range of minimal transverse energy between 10 GeV and 100 GeV. This constrains the dependence of two-parton distribution functions on parton momentum fractions and parton localization in impact parameter space. Novel information is to be expected about the transverse growth of hadronic distribution functions in the range of semi-hard Bjorken x (0.001 < x < 0.1) and high resolution Q^2. We discuss to what exten...

  5. 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

  6. Two-step interrogation then recognition of DNA binding site by Integration Host Factor: an architectural DNA-bending protein.

    Science.gov (United States)

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

    2018-02-28

    The dynamics and mechanism of how site-specific DNA-bending proteins initially interrogate potential binding sites prior to recognition have remained elusive for most systems. Here we present these dynamics for Integration Host factor (IHF), a nucleoid-associated architectural protein, using a μs-resolved T-jump approach. Our studies show two distinct DNA-bending steps during site recognition by IHF. While the faster (∼100 μs) step is unaffected by changes in DNA or protein sequence that alter affinity by >100-fold, the slower (1-10 ms) step is accelerated ∼5-fold when mismatches are introduced at DNA sites that are sharply kinked in the specific complex. The amplitudes of the fast phase increase when the specific complex is destabilized and decrease with increasing [salt], which increases specificity. Taken together, these results indicate that the fast phase is non-specific DNA bending while the slow phase, which responds only to changes in DNA flexibility at the kink sites, is specific DNA kinking during site recognition. Notably, the timescales for the fast phase overlap with one-dimensional diffusion times measured for several proteins on DNA, suggesting that these dynamics reflect partial DNA bending during interrogation of potential binding sites by IHF as it scans DNA.

  7. Burden of disease from toxic waste sites in India, Indonesia, and the Philippines in 2010.

    Science.gov (United States)

    Chatham-Stephens, Kevin; Caravanos, Jack; Ericson, Bret; Sunga-Amparo, Jennifer; Susilorini, Budi; Sharma, Promila; Landrigan, Philip J; Fuller, Richard

    2013-07-01

    Prior calculations of the burden of disease from toxic exposures have not included estimates of the burden from toxic waste sites due to the absence of exposure data. We developed a disability-adjusted life year (DALY)-based estimate of the disease burden attributable to toxic waste sites. We focused on three low- and middle-income countries (LMICs): India, Indonesia, and the Philippines. Sites were identified through the Blacksmith Institute's Toxic Sites Identification Program, a global effort to identify waste sites in LMICs. At least one of eight toxic chemicals was sampled in environmental media at each site, and the population at risk estimated. By combining estimates of disease incidence from these exposures with population data, we calculated the DALYs attributable to exposures at each site. We estimated that in 2010, 8,629,750 persons were at risk of exposure to industrial pollutants at 373 toxic waste sites in the three countries, and that these exposures resulted in 828,722 DALYs, with a range of 814,934-1,557,121 DALYs, depending on the weighting factor used. This disease burden is comparable to estimated burdens for outdoor air pollution (1,448,612 DALYs) and malaria (725,000 DALYs) in these countries. Lead and hexavalent chromium collectively accounted for 99.2% of the total DALYs for the chemicals evaluated. Toxic waste sites are responsible for a significant burden of disease in LMICs. Although some factors, such as unidentified and unscreened sites, may cause our estimate to be an underestimate of the actual burden of disease, other factors, such as extrapolation of environmental sampling to the entire exposed population, may result in an overestimate of the burden of disease attributable to these sites. Toxic waste sites are a major, and heretofore underrecognized, global health problem.

  8. 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.

  9. Influence of weak vibrational-electronic couplings on 2D electronic spectra and inter-site coherence in weakly coupled photosynthetic complexes

    Energy Technology Data Exchange (ETDEWEB)

    Monahan, Daniele M.; Whaley-Mayda, Lukas; Fleming, Graham R., E-mail: grfleming@lbl.gov [Department of Chemistry, University of California, Berkeley, California 94720 (United States); Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720 (United States); Kavli Energy NanoSciences Institute at Berkeley, Berkeley, California 94720 (United States); Ishizaki, Akihito [Institute for Molecular Science, National Institutes of Natural Sciences, Okazaki 444-8585 (Japan)

    2015-08-14

    Coherence oscillations measured in two-dimensional (2D) electronic spectra of pigment-protein complexes may have electronic, vibrational, or mixed-character vibronic origins, which depend on the degree of electronic-vibrational mixing. Oscillations from intrapigment vibrations can obscure the inter-site coherence lifetime of interest in elucidating the mechanisms of energy transfer in photosynthetic light-harvesting. Huang-Rhys factors (S) for low-frequency vibrations in Chlorophyll and Bacteriochlorophyll are quite small (S ≤ 0.05), so it is often assumed that these vibrations influence neither 2D spectra nor inter-site coherence dynamics. In this work, we explore the influence of S within this range on the oscillatory signatures in simulated 2D spectra of a pigment heterodimer. To visualize the inter-site coherence dynamics underlying the 2D spectra, we introduce a formalism which we call the “site-probe response.” By comparing the calculated 2D spectra with the site-probe response, we show that an on-resonance vibration with Huang-Rhys factor as small as S = 0.005 and the most strongly coupled off-resonance vibrations (S = 0.05) give rise to long-lived, purely vibrational coherences at 77 K. We moreover calculate the correlation between optical pump interactions and subsequent entanglement between sites, as measured by the concurrence. At 77 K, greater long-lived inter-site coherence and entanglement appear with increasing S. This dependence all but vanishes at physiological temperature, as environmentally induced fluctuations destroy the vibronic mixing.

  10. Novel Phosphorylation and Ubiquitination Sites Regulate Reactive Oxygen Species-dependent Degradation of Anti-apoptotic c-FLIP Protein*

    Science.gov (United States)

    Wilkie-Grantham, Rachel P.; Matsuzawa, Shu-Ichi; Reed, John C.

    2013-01-01

    The cytosolic protein c-FLIP (cellular Fas-associated death domain-like interleukin 1β-converting enzyme inhibitory protein) is an inhibitor of death receptor-mediated apoptosis that is up-regulated in a variety of cancers, contributing to apoptosis resistance. Several compounds found to restore sensitivity of cancer cells to TRAIL, a TNF family death ligand with promising therapeutic potential, act by targeting c-FLIP ubiquitination and degradation by the proteasome. The generation of reactive oxygen species (ROS) has been implicated in c-FLIP protein degradation. However, the mechanism by which ROS post-transcriptionally regulate c-FLIP protein levels is not well understood. We show here that treatment of prostate cancer PPC-1 cells with the superoxide generators menadione, paraquat, or buthionine sulfoximine down-regulates c-FLIP long (c-FLIPL) protein levels, which is prevented by the proteasome inhibitor MG132. Furthermore, pretreatment of PPC-1 cells with a ROS scavenger prevented ubiquitination and loss of c-FLIPL protein induced by menadione or paraquat. We identified lysine 167 as a novel ubiquitination site of c-FLIPL important for ROS-dependent degradation. We also identified threonine 166 as a novel phosphorylation site and demonstrate that Thr-166 phosphorylation is required for ROS-induced Lys-167 ubiquitination. The mutation of either Thr-166 or Lys-167 was sufficient to stabilize c-FLIP protein levels in PPC-1, HEK293T, and HeLa cancer cells treated with menadione or paraquat. Accordingly, expression of c-FLIP T166A or K167R mutants protected cells from ROS-mediated sensitization to TRAIL-induced cell death. Our findings reveal novel ROS-dependent post-translational modifications of the c-FLIP protein that regulate its stability, thus impacting sensitivity of cancer cells to TRAIL. PMID:23519470

  11. Feeding-Danger Trade-Offs Underlie Stopover Site Selection by Migrants

    Directory of Open Access Journals (Sweden)

    Andrea C. Pomeroy

    2008-06-01

    Full Text Available To migrate successfully, birds need to store adequate fat reserves to fuel each leg of the journey. Migrants acquire their fuel reserves at stopover sites; this often entails exposure to predators. Therefore, the safety attributes of sites may be as important as the feeding opportunities. Furthermore, site choice might depend on fuel load, with lean birds more willing to accept danger to obtain good feeding. Here, we evaluate the factors underlying stopover-site usage by migrant Western Sandpipers (Calidris mauri on a landscape scale. We measured the food and danger attributes of 17 potential stopover sites in the Strait of Georgia and Puget Sound region. We used logistic regression models to test whether food, safety, or both were best able to predict usage of these sites by Western Sandpipers. Eight of the 17 sites were used by sandpipers on migration. Generally, sites that were high in food and safety were used, whereas sites that were low in food and safety were not. However, dangerous sites were used if there was ample food abundance, and sites with low food abundance were used if they were safe. The model including both food and safety best-predicted site usage by sandpipers. Furthermore, lean sandpipers used the most dangerous sites, whereas heavier birds (which do not need to risk feeding in dangerous locations used safer sites. This study demonstrates that both food and danger attributes are considered by migrant birds when selecting stopover sites, thus both these attributes should be considered to prioritize and manage stopover sites for conservation.

  12. The Transcription Factor ABI4 Is Required for the Ascorbic Acid–Dependent Regulation of Growth and Regulation of Jasmonate-Dependent Defense Signaling Pathways in Arabidopsis[C][W

    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.

    2011-01-01

    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. PMID:21926335

  13. The brain-derived neurotrophic factor pathway, life stress, and chronic multi-site musculoskeletal pain.

    Science.gov (United States)

    Generaal, Ellen; Milaneschi, Yuri; Jansen, Rick; Elzinga, Bernet M; Dekker, Joost; Penninx, Brenda W J H

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) disturbances and life stress, both independently and in interaction, have been hypothesized to induce chronic pain. We examined whether (a) the BDNF pathway (val(66)met genotype, gene expression, and serum levels), (b) early and recent life stress, and (c) their interaction are associated with the presence and severity of chronic multi-site musculoskeletal pain. Cross-sectional data are from 1646 subjects of the Netherlands Study of Depression and Anxiety. The presence and severity of chronic multi-site musculoskeletal pain were determined using the Chronic Pain Grade (CPG) questionnaire. The BDNF val(66)met polymorphism, BDNF gene expression, and BDNF serum levels were measured. Early life stress before the age of 16 was assessed by calculating a childhood trauma index using the Childhood Trauma Interview. Recent life stress was assessed as the number of recent adverse life events using the List of Threatening Events Questionnaire. Compared to val(66)val, BDNF met carriers more often had chronic pain, whereas no differences were found for BDNF gene expression and serum levels. Higher levels of early and recent stress were both associated with the presence and severity of chronic pain (p stress in the associations with chronic pain presence and severity. This study suggests that the BDNF gene marks vulnerability for chronic pain. Although life stress did not alter the impact of BDNF on chronic pain, it seems an independent factor in the onset and persistence of chronic pain. © The Author(s) 2016.

  14. Tourism-Induced Livelihood Changes at Mount Sanqingshan World Heritage Site, China

    Science.gov (United States)

    Su, Ming Ming; Wall, Geoffrey; Xu, Kejian

    2016-05-01

    Although tourism has the potential to improve the wellbeing of residents, it may also disrupt livelihood systems, social processes, and cultural traditions. The livelihood changes at three rural villages at Mount Sanqingshan World Heritage Site, China, are assessed to determine the extent to which tourism strategies are contributing to local livelihoods. A sustainable livelihood framework is adopted to guide the analysis. The three villages exhibit different development patterns due to institutional, organizational, and location factors. New strategies involving tourism were constructed and incorporated into the traditional livelihood systems and they resulted in different outcomes for residents of different villages. Village location, including the relationship to the site tourism plan, affected the implications for rural livelihoods. High dependence on tourism as the single livelihood option can reduce sustainability. Practical implications are suggested to enhance livelihood sustainability at such rural heritage tourism sites.

  15. Tourism-Induced Livelihood Changes at Mount Sanqingshan World Heritage Site, China.

    Science.gov (United States)

    Su, Ming Ming; Wall, Geoffrey; Xu, Kejian

    2016-05-01

    Although tourism has the potential to improve the wellbeing of residents, it may also disrupt livelihood systems, social processes, and cultural traditions. The livelihood changes at three rural villages at Mount Sanqingshan World Heritage Site, China, are assessed to determine the extent to which tourism strategies are contributing to local livelihoods. A sustainable livelihood framework is adopted to guide the analysis. The three villages exhibit different development patterns due to institutional, organizational, and location factors. New strategies involving tourism were constructed and incorporated into the traditional livelihood systems and they resulted in different outcomes for residents of different villages. Village location, including the relationship to the site tourism plan, affected the implications for rural livelihoods. High dependence on tourism as the single livelihood option can reduce sustainability. Practical implications are suggested to enhance livelihood sustainability at such rural heritage tourism sites.

  16. Probabilistic Seismic Hazard Assessment Method for Nonlinear Soil Sites based on the Hazard Spectrum of Bedrock Sites

    International Nuclear Information System (INIS)

    Hahm, Dae Gi; Seo, Jeong Moon; Choi, In Kil

    2011-01-01

    For the probabilistic safety assessment of the nuclear power plants (NPP) under seismic events, the rational probabilistic seismic hazard estimation should be performed. Generally, the probabilistic seismic hazard of NPP site is represented by the uniform hazard spectrum (UHS) for the specific annual frequency. In most case, since that the attenuation equations were defined for the bedrock sites, the standard attenuation laws cannot be applied to the general soft soil sites. Hence, for the probabilistic estimation of the seismic hazard of soft soil sites, a methodology of probabilistic seismic hazard analysis (PSHA) coupled with nonlinear dynamic analyses of the soil column are required. Two methods are commonly used for the site response analysis considering the nonlinearity of sites. The one is the deterministic method and another is the probabilistic method. In the analysis of site response, there exist many uncertainty factors such as the variation of the magnitude and frequency contents of input ground motion, and material properties of soil deposits. Hence, nowadays, it is recommended that the adoption of the probabilistic method for the PSHA of soft soil deposits considering such uncertainty factors. In this study, we estimated the amplification factor of the surface of the soft soil deposits with considering the uncertainties of the input ground motions and the soil material properties. Then, we proposed the probabilistic methodology to evaluate the UHS of the soft soil site by multiplying the amplification factor to that of the bedrock site. The proposed method was applied to four typical target sites of KNGR and APR1400 NPP site categories

  17. Rapid high-throughput analysis of DNaseI hypersensitive sites using a modified Multiplex Ligation-dependent Probe Amplification approach

    Directory of Open Access Journals (Sweden)

    Sinclair Andrew H

    2009-09-01

    Full Text Available Abstract Background Mapping DNaseI hypersensitive sites is commonly used to identify regulatory regions in the genome. However, currently available methods are either time consuming and laborious, expensive or require large numbers of cells. We aimed to develop a quick and straightforward method for the analysis of DNaseI hypersensitive sites that overcomes these problems. Results We have developed a modified Multiplex Ligation-dependent Probe Amplification (MLPA approach for the identification and analysis of genomic regulatory regions. The utility of this approach was demonstrated by simultaneously analysing 20 loci from the ENCODE project for DNaseI hypersensitivity in a range of different cell lines. We were able to obtain reproducible results with as little as 5 × 104 cells per DNaseI treatment. Our results broadly matched those previously reported by the ENCODE project, and both technical and biological replicates showed high correlations, indicating the sensitivity and reproducibility of this method. Conclusion This new method will considerably facilitate the identification and analysis of DNaseI hypersensitive sites. Due to the multiplexing potential of MLPA (up to 50 loci can be examined it is possible to analyse dozens of DNaseI hypersensitive sites in a single reaction. Furthermore, the high sensitivity of MLPA means that fewer than 105 cells per DNaseI treatment can be used, allowing the discovery and analysis of tissue specific regulatory regions without the need for pooling. This method is quick and easy and results can be obtained within 48 hours after harvesting of cells or tissues. As no special equipment is required, this method can be applied by any laboratory interested in the analysis of DNaseI hypersensitive regions.

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

    International Nuclear Information System (INIS)

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

    2006-01-01

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

  19. What Factors Impact Consumer Perception of the Effectiveness of Health Information Sites? An Investigation of the Korean National Health Information Portal.

    Science.gov (United States)

    Choung, Ji Tae; Lee, Yoon Seong; Jo, Heui Sug; Shim, Minsun; Lee, Hun Jae; Jung, Su Mi

    2017-07-01

    Lay public's concerns around health and health information are increasing. In response, governments and government agencies are establishing websites to address such concerns and improve health literacy by providing better access to validated health information. Since 2011, the Korean government has constructed the National Health Information Portal (NHIP) website run in collaboration with the Korean Academy of Medical Sciences (KAMS). This study therefore aimed to 1) examine consumer use of NHIP, with respect to the usage patterns, evaluation on health information provided, and perceived effectiveness of the site; and 2) identify factors that may impact perceived effectiveness of the site. An online survey was conducted with 164 NHIP users, recruited through a popup window on the main screen of the portal website from October to November 2015. The significant predicting factors supported by the data include the relevance of health information on the site, the usefulness of information in making health decisions, and the effective visualization of information. These factors can inform future efforts to design more effective health information websites, possibly based on metadata systems, to further advance the lay public's information seeking and health literacy. © 2017 The Korean Academy of Medical Sciences.

  20. Site selection for new nuclear power plants

    Energy Technology Data Exchange (ETDEWEB)

    Rizzo, Paul C.; Dubinsky, Melissa; Tastan, Erdem Onur, E-mail: paul.rizzo@rizzoassoc.com, E-mail: melissa.dubinsky@rizzoassoc.com, E-mail: onur.tastan@rizzoassoc.com [RIZZO Associates Inc., Pittsburgh, PA (United States); Miano, Sandra C., E-mail: scm27@psu.edu [Eletrobras Termonuclear S.A. (ELETRONUCLEAR), RJ (Brazil); Pennsylvania State University, Department of Mechanical and Nuclear Engineering, State College, PA (United States)

    2015-07-01

    The current methodology for selecting the most advantageous site(s) for nuclear power plant (NPP) development is based on the latest evolution of protocols originally established in the 1990's by the Electric Power Research Institute (EPRI) and others for programs in the USA, and more recently by the International Atomic Energy Agency (IAEA), among others. The methodology includes protocols that account for lessons learned from both the Gen III projects and the catastrophic event at Fukushima, Japan. In general, the approach requires consideration of Exclusionary or 'fatal flaw' Criteria first, based on safety as well as significant impact to the environment or human health. Sites must meet all of these Exclusionary Criteria to be considered for NPP development. Next, the remaining sites are evaluated for Avoidance Criteria that affect primarily ease of construction and operations, which allow a ranking of sites best suited for NPP development. Finally, Suitability Criteria are applied to the potential sites to better differentiate between closely ranked sites. Generally, final selection of a Preferred and an Alternate Site will require balancing of factors, expert judgment, and client input, as sites being compared will differ in their scores associated with different Avoidance Criteria and Suitability Criteria. RIZZO Associates (RIZZO) offers in this paper a modification to this methodology for selecting the site for NPP development, which accords to the categories of Exclusionary, Avoidance and Suitability Criteria strict definitions which can be considered as Absolute Factors, Critical Factors, and Economic Factors for a more focused approach to site selection. Absolute Factors include all of the safety-related Exclusionary Criteria. Critical Factors are those that are difficult to overcome unless extraordinary mitigation measures are implemented; they have a significant impact on the ability of the project to be successful and may cause the

  1. Site selection for new nuclear power plants

    International Nuclear Information System (INIS)

    Rizzo, Paul C.; Dubinsky, Melissa; Tastan, Erdem Onur; Miano, Sandra C.

    2015-01-01

    The current methodology for selecting the most advantageous site(s) for nuclear power plant (NPP) development is based on the latest evolution of protocols originally established in the 1990's by the Electric Power Research Institute (EPRI) and others for programs in the USA, and more recently by the International Atomic Energy Agency (IAEA), among others. The methodology includes protocols that account for lessons learned from both the Gen III projects and the catastrophic event at Fukushima, Japan. In general, the approach requires consideration of Exclusionary or 'fatal flaw' Criteria first, based on safety as well as significant impact to the environment or human health. Sites must meet all of these Exclusionary Criteria to be considered for NPP development. Next, the remaining sites are evaluated for Avoidance Criteria that affect primarily ease of construction and operations, which allow a ranking of sites best suited for NPP development. Finally, Suitability Criteria are applied to the potential sites to better differentiate between closely ranked sites. Generally, final selection of a Preferred and an Alternate Site will require balancing of factors, expert judgment, and client input, as sites being compared will differ in their scores associated with different Avoidance Criteria and Suitability Criteria. RIZZO Associates (RIZZO) offers in this paper a modification to this methodology for selecting the site for NPP development, which accords to the categories of Exclusionary, Avoidance and Suitability Criteria strict definitions which can be considered as Absolute Factors, Critical Factors, and Economic Factors for a more focused approach to site selection. Absolute Factors include all of the safety-related Exclusionary Criteria. Critical Factors are those that are difficult to overcome unless extraordinary mitigation measures are implemented; they have a significant impact on the ability of the project to be successful and may cause the

  2. SU-C-304-07: Are Small Field Detector Correction Factors Strongly Dependent On Machine-Specific Characteristics?

    International Nuclear Information System (INIS)

    Mathew, D; Tanny, S; Parsai, E; Sperling, N

    2015-01-01

    Purpose: The current small field dosimetry formalism utilizes quality correction factors to compensate for the difference in detector response relative to dose deposited in water. The correction factors are defined on a machine-specific basis for each beam quality and detector combination. Some research has suggested that the correction factors may only be weakly dependent on machine-to-machine variations, allowing for determinations of class-specific correction factors for various accelerator models. This research examines the differences in small field correction factors for three detectors across two Varian Truebeam accelerators to determine the correction factor dependence on machine-specific characteristics. Methods: Output factors were measured on two Varian Truebeam accelerators for equivalently tuned 6 MV and 6 FFF beams. Measurements were obtained using a commercial plastic scintillation detector (PSD), two ion chambers, and a diode detector. Measurements were made at a depth of 10 cm with an SSD of 100 cm for jaw-defined field sizes ranging from 3×3 cm 2 to 0.6×0.6 cm 2 , normalized to values at 5×5cm 2 . Correction factors for each field on each machine were calculated as the ratio of the detector response to the PSD response. Percent change of correction factors for the chambers are presented relative to the primary machine. Results: The Exradin A26 demonstrates a difference of 9% for 6×6mm 2 fields in both the 6FFF and 6MV beams. The A16 chamber demonstrates a 5%, and 3% difference in 6FFF and 6MV fields at the same field size respectively. The Edge diode exhibits less than 1.5% difference across both evaluated energies. Field sizes larger than 1.4×1.4cm2 demonstrated less than 1% difference for all detectors. Conclusion: Preliminary results suggest that class-specific correction may not be appropriate for micro-ionization chamber. For diode systems, the correction factor was substantially similar and may be useful for class-specific reference

  3. SU-C-304-07: Are Small Field Detector Correction Factors Strongly Dependent On Machine-Specific Characteristics?

    Energy Technology Data Exchange (ETDEWEB)

    Mathew, D; Tanny, S; Parsai, E; Sperling, N [University of Toledo Medical Center, Toledo, OH (United States)

    2015-06-15

    Purpose: The current small field dosimetry formalism utilizes quality correction factors to compensate for the difference in detector response relative to dose deposited in water. The correction factors are defined on a machine-specific basis for each beam quality and detector combination. Some research has suggested that the correction factors may only be weakly dependent on machine-to-machine variations, allowing for determinations of class-specific correction factors for various accelerator models. This research examines the differences in small field correction factors for three detectors across two Varian Truebeam accelerators to determine the correction factor dependence on machine-specific characteristics. Methods: Output factors were measured on two Varian Truebeam accelerators for equivalently tuned 6 MV and 6 FFF beams. Measurements were obtained using a commercial plastic scintillation detector (PSD), two ion chambers, and a diode detector. Measurements were made at a depth of 10 cm with an SSD of 100 cm for jaw-defined field sizes ranging from 3×3 cm{sup 2} to 0.6×0.6 cm{sup 2}, normalized to values at 5×5cm{sup 2}. Correction factors for each field on each machine were calculated as the ratio of the detector response to the PSD response. Percent change of correction factors for the chambers are presented relative to the primary machine. Results: The Exradin A26 demonstrates a difference of 9% for 6×6mm{sup 2} fields in both the 6FFF and 6MV beams. The A16 chamber demonstrates a 5%, and 3% difference in 6FFF and 6MV fields at the same field size respectively. The Edge diode exhibits less than 1.5% difference across both evaluated energies. Field sizes larger than 1.4×1.4cm2 demonstrated less than 1% difference for all detectors. Conclusion: Preliminary results suggest that class-specific correction may not be appropriate for micro-ionization chamber. For diode systems, the correction factor was substantially similar and may be useful for class

  4. Radioactive contamination of soil-vegetation cover in some southern areas of Semipalatinsk test site

    International Nuclear Information System (INIS)

    Tuleubaev, B.A.; Zharikov, S.K.

    2001-01-01

    The nature of radioactive contamination of meadow-pasture lands in the south of the Semipalatinsk test site (STS) has been studied using experimental data. Individual parameters of radionuclide transport from soil into plants depending upon soil type and sub-type, extent of land use for hay-making and pasturing, and other nature-climatic and anthropogenic factors have been determined. (author)

  5. PKA regulates calcineurin function through the phosphorylation of RCAN1: Identification of a novel phosphorylation site

    International Nuclear Information System (INIS)

    Kim, Seon Sook; Lee, Eun Hye; Lee, Kooyeon; Jo, Su-Hyun; Seo, Su Ryeon

    2015-01-01

    Calcineurin is a calcium/calmodulin-dependent phosphatase that has been implicated in T cell activation through the induction of nuclear factors of activated T cells (NFAT). We have previously suggested that endogenous regulator of calcineurin (RCAN1, also known as DSCR1) is targeted by protein kinase A (PKA) for the control of calcineurin activity. In the present study, we characterized the PKA-mediated phosphorylation site in RCAN1 by mass spectrometric analysis and revealed that PKA directly phosphorylated RCAN1 at the Ser 93. PKA-induced phosphorylation and the increase in the half-life of the RCAN1 protein were prevented by the substitution of Ser 93 with Ala (S93A). Furthermore, the PKA-mediated phosphorylation of RCAN1 at Ser 93 potentiated the inhibition of calcineurin-dependent pro-inflammatory cytokine gene expression by RCAN1. Our results suggest the presence of a novel phosphorylation site in RCAN1 and that its phosphorylation influences calcineurin-dependent inflammatory target gene expression. - Highlights: • We identify novel phosphorylation sites in RCAN1 by LC-MS/MS analysis. • PKA-dependent phosphorylation of RCAN1 at Ser 93 inhibits calcineurin-mediated intracellular signaling. • We show the immunosuppressive function of RCAN1 phosphorylation at Ser 93 in suppressing cytokine expression

  6. Chronic low-grade inflammation, lipid risk factors and mortality in functionally dependent elderly

    Directory of Open Access Journals (Sweden)

    Vasović Olga

    2010-01-01

    Full Text Available Background/Aim. It has been proved that a highly sensitive C-reactive protein (hsCRP can be used as an established marker of chronic inflammation for cardiovascular risk assessment. Since mean values of both low-density cholesterol (LDL-C and high-density lipoprotein cholesterol (HDL-C decrease during aging, the knowledge that increased hsCRP concentration predicts mortality (Mt would influence therapy and treatment outcome. The aim of this study was to examine importance of chronic low grade inflammation and its association with lipid risk factors for all-cause Mt in functionally dependent elderly. Methods. The participants of this longitudinal prospective study were 257 functionally dependent elderly aged 65-99 years. Baseline measurements: anthropometric measurements, blood pressure, fasting plasma total cholesterol (TC, triglyceride (TG, HDL-C, LDL-C, non- HDL-C, hemoglobin A1c (HbA1c were recorded and different lipid ratios were calculated. Inflammation was assessed by the levels of white blood cells, fibrinogen and hsCRP. The participants with hsCRP grater than 10 mg/L were excluded from the study. The residual participants (77.4% women were divided into three groups according to their hsCRP levels: a low (< 1 mg/L, n = 70, average (1 to 3 mg/L, n = 69, and high (3-10 mg/L, n = 69 hsCRP group. Associations of all-cause Mt with different risk factors were examined using logistic regression analysis. Results. The hsCRP level showed a significant positive correlation with waist (r = 0.199, p = 0.004 and hip (r = 0.187, p = 0.007 circumferences, body mass index (r = 0.143, p = 0.040 and serum triglyceride level (r = 0.139, p = 0.045 and significant negative correlation with HDL-C (r = -0.164, p = 0.018. Ratios TC/HDL-C and TG/HDL-C were significantly smaller in the low hsCRP group compared to the average hsCRP group (p = 0.019, p = 0.045, respectively and without significant differences compared with the high hsCRP group. Two years after the

  7. 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.

  8. Abscisic acid-dependent multisite phosphorylation regulates the activity of a transcription activator AREB1.

    Science.gov (United States)

    Furihata, Takashi; Maruyama, Kyonoshin; Fujita, Yasunari; Umezawa, Taishi; Yoshida, Riichiro; Shinozaki, Kazuo; Yamaguchi-Shinozaki, Kazuko

    2006-02-07

    bZIP-type transcription factors AREBs/ABFs bind an abscisic acid (ABA)-responsive cis-acting element named ABRE and transactivate downstream gene expression in Arabidopsis. Because AREB1 overexpression could not induce downstream gene expression, activation of AREB1 requires ABA-dependent posttranscriptional modification. We confirmed that ABA activated 42-kDa kinase activity, which, in turn, phosphorylated Ser/Thr residues of R-X-X-S/T sites in the conserved regions of AREB1. Amino acid substitutions of R-X-X-S/T sites to Ala suppressed transactivation activity, and multiple substitution of these sites resulted in almost complete suppression of transactivation activity in transient assays. In contrast, substitution of the Ser/Thr residues to Asp resulted in high transactivation activity without exogenous ABA application. A phosphorylated, transcriptionally active form was achieved by substitution of Ser/Thr in all conserved R-X-X-S/T sites to Asp. Transgenic plants overexpressing the phosphorylated active form of AREB1 expressed many ABA-inducible genes, such as RD29B, without ABA treatment. These results indicate that the ABA-dependent multisite phosphorylation of AREB1 regulates its own activation in plants.

  9. 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...... are established for 44 European regions with the help of the RAINS model, an integrated assessment model that combines information on regional emission levels with information on long-range atmospheric transport to estimate patterns of deposition and concentration for comparison with critical loads and thresholds...

  10. 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.

  11. 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.

  12. Sequence-specific 1H NMR assignments, secondary structure, and location of the calcium binding site in the first epidermal growth factor like domain of blood coagulation factor IX

    International Nuclear Information System (INIS)

    Huang, L.H.; Cheng, H.; Sweeney, W.V.; Pardi, A.; Tam, J.P.

    1991-01-01

    Factor IX is a blood clotting protein that contains three regions, including a γ-carboxyglutamic acid (Gla) domain, two tandemly connected epidermal growth factor like (EGF-like) domains, and a serine protease region. The protein exhibits a high-affinity calcium binding site in the first EGF0like domain, in addition to calcium binding in the Gla domain. The first EGF-like domain, factor IX (45-87), has been synthesized. Sequence-specific resonance assignment of the peptide has been made by using 2D NMR techniques, and its secondary structure has been determined. The protein is found to have two antiparallel β-sheets, and preliminary distance geometry calculations indicate that the protein has two domains, separated by Trp 28 , with the overall structure being similar to that of EGF. An NMR investigation of the calcium-bound first EGF-like domain indicates the presence and location of a calcium binding site involving residues on both strands of one of the β-sheets as well as the N-terminal region of the peptide. These results suggest that calcium binding in the first EGF-like domain could induce long-range (possibly interdomain) conformational changes in factor IX, rather than causing structural alterations in the EGF-like domain itself

  13. Induction of Epstein-Barr Virus Oncoprotein LMP1 by Transcription Factors AP-2 and Early B Cell Factor

    Science.gov (United States)

    Noda, Chieko; Narita, Yohei; Watanabe, Takahiro; Yoshida, Masahiro; Ashio, Keiji; Sato, Yoshitaka; Goshima, Fumi; Kanda, Teru; Yoshiyama, Hironori; Tsurumi, Tatsuya; Kimura, Hiroshi

    2016-01-01

    ABSTRACT Latent membrane protein 1 (LMP1) is a major oncogene essential for primary B cell transformation by Epstein-Barr virus (EBV). Previous studies suggested that some transcription factors, such as PU.1, RBP-Jκ, NF-κB, and STAT, are involved in this expression, but the underlying mechanism is unclear. Here, we identified binding sites for PAX5, AP-2, and EBF in the proximal LMP1 promoter (ED-L1p). We first confirmed the significance of PU.1 and POU domain transcription factor binding for activation of the promoter in latency III. We then focused on the transcription factors AP-2 and early B cell factor (EBF). Interestingly, among the three AP-2-binding sites in the LMP1 promoter, two motifs were also bound by EBF. Overexpression, knockdown, and mutagenesis in the context of the viral genome indicated that AP-2 plays an important role in LMP1 expression in latency II in epithelial cells. In latency III B cells, on the other hand, the B cell-specific transcription factor EBF binds to the ED-L1p and activates LMP1 transcription from the promoter. IMPORTANCE Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) is crucial for B cell transformation and oncogenesis of other EBV-related malignancies, such as nasopharyngeal carcinoma and T/NK lymphoma. Its expression is largely dependent on the cell type or condition, and some transcription factors have been implicated in its regulation. However, these previous reports evaluated the significance of specific factors mostly by reporter assay. In this study, we prepared point-mutated EBV at the binding sites of such transcription factors and confirmed the importance of AP-2, EBF, PU.1, and POU domain factors. Our results will provide insight into the transcriptional regulation of the major oncogene LMP1. PMID:26819314

  14. Response and binding elements for ligand-dependent positive transcription factors integrate positive and negative regulation of gene expression

    International Nuclear Information System (INIS)

    Rosenfeld, M.G.; Glass, C.K.; Adler, S.; Crenshaw, E.B. III; He, X.; Lira, S.A.; Elsholtz, H.P.; Mangalam, H.J.; Holloway, J.M.; Nelson, C.; Albert, V.R.; Ingraham, H.A.

    1988-01-01

    Accurate, regulated initiation of mRNA transcription by RNA polymerase II is dependent on the actions of a variety of positive and negative trans-acting factors that bind cis-acting promoter and enhancer elements. These transcription factors may exert their actions in a tissue-specific manner or function under control of plasma membrane or intracellular ligand-dependent receptors. A major goal in the authors' laboratory has been to identify the molecular mechanisms responsible for the serial activation of hormone-encoding genes in the pituitary during development and the positive and negative regulation of their transcription. The anterior pituitary gland contains phenotypically distinct cell types, each of which expresses unique trophic hormones: adrenocorticotropic hormone, thyroid-stimulating hormone, prolactin, growth hormone, and follicle-stimulating hormone/luteinizing hormone. The structurally related prolactin and growth hormone genes are expressed in lactotrophs and somatotrophs, respectively, with their expression virtually limited to the pituitary gland. The reported transient coexpression of these two structurally related neuroendocrine genes raises the possibility that the prolactin and growth hormone genes are developmentally controlled by a common factor(s)

  15. 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.

  16. 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

  17. Influencing Factors of University Students’ Use of Social Network Sites: An Empirical Analysis in China

    Directory of Open Access Journals (Sweden)

    Liqiong Liu

    2018-03-01

    Full Text Available This paper explores the influencing factors of Chinese university students in accepting and using social networking sites (SNS to propose measures and recommendations that can guide and help these students correctly use SNS. In addition, this paper aims to provide theoretical support in increasing user loyalty for the SNS service providers and attract new users. The correlation and multiple regression analyses showed that perceived value, enjoyment, and influence positively influence the intention of individuals to use SNS.

  18. The Role of Thought Suppression, Meta-Cognitive Factors and Negative Emotions in Prediction of Substance Dependency Disorder

    Directory of Open Access Journals (Sweden)

    Omid Saed

    2011-08-01

    Full Text Available Introduction: This study investigated the role of thought suppression, meta- cognitive factors, and negative emotions in predicting of substance dependency disorder. Method: Subjects were 70 patients with substance dependence disorder and 70 normal individuals (total 140. Substance dependants were selected of outpatient treatment centers and the normal sample was selected of the general population too. Sampling methods in both samples were convenience sampling. All people were assessed by MCQ-30, White Bear Suppression Inventory, and Beck’s Anxiety and Depression Questionnaires. For data analysis, discriminant analysis were used. Results: Negative meta-cognitive beliefs about worry, depression, and thought suppression were the most significant predictors of substance dependence disorder. Conclusion: Through meta-cognitive beliefs, thought suppression and negative emotion (especially depression, substance dependency disorder can be predicted. Based on this model can be used to take a substance dependency disorder prevention approach and psychotherapy approach (based on cognitive and meta-cognitive therapies. In addition, the findings of this research can be applied in clinical and counseling environments to help substance dependant clients.

  19. Down-regulation of endothelin binding sites in rat vascular smooth muscle cells

    International Nuclear Information System (INIS)

    Roubert, P.; Gillard, V.; Plas, P.; Chabrier, P.E.; Braquet, P.

    1990-01-01

    In cultured rat aortic smooth muscle cells, [ 125 I]endothelin (ET-1) bound to an apparent single class of high affinity recognition sites with a dissociation constant of 1.84 +/- 0.29 nmol/L and a maximum binding of 62 +/- 10.5 fmol/10(6) cells. The binding was not affected by calcium antagonists or vasoactive substances, including angiotensin II, arginine vasopressin, atrial natriuretic factor and bradykinin. Exposure of the cells to ET-1 (0.01 nmol/L to 10 nmol/L) resulted in an apparent dose-dependent reduction of the number of endothelin binding sites with no significant modification of its binding affinity. The time course of the down-regulation of ET-1 binding sites showed that this effect was present after 30 min incubation and persisted after 18 h. This indicates that down-regulation of ET-1 binding sites can modulate the activity of ET-1 and suggests a rapid internalization of ET-1 in vascular cells

  20. A Comparative study of Personality as a common pathway in HIV Sero-positive and Alcohol dependent cases on Five Factor Model

    Directory of Open Access Journals (Sweden)

    Kalpana Srivastava

    2016-01-01

    Full Text Available Aim: The aim of this study was to identify the personality traits of alcohol and human immunodeficiency virus (HIV-positive patients and to compare them with normal controls. Materials and Methods: This cross-sectional study included 100 consecutive patients with alcohol dependence and HIV each and a control group of 100 normal cases without any physical or psychiatric illness. A score of 2 or less on the General Health Questionnaire was taken as cutoff, and the participants were included in the study with written informed consent. All participants were assessed with the NEO personality inventory revised and sensation-seeking scale (SSS. Results: There were significant differences among the study group on all the five factors, i.e., neuroticism (N, extraversion (E, conscientiousness (C, openness to experience (O, and agreeableness (A. On factor “N,” HIV and alcohol group scored significantly more as compared to normal group. Odds ratio revealed high neuroticism to be a risk factor in alcohol-dependent and HIV cases (P < 0.05. The normal group scored significantly higher on factor “E” as compared to HIV and alcohol cases. High scores on factor “E” and “C” have a protective. Odds ratio found low score of factor “C” as a risk factor; however, “O” did not emerge as a risk factor. The logistic regression revealed that high scores on “N” and “E” and low “A” score had a significant association with alcohol dependence (P < 0.05. Among HIV cases, high score on “N” and “E” and low “C” score emerged significant. Alcohol cases scored significantly more on boredom susceptibility (BS on SSS as compared to HIV and normal controls. On disinhibition (DIS, HIV cases and alcohol cases scored significantly higher as compared to normal group (P < 0.05. Conclusion: High “N” scores on NEO personality inventory are significantly associated with alcohol dependence and HIV while high scores on “E” and “C” have a

  1. Nerve growth factor enhances the CRE-dependent transcriptional activity activated by nobiletin in PC12 cells.

    Science.gov (United States)

    Takito, Jiro; Kimura, Junko; Kajima, Koji; Uozumi, Nobuyuki; Watanabe, Makoto; Yokosuka, Akihito; Mimaki, Yoshihiro; Nakamura, Masanori; Ohizumi, Yasushi

    2016-07-01

    Prevention and treatment of Alzheimer disease are urgent problems for elderly people in developed countries. We previously reported that nobiletin, a poly-methoxylated flavone from the citrus peel, improved the symptoms in various types of animal models of memory loss and activated the cAMP responsive element (CRE)-dependent transcription in PC12 cells. Nobiletin activated the cAMP/PKA/MEK/Erk/MAPK signaling pathway without using the TrkA signaling activated by nerve growth factor (NGF). Here, we examined the effect of combination of nobiletin and NGF on the CRE-dependent transcription in PC12 cells. Although NGF alone had little effect on the CRE-dependent transcription, NGF markedly enhanced the CRE-dependent transcription induced by nobiletin. The NGF-induced enhancement was neutralized by a TrkA antagonist, K252a. This effect of NGF was effective on the early signaling event elicited by nobiletin. These results suggested that there was crosstalk between NGF and nobiletin signaling in activating the CRE-dependent transcription in PC12 cells.

  2. Pre-operative and early post-operative factors associated with surgical site infection after laparoscopic sleeve gastrectomy.

    Science.gov (United States)

    Ruiz-Tovar, Jaime; Oller, Inmaculada; Llavero, Carolina; Arroyo, Antonio; Muñoz, Jose Luis; Calero, Alicia; Diez, María; Zubiaga, Lorea; Calpena, Rafael

    2013-08-01

    Surgical procedures on obese patients are expected to have a high incidence of surgical site infection (SSI). The identification of pre-operative or early post-operative risk factors for SSI may help the surgeon to identify subjects in risk and adequately optimize their status. We conducted a study of the association of comorbidities and pre- and post-operative analytical variables with SSI following laparoscopic sleeve gastrectomy for the treatment of morbid obesity. We performed a prospective study of all morbidly obese patients undergoing laparoscopic sleeve gastrectomy as a bariatric procedure between 2007 and 2011. An association of clinical and analytical variables with SSI was investigated. The study included 40 patients with a mean pre-operative body mass index (BMI) of 51.2±7.9 kg/m(2). Surgical site infections appeared in three patients (7.5%), of whom two had an intra-abdominal abscess located in the left hypochondrium and the third had a superficial incisional SSI. Pre-operatively, a BMI >45 kg/m(2) (OR 8.7; p=0.008), restrictive disorders identified by pulmonary function tests (OR 10.0; p=0.012), a serum total protein concentration 30 mcg/dL (OR 13.0; p=0.003), and a mean corpuscular volume (MCV) operative SSI. Post-operatively, a serum glucose >128 mg/dL (OR 4.7; p=0.012) and hemoglobin operative anemia and hyperglycemia as risk factors for SSI. In these situations, the surgeon must be aware of and seek to control these risk factors.

  3. Modifiable risk factors of ecstasy use: risk perception, current dependence, perceived control, and depression

    Science.gov (United States)

    Leung, Kit Sang; Ben Abdallah, Arbi; Cottler, Linda B.

    2009-01-01

    Risk perception, perceived behavioral control of obtaining ecstasy (PBC-obtaining), current ecstasy dependence, and recent depression have been associated with past ecstasy use, however, their utility in predicting ecstasy use has not been demonstrated. This study aimed to determine whether these four modifiable risk factors could predict ecstasy use after controlling for socio-demographic covariates and recent polydrug use. Data from 601 ecstasy users in the National Institute on Drug Abuse funded TriCity Study of Club Drug Use, Abuse and Dependence were analyzed using multivariate logistic regression. Participants were interviewed twice within a 2-week period using standardized instruments. Thirteen percent (n=80) of the participants reported using ecstasy between the two interviews. Low risk perception, high PBC-obtaining (an estimated ecstasy procurement time ecstasy dependence were statistically associated with ecstasy use between the two interviews. Recent depression was not a significant predictor. Despite not being a target predictor, recent polydrug use was also statistically associated with ecstasy use. The present findings may inform the development of interventions targeting ecstasy users. PMID:19880258

  4. 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

  5. Small Wind Site Assessment Guidelines

    Energy Technology Data Exchange (ETDEWEB)

    Olsen, Tim [Advanced Energy Systems LLC, Eugene, OR (United States); Preus, Robert [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2015-09-01

    Site assessment for small wind energy systems is one of the key factors in the successful installation, operation, and performance of a small wind turbine. A proper site assessment is a difficult process that includes wind resource assessment and the evaluation of site characteristics. These guidelines address many of the relevant parts of a site assessment with an emphasis on wind resource assessment, using methods other than on-site data collection and creating a small wind site assessment report.

  6. TALE activators regulate gene expression in a position- and strand-dependent manner in mammalian cells.

    Science.gov (United States)

    Uhde-Stone, Claudia; Cheung, Edna; Lu, Biao

    2014-01-24

    Transcription activator-like effectors (TALEs) are a class of transcription factors that are readily programmable to regulate gene expression. Despite their growing popularity, little is known about binding site parameters that influence TALE-mediated gene activation in mammalian cells. We demonstrate that TALE activators modulate gene expression in mammalian cells in a position- and strand-dependent manner. To study the effects of binding site location, we engineered TALEs customized to recognize specific DNA sequences located in either the promoter or the transcribed region of reporter genes. We found that TALE activators robustly activated reporter genes when their binding sites were located within the promoter region. In contrast, TALE activators inhibited the expression of reporter genes when their binding sites were located on the sense strand of the transcribed region. Notably, this repression was independent of the effector domain utilized, suggesting a simple blockage mechanism. We conclude that TALE activators in mammalian cells regulate genes in a position- and strand-dependent manner that is substantially different from gene activation by native TALEs in plants. These findings have implications for optimizing the design of custom TALEs for genetic manipulation in mammalian cells. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. CONTROLLING FACTORS OF POTENTIAL EVAPOTRANSPIRATION ABOVE GRASSLAND IN HUMID AND ARID AREA

    Directory of Open Access Journals (Sweden)

    . Yanto

    2013-05-01

    Full Text Available Potential evapotranspiration (PET is an importance process in water balance studies controlled by a number of meteorological factors such as temperature, wind speed, atmospheric pressure, solar radiation, vapor pressure gradient, relative humidity and biological factors such as vegetation type, canopy height and plant density that varied in time-scale and in spatial scale. Of all those variables, determining the most controlling factors of evapotranspiration in humid and arid area is of interest of this paper. Two sites representing humid and arid area i.e. Fermi Prairie site in Illinois and Audubon Research Ranch in Arizona respectively were investigated in this study.  The flux data employed in this study was acquired from Ameriflux Netwotk. Penmann-Monteith formula is employed in to estimate evapotranspiration rate in both sites. The result shows that the PET is in dependence on the considered meteorological factor such as shortwave radiation, vapor pressure, air temperature, wind speed, net radiation and vapor pressure deficit. It is also can be inferred from the analysis that PET is also strongly controlled by vegetation factors represented as stomatal resistance. Keywords: Potential evapotranspiration, Penmann-Monteith, humid, arid.

  8. Myth and Reality in Hydrogeological Site Characterization at DD and R Sites

    International Nuclear Information System (INIS)

    Rubin, Yoram

    2008-01-01

    . Different sites justify different definitions, depending on many environmental, economical and social factors. Despite the lack of consensus, it seems that a good place to start is in fact to recognize that there is a room for all these factors, and a need to balance between them. As experience is gained, through research and discussions among DD and R stakeholders, this may become less of a challenge. Regulations need to recognize the possibility of developing alternative, site-specific characterization strategies based on the various length and time scales that define specific environmental problems, including length scales of heterogeneity, source dimensions and distance to environmental targets. For example, point and distributed sources justify different characterization strategies. Development of problem- or site-specific strategies will create the context for defining innovative efficient DD and R strategies. Innovation in characterization can will also follow from recognizing the specific physiological aspects of the toxins and the related uncertainty. This will open the door for improving risk characterization not only from the hydrologic perspective, but also form the physiologic one

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  10. Taste perception: Risk factor or protection for dependents during drug use cessation

    Directory of Open Access Journals (Sweden)

    Carla Rosane Paz Arruda Teo

    2014-08-01

    Full Text Available The increase in appetite and, consequently, in body weight, evidenced in the majority of addicts under treatment, may be related to taste, since heavy drug use can lead to changes in taste buds. This study aimed to investigate the association between taste perception and nutritional status of drug addicts under treatment. The study was conducted in two therapeutic communities in the municipality of Chapecó, Santa Catarina state, with 39 male addicts over 18 years old. Primary data on weight and height were collected for assessment of nutritional status, and a taste acuity test was applied; also, secondary data were collected on age, length of stay, types of drugs used, and age of drug use onset, from the addicts’ records. It was possible to observe that 56.5% of dependents were at nutritional risk for being overweight. Taste acuity significantly differed for the basic tastes evaluated (p= 0.014, being higher for salty (94.9%, followed by sweet (89.7%, acid (79.5%, and bitter (38, 5% tastes, but it was not associated with the study variables. We conclude that the drug use cessation can have a similar effect to that of caloric deprivation on the taste acuity of dependents, interfering on excessive weight gain. However, it is suggested that the improvement of taste perception be oriented in the therapeutic setting, so that it becomes, in these conditions, a protection factor for dependents, strengthening them to overcome their condition of vulnerability.

  11. 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.

  12. Risk factors and outcomes of organ-space surgical site infections after elective colon and rectal surgery

    Directory of Open Access Journals (Sweden)

    Aina Gomila

    2017-04-01

    Full Text Available Abstract Background Organ-space surgical site infections (SSI are the most serious and costly infections after colorectal surgery. Most previous studies of risk factors for SSI have analysed colon and rectal procedures together. The aim of the study was to determine whether colon and rectal procedures have different risk factors and outcomes for organ-space SSI. Methods A multicentre observational prospective cohort study of adults undergoing elective colon and rectal procedures at 10 Spanish hospitals from 2011 to 2014. Patients were followed up until 30 days post-surgery. Surgical site infection was defined according to the Centers for Disease Control and Prevention criteria. Oral antibiotic prophylaxis (OAP was considered as the administration of oral antibiotics the day before surgery combined with systemic intravenous antibiotic prophylaxis. Results Of 3,701 patients, 2,518 (68% underwent colon surgery and 1,183 (32% rectal surgery. In colon surgery, the overall SSI rate was 16.4% and the organ-space SSI rate was 7.9%, while in rectal surgery the rates were 21.6% and 11.5% respectively (p < 0.001. Independent risk factors for organ-space SSI in colon surgery were male sex (Odds ratio -OR-: 1.57, 95% CI: 1.14–2.15 and ostomy creation (OR: 2.65, 95% CI: 1.8–3.92 while laparoscopy (OR: 0.5, 95% CI: 0.38–0.69 and OAP combined with intravenous antibiotic prophylaxis (OR: 0.7, 95% CI: 0.51–0.97 were protective factors. In rectal surgery, independent risk factors for organ-space SSI were male sex (OR: 2.11, 95% CI: 1.34–3.31 and longer surgery (OR: 1.49, 95% CI: 1.03–2.15, whereas OAP with intravenous antibiotic prophylaxis (OR: 0.49, 95% CI: 0.32–0.73 was a protective factor. Among patients with organ-space SSI, we found a significant difference in the overall 30-day mortality, being higher in colon surgery than in rectal surgery (11.5% vs 5.1%, p = 0.04. Conclusions Organ-space SSI in colon and rectal surgery has some

  13. Model of a ternary complex between activated factor VII, tissue factor and factor IX.

    Science.gov (United States)

    Chen, Shu-wen W; Pellequer, Jean-Luc; Schved, Jean-François; Giansily-Blaizot, Muriel

    2002-07-01

    Upon binding to tissue factor, FVIIa triggers coagulation by activating vitamin K-dependent zymogens, factor IX (FIX) and factor X (FX). To understand recognition mechanisms in the initiation step of the coagulation cascade, we present a three-dimensional model of the ternary complex between FVIIa:TF:FIX. This model was built using a full-space search algorithm in combination with computational graphics. With the known crystallographic complex FVIIa:TF kept fixed, the FIX docking was performed first with FIX Gla-EGF1 domains, followed by the FIX protease/EGF2 domains. Because the FIXa crystal structure lacks electron density for the Gla domain, we constructed a chimeric FIX molecule that contains the Gla-EGF1 domains of FVIIa and the EGF2-protease domains of FIXa. The FVIIa:TF:FIX complex has been extensively challenged against experimental data including site-directed mutagenesis, inhibitory peptide data, haemophilia B database mutations, inhibitor antibodies and a novel exosite binding inhibitor peptide. This FVIIa:TF:FIX complex provides a powerful tool to study the regulation of FVIIa production and presents new avenues for developing therapeutic inhibitory compounds of FVIIa:TF:substrate complex.

  14. Analysis of functional importance of binding sites in the Drosophila gap gene network model.

    Science.gov (United States)

    Kozlov, Konstantin; Gursky, Vitaly V; Kulakovskiy, Ivan V; Dymova, Arina; Samsonova, Maria

    2015-01-01

    The statistical thermodynamics based approach provides a promising framework for construction of the genotype-phenotype map in many biological systems. Among important aspects of a good model connecting the DNA sequence information with that of a molecular phenotype (gene expression) is the selection of regulatory interactions and relevant transcription factor bindings sites. As the model may predict different levels of the functional importance of specific binding sites in different genomic and regulatory contexts, it is essential to formulate and study such models under different modeling assumptions. We elaborate a two-layer model for the Drosophila gap gene network and include in the model a combined set of transcription factor binding sites and concentration dependent regulatory interaction between gap genes hunchback and Kruppel. We show that the new variants of the model are more consistent in terms of gene expression predictions for various genetic constructs in comparison to previous work. We quantify the functional importance of binding sites by calculating their impact on gene expression in the model and calculate how these impacts correlate across all sites under different modeling assumptions. The assumption about the dual interaction between hb and Kr leads to the most consistent modeling results, but, on the other hand, may obscure existence of indirect interactions between binding sites in regulatory regions of distinct genes. The analysis confirms the previously formulated regulation concept of many weak binding sites working in concert. The model predicts a more or less uniform distribution of functionally important binding sites over the sets of experimentally characterized regulatory modules and other open chromatin domains.

  15. Ontogeny of basic fibroblast growth factor binding sites in mouse ocular tissues

    International Nuclear Information System (INIS)

    Fayein, N.A.; Courtois, Y.; Jeanny, J.C.

    1990-01-01

    Basic fibroblast growth factor (bFGF) binding to ocular tissues has been studied by autoradiographical and biochemical approaches directly performed on sections during mouse embryonic and postnatal development. Frozen sections of embryos (9 to 18 days), newborns, and adults (1 day to 6 months) were incubated with iodinated bFGF. One specific FGF binding site (KD = 2.5 nM) is colocalized with heparan sulfate proteoglycans of the basement membranes and is heparitinase sensitive. It first appears at Day 9 around the neural tube, the optic vesicles, and below the head ectoderm and by Day 14 of embryonic development is found in all basement membranes of the eye. At Day 16, very intensely labeled patches appear, corresponding to mast cells which have been characterized by metachromatic staining of their heparin-rich granulations with toluidine blue. In addition to the latter binding, we have also observed a general diffuse distribution of silver grains on all tissues and preferentially in the ecto- and neuroectodermic tissues. From Days 17-18, there is heterogeneous labeling inside the retina, localized in the pigmented epithelium and in three different layers colocalized with the inner and outer plexiform layers and with the inner segments of the photoreceptors. This binding is heparitinase resistant but N-glycanase sensitive and may represent a second specific binding site corresponding to cellular FGF receptors (KD = 280 pM). Both types of binding patterns observed suggest a significant role for bFGF in eye development and physiology

  16. 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.

  17. 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

  18. Mental stress and psychosocial factors at work in relation to multiple-site musculoskeletal pain: a longitudinal study of kitchen workers.

    Science.gov (United States)

    Haukka, Eija; Leino-Arjas, Päivi; Ojajärvi, Anneli; Takala, Esa-Pekka; Viikari-Juntura, Eira; Riihimäki, Hilkka

    2011-04-01

    Among 385 female kitchen workers, we examined (1) whether mental stress and psychosocial factors at work (job control, skill discretion, supervisor support, co-worker relationships, and hurry) predict multiple-site musculoskeletal pain (MSP; defined as pain at ≥ 3 of seven sites) and (2) reversedly, whether MSP predicts these psychosocial factors. Data were collected by questionnaire at 3-month intervals during 2 years. Trajectory analysis was applied. Four trajectories of MSP prevalence emerged: Low, Descending, Ascending, and High. For the psychosocial factors, a two-trajectory model (Ascending or High vs. Low) yielded the best fit. In logistic regression analysis, with the Low MSP trajectory as reference, poor co-worker relationships (odds ratio [OR] 3.9), mental stress (3.1) and hurry (2.1) at baseline predicted belonging to the High MSP trajectory. Also MSP at baseline predicted the trajectories (Ascending vs. Low) of low job control (2.2) and mental stress (3.2). Adverse changes in most psychosocial factors were associated with belonging to the High (ORs between 2.3 and 8.6) and Ascending (2.7-5.5) MSP trajectories. In generalized estimating equations, time-lagged by 3 months, all psychosocial factors but two predicted MSP (1.4-2.1), allowing, e.g. for MSP at baseline, and vice versa, MSP predicted low job control, low supervisor support, and mental stress (1.4-2.0), after adjustment for e.g. the relevant psychosocial factor at baseline. In conclusion, we found that several psychosocial factors predicted MSP and that MSP predicted several psychosocial factors. The results suggest a cumulative process in which adverse psychosocial factors and MSP influence each other. Copyright © 2010 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

  19. Metal toxicity characterization factors for marine ecosystems: considering the importance of the estuary for freshwater emissions

    DEFF Research Database (Denmark)

    Dong, Yan; Rosenbaum, Ralph K.; Hauschild, Michael Zwicky

    2017-01-01

    The study develops site-dependent characterization factors (CFs) for marine ecotoxicity of metals emitted to freshwater, taking their passage of the estuary into account. To serve life cycle assessment (LCA) studies where emission location is often unknown, site-generic marine CFs were developed...... with an estuary removal process to calculate FF. BF and EF were taken from Dong et al. Environ Sci Technol 50:269–278 (2016). Site-generic marine CFs were derived from site-dependent marine CFs. Different averaging principles were tested, and the approach representing estuary discharge rate was identified...... between both methods. Accounting for estuary removal particularly influences marine ecotoxicity CFs for emission to freshwater of metals that have a strong tendency to complex-bind to particles. It indicates the importance of including estuary in the characterization modelling when dealing with those...

  20. Determination of the Sites with Conservation Priority in Research Forests of Yasouj University Based on Physiographic Factors

    Directory of Open Access Journals (Sweden)

    R. Zolfaghari

    2013-03-01

    Full Text Available Regarding high economic and conservative values of Zagros forests, and livelihood dependency of local people these recourses, determination of sites with higher conservation index can help us to maintain biodiversity of these forests more efficiently. Therefore, 49 plots with 450 m2 in area accompanied by 1, 10 and 45 m2 subplots were taken as systematic random design in research forests of Yasouj University. The number of species in each plot and subplot was recorded. The conservation values for different physiographic regions of forest were calculated using integrative parameters such as the number of species per plot, number of rare species per plot, number of tree species per plot, Jaccards similarity coefficient and slope of species-log(area. Comparing the conservation index in different physiographic sites revealed that the areas located in the north, hills and lower altitudes can be considered for in situ conservation due to higher number of trees, rare species and total plant species, species-log (area slope and lower amount of Jaccard similarity coefficient. But, vegetative sites located in lower slopes and south, because of lower conservation index, can be used for other multipurpose forestry activities. Using this index for different forest areas can be potentially conducted for better conservation and management of Zagros forests.

  1. GIS-based approach for optimized siting of municipal solid waste landfill

    International Nuclear Information System (INIS)

    Sumathi, V.R.; Natesan, Usha; Sarkar, Chinmoy

    2008-01-01

    The exponential rise in the urban population of the developing countries in the past few decades and the resulting accelerated urbanization phenomenon has brought to the fore the necessity to develop environmentally sustainable and efficient waste management systems. Sanitary landfill constitutes one of the primary methods of municipal solid waste disposal. Optimized siting decisions have gained considerable importance in order to ensure minimum damage to the various environmental sub-components as well as reduce the stigma associated with the residents living in its vicinity, thereby enhancing the overall sustainability associated with the life cycle of a landfill. This paper addresses the siting of a new landfill using a multi-criteria decision analysis (MCDA) and overlay analysis using a geographic information system (GIS). The proposed system can accommodate new information on the landfill site selection by updating its knowledge base. Several factors are considered in the siting process including geology, water supply resources, land use, sensitive sites, air quality and groundwater quality. Weightings were assigned to each criterion depending upon their relative importance and ratings in accordance with the relative magnitude of impact. The results from testing the system using different sites show the effectiveness of the system in the selection process

  2. Quantitative PET Imaging of Tissue Factor Expression Using 18F-Labeled Active Site-Inhibited Factor VII.

    Science.gov (United States)

    Nielsen, Carsten H; Erlandsson, Maria; Jeppesen, Troels E; Jensen, Mette M; Kristensen, Lotte K; Madsen, Jacob; Petersen, Lars C; Kjaer, Andreas

    2016-01-01

    Tissue factor (TF) is upregulated in many solid tumors, and its expression is linked to tumor angiogenesis, invasion, metastasis, and prognosis. A noninvasive assessment of tumor TF expression status is therefore of obvious clinical relevance. Factor VII is the natural ligand to TF. Here we report the development of a new PET tracer for specific imaging of TF using an (18)F-labeled derivative of factor VII. Active site-inhibited factor VIIa (FVIIai) was obtained by inactivation with phenylalanine-phenylalanine-arginine-chloromethyl ketone. FVIIai was radiolabeled with N-succinimidyl 4-(18)F-fluorobenzoate and purified. The corresponding product, (18)F-FVIIai, was injected into nude mice with subcutaneous human pancreatic xenograft tumors (BxPC-3) and investigated using small-animal PET/CT imaging 1, 2, and 4 h after injection. Ex vivo biodistribution was performed after the last imaging session, and tumor tissue was preserved for molecular analysis. A blocking experiment was performed in a second set of mice. The expression pattern of TF in the tumors was visualized by immunohistochemistry and the amount of TF in tumor homogenates was measured by enzyme-linked immunosorbent assay and correlated with the uptake of (18)F-FVIIai in the tumors measured in vivo by PET imaging. The PET images showed high uptake of (18)F-FVIIai in the tumor regions, with a mean uptake of 2.5 ± 0.3 percentage injected dose per gram (%ID/g) (mean ± SEM) 4 h after injection of 7.3-9.3 MBq of (18)F-FVIIai and with an average maximum uptake in the tumors of 7.1 ± 0.7 %ID/g at 4 h. In comparison, the muscle uptake was 0.2 ± 0.01 %ID/g at 4 h. At 4 h, the tumors had the highest uptake of any organ. Blocking with FVIIai significantly reduced the uptake of (18)F-FVIIai from 2.9 ± 0.1 to 1.4 ± 0.1 %ID/g (P < 0.001). The uptake of (18)F-FVIIai measured in vivo by PET imaging correlated (r = 0.72, P < 0.02) with TF protein level measured ex vivo. (18)F-FVIIai is a promising PET tracer for

  3. 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.

  4. SiteFind: A software tool for introducing a restriction site as a marker for successful site-directed mutagenesis

    Directory of Open Access Journals (Sweden)

    Evans Paul M

    2005-12-01

    and a double point mutation in the wild-type sequence for Krüppel-like factor 4, an epithelium-specific transcription factor. Conclusion SiteFind is an intuitive, web-based program that enables the user to introduce a novel restriction site into the mutated nucleotide sequence for use as a marker of successful mutation. It is freely available from http://www.utmb.edu/scccb/software/sitefind.html

  5. Quantifying Fast and Slow Responses of Terrestrial Carbon Exchange across a Water Availability Gradient in North American Flux Sites

    Science.gov (United States)

    Biederman, J. A.; Scott, R. L.; Goulden, M.

    2014-12-01

    Climate change is predicted to increase the frequency and severity of water limitation, altering terrestrial ecosystems and their carbon exchange with the atmosphere. Here we compare site-level temporal sensitivity of annual carbon fluxes to interannual variations in water availability against cross-site spatial patterns over a network of 19 eddy covariance flux sites. This network represents one order of magnitude in mean annual productivity and includes western North American desert shrublands and grasslands, savannahs, woodlands, and forests with continuous records of 4 to 12 years. Our analysis reveals site-specific patterns not identifiable in prior syntheses that pooled sites. We interpret temporal variability as an indicator of ecosystem response to annual water availability due to fast-changing factors such as leaf stomatal response and microbial activity, while cross-site spatial patterns are used to infer ecosystem adjustment to climatic water availability through slow-changing factors such as plant community and organic carbon pools. Using variance decomposition, we directly quantify how terrestrial carbon balance depends on slow- and fast-changing components of gross ecosystem production (GEP) and total ecosystem respiration (TER). Slow factors explain the majority of variance in annual net ecosystem production (NEP) across the dataset, and their relative importance is greater at wetter, forest sites than desert ecosystems. Site-specific offsets from spatial patterns of GEP and TER explain one third of NEP variance, likely due to slow-changing factors not directly linked to water, such as disturbance. TER and GEP are correlated across sites as previously shown, but our site-level analysis reveals surprisingly consistent linear relationships between these fluxes in deserts and savannahs, indicating fast coupling of TER and GEP in more arid ecosystems. Based on the uncertainty associated with slow and fast factors, we suggest a framework for improved

  6. Cerebral microbleeds: different prevalence, topography, and risk factors depending on dementia diagnosis—the Karolinska Imaging Dementia Study.

    Science.gov (United States)

    Shams, S; Martola, J; Granberg, T; Li, X; Shams, M; Fereshtehnejad, S M; Cavallin, L; Aspelin, P; Kristoffersen-Wiberg, M; Wahlund, L O

    2015-04-01

    Cerebral microbleeds are thought to represent cerebral amyloid angiopathy when in lobar regions of the brain and hypertensive arteriopathy when in deep and infratentorial locations. By studying cerebral microbleeds, their topography, and risk factors, we aimed to gain an insight into the vascular and amyloid pathology of dementia diagnoses and increase the understanding of cerebral microbleeds in dementia. We analyzed 1504 patients (53% women; mean age, 63 ± 10 years; 10 different dementia diagnoses) in this study. All patients underwent MR imaging as part of the dementia investigation, and all their clinical parameters were recorded. Among the 1504 patients with dementia, 22% had cerebral microbleeds. Cerebral microbleed topography was predominantly lobar (P = .01) and occipital (P = .007) in Alzheimer disease. Patients with cerebral microbleeds were significantly older (P < .001), were more frequently male (P < .001), had lower cognitive scores (P = .006), and more often had hypertension (P < .001). Risk factors for cerebral microbleeds varied depending on the dementia diagnosis. Odds ratios for having cerebral microbleeds increased with the number of risk factors (hypertension, hyperlipidemia, diabetes, male sex, and age 65 and older) in the whole patient group and increased differently in the separate dementia diagnoses. Prevalence, topography, and risk factors of cerebral microbleeds vary depending on the dementia diagnosis and reflect the inherent pathology of different dementia diagnoses. Because cerebral microbleeds are seen as possible predictors of intracerebral hemorrhage, their increasing prevalence with an increasing number of risk factors, as shown in our study, may require taking the number of risk factors into account when deciding on anticoagulant therapy in dementia. © 2015 by American Journal of Neuroradiology.

  7. The site selection process

    International Nuclear Information System (INIS)

    Kittel, J.H.

    1989-01-01

    One of the most arduous tasks associated with the management of radioactive wastes is the siting of new disposal facilities. Experience has shown that the performance of the disposal facility during and after disposal operations is critically dependent on the characteristics of the site itself. The site selection process consists of defining needs and objectives, identifying geographic regions of interest, screening and selecting candidate sites, collecting data on the candidate sites, and finally selecting the preferred site. Before the site selection procedures can be implemented, however, a formal legal system must be in place that defines broad objectives and, most importantly, clearly establishes responsibilities and accompanying authorities for the decision-making steps in the procedure. Site selection authorities should make every effort to develop trust and credibility with the public, local officials, and the news media. The responsibilities of supporting agencies must also be spelled out. Finally, a stable funding arrangement must be established so that activities such as data collection can proceed without interruption. Several examples, both international and within the US, are given

  8. 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.

  9. Gains and Losses of Transcription Factor Binding Sites in Saccharomyces cerevisiae and Saccharomyces paradoxus

    Science.gov (United States)

    Schaefke, Bernhard; Wang, Tzi-Yuan; Wang, Chuen-Yi; Li, Wen-Hsiung

    2015-01-01

    Gene expression evolution occurs through changes in cis- or trans-regulatory elements or both. Interactions between transcription factors (TFs) and their binding sites (TFBSs) constitute one of the most important points where these two regulatory components intersect. In this study, we investigated the evolution of TFBSs in the promoter regions of different Saccharomyces strains and species. We divided the promoter of a gene into the proximal region and the distal region, which are defined, respectively, as the 200-bp region upstream of the transcription starting site and as the 200-bp region upstream of the proximal region. We found that the predicted TFBSs in the proximal promoter regions tend to be evolutionarily more conserved than those in the distal promoter regions. Additionally, Saccharomyces cerevisiae strains used in the fermentation of alcoholic drinks have experienced more TFBS losses than gains compared with strains from other environments (wild strains, laboratory strains, and clinical strains). We also showed that differences in TFBSs correlate with the cis component of gene expression evolution between species (comparing S. cerevisiae and its sister species Saccharomyces paradoxus) and within species (comparing two closely related S. cerevisiae strains). PMID:26220934

  10. 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".

  11. Construction of Site Risk Model using Individual Unit Risk Model in a NPP Site

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Ho Gon; Han, Sang Hoon [KAERI, Daejeon (Korea, Republic of)

    2016-05-15

    Since Fukushima accident, strong needs to estimate site risk has been increased to identify the possibility of re-occurrence of such a tremendous disaster and prevent such a disaster. Especially, in a site which has large fleet of nuclear power plants, reliable site risk assessment is very emergent to confirm the safety. In Korea, there are several nuclear power plant site which have more than 6 NPPs. In general, risk model of a NPP in terms of PSA is very complicated and furthermore, it is expected that the site risk model is more complex than that. In this paper, the method for constructing site risk model is proposed by using individual unit risk model. Procedure for the development of site damage (risk) model was proposed in the present paper. Since the site damage model is complicated in the sense of the scale of the system and dependency of the components of the system, conventional method may not be applicable in many side of the problem.

  12. 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.

  13. Sivers asymmetry in the pion induced Drell-Yan process at COMPASS within transverse momentum dependent factorization

    Science.gov (United States)

    Wang, Xiaoyu; Lu, Zhun

    2018-03-01

    We investigate the Sivers asymmetry in the pion-induced single polarized Drell-Yan process in the theoretical framework of the transverse momentum dependent factorization up to next-to-leading logarithmic order of QCD. Within the TMD evolution formalism of parton distribution functions, the recently extracted nonperturbative Sudakov form factor for the pion distribution functions as well as the one for the Sivers function of the proton are applied to numerically estimate the Sivers asymmetry in the π-p Drell-Yan at the kinematics of the COMPASS at CERN. In the low b region, the Sivers function in b -space can be expressed as the convolution of the perturbatively calculable hard coefficients and the corresponding collinear correlation function, of which the Qiu-Sterman function is the most relevant one. The effect of the energy-scale dependence of the Qiu-Sterman function to the asymmetry is also studied. We find that our prediction on the Sivers asymmetries as functions of xp, xπ, xF and q⊥ is consistent with the recent COMPASS measurement.

  14. Site selection

    International Nuclear Information System (INIS)

    Olsen, C.W.

    1983-07-01

    The conditions and criteria for selecting a site for a nuclear weapons test at the Nevada Test Site are summarized. Factors considered are: (1) scheduling of drill rigs, (2) scheduling of site preparation (dirt work, auger hole, surface casing, cementing), (3) schedule of event (when are drill hole data needed), (4) depth range of proposed W.P., (5) geologic structure (faults, Pz contact, etc.), (6) stratigraphy (alluvium, location of Grouse Canyon Tuff, etc.), (7) material properties (particularly montmorillonite and CO 2 content), (8) water table depth, (9) potential drilling problems (caving), (10) adjacent collapse craters and chimneys, (11) adjacent expended but uncollapsed sites, (12) adjacent post-shot or other small diameter holes, (13) adjacent stockpile emplacement holes, (14) adjacent planned events (including LANL), (15) projected needs of Test Program for various DOB's and operational separations, and (16) optimal use of NTS real estate

  15. HHM motif at the CuH-site of peptidylglycine monooxygenase is a pH-dependent conformational switch.

    Science.gov (United States)

    Kline, Chelsey D; Mayfield, Mary; Blackburn, Ninian J

    2013-04-16

    Peptidylglycine monooxygenase is a copper-containing enzyme that catalyzes the amidation of neuropeptides hormones, the first step of which is the conversion of a glycine-extended pro-peptide to its α-hydroxyglcine intermediate. The enzyme contains two mononuclear Cu centers termed CuM (ligated to imidazole nitrogens of H242, H244 and the thioether S of M314) and CuH (ligated to imidazole nitrogens of H107, H108, and H172) with a Cu-Cu separation of 11 Å. During catalysis, the M site binds oxygen and substrate, and the H site donates the second electron required for hydroxylation. The WT enzyme shows maximum catalytic activity at pH 5.8 and undergoes loss of activity at lower pHs due to a protonation event with a pKA of 4.6. Low pH also causes a unique structural transition in which a new S ligand coordinates to copper with an identical pKA, manifest by a large increase in Cu-S intensity in the X- ray absorption spectroscopy. In previous work (Bauman, A. T., Broers, B. A., Kline, C. D., and Blackburn, N. J. (2011) Biochemistry 50, 10819-10828), we tentatively assigned the new Cu-S interaction to binding of M109 to the H-site (part of an HHM conserved motif common to all but one member of the family). Here we follow up on these findings via studies on the catalytic activity, pH-activity profiles, and spectroscopic (electron paramagnetic resonance, XAS, and Fourier transform infrared) properties of a number of H-site variants, including H107A, H108A, H172A, and M109I. Our results establish that M109 is indeed the coordinating ligand and confirm the prediction that the low pH structural transition with associated loss of activity is abrogated when the M109 thioether is absent. The histidine mutants show more complex behavior, but the almost complete lack of activity in all three variants coupled with only minor differences in their spectroscopic properties suggests that unique structural elements at H are critical for functionality. The data suggest a more general

  16. 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.

  17. 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.

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

    OpenAIRE

    L Schlenkrich; Dave Sewry

    2012-01-01

    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 rece...

  19. Source apportionment of PM2.5 at multiple Northwest U.S. sites: Assessing regional winter wood smoke impacts from residential wood combustion

    Science.gov (United States)

    Kotchenruther, Robert A.

    2016-10-01

    Wood smoke from residential wood combustion is a significant source of elevated PM2.5 in many communities across the Northwest U.S. Accurate representation of residential wood combustion in source-oriented regional scale air quality models is challenging because of multiple uncertainties. As an alternative to source-oriented source apportionment, this work provides, through receptor-oriented source apportionment, an assessment of winter residential wood combustion impacts at multiple Northwest U.S. locations. Source apportionment was performed on chemically speciated PM2.5 from 19 monitoring sites using the Positive Matrix Factorization (PMF) receptor model. Each site was modeled independently, but a common data preparation and modeling protocol was used so that results were as comparable as possible across sites. Model solutions had from 4 to 8 PMF factors, depending on the site. PMF factors at each site were associated with a source classification (e.g., primary wood smoke), a dominant chemical composition (e.g., ammonium nitrate), or were some mixture. 15 different sources or chemical compositions were identified as contributing to PM2.5 across the 19 sites. The 6 most common were; aged wood smoke and secondary organic carbon, motor vehicles, primary wood smoke, ammonium nitrate, ammonium sulfate, and fugitive dust. Wood smoke was identified at every site, with both aged and primary wood smoke identified at most sites. Wood smoke contributions to PM2.5 were averaged for the two winter months of December and January, the months when wood smoke in the Northwest U.S. is mainly from residential wood combustion. The total contribution of residential wood combustion, that from primary plus aged smoke, ranged from 11.4% to 92.7% of average December and January PM2.5 depending on the site, with the highest percent contributions occurring in smaller towns that have fewer expected sources of winter PM2.5. Receptor modeling at multiple sites, such as that conducted in this

  20. Determination of quality factors by microdosimetry

    International Nuclear Information System (INIS)

    Al-Affan, I.A.M.; Watt, D.E.

    1987-01-01

    The application of microdose parameters for the specification of a revised scale of quality factors which would be applicable at low doses and dose rates is examined in terms of an original proposal by Rossi. Two important modifications are suggested to enable an absolute scale of quality factors to be constructed. Allowance should be made to allow for the dependence of the saturation threshold of lineal energy on the type of heavy charged particle. Also, an artificial saturation threshold should be introduced for electron tracks as a means of modifying the measurements made in the microdosimeter to the more realistic site sizes of nanometer dimensions. The proposed absolute scale of quality factors nicely encompasses the high RBEs of around 3 observed at low doses for tritium β rays and is consistent with the recent recommendation of the ICRP that the quality factor for fast neutrons be increased by a factor of two, assuming that there is no biological repair for the reference radiation. (orig.)

  1. Determination of quality factors by microdosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Al-Affan, I.A.M.; Watt, D.E.

    1987-03-15

    The application of microdose parameters for the specification of a revised scale of quality factors which would be applicable at low doses and dose rates is examined in terms of an original proposal by Rossi. Two important modifications are suggested to enable an absolute scale of quality factors to be constructed. Allowance should be made to allow for the dependence of the saturation threshold of lineal energy on the type of heavy charged particle. Also, an artificial saturation threshold should be introduced for electron tracks as a means of modifying the measurements made in the microdosimeter to the more realistic site sizes of nanometer dimensions. The proposed absolute scale of quality factors nicely encompasses the high RBEs of around 3 observed at low doses for tritium ..beta.. rays and is consistent with the recent recommendation of the ICRP that the quality factor for fast neutrons be increased by a factor of two, assuming that there is no biological repair for the reference radiation.

  2. The influence of home-site factors on residents' willingness to pay: An application for power generation from scrubland in Galicia, Spain

    International Nuclear Information System (INIS)

    Solino, Mario; Farizo, Begona A.; Campos, Pablo

    2009-01-01

    The main objective of this paper is to measure how much home-site factors can help to explain the individual WTP for an environmental improvement in power generation in Galicia, Spain. The results show that home-site variables such as a dispersed population, local community income, population growth and coastal/inland emplacements have significant effects on the residents' WTP. Individual and home-site models are compared using goodness-of-fit measures, and implications for forestry resources management and energy planning are discussed. The results favor to take into account the home-site variables into the WTP function. Moreover, a different structure of preferences for coastal and inland inhabitants is identified. A cross-validity analysis shows that some home-site coefficients are common to both sub-samples, but the scale parameters are not homogenous. This analysis could be useful to inform and support the public energy policy when designing incentives that promote the electric use of biomass.

  3. Global Mapping of Transcription Factor Binding Sites by Sequencing Chromatin Surrogates: a Perspective on Experimental Design, Data Analysis, and Open Problems.

    Science.gov (United States)

    Wei, Yingying; Wu, George; Ji, Hongkai

    2013-05-01

    Mapping genome-wide binding sites of all transcription factors (TFs) in all biological contexts is a critical step toward understanding gene regulation. The state-of-the-art technologies for mapping transcription factor binding sites (TFBSs) couple chromatin immunoprecipitation (ChIP) with high-throughput sequencing (ChIP-seq) or tiling array hybridization (ChIP-chip). These technologies have limitations: they are low-throughput with respect to surveying many TFs. Recent advances in genome-wide chromatin profiling, including development of technologies such as DNase-seq, FAIRE-seq and ChIP-seq for histone modifications, make it possible to predict in vivo TFBSs by analyzing chromatin features at computationally determined DNA motif sites. This promising new approach may allow researchers to monitor the genome-wide binding sites of many TFs simultaneously. In this article, we discuss various experimental design and data analysis issues that arise when applying this approach. Through a systematic analysis of the data from the Encyclopedia Of DNA Elements (ENCODE) project, we compare the predictive power of individual and combinations of chromatin marks using supervised and unsupervised learning methods, and evaluate the value of integrating information from public ChIP and gene expression data. We also highlight the challenges and opportunities for developing novel analytical methods, such as resolving the one-motif-multiple-TF ambiguity and distinguishing functional and non-functional TF binding targets from the predicted binding sites. The online version of this article (doi:10.1007/s12561-012-9066-5) contains supplementary material, which is available to authorized users.

  4. Lentivector Integration Sites in Ependymal Cells From a Model of Metachromatic Leukodystrophy: Non-B DNA as a New Factor Influencing Integration

    Science.gov (United States)

    McAllister, Robert G; Liu, Jiahui; Woods, Matthew W; Tom, Sean K; Rupar, C Anthony; Barr, Stephen D

    2014-01-01

    The blood–brain barrier controls the passage of molecules from the blood into the central nervous system (CNS) and is a major challenge for treatment of neurological diseases. Metachromatic leukodystrophy is a neurodegenerative lysosomal storage disease caused by loss of arylsulfatase A (ARSA) activity. Gene therapy via intraventricular injection of a lentiviral vector is a potential approach to rapidly and permanently deliver therapeutic levels of ARSA to the CNS. We present the distribution of integration sites of a lentiviral vector encoding human ARSA (LV-ARSA) in murine brain choroid plexus and ependymal cells, administered via a single intracranial injection into the CNS. LV-ARSA did not exhibit a strong preference for integration in or near actively transcribed genes, but exhibited a strong preference for integration in or near satellite DNA. We identified several genomic hotspots for LV-ARSA integration and identified a consensus target site sequence characterized by two G-quadruplex-forming motifs flanking the integration site. In addition, our analysis identified several other non-B DNA motifs as new factors that potentially influence lentivirus integration, including human immunodeficiency virus type-1 in human cells. Together, our data demonstrate a clinically favorable integration site profile in the murine brain and identify non-B DNA as a potential new host factor that influences lentiviral integration in murine and human cells. PMID:25158091

  5. Hepatitis C Virus Replication Depends on Endosomal Cholesterol Homeostasis.

    Science.gov (United States)

    Stoeck, Ina Karen; Lee, Ji-Young; Tabata, Keisuke; Romero-Brey, Inés; Paul, David; Schult, Philipp; Lohmann, Volker; Kaderali, Lars; Bartenschlager, Ralf

    2018-01-01

    Similar to other positive-strand RNA viruses, hepatitis C virus (HCV) causes massive rearrangements of intracellular membranes, resulting in a membranous web (MW) composed of predominantly double-membrane vesicles (DMVs), the presumed sites of RNA replication. DMVs are enriched for cholesterol, but mechanistic details on the source and recruitment of cholesterol to the viral replication organelle are only partially known. Here we focused on selected lipid transfer proteins implicated in direct lipid transfer at various endoplasmic reticulum (ER)-membrane contact sites. RNA interference (RNAi)-mediated knockdown identified several hitherto unknown HCV dependency factors, such as steroidogenic acute regulatory protein-related lipid transfer domain protein 3 (STARD3), oxysterol-binding protein-related protein 1A and -B (OSBPL1A and -B), and Niemann-Pick-type C1 (NPC1), all residing at late endosome and lysosome membranes and required for efficient HCV RNA replication but not for replication of the closely related dengue virus. Focusing on NPC1, we found that knockdown or pharmacological inhibition caused cholesterol entrapment in lysosomal vesicles concomitant with decreased cholesterol abundance at sites containing the viral replicase factor NS5A. In untreated HCV-infected cells, unesterified cholesterol accumulated at the perinuclear region, partially colocalizing with NS5A at DMVs, arguing for NPC1-mediated endosomal cholesterol transport to the viral replication organelle. Consistent with cholesterol being an important structural component of DMVs, reducing NPC1-dependent endosomal cholesterol transport impaired MW integrity. This suggests that HCV usurps lipid transfer proteins, such as NPC1, at ER-late endosome/lysosome membrane contact sites to recruit cholesterol to the viral replication organelle, where it contributes to MW functionality. IMPORTANCE A key feature of the replication of positive-strand RNA viruses is the rearrangement of the host cell

  6. A conserved motif in the linker domain of STAT1 transcription factor is required for both recognition and release from high-affinity DNA-binding sites.

    Science.gov (United States)

    Hüntelmann, Bettina; Staab, Julia; Herrmann-Lingen, Christoph; Meyer, Thomas

    2014-01-01

    Binding to specific palindromic sequences termed gamma-activated sites (GAS) is a hallmark of gene activation by members of the STAT (signal transducer and activator of transcription) family of cytokine-inducible transcription factors. However, the precise molecular mechanisms involved in the signal-dependent finding of target genes by STAT dimers have not yet been very well studied. In this study, we have characterized a sequence motif in the STAT1 linker domain which is highly conserved among the seven human STAT proteins and includes surface-exposed residues in close proximity to the bound DNA. Using site-directed mutagenesis, we have demonstrated that a lysine residue in position 567 of the full-length molecule is required for GAS recognition. The substitution of alanine for this residue completely abolished both binding to high-affinity GAS elements and transcriptional activation of endogenous target genes in cells stimulated with interferon-γ (IFNγ), while the time course of transient nuclear accumulation and tyrosine phosphorylation were virtually unchanged. In contrast, two glutamic acid residues (E559 and E563) on each monomer are important for the dissociation of dimeric STAT1 from DNA and, when mutated to alanine, result in elevated levels of tyrosine-phosphorylated STAT1 as well as prolonged IFNγ-stimulated nuclear accumulation. In conclusion, our data indicate that the kinetics of signal-dependent GAS binding is determined by an array of glutamic acid residues located at the interior surface of the STAT1 dimer. These negatively charged residues appear to align the long axis of the STAT1 dimer in a position perpendicular to the DNA, thereby facilitating the interaction between lysine 567 and the phosphodiester backbone of a bound GAS element, which is a prerequisite for transient gene induction.

  7. A proposed parameterization of interface discontinuity factors depending on neighborhood for pin-by-pin diffusion computations for LWR

    International Nuclear Information System (INIS)

    Herrero, Jose Javier; Garcia-Herranz, Nuria; Ahnert, Carol

    2011-01-01

    There exists an interest in performing full core pin-by-pin computations for present nuclear reactors. In such type of problems the use of a transport approximation like the diffusion equation requires the introduction of correction parameters. Interface discontinuity factors can improve the diffusion solution to nearly reproduce a transport solution. Nevertheless, calculating accurate pin-by-pin IDF requires the knowledge of the heterogeneous neutron flux distribution, which depends on the boundary conditions of the pin-cell as well as the local variables along the nuclear reactor operation. As a consequence, it is impractical to compute them for each possible configuration. An alternative to generate accurate pin-by-pin interface discontinuity factors is to calculate reference values using zero-net-current boundary conditions and to synthesize afterwards their dependencies on the main neighborhood variables. In such way the factors can be accurately computed during fine-mesh diffusion calculations by correcting the reference values as a function of the actual environment of the pin-cell in the core. In this paper we propose a parameterization of the pin-by-pin interface discontinuity factors allowing the implementation of a cross sections library able to treat the neighborhood effect. First results are presented for typical PWR configurations. (author)

  8. A proposed parameterization of interface discontinuity factors depending on neighborhood for pin-by-pin diffusion computations for LWR

    Energy Technology Data Exchange (ETDEWEB)

    Herrero, Jose Javier; Garcia-Herranz, Nuria; Ahnert, Carol, E-mail: herrero@din.upm.es, E-mail: nuria@din.upm.es, E-mail: carol@din.upm.es [Departamento de Ingenieria Nuclear, Universidad Politecnica de Madrid (Spain)

    2011-07-01

    There exists an interest in performing full core pin-by-pin computations for present nuclear reactors. In such type of problems the use of a transport approximation like the diffusion equation requires the introduction of correction parameters. Interface discontinuity factors can improve the diffusion solution to nearly reproduce a transport solution. Nevertheless, calculating accurate pin-by-pin IDF requires the knowledge of the heterogeneous neutron flux distribution, which depends on the boundary conditions of the pin-cell as well as the local variables along the nuclear reactor operation. As a consequence, it is impractical to compute them for each possible configuration. An alternative to generate accurate pin-by-pin interface discontinuity factors is to calculate reference values using zero-net-current boundary conditions and to synthesize afterwards their dependencies on the main neighborhood variables. In such way the factors can be accurately computed during fine-mesh diffusion calculations by correcting the reference values as a function of the actual environment of the pin-cell in the core. In this paper we propose a parameterization of the pin-by-pin interface discontinuity factors allowing the implementation of a cross sections library able to treat the neighborhood effect. First results are presented for typical PWR configurations. (author)

  9. The sxa2-dependent inactivation of the P-factor mating pheromone in the fission yeast Schizosaccharomyces pombe

    DEFF Research Database (Denmark)

    Ladds, G; Rasmussen, E M; Young, T

    1996-01-01

    Haploid cells of the fission yeast Schizosaccharomyces pombe exist in one of two mating types, referred to as M and P. Conjugation occurs between cells of opposite mating type and is controlled by the reciprocal action of diffusible pheromones. Loss of function of the sxa2 gene in M cells causes...... hypersensitivity to the P-factor mating pheromone and a reduction in mating efficiency. Here we demonstrate the secretion of an sxa2-dependent carboxypeptidase that inactivates P-factor by removal of the C-terminal leucine residue....

  10. 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

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  12. Test-retest and between-site reliability in a multicenter fMRI study.

    Science.gov (United States)

    Friedman, Lee; Stern, Hal; Brown, Gregory G; Mathalon, Daniel H; Turner, Jessica; Glover, Gary H; Gollub, Randy L; Lauriello, John; Lim, Kelvin O; Cannon, Tyrone; Greve, Douglas N; Bockholt, Henry Jeremy; Belger, Aysenil; Mueller, Bryon; Doty, Michael J; He, Jianchun; Wells, William; Smyth, Padhraic; Pieper, Steve; Kim, Seyoung; Kubicki, Marek; Vangel, Mark; Potkin, Steven G

    2008-08-01

    In the present report, estimates of test-retest and between-site reliability of fMRI assessments were produced in the context of a multicenter fMRI reliability study (FBIRN Phase 1, www.nbirn.net). Five subjects were scanned on 10 MRI scanners on two occasions. The fMRI task was a simple block design sensorimotor task. The impulse response functions to the stimulation block were derived using an FIR-deconvolution analysis with FMRISTAT. Six functionally-derived ROIs covering the visual, auditory and motor cortices, created from a prior analysis, were used. Two dependent variables were compared: percent signal change and contrast-to-noise-ratio. Reliability was assessed with intraclass correlation coefficients derived from a variance components analysis. Test-retest reliability was high, but initially, between-site reliability was low, indicating a strong contribution from site and site-by-subject variance. However, a number of factors that can markedly improve between-site reliability were uncovered, including increasing the size of the ROIs, adjusting for smoothness differences, and inclusion of additional runs. By employing multiple steps, between-site reliability for 3T scanners was increased by 123%. Dropping one site at a time and assessing reliability can be a useful method of assessing the sensitivity of the results to particular sites. These findings should provide guidance toothers on the best practices for future multicenter studies.

  13. The commissioning of CMS sites: Improving the site reliability

    International Nuclear Information System (INIS)

    Belforte, S; Fisk, I; Flix, J; Hernandez, J M; Klem, J; Letts, J; Magini, N; Saiz, P; Sciaba, A

    2010-01-01

    The computing system of the CMS experiment works using distributed resources from more than 60 computing centres worldwide. These centres, located in Europe, America and Asia are interconnected by the Worldwide LHC Computing Grid. The operation of the system requires a stable and reliable behaviour of the underlying infrastructure. CMS has established a procedure to extensively test all relevant aspects of a Grid site, such as the ability to efficiently use their network to transfer data, the functionality of all the site services relevant for CMS and the capability to sustain the various CMS computing workflows at the required scale. This contribution describes in detail the procedure to rate CMS sites depending on their performance, including the complete automation of the program, the description of monitoring tools, and its impact in improving the overall reliability of the Grid from the point of view of the CMS computing system.

  14. 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

  15. Site characterization and site response in Port-au-Prince, Haiti

    Science.gov (United States)

    Hough, Susan E.; Yong, Alan K.; Altidor, Jean Robert; Anglade, Dieuseul; Given, Douglas D.; Mildor, Saint-Louis

    2011-01-01

    Waveform analysis of aftershocks of the Mw7.0 Haiti earthquake of 12 January 2010 reveals amplification of ground motions at sites within the Cul de Sac valley in which Port-au-Prince is situated. Relative to ground motions recorded at a hard-rock reference site, peak acceleration values are amplified by a factor of approximately 1.8 at sites on low-lying Mio-Pliocene deposits in central Port-au-Prince and by a factor of approximately 2.5–3 on a steep foothill ridge in the southern Port-au-Prince metropolitan region. The observed amplitude, predominant periods, variability, and polarization of amplification are consistent with predicted topographic amplification by a steep, narrow ridge. A swath of unusually high damage in this region corresponds with the extent of the ridge where high weak-motion amplifications are observed. We use ASTER (Advanced Spaceborne Thermal Emission and Reflection Radiometer) imagery to map local geomorphology, including characterization of both near-surface and of small-scale topographic structures that correspond to zones of inferred amplification.

  16. Age dependency of primary tumor sites and metastases in patients with Ewing sarcoma.

    Science.gov (United States)

    Worch, Jennifer; Ranft, Andreas; DuBois, Steven G; Paulussen, Michael; Juergens, Heribert; Dirksen, Uta

    2018-06-01

    The median age of patients with Ewing sarcoma (EwS) at diagnosis is around 14-15 years. Older age is associated with a worse outcome. The correlation of age at diagnosis on sites of disease has not been fully described. The goal of this study was to evaluate the differences in sites of primary tumor and metastatic tumor involvement according to age groups. EwS data from the Gesellschaft für Pädiatrische Onkologie und Hämatology (GPOH) database of the Cooperative Ewing Sarcoma Study (CESS) 81/86 and the European Intergroup Cooperative Ewing's Sarcoma Study EICESS 92 and the EUROpean Ewing tumor Working Initiative of National Groups-99-Protocol (EURO-E.W.I.N.G.-99) study were analyzed. Patient and tumor characteristics were evaluated statistically using chi square tests. The study population included 2,635 patients with bone EwS. Sites of primary and metastatic tumors differed according to the age groups of young children (0-9 years), early adolescence (10-14 years), late adolescence (15-19 years), young adults (20-24 years), and adults (more than 24 years). Young children demonstrated the most striking differences in site of disease with a lower proportion of pelvic primary and axial tumors. They presented less often with metastatic disease at diagnosis. Site of primary and metastatic tumor involvement in EwS differs according to patient age. The biological and developmental etiology for these differences requires further investigations. © 2018 Wiley Periodicals, Inc.

  17. 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

  18. 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.

  19. ABFs, a family of ABA-responsive element binding factors.

    Science.gov (United States)

    Choi, H; Hong, J; Ha, J; Kang, J; Kim, S Y

    2000-01-21

    Abscisic acid (ABA) plays an important role in environmental stress responses of higher plants during vegetative growth. One of the ABA-mediated responses is the induced expression of a large number of genes, which is mediated by cis-regulatory elements known as abscisic acid-responsive elements (ABREs). Although a number of ABRE binding transcription factors have been known, they are not specifically from vegetative tissues under induced conditions. Considering the tissue specificity of ABA signaling pathways, factors mediating ABA-dependent stress responses during vegetative growth phase may thus have been unidentified so far. Here, we report a family of ABRE binding factors isolated from young Arabidopsis plants under stress conditions. The factors, isolated by a yeast one-hybrid system using a prototypical ABRE and named as ABFs (ABRE binding factors) belong to a distinct subfamily of bZIP proteins. Binding site selection assay performed with one ABF showed that its preferred binding site is the strong ABRE, CACGTGGC. ABFs can transactivate an ABRE-containing reporter gene in yeast. Expression of ABFs is induced by ABA and various stress treatments, whereas their induction patterns are different from one another. Thus, a new family of ABRE binding factors indeed exists that have the potential to activate a large number of ABA/stress-responsive genes in Arabidopsis.

  20. Bioremediation techniques-classification based on site of application: principles, advantages, limitations and prospects.

    Science.gov (United States)

    Azubuike, Christopher Chibueze; Chikere, Chioma Blaise; Okpokwasili, Gideon Chijioke

    2016-11-01

    Environmental pollution has been on the rise in the past few decades owing to increased human activities on energy reservoirs, unsafe agricultural practices and rapid industrialization. Amongst the pollutants that are of environmental and public health concerns due to their toxicities are: heavy metals, nuclear wastes, pesticides, green house gases, and hydrocarbons. Remediation of polluted sites using microbial process (bioremediation) has proven effective and reliable due to its eco-friendly features. Bioremediation can either be carried out ex situ or in situ, depending on several factors, which include but not limited to cost, site characteristics, type and concentration of pollutants. Generally, ex situ techniques apparently are more expensive compared to in situ techniques as a result of additional cost attributable to excavation. However, cost of on-site installation of equipment, and inability to effectively visualize and control the subsurface of polluted sites are of major concerns when carrying out in situ bioremediation. Therefore, choosing appropriate bioremediation technique, which will effectively reduce pollutant concentrations to an innocuous state, is crucial for a successful bioremediation project. Furthermore, the two major approaches to enhance bioremediation are biostimulation and bioaugmentation provided that environmental factors, which determine the success of bioremediation, are maintained at optimal range. This review provides more insight into the two major bioremediation techniques, their principles, advantages, limitations and prospects.

  1. The Effects of Molecular Crowding on the Structure and Stability of G-Quadruplexes with an Abasic Site

    Science.gov (United States)

    Fujimoto, Takeshi; Nakano, Shu-ichi; Miyoshi, Daisuke; Sugimoto, Naoki

    2011-01-01

    Both cellular environmental factors and chemical modifications critically affect the properties of nucleic acids. However, the structure and stability of DNA containing abasic sites under cell-mimicking molecular crowding conditions remain unclear. Here, we investigated the molecular crowding effects on the structure and stability of the G-quadruplexes including a single abasic site. Structural analysis by circular dichroism showed that molecular crowding by PEG200 did not affect the topology of the G-quadruplex structure with or without an abasic site. Thermodynamic analysis further demonstrated that the degree of stabilization of the G-quadruplex by molecular crowding decreased with substitution of an abasic site for a single guanine. Notably, we found that the molecular crowding effects on the enthalpy change for G-quadruplex formation had a linear relationship with the abasic site effects depending on its position. These results are useful for predicting the structure and stability of G-quadruplexes with abasic sites in the cell-mimicking conditions. PMID:21949901

  2. Factors reducing the expected deflection in initial orientation in clock-shifted homing pigeons.

    Science.gov (United States)

    Gagliardo, Anna; Odetti, Francesca; Ioalè, Paolo

    2005-02-01

    To orient from familiar sites, homing pigeons can rely on both an olfactory map and visual familiar landmarks. The latter can in principle be used in two different ways: either within a topographical map exploited for piloting or in a so-called mosaic map associated with a compass bearing. One way to investigate the matter is to put the compass and the topographical information in conflict by releasing clock-shifted pigeons from familiar locations. Although the compass orientation is in general dominant over a piloting strategy, a stronger or weaker tendency to correct towards the home direction by clock-shifted pigeons released from very familiar sites has often been observed. To investigate which factors are involved in the reduction of the deviation due to clock-shift, we performed a series of releases with intact and anosmic pigeons from familiar sites in unshifted and clock-shifted conditions and a series of releases from the same sites with naive clock-shifted birds. Our data suggest that the following factors have a role in reducing deviation due to the clock-shift: familiarity with the release site, the lack of olfactory information and some unknown site-dependent features.

  3. Does your web site draw new patients?

    Science.gov (United States)

    Wallin, Wendy S

    2009-11-01

    The absence of scientific data forces orthodontists to guess at how best to design Internet sites that persuade prospective patients to call for appointments. This study was conducted to identify the Web-site factors that lead prospective patients to make appointments or, conversely, to reject a practice. Ten participants actively looking online for an orthodontist were recruited to participate. They reviewed 64 orthodontic Web sites in their geographic areas and rated their likelihood of calling each practice for an appointment. The sessions were videotaped. Analysis of participant comments, navigation patterns, and ratings suggested 25 distinguishing factors. Statistical analysis showed 10 Web-site characteristics that predict the success of an orthodontic Web site in attracting new patients.

  4. Energy-dependency correction factors for the digital dosimeters using in NMD environment dose assessment

    International Nuclear Information System (INIS)

    Lai, Y.C.; Huang, Y. F.; Chen, Y.W.

    2008-01-01

    Full text: Short-term environment dose-rate assessments using real-time digital dosimeters within a Nuclear Medicine Department (NMD) are gaining more world-wide uses recently. In the past, conventional ion chamber-type survey-meters are used dominantly in environmental dose rates evaluation. Although it has suffered less gamma energy-dependency, but it is less sensitive in comparison with other digital dosimeters and more bulky in design that can hardly make it into a pocket size application. With modern electronic advancement and its shrinking in physical size, real-time personal dosimeter nowadays has gaining more popular to use a miniature G-M counter or a solid-state diode sensor, or even a NaI(Tl) scintillation device for ambient radiation monitoring. Radiation sensor operated in pulse-mode can never been used in doses or dose rates determination since each digital pulse has carried no energy information of the impinging gamma ray being interactive with, especially in the G-M counter or the diode sensor case. The raw count rates measured from a pulse-mode device are heavily dependent on the packaging of the sensor to make it less energy-sensitive. The doses or dose rates are then calculated by using a built-in conversion factor, based on a Cs-137 beam source calibration data conducted by various manufacturing vendors, to convert its raw counts into a so-called dose or dose-rate unit. In this study, we have focused our interests in the low energy response of the digital dosimeters from several brands currently for our in-house uses. Mainly, Tc-99m and I-131 in point sources and water phantoms detection configurations have been deployed to simulate our NMD outpatients for environment radiation monitoring purpose. The energy-dependent correction factors of the digital dosimeters will be evaluated by using calibrated Tc-99m or I-131 standard sources directly that has much lower gamma energy than the Cs-137 beam source of 661 keV. In the near future, we would

  5. Expedited Site Characterization: A rapid, cost-effective process for preremedial site characterization

    International Nuclear Information System (INIS)

    Burton, J.C.; Walker, J.L.; Jennings, T.V.; Aggarwal, P.K.; Hastings, B.; Meyer, W.T.; Rose, C.M.; Rosignolo, C.L.

    1993-01-01

    Argonne National Laboratory has developed a unique, cost- and time-effective, technically innovative process for preremedial site characterization, referred to as Expedited Site Characterization (ESC). The cost of the ESC field sampling process ranges from 1/10 to 1/5 of the cost of traditional site characterization. The time required for this ESC field activity is approximately 1/30 of that for current methods. Argonne's preremedial site investigations based on this approach have been accepted by the appropriate regulatory agencies. The ESC process is flexible and neither site nor contaminant dependent. The process has been successfully tested and applied in site investigations of multiple contaminated landfills in New Mexico (for the US Department of the Interior's Bureau of Land Management [BLM]) and at former grain storage facilities in Nebraska and Kansas, contaminated with carbon tetrachloride (for the Department of Agriculture's Commodity Credit Corporation [CCC/USDA]). A working demonstration of this process was sponsored by the US Department of Energy (DOE) Office of Technology Development as a model of the methodology needed to accelerate site characterizations at DOE facilities. This report describes the application of the process in New Mexico, Nebraska and Kansas

  6. A RANDOMIZED CONTROLLED STUDY OF RISK FACTORS AND ROLE OF PROPHYLACTIC ANTIBIOTICS IN PREVENTION OF SURGICAL SITE INFECTIONS

    Directory of Open Access Journals (Sweden)

    Avijeet Mukherjee, Naveen N

    2015-01-01

    Full Text Available Background and Objectives: Surgical site infection (SSI is the most common nosocomial infection encountered in post operative surgical wards. The use of prophylactic antibiotic in clean elective surgical cases is still a subject of controversy to surgeons. The objective of the study is to identify the need for using prophylactic antibiotics in clean surgeries, prevalence of organisms in patients who are not given prophylactic antibiotics and to study whether the presence of risk factors increase the incidence of surgical site infection. Methodology: The comparative study consists of 100 cases admitted under two groups of 50 each: Group A was given prophylactic antibiotic and Group B didn’t receive any. All surgeries other than clean surgical cases were excluded from the study. Results: Out of 50 patients in group B who were not given prophylactic antibiotic, 2 patients had more than one risk factor for development of SSI and both of them developed SSI. Of the 50 patients who received prophylactic antibiotic, none developed SSI. The rate of infection in group A was nil and in Group B was 4%. Conclusion: Prophylactic antibiotics are not recommended for clean elective surgical cases as there is no statistically significant change in the infection rate seen in patients not receiving prophylactic antibiotic(P=0.4952. Meticulous surgical technique and correcting risk factors prior to surgery is a must for reducing incidence of SSI.

  7. 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.

  8. Comparison of the Radionuclides Dispersion at the UAE Barakah Site with that at the ROK Shin-Kori Site - Comparison of the radionuclides dispersion in Barakah site with that in Shin-Kori site

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung-yeop; Lee, Kun Jai; Chang, Soon Heung [Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon, 305-701 (Korea, Republic of); Beeley, Philip A. [Khalifa University of Science, Technology and Research, P.O. Box 127788, Abu Dhabi (United Arab Emirates)

    2014-07-01

    In order to understand the characteristics of atmospheric dispersion of radionuclides in the desert environment of Barakah site in UAE, comparison research with the results of other environments could be an appropriate way to facilitate it. Shin-Kori site is the proper comparison target because same reactor type of APR1400 with that in Barakah site is under construction. Hypothetical accident scenario was considered and accident source term which had been developed in previous research has been applied as releasing source. After reviewing several computation codes, ADMS5 has been selected as an atmospheric dispersion modeling tool which is installing advanced Gaussian plum model and plentiful options. The climate data of both Barakah and Shin-Kori were acquired and the environments of both sites have been simulated considering wind speed, wind direction, temperature, humidity, ground surface roughness and etc. Near field final human doses on the maps have been schematised regarding statistical meteorological data of both sites and dose conversion factors from the publications of ICRP and federal guidance report of EPA. The results of this research are expected to enhance the understanding about differences between two environments which have same reactor type and to improve the comprehension of desert environment of Barakah site as well. Applying different dose conversion factors to Barakah site considering the desert biosphere could be further study to obtain more accurate results. (authors)

  9. Co-Occurring Risk Factors for Arrest among Persons with Opioid Abuse and Dependence: Implications for Developing Interventions to Limit Criminal Justice Involvement

    Science.gov (United States)

    Fisher, William H.; Clark, Robin; Baxter, Jeffrey; Barton, Bruce; O’Connell, Elizabeth; Aweh, Gideon

    2015-01-01

    Persons who abuse opioids or are dependent on opioids are at elevated risk for arrest. Co-occurring behavioral health problems may exacerbate that risk, although the extent of any such increase has not been described. This study examines such risk factors among 40,238 individuals with a diagnosis of opioid abuse or dependence who were enrolled in the Massachusetts Medicaid program in 2010. Medicaid data were merged with statewide arrest data to assess the effects of co-existing mental illness, substance abuse, and previous arrests on arrest during 2010. Persons with serious mental illnesses (psychotic and bipolar disorders) and those with two or more pre-2010 arrests had significantly increased greater odds of arrest. We believe this to be the first study examining effects of co-occurring risk factors on arrest in a large population with opioid dependency/abuse. These findings identify predictors of arrest that could be used to design interventions targeting specific co-occurring risk factors. PMID:25012550

  10. Soil-to-Rice Seeds Transfer Factors of Radioiodine and Technetium for Paddy Fields around the Radioactive-Waste Disposal Site in Gyeongju

    International Nuclear Information System (INIS)

    Choi, Yong Ho; Lim, Kwang Muk; Jun, In; Park, Doo Won; Keum, Dong Kwon; Han, Moon Hee

    2010-01-01

    Radiotracer experiments were performed over two years using pot cultures in a greenhouse to investigate soil-torice seeds transfer factors of radioiodine and technetium for paddy fields around the radioactive-waste disposal site in Gyeongju. Before transplanting rice seedlings, the top about 20 cm soils were thoroughly mixed with 125 I (2007) and 99 Tc (2008), and the pots were irrigated to simulate flooded rice fields. Transfer factors were determined as the ratios of the radionuclide concentrations in dry rice seeds (brown rice) to those in dry soils. Transfer factors of radioiodine and technetium were in the ranges of 1.1 x 10 -3 ∼ 6.4 x 10 -3 (three soils) and 5.4 x 10 -4 ∼ 2.5 x 10 -3 (four soils), respectively, for different soils. It seems that the differences in the clay content among soils played a more important role for such variations than those in the organic matter content and pH. As the representative values of radioiodine and technetium transfer factors for rice seeds, 2.9 x 10 -3 and 1.1 x 10 -3 , respectively, were proposed. In order to obtain more highly representative values in the future, investigations for the sites of interest need to be carried out continuously

  11. Predicting transcription factor binding sites using local over-representation and comparative genomics

    Directory of Open Access Journals (Sweden)

    Touzet Hélène

    2006-08-01

    Full Text Available Abstract Background Identifying cis-regulatory elements is crucial to understanding gene expression, which highlights the importance of the computational detection of overrepresented transcription factor binding sites (TFBSs in coexpressed or coregulated genes. However, this is a challenging problem, especially when considering higher eukaryotic organisms. Results We have developed a method, named TFM-Explorer, that searches for locally overrepresented TFBSs in a set of coregulated genes, which are modeled by profiles provided by a database of position weight matrices. The novelty of the method is that it takes advantage of spatial conservation in the sequence and supports multiple species. The efficiency of the underlying algorithm and its robustness to noise allow weak regulatory signals to be detected in large heterogeneous data sets. Conclusion TFM-Explorer provides an efficient way to predict TFBS overrepresentation in related sequences. Promising results were obtained in a variety of examples in human, mouse, and rat genomes. The software is publicly available at http://bioinfo.lifl.fr/TFM-Explorer.

  12. Climate warming and the recent treeline shift in the European alps: the role of geomorphological factors in high-altitude sites.

    Science.gov (United States)

    Leonelli, Giovanni; Pelfini, Manuela; di Cella, Umberto Morra; Garavaglia, Valentina

    2011-05-01

    Global warming and the stronger regional temperature trends recently recorded over the European Alps have triggered several biological and physical dynamics in high-altitude environments. We defined the present treeline altitude in three valleys of a region in the western Italian Alps and reconstructed the past treeline position for the last three centuries in a nearly undisturbed site by means of a dendrochronological approach. We found that the treeline altitude in this region is mainly controlled by human impacts and geomorphological factors. The reconstruction of the altitudinal dynamics at the study site reveals that the treeline shifted upwards of 115 m over the period 1901-2000, reaching the altitude of 2505 m in 2000 and 2515 m in 2008. The recent treeline shift and the acceleration of tree colonization rates in the alpine belt can be mainly ascribed to the climatic input. However, we point out the increasing role of geomorphological factors in controlling the future treeline position and colonization patterns in high mountains.

  13. Siting Criteria for Low and Intermediate Level Radioactive Waste Disposal in Egypt (Proposal approach)

    International Nuclear Information System (INIS)

    Abdellatif, M.M.

    2012-01-01

    The objective of radioactive waste disposal is to isolate waste from the surrounding media so that it does not result in undue radiation exposure to humans and the environment. The required degree of isolation can be obtained by implementing various disposal methods and suitable criteria. Near surface disposal method has been practiced for some decades, with a wide variation in sites, types and amounts of wastes, and facility designs employed. Experience has shown that the effective and safe isolation of waste depends on the performance of the overall disposal system, which is formed by three major components or barriers: the site, the disposal facility and the waste form. The site selection process for low-level and intermediate level radioactive waste disposal facility addressed a wide range of public health, safety, environmental, social and economic factors. Establishing site criteria is the first step in the sitting process to identify a site that is capable of protecting public health, safety and the environment. This paper is concerning a proposal approach for the primary criteria for near surface disposal facility that could be applicable in Egypt.

  14. 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 (<50 y, 50-69 y, and ≥70 y), loss of appetite, weight loss, number of comorbidities, drugs and gastrointestinal symptoms significantly increased RoM in univariate statistical analysis. In patients ages ≥70 y, several disease- and lifestyle-related factors (not living at home, less frequent consumption of vegetables and whole meal bread, low physical activity, and smoking) were associated with RoM. Multivariate logistic regression model for the total study population identified weight loss (odds ratio [OR], 6.09; 95% confidence interval [CI], 4.14-8.83), loss of appetite (OR, 3.81; 95% CI, 2.52-5.78), age-specific low BMI (OR, 1.87; 95% CI, 1.18-2.97), number of drugs taken (OR, 1.19; 95% CI, 1.12-1.26), age (OR, 1.03; 95% CI, 1.02-1.04), and days per week with vegetable consumption (OR, 0.938; 95% CI, 0.89-0.99) as risk factors. 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.

  15. Analysis of the portfolio of sites to characterize for selecting a nuclear repository

    International Nuclear Information System (INIS)

    Keeney, R.L.

    1987-01-01

    The US Department of Energy has selected three sites, from five nominated, to characterize for a nuclear repository to permanently dispose of nuclear waste. This decision was made without the benefit of an analysis of this portfolio problem. This paper analyzes different portfolios of three sites for simultaneous characterization and strategies for sequential characterization. Characterization of each site, which involves significant subsurface excavation, is now estimated to cost $1 billion. Mainly because of the high characterization costs, sequential characterization strategies are identified which are the equivalent of $1.7-2.0 billion less expensive than the selected DOE simultaneous characterization of the three sites. If three sites are simultaneously characterized, one portfolio is estimated to be the equivalent of $100-400 million better than the selected DOE portfolio. Because of these potential savings and several other complicating factors that may influence the relative desirability of characterization strategies, a thorough analysis of characterization strategies that addresses the likelihood of finding disqualifying conditions during site characterization, uncertainties, and dependencies in forecast site repository costs, preclosure and postclosure health and safety impacts, potential delays of both sequential and simultaneous characterization strategies, and the environmental, socioeconomic, and health and safety impacts of characterization activities is recommended

  16. Modeling multisite streamflow dependence with maximum entropy copula

    Science.gov (United States)

    Hao, Z.; Singh, V. P.

    2013-10-01

    Synthetic streamflows at different sites in a river basin are needed for planning, operation, and management of water resources projects. Modeling the temporal and spatial dependence structure of monthly streamflow at different sites is generally required. In this study, the maximum entropy copula method is proposed for multisite monthly streamflow simulation, in which the temporal and spatial dependence structure is imposed as constraints to derive the maximum entropy copula. The monthly streamflows at different sites are then generated by sampling from the conditional distribution. A case study for the generation of monthly streamflow at three sites in the Colorado River basin illustrates the application of the proposed method. Simulated streamflow from the maximum entropy copula is in satisfactory agreement with observed streamflow.

  17. 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.

  18. Gains and Losses of Transcription Factor Binding Sites in Saccharomyces cerevisiae and Saccharomyces paradoxus.

    Science.gov (United States)

    Schaefke, Bernhard; Wang, Tzi-Yuan; Wang, Chuen-Yi; Li, Wen-Hsiung

    2015-07-27

    Gene expression evolution occurs through changes in cis- or trans-regulatory elements or both. Interactions between transcription factors (TFs) and their binding sites (TFBSs) constitute one of the most important points where these two regulatory components intersect. In this study, we investigated the evolution of TFBSs in the promoter regions of different Saccharomyces strains and species. We divided the promoter of a gene into the proximal region and the distal region, which are defined, respectively, as the 200-bp region upstream of the transcription starting site and as the 200-bp region upstream of the proximal region. We found that the predicted TFBSs in the proximal promoter regions tend to be evolutionarily more conserved than those in the distal promoter regions. Additionally, Saccharomyces cerevisiae strains used in the fermentation of alcoholic drinks have experienced more TFBS losses than gains compared with strains from other environments (wild strains, laboratory strains, and clinical strains). We also showed that differences in TFBSs correlate with the cis component of gene expression evolution between species (comparing S. cerevisiae and its sister species Saccharomyces paradoxus) and within species (comparing two closely related S. cerevisiae strains). © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  19. Factor XI dependent and independent activation of thrombin activatable fibrinolysis inhibitor (TAFI) in plasma associated with clot formation

    NARCIS (Netherlands)

    Bouma, B. N.; Mosnier, L. O.; Meijers, J. C.; Griffin, J. H.

    1999-01-01

    Thrombin Activatable Fibrinolysis Inhibitor (TAFI) also known as plasma procarboxypeptidase B is activated by relatively high concentrations of thrombin in a reaction stimulated by thrombomodulin. In plasma an intact factor XI-dependent feed back loop via the intrinsic pathway is necessary to

  20. Helicobacter pylori induces vascular endothelial growth factor production in gastric epithelial cells through hypoxia-inducible factor-1α-dependent pathway.

    Science.gov (United States)

    Kang, Min-Jung; Song, Eun-Jung; Kim, Bo-Yeon; Kim, Dong-Jae; Park, Jong-Hwan

    2014-12-01

    Although Helicobacter pylori have been known to induce vascular endothelial growth factor (VEGF) production in gastric epithelial cells, the precise mechanism for cellular signaling is incompletely understood. In this study, we investigated the role of bacterial virulence factor and host cellular signaling in VEGF production of H. pylori-infected gastric epithelial cells. We evaluated production of VEGF, activation of nuclear factor nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinases (MAPKs) and hypoxia-inducible factor-1α (HIF-1α) stabilization in gastric epithelial cells infected with H. pylori WT or isogenic mutants deficient in type IV secretion system (T4SS). H. pylori induced VEGF production in gastric epithelial cells via both T4SS-dependent and T4SS-independent pathways, although T4SS-independent pathway seems to be the dominant signaling. The inhibitor assay implicated that activation of NF-κB and MAPKs is dispensable for H. pylori-induced VEGF production in gastric epithelial cells. H. pylori led to HIF-1α stabilization in gastric epithelial cells independently of T4SS, NF-κB, and MAPKs, which was essential for VEGF production in these cells. N-acetyl-cysteine (NAC), a reactive oxygen species (ROS) inhibitor, treatment impaired H. pylori-induced HIF-1α stabilization and VEGF production in gastric epithelial cells. We defined the important role of ROS-HIF-1α axis in VEGF production of H. pylori-infected gastric epithelial cells, and bacterial T4SS has a minor role in H. pylori-induced VEGF production of gastric epithelial cells. © 2014 John Wiley & Sons Ltd.