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Sample records for accurate operon predictions

  1. A Novel Method for Accurate Operon Predictions in All SequencedProkaryotes

    Energy Technology Data Exchange (ETDEWEB)

    Price, Morgan N.; Huang, Katherine H.; Alm, Eric J.; Arkin, Adam P.

    2004-12-01

    We combine comparative genomic measures and the distance separating adjacent genes to predict operons in 124 completely sequenced prokaryotic genomes. Our method automatically tailors itself to each genome using sequence information alone, and thus can be applied to any prokaryote. For Escherichia coli K12 and Bacillus subtilis, our method is 85 and 83% accurate, respectively, which is similar to the accuracy of methods that use the same features but are trained on experimentally characterized transcripts. In Halobacterium NRC-1 and in Helicobacterpylori, our method correctly infers that genes in operons are separated by shorter distances than they are in E.coli, and its predictions using distance alone are more accurate than distance-only predictions trained on a database of E.coli transcripts. We use microarray data from sixphylogenetically diverse prokaryotes to show that combining intergenic distance with comparative genomic measures further improves accuracy and that our method is broadly effective. Finally, we survey operon structure across 124 genomes, and find several surprises: H.pylori has many operons, contrary to previous reports; Bacillus anthracis has an unusual number of pseudogenes within conserved operons; and Synechocystis PCC6803 has many operons even though it has unusually wide spacings between conserved adjacent genes.

  2. Inter-Protein Sequence Co-Evolution Predicts Known Physical Interactions in Bacterial Ribosomes and the Trp Operon.

    Science.gov (United States)

    Feinauer, Christoph; Szurmant, Hendrik; Weigt, Martin; Pagnani, Andrea

    2016-01-01

    Interaction between proteins is a fundamental mechanism that underlies virtually all biological processes. Many important interactions are conserved across a large variety of species. The need to maintain interaction leads to a high degree of co-evolution between residues in the interface between partner proteins. The inference of protein-protein interaction networks from the rapidly growing sequence databases is one of the most formidable tasks in systems biology today. We propose here a novel approach based on the Direct-Coupling Analysis of the co-evolution between inter-protein residue pairs. We use ribosomal and trp operon proteins as test cases: For the small resp. large ribosomal subunit our approach predicts protein-interaction partners at a true-positive rate of 70% resp. 90% within the first 10 predictions, with areas of 0.69 resp. 0.81 under the ROC curves for all predictions. In the trp operon, it assigns the two largest interaction scores to the only two interactions experimentally known. On the level of residue interactions we show that for both the small and the large ribosomal subunit our approach predicts interacting residues in the system with a true positive rate of 60% and 85% in the first 20 predictions. We use artificial data to show that the performance of our approach depends crucially on the size of the joint multiple sequence alignments and analyze how many sequences would be necessary for a perfect prediction if the sequences were sampled from the same model that we use for prediction. Given the performance of our approach on the test data we speculate that it can be used to detect new interactions, especially in the light of the rapid growth of available sequence data. PMID:26882169

  3. Inter-Protein Sequence Co-Evolution Predicts Known Physical Interactions in Bacterial Ribosomes and the Trp Operon.

    Directory of Open Access Journals (Sweden)

    Christoph Feinauer

    Full Text Available Interaction between proteins is a fundamental mechanism that underlies virtually all biological processes. Many important interactions are conserved across a large variety of species. The need to maintain interaction leads to a high degree of co-evolution between residues in the interface between partner proteins. The inference of protein-protein interaction networks from the rapidly growing sequence databases is one of the most formidable tasks in systems biology today. We propose here a novel approach based on the Direct-Coupling Analysis of the co-evolution between inter-protein residue pairs. We use ribosomal and trp operon proteins as test cases: For the small resp. large ribosomal subunit our approach predicts protein-interaction partners at a true-positive rate of 70% resp. 90% within the first 10 predictions, with areas of 0.69 resp. 0.81 under the ROC curves for all predictions. In the trp operon, it assigns the two largest interaction scores to the only two interactions experimentally known. On the level of residue interactions we show that for both the small and the large ribosomal subunit our approach predicts interacting residues in the system with a true positive rate of 60% and 85% in the first 20 predictions. We use artificial data to show that the performance of our approach depends crucially on the size of the joint multiple sequence alignments and analyze how many sequences would be necessary for a perfect prediction if the sequences were sampled from the same model that we use for prediction. Given the performance of our approach on the test data we speculate that it can be used to detect new interactions, especially in the light of the rapid growth of available sequence data.

  4. A new, accurate predictive model for incident hypertension

    DEFF Research Database (Denmark)

    Völzke, Henry; Fung, Glenn; Ittermann, Till;

    2013-01-01

    Data mining represents an alternative approach to identify new predictors of multifactorial diseases. This work aimed at building an accurate predictive model for incident hypertension using data mining procedures....

  5. Accurate Multisteps Traffic Flow Prediction Based on SVM

    OpenAIRE

    Zhang Mingheng; Zhen Yaobao; Hui Ganglong; Chen Gang

    2013-01-01

    Accurate traffic flow prediction is prerequisite and important for realizing intelligent traffic control and guidance, and it is also the objective requirement for intelligent traffic management. Due to the strong nonlinear, stochastic, time-varying characteristics of urban transport system, artificial intelligence methods such as support vector machine (SVM) are now receiving more and more attentions in this research field. Compared with the traditional single-step prediction method, the mul...

  6. Accurate Multisteps Traffic Flow Prediction Based on SVM

    Directory of Open Access Journals (Sweden)

    Zhang Mingheng

    2013-01-01

    Full Text Available Accurate traffic flow prediction is prerequisite and important for realizing intelligent traffic control and guidance, and it is also the objective requirement for intelligent traffic management. Due to the strong nonlinear, stochastic, time-varying characteristics of urban transport system, artificial intelligence methods such as support vector machine (SVM are now receiving more and more attentions in this research field. Compared with the traditional single-step prediction method, the multisteps prediction has the ability that can predict the traffic state trends over a certain period in the future. From the perspective of dynamic decision, it is far important than the current traffic condition obtained. Thus, in this paper, an accurate multi-steps traffic flow prediction model based on SVM was proposed. In which, the input vectors were comprised of actual traffic volume and four different types of input vectors were compared to verify their prediction performance with each other. Finally, the model was verified with actual data in the empirical analysis phase and the test results showed that the proposed SVM model had a good ability for traffic flow prediction and the SVM-HPT model outperformed the other three models for prediction.

  7. Detecting uber-operons in prokaryotic genomes.

    Science.gov (United States)

    Che, Dongsheng; Li, Guojun; Mao, Fenglou; Wu, Hongwei; Xu, Ying

    2006-01-01

    We present a study on computational identification of uber-operons in a prokaryotic genome, each of which represents a group of operons that are evolutionarily or functionally associated through operons in other (reference) genomes. Uber-operons represent a rich set of footprints of operon evolution, whose full utilization could lead to new and more powerful tools for elucidation of biological pathways and networks than what operons have provided, and a better understanding of prokaryotic genome structures and evolution. Our prediction algorithm predicts uber-operons through identifying groups of functionally or transcriptionally related operons, whose gene sets are conserved across the target and multiple reference genomes. Using this algorithm, we have predicted uber-operons for each of a group of 91 genomes, using the other 90 genomes as references. In particular, we predicted 158 uber-operons in Escherichia coli K12 covering 1830 genes, and found that many of the uber-operons correspond to parts of known regulons or biological pathways or are involved in highly related biological processes based on their Gene Ontology (GO) assignments. For some of the predicted uber-operons that are not parts of known regulons or pathways, our analyses indicate that their genes are highly likely to work together in the same biological processes, suggesting the possibility of new regulons and pathways. We believe that our uber-operon prediction provides a highly useful capability and a rich information source for elucidation of complex biological processes, such as pathways in microbes. All the prediction results are available at our Uber-Operon Database: http://csbl.bmb.uga.edu/uber, the first of its kind.

  8. Prediction of DtxR regulon: Identification of binding sites and operons controlled by Diphtheria toxin repressor in Corynebacterium diphtheriae

    Directory of Open Access Journals (Sweden)

    Hasnain Seyed

    2004-09-01

    Full Text Available Abstract Background The diphtheria toxin repressor, DtxR, of Corynebacterium diphtheriae has been shown to be an iron-activated transcription regulator that controls not only the expression of diphtheria toxin but also of iron uptake genes. This study aims to identify putative binding sites and operons controlled by DtxR to understand the role of DtxR in patho-physiology of Corynebacterium diphtheriae. Result Positional Shannon relative entropy method was used to build the DtxR-binding site recognition profile and the later was used to identify putative regulatory sites of DtxR within C. diphtheriae genome. In addition, DtxR-regulated operons were also identified taking into account the predicted DtxR regulatory sites and genome annotation. Few of the predicted motifs were experimentally validated by electrophoretic mobility shift assay. The analysis identifies motifs upstream to the novel iron-regulated genes that code for Formamidopyrimidine-DNA glycosylase (FpG, an enzyme involved in DNA-repair and starvation inducible DNA-binding protein (Dps which is involved in iron storage and oxidative stress defense. In addition, we have found the DtxR motifs upstream to the genes that code for sortase which catalyzes anchoring of host-interacting proteins to the cell wall of pathogenic bacteria and the proteins of secretory system which could be involved in translocation of various iron-regulated virulence factors including diphtheria toxin. Conclusions We have used an in silico approach to identify the putative binding sites and genes controlled by DtxR in Corynebacterium diphtheriae. Our analysis shows that DtxR could provide a molecular link between Fe+2-induced Fenton's reaction and protection of DNA from oxidative damage. DtxR-regulated Dps prevents lethal combination of Fe+2 and H2O2 and also protects DNA by nonspecific DNA-binding. In addition DtxR could play an important role in host interaction and virulence by regulating the levels of sortase

  9. Accurate prediction of secondary metabolite gene clusters in filamentous fungi

    DEFF Research Database (Denmark)

    Andersen, Mikael Rørdam; Nielsen, Jakob Blæsbjerg; Klitgaard, Andreas;

    2013-01-01

    Biosynthetic pathways of secondary metabolites from fungi are currently subject to an intense effort to elucidate the genetic basis for these compounds due to their large potential within pharmaceutics and synthetic biochemistry. The preferred method is methodical gene deletions to identify...... supporting enzymes for key synthases one cluster at a time. In this study, we design and apply a DNA expression array for Aspergillus nidulans in combination with legacy data to form a comprehensive gene expression compendium. We apply a guilt-by-association-based analysis to predict the extent...... of the biosynthetic clusters for the 58 synthases active in our set of experimental conditions. A comparison with legacy data shows the method to be accurate in 13 of 16 known clusters and nearly accurate for the remaining 3 clusters. Furthermore, we apply a data clustering approach, which identifies cross...

  10. Plant diversity accurately predicts insect diversity in two tropical landscapes.

    Science.gov (United States)

    Zhang, Kai; Lin, Siliang; Ji, Yinqiu; Yang, Chenxue; Wang, Xiaoyang; Yang, Chunyan; Wang, Hesheng; Jiang, Haisheng; Harrison, Rhett D; Yu, Douglas W

    2016-09-01

    Plant diversity surely determines arthropod diversity, but only moderate correlations between arthropod and plant species richness had been observed until Basset et al. (Science, 338, 2012 and 1481) finally undertook an unprecedentedly comprehensive sampling of a tropical forest and demonstrated that plant species richness could indeed accurately predict arthropod species richness. We now require a high-throughput pipeline to operationalize this result so that we can (i) test competing explanations for tropical arthropod megadiversity, (ii) improve estimates of global eukaryotic species diversity, and (iii) use plant and arthropod communities as efficient proxies for each other, thus improving the efficiency of conservation planning and of detecting forest degradation and recovery. We therefore applied metabarcoding to Malaise-trap samples across two tropical landscapes in China. We demonstrate that plant species richness can accurately predict arthropod (mostly insect) species richness and that plant and insect community compositions are highly correlated, even in landscapes that are large, heterogeneous and anthropogenically modified. Finally, we review how metabarcoding makes feasible highly replicated tests of the major competing explanations for tropical megadiversity. PMID:27474399

  11. Bayesian calibration of power plant models for accurate performance prediction

    International Nuclear Information System (INIS)

    Highlights: • Bayesian calibration is applied to power plant performance prediction. • Measurements from a plant in operation are used for model calibration. • A gas turbine performance model and steam cycle model are calibrated. • An integrated plant model is derived. • Part load efficiency is accurately predicted as a function of ambient conditions. - Abstract: Gas turbine combined cycles are expected to play an increasingly important role in the balancing of supply and demand in future energy markets. Thermodynamic modeling of these energy systems is frequently applied to assist in decision making processes related to the management of plant operation and maintenance. In most cases, model inputs, parameters and outputs are treated as deterministic quantities and plant operators make decisions with limited or no regard of uncertainties. As the steady integration of wind and solar energy into the energy market induces extra uncertainties, part load operation and reliability are becoming increasingly important. In the current study, methods are proposed to not only quantify various types of uncertainties in measurements and plant model parameters using measured data, but to also assess their effect on various aspects of performance prediction. The authors aim to account for model parameter and measurement uncertainty, and for systematic discrepancy of models with respect to reality. For this purpose, the Bayesian calibration framework of Kennedy and O’Hagan is used, which is especially suitable for high-dimensional industrial problems. The article derives a calibrated model of the plant efficiency as a function of ambient conditions and operational parameters, which is also accurate in part load. The article shows that complete statistical modeling of power plants not only enhances process models, but can also increases confidence in operational decisions

  12. Simple Mathematical Models Do Not Accurately Predict Early SIV Dynamics

    Directory of Open Access Journals (Sweden)

    Cecilia Noecker

    2015-03-01

    Full Text Available Upon infection of a new host, human immunodeficiency virus (HIV replicates in the mucosal tissues and is generally undetectable in circulation for 1–2 weeks post-infection. Several interventions against HIV including vaccines and antiretroviral prophylaxis target virus replication at this earliest stage of infection. Mathematical models have been used to understand how HIV spreads from mucosal tissues systemically and what impact vaccination and/or antiretroviral prophylaxis has on viral eradication. Because predictions of such models have been rarely compared to experimental data, it remains unclear which processes included in these models are critical for predicting early HIV dynamics. Here we modified the “standard” mathematical model of HIV infection to include two populations of infected cells: cells that are actively producing the virus and cells that are transitioning into virus production mode. We evaluated the effects of several poorly known parameters on infection outcomes in this model and compared model predictions to experimental data on infection of non-human primates with variable doses of simian immunodifficiency virus (SIV. First, we found that the mode of virus production by infected cells (budding vs. bursting has a minimal impact on the early virus dynamics for a wide range of model parameters, as long as the parameters are constrained to provide the observed rate of SIV load increase in the blood of infected animals. Interestingly and in contrast with previous results, we found that the bursting mode of virus production generally results in a higher probability of viral extinction than the budding mode of virus production. Second, this mathematical model was not able to accurately describe the change in experimentally determined probability of host infection with increasing viral doses. Third and finally, the model was also unable to accurately explain the decline in the time to virus detection with increasing viral

  13. Artificial neural network accurately predicts hepatitis B surface antigen seroclearance.

    Directory of Open Access Journals (Sweden)

    Ming-Hua Zheng

    Full Text Available BACKGROUND & AIMS: Hepatitis B surface antigen (HBsAg seroclearance and seroconversion are regarded as favorable outcomes of chronic hepatitis B (CHB. This study aimed to develop artificial neural networks (ANNs that could accurately predict HBsAg seroclearance or seroconversion on the basis of available serum variables. METHODS: Data from 203 untreated, HBeAg-negative CHB patients with spontaneous HBsAg seroclearance (63 with HBsAg seroconversion, and 203 age- and sex-matched HBeAg-negative controls were analyzed. ANNs and logistic regression models (LRMs were built and tested according to HBsAg seroclearance and seroconversion. Predictive accuracy was assessed with area under the receiver operating characteristic curve (AUROC. RESULTS: Serum quantitative HBsAg (qHBsAg and HBV DNA levels, qHBsAg and HBV DNA reduction were related to HBsAg seroclearance (P<0.001 and were used for ANN/LRM-HBsAg seroclearance building, whereas, qHBsAg reduction was not associated with ANN-HBsAg seroconversion (P = 0.197 and LRM-HBsAg seroconversion was solely based on qHBsAg (P = 0.01. For HBsAg seroclearance, AUROCs of ANN were 0.96, 0.93 and 0.95 for the training, testing and genotype B subgroups respectively. They were significantly higher than those of LRM, qHBsAg and HBV DNA (all P<0.05. Although the performance of ANN-HBsAg seroconversion (AUROC 0.757 was inferior to that for HBsAg seroclearance, it tended to be better than those of LRM, qHBsAg and HBV DNA. CONCLUSIONS: ANN identifies spontaneous HBsAg seroclearance in HBeAg-negative CHB patients with better accuracy, on the basis of easily available serum data. More useful predictors for HBsAg seroconversion are still needed to be explored in the future.

  14. Predicting promiscuous antigenic T cell epitopes of Mycobacterium tuberculosis mymA operon proteins binding to MHC Class I and Class II molecules.

    Science.gov (United States)

    Saraav, Iti; Pandey, Kirti; Sharma, Monika; Singh, Swati; Dutta, Prasun; Bhardwaj, Anshu; Sharma, Sadhna

    2016-10-01

    Limited efficacy of Bacillus Calmette-Guérin vaccine has raised the need to explore other immunogenic candidates to develop an effective vaccine against Mycobacterium tuberculosis (Mtb). Both CD4+ and CD8+ T cells play a critical role in host immunity to Mtb. Infection of macrophages with Mtb results in upregulation of mymA operon genes thereby suggesting their importance as immune targets. In the present study, after exclusion of self-peptides mymA operon proteins of Mtb were analyzed in silico for the presence of Human Leukocyte Antigen (HLA) Class I and Class II binding peptides using Bioinformatics and molecular analysis section, NetMHC 3.4, ProPred and Immune epitope database software. Out of 56 promiscuous epitopes obtained, 41 epitopes were predicted to be antigenic for MHC Class I. In MHC Class II, out of 336 promiscuous epitopes obtained, 142 epitopes were predicted to be antigenic. The comparative bioinformatics analysis of mymA operon proteins found Rv3083 to be the best vaccine candidate. Molecular docking was performed with the most antigenic peptides of Rv3083 (LASGAASVV with alleles HLA-B51:01, HAATSGTLI with HLA-A02, IVTATGLNI and EKIHYGLKVNTA with HLA-DRB1_01:01) to study the structural basis for recognition of peptides by various HLA molecules. The software binding prediction was validated by the obtained molecular docking score of peptide-HLA complex. These peptides can be further investigated for their immunological relevance in patients of tuberculosis using major histocompatibility complex tetramer approach. PMID:27389362

  15. Fast and accurate predictions of covalent bonds in chemical space

    Science.gov (United States)

    Chang, K. Y. Samuel; Fias, Stijn; Ramakrishnan, Raghunathan; von Lilienfeld, O. Anatole

    2016-05-01

    We assess the predictive accuracy of perturbation theory based estimates of changes in covalent bonding due to linear alchemical interpolations among molecules. We have investigated σ bonding to hydrogen, as well as σ and π bonding between main-group elements, occurring in small sets of iso-valence-electronic molecules with elements drawn from second to fourth rows in the p-block of the periodic table. Numerical evidence suggests that first order Taylor expansions of covalent bonding potentials can achieve high accuracy if (i) the alchemical interpolation is vertical (fixed geometry), (ii) it involves elements from the third and fourth rows of the periodic table, and (iii) an optimal reference geometry is used. This leads to near linear changes in the bonding potential, resulting in analytical predictions with chemical accuracy (˜1 kcal/mol). Second order estimates deteriorate the prediction. If initial and final molecules differ not only in composition but also in geometry, all estimates become substantially worse, with second order being slightly more accurate than first order. The independent particle approximation based second order perturbation theory performs poorly when compared to the coupled perturbed or finite difference approach. Taylor series expansions up to fourth order of the potential energy curve of highly symmetric systems indicate a finite radius of convergence, as illustrated for the alchemical stretching of H 2+ . Results are presented for (i) covalent bonds to hydrogen in 12 molecules with 8 valence electrons (CH4, NH3, H2O, HF, SiH4, PH3, H2S, HCl, GeH4, AsH3, H2Se, HBr); (ii) main-group single bonds in 9 molecules with 14 valence electrons (CH3F, CH3Cl, CH3Br, SiH3F, SiH3Cl, SiH3Br, GeH3F, GeH3Cl, GeH3Br); (iii) main-group double bonds in 9 molecules with 12 valence electrons (CH2O, CH2S, CH2Se, SiH2O, SiH2S, SiH2Se, GeH2O, GeH2S, GeH2Se); (iv) main-group triple bonds in 9 molecules with 10 valence electrons (HCN, HCP, HCAs, HSiN, HSi

  16. Fast and accurate predictions of covalent bonds in chemical space.

    Science.gov (United States)

    Chang, K Y Samuel; Fias, Stijn; Ramakrishnan, Raghunathan; von Lilienfeld, O Anatole

    2016-05-01

    We assess the predictive accuracy of perturbation theory based estimates of changes in covalent bonding due to linear alchemical interpolations among molecules. We have investigated σ bonding to hydrogen, as well as σ and π bonding between main-group elements, occurring in small sets of iso-valence-electronic molecules with elements drawn from second to fourth rows in the p-block of the periodic table. Numerical evidence suggests that first order Taylor expansions of covalent bonding potentials can achieve high accuracy if (i) the alchemical interpolation is vertical (fixed geometry), (ii) it involves elements from the third and fourth rows of the periodic table, and (iii) an optimal reference geometry is used. This leads to near linear changes in the bonding potential, resulting in analytical predictions with chemical accuracy (∼1 kcal/mol). Second order estimates deteriorate the prediction. If initial and final molecules differ not only in composition but also in geometry, all estimates become substantially worse, with second order being slightly more accurate than first order. The independent particle approximation based second order perturbation theory performs poorly when compared to the coupled perturbed or finite difference approach. Taylor series expansions up to fourth order of the potential energy curve of highly symmetric systems indicate a finite radius of convergence, as illustrated for the alchemical stretching of H2 (+). Results are presented for (i) covalent bonds to hydrogen in 12 molecules with 8 valence electrons (CH4, NH3, H2O, HF, SiH4, PH3, H2S, HCl, GeH4, AsH3, H2Se, HBr); (ii) main-group single bonds in 9 molecules with 14 valence electrons (CH3F, CH3Cl, CH3Br, SiH3F, SiH3Cl, SiH3Br, GeH3F, GeH3Cl, GeH3Br); (iii) main-group double bonds in 9 molecules with 12 valence electrons (CH2O, CH2S, CH2Se, SiH2O, SiH2S, SiH2Se, GeH2O, GeH2S, GeH2Se); (iv) main-group triple bonds in 9 molecules with 10 valence electrons (HCN, HCP, HCAs, HSiN, HSi

  17. Teaching the Big Ideas of Biology with Operon Models

    Science.gov (United States)

    Cooper, Robert A.

    2015-01-01

    This paper presents an activity that engages students in model-based reasoning, requiring them to predict the behavior of the trp and lac operons under different environmental conditions. Students are presented six scenarios for the "trp" operon and five for the "lac" operon. In most of the scenarios, specific mutations have…

  18. An Overview of Practical Applications of Protein Disorder Prediction and Drive for Faster, More Accurate Predictions

    Directory of Open Access Journals (Sweden)

    Xin Deng

    2015-07-01

    Full Text Available Protein disordered regions are segments of a protein chain that do not adopt a stable structure. Thus far, a variety of protein disorder prediction methods have been developed and have been widely used, not only in traditional bioinformatics domains, including protein structure prediction, protein structure determination and function annotation, but also in many other biomedical fields. The relationship between intrinsically-disordered proteins and some human diseases has played a significant role in disorder prediction in disease identification and epidemiological investigations. Disordered proteins can also serve as potential targets for drug discovery with an emphasis on the disordered-to-ordered transition in the disordered binding regions, and this has led to substantial research in drug discovery or design based on protein disordered region prediction. Furthermore, protein disorder prediction has also been applied to healthcare by predicting the disease risk of mutations in patients and studying the mechanistic basis of diseases. As the applications of disorder prediction increase, so too does the need to make quick and accurate predictions. To fill this need, we also present a new approach to predict protein residue disorder using wide sequence windows that is applicable on the genomic scale.

  19. Standardized EEG interpretation accurately predicts prognosis after cardiac arrest

    Science.gov (United States)

    Rossetti, Andrea O.; van Rootselaar, Anne-Fleur; Wesenberg Kjaer, Troels; Horn, Janneke; Ullén, Susann; Friberg, Hans; Nielsen, Niklas; Rosén, Ingmar; Åneman, Anders; Erlinge, David; Gasche, Yvan; Hassager, Christian; Hovdenes, Jan; Kjaergaard, Jesper; Kuiper, Michael; Pellis, Tommaso; Stammet, Pascal; Wanscher, Michael; Wetterslev, Jørn; Wise, Matt P.; Cronberg, Tobias

    2016-01-01

    Objective: To identify reliable predictors of outcome in comatose patients after cardiac arrest using a single routine EEG and standardized interpretation according to the terminology proposed by the American Clinical Neurophysiology Society. Methods: In this cohort study, 4 EEG specialists, blinded to outcome, evaluated prospectively recorded EEGs in the Target Temperature Management trial (TTM trial) that randomized patients to 33°C vs 36°C. Routine EEG was performed in patients still comatose after rewarming. EEGs were classified into highly malignant (suppression, suppression with periodic discharges, burst-suppression), malignant (periodic or rhythmic patterns, pathological or nonreactive background), and benign EEG (absence of malignant features). Poor outcome was defined as best Cerebral Performance Category score 3–5 until 180 days. Results: Eight TTM sites randomized 202 patients. EEGs were recorded in 103 patients at a median 77 hours after cardiac arrest; 37% had a highly malignant EEG and all had a poor outcome (specificity 100%, sensitivity 50%). Any malignant EEG feature had a low specificity to predict poor prognosis (48%) but if 2 malignant EEG features were present specificity increased to 96% (p EEG was found in 1% of the patients with a poor outcome. Conclusions: Highly malignant EEG after rewarming reliably predicted poor outcome in half of patients without false predictions. An isolated finding of a single malignant feature did not predict poor outcome whereas a benign EEG was highly predictive of a good outcome. PMID:26865516

  20. Is Three-Dimensional Soft Tissue Prediction by Software Accurate?

    Science.gov (United States)

    Nam, Ki-Uk; Hong, Jongrak

    2015-11-01

    The authors assessed whether virtual surgery, performed with a soft tissue prediction program, could correctly simulate the actual surgical outcome, focusing on soft tissue movement. Preoperative and postoperative computed tomography (CT) data for 29 patients, who had undergone orthognathic surgery, were obtained and analyzed using the Simplant Pro software. The program made a predicted soft tissue image (A) based on presurgical CT data. After the operation, we obtained actual postoperative CT data and an actual soft tissue image (B) was generated. Finally, the 2 images (A and B) were superimposed and analyzed differences between the A and B. Results were grouped in 2 classes: absolute values and vector values. In the absolute values, the left mouth corner was the most significant error point (2.36 mm). The right mouth corner (2.28 mm), labrale inferius (2.08 mm), and the pogonion (2.03 mm) also had significant errors. In vector values, prediction of the right-left side had a left-sided tendency, the superior-inferior had a superior tendency, and the anterior-posterior showed an anterior tendency. As a result, with this program, the position of points tended to be located more left, anterior, and superior than the "real" situation. There is a need to improve the prediction accuracy for soft tissue images. Such software is particularly valuable in predicting craniofacial soft tissues landmarks, such as the pronasale. With this software, landmark positions were most inaccurate in terms of anterior-posterior predictions.

  1. Standardized EEG interpretation accurately predicts prognosis after cardiac arrest

    Science.gov (United States)

    Rossetti, Andrea O.; van Rootselaar, Anne-Fleur; Wesenberg Kjaer, Troels; Horn, Janneke; Ullén, Susann; Friberg, Hans; Nielsen, Niklas; Rosén, Ingmar; Åneman, Anders; Erlinge, David; Gasche, Yvan; Hassager, Christian; Hovdenes, Jan; Kjaergaard, Jesper; Kuiper, Michael; Pellis, Tommaso; Stammet, Pascal; Wanscher, Michael; Wetterslev, Jørn; Wise, Matt P.; Cronberg, Tobias

    2016-01-01

    Objective: To identify reliable predictors of outcome in comatose patients after cardiac arrest using a single routine EEG and standardized interpretation according to the terminology proposed by the American Clinical Neurophysiology Society. Methods: In this cohort study, 4 EEG specialists, blinded to outcome, evaluated prospectively recorded EEGs in the Target Temperature Management trial (TTM trial) that randomized patients to 33°C vs 36°C. Routine EEG was performed in patients still comatose after rewarming. EEGs were classified into highly malignant (suppression, suppression with periodic discharges, burst-suppression), malignant (periodic or rhythmic patterns, pathological or nonreactive background), and benign EEG (absence of malignant features). Poor outcome was defined as best Cerebral Performance Category score 3–5 until 180 days. Results: Eight TTM sites randomized 202 patients. EEGs were recorded in 103 patients at a median 77 hours after cardiac arrest; 37% had a highly malignant EEG and all had a poor outcome (specificity 100%, sensitivity 50%). Any malignant EEG feature had a low specificity to predict poor prognosis (48%) but if 2 malignant EEG features were present specificity increased to 96% (p < 0.001). Specificity and sensitivity were not significantly affected by targeted temperature or sedation. A benign EEG was found in 1% of the patients with a poor outcome. Conclusions: Highly malignant EEG after rewarming reliably predicted poor outcome in half of patients without false predictions. An isolated finding of a single malignant feature did not predict poor outcome whereas a benign EEG was highly predictive of a good outcome. PMID:26865516

  2. Analytical method to accurately predict LMFBR core flow distribution

    International Nuclear Information System (INIS)

    An accurate and detailed representation of the flow distribution in LMFBR cores is very important as the starting point and basis of the thermal and structural core design. Previous experience indicated that the steady state and transient core design is as good as the core orificing; thus, a new orificing philosophy satisfying a priori all design constraints was developd. However, optimized orificing is a necessary, but not sufficient condition for achieving the optimum core flow distribution, which is affected by the hydraulic characteristics of the remainder of the primary system. Consequently, an analytical model of the overall primary system was developed, resulting in the CATFISH computer code, which, even though specifically written for LMFBRs, can be used for any reactor employing ducted assemblies

  3. Standardized EEG interpretation accurately predicts prognosis after cardiac arrest

    DEFF Research Database (Denmark)

    Westhall, Erik; Rossetti, Andrea O; van Rootselaar, Anne-Fleur;

    2016-01-01

    OBJECTIVE: To identify reliable predictors of outcome in comatose patients after cardiac arrest using a single routine EEG and standardized interpretation according to the terminology proposed by the American Clinical Neurophysiology Society. METHODS: In this cohort study, 4 EEG specialists...... patients. EEGs were recorded in 103 patients at a median 77 hours after cardiac arrest; 37% had a highly malignant EEG and all had a poor outcome (specificity 100%, sensitivity 50%). Any malignant EEG feature had a low specificity to predict poor prognosis (48%) but if 2 malignant EEG features were present...

  4. Predicting accurate absolute binding energies in aqueous solution

    DEFF Research Database (Denmark)

    Jensen, Jan Halborg

    2015-01-01

    Recent predictions of absolute binding free energies of host-guest complexes in aqueous solution using electronic structure theory have been encouraging for some systems, while other systems remain problematic. In this paper I summarize some of the many factors that could easily contribute 1-3 kcal......-represented by continuum models. While I focus on binding free energies in aqueous solution the approach also applies (with minor adjustments) to any free energy difference such as conformational or reaction free energy differences or activation free energies in any solvent....

  5. Novel Accurate Bacterial Discrimination by MALDI-Time-of-Flight MS Based on Ribosomal Proteins Coding in S10-spc-alpha Operon at Strain Level S10-GERMS

    Science.gov (United States)

    Tamura, Hiroto; Hotta, Yudai; Sato, Hiroaki

    2013-08-01

    Matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is one of the most widely used mass-based approaches for bacterial identification and classification because of the simple sample preparation and extremely rapid analysis within a few minutes. To establish the accurate MALDI-TOF MS bacterial discrimination method at strain level, the ribosomal subunit proteins coded in the S 10-spc-alpha operon, which encodes half of the ribosomal subunit protein and is highly conserved in eubacterial genomes, were selected as reliable biomarkers. This method, named the S10-GERMS method, revealed that the strains of genus Pseudomonas were successfully identified and discriminated at species and strain levels, respectively; therefore, the S10-GERMS method was further applied to discriminate the pathovar of P. syringae. The eight selected biomarkers (L24, L30, S10, S12, S14, S16, S17, and S19) suggested the rapid discrimination of P. syringae at the strain (pathovar) level. The S10-GERMS method appears to be a powerful tool for rapid and reliable bacterial discrimination and successful phylogenetic characterization. In this article, an overview of the utilization of results from the S10-GERMS method is presented, highlighting the characterization of the Lactobacillus casei group and discrimination of the bacteria of genera Bacillus and Sphingopyxis despite only two and one base difference in the 16S rRNA gene sequence, respectively.

  6. Copeptin does not accurately predict disease severity in imported malaria

    Directory of Open Access Journals (Sweden)

    van Wolfswinkel Marlies E

    2012-01-01

    Full Text Available Abstract Background Copeptin has recently been identified to be a stable surrogate marker for the unstable hormone arginine vasopressin (AVP. Copeptin has been shown to correlate with disease severity in leptospirosis and bacterial sepsis. Hyponatraemia is common in severe imported malaria and dysregulation of AVP release has been hypothesized as an underlying pathophysiological mechanism. The aim of the present study was to evaluate the performance of copeptin as a predictor of disease severity in imported malaria. Methods Copeptin was measured in stored serum samples of 204 patients with imported malaria that were admitted to our Institute for Tropical Diseases in Rotterdam in the period 1999-2010. The occurrence of WHO defined severe malaria was the primary end-point. The diagnostic performance of copeptin was compared to that of previously evaluated biomarkers C-reactive protein, procalcitonin, lactate and sodium. Results Of the 204 patients (141 Plasmodium falciparum, 63 non-falciparum infection, 25 had severe malaria. The Area Under the ROC curve of copeptin for severe disease (0.66 [95% confidence interval 0.59-0.72] was comparable to that of lactate, sodium and procalcitonin. C-reactive protein (0.84 [95% CI 0.79-0.89] had a significantly better performance as a biomarker for severe malaria than the other biomarkers. Conclusions C-reactive protein but not copeptin was found to be an accurate predictor for disease severity in imported malaria. The applicability of copeptin as a marker for severe malaria in clinical practice is limited to exclusion of severe malaria.

  7. Accurate theoretical prediction on positron lifetime of bulk materials

    CERN Document Server

    Zhang, Wenshuai; Liu, Jiandang; Ye, Bangjiao

    2015-01-01

    Based on the first-principles calculations, we perform an initiatory statistical assessment on the reliability level of theoretical positron lifetime of bulk material. We found the original generalized gradient approximation (GGA) form of the enhancement factor and correlation potentials overestimates the effect of the gradient factor. Furthermore, an excellent agreement between model and data with the difference being the noise level of the data is found in this work. In addition, we suggest a new GGA form of the correlation scheme which gives the best performance. This work demonstrates that a brand-new reliability level is achieved for the theoretical prediction on positron lifetime of bulk material and the accuracy of the best theoretical scheme can be independent on the type of materials.

  8. Change in BMI accurately predicted by social exposure to acquaintances.

    Directory of Open Access Journals (Sweden)

    Rahman O Oloritun

    Full Text Available Research has mostly focused on obesity and not on processes of BMI change more generally, although these may be key factors that lead to obesity. Studies have suggested that obesity is affected by social ties. However these studies used survey based data collection techniques that may be biased toward select only close friends and relatives. In this study, mobile phone sensing techniques were used to routinely capture social interaction data in an undergraduate dorm. By automating the capture of social interaction data, the limitations of self-reported social exposure data are avoided. This study attempts to understand and develop a model that best describes the change in BMI using social interaction data. We evaluated a cohort of 42 college students in a co-located university dorm, automatically captured via mobile phones and survey based health-related information. We determined the most predictive variables for change in BMI using the least absolute shrinkage and selection operator (LASSO method. The selected variables, with gender, healthy diet category, and ability to manage stress, were used to build multiple linear regression models that estimate the effect of exposure and individual factors on change in BMI. We identified the best model using Akaike Information Criterion (AIC and R(2. This study found a model that explains 68% (p<0.0001 of the variation in change in BMI. The model combined social interaction data, especially from acquaintances, and personal health-related information to explain change in BMI. This is the first study taking into account both interactions with different levels of social interaction and personal health-related information. Social interactions with acquaintances accounted for more than half the variation in change in BMI. This suggests the importance of not only individual health information but also the significance of social interactions with people we are exposed to, even people we may not consider as

  9. Mind-set and close relationships: when bias leads to (In)accurate predictions.

    Science.gov (United States)

    Gagné, F M; Lydon, J E

    2001-07-01

    The authors investigated whether mind-set influences the accuracy of relationship predictions. Because people are more biased in their information processing when thinking about implementing an important goal, relationship predictions made in an implemental mind-set were expected to be less accurate than those made in a more impartial deliberative mind-set. In Study 1, open-ended thoughts of students about to leave for university were coded for mind-set. In Study 2, mind-set about a major life goal was assessed using a self-report measure. In Study 3, mind-set was experimentally manipulated. Overall, mind-set interacted with forecasts to predict relationship survival. Forecasts were more accurate in a deliberative mind-set than in an implemental mind-set. This effect was more pronounced for long-term than for short-term relationship survival. Finally, deliberatives were not pessimistic; implementals were unduly optimistic.

  10. Modeling methodology for the accurate and prompt prediction of symptomatic events in chronic diseases.

    Science.gov (United States)

    Pagán, Josué; Risco-Martín, José L; Moya, José M; Ayala, José L

    2016-08-01

    Prediction of symptomatic crises in chronic diseases allows to take decisions before the symptoms occur, such as the intake of drugs to avoid the symptoms or the activation of medical alarms. The prediction horizon is in this case an important parameter in order to fulfill the pharmacokinetics of medications, or the time response of medical services. This paper presents a study about the prediction limits of a chronic disease with symptomatic crises: the migraine. For that purpose, this work develops a methodology to build predictive migraine models and to improve these predictions beyond the limits of the initial models. The maximum prediction horizon is analyzed, and its dependency on the selected features is studied. A strategy for model selection is proposed to tackle the trade off between conservative but robust predictive models, with respect to less accurate predictions with higher horizons. The obtained results show a prediction horizon close to 40min, which is in the time range of the drug pharmacokinetics. Experiments have been performed in a realistic scenario where input data have been acquired in an ambulatory clinical study by the deployment of a non-intrusive Wireless Body Sensor Network. Our results provide an effective methodology for the selection of the future horizon in the development of prediction algorithms for diseases experiencing symptomatic crises. PMID:27260782

  11. A highly accurate predictive-adaptive method for lithium-ion battery remaining discharge energy prediction in electric vehicle applications

    International Nuclear Information System (INIS)

    Highlights: • An energy prediction (EP) method is introduced for battery ERDE determination. • EP determines ERDE through coupled prediction of future states, parameters, and output. • The PAEP combines parameter adaptation and prediction to update model parameters. • The PAEP provides improved ERDE accuracy compared with DC and other EP methods. - Abstract: In order to estimate the remaining driving range (RDR) in electric vehicles, the remaining discharge energy (ERDE) of the applied battery system needs to be precisely predicted. Strongly affected by the load profiles, the available ERDE varies largely in real-world applications and requires specific determination. However, the commonly-used direct calculation (DC) method might result in certain energy prediction errors by relating the ERDE directly to the current state of charge (SOC). To enhance the ERDE accuracy, this paper presents a battery energy prediction (EP) method based on the predictive control theory, in which a coupled prediction of future battery state variation, battery model parameter change, and voltage response, is implemented on the ERDE prediction horizon, and the ERDE is subsequently accumulated and real-timely optimized. Three EP approaches with different model parameter updating routes are introduced, and the predictive-adaptive energy prediction (PAEP) method combining the real-time parameter identification and the future parameter prediction offers the best potential. Based on a large-format lithium-ion battery, the performance of different ERDE calculation methods is compared under various dynamic profiles. Results imply that the EP methods provide much better accuracy than the traditional DC method, and the PAEP could reduce the ERDE error by more than 90% and guarantee the relative energy prediction error under 2%, proving as a proper choice in online ERDE prediction. The correlation of SOC estimation and ERDE calculation is then discussed to illustrate the importance of an

  12. MycoperonDB: a database of computationally identified operons and transcriptional units in Mycobacteria

    Directory of Open Access Journals (Sweden)

    Ranjan Akash

    2006-12-01

    Full Text Available Abstract Background A key post genomics challenge is to identify how genes in an organism come together and perform physiological functions. An important first step in this direction is to identify transcriptional units, operons and regulons in a genome. Here we implement and report a strategy to computationally identify transcriptional units and operons of mycobacteria and construct a database-MycoperonDB. Description We have predicted transcriptional units and operons in mycobacteria and organized these predictions in the form of relational database called MycoperonDB. MycoperonDB database at present consists of 18053 genes organized as 8256 predicted operons and transcriptional units from five closely related species of mycobacteria. The database further provides literature links for experimentally characterized operons. All known promoters and related information is collected, analysed and stored. It provides a user friendly interface to allow a web based navigation of transcription units and operons. The web interface provides search tools to locate transcription factor binding DNA motif upstream to various genes. The reliability of operon prediction has been assessed by comparing the predicted operons with a set of known operons. Conclusion MycoperonDB is a publicly available structured relational database which has information about mycobacterial genes, transcriptional units and operons. We expect this database to assist molecular biologists/microbiologists in general, to hypothesize functional linkages between operonic genes of mycobacteria, their experimental characterization and validation. The database is freely available from our website http://www.cdfd.org.in/mycoperondb/index.html.

  13. Hash: a program to accurately predict protein H{sup {alpha}} shifts from neighboring backbone shifts

    Energy Technology Data Exchange (ETDEWEB)

    Zeng Jianyang, E-mail: zengjy@gmail.com [Tsinghua University, Institute for Interdisciplinary Information Sciences (China); Zhou Pei [Duke University Medical Center, Department of Biochemistry (United States); Donald, Bruce Randall [Duke University, Department of Computer Science (United States)

    2013-01-15

    Chemical shifts provide not only peak identities for analyzing nuclear magnetic resonance (NMR) data, but also an important source of conformational information for studying protein structures. Current structural studies requiring H{sup {alpha}} chemical shifts suffer from the following limitations. (1) For large proteins, the H{sup {alpha}} chemical shifts can be difficult to assign using conventional NMR triple-resonance experiments, mainly due to the fast transverse relaxation rate of C{sup {alpha}} that restricts the signal sensitivity. (2) Previous chemical shift prediction approaches either require homologous models with high sequence similarity or rely heavily on accurate backbone and side-chain structural coordinates. When neither sequence homologues nor structural coordinates are available, we must resort to other information to predict H{sup {alpha}} chemical shifts. Predicting accurate H{sup {alpha}} chemical shifts using other obtainable information, such as the chemical shifts of nearby backbone atoms (i.e., adjacent atoms in the sequence), can remedy the above dilemmas, and hence advance NMR-based structural studies of proteins. By specifically exploiting the dependencies on chemical shifts of nearby backbone atoms, we propose a novel machine learning algorithm, called Hash, to predict H{sup {alpha}} chemical shifts. Hash combines a new fragment-based chemical shift search approach with a non-parametric regression model, called the generalized additive model, to effectively solve the prediction problem. We demonstrate that the chemical shifts of nearby backbone atoms provide a reliable source of information for predicting accurate H{sup {alpha}} chemical shifts. Our testing results on different possible combinations of input data indicate that Hash has a wide rage of potential NMR applications in structural and biological studies of proteins.

  14. A Single Linear Prediction Filter that Accurately Predicts the AL Index

    Science.gov (United States)

    McPherron, R. L.; Chu, X.

    2015-12-01

    The AL index is a measure of the strength of the westward electrojet flowing along the auroral oval. It has two components: one from the global DP-2 current system and a second from the DP-1 current that is more localized near midnight. It is generally believed that the index a very poor measure of these currents because of its dependence on the distance of stations from the source of the two currents. In fact over season and solar cycle the coupling strength defined as the steady state ratio of the output AL to the input coupling function varies by a factor of four. There are four factors that lead to this variation. First is the equinoctial effect that modulates coupling strength with peaks (strongest coupling) at the equinoxes. Second is the saturation of the polar cap potential which decreases coupling strength as the strength of the driver increases. Since saturation occurs more frequently at solar maximum we obtain the result that maximum coupling strength occurs at equinox at solar minimum. A third factor is ionospheric conductivity with stronger coupling at summer solstice as compared to winter. The fourth factor is the definition of a solar wind coupling function appropriate to a given index. We have developed an optimum coupling function depending on solar wind speed, density, transverse magnetic field, and IMF clock angle which is better than previous functions. Using this we have determined the seasonal variation of coupling strength and developed an inverse function that modulates the optimum coupling function so that all seasonal variation is removed. In a similar manner we have determined the dependence of coupling strength on solar wind driver strength. The inverse of this function is used to scale a linear prediction filter thus eliminating the dependence on driver strength. Our result is a single linear filter that is adjusted in a nonlinear manner by driver strength and an optimum coupling function that is seasonal modulated. Together this

  15. Rapid yet accurate first principle based predictions of alkali halide crystal phases using alchemical perturbation

    CERN Document Server

    Solovyeva, Alisa

    2016-01-01

    We assess the predictive power of alchemical perturbations for estimating fundamental properties in ionic crystals. Using density functional theory we have calculated formation energies, lattice constants, and bulk moduli for all sixteen iso-valence-electronic combinations of pure pristine alkali halides involving elements $A \\in \\{$Na, K, Rb, Cs$\\}$ and $X \\in \\{$F, Cl, Br, I$\\}$. For rock salt, zincblende and cesium chloride symmetry, alchemical Hellmann-Feynman derivatives, evaluated along lattice scans of sixteen reference crystals, have been obtained for all respective 16$\\times$15 combinations of reference and predicted target crystals. Mean absolute errors (MAE) are on par with density functional theory level of accuracy for energies and bulk modulus. Predicted lattice constants are less accurate. NaCl is the best reference salt for alchemical estimates of relative energies (MAE $<$ 40 meV/atom) while alkali fluorides are the worst. By contrast, lattice constants are predicted best using NaF as a re...

  16. Rapid and accurate prediction and scoring of water molecules in protein binding sites.

    Directory of Open Access Journals (Sweden)

    Gregory A Ross

    Full Text Available Water plays a critical role in ligand-protein interactions. However, it is still challenging to predict accurately not only where water molecules prefer to bind, but also which of those water molecules might be displaceable. The latter is often seen as a route to optimizing affinity of potential drug candidates. Using a protocol we call WaterDock, we show that the freely available AutoDock Vina tool can be used to predict accurately the binding sites of water molecules. WaterDock was validated using data from X-ray crystallography, neutron diffraction and molecular dynamics simulations and correctly predicted 97% of the water molecules in the test set. In addition, we combined data-mining, heuristic and machine learning techniques to develop probabilistic water molecule classifiers. When applied to WaterDock predictions in the Astex Diverse Set of protein ligand complexes, we could identify whether a water molecule was conserved or displaced to an accuracy of 75%. A second model predicted whether water molecules were displaced by polar groups or by non-polar groups to an accuracy of 80%. These results should prove useful for anyone wishing to undertake rational design of new compounds where the displacement of water molecules is being considered as a route to improved affinity.

  17. Accurately Estimating the State of a Geophysical System with Sparse Observations: Predicting the Weather

    CERN Document Server

    An, Zhe; Abarbanel, Henry D I

    2014-01-01

    Utilizing the information in observations of a complex system to make accurate predictions through a quantitative model when observations are completed at time $T$, requires an accurate estimate of the full state of the model at time $T$. When the number of measurements $L$ at each observation time within the observation window is larger than a sufficient minimum value $L_s$, the impediments in the estimation procedure are removed. As the number of available observations is typically such that $L \\ll L_s$, additional information from the observations must be presented to the model. We show how, using the time delays of the measurements at each observation time, one can augment the information transferred from the data to the model, removing the impediments to accurate estimation and permitting dependable prediction. We do this in a core geophysical fluid dynamics model, the shallow water equations, at the heart of numerical weather prediction. The method is quite general, however, and can be utilized in the a...

  18. Highly Accurate Structure-Based Prediction of HIV-1 Coreceptor Usage Suggests Intermolecular Interactions Driving Tropism.

    Directory of Open Access Journals (Sweden)

    Chris A Kieslich

    Full Text Available HIV-1 entry into host cells is mediated by interactions between the V3-loop of viral glycoprotein gp120 and chemokine receptor CCR5 or CXCR4, collectively known as HIV-1 coreceptors. Accurate genotypic prediction of coreceptor usage is of significant clinical interest and determination of the factors driving tropism has been the focus of extensive study. We have developed a method based on nonlinear support vector machines to elucidate the interacting residue pairs driving coreceptor usage and provide highly accurate coreceptor usage predictions. Our models utilize centroid-centroid interaction energies from computationally derived structures of the V3-loop:coreceptor complexes as primary features, while additional features based on established rules regarding V3-loop sequences are also investigated. We tested our method on 2455 V3-loop sequences of various lengths and subtypes, and produce a median area under the receiver operator curve of 0.977 based on 500 runs of 10-fold cross validation. Our study is the first to elucidate a small set of specific interacting residue pairs between the V3-loop and coreceptors capable of predicting coreceptor usage with high accuracy across major HIV-1 subtypes. The developed method has been implemented as a web tool named CRUSH, CoReceptor USage prediction for HIV-1, which is available at http://ares.tamu.edu/CRUSH/.

  19. Highly Accurate Structure-Based Prediction of HIV-1 Coreceptor Usage Suggests Intermolecular Interactions Driving Tropism

    Science.gov (United States)

    Kieslich, Chris A.; Tamamis, Phanourios; Guzman, Yannis A.; Onel, Melis; Floudas, Christodoulos A.

    2016-01-01

    HIV-1 entry into host cells is mediated by interactions between the V3-loop of viral glycoprotein gp120 and chemokine receptor CCR5 or CXCR4, collectively known as HIV-1 coreceptors. Accurate genotypic prediction of coreceptor usage is of significant clinical interest and determination of the factors driving tropism has been the focus of extensive study. We have developed a method based on nonlinear support vector machines to elucidate the interacting residue pairs driving coreceptor usage and provide highly accurate coreceptor usage predictions. Our models utilize centroid-centroid interaction energies from computationally derived structures of the V3-loop:coreceptor complexes as primary features, while additional features based on established rules regarding V3-loop sequences are also investigated. We tested our method on 2455 V3-loop sequences of various lengths and subtypes, and produce a median area under the receiver operator curve of 0.977 based on 500 runs of 10-fold cross validation. Our study is the first to elucidate a small set of specific interacting residue pairs between the V3-loop and coreceptors capable of predicting coreceptor usage with high accuracy across major HIV-1 subtypes. The developed method has been implemented as a web tool named CRUSH, CoReceptor USage prediction for HIV-1, which is available at http://ares.tamu.edu/CRUSH/. PMID:26859389

  20. More accurate recombination prediction in HIV-1 using a robust decoding algorithm for HMMs

    Directory of Open Access Journals (Sweden)

    Brown Daniel G

    2011-05-01

    Full Text Available Abstract Background Identifying recombinations in HIV is important for studying the epidemiology of the virus and aids in the design of potential vaccines and treatments. The previous widely-used tool for this task uses the Viterbi algorithm in a hidden Markov model to model recombinant sequences. Results We apply a new decoding algorithm for this HMM that improves prediction accuracy. Exactly locating breakpoints is usually impossible, since different subtypes are highly conserved in some sequence regions. Our algorithm identifies these sites up to a certain error tolerance. Our new algorithm is more accurate in predicting the location of recombination breakpoints. Our implementation of the algorithm is available at http://www.cs.uwaterloo.ca/~jmtruszk/jphmm_balls.tar.gz. Conclusions By explicitly accounting for uncertainty in breakpoint positions, our algorithm offers more reliable predictions of recombination breakpoints in HIV-1. We also document a new domain of use for our new decoding approach in HMMs.

  1. Fucose-Mediated Transcriptional Activation of the fcs Operon by FcsR in Streptococcus pneumoniae.

    Science.gov (United States)

    Manzoor, Irfan; Shafeeq, Sulman; Afzal, Muhammad; Kuipers, Oscar P

    2015-01-01

    In this study, we explore the impact of fucose on the transcriptome of S. pneumoniae D39. The expression of various genes and operons, including the fucose uptake PTS and utilization operon (fcs operon) was altered in the presence of fucose. By means of quantitative RT-PCR and β-galactosidase analysis, we demonstrate the role of the transcriptional regulator FcsR, present upstream of the fcs operon, as a transcriptional activator of the fcs operon. We also predict a 19-bp putative FcsR regulatory site (5'-ATTTGAACATTATTCAAGT-3') in the promoter region of the fcs operon. The functionality of this predicted FcsR regulatory site was further confirmed by promoter-truncation experiments, where deletion of half of the FscR regulatory site or full deletion led to the abolition of expression of the fcs operon.

  2. Accurate approximation method for prediction of class I MHC affinities for peptides of length 8, 10 and 11 using prediction tools trained on 9mers

    DEFF Research Database (Denmark)

    Lundegaard, Claus; Lund, Ole; Nielsen, Morten

    2008-01-01

    Several accurate prediction systems have been developed for prediction of class I major histocompatibility complex (MHC):peptide binding. Most of these are trained on binding affinity data of primarily 9mer peptides. Here, we show how prediction methods trained on 9mer data can be used for accurate...

  3. Machine learning predictions of molecular properties: Accurate many-body potentials and nonlocality in chemical space

    International Nuclear Information System (INIS)

    Simultaneously accurate and efficient prediction of molecular properties throughout chemical compound space is a critical ingredient toward rational compound design in chemical and pharmaceutical industries. Aiming toward this goal, we develop and apply a systematic hierarchy of efficient empirical methods to estimate atomization and total energies of molecules. These methods range from a simple sum over atoms, to addition of bond energies, to pairwise interatomic force fields, reaching to the more sophisticated machine learning approaches that are capable of describing collective interactions between many atoms or bonds. In the case of equilibrium molecular geometries, even simple pairwise force fields demonstrate prediction accuracy comparable to benchmark energies calculated using density functional theory with hybrid exchange-correlation functionals; however, accounting for the collective many-body interactions proves to be essential for approaching the 'holy grail' of chemical accuracy of 1 kcal/mol for both equilibrium and out-of-equilibrium geometries. This remarkable accuracy is achieved by a vectorized representation of molecules (so-called Bag of Bonds model) that exhibits strong nonlocality in chemical space. The same representation allows us to predict accurate electronic properties of molecules, such as their polarizability and molecular frontier orbital energies

  4. LogGPO: An accurate communication model for performance prediction of MPI programs

    Institute of Scientific and Technical Information of China (English)

    CHEN WenGuang; ZHAI JiDong; ZHANG Jin; ZHENG WeiMin

    2009-01-01

    Message passing interface (MPI) is the de facto standard in writing parallel scientific applications on distributed memory systems. Performance prediction of MPI programs on current or future parallel sys-terns can help to find system bottleneck or optimize programs. To effectively analyze and predict per-formance of a large and complex MPI program, an efficient and accurate communication model is highly needed. A series of communication models have been proposed, such as the LogP model family, which assume that the sending overhead, message transmission, and receiving overhead of a communication is not overlapped and there is a maximum overlap degree between computation and communication. However, this assumption does not always hold for MPI programs because either sending or receiving overhead introduced by MPI implementations can decrease potential overlap for large messages. In this paper, we present a new communication model, named LogGPO, which captures the potential overlap between computation with communication of MPI programs. We design and implement a trace-driven simulator to verify the LogGPO model by predicting performance of point-to-point communication and two real applications CG and Sweep3D. The average prediction errors of LogGPO model are 2.4% and 2.0% for these two applications respectively, while the average prediction errors of LogGP model are 38.3% and 9.1% respectively.

  5. Microstructure-Dependent Gas Adsorption: Accurate Predictions of Methane Uptake in Nanoporous Carbons

    Energy Technology Data Exchange (ETDEWEB)

    Ihm, Yungok [University of Tennessee (UTK) and Oak Ridge National Laboratory (ORNL); Cooper, Valentino R [ORNL; Gallego, Nidia C [ORNL; Contescu, Cristian I [ORNL; Morris, James R [ORNL

    2014-01-01

    We demonstrate a successful, efficient framework for predicting gas adsorption properties in real materials based on first-principles calculations, with a specific comparison of experiment and theory for methane adsorption in activated carbons. These carbon materials have different pore size distributions, leading to a variety of uptake characteristics. Utilizing these distributions, we accurately predict experimental uptakes and heats of adsorption without empirical potentials or lengthy simulations. We demonstrate that materials with smaller pores have higher heats of adsorption, leading to a higher gas density in these pores. This pore-size dependence must be accounted for, in order to predict and understand the adsorption behavior. The theoretical approach combines: (1) ab initio calculations with a van der Waals density functional to determine adsorbent-adsorbate interactions, and (2) a thermodynamic method that predicts equilibrium adsorption densities by directly incorporating the calculated potential energy surface in a slit pore model. The predicted uptake at P=20 bar and T=298 K is in excellent agreement for all five activated carbon materials used. This approach uses only the pore-size distribution as an input, with no fitting parameters or empirical adsorbent-adsorbate interactions, and thus can be easily applied to other adsorbent-adsorbate combinations.

  6. The MIDAS touch for Accurately Predicting the Stress-Strain Behavior of Tantalum

    Energy Technology Data Exchange (ETDEWEB)

    Jorgensen, S. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2016-03-02

    Testing the behavior of metals in extreme environments is not always feasible, so material scientists use models to try and predict the behavior. To achieve accurate results it is necessary to use the appropriate model and material-specific parameters. This research evaluated the performance of six material models available in the MIDAS database [1] to determine at which temperatures and strain-rates they perform best, and to determine to which experimental data their parameters were optimized. Additionally, parameters were optimized for the Johnson-Cook model using experimental data from Lassila et al [2].

  7. Evolution and Biophysics of the Escherichia coli lac Operon

    Science.gov (United States)

    Ray, J. Christian; Igoshin, Oleg; Quan, Selwyn; Monds, Russell; Cooper, Tim; Balázsi, Gábor

    2011-03-01

    To understand, predict, and control the evolution of living organisms, we consider biophysical effects and molecular network architectures. The lactose utilization system of E. coli is among the most well-studied molecular networks in biology, making it an ideal candidate for such studies. Simulations show how the genetic architecture of the wild-type operon attenuates large metabolic intermediate fluctuations that are predicted to occur in an equivalent system with the component genes on separate operons. Quantification of gene expression in the lac operon evolved in growth conditions containing constant lactose, alternating with glucose, or constant glucose, shows characteristic gene expression patterns depending on conditions. We are simulating these conditions to show context-dependent biophysical sources and costs of different lac operon architectures.

  8. The post-transcriptional operon

    DEFF Research Database (Denmark)

    Tenenbaum, Scott A.; Christiansen, Jan; Nielsen, Henrik

    2011-01-01

    A post-transcriptional operon is a set of monocistronic mRNAs encoding functionally related proteins that are co-regulated by a group of RNA-binding proteins and/or small non-coding RNAs so that protein expression is coordinated at the post-transcriptional level. The post-transcriptional operon m...

  9. Physical modeling of real-world slingshots for accurate speed predictions

    CERN Document Server

    Yeats, Bob

    2016-01-01

    We discuss the physics and modeling of latex-rubber slingshots. The goal is to get accurate speed predictions inspite of the significant real world difficulties of force drift, force hysteresis, rubber ageing, and the very non- linear, non-ideal, force vs. pull distance curves of slingshot rubber bands. Slingshots are known to shoot faster under some circumstances when the bands are tapered rather than having constant width and stiffness. We give both qualitative understanding and numerical predictions of this effect. We consider two models. The first is based on conservation of energy and is easier to implement, but cannot determine the speeds along the rubber bands without making assumptions. The second, treats the bands as a series of mass points subject to being pulled by immediately adjacent mass points according to how much the rubber has been stretched on the two adjacent sides. This is a classic many-body F=ma problem but convergence requires using a particular numerical technique. It gives accurate p...

  10. Accurate Prediction of Radiation Exposures of Workers Involved in the Transport of NORM

    International Nuclear Information System (INIS)

    A study of the radiation exposures encountered by workers involved in the transport of minerals and mineral concentrates containing radionuclides of natural origin was undertaken during 2008–2012. Hundreds of measurements were made during road, rail and marine transport of NORM between mining and processing sites in Australia and within and between ports in Australia, China and Japan. The investigation was focused on minerals and mineral concentrates containing thorium and uranium (including ilmenite, rutile, zircon and monazite). It was found that the use of the ‘exclusion’ factor of 10 for the concentrations of radionuclides in natural materials in the IAEA Transport Regulations is appropriate and is to be maintained. The dose rates from all potential pathways of exposure of workers could be accurately predicted, based on the concentrations of thorium and uranium in the transported material. These dose rates remain the same, irrespective of whether the transport is by road, rail or sea. The information presented in the paper allows, by the use of simple charts, the accurate prediction of doses to workers involved in the transport of NORM. It is suggested that it can be used in any assessments of exposures of workers that may be required prior to the start of the NORM transport process, by both regulatory bodies and by the mining and mineral processing industry. (author)

  11. ILT based defect simulation of inspection images accurately predicts mask defect printability on wafer

    Science.gov (United States)

    Deep, Prakash; Paninjath, Sankaranarayanan; Pereira, Mark; Buck, Peter

    2016-05-01

    At advanced technology nodes mask complexity has been increased because of large-scale use of resolution enhancement technologies (RET) which includes Optical Proximity Correction (OPC), Inverse Lithography Technology (ILT) and Source Mask Optimization (SMO). The number of defects detected during inspection of such mask increased drastically and differentiation of critical and non-critical defects are more challenging, complex and time consuming. Because of significant defectivity of EUVL masks and non-availability of actinic inspection, it is important and also challenging to predict the criticality of defects for printability on wafer. This is one of the significant barriers for the adoption of EUVL for semiconductor manufacturing. Techniques to decide criticality of defects from images captured using non actinic inspection images is desired till actinic inspection is not available. High resolution inspection of photomask images detects many defects which are used for process and mask qualification. Repairing all defects is not practical and probably not required, however it's imperative to know which defects are severe enough to impact wafer before repair. Additionally, wafer printability check is always desired after repairing a defect. AIMSTM review is the industry standard for this, however doing AIMSTM review for all defects is expensive and very time consuming. Fast, accurate and an economical mechanism is desired which can predict defect printability on wafer accurately and quickly from images captured using high resolution inspection machine. Predicting defect printability from such images is challenging due to the fact that the high resolution images do not correlate with actual mask contours. The challenge is increased due to use of different optical condition during inspection other than actual scanner condition, and defects found in such images do not have correlation with actual impact on wafer. Our automated defect simulation tool predicts

  12. Genetic crossovers are predicted accurately by the computed human recombination map.

    Directory of Open Access Journals (Sweden)

    Pavel P Khil

    2010-01-01

    Full Text Available Hotspots of meiotic recombination can change rapidly over time. This instability and the reported high level of inter-individual variation in meiotic recombination puts in question the accuracy of the calculated hotspot map, which is based on the summation of past genetic crossovers. To estimate the accuracy of the computed recombination rate map, we have mapped genetic crossovers to a median resolution of 70 Kb in 10 CEPH pedigrees. We then compared the positions of crossovers with the hotspots computed from HapMap data and performed extensive computer simulations to compare the observed distributions of crossovers with the distributions expected from the calculated recombination rate maps. Here we show that a population-averaged hotspot map computed from linkage disequilibrium data predicts well present-day genetic crossovers. We find that computed hotspot maps accurately estimate both the strength and the position of meiotic hotspots. An in-depth examination of not-predicted crossovers shows that they are preferentially located in regions where hotspots are found in other populations. In summary, we find that by combining several computed population-specific maps we can capture the variation in individual hotspots to generate a hotspot map that can predict almost all present-day genetic crossovers.

  13. Intermolecular potentials and the accurate prediction of the thermodynamic properties of water

    Energy Technology Data Exchange (ETDEWEB)

    Shvab, I.; Sadus, Richard J., E-mail: rsadus@swin.edu.au [Centre for Molecular Simulation, Swinburne University of Technology, PO Box 218, Hawthorn, Victoria 3122 (Australia)

    2013-11-21

    The ability of intermolecular potentials to correctly predict the thermodynamic properties of liquid water at a density of 0.998 g/cm{sup 3} for a wide range of temperatures (298–650 K) and pressures (0.1–700 MPa) is investigated. Molecular dynamics simulations are reported for the pressure, thermal pressure coefficient, thermal expansion coefficient, isothermal and adiabatic compressibilities, isobaric and isochoric heat capacities, and Joule-Thomson coefficient of liquid water using the non-polarizable SPC/E and TIP4P/2005 potentials. The results are compared with both experiment data and results obtained from the ab initio-based Matsuoka-Clementi-Yoshimine non-additive (MCYna) [J. Li, Z. Zhou, and R. J. Sadus, J. Chem. Phys. 127, 154509 (2007)] potential, which includes polarization contributions. The data clearly indicate that both the SPC/E and TIP4P/2005 potentials are only in qualitative agreement with experiment, whereas the polarizable MCYna potential predicts some properties within experimental uncertainty. This highlights the importance of polarizability for the accurate prediction of the thermodynamic properties of water, particularly at temperatures beyond 298 K.

  14. Fast and accurate prediction of numerical relativity waveforms from binary black hole mergers using surrogate models

    CERN Document Server

    Blackman, Jonathan; Galley, Chad R; Szilagyi, Bela; Scheel, Mark A; Tiglio, Manuel; Hemberger, Daniel A

    2015-01-01

    Simulating a binary black hole coalescence by solving Einstein's equations is computationally expensive, requiring days to months of supercomputing time. In this paper, we construct an accurate and fast-to-evaluate surrogate model for numerical relativity (NR) waveforms from non-spinning binary black hole coalescences with mass ratios from $1$ to $10$ and durations corresponding to about $15$ orbits before merger. Our surrogate, which is built using reduced order modeling techniques, is distinct from traditional modeling efforts. We find that the full multi-mode surrogate model agrees with waveforms generated by NR to within the numerical error of the NR code. In particular, we show that our modeling strategy produces surrogates which can correctly predict NR waveforms that were {\\em not} used for the surrogate's training. For all practical purposes, then, the surrogate waveform model is equivalent to the high-accuracy, large-scale simulation waveform but can be evaluated in a millisecond to a second dependin...

  15. A fast and accurate method to predict 2D and 3D aerodynamic boundary layer flows

    International Nuclear Information System (INIS)

    A quasi-simultaneous interaction method is applied to predict 2D and 3D aerodynamic flows. This method is suitable for offshore wind turbine design software as it is a very accurate and computationally reasonably cheap method. This study shows the results for a NACA 0012 airfoil. The two applied solvers converge to the experimental values when the grid is refined. We also show that in separation the eigenvalues remain positive thus avoiding the Goldstein singularity at separation. In 3D we show a flow over a dent in which separation occurs. A rotating flat plat is used to show the applicability of the method for rotating flows. The shown capabilities of the method indicate that the quasi-simultaneous interaction method is suitable for design methods for offshore wind turbine blades

  16. A fast and accurate method to predict 2D and 3D aerodynamic boundary layer flows

    Science.gov (United States)

    Bijleveld, H. A.; Veldman, A. E. P.

    2014-12-01

    A quasi-simultaneous interaction method is applied to predict 2D and 3D aerodynamic flows. This method is suitable for offshore wind turbine design software as it is a very accurate and computationally reasonably cheap method. This study shows the results for a NACA 0012 airfoil. The two applied solvers converge to the experimental values when the grid is refined. We also show that in separation the eigenvalues remain positive thus avoiding the Goldstein singularity at separation. In 3D we show a flow over a dent in which separation occurs. A rotating flat plat is used to show the applicability of the method for rotating flows. The shown capabilities of the method indicate that the quasi-simultaneous interaction method is suitable for design methods for offshore wind turbine blades.

  17. Differential contribution of visual and auditory information to accurately predict the direction and rotational motion of a visual stimulus.

    Science.gov (United States)

    Park, Seoung Hoon; Kim, Seonjin; Kwon, MinHyuk; Christou, Evangelos A

    2016-03-01

    Vision and auditory information are critical for perception and to enhance the ability of an individual to respond accurately to a stimulus. However, it is unknown whether visual and auditory information contribute differentially to identify the direction and rotational motion of the stimulus. The purpose of this study was to determine the ability of an individual to accurately predict the direction and rotational motion of the stimulus based on visual and auditory information. In this study, we recruited 9 expert table-tennis players and used table-tennis service as our experimental model. Participants watched recorded services with different levels of visual and auditory information. The goal was to anticipate the direction of the service (left or right) and the rotational motion of service (topspin, sidespin, or cut). We recorded their responses and quantified the following outcomes: (i) directional accuracy and (ii) rotational motion accuracy. The response accuracy was the accurate predictions relative to the total number of trials. The ability of the participants to predict the direction of the service accurately increased with additional visual information but not with auditory information. In contrast, the ability of the participants to predict the rotational motion of the service accurately increased with the addition of auditory information to visual information but not with additional visual information alone. In conclusion, this finding demonstrates that visual information enhances the ability of an individual to accurately predict the direction of the stimulus, whereas additional auditory information enhances the ability of an individual to accurately predict the rotational motion of stimulus.

  18. In vitro transcription accurately predicts lac repressor phenotype in vivo in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Matthew Almond Sochor

    2014-07-01

    Full Text Available A multitude of studies have looked at the in vivo and in vitro behavior of the lac repressor binding to DNA and effector molecules in order to study transcriptional repression, however these studies are not always reconcilable. Here we use in vitro transcription to directly mimic the in vivo system in order to build a self consistent set of experiments to directly compare in vivo and in vitro genetic repression. A thermodynamic model of the lac repressor binding to operator DNA and effector is used to link DNA occupancy to either normalized in vitro mRNA product or normalized in vivo fluorescence of a regulated gene, YFP. An accurate measurement of repressor, DNA and effector concentrations were made both in vivo and in vitro allowing for direct modeling of the entire thermodynamic equilibrium. In vivo repression profiles are accurately predicted from the given in vitro parameters when molecular crowding is considered. Interestingly, our measured repressor–operator DNA affinity differs significantly from previous in vitro measurements. The literature values are unable to replicate in vivo binding data. We therefore conclude that the repressor-DNA affinity is much weaker than previously thought. This finding would suggest that in vitro techniques that are specifically designed to mimic the in vivo process may be necessary to replicate the native system.

  19. Measuring solar reflectance Part I: Defining a metric that accurately predicts solar heat gain

    Energy Technology Data Exchange (ETDEWEB)

    Levinson, Ronnen; Akbari, Hashem; Berdahl, Paul

    2010-05-14

    Solar reflectance can vary with the spectral and angular distributions of incident sunlight, which in turn depend on surface orientation, solar position and atmospheric conditions. A widely used solar reflectance metric based on the ASTM Standard E891 beam-normal solar spectral irradiance underestimates the solar heat gain of a spectrally selective 'cool colored' surface because this irradiance contains a greater fraction of near-infrared light than typically found in ordinary (unconcentrated) global sunlight. At mainland U.S. latitudes, this metric RE891BN can underestimate the annual peak solar heat gain of a typical roof or pavement (slope {le} 5:12 [23{sup o}]) by as much as 89 W m{sup -2}, and underestimate its peak surface temperature by up to 5 K. Using R{sub E891BN} to characterize roofs in a building energy simulation can exaggerate the economic value N of annual cool-roof net energy savings by as much as 23%. We define clear-sky air mass one global horizontal ('AM1GH') solar reflectance R{sub g,0}, a simple and easily measured property that more accurately predicts solar heat gain. R{sub g,0} predicts the annual peak solar heat gain of a roof or pavement to within 2 W m{sup -2}, and overestimates N by no more than 3%. R{sub g,0} is well suited to rating the solar reflectances of roofs, pavements and walls. We show in Part II that R{sub g,0} can be easily and accurately measured with a pyranometer, a solar spectrophotometer or version 6 of the Solar Spectrum Reflectometer.

  20. Highly Accurate Prediction of Protein-Protein Interactions via Incorporating Evolutionary Information and Physicochemical Characteristics

    Science.gov (United States)

    Li, Zheng-Wei; You, Zhu-Hong; Chen, Xing; Gui, Jie; Nie, Ru

    2016-01-01

    Protein-protein interactions (PPIs) occur at almost all levels of cell functions and play crucial roles in various cellular processes. Thus, identification of PPIs is critical for deciphering the molecular mechanisms and further providing insight into biological processes. Although a variety of high-throughput experimental techniques have been developed to identify PPIs, existing PPI pairs by experimental approaches only cover a small fraction of the whole PPI networks, and further, those approaches hold inherent disadvantages, such as being time-consuming, expensive, and having high false positive rate. Therefore, it is urgent and imperative to develop automatic in silico approaches to predict PPIs efficiently and accurately. In this article, we propose a novel mixture of physicochemical and evolutionary-based feature extraction method for predicting PPIs using our newly developed discriminative vector machine (DVM) classifier. The improvements of the proposed method mainly consist in introducing an effective feature extraction method that can capture discriminative features from the evolutionary-based information and physicochemical characteristics, and then a powerful and robust DVM classifier is employed. To the best of our knowledge, it is the first time that DVM model is applied to the field of bioinformatics. When applying the proposed method to the Yeast and Helicobacter pylori (H. pylori) datasets, we obtain excellent prediction accuracies of 94.35% and 90.61%, respectively. The computational results indicate that our method is effective and robust for predicting PPIs, and can be taken as a useful supplementary tool to the traditional experimental methods for future proteomics research. PMID:27571061

  1. Highly Accurate Prediction of Protein-Protein Interactions via Incorporating Evolutionary Information and Physicochemical Characteristics.

    Science.gov (United States)

    Li, Zheng-Wei; You, Zhu-Hong; Chen, Xing; Gui, Jie; Nie, Ru

    2016-01-01

    Protein-protein interactions (PPIs) occur at almost all levels of cell functions and play crucial roles in various cellular processes. Thus, identification of PPIs is critical for deciphering the molecular mechanisms and further providing insight into biological processes. Although a variety of high-throughput experimental techniques have been developed to identify PPIs, existing PPI pairs by experimental approaches only cover a small fraction of the whole PPI networks, and further, those approaches hold inherent disadvantages, such as being time-consuming, expensive, and having high false positive rate. Therefore, it is urgent and imperative to develop automatic in silico approaches to predict PPIs efficiently and accurately. In this article, we propose a novel mixture of physicochemical and evolutionary-based feature extraction method for predicting PPIs using our newly developed discriminative vector machine (DVM) classifier. The improvements of the proposed method mainly consist in introducing an effective feature extraction method that can capture discriminative features from the evolutionary-based information and physicochemical characteristics, and then a powerful and robust DVM classifier is employed. To the best of our knowledge, it is the first time that DVM model is applied to the field of bioinformatics. When applying the proposed method to the Yeast and Helicobacter pylori (H. pylori) datasets, we obtain excellent prediction accuracies of 94.35% and 90.61%, respectively. The computational results indicate that our method is effective and robust for predicting PPIs, and can be taken as a useful supplementary tool to the traditional experimental methods for future proteomics research. PMID:27571061

  2. Highly Accurate Prediction of Protein-Protein Interactions via Incorporating Evolutionary Information and Physicochemical Characteristics

    Directory of Open Access Journals (Sweden)

    Zheng-Wei Li

    2016-08-01

    Full Text Available Protein-protein interactions (PPIs occur at almost all levels of cell functions and play crucial roles in various cellular processes. Thus, identification of PPIs is critical for deciphering the molecular mechanisms and further providing insight into biological processes. Although a variety of high-throughput experimental techniques have been developed to identify PPIs, existing PPI pairs by experimental approaches only cover a small fraction of the whole PPI networks, and further, those approaches hold inherent disadvantages, such as being time-consuming, expensive, and having high false positive rate. Therefore, it is urgent and imperative to develop automatic in silico approaches to predict PPIs efficiently and accurately. In this article, we propose a novel mixture of physicochemical and evolutionary-based feature extraction method for predicting PPIs using our newly developed discriminative vector machine (DVM classifier. The improvements of the proposed method mainly consist in introducing an effective feature extraction method that can capture discriminative features from the evolutionary-based information and physicochemical characteristics, and then a powerful and robust DVM classifier is employed. To the best of our knowledge, it is the first time that DVM model is applied to the field of bioinformatics. When applying the proposed method to the Yeast and Helicobacter pylori (H. pylori datasets, we obtain excellent prediction accuracies of 94.35% and 90.61%, respectively. The computational results indicate that our method is effective and robust for predicting PPIs, and can be taken as a useful supplementary tool to the traditional experimental methods for future proteomics research.

  3. Highly Accurate Prediction of Protein-Protein Interactions via Incorporating Evolutionary Information and Physicochemical Characteristics.

    Science.gov (United States)

    Li, Zheng-Wei; You, Zhu-Hong; Chen, Xing; Gui, Jie; Nie, Ru

    2016-01-01

    Protein-protein interactions (PPIs) occur at almost all levels of cell functions and play crucial roles in various cellular processes. Thus, identification of PPIs is critical for deciphering the molecular mechanisms and further providing insight into biological processes. Although a variety of high-throughput experimental techniques have been developed to identify PPIs, existing PPI pairs by experimental approaches only cover a small fraction of the whole PPI networks, and further, those approaches hold inherent disadvantages, such as being time-consuming, expensive, and having high false positive rate. Therefore, it is urgent and imperative to develop automatic in silico approaches to predict PPIs efficiently and accurately. In this article, we propose a novel mixture of physicochemical and evolutionary-based feature extraction method for predicting PPIs using our newly developed discriminative vector machine (DVM) classifier. The improvements of the proposed method mainly consist in introducing an effective feature extraction method that can capture discriminative features from the evolutionary-based information and physicochemical characteristics, and then a powerful and robust DVM classifier is employed. To the best of our knowledge, it is the first time that DVM model is applied to the field of bioinformatics. When applying the proposed method to the Yeast and Helicobacter pylori (H. pylori) datasets, we obtain excellent prediction accuracies of 94.35% and 90.61%, respectively. The computational results indicate that our method is effective and robust for predicting PPIs, and can be taken as a useful supplementary tool to the traditional experimental methods for future proteomics research.

  4. An Accurate Calculation of the Big-Bang Prediction for the Abundance of Primordial Helium

    CERN Document Server

    López, R E; Lopez, Robert E.; Turner, Michael S.

    1999-01-01

    Within the standard model of particle physics and cosmology we have calculated the big-bang prediction for the primordial abundance of Helium to a theoretical uncertainty of $0.1 \\pct$ $(\\delta Y_P = \\pm 0.0002)$. At this accuracy the uncertainty in the abundance is dominated by the experimental uncertainty in the neutron mean lifetime, $\\tau_n = 885.3 \\pm 2.0 \\rm{sec}$. The following physical effects were included in the calculation: the zero and finite-temperature radiative, Coulomb and finite-nucleon mass corrections to the weak rates; order-$\\alpha$ quantum-electrodynamic correction to the plasma density, electron mass, and neutrino temperature; and incomplete neutrino decoupling. New results for the finite-temperature radiative correction and the QED plasma correction were used. In addition, we wrote a new and independent nucleosynthesis code to control numerical errors to less than 0.1\\pct. Our predictions for the \\EL[4]{He} abundance are summarized with an accurate fitting formula. Summarizing our work...

  5. ChIP-seq Accurately Predicts Tissue-Specific Activity of Enhancers

    Energy Technology Data Exchange (ETDEWEB)

    Visel, Axel; Blow, Matthew J.; Li, Zirong; Zhang, Tao; Akiyama, Jennifer A.; Holt, Amy; Plajzer-Frick, Ingrid; Shoukry, Malak; Wright, Crystal; Chen, Feng; Afzal, Veena; Ren, Bing; Rubin, Edward M.; Pennacchio, Len A.

    2009-02-01

    A major yet unresolved quest in decoding the human genome is the identification of the regulatory sequences that control the spatial and temporal expression of genes. Distant-acting transcriptional enhancers are particularly challenging to uncover since they are scattered amongst the vast non-coding portion of the genome. Evolutionary sequence constraint can facilitate the discovery of enhancers, but fails to predict when and where they are active in vivo. Here, we performed chromatin immunoprecipitation with the enhancer-associated protein p300, followed by massively-parallel sequencing, to map several thousand in vivo binding sites of p300 in mouse embryonic forebrain, midbrain, and limb tissue. We tested 86 of these sequences in a transgenic mouse assay, which in nearly all cases revealed reproducible enhancer activity in those tissues predicted by p300 binding. Our results indicate that in vivo mapping of p300 binding is a highly accurate means for identifying enhancers and their associated activities and suggest that such datasets will be useful to study the role of tissue-specific enhancers in human biology and disease on a genome-wide scale.

  6. A Simple and Accurate Model to Predict Responses to Multi-electrode Stimulation in the Retina.

    Directory of Open Access Journals (Sweden)

    Matias I Maturana

    2016-04-01

    Full Text Available Implantable electrode arrays are widely used in therapeutic stimulation of the nervous system (e.g. cochlear, retinal, and cortical implants. Currently, most neural prostheses use serial stimulation (i.e. one electrode at a time despite this severely limiting the repertoire of stimuli that can be applied. Methods to reliably predict the outcome of multi-electrode stimulation have not been available. Here, we demonstrate that a linear-nonlinear model accurately predicts neural responses to arbitrary patterns of stimulation using in vitro recordings from single retinal ganglion cells (RGCs stimulated with a subretinal multi-electrode array. In the model, the stimulus is projected onto a low-dimensional subspace and then undergoes a nonlinear transformation to produce an estimate of spiking probability. The low-dimensional subspace is estimated using principal components analysis, which gives the neuron's electrical receptive field (ERF, i.e. the electrodes to which the neuron is most sensitive. Our model suggests that stimulation proportional to the ERF yields a higher efficacy given a fixed amount of power when compared to equal amplitude stimulation on up to three electrodes. We find that the model captures the responses of all the cells recorded in the study, suggesting that it will generalize to most cell types in the retina. The model is computationally efficient to evaluate and, therefore, appropriate for future real-time applications including stimulation strategies that make use of recorded neural activity to improve the stimulation strategy.

  7. A Simple and Accurate Model to Predict Responses to Multi-electrode Stimulation in the Retina.

    Science.gov (United States)

    Maturana, Matias I; Apollo, Nicholas V; Hadjinicolaou, Alex E; Garrett, David J; Cloherty, Shaun L; Kameneva, Tatiana; Grayden, David B; Ibbotson, Michael R; Meffin, Hamish

    2016-04-01

    Implantable electrode arrays are widely used in therapeutic stimulation of the nervous system (e.g. cochlear, retinal, and cortical implants). Currently, most neural prostheses use serial stimulation (i.e. one electrode at a time) despite this severely limiting the repertoire of stimuli that can be applied. Methods to reliably predict the outcome of multi-electrode stimulation have not been available. Here, we demonstrate that a linear-nonlinear model accurately predicts neural responses to arbitrary patterns of stimulation using in vitro recordings from single retinal ganglion cells (RGCs) stimulated with a subretinal multi-electrode array. In the model, the stimulus is projected onto a low-dimensional subspace and then undergoes a nonlinear transformation to produce an estimate of spiking probability. The low-dimensional subspace is estimated using principal components analysis, which gives the neuron's electrical receptive field (ERF), i.e. the electrodes to which the neuron is most sensitive. Our model suggests that stimulation proportional to the ERF yields a higher efficacy given a fixed amount of power when compared to equal amplitude stimulation on up to three electrodes. We find that the model captures the responses of all the cells recorded in the study, suggesting that it will generalize to most cell types in the retina. The model is computationally efficient to evaluate and, therefore, appropriate for future real-time applications including stimulation strategies that make use of recorded neural activity to improve the stimulation strategy. PMID:27035143

  8. Can CO2 assimilation in maize leaves be predicted accurately from chlorophyll fluorescence analysis?

    Science.gov (United States)

    Edwards, G E; Baker, N R

    1993-08-01

    Analysis is made of the energetics of CO2 fixation, the photochemical quantum requirement per CO2 fixed, and sinks for utilising reductive power in the C4 plant maize. CO2 assimilation is the primary sink for energy derived from photochemistry, whereas photorespiration and nitrogen assimilation are relatively small sinks, particularly in developed leaves. Measurement of O2 exchange by mass spectrometry and CO2 exchange by infrared gas analysis under varying levels of CO2 indicate that there is a very close relationship between the true rate of O2 evolution from PS II and the net rate of CO2 fixation. Consideration is given to measurements of the quantum yields of PS II (φ PS II) from fluorescence analysis and of CO2 assimilation ([Formula: see text]) in maize over a wide range of conditions. The[Formula: see text] ratio was found to remain reasonably constant (ca. 12) over a range of physiological conditions in developed leaves, with varying temperature, CO2 concentrations, light intensities (from 5% to 100% of full sunlight), and following photoinhibition under high light and low temperature. A simple model for predicting CO2 assimilation from fluorescence parameters is presented and evaluated. It is concluded that under a wide range of conditions fluorescence parameters can be used to predict accurately and rapidly CO2 assimilation rates in maize. PMID:24317706

  9. Accurate First-Principles Spectra Predictions for Planetological and Astrophysical Applications at Various T-Conditions

    Science.gov (United States)

    Rey, M.; Nikitin, A. V.; Tyuterev, V.

    2014-06-01

    Knowledge of near infrared intensities of rovibrational transitions of polyatomic molecules is essential for the modeling of various planetary atmospheres, brown dwarfs and for other astrophysical applications 1,2,3. For example, to analyze exoplanets, atmospheric models have been developed, thus making the need to provide accurate spectroscopic data. Consequently, the spectral characterization of such planetary objects relies on the necessity of having adequate and reliable molecular data in extreme conditions (temperature, optical path length, pressure). On the other hand, in the modeling of astrophysical opacities, millions of lines are generally involved and the line-by-line extraction is clearly not feasible in laboratory measurements. It is thus suggested that this large amount of data could be interpreted only by reliable theoretical predictions. There exists essentially two theoretical approaches for the computation and prediction of spectra. The first one is based on empirically-fitted effective spectroscopic models. Another way for computing energies, line positions and intensities is based on global variational calculations using ab initio surfaces. They do not yet reach the spectroscopic accuracy stricto sensu but implicitly account for all intramolecular interactions including resonance couplings in a wide spectral range. The final aim of this work is to provide reliable predictions which could be quantitatively accurate with respect to the precision of available observations and as complete as possible. All this thus requires extensive first-principles quantum mechanical calculations essentially based on three necessary ingredients which are (i) accurate intramolecular potential energy surface and dipole moment surface components well-defined in a large range of vibrational displacements and (ii) efficient computational methods combined with suitable choices of coordinates to account for molecular symmetry properties and to achieve a good numerical

  10. The Life-cycle of Operons

    Energy Technology Data Exchange (ETDEWEB)

    Price, Morgan N.; Arkin, Adam P.; Alm, Eric J.

    2005-11-18

    Operons are a major feature of all prokaryotic genomes, but how and why operon structures vary is not well understood. To elucidate the life-cycle of operons, we compared gene order between Escherichia coli K12 and its relatives and identified the recently formed and destroyed operons in E. coli. This allowed us to determine how operons form, how they become closely spaced, and how they die. Our findings suggest that operon evolution is driven by selection on gene expression patterns. First, both operon creation and operon destruction lead to large changes in gene expression patterns. For example, the removal of lysA and ruvA from ancestral operons that contained essential genes allowed their expression to respond to lysine levels and DNA damage, respectively. Second, some operons have undergone accelerated evolution, with multiple new genes being added during a brief period. Third, although most operons are closely spaced because of a neutral bias towards deletion and because of selection against large overlaps, highly expressed operons tend to be widely spaced because of regulatory fine-tuning by intervening sequences. Although operon evolution seems to be adaptive, it need not be optimal: new operons often comprise functionally unrelated genes that were already in proximity before the operon formed.

  11. Predicting accurate fluorescent spectra for high molecular weight polycyclic aromatic hydrocarbons using density functional theory

    Science.gov (United States)

    Powell, Jacob; Heider, Emily C.; Campiglia, Andres; Harper, James K.

    2016-10-01

    The ability of density functional theory (DFT) methods to predict accurate fluorescence spectra for polycyclic aromatic hydrocarbons (PAHs) is explored. Two methods, PBE0 and CAM-B3LYP, are evaluated both in the gas phase and in solution. Spectra for several of the most toxic PAHs are predicted and compared to experiment, including three isomers of C24H14 and a PAH containing heteroatoms. Unusually high-resolution experimental spectra are obtained for comparison by analyzing each PAH at 4.2 K in an n-alkane matrix. All theoretical spectra visually conform to the profiles of the experimental data but are systematically offset by a small amount. Specifically, when solvent is included the PBE0 functional overestimates peaks by 16.1 ± 6.6 nm while CAM-B3LYP underestimates the same transitions by 14.5 ± 7.6 nm. These calculated spectra can be empirically corrected to decrease the uncertainties to 6.5 ± 5.1 and 5.7 ± 5.1 nm for the PBE0 and CAM-B3LYP methods, respectively. A comparison of computed spectra in the gas phase indicates that the inclusion of n-octane shifts peaks by +11 nm on average and this change is roughly equivalent for PBE0 and CAM-B3LYP. An automated approach for comparing spectra is also described that minimizes residuals between a given theoretical spectrum and all available experimental spectra. This approach identifies the correct spectrum in all cases and excludes approximately 80% of the incorrect spectra, demonstrating that an automated search of theoretical libraries of spectra may eventually become feasible.

  12. Towards accurate cosmological predictions for rapidly oscillating scalar fields as dark matter

    CERN Document Server

    Ureña-López, L Arturo

    2015-01-01

    As we are entering the era of precision cosmology, it is necessary to count on accurate cosmological predictions from any proposed model of dark matter. In this paper we present a novel approach to the cosmological evolution of scalar fields that eases their analytic and numerical analysis at the background and at the linear order of perturbations. We apply the method to a scalar field endowed with a quadratic potential and revisit its properties as dark matter. Some of the results known in the literature are recovered, and a better understanding of the physical properties of the model is provided. It is shown that the Jeans wavenumber defined as $k_J = a \\sqrt{mH}$ is directly related to the suppression of linear perturbations at wavenumbers $k>k_J$. We also discuss some semi-analytical results that are well satisfied by the full numerical solutions obtained from an amended version of the CMB code CLASS. Finally we draw some of the implications that this new treatment of the equations of motion may have in t...

  13. Cluster abundance in chameleon $f(R)$ gravity I: toward an accurate halo mass function prediction

    CERN Document Server

    Cataneo, Matteo; Lombriser, Lucas; Li, Baojiu

    2016-01-01

    We refine the mass and environment dependent spherical collapse model of chameleon $f(R)$ gravity by calibrating a phenomenological correction inspired by the parameterized post-Friedmann framework against high-resolution $N$-body simulations. We employ our method to predict the corresponding modified halo mass function, and provide fitting formulas to calculate the fractional enhancement of the $f(R)$ halo abundance with respect to that of General Relativity (GR) within a precision of $\\lesssim 5\\%$ from the results obtained in the simulations. Similar accuracy can be achieved for the full $f(R)$ mass function on the condition that the modeling of the reference GR abundance of halos is accurate at the percent level. We use our fits to forecast constraints on the additional scalar degree of freedom of the theory, finding that upper bounds competitive with current Solar System tests are within reach of cluster number count analyses from ongoing and upcoming surveys at much larger scales. Importantly, the flexi...

  14. Accurate prediction of band gaps and optical properties of HfO2

    Science.gov (United States)

    Ondračka, Pavel; Holec, David; Nečas, David; Zajíčková, Lenka

    2016-10-01

    We report on optical properties of various polymorphs of hafnia predicted within the framework of density functional theory. The full potential linearised augmented plane wave method was employed together with the Tran-Blaha modified Becke-Johnson potential (TB-mBJ) for exchange and local density approximation for correlation. Unit cells of monoclinic, cubic and tetragonal crystalline, and a simulated annealing-based model of amorphous hafnia were fully relaxed with respect to internal positions and lattice parameters. Electronic structures and band gaps for monoclinic, cubic, tetragonal and amorphous hafnia were calculated using three different TB-mBJ parametrisations and the results were critically compared with the available experimental and theoretical reports. Conceptual differences between a straightforward comparison of experimental measurements to a calculated band gap on the one hand and to a whole electronic structure (density of electronic states) on the other hand, were pointed out, suggesting the latter should be used whenever possible. Finally, dielectric functions were calculated at two levels, using the random phase approximation without local field effects and with a more accurate Bethe-Salpether equation (BSE) to account for excitonic effects. We conclude that a satisfactory agreement with experimental data for HfO2 was obtained only in the latter case.

  15. New insights into regulation of the tryptophan biosynthetic operon in Gram-positive bacteria.

    Science.gov (United States)

    Gutierrez-Preciado, A; Jensen, R A; Yanofsky, C; Merino, E

    2005-08-01

    The tryptophan operon of Bacillus subtilis serves as an excellent model for investigating transcription regulation in Gram-positive bacteria. In this article, we extend this knowledge by analyzing the predicted regulatory regions in the trp operons of other fully sequenced Gram-positive bacteria. Interestingly, it appears that in eight of the organisms examined, transcription of the trp operon appears to be regulated by tandem T-box elements. These regulatory elements have recently been described in the trp operons of two bacterial species. Single T-box elements are commonly found in Gram-positive bacteria in operons encoding aminoacyl tRNA synthetases and proteins performing other functions. Different regulatory mechanisms appear to be associated with variations of trp gene organization within the trp operon. PMID:15953653

  16. Accurate and Simplified Prediction of AVF for Delay and Energy Efficient Cache Design

    Institute of Scientific and Technical Information of China (English)

    An-Guo Ma; Yu Cheng; Zuo-Cheng Xing

    2011-01-01

    With continuous technology scaling, on-chip structures are becoming more and more susceptible to soft errors. Architectural vulnerability factor (AVF) has been introduced to quantify the architectural vulnerability of on-chip structures to soft errors. Recent studies have found that designing soft error protection techniques with the awareness of AVF is greatly helpful to achieve a tradeoff between performance and reliability for several structures (i.e., issue queue, reorder buffer). Cache is one of the most susceptible components to soft errors and is commonly protected with error correcting codes (ECC). However, protecting caches closer to the processor (i.e., L1 data cache (L1D)) using ECC could result in high overhead. Protecting caches without accurate knowledge of the vulnerability characteristics may lead to over-protection. Therefore, designing AVF-aware ECC is attractive for designers to balance among performance, power and reliability for cache, especially at early design stage. In this paper, we improve the methodology of cache AVF computation and develop a new AVF estimation framework, soft error reliability analysis based on SimpleScalar. Then we characterize dynamic vulnerability behavior of L1D and detect the correlations between LID AVF and various performance metrics. We propose to employ Bayesian additive regression trees to accurately model the variation of L1D AVF and to quantitatively explain the important effects of several key performance metrics on L1D AVF. Then, we employ bump hunting technique to reduce the complexity of L1D AVF prediction and extract some simple selecting rules based on several key performance metrics, thus enabling a simplified and fast estimation of L1D AVF. Based on the simplified and fast estimation of L1D AVF, intervals of high L1D AVF can be identified online, enabling us to develop the AVF-aware ECC technique to reduce the overhead of ECC. Experimental results show that compared with traditional ECC technique

  17. The Life-cycle of Operons

    Energy Technology Data Exchange (ETDEWEB)

    Price, Morgan N.; Arkin, Adam P.; Alm, Eric J.

    2007-03-15

    Operons are a major feature of all prokaryotic genomes, buthow and why operon structures vary is not well understood. To elucidatethe life-cycle of operons, we compared gene order between Escherichiacoli K12 and its relatives and identified the recently formed anddestroyed operons in E. coli. This allowed us to determine how operonsform, how they become closely spaced, and how they die. Our findingssuggest that operon evolution may be driven by selection on geneexpression patterns. First, both operon creation and operon destructionlead to large changes in gene expression patterns. For example, theremoval of lysA and ruvA from ancestral operons that contained essentialgenes allowed their expression to respond to lysine levels and DNAdamage, respectively. Second, some operons have undergone acceleratedevolution, with multiple new genes being added during a brief period.Third, although genes within operons are usually closely spaced becauseof a neutral bias toward deletion and because of selection against largeoverlaps, genes in highly expressed operons tend to be widely spacedbecause of regulatory fine-tuning by intervening sequences. Althoughoperon evolution may be adaptive, it need not be optimal: new operonsoften comprise functionally unrelated genes that were already inproximity before the operon formed.

  18. Problem-Solving Test: Tryptophan Operon Mutants

    Science.gov (United States)

    Szeberenyi, Jozsef

    2010-01-01

    This paper presents a problem-solving test that deals with the regulation of the "trp" operon of "Escherichia coli." Two mutants of this operon are described: in mutant A, the operator region of the operon carries a point mutation so that it is unable to carry out its function; mutant B expresses a "trp" repressor protein unable to bind…

  19. Accurate wavelength prediction of photonic crystal resonant reflection and applications in refractive index measurement

    DEFF Research Database (Denmark)

    Hermannsson, Pétur Gordon; Vannahme, Christoph; Smith, Cameron L. C.;

    2014-01-01

    In the past decade, photonic crystal resonant reflectors have been increasingly used as the basis for label-free biochemical assays in lab-on-a-chip applications. In both designing and interpreting experimental results, an accurate model describing the optical behavior of such structures is essen......In the past decade, photonic crystal resonant reflectors have been increasingly used as the basis for label-free biochemical assays in lab-on-a-chip applications. In both designing and interpreting experimental results, an accurate model describing the optical behavior of such structures...

  20. Towards more accurate wind and solar power prediction by improving NWP model physics

    Science.gov (United States)

    Steiner, Andrea; Köhler, Carmen; von Schumann, Jonas; Ritter, Bodo

    2014-05-01

    The growing importance and successive expansion of renewable energies raise new challenges for decision makers, economists, transmission system operators, scientists and many more. In this interdisciplinary field, the role of Numerical Weather Prediction (NWP) is to reduce the errors and provide an a priori estimate of remaining uncertainties associated with the large share of weather-dependent power sources. For this purpose it is essential to optimize NWP model forecasts with respect to those prognostic variables which are relevant for wind and solar power plants. An improved weather forecast serves as the basis for a sophisticated power forecasts. Consequently, a well-timed energy trading on the stock market, and electrical grid stability can be maintained. The German Weather Service (DWD) currently is involved with two projects concerning research in the field of renewable energy, namely ORKA*) and EWeLiNE**). Whereas the latter is in collaboration with the Fraunhofer Institute (IWES), the project ORKA is led by energy & meteo systems (emsys). Both cooperate with German transmission system operators. The goal of the projects is to improve wind and photovoltaic (PV) power forecasts by combining optimized NWP and enhanced power forecast models. In this context, the German Weather Service aims to improve its model system, including the ensemble forecasting system, by working on data assimilation, model physics and statistical post processing. This presentation is focused on the identification of critical weather situations and the associated errors in the German regional NWP model COSMO-DE. First steps leading to improved physical parameterization schemes within the NWP-model are presented. Wind mast measurements reaching up to 200 m height above ground are used for the estimation of the (NWP) wind forecast error at heights relevant for wind energy plants. One particular problem is the daily cycle in wind speed. The transition from stable stratification during

  1. A simple accurate method to predict time of ponding under variable intensity rainfall

    Science.gov (United States)

    Assouline, S.; Selker, J. S.; Parlange, J.-Y.

    2007-03-01

    The prediction of the time to ponding following commencement of rainfall is fundamental to hydrologic prediction of flood, erosion, and infiltration. Most of the studies to date have focused on prediction of ponding resulting from simple rainfall patterns. This approach was suitable to rainfall reported as average values over intervals of up to a day but does not take advantage of knowledge of the complex patterns of actual rainfall now commonly recorded electronically. A straightforward approach to include the instantaneous rainfall record in the prediction of ponding time and excess rainfall using only the infiltration capacity curve is presented. This method is tested against a numerical solution of the Richards equation on the basis of an actual rainfall record. The predicted time to ponding showed mean error ≤7% for a broad range of soils, with and without surface sealing. In contrast, the standard predictions had average errors of 87%, and worst-case errors exceeding a factor of 10. In addition to errors intrinsic in the modeling framework itself, errors that arise from averaging actual rainfall records over reporting intervals were evaluated. Averaging actual rainfall records observed in Israel over periods of as little as 5 min significantly reduced predicted runoff (75% for the sealed sandy loam and 46% for the silty clay loam), while hourly averaging gave complete lack of prediction of ponding in some of the cases.

  2. Combining Evolutionary Information and an Iterative Sampling Strategy for Accurate Protein Structure Prediction.

    Directory of Open Access Journals (Sweden)

    Tatjana Braun

    2015-12-01

    Full Text Available Recent work has shown that the accuracy of ab initio structure prediction can be significantly improved by integrating evolutionary information in form of intra-protein residue-residue contacts. Following this seminal result, much effort is put into the improvement of contact predictions. However, there is also a substantial need to develop structure prediction protocols tailored to the type of restraints gained by contact predictions. Here, we present a structure prediction protocol that combines evolutionary information with the resolution-adapted structural recombination approach of Rosetta, called RASREC. Compared to the classic Rosetta ab initio protocol, RASREC achieves improved sampling, better convergence and higher robustness against incorrect distance restraints, making it the ideal sampling strategy for the stated problem. To demonstrate the accuracy of our protocol, we tested the approach on a diverse set of 28 globular proteins. Our method is able to converge for 26 out of the 28 targets and improves the average TM-score of the entire benchmark set from 0.55 to 0.72 when compared to the top ranked models obtained by the EVFold web server using identical contact predictions. Using a smaller benchmark, we furthermore show that the prediction accuracy of our method is only slightly reduced when the contact prediction accuracy is comparatively low. This observation is of special interest for protein sequences that only have a limited number of homologs.

  3. The admixed population structure in Danish Jersey dairy cattle challenges accurate genomic predictions

    DEFF Research Database (Denmark)

    Thomasen, Jørn Rind; Sørensen, Anders Christian; Su, Guosheng;

    2013-01-01

    of Danish or US origin. Furthermore, it is investigated whether a model explicitly incorporating breed origin of animals, inferred either through the known pedigree or from SNP marker data, leads to improved genomic predictions compared to a model ignoring breed origin. The study of the population structure...... incorporated 1,730 genotyped Jersey animals. In total 39,542 SNP markers were included in the analysis. The 1,079 genotyped bulls with de-regressed proof for udder health were used in the analysis for the predictions of the genomic breeding values. A range of random regressions models that included the breed...... prediction models showed that including population structure in a random regression prediction model, did not clearly improve the reliabilities of the genomic predictions compared to a basic genomic model...

  4. A machine learning approach to the accurate prediction of multi-leaf collimator positional errors

    Science.gov (United States)

    Carlson, Joel N. K.; Park, Jong Min; Park, So-Yeon; In Park, Jong; Choi, Yunseok; Ye, Sung-Joon

    2016-03-01

    Discrepancies between planned and delivered movements of multi-leaf collimators (MLCs) are an important source of errors in dose distributions during radiotherapy. In this work we used machine learning techniques to train models to predict these discrepancies, assessed the accuracy of the model predictions, and examined the impact these errors have on quality assurance (QA) procedures and dosimetry. Predictive leaf motion parameters for the models were calculated from the plan files, such as leaf position and velocity, whether the leaf was moving towards or away from the isocenter of the MLC, and many others. Differences in positions between synchronized DICOM-RT planning files and DynaLog files reported during QA delivery were used as a target response for training of the models. The final model is capable of predicting MLC positions during delivery to a high degree of accuracy. For moving MLC leaves, predicted positions were shown to be significantly closer to delivered positions than were planned positions. By incorporating predicted positions into dose calculations in the TPS, increases were shown in gamma passing rates against measured dose distributions recorded during QA delivery. For instance, head and neck plans with 1%/2 mm gamma criteria had an average increase in passing rate of 4.17% (SD  =  1.54%). This indicates that the inclusion of predictions during dose calculation leads to a more realistic representation of plan delivery. To assess impact on the patient, dose volumetric histograms (DVH) using delivered positions were calculated for comparison with planned and predicted DVHs. In all cases, predicted dose volumetric parameters were in closer agreement to the delivered parameters than were the planned parameters, particularly for organs at risk on the periphery of the treatment area. By incorporating the predicted positions into the TPS, the treatment planner is given a more realistic view of the dose distribution as it will truly be

  5. How accurate do markets predict the outcome of an event? The Euro 2000 soccer championships experiment

    OpenAIRE

    Schmidt, Carsten; Werwatz, Axel

    2002-01-01

    For the Euro 2000 Soccer Championships an experimental asset market was condueted, with traders buying and selling contracts on the winners of individual matches. Market-generated probabilities are compared to professional bet quotas, and factors that are responsible for the quality of the market prognosis are identified. The comparison shows, that the market is more accurate than the random predictor and slightly better than professional bet quotas, in the sense of mean square error. Moreove...

  6. Accurate Prediction of the Ammonia Probes of a Variable Proton-to-Electron Mass Ratio

    CERN Document Server

    Owens, Alec; Thiel, Walter; Špirko, Vladimir

    2015-01-01

    A comprehensive study of the mass sensitivity of the vibration-rotation-inversion transitions of $^{14}$NH$_3$, $^{15}$NH$_3$, $^{14}$ND$_3$, and $^{15}$ND$_3$ is carried out variationally using the TROVE approach. Variational calculations are robust and accurate, offering a new way to compute sensitivity coefficients. Particular attention is paid to the $\\Delta k=\\pm 3$ transitions between the accidentally coinciding rotation-inversion energy levels of the $\

  7. Selective, accurate, and timely self-invalidation using last-touch prediction

    OpenAIRE

    Lai, An-Chow; Falsafi, Babak

    2000-01-01

    Communication in cache-coherent distributed shared memory (DSM) often requires invalidating (or writing back) cached copies of a memory block, incurring high overheads. This paper proposes Last-Touch Predictors (LTPs) that learn and predict the “last touch” to a memory block by one processor before the block is accessed and subsequently invalidated by another. By predicting a last-touch and (self-)invalidating the block in advance, an LTP hides the invalidation time, significantly reduc...

  8. Accurate microRNA target prediction correlates with protein repression levels

    Directory of Open Access Journals (Sweden)

    Simossis Victor A

    2009-09-01

    Full Text Available Abstract Background MicroRNAs are small endogenously expressed non-coding RNA molecules that regulate target gene expression through translation repression or messenger RNA degradation. MicroRNA regulation is performed through pairing of the microRNA to sites in the messenger RNA of protein coding genes. Since experimental identification of miRNA target genes poses difficulties, computational microRNA target prediction is one of the key means in deciphering the role of microRNAs in development and disease. Results DIANA-microT 3.0 is an algorithm for microRNA target prediction which is based on several parameters calculated individually for each microRNA and combines conserved and non-conserved microRNA recognition elements into a final prediction score, which correlates with protein production fold change. Specifically, for each predicted interaction the program reports a signal to noise ratio and a precision score which can be used as an indication of the false positive rate of the prediction. Conclusion Recently, several computational target prediction programs were benchmarked based on a set of microRNA target genes identified by the pSILAC method. In this assessment DIANA-microT 3.0 was found to achieve the highest precision among the most widely used microRNA target prediction programs reaching approximately 66%. The DIANA-microT 3.0 prediction results are available online in a user friendly web server at http://www.microrna.gr/microT

  9. Sensor Data Fusion for Accurate Cloud Presence Prediction Using Dempster-Shafer Evidence Theory

    Directory of Open Access Journals (Sweden)

    Jesse S. Jin

    2010-10-01

    Full Text Available Sensor data fusion technology can be used to best extract useful information from multiple sensor observations. It has been widely applied in various applications such as target tracking, surveillance, robot navigation, signal and image processing. This paper introduces a novel data fusion approach in a multiple radiation sensor environment using Dempster-Shafer evidence theory. The methodology is used to predict cloud presence based on the inputs of radiation sensors. Different radiation data have been used for the cloud prediction. The potential application areas of the algorithm include renewable power for virtual power station where the prediction of cloud presence is the most challenging issue for its photovoltaic output. The algorithm is validated by comparing the predicted cloud presence with the corresponding sunshine occurrence data that were recorded as the benchmark. Our experiments have indicated that comparing to the approaches using individual sensors, the proposed data fusion approach can increase correct rate of cloud prediction by ten percent, and decrease unknown rate of cloud prediction by twenty three percent.

  10. Using Monte Carlo transport to accurately predict isotope production and activation analysis rates at the University of Missouri research reactor

    International Nuclear Information System (INIS)

    A detailed Monte Carlo N-Particle Transport Code (MCNP5) model of the University of Missouri research reactor (MURR) has been developed. The ability of the model to accurately predict isotope production rates was verified by comparing measured and calculated neutron- capture reaction rates for numerous isotopes. In addition to thermal (1/v) monitors, the benchmarking included a number of isotopes whose (n, γ) reaction rates are very sensitive to the epithermal portion of the neutron spectrum. Using the most recent neutron libraries (ENDF/ B-VII.0), the model was able to accurately predict the measured reaction rates in all cases. The model was then combined with ORIGEN 2.2, via MONTEBURNS 2.0, to calculate production of 99Mo from fission of low-enriched uranium foils. The model was used to investigate both annular and plate LEU foil targets in a variety of arrangements in a graphite irradiation wedge to optimize the production of 99Mo. (author)

  11. Empirical approaches to more accurately predict benthic-pelagic coupling in biogeochemical ocean models

    Science.gov (United States)

    Dale, Andy; Stolpovsky, Konstantin; Wallmann, Klaus

    2016-04-01

    The recycling and burial of biogenic material in the sea floor plays a key role in the regulation of ocean chemistry. Proper consideration of these processes in ocean biogeochemical models is becoming increasingly recognized as an important step in model validation and prediction. However, the rate of organic matter remineralization in sediments and the benthic flux of redox-sensitive elements are difficult to predict a priori. In this communication, examples of empirical benthic flux models that can be coupled to earth system models to predict sediment-water exchange in the open ocean are presented. Large uncertainties hindering further progress in this field include knowledge of the reactivity of organic carbon reaching the sediment, the importance of episodic variability in bottom water chemistry and particle rain rates (for both the deep-sea and margins) and the role of benthic fauna. How do we meet the challenge?

  12. An endometrial gene expression signature accurately predicts recurrent implantation failure after IVF

    Science.gov (United States)

    Koot, Yvonne E. M.; van Hooff, Sander R.; Boomsma, Carolien M.; van Leenen, Dik; Groot Koerkamp, Marian J. A.; Goddijn, Mariëtte; Eijkemans, Marinus J. C.; Fauser, Bart C. J. M.; Holstege, Frank C. P.; Macklon, Nick S.

    2016-01-01

    The primary limiting factor for effective IVF treatment is successful embryo implantation. Recurrent implantation failure (RIF) is a condition whereby couples fail to achieve pregnancy despite consecutive embryo transfers. Here we describe the collection of gene expression profiles from mid-luteal phase endometrial biopsies (n = 115) from women experiencing RIF and healthy controls. Using a signature discovery set (n = 81) we identify a signature containing 303 genes predictive of RIF. Independent validation in 34 samples shows that the gene signature predicts RIF with 100% positive predictive value (PPV). The strength of the RIF associated expression signature also stratifies RIF patients into distinct groups with different subsequent implantation success rates. Exploration of the expression changes suggests that RIF is primarily associated with reduced cellular proliferation. The gene signature will be of value in counselling and guiding further treatment of women who fail to conceive upon IVF and suggests new avenues for developing intervention. PMID:26797113

  13. LocARNA-P: Accurate boundary prediction and improved detection of structural RNAs

    DEFF Research Database (Denmark)

    Will, Sebastian; Joshi, Tejal; Hofacker, Ivo L.;

    2012-01-01

    from AUC 0.71 to AUC 0.87, significantly reduces the cost of successive analysis steps. The ready-to-use software tool LocARNA-P produces structure-based multiple RNA alignments with associated columnwise STARs and predicts ncRNA boundaries. We provide additional results, a web server for Loc...... on sequence and structure similarity; we refer to these structure-based alignment reliabilities as STARs. The columnwise STARs of alignments, or STAR profiles, provide a versatile tool for the manual and automatic analysis of ncRNAs. In particular, we improve the boundary prediction of the widely...

  14. Characterization of the Primary Starch Utilization Operon in the Obligate Anaerobe Bacteroides fragilis: Regulation by Carbon Source and Oxygen

    OpenAIRE

    Spence, Cheryl; Wells, W. Greg; Smith, C. Jeffrey

    2006-01-01

    The opportunistic pathogen Bacteroides fragilis is a commensal organism in the large intestine, where it utilizes both dietary and host-derived polysaccharides as a source of carbon and energy. In this study, a four-gene operon required for starch utilization was identified. The operon also was found to be oxygen responsive and thus was designated osu for oxygen-induced starch utilization. The first three genes in the operon were predicted to encode outer membrane proteins involved in starch ...

  15. Predicting live birth chances for women with multiple consecutive failing IVF cycles: a simple and accurate prediction for routine medical practice

    Directory of Open Access Journals (Sweden)

    Porcu Géraldine

    2013-01-01

    Full Text Available Abstract Background Women having experienced several consecutive failing IVF cycles constitute a critical and particular subset of patients, for which growing perception of irremediable failure, increasing costs and IVF treatment related risks necessitate appropriate decision making when starting or not a new cycle. Predicting chances of LB might constitute a useful tool for discussion between the patient and the clinician. Our essential objective was to dispose of a simple and accurate prediction model for use in routine medical practice. The currently available predictive models applicable to general populations cannot be considered as accurate enough for this purpose. Methods Patients with at least four consecutive Failing cycles (CFCs were selected. We constructed a predictive model of LB occurrence during the last cycle, by using a stepwise logistic regression, using all the baseline patient characteristics and intermediate stage variables during the four first cycles. Results On as set of 151 patients, we identified five determinant predictors: the number of previous cycles with at least one gestational sac (NGS, the mean number of good-quality embryos, age, male infertility (MI aetiology and basal FSH. Our model was characterized by a much higher discrimination as the existing models (C-statistics=0.76, and an excellent calibration. Conclusions Couples having experienced multiple IVF failures need precise and appropriate information to decide to resume or interrupt their fertility project. Our essential objective was to dispose of a simple and accurate prediction model to allow a routine practice use. Our model is adapted to this purpose: It is very simple, combines five easily collected variables in a short calculation; it is more accurate than existing models, with a fair discrimination and a well calibrated prediction.

  16. Safe surgery: how accurate are we at predicting intra-operative blood loss?

    LENUS (Irish Health Repository)

    2012-02-01

    Introduction Preoperative estimation of intra-operative blood loss by both anaesthetist and operating surgeon is a criterion of the World Health Organization\\'s surgical safety checklist. The checklist requires specific preoperative planning when anticipated blood loss is greater than 500 mL. The aim of this study was to assess the accuracy of surgeons and anaesthetists at predicting intra-operative blood loss. Methods A 6-week prospective study of intermediate and major operations in an academic medical centre was performed. An independent observer interviewed surgical and anaesthetic consultants and registrars, preoperatively asking each to predict expected blood loss in millilitre. Intra-operative blood loss was measured and compared with these predictions. Parameters including the use of anticoagulation and anti-platelet therapy as well as intra-operative hypothermia and hypotension were recorded. Results One hundred sixty-eight operations were included in the study, including 142 elective and 26 emergency operations. Blood loss was predicted to within 500 mL of measured blood loss in 89% of cases. Consultant surgeons tended to underestimate blood loss, doing so in 43% of all cases, while consultant anaesthetists were more likely to overestimate (60% of all operations). Twelve patients (7%) had underestimation of blood loss of more than 500 mL by both surgeon and anaesthetist. Thirty per cent (n = 6\\/20) of patients requiring transfusion of a blood product within 24 hours of surgery had blood loss underestimated by more than 500 mL by both surgeon and anaesthetist. There was no significant difference in prediction between patients on anti-platelet or anticoagulation therapy preoperatively and those not on the said therapies. Conclusion Predicted intra-operative blood loss was within 500 mL of measured blood loss in 89% of operations. In 30% of patients who ultimately receive a blood transfusion, both the surgeon and anaesthetist significantly underestimate

  17. Accurate Prediction of Phase Transitions in Compressed Sensing via a Connection to Minimax Denoising

    CERN Document Server

    Donoho, David; Montanari, Andrea

    2011-01-01

    Compressed sensing posits that, within limits, one can undersample a sparse signal and yet reconstruct it accurately. Knowing the precise limits to such undersampling is important both for theory and practice. We present a formula precisely delineating the allowable degree of of undersampling of generalized sparse objects. The formula applies to Approximate Message Passing (AMP) algorithms for compressed sensing, which are here generalized to employ denoising operators besides the traditional scalar shrinkers (soft thresholding, positive soft thresholding and capping). This paper gives several examples including scalar shrinkers not derivable from convex optimization -- the firm shrinkage nonlinearity and the minimax} nonlinearity -- and also nonscalar denoisers -- block thresholding (both block soft and block James-Stein), monotone regression, and total variation minimization. Let the variables \\epsilon = k/N and \\delta = n/N denote the generalized sparsity and undersampling fractions for sampling the k-gene...

  18. FastRNABindR: Fast and Accurate Prediction of Protein-RNA Interface Residues.

    Science.gov (United States)

    El-Manzalawy, Yasser; Abbas, Mostafa; Malluhi, Qutaibah; Honavar, Vasant

    2016-01-01

    A wide range of biological processes, including regulation of gene expression, protein synthesis, and replication and assembly of many viruses are mediated by RNA-protein interactions. However, experimental determination of the structures of protein-RNA complexes is expensive and technically challenging. Hence, a number of computational tools have been developed for predicting protein-RNA interfaces. Some of the state-of-the-art protein-RNA interface predictors rely on position-specific scoring matrix (PSSM)-based encoding of the protein sequences. The computational efforts needed for generating PSSMs severely limits the practical utility of protein-RNA interface prediction servers. In this work, we experiment with two approaches, random sampling and sequence similarity reduction, for extracting a representative reference database of protein sequences from more than 50 million protein sequences in UniRef100. Our results suggest that random sampled databases produce better PSSM profiles (in terms of the number of hits used to generate the profile and the distance of the generated profile to the corresponding profile generated using the entire UniRef100 data as well as the accuracy of the machine learning classifier trained using these profiles). Based on our results, we developed FastRNABindR, an improved version of RNABindR for predicting protein-RNA interface residues using PSSM profiles generated using 1% of the UniRef100 sequences sampled uniformly at random. To the best of our knowledge, FastRNABindR is the only protein-RNA interface residue prediction online server that requires generation of PSSM profiles for query sequences and accepts hundreds of protein sequences per submission. Our approach for determining the optimal BLAST database for a protein-RNA interface residue classification task has the potential of substantially speeding up, and hence increasing the practical utility of, other amino acid sequence based predictors of protein-protein and protein

  19. Revisiting the blind tests in crystal structure prediction: accurate energy ranking of molecular crystals.

    Science.gov (United States)

    Asmadi, Aldi; Neumann, Marcus A; Kendrick, John; Girard, Pascale; Perrin, Marc-Antoine; Leusen, Frank J J

    2009-12-24

    In the 2007 blind test of crystal structure prediction hosted by the Cambridge Crystallographic Data Centre (CCDC), a hybrid DFT/MM method correctly ranked each of the four experimental structures as having the lowest lattice energy of all the crystal structures predicted for each molecule. The work presented here further validates this hybrid method by optimizing the crystal structures (experimental and submitted) of the first three CCDC blind tests held in 1999, 2001, and 2004. Except for the crystal structures of compound IX, all structures were reminimized and ranked according to their lattice energies. The hybrid method computes the lattice energy of a crystal structure as the sum of the DFT total energy and a van der Waals (dispersion) energy correction. Considering all four blind tests, the crystal structure with the lowest lattice energy corresponds to the experimentally observed structure for 12 out of 14 molecules. Moreover, good geometrical agreement is observed between the structures determined by the hybrid method and those measured experimentally. In comparison with the correct submissions made by the blind test participants, all hybrid optimized crystal structures (apart from compound II) have the smallest calculated root mean squared deviations from the experimentally observed structures. It is predicted that a new polymorph of compound V exists under pressure.

  20. Accurate single-sequence prediction of solvent accessible surface area using local and global features.

    Science.gov (United States)

    Faraggi, Eshel; Zhou, Yaoqi; Kloczkowski, Andrzej

    2014-11-01

    We present a new approach for predicting the Accessible Surface Area (ASA) using a General Neural Network (GENN). The novelty of the new approach lies in not using residue mutation profiles generated by multiple sequence alignments as descriptive inputs. Instead we use solely sequential window information and global features such as single-residue and two-residue compositions of the chain. The resulting predictor is both highly more efficient than sequence alignment-based predictors and of comparable accuracy to them. Introduction of the global inputs significantly helps achieve this comparable accuracy. The predictor, termed ASAquick, is tested on predicting the ASA of globular proteins and found to perform similarly well for so-called easy and hard cases indicating generalizability and possible usability for de-novo protein structure prediction. The source code and a Linux executables for GENN and ASAquick are available from Research and Information Systems at http://mamiris.com, from the SPARKS Lab at http://sparks-lab.org, and from the Battelle Center for Mathematical Medicine at http://mathmed.org. PMID:25204636

  1. Accurate structure prediction of peptide–MHC complexes for identifying highly immunogenic antigens

    Energy Technology Data Exchange (ETDEWEB)

    Park, Min-Sun; Park, Sung Yong; Miller, Keith R.; Collins, Edward J.; Lee, Ha Youn

    2013-11-01

    Designing an optimal HIV-1 vaccine faces the challenge of identifying antigens that induce a broad immune capacity. One factor to control the breadth of T cell responses is the surface morphology of a peptide–MHC complex. Here, we present an in silico protocol for predicting peptide–MHC structure. A robust signature of a conformational transition was identified during all-atom molecular dynamics, which results in a model with high accuracy. A large test set was used in constructing our protocol and we went another step further using a blind test with a wild-type peptide and two highly immunogenic mutants, which predicted substantial conformational changes in both mutants. The center residues at position five of the analogs were configured to be accessible to solvent, forming a prominent surface, while the residue of the wild-type peptide was to point laterally toward the side of the binding cleft. We then experimentally determined the structures of the blind test set, using high resolution of X-ray crystallography, which verified predicted conformational changes. Our observation strongly supports a positive association of the surface morphology of a peptide–MHC complex to its immunogenicity. Our study offers the prospect of enhancing immunogenicity of vaccines by identifying MHC binding immunogens.

  2. Revisiting the blind tests in crystal structure prediction: accurate energy ranking of molecular crystals.

    Science.gov (United States)

    Asmadi, Aldi; Neumann, Marcus A; Kendrick, John; Girard, Pascale; Perrin, Marc-Antoine; Leusen, Frank J J

    2009-12-24

    In the 2007 blind test of crystal structure prediction hosted by the Cambridge Crystallographic Data Centre (CCDC), a hybrid DFT/MM method correctly ranked each of the four experimental structures as having the lowest lattice energy of all the crystal structures predicted for each molecule. The work presented here further validates this hybrid method by optimizing the crystal structures (experimental and submitted) of the first three CCDC blind tests held in 1999, 2001, and 2004. Except for the crystal structures of compound IX, all structures were reminimized and ranked according to their lattice energies. The hybrid method computes the lattice energy of a crystal structure as the sum of the DFT total energy and a van der Waals (dispersion) energy correction. Considering all four blind tests, the crystal structure with the lowest lattice energy corresponds to the experimentally observed structure for 12 out of 14 molecules. Moreover, good geometrical agreement is observed between the structures determined by the hybrid method and those measured experimentally. In comparison with the correct submissions made by the blind test participants, all hybrid optimized crystal structures (apart from compound II) have the smallest calculated root mean squared deviations from the experimentally observed structures. It is predicted that a new polymorph of compound V exists under pressure. PMID:19950907

  3. Accurate prediction of interfacial residues in two-domain proteins using evolutionary information: implications for three-dimensional modeling.

    Science.gov (United States)

    Bhaskara, Ramachandra M; Padhi, Amrita; Srinivasan, Narayanaswamy

    2014-07-01

    With the preponderance of multidomain proteins in eukaryotic genomes, it is essential to recognize the constituent domains and their functions. Often function involves communications across the domain interfaces, and the knowledge of the interacting sites is essential to our understanding of the structure-function relationship. Using evolutionary information extracted from homologous domains in at least two diverse domain architectures (single and multidomain), we predict the interface residues corresponding to domains from the two-domain proteins. We also use information from the three-dimensional structures of individual domains of two-domain proteins to train naïve Bayes classifier model to predict the interfacial residues. Our predictions are highly accurate (∼85%) and specific (∼95%) to the domain-domain interfaces. This method is specific to multidomain proteins which contain domains in at least more than one protein architectural context. Using predicted residues to constrain domain-domain interaction, rigid-body docking was able to provide us with accurate full-length protein structures with correct orientation of domains. We believe that these results can be of considerable interest toward rational protein and interaction design, apart from providing us with valuable information on the nature of interactions.

  4. Accurate prediction of interfacial residues in two-domain proteins using evolutionary information: implications for three-dimensional modeling.

    Science.gov (United States)

    Bhaskara, Ramachandra M; Padhi, Amrita; Srinivasan, Narayanaswamy

    2014-07-01

    With the preponderance of multidomain proteins in eukaryotic genomes, it is essential to recognize the constituent domains and their functions. Often function involves communications across the domain interfaces, and the knowledge of the interacting sites is essential to our understanding of the structure-function relationship. Using evolutionary information extracted from homologous domains in at least two diverse domain architectures (single and multidomain), we predict the interface residues corresponding to domains from the two-domain proteins. We also use information from the three-dimensional structures of individual domains of two-domain proteins to train naïve Bayes classifier model to predict the interfacial residues. Our predictions are highly accurate (∼85%) and specific (∼95%) to the domain-domain interfaces. This method is specific to multidomain proteins which contain domains in at least more than one protein architectural context. Using predicted residues to constrain domain-domain interaction, rigid-body docking was able to provide us with accurate full-length protein structures with correct orientation of domains. We believe that these results can be of considerable interest toward rational protein and interaction design, apart from providing us with valuable information on the nature of interactions. PMID:24375512

  5. Meta-analytic approach to the accurate prediction of secreted virulence effectors in gram-negative bacteria

    Directory of Open Access Journals (Sweden)

    Sato Yoshiharu

    2011-11-01

    Full Text Available Abstract Background Many pathogens use a type III secretion system to translocate virulence proteins (called effectors in order to adapt to the host environment. To date, many prediction tools for effector identification have been developed. However, these tools are insufficiently accurate for producing a list of putative effectors that can be applied directly for labor-intensive experimental verification. This also suggests that important features of effectors have yet to be fully characterized. Results In this study, we have constructed an accurate approach to predicting secreted virulence effectors from Gram-negative bacteria. This consists of a support vector machine-based discriminant analysis followed by a simple criteria-based filtering. The accuracy was assessed by estimating the average number of true positives in the top-20 ranking in the genome-wide screening. In the validation, 10 sets of 20 training and 20 testing examples were randomly selected from 40 known effectors of Salmonella enterica serovar Typhimurium LT2. On average, the SVM portion of our system predicted 9.7 true positives from 20 testing examples in the top-20 of the prediction. Removal of the N-terminal instability, codon adaptation index and ProtParam indices decreased the score to 7.6, 8.9 and 7.9, respectively. These discrimination features suggested that the following characteristics of effectors had been uncovered: unstable N-terminus, non-optimal codon usage, hydrophilic, and less aliphathic. The secondary filtering process represented by coexpression analysis and domain distribution analysis further refined the average true positive counts to 12.3. We further confirmed that our system can correctly predict known effectors of P. syringae DC3000, strongly indicating its feasibility. Conclusions We have successfully developed an accurate prediction system for screening effectors on a genome-wide scale. We confirmed the accuracy of our system by external validation

  6. Can magnetic resonance imaging accurately predict concordant pain provocation during provocative disc injection?

    International Nuclear Information System (INIS)

    To correlate magnetic resonance (MR) image findings with pain response by provocation discography in patients with discogenic low back pain, with an emphasis on the combination analysis of a high intensity zone (HIZ) and disc contour abnormalities. Sixty-two patients (aged 17-68 years) with axial low back pain that was likely to be disc related underwent lumbar discography (178 discs tested). The MR images were evaluated for disc degeneration, disc contour abnormalities, HIZ, and endplate abnormalities. Based on the combination of an HIZ and disc contour abnormalities, four classes were determined: (1) normal or bulging disc without HIZ; (2) normal or bulging disc with HIZ; (3) disc protrusion without HIZ; (4) disc protrusion with HIZ. These MR image findings and a new combined MR classification were analyzed in the base of concordant pain determined by discography. Disc protrusion with HIZ [sensitivity 45.5%; specificity 97.8%; positive predictive value (PPV), 87.0%] correlated significantly with concordant pain provocation (P < 0.01). A normal or bulging disc with HIZ was not associated with reproduction of pain. Disc degeneration (sensitivity 95.4%; specificity 38.8%; PPV 33.9%), disc protrusion (sensitivity 68.2%; specificity 80.6%; PPV 53.6%), and HIZ (sensitivity 56.8%; specificity 83.6%; PPV 53.2%) were not helpful in the identification of a disc with concordant pain. The proposed MR classification is useful to predict a disc with concordant pain. Disc protrusion with HIZ on MR imaging predicted positive discography in patients with discogenic low back pain. (orig.)

  7. Can magnetic resonance imaging accurately predict concordant pain provocation during provocative disc injection?

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Chang Ho; Kim, Yun Hwan; Kim, Jung Hyuk; Chung, Kyoo Byung; Sung, Deuk Jae [Korea University Anam Hospital, Korea University College of Medicine, Department of Radiology, Seoul (Korea); Lee, Sang-Heon [Korea University Anam Hospital, Korea University College of Medicine, Department of Physical Medicine and Rehabilitation, Seoul (Korea); Derby, Richard [Spinal Diagnostics and Treatment Center, Daly City, CA (United States); Stanford University Medical Center, Division of Physical Medicine and Rehabilitation, Stanford, CA (United States)

    2009-09-15

    To correlate magnetic resonance (MR) image findings with pain response by provocation discography in patients with discogenic low back pain, with an emphasis on the combination analysis of a high intensity zone (HIZ) and disc contour abnormalities. Sixty-two patients (aged 17-68 years) with axial low back pain that was likely to be disc related underwent lumbar discography (178 discs tested). The MR images were evaluated for disc degeneration, disc contour abnormalities, HIZ, and endplate abnormalities. Based on the combination of an HIZ and disc contour abnormalities, four classes were determined: (1) normal or bulging disc without HIZ; (2) normal or bulging disc with HIZ; (3) disc protrusion without HIZ; (4) disc protrusion with HIZ. These MR image findings and a new combined MR classification were analyzed in the base of concordant pain determined by discography. Disc protrusion with HIZ [sensitivity 45.5%; specificity 97.8%; positive predictive value (PPV), 87.0%] correlated significantly with concordant pain provocation (P < 0.01). A normal or bulging disc with HIZ was not associated with reproduction of pain. Disc degeneration (sensitivity 95.4%; specificity 38.8%; PPV 33.9%), disc protrusion (sensitivity 68.2%; specificity 80.6%; PPV 53.6%), and HIZ (sensitivity 56.8%; specificity 83.6%; PPV 53.2%) were not helpful in the identification of a disc with concordant pain. The proposed MR classification is useful to predict a disc with concordant pain. Disc protrusion with HIZ on MR imaging predicted positive discography in patients with discogenic low back pain. (orig.)

  8. Can tritiated water-dilution space accurately predict total body water in chukar partridges

    International Nuclear Information System (INIS)

    Total body water (TBW) volumes determined from the dilution space of injected tritiated water have consistently overestimated actual water volumes (determined by desiccation to constant mass) in reptiles and mammals, but results for birds are controversial. We investigated potential errors in both the dilution method and the desiccation method in an attempt to resolve this controversy. Tritiated water dilution yielded an accurate measurement of water mass in vitro. However, in vivo, this method yielded a 4.6% overestimate of the amount of water (3.1% of live body mass) in chukar partridges, apparently largely because of loss of tritium from body water to sites of dissociable hydrogens on body solids. An additional source of overestimation (approximately 2% of body mass) was loss of tritium to the solids in blood samples during distillation of blood to obtain pure water for tritium analysis. Measuring tritium activity in plasma samples avoided this problem but required measurement of, and correction for, the dry matter content in plasma. Desiccation to constant mass by lyophilization or oven-drying also overestimated the amount of water actually in the bodies of chukar partridges by 1.4% of body mass, because these values included water adsorbed onto the outside of feathers. When desiccating defeathered carcasses, oven-drying at 70 degrees C yielded TBW values identical to those obtained from lyophilization, but TBW was overestimated (0.5% of body mass) by drying at 100 degrees C due to loss of organic substances as well as water

  9. Accurate prediction of hot spot residues through physicochemical characteristics of amino acid sequences

    KAUST Repository

    Chen, Peng

    2013-07-23

    Hot spot residues of proteins are fundamental interface residues that help proteins perform their functions. Detecting hot spots by experimental methods is costly and time-consuming. Sequential and structural information has been widely used in the computational prediction of hot spots. However, structural information is not always available. In this article, we investigated the problem of identifying hot spots using only physicochemical characteristics extracted from amino acid sequences. We first extracted 132 relatively independent physicochemical features from a set of the 544 properties in AAindex1, an amino acid index database. Each feature was utilized to train a classification model with a novel encoding schema for hot spot prediction by the IBk algorithm, an extension of the K-nearest neighbor algorithm. The combinations of the individual classifiers were explored and the classifiers that appeared frequently in the top performing combinations were selected. The hot spot predictor was built based on an ensemble of these classifiers and to work in a voting manner. Experimental results demonstrated that our method effectively exploited the feature space and allowed flexible weights of features for different queries. On the commonly used hot spot benchmark sets, our method significantly outperformed other machine learning algorithms and state-of-the-art hot spot predictors. The program is available at http://sfb.kaust.edu.sa/pages/software.aspx. © 2013 Wiley Periodicals, Inc.

  10. How Five Student Characteristics Accurately Predict For-Profit University Graduation Odds

    Directory of Open Access Journals (Sweden)

    Tim Gramling

    2013-07-01

    Full Text Available President Obama’s goal is for America to lead the world in college graduates by 2020. Although for-profit institutions have increased their output of graduates at ten times the rate of nonprofits over the past decade, Congress and the U.S. Department of Education have argued that these institutions exploit the ambitions of lower-performing students. In response, this study examined how student characteristics predicted graduation odds at a large, regionally accredited for-profit institution campus. A logistic regression predicted graduation for the full population of 2,548 undergraduate students enrolled from 2005 to 2009 with scheduled graduation by June 30, 2011. Sixteen independent predictors were identified from school records and organized in the Bean and Metzner framework. The regression model was more robust than any in the literature, with a Nagelkerke R2 of .663. Only five factors had a significant impact on log odds: (a grade point average (GPA, where higher values increased odds; (b half time enrollment, which had lower odds than full time; (c Blacks, who had higher odds than Whites; (d credits required, where fewer credits increased odds; and (e primary expected family contribution, where higher values increased odds. These findings imply that public policy will not increase college graduates by focusing on institution characteristics.

  11. The Compensatory Reserve For Early and Accurate Prediction Of Hemodynamic Compromise: A Review of the Underlying Physiology.

    Science.gov (United States)

    Convertino, Victor A; Wirt, Michael D; Glenn, John F; Lein, Brian C

    2016-06-01

    Shock is deadly and unpredictable if it is not recognized and treated in early stages of hemorrhage. Unfortunately, measurements of standard vital signs that are displayed on current medical monitors fail to provide accurate or early indicators of shock because of physiological mechanisms that effectively compensate for blood loss. As a result of new insights provided by the latest research on the physiology of shock using human experimental models of controlled hemorrhage, it is now recognized that measurement of the body's reserve to compensate for reduced circulating blood volume is the single most important indicator for early and accurate assessment of shock. We have called this function the "compensatory reserve," which can be accurately assessed by real-time measurements of changes in the features of the arterial waveform. In this paper, the physiology underlying the development and evaluation of a new noninvasive technology that allows for real-time measurement of the compensatory reserve will be reviewed, with its clinical implications for earlier and more accurate prediction of shock. PMID:26950588

  12. A novel method to predict visual field progression more accurately, using intraocular pressure measurements in glaucoma patients

    Science.gov (United States)

    Asaoka, Ryo; Fujino, Yuri; Murata, Hiroshi; Miki, Atsuya; Tanito, Masaki; Mizoue, Shiro; Mori, Kazuhiko; Suzuki, Katsuyoshi; Yamashita, Takehiro; Kashiwagi, Kenji; Shoji, Nobuyuki

    2016-01-01

    Visual field (VF) data were retrospectively obtained from 491 eyes in 317 patients with open angle glaucoma who had undergone ten VF tests (Humphrey Field Analyzer, 24-2, SITA standard). First, mean of total deviation values (mTD) in the tenth VF was predicted using standard linear regression of the first five VFs (VF1-5) through to using all nine preceding VFs (VF1-9). Then an ‘intraocular pressure (IOP)-integrated VF trend analysis’ was carried out by simply using time multiplied by IOP as the independent term in the linear regression model. Prediction errors (absolute prediction error or root mean squared error: RMSE) for predicting mTD and also point wise TD values of the tenth VF were obtained from both approaches. The mTD absolute prediction errors associated with the IOP-integrated VF trend analysis were significantly smaller than those from the standard trend analysis when VF1-6 through to VF1-8 were used (p < 0.05). The point wise RMSEs from the IOP-integrated trend analysis were significantly smaller than those from the standard trend analysis when VF1-5 through to VF1-9 were used (p < 0.05). This was especially the case when IOP was measured more frequently. Thus a significantly more accurate prediction of VF progression is possible using a simple trend analysis that incorporates IOP measurements. PMID:27562553

  13. The cyanase operon and cyanate metabolism.

    Science.gov (United States)

    Anderson, P M; Sung, Y C; Fuchs, J A

    1990-12-01

    Cyanase is an inducible enzyme in E. coli that catalyzes bicarbonate-dependent decomposition of cyanate. It is encoded as part of an operon we have named the cyn operon, which includes three genes in the following order: cynT (cyanate permease), cynS (cyanase), and cynX (protein of unknown function). The direction of transcription is opposite to that of the lac operon, and the 3'-end of the cyn operon overlaps the 3'-end of the lac operon by 98 nucleotides. The gene cynR (regulatory protein) is located upstream from the cyn operon, and its transcription is opposite that of the cyn operon. The genes of the cyn operon and the cynR gene have been cloned, sequenced and over-expressed. Cyanate at concentrations of about 1 mM is toxic to strains of E. coli lacking the cyanase gene, but strains in which the inducible gene for cyanase is present can grow on cyanate as the sole source of nitrogen at concentrations as high as 20 mM. The presence of cyanase itself is not sufficient to overcome cyanate toxicity--the permease must also be present. Strains lacking the cyanase gene, but having a functional permease gene, are extremely sensitive to cyanate. Uptake of cyanate involves the product of the permease gene in an energy-dependent process. It appears that the cyn operon has evolved to function in detoxification/decomposition of cyanate arising from both intra- and extracellular sources.

  14. Combining multiple regression and principal component analysis for accurate predictions for column ozone in Peninsular Malaysia

    Science.gov (United States)

    Rajab, Jasim M.; MatJafri, M. Z.; Lim, H. S.

    2013-06-01

    This study encompasses columnar ozone modelling in the peninsular Malaysia. Data of eight atmospheric parameters [air surface temperature (AST), carbon monoxide (CO), methane (CH4), water vapour (H2Ovapour), skin surface temperature (SSKT), atmosphere temperature (AT), relative humidity (RH), and mean surface pressure (MSP)] data set, retrieved from NASA's Atmospheric Infrared Sounder (AIRS), for the entire period (2003-2008) was employed to develop models to predict the value of columnar ozone (O3) in study area. The combined method, which is based on using both multiple regressions combined with principal component analysis (PCA) modelling, was used to predict columnar ozone. This combined approach was utilized to improve the prediction accuracy of columnar ozone. Separate analysis was carried out for north east monsoon (NEM) and south west monsoon (SWM) seasons. The O3 was negatively correlated with CH4, H2Ovapour, RH, and MSP, whereas it was positively correlated with CO, AST, SSKT, and AT during both the NEM and SWM season periods. Multiple regression analysis was used to fit the columnar ozone data using the atmospheric parameter's variables as predictors. A variable selection method based on high loading of varimax rotated principal components was used to acquire subsets of the predictor variables to be comprised in the linear regression model of the atmospheric parameter's variables. It was found that the increase in columnar O3 value is associated with an increase in the values of AST, SSKT, AT, and CO and with a drop in the levels of CH4, H2Ovapour, RH, and MSP. The result of fitting the best models for the columnar O3 value using eight of the independent variables gave about the same values of the R (≈0.93) and R2 (≈0.86) for both the NEM and SWM seasons. The common variables that appeared in both regression equations were SSKT, CH4 and RH, and the principal precursor of the columnar O3 value in both the NEM and SWM seasons was SSKT.

  15. Prognostic breast cancer signature identified from 3D culture model accurately predicts clinical outcome across independent datasets

    Energy Technology Data Exchange (ETDEWEB)

    Martin, Katherine J.; Patrick, Denis R.; Bissell, Mina J.; Fournier, Marcia V.

    2008-10-20

    One of the major tenets in breast cancer research is that early detection is vital for patient survival by increasing treatment options. To that end, we have previously used a novel unsupervised approach to identify a set of genes whose expression predicts prognosis of breast cancer patients. The predictive genes were selected in a well-defined three dimensional (3D) cell culture model of non-malignant human mammary epithelial cell morphogenesis as down-regulated during breast epithelial cell acinar formation and cell cycle arrest. Here we examine the ability of this gene signature (3D-signature) to predict prognosis in three independent breast cancer microarray datasets having 295, 286, and 118 samples, respectively. Our results show that the 3D-signature accurately predicts prognosis in three unrelated patient datasets. At 10 years, the probability of positive outcome was 52, 51, and 47 percent in the group with a poor-prognosis signature and 91, 75, and 71 percent in the group with a good-prognosis signature for the three datasets, respectively (Kaplan-Meier survival analysis, p<0.05). Hazard ratios for poor outcome were 5.5 (95% CI 3.0 to 12.2, p<0.0001), 2.4 (95% CI 1.6 to 3.6, p<0.0001) and 1.9 (95% CI 1.1 to 3.2, p = 0.016) and remained significant for the two larger datasets when corrected for estrogen receptor (ER) status. Hence the 3D-signature accurately predicts breast cancer outcome in both ER-positive and ER-negative tumors, though individual genes differed in their prognostic ability in the two subtypes. Genes that were prognostic in ER+ patients are AURKA, CEP55, RRM2, EPHA2, FGFBP1, and VRK1, while genes prognostic in ER patients include ACTB, FOXM1 and SERPINE2 (Kaplan-Meier p<0.05). Multivariable Cox regression analysis in the largest dataset showed that the 3D-signature was a strong independent factor in predicting breast cancer outcome. The 3D-signature accurately predicts breast cancer outcome across multiple datasets and holds prognostic

  16. nuMap:A Web Platform for Accurate Prediction of Nucleosome Positioning

    Institute of Scientific and Technical Information of China (English)

    Bader A Alharbi; Thamir H Alshammari; Nathan L Felton; Victor B Zhurkin; Feng Cui

    2014-01-01

    Nucleosome positioning is critical for gene expression and of major biological interest. The high cost of experimentally mapping nucleosomal arrangement signifies the need for computational approaches to predict nucleosome positions at high resolution. Here, we present a web-based application to fulfill this need by implementing two models, YR and W/S schemes, for the translational and rotational positioning of nucleosomes, respectively. Our methods are based on sequence-dependent anisotropic bending that dictates how DNA is wrapped around a histone octamer. This application allows users to specify a number of options such as schemes and param-eters for threading calculation and provides multiple layout formats. The nuMap is implemented in Java/Perl/MySQL and is freely available for public use at http://numap.rit.edu. The user manual, implementation notes, description of the methodology and examples are available at the site.

  17. Simplified versus geometrically accurate models of forefoot anatomy to predict plantar pressures: A finite element study.

    Science.gov (United States)

    Telfer, Scott; Erdemir, Ahmet; Woodburn, James; Cavanagh, Peter R

    2016-01-25

    Integration of patient-specific biomechanical measurements into the design of therapeutic footwear has been shown to improve clinical outcomes in patients with diabetic foot disease. The addition of numerical simulations intended to optimise intervention design may help to build on these advances, however at present the time and labour required to generate and run personalised models of foot anatomy restrict their routine clinical utility. In this study we developed second-generation personalised simple finite element (FE) models of the forefoot with varying geometric fidelities. Plantar pressure predictions from barefoot, shod, and shod with insole simulations using simplified models were compared to those obtained from CT-based FE models incorporating more detailed representations of bone and tissue geometry. A simplified model including representations of metatarsals based on simple geometric shapes, embedded within a contoured soft tissue block with outer geometry acquired from a 3D surface scan was found to provide pressure predictions closest to the more complex model, with mean differences of 13.3kPa (SD 13.4), 12.52kPa (SD 11.9) and 9.6kPa (SD 9.3) for barefoot, shod, and insole conditions respectively. The simplified model design could be produced in 3h in the case of the more detailed model, and solved on average 24% faster. FE models of the forefoot based on simplified geometric representations of the metatarsal bones and soft tissue surface geometry from 3D surface scans may potentially provide a simulation approach with improved clinical utility, however further validity testing around a range of therapeutic footwear types is required.

  18. The human skin/chick chorioallantoic membrane model accurately predicts the potency of cosmetic allergens.

    Science.gov (United States)

    Slodownik, Dan; Grinberg, Igor; Spira, Ram M; Skornik, Yehuda; Goldstein, Ronald S

    2009-04-01

    The current standard method for predicting contact allergenicity is the murine local lymph node assay (LLNA). Public objection to the use of animals in testing of cosmetics makes the development of a system that does not use sentient animals highly desirable. The chorioallantoic membrane (CAM) of the chick egg has been extensively used for the growth of normal and transformed mammalian tissues. The CAM is not innervated, and embryos are sacrificed before the development of pain perception. The aim of this study was to determine whether the sensitization phase of contact dermatitis to known cosmetic allergens can be quantified using CAM-engrafted human skin and how these results compare with published EC3 data obtained with the LLNA. We studied six common molecules used in allergen testing and quantified migration of epidermal Langerhans cells (LC) as a measure of their allergic potency. All agents with known allergic potential induced statistically significant migration of LC. The data obtained correlated well with published data for these allergens generated using the LLNA test. The human-skin CAM model therefore has great potential as an inexpensive, non-radioactive, in vivo alternative to the LLNA, which does not require the use of sentient animals. In addition, this system has the advantage of testing the allergic response of human, rather than animal skin. PMID:19054059

  19. The development and verification of a highly accurate collision prediction model for automated noncoplanar plan delivery

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Victoria Y.; Tran, Angelia; Nguyen, Dan; Cao, Minsong; Ruan, Dan; Low, Daniel A.; Sheng, Ke, E-mail: ksheng@mednet.ucla.edu [Department of Radiation Oncology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90024 (United States)

    2015-11-15

    attributed to phantom setup errors due to the slightly deformable and flexible phantom extremities. The estimated site-specific safety buffer distance with 0.001% probability of collision for (gantry-to-couch, gantry-to-phantom) was (1.23 cm, 3.35 cm), (1.01 cm, 3.99 cm), and (2.19 cm, 5.73 cm) for treatment to the head, lung, and prostate, respectively. Automated delivery to all three treatment sites was completed in 15 min and collision free using a digital Linac. Conclusions: An individualized collision prediction model for the purpose of noncoplanar beam delivery was developed and verified. With the model, the study has demonstrated the feasibility of predicting deliverable beams for an individual patient and then guiding fully automated noncoplanar treatment delivery. This work motivates development of clinical workflows and quality assurance procedures to allow more extensive use and automation of noncoplanar beam geometries.

  20. Industrial Compositional Streamline Simulation for Efficient and Accurate Prediction of Gas Injection and WAG Processes

    Energy Technology Data Exchange (ETDEWEB)

    Margot Gerritsen

    2008-10-31

    Gas-injection processes are widely and increasingly used for enhanced oil recovery (EOR). In the United States, for example, EOR production by gas injection accounts for approximately 45% of total EOR production and has tripled since 1986. The understanding of the multiphase, multicomponent flow taking place in any displacement process is essential for successful design of gas-injection projects. Due to complex reservoir geometry, reservoir fluid properties and phase behavior, the design of accurate and efficient numerical simulations for the multiphase, multicomponent flow governing these processes is nontrivial. In this work, we developed, implemented and tested a streamline based solver for gas injection processes that is computationally very attractive: as compared to traditional Eulerian solvers in use by industry it computes solutions with a computational speed orders of magnitude higher and a comparable accuracy provided that cross-flow effects do not dominate. We contributed to the development of compositional streamline solvers in three significant ways: improvement of the overall framework allowing improved streamline coverage and partial streamline tracing, amongst others; parallelization of the streamline code, which significantly improves wall clock time; and development of new compositional solvers that can be implemented along streamlines as well as in existing Eulerian codes used by industry. We designed several novel ideas in the streamline framework. First, we developed an adaptive streamline coverage algorithm. Adding streamlines locally can reduce computational costs by concentrating computational efforts where needed, and reduce mapping errors. Adapting streamline coverage effectively controls mass balance errors that mostly result from the mapping from streamlines to pressure grid. We also introduced the concept of partial streamlines: streamlines that do not necessarily start and/or end at wells. This allows more efficient coverage and avoids

  1. A Novel Fibrosis Index Comprising a Non-Cholesterol Sterol Accurately Predicts HCV-Related Liver Cirrhosis

    DEFF Research Database (Denmark)

    Ydreborg, Magdalena; Lisovskaja, Vera; Lagging, Martin;

    2014-01-01

    Diagnosis of liver cirrhosis is essential in the management of chronic hepatitis C virus (HCV) infection. Liver biopsy is invasive and thus entails a risk of complications as well as a potential risk of sampling error. Therefore, non-invasive diagnostic tools are preferential. The aim...... of the present study was to create a model for accurate prediction of liver cirrhosis based on patient characteristics and biomarkers of liver fibrosis, including a panel of non-cholesterol sterols reflecting cholesterol synthesis and absorption and secretion. We evaluated variables with potential predictive...... significance for liver fibrosis in 278 patients originally included in a multicenter phase III treatment trial for chronic HCV infection. A stepwise multivariate logistic model selection was performed with liver cirrhosis, defined as Ishak fibrosis stage 5-6, as the outcome variable. A new index, referred...

  2. Human Gut-Commensalic Lactobacillus ruminis ATCC 25644 Displays Sortase-Assembled Surface Piliation: Phenotypic Characterization of Its Fimbrial Operon through In Silico Predictive Analysis and Recombinant Expression in Lactococcus lactis.

    Directory of Open Access Journals (Sweden)

    Xia Yu

    Full Text Available Sortase-dependent surface pili (or fimbriae in Gram-positive bacteria are well documented as a key virulence factor for certain harmful opportunistic pathogens. However, it is only recently known that these multi-subunit protein appendages are also belonging to the "friendly" commensals and now, with this new perspective, they have come to be categorized as a niche-adaptation factor as well. In this regard, it was shown earlier that sortase-assembled piliation is a native fixture of two human intestinal commensalics (i.e., Lactobacillus rhamnosus and Bifidobacterium bifidum, and correspondingly where the pili involved have a significant role in cellular adhesion and immunomodulation processes. We now reveal that intestinal indigenous (or autochthonous Lactobacillus ruminis is another surface-piliated commensal lactobacillar species. Heeding to in silico expectations, the predicted loci for the LrpCBA-called pili are organized tandemly in the L. ruminis genome as a canonical fimbrial operon, which then encodes for three pilin-proteins and a single C-type sortase enzyme. Through electron microscopic means, we showed that these pilus formations are a surface assemblage of tip, basal, and backbone pilin subunits (respectively named LrpC, LrpB, and LrpA in L. ruminis, and also when expressed recombinantly in Lactococcus lactis. As well, by using the recombinant-piliated lactococci, we could define certain ecologically relevant phenotypic traits, such as the ability to adhere to extracellular matrix proteins and gut epithelial cells, but also to effectuate an induced dampening on Toll-like receptor 2 signaling and interleukin-8 responsiveness in immune-related cells. Within the context of the intestinal microcosm, by wielding such niche-advantageous cell-surface properties the LrpCBA pilus would undoubtedly have a requisite functional role in the colonization dynamics of L. ruminis indigeneity. Our study provides only the second description of a

  3. A cross-race effect in metamemory: Predictions of face recognition are more accurate for members of our own race.

    Science.gov (United States)

    Hourihan, Kathleen L; Benjamin, Aaron S; Liu, Xiping

    2012-09-01

    The Cross-Race Effect (CRE) in face recognition is the well-replicated finding that people are better at recognizing faces from their own race, relative to other races. The CRE reveals systematic limitations on eyewitness identification accuracy and suggests that some caution is warranted in evaluating cross-race identification. The CRE is a problem because jurors value eyewitness identification highly in verdict decisions. In the present paper, we explore how accurate people are in predicting their ability to recognize own-race and other-race faces. Caucasian and Asian participants viewed photographs of Caucasian and Asian faces, and made immediate judgments of learning during study. An old/new recognition test replicated the CRE: both groups displayed superior discriminability of own-race faces, relative to other-race faces. Importantly, relative metamnemonic accuracy was also greater for own-race faces, indicating that the accuracy of predictions about face recognition is influenced by race. This result indicates another source of concern when eliciting or evaluating eyewitness identification: people are less accurate in judging whether they will or will not recognize a face when that face is of a different race than they are. This new result suggests that a witness's claim of being likely to recognize a suspect from a lineup should be interpreted with caution when the suspect is of a different race than the witness.

  4. Interplay of gene expression noise and ultrasensitive dynamics affects bacterial operon organization.

    Directory of Open Access Journals (Sweden)

    J Christian J Ray

    Full Text Available Bacterial chromosomes are organized into polycistronic cotranscribed operons, but the evolutionary pressures maintaining them are unclear. We hypothesized that operons alter gene expression noise characteristics, resulting in selection for or against maintaining operons depending on network architecture. Mathematical models for 6 functional classes of network modules showed that three classes exhibited decreased noise and 3 exhibited increased noise with same-operon cotranscription of interacting proteins. Noise reduction was often associated with a decreased chance of reaching an ultrasensitive threshold. Stochastic simulations of the lac operon demonstrated that the predicted effects of transcriptional coupling hold for a complex network module. We employed bioinformatic analysis to find overrepresentation of noise-minimizing operon organization compared with randomized controls. Among constitutively expressed physically interacting protein pairs, higher coupling frequencies appeared at lower expression levels, where noise effects are expected to be dominant. Our results thereby suggest an important role for gene expression noise, in many cases interacting with an ultrasensitive switch, in maintaining or selecting for operons in bacterial chromosomes.

  5. Accurate prediction of sour gas hydrate equilibrium dissociation conditions by using an adaptive neuro fuzzy inference system

    International Nuclear Information System (INIS)

    Highlights: ► An ANFIS model is developed for predicting sour gas hydrate dissociation conditions. ► It can be used over wide ranges of operating conditions. ► At all H2S concentrations, the developed model outperforms the thermodynamic models. ► The presented model is useful for design of industrial sour gas handling systems. - Abstract: An adaptive neuro fuzzy inference system (ANFIS) has been proposed for predicting the sour gas hydrate equilibrium dissociation conditions. The proposed model predictions have been compared with those of the available thermodynamic models at different operating conditions. It is found that at all H2S concentrations especially at the concentrations higher than 10 mol%, the developed ANFIS model outperforms the existing thermodynamic models with the average absolute deviation of 2.18%. The proposed ANFIS model can be used for accurate and reliable predictions of sour gas hydrate equilibrium conditions over wide ranges of temperatures and acid gas concentrations and is a useful tool for proper design of sour natural gas flow assurance systems and gas hydrate energy storage processes in oil and gas industries.

  6. Accurate predictions for charged Higgs production: closing the $m_{H^{\\pm}}\\sim m_t$ window

    CERN Document Server

    Degrande, Celine; Hirschi, Valentin; Ubiali, Maria; Wiesemann, Marius; Zaro, Marco

    2016-01-01

    We present predictions for the total cross section for the production of a charged Higgs boson in a generic type-II two-Higgs-doublet model in the intermediate-mass range ($m_{H^{\\pm}}\\sim m_t$) at the LHC. Results are obtained at next-to-leading order (NLO) accuracy in QCD perturbation theory, by studying the full process $pp\\to H^\\pm W^\\mp b \\bar b$ in the complex-(top)-mass scheme with massive bottom quarks. Compared to lowest-order predictions, NLO corrections have a sizable impact: they increase the cross section by roughly 50% and reduce uncertainties due to scale variations by more than a factor of two. Our computation reliably interpolates between the low- and high-mass regime. Our results provide the first NLO prediction for charged Higgs production in the intermediate-mass range and therefore allow to have NLO accurate predictions in the full $m_{H^{\\pm}}$ range.

  7. Accurate prediction of unsteady and time-averaged pressure loads using a hybrid Reynolds-Averaged/large-eddy simulation technique

    Science.gov (United States)

    Bozinoski, Radoslav

    Significant research has been performed over the last several years on understanding the unsteady aerodynamics of various fluid flows. Much of this work has focused on quantifying the unsteady, three-dimensional flow field effects which have proven vital to the accurate prediction of many fluid and aerodynamic problems. Up until recently, engineers have predominantly relied on steady-state simulations to analyze the inherently three-dimensional ow structures that are prevalent in many of today's "real-world" problems. Increases in computational capacity and the development of efficient numerical methods can change this and allow for the solution of the unsteady Reynolds-Averaged Navier-Stokes (RANS) equations for practical three-dimensional aerodynamic applications. An integral part of this capability has been the performance and accuracy of the turbulence models coupled with advanced parallel computing techniques. This report begins with a brief literature survey of the role fully three-dimensional, unsteady, Navier-Stokes solvers have on the current state of numerical analysis. Next, the process of creating a baseline three-dimensional Multi-Block FLOw procedure called MBFLO3 is presented. Solutions for an inviscid circular arc bump, laminar at plate, laminar cylinder, and turbulent at plate are then presented. Results show good agreement with available experimental, numerical, and theoretical data. Scalability data for the parallel version of MBFLO3 is presented and shows efficiencies of 90% and higher for processes of no less than 100,000 computational grid points. Next, the description and implementation techniques used for several turbulence models are presented. Following the successful implementation of the URANS and DES procedures, the validation data for separated, non-reattaching flows over a NACA 0012 airfoil, wall-mounted hump, and a wing-body junction geometry are presented. Results for the NACA 0012 showed significant improvement in flow predictions

  8. The Genomic Pattern of tDNA Operon Expression in E. coli.

    Directory of Open Access Journals (Sweden)

    2005-06-01

    Full Text Available In fast-growing microorganisms, a tRNA concentration profile enriched in major isoacceptors selects for the biased usage of cognate codons. This optimizes translational rate for the least mass invested in the translational apparatus. Such translational streamlining is thought to be growth-regulated, but its genetic basis is poorly understood. First, we found in reanalysis of the E. coli tRNA profile that the degree to which it is translationally streamlined is nearly invariant with growth rate. Then, using least squares multiple regression, we partitioned tRNA isoacceptor pools to predicted tDNA operons from the E. coli K12 genome. Co-expression of tDNAs in operons explains the tRNA profile significantly better than tDNA gene dosage alone. Also, operon expression increases significantly with proximity to the origin of replication, oriC, at all growth rates. Genome location explains about 15% of expression variation in a form, at a given growth rate, that is consistent with replication-dependent gene concentration effects. Yet the change in the tRNA profile with growth rate is less than would be expected from such effects. We estimated per-copy expression rates for all tDNA operons that were consistent with independent estimates for rDNA operons. We also found that tDNA operon location, and the location dependence of expression, were significantly different in the leading and lagging strands. The operonic organization and genomic location of tDNA operons are significant factors influencing their expression. Nonrandom patterns of location and strandedness shown by tDNA operons in E. coli suggest that their genomic architecture may be under selection to satisfy physiological demand for tRNA expression at high growth rates.

  9. Use of the Operon Structure of the C. elegans Genome as a Tool to Identify Functionally Related Proteins

    Directory of Open Access Journals (Sweden)

    Silvia Dossena

    2013-12-01

    Full Text Available One of the most pressing challenges in the post genomic era is the identification and characterization of protein-protein interactions (PPIs, as these are essential in understanding the cellular physiology of health and disease. Experimental techniques suitable for characterizing PPIs (X-ray crystallography or nuclear magnetic resonance spectroscopy, among others are usually laborious, time-consuming and often difficult to apply to membrane proteins, and therefore require accurate prediction of the candidate interacting partners. High-throughput experimental methods (yeast two-hybrid and affinity purification succumb to the same shortcomings, and can also lead to high rates of false positive and negative results. Therefore, reliable tools for predicting PPIs are needed. The use of the operon structure in the eukaryote Caenorhabditis elegans genome is a valuable, though underserved, tool for identifying physically or functionally interacting proteins. Based on the concept that genes organized in the same operon may encode physically or functionally related proteins, this algorithm is easy to be applied and, importantly, gives a limited number of candidate partners of a given protein, allowing for focused experimental verification. Moreover, this approach can be successfully used to predict PPIs in the human system, including those of membrane proteins.

  10. An approach to estimating and extrapolating model error based on inverse problem methods: towards accurate numerical weather prediction

    International Nuclear Information System (INIS)

    Model error is one of the key factors restricting the accuracy of numerical weather prediction (NWP). Considering the continuous evolution of the atmosphere, the observed data (ignoring the measurement error) can be viewed as a series of solutions of an accurate model governing the actual atmosphere. Model error is represented as an unknown term in the accurate model, thus NWP can be considered as an inverse problem to uncover the unknown error term. The inverse problem models can absorb long periods of observed data to generate model error correction procedures. They thus resolve the deficiency and faultiness of the NWP schemes employing only the initial-time data. In this study we construct two inverse problem models to estimate and extrapolate the time-varying and spatial-varying model errors in both the historical and forecast periods by using recent observations and analogue phenomena of the atmosphere. Numerical experiment on Burgers' equation has illustrated the substantial forecast improvement using inverse problem algorithms. The proposed inverse problem methods of suppressing NWP errors will be useful in future high accuracy applications of NWP. (geophysics, astronomy, and astrophysics)

  11. A novel fibrosis index comprising a non-cholesterol sterol accurately predicts HCV-related liver cirrhosis.

    Directory of Open Access Journals (Sweden)

    Magdalena Ydreborg

    Full Text Available Diagnosis of liver cirrhosis is essential in the management of chronic hepatitis C virus (HCV infection. Liver biopsy is invasive and thus entails a risk of complications as well as a potential risk of sampling error. Therefore, non-invasive diagnostic tools are preferential. The aim of the present study was to create a model for accurate prediction of liver cirrhosis based on patient characteristics and biomarkers of liver fibrosis, including a panel of non-cholesterol sterols reflecting cholesterol synthesis and absorption and secretion. We evaluated variables with potential predictive significance for liver fibrosis in 278 patients originally included in a multicenter phase III treatment trial for chronic HCV infection. A stepwise multivariate logistic model selection was performed with liver cirrhosis, defined as Ishak fibrosis stage 5-6, as the outcome variable. A new index, referred to as Nordic Liver Index (NoLI in the paper, was based on the model: Log-odds (predicting cirrhosis = -12.17+ (age × 0.11 + (BMI (kg/m(2 × 0.23 + (D7-lathosterol (μg/100 mg cholesterol×(-0.013 + (Platelet count (x10(9/L × (-0.018 + (Prothrombin-INR × 3.69. The area under the ROC curve (AUROC for prediction of cirrhosis was 0.91 (95% CI 0.86-0.96. The index was validated in a separate cohort of 83 patients and the AUROC for this cohort was similar (0.90; 95% CI: 0.82-0.98. In conclusion, the new index may complement other methods in diagnosing cirrhosis in patients with chronic HCV infection.

  12. Ancient origin of the tryptophan operon and the dynamics of evolutionary change.

    Science.gov (United States)

    Xie, Gary; Keyhani, Nemat O; Bonner, Carol A; Jensen, Roy A

    2003-09-01

    The seven conserved enzymatic domains required for tryptophan (Trp) biosynthesis are encoded in seven genetic regions that are organized differently (whole-pathway operons, multiple partial-pathway operons, and dispersed genes) in prokaryotes. A comparative bioinformatics evaluation of the conservation and organization of the genes of Trp biosynthesis in prokaryotic operons should serve as an excellent model for assessing the feasibility of predicting the evolutionary histories of genes and operons associated with other biochemical pathways. These comparisons should provide a better understanding of possible explanations for differences in operon organization in different organisms at a genomics level. These analyses may also permit identification of some of the prevailing forces that dictated specific gene rearrangements during the course of evolution. Operons concerned with Trp biosynthesis in prokaryotes have been in a dynamic state of flux. Analysis of closely related organisms among the Bacteria at various phylogenetic nodes reveals many examples of operon scission, gene dispersal, gene fusion, gene scrambling, and gene loss from which the direction of evolutionary events can be deduced. Two milestone evolutionary events have been mapped to the 16S rRNA tree of Bacteria, one splitting the operon in two, and the other rejoining it by gene fusion. The Archaea, though less resolved due to a lesser genome representation, appear to exhibit more gene scrambling than the Bacteria. The trp operon appears to have been an ancient innovation; it was already present in the common ancestor of Bacteria and Archaea. Although the operon has been subjected, even in recent times, to dynamic changes in gene rearrangement, the ancestral gene order can be deduced with confidence. The evolutionary history of the genes of the pathway is discernible in rough outline as a vertical line of descent, with events of lateral gene transfer or paralogy enriching the analysis as interesting

  13. Predicting suitable optoelectronic properties of monoclinic VON semiconductor crystals for photovoltaics using accurate first-principles computations.

    Science.gov (United States)

    Harb, Moussab

    2015-10-14

    Using accurate first-principles quantum calculations based on DFT (including the DFPT) with the range-separated hybrid HSE06 exchange-correlation functional, we can predict the essential fundamental properties (such as bandgap, optical absorption co-efficient, dielectric constant, charge carrier effective masses and exciton binding energy) of two stable monoclinic vanadium oxynitride (VON) semiconductor crystals for solar energy conversion applications. In addition to the predicted band gaps in the optimal range for making single-junction solar cells, both polymorphs exhibit a relatively high absorption efficiency in the visible range, high dielectric constant, high charge carrier mobility and much lower exciton binding energy than the thermal energy at room temperature. Moreover, their optical absorption, dielectric and exciton dissociation properties were found to be better than those obtained for semiconductors frequently utilized in photovoltaic devices such as Si, CdTe and GaAs. These novel results offer a great opportunity for this stoichiometric VON material to be properly synthesized and considered as a new good candidate for photovoltaic applications. PMID:26351755

  14. Predicting suitable optoelectronic properties of monoclinic VON semiconductor crystals for photovoltaics using accurate first-principles computations

    KAUST Repository

    Harb, Moussab

    2015-08-26

    Using accurate first-principles quantum calculations based on DFT (including the perturbation theory DFPT) with the range-separated hybrid HSE06 exchange-correlation functional, we predict essential fundamental properties (such as bandgap, optical absorption coefficient, dielectric constant, charge carrier effective masses and exciton binding energy) of two stable monoclinic vanadium oxynitride (VON) semiconductor crystals for solar energy conversion applications. In addition to the predicted band gaps in the optimal range for making single-junction solar cells, both polymorphs exhibit relatively high absorption efficiencies in the visible range, high dielectric constants, high charge carrier mobilities and much lower exciton binding energies than the thermal energy at room temperature. Moreover, their optical absorption, dielectric and exciton dissociation properties are found to be better than those obtained for semiconductors frequently utilized in photovoltaic devices like Si, CdTe and GaAs. These novel results offer a great opportunity for this stoichiometric VON material to be properly synthesized and considered as a new good candidate for photovoltaic applications.

  15. Accurate electrical prediction of memory array through SEM-based edge-contour extraction using SPICE simulation

    Science.gov (United States)

    Shauly, Eitan; Rotstein, Israel; Peltinov, Ram; Latinski, Sergei; Adan, Ofer; Levi, Shimon; Menadeva, Ovadya

    2009-03-01

    The continues transistors scaling efforts, for smaller devices, similar (or larger) drive current/um and faster devices, increase the challenge to predict and to control the transistor off-state current. Typically, electrical simulators like SPICE, are using the design intent (as-drawn GDS data). At more sophisticated cases, the simulators are fed with the pattern after lithography and etch process simulations. As the importance of electrical simulation accuracy is increasing and leakage is becoming more dominant, there is a need to feed these simulators, with more accurate information extracted from physical on-silicon transistors. Our methodology to predict changes in device performances due to systematic lithography and etch effects was used in this paper. In general, the methodology consists on using the OPCCmaxTM for systematic Edge-Contour-Extraction (ECE) from transistors, taking along the manufacturing and includes any image distortions like line-end shortening, corner rounding and line-edge roughness. These measurements are used for SPICE modeling. Possible application of this new metrology is to provide a-head of time, physical and electrical statistical data improving time to market. In this work, we applied our methodology to analyze a small and large array's of 2.14um2 6T-SRAM, manufactured using Tower Standard Logic for General Purposes Platform. 4 out of the 6 transistors used "U-Shape AA", known to have higher variability. The predicted electrical performances of the transistors drive current and leakage current, in terms of nominal values and variability are presented. We also used the methodology to analyze an entire SRAM Block array. Study of an isolation leakage and variability are presented.

  16. Stochastic simulations of the tetracycline operon

    OpenAIRE

    Kaznessis Yiannis N; Daoutidis Prodromos; Biliouris Konstantinos

    2011-01-01

    Abstract Background The tetracycline operon is a self-regulated system. It is found naturally in bacteria where it confers resistance to antibiotic tetracycline. Because of the performance of the molecular elements of the tetracycline operon, these elements are widely used as parts of synthetic gene networks where the protein production can be efficiently turned on and off in response to the presence or the absence of tetracycline. In this paper, we investigate the dynamics of the tetracyclin...

  17. High IFIT1 expression predicts improved clinical outcome, and IFIT1 along with MGMT more accurately predicts prognosis in newly diagnosed glioblastoma.

    Science.gov (United States)

    Zhang, Jin-Feng; Chen, Yao; Lin, Guo-Shi; Zhang, Jian-Dong; Tang, Wen-Long; Huang, Jian-Huang; Chen, Jin-Shou; Wang, Xing-Fu; Lin, Zhi-Xiong

    2016-06-01

    Interferon-induced protein with tetratricopeptide repeat 1 (IFIT1) plays a key role in growth suppression and apoptosis promotion in cancer cells. Interferon was reported to induce the expression of IFIT1 and inhibit the expression of O-6-methylguanine-DNA methyltransferase (MGMT).This study aimed to investigate the expression of IFIT1, the correlation between IFIT1 and MGMT, and their impact on the clinical outcome in newly diagnosed glioblastoma. The expression of IFIT1 and MGMT and their correlation were investigated in the tumor tissues from 70 patients with newly diagnosed glioblastoma. The effects on progression-free survival and overall survival were evaluated. Of 70 cases, 57 (81.4%) tissue samples showed high expression of IFIT1 by immunostaining. The χ(2) test indicated that the expression of IFIT1 and MGMT was negatively correlated (r = -0.288, P = .016). Univariate and multivariate analyses confirmed high IFIT1 expression as a favorable prognostic indicator for progression-free survival (P = .005 and .017) and overall survival (P = .001 and .001), respectively. Patients with 2 favorable factors (high IFIT1 and low MGMT) had an improved prognosis as compared with others. The results demonstrated significantly increased expression of IFIT1 in newly diagnosed glioblastoma tissue. The negative correlation between IFIT1 and MGMT expression may be triggered by interferon. High IFIT1 can be a predictive biomarker of favorable clinical outcome, and IFIT1 along with MGMT more accurately predicts prognosis in newly diagnosed glioblastoma. PMID:26980050

  18. Stochastic simulations of the tetracycline operon

    Directory of Open Access Journals (Sweden)

    Kaznessis Yiannis N

    2011-01-01

    Full Text Available Abstract Background The tetracycline operon is a self-regulated system. It is found naturally in bacteria where it confers resistance to antibiotic tetracycline. Because of the performance of the molecular elements of the tetracycline operon, these elements are widely used as parts of synthetic gene networks where the protein production can be efficiently turned on and off in response to the presence or the absence of tetracycline. In this paper, we investigate the dynamics of the tetracycline operon. To this end, we develop a mathematical model guided by experimental findings. Our model consists of biochemical reactions that capture the biomolecular interactions of this intriguing system. Having in mind that small biological systems are subjects to stochasticity, we use a stochastic algorithm to simulate the tetracycline operon behavior. A sensitivity analysis of two critical parameters embodied this system is also performed providing a useful understanding of the function of this system. Results Simulations generate a timeline of biomolecular events that confer resistance to bacteria against tetracycline. We monitor the amounts of intracellular TetR2 and TetA proteins, the two important regulatory and resistance molecules, as a function of intrecellular tetracycline. We find that lack of one of the promoters of the tetracycline operon has no influence on the total behavior of this system inferring that this promoter is not essential for Escherichia coli. Sensitivity analysis with respect to the binding strength of tetracycline to repressor and of repressor to operators suggests that these two parameters play a predominant role in the behavior of the system. The results of the simulations agree well with experimental observations such as tight repression, fast gene expression, induction with tetracycline, and small intracellular TetR2 amounts. Conclusions Computer simulations of the tetracycline operon afford augmented insight into the

  19. Footprints of Optimal Protein Assembly Strategies in the Operonic Structure of Prokaryotes

    Directory of Open Access Journals (Sweden)

    Jan Ewald

    2015-04-01

    Full Text Available In this work, we investigate optimality principles behind synthesis strategies for protein complexes using a dynamic optimization approach. We show that the cellular capacity of protein synthesis has a strong influence on optimal synthesis strategies reaching from a simultaneous to a sequential synthesis of the subunits of a protein complex. Sequential synthesis is preferred if protein synthesis is strongly limited, whereas a simultaneous synthesis is optimal in situations with a high protein synthesis capacity. We confirm the predictions of our optimization approach through the analysis of the operonic organization of protein complexes in several hundred prokaryotes. Thereby, we are able to show that cellular protein synthesis capacity is a driving force in the dissolution of operons comprising the subunits of a protein complex. Thus, we also provide a tested hypothesis explaining why the subunits of many prokaryotic protein complexes are distributed across several operons despite the presumably less precise co-regulation.

  20. Formation of NO from N2/O2 mixtures in a flow reactor: Toward an accurate prediction of thermal NO

    DEFF Research Database (Denmark)

    Abian, Maria; Alzueta, Maria U.; Glarborg, Peter

    2015-01-01

    We have conducted flow reactor experiments for NO formation from N2/O2 mixtures at high temperatures and atmospheric pressure, controlling accurately temperature and reaction time. Under these conditions, atomic oxygen equilibrates rapidly with O2. The experimental results were interpreted......, is recommended for use in kinetic modeling....

  1. How accurately can subject-specific finite element models predict strains and strength of human femora? Investigation using full-field measurements.

    Science.gov (United States)

    Grassi, Lorenzo; Väänänen, Sami P; Ristinmaa, Matti; Jurvelin, Jukka S; Isaksson, Hanna

    2016-03-21

    Subject-specific finite element models have been proposed as a tool to improve fracture risk assessment in individuals. A thorough laboratory validation against experimental data is required before introducing such models in clinical practice. Results from digital image correlation can provide full-field strain distribution over the specimen surface during in vitro test, instead of at a few pre-defined locations as with strain gauges. The aim of this study was to validate finite element models of human femora against experimental data from three cadaver femora, both in terms of femoral strength and of the full-field strain distribution collected with digital image correlation. The results showed a high accuracy between predicted and measured principal strains (R(2)=0.93, RMSE=10%, 1600 validated data points per specimen). Femoral strength was predicted using a rate dependent material model with specific strain limit values for yield and failure. This provided an accurate prediction (strain accuracy was comparable to that obtained in state-of-the-art studies which validated their prediction accuracy against 10-16 strain gauge measurements. Fracture force was accurately predicted, with the predicted failure location being very close to the experimental fracture rim. Despite the low sample size and the single loading condition tested, the present combined numerical-experimental method showed that finite element models can predict femoral strength by providing a thorough description of the local bone mechanical response. PMID:26944687

  2. Random forest algorithm yields accurate quantitative prediction models of benthic light at intertidal sites affected by toxic Lyngbya majuscula blooms

    NARCIS (Netherlands)

    M.J. Kehoe; K. O’ Brien; A. Grinham; D. Rissik; K.S. Ahern; P. Maxwell

    2012-01-01

    It is shown that targeted high frequency monitoring and modern machine learning methods lead to highly predictive models of benthic light flux. A state-of-the-art machine learning technique was used in conjunction with a high frequency data set to calibrate and test predictive benthic lights models

  3. Accurately Predicting the Density and Hydrostatic Compression of Hexahydro-1,3,5-Trinitro-1,3,5-Triazine from First Principles

    Institute of Scientific and Technical Information of China (English)

    SONG HuarJie; HUANG Feng-Lei

    2011-01-01

    @@ We predict the densities of crystalline hexahydro-1,3,5-trinitro-1,3,5-triazine(RDX)by introducing a factor of(1+1.5×10(-4)T)into the wavefunction-based potential of RDX constructed from first principles using the symmetry-adapted perturbation theory and the Williams-Stone-Misquitta method.The predicted values are within an accuracy of 1%of the density from O to 430K and closely reproduced the RDX densities under hydrostatic compression.This work heralds a promising approach to predicting accurately the densities of high explosives at temperatures and pressures to which they are often subjected,which is a long-standing issue in the field of energetic materials.%We predict the densities of crystalline hexahydro-l,3,5-trinitro-l,3,5-triazine (RDX) by introducing a factor of (1+1.5 x 10~* T) into the wavefunction-based potential of RDX constructed from first principles using the symmetry-adapted perturbation theory and the Williams-Stone-Misquitta method. The predicted values are within an accuracy of 1% of the density from 0 to 430 K and closely reproduced the RDX densities under hydrostatic compression. This work heralds a promising approach to predicting accurately the densities of high explosives at temperatures and pressures to which they are often subjected, which is a long-standing issue in the Beld of energetic materials.

  4. PSSP-RFE: accurate prediction of protein structural class by recursive feature extraction from PSI-BLAST profile, physical-chemical property and functional annotations.

    Directory of Open Access Journals (Sweden)

    Liqi Li

    Full Text Available Protein structure prediction is critical to functional annotation of the massively accumulated biological sequences, which prompts an imperative need for the development of high-throughput technologies. As a first and key step in protein structure prediction, protein structural class prediction becomes an increasingly challenging task. Amongst most homological-based approaches, the accuracies of protein structural class prediction are sufficiently high for high similarity datasets, but still far from being satisfactory for low similarity datasets, i.e., below 40% in pairwise sequence similarity. Therefore, we present a novel method for accurate and reliable protein structural class prediction for both high and low similarity datasets. This method is based on Support Vector Machine (SVM in conjunction with integrated features from position-specific score matrix (PSSM, PROFEAT and Gene Ontology (GO. A feature selection approach, SVM-RFE, is also used to rank the integrated feature vectors through recursively removing the feature with the lowest ranking score. The definitive top features selected by SVM-RFE are input into the SVM engines to predict the structural class of a query protein. To validate our method, jackknife tests were applied to seven widely used benchmark datasets, reaching overall accuracies between 84.61% and 99.79%, which are significantly higher than those achieved by state-of-the-art tools. These results suggest that our method could serve as an accurate and cost-effective alternative to existing methods in protein structural classification, especially for low similarity datasets.

  5. An Accurate GPS-IMU/DR Data Fusion Method for Driverless Car Based on a Set of Predictive Models and Grid Constraints

    OpenAIRE

    Shiyao Wang; Zhidong Deng; Gang Yin

    2016-01-01

    A high-performance differential global positioning system (GPS)  receiver with real time kinematics provides absolute localization for driverless cars. However, it is not only susceptible to multipath effect but also unable to effectively fulfill precise error correction in a wide range of driving areas. This paper proposes an accurate GPS–inertial measurement unit (IMU)/dead reckoning (DR) data fusion method based on a set of predictive models and occupancy grid constraints. First, we employ...

  6. A time accurate prediction of the viscous flow in a turbine stage including a rotor in motion

    Science.gov (United States)

    Shavalikul, Akamol

    In this current study, the flow field in the Pennsylvania State University Axial Flow Turbine Research Facility (AFTRF) was simulated. This study examined four sets of simulations. The first two sets are for an individual NGV and for an individual rotor. The last two sets use a multiple reference frames approach for a complete turbine stage with two different interface models: a steady circumferential average approach called a mixing plane model, and a time accurate flow simulation approach called a sliding mesh model. The NGV passage flow field was simulated using a three-dimensional Reynolds Averaged Navier-Stokes finite volume solver (RANS) with a standard kappa -- epsilon turbulence model. The mean flow distributions on the NGV surfaces and endwall surfaces were computed. The numerical solutions indicate that two passage vortices begin to be observed approximately at the mid axial chord of the NGV suction surface. The first vortex is a casing passage vortex which occurs at the corner formed by the NGV suction surface and the casing. This vortex is created by the interaction of the passage flow and the radially inward flow, while the second vortex, the hub passage vortex, is observed near the hub. These two vortices become stronger towards the NGV trailing edge. By comparing the results from the X/Cx = 1.025 plane and the X/Cx = 1.09 plane, it can be concluded that the NGV wake decays rapidly within a short axial distance downstream of the NGV. For the rotor, a set of simulations was carried out to examine the flow fields associated with different pressure side tip extension configurations, which are designed to reduce the tip leakage flow. The simulation results show that significant reductions in tip leakage mass flow rate and aerodynamic loss reduction are possible by using suitable tip platform extensions located near the pressure side corner of the blade tip. The computations used realistic turbine rotor inlet flow conditions in a linear cascade arrangement

  7. Survival outcomes scores (SOFT, BAR, and Pedi-SOFT) are accurate in predicting post-liver transplant survival in adolescents.

    Science.gov (United States)

    Conjeevaram Selvakumar, Praveen Kumar; Maksimak, Brian; Hanouneh, Ibrahim; Youssef, Dalia H; Lopez, Rocio; Alkhouri, Naim

    2016-09-01

    SOFT and BAR scores utilize recipient, donor, and graft factors to predict the 3-month survival after LT in adults (≥18 years). Recently, Pedi-SOFT score was developed to predict 3-month survival after LT in young children (≤12 years). These scoring systems have not been studied in adolescent patients (13-17 years). We evaluated the accuracy of these scoring systems in predicting the 3-month post-LT survival in adolescents through a retrospective analysis of data from UNOS of patients aged 13-17 years who received LT between 03/01/2002 and 12/31/2012. Recipients of combined organ transplants, donation after cardiac death, or living donor graft were excluded. A total of 711 adolescent LT recipients were included with a mean age of 15.2±1.4 years. A total of 100 patients died post-LT including 33 within 3 months. SOFT, BAR, and Pedi-SOFT scores were all found to be good predictors of 3-month post-transplant survival outcome with areas under the ROC curve of 0.81, 0.80, and 0.81, respectively. All three scores provided good accuracy for predicting 3-month survival post-LT in adolescents and may help clinical decision making to optimize survival rate and organ utilization. PMID:27478012

  8. Accurate prediction of the toxicity of benzoic acid compounds in mice via oral without using any computer codes

    International Nuclear Information System (INIS)

    Highlights: ► A novel method is introduced for desk calculation of toxicity of benzoic acid derivatives. ► There is no need to use QSAR and QSTR methods, which are based on computer codes. ► The predicted results of 58 compounds are more reliable than those predicted by QSTR method. ► The present method gives good predictions for further 324 benzoic acid compounds. - Abstract: Most of benzoic acid derivatives are toxic, which may cause serious public health and environmental problems. Two novel simple and reliable models are introduced for desk calculations of the toxicity of benzoic acid compounds in mice via oral LD50 with more reliance on their answers as one could attach to the more complex outputs. They require only elemental composition and molecular fragments without using any computer codes. The first model is based on only the number of carbon and hydrogen atoms, which can be improved by several molecular fragments in the second model. For 57 benzoic compounds, where the computed results of quantitative structure–toxicity relationship (QSTR) were recently reported, the predicted results of two simple models of present method are more reliable than QSTR computations. The present simple method is also tested with further 324 benzoic acid compounds including complex molecular structures, which confirm good forecasting ability of the second model.

  9. Accurate prediction of the toxicity of benzoic acid compounds in mice via oral without using any computer codes

    Energy Technology Data Exchange (ETDEWEB)

    Keshavarz, Mohammad Hossein, E-mail: mhkeshavarz@mut-es.ac.ir [Department of Chemistry, Malek-ashtar University of Technology, Shahin-shahr P.O. Box 83145/115, Isfahan, Islamic Republic of Iran (Iran, Islamic Republic of); Gharagheizi, Farhad [Department of Chemical Engineering, Buinzahra Branch, Islamic Azad University, Buinzahra, Islamic Republic of Iran (Iran, Islamic Republic of); Shokrolahi, Arash; Zakinejad, Sajjad [Department of Chemistry, Malek-ashtar University of Technology, Shahin-shahr P.O. Box 83145/115, Isfahan, Islamic Republic of Iran (Iran, Islamic Republic of)

    2012-10-30

    Highlights: Black-Right-Pointing-Pointer A novel method is introduced for desk calculation of toxicity of benzoic acid derivatives. Black-Right-Pointing-Pointer There is no need to use QSAR and QSTR methods, which are based on computer codes. Black-Right-Pointing-Pointer The predicted results of 58 compounds are more reliable than those predicted by QSTR method. Black-Right-Pointing-Pointer The present method gives good predictions for further 324 benzoic acid compounds. - Abstract: Most of benzoic acid derivatives are toxic, which may cause serious public health and environmental problems. Two novel simple and reliable models are introduced for desk calculations of the toxicity of benzoic acid compounds in mice via oral LD{sub 50} with more reliance on their answers as one could attach to the more complex outputs. They require only elemental composition and molecular fragments without using any computer codes. The first model is based on only the number of carbon and hydrogen atoms, which can be improved by several molecular fragments in the second model. For 57 benzoic compounds, where the computed results of quantitative structure-toxicity relationship (QSTR) were recently reported, the predicted results of two simple models of present method are more reliable than QSTR computations. The present simple method is also tested with further 324 benzoic acid compounds including complex molecular structures, which confirm good forecasting ability of the second model.

  10. Externally validated HPV-based prognostic nomogram for oropharyngeal carcinoma patients yields more accurate predictions than TNM staging

    International Nuclear Information System (INIS)

    Purpose: Due to the established role of the human papillomavirus (HPV), the optimal treatment for oropharyngeal carcinoma is currently under debate. We evaluated the most important determinants of treatment outcome to develop a multifactorial predictive model that could provide individualized predictions of treatment outcome in oropharyngeal carcinoma patients. Methods: We analyzed the association between clinico-pathological factors and overall and progression-free survival in 168 OPSCC patients treated with curative radiotherapy or concurrent chemo-radiation. A multivariate model was validated in an external dataset of 189 patients and compared to the TNM staging system. This nomogram will be made publicly available at (www.predictcancer.org). Results: Predictors of unfavorable outcomes were negative HPV-status, moderate to severe comorbidity, T3–T4 classification, N2b–N3 stage, male gender, lower hemoglobin levels and smoking history of more than 30 pack years. Prediction of overall survival using the multi-parameter model yielded a C-index of 0.82 (95% CI, 0.76–0.88). Validation in an independent dataset yielded a C-index of 0.73 (95% CI, 0.66–0.79. For progression-free survival, the model’s C-index was 0.80 (95% CI, 0.76–0.88), with a validation C-index of 0.67, (95% CI, 0.59–0.74). Stratification of model estimated probabilities showed statistically different prognosis groups in both datasets (p < 0.001). Conclusion: This nomogram was superior to TNM classification or HPV status alone in an independent validation dataset for prediction of overall and progression-free survival in OPSCC patients, assigning patients to distinct prognosis groups. These individualized predictions could be used to stratify patients for treatment de-escalation trials

  11. Prognostic models and risk scores: can we accurately predict postoperative nausea and vomiting in children after craniotomy?

    Science.gov (United States)

    Neufeld, Susan M; Newburn-Cook, Christine V; Drummond, Jane E

    2008-10-01

    Postoperative nausea and vomiting (PONV) is a problem for many children after craniotomy. Prognostic models and risk scores help identify who is at risk for an adverse event such as PONV to help guide clinical care. The purpose of this article is to assess whether an existing prognostic model or risk score can predict PONV in children after craniotomy. The concepts of transportability, calibration, and discrimination are presented to identify what is required to have a valid tool for clinical use. Although previous work may inform clinical practice and guide future research, existing prognostic models and risk scores do not appear to be options for predicting PONV in children undergoing craniotomy. However, until risk factors are further delineated, followed by the development and validation of prognostic models and risk scores that include children after craniotomy, clinical judgment in the context of current research may serve as a guide for clinical care in this population. PMID:18939320

  12. Accurate prediction of secreted substrates and identification of a conserved putative secretion signal for type III secretion systems.

    Directory of Open Access Journals (Sweden)

    Ram Samudrala

    2009-04-01

    Full Text Available The type III secretion system is an essential component for virulence in many Gram-negative bacteria. Though components of the secretion system apparatus are conserved, its substrates--effector proteins--are not. We have used a novel computational approach to confidently identify new secreted effectors by integrating protein sequence-based features, including evolutionary measures such as the pattern of homologs in a range of other organisms, G+C content, amino acid composition, and the N-terminal 30 residues of the protein sequence. The method was trained on known effectors from the plant pathogen Pseudomonas syringae and validated on a set of effectors from the animal pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium after eliminating effectors with detectable sequence similarity. We show that this approach can predict known secreted effectors with high specificity and sensitivity. Furthermore, by considering a large set of effectors from multiple organisms, we computationally identify a common putative secretion signal in the N-terminal 20 residues of secreted effectors. This signal can be used to discriminate 46 out of 68 total known effectors from both organisms, suggesting that it is a real, shared signal applicable to many type III secreted effectors. We use the method to make novel predictions of secreted effectors in S. Typhimurium, some of which have been experimentally validated. We also apply the method to predict secreted effectors in the genetically intractable human pathogen Chlamydia trachomatis, identifying the majority of known secreted proteins in addition to providing a number of novel predictions. This approach provides a new way to identify secreted effectors in a broad range of pathogenic bacteria for further experimental characterization and provides insight into the nature of the type III secretion signal.

  13. How accurate is our prediction of biopsy outcome? PCA3-based nomograms in personalized diagnosis of prostate cancer

    OpenAIRE

    Salagierski, Maciej; Sosnowski, Marek; Schalken, Jack A.

    2012-01-01

    Purpose The sensitivity and specificity of prostate-specific antigen (PSA) alone to select men for prostate biopsy remain suboptimal. This review aims at presenting a review of current prostate cancer (PCa) nomograms that incorporate Prostate Cancer Gene 3 (PCA3), which was designed to outperform PSA at predicting biopsy outcome. Materials and methods The PubMed database and current literature search was conducted for reports on PCA3-based nomograms and tools for examining the risk of a posit...

  14. Accurate Prediction of Advanced Liver Fibrosis Using the Decision Tree Learning Algorithm in Chronic Hepatitis C Egyptian Patients

    Directory of Open Access Journals (Sweden)

    Somaya Hashem

    2016-01-01

    Full Text Available Background/Aim. Respectively with the prevalence of chronic hepatitis C in the world, using noninvasive methods as an alternative method in staging chronic liver diseases for avoiding the drawbacks of biopsy is significantly increasing. The aim of this study is to combine the serum biomarkers and clinical information to develop a classification model that can predict advanced liver fibrosis. Methods. 39,567 patients with chronic hepatitis C were included and randomly divided into two separate sets. Liver fibrosis was assessed via METAVIR score; patients were categorized as mild to moderate (F0–F2 or advanced (F3-F4 fibrosis stages. Two models were developed using alternating decision tree algorithm. Model 1 uses six parameters, while model 2 uses four, which are similar to FIB-4 features except alpha-fetoprotein instead of alanine aminotransferase. Sensitivity and receiver operating characteristic curve were performed to evaluate the performance of the proposed models. Results. The best model achieved 86.2% negative predictive value and 0.78 ROC with 84.8% accuracy which is better than FIB-4. Conclusions. The risk of advanced liver fibrosis, due to chronic hepatitis C, could be predicted with high accuracy using decision tree learning algorithm that could be used to reduce the need to assess the liver biopsy.

  15. An Optimized Method for Accurate Fetal Sex Prediction and Sex Chromosome Aneuploidy Detection in Non-Invasive Prenatal Testing.

    Science.gov (United States)

    Wang, Ting; He, Quanze; Li, Haibo; Ding, Jie; Wen, Ping; Zhang, Qin; Xiang, Jingjing; Li, Qiong; Xuan, Liming; Kong, Lingyin; Mao, Yan; Zhu, Yijun; Shen, Jingjing; Liang, Bo; Li, Hong

    2016-01-01

    Massively parallel sequencing (MPS) combined with bioinformatic analysis has been widely applied to detect fetal chromosomal aneuploidies such as trisomy 21, 18, 13 and sex chromosome aneuploidies (SCAs) by sequencing cell-free fetal DNA (cffDNA) from maternal plasma, so-called non-invasive prenatal testing (NIPT). However, many technical challenges, such as dependency on correct fetal sex prediction, large variations of chromosome Y measurement and high sensitivity to random reads mapping, may result in higher false negative rate (FNR) and false positive rate (FPR) in fetal sex prediction as well as in SCAs detection. Here, we developed an optimized method to improve the accuracy of the current method by filtering out randomly mapped reads in six specific regions of the Y chromosome. The method reduces the FNR and FPR of fetal sex prediction from nearly 1% to 0.01% and 0.06%, respectively and works robustly under conditions of low fetal DNA concentration (1%) in testing and simulation of 92 samples. The optimized method was further confirmed by large scale testing (1590 samples), suggesting that it is reliable and robust enough for clinical testing.

  16. An Optimized Method for Accurate Fetal Sex Prediction and Sex Chromosome Aneuploidy Detection in Non-Invasive Prenatal Testing.

    Directory of Open Access Journals (Sweden)

    Ting Wang

    Full Text Available Massively parallel sequencing (MPS combined with bioinformatic analysis has been widely applied to detect fetal chromosomal aneuploidies such as trisomy 21, 18, 13 and sex chromosome aneuploidies (SCAs by sequencing cell-free fetal DNA (cffDNA from maternal plasma, so-called non-invasive prenatal testing (NIPT. However, many technical challenges, such as dependency on correct fetal sex prediction, large variations of chromosome Y measurement and high sensitivity to random reads mapping, may result in higher false negative rate (FNR and false positive rate (FPR in fetal sex prediction as well as in SCAs detection. Here, we developed an optimized method to improve the accuracy of the current method by filtering out randomly mapped reads in six specific regions of the Y chromosome. The method reduces the FNR and FPR of fetal sex prediction from nearly 1% to 0.01% and 0.06%, respectively and works robustly under conditions of low fetal DNA concentration (1% in testing and simulation of 92 samples. The optimized method was further confirmed by large scale testing (1590 samples, suggesting that it is reliable and robust enough for clinical testing.

  17. Accurate microRNA target prediction using detailed binding site accessibility and machine learning on proteomics data

    Directory of Open Access Journals (Sweden)

    Martin eReczko

    2012-01-01

    Full Text Available MicroRNAs (miRNAs are a class of small regulatory genes regulating gene expression by targetingmessenger RNA. Though computational methods for miRNA target prediction are the prevailingmeans to analyze their function, they still miss a large fraction of the targeted genes and additionallypredict a large number of false positives. Here we introduce a novel algorithm called DIANAmicroT-ANN which combines multiple novel target site features through an artificial neural network(ANN and is trained using recently published high-throughput data measuring the change of proteinlevels after miRNA overexpression, providing positive and negative targeting examples. The featurescharacterizing each miRNA recognition element include binding structure, conservation level and aspecific profile of structural accessibility. The ANN is trained to integrate the features of eachrecognition element along the 3’ untranslated region into a targeting score, reproducing the relativerepression fold change of the protein. Tested on two different sets the algorithm outperforms otherwidely used algorithms and also predicts a significant number of unique and reliable targets notpredicted by the other methods. For 542 human miRNAs DIANA-microT-ANN predicts 120,000targets not provided by TargetScan 5.0. The algorithm is freely available athttp://microrna.gr/microT-ANN.

  18. An Optimized Method for Accurate Fetal Sex Prediction and Sex Chromosome Aneuploidy Detection in Non-Invasive Prenatal Testing

    Science.gov (United States)

    Li, Haibo; Ding, Jie; Wen, Ping; Zhang, Qin; Xiang, Jingjing; Li, Qiong; Xuan, Liming; Kong, Lingyin; Mao, Yan; Zhu, Yijun; Shen, Jingjing; Liang, Bo; Li, Hong

    2016-01-01

    Massively parallel sequencing (MPS) combined with bioinformatic analysis has been widely applied to detect fetal chromosomal aneuploidies such as trisomy 21, 18, 13 and sex chromosome aneuploidies (SCAs) by sequencing cell-free fetal DNA (cffDNA) from maternal plasma, so-called non-invasive prenatal testing (NIPT). However, many technical challenges, such as dependency on correct fetal sex prediction, large variations of chromosome Y measurement and high sensitivity to random reads mapping, may result in higher false negative rate (FNR) and false positive rate (FPR) in fetal sex prediction as well as in SCAs detection. Here, we developed an optimized method to improve the accuracy of the current method by filtering out randomly mapped reads in six specific regions of the Y chromosome. The method reduces the FNR and FPR of fetal sex prediction from nearly 1% to 0.01% and 0.06%, respectively and works robustly under conditions of low fetal DNA concentration (1%) in testing and simulation of 92 samples. The optimized method was further confirmed by large scale testing (1590 samples), suggesting that it is reliable and robust enough for clinical testing. PMID:27441628

  19. A highly accurate protein structural class prediction approach using auto cross covariance transformation and recursive feature elimination.

    Science.gov (United States)

    Li, Xiaowei; Liu, Taigang; Tao, Peiying; Wang, Chunhua; Chen, Lanming

    2015-12-01

    Structural class characterizes the overall folding type of a protein or its domain. Many methods have been proposed to improve the prediction accuracy of protein structural class in recent years, but it is still a challenge for the low-similarity sequences. In this study, we introduce a feature extraction technique based on auto cross covariance (ACC) transformation of position-specific score matrix (PSSM) to represent a protein sequence. Then support vector machine-recursive feature elimination (SVM-RFE) is adopted to select top K features according to their importance and these features are input to a support vector machine (SVM) to conduct the prediction. Performance evaluation of the proposed method is performed using the jackknife test on three low-similarity datasets, i.e., D640, 1189 and 25PDB. By means of this method, the overall accuracies of 97.2%, 96.2%, and 93.3% are achieved on these three datasets, which are higher than those of most existing methods. This suggests that the proposed method could serve as a very cost-effective tool for predicting protein structural class especially for low-similarity datasets.

  20. Sequencing and characterization of the xyl operon of a gram-positive bacterium, Tetragenococcus halophila.

    Science.gov (United States)

    Takeda, Y; Takase, K; Yamato, I; Abe, K

    1998-07-01

    The xyl operon of a gram-positive bacterium, Tetragenococcus halophila (previously called Pediococcus halophilus), was cloned and sequenced. The DNA was about 7.7 kb long and contained genes for a ribose binding protein and part of a ribose transporter, xylR (a putative regulatory gene), and the xyl operon, along with its regulatory region and transcription termination signal, in this order. The DNA was AT rich, the GC content being 35.8%, consistent with the GC content of this gram-positive bacterium. The xyl operon consisted of three genes, xylA, encoding a xylose isomerase, xylB, encoding a xylulose kinase, and xylE, encoding a xylose transporter, with predicted molecular weights of 49,400, 56,400, and 51,600, respectively. The deduced amino acid sequences of the XylR, XylA, XylB, and XylE proteins were similar to those of the corresponding proteins in other gram-positive and -negative bacteria, the similarities being 37 to 64%. Each polypeptide of XylB and XylE was expressed functionally in Escherichia coli. XylE transported D-xylose in a sodium ion-dependent manner, suggesting that it is the first described xylose/Na+ symporter. The XylR protein contained a consensus sequence for binding catabolites of glucose, such as glucose-6-phosphate, which has been discovered in glucose and fructose kinases in bacteria. Correspondingly, the regulatory region of this operon contained a putative binding site of XylR with a palindromic structure. Furthermore, it contained a consensus sequence, CRE (catabolite-responsive element), for binding CcpA (catabolite control protein A). We speculate that the transcriptional regulation of this operon resembles the regulation of catabolite-repressible operons such as the amy, lev, xyl, and gnt operons in various gram-positive bacteria. We discuss the significance of the regulation of gene expression of this operon in T. halophila. PMID:9647823

  1. Accurately Predicting the Density and Hydrostatic Compression of Hexahydro-1,3,5-Trinitro-1,3,5-Triazine from First Principles

    International Nuclear Information System (INIS)

    We predict the densities of crystalline hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) by introducing a factor of (1+1.5 × 10−4T) into the wavefunction-based potential of RDX constructed from first principles using the symmetry-adapted perturbation theory and the Williams—Stone—Misquitta method. The predicted values are within an accuracy of 1% of the density from 0 to 430 K and closely reproduced the RDX densities under hydrostatic compression. This work heralds a promising approach to predicting accurately the densities of high explosives at temperatures and pressures to which they are often subjected, which is a long-standing issue in the field of energetic materials. (condensed matter: structure, mechanical and thermal properties)

  2. aPPRove: An HMM-Based Method for Accurate Prediction of RNA-Pentatricopeptide Repeat Protein Binding Events

    Science.gov (United States)

    Harrison, Thomas; Ruiz, Jaime; Sloan, Daniel B.; Ben-Hur, Asa; Boucher, Christina

    2016-01-01

    Pentatricopeptide repeat containing proteins (PPRs) bind to RNA transcripts originating from mitochondria and plastids. There are two classes of PPR proteins. The P class contains tandem P-type motif sequences, and the PLS class contains alternating P, L and S type sequences. In this paper, we describe a novel tool that predicts PPR-RNA interaction; specifically, our method, which we call aPPRove, determines where and how a PLS-class PPR protein will bind to RNA when given a PPR and one or more RNA transcripts by using a combinatorial binding code for site specificity proposed by Barkan et al. Our results demonstrate that aPPRove successfully locates how and where a PPR protein belonging to the PLS class can bind to RNA. For each binding event it outputs the binding site, the amino-acid-nucleotide interaction, and its statistical significance. Furthermore, we show that our method can be used to predict binding events for PLS-class proteins using a known edit site and the statistical significance of aligning the PPR protein to that site. In particular, we use our method to make a conjecture regarding an interaction between CLB19 and the second intronic region of ycf3. The aPPRove web server can be found at www.cs.colostate.edu/~approve. PMID:27560805

  3. A 3D-CFD code for accurate prediction of fluid flows and fluid forces in seals

    Science.gov (United States)

    Athavale, M. M.; Przekwas, A. J.; Hendricks, R. C.

    1994-01-01

    Current and future turbomachinery requires advanced seal configurations to control leakage, inhibit mixing of incompatible fluids and to control the rotodynamic response. In recognition of a deficiency in the existing predictive methodology for seals, a seven year effort was established in 1990 by NASA's Office of Aeronautics Exploration and Technology, under the Earth-to-Orbit Propulsion program, to develop validated Computational Fluid Dynamics (CFD) concepts, codes and analyses for seals. The effort will provide NASA and the U.S. Aerospace Industry with advanced CFD scientific codes and industrial codes for analyzing and designing turbomachinery seals. An advanced 3D CFD cylindrical seal code has been developed, incorporating state-of-the-art computational methodology for flow analysis in straight, tapered and stepped seals. Relevant computational features of the code include: stationary/rotating coordinates, cylindrical and general Body Fitted Coordinates (BFC) systems, high order differencing schemes, colocated variable arrangement, advanced turbulence models, incompressible/compressible flows, and moving grids. This paper presents the current status of code development, code demonstration for predicting rotordynamic coefficients, numerical parametric study of entrance loss coefficients for generic annular seals, and plans for code extensions to labyrinth, damping, and other seal configurations.

  4. aPPRove: An HMM-Based Method for Accurate Prediction of RNA-Pentatricopeptide Repeat Protein Binding Events.

    Science.gov (United States)

    Harrison, Thomas; Ruiz, Jaime; Sloan, Daniel B; Ben-Hur, Asa; Boucher, Christina

    2016-01-01

    Pentatricopeptide repeat containing proteins (PPRs) bind to RNA transcripts originating from mitochondria and plastids. There are two classes of PPR proteins. The [Formula: see text] class contains tandem [Formula: see text]-type motif sequences, and the [Formula: see text] class contains alternating [Formula: see text], [Formula: see text] and [Formula: see text] type sequences. In this paper, we describe a novel tool that predicts PPR-RNA interaction; specifically, our method, which we call aPPRove, determines where and how a [Formula: see text]-class PPR protein will bind to RNA when given a PPR and one or more RNA transcripts by using a combinatorial binding code for site specificity proposed by Barkan et al. Our results demonstrate that aPPRove successfully locates how and where a PPR protein belonging to the [Formula: see text] class can bind to RNA. For each binding event it outputs the binding site, the amino-acid-nucleotide interaction, and its statistical significance. Furthermore, we show that our method can be used to predict binding events for [Formula: see text]-class proteins using a known edit site and the statistical significance of aligning the PPR protein to that site. In particular, we use our method to make a conjecture regarding an interaction between CLB19 and the second intronic region of ycf3. The aPPRove web server can be found at www.cs.colostate.edu/~approve. PMID:27560805

  5. Accurate prediction of secreted substrates and identification of a conserved putative secretion signal for type III secretion systems

    Energy Technology Data Exchange (ETDEWEB)

    Samudrala, Ram; Heffron, Fred; McDermott, Jason E.

    2009-04-24

    The type III secretion system is an essential component for virulence in many Gram-negative bacteria. Though components of the secretion system apparatus are conserved, its substrates, effector proteins, are not. We have used a machine learning approach to identify new secreted effectors. The method integrates evolutionary measures, such as the pattern of homologs in a range of other organisms, and sequence-based features, such as G+C content, amino acid composition and the N-terminal 30 residues of the protein sequence. The method was trained on known effectors from Salmonella typhimurium and validated on a corresponding set of effectors from Pseudomonas syringae, after eliminating effectors with detectable sequence similarity. The method was able to identify all of the known effectors in P. syringae with a specificity of 84% and sensitivity of 82%. The reciprocal validation, training on P. syringae and validating on S. typhimurium, gave similar results with a specificity of 86% when the sensitivity level was 87%. These results show that type III effectors in disparate organisms share common features. We found that maximal performance is attained by including an N-terminal sequence of only 30 residues, which agrees with previous studies indicating that this region contains the secretion signal. We then used the method to define the most important residues in this putative secretion signal. Finally, we present novel predictions of secreted effectors in S. typhimurium, some of which have been experimentally validated, and apply the method to predict secreted effectors in the genetically intractable human pathogen Chlamydia trachomatis. This approach is a novel and effective way to identify secreted effectors in a broad range of pathogenic bacteria for further experimental characterization and provides insight into the nature of the type III secretion signal.

  6. Predictive value of multi-detector computed tomography for accurate diagnosis of serous cystadenoma: Radiologic-pathologic correlation

    Institute of Scientific and Technical Information of China (English)

    Anjuli A Shah; Nisha I Sainani; Avinash Kambadakone Ramesh; Zarine K Shah; Vikram Deshpande; Peter F Hahn; Dushyant V Sahani

    2009-01-01

    AIM:To identify multi-detector computed tomography (MDCT) features mos t predi c t i ve of serous cystadenomas (SCAs),correlating with histopathology,and to study the impact of cyst size and MDCT technique on reader performance.METHODS:The MDCT scans of 164 patients with surgically verified pancreatic cystic lesions were reviewed by two readers to study the predictive value of various morphological features for establishing a diagnosis of SCAs.Accuracy in lesion characterization and reader confidence were correlated with lesion size (≤3 cm or ≥3 cm) and scanning protocols (dedicated vs routine).RESULTS:28/164 cysts (mean size,39 mm;range,8-92 mm) were diagnosed as SCA on pathology.The MDCT features predictive of diagnosis of SCA were microcystic appearance (22/28,78.6%),surface lobulations (25/28,89.3%) and central scar (9/28,32.4%).Stepwise logistic regression analysis showed that only microcystic appearance was significant for CT diagnosis of SCA (P=0.0001).The sensitivity,specificity and PPV of central scar and of combined microcystic appearance and lobulations were 32.4%/100%/100% and 68%/100%/100%,respectively.The reader confidence was higher for lesions>3 cm (P=0.02) and for MDCT scans performed using thin collimation (1.25-2.5 mm) compared to routine 5 mm collimation exams (P>0.05).CONCLUSION:Central scar on MDCT is diagnostic of SCA but is seen in only one third of SCAs.Microcystic morphology is the most significant CT feature in diagnosis of SCA.A combination of microcystic appearance and surface lobulations offers accuracy comparable to central scar with higher sensitivity.

  7. Predicting College Students' First Year Success: Should Soft Skills Be Taken into Consideration to More Accurately Predict the Academic Achievement of College Freshmen?

    Science.gov (United States)

    Powell, Erica Dion

    2013-01-01

    This study presents a survey developed to measure the skills of entering college freshmen in the areas of responsibility, motivation, study habits, literacy, and stress management, and explores the predictive power of this survey as a measure of academic performance during the first semester of college. The survey was completed by 334 incoming…

  8. Predicting Antimicrobial Resistance Prevalence and Incidence from Indicators of Antimicrobial Use: What Is the Most Accurate Indicator for Surveillance in Intensive Care Units?

    Directory of Open Access Journals (Sweden)

    Élise Fortin

    Full Text Available The optimal way to measure antimicrobial use in hospital populations, as a complement to surveillance of resistance is still unclear. Using respiratory isolates and antimicrobial prescriptions of nine intensive care units (ICUs, this study aimed to identify the indicator of antimicrobial use that predicted prevalence and incidence rates of resistance with the best accuracy.Retrospective cohort study including all patients admitted to three neonatal (NICU, two pediatric (PICU and four adult ICUs between April 2006 and March 2010. Ten different resistance/antimicrobial use combinations were studied. After adjustment for ICU type, indicators of antimicrobial use were successively tested in regression models, to predict resistance prevalence and incidence rates, per 4-week time period, per ICU. Binomial regression and Poisson regression were used to model prevalence and incidence rates, respectively. Multiplicative and additive models were tested, as well as no time lag and a one 4-week-period time lag. For each model, the mean absolute error (MAE in prediction of resistance was computed. The most accurate indicator was compared to other indicators using t-tests.Results for all indicators were equivalent, except for 1/20 scenarios studied. In this scenario, where prevalence of carbapenem-resistant Pseudomonas sp. was predicted with carbapenem use, recommended daily doses per 100 admissions were less accurate than courses per 100 patient-days (p = 0.0006.A single best indicator to predict antimicrobial resistance might not exist. Feasibility considerations such as ease of computation or potential external comparisons could be decisive in the choice of an indicator for surveillance of healthcare antimicrobial use.

  9. Integrating metabolic performance, thermal tolerance, and plasticity enables for more accurate predictions on species vulnerability to acute and chronic effects of global warming.

    Science.gov (United States)

    Magozzi, Sarah; Calosi, Piero

    2015-01-01

    Predicting species vulnerability to global warming requires a comprehensive, mechanistic understanding of sublethal and lethal thermal tolerances. To date, however, most studies investigating species physiological responses to increasing temperature have focused on the underlying physiological traits of either acute or chronic tolerance in isolation. Here we propose an integrative, synthetic approach including the investigation of multiple physiological traits (metabolic performance and thermal tolerance), and their plasticity, to provide more accurate and balanced predictions on species and assemblage vulnerability to both acute and chronic effects of global warming. We applied this approach to more accurately elucidate relative species vulnerability to warming within an assemblage of six caridean prawns occurring in the same geographic, hence macroclimatic, region, but living in different thermal habitats. Prawns were exposed to four incubation temperatures (10, 15, 20 and 25 °C) for 7 days, their metabolic rates and upper thermal limits were measured, and plasticity was calculated according to the concept of Reaction Norms, as well as Q10 for metabolism. Compared to species occupying narrower/more stable thermal niches, species inhabiting broader/more variable thermal environments (including the invasive Palaemon macrodactylus) are likely to be less vulnerable to extreme acute thermal events as a result of their higher upper thermal limits. Nevertheless, they may be at greater risk from chronic exposure to warming due to the greater metabolic costs they incur. Indeed, a trade-off between acute and chronic tolerance was apparent in the assemblage investigated. However, the invasive species P. macrodactylus represents an exception to this pattern, showing elevated thermal limits and plasticity of these limits, as well as a high metabolic control. In general, integrating multiple proxies for species physiological acute and chronic responses to increasing

  10. Characterization of the cyn operon in Escherichia coli K12.

    Science.gov (United States)

    Sung, Y C; Fuchs, J A

    1988-10-15

    Escherichia coli can overcome the toxicity of environmental cyanate by hydrolysis of cyanate to ammonia and bicarbonate. This reaction is catalyzed by the enzyme cyanase, encoded by the cynS gene. The nucleotide sequence of cynS has been reported (Sung, Y.-c., Anderson, P. M., and Fuchs, J. A. (1987) J. Bacteriol. 169, 5224-5230). The nucleotide sequence of the complete cyn operon has now been determined. The cyn operon is approximately 2600 base pairs and includes cynT, cynS, and cynX, which encode cyanate permease, cyanase, and a protein of unknown function, respectively. Two cyanate-inducible transcripts of 1500 and 2500 nucleotides, respectively, were detected by Northern blot analysis. S1 nuclease mapping experiments indicated that two different cyn mRNAs have a common 5'-end and two different 3'-ends. One 3'-end was located within the coding region of cynX, whereas the other 3'-end includes the entire DNA sequence of cynX. The longer transcript contained 98 nucleotides complementary to lac mRNA produced by the predominant lac transcription termination sequence. Termination vectors were used to show that both 3'-ends were generated by sequences that caused transcriptional termination in vivo. Expression vectors were used to demonstrate that a protein corresponding to the expected size was synthesized from the DNA fragment containing the open reading frame designated cynX. The predicted amino acid sequence of cynX indicates that it is a very hydrophobic protein. The level of cynX expression was significantly less than that of cynT or cynS expression.

  11. An Accurate GPS-IMU/DR Data Fusion Method for Driverless Car Based on a Set of Predictive Models and Grid Constraints.

    Science.gov (United States)

    Wang, Shiyao; Deng, Zhidong; Yin, Gang

    2016-01-01

    A high-performance differential global positioning system (GPS)  receiver with real time kinematics provides absolute localization for driverless cars. However, it is not only susceptible to multipath effect but also unable to effectively fulfill precise error correction in a wide range of driving areas. This paper proposes an accurate GPS-inertial measurement unit (IMU)/dead reckoning (DR) data fusion method based on a set of predictive models and occupancy grid constraints. First, we employ a set of autoregressive and moving average (ARMA) equations that have different structural parameters to build maximum likelihood models of raw navigation. Second, both grid constraints and spatial consensus checks on all predictive results and current measurements are required to have removal of outliers. Navigation data that satisfy stationary stochastic process are further fused to achieve accurate localization results. Third, the standard deviation of multimodal data fusion can be pre-specified by grid size. Finally, we perform a lot of field tests on a diversity of real urban scenarios. The experimental results demonstrate that the method can significantly smooth small jumps in bias and considerably reduce accumulated position errors due to DR. With low computational complexity, the position accuracy of our method surpasses existing state-of-the-arts on the same dataset and the new data fusion method is practically applied in our driverless car. PMID:26927108

  12. An Accurate GPS-IMU/DR Data Fusion Method for Driverless Car Based on a Set of Predictive Models and Grid Constraints

    Science.gov (United States)

    Wang, Shiyao; Deng, Zhidong; Yin, Gang

    2016-01-01

    A high-performance differential global positioning system (GPS)  receiver with real time kinematics provides absolute localization for driverless cars. However, it is not only susceptible to multipath effect but also unable to effectively fulfill precise error correction in a wide range of driving areas. This paper proposes an accurate GPS–inertial measurement unit (IMU)/dead reckoning (DR) data fusion method based on a set of predictive models and occupancy grid constraints. First, we employ a set of autoregressive and moving average (ARMA) equations that have different structural parameters to build maximum likelihood models of raw navigation. Second, both grid constraints and spatial consensus checks on all predictive results and current measurements are required to have removal of outliers. Navigation data that satisfy stationary stochastic process are further fused to achieve accurate localization results. Third, the standard deviation of multimodal data fusion can be pre-specified by grid size. Finally, we perform a lot of field tests on a diversity of real urban scenarios. The experimental results demonstrate that the method can significantly smooth small jumps in bias and considerably reduce accumulated position errors due to DR. With low computational complexity, the position accuracy of our method surpasses existing state-of-the-arts on the same dataset and the new data fusion method is practically applied in our driverless car. PMID:26927108

  13. An Accurate GPS-IMU/DR Data Fusion Method for Driverless Car Based on a Set of Predictive Models and Grid Constraints

    Directory of Open Access Journals (Sweden)

    Shiyao Wang

    2016-02-01

    Full Text Available A high-performance differential global positioning system (GPS  receiver with real time kinematics provides absolute localization for driverless cars. However, it is not only susceptible to multipath effect but also unable to effectively fulfill precise error correction in a wide range of driving areas. This paper proposes an accurate GPS–inertial measurement unit (IMU/dead reckoning (DR data fusion method based on a set of predictive models and occupancy grid constraints. First, we employ a set of autoregressive and moving average (ARMA equations that have different structural parameters to build maximum likelihood models of raw navigation. Second, both grid constraints and spatial consensus checks on all predictive results and current measurements are required to have removal of outliers. Navigation data that satisfy stationary stochastic process are further fused to achieve accurate localization results. Third, the standard deviation of multimodal data fusion can be pre-specified by grid size. Finally, we perform a lot of field tests on a diversity of real urban scenarios. The experimental results demonstrate that the method can significantly smooth small jumps in bias and considerably reduce accumulated position errors due to DR. With low computational complexity, the position accuracy of our method surpasses existing state-of-the-arts on the same dataset and the new data fusion method is practically applied in our driverless car.

  14. Tryptophan inhibits Proteus vulgaris TnaC leader peptide elongation, activating tna operon expression.

    Science.gov (United States)

    Cruz-Vera, Luis R; Yang, Rui; Yanofsky, Charles

    2009-11-01

    Expression of the tna operon of Escherichia coli and of Proteus vulgaris is induced by L-tryptophan. In E. coli, tryptophan action is dependent on the presence of several critical residues (underlined) in the newly synthesized TnaC leader peptide, WFNIDXXL/IXXXXP. These residues are conserved in TnaC of P. vulgaris and of other bacterial species. TnaC of P. vulgaris has one additional feature, distinguishing it from TnaC of E. coli; it contains two C-terminal lysine residues following the conserved proline residue. In the present study, we investigated L-tryptophan induction of the P. vulgaris tna operon, transferred on a plasmid into E. coli. Induction was shown to be L-tryptophan dependent; however, the range of induction was less than that observed for the E. coli tna operon. We compared the genetic organization of both operons and predicted similar folding patterns for their respective leader mRNA segments. However, additional analyses revealed that L-tryptophan action in the P. vulgaris tna operon involves inhibition of TnaC elongation, following addition of proline, rather than inhibition of leader peptide termination. Our findings also establish that the conserved residues in TnaC of P. vulgaris are essential for L-tryptophan induction, and for inhibition of peptide elongation. TnaC synthesis is thus an excellent model system for studies of regulation of both peptide termination and peptide elongation, and for studies of ribosome recognition of the features of a nascent peptide. PMID:19767424

  15. Profile-QSAR: a novel meta-QSAR method that combines activities across the kinase family to accurately predict affinity, selectivity, and cellular activity.

    Science.gov (United States)

    Martin, Eric; Mukherjee, Prasenjit; Sullivan, David; Jansen, Johanna

    2011-08-22

    Profile-QSAR is a novel 2D predictive model building method for kinases. This "meta-QSAR" method models the activity of each compound against a new kinase target as a linear combination of its predicted activities against a large panel of 92 previously studied kinases comprised from 115 assays. Profile-QSAR starts with a sparse incomplete kinase by compound (KxC) activity matrix, used to generate Bayesian QSAR models for the 92 "basis-set" kinases. These Bayesian QSARs generate a complete "synthetic" KxC activity matrix of predictions. These synthetic activities are used as "chemical descriptors" to train partial-least squares (PLS) models, from modest amounts of medium-throughput screening data, for predicting activity against new kinases. The Profile-QSAR predictions for the 92 kinases (115 assays) gave a median external R²(ext) = 0.59 on 25% held-out test sets. The method has proven accurate enough to predict pairwise kinase selectivities with a median correlation of R²(ext) = 0.61 for 958 kinase pairs with at least 600 common compounds. It has been further expanded by adding a "C(k)XC" cellular activity matrix to the KxC matrix to predict cellular activity for 42 kinase driven cellular assays with median R²(ext) = 0.58 for 24 target modulation assays and R²(ext) = 0.41 for 18 cell proliferation assays. The 2D Profile-QSAR, along with the 3D Surrogate AutoShim, are the foundations of an internally developed iterative medium-throughput screening (IMTS) methodology for virtual screening (VS) of compound archives as an alternative to experimental high-throughput screening (HTS). The method has been applied to 20 actual prospective kinase projects. Biological results have so far been obtained in eight of them. Q² values ranged from 0.3 to 0.7. Hit-rates at 10 uM for experimentally tested compounds varied from 25% to 80%, except in K5, which was a special case aimed specifically at finding "type II" binders, where none of the compounds were predicted to be

  16. Possible regulation of the Salmonella typhimurium histidine operon by adenosine triphosphate phosphoribosyltransferase: large metabolic effects.

    OpenAIRE

    Goitein, R K; Parsons, S. M.

    1980-01-01

    An effort to find growth conditions leading to conditional regulation of the histidine operon of Salmonella typhimurium by the allosteric first enzyme of the pathway, adenosine triphosphate phosphoribosyltransferase (EC 2.4.2.17), is reported. A strain deleting the enzyme, TR3343, behaved simply and predictably under all growth conditions, whereas histidine auxotrophs containing active enzyme behaved in complicated ways dependent upon the location of the histidine pathway lesion. hisE strains...

  17. Dose Addition Models Based on Biologically Relevant Reductions in Fetal Testosterone Accurately Predict Postnatal Reproductive Tract Alterations by a Phthalate Mixture in Rats.

    Science.gov (United States)

    Howdeshell, Kembra L; Rider, Cynthia V; Wilson, Vickie S; Furr, Johnathan R; Lambright, Christy R; Gray, L Earl

    2015-12-01

    Challenges in cumulative risk assessment of anti-androgenic phthalate mixtures include a lack of data on all the individual phthalates and difficulty determining the biological relevance of reduction in fetal testosterone (T) on postnatal development. The objectives of the current study were 2-fold: (1) to test whether a mixture model of dose addition based on the fetal T production data of individual phthalates would predict the effects of a 5 phthalate mixture on androgen-sensitive postnatal male reproductive tract development, and (2) to determine the biological relevance of the reductions in fetal T to induce abnormal postnatal reproductive tract development using data from the mixture study. We administered a dose range of the mixture (60, 40, 20, 10, and 5% of the top dose used in the previous fetal T production study consisting of 300 mg/kg per chemical of benzyl butyl (BBP), di(n)butyl (DBP), diethyl hexyl phthalate (DEHP), di-isobutyl phthalate (DiBP), and 100 mg dipentyl (DPP) phthalate/kg; the individual phthalates were present in equipotent doses based on their ability to reduce fetal T production) via gavage to Sprague Dawley rat dams on GD8-postnatal day 3. We compared observed mixture responses to predictions of dose addition based on the previously published potencies of the individual phthalates to reduce fetal T production relative to a reference chemical and published postnatal data for the reference chemical (called DAref). In addition, we predicted DA (called DAall) and response addition (RA) based on logistic regression analysis of all 5 individual phthalates when complete data were available. DA ref and DA all accurately predicted the observed mixture effect for 11 of 14 endpoints. Furthermore, reproductive tract malformations were seen in 17-100% of F1 males when fetal T production was reduced by about 25-72%, respectively. PMID:26350170

  18. PredictSNP2: A Unified Platform for Accurately Evaluating SNP Effects by Exploiting the Different Characteristics of Variants in Distinct Genomic Regions.

    Science.gov (United States)

    Bendl, Jaroslav; Musil, Miloš; Štourač, Jan; Zendulka, Jaroslav; Damborský, Jiří; Brezovský, Jan

    2016-05-01

    An important message taken from human genome sequencing projects is that the human population exhibits approximately 99.9% genetic similarity. Variations in the remaining parts of the genome determine our identity, trace our history and reveal our heritage. The precise delineation of phenotypically causal variants plays a key role in providing accurate personalized diagnosis, prognosis, and treatment of inherited diseases. Several computational methods for achieving such delineation have been reported recently. However, their ability to pinpoint potentially deleterious variants is limited by the fact that their mechanisms of prediction do not account for the existence of different categories of variants. Consequently, their output is biased towards the variant categories that are most strongly represented in the variant databases. Moreover, most such methods provide numeric scores but not binary predictions of the deleteriousness of variants or confidence scores that would be more easily understood by users. We have constructed three datasets covering different types of disease-related variants, which were divided across five categories: (i) regulatory, (ii) splicing, (iii) missense, (iv) synonymous, and (v) nonsense variants. These datasets were used to develop category-optimal decision thresholds and to evaluate six tools for variant prioritization: CADD, DANN, FATHMM, FitCons, FunSeq2 and GWAVA. This evaluation revealed some important advantages of the category-based approach. The results obtained with the five best-performing tools were then combined into a consensus score. Additional comparative analyses showed that in the case of missense variations, protein-based predictors perform better than DNA sequence-based predictors. A user-friendly web interface was developed that provides easy access to the five tools' predictions, and their consensus scores, in a user-understandable format tailored to the specific features of different categories of variations. To

  19. A phylogenomic analysis of the Actinomycetales mce operons

    Directory of Open Access Journals (Sweden)

    Riley Lee W

    2007-02-01

    Full Text Available Abstract Background The genome of Mycobacterium tuberculosis harbors four copies of a cluster of genes termed mce operons. Despite extensive research that has demonstrated the importance of these operons on infection outcome, their physiological function remains obscure. Expanding databases of complete microbial genome sequences facilitate a comparative genomic approach that can provide valuable insight into the role of uncharacterized proteins. Results The M. tuberculosis mce loci each include two yrbE and six mce genes, which have homology to ABC transporter permeases and substrate-binding proteins, respectively. Operons with an identical structure were identified in all Mycobacterium species examined, as well as in five other Actinomycetales genera. Some of the Actinomycetales mce operons include an mkl gene, which encodes an ATPase resembling those of ABC uptake transporters. The phylogenetic profile of Mkl orthologs exactly matched that of the Mce and YrbE proteins. Through topology and motif analyses of YrbE homologs, we identified a region within the penultimate cytoplasmic loop that may serve as the site of interaction with the putative cognate Mkl ATPase. Homologs of the exported proteins encoded adjacent to the M. tuberculosis mce operons were detected in a conserved chromosomal location downstream of the majority of Actinomycetales operons. Operons containing linked mkl, yrbE and mce genes, resembling the classic organization of an ABC importer, were found to be common in Gram-negative bacteria and appear to be associated with changes in properties of the cell surface. Conclusion Evidence presented suggests that the mce operons of Actinomycetales species and related operons in Gram-negative bacteria encode a subfamily of ABC uptake transporters with a possible role in remodeling the cell envelope.

  20. Discovery of a general method of solving the Schrödinger and dirac equations that opens a way to accurately predictive quantum chemistry.

    Science.gov (United States)

    Nakatsuji, Hiroshi

    2012-09-18

    Just as Newtonian law governs classical physics, the Schrödinger equation (SE) and the relativistic Dirac equation (DE) rule the world of chemistry. So, if we can solve these equations accurately, we can use computation to predict chemistry precisely. However, for approximately 80 years after the discovery of these equations, chemists believed that they could not solve SE and DE for atoms and molecules that included many electrons. This Account reviews ideas developed over the past decade to further the goal of predictive quantum chemistry. Between 2000 and 2005, I discovered a general method of solving the SE and DE accurately. As a first inspiration, I formulated the structure of the exact wave function of the SE in a compact mathematical form. The explicit inclusion of the exact wave function's structure within the variational space allows for the calculation of the exact wave function as a solution of the variational method. Although this process sounds almost impossible, it is indeed possible, and I have published several formulations and applied them to solve the full configuration interaction (CI) with a very small number of variables. However, when I examined analytical solutions for atoms and molecules, the Hamiltonian integrals in their secular equations diverged. This singularity problem occurred in all atoms and molecules because it originates from the singularity of the Coulomb potential in their Hamiltonians. To overcome this problem, I first introduced the inverse SE and then the scaled SE. The latter simpler idea led to immediate and surprisingly accurate solution for the SEs of the hydrogen atom, helium atom, and hydrogen molecule. The free complement (FC) method, also called the free iterative CI (free ICI) method, was efficient for solving the SEs. In the FC method, the basis functions that span the exact wave function are produced by the Hamiltonian of the system and the zeroth-order wave function. These basis functions are called complement

  1. Genome-Scale Metabolic Model for the Green Alga Chlorella vulgaris UTEX 395 Accurately Predicts Phenotypes under Autotrophic, Heterotrophic, and Mixotrophic Growth Conditions.

    Science.gov (United States)

    Zuñiga, Cristal; Li, Chien-Ting; Huelsman, Tyler; Levering, Jennifer; Zielinski, Daniel C; McConnell, Brian O; Long, Christopher P; Knoshaug, Eric P; Guarnieri, Michael T; Antoniewicz, Maciek R; Betenbaugh, Michael J; Zengler, Karsten

    2016-09-01

    The green microalga Chlorella vulgaris has been widely recognized as a promising candidate for biofuel production due to its ability to store high lipid content and its natural metabolic versatility. Compartmentalized genome-scale metabolic models constructed from genome sequences enable quantitative insight into the transport and metabolism of compounds within a target organism. These metabolic models have long been utilized to generate optimized design strategies for an improved production process. Here, we describe the reconstruction, validation, and application of a genome-scale metabolic model for C. vulgaris UTEX 395, iCZ843. The reconstruction represents the most comprehensive model for any eukaryotic photosynthetic organism to date, based on the genome size and number of genes in the reconstruction. The highly curated model accurately predicts phenotypes under photoautotrophic, heterotrophic, and mixotrophic conditions. The model was validated against experimental data and lays the foundation for model-driven strain design and medium alteration to improve yield. Calculated flux distributions under different trophic conditions show that a number of key pathways are affected by nitrogen starvation conditions, including central carbon metabolism and amino acid, nucleotide, and pigment biosynthetic pathways. Furthermore, model prediction of growth rates under various medium compositions and subsequent experimental validation showed an increased growth rate with the addition of tryptophan and methionine. PMID:27372244

  2. Genomics of pyrrolnitrin biosynthetic loci: evidence for conservation and whole-operon mobility within gram-negative bacteria.

    Science.gov (United States)

    Costa, Rodrigo; van Aarle, Ingrid M; Mendes, Rodrigo; van Elsas, Jan Dirk

    2009-01-01

    Pyrrolnitrin (PRN) is a tryptophan-derived secondary metabolite produced by a narrow range of gram-negative bacteria. The PRN biosynthesis by rhizobacteria presumably has a key role in their life strategies and in the biocontrol of plant diseases. The biosynthetic operon that encodes the pathway that converts tryptophan to PRN is composed of four genes, prnA through D, whose diversity, genomic context and spread over bacterial genomes are poorly understood. Therefore, we launched an endeavour aimed at retrieving, by in vitro and in silico means, diverse bacteria carrying the prnABCD biosynthetic loci in their genomes. Analysis of polymorphisms of the prnD gene sequences revealed a high level of conservation between Burkholderia, Pseudomonas and Serratia spp. derived sequences. Whole-operon- and prnD-based phylogeny resulted in tree topologies that are incongruent with the taxonomic status of the evaluated strains as predicted by 16S rRNA gene phylogeny. The genomic composition of c. 20 kb DNA fragments containing the PRN operon varied in different strains. Highly conserved and distinct transposase-encoding genes surrounding the PRN biosynthetic operons of Burkholderia pseudomallei strains were found. A prnABCD-deprived genomic region in B. pseudomallei strain K96243 contained the same gene composition as, and shared high homology with, the flanking regions of the PRN operon in B. pseudomallei strains 668, 1106a and 1710b. Our results strongly suggest that the PRN biosynthetic operon is mobile. The extent, frequency and promiscuity of this mobility remain to be understood. PMID:18793314

  3. Visualization of ribosomal RNA operon copy number distribution

    OpenAIRE

    DasGupta Indrani; Wu Martin; Rastogi Rajat; Fox George E

    2009-01-01

    Abstract Background Results of microbial ecology studies using 16S rRNA sequence information can be deceiving due to differences in rRNA operon copy number and genome size of the detected organisms. It therefore will be useful for investigators to have a better understanding of how these two parameters differ in various organism types. In this study, the number of ribosomal operons and genome size were separately mapped onto a Bacterial phylogenetic tree. Results A representative Bacterial tr...

  4. Evolution of bacterial trp operons and their regulation

    OpenAIRE

    Merino, Enrique; Jensen, Roy A.; Yanofsky, Charles

    2008-01-01

    Survival and replication of most bacteria require the ability to synthesize the amino acid L-tryptophan whenever it is not available from the environment. In this article we describe the genes, operons, proteins, and reactions involved in tryptophan biosynthesis in bacteria, and the mechanisms they use in regulating tryptophan formation. We show that although the reactions of tryptophan biosynthesis are essentially identical, gene organization varies among species - from whole-pathway operons...

  5. Genetic organization of the cellulose synthase operon in Acetobacter xylinum.

    OpenAIRE

    Wong, H C; Fear, A L; Calhoon, R D; Eichinger, G H; Mayer, R; Amikam, D; Benziman, M; Gelfand, D H; Meade, J H; Emerick, A W

    1990-01-01

    An operon encoding four proteins required for bacterial cellulose biosynthesis (bcs) in Acetobacter xylinum was isolated via genetic complementation with strains lacking cellulose synthase activity. Nucleotide sequence analysis indicated that the cellulose synthase operon is 9217 base pairs long and consists of four genes. The four genes--bcsA, bcsB, bcsC, and bcsD--appear to be translationally coupled and transcribed as a polycistronic mRNA with an initiation site 97 bases upstream of the co...

  6. Calibrating transition-metal energy levels and oxygen bands in first-principles calculations: Accurate prediction of redox potentials and charge transfer in lithium transition-metal oxides

    Science.gov (United States)

    Seo, Dong-Hwa; Urban, Alexander; Ceder, Gerbrand

    2015-09-01

    Transition-metal (TM) oxides play an increasingly important role in technology today, including applications such as catalysis, solar energy harvesting, and energy storage. In many of these applications, the details of their electronic structure near the Fermi level are critically important for their properties. We propose a first-principles-based computational methodology for the accurate prediction of oxygen charge transfer in TM oxides and lithium TM (Li-TM) oxides. To obtain accurate electronic structures, the Heyd-Scuseria-Ernzerhof (HSE06) hybrid functional is adopted, and the amount of exact Hartree-Fock exchange (mixing parameter) is adjusted to reproduce reference band gaps. We show that the HSE06 functional with optimal mixing parameter yields not only improved electronic densities of states, but also better energetics (Li-intercalation voltages) for LiCo O2 and LiNi O2 as compared to the generalized gradient approximation (GGA), Hubbard U corrected GGA (GGA +U ), and standard HSE06. We find that the optimal mixing parameters for TM oxides are system specific and correlate with the covalency (ionicity) of the TM species. The strong covalent (ionic) nature of TM-O bonding leads to lower (higher) optimal mixing parameters. We find that optimized HSE06 functionals predict stronger hybridization of the Co 3 d and O 2 p orbitals as compared to GGA, resulting in a greater contribution from oxygen states to charge compensation upon delithiation in LiCo O2 . We also find that the band gaps of Li-TM oxides increase linearly with the mixing parameter, enabling the straightforward determination of optimal mixing parameters based on GGA (α =0.0 ) and HSE06 (α =0.25 ) calculations. Our results also show that G0W0@GGA +U band gaps of TM oxides (M O ,M =Mn ,Co ,Ni ) and LiCo O2 agree well with experimental references, suggesting that G0W0 calculations can be used as a reference for the calibration of the mixing parameter in cases when no experimental band gap has been

  7. Deterministic and stochastic population-level simulations of an artificial lac operon genetic network

    Directory of Open Access Journals (Sweden)

    Zygourakis Kyriacos

    2011-07-01

    Full Text Available Abstract Background The lac operon genetic switch is considered as a paradigm of genetic regulation. This system has a positive feedback loop due to the LacY permease boosting its own production by the facilitated transport of inducer into the cell and the subsequent de-repression of the lac operon genes. Previously, we have investigated the effect of stochasticity in an artificial lac operon network at the single cell level by comparing corresponding deterministic and stochastic kinetic models. Results This work focuses on the dynamics of cell populations by incorporating the above kinetic scheme into two Monte Carlo (MC simulation frameworks. The first MC framework assumes stochastic reaction occurrence, accounts for stochastic DNA duplication, division and partitioning and tracks all daughter cells to obtain the statistics of the entire cell population. In order to better understand how stochastic effects shape cell population distributions, we develop a second framework that assumes deterministic reaction dynamics. By comparing the predictions of the two frameworks, we conclude that stochasticity can create or destroy bimodality, and may enhance phenotypic heterogeneity. Conclusions Our results show how various sources of stochasticity act in synergy with the positive feedback architecture, thereby shaping the behavior at the cell population level. Further, the insights obtained from the present study allow us to construct simpler and less computationally intensive models that can closely approximate the dynamics of heterogeneous cell populations.

  8. Defining the Most Accurate Measurable Dimension(s of the Liver in Predicting Liver Volume Based on CT Volumetery and Reconstruction

    Directory of Open Access Journals (Sweden)

    Reza Saadat Mostafavi

    2010-05-01

    Full Text Available Background/Objective: The presence of liver volume has a great effect on diagnosis and management of different diseases such as lymphoproliferative conditions. "nPatients and Methods: Abdominal CT scan of 100 patients without any findings for liver disease (in history and imaging was subjected to volumetry and reconstruction. Along with the liver volume, in axial series, the AP diameter of the left lobe (in midline and right lobe (mid-clavicular and lateral maximum diameter of the liver in the mid-axiliary line and maximum diameter to IVC were calculated. In the coronal mid-axillary and sagittal mid-clavicular plane, maximum superior-inferior dimensions were calculated with their various combinations (multiplying. Regression analysis between dimensions and volume were performed. "nResults: The most accurate combination was the superior inferior sagittal dimension multiplied by AP diameter of the right lobe (R squared 0.78, P-value<0.001 and the most solitary dimension was the lateral dimension to IVC in the axial plane (R squared 0.57, P-value<0.001 with an interval of 9-11cm for 68% of normal. "nConclusion: We recommend the lateral maximum diameter of liver from surface to IVC in the axial plane in ultrasound for liver volume prediction with an interval of 9-11cm for 68% of normal. Out of this range is regarded as abnormal.

  9. Accurate Prediction of Essential Fundamental Properties for Semiconductors Used in Solar-Energy Conversion Devices from Range-Separated Hybrid Density Functional Theory

    KAUST Repository

    Harb, Moussab

    2016-01-05

    An essential issue in developing new semiconductors for photovoltaics devices is to design materials with appropriate fundamental parameters related to the light absorption, photogenerated exciton dissociation and charge carrier diffusion. These phenomena are governed by intrinsic properties of the semiconductor like the bandgap, the dielectric constant, the charge carrier effective masses, and the exciton binding energy. We present here the results of a systematic theoretical study on the fundamental properties of a series of selected semiconductors widely used in inorganic photovoltaic and dye-sensitized solar cells such as Si, Ge, CdS, CdSe, CdTe, and GaAs. These intrinsic properties were computed in the framework of the density functional theory (DFT) along with the standard PBE and the range-separated hybrid (HSE06) exchange-correlation functionals. Our calculations clearly show that the computed values using HSE06 reproduce with high accuracy the experimental data. The evaluation and accurate prediction of these key properties using HSE06 open nice perspectives for in silico design of new suitable candidate materials for solar energy conversion applications.

  10. Bistable behavior of the lac operon in E. coli when induced with a mixture of lactose and TMG

    Directory of Open Access Journals (Sweden)

    Orlando Díaz-Hernández

    2010-07-01

    Full Text Available In this work we investigate multistability in the lac operon of Escherichia coli when it is induced by a mixture of lactose and the non-metabolizable thiomethyl galactoside (TMG. In accordance with previously published experimental results and computer simulations, our simulations predict that: (1 when the system is induced by TMG, the system shows a discernible bistable behavior while, (2 when the system is induced by lactose, bistability does not disappear but excessively high concentrations of lactose would be required to observe it. Finally, our simulation results predict that when a mixture of lactose and TMG is used, the bistability region in the extracellular glucose concentration vs. extracellular lactose concentration parameter space changes in such a way that the model predictions regarding bistability could be tested experimentally. These experiments could help to solve a recent controversy regarding the existence of bistability in the lac operon under natural conditions.

  11. Accurate Prediction of Hyperfine Coupling Constants in Muoniated and Hydrogenated Ethyl Radicals: Ab Initio Path Integral Simulation Study with Density Functional Theory Method.

    Science.gov (United States)

    Yamada, Kenta; Kawashima, Yukio; Tachikawa, Masanori

    2014-05-13

    We performed ab initio path integral molecular dynamics (PIMD) simulations with a density functional theory (DFT) method to accurately predict hyperfine coupling constants (HFCCs) in the ethyl radical (CβH3-CαH2) and its Mu-substituted (muoniated) compound (CβH2Mu-CαH2). The substitution of a Mu atom, an ultralight isotope of the H atom, with larger nuclear quantum effect is expected to strongly affect the nature of the ethyl radical. The static conventional DFT calculations of CβH3-CαH2 find that the elongation of one Cβ-H bond causes a change in the shape of potential energy curve along the rotational angle via the imbalance of attractive and repulsive interactions between the methyl and methylene groups. Investigation of the methyl-group behavior including the nuclear quantum and thermal effects shows that an unbalanced CβH2Mu group with the elongated Cβ-Mu bond rotates around the Cβ-Cα bond in a muoniated ethyl radical, quite differently from the CβH3 group with the three equivalent Cβ-H bonds in the ethyl radical. These rotations couple with other molecular motions such as the methylene-group rocking motion (inversion), leading to difficulties in reproducing the corresponding barrier heights. Our PIMD simulations successfully predict the barrier heights to be close to the experimental values and provide a significant improvement in muon and proton HFCCs given by the static conventional DFT method. Further investigation reveals that the Cβ-Mu/H stretching motion, methyl-group rotation, methylene-group rocking motion, and HFCC values deeply intertwine with each other. Because these motions are different between the radicals, a proper description of the structural fluctuations reflecting the nuclear quantum and thermal effects is vital to evaluate HFCC values in theory to be comparable to the experimental ones. Accordingly, a fundamental difference in HFCC between the radicals arises from their intrinsic molecular motions at a finite temperature, in

  12. A Quantitative bgl Operon Model for E. coli Requires BglF Conformational Change for Sugar Transport

    Science.gov (United States)

    Chopra, Paras; Bender, Andreas

    The bgl operon is responsible for the metabolism of β-glucoside sugars such as salicin or arbutin in E. coli. Its regulatory system involves both positive and negative feedback mechanisms and it can be assumed to be more complex than that of the more closely studied lac and trp operons. We have developed a quantitative model for the regulation of the bgl operon which is subject to in silico experiments investigating its behavior under different hypothetical conditions. Upon administration of 5mM salicin as an inducer our model shows 80-fold induction, which compares well with the 60-fold induction measured experimentally. Under practical conditions 5-10mM inducer are employed, which is in line with the minimum inducer concentration of 1mM required by our model. The necessity of BglF conformational change for sugar transport has been hypothesized previously, and in line with those hypotheses our model shows only minor induction if conformational change is not allowed. Overall, this first quantitative model for the bgl operon gives reasonable predictions that are close to experimental results (where measured). It will be further refined as values of the parameters are determined experimentally. The model was developed in Systems Biology Markup Language (SBML) and it is available from the authors and from the Biomodels repository [www.ebi.ac.uk/biomodels].

  13. Transcriptional Regulation of the Streptococcus salivarius 57.I Urease Operon

    OpenAIRE

    Chen, Yi-Ywan M.; Weaver, Cheryl A.; Mendelsohn, David R.; Burne, Robert A.

    1998-01-01

    The Streptococcus salivarius 57.I ure cluster was organized as an operon, beginning with ureI, followed by ureABC (structural genes) and ureEFGD (accessory genes). Northern analyses revealed transcripts encompassing structural genes and transcripts containing the entire operon. A ς70-like promoter could be mapped 5′ to ureI (PureI) by primer extension analysis. The intensity of the signal increased when cells were grown at an acidic pH and was further enhanced by excess carbohydrate. To deter...

  14. Dynamic model of gene regulation for the lac operon

    Energy Technology Data Exchange (ETDEWEB)

    Angelova, Maia; Ben-Halim, Asma, E-mail: maia.angelova@northumbria.ac.uk, E-mail: asma.benhalim@northumbria.ac.uk [Intelligent Modelling Lab, School of Computing, Engineering and Information Sciences, Northumbria University, Newcastle upon Tyne NE2 1XE (United Kingdom)

    2011-03-01

    Gene regulatory network is a collection of DNA which interact with each other and with other matter in the cell. The lac operon is an example of a relatively simple genetic network and is one of the best-studied structures in the Escherichia coli bacteria. In this work we consider a deterministic model of the lac operon with a noise term, representing the stochastic nature of the regulation. The model is written in terms of a system of simultaneous first order differential equations with delays. We investigate an analytical and numerical solution and analyse the range of values for the parameters corresponding to a stable solution.

  15. Functional analysis of an intergenic non-coding sequence within mce1 operon of M.tuberculosis

    Directory of Open Access Journals (Sweden)

    Bose Mridula

    2010-04-01

    Full Text Available Abstract Background The mce operons play an important role in the entry of M. tuberculosis into macrophages and non-phagocytic cells. Their non-redundant function as well as complex regulation is implied by the phenotype of mce mutants. Recently, mce1 operon was found to extend over 13 genes, fadD5 (Rv0166 being the first gene of the operon. The presence of a non-coding sequence of 200 base pairs between Rv0166 and Rv0167 is peculiar to mce1 among the four mce operons of M.tuberculosis. We have examined the function of this region. Results We predicted putative promoter activity of the 200 base pairs of non-coding, intergenic region between Rv0166 and Rv0167 in silico using MEME software and designate it as intergenic promoter, IGPr. We demonstrate both promoter activity and a putative negative regulatory function of this fragment by reporter assays carried out in the surrogate host M.smegmatis. We find that the repressive elements not only control the native promoter but also repress a heterologous promoter of M.smegmatis. The higher activity of the intergenic promoter in a clinical isolate in comparison with the wild type sequence from M.tuberculosis H37Rv could be correlated with a point mutation within the negative element. We have mapped two transcription start sites for mce1 operon both of which are utilized in M.tuberculosis H37Rv as well as the clinical isolate VPCI591. Our studies show that the promoter activity in the non-coding region is relevant not only in reporter gene expression but also in the expression of mce1 operon in M. tuberculosis cells grown in synthetic medium. Conclusion The mce operon of M.tuberculosis H37Rv potentially can be transcribed from two promoters P1 and P2, former mapping upstream of Rv0166 and the latter in the non-coding intergenic region between Rv0166 and Rv0167. The transcription initiation from P1 results in a transcript with Rv0166 while that from P2 will be without it. The sequences between the

  16. Operon Formation is Driven by Co-Regulation and Not by Horizontal Gene Transfer

    Energy Technology Data Exchange (ETDEWEB)

    Price, Morgan N.; Huang, Katherine H.; Arkin, Adam P.; Alm, Eric J.

    2005-04-12

    Although operons are often subject to horizontal gene transfer (HGT), non-HGT genes are particularly likely to be in operons. To resolve this apparent discrepancy and to determine whether HGT is involved in operon formation, we examined the evolutionary history of the genes and operons in Escherichia coli K12. We show that genes that have homologs in distantly related bacteria but not in close relatives of E. coli (indicating HGTi) form new operons at about the same rates as native genes. Furthermore, genes in new operons are no more likely than other genes to have phylogenetic trees that are inconsistent with the species tree. In contrast, essential genes and ubiquitous genes without paralogs (genes believed to undergo HGT rarely) often form new operons. We conclude that HGT is not associated with operon formation, but instead promotes the prevalence of pre-existing operons. To explain operon formation, we propose that new operons reduce the amount of regulatory information required to specify optimal expression patterns. Consistent with this hypothesis, operons have greater amounts of conserved regulatory sequences than do individually transcribed genes.

  17. Role of leader peptide synthesis in tryptophanase operon expression in Escherichia coli K-12.

    OpenAIRE

    Stewart, V; Yanofsky, C

    1986-01-01

    We used site-directed mutagenesis to replace the Escherichia coli tryptophanase (tna) operon leader peptide start codon with AUC. This change greatly decreased the uninduced rate of tna operon expression, and it also lowered the response to inducer. We conclude that leader peptide synthesis plays an essential role in tna operon expression.

  18. Characterization of the Cobalamin and Fep Operons in Methylobium petrolphilum PM1

    Energy Technology Data Exchange (ETDEWEB)

    Ewing, J

    2005-09-06

    The bacterium Methylobium petroleophilum PM1 is economically important due to its ability to degrade methyl tert-butyl ether (MTBE), a fuel additive. Because PM1 is a representative of all MTBE degraders, it is important to understand the transport pathways critical for the organism to survive in its particular environment. In this study, the cobalamin pathway and select iron transport genes will be characterized to help further understand all metabolic pathways in PM1. PM1 contains a total of four cobalamin operons. A single operon is located on the chromosome. Located on the megaplasmid are two tandem repeats of cob operons and a very close representative of the cob operon located on the chromosome. The fep operon, an iron transport mechanism, lies within the multiple copies of the cob operon. The cob operon and the fep operon appear to be unrelated except for a shared need for the T-on-B-dependent energy transduction complex to assist the operons in moving large molecules across the outer membrane of the cell. A genomic study of the cob and the fep operons with that of phylogenetically related organisms helped to confirm the identity of the cob and fep operons and to represent the pathways. More study of the pathways should be done to find the relationship that positions the two seemingly unrelated cob and fep genes together in what appears to be one operon.

  19. Fucose-Mediated Transcriptional Activation of the fcs Operon by FcsR in Streptococcus pneumoniae

    NARCIS (Netherlands)

    Manzoor, Irfan; Shafeeq, Sulman; Afzal, Muhammad; Kuipers, Oscar P

    2015-01-01

    In this study, we explore the impact of fucose on the transcriptome of S. pneumoniae D39. The expression of various genes and operons, including the fucose uptake PTS and utilization operon (fcs operon) was altered in the presence of fucose. By means of quantitative RT-PCR and β-galactosidase analys

  20. Visualization of ribosomal RNA operon copy number distribution

    Directory of Open Access Journals (Sweden)

    DasGupta Indrani

    2009-09-01

    Full Text Available Abstract Background Results of microbial ecology studies using 16S rRNA sequence information can be deceiving due to differences in rRNA operon copy number and genome size of the detected organisms. It therefore will be useful for investigators to have a better understanding of how these two parameters differ in various organism types. In this study, the number of ribosomal operons and genome size were separately mapped onto a Bacterial phylogenetic tree. Results A representative Bacterial tree was constructed using 31 marker genes found in 578 bacterial genome sequences. Organism names are displayed on the trees using graduations of color such that similar colors indicate similar numbers of operons or genome size. The resulting images provide an intuitive understanding of how copy number and genome size vary in different Bacterial phyla. Conclusion Once the phylogenetic position of a novel organism is known the number of rRNA operons, and to a lesser extent the genome size, can be estimated by examination of the colored maps. Further detail can then be obtained for members of relevant taxa from the rrnDB database.

  1. NMR studies of the allosteric effectors of the lac operon

    NARCIS (Netherlands)

    Romanuka, J.

    2009-01-01

    The aim of this thesis is to characterize the regulatory mechanism of the Lac repressor which is the molecular switch of the lac operon. Lac repressor binds to its cognate DNA operator and inhibits transcription. When an inducer binds to the protein, it triggers a conformational change that releases

  2. The use of a hands-on model in learning the regulation of an inducible operon and the development of a gene regulation concept inventory

    Science.gov (United States)

    Stefanski, Katherine M.

    A central concept in genetics is the regulation of gene expression. Inducible gene expression is often taught in undergraduate biology courses using the lac operon of Escherichia coli (E. coli ). With national calls for reform in undergraduate biology education and a body of literature that supports the use of active learning techniques including hands-on learning and analogies we were motivated to develop a hands-on analogous model of the lac operon. The model was developed over two iterations and was administered to genetics students. To determine the model's worth as a learning tool a concept inventory (CI) was developed using rigorous protocols. Concept inventories are valuable tools which can be used to assess students' understanding of a topic and pinpoint commonly held misconceptions as well as the value of educational tools. Through in-class testing (n =115) the lac operon concept inventory (LOCI) was demonstrated to be valid, predictive, and reliable (? coefficient = 0.994). LOCI scores for students who participated in the hands-on activity (n = 67) were 7.5% higher (t = -2.281, P students who did not ( n = 62). Use of the model is also supported by student feedback from two surveys. This study provides an effective activity that aids students' understanding of the lac operon. We were able to determine the efficacy of the activity and identify misconceptions held by students about the lac operon because of the use of a valid and reliable CI.

  3. A tenth atp gene and the conserved atpI gene of a Bacillus atp operon have a role in Mg2+ uptake

    OpenAIRE

    Hicks, David B.; Wang, Zhenxiong; Wei, Yi; Kent, Rebecca; Guffanti, Arthur A.; Banciu, Horia; Bechhofer, David H.; Krulwich, Terry A.

    2003-01-01

    The atp operon of alkaliphilic Bacillus pseudofirmus OF4, as in most prokaryotes, contains the eight structural genes for the F-ATPase (ATP synthase), which are preceded by an atpI gene that encodes a membrane protein of unknown function. A tenth gene, atpZ, has been found in this operon, which is upstream of and overlapping with atpI. Most Bacillus species, and some other bacteria, possess atpZ homologues. AtpZ is predicted to be a membrane protein with a hairpin ...

  4. NetMHC-3.0: accurate web accessible predictions of human, mouse and monkey MHC class I affinities for peptides of length 8-11

    DEFF Research Database (Denmark)

    Lundegaard, Claus; Lamberth, K; Harndahl, M;

    2008-01-01

    NetMHC-3.0 is trained on a large number of quantitative peptide data using both affinity data from the Immune Epitope Database and Analysis Resource (IEDB) and elution data from SYFPEITHI. The method generates high-accuracy predictions of major histocompatibility complex (MHC): peptide binding....... The predictions are based on artificial neural networks trained on data from 55 MHC alleles (43 Human and 12 non-human), and position-specific scoring matrices (PSSMs) for additional 67 HLA alleles. As only the MHC class I prediction server is available, predictions are possible for peptides of length 8......–11 for all 122 alleles. artificial neural network predictions are given as actual IC50 values whereas PSSM predictions are given as a log-odds likelihood scores. The output is optionally available as download for easy post-processing. The training method underlying the server is the best available, and has...

  5. 单核细胞增生李斯特菌新疆野毒株XS5SigmaB操纵子的克隆、序列分析及其编码蛋白结构预测%Cloning, Sequence Analysis and the Prediction of the Protein Structure of SigmaB Operon Sequence of Xinjiang Strain XS5 of Listeria monocytogenes

    Institute of Scientific and Technical Information of China (English)

    杨丽红; 张再超; 孟庆玲; 乔军; 才学鹏; 蔡扩军; 王为升; 王俊伟; 陈创夫

    2012-01-01

    为了解单核细胞增生李斯特菌(Listeria monocytogenes LM.)新疆野毒株XS5 SigmaB操纵子的分子生物学特征.对LM-XS5的SigmaB操纵子部分基因序列进行了克隆与序列分析,预测该操纵子各基因编码蛋白质的二三级结构及功能活性位点,分析其同源性.结果表明:成功扩增出3000bp的SigmaB操纵子片段,序列分析显示该片段中包含RsbV、RsbW、RsbX和SigmaB4个基因,它们编码的蛋白质含有不同的功能活性位点,其中RsbV的5~102位AA为“STAS-抗-抗-SigamB因子”,RsbW的43~157位AA间为HATPase_c功能域,RsbX的32~198位AA间为PP2Cc超家族区域,SigmaB的8~264位AA为RNA聚合酶全酶中的SigmaB因子的区域.LM-XS5与其他3种革兰氏阳性菌的SigmaB基因的同源率在50%左右,与LM参考株的同源率在92.18%~100%之间.%In order to understand the biological characteristics of the SigmaB operon of Xinjiang Strain XS5 of Listeria monocytogenes, a part of SigmaB operon sequences of XS5 was amplified using PCR technique, then cloned and analyzed. The secondary and tertiary structure were predicted and analyzed for all the genes in SigmaB operon. Identity of SigmaB gene was analyzed among LM-XS5 and reference strains of LM together with other three kinds of gram-positive bacteria, and then Phylogenetic trees was constructed by MEGA5. The results showed that the amplified fragment of 3000 bp contained four genes (RsbV, RsbW, RsbX and SigmaB). All of them had different functional domains which were structural basis of their functions. The 5 to 102 AA of Rsb V was "STAS-anti-anti-5igam B factor"; the 43 to 157 AA of RsbW was HATPase_c; the 32 to 198 AA of RsbX belonged to PP2Cc super family; the 8 to 264 AA of SigmaB was SigmaB factor of RNA polymerase. Compared with the SigmaB gene sequence of other three kinds of gram-positive bacteria, the identities were around 50%, and the identities among strains of LM ranged from 92.18% to 100%.

  6. NetMHC-3.0: accurate web accessible predictions of human, mouse and monkey MHC class I affinities for peptides of length 8-11.

    Science.gov (United States)

    Lundegaard, Claus; Lamberth, Kasper; Harndahl, Mikkel; Buus, Søren; Lund, Ole; Nielsen, Morten

    2008-07-01

    NetMHC-3.0 is trained on a large number of quantitative peptide data using both affinity data from the Immune Epitope Database and Analysis Resource (IEDB) and elution data from SYFPEITHI. The method generates high-accuracy predictions of major histocompatibility complex (MHC): peptide binding. The predictions are based on artificial neural networks trained on data from 55 MHC alleles (43 Human and 12 non-human), and position-specific scoring matrices (PSSMs) for additional 67 HLA alleles. As only the MHC class I prediction server is available, predictions are possible for peptides of length 8-11 for all 122 alleles. artificial neural network predictions are given as actual IC(50) values whereas PSSM predictions are given as a log-odds likelihood scores. The output is optionally available as download for easy post-processing. The training method underlying the server is the best available, and has been used to predict possible MHC-binding peptides in a series of pathogen viral proteomes including SARS, Influenza and HIV, resulting in an average of 75-80% confirmed MHC binders. Here, the performance is further validated and benchmarked using a large set of newly published affinity data, non-redundant to the training set. The server is free of use and available at: http://www.cbs.dtu.dk/services/NetMHC.

  7. Is scoring system of computed tomography based metric parameters can accurately predicts shock wave lithotripsy stone-free rates and aid in the development of treatment strategies?

    Directory of Open Access Journals (Sweden)

    Yasser ALI Badran

    2016-01-01

    Conclusion: Stone size, stone density (HU, and SSD is simple to calculate and can be reported by radiologists to applying combined score help to augment predictive power of SWL, reduce cost, and improving of treatment strategies.

  8. c-myc, not her-2/neu, can predict the prognosis of breast cancer patients: how novel, how accurate, and how significant?

    International Nuclear Information System (INIS)

    The predictive and prognostic implication of oncogene amplification in breast cancer has received great attention in the past two decades. her-2/neu and c-myc are two oncogenes that are frequently amplified and overexpressed in breast carcinomas. Despite the extensive data on these oncogenes, their prognostic and predictive impact on breast cancer patients remains controversial. Schlotter and colleagues have recently suggested that c-myc, and not her-2/neu, could predict the recurrence and mortality of patients with node-negative breast carcinomas. Regardless of the promising results, caution should be exercised in the interpretation of data from studies assessing gene amplification without in situ analysis. We address the novelty, accuracy and clinical significance of the study by Schlotter and colleagues

  9. The accurate definition of metabolic volumes on 18F-FDG-PET before treatment allows the response to chemoradiotherapy to be predicted in the case of oesophagus cancers

    International Nuclear Information System (INIS)

    This study aims at assessing the possibility of prediction of the response of locally advanced oesophagus cancers, even before the beginning of treatment, by using metabolic volume measurements performed on 18F-FDG PET images made before the treatment. Medical files of 50 patients have been analyzed. According to the observed responses, and to metabolic volume and Total Lesion Glycosis (TLG) values, it appears that the images allow the extraction of parameters, such as the TLG, which are criteria for the prediction of the therapeutic response. Short communication

  10. Evolution of bacterial trp operons and their regulation.

    Science.gov (United States)

    Merino, Enrique; Jensen, Roy A; Yanofsky, Charles

    2008-04-01

    Survival and replication of most bacteria require the ability to synthesize the amino acid L-tryptophan whenever it is not available from the environment. In this article we describe the genes, operons, proteins, and reactions involved in tryptophan biosynthesis in bacteria, and the mechanisms they use in regulating tryptophan formation. We show that although the reactions of tryptophan biosynthesis are essentially identical, gene organization varies among species--from whole-pathway operons to completely dispersed genes. We also show that the regulatory mechanisms used for these genes vary greatly. We address the question--what are some potential advantages of the gene organization and regulation variation associated with this conserved, important pathway? PMID:18374625

  11. Elucidation of operon structures across closely related bacterial genomes.

    Science.gov (United States)

    Zhou, Chuan; Ma, Qin; Li, Guojun

    2014-01-01

    About half of the protein-coding genes in prokaryotic genomes are organized into operons to facilitate co-regulation during transcription. With the evolution of genomes, operon structures are undergoing changes which could coordinate diverse gene expression patterns in response to various stimuli during the life cycle of a bacterial cell. Here we developed a graph-based model to elucidate the diversity of operon structures across a set of closely related bacterial genomes. In the constructed graph, each node represents one orthologous gene group (OGG) and a pair of nodes will be connected if any two genes, from the corresponding two OGGs respectively, are located in the same operon as immediate neighbors in any of the considered genomes. Through identifying the connected components in the above graph, we found that genes in a connected component are likely to be functionally related and these identified components tend to form treelike topology, such as paths and stars, corresponding to different biological mechanisms in transcriptional regulation as follows. Specifically, (i) a path-structure component integrates genes encoding a protein complex, such as ribosome; and (ii) a star-structure component not only groups related genes together, but also reflects the key functional roles of the central node of this component, such as the ABC transporter with a transporter permease and substrate-binding proteins surrounding it. Most interestingly, the genes from organisms with highly diverse living environments, i.e., biomass degraders and animal pathogens of clostridia in our study, can be clearly classified into different topological groups on some connected components.

  12. Elucidation of operon structures across closely related bacterial genomes.

    Directory of Open Access Journals (Sweden)

    Chuan Zhou

    Full Text Available About half of the protein-coding genes in prokaryotic genomes are organized into operons to facilitate co-regulation during transcription. With the evolution of genomes, operon structures are undergoing changes which could coordinate diverse gene expression patterns in response to various stimuli during the life cycle of a bacterial cell. Here we developed a graph-based model to elucidate the diversity of operon structures across a set of closely related bacterial genomes. In the constructed graph, each node represents one orthologous gene group (OGG and a pair of nodes will be connected if any two genes, from the corresponding two OGGs respectively, are located in the same operon as immediate neighbors in any of the considered genomes. Through identifying the connected components in the above graph, we found that genes in a connected component are likely to be functionally related and these identified components tend to form treelike topology, such as paths and stars, corresponding to different biological mechanisms in transcriptional regulation as follows. Specifically, (i a path-structure component integrates genes encoding a protein complex, such as ribosome; and (ii a star-structure component not only groups related genes together, but also reflects the key functional roles of the central node of this component, such as the ABC transporter with a transporter permease and substrate-binding proteins surrounding it. Most interestingly, the genes from organisms with highly diverse living environments, i.e., biomass degraders and animal pathogens of clostridia in our study, can be clearly classified into different topological groups on some connected components.

  13. Regulation of Tryptophan Operon Expression in the Archaeon Methanothermobacter thermautotrophicus

    OpenAIRE

    Xie, Yunwei; Reeve, John N.

    2005-01-01

    Conserved trp genes encode enzymes that catalyze tryptophan biosynthesis in all three biological domains, and studies of their expression in Bacteria and eukaryotes have revealed a variety of different regulatory mechanisms. The results reported here provide the first detailed description of an archaeal trp gene regulatory system. We have established that the trpEGCFBAD operon in Methanothermobacter thermautotrophicus is transcribed divergently from a gene (designated trpY) that encodes a try...

  14. Regulation of tryptophan operon expression in the archaeon Methanothermobacter thermautotrophicus.

    Science.gov (United States)

    Xie, Yunwei; Reeve, John N

    2005-09-01

    Conserved trp genes encode enzymes that catalyze tryptophan biosynthesis in all three biological domains, and studies of their expression in Bacteria and eukaryotes have revealed a variety of different regulatory mechanisms. The results reported here provide the first detailed description of an archaeal trp gene regulatory system. We have established that the trpEGCFBAD operon in Methanothermobacter thermautotrophicus is transcribed divergently from a gene (designated trpY) that encodes a tryptophan-sensitive transcription regulator. TrpY binds to TRP box sequences (consensus, TGTACA) located in the overlapping promoter regions between trpY and trpE, inhibiting trpY transcription in the absence of tryptophan and both trpY and trpEGCFBAD transcription in the presence of tryptophan. TrpY apparently inhibits trpY transcription by blocking RNA polymerase access to the site of trpY transcription initiation and represses trpEGCFBAD transcription by preventing TATA box binding protein (TBP) binding to the TATA box sequence. Given that residue 2 (W2) is the only tryptophan in TrpY and in TrpY homologues in other Euryarchaea and that there is only one tryptophan codon in the entire trpEGCFBAD operon (trpB encodes W175), expression of the trp operon may also be regulated in vivo by the supply of charged tRNA(Trp) available to translate the second codon of the trpY mRNA. PMID:16159776

  15. Use of quantitative shape-activity relationships to model the photoinduced toxicity of polycyclic aromatic hydrocarbons: Electron density shape features accurately predict toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Mezey, P.G.; Zimpel, Z.; Warburton, P.; Walker, P.D.; Irvine, D.G. [Univ. of Saskatchewan, Saskatoon, Saskatchewan (Canada); Huang, X.D.; Dixon, D.G.; Greenberg, B.M. [Univ. of Waterloo, Ontario (Canada). Dept. of Biology

    1998-07-01

    The quantitative shape-activity relationship (QShAR) methodology, based on accurate three-dimensional electron densities and detailed shape analysis methods, has been applied to a Lemna gibba photoinduced toxicity data set of 16 polycyclic aromatic hydrocarbon (PAH) molecules. In the first phase of the studies, a shape fragment QShAR database of PAHs was developed. The results provide a very good match to toxicity based on a combination of the local shape features of single rings in comparison to the central ring of anthracene and a more global shape feature involving larger molecular fragments. The local shape feature appears as a descriptor of the susceptibility of PAHs to photomodification and the global shape feature is probably related to photosensitization activity.

  16. Insights into arsenic multi-operons expression and arsenic resistance mechanisms in Rhodopseudomonas palustris CGA009

    Directory of Open Access Journals (Sweden)

    Chungui eZhao

    2015-09-01

    Full Text Available Arsenic (As is widespread in the environment and causes numerous health problems. Rhodopseudomonas palustris has been regarded as a good model organism for studying arsenic detoxification since it was first demonstrated to methylate environmental arsenic by conversion to soluble or gaseous methylated species. However, the detailed arsenic resistance mechanisms remain unknown though there are at least three arsenic-resistance operons (ars1, ars2 and ars3 in R. palustris. In this study, we investigated how arsenic multi-operons contributed to arsenic detoxification in R. palustris. The expression of ars2 or ars3 operons increased with increasing environmental arsenite (As(III concentrations (up to 1.0 mM while transcript of ars1 operon was not detected in the middle log-phase (55 h. ars2 operon was actively expressed even at the low concentration of As(III (0.01 μM, whereas the ars3 operon was expressed at 1.0 µM of As(III, indicating that there was a differential regulation mechanism for the three arsenic operons. Furthermore, ars2 and ars3 operons were maximally transcribed in the early log-phase where ars2 operon was 5.4-fold higher than that of ars3 operon. A low level of ars1 transcript was only detected at 43 h (early log-phase. Arsenic speciation analysis demonstrated that R. palustris could reduce As(V to As(III.

  17. Fecal Calprotectin is an Accurate Tool and Correlated to Seo Index in Prediction of Relapse in Iranian Patients With Ulcerative Colitis

    OpenAIRE

    Hosseini, Seyed Vahid; Jafari, Peyman; Taghavi, Seyed Alireza; Safarpour, Ali Reza; Rezaianzadeh, Abbas; Moini, Maryam; Mehrabi, Manoosh

    2015-01-01

    Background: The natural clinical course of Ulcerative Colitis (UC) is characterized by episodes of relapse and remission. Fecal Calprotectin (FC) is a relatively new marker of intestinal inflammation and is an available, non-expensive tool for predicting relapse of quiescent UC. The Seo colitis activity index is a clinical index for assessment of the severity of UC. Objectives: The present study aimed to evaluate the accuracy of FC and the Seo colitis activity index and their correlation in p...

  18. PredPPCrys: accurate prediction of sequence cloning, protein production, purification and crystallization propensity from protein sequences using multi-step heterogeneous feature fusion and selection.

    Directory of Open Access Journals (Sweden)

    Huilin Wang

    Full Text Available X-ray crystallography is the primary approach to solve the three-dimensional structure of a protein. However, a major bottleneck of this method is the failure of multi-step experimental procedures to yield diffraction-quality crystals, including sequence cloning, protein material production, purification, crystallization and ultimately, structural determination. Accordingly, prediction of the propensity of a protein to successfully undergo these experimental procedures based on the protein sequence may help narrow down laborious experimental efforts and facilitate target selection. A number of bioinformatics methods based on protein sequence information have been developed for this purpose. However, our knowledge on the important determinants of propensity for a protein sequence to produce high diffraction-quality crystals remains largely incomplete. In practice, most of the existing methods display poorer performance when evaluated on larger and updated datasets. To address this problem, we constructed an up-to-date dataset as the benchmark, and subsequently developed a new approach termed 'PredPPCrys' using the support vector machine (SVM. Using a comprehensive set of multifaceted sequence-derived features in combination with a novel multi-step feature selection strategy, we identified and characterized the relative importance and contribution of each feature type to the prediction performance of five individual experimental steps required for successful crystallization. The resulting optimal candidate features were used as inputs to build the first-level SVM predictor (PredPPCrys I. Next, prediction outputs of PredPPCrys I were used as the input to build second-level SVM classifiers (PredPPCrys II, which led to significantly enhanced prediction performance. Benchmarking experiments indicated that our PredPPCrys method outperforms most existing procedures on both up-to-date and previous datasets. In addition, the predicted crystallization

  19. Race-specific genetic risk score is more accurate than nonrace-specific genetic risk score for predicting prostate cancer and high-grade diseases

    Science.gov (United States)

    Na, Rong; Ye, Dingwei; Qi, Jun; Liu, Fang; Lin, Xiaoling; Helfand, Brian T; Brendler, Charles B; Conran, Carly; Gong, Jian; Wu, Yishuo; Gao, Xu; Chen, Yaqing; Zheng, S Lilly; Mo, Zengnan; Ding, Qiang; Sun, Yinghao; Xu, Jianfeng

    2016-01-01

    Genetic risk score (GRS) based on disease risk-associated single nucleotide polymorphisms (SNPs) is an informative tool that can be used to provide inherited information for specific diseases in addition to family history. However, it is still unknown whether only SNPs that are implicated in a specific racial group should be used when calculating GRSs. The objective of this study is to compare the performance of race-specific GRS and nonrace-specific GRS for predicting prostate cancer (PCa) among 1338 patients underwent prostate biopsy in Shanghai, China. A race-specific GRS was calculated with seven PCa risk-associated SNPs implicated in East Asians (GRS7), and a nonrace-specific GRS was calculated based on 76 PCa risk-associated SNPs implicated in at least one racial group (GRS76). The means of GRS7 and GRS76 were 1.19 and 1.85, respectively, in the study population. Higher GRS7 and GRS76 were independent predictors for PCa and high-grade PCa in univariate and multivariate analyses. GRS7 had a better area under the receiver-operating curve (AUC) than GRS76 for discriminating PCa (0.602 vs 0.573) and high-grade PCa (0.603 vs 0.575) but did not reach statistical significance. GRS7 had a better (up to 13% at different cutoffs) positive predictive value (PPV) than GRS76. In conclusion, a race-specific GRS is more robust and has a better performance when predicting PCa in East Asian men than a GRS calculated using SNPs that are not shown to be associated with East Asians. PMID:27140652

  20. A random forest based risk model for reliable and accurate prediction of receipt of transfusion in patients undergoing percutaneous coronary intervention.

    Directory of Open Access Journals (Sweden)

    Hitinder S Gurm

    Full Text Available BACKGROUND: Transfusion is a common complication of Percutaneous Coronary Intervention (PCI and is associated with adverse short and long term outcomes. There is no risk model for identifying patients most likely to receive transfusion after PCI. The objective of our study was to develop and validate a tool for predicting receipt of blood transfusion in patients undergoing contemporary PCI. METHODS: Random forest models were developed utilizing 45 pre-procedural clinical and laboratory variables to estimate the receipt of transfusion in patients undergoing PCI. The most influential variables were selected for inclusion in an abbreviated model. Model performance estimating transfusion was evaluated in an independent validation dataset using area under the ROC curve (AUC, with net reclassification improvement (NRI used to compare full and reduced model prediction after grouping in low, intermediate, and high risk categories. The impact of procedural anticoagulation on observed versus predicted transfusion rates were assessed for the different risk categories. RESULTS: Our study cohort was comprised of 103,294 PCI procedures performed at 46 hospitals between July 2009 through December 2012 in Michigan of which 72,328 (70% were randomly selected for training the models, and 30,966 (30% for validation. The models demonstrated excellent calibration and discrimination (AUC: full model  = 0.888 (95% CI 0.877-0.899, reduced model AUC = 0.880 (95% CI, 0.868-0.892, p for difference 0.003, NRI = 2.77%, p = 0.007. Procedural anticoagulation and radial access significantly influenced transfusion rates in the intermediate and high risk patients but no clinically relevant impact was noted in low risk patients, who made up 70% of the total cohort. CONCLUSIONS: The risk of transfusion among patients undergoing PCI can be reliably calculated using a novel easy to use computational tool (https://bmc2.org/calculators/transfusion. This risk prediction

  1. Stable, high-order SBP-SAT finite difference operators to enable accurate simulation of compressible turbulent flows on curvilinear grids, with application to predicting turbulent jet noise

    Science.gov (United States)

    Byun, Jaeseung; Bodony, Daniel; Pantano, Carlos

    2014-11-01

    Improved order-of-accuracy discretizations often require careful consideration of their numerical stability. We report on new high-order finite difference schemes using Summation-By-Parts (SBP) operators along with the Simultaneous-Approximation-Terms (SAT) boundary condition treatment for first and second-order spatial derivatives with variable coefficients. In particular, we present a highly accurate operator for SBP-SAT-based approximations of second-order derivatives with variable coefficients for Dirichlet and Neumann boundary conditions. These terms are responsible for approximating the physical dissipation of kinetic and thermal energy in a simulation, and contain grid metrics when the grid is curvilinear. Analysis using the Laplace transform method shows that strong stability is ensured with Dirichlet boundary conditions while weaker stability is obtained for Neumann boundary conditions. Furthermore, the benefits of the scheme is shown in the direct numerical simulation (DNS) of a Mach 1.5 compressible turbulent supersonic jet using curvilinear grids and skew-symmetric discretization. Particularly, we show that the improved methods allow minimization of the numerical filter often employed in these simulations and we discuss the qualities of the simulation.

  2. Modification of the rib operon derived from Bacillus subtilis and its expression in Escherichia coli

    Institute of Scientific and Technical Information of China (English)

    Zhang Huitu; Meng Kun; Wang Yaru; Luo Huiying; Yuan Tiezheng; Yang Peilong; Bai Yingguo; Yao Bin; Fan Yunliu

    2007-01-01

    A riboflavin operon(rib operon)derived from Bacillus subtilis 368 was modified on structure and the resulting operons were expressed in various strains of Escherichia coli. The results showed that the optimization of the rib operon and the host strain used for expression are two main factors affecting the riboflavin production. Replacing the promoter l and rfn box of the rib operon with a strong constructive promoter spo l drastically increased the expression of the rib genes. When E. Coli JMl09 was used as the host strain, the highest riboflavin production reached 95.3μg/mL(about eight times higher than that 0f the unmodified rib operon). In addition, when tetracycline(20 μg/mL)was used as the selective pressure, compared with the ampicillin resistant transformants, a higher riboflavin yield Was obtained in tetracycline resistant host strain.

  3. Effect of Riboflavin Operon Dosage on Riboflavin Productivity in Bacillus Subtilis

    Institute of Scientific and Technical Information of China (English)

    CHEN Tao; CHEN Xun; WANG Jingyu; ZHAO Xueming

    2005-01-01

    After deregulating the purine and riboflavin synthesis in the Gram-positive bacterium Bacillus subtilis,it is critical to amplify riboflavin operon with appropriate dosage in the host strain for remarkable increase of riboflavin production.Bacillus subtilis RH13, a riboflavin-producing strain, was selected as host strain in the construction of engineering strains by protoplast fusion. The integrative plasmid pRB63 and autonomous plasmid pRB49, pRB62 containing riboflavin operon of B.subtilis 24 were constructed and transformed into the host strain respectively. Increasing one operon copy in B.subtilis RH13 results in about 0.4 g/L improvement in riboflavin yield and the appropriate number of operon copies was about 7-8. Amplifying more riboflavin operons is of no use for further improvement of yield of riboflavin. Furthermore, excessive operon dosage results in metabolic unbalance and is fatal to the host cells producing riboflavin.

  4. A New Strategy for Accurately Predicting I-V Electrical Characteristics of PV Modules Using a Nonlinear Five-Point Model

    Directory of Open Access Journals (Sweden)

    Sakaros Bogning Dongue

    2013-01-01

    Full Text Available This paper presents the modelling of electrical I-V response of illuminated photovoltaic crystalline modules. As an alternative method to the linear five-parameter model, our strategy uses advantages of a nonlinear analytical five-point model to take into account the effects of nonlinear variations of current with respect to solar irradiance and of voltage with respect to cells temperature. We succeeded in this work to predict with great accuracy the I-V characteristics of monocrystalline shell SP75 and polycrystalline GESOLAR GE-P70 photovoltaic modules. The good comparison of our calculated results to experimental data provided by the modules manufacturers makes it possible to appreciate the contribution of taking into account the nonlinear effect of operating conditions data on I-V characteristics of photovoltaic modules.

  5. Anthropometric variables accurately predict dual energy x-ray absorptiometric-derived body composition and can be used to screen for diabetes.

    Directory of Open Access Journals (Sweden)

    Reza Yavari

    Full Text Available The current world-wide epidemic of obesity has stimulated interest in developing simple screening methods to identify individuals with undiagnosed diabetes mellitus type 2 (DM2 or metabolic syndrome (MS. Prior work utilizing body composition obtained by sophisticated technology has shown that the ratio of abdominal fat to total fat is a good predictor for DM2 or MS. The goals of this study were to determine how well simple anthropometric variables predict the fat mass distribution as determined by dual energy x-ray absorptometry (DXA, and whether these are useful to screen for DM2 or MS within a population. To accomplish this, the body composition of 341 females spanning a wide range of body mass indices and with a 23% prevalence of DM2 and MS was determined using DXA. Stepwise linear regression models incorporating age, weight, height, waistline, and hipline predicted DXA body composition (i.e., fat mass, trunk fat, fat free mass, and total mass with good accuracy. Using body composition as independent variables, nominal logistic regression was then performed to estimate the probability of DM2. The results show good discrimination with the receiver operating characteristic (ROC having an area under the curve (AUC of 0.78. The anthropometrically-derived body composition equations derived from the full DXA study group were then applied to a group of 1153 female patients selected from a general endocrinology practice. Similar to the smaller study group, the ROC from logistical regression using body composition had an AUC of 0.81 for the detection of DM2. These results are superior to screening based on questionnaires and compare favorably with published data derived from invasive testing, e.g., hemoglobin A1c. This anthropometric approach offers promise for the development of simple, inexpensive, non-invasive screening to identify individuals with metabolic dysfunction within large populations.

  6. Is the predicted postoperative FEV1 estimated by planar lung perfusion scintigraphy accurate in patients undergoing pulmonary resection? Comparison of two processing methods

    International Nuclear Information System (INIS)

    Estimation of postoperative forced expiratory volume in 1 s (FEV1) with radionuclide lung scintigraphy is frequently used to define functional operability in patients undergoing lung resection. We conducted a study to outline the reliability of planar quantitative lung perfusion scintigraphy (QLPS) with two different processing methods to estimate the postoperative lung function in patients with resectable lung disease. Forty-one patients with a mean age of 57±12 years who underwent either a pneumonectomy (n=14) or a lobectomy (n=27) were included in the study. QLPS with Tc-99m macroaggregated albumin was performed. Both three equal zones were generated for each lung [zone method (ZM)] and more precise regions of interest were drawn according to their anatomical shape in the anterior and posterior projections [lobe mapping method (LMM)] for each patient. The predicted postoperative (ppo) FEV1 values were compared with actual FEV1 values measured on postoperative day 1 (pod1 FEV1) and day 7 (pod7 FEV1). The mean of preoperative FEV 1 and ppoFEV1 values was 2.10±0.57 and 1.57±0.44 L, respectively. The mean of Pod1FEV1 (1.04±0.30 L) was lower than ppoFEV1 (p0.05). PpoFEV1 values predicted by both the zone and LMMs overestimated the actual measured lung volumes in patients undergoing pulmonary resection in the early postoperative period. LMM is not superior to ZM. (author)

  7. The 17-Gene Ethanolamine (eut) Operon of Salmonella typhimurium Encodes Five Homologues of Carboxysome Shell Proteins

    OpenAIRE

    Kofoid, Eric; Rappleye, Chad; Stojiljkovic, Igor; Roth, John

    1999-01-01

    The eut operon of Salmonella typhimurium encodes proteins involved in the cobalamin-dependent degradation of ethanolamine. Previous genetic analysis revealed six eut genes that are needed for aerobic use of ethanolamine; one (eutR), encodes a positive regulator which mediates induction of the operon by vitamin B12 plus ethanolamine. The DNA sequence of the eut operon included 17 genes, suggesting a more complex pathway than that revealed genetically. We have correlated an open reading frame i...

  8. The pseudogenes of Mycobacterium leprae reveal the functional relevance of gene order within operons

    OpenAIRE

    Muro, E.M.; Mah, N.; Moreno-Hagelsieb, G.; Andrade-Navarro, M A

    2010-01-01

    Almost 50 years following the discovery of the prokaryotic operon, the functional relevance of gene order within operons remains unclear. In this work, we take advantage of the eroded genome of Mycobacterium leprae to add evidence supporting the notion that functionally less important genes have a tendency to be located at the end of its operons. M. leprae's genome includes 1133 pseudogenes and 1614 protein-coding genes and can be compared with the close genome of M. tuberculosis. Assuming M....

  9. The complete nucleotide sequence of the ilvGMEDA operon of Escherichia coli K-12

    OpenAIRE

    1987-01-01

    In this report we present the complete nucleotide sequence of the ilvGMEDA operon of Escherichia coli. This operon contains five genes encoding four of the five enzymes required for the biosynthesis of isoleucine and valine. We identify and describe the coding regions for these five structural genes and the structural and functional features of the flanking and internal regulatory regions of this operon. This new information contributes to a more complete understanding of the overall control ...

  10. Accurate prediction of the binding free energy and analysis of the mechanism of the interaction of replication protein A (RPA) with ssDNA.

    Science.gov (United States)

    Carra, Claudio; Cucinotta, Francis A

    2012-06-01

    The eukaryotic replication protein A (RPA) has several pivotal functions in the cell metabolism, such as chromosomal replication, prevention of hairpin formation, DNA repair and recombination, and signaling after DNA damage. Moreover, RPA seems to have a crucial role in organizing the sequential assembly of DNA processing proteins along single stranded DNA (ssDNA). The strong RPA affinity for ssDNA, K(A) between 10(-9)-10(-10) M, is characterized by a low cooperativity with minor variation for changes on the nucleotide sequence. Recently, new data on RPA interactions was reported, including the binding free energy of the complex RPA70AB with dC(8) and dC(5), which has been estimated to be -10 ± 0.4 kcal mol(-1) and -7 ± 1 kcal mol(-1), respectively. In view of these results we performed a study based on molecular dynamics aimed to reproduce the absolute binding free energy of RPA70AB with the dC(5) and dC(8) oligonucleotides. We used several tools to analyze the binding free energy, rigidity, and time evolution of the complex. The results obtained by MM-PBSA method, with the use of ligand free geometry as a reference for the receptor in the separate trajectory approach, are in excellent agreement with the experimental data, with ±4 kcal mol(-1) error. This result shows that the MM-PB(GB)SA methods can provide accurate quantitative estimates of the binding free energy for interacting complexes when appropriate geometries are used for the receptor, ligand and complex. The decomposition of the MM-GBSA energy for each residue in the receptor allowed us to correlate the change of the affinity of the mutated protein with the ΔG(gas+sol) contribution of the residue considered in the mutation. The agreement with experiment is optimal and a strong change in the binding free energy can be considered as the dominant factor in the loss for the binding affinity resulting from mutation. PMID:22116609

  11. Comparison of tryptophan biosynthetic operon regulation in different Gram-positive bacterial species.

    Science.gov (United States)

    Gutiérrez-Preciado, Ana; Yanofsky, Charles; Merino, Enrique

    2007-09-01

    The tryptophan biosynthetic operon has been widely used as a model system for studying transcription regulation. In Bacillus subtilis, the trp operon is primarily regulated by a tryptophan-activated RNA-binding protein, TRAP. Here we show that in many other Gram-positive species the trp operon is regulated differently, by tRNA(Trp) sensing by the RNA-based T-box mechanism, with T-boxes arranged in tandem. Our analyses reveal an apparent relationship between trp operon organization and the specific regulatory mechanism(s) used. PMID:17555843

  12. Accurate prediction of hard-sphere virial coefficients B6 to B12 from a compressibility-based equation of state

    Science.gov (United States)

    Hansen-Goos, Hendrik

    2016-04-01

    We derive an analytical equation of state for the hard-sphere fluid that is within 0.01% of computer simulations for the whole range of the stable fluid phase. In contrast, the commonly used Carnahan-Starling equation of state deviates by up to 0.3% from simulations. The derivation uses the functional form of the isothermal compressibility from the Percus-Yevick closure of the Ornstein-Zernike relation as a starting point. Two additional degrees of freedom are introduced, which are constrained by requiring the equation of state to (i) recover the exact fourth virial coefficient B4 and (ii) involve only integer coefficients on the level of the ideal gas, while providing best possible agreement with the numerical result for B5. Virial coefficients B6 to B10 obtained from the equation of state are within 0.5% of numerical computations, and coefficients B11 and B12 are within the error of numerical results. We conjecture that even higher virial coefficients are reliably predicted.

  13. nasST, two genes involved in the induction of the assimilatory nitrite-nitrate reductase operon (nasAB) of Azotobacter vinelandii.

    Science.gov (United States)

    Gutierrez, J C; Ramos, F; Ortner, L; Tortolero, M

    1995-11-01

    An operon including two new genes (nasS and nasT) has been defined, cloned and sequenced. The deduced NASS protein is homologous to NRTA from Synechococcus sp. and to NASF from Klebsiella pneumoniae, two proteins involved in nitrate uptake. The predicted NAST polypeptide is homologous to the regulator proteins of the two-component regulatory systems. NASS plays a negative regulatory role in the synthesis of the nitrate and nitrite reductase. NAST is required for the expression of the nitrite-nitrate reductase operon (nasAB). Expression of the nasST operon is not under the control of the NTR system and is not regulated by the nitrogen source. A Phi(nasA-lacZ) fusion has been used to analyse expression of the nasAB operon in three different genetic backgrounds with altered nitrate reductase activity. Beta-galactosidase activity in two of them was independent of nitrate but in a mutant unable to reduce nitrate, nas-4, it was normally induced by nitrate. PMID:8748040

  14. Dynamic behavior in mathematical models of the tryptophan operon

    Science.gov (United States)

    Santillán, Moisés; Mackey, Michael C.

    2001-03-01

    This paper surveys the general theory of operon regulation as first formulated by Goodwin and Griffith, and then goes on to consider in detail models of regulation of tryptophan production by Bliss, Sinha, and Santillán and Mackey, and the interrelationships between them. We further give a linear stability analysis of the Santillán and Mackey model for wild type E. coli as well as three different mutant strains that have been previously studied in the literature. This stability analysis indicates that the tryptophan production systems should be stable, which is in accord with our numerical results.

  15. Economy of operon formation: cotranscription minimizes shortfall in protein complexes.

    Science.gov (United States)

    Sneppen, Kim; Pedersen, Steen; Krishna, Sandeep; Dodd, Ian; Semsey, Szabolcs

    2010-01-01

    Genes of prokaryotes and Archaea are often organized in cotranscribed groups, or operons. In contrast, eukaryotic genes are generally transcribed independently. Here we show that there is a substantial economic gain for the cell to cotranscribe genes encoding protein complexes because it synchronizes the fluctuations, or noise, in the levels of the different components. This correlation substantially reduces the shortfall in production of the complex. This benefit is relatively large in small cells such as bacterial cells, in which there are few mRNAs and proteins per cell, and is diminished in larger cells such as eukaryotic cells. PMID:20877578

  16. act Operon Control of Developmental Gene Expression in Myxococcus xanthus

    OpenAIRE

    Gronewold, Thomas M. A.; Kaiser, Dale

    2002-01-01

    Cell-bound C-signal guides the building of a fruiting body and triggers the differentiation of myxospores. Earlier work has shown that transcription of the csgA gene, which encodes the C-signal, is directed by four genes of the act operon. To see how expression of the genes encoding components of the aggregation and sporulation processes depends on C-signaling, mutants with loss-of-function mutations in each of the act genes were investigated. These mutations were found to have no effect on g...

  17. The M. D. Anderson Symptom Inventory-Head and Neck Module, a Patient-Reported Outcome Instrument, Accurately Predicts the Severity of Radiation-Induced Mucositis

    International Nuclear Information System (INIS)

    Purpose: To compare the M. D. Anderson Symptom Inventory-Head and Neck (MDASI-HN) module, a symptom burden instrument, with the Functional Assessment of Cancer Therapy-Head and Neck (FACT-HN) module, a quality-of-life instrument, for the assessment of mucositis in patients with head-and-neck cancer treated with radiotherapy and to identify the most distressing symptoms from the patient's perspective. Methods and Materials: Consecutive patients with head-and-neck cancer (n = 134) completed the MDASI-HN and FACT-HN before radiotherapy (time 1) and after 6 weeks of radiotherapy or chemoradiotherapy (time 2). The mean global and subscale scores for each instrument were compared with the objective mucositis scores determined from the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0. Results: The global and subscale scores for each instrument showed highly significant changes from time 1 to time 2 and a significant correlation with the objective mucositis scores at time 2. Only the MDASI scores, however, were significant predictors of objective Common Terminology Criteria for Adverse Events mucositis scores on multivariate regression analysis (standardized regression coefficient, 0.355 for the global score and 0.310 for the head-and-neck cancer-specific score). Most of the moderate and severe symptoms associated with mucositis as identified on the MDASI-HN are not present on the FACT-HN. Conclusion: Both the MDASI-HN and FACT-HN modules can predict the mucositis scores. However, the MDASI-HN, a symptom burden instrument, was more closely associated with the severity of radiation-induced mucositis than the FACT-HN on multivariate regression analysis. This greater association was most likely related to the inclusion of a greater number of face-valid mucositis-related items in the MDASI-HN compared with the FACT-HN

  18. Rapid identification of sequences for orphan enzymes to power accurate protein annotation.

    Science.gov (United States)

    Ramkissoon, Kevin R; Miller, Jennifer K; Ojha, Sunil; Watson, Douglas S; Bomar, Martha G; Galande, Amit K; Shearer, Alexander G

    2013-01-01

    The power of genome sequencing depends on the ability to understand what those genes and their proteins products actually do. The automated methods used to assign functions to putative proteins in newly sequenced organisms are limited by the size of our library of proteins with both known function and sequence. Unfortunately this library grows slowly, lagging well behind the rapid increase in novel protein sequences produced by modern genome sequencing methods. One potential source for rapidly expanding this functional library is the "back catalog" of enzymology--"orphan enzymes," those enzymes that have been characterized and yet lack any associated sequence. There are hundreds of orphan enzymes in the Enzyme Commission (EC) database alone. In this study, we demonstrate how this orphan enzyme "back catalog" is a fertile source for rapidly advancing the state of protein annotation. Starting from three orphan enzyme samples, we applied mass-spectrometry based analysis and computational methods (including sequence similarity networks, sequence and structural alignments, and operon context analysis) to rapidly identify the specific sequence for each orphan while avoiding the most time- and labor-intensive aspects of typical sequence identifications. We then used these three new sequences to more accurately predict the catalytic function of 385 previously uncharacterized or misannotated proteins. We expect that this kind of rapid sequence identification could be efficiently applied on a larger scale to make enzymology's "back catalog" another powerful tool to drive accurate genome annotation.

  19. Unprecedented high-resolution view of bacterial operon architecture revealed by RNA sequencing.

    Science.gov (United States)

    Conway, Tyrrell; Creecy, James P; Maddox, Scott M; Grissom, Joe E; Conkle, Trevor L; Shadid, Tyler M; Teramoto, Jun; San Miguel, Phillip; Shimada, Tomohiro; Ishihama, Akira; Mori, Hirotada; Wanner, Barry L

    2014-01-01

    We analyzed the transcriptome of Escherichia coli K-12 by strand-specific RNA sequencing at single-nucleotide resolution during steady-state (logarithmic-phase) growth and upon entry into stationary phase in glucose minimal medium. To generate high-resolution transcriptome maps, we developed an organizational schema which showed that in practice only three features are required to define operon architecture: the promoter, terminator, and deep RNA sequence read coverage. We precisely annotated 2,122 promoters and 1,774 terminators, defining 1,510 operons with an average of 1.98 genes per operon. Our analyses revealed an unprecedented view of E. coli operon architecture. A large proportion (36%) of operons are complex with internal promoters or terminators that generate multiple transcription units. For 43% of operons, we observed differential expression of polycistronic genes, despite being in the same operons, indicating that E. coli operon architecture allows fine-tuning of gene expression. We found that 276 of 370 convergent operons terminate inefficiently, generating complementary 3' transcript ends which overlap on average by 286 nucleotides, and 136 of 388 divergent operons have promoters arranged such that their 5' ends overlap on average by 168 nucleotides. We found 89 antisense transcripts of 397-nucleotide average length, 7 unannotated transcripts within intergenic regions, and 18 sense transcripts that completely overlap operons on the opposite strand. Of 519 overlapping transcripts, 75% correspond to sequences that are highly conserved in E. coli (>50 genomes). Our data extend recent studies showing unexpected transcriptome complexity in several bacteria and suggest that antisense RNA regulation is widespread. Importance: We precisely mapped the 5' and 3' ends of RNA transcripts across the E. coli K-12 genome by using a single-nucleotide analytical approach. Our resulting high-resolution transcriptome maps show that ca. one-third of E. coli operons are

  20. Transcriptional Regulation of the Streptococcus salivarius 57.I Urease Operon

    Science.gov (United States)

    Chen, Yi-Ywan M.; Weaver, Cheryl A.; Mendelsohn, David R.; Burne, Robert A.

    1998-01-01

    The Streptococcus salivarius 57.I ure cluster was organized as an operon, beginning with ureI, followed by ureABC (structural genes) and ureEFGD (accessory genes). Northern analyses revealed transcripts encompassing structural genes and transcripts containing the entire operon. A ς70-like promoter could be mapped 5′ to ureI (PureI) by primer extension analysis. The intensity of the signal increased when cells were grown at an acidic pH and was further enhanced by excess carbohydrate. To determine the function(s) of two inverted repeats located 5′ to PureI, transcriptional fusions of the full-length promoter region (PureI), or a deletion derivative (PureIΔ100), and a promoterless chloramphenicol acetyltransferase (CAT) gene were constructed and integrated into the chromosome to generate strains PureICAT and PureIΔ100CAT, respectively. CAT specific activities of PureICAT were repressed at pH 7.0 and induced at pH 5.5 and by excess carbohydrate. In PureIΔ100CAT, CAT activity was 60-fold higher than in PureICAT at pH 7.0 and pH induction was nearly eliminated, indicating that expression was negatively regulated. Thus, it was concluded that PureI was the predominant, regulated promoter and that regulation was governed by a mechanism differing markedly from other known mechanisms for bacterial urease expression. PMID:9791132

  1. RNase III cleavage of Escherichia coli beta-galactosidase and tryptophan operon mRNA.

    OpenAIRE

    Shen, V; Imamoto, F; Schlessinger, D

    1982-01-01

    Purified RNase III of Escherichia coli cleaved the initial 479-nucleotide sequence of lac operon mRNA at four specific sites and also gave limited cleavage of trp operon mRNA. This action explains the inactivation of mRNA coding capacity by RNase III in vitro.

  2. Metabolic diversification--independent assembly of operon-like gene clusters in different plants.

    Science.gov (United States)

    Field, Ben; Osbourn, Anne E

    2008-04-25

    Operons are clusters of unrelated genes with related functions that are a feature of prokaryotic genomes. Here, we report on an operon-like gene cluster in the plant Arabidopsis thaliana that is required for triterpene synthesis (the thalianol pathway). The clustered genes are coexpressed, as in bacterial operons. However, despite the resemblance to a bacterial operon, this gene cluster has been assembled from plant genes by gene duplication, neofunctionalization, and genome reorganization, rather than by horizontal gene transfer from bacteria. Furthermore, recent assembly of operon-like gene clusters for triterpene synthesis has occurred independently in divergent plant lineages (Arabidopsis and oat). Thus, selection pressure may act during the formation of certain plant metabolic pathways to drive gene clustering.

  3. Metabolic diversification--independent assembly of operon-like gene clusters in different plants.

    Science.gov (United States)

    Field, Ben; Osbourn, Anne E

    2008-04-25

    Operons are clusters of unrelated genes with related functions that are a feature of prokaryotic genomes. Here, we report on an operon-like gene cluster in the plant Arabidopsis thaliana that is required for triterpene synthesis (the thalianol pathway). The clustered genes are coexpressed, as in bacterial operons. However, despite the resemblance to a bacterial operon, this gene cluster has been assembled from plant genes by gene duplication, neofunctionalization, and genome reorganization, rather than by horizontal gene transfer from bacteria. Furthermore, recent assembly of operon-like gene clusters for triterpene synthesis has occurred independently in divergent plant lineages (Arabidopsis and oat). Thus, selection pressure may act during the formation of certain plant metabolic pathways to drive gene clustering. PMID:18356490

  4. The mitochondrial genome and ribosomal operon of Brachycladium goliath (Digenea: Brachycladiidae) recovered from a stranded minke whale.

    Science.gov (United States)

    Briscoe, Andrew G; Bray, Rodney A; Brabec, Jan; Littlewood, D T J

    2016-06-01

    Members of the Brachycladiidae are known to cause pathologies implicated in cetacean strandings and it is important to develop accurate diagnostic markers to differentiate these and other helminths found in cetaceans. Brachycladium goliath (van Beneden, 1858) is a large trematode found, as adults, usually in the hepatic (bile) and pancreatic ducts of various cetaceans. Complete sequences were determined for the entire mitochondrial genome, and phylogenetically informative nuclear genes contained within the ribosomal operon, from a small piece of an individual worm taken from a common minke whale Balaenoptera acutorostrata Lacépède, 1804. Genomic DNA was sequenced using an Illumina MiSeq platform. The mtDNA is 15,229 bp in length consisting of 12 protein-coding genes, 22 tRNA genes, 2 rRNA genes and 2 non-coding regions of which the larger is comprised of 4 tandemly repeated units (260 bp each). The ribosomal RNA operon is 9297 bp long. These data provide a rich resource of molecular markers for diagnostics, phylogenetics and population genetics in order to better understand the role, and associated pathology of helminth infections in cetaceans. PMID:26883466

  5. Statistical analysis of accurate prediction of local atmospheric optical attenuation with a new model according to weather together with beam wandering compensation system: a season-wise experimental investigation

    Science.gov (United States)

    Arockia Bazil Raj, A.; Padmavathi, S.

    2016-07-01

    Atmospheric parameters strongly affect the performance of Free Space Optical Communication (FSOC) system when the optical wave is propagating through the inhomogeneous turbulent medium. Developing a model to get an accurate prediction of optical attenuation according to meteorological parameters becomes significant to understand the behaviour of FSOC channel during different seasons. A dedicated free space optical link experimental set-up is developed for the range of 0.5 km at an altitude of 15.25 m. The diurnal profile of received power and corresponding meteorological parameters are continuously measured using the developed optoelectronic assembly and weather station, respectively, and stored in a data logging computer. Measured meteorological parameters (as input factors) and optical attenuation (as response factor) of size [177147 × 4] are used for linear regression analysis and to design the mathematical model that is more suitable to predict the atmospheric optical attenuation at our test field. A model that exhibits the R2 value of 98.76% and average percentage deviation of 1.59% is considered for practical implementation. The prediction accuracy of the proposed model is investigated along with the comparative results obtained from some of the existing models in terms of Root Mean Square Error (RMSE) during different local seasons in one-year period. The average RMSE value of 0.043-dB/km is obtained in the longer range dynamic of meteorological parameters variations.

  6. vanO, a new glycopeptide resistance operon in environmental Rhodococcus equi isolates

    DEFF Research Database (Denmark)

    Gudeta, Dereje Dadi; Moodley, Arshnee; Bortolaia, Valeria;

    2014-01-01

    We describe sequence and gene organization of a new glycopeptide resistance operon (vanO) in Rhodococcus equi from soil. The vanO operon has low homology to enterococccal van operons and harbors a vanHOX cluster transcribed in opposite direction to the vanS-vanR regulatory system and comprised be...

  7. The rise of operon-like gene clusters in plants.

    Science.gov (United States)

    Boycheva, Svetlana; Daviet, Laurent; Wolfender, Jean-Luc; Fitzpatrick, Teresa B

    2014-07-01

    Gene clusters are common features of prokaryotic genomes also present in eukaryotes. Most clustered genes known are involved in the biosynthesis of secondary metabolites. Although horizontal gene transfer is a primary source of prokaryotic gene cluster (operon) formation and has been reported to occur in eukaryotes, the predominant source of cluster formation in eukaryotes appears to arise de novo or through gene duplication followed by neo- and sub-functionalization or translocation. Here we aim to provide an overview of the current knowledge and open questions related to plant gene cluster functioning, assembly, and regulation. We also present potential research approaches and point out the benefits of a better understanding of gene clusters in plants for both fundamental and applied plant science.

  8. Evolution of the Leukotoxin Operon in Genus Mannheimia

    DEFF Research Database (Denmark)

    Larsen, Jesper; Pedersen, Anders Gorm; Christensen, Henrik;

    The leukotoxin protein of Mannheimia haemolytica belongs to the HlyA-like subfamily of cytotoxic RTX (repeats in toxin) proteins. To test the hypothesis that different lineages of genus Mannheimia gained the leukotoxin operon via horizontal gene transfer we used a strategy that combines......RNA sequences; (iii) phylogeny of 24 leukotoxin gene sequences and 16 homologous genes retrieved from SWISS-PROT by using PSI-BLAST. Our data show no evidence for horizontal gene transfer into this clade. We propose that vertical descent from the common ancestor of genus Mannheimia, with subsequent loss...... of these genes in many strains can explain the patchy distribution of leukotoxin in this clade. Finally, we argue that antagonistic pleiotropy was the main contributor to gene loss in the radiating M. ruminalis lines, which have adapted to different ecological niches in the rumen offering different conditions...

  9. Evolution of the leukotoxin operon in genus Mannheimia

    DEFF Research Database (Denmark)

    Larsen, J.; Pedersen, A. G.; Christensen, H.;

    2005-01-01

    The leukotoxin protein of Mannheimia haemolytica belongs to the HlyA-like subfamily of cytotoxic RTX (repeats in toxin) proteins. To test the hypothesis that different lineages of genus Mannheimia gained the leukotoxin operon via horizontal gene transfer we used a strategy that combines......RNA sequences; (iii) phylogeny of 24 leukotoxin gene sequences and 16 homologous genes retrieved from SWISS-PROT by using PSI-BLAST. Our data show no evidence for horizontal gene transfer into this clade. We propose that vertical descent from the common ancestor of genus Mannheimia, with subsequent loss...... of these genes in many strains can explain the patchy distribution of leukotoxin in this clade. Finally, we argue that antagonistic pleiotropy was the main contributor to gene loss in the radiating M. ruminalis lines, which have adapted to different ecological niches in the rumen offering different conditions...

  10. The role of FIS in trans activation of stable RNA operons of E. coli.

    Science.gov (United States)

    Nilsson, L; Vanet, A; Vijgenboom, E; Bosch, L

    1990-03-01

    The thrU(tufB) operon of Escherichia coli is endowed with a cis-acting region upstream of the promoter, designated UAS for Upstream Activator Sequence. A protein fraction has been isolated that binds specifically to DNA fragments of the UAS, thus forming three protein-DNA complexes corresponding to three binding sites on the UAS. It stimulates in vitro transcription of the operon by facilitating the binding of the RNA polymerase to the promoter. All three protein-DNA complexes contain one and the same protein. Dissociation constants for the three complexes have been determined, the lowest being in the sub-nanomolar range. The protein also binds to the UAS of the tyrT operon and to the UAS upstream of the P1 promoter of the rrnB operon, suggesting that transcription of the three operons, if not of more stable RNA operons, is activated by a common trans activator. We demonstrate that the E.coli protein FIS (Factor for Inversion Stimulation) also binds to the UAS of the thrU(tufB) operon forming three protein-DNA complexes. A burst of UAS- and FIS-dependent promoter activity is observed after reinitiation of growth of stationary cultures in fresh medium. PMID:1690124

  11. Regulation of gene expression: Cryptic β-glucoside (bgl operon of Escherichia coli as a paradigm

    Directory of Open Access Journals (Sweden)

    Dharmesh Harwani

    2014-12-01

    Full Text Available Bacteria have evolved various mechanisms to extract utilizable substrates from available resources and consequently acquire fitness advantage over competitors. One of the strategies is the exploitation of cryptic cellular functions encoded by genetic systems that are silent under laboratory conditions, such as the bgl (β-glucoside operon of E. coli. The bgl operon of Escherichia coli, involved in the uptake and utilization of aromatic β-glucosides salicin and arbutin, is maintained in a silent state in the wild type organism by the presence of structural elements in the regulatory region. This operon can be activated by mutations that disrupt these negative elements. The fact that the silent bgl operon is retained without accumulating deleterious mutations seems paradoxical from an evolutionary view point. Although this operon appears to be silent, specific physiological conditions might be able to regulate its expression and/or the operon might be carrying out function(s apart from the utilization of aromatic β-glucosides. This is consistent with the observations that the activated operon confers a Growth Advantage in Stationary Phase (GASP phenotype to Bgl+ cells and exerts its regulation on at least twelve downstream target genes.

  12. Characterization of transcriptional regulation of the kdp operon of Salmonella typhimurium.

    OpenAIRE

    Frymier, J S; Reed, T. D.; Fletcher, S A; Csonka, L N

    1997-01-01

    The transcriptional control of the kdpFABC (K+ transport) operon of Salmonella typhimurium was characterized with a lacZ fusion. The kdpFABC operon of this organism was induced by K+ limitation and high osmolality, and osmotic induction was antagonized by a high concentration of K+. In the trkA (sapG) kdp+ mutant background, high concentrations of K+ inhibited growth, along with repressing the kdp operon. This result, which has not been reported for Escherichia coli, is inconsistent with the ...

  13. Autogenous regulation of ethanolamine utilization by a transcriptional activator of the eut operon in Salmonella typhimurium.

    OpenAIRE

    Roof, D M; Roth, J R

    1992-01-01

    The genes required for use of ethanolamine as a carbon and nitrogen source are encoded by a single operon (eut) whose expression is induced by the simultaneous presence of both ethanolamine and cobalamin (vitamin B12). The action of B12 as an inducer of this operon reflects the fact that this cofactor is required by the degradative enzyme ethanolamine lyase (eutBC). The eutR gene encodes a protein that activates transcription of the eut operon in response to the simultaneous presence of B12 a...

  14. Repression of the Escherichia coli modABCD (molybdate transport) operon by ModE.

    OpenAIRE

    Grunden, A M; Ray, R M; Rosentel, J K; Healy, F. G.; Shanmugam, K. T.

    1996-01-01

    The modABC gene products constitute the molybdate-specific transport system in Escherichia coli. Another operon coding for two proteins which diverges from the modABCD operon has been identified. The first gene of this operon codes for a 262-amino-acid protein, designated ModE (28 kDa), and the second genes codes for a 490-amino-acid protein. ModF (54 kDa). The role of ModF has not yet been determined; however, mutations in modE depressed modABCD transcription even in the presence of molybdat...

  15. BIOINFORMATICS AND BIOSYNTHESIS ANALYSIS OF CELLULOSE SYNTHASE OPERON IN ZYMOMONAS MOBILIS ZM4

    OpenAIRE

    Sheik Abdul Kader Sheik Asraf, K. Narayanan Rajnish, and Paramasamy Gunasekaran

    2011-01-01

    Biosynthesis of cellulose has been reported in many species of bacteria. The genes encoding cellulose biosynthetic enzymes of Z. mobilis have not been studied so far. Preliminary sequence analysis of the Z. mobilis ZM4 genome revealed the presence of a cellulose synthase operon comprised of Open Reading Frames (ORFs) ZMO01083 (bcsA), ZMO1084 (bcsB) and ZMO1085 (bcsC). The first gene of the operon bcsA encodes the cellulose synthase catalytic subunit BcsA. The second gene of the operon bcsB en...

  16. Identification of anthranilate and benzoate metabolic operons of Pseudomonas fluorescens and functional characterization of their promoter regions

    Directory of Open Access Journals (Sweden)

    Lee Vincent D

    2006-01-01

    Full Text Available Abstract Background In an effort to identify alternate recombinant gene expression systems in Pseudomonas fluorescens, we identified genes encoding two native metabolic pathways that were inducible with inexpensive compounds: the anthranilate operon (antABC and the benzoate operon (benABCD. Results The antABC and benABCD operons were identified by homology to the Acinetobacter sp. anthranilate operon and Pseudomonas putida benzoate operon, and were confirmed to be regulated by anthranilate or benzoate, respectively. Fusions of the putative promoter regions to the E. coli lacZ gene were constructed to confirm inducible gene expression. Each operon was found to be controlled by an AraC family transcriptional activator, located immediately upstream of the first structural gene in each respective operon (antR or benR. Conclusion We have found the anthranilate and benzoate promoters to be useful for tightly controlling recombinant gene expression at both small (

  17. Parallel Evolution and Horizontal Gene Transfer of the pst Operon in Firmicutes from Oligotrophic Environments

    Directory of Open Access Journals (Sweden)

    Alejandra Moreno-Letelier

    2011-01-01

    Full Text Available The high affinity phosphate transport system (pst is crucial for phosphate uptake in oligotrophic environments. Cuatro Cienegas Basin (CCB has extremely low P levels and its endemic Bacillus are closely related to oligotrophic marine Firmicutes. Thus, we expected the pst operon of CCB to share the same evolutionary history and protein similarity to marine Firmicutes. Orthologs of the pst operon were searched in 55 genomes of Firmicutes and 13 outgroups. Phylogenetic reconstructions were performed for the pst operon and 14 concatenated housekeeping genes using maximum likelihood methods. Conserved domains and 3D structures of the phosphate-binding protein (PstS were also analyzed. The pst operon of Firmicutes shows two highly divergent clades with no correlation to the type of habitat nor a phylogenetic congruence, suggesting horizontal gene transfer. Despite sequence divergence, the PstS protein had a similar 3D structure, which could be due to parallel evolution after horizontal gene transfer events.

  18. Cycling expression and cooperative operator interaction in the trp operon of Escherichia coli.

    Science.gov (United States)

    Hernández-Valdez, Areli; Santillán, Moisés; Zeron, Eduardo S

    2010-04-01

    Oscillatory behaviour in the tryptophan operon of an Escherichia coli mutant strain lacking the enzyme-inhibition regulatory mechanism has been observed by Bliss et al. but not confirmed by others. This behaviour could be important from the standpoint of synthetic biology, whose goals include the engineering of intracellular genetic oscillators. This work is devoted to investigating, from a mathematical modelling point of view, the possibility that the trp operon of the E. coli inhibition-free strain expresses cyclically. For that we extend a previously introduced model for the regulatory pathway of the tryptophan operon in Escherichia coli to account for the observed multiplicity and cooperativity of repressor binding sites. Thereafter we investigate the model dynamics using deterministic numeric solutions, stochastic simulations, and analytic studies. Our results suggest that a quasi-periodic behaviour could be observed in the trp operon expression level of single bacteria. PMID:20004672

  19. Physiological studies of tryptophan transport and tryptophanase operon induction in Escherichia coli.

    OpenAIRE

    Yanofsky, C; Horn, V.; Gollnick, P

    1991-01-01

    Escherichia coli forms three permeases that can transport the amino acid tryptophan: Mtr, AroP, and TnaB. The structural genes for these permeases reside in separate operons that are subject to different mechanisms of regulation. We have exploited the fact that the tryptophanase (tna) operon is induced by tryptophan to infer how tryptophan transport is influenced by the growth medium and by mutations that inactivate each of the permease proteins. In an acid-hydrolyzed casein medium, high leve...

  20. Identification and characterization of an operon in Salmonella typhimurium involved in thiamine biosynthesis.

    OpenAIRE

    Petersen, L A; Downs, D M

    1997-01-01

    Thiamine pyrophosphate (TPP) is synthesized de novo in Salmonella typhimurium and is a required cofactor for many enzymes in the cell. Five kinase activities have been implicated in TPP synthesis, which involves joining a 4-methyl-5-(beta-hydroxyethyl)thiazole (THZ) moiety and a 4-amino-5-hydroxymethyl-2-methylpyrimidine (HMP) moiety. We report here identification of a 2-gene operon involved in thiamine biosynthesis and present evidence that the genes in this operon, thiMD, encode two previou...

  1. Analysis of the puc Operon Promoter from Rhodobacter capsulatus

    Science.gov (United States)

    Nickens, David G.; Bauer, Carl E.

    1998-01-01

    Expression of the Rhodobacter capsulatus puc operon, which codes for structural polypeptides of the light-harvesting-II peripheral antenna complex, is highly regulated in response to alterations in oxygen tension and light intensity. To obtain an understanding of the puc promoter region we report the high-resolution 5′ mapping of the puc mRNA transcriptional start site and DNA sequence analysis of the puc upstream regulatory sequence (pucURS). A ς70-type promoter sequence was identified (pucP1) which has a high degree of sequence similarity with carotenoid and bacteriochlorophyll biosynthesis promoters. Inspection of the DNA sequence also indicated the presence of two CrtJ and four integration host factor (IHF) binding sites. Transcriptional fusions of the pucURS fused to lacZ also confirmed that puc promoter activity is regulated by the transcriptional regulators IHF, CrtJ, and RegA. Gel retardation analysis using cell extracts indicates that mutations in IHF and RegA disrupt protein binding to DNA fragments containing the pucURS. PMID:9696778

  2. Sequence analysis of the Legionella micdadei groELS operon

    DEFF Research Database (Denmark)

    Hindersson, P; Høiby, N; Bangsborg, Jette Marie

    1991-01-01

    A 2.7 kb DNA fragment encoding the 60 kDa common antigen (CA) and a 13 kDa protein of Legionella micdadei was sequenced. Two open reading frames of 57,677 and 10,456 Da were identified, corresponding to the heat shock proteins GroEL and GroES, respectively. Typical -35, -10, and Shine-Dalgarno he......, Western blot analysis with an L. micdadei specific anti-groEL antibody did not reveal a significant increase in the amount of the GroEL protein during heat shock in L. micdadei or in the recombinant E. coli expressing L. micdadei GroEL.......A 2.7 kb DNA fragment encoding the 60 kDa common antigen (CA) and a 13 kDa protein of Legionella micdadei was sequenced. Two open reading frames of 57,677 and 10,456 Da were identified, corresponding to the heat shock proteins GroEL and GroES, respectively. Typical -35, -10, and Shine-Dalgarno heat...... shock expression signals were identified upstream of the L. micdadei groEL gene. Further upstream, a poly-T region, also a feature of the sigma 32-regulated Escherichia coli groELS heat shock operon, was found. Despite the high degree of homology of the expression signals in E. coli and L. micdadei...

  3. Bacterial cellulose biosynthesis: diversity of operons, subunits, products and functions

    Science.gov (United States)

    Römling, Ute; Galperin, Michael Y.

    2015-01-01

    Summary Recent studies of bacterial cellulose biosynthesis, including structural characterization of a functional cellulose synthase complex, provided the first mechanistic insight into this fascinating process. In most studied bacteria, just two subunits, BcsA and BcsB, are necessary and sufficient for the formation of the polysaccharide chain in vitro. Other subunits – which differ among various taxa – affect the enzymatic activity and product yield in vivo by modulating expression of biosynthesis apparatus, export of the nascent β-D-glucan polymer to the cell surface, and the organization of cellulose fibers into a higher-order structure. These auxiliary subunits play key roles in determining the quantity and structure of the resulting biofilm, which is particularly important for interactions of bacteria with higher organisms that lead to rhizosphere colonization and modulate virulence of cellulose-producing bacterial pathogens inside and outside of host cells. Here we review the organization of four principal types of cellulose synthase operons found in various bacterial genomes, identify additional bcs genes that encode likely components of the cellulose biosynthesis and secretion machinery, and propose a unified nomenclature for these genes and subunits. We also discuss the role of cellulose as a key component of biofilms formed by a variety of free-living and pathogenic bacteria and, for the latter, in the choice between acute infection and persistence in the host. PMID:26077867

  4. Organization and expression of photosynthesis genes and operons in anoxygenic photosynthetic proteobacteria.

    Science.gov (United States)

    Liotenberg, Sylviane; Steunou, Anne-Soisig; Picaud, Martine; Reiss-Husson, Françoise; Astier, Chantal; Ouchane, Soufian

    2008-09-01

    Genes belonging to the same metabolic route are usually organized in operons in microbial genomes. For instance, most genes involved in photosynthesis were found clustered and organized in operons in photosynthetic Alpha- and Betaproteobacteria. The discovery of Gammaproteobacteria with a conserved photosynthetic gene cluster revives the questions on the role and the maintenance of such organization in proteobacteria. In this paper, we report the analysis of the structure and expression of the 14 kb cluster (crtEF-bchCXYZ-pufBALMC-crtADC) in the photosynthetic betaproteobacterium Rubrivivax gelatinosus, with the purpose of understanding the reasons and the biological constraints that might have led to the clustering of photosynthesis genes. The genetic analyses are substantiated by reverse transcription-PCR data which reveal the presence of a transcript encompassing the 14 genes and provide evidence of a polycistronic 'super-operon' organization starting at crtE and ending 14 kb downstream at the crtC gene. Furthermore, genetic analyses suggest that one of the selection pressures that may have driven and maintained the photosynthesis operons/super-operons in proteobacteria could very likely be the coexpression and regulation of the clustered genes/operon.

  5. Solving a discrete model of the lac operon using Z3

    Science.gov (United States)

    Gutierrez, Natalia A.

    2014-05-01

    A discrete model for the Lcac Operon is solved using the SMT-solver Z3. Traditionally the Lac Operon is formulated in a continuous math model. This model is a system of ordinary differential equations. Here, it was considerated as a discrete model, based on a Boolean red. The biological problem of Lac Operon is enunciated as a problem of Boolean satisfiability, and it is solved using an STM-solver named Z3. Z3 is a powerful solver that allows understanding the basic dynamic of the Lac Operon in an easier and more efficient way. The multi-stability of the Lac Operon can be easily computed with Z3. The code that solves the Boolean red can be written in Python language or SMT-Lib language. Both languages were used in local version of the program as online version of Z3. For future investigations it is proposed to solve the Boolean red of Lac Operon using others SMT-solvers as cvc4, alt-ergo, mathsat and yices.

  6. The Rhodomonas salina mitochondrial genome: bacteria-like operons, compact gene arrangement and complex repeat region.

    Science.gov (United States)

    Hauth, Amy M; Maier, Uwe G; Lang, B Franz; Burger, Gertraud

    2005-01-01

    To gain insight into the mitochondrial genome structure and gene content of a putatively ancestral group of eukaryotes, the cryptophytes, we sequenced the complete mitochondrial DNA of Rhodomonas salina. The 48 063 bp circular-mapping molecule codes for 2 rRNAs, 27 tRNAs and 40 proteins including 23 components of oxidative phosphorylation, 15 ribosomal proteins and two subunits of tat translocase. One potential protein (ORF161) is without assigned function. Only two introns occur in the genome; both are present within cox1 belong to group II and contain RT open reading frames. Primitive genome features include bacteria-like rRNAs and tRNAs, ribosomal protein genes organized in large clusters resembling bacterial operons and the presence of the otherwise rare genes such as rps1 and tatA. The highly compact gene organization contrasts with the presence of a 4.7 kb long, repeat-containing intergenic region. Repeat motifs approximately 40-700 bp long occur up to 31 times, forming a complex repeat structure. Tandem repeats are the major arrangement but the region also includes a large, approximately 3 kb, inverted repeat and several potentially stable approximately 40-80 bp long hairpin structures. We provide evidence that the large repeat region is involved in replication and transcription initiation, predict a promoter motif that occurs in three locations and discuss two likely scenarios of how this highly structured repeat region might have evolved.

  7. The nasFEDCBA operon for nitrate and nitrite assimilation in Klebsiella pneumoniae M5al.

    Science.gov (United States)

    Lin, J T; Goldman, B S; Stewart, V

    1994-05-01

    Klebsiella pneumoniae can use nitrate and nitrite as sole nitrogen sources through the nitrate assimilation pathway. We previously identified structural genes for assimilatory nitrate and nitrite reductases, nasA and nasB, respectively. We report here our further identification of four genes, nasFEDC, upstream of the nasBA genes. The nasFEDCBA genes probably form an operon. Mutational and complementation analyses indicated that both the nasC and nasA genes are required for nitrate assimilation. The predicted NASC protein is homologous to a variety of NADH-dependent oxidoreductases. Thus, the NASC protein probably mediates electron transfer from NADH to the NASA protein, which contains the active site for nitrate reduction. The deduced NASF, NASE, and NASD proteins are homologous to the NRTA, NRTB, and NRTD proteins, respectively, that are involved in nitrate uptake in Synechococcus sp. (T. Omata, X. Andriesse, and A. Hirano, Mol. Gen. Genet. 236:193-202, 1993). Mutational and complementation studies indicated that the nasD gene is required for nitrate but not nitrite assimilation. By analogy with the Synechococcus nrt genes, we propose that the nasFED genes are involved in nitrate transport in K. pneumoniae. PMID:8169203

  8. Tandem attenuators control expression of the Salmonella mgtCBR virulence operon.

    Science.gov (United States)

    Lee, Eun-Jin; Groisman, Eduardo A

    2012-10-01

    The mgtCBR operon from Salmonella enterica serovar Typhimurium specifies the virulence protein MgtC, the Mg(2+) transporter MgtB and the regulatory peptide MgtR. The mgtCBR transcript includes a long leader region harbouring two short open reading frames (ORFs). Translation of these ORFs is anticipated to impact the formation of particular stem-loop structures and control transcription of the coding region by an attenuation-like mechanism. We previously reported that ORF mgtM enables Salmonella to promote transcription of the mgtC and mgtB coding regions when experiencing a rise in cytoplasmic ATP levels. We now show that the proline codon-rich ORF mgtP mediates an increase in transcription of the mgtC and mgtB coding regions under conditions predicted to decrease the levels of proline-charged tRNA(Pro) . The high ATP and low proline signals act independently in an additive form. Replacing conserved mgtP proline codons with codons specifying other amino acids abolished the response to proline limitation but had no effect on the response to ATP. Substitution of conserved adenine nucleotides in mgtM abolished the response to ATP but had no effect in the response to proline limitation. This provides a singular example of a leader mRNA with tandem attenuators responding to different signals. PMID:22857388

  9. FIS-dependent trans activation of stable RNA operons of Escherichia coli under various growth conditions.

    Science.gov (United States)

    Nilsson, L; Verbeek, H; Vijgenboom, E; van Drunen, C; Vanet, A; Bosch, L

    1992-02-01

    In Escherichia coli transcription of the tRNA operon thrU (tufB) and the rRNA operon rrnB is trans-activated by the protein FIS. This protein, which stimulates the inversion of various viral DNA segments, binds specifically to a cis-acting sequence (designated UAS) upstream of the promoter of thrU (tufB) and the P1 promoter of the rrnB operon. There are indications that this type of regulation is representative for the regulation of more stable RNA operons. In the present investigation we have studied UAS-dependent transcription activation of the thrU (tufB) operon in the presence and absence of FIS during a normal bacterial growth cycle and after a nutritional shift-up. In early log phase the expression of the operon rises steeply in wild-type cells, whereafter it declines. Concomitantly, a peak of the cellular FIS concentration is observed. Cells in the stationary phase are depleted of FIS. The rather abrupt increase of transcription activation depends on the nutritional quality of the medium. It is not seen in minimal medium. After a shift from minimal to rich medium, a peak of transcription activation and of FIS concentration is measured. This peak gets higher as the medium gets more strongly enriched. We conclude that a correlation between changes of the UAS-dependent activation of the thrU (tufB) operon and changes of the cellular FIS concentration under a variety of experimental conditions exists. This correlation strongly suggests that the production of FIS responds to environmental signals, thereby trans-activating the operon. Cells unable to produce FIS (fis cells) also show an increase of operon transcription in the early log phase and after a nutritional shift-up, albeit less pronounced than that wild-type cells. Presumably it is controlled by the ribosome feedback regulatory system. cis activation of the operon by the upstream activator sequence is apparent in the absence of FIS. This activation is constant throughout the entire growth cycle and is

  10. Cloning of the cnr operon into a strain of Bacillaceae bacterium for the development of a suitable biosorbent.

    Science.gov (United States)

    Fosso-Kankeu, Elvis; Mulaba-Bafubiandi, Antoine F; Piater, Lizelle A; Tlou, Matsobane G

    2016-07-01

    In this study, a potential microbial biosorbent was engineered to improve its capacity to remediate heavy metal contaminated water resources. A Bacillaceae bacterium isolated from a mining area was transformed with a plasmid carrying the (pECD312)-based cnr operon that encodes nickel and cobalt resistance. The bioadsorption ability of the transformed strain was evaluated for removal of nickel from metallurgical water relative to the wildtype strain. Results showed that transformation improved the adsorption capacity of the bacterium by 37 % at nickel concentrations equivalent to 150 mg/L. Furthermore it was possible to apply prediction modelling to study the bioadsorption behaviour of the transformed strain. As such, this work may be extended to the design of a nickel bioremediation plant utilising the newly developed Bacillaceae bacterium as a biosorbent. PMID:27263009

  11. Prediction

    CERN Document Server

    Sornette, Didier

    2010-01-01

    This chapter first presents a rather personal view of some different aspects of predictability, going in crescendo from simple linear systems to high-dimensional nonlinear systems with stochastic forcing, which exhibit emergent properties such as phase transitions and regime shifts. Then, a detailed correspondence between the phenomenology of earthquakes, financial crashes and epileptic seizures is offered. The presented statistical evidence provides the substance of a general phase diagram for understanding the many facets of the spatio-temporal organization of these systems. A key insight is to organize the evidence and mechanisms in terms of two summarizing measures: (i) amplitude of disorder or heterogeneity in the system and (ii) level of coupling or interaction strength among the system's components. On the basis of the recently identified remarkable correspondence between earthquakes and seizures, we present detailed information on a class of stochastic point processes that has been found to be particu...

  12. Speaking Fluently And Accurately

    Institute of Scientific and Technical Information of China (English)

    JosephDeVeto

    2004-01-01

    Even after many years of study,students make frequent mistakes in English. In addition, many students still need a long time to think of what they want to say. For some reason, in spite of all the studying, students are still not quite fluent.When I teach, I use one technique that helps students not only speak more accurately, but also more fluently. That technique is dictations.

  13. Accurate Finite Difference Algorithms

    Science.gov (United States)

    Goodrich, John W.

    1996-01-01

    Two families of finite difference algorithms for computational aeroacoustics are presented and compared. All of the algorithms are single step explicit methods, they have the same order of accuracy in both space and time, with examples up to eleventh order, and they have multidimensional extensions. One of the algorithm families has spectral like high resolution. Propagation with high order and high resolution algorithms can produce accurate results after O(10(exp 6)) periods of propagation with eight grid points per wavelength.

  14. Frequency of pap and pil operons in Escherichia coli strains associated with urinary infections.

    Science.gov (United States)

    Perugini, M R; Vidotto, M C

    1996-03-01

    Strains of E. coli isolated from patients with urinary tract infection were examined for P and type 1 adhesin production by colony hybridization with pap and pil operons. The P pili probe detected 45 (46.4%) of the total of 97 strains studied and the type 1 pili probe detected 83 (85.6%). The pap operon was detected in 39 (53.4%) of 73 strains isolated from urine of patients with urinary disease and in 6 (25.0%) of 24 strains isolated from feces of healthy individuals employed as controls (P = 0.029), and the pil operon was detected in 67 (91.8%) of the urinary strains and in 16 (66.6%) of the fecal strains (P = 0.007). Our data did not show significant differences in frequency of P pili among isolates from pyelonephritis (78.5%), cystitis (45.8%) and asymptomatic bacteriuria (54.5%). Type 1 pili were not associated with the different types of infection; the frequency of these pili was 100% in pyelonephritis and in asymptomatic bacteriuria, and 87.5% in cystitis. The incidence of pap operon in strains isolated from pyelonephritis and from asymptomatic bacteriuria was higher in 11- to 40-year old women. These data show a high frequency of pap and pil operons among uropathogenic strains of E. coli, which seems to be an important factor in the development of urinary infection.

  15. Artificial citrate operon and Vitreoscilla hemoglobin gene enhanced mineral phosphate solubilizing ability of Enterobacter hormaechei DHRSS.

    Science.gov (United States)

    Yadav, Kavita; Kumar, Chanchal; Archana, G; Kumar, G Naresh

    2014-10-01

    Mineral phosphate solubilization by bacteria is mediated through secretion of organic acids, among which citrate is one of the most effective. To overproduce citrate in bacterial systems, an artificial citrate operon comprising of genes encoding NADH-insensitive citrate synthase of E. coli and Salmonella typhimurium sodium-dependent citrate transporter was constructed. In order to improve its mineral phosphate solubilizing (MPS) ability, the citrate operon was incorporated into E. hormaechei DHRSS. The artificial citrate operon transformant secreted 7.2 mM citric acid whereas in the native strain, it was undetectable. The transformant released 0.82 mM phosphate in flask studies in buffered medium containing rock phosphate as sole P source. In fermenter studies, similar phenotype was observed under aerobic conditions. However, under microaerobic conditions, no citrate was detected and P release was not observed. Therefore, an artificial citrate gene cluster containing Vitreoscilla hemoglobin (vgb) gene under its native promoter, along with artificial citrate operon under constitutive tac promoter, was constructed and transformed into E. hormaechei DHRSS. This transformant secreted 9 mM citric acid under microaerobic conditions and released 1.0 mM P. Thus, incorporation of citrate operon along with vgb gene improves MPS ability of E. hormaechei DHRSS under buffered, microaerobic conditions mimicking rhizospheric environment.

  16. The pyrimidine operon pyrRPB-carA from Lactococcus lactis

    DEFF Research Database (Denmark)

    Martinussen, Jan; Schallert, J.; Andersen, Birgit;

    2001-01-01

    The four genes pyrR, pyrP, pyrB, and carA were found to constitute an operon in Lactococcus lactis subsp, lactis MG1363. The functions of the different genes were established by mutational analysis. The first gene in the operon is the pyrimidine regulatory gene, pyrR, which is responsible for the...... regulation of the expression of the pyrimidine biosynthetic genes leading to UMP formation. The second gene encodes a membrane-bound high-affinity uracil permease, required for utilization of exogenous uracil. The last two genes in the operon, pyrB and carA, encode pyrimidine biosynthetic enzymes; aspartate...... transcarbamoylase (pyrB) is the second enzyme in the pathway, whereas carbamoyl-phosphate synthetase subunit A (carA) is the small subunit of a heterodimeric enzyme, catalyzing the formation of carbamoyl phosphate. The carA gene product is shown to be required for both pyrimidine and arginine biosynthesis. The...

  17. The diversity of membrane transporters encoded in bacterial arsenic-resistance operons

    Directory of Open Access Journals (Sweden)

    Yiren Yang

    2015-05-01

    Full Text Available Transporter-facilitated arsenite extrusion is the major pathway of arsenic resistance within bacteria. So far only two types of membrane-bound transporter proteins, ArsB and ArsY (ACR3, have been well studied, although the arsenic transporters in bacteria display considerable diversity. Utilizing accumulated genome sequence data, we searched arsenic resistance (ars operons in about 2,500 bacterial strains and located over 700 membrane-bound transporters which are encoded in these operons. Sequence analysis revealed at least five distinct transporter families, with ArsY being the most dominant, followed by ArsB, ArsP (a recently reported permease family, Major Facilitator protein Superfamily (MFS and Major Intrinsic Protein (MIP. In addition, other types of transporters encoded in the ars operons were found, but in much lower frequencies. The diversity and evolutionary relationships of these transporters with regard to arsenic resistance will be discussed.

  18. Expression and regulation of the ery operon of Brucella melitensis in human trophoblast cells

    Science.gov (United States)

    Zhang, Hui; Dou, Xiaoxia; Li, Zhiqiang; Zhang, Yu; Zhang, Jing; Guo, Fei; Wang, Yuanzhi; Wang, Zhen; Li, Tiansen; Gu, Xinli; Chen, Chuangfu

    2016-01-01

    Brucellosis is primarily a disease of domestic animals in which the bacteria localizes to fetal tissues such as embryonic trophoblast cells and fluids containing erythritol, which stimulates Brucella spp. growth. The utilization of erythritol is a characteristic of the genus Brucella. The ery operon contains four genes (eryA, eryB, eryC and eryD) for the utilization of erythritol, and plays a major role in the survival and multiplication of Brucella spp. The objective of the present study was to conduct a preliminary characterization of differential genes expression of the ery operon at several time points after Brucella infected embryonic trophoblast cells (HPT-8 cells). The result showed that the ery operon expression was higher in HPT-8 cells compared with the medium. The relative expression of eryA, eryB and eryC peaked at 2 h post-infection in HPT-8 cells, and eryD expression peaked at 3 h post-infection. The expression of eryA, eryB and eryC may be inhibited by increased eryD expression. However, the expression of the ery operon was stable in the presence of erythritol in cells. 2308Δery and 027Δery mutants of the ery operon were successfully constructed by homologous recombination, which were attenuated in RAW 264.7 murine macrophages. The characterization of the ery operon genes and their expression profiles in response to Brucella infection further contributes to our understanding of the molecular mechanisms of infection and the pathogenesis of brucellosis. PMID:27698777

  19. Interplay of protein and DNA structure revealed in simulations of the lac operon.

    Directory of Open Access Journals (Sweden)

    Luke Czapla

    Full Text Available The E. coli Lac repressor is the classic textbook example of a protein that attaches to widely spaced sites along a genome and forces the intervening DNA into a loop. The short loops implicated in the regulation of the lac operon suggest the involvement of factors other than DNA and repressor in gene control. The molecular simulations presented here examine two likely structural contributions to the in-vivo looping of bacterial DNA: the distortions of the double helix introduced upon association of the highly abundant, nonspecific nucleoid protein HU and the large-scale deformations of the repressor detected in low-resolution experiments. The computations take account of the three-dimensional arrangements of nucleotides and amino acids found in crystal structures of DNA with the two proteins, the natural rest state and deformational properties of protein-free DNA, and the constraints on looping imposed by the conformation of the repressor and the orientation of bound DNA. The predicted looping propensities capture the complex, chain-length-dependent variation in repression efficacy extracted from gene expression studies and in vitro experiments and reveal unexpected chain-length-dependent variations in the uptake of HU, the deformation of repressor, and the folding of DNA. Both the opening of repressor and the presence of HU, at levels approximating those found in vivo, enhance the probability of loop formation. HU affects the global organization of the repressor and the opening of repressor influences the levels of HU binding to DNA. The length of the loop determines whether the DNA adopts antiparallel or parallel orientations on the repressor, whether the repressor is opened or closed, and how many HU molecules bind to the loop. The collective behavior of proteins and DNA is greater than the sum of the parts and hints of ways in which multiple proteins may coordinate the packaging and processing of genetic information.

  20. Evidence for Vertical Inheritance and Loss of the Leukotoxin Operon in Genus Mannheimia

    DEFF Research Database (Denmark)

    Larsen, Jesper; Pedersen, Anders Gorm; Christensen, Henrik;

    2007-01-01

    as a commensal in the ovine rumen. We have tested the hypothesis that horizontal gene transfer of the leukotoxin operon has catalyzed pathogenic adaptation and speciation of M. haemolytica + M. glucosida, or other major subclades, by using a strategy that combines compositional and phylogenetic methods. We show....... On one hand, it opposes the hypothesis of horizontal gene transfer as a catalyst of pathogenic adaptation and speciation. On the other hand, it indicates that losses of the leukotoxin operons in the radiating lineages of M. ruminalis have catalyzed their adaptation to a commensal environment...

  1. Regulation of the Bacillus subtilis ytmI Operon, Involved in Sulfur Metabolism

    OpenAIRE

    Burguière, Pierre; Fert, Juliette; Guillouard, Isabelle; Auger, Sandrine; Danchin, Antoine; Martin-Verstraete, Isabelle

    2005-01-01

    The YtlI regulator of Bacillus subtilis activates the transcription of the ytmI operon encoding an l-cystine ABC transporter, a riboflavin kinase, and proteins of unknown function. The expression of the ytlI gene and the ytmI operon was high with methionine and reduced with sulfate. Using deletions and site-directed mutagenesis, a cis-acting DNA sequence important for YtlI-dependent regulation was identified upstream from the −35 box of ytmI. Gel mobility shift assays confirmed that YtlI spec...

  2. Sequencing and Characterization of the xyl Operon of a Gram-Positive Bacterium, Tetragenococcus halophila

    OpenAIRE

    TAKEDA, YASUO; Takase, Kazuma; Yamato, Ichiro; Abe, Keietsu

    1998-01-01

    The xyl operon of a gram-positive bacterium, Tetragenococcus halophila (previously called Pediococcus halophilus), was cloned and sequenced. The DNA was about 7.7 kb long and contained genes for a ribose binding protein and part of a ribose transporter, xylR (a putative regulatory gene), and the xyl operon, along with its regulatory region and transcription termination signal, in this order. The DNA was AT rich, the GC content being 35.8%, consistent with the GC content of this gram-positive ...

  3. Autoregulation of the stability operon of IncFII plasmid NR1.

    OpenAIRE

    Tabuchi, A; Min, Y N; Womble, D D; Rownd, R H

    1992-01-01

    The stb locus of IncFII plasmid NR1, which mediates stable inheritance of the plasmid, is composed of an essential cis-acting DNA site located upstream from two tandem genes that encode essential stability proteins. The two tandem genes, stbA and stbB, are transcribed as an operon from promoter PAB. Using PAB-lacZ gene fusions, it was found that the stb operon is autoregulated. A low-copy-number stb+ plasmid introduced into the same cell with the PAB-lacZ fusion plasmid repressed beta-galacto...

  4. Molecular characterization of the mde operon involved in L-methionine catabolism of Pseudomonas putida.

    OpenAIRE

    H. Inoue; Inagaki, K.; Eriguchi, S I; Tamura, T.; Esaki, N; Soda, K; Tanaka, H.

    1997-01-01

    A 15-kb region of Pseudomonas putida chromosomal DNA containing the mde operon and an upstream regulatory gene (mdeR) has been cloned and sequenced. The mde operon contains two structural genes involved in L-methionine degradative metabolism: the already-identified mdeA, which encodes L-methionine gamma-lyase (H. Inoue, K. Inagaki, M. Sugimoto, N. Esaki, K. Soda, and H. Tanaka. J. Biochem. (Tokyo) 117:1120-1125, 1995), and mdeB, which encodes a homologous protein to the homodimeric-type E1 co...

  5. Molecular cloning of the wild-type phoM operon in Escherichia coli K-12.

    OpenAIRE

    Wanner, B L; Wilmes, M R; Hunter, E

    1988-01-01

    A metastable bacterial alkaline phosphatase (Bap) phenotype is seen in phoR mutants, which alternately express a Bap-constitutive or -negative phenotype. The alteration is affected by mutations in the phoM region near 0 min. By molecular cloning of the wild-type phoM operon onto a multicopy plasmid and recombining onto the plasmid the pho-510 mutation that abolishes variation, the phoM operon, rather than some nearby gene, was shown to control variation. Complementation tests indicated that t...

  6. Positions of Trp Codons in the Leader Peptide-Coding Region of the at Operon Influence Anti-Trap Synthesis and trp Operon Expression in Bacillus licheniformis▿

    OpenAIRE

    Levitin, Anastasia; Yanofsky, Charles

    2010-01-01

    Tryptophan, phenylalanine, tyrosine, and several other metabolites are all synthesized from a common precursor, chorismic acid. Since tryptophan is a product of an energetically expensive biosynthetic pathway, bacteria have developed sensing mechanisms to downregulate synthesis of the enzymes of tryptophan formation when synthesis of the amino acid is not needed. In Bacillus subtilis and some other Gram-positive bacteria, trp operon expression is regulated by two proteins, TRAP (the tryptopha...

  7. Positions of Trp codons in the leader peptide-coding region of the at operon influence anti-trap synthesis and trp operon expression in Bacillus licheniformis.

    Science.gov (United States)

    Levitin, Anastasia; Yanofsky, Charles

    2010-03-01

    Tryptophan, phenylalanine, tyrosine, and several other metabolites are all synthesized from a common precursor, chorismic acid. Since tryptophan is a product of an energetically expensive biosynthetic pathway, bacteria have developed sensing mechanisms to downregulate synthesis of the enzymes of tryptophan formation when synthesis of the amino acid is not needed. In Bacillus subtilis and some other Gram-positive bacteria, trp operon expression is regulated by two proteins, TRAP (the tryptophan-activated RNA binding protein) and AT (the anti-TRAP protein). TRAP is activated by bound tryptophan, and AT synthesis is increased upon accumulation of uncharged tRNA(Trp). Tryptophan-activated TRAP binds to trp operon leader RNA, generating a terminator structure that promotes transcription termination. AT binds to tryptophan-activated TRAP, inhibiting its RNA binding ability. In B. subtilis, AT synthesis is upregulated both transcriptionally and translationally in response to the accumulation of uncharged tRNA(Trp). In this paper, we focus on explaining the differences in organization and regulatory functions of the at operon's leader peptide-coding region, rtpLP, of B. subtilis and Bacillus licheniformis. Our objective was to correlate the greater growth sensitivity of B. licheniformis to tryptophan starvation with the spacing of the three Trp codons in its at operon leader peptide-coding region. Our findings suggest that the Trp codon location in rtpLP of B. licheniformis is designed to allow a mild charged-tRNA(Trp) deficiency to expose the Shine-Dalgarno sequence and start codon for the AT protein, leading to increased AT synthesis. PMID:20061467

  8. Konstruktie van plasmiden met genen van het tryptofaan operon van Escherichia coli K12 als genetische kenmerken

    NARCIS (Netherlands)

    Enger-Valk, B.E.

    1981-01-01

    Chapter 1CONSTRUCTION OF NEW CLONING VEHICLES WITH GENES OF THETRYPTOPHAN OPERON OF Escherichia coli AS GENETIC MARKERSIn vitro recombination techniques were used to construct a series of new cloning vehicles with genes of the tryptophan (trp) operon of Escherichia coli as selective marker. To const

  9. GLYCOGEN IN BACILLUS-SUBTILIS - MOLECULAR CHARACTERIZATION OF AN OPERON ENCODING ENZYMES INVOLVED IN GLYCOGEN BIOSYNTHESIS AND DEGRADATION

    NARCIS (Netherlands)

    KIEL, JAKW; BOELS, JM; BELDMAN, G; VENEMA, G

    1994-01-01

    Although it has never been reported that Bacillus subtilis is capable of accumulating glycogen, we have isolated a region from the chromosome of B. subtilis containing a glycogen operon. The operon is located directly downstream from trnB, which maps at 275 degrees on the B. subtilis chromosome. It

  10. Valine-Resistant Escherichia coli K-12 Strains with Mutations in the ilvB Operon

    OpenAIRE

    Sutton, Ann; Newman, Thomas; Francis, Marilyn; Freundlich, Martin

    1981-01-01

    Escherichia coli K-12 mutants resistant to growth inhibition by valine were isolated. These strains contained mutations in the ilvB operon effecting either the regulation of acetohydroxy acid synthase I or the sensitivity of the enzyme to end product inhibition by valine.

  11. Regulation of the metC-cysK Operon, Involved in Sulfur Metabolism in Lactococcus lactis

    NARCIS (Netherlands)

    Fernández, María; Kleerebezem, Michiel; Kuipers, Oscar P.; Siezen, Roland J.; Kranenburg, Richard van

    2002-01-01

    Sulfur metabolism in gram-positive bacteria is poorly characterized. Information on the molecular mechanisms of regulation of genes involved in sulfur metabolism is limited, and no regulator genes have been identified. Here we describe the regulation of the lactococcal metC-cysK operon, encoding a c

  12. Tryptophan auxotrophs were obtained by random transposon insertions in the Methanococcus maripaludis tryptophan operon.

    Science.gov (United States)

    Porat, Iris; Whitman, William B

    2009-08-01

    Methanococcus maripaludis is an anaerobic, methane-producing archaeon that utilizes H(2) or formate for the reduction of CO(2) to methane. Tryptophan auxotrophs were constructed by in vitro insertions of the Tn5 transposon into the tryptophan operon, followed by transformation into M. maripaludis. This method could serve for rapid insertions into large cloned DNA regions. PMID:19566682

  13. Tryptophan auxotrophs were obtained by random transposon insertions in the Methanonococcus maripaludis tryptophan operon

    OpenAIRE

    Porat, Iris; Whitman, William B.

    2009-01-01

    Methanococcus maripaludis is an anaerobic, methane-producing archaeon that utilizes H2 or formate for the reduction of CO2 to methane. Tryptophan auxotrophs were constructed by in vitro insertions of the Tn5 transposon into the tryptophan operon, followed by transformation into M. maripaludis. This method could serve for rapid insertions into large cloned DNA regions.

  14. Decreases in average bacterial community rRNA operon copy number during succession

    Science.gov (United States)

    Nemergut, Diana R; Knelman, Joseph E; Ferrenberg, Scott; Bilinski, Teresa; Melbourne, Brett; Jiang, Lin; Violle, Cyrille; Darcy, John L; Prest, Tiffany; Schmidt, Steven K; Townsend, Alan R

    2016-01-01

    Trait-based studies can help clarify the mechanisms driving patterns of microbial community assembly and coexistence. Here, we use a trait-based approach to explore the importance of rRNA operon copy number in microbial succession, building on prior evidence that organisms with higher copy numbers respond more rapidly to nutrient inputs. We set flasks of heterotrophic media into the environment and examined bacterial community assembly at seven time points. Communities were arrayed along a geographic gradient to introduce stochasticity via dispersal processes and were analyzed using 16 S rRNA gene pyrosequencing, and rRNA operon copy number was modeled using ancestral trait reconstruction. We found that taxonomic composition was similar between communities at the beginning of the experiment and then diverged through time; as well, phylogenetic clustering within communities decreased over time. The average rRNA operon copy number decreased over the experiment, and variance in rRNA operon copy number was lowest both early and late in succession. We then analyzed bacterial community data from other soil and sediment primary and secondary successional sequences from three markedly different ecosystem types. Our results demonstrate that decreases in average copy number are a consistent feature of communities across various drivers of ecological succession. Importantly, our work supports the scaling of the copy number trait over multiple levels of biological organization, ranging from cells to populations and communities, with implications for both microbial ecology and evolution. PMID:26565722

  15. ISOLATION OF AN OPERON INVOLVED IN XYLITOL METABOLISM FROM PANTOEA ANANATIS

    Science.gov (United States)

    An operon involved in xylitol metabolism in a xylitol-utilizing Pantoea ananatis mutant was cloned by the transposon tagging method. Sequencing analysis revealed that seven consecutive open reading frames (ORFs) are located in the same strand (xytA-G). Sequence homology search suggested that the o...

  16. Mutational analysis of the regulatory region of the srfA operon in Bacillus subtilis.

    OpenAIRE

    Nakano, M M; Zuber, P

    1993-01-01

    Transcription of the Bacillus subtilis srfA operon is dependent on the transcriptional activator ComA. Mutational analysis of the srfA regulatory region suggests that two regions of dyad symmetry upstream of the srfA promoter may function in transcriptional activation by facilitating a cooperative interaction between ComA dimers.

  17. Characterization of structural and free energy properties of promoters associated with Primary and Operon TSS in Helicobacter pylori genome and their orthologs

    Indian Academy of Sciences (India)

    Aditya Kumar; Manju Bansal

    2012-07-01

    Promoter regions in the genomes of all domains of life show similar trends in several structural properties such as stability, bendability, curvature, etc. In current study we analysed the stability and bendability of various classes of promoter regions (based on the recent identification of different classes of transcription start sites) of Helicobacter pylori 26695 strain. It is found that primary TSS and operon-associated TSS promoters show significantly strong features in their promoter regions. DNA free-energy-based promoter prediction tool PromPredict was used to annotate promoters of different classes, and very high recall values (∼80%) are obtained for primary TSS. Orthologous genes from other strains of H. pylori show conservation of structural properties in promoter regions as well as coding regions. PromPredict annotates promoters of orthologous genes with very high recall and precision.

  18. BIOINFORMATICS AND BIOSYNTHESIS ANALYSIS OF CELLULOSE SYNTHASE OPERON IN ZYMOMONAS MOBILIS ZM4

    Directory of Open Access Journals (Sweden)

    Sheik Abdul Kader Sheik Asraf, K. Narayanan Rajnish, and Paramasamy Gunasekaran

    2011-03-01

    Full Text Available Biosynthesis of cellulose has been reported in many species of bacteria. The genes encoding cellulose biosynthetic enzymes of Z. mobilis have not been studied so far. Preliminary sequence analysis of the Z. mobilis ZM4 genome revealed the presence of a cellulose synthase operon comprised of Open Reading Frames (ORFs ZMO01083 (bcsA, ZMO1084 (bcsB and ZMO1085 (bcsC. The first gene of the operon bcsA encodes the cellulose synthase catalytic subunit BcsA. The second gene of the operon bcsB encodes the cellulose synthase subunit B (BcsB, which shows the presence of BcsB multi-domain and is inferred to bind c-di-GMP, the regulator of cellulose biosynthesis. The third gene of the operon bcsC encodes the cellulose synthase operon C domain protein (BcsC, which belongs to super family of teratrico peptide repeat (TPR that are believed to mediate protein – protein interactions for the formation of cellulose. Multiple sequence alignment of the deduced amino acid sequences of BcsA and BcsC with other closely related homologs showed the presence of PVDPYE, HAKAGNLN, DCD motif and TPR motif, the characteristic motifs of bacterial cellulose synthases. Analysis of the nucleotide sequence of the ORF ZMO1085 and neighboring ORFs namely ZMO1083 and ZMO1084 indicated that all the ORFs are translationally linked and form an operon. Transcript analysis using Real-time PCR indicated the expression of the genes involved in cellulose synthase operon in Zymomonas mobilis ZM4. Z. mobilis colonies grown on RM-glucose containing Congo red displayed a characteristic bright red-brown colour. Z. mobilis colonies grown on RM-glucose medium supplemented with Calcoflour exhibited fluorescence. The arrangement of Calcofluor stained microfibrils can be seen in fluorescence microscopy which is an indicative for cellulose biosynthesis. AFM micrograph of the extracellular matrix of Z. mobilis shows a relatively dense matrix with bacterial cell residues. The presence of cellulose was

  19. Physiological studies of tryptophan transport and tryptophanase operon induction in Escherichia coli.

    Science.gov (United States)

    Yanofsky, C; Horn, V; Gollnick, P

    1991-10-01

    Escherichia coli forms three permeases that can transport the amino acid tryptophan: Mtr, AroP, and TnaB. The structural genes for these permeases reside in separate operons that are subject to different mechanisms of regulation. We have exploited the fact that the tryptophanase (tna) operon is induced by tryptophan to infer how tryptophan transport is influenced by the growth medium and by mutations that inactivate each of the permease proteins. In an acid-hydrolyzed casein medium, high levels of tryptophan are ordinarily required to obtain maximum tna operon induction. High levels are necessary because much of the added tryptophan is degraded by tryptophanase. An alternate inducer that is poorly cleaved by tryptophanase, 1-methyltryptophan, induces efficiently at low concentrations in both tna+ strains and tna mutants. In an acid-hydrolyzed casein medium, the TnaB permease is most critical for tryptophan uptake; i.e., only mutations in tnaB reduce tryptophanase induction. However, when 1-methyltryptophan replaces tryptophan as the inducer in this medium, mutations in both mtr and tnaB are required to prevent maximum induction. In this medium, AroP does not contribute to tryptophan uptake. However, in a medium lacking phenylalanine and tyrosine the AroP permease is active in tryptophan transport; under these conditions it is necessary to inactivate the three permeases to eliminate tna operon induction. The Mtr permease is principally responsible for transporting indole, the degradation product of tryptophan produced by tryptophanase action. The TnaB permease is essential for growth on tryptophan as the sole carbon source. When cells with high levels of tryptophanase are transferred to tryptophan-free growth medium, the expression of the tryptophan (trp) operon is elevated. This observation suggests that the tryptophanase present in these cells degrades some of the synthesized tryptophan, thereby creating a mild tryptophan deficiency. Our studies assign roles to

  20. Konstruktie van plasmiden met genen van het tryptofaan operon van Escherichia coli K12 als genetische kenmerken

    OpenAIRE

    Enger-Valk, B E

    1981-01-01

    Chapter 1CONSTRUCTION OF NEW CLONING VEHICLES WITH GENES OF THETRYPTOPHAN OPERON OF Escherichia coli AS GENETIC MARKERSIn vitro recombination techniques were used to construct a series of new cloning vehicles with genes of the tryptophan (trp) operon of Escherichia coli as selective marker. To construct these plasmids we have made a restriction cleavage map of the trp operon for the enzymes Aos I, Ava I, Bgl I, Bgl II, Hind III, Hpa I, Pvu II, Sal I, Sst I and Xho I.The constructed plasmids p...

  1. Identification of a Positive Transcription Regulatory Element within the Coding Region of the nifLA Operon in Azotobacter vinelandii

    OpenAIRE

    Mitra, Ranjana; Das, Hirendra K.; Dixit, Aparna

    2005-01-01

    Nitrogen fixation in Azotobacter vinelandii is regulated by the nifLA operon. NifA activates the transcription of nif genes, while NifL antagonizes the transcriptional activator NifA in response to fixed nitrogen and molecular oxygen levels. However, transcriptional regulation of the nifLA operon of A. vinelandii itself is not fully understood. Using the S1 nuclease assay, we mapped the transcription start site of the nifLA operon, showing it to be similar to the σ54-dependent promoters. We a...

  2. Feedback about more accurate versus less accurate trials: differential effects on self-confidence and activation.

    Science.gov (United States)

    Badami, Rokhsareh; VaezMousavi, Mohammad; Wulf, Gabriele; Namazizadeh, Mahdi

    2012-06-01

    One purpose of the present study was to examine whether self-confidence or anxiety would be differentially affected byfeedback from more accurate rather than less accurate trials. The second purpose was to determine whether arousal variations (activation) would predict performance. On day 1, participants performed a golf putting task under one of two conditions: one group received feedback on the most accurate trials, whereas another group received feedback on the least accurate trials. On day 2, participants completed an anxiety questionnaire and performed a retention test. Shin conductance level, as a measure of arousal, was determined. The results indicated that feedback about more accurate trials resulted in more effective learning as well as increased self-confidence. Also, activation was a predictor of performance. PMID:22808705

  3. Genome-wide de novo prediction of cis-regulatory binding sites in prokaryotes

    Science.gov (United States)

    Zhang, Shaoqiang; Xu, Minli; Su, Zhengchang

    2009-01-01

    Although cis-regulatory binding sites (CRBSs) are at least as important as the coding sequences in a genome, our general understanding of them in most sequenced genomes is very limited due to the lack of efficient and accurate experimental and computational methods for their characterization, which has largely hindered our understanding of many important biological processes. In this article, we describe a novel algorithm for genome-wide de novo prediction of CRBSs with high accuracy. We designed our algorithm to circumvent three identified difficulties for CRBS prediction using comparative genomics principles based on a new method for the selection of reference genomes, a new metric for measuring the similarity of CRBSs, and a new graph clustering procedure. When operon structures are correctly predicted, our algorithm can predict 81% of known individual binding sites belonging to 94% of known cis-regulatory motifs in the Escherichia coli K12 genome, while achieving high prediction specificity. Our algorithm has also achieved similar prediction accuracy in the Bacillus subtilis genome, suggesting that it is very robust, and thus can be applied to any other sequenced prokaryotic genome. When compared with the prior state-of-the-art algorithms, our algorithm outperforms them in both prediction sensitivity and specificity. PMID:19383880

  4. Assessing the most accurate formula to predict the risk of lymph node metastases from prostate cancer in contemporary patients treated with radical prostatectomy and extended pelvic lymph node dissection

    International Nuclear Information System (INIS)

    Background and purpose: The aim of this study was to perform a head-to-head comparison of the Roach formula vs. two other newly developed prediction tools for lymph node invasion (LNI) in prostate cancer, namely the Nguyen and the Yu formulas. Material and methods: We included 3115 patients treated with radical prostatectomy and extended pelvic lymph node dissection (ePLND), between 2000 and 2010 at a single center. The predictive accuracy of the three formulas was assessed and compared using the area-under-curve (AUC) and calibration methods. Moreover, decision curve analysis compared the net-benefit of the three formulas in a head-to-head fashion. Results: Overall, 10.8% of patients had LNI. The LNI-predicted risk was >15% in 25.5%, 3.4%, and 10.2% of patients according to the Roach, Nguyen and Yu formula, respectively. The AUC was 80.5%, 80.5% and 79%, respectively (all p > 0.05). However, the Roach formula demonstrated more favorable calibration and generated the highest net-benefit relative to the other examined formulas in decision curve analysis. Conclusions: All formulas demonstrated high and comparable discrimination accuracy in predicting LNI, when externally validated on ePLND treated patients. However, the Roach formula showed the most favorable characteristics. Therefore, its use should be preferred over the two other tools

  5. Repression of the pyr operon in Lactobacillus plantarum prevents its ability to grow at low carbon dioxide levels

    DEFF Research Database (Denmark)

    Nicoloff, Hervé; Elagöz, Aram; Arsène-Ploetze, Florence;

    2005-01-01

    Carbamoyl phosphate is a precursor for both arginine and pyrimidine biosynthesis. In Lactobacillus plantarum, carbamoyl phosphate is synthesized from glutamine, ATP, and carbon dioxide by two sets of identified genes encoding carbamoyl phosphate synthase (CPS). The expression of the carAB operon...... (encoding CPS-A) responds to arginine availability, whereas pyrAaAb (encoding CPS-P) is part of the pyrR1BCAaAbDFE operon coding for the de novo pyrimidine pathway repressed by exogenous uracil. The pyr operon is regulated by transcription attenuation mediated by a trans-acting repressor that binds...... is the limiting step in pyrimidine synthesis. FB335 is unable to grow in the presence of uracil due to a lack of sufficient carbamoyl phosphate required for arginine biosynthesis. Forty independent spontaneous FB335-derived mutants that have lost regulation of the pyr operon were readily obtained by their ability...

  6. The different roles of tryptophan transfer RNA in regulating trp operon expression in E. coli versus B. subtilis.

    Science.gov (United States)

    Yanofsky, Charles

    2004-08-01

    Escherichia coli and Bacillus subtilis use different mechanisms of sensing and responding to tryptophan and uncharged tRNA(Trp) as regulatory signals. In E. coli, tryptophan activates a repressor that binds to the trp promoter- operator, inhibiting transcription initiation. In B. subtilis, tryptophan activates an RNA-binding protein, TRAP, which binds to the trp operon leader RNA, causing transcription termination. In E. coli uncharged tRNA(Trp) accumulation stalls the ribosome attempting translation of tandem Trp codons in the leader-peptide coding region of the operon. This stalling permits the formation of an RNA antiterminator structure, preventing transcription termination. In B. subtilis uncharged tRNA(Trp) accumulation activates transcription and translation of the at operon. AT protein inhibits tryptophan-activated TRAP, thereby preventing TRAP-mediated transcription termination. These differences might reflect the unique organizational features of the respective trp operons and their ancestry. PMID:15262409

  7. Requirement of duplicated operons for maximal metabolism of phthalate by Rhodococcus sp. strain DK17.

    Science.gov (United States)

    Choi, Ki Young; Kim, Dockyu; Chae, Jong-Chan; Zylstra, Gerben J; Kim, Eungbin

    2007-06-01

    The operons encoding the transformation of phthalate to protocatechuate are duplicated and present on two different megaplasmids [pDK2 (330 kb) and pDK3 (750 kb)] in Rhodococcus sp. strain DK17. RT-PCR experiments using gene-specific primers showed that both the pDK2- and the pDK3-encoded dihydroxyphthalate decarboxylase genes are simultaneously expressed during growth on phthalate. The doubling time of the pDK2-cured mutant strain DK176 in minimal liquid medium with 5mM phthalate is 52.5% of that of the wild-type strain DK17. The data indicate that both copies of the phthalate operon are equally functional in DK17, and gene dosage is the main reason for slower growth of DK176 on phthalate. PMID:17449009

  8. Agrobacterium tumefaciens virE operon encodes a single-stranded DNA-binding protein.

    Science.gov (United States)

    Das, A

    1988-05-01

    The virulence (vir) genes of Agrobacterium tumefaciens Ti plasmid are essential for transformation of plant cells. Overproduction of a virE-encoded gene product in Escherichia coli was achieved by construction of an operon fusion with the E. coli tryptophan (trp) operon. The virE2 gene product in E. coli partitioned into the insoluble membrane fraction. The protein was solubilized by treatment with 4 M urea at 0 degree C. DNA-protein binding experiments showed that a strong single-stranded (ss) DNA-binding activity was present in protein fractions containing the virE2 gene product. The binding was highly specific with little or no binding observed with either double-stranded DNA or ssRNA. No significant binding to Ti plasmid DNA sequences was observed. Protein blotting studies indicated that the ssDNA-binding activity was associated with the 68-kDa virE2 polypeptide. PMID:2452439

  9. Overexpression, purification and crystallization of the tetrameric form of SorC sorbitol operon regulator

    Energy Technology Data Exchange (ETDEWEB)

    Sanctis, Daniele de; Rêgo, Ana T.; Marçal, David; McVey, Colin E.; Carrondo, Maria A. [Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Avenida da República, Apartado 127, 2781-901 Oeiras (Portugal); Enguita, Francisco J., E-mail: fenguita@fm.ul.pt [Instituto de Medicina Molecular, Avenida Professor Egas Moniz, 1649-028 Lisboa (Portugal); Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Avenida da República, Apartado 127, 2781-901 Oeiras (Portugal)

    2008-01-01

    The sorbitol operon regulator from K. pneumoniae has been overexpressed in E. coli, purified and crystallized. Diffraction data were collected to 3.2 Å. The sorbitol operon regulator (SorC) regulates the metabolism of l-sorbose in Klebsiella pneumonia. SorC was overexpressed in Escherichia coli and purified, and crystals were obtained of a tetrameric form. A single crystal showed X-ray diffraction to 3.20 Å. The crystal belongs to space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 91.6, b = 113.3, c = 184.1 Å. Analysis of the molecular-replacement solution indicates the presence of four SorC molecules in the asymmetric unit.

  10. Rule-based modeling of transcriptional attenuation at the tryptophan operon

    OpenAIRE

    Kuttler, Céline; Lhoussaine, Cédric; Nebut, Mirabelle

    2010-01-01

    International audience Transcriptional attenuation at E.coli's tryptophan operon is a prime example of RNA-mediated gene regulation. In this paper, we present a discrete stochastic model of the fine-grained control of attenuation, based on chemical reactions. Stochastic simulation of our model confirms results that were previously obtained by master or differential equations. Our approach is easier to understand than master equations, although mathematically well founded. It is compact due...

  11. Polymerase chain reaction for detection of the cholera enterotoxin operon of Vibrio cholerae.

    OpenAIRE

    1991-01-01

    We report a set of oligonucleotide primers and amplification conditions for the polymerase chain reaction to detect the ctx operon of Vibrio cholerae. The results of this assay on strains of V. cholerae and related organisms were identical with those obtained by the DNA colony hybridization test with the polynucleotide probe. The detection limit of this system was 1 pg of chromosomal DNA or broth culture containing three viable cells. The polymerase chain reaction method could directly detect...

  12. Promoter analysis of the Xanthomonas campestris pv. campestris gum operon directing biosynthesis of the xanthan polysaccharide.

    OpenAIRE

    Katzen, F; Becker, A.; Zorreguieta, A; Pühler, A; Ielpi, L

    1996-01-01

    The Xanthomonas campestris gum gene cluster is composed of 12 genes designated gumB, -C, -D, -E, -F, -G, -H, -I, -J, -K, -L, and -M. The transcriptional organization of this gene cluster was analyzed by the construction of gum-lacZ transcriptional fusions in association with plasmid integration mutagenesis. This analysis, coupled with primer extension assays, indicated that the gum region was mainly expressed as an operon from a promoter located upstream of the first gene, gumB.

  13. Unprecedented High-Resolution View of Bacterial Operon Architecture Revealed by RNA Sequencing

    OpenAIRE

    Conway, Tyrrell; Creecy, James P.; Maddox, Scott M.; Grissom, Joe E; Conkle, Trevor L.; Shadid, Tyler M.; Teramoto, Jun; San Miguel, Phillip; Shimada, Tomohiro; Ishihama, Akira; Mori, Hirotada; Wanner, Barry L.

    2014-01-01

    ABSTRACT We analyzed the transcriptome of Escherichia coli K-12 by strand-specific RNA sequencing at single-nucleotide resolution during steady-state (logarithmic-phase) growth and upon entry into stationary phase in glucose minimal medium. To generate high-resolution transcriptome maps, we developed an organizational schema which showed that in practice only three features are required to define operon architecture: the promoter, terminator, and deep RNA sequence read coverage. We precisely ...

  14. Control of a Salmonella virulence operon by proline-charged tRNAPro

    OpenAIRE

    Lee, Eun-Jin; Choi, Jeongjoon; Groisman, Eduardo A.

    2014-01-01

    Pathogens must express their virulence genes in the correct locales to cause disease. This task requires a pathogen’s ability to sense host signals and to transduce this information to its expression machinery. Here we establish that the facultative intracellular pathogen Salmonella enterica responds to a decrease in the levels of proline-charged tRNAPro by promoting expression of the mgtCBR virulence operon. We determine that hyperosmotic stress and proline limitation reduce proline-charged ...

  15. Repression is relieved before attenuation in the trp operon of Escherichia coli as tryptophan starvation becomes increasingly severe.

    OpenAIRE

    Yanofsky, C; Kelley, R.L.; Horn, V.

    1984-01-01

    Expression of the tryptophan operon of Escherichia coli is regulated over about a 500- to 600-fold range by the combined action of repression and attenuation. Repression regulates transcription initiation in response to variation in the intracellular concentration of tryptophan. Attenuation regulates transcription termination at a site in the leader region of the operon in response to changes in the extent of charging of tRNATrp. We measured repression independently of attenuation to ascertai...

  16. BigR, a Transcriptional Repressor from Plant-Associated Bacteria, Regulates an Operon Implicated in Biofilm Growth▿

    OpenAIRE

    Barbosa, Rosicler L.; Benedetti, Celso E.

    2007-01-01

    Xylella fastidiosa is a plant pathogen that colonizes the xylem vessels, causing vascular occlusion due to bacterial biofilm growth. However, little is known about the molecular mechanisms driving biofilm formation in Xylella-plant interactions. Here we show that BigR (for “biofilm growth-associated repressor”) is a novel helix-turn-helix repressor that controls the transcription of an operon implicated in biofilm growth. This operon, which encodes BigR, membrane proteins, and an unusual beta...

  17. Structure and copy number of gene clusters related to the pap P-adhesin operon of uropathogenic Escherichia coli.

    OpenAIRE

    Arthur, M; Campanelli, C; Arbeit, R D; Kim, C.; Steinbach, S; C. E. Johnson; Rubin, R H; Goldstein, R.

    1989-01-01

    The structurally related pap and prs operons of the uropathogenic Escherichia coli isolate J96 encode a P and an F adhesin that mediate bacterial attachment to the human P blood group antigen and the Forssman antigen, respectively. Using probes prepared from different segments of the pap operon, Southern blot hybridizations were performed to characterize pap-related sequences of 30 E. coli clinical isolates expressing different adhesin phenotypes. Gene clusters encoding P and F adhesins displ...

  18. OpWise: Operons aid the identification of differentially expressed genes in bacterial microarray experiments

    Directory of Open Access Journals (Sweden)

    Arkin Adam P

    2006-01-01

    Full Text Available Abstract Background Differentially expressed genes are typically identified by analyzing the variation between replicate measurements. These procedures implicitly assume that there are no systematic errors in the data even though several sources of systematic error are known. Results OpWise estimates the amount of systematic error in bacterial microarray data by assuming that genes in the same operon have matching expression patterns. OpWise then performs a Bayesian analysis of a linear model to estimate significance. In simulations, OpWise corrects for systematic error and is robust to deviations from its assumptions. In several bacterial data sets, significant amounts of systematic error are present, and replicate-based approaches overstate the confidence of the changers dramatically, while OpWise does not. Finally, OpWise can identify additional changers by assigning genes higher confidence if they are consistent with other genes in the same operon. Conclusion Although microarray data can contain large amounts of systematic error, operons provide an external standard and allow for reasonable estimates of significance. OpWise is available at http://microbesonline.org/OpWise.

  19. Artificial citrate operon confers mineral phosphate solubilization ability to diverse fluorescent pseudomonads.

    Directory of Open Access Journals (Sweden)

    Hemanta Adhikary

    Full Text Available Citric acid is a strong acid with good cation chelating ability and can be very efficient in solubilizing mineral phosphates. Only a few phosphate solubilizing bacteria and fungi are known to secrete citric acids. In this work, we incorporated artificial citrate operon containing NADH insensitive citrate synthase (gltA1 and citrate transporter (citC genes into the genome of six-plant growth promoting P. fluorescens strains viz., PfO-1, Pf5, CHAO1, P109, ATCC13525 and Fp315 using MiniTn7 transposon gene delivery system. Comprehensive biochemical characterization of the genomic integrants and their comparison with plasmid transformants of the same operon in M9 minimal medium reveals the highest amount of ∼7.6±0.41 mM citric and 29.95±2.8 mM gluconic acid secretion along with ∼43.2±3.24 mM intracellular citrate without affecting the growth of these P. fluorescens strains. All genomic integrants showed enhanced citric and gluconic acid secretion on Tris-Cl rock phosphate (TRP buffered medium, which was sufficient to release 200-1000 µM Pi in TRP medium. This study demonstrates that MPS ability could be achieved in natural fluorescent pseudomonads by incorporation of artificial citrate operon not only as plasmid but also by genomic integration.

  20. The Mannitol Operon Repressor MTIR belongs to a new class of transcription regulators in bacteria.

    Energy Technology Data Exchange (ETDEWEB)

    Tan, K.; Borovilos, M.; Zhou, M; Horer, S; Clancy, S; Moy, S; Volkart, LL; Sassoon, J; Baumann, U; Joachimiak, A (Biosciences Division); (Univ. of Berne)

    2009-12-25

    Many bacteria express phosphoenolpyruvate-dependent phosphotransferase systems (PTS). The mannitol-specific PTS catalyze the uptake and phosphorylation of d-mannitol. The uptake system comprises several genes encoded in the single operon. The expression of the mannitol operon is regulated by a proposed transcriptional factor, mannitol operon repressor (MtlR) that was first studied in Escherichia coli. Here we report the first crystal structures of MtlR from Vibrio parahemeolyticus (Vp-MtlR) and its homolog YggD protein from Shigella flexneri (Sf-YggD). MtlR and YggD belong to the same protein family (Pfam05068). Although Vp-MtlR and Sf-YggD share low sequence identity (22%), their overall structures are very similar, representing a novel all {alpha}-helical fold, and indicate similar function. However, their lack of any known DNA-binding structural motifs and their unfavorable electrostatic properties imply that MtlR/YggD are unlikely to bind a specific DNA operator directly as proposed earlier. This structural observation is further corroborated by in vitro DNA-binding studies of E. coli MtlR (Ec-MtlR), which detected no interaction of Ec-MtlR with the well characterized mannitol operator/promoter region. Therefore, MtlR/YggD belongs to a new class of transcription factors in bacteria that may regulate gene expression indirectly as a part of a larger transcriptional complex.

  1. OpWise: Operons aid the identification of differentially expressedgenes in bacterial microarray experiments

    Energy Technology Data Exchange (ETDEWEB)

    Price, Morgan N.; Arkin, Adam P.; Alm, Eric J.

    2005-11-23

    Differentially expressed genes are typically identified by analyzing the variation between replicate measurements. These procedures implicitly assume that there are no systematic errors in the data even though several sources of systematic error are known. Results-OpWise estimates the amount of systematic error in bacterial microarray data by assuming that genes in the same operon have matching expression patterns. OpWise then performs a Bayesian analysis of a linear model to estimate significance. In simulations, OpWise corrects for systematic error and is robust to deviations from its assumptions. In several bacterial data sets, significant amounts of systematic error are present, and replicate-based approaches overstate the confidence of the changers dramatically, while OpWise does not. Finally, OpWise can identify additional changers by assigning genes higher confidence if they are consistent with other genes in the same operon. Although microarray data can contain large amounts of systematic error, operons provide an external standard and allow for reasonable estimates of significance. OpWise is available at http://microbesonline.org/OpWise.

  2. Artificial citrate operon confers mineral phosphate solubilization ability to diverse fluorescent pseudomonads.

    Science.gov (United States)

    Adhikary, Hemanta; Sanghavi, Paulomi B; Macwan, Silviya R; Archana, Gattupalli; Naresh Kumar, G

    2014-01-01

    Citric acid is a strong acid with good cation chelating ability and can be very efficient in solubilizing mineral phosphates. Only a few phosphate solubilizing bacteria and fungi are known to secrete citric acids. In this work, we incorporated artificial citrate operon containing NADH insensitive citrate synthase (gltA1) and citrate transporter (citC) genes into the genome of six-plant growth promoting P. fluorescens strains viz., PfO-1, Pf5, CHAO1, P109, ATCC13525 and Fp315 using MiniTn7 transposon gene delivery system. Comprehensive biochemical characterization of the genomic integrants and their comparison with plasmid transformants of the same operon in M9 minimal medium reveals the highest amount of ∼7.6±0.41 mM citric and 29.95±2.8 mM gluconic acid secretion along with ∼43.2±3.24 mM intracellular citrate without affecting the growth of these P. fluorescens strains. All genomic integrants showed enhanced citric and gluconic acid secretion on Tris-Cl rock phosphate (TRP) buffered medium, which was sufficient to release 200-1000 µM Pi in TRP medium. This study demonstrates that MPS ability could be achieved in natural fluorescent pseudomonads by incorporation of artificial citrate operon not only as plasmid but also by genomic integration. PMID:25259527

  3. Distinct noise-controlling roles of multiple negative feedback mechanisms in a prokaryotic operon system.

    Science.gov (United States)

    Nguyen, L K; Kulasiri, D

    2011-03-01

    Molecular fluctuations are known to affect dynamics of cellular systems in important ways. Studies aimed at understanding how molecular systems of certain regulatory architectures control noise therefore become essential. The interplay between feedback regulation and noise has been previously explored for cellular networks governed by a single negative feedback loop. However, similar issues within networks consisting of more complex regulatory structures remain elusive. The authors investigate how negative feedback loops manage noise within a biochemical cascade concurrently governed by multiple negative feedback loops, using the prokaryotic tryptophan (trp) operon system in Escherechia coli as the model system. To the authors knowledge, this is the first study of noise in the trp operon system. They show that the loops in the trp operon system possess distinct, even opposing, noise-controlling effects despite their seemingly analogous feedback structures. The enzyme inhibition loop, although controlling the last reaction of the cascade, was found to suppress noise not only for the tryptophan output but also for other upstream components. In contrast, the Repression (Rep) loop enhances noise for all systems components. Attenuation (Att) poses intermediate effects by attenuating noise for the upstream components but promoting noise for components downstream of its target. Regarding noise at the output tryptophan, Rep and Att can be categorised as noise-enhancing loops whereas Enzyme Inhibition as a noise-reducing loop. These findings suggest novel implications in how cellular systems with multiple feedback mechanisms control noise. [Includes supplementary material]. PMID:21405203

  4. Accurate backgrounds to Higgs production at the LHC

    CERN Document Server

    Kauer, N

    2007-01-01

    Corrections of 10-30% for backgrounds to the H --> WW --> l^+l^-\\sla{p}_T search in vector boson and gluon fusion at the LHC are reviewed to make the case for precise and accurate theoretical background predictions.

  5. Nonsurgical giant cell tumour of the tendon sheath or of the diffuse type: Are MRI or {sup 18}F-FDG PET/CT able to provide an accurate prediction of long-term outcome?

    Energy Technology Data Exchange (ETDEWEB)

    Dercle, Laurent [IUCT-Oncopole/Institut Claudius Regaud, Department of Nuclear Medicine, Toulouse (France); Institut Gustave Roussy, Department of Radiology, Villejuif (France); Institut Gustave Roussy, Department of Nuclear Medicine, Villejuif (France); Chisin, Roland [Hebrew University Hadassah Medical Center, Department of Medical Biophysics and Nuclear Medicine, Jerusalem (Israel); Ammari, Samy [Institut Gustave Roussy, Department of Radiology, Villejuif (France); Gillebert, Quentin [Hopital tenon, Hopitaux Universitaires Est Parisien, Department of Nuclear Medicine, Paris (France); Ouali, Monia [Institut Claudius Regaud, Department of Biostatistics, Toulouse (France); Jaudet, Cyril; Dierickx, Lawrence; Zerdoud, Slimane; Courbon, Frederic [IUCT-Oncopole/Institut Claudius Regaud, Department of Nuclear Medicine, Toulouse (France); Delord, Jean-Pierre [Institut Claudius Regaud, Department of Clinical Research, Toulouse (France); Schlumberger, Martin [Institut Gustave Roussy, Department of Nuclear Medicine, Villejuif (France)

    2014-11-01

    To investigate whether MRI (RECIST 1.1, WHO criteria and the volumetric approach) or {sup 18}F-FDG PET/CT (PERCIST 1.0) are able to predict long-term outcome in nonsurgical patients with giant cell tumour of the tendon sheath or of the diffuse type (GCT-TS/DT). Fifteen ''nonsurgical'' patients with a histological diagnosis of GCT-TS/DT were divided into two groups: symptomatic patients receiving targeted therapy and asymptomatic untreated patients. All 15 patients were evaluated by MRI of whom 10 were treated, and a subgroup of 7 patients were evaluated by PET/CT of whom 4 were treated. Early evolution was assessed according to MRI and PET/CT scans at baseline and during follow-up. Cohen's kappa coefficient was used to evaluate the degree of agreement between PERCIST 1.0, RECIST 1.1, WHO criteria, volumetric approaches and the reference standard (long-term outcome, delay 505 ± 457 days). The response rate in symptomatic patients with GCT-TS/DT receiving targeted therapy was also assessed in a larger population that included additional patients obtained from a review of the literature. The kappa coefficients for agreement between RECIST/WHO/volumetric criteria and outcome (15 patients) were respectively: 0.35 (p = 0.06), 0.26 (p = 0.17) and 0.26 (p = 0.17). In the PET/CT subgroup (7 patients), PERCIST was in perfect agreement with the late symptomatic evolution (kappa = 1, p < 0.05). In the treated symptomatic group including the additional patients from the literature the response rates to targeted therapies according to late symptomatic assessment, and PERCIST and RECIST criteria were: 65 % (22/34), 77 % (10/13) and 26 % (10/39). {sup 18}F-FDG PET/CT with PERCIST is a promising approach to the prediction of the long-term outcome in GCT-TS/DT and may avoid unnecessary treatments, toxicity and costs. On MRI, WHO and volumetric approaches are not more effective than RECIST using the current thresholds. (orig.)

  6. CcpA affects expression of the groESL and dnaK operons in Lactobacillus plantarum

    Directory of Open Access Journals (Sweden)

    Marasco Rosangela

    2006-11-01

    Full Text Available Abstract Background Lactic acid bacteria (LAB are widely used in food industry and their growth performance is important for the quality of the fermented product. During industrial processes changes in temperature may represent an environmental stress to be overcome by starters and non-starters LAB. Studies on adaptation to heat shock have shown the involvement of the chaperon system-proteins in various Gram-positive bacteria. The corresponding operons, namely the dnaK and groESL operons, are controlled by a negative mechanism involving the HrcA repressor protein binding to the cis acting element CIRCE. Results We studied adaptation to heat shock in the lactic acid bacterium Lactobacillus plantarum. The LM3-2 strain, carrying a null mutation in the ccpA gene, encoding the catabolite control protein A (CcpA, showed a lower percent of survival to high temperature with respect to the LM3 wild type strain. Among proteins differentially expressed in the two strains, the GroES chaperon was more abundant in the wild type strain compared to the mutant strain under standard growth conditions. Transcriptional studies showed that class I heat shock operons were differentially expressed upon heat shock in both strains. Indeed, the dnaK and groESL operons were induced about two times more in the LM3 strain compared to the LM3-2 strain. Analysis of the regulatory region of the two operons showed the presence of cre sequences, putative binding sites for the CcpA protein. Conclusion The L. plantarum dnaK and groESL operons are characterized by the presence of the cis acting sequence CIRCE in the promoter region, suggesting a negative regulation by the HrcA/CIRCE system, which is a common type of control among the class I heat shock operons of Gram-positive bacteria. We found an additional system of regulation, based on a positive control exerted by the CcpA protein, which would interact with cre sequences present in the regulatory region of the dnaK and gro

  7. The Mercury Resistance Operon: From an Origin in a Geothermal Environment to an Efficient Detoxification Machine

    Directory of Open Access Journals (Sweden)

    Eric eBoyd

    2012-10-01

    Full Text Available Mercuric mercury (Hg[II] is a highly toxic and mobile element that is likely to have had a pronounced and adverse effect on biology since Earth’s oxygenation ~2.4 Gy ago due to its high affinity for protein sulfhydryl groups, which upon binding destabilizes protein structure and decreases enzyme activity, resulting in a decreased organismal fitness. The central enzyme in the microbial mercury detoxification system is the mercuric reductase (MerA protein, which catalyzes the reduction of Hg2+ to volatile Hg0. In addition to MerA, mer operons encode for proteins involved in regulation, Hg binding, and organomercury degradation. Here, we examine the composition of 272 individual mer operons and quantitatively map the distribution of mer-encoded functions on both taxonomic SSU rRNA gene and MerA protein phylogenies. The results indicate an origin and early evolution of MerA among thermophilic bacteria and an overall increase in the complexity of mer operons and in the sophistication of transcriptional regulation through evolutionary time, suggesting continual gene recruitment and evolution leading to an improved efficiency and functionality of the Mer detoxification system. Consistent with a positive relationship between the evolutionary history and topology of MerA and SSU rRNA gene phylogeneties (Mantel R = 0.81, p < 0.01, the distribution of the majority of mer functions, when mapped on these phylograms, indicates an overall tendency to inherit mer-encoded functions through vertical descent. However, individual mer functions display evidence of a variable degree of vertical inheritance, with several genes exhibiting strong evidence for acquisition via lateral gene transfer and/or gene loss. These data suggest that (i mer has evolved from a simple system in geothermal environments to a widely distributed and more complex and efficient detoxification system, and (ii MerA is a suitable taxonomic marker for examining the functional diversity of mer.

  8. Fate of the H-NS-repressed bgl operon in evolution of Escherichia coli.

    Directory of Open Access Journals (Sweden)

    T Sabari Sankar

    2009-03-01

    Full Text Available In the enterobacterial species Escherichia coli and Salmonella enterica, expression of horizontally acquired genes with a higher than average AT content is repressed by the nucleoid-associated protein H-NS. A classical example of an H-NS-repressed locus is the bgl (aryl-beta,D-glucoside operon of E. coli. This locus is "cryptic," as no laboratory growth conditions are known to relieve repression of bgl by H-NS in E. coli K12. However, repression can be relieved by spontaneous mutations. Here, we investigated the phylogeny of the bgl operon. Typing of bgl in a representative collection of E. coli demonstrated that it evolved clonally and that it is present in strains of the phylogenetic groups A, B1, and B2, while it is presumably replaced by a cluster of ORFans in the phylogenetic group D. Interestingly, the bgl operon is mutated in 20% of the strains of phylogenetic groups A and B1, suggesting erosion of bgl in these groups. However, bgl is functional in almost all B2 isolates and, in approximately 50% of them, it is weakly expressed at laboratory growth conditions. Homologs of bgl genes exist in Klebsiella, Enterobacter, and Erwinia species and also in low GC-content Gram-positive bacteria, while absent in E. albertii and Salmonella sp. This suggests horizontal transfer of bgl genes to an ancestral Enterobacterium. Conservation and weak expression of bgl in isolates of phylogenetic group B2 may indicate a functional role of bgl in extraintestinal pathogenic E. coli.

  9. The effect of stochasticity on the lac operon: an evolutionary perspective.

    Directory of Open Access Journals (Sweden)

    Milan van Hoek

    2007-06-01

    Full Text Available The role of stochasticity on gene expression is widely discussed. Both potential advantages and disadvantages have been revealed. In some systems, noise in gene expression has been quantified, in among others the lac operon of Escherichia coli. Whether stochastic gene expression in this system is detrimental or beneficial for the cells is, however, still unclear. We are interested in the effects of stochasticity from an evolutionary point of view. We study this question in the lac operon, taking a computational approach: using a detailed, quantitative, spatial model, we evolve through a mutation-selection process the shape of the promoter function and therewith the effective amount of stochasticity. We find that noise values for lactose, the natural inducer, are much lower than for artificial, nonmetabolizable inducers, because these artificial inducers experience a stronger positive feedback. In the evolved promoter functions, noise due to stochasticity in gene expression, when induced by lactose, only plays a very minor role in short-term physiological adaptation, because other sources of population heterogeneity dominate. Finally, promoter functions evolved in the stochastic model evolve to higher repressed transcription rates than those evolved in a deterministic version of the model. This causes these promoter functions to experience less stochasticity in gene expression. We show that a high repression rate and hence high stochasticity increases the delay in lactose uptake in a variable environment. We conclude that the lac operon evolved such that the impact of stochastic gene expression is minor in its natural environment, but happens to respond with much stronger stochasticity when confronted with artificial inducers. In this particular system, we have shown that stochasticity is detrimental. Moreover, we demonstrate that in silico evolution in a quantitative model, by mutating the parameters of interest, is a promising way to unravel

  10. Demand theory of gene regulation. II. Quantitative application to the lactose and maltose operons of Escherichia coli.

    Science.gov (United States)

    Savageau, M A

    1998-08-01

    Induction of gene expression can be accomplished either by removing a restraining element (negative mode of control) or by providing a stimulatory element (positive mode of control). According to the demand theory of gene regulation, which was first presented in qualitative form in the 1970s, the negative mode will be selected for the control of a gene whose function is in low demand in the organism's natural environment, whereas the positive mode will be selected for the control of a gene whose function is in high demand. This theory has now been further developed in a quantitative form that reveals the importance of two key parameters: cycle time C, which is the average time for a gene to complete an ON/OFF cycle, and demand D, which is the fraction of the cycle time that the gene is ON. Here we estimate nominal values for the relevant mutation rates and growth rates and apply the quantitative demand theory to the lactose and maltose operons of Escherichia coli. The results define regions of the C vs. D plot within which selection for the wild-type regulatory mechanisms is realizable, and these in turn provide the first estimates for the minimum and maximum values of demand that are required for selection of the positive and negative modes of gene control found in these systems. The ratio of mutation rate to selection coefficient is the most relevant determinant of the realizable region for selection, and the most influential parameter is the selection coefficient that reflects the reduction in growth rate when there is superfluous expression of a gene. The quantitative theory predicts the rate and extent of selection for each mode of control. It also predicts three critical values for the cycle time. The predicted maximum value for the cycle time C is consistent with the lifetime of the host. The predicted minimum value for C is consistent with the time for transit through the intestinal tract without colonization. Finally, the theory predicts an optimum value

  11. Expression of the ompATb operon accelerates ammonia secretion and adaptation of Mycobacterium tuberculosis to acidic environments.

    Science.gov (United States)

    Song, Houhui; Huff, Jason; Janik, Katharine; Walter, Kerstin; Keller, Christine; Ehlers, Stefan; Bossmann, Stefan H; Niederweis, Michael

    2011-05-01

    Homeostasis of intracellular pH is a trait critical for survival of Mycobacterium tuberculosis in macrophages. However, mechanisms by which M. tuberculosis adapts to acidic environments are poorly understood. In this study, we analysed the physiological functions of OmpATb, a surface-accessible protein of M. tuberculosis. OmpATb did not complement the permeability defects of a Mycobacterium smegmatis porin mutant to glucose, serine and glycerol, in contrast to the porin MspA. Uptake rates of these solutes were unchanged in an ompATb operon mutant of M. tuberculosis indicating that OmpATb is not a general porin. Chemical analysis of low-pH culture filtrates showed that the proteins encoded by the ompATb operon are involved in generating a rapid ammonia burst, which neutralized medium pH and preceded exponential growth of M. tuberculosis. Addition of ammonia accelerated growth of the ompATb operon mutant demonstrating that ammonia secretion is indeed a mechanism by which M. tuberculosis neutralizes acidic environments. Infection experiments revealed that the ompATb operon was not required for full virulence in mice suggesting that M. tuberculosis has multiple mechanisms of resisting phagosomal acidification. Taken together, these results show that the ompATb operon is necessary for rapid ammonia secretion and adaptation of M. tuberculosis to acidic environments in vitro but not in mice. PMID:21410778

  12. Opine-based Agrobacterium competitiveness: dual expression control of the agrocinopine catabolism (acc) operon by agrocinopines and phosphate levels.

    Science.gov (United States)

    Kim, H Stanley; Yi, Hyojeong; Myung, Jaehee; Piper, Kevin R; Farrand, Stephen K

    2008-05-01

    Agrobacterium tumefaciens strain C58 can transform plant cells to produce and secrete the sugar-phosphate conjugate opines agrocinopines A and B. The bacterium then moves in response to the opines and utilizes them as exclusive sources of carbon, energy, and phosphate via the functions encoded by the acc operon. These privileged opine-involved activities contribute to the formation of agrobacterial niches in the environment. We found that the expression of the acc operon is induced by agrocinopines and also by limitation of phosphate. The main promoter is present in front of the first gene, accR, which codes for a repressor. This operon structure enables efficient repression when opine levels are low. The promoter contains two putative operators, one overlapping the -10 sequence and the other in the further upstream from it; two partly overlapped putative pho boxes between the two operators; and two consecutive transcription start sites. DNA fragments containing either of the operators bound purified repressor AccR in the absence of agrocinopines but not in the presence of the opines, demonstrating the on-off switch of the promoter. Induction of the acc operon can occur under low-phosphate conditions in the absence of agrocinopines and further increases when the opines also are present. Such opine-phosphate dual regulatory system of the operon may ensure maximum utilization of agrocinopines when available and thereby increase the chances of agrobacterial survival in the highly competitive environment with limited general food sources. PMID:18344359

  13. A mutation in a new gene bglJ, activates the bgl operon in Escherichia coli K-12

    Energy Technology Data Exchange (ETDEWEB)

    Giel, M.; Desnoyer, M.; Lopilato, J. [Simmons College, Boston, MA (United States)

    1996-06-01

    A new mutation , bglJ4, has been characterized that results in the expression of the silent bgl operon. The bgl operon encodes proteins necessary for the transport and utilization of the aromatic {beta}-glucosides arbutin and salicin. A variety of mutations activate the operon and result in a Bgl{sup +} phenotype. Activating mutations are located upstream of the bgl promoter and in genes located elsewhere on the chromosome. Mutations outside of the bgl operon occur in the genes encoding DNA gyrase and in the gene encoding the nucleoid associated protein H-NS. The mutation described here, bglJ4, has been mapped to a new locus at min 99 on the Escherichia coli K-12 genetic map. The putative protein encoded by the bglJ gene has homology to a family of transcriptional activators. Evidence is presented that increased expression of the bglJ product is needed for activation of the bgl operon. 56 refs., 3 figs., 3 tabs.

  14. Aromatic acid metabolites of Escherichia coli K-12 can induce the marRAB operon.

    Science.gov (United States)

    Chubiz, Lon M; Rao, Christopher V

    2010-09-01

    MarR is a key regulator of the marRAB operon involved in antibiotic resistance and solvent stress tolerance in Escherichia coli. We show that two metabolic intermediates, 2,3-dihydroxybenzoate and anthranilate, involved in enterobactin and tryptophan biosynthesis, respectively, can activate marRAB transcription. We also found that a third intermediate involved in ubiquinone biosynthesis, 4-hydroxybenzoate, activates marRAB transcription in the absence of TolC. Of the three, however, only 2,3-dihydroxybenzoate directly binds MarR and affects its activity. PMID:20639340

  15. Role of P27 -P55 operon from Mycobacterium tuberculosis in the resistance to toxic compounds

    Directory of Open Access Journals (Sweden)

    Cataldi Angel A

    2011-07-01

    Full Text Available Abstract Background The P27-P55 (lprG-Rv1410c operon is crucial for the survival of Mycobacterium tuberculosis, the causative agent of human tuberculosis, during infection in mice. P55 encodes an efflux pump that has been shown to provide Mycobacterium smegmatis and Mycobacterium bovis BCG with resistance to several drugs, while P27 encodes a mannosylated glycoprotein previously described as an antigen that modulates the immune response against mycobacteria. The objective of this study was to determine the individual contribution of the proteins encoded in the P27-P55 operon to the resistance to toxic compounds and to the cell wall integrity of M. tuberculosis. Method In order to test the susceptibility of a mutant of M. tuberculosis H37Rv in the P27-P55 operon to malachite green, sodium dodecyl sulfate, ethidium bromide, and first-line antituberculosis drugs, this strain together with the wild type strain and a set of complemented strains were cultivated in the presence and in the absence of these drugs. In addition, the malachite green decolorization rate of each strain was obtained from decolorization curves of malachite green in PBS containing bacterial suspensions. Results The mutant strain decolorized malachite green faster than the wild type strain and was hypersensitive to both malachite green and ethidium bromide, and more susceptible to the first-line antituberculosis drugs: isoniazid and ethambutol. The pump inhibitor reserpine reversed M. tuberculosis resistance to ethidium bromide. These results suggest that P27-P55 functions through an efflux-pump like mechanism. In addition, deletion of the P27-P55 operon made M. tuberculosis susceptible to sodium dodecyl sulfate, suggesting that the lack of both proteins causes alterations in the cell wall permeability of the bacterium. Importantly, both P27 and P55 are required to restore the wild type phenotypes in the mutant. Conclusions The results clearly indicate that P27 and P55 are

  16. A mutant crp allele that differentially activates the operons of the fuc regulon in Escherichia coli.

    OpenAIRE

    Zhu, Y; Lin, E C

    1988-01-01

    L-Fucose is used by Escherichia coli through an inducible pathway mediated by a fucP-encoded permease, a fucI-encoded isomerase, a fucK-encoded kinase, and a fucA-encoded aldolase. The adolase catalyzes the formation of dihydroxyacetone phosphate and L-lactaldehyde. Anaerobically, lactaldehyde is converted by a fucO-encoded oxidoreductase to L-1,2-propanediol, which is excreted. The fuc genes belong to a regulon comprising four linked operons: fucO, fucA, fucPIK, and fucR. The positive regula...

  17. Genetic analysis of the modABCD (molybdate transport) operon of Escherichia coli.

    OpenAIRE

    Maupin-Furlow, J A; Rosentel, J K; Lee, J.H.; Deppenmeier, U; Gunsalus, R P; Shanmugam, K. T.

    1995-01-01

    DNA sequence analysis of the modABCD operon of Escherichia coli revealed the presence of four open reading frames. The first gene, modA, codes for a 257-amino-acid periplasmic binding protein enunciated by the presence of a signal peptide-like sequence. The second gene (modB) encodes a 229-amino-acid protein with a potential membrane location, while the 352-amino-acid ModC protein (modC product) contains a nucleotide-binding motif. On the basis of sequence similarities with proteins from othe...

  18. The nasFEDCBA operon for nitrate and nitrite assimilation in Klebsiella pneumoniae M5al.

    OpenAIRE

    Lin, J. T.; Goldman, B. S.; Stewart, V

    1994-01-01

    Klebsiella pneumoniae can use nitrate and nitrite as sole nitrogen sources through the nitrate assimilation pathway. We previously identified structural genes for assimilatory nitrate and nitrite reductases, nasA and nasB, respectively. We report here our further identification of four genes, nasFEDC, upstream of the nasBA genes. The nasFEDCBA genes probably form an operon. Mutational and complementation analyses indicated that both the nasC and nasA genes are required for nitrate assimilatio...

  19. The stb operon balances the requirements for vegetative stability and conjugative transfer of plasmid R388

    OpenAIRE

    Catherine Guynet; Ana Cuevas; Gabriel Moncalián; Fernando de la Cruz

    2011-01-01

    The conjugative plasmid R388 and a number of other plasmids carry an operon, stbABC, adjacent to the origin of conjugative transfer. We investigated the role of the stbA, stbB, and stbC genes. Deletion of stbA affected both conjugation and stability. It led to a 50-fold increase in R388 transfer frequency, as well as to high plasmid loss. In contrast, deletion of stbB abolished conjugation but provoked no change in plasmid stability. Deletion of stbC showed no effect, neither in conjugation n...

  20. Transcription of the extended hyp-operon in Nostoc sp. strain PCC 7120

    Directory of Open Access Journals (Sweden)

    Lindblad Peter

    2008-04-01

    Full Text Available Abstract Background The maturation of hydrogenases into active enzymes is a complex process and e.g. a correctly assembled active site requires the involvement of at least seven proteins, encoded by hypABCDEF and a hydrogenase specific protease, encoded either by hupW or hoxW. The N2-fixing cyanobacterium Nostoc sp. strain PCC 7120 may contain both an uptake and a bidirectional hydrogenase. The present study addresses the presence and expression of hyp-genes in Nostoc sp. strain PCC 7120. Results RT-PCRs demonstrated that the six hyp-genes together with one ORF may be transcribed as a single operon. Transcriptional start points (TSPs were identified 280 bp upstream from hypF and 445 bp upstream of hypC, respectively, demonstrating the existence of several transcripts. In addition, five upstream ORFs located in between hupSL, encoding the small and large subunits of the uptake hydrogenase, and the hyp-operon, and two downstream ORFs from the hyp-genes were shown to be part of the same transcript unit. A third TSP was identified 45 bp upstream of asr0689, the first of five ORFs in this operon. The ORFs are annotated as encoding unknown proteins, with the exception of alr0692 which is identified as a NifU-like protein. Orthologues of the four ORFs asr0689-alr0692, with a highly conserved genomic arrangement positioned between hupSL, and the hyp genes are found in several other N2-fixing cyanobacteria, but are absent in non N2-fixing cyanobacteria with only the bidirectional hydrogenase. Short conserved sequences were found in six intergenic regions of the extended hyp-operon, appearing between 11 and 79 times in the genome. Conclusion This study demonstrated that five ORFs upstream of the hyp-gene cluster are co-transcribed with the hyp-genes, and identified three TSPs in the extended hyp-gene cluster in Nostoc sp. strain PCC 7120. This may indicate a function related to the assembly of a functional uptake hydrogenase, hypothetically in the

  1. Tandem attenuators control expression of the Salmonella mgtCBR virulence operon

    OpenAIRE

    Lee, Eun-Jin; Groisman, Eduardo A.

    2012-01-01

    The mgtCBR operon from Salmonella enterica serovar Typhimurium specifies the virulence protein MgtC, the Mg2+ transporter MgtB and the regulatory peptide MgtR. The mgtCBR transcript includes a long leader region harbouring two short open reading frames (ORFs). Translation of these ORFs is anticipated to impact the formation of particular stem-loop structures and control transcription of the coding region by an attenuation-like mechanism. We previously reported that ORF mgtM enables Salmonella...

  2. Towards accurate emergency response behavior

    International Nuclear Information System (INIS)

    Nuclear reactor operator emergency response behavior has persisted as a training problem through lack of information. The industry needs an accurate definition of operator behavior in adverse stress conditions, and training methods which will produce the desired behavior. Newly assembled information from fifty years of research into human behavior in both high and low stress provides a more accurate definition of appropriate operator response, and supports training methods which will produce the needed control room behavior. The research indicates that operator response in emergencies is divided into two modes, conditioned behavior and knowledge based behavior. Methods which assure accurate conditioned behavior, and provide for the recovery of knowledge based behavior, are described in detail

  3. Carbonic anhydrase in Escherichia coli. A product of the cyn operon.

    Science.gov (United States)

    Guilloton, M B; Korte, J J; Lamblin, A F; Fuchs, J A; Anderson, P M

    1992-02-25

    The product of the cynT gene of the cyn operon in Escherichia coli has been identified as a carbonic anhydrase. The cyn operon also includes the gene cynS, encoding the enzyme cyanase. Cyanase catalyzes the reaction of cyanate with bicarbonate to give ammonia and carbon dioxide. The carbonic anhydrase was isolated from an Escherichia coli strain overexpressing the cynT gene and characterized. The purified enzyme was shown to contain 1 Zn2+/subunit (24 kDa) and was found to behave as an oligomer in solution; the presence of bicarbonate resulted in partial dissociation of the oligomeric enzyme. The kinetic properties of the enzyme are similar to those of carbonic anhydrases from other species, including inhibition by sulfonamides and cyanate. The amino acid sequence shows a high degree of identity with the sequences of two plant carbonic anhydrases. but not with animal and algal carbonic anhydrases. Since carbon dioxide formed in the bicarbonate-dependent decomposition of cyanate diffuses out of the cell faster than it would be hydrated to bicarbonate, the apparent function of the induced carbonic anhydrase is to catalyze hydration of carbon dioxide and thus prevent depletion of cellular bicarbonate.

  4. The structure of a ribosomal protein S8/spc operon mRNA complex.

    Science.gov (United States)

    Merianos, Helen J; Wang, Jimin; Moore, Peter B

    2004-06-01

    In bacteria, translation of all the ribosomal protein cistrons in the spc operon mRNA is repressed by the binding of the product of one of them, S8, to an internal sequence at the 5' end of the L5 cistron. The way in which the first two genes of the spc operon are regulated, retroregulation, is mechanistically distinct from translational repression by S8 of the genes from L5 onward. A 2.8 A resolution crystal structure has been obtained of Escherichia coli S8 bound to this site. Despite sequence differences, the structure of this complex is almost identical to that of the S8/helix 21 complex seen in the small ribosomal subunit, consistent with the hypothesis that autogenous regulation of ribosomal protein synthesis results from conformational similarities between mRNAs and rRNAs. S8 binding must repress the translation of its own mRNA by inhibiting the formation of a ribosomal initiation complex at the start of the L5 cistron.

  5. Toward Bioremediation of Methylmercury Using Silica Encapsulated Escherichia coli Harboring the mer Operon.

    Science.gov (United States)

    Kane, Aunica L; Al-Shayeb, Basem; Holec, Patrick V; Rajan, Srijay; Le Mieux, Nicholas E; Heinsch, Stephen C; Psarska, Sona; Aukema, Kelly G; Sarkar, Casim A; Nater, Edward A; Gralnick, Jeffrey A

    2016-01-01

    Mercury is a highly toxic heavy metal and the ability of the neurotoxin methylmercury to biomagnify in the food chain is a serious concern for both public and environmental health globally. Because thousands of tons of mercury are released into the environment each year, remediation strategies are urgently needed and prompted this study. To facilitate remediation of both organic and inorganic forms of mercury, Escherichia coli was engineered to harbor a subset of genes (merRTPAB) from the mercury resistance operon. Protein products of the mer operon enable transport of mercury into the cell, cleavage of organic C-Hg bonds, and subsequent reduction of ionic mercury to the less toxic elemental form, Hg(0). E. coli containing merRTPAB was then encapsulated in silica beads resulting in a biological-based filtration material. Performing encapsulation in aerated mineral oil yielded silica beads that were smooth, spherical, and similar in diameter. Following encapsulation, E. coli containing merRTPAB retained the ability to degrade methylmercury and performed similarly to non-encapsulated cells. Due to the versatility of both the engineered mercury resistant strain and silica bead technology, this study provides a strong foundation for use of the resulting biological-based filtration material for methylmercury remediation. PMID:26761437

  6. Toward Bioremediation of Methylmercury Using Silica Encapsulated Escherichia coli Harboring the mer Operon.

    Directory of Open Access Journals (Sweden)

    Aunica L Kane

    Full Text Available Mercury is a highly toxic heavy metal and the ability of the neurotoxin methylmercury to biomagnify in the food chain is a serious concern for both public and environmental health globally. Because thousands of tons of mercury are released into the environment each year, remediation strategies are urgently needed and prompted this study. To facilitate remediation of both organic and inorganic forms of mercury, Escherichia coli was engineered to harbor a subset of genes (merRTPAB from the mercury resistance operon. Protein products of the mer operon enable transport of mercury into the cell, cleavage of organic C-Hg bonds, and subsequent reduction of ionic mercury to the less toxic elemental form, Hg(0. E. coli containing merRTPAB was then encapsulated in silica beads resulting in a biological-based filtration material. Performing encapsulation in aerated mineral oil yielded silica beads that were smooth, spherical, and similar in diameter. Following encapsulation, E. coli containing merRTPAB retained the ability to degrade methylmercury and performed similarly to non-encapsulated cells. Due to the versatility of both the engineered mercury resistant strain and silica bead technology, this study provides a strong foundation for use of the resulting biological-based filtration material for methylmercury remediation.

  7. Glucose & sodium chloride induced biofilm production & ica operon in clinical isolates of staphylococci

    Directory of Open Access Journals (Sweden)

    Astha Agarwal

    2013-01-01

    Full Text Available Background & objectives: All colonizing and invasive staphylococcal isolates may not produce biofilm but may turn biofilm producers in certain situations due to change in environmental factors. This study was done to test the hypothesis that non biofilm producing clinical staphylococci isolates turn biofilm producers in presence of sodium chloride (isotonic and high concentration of glucose, irrespective of presence or absence of ica operon. Methods: Clinical isolates of 100 invasive, 50 colonizing and 50 commensal staphylococci were tested for biofilm production by microtiter plate method in different culture media (trypticase soy broth alone or supplemented with 0.9% NaCl/ 5 or 10% glucose. All isolates were tested for the presence of ica ADBC genes by PCR. Results: Biofilm production significantly increased in the presence of glucose and saline, most, when both glucose and saline were used together. All the ica positive staphylococcal isolates and some ica negative isolates turned biofilm producer in at least one of the tested culture conditions. Those remained biofilm negative in different culture conditions were all ica negative. Interpretation & conclusions: The present results showed that the use of glucose or NaCl or combination of both enhanced biofilm producing capacity of staphylococcal isolates irrespective of presence or absence of ica operon.

  8. Rv2031c of Mycobacterium tuberculosis: a master regulator of Rv2028-Rv2031 (HspX operon

    Directory of Open Access Journals (Sweden)

    Khurram eMushtaq

    2015-04-01

    Full Text Available AbstractGenes belonging to the same operon are transcribed as a single mRNA molecule in all prokaryotes. The genes of the same operon are presumed to be involved in similar metabolic and physiological processes. Hence, computational analysis of constituent proteins could provide important clues to the functional relationships within the operonic genes. This tends to be more fruitful in the case of Mycobacterium tuberculosis (Mtb, considering the number of hypothetical genes with unknown functions and interacting partners. Dramatic advances in the past decade have increased our knowledge of the mechanisms that tubercle bacilli employ to survive within the host. But the phenomenon of Mtb latency continues to baffle all. Rv2031c belonging to dormancy regulon of Mtb is predominantly expressed during latency, with myriad immunological roles. Thus we attempted to analyze the operon comprising Rv2031c protein to gain insights into its role during latency. In the current study, we have carried out computational analysis of proteins encoded by genes known to be a part of this operon. Our study includes phylogenetic analysis, modeling of protein 3D structures, and protein interaction network analysis. We describe the mechanistic role in the establishment of latency and regulation of DevS/DevR component system. Additionally, we have identified the probable role of these proteins in carbohydrate metabolism, erythromycin tolerance and nucleotide synthesis. Hence, these proteins can modulate the metabolism of mycobacterium inside the host cells and can be important for its survival in latency. The functional characterization and interactome of this important operon can give insight into its role during latency along with the exploitation of constituent proteins as drug targets and vaccine candidates.

  9. Phylogenetic conservation of RNA secondary and tertiary structure in the trpEDCFBA operon leader transcript in Bacillus.

    Science.gov (United States)

    Schaak, Janell E; Babitzke, Paul; Bevilacqua, Philip C

    2003-12-01

    Expression of the trpEDCFBA operon of Bacillus subtilis is regulated by transcription attenuation and translation control mechanisms. We recently determined that the B. subtilis trp leader readthrough transcript can adopt a Mg(2+)-dependent tertiary structure that appears to interfere with TRAP-mediated translation control of trpE. In the present study, sequence comparisons to trp leaders from three other Bacillus sp. were made, suggesting that RNA secondary and tertiary structures are phylogenetically conserved. To test this hypothesis, experiments were carried out with the trp leader transcript from Bacillus stearothermophilus. Structure mapping experiments confirmed the predicted secondary structure. Native gel experiments identified a faster mobility species in the presence of Mg(2+), suggesting that a Mg(2+)-dependent tertiary structure forms. Mg(2+)-dependent protection of residues within the first five triplet repeats of the TRAP binding target and a pyrimidine-rich internal loop were observed, consistent with tertiary structure formation between these regions. Structure mapping in the presence of a competitor DNA oligonucleotide allowed the interacting partners to be identified as a single-stranded portion of the purine-rich TRAP binding target and the large downstream pyrimidine-rich internal loop. Thermal denaturation experiments revealed a Mg(2+)- and pH-dependent unfolding transition that was absent for a transcript missing the first five triplet repeats. The stability of several mutant transcripts allowed a large portion of the base-pairing register for the tertiary interaction to be determined. These data indicate that RNA secondary and tertiary structures involved in TRAP-mediated translation control are conserved in at least four Bacillus species. PMID:14624006

  10. Accurate Modeling of Advanced Reflectarrays

    DEFF Research Database (Denmark)

    Zhou, Min

    Analysis and optimization methods for the design of advanced printed re ectarrays have been investigated, and the study is focused on developing an accurate and efficient simulation tool. For the analysis, a good compromise between accuracy and efficiency can be obtained using the spectral domain...

  11. Modulating TRAP-mediated transcription termination by AT during transcription of the leader region of the Bacillus subtilis trp operon

    OpenAIRE

    Sharma, Shraddha; Gollnick, Paul

    2014-01-01

    An 11-subunit protein called trp RNA binding Attenuation Protein (TRAP) controls attenuation of the tryptophan biosynthetic (trpEDCFBA) operon in Bacillus subtilis. Tryptophan-activated TRAP binds to 11 (G/U)AG repeats in the 5′ leader region of trp mRNAs, and downregulates expression of the operon by promoting transcription termination prior to the structural genes. Anti-TRAP (AT) is an antagonist that binds to tryptophan-activated TRAP and prevents TRAP from binding to RNA, thereby upregula...

  12. Structural organization of the transfer RNA operon I of Vibrio cholerae: Differences between classical and El Tor strains

    Indian Academy of Sciences (India)

    Atreyi Ghatak; Anasuya Majumdar; Ranajit K Ghosh

    2005-09-01

    Nine major transfer RNA (tRNA) gene clusters were analysed in various Vibrio cholerae strains. Of these, only the tRNA operon I was found to differ significantly in V. cholerae classical (sixth pandemic) and El Tor (seventh pandemic) strains. Amongst the sixteen tRNA genes contained in this operon, genes for tRNA Gln3 (CAA) and tRNA Leu6 (CUA) were absent in classical strains as compared to El Tor strains. The observation strongly supported the view that the above two pandemic strains constitute two different clones.

  13. Ethics and epistemology of accurate prediction in clinical research.

    Science.gov (United States)

    Hey, Spencer Phillips

    2015-07-01

    All major research ethics policies assert that the ethical review of clinical trial protocols should include a systematic assessment of risks and benefits. But despite this policy, protocols do not typically contain explicit probability statements about the likely risks or benefits involved in the proposed research. In this essay, I articulate a range of ethical and epistemic advantages that explicit forecasting would offer to the health research enterprise. I then consider how some particular confidence levels may come into conflict with the principles of ethical research.

  14. Copeptin does not accurately predict disease severity in imported malaria

    NARCIS (Netherlands)

    M.E. van Wolfswinkel (Marlies); D.A. Hesselink (Dennis); E.J. Hoorn (Ewout); Y.B. de Rijke (Yolanda); R. Koelewijn (Rob); J.J. van Hellemond (Jaap); P.J.J. van Genderen (Perry)

    2012-01-01

    textabstractBackground: Copeptin has recently been identified to be a stable surrogate marker for the unstable hormone arginine vasopressin (AVP). Copeptin has been shown to correlate with disease severity in leptospirosis and bacterial sepsis. Hyponatraemia is common in severe imported malaria and

  15. An Innovative Imputation and Classification Approach for Accurate Disease Prediction

    OpenAIRE

    UshaRani, Yelipe; Sammulal, P.

    2016-01-01

    Imputation of missing attribute values in medical datasets for extracting hidden knowledge from medical datasets is an interesting research topic of interest which is very challenging. One cannot eliminate missing values in medical records. The reason may be because some tests may not been conducted as they are cost effective, values missed when conducting clinical trials, values may not have been recorded to name some of the reasons. Data mining researchers have been proposing various approa...

  16. Profitable capitation requires accurate costing.

    Science.gov (United States)

    West, D A; Hicks, L L; Balas, E A; West, T D

    1996-01-01

    In the name of costing accuracy, nurses are asked to track inventory use on per treatment basis when more significant costs, such as general overhead and nursing salaries, are usually allocated to patients or treatments on an average cost basis. Accurate treatment costing and financial viability require analysis of all resources actually consumed in treatment delivery, including nursing services and inventory. More precise costing information enables more profitable decisions as is demonstrated by comparing the ratio-of-cost-to-treatment method (aggregate costing) with alternative activity-based costing methods (ABC). Nurses must participate in this costing process to assure that capitation bids are based upon accurate costs rather than simple averages. PMID:8788799

  17. Cross-Regulation between the phz1 and phz2 Operons Maintain a Balanced Level of Phenazine Biosynthesis in Pseudomonas aeruginosa PAO1.

    Directory of Open Access Journals (Sweden)

    Qinna Cui

    Full Text Available Gene duplication often provides selective advantages for the survival of microorganisms in adapting to varying environmental conditions. P. aeruginosa PAO1 possesses two seven-gene operons [phz1 (phzA1B1C1D1E1F1G1 and phz2 (phzA2B2C2D2E2F2G2] that are involved in the biosynthesis of phenazine-1-carboxylic acid and its derivatives. Although the two operons are highly homologous and their functions are well known, it is unclear how the two phz operons coordinate their expressions to maintain the phenazine biosynthesis. By constructing single and double deletion mutants of the two phz operons, we found that the phz1-deletion mutant produced the same or less amount of phenazine-1-carboxylic acid and pyocyanin in GA medium than the phz2-knockout mutant while the phz1-phz2 double knockout mutant did not produce any phenazines. By generating phzA1 and phzA2 translational and transcriptional fusions with a truncated lacZ reporter, we found that the expression of the phz1 operon increased significantly at the post-transcriptional level and did not alter at the transcriptional level in the absence of the phz2 operon. Surprisingly, the expression the phz2 operon increased significantly at the post-transcriptional level and only moderately at the transcriptional level in the absence of the phz1 operon. Our findings suggested that a complex cross-regulation existed between the phz1 and phz2 operons. By mediating the upregulation of one phz operon expression while the other was deleted, this crosstalk would maintain the homeostatic balance of phenazine biosynthesis in P. aeruginosa PAO1.

  18. Role of the ganSPQAB Operon in Degradation of Galactan by Bacillus subtilis.

    Science.gov (United States)

    Watzlawick, Hildegard; Morabbi Heravi, Kambiz; Altenbuchner, Josef

    2016-10-15

    Bacillus subtilis possesses different enzymes for the utilization of plant cell wall polysaccharides. This includes a gene cluster containing galactan degradation genes (ganA and ganB), two transporter component genes (ganQ and ganP), and the sugar-binding lipoprotein-encoding gene ganS (previously known as cycB). These genes form an operon that is regulated by GanR. The degradation of galactan by B. subtilis begins with the activity of extracellular GanB. GanB is an endo-β-1,4-galactanase and is a member of glycoside hydrolase (GH) family 53. This enzyme was active on high-molecular-weight arabinose-free galactan and mainly produced galactotetraose as well as galactotriose and galactobiose. These galacto-oligosaccharides may enter the cell via the GanQP transmembrane proteins of the galactan ABC transporter. The specificity of the galactan ABC transporter depends on the sugar-binding lipoprotein, GanS. Purified GanS was shown to bind galactotetraose and galactotriose using thermal shift assay. The energy for this transport is provided by MsmX, an ATP-binding protein. The transported galacto-oligosaccharides are further degraded by GanA. GanA is a β-galactosidase that belongs to GH family 42. The GanA enzyme was able to hydrolyze short-chain β-1,4-galacto-oligosaccharides as well as synthetic β-galactopyranosides into galactose. Thermal shift assay as well as electrophoretic mobility shift assay demonstrated that galactobiose is the inducer of the galactan operon regulated by GanR. DNase I footprinting revealed that the GanR protein binds to an operator overlapping the -35 box of the σ(A)-type promoter of Pgan, which is located upstream of ganS IMPORTANCE: Bacillus subtilis is a Gram-positive soil bacterium that utilizes different types of carbohydrates, such as pectin, as carbon sources. So far, most of the pectin degradation systems and enzymes have been thoroughly studied in B. subtilis Nevertheless, the B. subtilis utilization system of galactan, which is

  19. Genomics of pyrrolnitrin biosynthetic loci : evidence for conservation and whole-operon mobility within Gram-negative bacteria

    NARCIS (Netherlands)

    Costa, Rodrigo; van Aarle, Ingrid M.; Mendes, Rodrigo; van Elsas, Jan Dirk

    2009-01-01

    Pyrrolnitrin (PRN) is a tryptophan-derived secondary metabolite produced by a narrow range of Gram-negative bacteria. The PRN biosynthesis by rhizobacteria presumably has a key role in their life strategies and in the biocontrol of plant diseases. The biosynthetic operon that encodes the pathway tha

  20. Five phosphonate operon gene products as components of a multi-subunit complex of the carbon-phosphorus lyase pathway

    DEFF Research Database (Denmark)

    Jochimsen, Bjarne; Lolle, Signe; McSorley, Fern R.;

    2011-01-01

    Organophosphonate utilization by Escherichia coli requires the 14 cistrons of the phnCDEFGHIJKLMNOP operon, of which the carbon-phosphorus lyase has been postulated to consist of the seven polypeptides specified by phnG to phnM. A 5,660-bp DNA fragment encompassing phnGHIJKLM is cloned, followed ...

  1. Identification and functional characterization of the Lactococcus lactis rfb operon, required for dTDP-rhamnose biosynthesis

    NARCIS (Netherlands)

    Boels, I.C.; Beerthuyzen, M.M.; Kosters, M.H.; Kaauwen, van M.P.W.; Kleerebezem, M.; Vos, de W.M.

    2004-01-01

    dTDP-rhamnose is an important precursor of cell wall polysaccharides and rhamnose-containing exopolysaccharides (EPS) in Lactococcus lactis. We cloned the rfbACBD operon from L. lactis MG1363, which comprises four genes involved in dTDP-rhamnose biosynthesis. When expressed in Escherichia coli, the

  2. Influence of the feedback loops in the trp operon of B. subtilis on the system dynamic response and noise amplitude.

    Science.gov (United States)

    Zamora-Chimal, Criseida; Santillán, Moisés; Rodríguez-González, Jesús

    2012-10-01

    In this paper we introduce a mathematical model for the tryptophan operon regulatory pathway in Bacillus subtilis. This model considers the transcription-attenuation, and the enzyme-inhibition regulatory mechanisms. Special attention is paid to the estimation of all the model parameters from reported experimental data. With the aid of this model we investigate, from a mathematical-modeling point of view, whether the existing multiplicity of regulatory feedback loops is advantageous in some sense, regarding the dynamic response and the biochemical noise in the system. The tryptophan operon dynamic behavior is studied by means of deterministic numeric simulations, while the biochemical noise is analyzed with the aid of stochastic simulations. The model feasibility is tested comparing its stochastic and deterministic results with experimental reports. Our results for the wildtype and for a couple of mutant bacterial strains suggest that the enzyme-inhibition feedback loop, dynamically accelerates the operon response, and plays a major role in the reduction of biochemical noise. Also, the transcription-attenuation feedback loop makes the trp operon sensitive to changes in the endogenous tryptophan level, and increases the amplitude of the biochemical noise. PMID:22713856

  3. Optimal performance of the tryptophan operon of E. coli: a stochastic, dynamical, mathematical-modeling approach.

    Science.gov (United States)

    Salazar-Cavazos, Emanuel; Santillán, Moisés

    2014-02-01

    In this work, we develop a detailed, stochastic, dynamical model for the tryptophan operon of E. coli, and estimate all of the model parameters from reported experimental data. We further employ the model to study the system performance, considering the amount of biochemical noise in the trp level, the system rise time after a nutritional shift, and the amount of repressor molecules necessary to maintain an adequate level of repression, as indicators of the system performance regime. We demonstrate that the level of cooperativity between repressor molecules bound to the first two operators in the trp promoter affects all of the above enlisted performance characteristics. Moreover, the cooperativity level found in the wild-type bacterial strain optimizes a cost-benefit function involving low biochemical noise in the tryptophan level, short rise time after a nutritional shift, and low number of regulatory molecules. PMID:24307084

  4. A mutant crp allele that differentially activates the operons of the fuc regulon in Escherichia coli.

    Science.gov (United States)

    Zhu, Y; Lin, E C

    1988-05-01

    L-Fucose is used by Escherichia coli through an inducible pathway mediated by a fucP-encoded permease, a fucI-encoded isomerase, a fucK-encoded kinase, and a fucA-encoded aldolase. The adolase catalyzes the formation of dihydroxyacetone phosphate and L-lactaldehyde. Anaerobically, lactaldehyde is converted by a fucO-encoded oxidoreductase to L-1,2-propanediol, which is excreted. The fuc genes belong to a regulon comprising four linked operons: fucO, fucA, fucPIK, and fucR. The positive regulator encoded by fucR responds to fuculose 1-phosphate as the effector. Mutants serially selected for aerobic growth on propanediol became constitutive in fucO and fucA [fucO(Con) fucA(Con)], but noninducible in fucPIK [fucPIK(Non)]. An external suppressor mutation that restored growth on fucose caused constitutive expression of fucPIK. Results from this study indicate that this suppressor mutation occurred in crp, which encodes the cyclic AMP-binding (or receptor) protein. When the suppressor allele (crp-201) was transduced into wild-type strains, the recipient became fucose negative and fucose sensitive (with glycerol as the carbon and energy source) because of impaired expression of fucA. The fucPIK operon became hyperinducible. The growth rate on maltose was significantly reduced, but growth on L-rhamnose, D-galactose, L-arabinose, glycerol, or glycerol 3-phosphate was close to normal. Lysogenization of fuc+ crp-201 cells by a lambda bacteriophage bearing crp+ restored normal growth ability on fucose. In contrast, lysogenization of [fucO(Con)fucA(Con)fucPIK(Non)crp-201] cells by the same phage retarded their growth on fucose. PMID:2834341

  5. Synthesis and degradation of the mRNA of the Tn21 mer operon.

    Science.gov (United States)

    Gambill, B D; Summers, A O

    1992-05-20

    The mercury resistance locus encoded by Tn21 on the monocopy IncFII plasmid R100 (merTn21) consists of a metal-responsive activator/repressor, merR, which controls initiation of a polycistronic message that includes genes for the uptake (merTPC) and reduction (merA) of Hg2+ and merD, which may also play a minor regulatory role. Comparison of the relative abundance of the 5' and 3' ends of the merTPCAD transcript revealed a strong transcriptional gradient in the operon, consistent with previous observations of lower relative abundance of the more promoter-distal gene products. In vivo mRNA degradation rates varied only slightly for the different genes: however, the rates of mRNA synthesis varied considerably from the beginning to the end of the operon. Specifically, mRNA corresponding to the promoter-proximal genes, merTPC, achieved a maximum in vivo synthesis rate between 60 and 120 seconds after induction; this rate was maintained for approximately ten minutes. In contrast, the synthesis rates of mRNA corresponding to the promoter-distal genes merA and merD, were initially fivefold lower than the rates of the promoter-proximal genes for the first five minutes after induction, and then rose gradually to approximately 50% of the merTPC synthesis rates. These data suggested that early after induction only 20% of the transcripts initiating at merT proceed beyond merC. At later times after induction approximately 50% of the transcripts proceed beyond merC. Nuclease end mapping did not reveal any discrete termination events in the merPCA region, thus, premature termination may occur at many sites.

  6. Contribution of the nos-pdt operon to virulence phenotypes in methicillin-sensitive Staphylococcus aureus.

    Directory of Open Access Journals (Sweden)

    April M Sapp

    Full Text Available Nitric oxide (NO is emerging as an important regulator of bacterial stress resistance, biofilm development, and virulence. One potential source of endogenous NO production in the pathogen Staphylococcus aureus is its NO-synthase (saNOS enzyme, encoded by the nos gene. Although a role for saNOS in oxidative stress resistance, antibiotic resistance, and virulence has been recently-described, insights into the regulation of nos expression and saNOS enzyme activity remain elusive. To this end, transcriptional analysis of the nos gene in S. aureus strain UAMS-1 was performed, which revealed that nos expression increases during low-oxygen growth and is growth-phase dependent. Furthermore, nos is co-transcribed with a downstream gene, designated pdt, which encodes a prephenate dehydratase (PDT enzyme involved in phenylalanine biosynthesis. Deletion of pdt significantly impaired the ability of UAMS-1 to grow in chemically-defined media lacking phenylalanine, confirming the function of this enzyme. Bioinformatics analysis revealed that the operon organization of nos-pdt appears to be unique to the staphylococci. As described for other S. aureus nos mutants, inactivation of nos in UAMS-1 conferred sensitivity to oxidative stress, while deletion of pdt did not affect this phenotype. The nos mutant also displayed reduced virulence in a murine sepsis infection model, and increased carotenoid pigmentation when cultured on agar plates, both previously-undescribed nos mutant phenotypes. Utilizing the fluorescent stain 4-Amino-5-Methylamino-2',7'-Difluorofluorescein (DAF-FM diacetate, decreased levels of intracellular NO/reactive nitrogen species (RNS were detected in the nos mutant on agar plates. These results reinforce the important role of saNOS in S. aureus physiology and virulence, and have identified an in vitro growth condition under which saNOS activity appears to be upregulated. However, the significance of the operon organization of nos-pdt and

  7. The stb operon balances the requirements for vegetative stability and conjugative transfer of plasmid R388.

    Directory of Open Access Journals (Sweden)

    Catherine Guynet

    2011-05-01

    Full Text Available The conjugative plasmid R388 and a number of other plasmids carry an operon, stbABC, adjacent to the origin of conjugative transfer. We investigated the role of the stbA, stbB, and stbC genes. Deletion of stbA affected both conjugation and stability. It led to a 50-fold increase in R388 transfer frequency, as well as to high plasmid loss. In contrast, deletion of stbB abolished conjugation but provoked no change in plasmid stability. Deletion of stbC showed no effect, neither in conjugation nor in stability. Deletion of the entire stb operon had no effect on conjugation, which remained as in the wild-type plasmid, but led to a plasmid loss phenotype similar to that of the R388ΔstbA mutant. We concluded that StbA is required for plasmid stability and that StbA and StbB control conjugation. We next observed the intracellular positioning of R388 DNA molecules and showed that they localize as discrete foci evenly distributed in live Escherichia coli cells. Plasmid instability of the R388ΔΔstbA mutant correlated with aberrant localization of the plasmid DNA molecules as clusters, either at one cell pole, at both poles, or at the cell center. In contrast, plasmid molecules in the R388ΔΔstbB mutant were mostly excluded from the cell poles. Thus, results indicate that defects in both plasmid maintenance and transfer are a consequence of variations in the intracellular positioning of plasmid DNA. We propose that StbA and StbB constitute an atypical plasmid stabilization system that reconciles two modes of plasmid R388 physiology: a maintenance mode (replication and segregation and a propagation mode (conjugation. The consequences of this novel concept in plasmid physiology will be discussed.

  8. Accurate determination of antenna directivity

    DEFF Research Database (Denmark)

    Dich, Mikael

    1997-01-01

    The derivation of a formula for accurate estimation of the total radiated power from a transmitting antenna for which the radiated power density is known in a finite number of points on the far-field sphere is presented. The main application of the formula is determination of directivity from power......-pattern measurements. The derivation is based on the theory of spherical wave expansion of electromagnetic fields, which also establishes a simple criterion for the required number of samples of the power density. An array antenna consisting of Hertzian dipoles is used to test the accuracy and rate of convergence...

  9. Crosstalk between virulence loci: regulation of Salmonella enterica pathogenicity island 1 (SPI-1) by products of the std fimbrial operon.

    Science.gov (United States)

    López-Garrido, Javier; Casadesús, Josep

    2012-01-01

    Invasion of intestinal epithelial cells is a critical step in Salmonella infection and requires the expression of genes located in Salmonella pathogenicity island 1 (SPI-1). A key factor for SPI-1 expression is DNA adenine (Dam) methylation, which activates synthesis of the SPI-1 transcriptional activator HilD. Dam-dependent regulation of hilD is postranscriptional (and therefore indirect), indicating the involvement of unknown cell functions under Dam methylation control. A genetic screen has identified the std fimbrial operon as the missing link between Dam methylation and SPI-1. We show that all genes in the std operon are part of a single transcriptional unit, and describe three previously uncharacterized ORFs (renamed stdD, stdE, and stdF). We present evidence that two such loci (stdE and stdF) are involved in Dam-dependent control of Salmonella SPI-1: in a Dam(-) background, deletion of stdE or stdF suppresses SPI-1 repression; in a Dam(+) background, constitutive expression of StdE and/or StdF represses SPI-1. Repression of SPI-1 by products of std operon explains the invasion defect of Salmonella Dam(-) mutants, which constitutively express the std operon. Dam-dependent repression of std in the ileum may be required to permit invasion, as indicated by two observations: constitutive expression of StdE and StdF reduces invasion of epithelial cells in vitro (1,000 fold) and attenuates Salmonella virulence in the mouse model (>60 fold). In turn, crosstalk between std and SPI-1 may play a role in intestinal infections by preventing expression of SPI-1 in the caecum, an intestinal compartment in which the std operon is known to be expressed.

  10. Identification of a positive transcription regulatory element within the coding region of the nifLA operon in Azotobacter vinelandii.

    Science.gov (United States)

    Mitra, Ranjana; Das, Hirendra K; Dixit, Aparna

    2005-07-01

    Nitrogen fixation in Azotobacter vinelandii is regulated by the nifLA operon. NifA activates the transcription of nif genes, while NifL antagonizes the transcriptional activator NifA in response to fixed nitrogen and molecular oxygen levels. However, transcriptional regulation of the nifLA operon of A. vinelandii itself is not fully understood. Using the S1 nuclease assay, we mapped the transcription start site of the nifLA operon, showing it to be similar to the sigma54-dependent promoters. We also identified a positive cis-acting regulatory element (+134 to +790) of the nifLA operon within the coding region of the nifL gene of A. vinelandii. Deletion of this element results in complete loss of promoter activity. Several protein factors bind to this region, and the specific binding sites have been mapped by DNase I foot printing. Two of these sites, namely dR1 (+134 to +204) and dR2 (+745 to +765), are involved in regulating the nifLA promoter activity. The absence of NtrC-like binding sites in the upstream region of the nifLA operon in A. vinelandii makes the identification of these downstream elements a highly significant finding. The interaction of the promoter with the proteins binding to the dR2 region spanning +745 to +765 appears to be dependent on the face of the helix as introduction of 4 bases just before this region completely disrupts promoter activity. Thus, the positive regulatory element present within the BglII-BglII fragment may play, in part; an important role in nifLA regulation in A. vinelandii. PMID:16000781

  11. The use of amino sugars by Bacillus subtilis: presence of a unique operon for the catabolism of glucosamine.

    Science.gov (United States)

    Gaugué, Isabelle; Oberto, Jacques; Putzer, Harald; Plumbridge, Jacqueline

    2013-01-01

    B. subtilis grows more rapidly using the amino sugar glucosamine as carbon source, than with N-acetylglucosamine. Genes for the transport and metabolism of N-acetylglucosamine (nagP and nagAB) are found in all the sequenced Bacilli (except Anoxybacillus flavithermus). In B. subtilis there is an additional operon (gamAP) encoding second copies of genes for the transport and catabolism of glucosamine. We have developed a method to make multiple deletion mutations in B. subtilis employing an excisable spectinomycin resistance cassette. Using this method we have analysed the contribution of the different genes of the nag and gam operons for their role in utilization of glucosamine and N-acetylglucosamine. Faster growth on glucosamine is due to the presence of the gamAP operon, which is strongly induced by glucosamine. Although the gamA and nagB genes encode isozymes of GlcN6P deaminase, catabolism of N-acetylglucosamine relies mostly upon the gamA gene product. The genes for use of N-acetylglucosamine, nagAB and nagP, are repressed by YvoA (NagR), a GntR family regulator, whose gene is part of the nagAB yvoA(nagR) operon. The gamAP operon is repressed by YbgA, another GntR family repressor, whose gene is expressed divergently from gamAP. The nagAB yvoA synton is found throughout the Bacilli and most firmicutes. On the other hand the ybgA-gamAP synton, which includes the ybgB gene for a small protein of unknown provenance, is only found in B. subtilis (and a few very close relatives). The origin of ybgBA-gamAP grouping is unknown but synteny analysis suggests lateral transfer from an unidentified donor. The presence of gamAP has enabled B. subtilis to efficiently use glucosamine as carbon source.

  12. Parameters for accurate genome alignment

    Directory of Open Access Journals (Sweden)

    Hamada Michiaki

    2010-02-01

    Full Text Available Abstract Background Genome sequence alignments form the basis of much research. Genome alignment depends on various mundane but critical choices, such as how to mask repeats and which score parameters to use. Surprisingly, there has been no large-scale assessment of these choices using real genomic data. Moreover, rigorous procedures to control the rate of spurious alignment have not been employed. Results We have assessed 495 combinations of score parameters for alignment of animal, plant, and fungal genomes. As our gold-standard of accuracy, we used genome alignments implied by multiple alignments of proteins and of structural RNAs. We found the HOXD scoring schemes underlying alignments in the UCSC genome database to be far from optimal, and suggest better parameters. Higher values of the X-drop parameter are not always better. E-values accurately indicate the rate of spurious alignment, but only if tandem repeats are masked in a non-standard way. Finally, we show that γ-centroid (probabilistic alignment can find highly reliable subsets of aligned bases. Conclusions These results enable more accurate genome alignment, with reliability measures for local alignments and for individual aligned bases. This study was made possible by our new software, LAST, which can align vertebrate genomes in a few hours http://last.cbrc.jp/.

  13. The accurate definition of metabolic volumes on {sup 18}F-FDG-PET before treatment allows the response to chemoradiotherapy to be predicted in the case of oesophagus cancers; La definition precise des volumes metaboliques sur TEP au 18F-FDG avant traitement permet la prediction de la reponse a la chimioradiotherapie dans les cancers de l'oesophage

    Energy Technology Data Exchange (ETDEWEB)

    Hatt, M.; Cheze-Le Rest, C.; Visvikis, D. [Inserm U650, Brest (France); Pradier, O. [Radiotherapie, CHRU Morvan, Brest (France)

    2011-10-15

    This study aims at assessing the possibility of prediction of the response of locally advanced oesophagus cancers, even before the beginning of treatment, by using metabolic volume measurements performed on {sup 18}F-FDG PET images made before the treatment. Medical files of 50 patients have been analyzed. According to the observed responses, and to metabolic volume and Total Lesion Glycosis (TLG) values, it appears that the images allow the extraction of parameters, such as the TLG, which are criteria for the prediction of the therapeutic response. Short communication

  14. Toward Accurate and Quantitative Comparative Metagenomics

    Science.gov (United States)

    Nayfach, Stephen; Pollard, Katherine S.

    2016-01-01

    Shotgun metagenomics and computational analysis are used to compare the taxonomic and functional profiles of microbial communities. Leveraging this approach to understand roles of microbes in human biology and other environments requires quantitative data summaries whose values are comparable across samples and studies. Comparability is currently hampered by the use of abundance statistics that do not estimate a meaningful parameter of the microbial community and biases introduced by experimental protocols and data-cleaning approaches. Addressing these challenges, along with improving study design, data access, metadata standardization, and analysis tools, will enable accurate comparative metagenomics. We envision a future in which microbiome studies are replicable and new metagenomes are easily and rapidly integrated with existing data. Only then can the potential of metagenomics for predictive ecological modeling, well-powered association studies, and effective microbiome medicine be fully realized. PMID:27565341

  15. Toward Accurate and Quantitative Comparative Metagenomics.

    Science.gov (United States)

    Nayfach, Stephen; Pollard, Katherine S

    2016-08-25

    Shotgun metagenomics and computational analysis are used to compare the taxonomic and functional profiles of microbial communities. Leveraging this approach to understand roles of microbes in human biology and other environments requires quantitative data summaries whose values are comparable across samples and studies. Comparability is currently hampered by the use of abundance statistics that do not estimate a meaningful parameter of the microbial community and biases introduced by experimental protocols and data-cleaning approaches. Addressing these challenges, along with improving study design, data access, metadata standardization, and analysis tools, will enable accurate comparative metagenomics. We envision a future in which microbiome studies are replicable and new metagenomes are easily and rapidly integrated with existing data. Only then can the potential of metagenomics for predictive ecological modeling, well-powered association studies, and effective microbiome medicine be fully realized. PMID:27565341

  16. Accurate renormalization group analyses in neutrino sector

    Energy Technology Data Exchange (ETDEWEB)

    Haba, Naoyuki [Graduate School of Science and Engineering, Shimane University, Matsue 690-8504 (Japan); Kaneta, Kunio [Kavli IPMU (WPI), The University of Tokyo, Kashiwa, Chiba 277-8568 (Japan); Takahashi, Ryo [Graduate School of Science and Engineering, Shimane University, Matsue 690-8504 (Japan); Yamaguchi, Yuya [Department of Physics, Faculty of Science, Hokkaido University, Sapporo 060-0810 (Japan)

    2014-08-15

    We investigate accurate renormalization group analyses in neutrino sector between ν-oscillation and seesaw energy scales. We consider decoupling effects of top quark and Higgs boson on the renormalization group equations of light neutrino mass matrix. Since the decoupling effects are given in the standard model scale and independent of high energy physics, our method can basically apply to any models beyond the standard model. We find that the decoupling effects of Higgs boson are negligible, while those of top quark are not. Particularly, the decoupling effects of top quark affect neutrino mass eigenvalues, which are important for analyzing predictions such as mass squared differences and neutrinoless double beta decay in an underlying theory existing at high energy scale.

  17. Accurate ab initio spin densities

    CERN Document Server

    Boguslawski, Katharina; Legeza, Örs; Reiher, Markus

    2012-01-01

    We present an approach for the calculation of spin density distributions for molecules that require very large active spaces for a qualitatively correct description of their electronic structure. Our approach is based on the density-matrix renormalization group (DMRG) algorithm to calculate the spin density matrix elements as basic quantity for the spatially resolved spin density distribution. The spin density matrix elements are directly determined from the second-quantized elementary operators optimized by the DMRG algorithm. As an analytic convergence criterion for the spin density distribution, we employ our recently developed sampling-reconstruction scheme [J. Chem. Phys. 2011, 134, 224101] to build an accurate complete-active-space configuration-interaction (CASCI) wave function from the optimized matrix product states. The spin density matrix elements can then also be determined as an expectation value employing the reconstructed wave function expansion. Furthermore, the explicit reconstruction of a CA...

  18. The Accurate Particle Tracer Code

    CERN Document Server

    Wang, Yulei; Qin, Hong; Yu, Zhi

    2016-01-01

    The Accurate Particle Tracer (APT) code is designed for large-scale particle simulations on dynamical systems. Based on a large variety of advanced geometric algorithms, APT possesses long-term numerical accuracy and stability, which are critical for solving multi-scale and non-linear problems. Under the well-designed integrated and modularized framework, APT serves as a universal platform for researchers from different fields, such as plasma physics, accelerator physics, space science, fusion energy research, computational mathematics, software engineering, and high-performance computation. The APT code consists of seven main modules, including the I/O module, the initialization module, the particle pusher module, the parallelization module, the field configuration module, the external force-field module, and the extendible module. The I/O module, supported by Lua and Hdf5 projects, provides a user-friendly interface for both numerical simulation and data analysis. A series of new geometric numerical methods...

  19. Accurate thickness measurement of graphene

    Science.gov (United States)

    Shearer, Cameron J.; Slattery, Ashley D.; Stapleton, Andrew J.; Shapter, Joseph G.; Gibson, Christopher T.

    2016-03-01

    Graphene has emerged as a material with a vast variety of applications. The electronic, optical and mechanical properties of graphene are strongly influenced by the number of layers present in a sample. As a result, the dimensional characterization of graphene films is crucial, especially with the continued development of new synthesis methods and applications. A number of techniques exist to determine the thickness of graphene films including optical contrast, Raman scattering and scanning probe microscopy techniques. Atomic force microscopy (AFM), in particular, is used extensively since it provides three-dimensional images that enable the measurement of the lateral dimensions of graphene films as well as the thickness, and by extension the number of layers present. However, in the literature AFM has proven to be inaccurate with a wide range of measured values for single layer graphene thickness reported (between 0.4 and 1.7 nm). This discrepancy has been attributed to tip-surface interactions, image feedback settings and surface chemistry. In this work, we use standard and carbon nanotube modified AFM probes and a relatively new AFM imaging mode known as PeakForce tapping mode to establish a protocol that will allow users to accurately determine the thickness of graphene films. In particular, the error in measuring the first layer is reduced from 0.1-1.3 nm to 0.1-0.3 nm. Furthermore, in the process we establish that the graphene-substrate adsorbate layer and imaging force, in particular the pressure the tip exerts on the surface, are crucial components in the accurate measurement of graphene using AFM. These findings can be applied to other 2D materials.

  20. Accurate thickness measurement of graphene.

    Science.gov (United States)

    Shearer, Cameron J; Slattery, Ashley D; Stapleton, Andrew J; Shapter, Joseph G; Gibson, Christopher T

    2016-03-29

    Graphene has emerged as a material with a vast variety of applications. The electronic, optical and mechanical properties of graphene are strongly influenced by the number of layers present in a sample. As a result, the dimensional characterization of graphene films is crucial, especially with the continued development of new synthesis methods and applications. A number of techniques exist to determine the thickness of graphene films including optical contrast, Raman scattering and scanning probe microscopy techniques. Atomic force microscopy (AFM), in particular, is used extensively since it provides three-dimensional images that enable the measurement of the lateral dimensions of graphene films as well as the thickness, and by extension the number of layers present. However, in the literature AFM has proven to be inaccurate with a wide range of measured values for single layer graphene thickness reported (between 0.4 and 1.7 nm). This discrepancy has been attributed to tip-surface interactions, image feedback settings and surface chemistry. In this work, we use standard and carbon nanotube modified AFM probes and a relatively new AFM imaging mode known as PeakForce tapping mode to establish a protocol that will allow users to accurately determine the thickness of graphene films. In particular, the error in measuring the first layer is reduced from 0.1-1.3 nm to 0.1-0.3 nm. Furthermore, in the process we establish that the graphene-substrate adsorbate layer and imaging force, in particular the pressure the tip exerts on the surface, are crucial components in the accurate measurement of graphene using AFM. These findings can be applied to other 2D materials.

  1. A More Accurate Fourier Transform

    CERN Document Server

    Courtney, Elya

    2015-01-01

    Fourier transform methods are used to analyze functions and data sets to provide frequencies, amplitudes, and phases of underlying oscillatory components. Fast Fourier transform (FFT) methods offer speed advantages over evaluation of explicit integrals (EI) that define Fourier transforms. This paper compares frequency, amplitude, and phase accuracy of the two methods for well resolved peaks over a wide array of data sets including cosine series with and without random noise and a variety of physical data sets, including atmospheric $\\mathrm{CO_2}$ concentrations, tides, temperatures, sound waveforms, and atomic spectra. The FFT uses MIT's FFTW3 library. The EI method uses the rectangle method to compute the areas under the curve via complex math. Results support the hypothesis that EI methods are more accurate than FFT methods. Errors range from 5 to 10 times higher when determining peak frequency by FFT, 1.4 to 60 times higher for peak amplitude, and 6 to 10 times higher for phase under a peak. The ability t...

  2. Recombination and selectional forces in cyanopeptolin NRPS operons from highly similar, but geographically remote Planktothrix strains

    Directory of Open Access Journals (Sweden)

    Kristensen Tom

    2008-08-01

    Full Text Available Abstract Background Cyanopeptolins are nonribosomally produced heptapetides showing a highly variable composition. The cyanopeptolin synthetase operon has previously been investigated in three strains from the genera Microcystis, Planktothrix and Anabaena. Cyanopeptolins are displaying protease inhibitor activity, but the biological function(s is (are unknown. Cyanopeptolin gene cluster variability and biological functions of the peptide variants are likely to be interconnected. Results We have investigated two cyanopeptolin gene clusters from highly similar, but geographically remote strains of the same genus. Sequencing of a nonribosomal peptide synthetase (NRPS cyanopeptolin gene cluster from the Japanese strain Planktothrix NIES 205 (205-oci, showed the 30 kb gene cluster to be highly similar to the oci gene cluster previously described in Planktothrix NIVA CYA 116, isolated in Norway. Both operons contained seven NRPS modules, a sulfotransferase (S and a glyceric acid loading (GA-domain. Sequence analyses showed a high degree of conservation, except for the presence of an epimerase domain in NIES 205 and the regions around the epimerase, showing high substitution rates and Ka/Ks values above 1. The two strains produce almost identical cyanopeptolins, cyanopeptolin-1138 and oscillapeptin E respectively, but with slight differences regarding the production of minor cyanopeptolin variants. These variants may be the result of relaxed adenylation (A-domain specificity in the nonribosomal enzyme complex. Other genetic markers (16S rRNA, ntcA and the phycocyanin cpcBA spacer were identical, supporting that these geographically separated Planktothrix strains are closely related. Conclusion A horizontal gene transfer event resulting in exchange of a whole module-encoding region was observed. Nucleotide statistics indicate that both purifying selection and positive selection forces are operating on the gene cluster. The positive selection forces are

  3. Accurately Detecting Students' Lies regarding Relational Aggression by Correctional Instructions

    Science.gov (United States)

    Dickhauser, Oliver; Reinhard, Marc-Andre; Marksteiner, Tamara

    2012-01-01

    This study investigates the effect of correctional instructions when detecting lies about relational aggression. Based on models from the field of social psychology, we predict that correctional instruction will lead to a less pronounced lie bias and to more accurate lie detection. Seventy-five teachers received videotapes of students' true denial…

  4. The extent of co-metabolism of glucose and galactose by L. lactis changes with the expression of the lacSZ operon from Streptococcus thermophilus

    DEFF Research Database (Denmark)

    Solem, Christian; Købmann, Brian Jensen; Jensen, Peter Ruhdal

    2008-01-01

    The lactose transporter and β-galactosidase from Streptococcus thermophilus, encoded by the lacSZ operon, were introduced into the lactose-negative strain Lactococcus lactis MG1363 and the expression of the lacSZ operon was modulated by substitution of the native promoter with randomized synthetic...... and only glucose was metabolized in glycolysis. Interestingly, strains with low expression of the operon showed a mixed acid metabolism and co-metabolism of galactose and glucose. The lactose flux increased gradually with increasing expression of the lacSZ operon until an optimum was observed...... promoters. A series of strains with various expression levels of lacSZ were examined for their fermentation of lactose. Strains with a high expression level were found to metabolize lactose in a similar manner to S. thermophilus, i.e. the galactose moiety of lactose was excreted to the growth medium...

  5. The pvc Operon Regulates the Expression of the Pseudomonas aeruginosa Fimbrial Chaperone/Usher Pathway (Cup) Genes

    OpenAIRE

    Uzma Qaisar; Liming Luo; Haley, Cecily L.; Brady, Sean F.; Carty, Nancy L.; Colmer-Hamood, Jane A.; Hamood, Abdul N.

    2013-01-01

    The Pseudomonas aeruginosa fimbrial structures encoded by the cup gene clusters (cupB and cupC) contribute to its attachment to abiotic surfaces and biofilm formation. The P. aeruginosa pvcABCD gene cluster encodes enzymes that synthesize a novel isonitrile functionalized cumarin, paerucumarin. Paerucumarin has already been characterized chemically, but this is the first report elucidating its role in bacterial biology. We examined the relationship between the pvc operon and the cup gene clus...

  6. Heterogeneity of outer membrane proteins in Borrelia burgdorferi: comparison of osp operons of three isolates of different geographic origins.

    OpenAIRE

    JONSSON, M; Noppa, L; Barbour, A G; Bergström, S

    1992-01-01

    Biochemical and immunochemical studies of the outer membrane proteins of Borrelia burgdorferi have shown that the OspA and OspB proteins from strains of different geographic origins may differ considerably in their reactivities with monoclonal antibodies and in their apparent molecular weights. To further characterize this variation in Osp proteins between strains, the osp operons and deduced translation products from two strains, one from Sweden (ACAI) and one from eastern Russia (Ip90), wer...

  7. Characterisation of the mgo operon in Pseudomonas syringae pv. syringae UMAF0158 that is required for mangotoxin production

    Directory of Open Access Journals (Sweden)

    Arrebola Eva

    2012-01-01

    Full Text Available Abstract Background Mangotoxin is an antimetabolite toxin that is produced by strains of Pseudomonas syringae pv. syringae; mangotoxin-producing strains are primarily isolated from mango tissues with symptoms of bacterial apical necrosis. The toxin is an oligopeptide that inhibits ornithine N-acetyl transferase (OAT, a key enzyme in the biosynthetic pathway of the essential amino acids ornithine and arginine. The involvement of a putative nonribosomal peptide synthetase gene (mgoA in mangotoxin production and virulence has been reported. Results In the present study, we performed a RT-PCR analysis, insertional inactivation mutagenesis, a promoter expression analysis and terminator localisation to study the gene cluster containing the mgoA gene. Additionally, we evaluated the importance of mgoC, mgoA and mgoD in mangotoxin production. A sequence analysis revealed an operon-like organisation. A promoter sequence was located upstream of the mgoB gene and was found to drive lacZ transcription. Two terminators were located downstream of the mgoD gene. RT-PCR experiments indicated that the four genes (mgoBCAD constitute a transcriptional unit. This operon is similar in genetic organisation to those in the three other P. syringae pathovars for which complete genomes are available (P. syringae pv. syringae B728a, P. syringae pv. tomato DC3000 and P. syringae pv. phaseolicola 1448A. Interestingly, none of these three reference strains is capable of producing mangotoxin. Additionally, extract complementation resulted in a recovery of mangotoxin production when the defective mutant was complemented with wild-type extracts. Conclusions The results of this study confirm that mgoB, mgoC, mgoA and mgoD function as a transcriptional unit and operon. While this operon is composed of four genes, only the last three are directly involved in mangotoxin production.

  8. Synthetic operon for (R,R)-2,3-butanediol production in Bacillus subtilis and Escherichia coli.

    Science.gov (United States)

    de Oliveira, Rafael R; Nicholson, Wayne L

    2016-01-01

    To reduce dependence on petroleum, an alternative route to production of the chemical feedstock 2,3-butanediol (2,3-BD) from renewable lignocellulosic sources is desirable. In this communication, the genes encoding the pathway from pyruvate to 2,3-BD (alsS, alsD, and bdhA encoding acetolactate synthase, acetolactate decarboxylase, and butanediol dehydrogenase, respectively) from Bacillus subtilis were engineered into a single tricistronic operon under control of the isopropyl β-D-1-thiogalactopyranoside (IPTG)-inducible Pspac promoter in a shuttle plasmid capable of replication and expression in either B. subtilis or Escherichia coli. We describe the construction and performance of a shuttle plasmid carrying the IPTG-inducible synthetic operon alsSDbdhA coding for 2,3-BD pathway capable of (i) expression in two important representative model microorganisms, the gram-positive B. subtilis and the gram-negative E. coli; (ii) increasing 2,3-BD production in B. subtilis; and (iii) successfully introducing the B. subtilis 2,3-BD pathway into E. coli. The synthetic alsSDbdhA operon constructed using B. subtilis native genes not only increased the 2,3-BD production in its native host but also efficiently expressed the pathway in the heterologous organism E. coli. Construction of an efficient shuttle plasmid will allow investigation of 2,3-BD production performance in related organisms with industrial potential for production of bio-based chemicals.

  9. A distinct alleles and genetic recombination of pmrCAB operon in species of Acinetobacter baumannii complex isolates.

    Science.gov (United States)

    Kim, Dae Hun; Ko, Kwan Soo

    2015-07-01

    To investigate pmrCAB sequence divergence in 5 species of Acinetobacter baumannii complex, a total of 80 isolates from a Korean hospital were explored. We evaluated nucleotide and amino acid polymorphisms of pmrCAB operon, and phylogenetic trees were constructed for each gene of prmCAB operon. Colistin and polymyxin B susceptibility was determined for all isolates, and multilocus sequence typing was also performed for A. baumannii isolates. Our results showed that each species of A. baumannii complex has divergent pmrCAB operon sequences. We identified a distinct pmrCAB allele allied with Acinetobacter nosocomialis in gene trees. Different grouping in each gene tree suggests sporadic recombination or emergence of pmrCAB genes among Acinetobacter species. Sequence polymorphisms among Acinetobacter species might not be associated with colistin resistance. We revealed that a distinct pmrCAB allele may be widespread across the continents such as North America and Asia and that sporadic genetic recombination or emergence of pmrCAB genes might occur.

  10. [Insertional Inactivation of Virulence Operon in Population of Persistent Bordetella pertussis Bacteria].

    Science.gov (United States)

    Karataev, G I; Sinyashina, L N; Medkova, A Yu; Semin, E G; Shevtsova, Z V; Matua, A Z; Kondzariya, I G; Amichba, A A; Kubrava, D T; Mikvabia, Z Ya

    2016-04-01

    Avirulent B. pertussis bacteria containing IS elements in the bvgAS operon were detected during the study of whooping cough patients and bacilli carriers. The present work is devoted to the study of the accumulation dynamics and the mechanisms of generation of persistent forms of the B. pertussis bacteria in lower monkeys as the most adequate model for extrapolation ofthe experiment results to humans. By means of the real-time PCR method, it was established that the B. pertussis bacteria lived more than three months in the upper respiratory tract after a single intranasal monkey infection; the period was reduced to 14-28 days during repeated infection. An increase in the portion of B. pertussis Bvg mutants in the population to tens of percent from the total number of registered bacteria was registered. The experimental confirmation ofthe development and accumulation of avirulent B. pertussis Bvg mutants during the development of the infectious process was obtained. Further study of the composition of the B. pertussis persistent bacteria population at different stages of the disease will make it possible to formulate new approaches to the whooping cough diagnostics and prevention and creation of fundamentally new drugs.

  11. Characterization of the glnK-amtB operon of Azotobacter vinelandii.

    Science.gov (United States)

    Meletzus, D; Rudnick, P; Doetsch, N; Green, A; Kennedy, C

    1998-06-01

    To determine whether in Azotobacter vinelandii the PII protein influences the regulation of nif gene expression in response to fluxes in the ammonium supply, the gene encoding PII was isolated and characterized. Its deduced translation product was highly similar to PII proteins from other organisms, with the greatest degree of relatedness being exhibited to the Escherichia coli glnK gene product. A gene designated amtB was found downstream of and was contranscribed with glnK as in E. coli. The AmtB protein is similar to functionally characterized ammonium transport proteins from a few other eukaryotes and one other prokaryote. glnK and amtB comprise an operon. Attempts to isolate a stable glnK mutant strain were unsuccessful, suggesting that glnK, like glnA, is an essential gene in A. vinelandii. amtB mutants were isolated, and although growth on limiting amounts of ammonium was similar in the mutant and wild-type strains, the mutants were unable to transport [14C]methylammonium. PMID:9620984

  12. Autonomous expression of the slo gene of the bicistronic nga-slo operon of Streptococcus pyogenes.

    Science.gov (United States)

    Savic, Dragutin J; McShan, William M; Ferretti, Joseph J

    2002-05-01

    A recent model for cytolysin-mediated translocation in Streptococcus pyogenes proposes that NAD-glycohydrolase is translocated through streptolysin O-generated pores into a host cell (J. Madden, N. Ruiz, and M. Caparon, Cell 104:143-152, 2001). This model also assumes that the NAD-glycohydrolase (nga) and streptolysin O (slo) genes that code for these products are organized in an operon-like structure expressed from a single promoter only (nga). We expand this model by showing that slo possesses its own autonomous promoter, which is located 155 bp upstream of the slo gene. Under experimental conditions in which S. pyogenes is grown in THY medium, the strength of the slo promoter, as measured by the activity of a lacZ reporter gene, resulted in low but highly reproducible values. Finally, we demonstrated that sloR, a S. pyogenes gene that closely resembles the Clostridium perfringens pfoR gene, exerts a negative effect on the expression of the slo gene. PMID:11953421

  13. Prediction of Unsteady Transonic Aerodynamics Project

    Data.gov (United States)

    National Aeronautics and Space Administration — An accurate prediction of aero-elastic effects depends on an accurate prediction of the unsteady aerodynamic forces. Perhaps the most difficult speed regime is...

  14. Distribution and degree of heterogeneity of the afimbrial-adhesin-encoding operon (afa) among uropathogenic Escherichia coli isolates.

    Science.gov (United States)

    Labigne-Roussel, A; Falkow, S

    1988-03-01

    The afimbrial adhesin (AFA-I) from a pyelonephritic Escherichia coli isolate (KS52) is a mannose-resistant, P-independent, X-binding adhesin, expressed by the afa-1 operon. It is distinct from the E. coli X-binding adhesins with M and S specificity. A total of 138 E. coli isolates belonging to various serotypes, mostly from urinary tract infections, were screened for the presence of DNA sequences related to the afa operon and for the expression of an X-adhesin able to mediate mannose-resistant hemagglutination (MRHA) and adhesion to uroepithelial cells. Fifteen strains were shown to harbor DNA sequences related to the AFA-I-encoding operon, and 13 of them expressed an X-adhesin. Using as probes different DNA segments of the AFA-I-encoding operon in Southern experiments, we demonstrated that only three of these clinical isolates contained genetic determinants closely related to those identified in the original afa prototype strain (KS52): presence of the afaA, afaB, afaC, afaD, and afaE genes associated with the expression of a 16,000-dalton hemagglutinin-adhesin which strongly cross-reacted with AFA-I-specific antibodies. The other E. coli isolates harbored DNA sequences homologous to the afaA, afaB, afaC, and afaD genes, but lacked the sequence corresponding to the adhesin-producing gene afaE; Western blots allowed the detection of polypeptides (15,000, 15,500, or 16,000 daltons) in these strains which cross-reacted with variable intensity with antibodies raised against the denatured AFA-I protein, but did not cross-react with native AFA-I-specific antibodies. Following DNA cloning experiments from chromosomal DNA of two of those strains (A22 and A30), we demonstrated that although the AFA-related operon in A22 and A30 strains lacked the AFA-I adhesin-encoding gene, they synthesized a functional X-adhesin. Thus, strains A22 and A30 encode adhesins designated AFA-II and AFA-III, which were cloned on recombinant plasmids pILL72 and pILL61, respectively. Southern

  15. 38 CFR 4.46 - Accurate measurement.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Accurate measurement. 4... RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.46 Accurate measurement. Accurate measurement of the length of stumps, excursion of joints, dimensions and location of scars with respect...

  16. Biomolecular Mechanisms of Mercury Transfers and Transformations by Proteins of the Mer Operon

    Science.gov (United States)

    Miller, S. M.; Hong, B.; Nauss, R.; Momany, C.; Summers, A. O.; Feng, X.; Harwood, I.; Stroud, R.

    2008-12-01

    Aerobic bacteria exhibiting resistance to the toxic effects of Hg(II) and organomercurials [RHg(I), e.g. MeHg(I)] and are widely found in both pristine and mercury contaminated environments. Resistance, afforded by a plasmid- or transposon-associated mer operon, involves an unusual pathway where Hg(II) and organomercurials [RHg(I)] undergo facilitated entry into the bacterial cytoplasm via an integral membrane transport protein (MerT) and are then "detoxified" by the concerted effort of two enzymes, organomercurial lyase (MerB), which catalyzes dealkylation (i.e., demethylation) of RHg(I) to Hg(II) and a hydrocarbon, and mercuric ion reductase (MerA), which catalyzes reduction of Hg(II) to Hg(0) as the ultimate detoxification for the organism. With a widespread distribution, these bacterial transformations play a significant role in the fate of mercury in the environment. Our focus is on elucidation of the molecular mechanisms for the transport and catalytic transformations of RHg(I) and Hg(II) by these proteins and the factors that influence the overall efficiency of the process. Current efforts are focused primarily on elucidating details of RHg(I) binding and dealkylation by MerB as well as the mechanism for transfer of the Hg(II) product to MerA. Key findings include the demonstration of a non-cysteine residue as essential for the catalytic activity and demonstration that direct transfer of Hg(II) to MerA proceeds more rapidly and more completely than transfer to small MW thiols such as cysteines or glutathione. Reuslts of these studies as well as an overview of our current understanding of the whole system will be presented.

  17. The cabABC Operon Essential for Biofilm and Rugose Colony Development in Vibrio vulnificus.

    Directory of Open Access Journals (Sweden)

    Jin Hwan Park

    2015-09-01

    Full Text Available A transcriptome analysis identified Vibrio vulnificus cabABC genes which were preferentially expressed in biofilms. The cabABC genes were transcribed as a single operon. The cabA gene was induced by elevated 3',5'-cyclic diguanylic acid (c-di-GMP and encoded a calcium-binding protein CabA. Comparison of the biofilms produced by the cabA mutant and its parent strain JN111 in microtiter plates using crystal-violet staining demonstrated that CabA contributed to biofilm formation in a calcium-dependent manner under elevated c-di-GMP conditions. Genetic and biochemical analyses revealed that CabA was secreted to the cell exterior through functional CabB and CabC, distributed throughout the biofilm matrix, and produced as the biofilm matured. These results, together with the observation that CabA also contributes to the development of rugose colony morphology, indicated that CabA is a matrix-associated protein required for maturation, rather than adhesion involved in the initial attachment, of biofilms. Microscopic comparison of the structure of biofilms produced by JN111 and the cabA mutant demonstrated that CabA is an extracellular matrix component essential for the development of the mature biofilm structures in flow cells and on oyster shells. Exogenously providing purified CabA restored the biofilm- and rugose colony-forming abilities of the cabA mutant when calcium was available. Circular dichroism and size exclusion analyses revealed that calcium binding induces CabA conformational changes which may lead to multimerization. Extracellular complementation experiments revealed that CabA can assemble a functional matrix only when exopolysaccharides coexist. Consequently, the combined results suggested that CabA is a structural protein of the extracellular matrix and multimerizes to a conformation functional in building robust biofilms, which may render V. vulnificus to survive in hostile environments and reach a concentrated infective dose.

  18. Positive control of lac operon expression in vitro by guanosine 5'-diphosphate 3'-diphosphate.

    Science.gov (United States)

    Primakoff, P; Artz, S W

    1979-04-01

    Maximal expression of the Escherichia coli lactose operon in a coupled in vitro transcription-translation system from a Salmonella typhimurium relA mutant was strongly dependent upon addition of guanosine 5'-diphosphate 3'-diphosphate (ppGpp). Without added ppGpp, at saturating 3',5'-cyclic AMP (cAMP) concentrations, synthesis of beta-galactosidase (beta-D-galactoside galactohydrolase, EC 3.2.1.23) was reproducibly only 5-7% of that which can be obtained with 0.5-0.8 mM ppGpp. Experiments in which transcription was uncoupled from translation indicated that this 14- to 20-fold stimulation by ppGpp occurred at the level of transcription. When coupled beta-galactosidase synthesis was primed with a template containing a well-characterized mutant lac promoter (lacP(r)L8UV5), the dependence on ppGpp was greatly reduced. This result provides an important experimental control previously unavailable for verifying the significance of ppGpp effects on gene regulation in vitro; it indicates that activation of lacP(+) expression by ppGpp is specifically an effect of increased transcription initiations. Furthermore, the large ppGpp stimulation of lacP(+) DNA enabled the level of expression of this template to approach that of lacP(r)L8UV5 DNA, an observation expected from results in vivo but not obtained with other transcription-translation systems in vitro. The importance of these results is considered with respect to previous ideas on the physiological role of ppGpp as a supercontrol molecule in bacterial regulation. PMID:109832

  19. Effect of growth conditions on expression of the acid phosphatase (cyx-appA) operon and the appY gene, which encodes a transcriptional activator of Escherichia coli

    DEFF Research Database (Denmark)

    Brøndsted, Lone; Atlung, Tove

    1996-01-01

    The expression and transcriptional regulation of the Escherichia coli cyx-appA operon and the appY gene has been investigated during different environmental conditions using single copy transcriptional lacZ fusions. The cyx-appA operon encodes acid phosphatase and a putative cytochrome oxidase.......ArcA and AppY activated transcription of the cyx-appA operon during entry into stationary phase and under anaerobic growth conditions. The expression of the cyx-appA operon was affected by the anaerobic energy metabolism.The presence of the electron acceptors nitrate and fumarate repressed the expression...... of the cyx-appA operon. The nitrate repression was partially dependent on NarL. A high expression of the operon was obtained in glucose medium supplemented with formate, where E.coli obtains energy by fermentation. The formate induction was independent of the fhlA gene product. The results presented...

  20. Nitrite-Responsive Activation of the Nitrate Assimilation Operon in Cyanobacteria Plays an Essential Role in Up-Regulation of Nitrate Assimilation Activities under Nitrate-Limited Growth Conditions

    OpenAIRE

    Aichi, Makiko; Maeda, Shin-Ichi; Ichikawa, Kazuhiro; Omata, Tatsuo

    2004-01-01

    NtcB of the cyanobacterium Synechococcus elongatus strain PCC 7942 is a LysR family protein that enhances expression of the nitrate assimilation operon (nirA operon) in response to the presence of nitrite, an intermediate of assimilatory nitrate reduction. Inactivation of ntcB in this cyanobacterium specifically abolishes the nitrite responsiveness of nirA operon expression, but under nitrate-replete conditions (wherein negative feedback by intracellularly generated ammonium prevails over the...

  1. Accurate genetic switch in Escherichia coli: novel mechanism of regulation by co-repressor.

    Science.gov (United States)

    Tabaka, Marcin; Cybulski, Olgierd; Hołyst, Robert

    2008-04-01

    Understanding a biological module involves recognition of its structure and the dynamics of its principal components. In this report we present an analysis of the dynamics of the repression module within the regulation of the trp operon in Escherichia coli. We combine biochemical data for reaction rate constants for the trp repressor binding to trp operator and in vivo data of a number of tryptophan repressors (TrpRs) that bind to the operator. The model of repression presented in this report greatly differs from previous mathematical models. One, two or three TrpRs can bind to the operator and repress the transcription. Moreover, reaction rates for detachment of TrpRs from the operator strongly depend on tryptophan (Trp) concentration, since Trp can also bind to the repressor-operator complex and stabilize it. From the mathematical modeling and analysis of reaction rates and equilibrium constants emerges a high-quality, accurate and effective module of trp repression. This genetic switch responds accurately to fast consumption of Trp from the interior of a cell. It switches with minimal dispersion when the concentration of Trp drops below a thousand molecules per cell. PMID:18313075

  2. Simple and accurate analytical calculation of shortest path lengths

    CERN Document Server

    Melnik, Sergey

    2016-01-01

    We present an analytical approach to calculating the distribution of shortest paths lengths (also called intervertex distances, or geodesic paths) between nodes in unweighted undirected networks. We obtain very accurate results for synthetic random networks with specified degree distribution (the so-called configuration model networks). Our method allows us to accurately predict the distribution of shortest path lengths on real-world networks using their degree distribution, or joint degree-degree distribution. Compared to some other methods, our approach is simpler and yields more accurate results. In order to obtain the analytical results, we use the analogy between an infection reaching a node in $n$ discrete time steps (i.e., as in the susceptible-infected epidemic model) and that node being at a distance $n$ from the source of the infection.

  3. Predicting toxicity of nanoparticles

    OpenAIRE

    BURELLO ENRICO; Worth, Andrew

    2011-01-01

    A statistical model based on a quantitative structure–activity relationship accurately predicts the cytotoxicity of various metal oxide nanoparticles, thus offering a way to rapidly screen nanomaterials and prioritize testing.

  4. Accurate multireference study of Si3 electronic manifold

    CERN Document Server

    Goncalves, Cayo Emilio Monteiro; Braga, Joao Pedro

    2016-01-01

    Since it has been shown that the silicon trimer has a highly multi-reference character, accurate multi-reference configuration interaction calculations are performed to elucidate its electronic manifold. Emphasis is given to the long range part of the potential, aiming to understand the atom-diatom collisions dynamical aspects, to describe conical intersections and important saddle points along the reactive path. Potential energy surface main features analysis are performed for benchmarking, and highly accurate values for structures, vibrational constants and energy gaps are reported, as well as the unpublished spin-orbit coupling magnitude. The results predict that inter-system crossings will play an important role in dynamical simulations, specially in triplet state quenching, making the problem of constructing a precise potential energy surface more complicated and multi-layer dependent. The ground state is predicted to be the singlet one, but since the singlet-triplet gap is rather small (2.448 kJ/mol) bo...

  5. Variability of rRNA operon copy number and growth rate dynamics of Bacillus isolated from an extremely oligotrophic aquatic ecosystem

    Directory of Open Access Journals (Sweden)

    Jorge Antonio Valdivia-Anistro

    2016-01-01

    Full Text Available The ribosomal RNA (rrn operon is a key suite of genes related to the production of protein synthesis machinery and thus to bacterial growth physiology. Experimental evidence has suggested an intrinsic relationship between the number of copies of this operon and environmental resource availability, especially the availability of phosphorus (P, because bacteria that live in oligotrophic ecosystems usually have few rrn operons and a slow growth rate. The Cuatro Ciénegas Basin (CCB is a complex aquatic ecosystem that contains an unusually high microbial diversity that is able to persist under highly oligotrophic conditions. These environmental conditions impose a variety of strong selective pressures that shape the genome dynamics of their inhabitants. The genus Bacillus is one of the most abundant cultivable bacterial groups in the CCB and usually possesses a relatively large number of rrn operon copies (6-15 copies. The main goal of this study was to analyze the variation in the number of rrn operon copies of Bacillus in the CCB and to assess their growth-related properties as well as their stoichiometric balance (N and P content. We defined 18 phylogenetic groups within the Bacilli clade and documented a range of from six to 14 copies of the rrn operon. The growth dynamic of these Bacilli was heterogeneous and did not show a direct relation to the number of operon copies. Physiologically, our results were not consistent with the Growth Rate Hypothesis, since the copies of the rrn operon were decoupled from growth rate. However, we speculate that the diversity of the growth properties of these Bacilli as well as the low P content of their cells in an ample range of rrn copy number is an adaptive response to oligotrophy of the CCB and could represent an ecological mechanism that allows these taxa to coexist. These findings increase the knowledge of the variability in the number of copies of the rrn operon in the genus Bacillus and give insights

  6. In vitro transcriptional studies of the bkd operon of Pseudomonas putida: L-branched-chain amino acids and D-leucine are the inducers.

    Science.gov (United States)

    Madhusudhan, K T; Luo, J; Sokatch, J R

    1999-05-01

    BkdR is the transcriptional activator of the bkd operon, which encodes the four proteins of the branched-chain keto acid dehydrogenase multienzyme complex of Pseudomonas putida. In this study, hydroxyl radical footprinting revealed that BkdR bound to only one face of DNA over the same region identified in DNase I protection assays. Deletions of even a few bases in the 5' region of the BkdR-binding site greatly reduced transcription, confirming that the entire protected region is necessary for transcription. In vitro transcription of the bkd operon was obtained by using a vector containing the bkdR-bkdA1 intergenic region plus the putative rho-independent terminator of the bkd operon. Substrate DNA, BkdR, and any of the L-branched-chain amino acids or D-leucine was required for transcription. Branched-chain keto acids, D-valine, and D-isoleucine did not promote transcription. Therefore, the L-branched-chain amino acids and D-leucine are the inducers of the bkd operon. The concentration of L-valine required for half-maximal transcription was 2.8 mM, which is similar to that needed to cause half-maximal proteolysis due to a conformational change in BkdR. A model for transcriptional activation of the bkd operon by BkdR during enzyme induction which incorporates these results is presented. PMID:10217783

  7. HosA, a MarR Family Transcriptional Regulator, Represses Nonoxidative Hydroxyarylic Acid Decarboxylase Operon and Is Modulated by 4-Hydroxybenzoic Acid.

    Science.gov (United States)

    Roy, Ajit; Ranjan, Akash

    2016-02-23

    Members of the Multiple antibiotic resistance Regulator (MarR) family of DNA binding proteins regulate transcription of a wide array of genes required for virulence and pathogenicity of bacteria. The present study reports the molecular characterization of HosA (Homologue of SlyA), a MarR protein, with respect to its target gene, DNA recognition motif, and nature of its ligand. Through a comparative genomics approach, we demonstrate that hosA is in synteny with nonoxidative hydroxyarylic acid decarboxylase (HAD) operon and is present exclusively within the mutS-rpoS polymorphic region in nine different genera of Enterobacteriaceae family. Using molecular biology and biochemical approach, we demonstrate that HosA binds to a palindromic sequence downstream to the transcription start site of divergently transcribed nonoxidative HAD operon and represses its expression. Furthermore, in silico analysis showed that the recognition motif for HosA is highly conserved in the upstream region of divergently transcribed operon in different genera of Enterobacteriaceae family. A systematic chemical search for the physiological ligand revealed that 4-hydroxybenzoic acid (4-HBA) interacts with HosA and derepresses HosA mediated repression of the nonoxidative HAD operon. Based on our study, we propose a model for molecular mechanism underlying the regulation of nonoxidative HAD operon by HosA in Enterobacteriaceae family. PMID:26818787

  8. Mutations in PurBox1 of the Bacillus subtilis pur operon control site affect adenine-regulated expression in vivo

    Institute of Scientific and Technical Information of China (English)

    XUAN; Jinsong; Howard; Zalkin; WENG; Manli

    2005-01-01

    Transcription of the Bacillus subtilis pur operon is regulated by a purine repressor (PurR)-DNA control site interaction. The pur operon control site has two PurBoxes that are required for high-affinity PurR binding. An upstream, strong-binding PurBox1 is at position -81 to -68 relative to the transcription start site and a downstream weak-binding PurBox2 is at position -49 to -36. We constructed three PurBox1 mutations and the effects on binding of PurR to the control region in vitro and on regulation of pur operon expression in vivo were investigated. The mutations significantly reduced the binding of PurR to control region DNA. In strains with G-75A, G-75T and a five bp deletion (△5) pur operon repression was defective in vivo. In addition in vivo PurR titration was used to confirm that sequences flanking PurBox1 and PurBox2 are required for PurR binding to the pur operon control site.

  9. Opine-Based Agrobacterium Competitiveness: Dual Expression Control of the Agrocinopine Catabolism (acc) Operon by Agrocinopines and Phosphate Levels ▿ †

    Science.gov (United States)

    Kim, H. Stanley; Yi, Hyojeong; Myung, Jaehee; Piper, Kevin R.; Farrand, Stephen K.

    2008-01-01

    Agrobacterium tumefaciens strain C58 can transform plant cells to produce and secrete the sugar-phosphate conjugate opines agrocinopines A and B. The bacterium then moves in response to the opines and utilizes them as exclusive sources of carbon, energy, and phosphate via the functions encoded by the acc operon. These privileged opine-involved activities contribute to the formation of agrobacterial niches in the environment. We found that the expression of the acc operon is induced by agrocinopines and also by limitation of phosphate. The main promoter is present in front of the first gene, accR, which codes for a repressor. This operon structure enables efficient repression when opine levels are low. The promoter contains two putative operators, one overlapping the −10 sequence and the other in the further upstream from it; two partly overlapped putative pho boxes between the two operators; and two consecutive transcription start sites. DNA fragments containing either of the operators bound purified repressor AccR in the absence of agrocinopines but not in the presence of the opines, demonstrating the on-off switch of the promoter. Induction of the acc operon can occur under low-phosphate conditions in the absence of agrocinopines and further increases when the opines also are present. Such opine-phosphate dual regulatory system of the operon may ensure maximum utilization of agrocinopines when available and thereby increase the chances of agrobacterial survival in the highly competitive environment with limited general food sources. PMID:18344359

  10. Genetic analysis of the virE operon of the Agrobacterium Ti plasmid pTiA6.

    OpenAIRE

    McBride, K E; Knauf, V C

    1988-01-01

    The virE operon of the Agrobacterium tumefaciens Ti plasmid pTiA6 encodes at least one trans-acting protein involved in the expression of virulence. Two open reading frames designated virE1 and virE2 code for polypeptides of 7 and 60 kilodaltons (kDa), respectively, that can be visualized after expression in Escherichia coli minicells. To determine which virE sequences are required for virulence, a strain deleted for the entire locus [strain KE1(pTiA6 delta E)] was constructed and tested for ...

  11. Identification of a Bordetella pertussis regulatory factor required for transcription of the pertussis toxin operon in Escherichia coli.

    OpenAIRE

    DeShazer, D; Wood, G E; Friedman, R L

    1995-01-01

    Transcription of the pertussis toxin operon (ptx) is positively regulated in Bordetella pertussis by the bvgAS locus. However, a ptx-lacZ transcriptional fusion in Escherichia coli cannot be activated by bvgAS in trans. This suggests that an additional factor(s) is required for transcription of ptx. A gene encoding a Bvg accessory factor (Baf) was identified by its ability to activate an E. coli ptx-lacZ fusion in the presence of bvgAS. The expression of ptx-lacZ was decreased by the addition...

  12. In vivo and in vitro detection of the leader RNA of the histidine operon of Escherichia coli K-12.

    OpenAIRE

    Frunzio, R; Bruni, C B; Blasi, F.

    1981-01-01

    The DNA of the attenuator region of the histidine operon of Escherichia coli has been transcribed in a purified in vitro system and found to synthesize two major RNA transcripts. The first one, 180 nucleotides long, has been identified as the histidine-specific leader RNA. It contains the coding sequence for the leader peptide [Di Nocera, P. P., Blasi, F., Di Lauro, R., Frunzio, R. & Bruni, C. B. (1978) Proc. Natl. Acad. Sci. USA 75, 4276-4280] and is terminated at the attenuator site. Termin...

  13. 木醋杆菌纤维素合成操纵子的克隆及棉花转化%Cloning Whole Cellulose-Synthesizing Operon (ayacs Operon) from Acetobacter xylinum and Transforming It into Cultivated Cotton Plants

    Institute of Scientific and Technical Information of China (English)

    卢迎春; 魏刚; 朱玉贤

    2002-01-01

    The gram-negative bacterium Acetobacter xylinum synthesizes an extracellular ribbon of cellulose microfibrils that possess unique structural and mechanical properties when compared to higher plant cellulose. All four genes in the cellulose-synthesizing operon (ayacs operon) of A. xylinum Ay201 were amplified by polymerase chain reaction (PCR) using oligonucleotide primers designed according to published acs operon sequence of A. xylinum ATCC 53582. Alignment of the two operons showed that they were highly homologous (98% similarity, 97% identity). AcsA and acsB gene were cloned in pCAMBIA 1301 vector while acsC and acsD were cloned in pCOB302-3 under the control of CaM 35S promoter. The constructs were introduced into cotton by the pollen-tube-pathway method and seeds obtained from putative transgenic plants were germinated on media containing hygromycin and phosphinothricin (PPT). Five seedlings out of 934 seeds were proved to contain all four foreign genes by PCR amplification. This is the first time that a whole operon encoding four different bacterial enzymes with various biological functions is transformed into cultivated cotton plants.%革兰氏阴性菌木醋杆菌(Acetobacter xylinum (Brown) Yamada)合成一种由纤维素微纤丝组成的胞外带状物.与高等植物纤维素相比,它具有独特的结构和机械性能.根据从木醋杆菌ATCC 53582克隆的acs纤维素合成操纵子序列设计引物, 用PCR的方法从木醋杆菌Ay201中克隆了ayacs纤维素合成操纵子的全部4个基因.序列比较发现,两者高度同源.将连上CaMV 35S启动子的acsA、acsB克隆到植物表达载体pCAMBIA 1301上,acsC、acsD克隆到pCOB302-3中.然后通过花粉管通道法转化棉花(Gossypium hirsutum)胚珠,收获的种子在含有卡那霉素和除草剂的双抗培养基上进行筛选.PCR检测发现934粒种子中有5棵植株含有全部4个基因.这是首次将编码4个功能蛋白的细菌操纵子成功地转入棉花.

  14. Characterization of TRAP-mediated regulation of the B. subtilis trp operon using in vitro transcription and transcriptional reporter fusions in vivo.

    Science.gov (United States)

    McAdams, Natalie M; Gollnick, Paul

    2015-01-01

    In Bacillus subtilis, transcription of the tryptophan biosynthetic operon is regulated by an attenuation mechanism involving two alternative RNA secondary structures in the 5' leader region upstream of the structural genes. Regulation is accomplished, at least in part, by controlling which RNA structure forms during transcription of the operon. When intracellular tryptophan levels are high, the trp RNA-binding attenuation protein (TRAP) binds to the nascent trp mRNA to promote formation of a transcription terminator structure so as to induce transcription termination prior to the structural genes. In limiting tryptophan, TRAP does not bind, the alternative antiterminator RNA structure forms, and the operon is transcribed. Several in vitro and in vivo assays have been utilized to study TRAP-mediated regulation of both transcription and translation. Here, we describe using in vitro transcription attenuation assays and in vivo trp-lacZ fusions to examine TRAP-mediated regulation of the trp genes. PMID:25579595

  15. The operon for cytokinin biosynthesis of Erwinia herbicola pv. gypsophilae contains two promoters and is plant induced.

    Science.gov (United States)

    Guo, M; Manulis, S; Barash, I; Lichter, A

    2001-12-01

    The operon for cytokinin biosynthesis in the gall-forming bacterium Erwinia herbicola pv. gypsophilae (Ehg) has been previously shown to reside on an indigenous plasmid (pPATH(Ehg)) that is mandatory for pathogenicity. This operon consists of two genes: the first open reading frame (pre-etz) is of unknown function, whereas the second one (etz) encodes for isopentenyl transferase. Northern hybridization performed with the wild-type strain Ehg824-1 grown in Luria-Bertani broth demonstrated two transcripts of which an etz-specific transcript (1.0 kb) was predominant. Fusion of upstream DNA fragments of both pre-etz and etz to the ice nucleation reporter gene inaZ in pVSP61 showed high ice nucleation activity in both cultures, confirming the presence of two independent promoters. An increase of 1-1.5 orders in transcriptional activity of these promoters was observed following inoculation of gypsophila cuttings. Mutants of Ehg824-1 were generated by insertion of inaZ into pre-etz and etz using the transposon reporter Tn3-Spice. An increase of about two orders in transcriptional activity was recorded with both mutants following inoculation of gypsophila or bean cuttings. A similar induction was also observed when the bacteria were applied to the leaf surface of these plants. Unlike other virulence genes present on the pPATH(Ehg), neither pre-etz nor etz was regulated by the adjacent hrp gene cluster. PMID:11822839

  16. rRNA operons and genome size of 'Candidatus Liberibacter americanus', a bacterium associated with citrus huanglongbing in Brazil.

    Science.gov (United States)

    Wulff, N A; Eveillard, S; Foissac, X; Ayres, A J; Bové, J-M

    2009-08-01

    Huanglongbing is one of the most severe diseases of citrus worldwide and is associated with 'Candidatus (Ca.) Liberibacter africanus' in Africa, 'Ca. Liberibacter asiaticus' in Asia and the Americas (Brazil, USA and Cuba) and 'Ca. Liberibacter americanus' (Lam) in Brazil. In the absence of axenic cultures, genetic information on liberibacters is scarce. The sequences of the entire 23S rRNA and 5S rRNA genes from Lam have now been obtained, using a consensus primer designed on known tRNAMet sequences of rhizobia. The size of the Lam genome was determined by PFGE, using Lam-infected periwinkle plants for bacterial enrichment, and was found to be close to 1.31 Mbp. In order to determine the number of ribosomal operons on the Lam genome, probes designed to detect the 16S rRNA gene and the 3' end of the 23S rRNA gene were developed and used for Southern hybridization with I-CeuI-treated genomic DNA. Our results suggest that there are three ribosomal operons in a circular genome. Lam is the first liberibacter species for which such data are available.

  17. Modulating TRAP-mediated transcription termination by AT during transcription of the leader region of the Bacillus subtilis trp operon.

    Science.gov (United States)

    Sharma, Shraddha; Gollnick, Paul

    2014-05-01

    An 11-subunit protein called trp RNA binding Attenuation Protein (TRAP) controls attenuation of the tryptophan biosynthetic (trpEDCFBA) operon in Bacillus subtilis. Tryptophan-activated TRAP binds to 11 (G/U)AG repeats in the 5' leader region of trp mRNAs, and downregulates expression of the operon by promoting transcription termination prior to the structural genes. Anti-TRAP (AT) is an antagonist that binds to tryptophan-activated TRAP and prevents TRAP from binding to RNA, thereby upregulating expression of the trp genes. AT forms trimers, and multiple trimers bind to a TRAP 11mer. It is not known how many trimers must bind to TRAP in order to interfere with RNA binding. Studies of isolated TRAP and AT showed that AT can prevent TRAP from binding to the trp leader RNA but cannot dissociate a pre-formed TRAP-RNA complex. Here, we show that AT can prevent TRAP-mediated termination of transcription by inducing dissociation of TRAP from the nascent RNA when it has bound to fewer than all 11 (G/U)AG repeats. The 5'-most region of the TRAP binding site in the nascent transcript is most susceptible to dissociation from TRAP. We also show that one AT trimer bound to TRAP 11mer reduces the affinity of TRAP for RNA and eliminates TRAP-mediated transcription termination in vitro. PMID:24682818

  18. The rate of TRAP binding to RNA is crucial for transcription attenuation control of the B. subtilis trp operon.

    Science.gov (United States)

    Barbolina, Maria V; Kristoforov, Roman; Manfredo, Amanda; Chen, Yanling; Gollnick, Paul

    2007-07-27

    The trp RNA-binding attenuation protein (TRAP) regulates expression of the tryptophan biosynthetic and transport genes in Bacillus subtilis in response to changes in the levels of intracellular tryptophan. Transcription of the trpEDCFBA operon is controlled by an attenuation mechanism involving two overlapping RNA secondary structures in the 5' leader region of the trp transcript; TRAP binding promotes formation of a transcription terminator structure that halts transcription prior to the structural genes. TRAP consists of 11 identical subunits and is activated to bind RNA by binding up to 11 molecules of L-tryptophan. The TRAP binding site in the leader region of the trp operon mRNA consists of 11 (G/U)AG repeats. We examined the importance of the rate of TRAP binding to RNA for the transcription attenuation mechanism. We compared the properties of two types of TRAP 11-mers: homo-11-mers composed of 11 wild-type subunits, and hetero-11-mers with only one wild-type subunit and ten mutant subunits defective in binding either RNA or tryptophan. The hetero-11-mers bound RNA with only slightly diminished equilibrium binding affinity but with slower on-rates as compared to WT TRAP. The hetero-11-mers showed significantly decreased ability to induce transcription termination in the trp leader region when examined using an in vitro attenuation system. Together these results indicate that the rate of TRAP binding to RNA is a crucial factor in TRAP's ability to control attenuation. PMID:17555767

  19. Role of translation in the UTP-modulated attenuation at the pyrBI operon of Escherichia coli

    DEFF Research Database (Denmark)

    Clemmesen, Kåre; Bonekamp, Fons; Karlström, Olle;

    1985-01-01

    A 273 bp DNA fragment containing the attenuator of the pyrBI operon was inserted into a synthetic cloning site early in the lacZ gene on a plasmid. By this operation the first few codons of lacZ were joined through a linker to the last 39 codons of the open reading frame for the putative pyr...... as for the native pyrB gene. This is probably because the substitution of the normal start of the leader peptide by the start of lacZ alters the coupling between transcription and translation and thereby the attenuation frequency. It cannot, however, be ruled out that the pyrBI operon is regulated at the promoters......B leader peptide. In addition a gene fusion encoding a hybrid protein with -galactosidase activity was formed between the pyrB start and the rest of lacZ. This gene fusion is expressed from the lac promoter and the transcript is subject to facultative termination at the pyrBI attenuator. Different variants...

  20. Predictive modeling of complications.

    Science.gov (United States)

    Osorio, Joseph A; Scheer, Justin K; Ames, Christopher P

    2016-09-01

    Predictive analytic algorithms are designed to identify patterns in the data that allow for accurate predictions without the need for a hypothesis. Therefore, predictive modeling can provide detailed and patient-specific information that can be readily applied when discussing the risks of surgery with a patient. There are few studies using predictive modeling techniques in the adult spine surgery literature. These types of studies represent the beginning of the use of predictive analytics in spine surgery outcomes. We will discuss the advancements in the field of spine surgery with respect to predictive analytics, the controversies surrounding the technique, and the future directions. PMID:27286683

  1. Nitrate and nitrite-mediated transcription antitermination control of nasF (nitrate assimilation) operon expression in Klebsiella pheumoniae M5al.

    Science.gov (United States)

    Lin, J T; Stewart, V

    1996-03-01

    Klebsiella pneumoniae can use nitrate and nitrite as sole nitrogen sources during aerobic growth. Nitrate is converted through nitrite to ammonium by assimilatory nitrate and nitrite reductase, respectively. Enzymes required for nitrate assimilation are encoded by the nasFEDCBA operon of K. pneumoniae; nasF operon expression is subject to both general nitrogen control and pathway-specific nitrate/nitrite induction, mediated by the NtrC and NasR proteins, respectively. Sequence inspection revealed a presumptive sigmaN (sigma54)-dependent promoter as well as two presumptive upstream NtrC protein binding sites. Site-specific mutational and primer extension analyses confirmed the identity of the sigmaN-dependent promoter. Deletions removing the apparent NtrC protein binding sites greatly reduced NtrC-dependent regulation, indicating that these sites are involved in general nitrogen control. However, deletions removing most of the sequence upstream of the promoter had little effect on nitrate/nitrite regulation, suggesting that the nasF leader region is involved in nitrate/nitrite regulation. The 119 nucleotide long transcribed leader region contains an apparent factor-independent transcription terminator. Promoter replacement experiments demonstrated that the leader region is involved in nitrate/nitrite regulation of nasF operon expression. Deletions removing the transcription terminator structure resulted in a nitrate-blind constitutive phenotype, indicating that the transcription terminator structure serves a negative function. Other deletions, removing proximal portions of the leader region, resulted in an uninducible phenotype, indicating that this region serves a positive function. These results indicate that nitrate/nitrite regulation of nasF operon expression is determined by a transcription attenuation mechanism. We hypothesize that in the absence of nitrate or nitrite, the terminator structure abrogates transcription readthrough into the nasF operon. In the

  2. More-Accurate Model of Flows in Rocket Injectors

    Science.gov (United States)

    Hosangadi, Ashvin; Chenoweth, James; Brinckman, Kevin; Dash, Sanford

    2011-01-01

    An improved computational model for simulating flows in liquid-propellant injectors in rocket engines has been developed. Models like this one are needed for predicting fluxes of heat in, and performances of, the engines. An important part of predicting performance is predicting fluctuations of temperature, fluctuations of concentrations of chemical species, and effects of turbulence on diffusion of heat and chemical species. Customarily, diffusion effects are represented by parameters known in the art as the Prandtl and Schmidt numbers. Prior formulations include ad hoc assumptions of constant values of these parameters, but these assumptions and, hence, the formulations, are inaccurate for complex flows. In the improved model, these parameters are neither constant nor specified in advance: instead, they are variables obtained as part of the solution. Consequently, this model represents the effects of turbulence on diffusion of heat and chemical species more accurately than prior formulations do, and may enable more-accurate prediction of mixing and flows of heat in rocket-engine combustion chambers. The model has been implemented within CRUNCH CFD, a proprietary computational fluid dynamics (CFD) computer program, and has been tested within that program. The model could also be implemented within other CFD programs.

  3. Sequencing and expression of two arsenic resistance operons with different functions in the highly arsenic-resistant strain Ochrobactrum tritici SCII24T

    Directory of Open Access Journals (Sweden)

    Chung Ana-Paula

    2008-06-01

    Full Text Available Abstract Background Arsenic (As is a natural metalloid, widely used in anthropogenic activities, that can exist in different oxidation states. Throughout the world, there are several environments contaminated with high amounts of arsenic where many organisms can survive. The most stable arsenical species are arsenate and arsenite that can be subject to chemically and microbiologically oxidation, reduction and methylation reactions. Organisms surviving in arsenic contaminated environments can have a diversity of mechanisms to resist to the harmful effects of arsenical compounds. Results The highly metal resistant Ochrobactrum tritici SCII24 was able to grow in media with arsenite (50 mM, arsenate (up to 200 mM and antimonite (10 mM. This strain contains two arsenic and antimony resistance operons (ars1 and ars2, which were cloned and sequenced. Sequence analysis indicated that ars1 operon contains five genes encoding the following proteins: ArsR, ArsD, ArsA, CBS-domain-containing protein and ArsB. The ars2 operon is composed of six genes that encode two other ArsR, two ArsC (belonging to different families of arsenate reductases, one ACR3 and one ArsH-like protein. The involvement of ars operons in arsenic resistance was confirmed by cloning both of them in an Escherichia coli ars-mutant. The ars1 operon conferred resistance to arsenite and antimonite on E. coli cells, whereas the ars2 operon was also responsible for resistance to arsenite and arsenate. Although arsH was not required for arsenate resistance, this gene seems to be important to confer high levels of arsenite resistance. None of ars1 genes were detected in the other type strains of genus Ochrobactrum, but sequences homologous with ars2 operon were identified in some strains. Conclusion A new strategy for bacterial arsenic resistance is described in this work. Two operons involved in arsenic resistance, one giving resistance to arsenite and antimonite and the other giving resistance

  4. Transcriptional Regulation of the Vanillate Utilization Genes (vanABK Operon) of Corynebacterium glutamicum by VanR, a PadR-Like Repressor

    OpenAIRE

    Morabbi Heravi, Kambiz; Lange, Julian; Watzlawick, Hildegard; Kalinowski, Jörn; Altenbuchner, Josef

    2014-01-01

    Corynebacterium glutamicum is able to utilize vanillate, the product of lignin degradation, as the sole carbon source. The vanillate utilization components are encoded by the vanABK operon. The vanA and vanB genes encode the subunits of vanillate O-demethylase, converting vanillate to protocatechuate, while VanK is the specific vanillate transporter. The vanABK operon is regulated by a PadR-type repressor, VanR. Heterologous gene expression and variations of the vanR open reading frame reveal...

  5. Posttranscriptional repression of the cel gene of the ColE7 operon by the RNA-binding protein CsrA of Escherichia coli

    OpenAIRE

    Yang, Tsung-Yeh; Sung, Yun-Min; Lei, Guang-Sheng; Romeo, Tony; Chak, Kin-Fu

    2010-01-01

    Carbon storage regulator (CsrA) is a eubacterial RNA-binding protein that acts as a global regulator of many functionally diverse chromosomal genes. Here, we reveal that CsrA represses expression from an extrachromosomal element of Escherichia coli, the lysis gene (cel) of the ColE7 operon (cea-cei-cel). This operon and colicin expression are activated upon SOS response. Disruption of csrA caused ∼5-fold increase of the lysis protein. Gel mobility shift assays established that both the single...

  6. Modified nucleotides m2G966/m5C967 of Escherichia coli 16S rRNA are required for attenuation of tryptophan operon

    OpenAIRE

    Prokhorova, Irina V.; Osterman, Ilya A.; Burakovsky, Dmitry E.; Serebryakova, Marina V.; Galyamina, Maria A.; Pobeguts, Olga V.; Altukhov, Ilya; Kovalchuk, Sergey; Alexeev, Dmitry G.; Govorun, Vadim M.; Bogdanov, Alexey A.; Sergiev, Petr V.; Dontsova, Olga A

    2013-01-01

    Ribosomes contain a number of modifications in rRNA, the function of which is unclear. Here we show – using proteomic analysis and dual fluorescence reporter in vivo assays – that m2G966 and m5C967 in 16S rRNA of Escherichia coli ribosomes are necessary for correct attenuation of tryptophan (trp) operon. Expression of trp operon is upregulated in the strain where RsmD and RsmB methyltransferases were deleted, which results in the lack of m2G966 and m5C967 modifications. The upregulation requi...

  7. Chromosomal insertion of the entire Escherichia coli lactose operon, into two strains of Pseudomonas, using a modified mini-Tn5 delivery system

    DEFF Research Database (Denmark)

    Hansen, L. H.; Sørensen, S. J.; Jensen, Lars Bogø

    1997-01-01

    A 12-kb PstI fragment including the entire E. coli lactose operon (lacIPOZYA) was inserted in one copy into the chromosome of Pseudomonas putida, Pseudomonas fluorescens and an E. coli strain with lac(-) phenotype. This was made possible by improvements of an already existing mini-Tn5 transposon...... flanked by NotI sites needed in the mini-Tn5 delivery system; (b) the generation of E. coli nonlysogenic strains expressing the pi protein thus being capable of maintaining and delivering R6K-based mini-Tn5 vectors to other E. coli strains; (c) the successful insertion of the E. coli lactose operon...

  8. Laboratory Building for Accurate Determination of Plutonium

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    <正>The accurate determination of plutonium is one of the most important assay techniques of nuclear fuel, also the key of the chemical measurement transfer and the base of the nuclear material balance. An

  9. Accurate thermoelastic tensor and acoustic velocities of NaCl

    Energy Technology Data Exchange (ETDEWEB)

    Marcondes, Michel L., E-mail: michel@if.usp.br [Physics Institute, University of Sao Paulo, Sao Paulo, 05508-090 (Brazil); Chemical Engineering and Material Science, University of Minnesota, Minneapolis, 55455 (United States); Shukla, Gaurav, E-mail: shukla@physics.umn.edu [School of Physics and Astronomy, University of Minnesota, Minneapolis, 55455 (United States); Minnesota supercomputer Institute, University of Minnesota, Minneapolis, 55455 (United States); Silveira, Pedro da [Chemical Engineering and Material Science, University of Minnesota, Minneapolis, 55455 (United States); Wentzcovitch, Renata M., E-mail: wentz002@umn.edu [Chemical Engineering and Material Science, University of Minnesota, Minneapolis, 55455 (United States); Minnesota supercomputer Institute, University of Minnesota, Minneapolis, 55455 (United States)

    2015-12-15

    Despite the importance of thermoelastic properties of minerals in geology and geophysics, their measurement at high pressures and temperatures are still challenging. Thus, ab initio calculations are an essential tool for predicting these properties at extreme conditions. Owing to the approximate description of the exchange-correlation energy, approximations used in calculations of vibrational effects, and numerical/methodological approximations, these methods produce systematic deviations. Hybrid schemes combining experimental data and theoretical results have emerged as a way to reconcile available information and offer more reliable predictions at experimentally inaccessible thermodynamics conditions. Here we introduce a method to improve the calculated thermoelastic tensor by using highly accurate thermal equation of state (EoS). The corrective scheme is general, applicable to crystalline solids with any symmetry, and can produce accurate results at conditions where experimental data may not exist. We apply it to rock-salt-type NaCl, a material whose structural properties have been challenging to describe accurately by standard ab initio methods and whose acoustic/seismic properties are important for the gas and oil industry.

  10. Efficient and accurate sound propagation using adaptive rectangular decomposition.

    Science.gov (United States)

    Raghuvanshi, Nikunj; Narain, Rahul; Lin, Ming C

    2009-01-01

    Accurate sound rendering can add significant realism to complement visual display in interactive applications, as well as facilitate acoustic predictions for many engineering applications, like accurate acoustic analysis for architectural design. Numerical simulation can provide this realism most naturally by modeling the underlying physics of wave propagation. However, wave simulation has traditionally posed a tough computational challenge. In this paper, we present a technique which relies on an adaptive rectangular decomposition of 3D scenes to enable efficient and accurate simulation of sound propagation in complex virtual environments. It exploits the known analytical solution of the Wave Equation in rectangular domains, and utilizes an efficient implementation of the Discrete Cosine Transform on Graphics Processors (GPU) to achieve at least a 100-fold performance gain compared to a standard Finite-Difference Time-Domain (FDTD) implementation with comparable accuracy, while also being 10-fold more memory efficient. Consequently, we are able to perform accurate numerical acoustic simulation on large, complex scenes in the kilohertz range. To the best of our knowledge, it was not previously possible to perform such simulations on a desktop computer. Our work thus enables acoustic analysis on large scenes and auditory display for complex virtual environments on commodity hardware. PMID:19590105

  11. Genetic analysis of the virE operon of the Agrobacterium Ti plasmid pTiA6.

    Science.gov (United States)

    McBride, K E; Knauf, V C

    1988-04-01

    The virE operon of the Agrobacterium tumefaciens Ti plasmid pTiA6 encodes at least one trans-acting protein involved in the expression of virulence. Two open reading frames designated virE1 and virE2 code for polypeptides of 7 and 60 kilodaltons (kDa), respectively, that can be visualized after expression in Escherichia coli minicells. To determine which virE sequences are required for virulence, a strain deleted for the entire locus [strain KE1(pTiA6 delta E)] was constructed and tested for the ability to be complemented by subclones with and without site-directed mutations in the virE operon. One subclone containing only virE1 and virE2 as well as upstream promoter sequences was sufficient to restore full virulence on the host plant Kalanchoe daigremontiana. However, some other virulence locus representing a host range determinant appeared to be deleted from strain KE1(pTiA6 delta E), since virE1 and virE2 were not sufficient to fully restore virulence on wounded tomato plants. virE operon constructs with specific lesions in either virE1 or virE2 were impaired for complementation of pTiA6 delta E. Several mutations specific for the promoter-proximal virE1 locus appeared to have a polar effect on expression of the virE2-encoded 60-kDa protein. However, virE2::lacZ fusion constructs suggest that this effect is not at the level of transcription or translation. Collectively, these data indicate that both the 7- and the 60-kDa polypeptides are virulence determinants for the Ti plasmid pTiA6 and suggest that the 60-kDa protein may be less stable in the absence of the 7-kDa protein. PMID:2832362

  12. Inter-genomic displacement via lateral gene transfer of bacterial trp operons in an overall context of vertical genealogy

    Directory of Open Access Journals (Sweden)

    Keyhani Nemat O

    2004-06-01

    Full Text Available Abstract Background The growing conviction that lateral gene transfer plays a significant role in prokaryote genealogy opens up a need for comprehensive evaluations of gene-enzyme systems on a case-by-case basis. Genes of tryptophan biosynthesis are frequently organized as whole-pathway operons, an attribute that is expected to facilitate multi-gene transfer in a single step. We have asked whether events of lateral gene transfer are sufficient to have obscured our ability to track the vertical genealogy that underpins tryptophan biosynthesis. Results In 47 complete-genome Bacteria, the genes encoding the seven catalytic domains that participate in primary tryptophan biosynthesis were distinguished from any paralogs or xenologs engaged in other specialized functions. A reliable list of orthologs with carefully ascertained functional roles has thus been assembled and should be valuable as an annotation resource. The protein domains associated with primary tryptophan biosynthesis were then concatenated, yielding single amino-acid sequence strings that represent the entire tryptophan pathway. Lateral gene transfer of several whole-pathway trp operons was demonstrated by use of phylogenetic analysis. Lateral gene transfer of partial-pathway trp operons was also shown, with newly recruited genes functioning either in primary biosynthesis (rarely or specialized metabolism (more frequently. Conclusions (i Concatenated tryptophan protein trees are congruent with 16S rRNA subtrees provided that the genomes represented are of sufficiently close phylogenetic spacing. There are currently seven tryptophan congruency groups in the Bacteria. Recognition of a succession of others can be expected in the near future, but ultimately these should coalesce to a single grouping that parallels the 16S rRNA tree (except for cases of lateral gene transfer. (ii The vertical trace of evolution for tryptophan biosynthesis can be deduced. The daunting complexities engendered

  13. The FLUKA code: An accurate simulation tool for particle therapy

    CERN Document Server

    Battistoni, Giuseppe; Böhlen, Till T; Cerutti, Francesco; Chin, Mary Pik Wai; Dos Santos Augusto, Ricardo M; Ferrari, Alfredo; Garcia Ortega, Pablo; Kozlowska, Wioletta S; Magro, Giuseppe; Mairani, Andrea; Parodi, Katia; Sala, Paola R; Schoofs, Philippe; Tessonnier, Thomas; Vlachoudis, Vasilis

    2016-01-01

    Monte Carlo (MC) codes are increasingly spreading in the hadrontherapy community due to their detailed description of radiation transport and interaction with matter. The suitability of a MC code for application to hadrontherapy demands accurate and reliable physical models capable of handling all components of the expected radiation field. This becomes extremely important for correctly performing not only physical but also biologically-based dose calculations, especially in cases where ions heavier than protons are involved. In addition, accurate prediction of emerging secondary radiation is of utmost importance in innovative areas of research aiming at in-vivo treatment verification. This contribution will address the recent developments of the FLUKA MC code and its practical applications in this field. Refinements of the FLUKA nuclear models in the therapeutic energy interval lead to an improved description of the mixed radiation field as shown in the presented benchmarks against experimental data with bot...

  14. Method for Accurately Calibrating a Spectrometer Using Broadband Light

    Science.gov (United States)

    Simmons, Stephen; Youngquist, Robert

    2011-01-01

    A novel method has been developed for performing very fine calibration of a spectrometer. This process is particularly useful for modern miniature charge-coupled device (CCD) spectrometers where a typical factory wavelength calibration has been performed and a finer, more accurate calibration is desired. Typically, the factory calibration is done with a spectral line source that generates light at known wavelengths, allowing specific pixels in the CCD array to be assigned wavelength values. This method is good to about 1 nm across the spectrometer s wavelength range. This new method appears to be accurate to about 0.1 nm, a factor of ten improvement. White light is passed through an unbalanced Michelson interferometer, producing an optical signal with significant spectral variation. A simple theory can be developed to describe this spectral pattern, so by comparing the actual spectrometer output against this predicted pattern, errors in the wavelength assignment made by the spectrometer can be determined.

  15. Long Range Aircraft Trajectory Prediction

    OpenAIRE

    Magister, Tone

    2009-01-01

    The subject of the paper is the improvement of the aircraft future trajectory prediction accuracy for long-range airborne separation assurance. The strategic planning of safe aircraft flights and effective conflict avoidance tactics demand timely and accurate conflict detection based upon future four–dimensional airborne traffic situation prediction which is as accurate as each aircraft flight trajectory prediction. The improved kinematics model of aircraft relative flight considering flight ...

  16. Influence of sporulation medium composition on transcription of ger operons and the germination response of spores of Bacillus cereus ATCC 14579

    NARCIS (Netherlands)

    Hornstra, L.M.; Vries, de Y.P.; Vos, de W.M.; Abee, T.

    2006-01-01

    Bacillus cereus ATCC 14579 endospores were produced in Y1 medium, a nutrient-rich, chemically defined sporulation medium, and in modified G medium, containing low amounts of nutrients. The average transcription level of the seven ger operons per cell was 3.5 times higher in Y1 medium, and the spores

  17. MALDI-TOF MS analysis of ribosomal proteins coded in S10 and spc operons rapidly classified the Sphingomonadaceae as alkylphenol polyethoxylate-degrading bacteria from the environment.

    Science.gov (United States)

    Hotta, Yudai; Sato, Hiroaki; Hosoda, Akifumi; Tamura, Hiroto

    2012-05-01

    Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) using ribosomal subunit proteins coded in the S10-spc-alpha operon as biomarkers was applied for the classification of the Sphingomonadaceae from the environment. To construct a ribosomal protein database, S10-spc-alpha operon of type strains of the Sphingomonadaceae and their related alkylphenol polyethoxylate (APEO(n) )-degrading bacteria were sequenced using specific primers designed based on nucleotide sequences of genome-sequenced strains. The observed MALDI mass spectra of intact cells were compared with the theoretical mass of the constructed ribosomal protein database. The nine selected biomarkers coded in the S10-spc-alpha operon, L18, L22, L24, L29, L30, S08, S14, S17, and S19, could successfully distinguish the Sphingopyxis terrae NBRC 15098(T) and APEO(n) -degrading bacteria strain BSN20, despite only one base difference in the 16S rRNA gene sequence. This method, named the S10-GERMS (S10-spc-alpha operon gene-encoded ribosomal protein mass spectrum) method, is a significantly useful tool for bacterial discrimination of the Sphingomonadaceae at the strain level and can detect and monitor the main APEO(n) -degrading bacteria in the environment.

  18. Classification of genus Pseudomonas by MALDI-TOF MS based on ribosomal protein coding in S10-spc-alpha operon at strain level.

    Science.gov (United States)

    Hotta, Yudai; Teramoto, Kanae; Sato, Hiroaki; Yoshikawa, Hiromichi; Hosoda, Akifumi; Tamura, Hiroto

    2010-12-01

    We have proposed a rapid phylogenetic classification at the strain level by MALDI-TOF MS using ribosomal protein matching profiling. In this study, the S10-spc-alpha operon, encoding half of the ribosomal subunit proteins and highly conserved in eubacterial genomes, was selected for construction of the ribosomal protein database as biomarkers for bacterial identification by MALDI-TOF MS analysis to establish a more reliable phylogenetic classification. Our method revealed that the 14 reliable and reproducible ribosomal subunit proteins with less than m/z 15,000, except for L14, coded in the S10-spc-alpha operon were significantly useful biomarkers for bacterial classification at species and strain levels by MALDI-TOF MS analysis of genus Pseudomonas strains. The obtained phylogenetic tree was consisted with that based on genetic sequence (gyrB). Since S10-spc-alpha operons of genus Pseudomonas strains were sequenced using specific primers designed based on nucleotide sequences of genome-sequenced strains, the ribosomal subunit proteins encoded in S10-spc-alpha operon were suitable biomarkers for construction and correction of the database. MALDI-TOF MS analysis using these 14 selected ribosomal proteins is a rapid, efficient, and versatile bacterial identification method with the validation procedure for the obtained results.

  19. Modified nucleotides m2G966/m5C967 of Escherichia coli 16S rRNA are required for attenuation of tryptophan operon

    Science.gov (United States)

    Prokhorova, Irina V.; Osterman, Ilya A.; Burakovsky, Dmitry E.; Serebryakova, Marina V.; Galyamina, Maria A.; Pobeguts, Olga V.; Altukhov, Ilya; Kovalchuk, Sergey; Alexeev, Dmitry G.; Govorun, Vadim M.; Bogdanov, Alexey A.; Sergiev, Petr V.; Dontsova, Olga A.

    2013-11-01

    Ribosomes contain a number of modifications in rRNA, the function of which is unclear. Here we show - using proteomic analysis and dual fluorescence reporter in vivo assays - that m2G966 and m5C967 in 16S rRNA of Escherichia coli ribosomes are necessary for correct attenuation of tryptophan (trp) operon. Expression of trp operon is upregulated in the strain where RsmD and RsmB methyltransferases were deleted, which results in the lack of m2G966 and m5C967 modifications. The upregulation requires the trpL attenuator, but is independent of the promotor of trp operon, ribosome binding site of the trpE gene, which follows trp attenuator and even Trp codons in the trpL sequence. Suboptimal translation initiation efficiency in the rsmB/rsmD knockout strain is likely to cause a delay in translation relative to transcription which causes misregulation of attenuation control of trp operon.

  20. Sequencing and promoter analysis of the nifENXorf3orf5fdxAnifQ operon from Azospirillum brasilense Sp7

    Directory of Open Access Journals (Sweden)

    Potrich D.P.

    2001-01-01

    Full Text Available A 40-kb DNA region containing the major cluster of nif genes has been isolated from the Azospirillum brasilense Sp7 genome. In this region three nif operons have been identified: nifHDKorf1Y, nifENXorf3orf5fdxAnifQ and orf2nifUSVorf4. The operons containing nifENX and nifUSV genes are separated from the structural nifHDKorf1Y operon by about 5 kb and 10 kb, respectively. The present study shows the sequence analysis of the 6045-bp DNA region containing the nifENX genes. The deduced amino acid sequences from the open reading frames were compared to the nif gene products of other diazotrophic bacteria and indicate the presence of seven ORFs, all reading in the same direction as that of the nifHDKorf1Y operon. Consensus sigma54 and NifA-binding sites are present only in the promoter region upstream of the nifE gene. This promoter is activated by NifA protein and is approximately two-times less active than the nifH promoter, as indicated by the ß-galactosidase assays. This result suggests the differential expression of the nif genes and their respective products in Azospirillum.

  1. recA mediated spontaneous deletions of the icaADBC operon of clinical Staphylococcus epidermidis isolates : a new mechanism of phenotypic variations

    NARCIS (Netherlands)

    Nuryastuti, Titik; van der Mei, Henny C.; Busscher, Henk J.; Kuijer, Roel; Aman, Abu T.; Krom, Bastiaan P.

    2008-01-01

    Phenotypic variation of Staphylococcus epidermidis involving the slime related ica operon results in heterogeneity in surface characteristics of individual bacteria in axenic cultures. Five clinical S. epidermidis isolates demonstrated phenotypic variation, i.e. both black and red colonies on Congo

  2. The davDT operon of Pseudomonas putida, involved in lysine catabolism, is induced in response to the pathway intermediate delta-aminovaleric acid

    DEFF Research Database (Denmark)

    Revelles, O.; Espinosa-Urgel, M.; Molin, Søren;

    2004-01-01

    to the addition of exogenous lysine to the culture medium. However, the true inducer of this operon seems to be delta-aminovaleric acid because in a mutant unable to metabolize lysine to delta-aminovaleric acid, this compound, but not lysine, acted as an effector. Effective induction of the P. putida P...

  3. Decaffeination and measurement of caffeine content by addicted Escherichia coli with a refactored N-demethylation operon from Pseudomonas putida CBB5.

    Science.gov (United States)

    Quandt, Erik M; Hammerling, Michael J; Summers, Ryan M; Otoupal, Peter B; Slater, Ben; Alnahhas, Razan N; Dasgupta, Aurko; Bachman, James L; Subramanian, Mani V; Barrick, Jeffrey E

    2013-06-21

    The widespread use of caffeine (1,3,7-trimethylxanthine) and other methylxanthines in beverages and pharmaceuticals has led to significant environmental pollution. We have developed a portable caffeine degradation operon by refactoring the alkylxanthine degradation (Alx) gene cluster from Pseudomonas putida CBB5 to function in Escherichia coli. In the process, we discovered that adding a glutathione S-transferase from Janthinobacterium sp. Marseille was necessary to achieve N 7 -demethylation activity. E. coli cells with the synthetic operon degrade caffeine to the guanine precursor, xanthine. Cells deficient in de novo guanine biosynthesis that contain the refactored operon are ″addicted″ to caffeine: their growth density is limited by the availability of caffeine or other xanthines. We show that the addicted strain can be used as a biosensor to measure the caffeine content of common beverages. The synthetic N-demethylation operon could be useful for reclaiming nutrient-rich byproducts of coffee bean processing and for the cost-effective bioproduction of methylxanthine drugs.

  4. Synthesis of lactococcin 972, a bacteriocin produced by Lactococcus lactis IPLA 972, depends on the expression of a plasmid-encoded bicistronic operon

    NARCIS (Netherlands)

    Martínez, B.; Fernández, M.; Suárez, J.E.; Rodríguez, A.

    1999-01-01

    Synthesis of lactococcin 972 is plasmid-encoded. An operon composed of two genes that encode pre-bacteriocin and a putative immunity protein has been identified. The first gene encodes a 91-residue polypeptide that is exported via a sec-dependent system to give the mature 66-aa bacteriocin. The immu

  5. gerR, a novel ger operon involved in L-alanine- and inosine-initiated germination of Bacillus cereus ATCC 14579

    NARCIS (Netherlands)

    Hornstra, L.M.; Vries, de Y.P.; Vos, de W.M.; Abee, T.; Wells-Bennik, M.H.J.

    2005-01-01

    Bacillus cereus endospores germinate in response to particular nutrients. Spores are able to sense these nutrients in the environment by receptors encoded by the gerA family of operons. Analysis of the Bacillus cereus ATCC 14579 genome revealed seven gerA family homologues. Using a transposon Tn917-

  6. Modified nucleotides m(2)G966/m(5)C967 of Escherichia coli 16S rRNA are required for attenuation of tryptophan operon.

    Science.gov (United States)

    Prokhorova, Irina V; Osterman, Ilya A; Burakovsky, Dmitry E; Serebryakova, Marina V; Galyamina, Maria A; Pobeguts, Olga V; Altukhov, Ilya; Kovalchuk, Sergey; Alexeev, Dmitry G; Govorun, Vadim M; Bogdanov, Alexey A; Sergiev, Petr V; Dontsova, Olga A

    2013-01-01

    Ribosomes contain a number of modifications in rRNA, the function of which is unclear. Here we show--using proteomic analysis and dual fluorescence reporter in vivo assays--that m(2)G966 and m(5)C967 in 16S rRNA of Escherichia coli ribosomes are necessary for correct attenuation of tryptophan (trp) operon. Expression of trp operon is upregulated in the strain where RsmD and RsmB methyltransferases were deleted, which results in the lack of m(2)G966 and m(5)C967 modifications. The upregulation requires the trpL attenuator, but is independent of the promotor of trp operon, ribosome binding site of the trpE gene, which follows trp attenuator and even Trp codons in the trpL sequence. Suboptimal translation initiation efficiency in the rsmB/rsmD knockout strain is likely to cause a delay in translation relative to transcription which causes misregulation of attenuation control of trp operon. PMID:24241179

  7. Invariant Image Watermarking Using Accurate Zernike Moments

    Directory of Open Access Journals (Sweden)

    Ismail A. Ismail

    2010-01-01

    Full Text Available problem statement: Digital image watermarking is the most popular method for image authentication, copyright protection and content description. Zernike moments are the most widely used moments in image processing and pattern recognition. The magnitudes of Zernike moments are rotation invariant so they can be used just as a watermark signal or be further modified to carry embedded data. The computed Zernike moments in Cartesian coordinate are not accurate due to geometrical and numerical error. Approach: In this study, we employed a robust image-watermarking algorithm using accurate Zernike moments. These moments are computed in polar coordinate, where both approximation and geometric errors are removed. Accurate Zernike moments are used in image watermarking and proved to be robust against different kind of geometric attacks. The performance of the proposed algorithm is evaluated using standard images. Results: Experimental results show that, accurate Zernike moments achieve higher degree of robustness than those approximated ones against rotation, scaling, flipping, shearing and affine transformation. Conclusion: By computing accurate Zernike moments, the embedded bits watermark can be extracted at low error rate.

  8. Transcriptional activation of multiple operons involved in para-nitrophenol degradation by Pseudomonas sp. Strain WBC-3.

    Science.gov (United States)

    Zhang, Wen-Mao; Zhang, Jun-Jie; Jiang, Xuan; Chao, Hongjun; Zhou, Ning-Yi

    2015-01-01

    Pseudomonas sp. strain WBC-3 utilizes para-nitrophenol (PNP) as a sole carbon and energy source. The genes involved in PNP degradation are organized in the following three operons: pnpA, pnpB, and pnpCDEFG. How the expression of the genes is regulated is unknown. In this study, an LysR-type transcriptional regulator (LTTR) is identified to activate the expression of the genes in response to the specific inducer PNP. While the LTTR coding gene pnpR was found to be not physically linked to any of the three catabolic operons, it was shown to be essential for the growth of strain WBC-3 on PNP. Furthermore, PnpR positively regulated its own expression, which is different from the function of classical LTTRs. A regulatory binding site (RBS) with a 17-bp imperfect palindromic sequence (GTT-N11-AAC) was identified in all pnpA, pnpB, pnpC, and pnpR promoters. Through electrophoretic mobility shift assays and mutagenic analyses, this motif was proven to be necessary for PnpR binding. This consensus motif is centered at positions approximately -55 bp relative to the four transcriptional start sites (TSSs). RBS integrity was required for both high-affinity PnpR binding and transcriptional activation of pnpA, pnpB, and pnpR. However, this integrity was essential only for high-affinity PnpR binding to the promoter of pnpCDEFG and not for its activation. Intriguingly, unlike other LTTRs studied, no changes in lengths of the PnpR binding regions of the pnpA and pnpB promoters were observed after the addition of the inducer PNP in DNase I footprinting.

  9. 23S rRNA nucleotides in the peptidyl transferase center are essential for tryptophanase operon induction.

    Science.gov (United States)

    Yang, Rui; Cruz-Vera, Luis R; Yanofsky, Charles

    2009-06-01

    Distinct features of the ribosomal peptide exit tunnel are known to be essential for recognition of specific amino acids of a nascent peptidyl-tRNA. Thus, a tryptophan residue at position 12 of the peptidyl-tRNA TnaC-tRNA(Pro) leads to the creation of a free tryptophan binding site within the ribosome at which bound tryptophan inhibits normal ribosome functions. The ribosomal processes that are inhibited are hydrolysis of TnaC-tRNA(Pro) by release factor 2 and peptidyl transfer of TnaC of TnaC-tRNA(Pro) to puromycin. These events are normally performed in the ribosomal peptidyl transferase center. In the present study, changes of 23S rRNA nucleotides in the 2585 region of the peptidyl transferase center, G2583A and U2584C, were observed to reduce maximum induction of tna operon expression by tryptophan in vivo without affecting the concentration of tryptophan necessary to obtain 50% induction. The growth rate of strains with ribosomes with either of these changes was not altered appreciably. In vitro analyses with mutant ribosomes with these changes showed that tryptophan was not as efficient in protecting TnaC-tRNA(Pro) from puromycin action as wild-type ribosomes. However, added tryptophan did prevent sparsomycin action as it normally does with wild-type ribosomes. These findings suggest that these two mutational changes act by reducing the ability of ribosome-bound tryptophan to inhibit peptidyl transferase activity rather than by reducing the ability of the ribosome to bind tryptophan. Thus, the present study identifies specific nucleotides within the ribosomal peptidyl transferase center that appear to be essential for effective tryptophan induction of tna operon expression. PMID:19329641

  10. Expression of a humanized viral 2A-mediated lux operon efficiently generates autonomous bioluminescence in human cells.

    Directory of Open Access Journals (Sweden)

    Tingting Xu

    Full Text Available Expression of autonomous bioluminescence from human cells was previously reported to be impossible, suggesting that all bioluminescent-based mammalian reporter systems must therefore require application of a potentially influential chemical substrate. While this was disproven when the bacterial luciferase (lux cassette was demonstrated to function in a human cell, its expression required multiple genetic constructs, was functional in only a single cell type, and generated a significantly reduced signal compared to substrate-requiring systems. Here we investigate the use of a humanized, viral 2A-linked lux genetic architecture for the efficient introduction of an autobioluminescent phenotype across a variety of human cell lines.The lux cassette was codon optimized and assembled into a synthetic human expression operon using viral 2A elements as linker regions. Human kidney, breast cancer, and colorectal cancer cell lines were both transiently and stably transfected with the humanized operon and the resulting autobioluminescent phenotype was evaluated using common imaging instrumentation. Autobioluminescent cells were screened for cytotoxic effects resulting from lux expression and their utility as bioreporters was evaluated through the demonstration of repeated monitoring of single populations over a prolonged period using both a modified E-SCREEN assay for estrogen detection and a classical cytotoxic compound detection assay for the antibiotic Zeocin. Furthermore, the use of self-directed bioluminescent initiation in response to target detection was assessed to determine its amenability towards deployment as fully autonomous sensors. In all cases, bioluminescent measurements were supported with traditional genetic and transcriptomic evaluations.Our results demonstrate that the viral 2A-linked, humanized lux genetic architecture successfully produced autobioluminescent phenotypes in all cell lines tested without the induction of cytotoxicity

  11. A Phenotypically Silent vanB2 Operon Carried on a Tn1549-Like Element in Clostridium difficile

    Science.gov (United States)

    Knight, Daniel R.; Androga, Grace O.; Ballard, Susan A.; Howden, Benjamin P.

    2016-01-01

    ABSTRACT In the last decade, Clostridium difficile infection (CDI) has reached an epidemic state with increasing incidence and severity in both health care and community settings. Vancomycin is an important first-line therapy for CDI, and the emergence of resistance would have significant clinical consequences. In this study, we describe for the first time a vanB2 vancomycin resistance operon in C. difficile, isolated from an Australian veal calf at slaughter. The operon was carried on an ~42-kb element showing significant homology and synteny to Tn1549, a conjugative transposon linked with the emergence and global dissemination of vancomycin-resistant enterococci (VRE). Notably, the C. difficile strain did not show any reduced susceptibility to vancomycin in vitro (MIC, 1 mg/liter), possibly as a result of an aberrant vanRB gene. As observed for other anaerobic species of the animal gut microbiota, C. difficile may be a reservoir of clinically important vancomycin resistance genes. IMPORTANCE In an era when the development of new antimicrobial drugs is slow, vancomycin remains the preferred antimicrobial therapy for Clostridium difficile infection (CDI), the most important health care-related infection in the world today. The emergence of resistance to vancomycin would have significant consequences in relation to treating patients with CDI. In this paper, we describe for the first time a complete set of vancomycin resistance genes in C. difficile. The genes were very similar to genes found in vancomycin-resistant enterococci (VRE) that were associated with the emergence and global dissemination of this organism. Fortunately, the C. difficile strain did not show any reduced susceptibility to vancomycin in vitro (MIC, 1 mg/liter), possibly because of a small difference in one gene. However, this observation signals that we may be very close to seeing a fully vancomycin-resistant strain of C. difficile. PMID:27536735

  12. A Phenotypically Silent vanB2 Operon Carried on a Tn1549-Like Element in Clostridium difficile.

    Science.gov (United States)

    Knight, Daniel R; Androga, Grace O; Ballard, Susan A; Howden, Benjamin P; Riley, Thomas V

    2016-01-01

    In the last decade, Clostridium difficile infection (CDI) has reached an epidemic state with increasing incidence and severity in both health care and community settings. Vancomycin is an important first-line therapy for CDI, and the emergence of resistance would have significant clinical consequences. In this study, we describe for the first time a vanB2 vancomycin resistance operon in C. difficile, isolated from an Australian veal calf at slaughter. The operon was carried on an ~42-kb element showing significant homology and synteny to Tn1549, a conjugative transposon linked with the emergence and global dissemination of vancomycin-resistant enterococci (VRE). Notably, the C. difficile strain did not show any reduced susceptibility to vancomycin in vitro (MIC, 1 mg/liter), possibly as a result of an aberrant vanRB gene. As observed for other anaerobic species of the animal gut microbiota, C. difficile may be a reservoir of clinically important vancomycin resistance genes. IMPORTANCE In an era when the development of new antimicrobial drugs is slow, vancomycin remains the preferred antimicrobial therapy for Clostridium difficile infection (CDI), the most important health care-related infection in the world today. The emergence of resistance to vancomycin would have significant consequences in relation to treating patients with CDI. In this paper, we describe for the first time a complete set of vancomycin resistance genes in C. difficile. The genes were very similar to genes found in vancomycin-resistant enterococci (VRE) that were associated with the emergence and global dissemination of this organism. Fortunately, the C. difficile strain did not show any reduced susceptibility to vancomycin in vitro (MIC, 1 mg/liter), possibly because of a small difference in one gene. However, this observation signals that we may be very close to seeing a fully vancomycin-resistant strain of C. difficile. PMID:27536735

  13. Identification and functional analysis of a nitrate assimilation operon nasACKBDEF from Amycolatopsis mediterranei U32.

    Science.gov (United States)

    Shao, Zhihui; Gao, Jin; Ding, Xiaoming; Wang, Jin; Chiao, Juishen; Zhao, Guoping

    2011-07-01

    Nitrate assimilation has been well studied for Gram-negative bacteria but not so much in the Gram-positive actinomycetes up to date. In a rifamycin SV-producing actinomycete, Amycolatopsis mediterranei strain U32, nitrate not only can be used as a sole nitrogen source but also remarkably stimulates the antibiotic production along with regulating the related metabolic enzymes. A gene cluster of nasACKBDEF was cloned from a U32 genomic library by in situ hybridization screening with a heterogeneous nasB probe and confirmed later by whole genome sequence, corresponding to the protein coding genes of AMED_1121 to AMED_1127. These genes were co-transcribed as an operon, concomitantly repressed by ammonium while activated with supplement of either nitrate or nitrite. Genetic and biochemical analyses identified the essential nitrate/nitrite assimilation functions of the encoded proteins, orderly, the assimilatory nitrate reductase catalytic subunit (NasA), nitrate reductase electron transfer subunit (NasC), nitrate/nitrite transporter (NasK), assimilatory nitrite reductase large subunit (NasB) and small subunit (NasD), bifunctional uroporphyrinogen-III synthase (NasE), and an unknown function protein (NasF). Comparing rifamycin SV production and the level of transcription of nasB and rifE from U32 and its individual nas mutants in Bennet medium with or without nitrate indicated that nitrate assimilation function encoded by the nas operon played an essential role in the "nitrate stimulated" rifamycin production but had no effect upon the transcription regulation of the primary and secondary metabolic genes related to rifamycin biosynthesis. PMID:21424691

  14. The pvc operon regulates the expression of the Pseudomonas aeruginosa fimbrial chaperone/usher pathway (cup genes.

    Directory of Open Access Journals (Sweden)

    Uzma Qaisar

    Full Text Available The Pseudomonas aeruginosa fimbrial structures encoded by the cup gene clusters (cupB and cupC contribute to its attachment to abiotic surfaces and biofilm formation. The P. aeruginosa pvcABCD gene cluster encodes enzymes that synthesize a novel isonitrile functionalized cumarin, paerucumarin. Paerucumarin has already been characterized chemically, but this is the first report elucidating its role in bacterial biology. We examined the relationship between the pvc operon and the cup gene clusters in the P. aeruginosa strain MPAO1. Mutations within the pvc genes compromised biofilm development and significantly reduced the expression of cupB1-6 and cupC1-3, as well as different genes of the cupB/cupC two-component regulatory systems, roc1/roc2. Adjacent to pvc is the transcriptional regulator ptxR. A ptxR mutation in MPAO1 significantly reduced the expression of the pvc genes, the cupB/cupC genes, and the roc1/roc2 genes. Overexpression of the intact chromosomally-encoded pvc operon by a ptxR plasmid significantly enhanced cupB2, cupC2, rocS1, and rocS2 expression and biofilm development. Exogenously added paerucumarin significantly increased the expression of cupB2, cupC2, rocS1 and rocS2 in the pvcA mutant. Our results suggest that pvc influences P. aeruginosa biofilm development through the cup gene clusters in a pathway that involves paerucumarin, PtxR, and different cup regulators.

  15. The pvc operon regulates the expression of the Pseudomonas aeruginosa fimbrial chaperone/usher pathway (cup) genes.

    Science.gov (United States)

    Qaisar, Uzma; Luo, Liming; Haley, Cecily L; Brady, Sean F; Carty, Nancy L; Colmer-Hamood, Jane A; Hamood, Abdul N

    2013-01-01

    The Pseudomonas aeruginosa fimbrial structures encoded by the cup gene clusters (cupB and cupC) contribute to its attachment to abiotic surfaces and biofilm formation. The P. aeruginosa pvcABCD gene cluster encodes enzymes that synthesize a novel isonitrile functionalized cumarin, paerucumarin. Paerucumarin has already been characterized chemically, but this is the first report elucidating its role in bacterial biology. We examined the relationship between the pvc operon and the cup gene clusters in the P. aeruginosa strain MPAO1. Mutations within the pvc genes compromised biofilm development and significantly reduced the expression of cupB1-6 and cupC1-3, as well as different genes of the cupB/cupC two-component regulatory systems, roc1/roc2. Adjacent to pvc is the transcriptional regulator ptxR. A ptxR mutation in MPAO1 significantly reduced the expression of the pvc genes, the cupB/cupC genes, and the roc1/roc2 genes. Overexpression of the intact chromosomally-encoded pvc operon by a ptxR plasmid significantly enhanced cupB2, cupC2, rocS1, and rocS2 expression and biofilm development. Exogenously added paerucumarin significantly increased the expression of cupB2, cupC2, rocS1 and rocS2 in the pvcA mutant. Our results suggest that pvc influences P. aeruginosa biofilm development through the cup gene clusters in a pathway that involves paerucumarin, PtxR, and different cup regulators. PMID:23646138

  16. Identification and characterization of MalA in the maltose/maltodextrin operon of Sulfolobus acidocaldarius DSM639.

    Science.gov (United States)

    Choi, Kyoung-Hwa; Hwang, Sungmin; Cha, Jaeho

    2013-04-01

    A putative maltose/maltodextrin operon was found in the Sulfolobus acidocaldarius DSM639 genome. The gene cluster consisted of 7 genes (malA, trmB, amyA, malG, malF, malE, and malK). Here, we report the identification of MalA, which is responsible for the hydrolysis of maltose or maltodextrin to glucose in S. acidocaldarius. The transcription level of malA was increased 3-fold upon the addition of maltose or starch to the medium. Moreover, the α-glucosidase activity for maltose as a substrate in cell extracts of S. acidocaldarius DSM639 was also 11- and 10-fold higher during growth in YT medium (Brock's mineral salts, 0.1% [wt/vol] tryptone, and 0.005% [wt/vol] yeast extract) containing maltose or starch, respectively, than during growth on other sugars. The gene encoding MalA was cloned and expressed in S. acidocaldarius. The enzyme purified from the organism was a dodecamer in its active state and showed strong maltose-hydrolyzing activity at 100°C and pH 5.0. MalA was remarkably thermostable, with half-lives of 33.8 h, 10.6 h, and 1.8 h at 95°C, 100°C, and 105°C, respectively. Substrate specificity and kinetic studies of MalA with maltooligosaccharides indicated that MalA efficiently hydrolyzed maltose to maltopentaose, which is a typical characteristic of GH31-type α-glucosidases. However, glycogen or starch was not hydrolyzed. Reverse transcription-PCR, sugar uptake, and growth studies of the wild-type DSM639 and ΔmalEFG mutant on different sugars demonstrated that MalA located in the mal operon gene cluster is involved in maltose and starch metabolism in S. acidocaldarius.

  17. Molecular basis of TRAP-5'SL RNA interaction in the Bacillus subtilis trp operon transcription attenuation mechanism.

    Science.gov (United States)

    McGraw, Adam P; Mokdad, Ali; Major, François; Bevilacqua, Philip C; Babitzke, Paul

    2009-01-01

    Expression of the Bacillus subtilis trpEDCFBA operon is regulated by the interaction of tryptophan-activated TRAP with 11 (G/U)AG trinucleotide repeats that lie in the leader region of the nascent trp transcript. Bound TRAP prevents folding of an antiterminator structure and favors formation of an overlapping intrinsic terminator hairpin upstream of the trp operon structural genes. A 5'-stem-loop (5'SL) structure that forms just upstream of the triplet repeat region increases the affinity of TRAP-trp RNA interaction, thereby increasing the efficiency of transcription termination. Single-stranded nucleotides in the internal loop and in the hairpin loop of the 5'SL are important for TRAP binding. We show here that altering the distance between these two loops suggests that G7, A8, and A9 from the internal loop and A19 and G20 from the hairpin loop constitute two structurally discrete TRAP-binding regions. Photochemical cross-linking experiments also show that the hairpin loop of the 5'SL is in close proximity to the flexible loop region of TRAP during TRAP-5'SL interaction. The dimensions of B. subtilis TRAP and of a three-dimensional model of the 5'SL generated using the MC-Sym and MC-Fold pipeline imply that the 5'SL binds the protein in an orientation where the helical axis of the 5'SL is perpendicular to the plane of TRAP. This interaction not only increases the affinity of TRAP-trp leader RNA interaction, but also orients the downstream triplet repeats for interaction with the 11 KKR motifs that lie on TRAP's perimeter, increasing the likelihood that TRAP will bind in time to promote termination. PMID:19033375

  18. Accurate studies on dissociation energies of diatomic molecules

    Institute of Scientific and Technical Information of China (English)

    SUN; WeiGuo; FAN; QunChao

    2007-01-01

    The molecular dissociation energies of some electronic states of hydride and N2 molecules were studied using a parameter-free analytical formula suggested in this study and the algebraic method (AM) proposed recently. The results show that the accurate AM dissociation energies DeAM agree excellently with experimental dissociation energies Deexpt, and that the dissociation energy of an electronic state such as the 23△g state of 7Li2 whose experimental value is not available can be predicted using the new formula.

  19. Accurate characterisation of post moulding shrinkage of polymer parts

    DEFF Research Database (Denmark)

    Neves, L. C.; De Chiffre, L.; González-Madruga, D.;

    2015-01-01

    The work deals with experimental determination of the shrinkage of polymer parts after injection moulding. A fixture for length measurements on 8 parts at the same time was designed and manufactured in Invar, mounted with 8 electronic gauges, and provided with 3 temperature sensors. The fixture...... were compensated with respect to the effect from temperature variations during the measurements. Prediction of the length after stabilisation was carried out by fitting data at different stages of shrinkage. Uncertainty estimations were carried out and a procedure for the accurate characterisation...... of post moulding shrinkage of polymer parts was developed. Expanded uncertainties (k=2) of 3 μm were obtained....

  20. Accurate tracking control in LOM application

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    The fabrication of accurate prototype from CAD model directly in short time depends on the accurate tracking control and reference trajectory planning in (Laminated Object Manufacture) LOM application. An improvement on contour accuracy is acquired by the introduction of a tracking controller and a trajectory generation policy. A model of the X-Y positioning system of LOM machine is developed as the design basis of tracking controller. The ZPETC (Zero Phase Error Tracking Controller) is used to eliminate single axis following error, thus reduce the contour error. The simulation is developed on a Maltab model based on a retrofitted LOM machine and the satisfied result is acquired.

  1. The conserved nhaAR operon is drastically divergent between B2 and non-B2 Escherichia coli and is involved in extra-intestinal virulence.

    Directory of Open Access Journals (Sweden)

    Mathilde Lescat

    Full Text Available The Escherichia coli species is divided in phylogenetic groups that differ in their virulence and commensal distribution. Strains belonging to the B2 group are involved in extra-intestinal pathologies but also appear to be more prevalent as commensals among human occidental populations. To investigate the genetic specificities of B2 sub-group, we used 128 sequenced genomes and identified genes of the core genome that showed marked difference between B2 and non-B2 genomes. We focused on the gene and its surrounding region with the strongest divergence between B2 and non-B2, the antiporter gene nhaA. This gene is part of the nhaAR operon, which is in the core genome but flanked by mobile regions, and is involved in growth at high pH and high sodium concentrations. Consistently, we found that a panel of non-B2 strains grew faster than B2 at high pH and high sodium concentrations. However, we could not identify differences in expression of the nhaAR operon using fluorescence reporter plasmids. Furthermore, the operon deletion had no differential impact between B2 and non-B2 strains, and did not result in a fitness modification in a murine model of gut colonization. Nevertheless, sequence analysis and experiments in a murine model of septicemia revealed that recombination in nhaA among B2 strains was observed in strains with low virulence. Finally, nhaA and nhaAR operon deletions drastically decreased virulence in one B2 strain. This effect of nhaAR deletion appeared to be stronger than deletion of all pathogenicity islands. Thus, a population genetic approach allowed us to identify an operon in the core genome without strong effect in commensalism but with an important role in extra-intestinal virulence, a landmark of the B2 strains.

  2. Accurate atomic data for industrial plasma applications

    Energy Technology Data Exchange (ETDEWEB)

    Griesmann, U.; Bridges, J.M.; Roberts, J.R.; Wiese, W.L.; Fuhr, J.R. [National Inst. of Standards and Technology, Gaithersburg, MD (United States)

    1997-12-31

    Reliable branching fraction, transition probability and transition wavelength data for radiative dipole transitions of atoms and ions in plasma are important in many industrial applications. Optical plasma diagnostics and modeling of the radiation transport in electrical discharge plasmas (e.g. in electrical lighting) depend on accurate basic atomic data. NIST has an ongoing experimental research program to provide accurate atomic data for radiative transitions. The new NIST UV-vis-IR high resolution Fourier transform spectrometer has become an excellent tool for accurate and efficient measurements of numerous transition wavelengths and branching fractions in a wide wavelength range. Recently, the authors have also begun to employ photon counting techniques for very accurate measurements of branching fractions of weaker spectral lines with the intent to improve the overall accuracy for experimental branching fractions to better than 5%. They have now completed their studies of transition probabilities of Ne I and Ne II. The results agree well with recent calculations and for the first time provide reliable transition probabilities for many weak intercombination lines.

  3. Complete Deletion of the Fucose Operon in Haemophilus influenzae Is Associated with a Cluster in Multilocus Sequence Analysis-Based Phylogenetic Group II Related to Haemophilus haemolyticus: Implications for Identification and Typing.

    Science.gov (United States)

    de Gier, Camilla; Kirkham, Lea-Ann S; Nørskov-Lauritsen, Niels

    2015-12-01

    Nonhemolytic variants of Haemophilus haemolyticus are difficult to differentiate from Haemophilus influenzae despite a wide difference in pathogenic potential. A previous investigation characterized a challenging set of 60 clinical strains using multiple PCRs for marker genes and described strains that could not be unequivocally identified as either species. We have analyzed the same set of strains by multilocus sequence analysis (MLSA) and near-full-length 16S rRNA gene sequencing. MLSA unambiguously allocated all study strains to either of the two species, while identification by 16S rRNA sequence was inconclusive for three strains. Notably, the two methods yielded conflicting identifications for two strains. Most of the "fuzzy species" strains were identified as H. influenzae that had undergone complete deletion of the fucose operon. Such strains, which are untypeable by the H. influenzae multilocus sequence type (MLST) scheme, have sporadically been reported and predominantly belong to a single branch of H. influenzae MLSA phylogenetic group II. We also found evidence of interspecies recombination between H. influenzae and H. haemolyticus within the 16S rRNA genes. Establishing an accurate method for rapid and inexpensive identification of H. influenzae is important for disease surveillance and treatment.

  4. Can blind persons accurately assess body size from the voice?

    Science.gov (United States)

    Pisanski, Katarzyna; Oleszkiewicz, Anna; Sorokowska, Agnieszka

    2016-04-01

    Vocal tract resonances provide reliable information about a speaker's body size that human listeners use for biosocial judgements as well as speech recognition. Although humans can accurately assess men's relative body size from the voice alone, how this ability is acquired remains unknown. In this study, we test the prediction that accurate voice-based size estimation is possible without prior audiovisual experience linking low frequencies to large bodies. Ninety-one healthy congenitally or early blind, late blind and sighted adults (aged 20-65) participated in the study. On the basis of vowel sounds alone, participants assessed the relative body sizes of male pairs of varying heights. Accuracy of voice-based body size assessments significantly exceeded chance and did not differ among participants who were sighted, or congenitally blind or who had lost their sight later in life. Accuracy increased significantly with relative differences in physical height between men, suggesting that both blind and sighted participants used reliable vocal cues to size (i.e. vocal tract resonances). Our findings demonstrate that prior visual experience is not necessary for accurate body size estimation. This capacity, integral to both nonverbal communication and speech perception, may be present at birth or may generalize from broader cross-modal correspondences. PMID:27095264

  5. The economic value of accurate wind power forecasting to utilities

    Energy Technology Data Exchange (ETDEWEB)

    Watson, S.J. [Rutherford Appleton Lab., Oxfordshire (United Kingdom); Giebel, G.; Joensen, A. [Risoe National Lab., Dept. of Wind Energy and Atmospheric Physics, Roskilde (Denmark)

    1999-03-01

    With increasing penetrations of wind power, the need for accurate forecasting is becoming ever more important. Wind power is by its very nature intermittent. For utility schedulers this presents its own problems particularly when the penetration of wind power capacity in a grid reaches a significant level (>20%). However, using accurate forecasts of wind power at wind farm sites, schedulers are able to plan the operation of conventional power capacity to accommodate the fluctuating demands of consumers and wind farm output. The results of a study to assess the value of forecasting at several potential wind farm sites in the UK and in the US state of Iowa using the Reading University/Rutherford Appleton Laboratory National Grid Model (NGM) are presented. The results are assessed for different types of wind power forecasting, namely: persistence, optimised numerical weather prediction or perfect forecasting. In particular, it will shown how the NGM has been used to assess the value of numerical weather prediction forecasts from the Danish Meteorological Institute model, HIRLAM, and the US Nested Grid Model, which have been `site tailored` by the use of the linearized flow model WA{sup s}P and by various Model output Statistics (MOS) and autoregressive techniques. (au)

  6. A rationale for autoinduction of a transcriptional activator: ethanolamine ammonia-lyase (EutBC) and the operon activator (EutR) compete for adenosyl-cobalamin in Salmonella typhimurium.

    OpenAIRE

    Sheppard, D E; Roth, J R

    1994-01-01

    The ethanolamine utilization (eut) operon of Salmonella typhimurium is controlled by a positive regulatory protein (EutR) which stimulates eut operon expression in response to the simultaneous presence of two effectors, ethanolamine and adenosyl-cobalamin (Ado-B12). Ado-B12 is a cofactor for ethanolamine ammonia-lyase (lyase), the first enzyme in the ethanolamine-degradative pathway. The dependence of this pathway on the use of Ado-B12 as an effector in eut operon induction may be explained b...

  7. Accurate estimation of indoor travel times

    DEFF Research Database (Denmark)

    Prentow, Thor Siiger; Blunck, Henrik; Stisen, Allan;

    2014-01-01

    are collected within the building complex. Results indicate that InTraTime is superior with respect to metrics such as deployment cost, maintenance cost and estimation accuracy, yielding an average deviation from actual travel times of 11.7 %. This accuracy was achieved despite using a minimal-effort setup......The ability to accurately estimate indoor travel times is crucial for enabling improvements within application areas such as indoor navigation, logistics for mobile workers, and facility management. In this paper, we study the challenges inherent in indoor travel time estimation, and we propose...... the InTraTime method for accurately estimating indoor travel times via mining of historical and real-time indoor position traces. The method learns during operation both travel routes, travel times and their respective likelihood---both for routes traveled as well as for sub-routes thereof. In...

  8. Accurate guitar tuning by cochlear implant musicians.

    Directory of Open Access Journals (Sweden)

    Thomas Lu

    Full Text Available Modern cochlear implant (CI users understand speech but find difficulty in music appreciation due to poor pitch perception. Still, some deaf musicians continue to perform with their CI. Here we show unexpected results that CI musicians can reliably tune a guitar by CI alone and, under controlled conditions, match simultaneously presented tones to <0.5 Hz. One subject had normal contralateral hearing and produced more accurate tuning with CI than his normal ear. To understand these counterintuitive findings, we presented tones sequentially and found that tuning error was larger at ∼ 30 Hz for both subjects. A third subject, a non-musician CI user with normal contralateral hearing, showed similar trends in performance between CI and normal hearing ears but with less precision. This difference, along with electric analysis, showed that accurate tuning was achieved by listening to beats rather than discriminating pitch, effectively turning a spectral task into a temporal discrimination task.

  9. Accurate Finite Difference Methods for Option Pricing

    OpenAIRE

    Persson, Jonas

    2006-01-01

    Stock options are priced numerically using space- and time-adaptive finite difference methods. European options on one and several underlying assets are considered. These are priced with adaptive numerical algorithms including a second order method and a more accurate method. For American options we use the adaptive technique to price options on one stock with and without stochastic volatility. In all these methods emphasis is put on the control of errors to fulfill predefined tolerance level...

  10. Accurate variational forms for multiskyrmion configurations

    Energy Technology Data Exchange (ETDEWEB)

    Jackson, A.D.; Weiss, C.; Wirzba, A.; Lande, A.

    1989-04-17

    Simple variational forms are suggested for the fields of a single skyrmion on a hypersphere, S/sub 3/(L), and of a face-centered cubic array of skyrmions in flat space, R/sub 3/. The resulting energies are accurate at the level of 0.2%. These approximate field configurations provide a useful alternative to brute-force solutions of the corresponding Euler equations.

  11. Efficient Accurate Context-Sensitive Anomaly Detection

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    For program behavior-based anomaly detection, the only way to ensure accurate monitoring is to construct an efficient and precise program behavior model. A new program behavior-based anomaly detection model,called combined pushdown automaton (CPDA) model was proposed, which is based on static binary executable analysis. The CPDA model incorporates the optimized call stack walk and code instrumentation technique to gain complete context information. Thereby the proposed method can detect more attacks, while retaining good performance.

  12. Programming Useful Life Prediction (PULP) Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Accurately predicting Remaining Useful Life (RUL) provides significant benefits—it increases safety and reduces financial and labor resource requirements....

  13. Accurate phase-shift velocimetry in rock

    Science.gov (United States)

    Shukla, Matsyendra Nath; Vallatos, Antoine; Phoenix, Vernon R.; Holmes, William M.

    2016-06-01

    Spatially resolved Pulsed Field Gradient (PFG) velocimetry techniques can provide precious information concerning flow through opaque systems, including rocks. This velocimetry data is used to enhance flow models in a wide range of systems, from oil behaviour in reservoir rocks to contaminant transport in aquifers. Phase-shift velocimetry is the fastest way to produce velocity maps but critical issues have been reported when studying flow through rocks and porous media, leading to inaccurate results. Combining PFG measurements for flow through Bentheimer sandstone with simulations, we demonstrate that asymmetries in the molecular displacement distributions within each voxel are the main source of phase-shift velocimetry errors. We show that when flow-related average molecular displacements are negligible compared to self-diffusion ones, symmetric displacement distributions can be obtained while phase measurement noise is minimised. We elaborate a complete method for the production of accurate phase-shift velocimetry maps in rocks and low porosity media and demonstrate its validity for a range of flow rates. This development of accurate phase-shift velocimetry now enables more rapid and accurate velocity analysis, potentially helping to inform both industrial applications and theoretical models.

  14. Accurate structural correlations from maximum likelihood superpositions.

    Directory of Open Access Journals (Sweden)

    Douglas L Theobald

    2008-02-01

    Full Text Available The cores of globular proteins are densely packed, resulting in complicated networks of structural interactions. These interactions in turn give rise to dynamic structural correlations over a wide range of time scales. Accurate analysis of these complex correlations is crucial for understanding biomolecular mechanisms and for relating structure to function. Here we report a highly accurate technique for inferring the major modes of structural correlation in macromolecules using likelihood-based statistical analysis of sets of structures. This method is generally applicable to any ensemble of related molecules, including families of nuclear magnetic resonance (NMR models, different crystal forms of a protein, and structural alignments of homologous proteins, as well as molecular dynamics trajectories. Dominant modes of structural correlation are determined using principal components analysis (PCA of the maximum likelihood estimate of the correlation matrix. The correlations we identify are inherently independent of the statistical uncertainty and dynamic heterogeneity associated with the structural coordinates. We additionally present an easily interpretable method ("PCA plots" for displaying these positional correlations by color-coding them onto a macromolecular structure. Maximum likelihood PCA of structural superpositions, and the structural PCA plots that illustrate the results, will facilitate the accurate determination of dynamic structural correlations analyzed in diverse fields of structural biology.

  15. High Frequency QRS ECG Accurately Detects Cardiomyopathy

    Science.gov (United States)

    Schlegel, Todd T.; Arenare, Brian; Poulin, Gregory; Moser, Daniel R.; Delgado, Reynolds

    2005-01-01

    High frequency (HF, 150-250 Hz) analysis over the entire QRS interval of the ECG is more sensitive than conventional ECG for detecting myocardial ischemia. However, the accuracy of HF QRS ECG for detecting cardiomyopathy is unknown. We obtained simultaneous resting conventional and HF QRS 12-lead ECGs in 66 patients with cardiomyopathy (EF = 23.2 plus or minus 6.l%, mean plus or minus SD) and in 66 age- and gender-matched healthy controls using PC-based ECG software recently developed at NASA. The single most accurate ECG parameter for detecting cardiomyopathy was an HF QRS morphological score that takes into consideration the total number and severity of reduced amplitude zones (RAZs) present plus the clustering of RAZs together in contiguous leads. This RAZ score had an area under the receiver operator curve (ROC) of 0.91, and was 88% sensitive, 82% specific and 85% accurate for identifying cardiomyopathy at optimum score cut-off of 140 points. Although conventional ECG parameters such as the QRS and QTc intervals were also significantly longer in patients than controls (P less than 0.001, BBBs excluded), these conventional parameters were less accurate (area under the ROC = 0.77 and 0.77, respectively) than HF QRS morphological parameters for identifying underlying cardiomyopathy. The total amplitude of the HF QRS complexes, as measured by summed root mean square voltages (RMSVs), also differed between patients and controls (33.8 plus or minus 11.5 vs. 41.5 plus or minus 13.6 mV, respectively, P less than 0.003), but this parameter was even less accurate in distinguishing the two groups (area under ROC = 0.67) than the HF QRS morphologic and conventional ECG parameters. Diagnostic accuracy was optimal (86%) when the RAZ score from the HF QRS ECG and the QTc interval from the conventional ECG were used simultaneously with cut-offs of greater than or equal to 40 points and greater than or equal to 445 ms, respectively. In conclusion 12-lead HF QRS ECG employing

  16. Coordination of the arc regulatory system and pheromone-mediated positive feedback in controlling the Vibrio fischeri lux operon.

    Directory of Open Access Journals (Sweden)

    Alecia N Septer

    Full Text Available Bacterial pheromone signaling is often governed both by environmentally responsive regulators and by positive feedback. This regulatory combination has the potential to coordinate a group response among distinct subpopulations that perceive key environmental stimuli differently. We have explored the interplay between an environmentally responsive regulator and pheromone-mediated positive feedback in intercellular signaling by Vibrio fischeri ES114, a bioluminescent bacterium that colonizes the squid Euprymna scolopes. Bioluminescence in ES114 is controlled in part by N-(3-oxohexanoyl-L-homoserine lactone (3OC6, a pheromone produced by LuxI that together with LuxR activates transcription of the luxICDABEG operon, initiating a positive feedback loop and inducing luminescence. The lux operon is also regulated by environmentally responsive regulators, including the redox-responsive ArcA/ArcB system, which directly represses lux in culture. Here we show that inactivating arcA leads to increased 3OC6 accumulation to initiate positive feedback. In the absence of positive feedback, arcA-mediated control of luminescence was only ∼2-fold, but luxI-dependent positive feedback contributed more than 100 fold to the net induction of luminescence in the arcA mutant. Consistent with this overriding importance of positive feedback, 3OC6 produced by the arcA mutant induced luminescence in nearby wild-type cells, overcoming their ArcA repression of lux. Similarly, we found that artificially inducing ArcA could effectively repress luminescence before, but not after, positive feedback was initiated. Finally, we show that 3OC6 produced by a subpopulation of symbiotic cells can induce luminescence in other cells co-colonizing the host. Our results suggest that even transient loss of ArcA-mediated regulation in a sub-population of cells can induce luminescence in a wider community. Moreover, they indicate that 3OC6 can communicate information about both cell density

  17. Identification and structure of the nasR gene encoding a nitrate- and nitrite-responsive positive regulator of nasFEDCBA (nitrate assimilation) operon expression in Klebsiella pneumoniae M5al.

    Science.gov (United States)

    Goldman, B S; Lin, J T; Stewart, V

    1994-08-01

    Klebsiella pneumoniae can use nitrate and nitrite as sole nitrogen sources through the nitrate assimilatory pathway. The structural genes for assimilatory nitrate and nitrite reductases together with genes necessary for nitrate transport form an operon, nasFEDCBA. Expression of the nasF operon is regulated both by general nitrogen control and also by nitrate or nitrite induction. We have identified a gene, nasR, that is necessary for nitrate and nitrite induction. The nasR gene, located immediately upstream of the nasFEDCBA operon, encodes a 44-kDa protein. The NasR protein shares carboxyl-terminal sequence similarity with the AmiR protein of Pseudomonas aeruginosa, the positive regulator of amiE (aliphatic amidase) gene expression. In addition, we present evidence that the nasF operon is not autogenously regulated. PMID:8051020

  18. Accurate measurement of unsteady state fluid temperature

    Science.gov (United States)

    Jaremkiewicz, Magdalena

    2016-07-01

    In this paper, two accurate methods for determining the transient fluid temperature were presented. Measurements were conducted for boiling water since its temperature is known. At the beginning the thermometers are at the ambient temperature and next they are immediately immersed into saturated water. The measurements were carried out with two thermometers of different construction but with the same housing outer diameter equal to 15 mm. One of them is a K-type industrial thermometer widely available commercially. The temperature indicated by the thermometer was corrected considering the thermometers as the first or second order inertia devices. The new design of a thermometer was proposed and also used to measure the temperature of boiling water. Its characteristic feature is a cylinder-shaped housing with the sheath thermocouple located in its center. The temperature of the fluid was determined based on measurements taken in the axis of the solid cylindrical element (housing) using the inverse space marching method. Measurements of the transient temperature of the air flowing through the wind tunnel using the same thermometers were also carried out. The proposed measurement technique provides more accurate results compared with measurements using industrial thermometers in conjunction with simple temperature correction using the inertial thermometer model of the first or second order. By comparing the results, it was demonstrated that the new thermometer allows obtaining the fluid temperature much faster and with higher accuracy in comparison to the industrial thermometer. Accurate measurements of the fast changing fluid temperature are possible due to the low inertia thermometer and fast space marching method applied for solving the inverse heat conduction problem.

  19. How accurate are the weather forecasts for Bierun (southern Poland)?

    Science.gov (United States)

    Gawor, J.

    2012-04-01

    Weather forecast accuracy has increased in recent times mainly thanks to significant development of numerical weather prediction models. Despite the improvements, the forecasts should be verified to control their quality. The evaluation of forecast accuracy can also be an interesting learning activity for students. It joins natural curiosity about everyday weather and scientific process skills: problem solving, database technologies, graph construction and graphical analysis. The examination of the weather forecasts has been taken by a group of 14-year-old students from Bierun (southern Poland). They participate in the GLOBE program to develop inquiry-based investigations of the local environment. For the atmospheric research the automatic weather station is used. The observed data were compared with corresponding forecasts produced by two numerical weather prediction models, i.e. COAMPS (Coupled Ocean/Atmosphere Mesoscale Prediction System) developed by Naval Research Laboratory Monterey, USA; it runs operationally at the Interdisciplinary Centre for Mathematical and Computational Modelling in Warsaw, Poland and COSMO (The Consortium for Small-scale Modelling) used by the Polish Institute of Meteorology and Water Management. The analysed data included air temperature, precipitation, wind speed, wind chill and sea level pressure. The prediction periods from 0 to 24 hours (Day 1) and from 24 to 48 hours (Day 2) were considered. The verification statistics that are commonly used in meteorology have been applied: mean error, also known as bias, for continuous data and a 2x2 contingency table to get the hit rate and false alarm ratio for a few precipitation thresholds. The results of the aforementioned activity became an interesting basis for discussion. The most important topics are: 1) to what extent can we rely on the weather forecasts? 2) How accurate are the forecasts for two considered time ranges? 3) Which precipitation threshold is the most predictable? 4) Why

  20. New law requires 'medically accurate' lesson plans.

    Science.gov (United States)

    1999-09-17

    The California Legislature has passed a bill requiring all textbooks and materials used to teach about AIDS be medically accurate and objective. Statements made within the curriculum must be supported by research conducted in compliance with scientific methods, and published in peer-reviewed journals. Some of the current lesson plans were found to contain scientifically unsupported and biased information. In addition, the bill requires material to be "free of racial, ethnic, or gender biases." The legislation is supported by a wide range of interests, but opposed by the California Right to Life Education Fund, because they believe it discredits abstinence-only material.

  1. Niche Genetic Algorithm with Accurate Optimization Performance

    Institute of Scientific and Technical Information of China (English)

    LIU Jian-hua; YAN De-kun

    2005-01-01

    Based on crowding mechanism, a novel niche genetic algorithm was proposed which can record evolutionary direction dynamically during evolution. After evolution, the solutions's precision can be greatly improved by means of the local searching along the recorded direction. Simulation shows that this algorithm can not only keep population diversity but also find accurate solutions. Although using this method has to take more time compared with the standard GA, it is really worth applying to some cases that have to meet a demand for high solution precision.

  2. Investigations on Accurate Analysis of Microstrip Reflectarrays

    DEFF Research Database (Denmark)

    Zhou, Min; Sørensen, S. B.; Kim, Oleksiy S.;

    2011-01-01

    An investigation on accurate analysis of microstrip reflectarrays is presented. Sources of error in reflectarray analysis are examined and solutions to these issues are proposed. The focus is on two sources of error, namely the determination of the equivalent currents to calculate the radiation...... pattern, and the inaccurate mutual coupling between array elements due to the lack of periodicity. To serve as reference, two offset reflectarray antennas have been designed, manufactured and measured at the DTUESA Spherical Near-Field Antenna Test Facility. Comparisons of simulated and measured data are...

  3. Accurate diagnosis is essential for amebiasis

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    @@ Amebiasis is one of the three most common causes of death from parasitic disease, and Entamoeba histolytica is the most widely distributed parasites in the world. Particularly, Entamoeba histolytica infection in the developing countries is a significant health problem in amebiasis-endemic areas with a significant impact on infant mortality[1]. In recent years a world wide increase in the number of patients with amebiasis has refocused attention on this important infection. On the other hand, improving the quality of parasitological methods and widespread use of accurate tecniques have improved our knowledge about the disease.

  4. Universality: Accurate Checks in Dyson's Hierarchical Model

    Science.gov (United States)

    Godina, J. J.; Meurice, Y.; Oktay, M. B.

    2003-06-01

    In this talk we present high-accuracy calculations of the susceptibility near βc for Dyson's hierarchical model in D = 3. Using linear fitting, we estimate the leading (γ) and subleading (Δ) exponents. Independent estimates are obtained by calculating the first two eigenvalues of the linearized renormalization group transformation. We found γ = 1.29914073 ± 10 -8 and, Δ = 0.4259469 ± 10-7 independently of the choice of local integration measure (Ising or Landau-Ginzburg). After a suitable rescaling, the approximate fixed points for a large class of local measure coincide accurately with a fixed point constructed by Koch and Wittwer.

  5. Conserved residues Asp16 and Pro24 of TnaC-tRNAPro participate in tryptophan induction of Tna operon expression.

    Science.gov (United States)

    Cruz-Vera, Luis R; Yanofsky, Charles

    2008-07-01

    In Escherichia coli, interactions between the nascent TnaC-tRNA(Pro) peptidyl-tRNA and the translating ribosome create a tryptophan binding site in the ribosome where bound tryptophan inhibits TnaC-tRNA(Pro) cleavage. This inhibition delays ribosome release, thereby inhibiting Rho factor binding and action, resulting in increased tna operon transcription. Replacing Trp12 of TnaC with any other amino acid residue was previously shown to prevent tryptophan binding and induction of tna operon expression. Genome-wide comparisons of TnaC amino acid sequences identify Asp16 and Pro24, as well as Trp12, as highly conserved TnaC residues. Replacing these residues with other residues was previously shown to influence tryptophan induction of tna operon expression. In this study, in vitro analyses were performed to examine the potential roles of Asp16 and Pro24 in tna operon induction. Replacing Asp16 or Pro24 of TnaC of E. coli with other amino acids established that these residues are essential for free tryptophan binding and inhibition of TnaC-tRNA(Pro) cleavage at the peptidyl transferase center. Asp16 and Pro24 are in fact located in spatial positions corresponding to critical residues of AAP, another ribosome regulatory peptide. Sparsomycin-methylation protection studies further suggested that segments of 23S RNA were arranged differently in ribosomes bearing TnaCs with either the Asp16Ala or the Pro24Ala change. Thus, features of the amino acid sequence of TnaC of the nascent TnaC-tRNA(Pro) peptidyl-tRNA, in addition to the presence of Trp12, are necessary for the nascent peptide to create a tryptophan binding/inhibition site in the translating ribosome. PMID:18424524

  6. Salmonella enterica Typhimurium fljBA operon stability: implications regarding the origin of Salmonella enterica I 4,[5],12:i:.

    Science.gov (United States)

    Tomiyama, M P O; Werle, C H; Milanez, G P; Nóbrega, D B; Pereira, J P; Calarga, A P; Flores, F; Brocchi, M

    2015-12-29

    Salmonella enterica subsp enterica serovar 4,5,12:i:- has been responsible for many recent Salmonella outbreaks worldwide. Several studies indicate that this serovar originated from S. enterica subsp enterica serovar Typhimurium, by the loss of the flagellar phase II gene (fljB) and adjacent sequences. However, at least two different clones of S. enterica 4,5,12:i:- exist that differs in the molecular events responsible for fljB deletion. The aim of this study was to test the stability of the fljBA operon responsible for the flagellar phase variation under different growth conditions in order to verify if its deletion is a frequent event that could explain the origin and dissemination of this serovar. In fact, coding sequences for transposons are present near this operon and in some strains, such as S. enterica Typhimurium LT2, the Fels-2 prophage gene is inserted near this operon. The presence of mobile DNA could confer instability to this region. In order to examine this, the cat (chloramphenicol acetyltransferase) gene was inserted adjacent to the fljBA operon so that deletions involving this genomic region could be identified. After growing S. enterica chloramphenicol-resistant strains under different conditions, more than 104 colonies were tested for the loss of chloramphenicol resistance. However, none of the colonies were sensitive to chloramphenicol. These data suggest that the origin of S. enterica serovar 4,5,12:i:- from Typhimurium by fljBA deletion is not a frequent event. The origin and dissemination of 4,5,12:i:- raise several questions about the role of flagellar phase variation in virulence.

  7. The essential yhcSR two-component signal transduction system directly regulates the lac and opuCABCD operons of Staphylococcus aureus.

    Directory of Open Access Journals (Sweden)

    Meiying Yan

    Full Text Available Our previous studies suggested that the essential two-component signal transduction system, YhcSR, regulates the opuCABCD operon at the transcriptional level, and the Pspac-driven opuCABCD partially complements the lethal effects of yhcS antisense RNA expression in Staphylococcus aureus. However, the reason why yhcSR regulon is required for growth is still unclear. In this report, we present that the lac and opuC operons are directly transcriptionally regulated by YhcSR. Using real-time RT-PCR we showed that the down-regulation of yhcSR expression affected the transcription of lacA encoding galactose-6-phosphotase isomerase subunit LacA, and opuCA encoding a subunit of a glycine betaine/carnitine/choline ABC transporter. Promoter-lux reporter fusion studies further confirmed the transcriptional regulation of lac by YhcSR. Gel shift assays revealed that YhcR binds to the promoter regions of the lac and opuC operons. Moreover, the Pspac-driven lacABC expression in trans was able to partially complement the lethal effect of induced yhcS antisense RNA. Likewise, the Pspac-driven opuCABCD expression in trans complemented the growth defect of S. aureus in a high osmotic strength medium during the depletion of YhcSR. Taken together, the above data indicate that the yhcSR system directly regulates the expression of lac and opuC operons, which, in turn, may be partially associated with the essentiality of yhcSR in S. aureus. These results provide a new insight into the biological functions of the yhcSR, a global regulator.

  8. Technological Basis and Scientific Returns for Absolutely Accurate Measurements

    Science.gov (United States)

    Dykema, J. A.; Anderson, J.

    2011-12-01

    The 2006 NRC Decadal Survey fostered a new appreciation for societal objectives as a driving motivation for Earth science. Many high-priority societal objectives are dependent on predictions of weather and climate. These predictions are based on numerical models, which derive from approximate representations of well-founded physics and chemistry on space and timescales appropriate to global and regional prediction. These laws of chemistry and physics in turn have a well-defined quantitative relationship with physical measurement units, provided these measurement units are linked to international measurement standards that are the foundation of contemporary measurement science and standards for engineering and commerce. Without this linkage, measurements have an ambiguous relationship to scientific principles that introduces avoidable uncertainty in analyses, predictions, and improved understanding of the Earth system. Since the improvement of climate and weather prediction is fundamentally dependent on the improvement of the representation of physical processes, measurement systems that reduce the ambiguity between physical truth and observations represent an essential component of a national strategy for understanding and living with the Earth system. This paper examines the technological basis and potential science returns of sensors that make measurements that are quantitatively tied on-orbit to international measurement standards, and thus testable to systematic errors. This measurement strategy provides several distinct benefits. First, because of the quantitative relationship between these international measurement standards and fundamental physical constants, measurements of this type accurately capture the true physical and chemical behavior of the climate system and are not subject to adjustment due to excluded measurement physics or instrumental artifacts. In addition, such measurements can be reproduced by scientists anywhere in the world, at any time

  9. Predicting protein linkages in bacteria: Which method is best depends on task

    Directory of Open Access Journals (Sweden)

    Leach Sonia M

    2008-09-01

    Full Text Available Abstract Background Applications of computational methods for predicting protein functional linkages are increasing. In recent years, several bacteria-specific methods for predicting linkages have been developed. The four major genomic context methods are: Gene cluster, Gene neighbor, Rosetta Stone, and Phylogenetic profiles. These methods have been shown to be powerful tools and this paper provides guidelines for when each method is appropriate by exploring different features of each method and potential improvements offered by their combination. We also review many previous treatments of these prediction methods, use the latest available annotations, and offer a number of new observations. Results Using Escherichia coli K12 and Bacillus subtilis, linkage predictions made by each of these methods were evaluated against three benchmarks: functional categories defined by COG and KEGG, known pathways listed in EcoCyc, and known operons listed in RegulonDB. Each evaluated method had strengths and weaknesses, with no one method dominating all aspects of predictive ability studied. For functional categories, as previous studies have shown, the Rosetta Stone method was individually best at detecting linkages and predicting functions among proteins with shared KEGG categories while the Phylogenetic profile method was best for linkage detection and function prediction among proteins with common COG functions. Differences in performance under COG versus KEGG may be attributable to the presence of paralogs. Better function prediction was observed when using a weighted combination of linkages based on reliability versus using a simple unweighted union of the linkage sets. For pathway reconstruction, 99 complete metabolic pathways in E. coli K12 (out of the 209 known, non-trivial pathways and 193 pathways with 50% of their proteins were covered by linkages from at least one method. Gene neighbor was most effective individually on pathway reconstruction

  10. Accurate location estimation of moving object with energy constraint & adaptive update algorithms to save data

    CERN Document Server

    Semwal, Vijay Bhaskar; Bhaskar, Vinay S; Sati, Meenakshi

    2011-01-01

    In research paper "Accurate estimation of the target location of object with energy constraint & Adaptive Update Algorithms to Save Data" one of the central issues in sensor networks is track the location, of moving object which have overhead of saving data, an accurate estimation of the target location of object with energy constraint .We do not have any mechanism which control and maintain data .The wireless communication bandwidth is also very limited. Some field which is using this technique are flood and typhoon detection, forest fire detection, temperature and humidity and ones we have these information use these information back to a central air conditioning and ventilation system. In this research paper, we propose protocol based on the prediction and adaptive based algorithm which is using less sensor node reduced by an accurate estimation of the target location. we are using minimum three sensor node to get the accurate position .We can extend it upto four or five to find more accurate location ...

  11. Identification and structure of the nasR gene encoding a nitrate- and nitrite-responsive positive regulator of nasFEDCBA (nitrate assimilation) operon expression in Klebsiella pneumoniae M5al.

    OpenAIRE

    Goldman, B. S.; Lin, J. T.; Stewart, V

    1994-01-01

    Klebsiella pneumoniae can use nitrate and nitrite as sole nitrogen sources through the nitrate assimilatory pathway. The structural genes for assimilatory nitrate and nitrite reductases together with genes necessary for nitrate transport form an operon, nasFEDCBA. Expression of the nasF operon is regulated both by general nitrogen control and also by nitrate or nitrite induction. We have identified a gene, nasR, that is necessary for nitrate and nitrite induction. The nasR gene, located immed...

  12. Classification of the genus Bacillus based on MALDI-TOF MS analysis of ribosomal proteins coded in S10 and spc operons.

    Science.gov (United States)

    Hotta, Yudai; Sato, Jun; Sato, Hiroaki; Hosoda, Akifumi; Tamura, Hiroto

    2011-05-25

    A rapid bacterial identification method by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) using ribosomal proteins coded in S10 and spc operons as biomarkers, named the S10-GERMS (the S10-spc-alpha operon gene encoded ribosomal protein mass spectrum) method, was applied for the genus Bacillus a Gram-positive bacterium. The S10-GERMS method could successfully distinguish the difference between B. subtilis subsp. subtilis NBRC 13719(T) and B. subtilis subsp. spizizenii NBRC 101239(T) because of the mass difference of 2 ribosomal subunit proteins, despite the difference of only 2 bases in the 16S rRNA gene between them. The 8 selected reliable and reproducible ribosomal subunit proteins without disturbance of S/N level on MALDI-TOF MS analysis, S10, S14, S19, L18, L22, L24, L29, and L30, coded in S10 and spc operons were significantly useful biomarkers for rapid bacterial classification at species and strain levels by the S10-GERMS method of genus Bacillus strains without purification of ribosomal proteins.

  13. Legionella dumoffii Tex-KL Mutated in an Operon Homologous to traC-traD is Defective in Epithelial Cell Invasion

    Institute of Scientific and Technical Information of China (English)

    QIN Tian; Iida Ken-ichiro; REN Hong Yu; ZHOU Hai Jian; Shin-ichi Yoshida

    2016-01-01

    Objective To understand the mechanism of invasion by Legionella dumoffii. Methods The L. dumoffii strain Tex-KL was mutated using the Tn903 derivative, Tn903dIIlacZ. After screening 799 transposon insertion mutants, we isolated one defective mutant. We then constructed the gene-disrupted mutant, KL16, and studied its invasion of and intracellular growth in HeLa and A549 cells, and in A/J mice survival experiments. The structure of traC-traD operon was analyzed by RT-PCR. Results The transposon insertion was in a gene homologous to Salmonella typhi traC, which is required for the assembly of F pilin into the mature F pilus structure and for conjugal DNA transmission. Results from RT-PCR suggested that the traC-traD region formed an operon. We found that when the traC gene was disrupted, invasion and intracellular growth of L. dumoffii Tex-KL were impaired in human epithelial cells. When mice were infected by intranasal inoculation with a traC deficient mutant, their survival significantly increased when compared to mice infected with the wild-type strain. Conclusion Our results indicated that the traC-traD operon is required for the invasion and intracellular growth abilities of L. dumoffii Tex-KL in epithelial cells.

  14. On multiple regulatory mechanisms in the tryptophan operon system in Escherichia coli: in silico study of perturbation dynamics.

    Science.gov (United States)

    Nguyen, Lan K; Kulasiri, Don

    2008-01-01

    Living organisms often exist in uncertain environments where changes are the norm. Cellular systems therefore require resilient regulatory mechanisms for timely and stable adaptation. Among various regulation motifs, multiple feedback control emerges as a common theme. The tryptophan operon system in Escherichia coli regulates the production ofintracellular tryptophan using an apparatus of three feedback mechanisms: repression, attenuation and enzyme inhibition; each provides essentially the same function but operates in distinctly different ways. Here we aim to understand the roles of each loop by studying transient dynamics of the system to perturbations of different types; to reveal the underlying relationships between individual control mechanisms and macroscopic behaviour. We develop an S-systems approximation of an existing model for the system and characterise transient dynamics by introducing two measurable quantities: maximum disturbance (MD) and recovery time (RT). Our simulation results showed that combined regulation using all three feedback mechanisms significantly increases system stability, broadening the range of kinetic parameters for stable behaviour. Enzyme inhibition was shown to directly control the disturbance level in system variables after perturbations. Attenuation, on the other hand, was found to speed up system recovery whereas repression lengthens recovery time. The method developed in this paper and the defined transient dynamics measurements can be applied to other cellular systems. PMID:19374133

  15. Nucleotide sequence and expression of the mercurial-resistance operon from Staphylococcus aureus plasmid pI258

    International Nuclear Information System (INIS)

    The mercurial-resistance determinant from Staphylococcus aureus plasmid pI258 is located on a 6.4-kilobase-pair Bgl II fragment. The determinant was cloned into both Bacillus subtilis and Escherichia coli. Mercury resistance was found only in B. subtilis. The 6404-base-pair DNA sequence of the Bgl II fragment was determined. The mer DNA sequence includes seven open reading frames, two of which have been identified by homology with the merA (mercuric reductase) and merB (organomercurial lyase) genes from the mercurial-resistance determinants of Gram-negative bacteria. Whereas 40% of the amino acid residues overall were identical between the pI258 merA polypeptide product and mercuric reductases from Gram-negative bacteria, the percentage identity in the active-site positions and those thought to be involved in NADPH and FAD contacts was above 90%. The 216 amino acid organomercurial lyase sequence was 39% identical with that from a Serratia plasmid, with higher conservation in the middle of the sequences and lower homologies at the amino and carboxyl termini. The remaining five open reading frames in the pI258 mer sequence have no significant homologies with the genes from previously sequenced Gram-negative mer operons

  16. Mycobacterium tuberculosis co-operonic PE32/PPE65 proteins alter host immune responses by hampering Th1 response

    Directory of Open Access Journals (Sweden)

    Mohd eKhubaib

    2016-05-01

    Full Text Available PE/PPE genes, present in cluster with ESAT-6 like genes, are suspected to have a role in antigenic variation and virulence of Mycobacterium tuberculosis. Their roles in immune evasion and immune modulation of host are also well documented. We present evidence that PE32/PPE65 present within the RD8 region are co-operonic, co-transcribed and co-translated, and play role in modulating host immune responses. Experiments with macrophage cell lines revealed that this protein complex suppresses pro-inflammatory cytokines such as TNF-α and IL-6 whereas also inducing high expression of anti-inflammatory IL-10. Immunization of mice with these recombinant proteins dampens an effective Th1 response as evident from reduced frequency of IFN-g and IL-2 producing CD4+ and CD8+ T cells. IgG sub-typing from serum of immunized mice revealed high levels of IgG1 when compared with IgG2a and IgG2b. Further IgG1/IgG2a ratio clearly demonstrated that the protein complex manipulates the host immune response favourable to the pathogen. Our results demonstrate that the co-transcribed and co-translated PE32 and PPE65 antigens are involved specifically in modulating anti-mycobacterial host immune response by hampering Th1 response.

  17. Disruption of the Operon Encoding Ehb Hydrogenase Limits AnabolicCO2 Assimilation in the Archaeon Methanococcus maripaludis

    Energy Technology Data Exchange (ETDEWEB)

    Porat, Iris; Kim, Wonduck; Hendrickson, Erik L.; Xia, Qiangwei; Zhang, Yi; Wang, Tiansong; Taub, Fred; Moore, Brian C.; Anderson, IainJ.; Hackett, Murray; Leigh, John A.; Whitman, William B.

    2006-02-01

    Methanococcus maripaludis is a mesophilic archaeon thatreduces CO2 to methane with H2 or formate as an energy source. Itcontains two membrane-bound energy-conserving hydrogenases, Eha and Ehb.To determine therole of Ehb, a deletion in the ehb operon wasconstructed to yield the mutant, strain S40. Growth of S40 was severelyimpaired in minimal medium. Both acetate and yeast extract were necessaryto restore growth to nearly wild-type levels, suggesting that Ehb wasinvolved in multiple steps in carbon assimilation. However, nodifferences in the total hydrogenase specific activities were foundbetween the wild type and mutant in either cell extracts ormembrane-purified fractions. Methanogenesis by resting cells withpyruvate as the electron donor was also reduced by 30 percent in S40,suggesting a defect in pyruvate oxidation. CO dehydrogenase/acetylcoenzyme A (CoA) synthase and pyruvate oxidoreductase had higher specificactivities in the mutant, and genes encoding these enzymes, as well asAMP-forming acetyl-CoA synthetase, were expressed at increased levels.These observations support a role for Ehb in anabolic CO2 assimilation inmethanococci.

  18. Terminator Operon Reporter: combining a transcription termination switch with reporter technology for improved gene synthesis and synthetic biology applications.

    Science.gov (United States)

    Zampini, Massimiliano; Mur, Luis A J; Rees Stevens, Pauline; Pachebat, Justin A; Newbold, C James; Hayes, Finbarr; Kingston-Smith, Alison

    2016-01-01

    Synthetic biology is characterized by the development of novel and powerful DNA fabrication methods and by the application of engineering principles to biology. The current study describes Terminator Operon Reporter (TOR), a new gene assembly technology based on the conditional activation of a reporter gene in response to sequence errors occurring at the assembly stage of the synthetic element. These errors are monitored by a transcription terminator that is placed between the synthetic gene and reporter gene. Switching of this terminator between active and inactive states dictates the transcription status of the downstream reporter gene to provide a rapid and facile readout of the accuracy of synthetic assembly. Designed specifically and uniquely for the synthesis of protein coding genes in bacteria, TOR allows the rapid and cost-effective fabrication of synthetic constructs by employing oligonucleotides at the most basic purification level (desalted) and without the need for costly and time-consuming post-synthesis correction methods. Thus, TOR streamlines gene assembly approaches, which are central to the future development of synthetic biology. PMID:27220405

  19. Accurate radiative transfer calculations for layered media.

    Science.gov (United States)

    Selden, Adrian C

    2016-07-01

    Simple yet accurate results for radiative transfer in layered media with discontinuous refractive index are obtained by the method of K-integrals. These are certain weighted integrals applied to the angular intensity distribution at the refracting boundaries. The radiative intensity is expressed as the sum of the asymptotic angular intensity distribution valid in the depth of the scattering medium and a transient term valid near the boundary. Integrated boundary equations are obtained, yielding simple linear equations for the intensity coefficients, enabling the angular emission intensity and the diffuse reflectance (albedo) and transmittance of the scattering layer to be calculated without solving the radiative transfer equation directly. Examples are given of half-space, slab, interface, and double-layer calculations, and extensions to multilayer systems are indicated. The K-integral method is orders of magnitude more accurate than diffusion theory and can be applied to layered scattering media with a wide range of scattering albedos, with potential applications to biomedical and ocean optics. PMID:27409700

  20. Accurate pose estimation for forensic identification

    Science.gov (United States)

    Merckx, Gert; Hermans, Jeroen; Vandermeulen, Dirk

    2010-04-01

    In forensic authentication, one aims to identify the perpetrator among a series of suspects or distractors. A fundamental problem in any recognition system that aims for identification of subjects in a natural scene is the lack of constrains on viewing and imaging conditions. In forensic applications, identification proves even more challenging, since most surveillance footage is of abysmal quality. In this context, robust methods for pose estimation are paramount. In this paper we will therefore present a new pose estimation strategy for very low quality footage. Our approach uses 3D-2D registration of a textured 3D face model with the surveillance image to obtain accurate far field pose alignment. Starting from an inaccurate initial estimate, the technique uses novel similarity measures based on the monogenic signal to guide a pose optimization process. We will illustrate the descriptive strength of the introduced similarity measures by using them directly as a recognition metric. Through validation, using both real and synthetic surveillance footage, our pose estimation method is shown to be accurate, and robust to lighting changes and image degradation.