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

    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.

  2. Predicting Tissue-Specific Enhancers in the Human Genome

    Pennacchio, Len A.; Loots, Gabriela G.; Nobrega, Marcelo A.; Ovcharenko, Ivan

    2006-07-01

    Determining how transcriptional regulatory signals areencoded in vertebrate genomes is essential for understanding the originsof multi-cellular complexity; yet the genetic code of vertebrate generegulation remains poorly understood. In an attempt to elucidate thiscode, we synergistically combined genome-wide gene expression profiling,vertebrate genome comparisons, and transcription factor binding siteanalysis to define sequence signatures characteristic of candidatetissue-specific enhancers in the human genome. We applied this strategyto microarray-based gene expression profiles from 79 human tissues andidentified 7,187 candidate enhancers that defined their flanking geneexpression, the majority of which were located outside of knownpromoters. We cross-validated this method for its ability to de novopredict tissue-specific gene expression and confirmed its reliability in57 of the 79 available human tissues, with an average precision inenhancer recognition ranging from 32 percent to 63 percent, and asensitivity of 47 percent. We used the sequence signatures identified bythis approach to assign tissue-specific predictions to ~;328,000human-mouse conserved noncoding elements in the human genome. Byoverlapping these genome-wide predictions with a large in vivo dataset ofenhancers validated in transgenic mice, we confirmed our results with a28 percent sensitivity and 50 percent precision. These results indicatethe power of combining complementary genomic datasets as an initialcomputational foray into the global view of tissue-specific generegulation in vertebrates.

  3. Predicting tissue-specific expressions based on sequence characteristics

    Paik, Hyojung

    2011-04-30

    In multicellular organisms, including humans, understanding expression specificity at the tissue level is essential for interpreting protein function, such as tissue differentiation. We developed a prediction approach via generated sequence features from overrepresented patterns in housekeeping (HK) and tissue-specific (TS) genes to classify TS expression in humans. Using TS domains and transcriptional factor binding sites (TFBSs), sequence characteristics were used as indices of expressed tissues in a Random Forest algorithm by scoring exclusive patterns considering the biological intuition; TFBSs regulate gene expression, and the domains reflect the functional specificity of a TS gene. Our proposed approach displayed better performance than previous attempts and was validated using computational and experimental methods.

  4. Genome-wide de Novo Prediction of Proximal and Distal Tissue-Specific Enhancers

    Loots, G G; Ovcharenko, I V

    2005-11-03

    Determining how transcriptional regulatory networks are encoded in the human genome is essential for understanding how cellular processes are directed. Here, we present a novel approach for systematically predicting tissue specific regulatory elements (REs) that blends genome-wide expression profiling, vertebrate genome comparisons, and pattern analysis of transcription factor binding sites. This analysis yields 4,670 candidate REs in the human genome with distinct tissue specificities, the majority of which reside far away from transcription start sites. We identify key transcription factors (TFs) for 34 distinct tissues and demonstrate that tissue-specific gene expression relies on multiple regulatory pathways employing similar, but different cohorts of interacting TFs. The methods and results we describe provide a global view of tissue specific gene regulation in humans, and propose a strategy for deciphering the transcriptional regulatory code in eukaryotes.

  5. Genome-wide Transcription Factor Gene Prediction and their Expressional Tissue-Specificities in Maize

    Yi Jiang; Biao Zeng; Hainan Zhao; Mei Zhang; Shaojun Xie; Jinsheng Lai

    2012-01-01

    Transcription factors (TFs) are important regulators of gene expression.To better understand TFencoding genes in maize (Zea mays L.),a genome-wide TF prediction was performed using the updated B73 reference genome.A total of 2 298 TF genes were identified,which can be classified into 56 families.The largest family,known as the MYB superfamily,comprises 322 MYB and MYB-related TF genes.The expression patterns of 2014 (87.64%) TF genes were examined using RNA-seq data,which resulted in the identification of a subset of TFs that are specifically expressed in particular tissues (including root,shoot,leaf,ear,tassel and kernel).Similarly,98 kernel-specific TF genes were further analyzed,and it was observed that 29 of the kernel-specific genes were preferentially expressed in the early kernel developmental stage,while 69 of the genes were expressed in the late kernel developmental stage.Identification of these TFs,particularly the tissue-specific ones,provides important information for the understanding of development and transcriptional regulation of maize.

  6. You Can Accurately Predict Land Acquisition Costs.

    Garrigan, Richard

    1967-01-01

    Land acquisition costs were tested for predictability based upon the 1962 assessed valuations of privately held land acquired for campus expansion by the University of Wisconsin from 1963-1965. By correlating the land acquisition costs of 108 properties acquired during the 3 year period with--(1) the assessed value of the land, (2) the assessed…

  7. How accurate can genetic predictions be?

    Dreyfuss Jonathan M

    2012-07-01

    Full Text Available Abstract Background Pre-symptomatic prediction of disease and drug response based on genetic testing is a critical component of personalized medicine. Previous work has demonstrated that the predictive capacity of genetic testing is constrained by the heritability and prevalence of the tested trait, although these constraints have only been approximated under the assumption of a normally distributed genetic risk distribution. Results Here, we mathematically derive the absolute limits that these factors impose on test accuracy in the absence of any distributional assumptions on risk. We present these limits in terms of the best-case receiver-operating characteristic (ROC curve, consisting of the best-case test sensitivities and specificities, and the AUC (area under the curve measure of accuracy. We apply our method to genetic prediction of type 2 diabetes and breast cancer, and we additionally show the best possible accuracy that can be obtained from integrated predictors, which can incorporate non-genetic features. Conclusion Knowledge of such limits is valuable in understanding the implications of genetic testing even before additional associations are identified.

  8. A new, accurate predictive model for incident hypertension

    Völzke, Henry; Fung, Glenn; Ittermann, Till; Yu, Shipeng; Baumeister, Sebastian E; Dörr, Marcus; Lieb, Wolfgang; Völker, Uwe; Linneberg, Allan; Jørgensen, Torben; Felix, Stephan B; Rettig, Rainer; Rao, Bharat; Kroemer, Heyo K

    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.......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....

  9. DOMAC: an accurate, hybrid protein domain prediction server

    Cheng, Jianlin

    2007-01-01

    Protein domain prediction is important for protein structure prediction, structure determination, function annotation, mutagenesis analysis and protein engineering. Here we describe an accurate protein domain prediction server (DOMAC) combining both template-based and ab initio methods. The preliminary version of the server was ranked among the top domain prediction servers in the seventh edition of Critical Assessment of Techniques for Protein Structure Prediction (CASP7), 2006. DOMAC server...

  10. HA novel approach to investigate tissue-specific trinucleotide repeat instability

    Boily Marie-Josee

    2010-03-01

    Full Text Available Abstract Background In Huntington's disease (HD, an expanded CAG repeat produces characteristic striatal neurodegeneration. Interestingly, the HD CAG repeat, whose length determines age at onset, undergoes tissue-specific somatic instability, predominant in the striatum, suggesting that tissue-specific CAG length changes could modify the disease process. Therefore, understanding the mechanisms underlying the tissue specificity of somatic instability may provide novel routes to therapies. However progress in this area has been hampered by the lack of sensitive high-throughput instability quantification methods and global approaches to identify the underlying factors. Results Here we describe a novel approach to gain insight into the factors responsible for the tissue specificity of somatic instability. Using accurate genetic knock-in mouse models of HD, we developed a reliable, high-throughput method to quantify tissue HD CAG repeat instability and integrated this with genome-wide bioinformatic approaches. Using tissue instability quantified in 16 tissues as a phenotype and tissue microarray gene expression as a predictor, we built a mathematical model and identified a gene expression signature that accurately predicted tissue instability. Using the predictive ability of this signature we found that somatic instability was not a consequence of pathogenesis. In support of this, genetic crosses with models of accelerated neuropathology failed to induce somatic instability. In addition, we searched for genes and pathways that correlated with tissue instability. We found that expression levels of DNA repair genes did not explain the tissue specificity of somatic instability. Instead, our data implicate other pathways, particularly cell cycle, metabolism and neurotransmitter pathways, acting in combination to generate tissue-specific patterns of instability. Conclusion Our study clearly demonstrates that multiple tissue factors reflect the level of

  11. Accurate Multisteps Traffic Flow Prediction Based on SVM

    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...

  12. Accurate Identification of Fear Facial Expressions Predicts Prosocial Behavior

    Marsh, Abigail A.; Kozak, Megan N.; Ambady, Nalini

    2007-01-01

    The fear facial expression is a distress cue that is associated with the provision of help and prosocial behavior. Prior psychiatric studies have found deficits in the recognition of this expression by individuals with antisocial tendencies. However, no prior study has shown accuracy for recognition of fear to predict actual prosocial or antisocial behavior in an experimental setting. In 3 studies, the authors tested the prediction that individuals who recognize fear more accurately will beha...

  13. Accurate Multisteps Traffic Flow Prediction Based on SVM

    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.

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

    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

  15. Passive samplers accurately predict PAH levels in resident crayfish.

    Paulik, L Blair; Smith, Brian W; Bergmann, Alan J; Sower, Greg J; Forsberg, Norman D; Teeguarden, Justin G; Anderson, Kim A

    2016-02-15

    Contamination of resident aquatic organisms is a major concern for environmental risk assessors. However, collecting organisms to estimate risk is often prohibitively time and resource-intensive. Passive sampling accurately estimates resident organism contamination, and it saves time and resources. This study used low density polyethylene (LDPE) passive water samplers to predict polycyclic aromatic hydrocarbon (PAH) levels in signal crayfish, Pacifastacus leniusculus. Resident crayfish were collected at 5 sites within and outside of the Portland Harbor Superfund Megasite (PHSM) in the Willamette River in Portland, Oregon. LDPE deployment was spatially and temporally paired with crayfish collection. Crayfish visceral and tail tissue, as well as water-deployed LDPE, were extracted and analyzed for 62 PAHs using GC-MS/MS. Freely-dissolved concentrations (Cfree) of PAHs in water were calculated from concentrations in LDPE. Carcinogenic risks were estimated for all crayfish tissues, using benzo[a]pyrene equivalent concentrations (BaPeq). ∑PAH were 5-20 times higher in viscera than in tails, and ∑BaPeq were 6-70 times higher in viscera than in tails. Eating only tail tissue of crayfish would therefore significantly reduce carcinogenic risk compared to also eating viscera. Additionally, PAH levels in crayfish were compared to levels in crayfish collected 10years earlier. PAH levels in crayfish were higher upriver of the PHSM and unchanged within the PHSM after the 10-year period. Finally, a linear regression model predicted levels of 34 PAHs in crayfish viscera with an associated R-squared value of 0.52 (and a correlation coefficient of 0.72), using only the Cfree PAHs in water. On average, the model predicted PAH concentrations in crayfish tissue within a factor of 2.4±1.8 of measured concentrations. This affirms that passive water sampling accurately estimates PAH contamination in crayfish. Furthermore, the strong predictive ability of this simple model suggests

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

    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

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

    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

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

    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

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

    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.

  20. Accurate contact predictions using covariation techniques and machine learning.

    Kosciolek, T.; Jones, D T

    2015-01-01

    Here we present the results of residue-residue contact predictions achieved in CASP11 by the CONSIP2 server, which is based around our MetaPSICOV contact prediction method. On a set of 40 target domains with a median family size of around 40 effective sequences, our server achieved an average top-L/5 long-range contact precision of 27%. MetaPSICOV method bases on a combination of classical contact prediction features, enhanced with three distinct covariation methods embedded in a two-stage ne...

  1. Mouse models of human AML accurately predict chemotherapy response

    Zuber, Johannes; Radtke, Ina; Pardee, Timothy S.; Zhao, Zhen; Rappaport, Amy R.; Luo, Weijun; McCurrach, Mila E.; Yang, Miao-Miao; Dolan, M. Eileen; Kogan, Scott C.; Downing, James R.; Lowe, Scott W.

    2009-01-01

    The genetic heterogeneity of cancer influences the trajectory of tumor progression and may underlie clinical variation in therapy response. To model such heterogeneity, we produced genetically and pathologically accurate mouse models of common forms of human acute myeloid leukemia (AML) and developed methods to mimic standard induction chemotherapy and efficiently monitor therapy response. We see that murine AMLs harboring two common human AML genotypes show remarkably diverse responses to co...

  2. Towards more accurate and reliable predictions for nuclear applications

    The need for nuclear data far from the valley of stability, for applications such as nuclear astrophysics or future nuclear facilities, challenges the robustness as well as the predictive power of present nuclear models. Most of the nuclear data evaluation and prediction are still performed on the basis of phenomenological nuclear models. For the last decades, important progress has been achieved in fundamental nuclear physics, making it now feasible to use more reliable, but also more complex microscopic or semi-microscopic models in the evaluation and prediction of nuclear data for practical applications. In the present contribution, the reliability and accuracy of recent nuclear theories are discussed for most of the relevant quantities needed to estimate reaction cross sections and beta-decay rates, namely nuclear masses, nuclear level densities, gamma-ray strength, fission properties and beta-strength functions. It is shown that nowadays, mean-field models can be tuned at the same level of accuracy as the phenomenological models, renormalized on experimental data if needed, and therefore can replace the phenomenogical inputs in the prediction of nuclear data. While fundamental nuclear physicists keep on improving state-of-the-art models, e.g. within the shell model or ab initio models, nuclear applications could make use of their most recent results as quantitative constraints or guides to improve the predictions in energy or mass domain that will remain inaccessible experimentally. (orig.)

  3. Standardized EEG interpretation accurately predicts prognosis after cardiac arrest

    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

  4. Analytical method to accurately predict LMFBR core flow distribution

    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

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

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

    2015-01-01

    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 $\\sigma$ bonding to hydrogen, as well as $\\sigma$ and $\\pi$ bonding between main-group elements, occurring in small sets of iso-valence-electronic molecular species with elements drawn from second to fourth rows in the $p$-block of the periodic table. Numerical evidence suggests that first order estimates of coval...

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

    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

    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.

    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. Predicting accurate line shape parameters for CO2 transitions

    The vibrational dependence of CO2 half-widths and line shifts are given by a modification of the model proposed by Gamache and Hartmann [Gamache R, Hartmann J-M. J Quant Spectrosc Radiat Transfer 2004;83:119]. This model allows the half-widths and line shifts for a ro-vibrational transition to be expressed in terms of the number of vibrational quanta exchanged in the transition raised to a power and a reference ro-vibrational transition. Calculations were made for 24 bands for lower rotational quantum numbers from 0 to 160 for N2-, O2-, air-, and self-collisions with CO2. These data were extrapolated to J″=200 to accommodate several databases. Comparison of the CRB calculations with measurement gives very high confidence in the data. In the model a Quantum Coordinate is defined by (c1 |Δν1|+c2 |Δν2|+c3|Δν3|)p. The power p is adjusted and a linear least-squares fit to the data by the model expression is made. The procedure is iterated on the correlation coefficient, R, until [|R|−1] is less than a threshold. The results demonstrate the appropriateness of the model. The model allows the determination of the slope and intercept as a function of rotational transition, broadening gas, and temperature. From the data of the fits, the half-width, line shift, and the temperature dependence of the half-width can be estimated for any ro-vibrational transition, allowing spectroscopic CO2 databases to have complete information for the line shape parameters. -- Highlights: • Development of a quantum coordinate model for the half-width and line shift. • Calculations of γ and δ for N2-, O2-, air-, and CO2–CO2 systems for 24 bands. • J″=0–160, bands up to Δν1=3, Δν2=5, Δν3=9, 9 temperatures from 200–2000 K. • γ, n, δ, prediction routines for all ro-vibrational transitions up to J″=200

  10. Tissue-specific RNA expression marks distant-acting developmental enhancers.

    Han Wu

    2014-09-01

    Full Text Available Short non-coding transcripts can be transcribed from distant-acting transcriptional enhancer loci, but the prevalence of such enhancer RNAs (eRNAs within the transcriptome, and the association of eRNA expression with tissue-specific enhancer activity in vivo remain poorly understood. Here, we investigated the expression dynamics of tissue-specific non-coding RNAs in embryonic mouse tissues via deep RNA sequencing. Overall, approximately 80% of validated in vivo enhancers show tissue-specific RNA expression that correlates with tissue-specific enhancer activity. Globally, we identified thousands of tissue-specifically transcribed non-coding regions (TSTRs displaying various genomic hallmarks of bona fide enhancers. In transgenic mouse reporter assays, over half of tested TSTRs functioned as enhancers with reproducible activity in the predicted tissue. Together, our results demonstrate that tissue-specific eRNA expression is a common feature of in vivo enhancers, as well as a major source of extragenic transcription, and that eRNA expression signatures can be used to predict tissue-specific enhancers independent of known epigenomic enhancer marks.

  11. Positional bias of general and tissue-specific regulatory motifs in mouse gene promoters

    Farré Domènec

    2007-12-01

    Full Text Available Abstract Background The arrangement of regulatory motifs in gene promoters, or promoter architecture, is the result of mutation and selection processes that have operated over many millions of years. In mammals, tissue-specific transcriptional regulation is related to the presence of specific protein-interacting DNA motifs in gene promoters. However, little is known about the relative location and spacing of these motifs. To fill this gap, we have performed a systematic search for motifs that show significant bias at specific promoter locations in a large collection of housekeeping and tissue-specific genes. Results We observe that promoters driving housekeeping gene expression are enriched in particular motifs with strong positional bias, such as YY1, which are of little relevance in promoters driving tissue-specific expression. We also identify a large number of motifs that show positional bias in genes expressed in a highly tissue-specific manner. They include well-known tissue-specific motifs, such as HNF1 and HNF4 motifs in liver, kidney and small intestine, or RFX motifs in testis, as well as many potentially novel regulatory motifs. Based on this analysis, we provide predictions for 559 tissue-specific motifs in mouse gene promoters. Conclusion The study shows that motif positional bias is an important feature of mammalian proximal promoters and that it affects both general and tissue-specific motifs. Motif positional constraints define very distinct promoter architectures depending on breadth of expression and type of tissue.

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

    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

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

    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

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

    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.

  15. Accurate Prediction of Ligand Affinities for a Proton-Dependent Oligopeptide Transporter.

    Samsudin, Firdaus; Parker, Joanne L; Sansom, Mark S P; Newstead, Simon; Fowler, Philip W

    2016-02-18

    Membrane transporters are critical modulators of drug pharmacokinetics, efficacy, and safety. One example is the proton-dependent oligopeptide transporter PepT1, also known as SLC15A1, which is responsible for the uptake of the ?-lactam antibiotics and various peptide-based prodrugs. In this study, we modeled the binding of various peptides to a bacterial homolog, PepTSt, and evaluated a range of computational methods for predicting the free energy of binding. Our results show that a hybrid approach (endpoint methods to classify peptides into good and poor binders and a theoretically exact method for refinement) is able to accurately predict affinities, which we validated using proteoliposome transport assays. Applying the method to a homology model of PepT1 suggests that the approach requires a high-quality structure to be accurate. Our study provides a blueprint for extending these computational methodologies to other pharmaceutically important transporter families. PMID:27028887

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

    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...

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

    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.

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

    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

    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. Highly accurate prediction of emotions surrounding the attacks of September 11, 2001 over 1-, 2-, and 7-year prediction intervals.

    Doré, Bruce P; Meksin, Robert; Mather, Mara; Hirst, William; Ochsner, Kevin N

    2016-06-01

    In the aftermath of a national tragedy, important decisions are predicated on judgments of the emotional significance of the tragedy in the present and future. Research in affective forecasting has largely focused on ways in which people fail to make accurate predictions about the nature and duration of feelings experienced in the aftermath of an event. Here we ask a related but understudied question: can people forecast how they will feel in the future about a tragic event that has already occurred? We found that people were strikingly accurate when predicting how they would feel about the September 11 attacks over 1-, 2-, and 7-year prediction intervals. Although people slightly under- or overestimated their future feelings at times, they nonetheless showed high accuracy in forecasting (a) the overall intensity of their future negative emotion, and (b) the relative degree of different types of negative emotion (i.e., sadness, fear, or anger). Using a path model, we found that the relationship between forecasted and actual future emotion was partially mediated by current emotion and remembered emotion. These results extend theories of affective forecasting by showing that emotional responses to an event of ongoing national significance can be predicted with high accuracy, and by identifying current and remembered feelings as independent sources of this accuracy. (PsycINFO Database Record PMID:27100309

  1. An accurate model for numerical prediction of piezoelectric energy harvesting from fluid structure interaction problems

    Piezoelectric energy harvesting (PEH) from ambient energy sources, particularly vibrations, has attracted considerable interest throughout the last decade. Since fluid flow has a high energy density, it is one of the best candidates for PEH. Indeed, a piezoelectric energy harvesting process from the fluid flow takes the form of natural three-way coupling of the turbulent fluid flow, the electromechanical effect of the piezoelectric material and the electrical circuit. There are some experimental and numerical studies about piezoelectric energy harvesting from fluid flow in literatures. Nevertheless, accurate modeling for predicting characteristics of this three-way coupling has not yet been developed. In the present study, accurate modeling for this triple coupling is developed and validated by experimental results. A new code based on this modeling in an openFOAM platform is developed. (paper)

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

    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.

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

    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. Development and Validation of a Multidisciplinary Tool for Accurate and Efficient Rotorcraft Noise Prediction (MUTE)

    Liu, Yi; Anusonti-Inthra, Phuriwat; Diskin, Boris

    2011-01-01

    A physics-based, systematically coupled, multidisciplinary prediction tool (MUTE) for rotorcraft noise was developed and validated with a wide range of flight configurations and conditions. MUTE is an aggregation of multidisciplinary computational tools that accurately and efficiently model the physics of the source of rotorcraft noise, and predict the noise at far-field observer locations. It uses systematic coupling approaches among multiple disciplines including Computational Fluid Dynamics (CFD), Computational Structural Dynamics (CSD), and high fidelity acoustics. Within MUTE, advanced high-order CFD tools are used around the rotor blade to predict the transonic flow (shock wave) effects, which generate the high-speed impulsive noise. Predictions of the blade-vortex interaction noise in low speed flight are also improved by using the Particle Vortex Transport Method (PVTM), which preserves the wake flow details required for blade/wake and fuselage/wake interactions. The accuracy of the source noise prediction is further improved by utilizing a coupling approach between CFD and CSD, so that the effects of key structural dynamics, elastic blade deformations, and trim solutions are correctly represented in the analysis. The blade loading information and/or the flow field parameters around the rotor blade predicted by the CFD/CSD coupling approach are used to predict the acoustic signatures at far-field observer locations with a high-fidelity noise propagation code (WOPWOP3). The predicted results from the MUTE tool for rotor blade aerodynamic loading and far-field acoustic signatures are compared and validated with a variation of experimental data sets, such as UH60-A data, DNW test data and HART II test data.

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

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

    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.

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

    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].

  8. An accurate and efficient numerical framework for adaptive numerical weather prediction

    Tumolo, G

    2014-01-01

    We present an accurate and efficient discretization approach for the adaptive discretization of typical model equations employed in numerical weather prediction. A semi-Lagrangian approach is combined with the TR-BDF2 semi-implicit time discretization method and with a spatial discretization based on adaptive discontinuous finite elements. The resulting method has full second order accuracy in time and can employ polynomial bases of arbitrarily high degree in space, is unconditionally stable and can effectively adapt the number of degrees of freedom employed in each element, in order to balance accuracy and computational cost. The p-adaptivity approach employed does not require remeshing, therefore it is especially suitable for applications, such as numerical weather prediction, in which a large number of physical quantities are associated with a given mesh. Furthermore, although the proposed method can be implemented on arbitrary unstructured and nonconforming meshes, even its application on simple Cartesian...

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

    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

    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. Accurate prediction of helix interactions and residue contacts in membrane proteins.

    Hönigschmid, Peter; Frishman, Dmitrij

    2016-04-01

    Accurate prediction of intra-molecular interactions from amino acid sequence is an important pre-requisite for obtaining high-quality protein models. Over the recent years, remarkable progress in this area has been achieved through the application of novel co-variation algorithms, which eliminate transitive evolutionary connections between residues. In this work we present a new contact prediction method for α-helical transmembrane proteins, MemConP, in which evolutionary couplings are combined with a machine learning approach. MemConP achieves a substantially improved accuracy (precision: 56.0%, recall: 17.5%, MCC: 0.288) compared to the use of either machine learning or co-evolution methods alone. The method also achieves 91.4% precision, 42.1% recall and a MCC of 0.490 in predicting helix-helix interactions based on predicted contacts. The approach was trained and rigorously benchmarked by cross-validation and independent testing on up-to-date non-redundant datasets of 90 and 30 experimental three dimensional structures, respectively. MemConP is a standalone tool that can be downloaded together with the associated training data from http://webclu.bio.wzw.tum.de/MemConP. PMID:26851352

  12. Enhancing the prioritization of disease-causing genes through tissue specific protein interaction networks.

    Oded Magger

    Full Text Available The prioritization of candidate disease-causing genes is a fundamental challenge in the post-genomic era. Current state of the art methods exploit a protein-protein interaction (PPI network for this task. They are based on the observation that genes causing phenotypically-similar diseases tend to lie close to one another in a PPI network. However, to date, these methods have used a static picture of human PPIs, while diseases impact specific tissues in which the PPI networks may be dramatically different. Here, for the first time, we perform a large-scale assessment of the contribution of tissue-specific information to gene prioritization. By integrating tissue-specific gene expression data with PPI information, we construct tissue-specific PPI networks for 60 tissues and investigate their prioritization power. We find that tissue-specific PPI networks considerably improve the prioritization results compared to those obtained using a generic PPI network. Furthermore, they allow predicting novel disease-tissue associations, pointing to sub-clinical tissue effects that may escape early detection.

  13. Tissue-specific tagging of endogenous loci in Drosophila melanogaster

    Kate Koles

    2016-01-01

    Full Text Available Fluorescent protein tags have revolutionized cell and developmental biology, and in combination with binary expression systems they enable diverse tissue-specific studies of protein function. However these binary expression systems often do not recapitulate endogenous protein expression levels, localization, binding partners and/or developmental windows of gene expression. To address these limitations, we have developed a method called T-STEP (tissue-specific tagging of endogenous proteins that allows endogenous loci to be tagged in a tissue specific manner. T-STEP uses a combination of efficient CRISPR/Cas9-enhanced gene targeting and tissue-specific recombinase-mediated tag swapping to temporally and spatially label endogenous proteins. We have employed this method to GFP tag OCRL (a phosphoinositide-5-phosphatase in the endocytic pathway and Vps35 (a Parkinson's disease-implicated component of the endosomal retromer complex in diverse Drosophila tissues including neurons, glia, muscles and hemocytes. Selective tagging of endogenous proteins allows, for the first time, cell type-specific live imaging and proteomics in complex tissues.

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

    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.

  15. Fast and Accurate Prediction of Numerical Relativity Waveforms from Binary Black Hole Coalescences Using Surrogate Models

    Blackman, Jonathan; Field, Scott E.; Galley, Chad R.; Szilágyi, Béla; Scheel, Mark A.; Tiglio, Manuel; Hemberger, Daniel A.

    2015-09-01

    Simulating a binary black hole coalescence by solving Einstein's equations is computationally expensive, requiring days to months of supercomputing time. Using reduced order modeling techniques, we construct an accurate surrogate model, which is evaluated in a millisecond to a second, for numerical relativity (NR) waveforms from nonspinning binary black hole coalescences with mass ratios in [1, 10] and durations corresponding to about 15 orbits before merger. We assess the model's uncertainty and show that our modeling strategy predicts NR waveforms not used for the surrogate's training with errors nearly as small as the numerical error of the NR code. Our model includes all spherical-harmonic -2Yℓm waveform modes resolved by the NR code up to ℓ=8 . We compare our surrogate model to effective one body waveforms from 50 M⊙ to 300 M⊙ for advanced LIGO detectors and find that the surrogate is always more faithful (by at least an order of magnitude in most cases).

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

    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...

  17. Improvement of a land surface model for accurate prediction of surface energy and water balances

    In order to predict energy and water balances between the biosphere and atmosphere accurately, sophisticated schemes to calculate evaporation and adsorption processes in the soil and cloud (fog) water deposition on vegetation were implemented in the one-dimensional atmosphere-soil-vegetation model including CO2 exchange process (SOLVEG2). Performance tests in arid areas showed that the above schemes have a significant effect on surface energy and water balances. The framework of the above schemes incorporated in the SOLVEG2 and instruction for running the model are documented. With further modifications of the model to implement the carbon exchanges between the vegetation and soil, deposition processes of materials on the land surface, vegetation stress-growth-dynamics etc., the model is suited to evaluate an effect of environmental loads to ecosystems by atmospheric pollutants and radioactive substances under climate changes such as global warming and drought. (author)

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

    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

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

    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.

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

    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.

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

    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. Poly(A) code analyses reveal key determinants for tissue-specific mRNA alternative polyadenylation.

    Weng, Lingjie; Li, Yi; Xie, Xiaohui; Shi, Yongsheng

    2016-06-01

    mRNA alternative polyadenylation (APA) is a critical mechanism for post-transcriptional gene regulation and is often regulated in a tissue- and/or developmental stage-specific manner. An ultimate goal for the APA field has been to be able to computationally predict APA profiles under different physiological or pathological conditions. As a first step toward this goal, we have assembled a poly(A) code for predicting tissue-specific poly(A) sites (PASs). Based on a compendium of over 600 features that have known or potential roles in PAS selection, we have generated and refined a machine-learning algorithm using multiple high-throughput sequencing-based data sets of tissue-specific and constitutive PASs. This code can predict tissue-specific PASs with >85% accuracy. Importantly, by analyzing the prediction performance based on different RNA features, we found that PAS context, including the distance between alternative PASs and the relative position of a PAS within the gene, is a key feature for determining the susceptibility of a PAS to tissue-specific regulation. Our poly(A) code provides a useful tool for not only predicting tissue-specific APA regulation, but also for studying its underlying molecular mechanisms. PMID:27095026

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

    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...

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

    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

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

    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.

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

    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

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

    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

    2016-01-01

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

    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

  9. Energy expenditure during level human walking: seeking a simple and accurate predictive solution.

    Ludlow, Lindsay W; Weyand, Peter G

    2016-03-01

    Accurate prediction of the metabolic energy that walking requires can inform numerous health, bodily status, and fitness outcomes. We adopted a two-step approach to identifying a concise, generalized equation for predicting level human walking metabolism. Using literature-aggregated values we compared 1) the predictive accuracy of three literature equations: American College of Sports Medicine (ACSM), Pandolf et al., and Height-Weight-Speed (HWS); and 2) the goodness-of-fit possible from one- vs. two-component descriptions of walking metabolism. Literature metabolic rate values (n = 127; speed range = 0.4 to 1.9 m/s) were aggregated from 25 subject populations (n = 5-42) whose means spanned a 1.8-fold range of heights and a 4.2-fold range of weights. Population-specific resting metabolic rates (V̇o2 rest) were determined using standardized equations. Our first finding was that the ACSM and Pandolf et al. equations underpredicted nearly all 127 literature-aggregated values. Consequently, their standard errors of estimate (SEE) were nearly four times greater than those of the HWS equation (4.51 and 4.39 vs. 1.13 ml O2·kg(-1)·min(-1), respectively). For our second comparison, empirical best-fit relationships for walking metabolism were derived from the data set in one- and two-component forms for three V̇o2-speed model types: linear (∝V(1.0)), exponential (∝V(2.0)), and exponential/height (∝V(2.0)/Ht). We found that the proportion of variance (R(2)) accounted for, when averaged across the three model types, was substantially lower for one- vs. two-component versions (0.63 ± 0.1 vs. 0.90 ± 0.03) and the predictive errors were nearly twice as great (SEE = 2.22 vs. 1.21 ml O2·kg(-1)·min(-1)). Our final analysis identified the following concise, generalized equation for predicting level human walking metabolism: V̇o2 total = V̇o2 rest + 3.85 + 5.97·V(2)/Ht (where V is measured in m/s, Ht in meters, and V̇o2 in ml O2·kg(-1)·min(-1)). PMID:26679617

  10. Tissue-Specific Posttranslational Modification Allows Functional Targeting of Thyrotropin

    Keisuke Ikegami; Xiao-Hui Liao; Yuta Hoshino; Hiroko Ono; Wataru Ota; Yuka Ito; Taeko Nishiwaki-Ohkawa; Chihiro Sato; Ken Kitajima; Masayuki Iigo; Yasufumi Shigeyoshi; Masanobu Yamada; Yoshiharu Murata; Samuel Refetoff; Takashi Yoshimura

    2014-01-01

    Thyroid-stimulating hormone (TSH; thyrotropin) is a glycoprotein secreted from the pituitary gland. Pars distalis-derived TSH (PD-TSH) stimulates the thyroid gland to produce thyroid hormones (THs), whereas pars tuberalis-derived TSH (PT-TSH) acts on the hypothalamus to regulate seasonal physiology and behavior. However, it had not been clear how these two TSHs avoid functional crosstalk. Here, we show that this regulation is mediated by tissue-specific glycosylation. Although PT-TSH is relea...

  11. Housekeeping and tissue-specific genes in mouse tissues

    St-Amand Jonny

    2007-05-01

    Full Text Available Abstract Background This study aims to characterize the housekeeping and tissue-specific genes in 15 mouse tissues by using the serial analysis of gene expression (SAGE strategy which indicates the relative level of expression for each transcript matched to the tag. Results Here, we identified constantly expressed housekeeping genes, such as eukaryotic translation elongation factor 2, which is expressed in all tissues without significant difference in expression levels. Moreover, most of these genes were not regulated by experimental conditions such as steroid hormones, adrenalectomy and gonadectomy. In addition, we report previously postulated housekeeping genes such as peptidyl-prolyl cis-trans isomerase A, glyceraldehyde-3-phosphate dehydrogenase and beta-actin, which are expressed in all the tissues, but with significant difference in their expression levels. We have also identified genes uniquely detected in each of the 15 tissues and other tissues from public databases. Conclusion These identified housekeeping genes could represent appropriate controls for RT-PCR and northern blot when comparing the expression levels of genes in several tissues. The results reveal several tissue-specific genes highly expressed in testis and pituitary gland. Furthermore, the main function of tissue-specific genes expressed in liver, lung and bone is the cell defence, whereas several keratins involved in cell structure function are exclusively detected in skin and vagina. The results from this study can be used for example to target a tissue for agent delivering by using the promoter of tissue-specific genes. Moreover, this study could be used as basis for further researches on physiology and pathology of these tissues.

  12. Housekeeping and tissue-specific genes in mouse tissues

    St-Amand Jonny; Yoshioka Mayumi; Cadrin-Girard Jean F; Nishida Yuichiro; Kouadjo Kouame E

    2007-01-01

    Abstract Background This study aims to characterize the housekeeping and tissue-specific genes in 15 mouse tissues by using the serial analysis of gene expression (SAGE) strategy which indicates the relative level of expression for each transcript matched to the tag. Results Here, we identified constantly expressed housekeeping genes, such as eukaryotic translation elongation factor 2, which is expressed in all tissues without significant difference in expression levels. Moreover, most of the...

  13. Tissue-specific splicing factor gene expression signatures

    Grosso, A. R.; Gomes, Anita; Barbosa-Morais, Nuno; Caldeira, Sandra; Thorne, Natalie; Grech, Godfrey; Lindern, Marieke; Carmo-Fonseca, Maria

    2008-01-01

    textabstractThe alternative splicing code that controls and coordinates the transcriptome in complex multicellular organisms remains poorly understood. It has long been argued that regulation of alternative splicing relies on combinatorial interactions between multiple proteins, and that tissue-specific splicing decisions most likely result from differences in the concentration and/or activity of these proteins. However, large-scale data to systematically address this issue have just recently...

  14. Laminin Mediates Tissue-specific Gene Expression in Mammary Epithelia

    Streuli, Charles H

    2011-01-01

    Tissue-specific gene expression in mammary epithelium is dependent on the extracellular matrix as well as hormones. There is good evidence that the basement membrane provides signals for regulating beta-casein expression, and that integrins are involved in this process. Here, we demonstrate that in the presence of lactogenic hormones, laminin can direct expression of the beta-casein gene. Mouse mammary epithelial cells plated on gels of native laminin or laminin-entactin undergo functional di...

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

    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...

  16. Fast and Accurate Prediction of Numerical Relativity Waveforms from Binary Black Hole Coalescences Using Surrogate Models.

    Blackman, Jonathan; Field, Scott E; Galley, Chad R; Szilágyi, Béla; Scheel, Mark A; Tiglio, Manuel; Hemberger, Daniel A

    2015-09-18

    Simulating a binary black hole coalescence by solving Einstein's equations is computationally expensive, requiring days to months of supercomputing time. Using reduced order modeling techniques, we construct an accurate surrogate model, which is evaluated in a millisecond to a second, for numerical relativity (NR) waveforms from nonspinning binary black hole coalescences with mass ratios in [1, 10] and durations corresponding to about 15 orbits before merger. We assess the model's uncertainty and show that our modeling strategy predicts NR waveforms not used for the surrogate's training with errors nearly as small as the numerical error of the NR code. Our model includes all spherical-harmonic _{-2}Y_{ℓm} waveform modes resolved by the NR code up to ℓ=8. We compare our surrogate model to effective one body waveforms from 50M_{⊙} to 300M_{⊙} for advanced LIGO detectors and find that the surrogate is always more faithful (by at least an order of magnitude in most cases). PMID:26430979

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

    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...

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

    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

  19. miTALOS v2: Analyzing Tissue Specific microRNA Function.

    Preusse, Martin; Theis, Fabian J; Mueller, Nikola S

    2016-01-01

    MicroRNAs are involved in almost all biological processes and have emerged as regulators of signaling pathways. We show that miRNA target genes and pathway genes are not uniformly expressed across human tissues. To capture tissue specific effects, we developed a novel methodology for tissue specific pathway analysis of miRNAs. We incorporated the most recent and highest quality miRNA targeting data (TargetScan and StarBase), RNA-seq based gene expression data (EBI Expression Atlas) and multiple new pathway data sources to increase the biological relevance of the predicted miRNA-pathway associations. We identified new potential roles of miR-199a-3p, miR-199b-3p and the miR-200 family in hepatocellular carcinoma, involving the regulation of metastasis through MAPK and Wnt signaling. Also, an association of miR-571 and Notch signaling in liver fibrosis was proposed. To facilitate data update and future extensions of our tool, we developed a flexible database backend using the graph database neo4j. The new backend as well as the novel methodology were included in the updated miTALOS v2, a tool that provides insights into tissue specific miRNA regulation of biological pathways. miTALOS v2 is available at http://mips.helmholtz-muenchen.de/mitalos. PMID:26998997

  20. Genome-wide prediction and analysis of human tissue-selective genes using microarray expression data

    Teng Shaolei

    2013-01-01

    Full Text Available Abstract Background Understanding how genes are expressed specifically in particular tissues is a fundamental question in developmental biology. Many tissue-specific genes are involved in the pathogenesis of complex human diseases. However, experimental identification of tissue-specific genes is time consuming and difficult. The accurate predictions of tissue-specific gene targets could provide useful information for biomarker development and drug target identification. Results In this study, we have developed a machine learning approach for predicting the human tissue-specific genes using microarray expression data. The lists of known tissue-specific genes for different tissues were collected from UniProt database, and the expression data retrieved from the previously compiled dataset according to the lists were used for input vector encoding. Random Forests (RFs and Support Vector Machines (SVMs were used to construct accurate classifiers. The RF classifiers were found to outperform SVM models for tissue-specific gene prediction. The results suggest that the candidate genes for brain or liver specific expression can provide valuable information for further experimental studies. Our approach was also applied for identifying tissue-selective gene targets for different types of tissues. Conclusions A machine learning approach has been developed for accurately identifying the candidate genes for tissue specific/selective expression. The approach provides an efficient way to select some interesting genes for developing new biomedical markers and improve our knowledge of tissue-specific expression.

  1. Unilateral Prostate Cancer Cannot be Accurately Predicted in Low-Risk Patients

    Purpose: Hemiablative therapy (HAT) is increasing in popularity for treatment of patients with low-risk prostate cancer (PCa). The validity of this therapeutic modality, which exclusively treats PCa within a single prostate lobe, rests on accurate staging. We tested the accuracy of unilaterally unremarkable biopsy findings in cases of low-risk PCa patients who are potential candidates for HAT. Methods and Materials: The study population consisted of 243 men with clinical stage ≤T2a, a prostate-specific antigen (PSA) concentration of <10 ng/ml, a biopsy-proven Gleason sum of ≤6, and a maximum of 2 ipsilateral positive biopsy results out of 10 or more cores. All men underwent a radical prostatectomy, and pathology stage was used as the gold standard. Univariable and multivariable logistic regression models were tested for significant predictors of unilateral, organ-confined PCa. These predictors consisted of PSA, %fPSA (defined as the quotient of free [uncomplexed] PSA divided by the total PSA), clinical stage (T2a vs. T1c), gland volume, and number of positive biopsy cores (2 vs. 1). Results: Despite unilateral stage at biopsy, bilateral or even non-organ-confined PCa was reported in 64% of all patients. In multivariable analyses, no variable could clearly and independently predict the presence of unilateral PCa. This was reflected in an overall accuracy of 58% (95% confidence interval, 50.6-65.8%). Conclusions: Two-thirds of patients with unilateral low-risk PCa, confirmed by clinical stage and biopsy findings, have bilateral or non-organ-confined PCa at radical prostatectomy. This alarming finding questions the safety and validity of HAT.

  2. Bioprinting Cellularized Constructs Using a Tissue-specific Hydrogel Bioink.

    Skardal, Aleksander; Devarasetty, Mahesh; Kang, Hyun-Wook; Seol, Young-Joon; Forsythe, Steven D; Bishop, Colin; Shupe, Thomas; Soker, Shay; Atala, Anthony

    2016-01-01

    Bioprinting has emerged as a versatile biofabrication approach for creating tissue engineered organ constructs. These constructs have potential use as organ replacements for implantation in patients, and also, when created on a smaller size scale as model "organoids" that can be used in in vitro systems for drug and toxicology screening. Despite development of a wide variety of bioprinting devices, application of bioprinting technology can be limited by the availability of materials that both expedite bioprinting procedures and support cell viability and function by providing tissue-specific cues. Here we describe a versatile hyaluronic acid (HA) and gelatin-based hydrogel system comprised of a multi-crosslinker, 2-stage crosslinking protocol, which can provide tissue specific biochemical signals and mimic the mechanical properties of in vivo tissues. Biochemical factors are provided by incorporating tissue-derived extracellular matrix materials, which include potent growth factors. Tissue mechanical properties are controlled combinations of PEG-based crosslinkers with varying molecular weights, geometries (linear or multi-arm), and functional groups to yield extrudable bioinks and final construct shear stiffness values over a wide range (100 Pa to 20 kPa). Using these parameters, hydrogel bioinks were used to bioprint primary liver spheroids in a liver-specific bioink to create in vitro liver constructs with high cell viability and measurable functional albumin and urea output. This methodology provides a general framework that can be adapted for future customization of hydrogels for biofabrication of a wide range of tissue construct types. PMID:27166839

  3. A hierarchy of ECM-mediated signalling tissue-specific gene expression regulates tissue-specific gene expression

    Roskelley, Calvin D; Srebrow, Anabella; Bissell, Mina J

    1995-10-07

    A dynamic and reciprocal flow of information between cells and the extracellular matrix contributes significantly to the regulation of form and function in developing systems. Signals generated by the extracellular matrix do not act in isolation. Instead, they are processed within the context of global signalling hierarchies whose constituent inputs and outputs are constantly modulated by all the factors present in the cell's surrounding microenvironment. This is particularly evident in the mammary gland, where the construction and subsequent destruction of such a hierarchy regulates changes in tissue-specific gene expression, morphogenesis and apoptosis during each developmental cycle of pregnancy, lactation and involution.

  4. Polymorph stability prediction: On the importance of accurate structures: A case study of pyrazinamide

    Wahlberg, N.; Ciochon, P.; Petříček, Václav; Madsen, A. O.

    2014-01-01

    Roč. 14, č. 1 (2014), s. 381-388. ISSN 1528-7483 Institutional support: RVO:68378271 Keywords : accurate structures * disorder * twinning Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 4.891, year: 2014

  5. Tissue specific metal characterization of selected fish species in Pakistan.

    Ahmed, Mukhtiar; Ahmad, Taufiq; Liaquat, Muhammad; Abbasi, Kashif Sarfraz; Farid, Ibrahim Bayoumi Abdel; Jahangir, Muhammad

    2016-04-01

    Concentration of various metals, i.e., zinc (Zn), copper (Cu), lead (Pb), nickel (Ni), iron (Fe), manganese (Mn), chromium (Cr), and silver (Ag), was evaluated in five indigenous fish species (namely, silver carp, common carp, mahseer, thela fish, and rainbow trout), by using atomic absorption spectrophotometer. It is proved from this study that, overall, mahseer and rainbow trout had high amount of zinc, whereas thela fish and silver carp had high concentration of copper, chromium, silver, nickel, and lead, while common carp had highest amount of iron contents. Furthermore, a tissue-specific discrimination among various fish species was observed, where higher metal concentrations were noticed in fish liver, with decreasing concentration in other organs like skin, gills, and finally the least contents in fish muscle. Multivariate data analysis showed not only a variation in heavy metals among the tissues but also discrimination among the selected fish species. PMID:26951449

  6. Tissue-specific splicing mutation in acute intermittent porphyria

    An inherited deficiency of porphobilinogen deaminase in humans is responsible for the autosomal dominant disease acute intermittent porphyria. Different classes of mutations have been described at the protein level suggesting that this is a heterogeneous disease. It was previously demonstrated that porphobilinogen deaminase is encoded by two distinct mRNA species expressed in a tissue-specific manner. Analysis of the genomic sequences indicated that these two mRNAs are transcribed from two promoters and only differ in their first exon. The first mutation identified in the human porphobilinogen deaminase gene is a single-base substitution (G → A) in the canonical 5' splice donor site of intron 1. This mutation leads to a particular subtype of acute intermittent porphyria characterized by the restriction of the enzymatic defect to nonerythropoietic tissues. Hybridization analysis using olignonucleotide probes after in vitro amplification of genomic DNA offers another possibility of detecting asymptomatic carriers of the mutation in affected families

  7. Tissue-specific splicing mutation in acute intermittent porphyria

    Grandchamp, B.; Picat, C. (Laboratoire de Genetique Moleculaire, Paris (France)); Mignotte, V.; Romeo, P.H.; Goossens, M. (Institut National de la Sante et de la Recherche Medicale, Creteil (France)); Wilson, J.H.P.; Sandkuyl, L. (Erasmus Univ., Rotterdam (Netherlands)); Te Velde, K. (Saint Geertruiden Hospital, Deventer (Netherlands)); Nordmann, Y. (Hopital Louis Mourier, Colombes (France))

    1989-01-01

    An inherited deficiency of porphobilinogen deaminase in humans is responsible for the autosomal dominant disease acute intermittent porphyria. Different classes of mutations have been described at the protein level suggesting that this is a heterogeneous disease. It was previously demonstrated that porphobilinogen deaminase is encoded by two distinct mRNA species expressed in a tissue-specific manner. Analysis of the genomic sequences indicated that these two mRNAs are transcribed from two promoters and only differ in their first exon. The first mutation identified in the human porphobilinogen deaminase gene is a single-base substitution (G {yields} A) in the canonical 5{prime} splice donor site of intron 1. This mutation leads to a particular subtype of acute intermittent porphyria characterized by the restriction of the enzymatic defect to nonerythropoietic tissues. Hybridization analysis using olignonucleotide probes after in vitro amplification of genomic DNA offers another possibility of detecting asymptomatic carriers of the mutation in affected families.

  8. Repressor-mediated tissue-specific gene expression in plants

    Meagher, Richard B.; Balish, Rebecca S.; Tehryung, Kim; McKinney, Elizabeth C.

    2009-02-17

    Plant tissue specific gene expression by way of repressor-operator complexes, has enabled outcomes including, without limitation, male sterility and engineered plants having root-specific gene expression of relevant proteins to clean environmental pollutants from soil and water. A mercury hyperaccumulation strategy requires that mercuric ion reductase coding sequence is strongly expressed. The actin promoter vector, A2pot, engineered to contain bacterial lac operator sequences, directed strong expression in all plant vegetative organs and tissues. In contrast, the expression from the A2pot construct was restricted primarily to root tissues when a modified bacterial repressor (LacIn) was coexpressed from the light-regulated rubisco small subunit promoter in above-ground tissues. Also provided are analogous repressor operator complexes for selective expression in other plant tissues, for example, to produce male sterile plants.

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

    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

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

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

    2014-01-01

    superstrate materials. The importance of accounting for material dispersion in order to obtain accurate simulation results is highlighted, and a method for doing so using an iterative approach is demonstrated. Furthermore, an application for the model is demonstrated, in which the material dispersion of a...

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

    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

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

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

    2016-03-21

    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

  13. LOCUSTRA: accurate prediction of local protein structure using a two-layer support vector machine approach.

    Zimmermann, Olav; Hansmann, Ulrich H E

    2008-09-01

    Constraint generation for 3d structure prediction and structure-based database searches benefit from fine-grained prediction of local structure. In this work, we present LOCUSTRA, a novel scheme for the multiclass prediction of local structure that uses two layers of support vector machines (SVM). Using a 16-letter structural alphabet from de Brevern et al. (Proteins: Struct., Funct., Bioinf. 2000, 41, 271-287), we assess its prediction ability for an independent test set of 222 proteins and compare our method to three-class secondary structure prediction and direct prediction of dihedral angles. The prediction accuracy is Q16=61.0% for the 16 classes of the structural alphabet and Q3=79.2% for a simple mapping to the three secondary classes helix, sheet, and coil. We achieve a mean phi(psi) error of 24.74 degrees (38.35 degrees) and a median RMSDA (root-mean-square deviation of the (dihedral) angles) per protein chain of 52.1 degrees. These results compare favorably with related approaches. The LOCUSTRA web server is freely available to researchers at http://www.fz-juelich.de/nic/cbb/service/service.php. PMID:18763837

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

    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...

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

    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 $\

  16. PconsD: ultra rapid, accurate model quality assessment for protein structure prediction

    Skwark, M. J.; Elofsson, A.

    2013-01-01

    Clustering methods are often needed for accurately assessing the quality of modeled protein structures. Recent blind evaluation of quality assessment methods in CASP10 showed that there is very little difference between many different methods as far as ranking models and selecting best model are concerned. When comparing many models the computational cost of the model comparison can become significant. Here, we present PconsD, a very fast, stream-computing method for distance-driven model qua...

  17. Accurate microRNA target prediction correlates with protein repression levels

    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

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

    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...

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

    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.

  20. Tissue-specific patterns of allelically-skewed DNA methylation

    Marzi, Sarah J.; Meaburn, Emma L.; Dempster, Emma L.; Lunnon, Katie; Paya-Cano, Jose L.; Smith, Rebecca G.; Volta, Manuela; Troakes, Claire; Schalkwyk, Leonard C.; Mill, Jonathan

    2016-01-01

    ABSTRACT While DNA methylation is usually thought to be symmetrical across both alleles, there are some notable exceptions. Genomic imprinting and X chromosome inactivation are two well-studied sources of allele-specific methylation (ASM), but recent research has indicated a more complex pattern in which genotypic variation can be associated with allelically-skewed DNA methylation in cis. Given the known heterogeneity of DNA methylation across tissues and cell types we explored inter- and intra-individual variation in ASM across several regions of the human brain and whole blood from multiple individuals. Consistent with previous studies, we find widespread ASM with > 4% of the ∼220,000 loci interrogated showing evidence of allelically-skewed DNA methylation. We identify ASM flanking known imprinted regions, and show that ASM sites are enriched in DNase I hypersensitivity sites and often located in an extended genomic context of intermediate DNA methylation. We also detect examples of genotype-driven ASM, some of which are tissue-specific. These findings contribute to our understanding of the nature of differential DNA methylation across tissues and have important implications for genetic studies of complex disease. As a resource to the community, ASM patterns across each of the tissues studied are available in a searchable online database: http://epigenetics.essex.ac.uk/ASMBrainBlood. PMID:26786711

  1. Tissue specific regulation of lipogenesis by thyroid hormone

    Blennemann, B.; Freake, H. (Univ. of Connecticut, Storrs (United States))

    1990-02-26

    Thyroid hormone stimulates long chain fatty acid synthesis in rat liver by increasing the amounts of key lipogenic enzymes. Sparse and conflicting data exist concerning its action on this pathway in other tissues. The authors recently showed that, in contrast to liver, hypothyroidism stimulates lipogenesis in brown adipose tissue and have now systematically examined the effects of thyroid state on fatty acid synthesis in other rat tissues. Lipogenesis was assessed by tritiated water incorporation. Euthyroid hepatic fatty acid synthesis (16.6um H/g/h) was reduced to 30% in hypothyroid rats and increased 3 fold in hyperthyroidism. Lipogenesis was detected in euthyroid kidney and heart and these levels were also stimulated by thyroid hormone treatment. Brown adipose tissue was unique in showing increased lipogenesis in the hypothyroid state. Hyperthyroid levels were not different from euthyroid. Effects in white adipose tissue were small and inconsistent. Brain, skin and lung were all lipogenically active, but did not respond to changes in thyroid state. Low but detectable levels of fatty acid synthesis were measured in muscle, which also were non-responsive. A wide spectrum of responses to thyroid hormone are seen in different rat tissues and thus the pathway of long chain fatty acid synthesis would appear to be an excellent model for examining the tissue specific regulation of gene expression by thyroid hormone.

  2. Tissue-Specific Posttranslational Modification Allows Functional Targeting of Thyrotropin

    Keisuke Ikegami

    2014-11-01

    Full Text Available Thyroid-stimulating hormone (TSH; thyrotropin is a glycoprotein secreted from the pituitary gland. Pars distalis-derived TSH (PD-TSH stimulates the thyroid gland to produce thyroid hormones (THs, whereas pars tuberalis-derived TSH (PT-TSH acts on the hypothalamus to regulate seasonal physiology and behavior. However, it had not been clear how these two TSHs avoid functional crosstalk. Here, we show that this regulation is mediated by tissue-specific glycosylation. Although PT-TSH is released into the circulation, it does not stimulate the thyroid gland. PD-TSH is known to have sulfated biantennary N-glycans, and sulfated TSH is rapidly metabolized in the liver. In contrast, PT-TSH has sialylated multibranched N-glycans; in the circulation, it forms the macro-TSH complex with immunoglobulin or albumin, resulting in the loss of its bioactivity. Glycosylation is fundamental to a wide range of biological processes. This report demonstrates its involvement in preventing functional crosstalk of signaling molecules in the body.

  3. Global Patterns of Tissue-Specific Alternative Polyadenylation in Drosophila

    Peter Smibert

    2012-03-01

    Full Text Available We analyzed the usage and consequences of alternative cleavage and polyadenylation (APA in Drosophila melanogaster by using >1 billion reads of stranded mRNA-seq across a variety of dissected tissues. Beyond demonstrating that a majority of fly transcripts are subject to APA, we observed broad trends for 3′ untranslated region (UTR shortening in the testis and lengthening in the central nervous system (CNS; the latter included hundreds of unannotated extensions ranging up to 18 kb. Extensive northern analyses validated the accumulation of full-length neural extended transcripts, and in situ hybridization indicated their spatial restriction to the CNS. Genes encoding RNA binding proteins (RBPs and transcription factors were preferentially subject to 3′ UTR extensions. Motif analysis indicated enrichment of miRNA and RBP sites in the neural extensions, and their termini were enriched in canonical cis elements that promote cleavage and polyadenylation. Altogether, we reveal broad tissue-specific patterns of APA in Drosophila and transcripts with unprecedented 3′ UTR length in the nervous system.

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

    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)

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

    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?

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

    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...

  7. Accurate Prediction of Transposon-Derived piRNAs by Integrating Various Sequential and Physicochemical Features

    Luo, Longqiang; Li, Dingfang; Zhang, Wen; Tu, Shikui; Zhu, Xiaopeng; Tian, Gang

    2016-01-01

    Background Piwi-interacting RNA (piRNA) is the largest class of small non-coding RNA molecules. The transposon-derived piRNA prediction can enrich the research contents of small ncRNAs as well as help to further understand generation mechanism of gamete. Methods In this paper, we attempt to differentiate transposon-derived piRNAs from non-piRNAs based on their sequential and physicochemical features by using machine learning methods. We explore six sequence-derived features, i.e. spectrum profile, mismatch profile, subsequence profile, position-specific scoring matrix, pseudo dinucleotide composition and local structure-sequence triplet elements, and systematically evaluate their performances for transposon-derived piRNA prediction. Finally, we consider two approaches: direct combination and ensemble learning to integrate useful features and achieve high-accuracy prediction models. Results We construct three datasets, covering three species: Human, Mouse and Drosophila, and evaluate the performances of prediction models by 10-fold cross validation. In the computational experiments, direct combination models achieve AUC of 0.917, 0.922 and 0.992 on Human, Mouse and Drosophila, respectively; ensemble learning models achieve AUC of 0.922, 0.926 and 0.994 on the three datasets. Conclusions Compared with other state-of-the-art methods, our methods can lead to better performances. In conclusion, the proposed methods are promising for the transposon-derived piRNA prediction. The source codes and datasets are available in S1 File. PMID:27074043

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

    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

  9. L1 Antisense Promoter Drives Tissue-Specific Transcription of Human Genes

    2006-01-01

    Full Text Available Transcription of transposable elements interspersed in the genome is controlled by complex interactions between their regulatory elements and host factors. However, the same regulatory elements may be occasionally used for the transcription of host genes. One such example is the human L1 retrotransposon, which contains an antisense promoter (ASP driving transcription into adjacent genes yielding chimeric transcripts. We have characterized 49 chimeric mRNAs corresponding to sense and antisense strands of human genes. Here we show that L1 ASP is capable of functioning as an alternative promoter, giving rise to a chimeric transcript whose coding region is identical to the ORF of mRNA of the following genes: KIAA1797, CLCN5, and SLCO1A2. Furthermore, in these cases the activity of L1 ASP is tissue-specific and may expand the expression pattern of the respective gene. The activity of L1 ASP is tissue-specific also in cases where L1 ASP produces antisense RNAs complementary to COL11A1 and BOLL mRNAs. Simultaneous assessment of the activity of L1 ASPs in multiple loci revealed the presence of L1 ASP-derived transcripts in all human tissues examined. We also demonstrate that L1 ASP can act as a promoter in vivo and predict that it has a heterogeneous transcription initiation site. Our data suggest that L1 ASP-driven transcription may increase the transcriptional flexibility of several human genes.

  10. Accurate and efficient target prediction using a potency-sensitive influence-relevance voter

    Lusci, Alessandro; Browning, Michael; Fooshee, David; Swamidass, Joshua; Baldi, Pierre

    2015-01-01

    Background A number of algorithms have been proposed to predict the biological targets of diverse molecules. Some are structure-based, but the most common are ligand-based and use chemical fingerprints and the notion of chemical similarity. These methods tend to be computationally faster than others, making them particularly attractive tools as the amount of available data grows. Results Using a ChEMBL-derived database covering 490,760 molecule-protein interactions and 3236 protein targets, w...

  11. Bedside tracer gas technique accurately predicts outcome in aspiration of spontaneous pneumothorax

    Kiely, D; Ansari, S.; Davey, W.; Mahadevan, V.; Taylor, G.; Seaton, D

    2001-01-01

    BACKGROUND—There is no technique in general use that reliably predicts the outcome of manual aspiration of spontaneous pneumothorax. We have hypothesised that the absence of a pleural leak at the time of aspiration will identify a group of patients in whom immediate discharge is unlikely to be complicated by early lung re-collapse and have tested this hypothesis by using a simple bedside tracer gas technique.
METHODS—Eighty four episodes of primary spontaneous pneumothora...

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

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

    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...

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

    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

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

    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.

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

    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

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

    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

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

    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.)

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

    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.)

  19. Accurate prediction of cellular co-translational folding indicates proteins can switch from post- to co-translational folding

    Nissley, Daniel A.; Sharma, Ajeet K.; Ahmed, Nabeel; Friedrich, Ulrike A.; Kramer, Günter; Bukau, Bernd; O'Brien, Edward P.

    2016-02-01

    The rates at which domains fold and codons are translated are important factors in determining whether a nascent protein will co-translationally fold and function or misfold and malfunction. Here we develop a chemical kinetic model that calculates a protein domain's co-translational folding curve during synthesis using only the domain's bulk folding and unfolding rates and codon translation rates. We show that this model accurately predicts the course of co-translational folding measured in vivo for four different protein molecules. We then make predictions for a number of different proteins in yeast and find that synonymous codon substitutions, which change translation-elongation rates, can switch some protein domains from folding post-translationally to folding co-translationally--a result consistent with previous experimental studies. Our approach explains essential features of co-translational folding curves and predicts how varying the translation rate at different codon positions along a transcript's coding sequence affects this self-assembly process.

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

    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

  1. Accurate predictions of dielectrophoretic force and torque on particles with strong mutual field, particle, and wall interactions

    Liu, Qianlong; Reifsnider, Kenneth

    2012-11-01

    The basis of dielectrophoresis (DEP) is the prediction of the force and torque on particles. The classical approach to the prediction is based on the effective moment method, which, however, is an approximate approach, assumes infinitesimal particles. Therefore, it is well-known that for finite-sized particles, the DEP approximation is inaccurate as the mutual field, particle, wall interactions become strong, a situation presently attracting extensive research for practical significant applications. In the present talk, we provide accurate calculations of the force and torque on the particles from first principles, by directly resolving the local geometry and properties and accurately accounting for the mutual interactions for finite-sized particles with both dielectric polarization and conduction in a sinusoidally steady-state electric field. Since the approach has a significant advantage, compared to other numerical methods, to efficiently simulate many closely packed particles, it provides an important, unique, and accurate technique to investigate complex DEP phenomena, for example heterogeneous mixtures containing particle chains, nanoparticle assembly, biological cells, non-spherical effects, etc. This study was supported by the Department of Energy under funding for an EFRC (the HeteroFoaM Center), grant no. DE-SC0001061.

  2. Size-extensivity-corrected multireference configuration interaction schemes to accurately predict bond dissociation energies of oxygenated hydrocarbons.

    Oyeyemi, Victor B; Krisiloff, David B; Keith, John A; Libisch, Florian; Pavone, Michele; Carter, Emily A

    2014-01-28

    Oxygenated hydrocarbons play important roles in combustion science as renewable fuels and additives, but many details about their combustion chemistry remain poorly understood. Although many methods exist for computing accurate electronic energies of molecules at equilibrium geometries, a consistent description of entire combustion reaction potential energy surfaces (PESs) requires multireference correlated wavefunction theories. Here we use bond dissociation energies (BDEs) as a foundational metric to benchmark methods based on multireference configuration interaction (MRCI) for several classes of oxygenated compounds (alcohols, aldehydes, carboxylic acids, and methyl esters). We compare results from multireference singles and doubles configuration interaction to those utilizing a posteriori and a priori size-extensivity corrections, benchmarked against experiment and coupled cluster theory. We demonstrate that size-extensivity corrections are necessary for chemically accurate BDE predictions even in relatively small molecules and furnish examples of unphysical BDE predictions resulting from using too-small orbital active spaces. We also outline the specific challenges in using MRCI methods for carbonyl-containing compounds. The resulting complete basis set extrapolated, size-extensivity-corrected MRCI scheme produces BDEs generally accurate to within 1 kcal/mol, laying the foundation for this scheme's use on larger molecules and for more complex regions of combustion PESs. PMID:25669533

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

    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.

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

    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

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

    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.

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

    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

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

    Thomasen, Jørn Rind; Sørensen, Anders Christian; Su, Guosheng; Madsen, Per; Lund, Mogens Sandø; Guldbrandtsen, Bernt

    2013-01-01

    The main purpose of this study is to evaluate whether the population structure in Danish Jersey known from the history of the breed also is reflected in the markers. This is done by comparing the linkage disequilibrium and persistence of phase for subgroups of Jersey animals with high proportions...... 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 origin were analyzed and compared to a basic genomic model that assumes a homogeneous breed structure. The main finding in this study is that the importation of germ plasma from the US Jersey population is readily reflected in the genomes of modern Danish Jersey animals. Firstly, linkage...

  8. nuMap: a web platform for accurate prediction of nucleosome positioning.

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

    2014-10-01

    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 parameters 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. PMID:25220945

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

    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.

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

    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

  11. A Comparison of Digital Elevation Models to Accurately Predict Stream Locations

    Trowbridge, Spencer

    Three separate digital elevation models (DEMs) were compared in their ability to predict stream locations. The first DEM from the Shuttle Radar Topography Mission had a resolution of 90 meters, the second DEM from the National Elevation Dataset had a resolution of 30 meters, and the third DEM was created from Light Detection and Ranging (LiDAR) data and had a resolution of 4.34 meters. Ultimately, stream locations were created from these DEMs and compared to the National Hydrography Dataset (NHD) and stream channels traced from aerial photographs. Each bank of the named streams of the Papillion Creek Watershed were traced and samples were obtained that represent error in the placement of the derived stream locations. Measurements were taken from the centerline of the traced stream channels to where orthogonal transects intersected with the derived stream channel of the DEMs and the streams of the NHD. This study found that DEMs with differing resolutions will delineate stream channels differently and that without human assistance in processing elevation data, the finest resolution DEM was not the best at reproducing stream locations.

  12. Mini-Mental Status Examination: a short form of MMSE was as accurate as the original MMSE in predicting dementia

    Schultz-Larsen, Kirsten; Lomholt, Rikke Kirstine; Kreiner, Svend

    2006-01-01

    OBJECTIVES: This study assesses the properties of the Mini-Mental State Examination (MMSE) with the purpose of improving the efficiencies of the methods of screening for cognitive impairment and dementia. A specific purpose was to determine whether an abbreviated version would be as accurate as the.......4%), and positive predictive value (71.0%) but equal area under the receiver operating characteristic curve. Cross-validation on follow-up data confirmed the results. CONCLUSION: A short, valid MMSE, which is as sensitive and specific as the original MMSE for the screening of cognitive impairments and...

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

    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.

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

    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

  15. Evaluating Mesoscale Numerical Weather Predictions and Spatially Distributed Meteorologic Forcing Data for Developing Accurate SWE Forecasts over Large Mountain Basins

    Hedrick, A. R.; Marks, D. G.; Winstral, A. H.; Marshall, H. P.

    2014-12-01

    The ability to forecast snow water equivalent, or SWE, in mountain catchments would benefit many different communities ranging from avalanche hazard mitigation to water resource management. Historical model runs of Isnobal, the physically based energy balance snow model, have been produced over the 2150 km2 Boise River Basin for water years 2012 - 2014 at 100-meter resolution. Spatially distributed forcing parameters such as precipitation, wind, and relative humidity are generated from automated weather stations located throughout the watershed, and are supplied to Isnobal at hourly timesteps. Similarly, the Weather Research & Forecasting (WRF) Model provides hourly predictions of the same forcing parameters from an atmospheric physics perspective. This work aims to quantitatively compare WRF model output to the spatial meteorologic fields developed to force Isnobal, with the hopes of eventually using WRF predictions to create accurate hourly forecasts of SWE over a large mountainous basin.

  16. Accurate prediction of interference minima in linear molecular harmonic spectra by a modified two-center model

    Xin, Cui; Di-Yu, Zhang; Gao, Chen; Ji-Gen, Chen; Si-Liang, Zeng; Fu-Ming, Guo; Yu-Jun, Yang

    2016-03-01

    We demonstrate that the interference minima in the linear molecular harmonic spectra can be accurately predicted by a modified two-center model. Based on systematically investigating the interference minima in the linear molecular harmonic spectra by the strong-field approximation (SFA), it is found that the locations of the harmonic minima are related not only to the nuclear distance between the two main atoms contributing to the harmonic generation, but also to the symmetry of the molecular orbital. Therefore, we modify the initial phase difference between the double wave sources in the two-center model, and predict the harmonic minimum positions consistent with those simulated by SFA. Project supported by the National Basic Research Program of China (Grant No. 2013CB922200) and the National Natural Science Foundation of China (Grant Nos. 11274001, 11274141, 11304116, 11247024, and 11034003), and the Jilin Provincial Research Foundation for Basic Research, China (Grant Nos. 20130101012JC and 20140101168JC).

  17. Tissue-Specific Expression of the Chicken Calpain2 Gene

    Qing Zhu; Yi-Ping Liu; Xiao-Cheng Li; Hua-Rui Du; Xiao-Song Jiang; Zeng-Rong Zhang

    2010-01-01

    We quantified chicken calpain 2 (CAPN2) expression in two Chinese chicken breeds (mountainous black-bone chicken breed [MB] and a commercial meat type chicken breed [S01]) to discern the tissue and ontogenic expression pattern and its effect on muscle metabolism. Real-time quantitative PCR assay was developed for accurate measurement of the CAPN2 mRNA expression in various tissues from chickens of different ages (0, 2, 4, 6, 8, 10, and 12 weeks). Results showed that the breast muscle and leg ...

  18. Construction and analyses of human large-scale tissue specific networks.

    Wei Liu

    Full Text Available Construction and analyses of tissue specific networks is crucial to unveil the function and organizational structure of biological systems. As a direct method to detect protein dynamics, human proteome-wide expression data provide an valuable resource to investigate the tissue specificity of proteins and interactions. By integrating protein expression data with large-scale interaction network, we constructed 30 tissue/cell specific networks in human and analyzed their properties and functions. Rather than the tissue specificity of proteins, we mainly focused on the tissue specificity of interactions to distill tissue specific networks. Through comparing our tissue specific networks with those inferred from gene expression data, we found our networks have larger scales and higher reliability. Furthermore, we investigated the similar extent of multiple tissue specific networks, which proved that tissues with similar functions tend to contain more common interactions. Finally, we found that the tissue specific networks differed from the static network in multiple topological properties. The proteins in tissue specific networks are interacting looser and the hubs play more important roles than those in the static network.

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

    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.

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

    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.

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

    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

  2. Small-scale field experiments accurately scale up to predict density dependence in reef fish populations at large scales.

    Steele, Mark A; Forrester, Graham E

    2005-09-20

    Field experiments provide rigorous tests of ecological hypotheses but are usually limited to small spatial scales. It is thus unclear whether these findings extrapolate to larger scales relevant to conservation and management. We show that the results of experiments detecting density-dependent mortality of reef fish on small habitat patches scale up to have similar effects on much larger entire reefs that are the size of small marine reserves and approach the scale at which some reef fisheries operate. We suggest that accurate scaling is due to the type of species interaction causing local density dependence and the fact that localized events can be aggregated to describe larger-scale interactions with minimal distortion. Careful extrapolation from small-scale experiments identifying species interactions and their effects should improve our ability to predict the outcomes of alternative management strategies for coral reef fishes and their habitats. PMID:16150721

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

    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)

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

    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.

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

    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

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

    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.

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

    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.

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

    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

  9. Annotation of loci from genome-wide association studies using tissue-specific quantitative interaction proteomics

    Lundby, Alicia; Rossin, Elizabeth J.; Steffensen, Annette B.;

    2014-01-01

    Genome-wide association studies (GWAS) have identified thousands of loci associated with complex traits, but it is challenging to pinpoint causal genes in these loci and to exploit subtle association signals. We used tissue-specific quantitative interaction proteomics to map a network of five genes...... propose candidates in GWAS loci for functional studies and to systematically filter subtle association signals using tissue-specific quantitative interaction proteomics....

  10. Dnmt3 and G9a Cooperate for Tissue-specific Development in Zebrafish*

    Rai, Kunal; Jafri, Itrat F.; Chidester, Stephanie; James, Smitha R.; Karpf, Adam R.; Cairns, Bradley R.; Jones, David A.

    2009-01-01

    Although DNA methylation is critical for proper embryonic and tissue-specific development, how different DNA methyltransferases affect tissue-specific development and their targets remains unknown. We address this issue in zebrafish through antisense-based morpholino knockdown of Dnmt3 and Dnmt1. Our data reveal that Dnmt3 is required for proper neurogenesis, and its absence results in profound defects in brain and retina. Interestingly, other organs such as intestine remain unaffected sugges...

  11. A comprehensive functional analysis of tissue specificity of human gene expression

    Guryanov Alexey; Brennan Richard J; Rakhmatulin Eugene; Bugrim Andrej; Dosymbekov Damir; Serebriyskaya Tatiana; Shi Weiwei; Sviridov Evgeny; Nikolsky Yuri; Dezső Zoltán (1947-) (fizikus); Li Kelly; Blake Julie; Samaha Raymond R; Nikolskaya Tatiana

    2008-01-01

    Abstract Background In recent years, the maturation of microarray technology has allowed the genome-wide analysis of gene expression patterns to identify tissue-specific and ubiquitously expressed ('housekeeping') genes. We have performed a functional and topological analysis of housekeeping and tissue-specific networks to identify universally necessary biological processes, and those unique to or characteristic of particular tissues. Results We measured whole genome expression in 31 human ti...

  12. A comprehensive functional analysis of tissue specificity of human gene expression

    Guryanov Alexey

    2008-11-01

    Full Text Available Abstract Background In recent years, the maturation of microarray technology has allowed the genome-wide analysis of gene expression patterns to identify tissue-specific and ubiquitously expressed ('housekeeping' genes. We have performed a functional and topological analysis of housekeeping and tissue-specific networks to identify universally necessary biological processes, and those unique to or characteristic of particular tissues. Results We measured whole genome expression in 31 human tissues, identifying 2374 housekeeping genes expressed in all tissues, and genes uniquely expressed in each tissue. Comprehensive functional analysis showed that the housekeeping set is substantially larger than previously thought, and is enriched with vital processes such as oxidative phosphorylation, ubiquitin-dependent proteolysis, translation and energy metabolism. Network topology of the housekeeping network was characterized by higher connectivity and shorter paths between the proteins than the global network. Ontology enrichment scoring and network topology of tissue-specific genes were consistent with each tissue's function and expression patterns clustered together in accordance with tissue origin. Tissue-specific genes were twice as likely as housekeeping genes to be drug targets, allowing the identification of tissue 'signature networks' that will facilitate the discovery of new therapeutic targets and biomarkers of tissue-targeted diseases. Conclusion A comprehensive functional analysis of housekeeping and tissue-specific genes showed that the biological function of housekeeping and tissue-specific genes was consistent with tissue origin. Network analysis revealed that tissue-specific networks have distinct network properties related to each tissue's function. Tissue 'signature networks' promise to be a rich source of targets and biomarkers for disease treatment and diagnosis.

  13. Motif Discovery in Tissue-Specific Regulatory Sequences Using Directed Information

    James Douglas Engel

    2007-12-01

    Full Text Available Motif discovery for the identification of functional regulatory elements underlying gene expression is a challenging problem. Sequence inspection often leads to discovery of novel motifs (including transcription factor sites with previously uncharacterized function in gene expression. Coupled with the complexity underlying tissue-specific gene expression, there are several motifs that are putatively responsible for expression in a certain cell type. This has important implications in understanding fundamental biological processes such as development and disease progression. In this work, we present an approach to the identification of motifs (not necessarily transcription factor sites and examine its application to some questions in current bioinformatics research. These motifs are seen to discriminate tissue-specific gene promoter or regulatory regions from those that are not tissue-specific. There are two main contributions of this work. Firstly, we propose the use of directed information for such classification constrained motif discovery, and then use the selected features with a support vector machine (SVM classifier to find the tissue specificity of any sequence of interest. Such analysis yields several novel interesting motifs that merit further experimental characterization. Furthermore, this approach leads to a principled framework for the prospective examination of any chosen motif to be discriminatory motif for a group of coexpressed/coregulated genes, thereby integrating sequence and expression perspectives. We hypothesize that the discovery of these motifs would enable the large-scale investigation for the tissue-specific regulatory role of any conserved sequence element identified from genome-wide studies.

  14. Motif Discovery in Tissue-Specific Regulatory Sequences Using Directed Information

    States David

    2007-01-01

    Full Text Available Motif discovery for the identification of functional regulatory elements underlying gene expression is a challenging problem. Sequence inspection often leads to discovery of novel motifs (including transcription factor sites with previously uncharacterized function in gene expression. Coupled with the complexity underlying tissue-specific gene expression, there are several motifs that are putatively responsible for expression in a certain cell type. This has important implications in understanding fundamental biological processes such as development and disease progression. In this work, we present an approach to the identification of motifs (not necessarily transcription factor sites and examine its application to some questions in current bioinformatics research. These motifs are seen to discriminate tissue-specific gene promoter or regulatory regions from those that are not tissue-specific. There are two main contributions of this work. Firstly, we propose the use of directed information for such classification constrained motif discovery, and then use the selected features with a support vector machine (SVM classifier to find the tissue specificity of any sequence of interest. Such analysis yields several novel interesting motifs that merit further experimental characterization. Furthermore, this approach leads to a principled framework for the prospective examination of any chosen motif to be discriminatory motif for a group of coexpressed/coregulated genes, thereby integrating sequence and expression perspectives. We hypothesize that the discovery of these motifs would enable the large-scale investigation for the tissue-specific regulatory role of any conserved sequence element identified from genome-wide studies.

  15. Tissue-specific transcriptomics of the exotic invasive insect pest emerald ash borer (Agrilus planipennis.

    Omprakash Mittapalli

    Full Text Available BACKGROUND: The insect midgut and fat body represent major tissue interfaces that deal with several important physiological functions including digestion, detoxification and immune response. The emerald ash borer (Agrilus planipennis, is an exotic invasive insect pest that has killed millions of ash trees (Fraxinus spp. primarily in the Midwestern United States and Ontario, Canada. However, despite its high impact status little knowledge exists for A. planipennis at the molecular level. METHODOLOGY AND PRINCIPAL FINDINGS: Newer-generation Roche-454 pyrosequencing was used to obtain 126,185 reads for the midgut and 240,848 reads for the fat body, which were assembled into 25,173 and 37,661 high quality expressed sequence tags (ESTs for the midgut and the fat body of A. planipennis larvae, respectively. Among these ESTs, 36% of the midgut and 38% of the fat body sequences showed similarity to proteins in the GenBank nr database. A high number of the midgut sequences contained chitin-binding peritrophin (248and trypsin (98 domains; while the fat body sequences showed high occurrence of cytochrome P450s (85 and protein kinase (123 domains. Further, the midgut transcriptome of A. planipennis revealed putative microbial transcripts encoding for cell-wall degrading enzymes such as polygalacturonases and endoglucanases. A significant number of SNPs (137 in midgut and 347 in fat body and microsatellite loci (317 in midgut and 571 in fat body were predicted in the A. planipennis transcripts. An initial assessment of cytochrome P450s belonging to various CYP clades revealed distinct expression patterns at the tissue level. CONCLUSIONS AND SIGNIFICANCE: To our knowledge this study is one of the first to illuminate tissue-specific gene expression in an invasive insect of high ecological and economic consequence. These findings will lay the foundation for future gene expression and functional studies in A. planipennis.

  16. Tissue-Specific Transcriptome Profiling of Plutella Xylostella Third Instar Larval Midgut

    Wen Xie, Yanyuan Lei, Wei Fu, Zhongxia Yang, Xun Zhu, Zhaojiang Guo, Qingjun Wu, Shaoli Wang, Baoyun Xu, Xuguo Zhou, Youjun Zhang

    2012-01-01

    Full Text Available The larval midgut of diamondback moth, Plutella xylostella, is a dynamic tissue that interfaces with a diverse array of physiological and toxicological processes, including nutrient digestion and allocation, xenobiotic detoxification, innate and adaptive immune response, and pathogen defense. Despite its enormous agricultural importance, the genomic resources for P. xylostella are surprisingly scarce. In this study, a Bt resistant P. xylostella strain was subjected to the in-depth transcriptome analysis to identify genes and gene networks putatively involved in various physiological and toxicological processes in the P. xylostella larval midgut.Using Illumina deep sequencing, we obtained roughly 40 million reads containing approximately 3.6 gigabases of sequence data. De novo assembly generated 63,312 ESTs with an average read length of 416bp, and approximately half of the P. xylostella sequences (45.4%, 28,768 showed similarity to the non-redundant database in GenBank with a cut-off E-value below 10-5. Among them, 11,092 unigenes were assigned to one or multiple GO terms and 16,732 unigenes were assigned to 226 specific pathways. In-depth analysis indentified genes putatively involved in insecticide resistance, nutrient digestion, and innate immune defense. Besides conventional detoxification enzymes and insecticide targets, novel genes, including 28 chymotrypsins and 53 ABC transporters, have been uncovered in the P. xylostella larval midgut transcriptome; which are potentially linked to the Bt toxicity and resistance. Furthermore, an unexpectedly high number of ESTs, including 46 serpins and 7 lysozymes, were predicted to be involved in the immune defense.As the first tissue-specific transcriptome analysis of P. xylostella, this study sheds light on the molecular understanding of insecticide resistance, especially Bt resistance in an agriculturally important insect pest, and lays the foundation for future functional genomics research. In

  17. Tissue-Specific Transcriptomics of the Exotic Invasive Insect Pest Emerald Ash Borer (Agrilus planipennis)

    Mittapalli, Omprakash; Bai, Xiaodong; Bonello, Pierluigi; Herms, Daniel A.

    2010-01-01

    Background The insect midgut and fat body represent major tissue interfaces that deal with several important physiological functions including digestion, detoxification and immune response. The emerald ash borer (Agrilus planipennis), is an exotic invasive insect pest that has killed millions of ash trees (Fraxinus spp.) primarily in the Midwestern United States and Ontario, Canada. However, despite its high impact status little knowledge exists for A. planipennis at the molecular level. Methodology and Principal Findings Newer-generation Roche-454 pyrosequencing was used to obtain 126,185 reads for the midgut and 240,848 reads for the fat body, which were assembled into 25,173 and 37,661 high quality expressed sequence tags (ESTs) for the midgut and the fat body of A. planipennis larvae, respectively. Among these ESTs, 36% of the midgut and 38% of the fat body sequences showed similarity to proteins in the GenBank nr database. A high number of the midgut sequences contained chitin-binding peritrophin (248)and trypsin (98) domains; while the fat body sequences showed high occurrence of cytochrome P450s (85) and protein kinase (123) domains. Further, the midgut transcriptome of A. planipennis revealed putative microbial transcripts encoding for cell-wall degrading enzymes such as polygalacturonases and endoglucanases. A significant number of SNPs (137 in midgut and 347 in fat body) and microsatellite loci (317 in midgut and 571 in fat body) were predicted in the A. planipennis transcripts. An initial assessment of cytochrome P450s belonging to various CYP clades revealed distinct expression patterns at the tissue level. Conclusions and Significance To our knowledge this study is one of the first to illuminate tissue-specific gene expression in an invasive insect of high ecological and economic consequence. These findings will lay the foundation for future gene expression and functional studies in A. planipennis. PMID:21060843

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

    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

  19. Tissue-specific alterations in thyroid hormone homeostasis in combined Mct10 and Mct8 deficiency

    J. Müller (Julia); S. Mayerl (Steffen); T.J. Visser (Ton); V.M. Darras (Veerle); A. Boelen (Anita); L. Frappart (Lucien); L. Mariotta (Luca); F. Verrey; H. Heuer (Heike)

    2014-01-01

    textabstractThe monocarboxylate transporter Mct10 (Slc16a10; T-type amino acid transporter) facilitates the cellular transport of thyroid hormone (TH) and shows an overlapping expression with the wellestablished TH transporter Mct8. Because Mct8 deficiency is associated with distinct tissue-specific

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

    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.

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

    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.

  2. Accurate and computationally efficient prediction of thermochemical properties of biomolecules using the generalized connectivity-based hierarchy.

    Sengupta, Arkajyoti; Ramabhadran, Raghunath O; Raghavachari, Krishnan

    2014-08-14

    In this study we have used the connectivity-based hierarchy (CBH) method to derive accurate heats of formation of a range of biomolecules, 18 amino acids and 10 barbituric acid/uracil derivatives. The hierarchy is based on the connectivity of the different atoms in a large molecule. It results in error-cancellation reaction schemes that are automated, general, and can be readily used for a broad range of organic molecules and biomolecules. Herein, we first locate stable conformational and tautomeric forms of these biomolecules using an accurate level of theory (viz. CCSD(T)/6-311++G(3df,2p)). Subsequently, the heats of formation of the amino acids are evaluated using the CBH-1 and CBH-2 schemes and routinely employed density functionals or wave function-based methods. The calculated heats of formation obtained herein using modest levels of theory and are in very good agreement with those obtained using more expensive W1-F12 and W2-F12 methods on amino acids and G3 results on barbituric acid derivatives. Overall, the present study (a) highlights the small effect of including multiple conformers in determining the heats of formation of biomolecules and (b) in concurrence with previous CBH studies, proves that use of the more effective error-cancelling isoatomic scheme (CBH-2) results in more accurate heats of formation with modestly sized basis sets along with common density functionals or wave function-based methods. PMID:25068299

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

    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...

  4. Knowledge-guided docking: Accurate prospective prediction of bound configurations of novel ligands using Surflex-Dock

    Cleves, AE; Jain, AN

    2015-01-01

    © 2015 The Author(s). Prediction of the bound configuration of small-molecule ligands that differ substantially from the cognate ligand of a protein co-crystal structure is much more challenging than re-docking the cognate ligand. Success rates for cross-docking in the range of 20-30 % are common. We present an approach that uses structural information known prior to a particular cutoff-date to make predictions on ligands whose bounds structures were determined later. The knowledge-guided doc...

  5. Cells determine cell density using a small protein bound to a unique tissue-specific phospholipid

    Christopher J. Petzold

    2013-10-01

    bone cofactor was identified as a lipid containing a ceramide phosphate, a single chained glycerol lipid and a linker. Tendon uses a different cofactor made up of two fatty acid chains linked directly to the phosphate yielding a molecule about half the size. Moreover, adding the tendon factor/cofactor to osteosarcoma cells causes them to stop growing, which is opposite to its role with tendon cells. Thus, the cofactor is cell type specific both in composition and in the triggered response. Further support of its proposed role came from frozen sections from 5 week old mice where an antibody to the factor stained strongly at the growing ends of the tendon as predicted. In conclusion, the molecule needed for cell density signaling is a small protein bound to a unique, tissue-specific phospholipid yielding a membrane associated but diffusible molecule. Signal transduction is postulated to occur by an increased ordering of the plasma membrane as the concentration of this protein/lipid increases with cell density.

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

    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.

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

    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.

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

    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

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

    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

  10. Analysis of tissue-specific region in sericin 1 gene promoter of Bombyx mori

    The gene encoding sericin 1 (Ser1) of silkworm (Bombyx mori) is specifically expressed in the middle silk gland cells. To identify element involved in this transcription-dependent spatial restriction, truncation of the 5' terminal from the sericin 1 (Ser1) promoter is studied in vivo. A 209 bp DNA sequence upstream of the transcriptional start site (-586 to -378) is found to be responsible for promoting tissue-specific transcription. Analysis of this 209 bp region by overlapping deletion studies showed that a 25 bp region (-500 to -476) suppresses the ectopic expression of the Ser1 promoter. An unknown factor abundant in fat body nuclear extracts is shown to bind to this 25 bp fragment. These results suggest that this 25 bp region and the unknown factor are necessary for determining the tissue-specificity of the Ser1 promoter

  11. Research Resource: Tissue-Specific Transcriptomics and Cistromics of Nuclear Receptor Signaling: A Web Research Resource

    Ochsner, Scott A.; Watkins, Christopher M.; LaGrone, Benjamin S.; Steffen, David L.; McKenna, Neil J

    2010-01-01

    Nuclear receptors (NRs) are ligand-regulated transcription factors that recruit coregulators and other transcription factors to gene promoters to effect regulation of tissue-specific transcriptomes. The prodigious rate at which the NR signaling field has generated high content gene expression and, more recently, genome-wide location analysis datasets has not been matched by a committed effort to archiving this information for routine access by bench and clinical scientists. As a first step to...

  12. Tissue-specific post-translational modification allows functional targeting of thyrotropin

    IKEGAMI, Keisuke; Liao, Xiao-Hui; Hoshino, Yuta; Ono, Hiroko; Ota, Wataru; Ito, Yuka; Nishiwaki-Ohkawa, Taeko; Sato, Chihiro; Kitajima, Ken; Iigo, Masayuki; Shigeyoshi, Yasufumi; Yamada, Masanobu; Murata, Yoshiharu; Refetoff, Samuel; Yoshimura, Takashi

    2014-01-01

    Thyroid-stimulating hormone (TSH: thyrotropin) is a glycoprotein secreted from the pituitary gland. Pars distalis-derived TSH (PD-TSH) stimulates the thyroid gland to produce thyroid hormones (THs), whereas pars tuberalis-derived TSH (PT-TSH) acts on the hypothalamus to regulate seasonal physiology and behavior. However, it had not been clear how these two TSHs avoid functional crosstalk. Here, we show that this regulation is mediated by tissue-specific glycosylation. Although PT-TSH is relea...

  13. Altering the distribution of Foxp3+ regulatory T cells results in tissue-specific inflammatory disease

    Sather, Blythe D.; Treuting, Piper; Perdue, Nikole; Miazgowicz, Mike; Fontenot, Jason D.; Rudensky, Alexander Y.; Campbell, Daniel J.

    2007-01-01

    CD4+Foxp3+ regulatory T cells (T reg) are essential for maintaining self-tolerance, but their functional mechanisms and sites of action in vivo are poorly defined. We examined the homing receptor expression and tissue distribution of T reg cells in the steady state and determined whether altering their distribution by removal of a single chemokine receptor impairs their ability to maintain tissue-specific peripheral tolerance. We found that T reg cells are distributed throughout all nonlympho...

  14. Behavioral and electrophysiological outcomes of tissue-specific Smn knockdown in Drosophila melanogaster

    Timmerman, Christina; Sanyal, Subhabrata

    2012-01-01

    Severe reduction in Survival Motor Neuron 1 (SMN1) protein in humans causes Spinal Muscular Atrophy (SMA), a debilitating childhood disease that leads to progressive impairment of the neuro-muscular system. Although previous studies have attempted to identify the tissue(s) in which SMN1 loss most critically leads to disease, tissue-specific functions for this widely expressed protein still remain unclear. Here, we have leveraged RNA interference methods to manipulate SMN function selectively ...

  15. Tissue-Specific Peroxisome Proliferator Activated Receptor Gamma Expression and Metabolic Effects of Telmisartan

    Zídek, Václav; Mlejnek, Petr; Šimáková, Miroslava; Šilhavý, Jan; Landa, Vladimír; Kazdová, L.; Pravenec, Michal; Kurtz, T. W.

    2013-01-01

    Roč. 26, č. 6 (2013), s. 829-835. ISSN 0895-7061 R&D Projects: GA ČR(CZ) GAP303/10/0505; GA MŠk(CZ) LH11049; GA MŠk(CZ) LL1204; GA MŠk(CZ) 7E10067 Institutional support: RVO:67985823 Keywords : telmisartan * metabolic effects * tissue-specific Pparg knockout mice Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.402, year: 2013

  16. Transgenic zebrafish reveal tissue-specific differences in estrogen signaling in response to environmental water samples

    Gorelick, Daniel A.; Iwanowicz, Luke R.; Hung, Alice L.; Blazer, Vicki; Halpern, Marnie E.

    2014-01-01

    Background: Environmental endocrine disruptors (EED) are exogenous chemicals that mimic endogenous hormones, such as estrogens. Previous studies using a zebrafish transgenic reporter demonstrated that the EEDs bisphenol A and genistein preferentially activate estrogen receptors (ER) in the larval heart compared to the liver. However, it was not known whether the transgenic zebrafish reporter was sensitive enough to detect estrogens from environmental samples, whether environmental estrogens would exhibit similar tissue-specific effects as BPA and genistein or why some compounds preferentially target receptors in the heart. Methods: We tested surface water samples using a transgenic zebrafish reporter with tandem estrogen response elements driving green fluorescent protein expression (5xERE:GFP). Reporter activation was colocalized with tissue-specific expression of estrogen receptor genes by RNA in situ hybridization. Results: Selective patterns of ER activation were observed in transgenic fish exposed to river water samples from the Mid-Atlantic United States, with several samples preferentially activating receptors in embryonic and larval heart valves. We discovered that tissue-specificity in ER activation is due to differences in the expression of estrogen receptor subtypes. ERα is expressed in developing heart valves but not in the liver, whereas ERβ2 has the opposite profile. Accordingly, subtype-specific ER agonists activate the reporter in either the heart valves or the liver. Conclusion: The use of 5xERE:GFP transgenic zebrafish has revealed an unexpected tissue-specific difference in the response to environmentally relevant estrogenic compounds. Exposure to estrogenic EEDs in utero is associated with adverse health effects, with the potentially unanticipated consequence of targeting developing heart valves.

  17. Accurate and efficient prediction of fine-resolution hydrologic and carbon dynamic simulations from coarse-resolution models

    Pau, George Shu Heng; Shen, Chaopeng; Riley, William J.; Liu, Yaning

    2016-02-01

    The topography, and the biotic and abiotic parameters are typically upscaled to make watershed-scale hydrologic-biogeochemical models computationally tractable. However, upscaling procedure can produce biases when nonlinear interactions between different processes are not fully captured at coarse resolutions. Here we applied the Proper Orthogonal Decomposition Mapping Method (PODMM) to downscale the field solutions from a coarse (7 km) resolution grid to a fine (220 m) resolution grid. PODMM trains a reduced-order model (ROM) with coarse-resolution and fine-resolution solutions, here obtained using PAWS+CLM, a quasi-3-D watershed processes model that has been validated for many temperate watersheds. Subsequent fine-resolution solutions were approximated based only on coarse-resolution solutions and the ROM. The approximation errors were efficiently quantified using an error estimator. By jointly estimating correlated variables and temporally varying the ROM parameters, we further reduced the approximation errors by up to 20%. We also improved the method's robustness by constructing multiple ROMs using different set of variables, and selecting the best approximation based on the error estimator. The ROMs produced accurate downscaling of soil moisture, latent heat flux, and net primary production with O(1000) reduction in computational cost. The subgrid distributions were also nearly indistinguishable from the ones obtained using the fine-resolution model. Compared to coarse-resolution solutions, biases in upscaled ROM solutions were reduced by up to 80%. This method has the potential to help address the long-standing spatial scaling problem in hydrology and enable long-time integration, parameter estimation, and stochastic uncertainty analysis while accurately representing the heterogeneities.

  18. Tissue-Specific Immune Gene Expression in the Migratory Locust, Locusta Migratoria

    Tamara Pulpitel

    2015-04-01

    Full Text Available The ability of hosts to respond to infection involves several complex immune recognition pathways. Broadly conserved pathogen-associated molecular patterns (PAMPs allow individuals to target a range of invading microbes. Recently, studies on insect innate immunity have found evidence that a single pathogen can activate different immune pathways across species. In this study, expression changes in immune genes encoding peptidoglycan-recognition protein SA (PGRP-SA, gram-negative binding protein 1 (GNBP1 and prophenoloxidase (ProPO were investigated in Locusta migratoria, following an immune challenge using injected lipopolysaccharide (LPS solution from Escherichia coli. Since immune activation might also be tissue-specific, gene expression levels were followed across a range of tissue types. For PGRP-SA, expression increased in response to LPS within all seven of the tissue-types assayed and differed significantly between tissues. Expression of GNBP1 similarly varied across tissue types, yet showed no clear expression difference between LPS-injected and uninfected locusts. Increases in ProPO expression in response to LPS, however, could only be detected in the gut sections. This study has revealed tissue-specific immune response to add a new level of complexity to insect immune studies. In addition to variation in recognition pathways identified in previous works, tissue-specificity should be carefully considered in similar works.

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

    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...

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

    Somaya Hashem; Gamal Esmat; Wafaa Elakel; Shahira Habashy; Safaa Abdel Raouf; Samar Darweesh; Mohamad Soliman; Mohamed Elhefnawi; Mohamed El-Adawy; Mahmoud ElHefnawi

    2016-01-01

    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...

  1. ADMET evaluation in drug discovery: 15. Accurate prediction of rat oral acute toxicity using relevance vector machine and consensus modeling

    Lei, Tailong; Li, Youyong; Song, Yunlong; Li, Dan; Sun, Huiyong; Hou, Tingjun

    2016-01-01

    Background Determination of acute toxicity, expressed as median lethal dose (LD50), is one of the most important steps in drug discovery pipeline. Because in vivo assays for oral acute toxicity in mammals are time-consuming and costly, there is thus an urgent need to develop in silico prediction models of oral acute toxicity. Results In this study, based on a comprehensive data set containing 7314 diverse chemicals with rat oral LD50 values, relevance vector machine (RVM) technique was employ...

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

    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

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

    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.

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

    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.

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

    Hashem, Somaya; Esmat, Gamal; Elakel, Wafaa; Habashy, Shahira; Abdel Raouf, Safaa; Darweesh, Samar; Soliman, Mohamad; Elhefnawi, Mohamed; El-Adawy, Mohamed; ElHefnawi, Mahmoud

    2016-01-01

    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. PMID:26880886

  6. Tissue-specific effects of genetic and epigenetic variation on gene regulation and splicing.

    Maria Gutierrez-Arcelus

    2015-01-01

    Full Text Available Understanding how genetic variation affects distinct cellular phenotypes, such as gene expression levels, alternative splicing and DNA methylation levels, is essential for better understanding of complex diseases and traits. Furthermore, how inter-individual variation of DNA methylation is associated to gene expression is just starting to be studied. In this study, we use the GenCord cohort of 204 newborn Europeans' lymphoblastoid cell lines, T-cells and fibroblasts derived from umbilical cords. The samples were previously genotyped for 2.5 million SNPs, mRNA-sequenced, and assayed for methylation levels in 482,421 CpG sites. We observe that methylation sites associated to expression levels are enriched in enhancers, gene bodies and CpG island shores. We show that while the correlation between DNA methylation and gene expression can be positive or negative, it is very consistent across cell-types. However, this epigenetic association to gene expression appears more tissue-specific than the genetic effects on gene expression or DNA methylation (observed in both sharing estimations based on P-values and effect size correlations between cell-types. This predominance of genetic effects can also be reflected by the observation that allele specific expression differences between individuals dominate over tissue-specific effects. Additionally, we discover genetic effects on alternative splicing and interestingly, a large amount of DNA methylation correlating to alternative splicing, both in a tissue-specific manner. The locations of the SNPs and methylation sites involved in these associations highlight the participation of promoter proximal and distant regulatory regions on alternative splicing. Overall, our results provide high-resolution analyses showing how genome sequence variation has a broad effect on cellular phenotypes across cell-types, whereas epigenetic factors provide a secondary layer of variation that is more tissue-specific. Furthermore

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

    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)

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

    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

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

    Keshavarz, Mohammad Hossein; Gharagheizi, Farhad; Shokrolahi, Arash; Zakinejad, Sajjad

    2012-10-30

    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(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. PMID:22959133

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

    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…

  11. The first insight into the tissue specific taxus transcriptome via Illumina second generation sequencing.

    Da Cheng Hao

    Full Text Available BACKGROUND: Illumina second generation sequencing is now an efficient route for generating enormous sequence collections that represent expressed genes and quantitate expression level. Taxus is a world-wide endangered gymnosperm genus and forms an important anti-cancer medicinal resource, but the large and complex genomes of Taxus have hindered the development of genomic resources. The research of its tissue-specific transcriptome is absent. There is also no study concerning the association between the plant transcriptome and metabolome with respect to the plant tissue type. METHODOLOGY/PRINCIPAL FINDINGS: We performed the de novo assembly of Taxus mairei transcriptome using Illumina paired-end sequencing technology. In a single run, we produced 13,737,528 sequencing reads corresponding to 2.03 Gb total nucleotides. These reads were assembled into 36,493 unique sequences. Based on similarity search with known proteins, 23,515 Unigenes were identified to have the Blast hit with a cut-off E-value above 10⁻⁵. Furthermore, we investigated the transcriptome difference of three Taxus tissues using a tag-based digital gene expression system. We obtained a sequencing depth of over 3.15 million tags per sample and identified a large number of genes associated with tissue specific functions and taxane biosynthetic pathway. The expression of the taxane biosynthetic genes is significantly higher in the root than in the leaf and the stem, while high activity of taxane-producing pathway in the root was also revealed via metabolomic analyses. Moreover, many antisense transcripts and novel transcripts were found; clusters with similar differential expression patterns, enriched GO terms and enriched metabolic pathways with regard to the differentially expressed genes were revealed for the first time. CONCLUSIONS/SIGNIFICANCE: Our data provides the most comprehensive sequence resource available for Taxus study and will help define mechanisms of tissue

  12. Single cell analysis reveals gametic and tissue-specific instability of the SCA1 CAG repeat

    Chong, S.S.; McCall, A.E.; Cota, J. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1994-09-01

    Spinocerebellar ataxia type 1 is an autosomal dominant neurodegenerative disease caused by expansion of a CAG trinucleotide repeat within the SCA1 gene on chromosome 6p22-23. We performed a comparative analysis of the SCA1 CAG repeat from blood and sperm of an affected male. Genomic amplification revealed a broader smear of the SCA1 allele product from sperm compared to that from peripheral blood leukocytes (PBL). To resolve this observed difference, we analyzed single sperm directly and demonstrate that the SCA1 allele in PBL is also heterogeneous, although the range of variability in allele sizes is much less than that observed in sperm. Limited genome analysis was also performed on PBL DNA from an unaffected individual with an upper normal allele of 36 repeats in parallel with an affected individual with an expanded allele of 40 repeats. The 36 repeat normal allele, which contains a CAT interruption, was completely stable compared to the uninterrupted repeat of the SCA1 allele, demonstrating a direct correlation between absence of a CAT interruption and somatic instability of the repeat. We also analyzed the size of the CAG repeat in tissues derived from various brain regions from a patient with juvenile-onset disease to determine if the size of the expansion correlated with the site of neuropathology. The results clearly show tissue-specific differences in mosaicism of repeat length. More importantly, the pattern of tissue-specific differences in repeat-length mosaicism in SCA1 within the brain parallels those seen in Huntington disease. In both disorders the expanded alleles are smaller in cerebellar tissue. These results suggest that the observed tissue-specific differences in instability of the SCA1 CAG repeat, either within the brain or between blood and sperm, are a function of the intracellular milieu or the intrinsic replicative potential of the various celltypes.

  13. Novel strong tissue specific promoter for gene expression in human germ cells

    Kuzmin Denis

    2010-08-01

    Full Text Available Abstract Background Tissue specific promoters may be utilized for a variety of applications, including programmed gene expression in cell types, tissues and organs of interest, for developing different cell culture models or for use in gene therapy. We report a novel, tissue-specific promoter that was identified and engineered from the native upstream regulatory region of the human gene NDUFV1 containing an endogenous retroviral sequence. Results Among seven established human cell lines and five primary cultures, this modified NDUFV1 upstream sequence (mNUS was active only in human undifferentiated germ-derived cells (lines Tera-1 and EP2102, where it demonstrated high promoter activity (~twice greater than that of the SV40 early promoter, and comparable to the routinely used cytomegaloviral promoter. To investigate the potential applicability of the mNUS promoter for biotechnological needs, a construct carrying a recombinant cytosine deaminase (RCD suicide gene under the control of mNUS was tested in cell lines of different tissue origin. High cytotoxic effect of RCD with a cell-death rate ~60% was observed only in germ-derived cells (Tera-1, whereas no effect was seen in a somatic, kidney-derived control cell line (HEK293. In further experiments, we tested mNUS-driven expression of a hyperactive Sleeping Beauty transposase (SB100X. The mNUS-SB100X construct mediated stable transgene insertions exclusively in germ-derived cells, thereby providing further evidence of tissue-specificity of the mNUS promoter. Conclusions We conclude that mNUS may be used as an efficient promoter for tissue-specific gene expression in human germ-derived cells in many applications. Our data also suggest that the 91 bp-long sequence located exactly upstream NDUFV1 transcriptional start site plays a crucial role in the activity of this gene promoter in vitro in the majority of tested cell types (10/12, and an important role - in the rest two cell lines.

  14. Tissue- Specific Expression Analysis of Anthocyanin Biosynthetic Genes in White- and Red-Fleshed Grape Cultivars

    Sha Xie; Changzheng Song; Xingjie Wang; Meiying Liu; Zhenwen Zhang; Zhumei Xi

    2015-01-01

    Yan73, a teinturier (dyer) grape variety in China, is one of the few Vitis vinifera cultivars with red-coloured berry flesh. To examine the tissue-specific expression of genes associated with berry colour in Yan73, we analysed the differential accumulation of anthocyanins in the skin and flesh tissues of two red-skinned grape varieties with either red (Yan73) or white flesh (Muscat Hamburg) based on HPLC-MS analysis, as well as the differential expression of 18 anthocyanin biosynthesis genes ...

  15. Shade-induced stem elongation in rice seedlings: Implication of tissue-specific phytohormone regulation.

    Liu, Huihui; Yang, Chuanwei; Li, Lin

    2016-07-01

    A better understanding of shade avoidance syndrome (SAS) is an urgent need because of its effect on energy reallocation. Leverage-related mechanism in crops is of potential economic interest for agricultural applications. Here we report the SAS phenotype at tissue level rice seedlings. Tissue-specific RNA-sequencing indicates auxin plays different roles between coleoptile and the first leaf. Phenotypes of wild type treated by gibberellin and brassinosteroid biosynthesis inhibitors and of related mutants suggest these two hormones positively regulate SAS. Our work reveals the diversity of hormone responses in different organs and different species in shade conditions. PMID:26888633

  16. Tissue-specific expression of the rat beta-casein gene in transgenic mice.

    Lee, K. F.; DeMayo, F J; Atiee, S H; Rosen, J. M.

    1988-01-01

    The rat beta-casein gene is a member of a small gene family, encoding the principal milk proteins. In order to understand the mechanisms by which its stage- and tissue-specific expression are regulated, initially, a 14 kb genomic clone containing the entire 7.5 kb rat beta-casein gene with 3.5 kb of 5' and 3.0 kb of 3' flanking DNA was microinjected into the germline of mice. Eight F0 transgenic mice were generated with copy numbers ranging from 1-10; five transmitted the transgene to their o...

  17. De novo assembly and analysis of tissue-specific transcriptomes revealed the tissue-specific genes and profile of immunity from Strongylocentrotus intermedius.

    Chen, Yadong; Chang, Yaqing; Wang, Xiuli; Qiu, Xuemei; Liu, Yang

    2015-10-01

    Strongylocentrotus intermedius is an important marine species in north China and Japan. Recent years, diseases are threating the sea urchin aquaculture industry seriously. To provide a genetic resource for S. intermedius as well as overview the immune-related genes of S. intermedius, we performed transcriptome sequencing of three cDNA libraries representing three tissues, coelomocytes, gut and peristomial membrane respectively. In total 138,421 contigs were assembled from all sequencing data. 96,764 contigs were annotated according to bioinformatics databases, including NT, nr, Swiss-Prot, KEGG, COG. 49,336 Contigs were annotated as CDS. In this study, we obtained 24,778 gene families from S. intermedius transcriptome. The gene expression analysis revealed that more genes were expressed in gut, more high expression level genes in coelomocytes when compared with other tissues. Specific expressed contigs in coelomocytes, gut, and peristomial membrane were 546, 1136, and 1012 respectively. Pathway analysis suggested 25, 17 and 36 potential specifically pathways may specific progressed in peristomial membrane, gut and coelomocytes respectively. Similarities and differences between S. intermedius and other echinoderms were analyzed. S. intermedius was more homology to Strongylocentrotus purpuratus than others sea urchin. Of 24,778 genes, 1074 genes are immune-related, immune genes were expressed with a higher level in coelomocytes than other tissues. Complement system may be the most important immune system in sea urchin. We also identified 2438 SSRs and 16,236 SNPs for S. intermedius. These results provide a transcriptome resource and foundation to study molecular mechanisms of sea urchin immune system. PMID:26253994

  18. Tissue-specific assimilation, depuration and toxicity of nickel in Mytilus edulis

    The tissue-specific accumulation and time-dependent depuration of radioactive 63Ni by the byssus, gut, foot, gills, kidney, adductor muscle and faeces of Mytilus edulis has been investigated using a pulse-chase technique. The rate and extent of depuration of 63Ni varied between tissues and, after 168 h, the concentration factors and assimilation efficiencies ranged from 1 to 35 L kg−1 and 5%–13%, respectively. Mussels were also exposed to a range of environmentally-realistic concentrations of dissolved Ni, prior to the analysis of biological endpoints. The clearance rate was concentration-dependent and at the highest concentration decreased by 30%. Neutral red retention (NRR) assays indicated a cytotoxic response and DNA strand breaks were observed in the haemocytes. The association of DNA damage with that of physiological and cytotoxic effects suggests that Ni exerts a significant impact on Mytilus edulis at cellular and genetic levels. - Highlights: ► Tissue-specific accumulation and depuration of nickel by marine mussels was evaluated. ► Concentration factors for nickel in mussel tissues were lower than recommended values. ► Cytotoxic and genotoxic effects were detected in mussel haemocytes in the presence of dissolved nickel. ► Nickel exerts a significant effect on mussels at cellular and genetic levels. - Nickel is accumulated preferentially in the byssus and gut of marine mussels and it exerts a cytotoxic and genotoxic response in their haemocytes.

  19. Biliary and reticuloendothelial impairment in hepatocarcinogenesis: the diagnostic role of tissue-specific MR contrast media

    Bartolozzi, Carlo; Crocetti, Laura; Lencioni, Riccardo; Cioni, Dania; Della Pina, Clotilde [University of Pisa, Division of Diagnostic and Interventional Radiology, Department of Oncology, Transplant and Advanced Technologies in Medicine, Pisa (Italy); Campani, Daniela [University of Pisa, Division of Pathology, Department of Oncology, Transplant and Advanced Technologies in Medicine, Pisa (Italy)

    2007-10-15

    The development and progression of a hepatocellular carcinoma (HCC) in a chronically diseased liver, i.e., the carcinogenesis, comprise a multistep and long-term process. Morphologically, this process is associated with the presence of distinct nodular lesions in the liver that are called 'preneoplastic lesions.' These preneoplastic lesions are associated with and can precede the growth and progression of well-differentiated HCCs. The characterization of nodular lesions and demonstration of the multistep development of HCC in the cirrhotic liver by imaging modalities represent a challenging issue. The arterial hypervascular supply, depicted by different dynamic studies, represents a fundamental radiological criterion for the diagnosis of HCC in cirrhosis. Magnetic resonance (MR) imaging performed with tissue-specific contrast media can help to investigate the ''grey area'' of carcinogenesis, in which significant histological changes are already present without any imaging evidence of neoangiogenesis. The purpose of this review is to provide information on the properties of tissue-specific MR contrast agents and on their usefulness in the demonstration of the pathologic changes that take place at the level of the biliary and reticuloendothelial systems during the carcinogenetic process in liver cirrhosis. (orig.)

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

    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.

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

    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

  2. Tissue-specific mRNA expression profiling in grape berry tissues

    Cramer Grant R

    2007-06-01

    Full Text Available Abstract Background Berries of grape (Vitis vinifera contain three major tissue types (skin, pulp and seed all of which contribute to the aroma, color, and flavor characters of wine. The pericarp, which is composed of the exocarp (skin and mesocarp (pulp, not only functions to protect and feed the developing seed, but also to assist in the dispersal of the mature seed by avian and mammalian vectors. The skin provides volatile and nonvolatile aroma and color compounds, the pulp contributes organic acids and sugars, and the seeds provide condensed tannins, all of which are important to the formation of organoleptic characteristics of wine. In order to understand the transcriptional network responsible for controlling tissue-specific mRNA expression patterns, mRNA expression profiling was conducted on each tissue of mature berries of V. vinifera Cabernet Sauvignon using the Affymetrix GeneChip® Vitis oligonucleotide microarray ver. 1.0. In order to monitor the influence of water-deficit stress on tissue-specific expression patterns, mRNA expression profiles were also compared from mature berries harvested from vines subjected to well-watered or water-deficit conditions. Results Overall, berry tissues were found to express approximately 76% of genes represented on the Vitis microarray. Approximately 60% of these genes exhibited significant differential expression in one or more of the three major tissue types with more than 28% of genes showing pronounced (2-fold or greater differences in mRNA expression. The largest difference in tissue-specific expression was observed between the seed and pulp/skin. Exocarp tissue, which is involved in pathogen defense and pigment production, showed higher mRNA abundance relative to other berry tissues for genes involved with flavonoid biosynthesis, pathogen resistance, and cell wall modification. Mesocarp tissue, which is considered a nutritive tissue, exhibited a higher mRNA abundance of genes involved in cell

  3. Rodent Aanat: Intronic E-box sequences control tissue specificity but not rhythmic expression in the pineal gland

    2007-01-01

    Rodent Aanat: Intronic E-box sequences control tissue specificity but not rhythmic expression in the pineal gland UNITED KINGDOM (Humphries, Ann) UNITED KINGDOM Received: 2006-12-30 Revised: 2007-02-07 Accepted: 2007-02-07

  4. Adipocyte dysfunction in a mouse model of polycystic ovary syndrome (PCOS: evidence of adipocyte hypertrophy and tissue-specific inflammation.

    Joseph S Marino

    Full Text Available Clinical research shows an association between polycystic ovary syndrome (PCOS and chronic inflammation, a pathological state thought to contribute to insulin resistance. The underlying pathways, however, have not been defined. The purpose of this study was to characterize the inflammatory state of a novel mouse model of PCOS. Female mice lacking leptin and insulin receptors in pro-opiomelanocortin neurons (IR/LepR(POMC mice and littermate controls were evaluated for estrous cyclicity, ovarian and adipose tissue morphology, and body composition by QMR and CT scan. Tissue-specific macrophage infiltration and cytokine mRNA expression were measured, as well as circulating cytokine levels. Finally, glucose regulation during pregnancy was evaluated as a measure of risk for diabetes development. Forty-five percent of IR/LepR(POMC mice showed reduced or absent ovulation. IR/LepR(POMC mice also had increased fat mass and adipocyte hypertrophy. These traits accompanied elevations in macrophage accumulation and inflammatory cytokine production in perigonadal adipose tissue, liver, and ovary. These mice also exhibited gestational hyperglycemia as predicted. This report is the first to show the presence of inflammation in IR/LepR(POMC mice, which develop a PCOS-like phenotype. Thus, IR/LepR(POMC mice may serve as a new mouse model to clarify the involvement of adipose and liver tissue in the pathogenesis and etiology of PCOS, allowing more targeted research on the development of PCOS and potential therapeutic interventions.

  5. Tissue specific phosphorylation of mitochondrial proteins isolated from rat liver, heart muscle, and skeletal muscle

    Bak, Steffen; León, Ileana R; Jensen, Ole Nørregaard;

    2013-01-01

    Phosphorylation of mitochondrial proteins in a variety of biological processes is increasingly being recognized and may contribute to the differences in function and energy demands observed in mitochondria from different tissues such as liver, heart, and skeletal muscle. Here, we used a combination...... of TiO2 phosphopeptide-enrichment, HILIC fractionation, and LC-MS/MS on isolated mitochondria to investigate the tissue-specific mitochondrial phosphoproteomes of rat liver, heart, and skeletal muscle. In total, we identified 899 phosphorylation sites in 354 different mitochondrial proteins including...... enrichment for phosphoproteins involved in amino acid and fatty acid metabolism in liver mitochondria, whereas heart and skeletal muscle were enriched for phosphoproteins involved in energy metabolism, in particular, tricarboxylic acid cycle and oxidative phosphorylation. Multiple tissue...

  6. Tissue Specific Effects of Loss of Estrogen During Menopause and Aging

    Korinna eWend

    2012-02-01

    Full Text Available The roles of estrogens have been best studied in the breast, breast cancers and in the female reproductive tract. However, estrogens have important functions in almost every tissue in the body. Recent clinical trials such as the Women’s Health Initiative have highlighted both the importance of estrogens and how little we know about the molecular mechanism of estrogens in these other tissues. In this review, we illustrate the diverse functions of estrogens in the bone, adipose tissue, skin, hair, brain, skeletal muscle and cardiovascular system, and how the loss of estrogens during aging affects these tissues. Early transcriptional targets of estrogen are reviewed in each tissue. We also describe the tissue-specific effects of selective estrogen receptor modulators (SERMs used for the treatment of breast cancers and post-menopausal symptoms.

  7. Turning on Myogenin in Muscle: A Paradigm for Understanding Mechanisms of Tissue-Specific Gene Expression

    Herve Faralli

    2012-01-01

    Full Text Available Expression of the myogenin (Myog gene is restricted to skeletal muscle cells where the transcriptional activator turns on a gene expression program that permits the transition from proliferating myoblasts to differentiating myotubes. The strict temporal and spatial regulation on Myog expression in the embryo makes it an ideal gene to study the developmental regulation of tissue-specific expression. Over the last 20 years, our knowledge of the regulation of Myog expression has evolved from the identification of the minimal promoter elements necessary for the gene to be transcribed in muscle, to a mechanistic understanding of how the proteins that bind these DNA elements work together to establish transcriptional competence. Here we present our current understanding of the developmental regulation of gene expression gained from studies of the Myog gene.

  8. Tissue-specific and substrate-specific mitochondrial bioenergetics in feline cardiac and skeletal muscles

    Christiansen, Liselotte Bruun; Dela, Flemming; Koch, Jørgen;

    2015-01-01

    No studies have investigated the mitochondrial function in permeabilized muscle fiber from cats. The aim of this study was to investigate tissue-specific and substrate-specific characteristics of mitochondrial oxidative phosphorylation (OXPHOS) capacity in feline permeabilized oxidative muscle...... fibers. Biopsies of left ventricular cardiac muscle and soleus muscle, a type I-rich oxidative skeletal muscle, were obtained from 15 healthy domestic cats. Enzymatic activity of citrate synthase (CS), a biomarker of mitochondrial content, was measured. Mitochondrial OXPHOS capacity with various kinds of...... non-fatty-acid substrates and fatty-acid substrate in permeabilized muscle fiber was measured by using high-resolution respirometry. CS activity in the heart was 3 times higher than in the soleus muscle. Mitochondrial state 3 respiration, ADP-stimulated respiration, with complex I-linked and complex I...

  9. Tissue-specific direct targets of Caenorhabditis elegans Rb/E2F dictate distinct somatic and germline programs

    Kudron, Michelle; Niu, Wei; Lu, Zhi; Wang, Guilin; Gerstein, Mark; Snyder, Michael; Reinke, Valerie

    2013-01-01

    Background The tumor suppressor Rb/E2F regulates gene expression to control differentiation in multiple tissues during development, although how it directs tissue-specific gene regulation in vivo is poorly understood. Results We determined the genome-wide binding profiles for Caenorhabditis elegans Rb/E2F-like components in the germline, in the intestine and broadly throughout the soma, and uncovered highly tissue-specific binding patterns and target genes. Chromatin association by LIN-35, th...

  10. Tension of knotted surgical sutures shows tissue specific rapid loss in a rodent model

    Klink Christian D

    2011-12-01

    Full Text Available Abstract Background Every surgical suture compresses the enclosed tissue with a tension that depends from the knotting force and the resistance of the tissue. The aim of this study was to identify the dynamic change of applied suture tension with regard to the tissue specific cutting reaction. Methods In rabbits we placed single polypropylene sutures (3/0 in skin, muscle, liver, stomach and small intestine. Six measurements for each single organ were determined by tension sensors for 60 minutes. We collected tissue specimens to analyse the connective tissue stability by measuring the collagen/protein content. Results We identified three phases in the process of suture loosening. The initial rapid loss of the first phase lasts only one minute. It can be regarded as cutting through damage of the tissue. The percentage of lost tension is closely related to the collagen content of the tissue (r = -0.424; p = 0.016. The second phase is characterized by a slower decrease of suture tension, reflecting a tissue specific plastic deformation. Phase 3 is characterized by a plateau representing the remaining structural stability of the tissue. The ratio of remaining tension to initial tension of phase 1 is closely related to the collagen content of the tissue (r = 0.392; p = 0.026. Conclusions Knotted non-elastic monofilament sutures rapidly loose tension. The initial phase of high tension may be narrowed by reduction of the surgeons' initial force of the sutures' elasticity to those of the tissue. Further studies have to confirm, whether reduced tissue compression and less local damage permits improved wound healing.

  11. Comparative Transcriptome Analysis Reveals Substantial Tissue Specificity in Human Aortic Valve

    Wang, Jun; Wang, Ying; Gu, Weidong; Ni, Buqing; Sun, Haoliang; Yu, Tong; Gu, Wanjun; Chen, Liang; Shao, Yongfeng

    2016-01-01

    RNA sequencing (RNA-seq) has revolutionary roles in transcriptome identification and quantification of different types of tissues and cells in many organisms. Although numerous RNA-seq data derived from many types of human tissues and cell lines, little is known on the transcriptome repertoire of human aortic valve. In this study, we sequenced the total RNA prepared from two calcified human aortic valves and reported the whole transcriptome of human aortic valve. Integrating RNA-seq data of 13 human tissues from Human Body Map 2 Project, we constructed a transcriptome repertoire of human tissues, including 19,505 protein-coding genes and 4,948 long intergenic noncoding RNAs (lincRNAs). Among them, 263 lincRNAs were identified as novel noncoding transcripts in our data. By comparing transcriptome data among different human tissues, we observed substantial tissue specificity of RNA transcripts, both protein-coding genes and lincRNAs, in human aortic valve. Further analysis revealed that aortic valve-specific lincRNAs were more likely to be recently derived from repetitive elements in the primate lineage, but were less likely to be conserved at the nucleotide level. Expression profiling analysis showed significant lower expression levels of aortic valve-specific protein-coding genes and lincRNA genes, when compared with genes that were universally expressed in various tissues. Isoform-level expression analysis also showed that a majority of mRNA genes had a major isoform expressed in the human aortic valve. To our knowledge, this is the first comparative transcriptome analysis between human aortic valve and other human tissues. Our results are helpful to understand the transcriptome diversity of human tissues and the underlying mechanisms that drive tissue specificity of protein-coding genes and lincRNAs in human aortic valve. PMID:27493474

  12. Multiple novel nesprin-1 and nesprin-2 variants act as versatile tissue-specific intracellular scaffolds.

    Dipen Rajgor

    Full Text Available BACKGROUND: Nesprins (Nuclear envelope spectrin-repeat proteins are a novel family of giant spectrin-repeat containing proteins. The nesprin-1 and nesprin-2 genes consist of 146 and 116 exons which encode proteins of ∼1mDa and ∼800 kDa is size respectively when all the exons are utilised in translation. However emerging data suggests that the nesprins have multiple alternative start and termination sites throughout their genes allowing the generation of smaller isoforms. RESULTS: In this study we set out to identify novel alternatively transcribed nesprin variants by screening the EST database and by using RACE analysis to identify cDNA ends. These two methods provided potential hits for alternative start and termination sites that were validated by PCR and DNA sequencing. We show that these alternative sites are not only expressed in a tissue specific manner but by combining different sites together it is possible to create a wide array of nesprin variants. By cloning and expressing small novel nesprin variants into human fibroblasts and U2OS cells we show localization to actin stress-fibres, focal adhesions, microtubules, the nucleolus, nuclear matrix and the nuclear envelope (NE. Furthermore we show that the sub-cellular localization of individual nesprin variants can vary depending on the cell type, suggesting any single nesprin variant may have different functions in different cell types. CONCLUSIONS: These studies suggest nesprins act as highly versatile tissue specific intracellular protein scaffolds and identify potential novel functions for nesprins beyond cytoplasmic-nuclear coupling. These alternate functions may also account for the diverse range of disease phenotypes observed when these genes are mutated.

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

    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

  14. Timing of Tissue-specific Cell Division Requires a Differential Onset of Zygotic Transcription during Metazoan Embryogenesis.

    Wong, Ming-Kin; Guan, Daogang; Ng, Kaoru Hon Chun; Ho, Vincy Wing Sze; An, Xiaomeng; Li, Runsheng; Ren, Xiaoliang; Zhao, Zhongying

    2016-06-10

    Metazoan development demands not only precise cell fate differentiation but also accurate timing of cell division to ensure proper development. How cell divisions are temporally coordinated during development is poorly understood. Caenorhabditis elegans embryogenesis provides an excellent opportunity to study this coordination due to its invariant development and widespread division asynchronies. One of the most pronounced asynchronies is a significant delay of cell division in two endoderm progenitor cells, Ea and Ep, hereafter referred to as E2, relative to its cousins that mainly develop into mesoderm organs and tissues. To unravel the genetic control over the endoderm-specific E2 division timing, a total of 822 essential and conserved genes were knocked down using RNAi followed by quantification of cell cycle lengths using in toto imaging of C. elegans embryogenesis and automated lineage. Intriguingly, knockdown of numerous genes encoding the components of general transcription pathway or its regulatory factors leads to a significant reduction in the E2 cell cycle length but an increase in cell cycle length of the remaining cells, indicating a differential requirement of transcription for division timing between the two. Analysis of lineage-specific RNA-seq data demonstrates an earlier onset of transcription in endoderm than in other germ layers, the timing of which coincides with the birth of E2, supporting the notion that the endoderm-specific delay in E2 division timing demands robust zygotic transcription. The reduction in E2 cell cycle length is frequently associated with cell migration defect and gastrulation failure. The results suggest that a tissue-specific transcriptional activation is required to coordinate fate differentiation, division timing, and cell migration to ensure proper development. PMID:27056332

  15. Tissue-specific MR contrast agents. Impact on imaging diagnosis and future prospects

    Superparamagnetic iron oxide (SPIO) is the only tissue-specific MR agent currently available in Japan. It is quickly taken up by Kupffer cells at the first pass (either arterial or portal) and becomes clustered in the lysosome, providing characteristic T2* and T2 shortening effects that suppresses the signal of normal or non-tumorous liver tissue. SPIO has dramatically changed the diagnostic algorithm of liver metastasis in clinical practice, now serving as the gold standard instead of CT during arterial portography (CTAP). Its role in the diagnosis of hepatocellular carcinoma (HCC), however, is somewhat complicated, owing to its heterogeneous uptake by the background cirrhotic liver, as well as by some of the HCCs themselves. It has been shown to be useful in the diagnosis of pseudolesions (arterioportal shunts) and some benign hepatocellular lesions (focal nodular hyperplasia or adenoma) by their complete or partial uptake of SPIO, in contrast to an absence of uptake by true liver lesions. It has also been suggested that the histological grade of HCC affects the degree of SPIO uptake. Thus, SPIO serves as a complementary tool to the primary modalities of vascular survey, namely, dynamic CT/MR and CT during hepatic arteriography (CTHA)/CTAP, in the diagnosis of HCC. Gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) is a novel hepatobiliary contrast agent that is not yet available but is supposed to be approved by the Ministry of Health, Labour, and Welfare of Japan in the near future. It is taken up by hepatocytes and excreted into the bile, providing a T1-shortening effect that enhances the normal or non-tumorous liver tissue. It has also been shown to have the effect of positive enhancement of hypervascular liver tumors on the arterial phase, just like the usual extracellular contrast agent (gadopentetate dimeglumine: Gd-DTPA). Thus, Gd-EOB-DTPA was once thought to be an ideal contrast agent for liver tumors, providing information on both

  16. Characterization and tissue-specific expression patterns of the Plasmodium chabaudi cir multigene family

    Krücken Jürgen

    2011-09-01

    Full Text Available Abstract Background Variant antigens expressed on the surface of parasitized red blood cells (pRBCs are important virulence factors of malaria parasites. Whereas Plasmodium falciparum erythrocyte membrane proteins 1 (PfEMP1 are responsible for sequestration of mature parasites, little is known about putative ligands mediating cytoadherence to host receptors in other Plasmodium species. Candidates include members of the pir superfamily found in the human parasite Plasmodium vivax (vir, in the simian pathogen Plasmodium knowlesi (kir and in the rodent malarias Plasmodium yoelii (yir, Plasmodium berghei (bir and Plasmodium chabaudi (cir. The aim of this study was to reveal a potential involvement of cir genes in P. chabaudi sequestration. Methods Subfamilies of cir genes were identified by bioinformatic analyses of annotated sequence data in the Plasmodium Genome Database. In order to examine tissue-specific differences in the expression of cir mRNAs, RT-PCR with subfamily-specific primers was used. In total, 432 cDNA clones derived from six different tissues were sequenced to characterize the transcribed cir gene repertoire. To confirm differences in transcription profiles of cir genes, restriction fragment length polymorphism (RFLP analyses were performed to compare different host tissues and to identify changes during the course of P. chabaudi infections in immunocompetent mice. Results The phylogenetic analysis of annotated P. chabaudi putative CIR proteins identified two major subfamilies. Comparison of transcribed cir genes from six different tissues revealed significant differences in the frequency clones belonging to individual cir gene subgroups were obtained from different tissues. Further hints of difference in the transcription of cir genes in individual tissues were obtained by RFLP. Whereas only minimal changes in the transcription pattern of cir genes could be detected during the developmental cycle of the parasites, switching to

  17. Whole-organ isolation approach as a basis for tissue-specific analyses in Schistosoma mansoni.

    Steffen Hahnel

    Full Text Available BACKGROUND: Schistosomiasis is one of the most important parasitic diseases worldwide, second only to malaria. Schistosomes exhibit an exceptional reproductive biology since the sexual maturation of the female, which includes the differentiation of the reproductive organs, is controlled by pairing. Pathogenicity originates from eggs, which cause severe inflammation in their hosts. Elucidation of processes contributing to female maturation is not only of interest to basic science but also considering novel concepts combating schistosomiasis. METHODOLOGY/PRINCIPAL FINDINGS: To get direct access to the reproductive organs, we established a novel protocol using a combined detergent/protease-treatment removing the tegument and the musculature of adult Schistosoma mansoni. All steps were monitored by scanning electron microscopy (SEM and bright-field microscopy (BF. We focused on the gonads of adult schistosomes and demonstrated that isolated and purified testes and ovaries can be used for morphological and structural studies as well as sources for RNA and protein of sufficient amounts for subsequent analyses such as RT-PCR and immunoblotting. To this end, first exemplary evidence was obtained for tissue-specific transcription within the gonads (axonemal dynein intermediate chain gene SmAxDynIC; aquaporin gene SmAQP as well as for post-transcriptional regulation (SmAQP. CONCLUSIONS/SIGNIFICANCE: The presented method provides a new way of getting access to tissue-specific material of S. mansoni. With regard to many still unanswered questions of schistosome biology, such as elucidating the molecular processes involved in schistosome reproduction, this protocol provides opportunities for, e.g., sub-transcriptomics and sub-proteomics at the organ level. This will promote the characterisation of gene-expression profiles, or more specifically to complete knowledge of signalling pathways contributing to differentiation processes, so discovering involved

  18. Tissue-specific targeting of cell fate regulatory genes by E2f factors.

    Julian, L M; Liu, Y; Pakenham, C A; Dugal-Tessier, D; Ruzhynsky, V; Bae, S; Tsai, S-Y; Leone, G; Slack, R S; Blais, A

    2016-04-01

    Cell cycle proteins are important regulators of diverse cell fate decisions, and in this capacity have pivotal roles in neurogenesis and brain development. The mechanisms by which cell cycle regulation is integrated with cell fate control in the brain and other tissues are poorly understood, and an outstanding question is whether the cell cycle machinery regulates fate decisions directly or instead as a secondary consequence of proliferative control. Identification of the genes targeted by E2 promoter binding factor (E2f) transcription factors, effectors of the pRb/E2f cell cycle pathway, will provide essential insights into these mechanisms. We identified the promoter regions bound by three neurogenic E2f factors in neural precursor cells in a genome-wide manner. Through bioinformatic analyses and integration of published genomic data sets we uncovered hundreds of transcriptionally active E2f-bound promoters corresponding to genes that control cell fate processes, including key transcriptional regulators and members of the Notch, fibroblast growth factor, Wnt and Tgf-β signaling pathways. We also demonstrate a striking enrichment of the CCCTC binding factor transcription factor (Ctcf) at E2f3-bound nervous system-related genes, suggesting a potential regulatory co-factor for E2f3 in controlling differentiation. Finally, we provide the first demonstration of extensive tissue specificity among E2f target genes in mammalian cells, whereby E2f3 promoter binding is well conserved between neural and muscle precursors at genes associated with cell cycle processes, but is tissue-specific at differentiation-associated genes. Our findings implicate the cell cycle pathway as a widespread regulator of cell fate genes, and suggest that E2f3 proteins control cell type-specific differentiation programs by regulating unique sets of target genes. This work significantly enhances our understanding of how the cell cycle machinery impacts cell fate and differentiation, and will

  19. Tissue-Specific Ablation of Prkar1a Causes Schwannomas by Suppressing Neurofibromatosis Protein Production

    Georgette N. Jones

    2008-11-01

    Full Text Available Signaling events leading to Schwann cell tumor initiation have been extensively characterized in the context of neurofibromatosis (NF. Similar tumors are also observed in patients with the endocrine neoplasia syndrome Carney complex, which results from inactivating mutations in PRKAR1A. Loss of PRKAR1A causes enhanced protein kinase A activity, although the pathways leading to tumorigenesis are not well characterized. Tissue-specific ablation of Prkar1a in neural crest precursor cells (TEC3KO mice causes schwannomas with nearly 80% penetrance by 10 months. These heterogeneous neoplasms were clinically characterized as genetically engineered mouse schwannomas, grades II and III. At the molecular level, analysis of the tumors revealed almost complete loss of both NF proteins, despite the fact that transcript levels were increased, implying posttranscriptional regulation. Although Erk and Akt signaling are typically enhanced in NF-associated tumors, we observed no activation of either of these pathways in TEC3KO tumors. Furthermore, the small G proteins Ras, Rac1, and RhoA are all known to be involved with NF signaling. In TEC3KO tumors, all three molecules showed modest increases in total protein, but only Rac1 showed significant activation. These data suggest that dysregulated protein kinase A activation causes tumorigenesis through pathways that overlap but are distinct from those described in NF tumorigenesis.

  20. An Arabidopsis tissue-specific RNAi method for studying genes essential to mitosis.

    Burgos-Rivera, Brunilís; Dawe, R Kelly

    2012-01-01

    A large fraction of the genes in plants can be considered essential in the sense that when absent the plant fails to develop past the first few cell divisions. The fact that angiosperms pass through a haploid gametophyte stage can make it challenging to propagate such mutants even in the heterozygous condition. Here we describe a tissue-specific RNAi method that allows us to visualize cell division phenotypes in petals, which are large dispensable organs. Portions of the APETALA (AP3) and PISTILLATA (PI) promoters confer early petal-specific expression. We show that when either promoter is used to drive the expression of a beta-glucuronidase (GUS) RNAi transgene in plants uniformly expressing GUS, GUS expression is knocked down specifically in petals. We further tested the system by targeting the essential kinetochore protein CENPC and two different components of the Spindle Assembly Checkpoint (MAD2 and BUBR1). Plant lines expressing petal-specific RNAi hairpins targeting these genes exhibited an array of petal phenotypes. Cytological analyses of the affected flower buds confirmed that CENPC knockdown causes cell cycle arrest but provided no evidence that either MAD2 or BUBR1 are required for mitosis (although both genes are required for petal growth by this assay). A key benefit of the petal-specific RNAi method is that the phenotypes are not expressed in the lineages leading to germ cells, and the phenotypes are faithfully transmitted for at least four generations despite their pronounced effects on growth. PMID:23236491

  1. Nuclear factor 1 regulates adipose tissue-specific expression in the mouse GLUT4 gene

    Previous studies demonstrated that an adipose tissue-specific element(s) (ASE) of the murine GLUT4 gene is located between -551 and -506 in the 5'-flanking sequence and that a high-fat responsive element(s) for down-regulation of the GLUT4 gene is located between bases -701 and -552. A binding site for nuclear factor 1 (NF1), that mediates insulin and cAMP-induced repression of GLUT4 in 3T3-L1 adipocytes is located between bases -700 and -688. To examine the role of NF1 in the regulation of GLUT4 gene expression in white adipose tissues (WAT) in vivo, we created two types of transgenic mice harboring mutated either 5' or 3' half-site of NF1-binding sites in GLUT4 minigene constructs. In both cases, the GLUT4 minigene was not expressed in WAT, while expression was maintained in brown adipose tissue, skeletal muscle, and heart. This was an unexpected finding, since a -551 GLUT4 minigene that did not have the NF1-binding site was expressed in WAT. We propose a model that explains the requirement for both the ASE and the NF1-binding site for expression of GLUT4 in WAT

  2. Expression of PIN Genes in Rice (Oryza sativa L.):Tissue Specificity and Regulation by Hormones

    Ji-Rong Wang; Han Hu; Gao-Hang Wang; Jing Li; Jie-Yu Chen; Ping Wu

    2009-01-01

    Twelve genes of the PIN family in rice were analyzed for gene and protein structures and an evolutionary relationship with reported AtPINs in Arabidopsis.Four members of PIN1 (designated as OsPIN1a-d),one gene paired with AtPIN2 (OsPIN2),three members of PIN5 (OsPIN5a-c),one gene paired with AtPIN8 (OsPIN8),and three monocot-specific PiNs (OsPINg,OsPIN10a,and b) were identified from the phylogenetic analysis.Tissue-specific expression patterns of nine PIN genes among them were investigated using RT-PCR and GUS reporter.The wide variations in the expression domain in different tissues of the PIN genes were observed.In general,PIN genes are up-regulated by exogenous auxin,while different responses of different PIN genes to other hormones were found.

  3. Tissue-specific concentrations and patterns of perfluoroalkyl carboxylates and sulfonates in East Greenland polar bears.

    Greaves, Alana K; Letcher, Robert J; Sonne, Christian; Dietz, Rune; Born, Erik W

    2012-11-01

    Several perfluoroalkyl carboxylates (PFCAs) and perfluoroalkyl sulfonates (PFSAs) of varying chain length are bioaccumulative in biota. However, wildlife reports have focused on liver and with very little examination of other tissues, and thus there is a limited understanding of their distribution and potential effects in the mammalian body. In the present study, the comparative accumulation of C(6) to C(15) PFCAs, C(4), C(6), C(8) and C(10) PFSAs, and select precursors were examined in the liver, blood, muscle, adipose, and brain of 20 polar bears (Ursus maritimus) from Scoresby Sound, Central East Greenland. Overall, PFSA and PFCA concentrations were highest in liver followed by blood > brain > muscle ≈ adipose. Liver and blood samples contained proportionally more of the shorter/medium chain length (C(6) to C(11)) PFCAs, whereas adipose and brain samples were dominated by longer chain (C(13) to C(15)) PFCAs. PFCAs with lower lipophilicities accumulated more in the liver, whereas the brain accumulated PFCAs with higher lipophilicities. The concentration ratios (±SE) between perfluorooctane sulfonate and its precursor perfluorooctane sulfonamide varied among tissues from 9 (±1):1 (muscle) to 36 (±7):1 (liver). PFCA and PFSA patterns in polar bears indicate that the pharmacokinetics of these compounds are to some extent tissue-specific, and are the result of several factors that may include differing protein interactions throughout the body. PMID:23057644

  4. Generation and Characterization of a Tissue-Specific Centrosome Indicator Mouse Line.

    Hirai, Maretoshi; Chen, Ju; Evans, Sylvia M

    2016-05-01

    Centrosomes are major microtubule organizing centers (MTOCs) that play an important role in chromosome segregation during cell division. Centrosomes provide a stable anchor for microtubules, constituting the centers of the spindle poles in mitotic cells, and determining the orientation of cell division. However, visualization of centrosomes is challenging because of their small size. Especially in mouse tissues, it has been extremely challenging to observe centrosomes belonging to a specific cell type of interest among multiple comingled cell types. To overcome this obstacle, we generated a tissue-specific centrosome indicator. In this mouse line, a construct containing a floxed neomyocin resistance gene with a triplicate polyA sequence followed by an EGFP-Centrin1 fusion cassette was knocked into the Rosa locus. Upon Cre-mediated excision, EGFP-Centrin1 was expressed under the control of the Rosa locus. Experiments utilizing mouse embryo fibroblasts (MEFs) demonstrated the feasibility of real-time imaging, and showed that EGFP-Centrin1 expression mirrored the endogenous centrosome cycle, undergoing precisely one round of duplication through the cell cycle. Moreover, experiments using embryo and adult mouse tissues demonstrated that EGFP-Centrin1 specifically mirrors the localization of endogenous centrosomes. genesis 54:286-296, 2016. © 2016 The Authors. Genesis Published by Wiley Periodicals, Inc. PMID:26990996

  5. Tissue-specific alterations in expression and function of P-glycoprotein in streptozotocininduced diabetic rats

    Lu-lu ZHANG; Guang-ji WANG; Lin XIE; Liang LU; Shi JIN; Xin-yue JING; Dan YAO; Nan HU; Li LIU; Ru DUAN; Xiao-dong LIU

    2011-01-01

    Aim: To investigate the changes of expression and function of P-glycoprotein (P-GP) in cerebral cortex, hippocampus, liver, intestinal mucosa and kidney of streptozocin-induced diabetic rats.Methods: Diabetic rats were prepared via a single dose of streptozocin (65 mg/kg, ip). Abcb1/P-GP mRNA and protein expression levels in tissues were evaluated using quantitative real time polymerase chain reaction (QRT-PCR) analysis and Western blot, respectively.P-GP function was investigated via measuring tissue-to-plasma concentration ratios and body fluid excretion percentages of rhodamine 123.Results: In 5- and 8-week diabetic rats, Abcb1a mRNA levels were significantly decreased in cerebral cortices and intestinal mucosa,but dramatically increased in hippocampus and kidney. In liver, the level was increased in 5-week diabetic rats, and decreased in 8-week diabetic rats. Abcb1b mRNA levels were increased in cerebral cortex, hippocampus and kidney, but reduced in liver and intestinal mucosa in the diabetic rats. Western blot results were in accordance with the alterations of Abcb1a mRNA levels in most tissues examined. P-GP activity was markedly decreased in most tissues of diabetic rats, except kidney tissues.Conclusion: Alterations in the expression and function of Abcb1/P-GP under diabetic conditions are tissue specific, Abcb1 specific and diabetic duration-dependent.

  6. Tissue-Specific Suppression of Thyroid Hormone Signaling in Various Mouse Models of Aging.

    W Edward Visser

    Full Text Available DNA damage contributes to the process of aging, as underscored by premature aging syndromes caused by defective DNA repair. Thyroid state changes during aging, but underlying mechanisms remain elusive. Since thyroid hormone (TH is a key regulator of metabolism, changes in TH signaling have widespread effects. Here, we reveal a significant common transcriptomic signature in livers from hypothyroid mice, DNA repair-deficient mice with severe (Csbm/m/Xpa-/- or intermediate (Ercc1-/Δ-7 progeria and naturally aged mice. A strong induction of TH-inactivating deiodinase D3 and decrease of TH-activating D1 activities are observed in Csbm/m/Xpa-/- livers. Similar findings are noticed in Ercc1-/Δ-7, in naturally aged animals and in wild-type mice exposed to a chronic subtoxic dose of DNA-damaging agents. In contrast, TH signaling in muscle, heart and brain appears unaltered. These data show a strong suppression of TH signaling in specific peripheral organs in premature and normal aging, probably lowering metabolism, while other tissues appear to preserve metabolism. D3-mediated TH inactivation is unexpected, given its expression mainly in fetal tissues. Our studies highlight the importance of DNA damage as the underlying mechanism of changes in thyroid state. Tissue-specific regulation of deiodinase activities, ensuring diminished TH signaling, may contribute importantly to the protective metabolic response in aging.

  7. Tissue-Specific Suppression of Thyroid Hormone Signaling in Various Mouse Models of Aging

    Visser, W. Edward; Barnhoorn, Sander; Ottaviani, Alexandre; van der Pluijm, Ingrid; Brandt, Renata; Kaptein, Ellen; van Heerebeek, Ramona; van Toor, Hans; Garinis, George A.; Peeters, Robin P.; Medici, Marco; van Ham, Willy; Vermeij, Wilbert P.; de Waard, Monique C.; de Krijger, Ronald R.; Boelen, Anita; Kwakkel, Joan; Kopchick, John J.; List, Edward O.; Melis, Joost P. M.; Darras, Veerle M.; Dollé, Martijn E. T.; van der Horst, Gijsbertus T. J.; Hoeijmakers, Jan H. J.; Visser, Theo J.

    2016-01-01

    DNA damage contributes to the process of aging, as underscored by premature aging syndromes caused by defective DNA repair. Thyroid state changes during aging, but underlying mechanisms remain elusive. Since thyroid hormone (TH) is a key regulator of metabolism, changes in TH signaling have widespread effects. Here, we reveal a significant common transcriptomic signature in livers from hypothyroid mice, DNA repair-deficient mice with severe (Csbm/m/Xpa-/-) or intermediate (Ercc1-/Δ-7) progeria and naturally aged mice. A strong induction of TH-inactivating deiodinase D3 and decrease of TH-activating D1 activities are observed in Csbm/m/Xpa-/- livers. Similar findings are noticed in Ercc1-/Δ-7, in naturally aged animals and in wild-type mice exposed to a chronic subtoxic dose of DNA-damaging agents. In contrast, TH signaling in muscle, heart and brain appears unaltered. These data show a strong suppression of TH signaling in specific peripheral organs in premature and normal aging, probably lowering metabolism, while other tissues appear to preserve metabolism. D3-mediated TH inactivation is unexpected, given its expression mainly in fetal tissues. Our studies highlight the importance of DNA damage as the underlying mechanism of changes in thyroid state. Tissue-specific regulation of deiodinase activities, ensuring diminished TH signaling, may contribute importantly to the protective metabolic response in aging. PMID:26953569

  8. Tissue specific characterisation of Lim-kinase 1 expression during mouse embryogenesis.

    Lindström, Nils O; Neves, Carlos; McIntosh, Rebecca; Miedzybrodzka, Zosia; Vargesson, Neil; Collinson, J Martin

    2011-01-01

    The Lim-kinase (LIMK) proteins are important for the regulation of the actin cytoskeleton, in particular the control of actin nucleation and depolymerisation via regulation of cofilin, and hence may control a large number of processes during development, including cell tensegrity, migration, cell cycling, and axon guidance. LIMK1/LIMK2 knockouts disrupt spinal cord morphogenesis and synapse formation but other tissues and developmental processes that require LIMK are yet to be fully determined. To identify tissues and cell-types that may require LIMK, we characterised the pattern of LIMK1 protein during mouse embryogenesis. We showed that LIMK1 displays an expression pattern that is temporally dynamic and tissue-specific. In several tissues LIMK1 is detected in cell-types that also express Wilms' tumour protein 1 and that undergo transitions between epithelial and mesenchymal states, including the pleura, epicardium, kidney nephrons, and gonads. LIMK1 was also found in a subset of cells in the dorsal retina, and in mesenchymal cells surrounding the peripheral nerves. This detailed study of the spatial and temporal expression of LIMK1 shows that LIMK1 expression is more dynamic than previously reported, in particular at sites of tissue-tissue interactions guiding multiple developmental processes. PMID:21167960

  9. Metabolic profiling of the tissue-specific responses in mussel Mytilus galloprovincialis towards Vibrio harveyi challenge.

    Liu, Xiaoli; Ji, Chenglong; Zhao, Jianmin; Wang, Qing; Li, Fei; Wu, Huifeng

    2014-08-01

    Mussel Mytilus galloprovincialis is a marine aquaculture shellfish distributing widely along the coast in north China. In this work, we studied the differential metabolic responses induced by Vibrio harveyi in digestive gland and gill tissues from M. galloprovincialis using NMR-based metabolomics. The differential metabolic responses in the two tissue types were detected, except the similarly altered taurine and betaine. These metabolic responses suggested that V. harveyi mainly induced osmotic disruption and reduced energy demand via the metabolic pathways of glucose synthesis and ATP/AMP conversion in mussel digestive gland. In mussel gill tissues, V. harveyi basically caused osmotic stress and possible reduced energy demand as shown by the elevated phosphocholine that is involved in one of the metabolic pathways of ATP synthesis from ADP and phosphocholine. The altered mRNA expression levels of related genes (superoxide dismutase with copper and zinc, heat shock protein 90, defensin and lysozyme) suggested that V. harveyi induced clear oxidative and immune stresses in both digestive gland and gill tissues. However, the mRNA expression levels of both lysozyme and defensin in digestive gland were more significantly up-regulated than those in gill from V. harveyi-challenged mussel M. galloprovincialis, meaning that the immune organ, digestive gland, was more sensitive than gill. Overall, our results indicated that V. harveyi could induce tissue-specific metabolic responses in mussel M. galloprovincialis. PMID:24911264

  10. Intermittent fasting results in tissue-specific changes in bioenergetics and redox state.

    Bruno Chausse

    Full Text Available Intermittent fasting (IF is a dietary intervention often used as an alternative to caloric restriction (CR and characterized by 24 hour cycles alternating ad libitum feeding and fasting. Although the consequences of CR are well studied, the effects of IF on redox status are not. Here, we address the effects of IF on redox state markers in different tissues in order to uncover how changes in feeding frequency alter redox balance in rats. IF rats displayed lower body mass due to decreased energy conversion efficiency. Livers in IF rats presented increased mitochondrial respiratory capacity and enhanced levels of protein carbonyls. Surprisingly, IF animals also presented an increase in oxidative damage in the brain that was not related to changes in mitochondrial bioenergetics. Conversely, IF promoted a substantial protection against oxidative damage in the heart. No difference in mitochondrial bioenergetics or redox homeostasis was observed in skeletal muscles of IF animals. Overall, IF affects redox balance in a tissue-specific manner, leading to redox imbalance in the liver and brain and protection against oxidative damage in the heart.

  11. Regulating expression of cell and tissue-specific genes by modifying transcription

    Beachy, Roger N; Dai, Shunhong

    2010-06-14

    Transcriptional regulation is the primary step to control gene expression, therefore function. Such regulation is achieved primarily via a combination of the activities of the promoter cis regulatory DNA elements and trans regulatory proteins that function through binding to these DNA elements. Rice bZIP transcription factors RF2a, RF2b and RLP1 play key roles in regulating the activity of a vascular tissue specific promoter isolated from Rice Tungro Bacilliform Virus (RTBV), through their interactions with the Box II essential cis element located in the promoter (Dai et al., 2006., Dai et al., 2004., Yin et al., 1997). RF2a, RF2b and RLP1 possess multiple regulatory domains. Functional characterization reveals that those domains can activate or repress the activity of the RTBV promoter. It is equally as important to recognize that these proteins control plant development by regulating differentiation and/or function of the vascular tissues. Studies of transcriptional regulation of the RTBV promoter by this group of bZIP proteins will not only provide insights about gene expression in the vascular tissue, but also insights about general mechanisms of transcription activation and repression. The knowledge gained from this research will also enable us to develop a well-described set of tools that can be used to control expression of multiple genes in transgenic plants. We have proposed characterize the function domains of RF2a, RF2b and RLP1 and explore the biological function of the transcription repressor RLP1.

  12. Regulating expressin of cell and tissue-specific genes by modifying transcription

    Beachy, R N; Dai, Shunhong

    2009-12-15

    Transcriptional regulation is the primary step to control gene expression, therefore function. Such regulation is achieved primarily via a combination of the activities of the promoter cis regulatory DNA elements and trans regulatory proteins that function through binding to these DNA elements. Our research supported by this program has led to the identification of rice bZIP transcription factors RF2a, RF2b and RLP1 that play key roles in regulating the activity of a vascular tissue specific promoter isolated from Rice Tungro Bacilliform Virus (RTBV) through their interactions with the Box II essential cis element located in the promoter. RF2a, RF2b and RLP1 possess multiple regulatory domains. Functional characterization reveals that those domains can activate or repress the activity of the RTBV promoter. Studies of transcriptional regulation of the RTBV promoter by this group of bZIP proteins not only provide insights about gene expression in the vascular tissue, but also insights about general mechanisms of transcription activation and repression. The knowledge gained from this research will also enable us to develop a well-described set of tools that can be used to control expression of multiple genes in transgenic plants and to improve biofuel feedstock.

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

    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.

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

    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.

  15. Differential Selective Constraints Shaping Codon Usage Pattern of Housekeeping and Tissue-specific Homologous Genes of Rice and Arabidopsis

    Mukhopadhyay, Pamela; Basak, Surajit; Ghosh, Tapash Chandra

    2008-01-01

    Intra-genomic variation between housekeeping and tissue-specific genes has always been a study of interest in higher eukaryotes. To-date, however, no such investigation has been done in plants. Availability of whole genome expression data for both rice and Arabidopsis has made it possible to examine the evolutionary forces in shaping codon usage pattern in both housekeeping and tissue-specific genes in plants. In the present work, we have taken 4065 rice–Arabidopsis homologous gene pairs to s...

  16. Interference with virus and bacteria replication by the tissue specific expression of antibodies and interfering molecules.

    Enjuanes, L; Sola, I; Izeta, A; Sánchez-Morgado, J M; González, J M; Alonso, S; Escors, D; Sánchez, C M

    1999-01-01

    Historically, protection against virus infections has relied on the use of vaccines, but the induction of an immune response requires several days and in certain situations, like in newborn animals that may be infected at birth and die in a few days, there is not sufficient time to elicit a protective immune response. Immediate protection in new born could be provided either by vectors that express virus-interfering molecules in a tissue specific form, or by the production of animals expressing resistance to virus replication. The mucosal surface is the largest body surface susceptible to virus infection that can serve for virus entry. Then, it is of high interest to develop strategies to prevent infections of these areas. Virus growth can be interfered intracellularly, extracellularly or both. The antibodies neutralize virus intra- and extracellularly and their molecular biology is well known. In addition, antibodies efficiently neutralize viruses in the mucosal areas. The autonomy of antibody molecules in virus neutralization makes them functional in cells different from those that produce the antibodies and in the extracellular medium. These properties have identified antibodies as very useful molecules to be expressed by vectors or in transgenic animals to provide resistance to virus infection. A similar role could be played by antimicrobial peptides in the case of bacteria. Intracellular interference with virus growth (intracellular immunity) can be mediated by molecules of very different nature: (i) full length or single chain antibodies; (ii) mutant viral proteins that strongly interfere with the replication of the wild type virus (dominant-negative mutants); (iii) antisense RNA and ribozyme sequences; and (iv) the product of antiviral genes such as the Mx proteins. All these molecules inhibiting virus replication may be used to obtain transgenic animals with resistance to viral infection built in their genomes. We have developed two strategies to target

  17. Tissue-Specific Gain of RTK Signalling Uncovers Selective Cell Vulnerability during Embryogenesis.

    Yannan Fan

    Full Text Available The successive events that cells experience throughout development shape their intrinsic capacity to respond and integrate RTK inputs. Cellular responses to RTKs rely on different mechanisms of regulation that establish proper levels of RTK activation, define duration of RTK action, and exert quantitative/qualitative signalling outcomes. The extent to which cells are competent to deal with fluctuations in RTK signalling is incompletely understood. Here, we employ a genetic system to enhance RTK signalling in a tissue-specific manner. The chosen RTK is the hepatocyte growth factor (HGF receptor Met, an appropriate model due to its pleiotropic requirement in distinct developmental events. Ubiquitously enhanced Met in Cre/loxP-based Rosa26(stopMet knock-in context (Del-R26(Met reveals that most tissues are capable of buffering enhanced Met-RTK signalling thus avoiding perturbation of developmental programs. Nevertheless, this ubiquitous increase of Met does compromise selected programs such as myoblast migration. Using cell-type specific Cre drivers, we genetically showed that altered myoblast migration results from ectopic Met expression in limb mesenchyme rather than in migrating myoblasts themselves. qRT-PCR analyses show that ectopic Met in limbs causes molecular changes such as downregulation in the expression levels of Notum and Syndecan4, two known regulators of morphogen gradients. Molecular and functional studies revealed that ectopic Met expression in limb mesenchyme does not alter HGF expression patterns and levels, but impairs HGF bioavailability. Together, our findings show that myoblasts, in which Met is endogenously expressed, are capable of buffering increased RTK levels, and identify mesenchymal cells as a cell type vulnerable to ectopic Met-RTK signalling. These results illustrate that embryonic cells are sensitive to alterations in the spatial distribution of RTK action, yet resilient to fluctuations in signalling levels of an

  18. Tissue-specific methylation of human insulin gene and PCR assay for monitoring beta cell death.

    Mohamed I Husseiny

    Full Text Available The onset of metabolic dysregulation in type 1 diabetes (T1D occurs after autoimmune destruction of the majority of pancreatic insulin-producing beta cells. We previously demonstrated that the DNA encoding the insulin gene is uniquely unmethylated in these cells and then developed a methylation-specific PCR (MSP assay to identify circulating beta cell DNA in streptozotocin-treated mice prior to the rise in blood glucose. The current study extends to autoimmune non-obese diabetic (NOD mice and humans, showing in NOD mice that beta cell death occurs six weeks before the rise in blood sugar and coincides with the onset of islet infiltration by immune cells, demonstrating the utility of MSP for monitoring T1D. We previously reported unique patterns of methylation of the human insulin gene, and now extend this to other human tissues. The methylation patterns of the human insulin promoter, intron 1, exon 2, and intron 2 were determined in several normal human tissues. Similar to our previous report, the human insulin promoter was unmethylated in beta cells, but methylated in all other tissues tested. In contrast, intron 1, exon 2 and intron 2 did not exhibit any tissue-specific DNA methylation pattern. Subsequently, a human MSP assay was developed based on the methylation pattern of the insulin promoter and human islet DNA was successfully detected in circulation of T1D patients after islet transplantation therapy. Signal levels of normal controls and pre-transplant samples were shown to be similar, but increased dramatically after islet transplantation. In plasma the signal declines with time but in whole blood remains elevated for at least two weeks, indicating that association of beta cell DNA with blood cells prolongs the signal. This assay provides an effective method to monitor beta cell destruction in early T1D and in islet transplantation therapy.

  19. Tissue-Specific Methylation of Human Insulin Gene and PCR Assay for Monitoring Beta Cell Death

    Husseiny, Mohamed I.; Kaye, Alexander; Zebadua, Emily; Kandeel, Fouad; Ferreri, Kevin

    2014-01-01

    The onset of metabolic dysregulation in type 1 diabetes (T1D) occurs after autoimmune destruction of the majority of pancreatic insulin-producing beta cells. We previously demonstrated that the DNA encoding the insulin gene is uniquely unmethylated in these cells and then developed a methylation-specific PCR (MSP) assay to identify circulating beta cell DNA in streptozotocin-treated mice prior to the rise in blood glucose. The current study extends to autoimmune non-obese diabetic (NOD) mice and humans, showing in NOD mice that beta cell death occurs six weeks before the rise in blood sugar and coincides with the onset of islet infiltration by immune cells, demonstrating the utility of MSP for monitoring T1D. We previously reported unique patterns of methylation of the human insulin gene, and now extend this to other human tissues. The methylation patterns of the human insulin promoter, intron 1, exon 2, and intron 2 were determined in several normal human tissues. Similar to our previous report, the human insulin promoter was unmethylated in beta cells, but methylated in all other tissues tested. In contrast, intron 1, exon 2 and intron 2 did not exhibit any tissue-specific DNA methylation pattern. Subsequently, a human MSP assay was developed based on the methylation pattern of the insulin promoter and human islet DNA was successfully detected in circulation of T1D patients after islet transplantation therapy. Signal levels of normal controls and pre-transplant samples were shown to be similar, but increased dramatically after islet transplantation. In plasma the signal declines with time but in whole blood remains elevated for at least two weeks, indicating that association of beta cell DNA with blood cells prolongs the signal. This assay provides an effective method to monitor beta cell destruction in early T1D and in islet transplantation therapy. PMID:24722187

  20. Tissue-specific modulation of mitochondrial DNA segregation by a defect in mitochondrial division.

    Jokinen, Riikka; Marttinen, Paula; Stewart, James B; Neil Dear, T; Battersby, Brendan J

    2016-02-15

    Mitochondria are dynamic organelles that divide and fuse by remodeling an outer and inner membrane in response to developmental, physiological and stress stimuli. These events are coordinated by conserved dynamin-related GTPases. The dynamics of mitochondrial morphology require coordination with mitochondrial DNA (mtDNA) to ensure faithful genome transmission, however, this process remains poorly understood. Mitochondrial division is linked to the segregation of mtDNA but how it affects cases of mtDNA heteroplasmy, where two or more mtDNA variants/mutations co-exist in a cell, is unknown. Segregation of heteroplasmic human pathogenic mtDNA mutations is a critical factor in the onset and severity of human mitochondrial diseases. Here, we investigated the coupling of mitochondrial morphology to the transmission and segregation of mtDNA in mammals by taking advantage of two genetically modified mouse models: one with a dominant-negative mutation in the dynamin-related protein 1 (Drp1 or Dnm1l) that impairs mitochondrial fission and the other, heteroplasmic mice segregating two neutral mtDNA haplotypes (BALB and NZB). We show a tissue-specific response to mtDNA segregation from a defect in mitochondrial fission. Only mtDNA segregation in the hematopoietic compartment is modulated from impaired Dnm1l function. In contrast, no effect was observed in other tissues arising from the three germ layers during development and in mtDNA transmission through the female germline. Our data suggest a robust organization of a heteroplasmic mtDNA segregating unit across mammalian cell types that can overcome impaired mitochondrial division to ensure faithful transmission of the mitochondrial genome. PMID:26681804

  1. Depleted uranium induces sex- and tissue-specific methylation patterns in adult zebrafish.

    Gombeau, Kewin; Pereira, Sandrine; Ravanat, Jean-Luc; Camilleri, Virginie; Cavalie, Isabelle; Bourdineaud, Jean-Paul; Adam-Guillermin, Christelle

    2016-04-01

    We examined the effects of chronic exposure to different concentrations (2 and 20 μg L(-)(1)) of environmentally relevant waterborne depleted uranium (DU) on the DNA methylation patterns both at HpaII restriction sites (5'-CCGG-3') and across the whole genome in the zebrafish brain, gonads, and eyes. We first identified sex-dependent differences in the methylation level of HpaII sites after exposure. In males, these effects were present as early as 7 days after exposure to 20 μg L(-)(1) DU, and were even more pronounced in the brain, gonads, and eyes after 24 days. However, in females, hypomethylation was only observed in the gonads after exposure to 20 μg L(-)(1) DU for 24 days. Sex-specific effects of DU were also apparent at the whole-genome level, because in males, exposure to 20 μg L(-)(1) DU for 24 days resulted in cytosine hypermethylation in the brain and eyes and hypomethylation in the gonads. In contrast, in females, hypermethylation was observed in the brain after exposure to both concentrations of DU for 7 days. Based on our current knowledge of uranium toxicity, several hypotheses are proposed to explain these findings, including the involvement of oxidative stress, alteration of demethylation enzymes and the calcium signaling pathway. This study reports, for the first time, the sex- and tissue-specific epigenetic changes that occur in a nonhuman organism after exposure to environmentally relevant concentrations of uranium, which could induce transgenerational epigenetic effects. PMID:26829549

  2. Tissue-specific gene expression in maize seeds during colonization by Aspergillus flavus and Fusarium verticillioides.

    Shu, Xiaomei; Livingston, David P; Franks, Robert G; Boston, Rebecca S; Woloshuk, Charles P; Payne, Gary A

    2015-09-01

    Aspergillus flavus and Fusarium verticillioides are fungal pathogens that colonize maize kernels and produce the harmful mycotoxins aflatoxin and fumonisin, respectively. Management practice based on potential host resistance to reduce contamination by these mycotoxins has proven difficult, resulting in the need for a better understanding of the infection process by these fungi and the response of maize seeds to infection. In this study, we followed the colonization of seeds by histological methods and the transcriptional changes of two maize defence-related genes in specific seed tissues by RNA in situ hybridization. Maize kernels were inoculated with either A. flavus or F. verticillioides 21-22 days after pollination, and harvested at 4, 12, 24, 48, 72, 96 and 120 h post-inoculation. The fungi colonized all tissues of maize seed, but differed in their interactions with aleurone and germ tissues. RNA in situ hybridization showed the induction of the maize pathogenesis-related protein, maize seed (PRms) gene in the aleurone and scutellum on infection by either fungus. Transcripts of the maize sucrose synthase-encoding gene, shrunken-1 (Sh1), were observed in the embryo of non-infected kernels, but were induced on infection by each fungus in the aleurone and scutellum. By comparing histological and RNA in situ hybridization results from adjacent serial sections, we found that the transcripts of these two genes accumulated in tissue prior to the arrival of the advancing pathogens in the seeds. A knowledge of the patterns of colonization and tissue-specific gene expression in response to these fungi will be helpful in the development of resistance. PMID:25469958

  3. Tissue-specific promoters active in CD44+CD24-/low breast cancer cells.

    Bauerschmitz, Gerd J; Ranki, Tuuli; Kangasniemi, Lotta; Ribacka, Camilla; Eriksson, Minna; Porten, Marius; Herrmann, Isabell; Ristimäki, Ari; Virkkunen, Pekka; Tarkkanen, Maija; Hakkarainen, Tanja; Kanerva, Anna; Rein, Daniel; Pesonen, Sari; Hemminki, Akseli

    2008-07-15

    It has been proposed that human tumors contain stem cells that have a central role in tumor initiation and posttreatment relapse. Putative breast cancer stem cells may reside in the CD44(+)CD24(-/low) population. Oncolytic adenoviruses are attractive for killing of these cells because they enter through infection and are therefore not susceptible to active and passive mechanisms that render stem cells resistant to many drugs. Although adenoviruses have been quite safe in cancer trials, preclinical work suggests that toxicity may eventually be possible with more active agents. Therefore, restriction of virus replication to target tissues with tissues-specific promoters is appealing for improving safety and can be achieved without loss of efficacy. We extracted CD44(+)CD24(-/low) cells from pleural effusions of breast cancer patients and found that modification of adenovirus type 5 tropism with the serotype 3 knob increased gene delivery to CD44(+)CD24(-/low) cells. alpha-Lactalbumin, cyclo-oxygenase 2, telomerase, and multidrug resistance protein promoters were studied for activity in CD44(+)CD24(-/low) cells, and a panel of oncolytic viruses was subsequently constructed. Each virus featured 5/3 chimerism of the fiber and a promoter controlling expression of E1A, which was also deleted in the Rb binding domain for additional tumor selectivity. Cell killing assays identified Ad5/3-cox2L-d24 and Ad5/3-mdr-d24 as the most active agents, and these viruses were able to completely eradicate CD44(+)CD24(-/low) cells in vitro. In vivo, these viruses had significant antitumor activity in CD44(+)CD24(-/low)-derived tumors. These findings may have relevance for elimination of cancer stem cells in humans. PMID:18632604

  4. Tissue specificity in rat peripheral nerve regeneration through combined skeletal muscle and vein conduit grafts.

    Tos, P; Battiston, B; Geuna, S; Giacobini-Robecchi, M G; Hill, M A; Lanzetta, M; Owen, E R

    2000-01-01

    Diffusible factors from the distal stumps of transected peripheral nerves exert a neurotropic effect on regenerating nerves in vivo (specificity). This morphological study was designed to investigate the existence of tissue specificity in peripheral nerve fiber regeneration through a graft of vein filled with fresh skeletal muscle. This tubulization technique demonstrated experimental and clinical results similar to those obtained with traditional autologous nerve grafts. Specifically, we used Y-shaped grafts to assess the orientation pattern of regenerating axons in the distal stump tissue. Animal models were divided into four experimental groups. The proximal part of the Y-shaped conduit was sutured to a severed tibial nerve in all experiments. The two distal stumps were sutured to different targets: group A to two intact nerves (tibial and peroneal), group B to an intact nerve and an unvascularized tendon, group C to an intact nerve and a vascularized tendon, and group D to a nerve graft and an unvascularized tendon. Morphological evaluation by light and electron microscopy was conducted in the distal forks of the Y-shaped tube. Data showed that almost all regenerating nerve fibers spontaneously oriented towards the nerve tissue (attached or not to the peripheral innervation field), showing a good morphological pattern of regeneration in both the early and late phases of regeneration. When the distal choice was represented by a tendon (vascularized or not), very few nerve fibers were detected in the corresponding distal fork of the Y-shaped graft. These results show that, using the muscle-vein-combined grafting technique, regenerating axons are able to correctly grow and orientate within the basement membranes of the graft guided by the neurotropic lure of the distal nerve stump. PMID:10702739

  5. Detection of neuronal tissue in meat using tissue specific DNA modifications

    Harris N.

    2004-01-01

    Full Text Available A method has been developed to differentiate between non-muscle tissues such as liver, kidney and heart and that of muscle in meat samples using tissue specific DNA detection. Only muscle tissue is considered meat from the point of view of labelling (Food Labelling [Amendment] (England Regulations 2003 and Quantitative Ingredient Declaration (QUID, and also certain parts of the carcass are prohibited to be used in raw meat products (Meat Products [England] Regulations 2003. Included in the prohibited offal are brain and spinal cord. The described methodology has therefore been developed primarily to enforce labelling rules but also to contribute to the enforcement of BSE legislation on the detection of Central Nervous System (CNS tissue. The latter requires the removal of Specified Risk Material (SRM, such as bovine and ovine brain and spinal cord, from the food chain. Current methodologies for detection of CNS tissue include histological examination, analysis of cholesterol content and immunodetection. These can potentially be time consuming, less applicable to processed samples and may not be readily adapted to high throughput sample analysis. The objective of this work was therefore to develop a DNAbased detection assay that exploits the sensitivity and specificity of PCR and is potentially applicable to more highly processed food samples. For neuronal tissue, the DNA target selected was the promoter for Glial Fibrillary Acidic Protein (GFAP, a gene whose expression is restricted to astroglial cells within CNS tissue. The promoter fragments from both cattle and sheep have been isolated and key differences in the methylation patterns of certain CpG dinucleotides in the sequences from bovine and sheep brain and spinal cord and the corresponding skeletal muscle identified. These have been used to design a PCR assay exploiting Methylation Specific PCR (MSP to specifically amplify the neuronal tissue derived sequence and therefore identify the

  6. Weak mitochondrial targeting sequence determines tissue-specific subcellular localization of glutamine synthetase in liver and brain cells.

    Matthews, Gideon D; Gur, Noa; Koopman, Werner J H; Pines, Ophry; Vardimon, Lily

    2010-02-01

    Evolution of the uricotelic system for ammonia detoxification required a mechanism for tissue-specific subcellular localization of glutamine synthetase (GS). In uricotelic vertebrates, GS is mitochondrial in liver cells and cytoplasmic in brain. Because these species contain a single copy of the GS gene, it is not clear how tissue-specific subcellular localization is achieved. Here we show that in chicken, which utilizes the uricotelic system, the GS transcripts of liver and brain cells are identical and, consistently, there is no difference in the amino acid sequence of the protein. The N-terminus of GS, which constitutes a 'weak' mitochondrial targeting signal (MTS), is sufficient to direct a chimeric protein to the mitochondria in hepatocytes and to the cytoplasm in astrocytes. Considering that a weak MTS is dependent on a highly negative mitochondrial membrane potential (DeltaPsi) for import, we examined the magnitude of DeltaPsi in hepatocytes and astrocytes. Our results unexpectedly revealed that DeltaPsi in hepatocytes is considerably more negative than that of astrocytes and that converting the targeting signal into 'strong' MTS abolished the capability to confer tissue-specific subcellular localization. We suggest that evolutional selection of weak MTS provided a tool for differential targeting of an identical protein by taking advantage of tissue-specific differences in DeltaPsi. PMID:20053634

  7. A comparative approach to understanding tissue-specific expression of uncoupling protein 1 expression in adipose tissue

    Andrew eShore

    2013-01-01

    Full Text Available The thermoregulatory function of brown adipose tissue (BAT is due to the tissue-specific expression of uncoupling protein 1 (UCP1 which is thought to have evolved in early mammals. We report that a CpG island close to the UCP1 transcription start site is highly conserved in all 29 vertebrates examined apart from the mouse and xenopus. Using methylation sensitive restriction digest and bisulphite mapping we show that the CpG island in both the bovine and human is largely un-methylated and is not related to differences in UCP1 expression between white and brown adipose tissue. Tissue-specific expression of UCP1 has been proposed to be regulated by a conserved 5’ distal enhancer which has been reported to be absent in marsupials. We demonstrate that the enhancer, is also absent in 5 eutherians as well as marsupials, monotremes, amphibians and fish, is present in pigs despite UCP1 having become a pseudogene, and that absence of the enhancer element does not relate to brown adipose tissue-specific UCP1 expression. We identify an additional putative 5’ regulatory unit which is conserved in 14 eutherian species but absent in other eutherians and vertebrates, but again unrelated to UCP1 expression. We conclude that despite clear evidence of conservation of regulatory elements in the UCP1 5’ untranslated region, this does not appear to be related to species or tissues-specific expression of UCP1.

  8. Genomic organization of mouse orexin receptors: characterization of two novel tissue-specific splice variants.

    Chen, Jing; Randeva, Harpal S

    2004-11-01

    In humans and rat, orexins orchestrate divergent actions through their G protein-coupled receptors, orexin-1 (OX1R) and orexin-2 (OX2R). Orexins also play an important physiological role in mouse, but the receptors through which they function are not characterized. To characterize the physiological role(s) of orexins in the mouse, we cloned and characterized the mouse orexin receptor(s), mOX1R and mOX2R, using rapid amplification of cDNA (mouse brain) ends, RT-PCR, and gene structure analysis. The mOX1R cDNA encodes a 416-amino acid (aa) receptor. We have identified two alternative C terminus splice variants of the mOX2R; mOX2 alpha R (443 aa) and mOX2 beta R (460 aa). Binding studies in human embryonic kidney 293 cells transfected with mOX1R, mOX2 alpha R, and the mOX2 beta R revealed specific, saturable sites for both orexin-A and -B. Activation of these receptors by orexins induced inositol triphosphate (IP(3)) turnover. However, human embryonic kidney 293 cells transfected with mOXRs demonstrated no cAMP response to either orexin-A or orexin-B challenge, although forskolin and GTP gamma S revealed a dose-dependent increase in cAMP. Although, orexin-A and -B showed no difference in binding characteristics between the splice variants; interestingly, orexin-B led to an increase in IP(3) production at all concentrations in the mOX2 beta R variant. Orexin-A, however, showed no difference in IP(3) production between the two variants. Additionally, in the mouse, we demonstrate that these splice variants are distributed in a tissue-specific manner, where OX2 alpha R mRNA was undetectable in skeletal muscle and kidney. Moreover, food deprivation led to a greater increase in hypothalamic mOX2 beta R gene expression, compared with both mOX1R and mOX2 alpha R. This potentially implicates a fundamental physiological role for these splice variants. PMID:15256537

  9. Acquisition and evolution of plant pathogenesis-associated gene clusters and candidate determinants of tissue-specificity in xanthomonas.

    Hong Lu

    Full Text Available BACKGROUND: Xanthomonas is a large genus of plant-associated and plant-pathogenic bacteria. Collectively, members cause diseases on over 392 plant species. Individually, they exhibit marked host- and tissue-specificity. The determinants of this specificity are unknown. METHODOLOGY/PRINCIPAL FINDINGS: To assess potential contributions to host- and tissue-specificity, pathogenesis-associated gene clusters were compared across genomes of eight Xanthomonas strains representing vascular or non-vascular pathogens of rice, brassicas, pepper and tomato, and citrus. The gum cluster for extracellular polysaccharide is conserved except for gumN and sequences downstream. The xcs and xps clusters for type II secretion are conserved, except in the rice pathogens, in which xcs is missing. In the otherwise conserved hrp cluster, sequences flanking the core genes for type III secretion vary with respect to insertion sequence element and putative effector gene content. Variation at the rpf (regulation of pathogenicity factors cluster is more pronounced, though genes with established functional relevance are conserved. A cluster for synthesis of lipopolysaccharide varies highly, suggesting multiple horizontal gene transfers and reassortments, but this variation does not correlate with host- or tissue-specificity. Phylogenetic trees based on amino acid alignments of gum, xps, xcs, hrp, and rpf cluster products generally reflect strain phylogeny. However, amino acid residues at four positions correlate with tissue specificity, revealing hpaA and xpsD as candidate determinants. Examination of genome sequences of xanthomonads Xylella fastidiosa and Stenotrophomonas maltophilia revealed that the hrp, gum, and xcs clusters are recent acquisitions in the Xanthomonas lineage. CONCLUSIONS/SIGNIFICANCE: Our results provide insight into the ancestral Xanthomonas genome and indicate that differentiation with respect to host- and tissue-specificity involved not major

  10. Tissue specific promoters improve the localization of radiation-inducible gene expression

    expression was quantified in vascular endothelial cells from large vessel (HUVEC) and small vessels (HMEC). We found cell-type specificity of radiation-induction. The promoter region from the ELAM gene gave no expression in cells that were not of endothelial cell origin and x-ray-induction of ELAM in the endothelium required the NFkB binding cis-acting element. ELAM induction was achieved at doses as low as 1 Gy, whereas induction of other radiation inducible genes required 5 to 10 Gy. Cells transfected with the minimal promoter (plasmid pTK-CAT) demonstrated no radiation induction. Expression of the CMV-LacZ genetic construct that was used as a negative control in each transfection was not altered by x-irradiation. Moreover, intravenous administration of liposomes containing a reporter gene linked to the ELAM promoter and a transcriptional amplification system were induced specifically at sites of x-irradiation in an animal model. Conclusions: Activation of transcription of the ELAM-1 promoter by ionizing radiation is a means of activating gene therapy within the vascular endothelium and demonstrates the feasibility of treating vascular lesions with noninvasive procedures. Tissue specific promoters (e. g., ELAM-1) combined with radiation inducible gene therapy improves the localization of gene therapy expression. These results have applications in intravascular brachytherapy for the prevention of blood vessel restenosis

  11. Identification of CTLA2A, DEFB29, WFDC15B, SERPINA1F and MUP19 as Novel Tissue-Specific Secretory Factors in Mouse.

    Jibin Zhang

    Full Text Available Secretory factors in animals play an important role in communication between different cells, tissues and organs. Especially, the secretory factors with specific expression in one tissue may reflect important functions and unique status of that tissue in an organism. In this study, we identified potential tissue-specific secretory factors in the fat, muscle, heart, lung, kidney and liver in the mouse by analyzing microarray data from NCBI's Gene Expression Omnibus (GEO public repository and searching and predicting their subcellular location in GeneCards and WoLF PSORT, and then confirmed tissue-specific expression of the genes using semi-quantitative PCR reactions. With this approach, we confirmed 11 lung, 7 liver, 2 heart, 1 heart and muscle, 7 kidney and 2 adipose and liver-specific secretory factors. Among these genes, 1 lung-specific gene--CTLA2A (cytotoxic T lymphocyte-associated protein 2 alpha, 3 kidney-specific genes--SERPINA1F (serpin peptidase inhibitor, Clade A, member 1F, WFDC15B (WAP four-disulfide core domain 15B and DEFB29 (defensin beta 29 and 1 liver-specific gene--MUP19 (major urinary protein 19 have not been reported as secretory factors. These genes were tagged with hemagglutinin at the 3'end and then transiently transfected to HEK293 cells. Through protein detection in cell lysate and media using Western blotting, we verified secretion of the 5 genes and predicted the potential pathways in which they may participate in the specific tissue through data analysis of GEO profiles. In addition, alternative splicing was detected in transcripts of CTLA2A and SERPINA1F and the corresponding proteins were found not to be secreted in cell culture media. Identification of novel secretory factors through the current study provides a new platform to explore novel secretory factors and a general direction for further study of these genes in the future.

  12. Starvation resistance and tissue-specific gene expression of stress-related genes in a naturally inbred ant population.

    Bos, Nick; Pulliainen, Unni; Sundström, Liselotte; Freitak, Dalial

    2016-04-01

    Starvation is one of the most common and severe stressors in nature. Not only does it lead to death if not alleviated, it also forces the starved individual to allocate resources only to the most essential processes. This creates energetic trade-offs which can lead to many secondary challenges for the individual. These energetic trade-offs could be exacerbated in inbred individuals, which have been suggested to have a less efficient metabolism. Here, we studied the effect of inbreeding on starvation resistance in a natural population of Formica exsecta ants, with a focus on survival and tissue-specific expression of stress, metabolism and immunity-related genes. Starvation led to large tissue-specific changes in gene expression, but inbreeding had little effect on most of the genes studied. Our results illustrate the importance of studying stress responses in different tissues instead of entire organisms. PMID:27152219

  13. The three mouse multidrug resistance (mdr) genes are expressed in a tissue-specific manner in normal mouse tissues.

    Croop, J M; Raymond, M; Haber, D; Devault, A; Arceci, R. J.; Gros, P.; Housman, D.E.

    1989-01-01

    The gene responsible for multidrug resistance (mdr), which encodes the P-glycoprotein, is a member of a multigene family. We have identified distinct mdr gene transcripts encoded by three separate mdr genes in the mouse. Expression levels of each mdr gene are dramatically different in various mouse tissues. Specific mdr RNA transcripts of approximately 4.5, 5, and 6 kilobases have been detected. Each of the mdr genes has a specific RNA transcript pattern. These results should be considered in...

  14. Glow in the Dark: Fluorescent Proteins as Cell and Tissue-Specific Markers in Plants

    Wenzislava Ckurshumova; Adriana E. Caragea; Rochelle S. Goldstein; Thomas Berleth

    2011-01-01

    Since the hallmark discovery of Aequorea victoria's Green Fluorescent Protein (GFP) and its adaptation for efficient use in plants,fluorescent protein tags marking expression profiles or genuine proteins of interest have been used to recognize plant tissues and cell types,to monitor dynamic cell fate selection processes,and to obtain cell type-specific transcriptomes.Fluorescent tagging enabled visualization in living tissues and the precise recordings of dynamic expression pattern changes.The resulting accurate recording of cell fate acquisition kinetics in space and time has strongly stimulated mathematical modeling of self-organizing feedback mechanisms.In developmental studies,the use of fluorescent proteins has become critical,where morphological markers of tissues,cell types,or differentiation stages are either not known or not easily recognizable.In this review,we focus on the use of fluorescent markers to identify and illuminate otherwise invisible cell states in plant development.

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

    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...

  16. 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?

    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.

  17. Use of mouse models to understand the molecular basis of tissue-specific tumorigenesis in the Carney complex.

    Kirschner, L S

    2009-07-01

    Carney complex (CNC) is an autosomal dominant, multiple endocrine neoplasia syndrome comprised of spotty skin pigmentation, myxomatosis, endocrine tumours and schwannomas. The majority of cases are due to inactivating mutations in PRKAR1A, the gene encoding the type 1A regulatory subunit of the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase, PKA (protein kinase A). In order to understand the molecular basis for tumorigenesis associated with PRKAR1A mutations, we have developed conventional and conditional Prkar1a knockout (KO) mice as well as primary cell culture models corresponding to these genetic manipulations. At the biochemical level, removal of Prkar1a from cells causes enhanced PKA activity, the same effect which has been observed in tumours isolated from CNC patients. Mice heterozygous for Prkar1a mutations (the exact genetic model for CNC patients) are born at expected frequencies and are tumour prone, developing neoplasms in cAMP-responsive cell types such as Schwann cells, osteoblasts and thyrocytes. In order to understand the basis of tissue-specific tumour formation, we have created tissue-specific KOs of the gene from three different tissues: the neural crest (Schwann cells), the pituitary gland and the heart. In the neural crest and the pituitary, ablation of Prkar1a leads to excess proliferation and tumorigenesis, whereas the same manipulation in developing cardiomyocytes leads to reduced proliferation and embryonic demise. The KO hearts also exhibit myxomatous changes suggesting a connection between PKA activation and myxomagenesis, although the nature of this relationship has not yet been determined. This work confirms the role of Prkar1a as a tissue-specific tumour suppressor, and ongoing work is focused on identifying the key downstream signalling targets affected by dysregulation of PKA. PMID:19522826

  18. High-fat diet leads to tissue-specific changes reflecting risk factors for diseases in DBA/2J mice

    Hageman, Rachael S.; Wagener, Asja; Hantschel, Claudia; Svenson, Karen L.; Churchill, Gary A; Brockmann, Gudrun A., 1958-

    2010-01-01

    The aim of this study was to characterize the responses of individual tissues to high-fat feeding as a function of mass, fat composition, and transcript abundance. We examined a panel of eight tissues [5 white adipose tissues (WAT), brown adipose tissue (BAT), liver, muscle] obtained from DBA/2J mice on either a standard breeding diet (SBD) or a high-fat diet (HFD). HFD led to weight gain, decreased insulin sensitivity, and tissue-specific responses, including inflammation, in these mice. The...

  19. Epigenetic Modifications of Distinct Sequences of the p1 Regulatory Gene Specify Tissue-Specific Expression Patterns in Maize

    Sekhon, Rajandeep S.; Peterson, Thomas; Chopra, Surinder

    2007-01-01

    Tandemly repeated endogenous genes are common in plants, but their transcriptional regulation is not well characterized. In maize, the P1-wr allele of pericarp color1 is composed of multiple copies arranged in a head-to-tail fashion. P1-wr confers a white kernel pericarp and red cob glume pigment phenotype that is stably inherited over generations. To understand the molecular mechanisms that regulate tissue-specific expression of P1-wr, we have characterized P1-wr*, a spontaneous loss-of-func...

  20. Diverse and Tissue Specific Mitochondrial Respiratory Response in A Mouse Model of Sepsis-Induced Multiple Organ Failure

    Karlsson, Michael; Hara, Naomi; Morata, Saori;

    2016-01-01

    -production was detected.Liver homogenate from the septic mice displayed a significant increase of the respiratory control ratio at 6 hours. In the 24-hour group, the rate of maximal oxidative phosphorylation, as well as LEAK respiration, was significantly increased compared to controls and the resultant respiratory...... control ratio was also significantly increased. Maximal Protonophore-induced respiratory (uncoupled) capacity was similar between the two treatment groups.The present study suggests a diverse and tissue specific mitochondrial respiratory response to sepsis. The brain displayed an early impaired...... mitochondrial respiratory efficiency. In the liver the primary finding was a substantial activation of the maximal phosphorylating capacity....

  1. Global expression differences and tissue specific expression differences in rice evolution result in two contrasting types of differentially expressed genes

    Horiuchi, Youko

    2015-12-23

    Background Since the development of transcriptome analysis systems, many expression evolution studies characterized evolutionary forces acting on gene expression, without explicit discrimination between global expression differences and tissue specific expression differences. However, different types of gene expression alteration should have different effects on an organism, the evolutionary forces that act on them might be different, and different types of genes might show different types of differential expression between species. To confirm this, we studied differentially expressed (DE) genes among closely related groups that have extensive gene expression atlases, and clarified characteristics of different types of DE genes including the identification of regulating loci for differential expression using expression quantitative loci (eQTL) analysis data. Results We detected differentially expressed (DE) genes between rice subspecies in five homologous tissues that were verified using japonica and indica transcriptome atlases in public databases. Using the transcriptome atlases, we classified DE genes into two types, global DE genes and changed-tissues DE genes. Global type DE genes were not expressed in any tissues in the atlas of one subspecies, however changed-tissues type DE genes were expressed in both subspecies with different tissue specificity. For the five tissues in the two japonica-indica combinations, 4.6 ± 0.8 and 5.9 ± 1.5 % of highly expressed genes were global and changed-tissues DE genes, respectively. Changed-tissues DE genes varied in number between tissues, increasing linearly with the abundance of tissue specifically expressed genes in the tissue. Molecular evolution of global DE genes was rapid, unlike that of changed-tissues DE genes. Based on gene ontology, global and changed-tissues DE genes were different, having no common GO terms. Expression differences of most global DE genes were regulated by cis-eQTLs. Expression

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

    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

  3. 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

    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

  4. MREdictor: a two-step dynamic interaction model that accounts for mRNA accessibility and Pumilio binding accurately predicts microRNA targets.

    Incarnato, Danny; Neri, Francesco; Diamanti, Daniela; Oliviero, Salvatore

    2013-10-01

    The prediction of pairing between microRNAs (miRNAs) and the miRNA recognition elements (MREs) on mRNAs is expected to be an important tool for understanding gene regulation. Here, we show that mRNAs that contain Pumilio recognition elements (PRE) in the proximity of predicted miRNA-binding sites are more likely to form stable secondary structures within their 3'-UTR, and we demonstrated using a PUM1 and PUM2 double knockdown that Pumilio proteins are general regulators of miRNA accessibility. On the basis of these findings, we developed a computational method for predicting miRNA targets that accounts for the presence of PRE in the proximity of seed-match sequences within poorly accessible structures. Moreover, we implement the miRNA-MRE duplex pairing as a two-step model, which better fits the available structural data. This algorithm, called MREdictor, allows for the identification of miRNA targets in poorly accessible regions and is not restricted to a perfect seed-match; these features are not present in other computational prediction methods. PMID:23863844

  5. Tissue-specific congener composition of organohalogen and metabolite contaminants in East Greenland polar bears (Ursus maritimus)

    Congener patterns of the major organohalogen contaminant classes of PCBs, PBDEs and their metabolites and/or by-products (OH-PCBs, MeSO2-PCBs, OH-PBDEs and MeO-PBDEs) were examined in adipose tissue, liver, brain and blood of East Greenland polar bears (Ursus maritimus). PCB, OH-PCB, MeSO2-PCB and PBDE congener patterns showed significant differences (p ≤ 0.05) mainly in the liver and the brain relative to the adipose tissue and the blood. OH-PBDEs and MeO-PBDEs were not detected in the brain and liver, but had different patterns in blood versus the adipose tissue. Novel OH-polybrominated biphenyls (OH-PBBs), one tri- and two tetra-brominated OH-PBBs were detected in all tissues and blood. Congener pattern differences among tissues and blood are likely due to a combination of factors, e.g., biotransformation and retention in the liver, retention in the blood and blood-brain barrier transport. Our findings suggest that different congener pattern exposures to these classes of contaminants should be considered with respect to potential target tissue-specific effects in East Greenland polar bears. - Tissues-specific (adipose tissue, liver, brain and blood) differences exist for the congener patterns of PCBs, PBDEs and their metabolites/degradation products in East Greenland polar bears

  6. Tissue-specific congener composition of organohalogen and metabolite contaminants in East Greenland polar bears (Ursus maritimus)

    Gebbink, Wouter A. [National Wildlife Research Centre, Science and Technology Branch, Environment Canada, Carleton University, Ottawa, Ontario K1S 5B6 (Canada); Department of Chemistry, Carleton University, Ottawa, Ontario K1S 5B6 (Canada); Sonne, Christian; Dietz, Rune; Kirkegaard, Maja; Riget, Frank F. [Department of Arctic Environment, National Environmental Research Institute, University of Aarhus, Frederiksborgvej 399, DK-4000 Roskilde (Denmark); Born, Erik W. [Greenland Institute of Natural Resources, P.O. Box 570, DK-3900 Nuuk, Greenland (Denmark); Muir, Derek C.G. [Water Science and Technology Directorate, Environment Canada, Burlington, Ontario L7R 4A6 (Canada); Letcher, Robert J. [National Wildlife Research Centre, Science and Technology Branch, Environment Canada, Carleton University, Ottawa, Ontario K1S 5B6 (Canada); Department of Chemistry, Carleton University, Ottawa, Ontario K1S 5B6 (Canada)], E-mail: robert.letcher@ec.gc.ca

    2008-04-15

    Congener patterns of the major organohalogen contaminant classes of PCBs, PBDEs and their metabolites and/or by-products (OH-PCBs, MeSO{sub 2}-PCBs, OH-PBDEs and MeO-PBDEs) were examined in adipose tissue, liver, brain and blood of East Greenland polar bears (Ursus maritimus). PCB, OH-PCB, MeSO{sub 2}-PCB and PBDE congener patterns showed significant differences (p {<=} 0.05) mainly in the liver and the brain relative to the adipose tissue and the blood. OH-PBDEs and MeO-PBDEs were not detected in the brain and liver, but had different patterns in blood versus the adipose tissue. Novel OH-polybrominated biphenyls (OH-PBBs), one tri- and two tetra-brominated OH-PBBs were detected in all tissues and blood. Congener pattern differences among tissues and blood are likely due to a combination of factors, e.g., biotransformation and retention in the liver, retention in the blood and blood-brain barrier transport. Our findings suggest that different congener pattern exposures to these classes of contaminants should be considered with respect to potential target tissue-specific effects in East Greenland polar bears. - Tissues-specific (adipose tissue, liver, brain and blood) differences exist for the congener patterns of PCBs, PBDEs and their metabolites/degradation products in East Greenland polar bears.

  7. Tissue-Specific Contributions of Paternally Expressed Gene 3 in Lactation and Maternal Care of Mus musculus.

    Wesley D Frey

    Full Text Available Paternally Expressed Gene 3 (Peg3 is an imprinted gene that controls milk letdown and maternal-caring behaviors. In this study, a conditional knockout allele has been developed in Mus musculus to further characterize these known functions of Peg3 in a tissue-specific manner. The mutant line was first crossed with a germline Cre. The progeny of this cross displayed growth retardation phenotypes. This is consistent with those seen in the previous mutant lines of Peg3, confirming the usefulness of the new mutant allele. The mutant line was subsequently crossed individually with MMTV- and Nkx2.1-Cre lines to test Peg3's roles in the mammary gland and hypothalamus, respectively. According to the results, the milk letdown process was impaired in the nursing females with the Peg3 mutation in the mammary gland, but not in the hypothalamus. This suggests that Peg3's roles in the milk letdown process are more critical in the mammary gland than in the hypothalamus. In contrast, one of the maternal-caring behaviors, nest-building, was interrupted in the females with the mutation in both MMTV- and Nkx2.1-driven lines. Overall, this is the first study to introduce a conditional knockout allele of Peg3 and to further dissect its contribution to mammalian reproduction in a tissue-specific manner.

  8. Tissue-specific metallothionein gene expression in liver and intestine by dexamethasone, interleukin-1α and elevated zinc status

    Intestinal metallothionein has been implicated in the regulation of zinc absorption. Glucocorticoids and cytokines mediate hepatic metallothionein gene expression but the effects of these hormones in the small intestine are unclear. In this experiment, rats were injected ip with dexamethasone (DEX), recombinant human interleukin-1α (ILK-1), or ZnSO4. Data collected 0. 3, 6,9, or 12 hour post-injection showed tissue specific regulation of metallothionein gene expression. Liver metallothionein mRNA (determined by hybridization analysis) were increased by DEX, IL-1 and ZnSO4. In contrast, the intestine was completely refractory to IL-1. DEX did not affect intestinal metallothionein but did enhance mucosal accumulation of 65Zn by ligated duodenal loops. Absorption of 65Zn was not affected by IL-1 or DEX but was inversely related to elevated intestinal metallothionein protein induced in response to ZnSO. Plasma zinc was depressed by DEX and IL-1 and elevated in rats injected with ZnSO4 but was not related to 54Zn absorption. Tissue-specific induction of metallothionein may constitute a mechanism for independently regulating both tissue zinc distribution and zinc absorption

  9. Tissue Discrimination by Uncorrected Autofluorescence Spectra: A Proof-of-Principle Study for Tissue-Specific Laser Surgery

    Katja Tangermann-Gerk

    2013-10-01

    Full Text Available Laser surgery provides a number of advantages over conventional surgery. However, it implies large risks for sensitive tissue structures due to its characteristic non-tissue-specific ablation. The present study investigates the discrimination of nine different ex vivo tissue types by using uncorrected (raw autofluorescence spectra for the development of a remote feedback control system for tissue-selective laser surgery. Autofluorescence spectra (excitation wavelength 377 ± 50 nm were measured from nine different ex vivo tissue types, obtained from 15 domestic pig cadavers. For data analysis, a wavelength range between 450 nm and 650 nm was investigated. Principal Component Analysis (PCA and Quadratic Discriminant Analysis (QDA were used to discriminate the tissue types. ROC analysis showed that PCA, followed by QDA, could differentiate all investigated tissue types with AUC results between 1.00 and 0.97. Sensitivity reached values between 93% and 100% and specificity values between 94% and 100%. This ex vivo study shows a high differentiation potential for physiological tissue types when performing autofluorescence spectroscopy followed by PCA and QDA. The uncorrected autofluorescence spectra are suitable for reliable tissue discrimination and have a high potential to meet the challenges necessary for an optical feedback system for tissue-specific laser surgery.

  10. Tissue-specific changes of glutamine synthetase activity in oats after rhizosphere infestation by Pseudomonas syringae pv. tabaci. Final report

    Knight, T.J. [Univ. of Southern Maine, Portland, ME (United States); Temple, S.; Sengupta-Gopalan, C. [New Mexico State Univ., Las Curces, NM (United States)] [and others

    1996-05-15

    Oats (Avena sativa L. lodi) tolerant of rhizosphere infestation by Pseudomonas syringae pv. tabaci when challenged by the pathogen experience tissue-specific alterations of ammonia assimilatory capabilities. Altered ammonia assimilatory potentials between root and leaf tissue result from selective inactivation of glutamine synthetase (GS) by the toxin Tabtoxinine-B-lactam (TBL). Root GS is sensitive and leaf GSs are resistant to TBL inactivation. With prolonged challenge by the pathogen root GS activity decreases but leaf GS specific activity increase. Higher leaf GS activity is due to decreased rates of degradation rather than increased GS synthesis. Higher leaf GS activity and elevated levels of GS polypeptide appear to result from a limited interaction between GS and TBL leading to the accumulation of a less active but more stable GS holoenzyme. Tolerant challenged oats besides surviving rhizosphere infestation, experience enhanced growth. A strong correlation exists between leaf GS activity and whole plant fresh weight, suggesting that tissue-specific changes in ammonia assimilatory capability provides the plant a more efficient mechanism for uptake and utilization of nitrogen.

  11. Tissue-specific bioaccumulation and oxidative stress responses in juvenile Japanese flounder (Paralichthys olivaceus) exposed to mercury

    HUANG Wei; CAO Liang; YE Zhenjiang; LIN Longshan; CHEN Quanzhen; DOU Shuozeng

    2012-01-01

    To understand mercury (Hg) toxicity in marine fish,we measured Hg accumulation in juvenile Japanese flounder (Paralichthys olivaceus) and assessed the effects on growth and antioxidant responses.After Hg exposure (control,5,40,and 160 μg/L Hg) for 28 d,fish growth was significantly reduced.The accumulation of Hg in fish was dose-dependent and tissue-specific,with the maximum accumulation in kidney and liver,followed by gills,bone,and muscle.Different antioxidants responded differently to Hg exposure to cope with the induction of lipid peroxidation (LPO),which was also tissue-specific and dosedependent.As Hg concentration increased,superoxide dismutase (SOD) and catalase (CAT) activities increased significantly,whereas glutathione S-transferase (GST) activity and glutathione (GSH) levels decreased significantly in the gills.SOD and glutathione peroxidase (GPx) activities and the GSH level increased significantly in the liver.SOD activity and GSH levels increased significantly,but CAT activity decreased significantly with an increase in Hg concentration in the kidney.LPO was induced significantly by elevated Hg in the gills and kidney but was least affected in the liver.Therefore,oxidative stress biomarkers in gills were more sensitive than those in the liver and kidney to Hg exposure.Thus,the gills have potential as bioindicators for evaluating Hg toxicity in juvenile flounder.

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

    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...

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

    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

  14. Normal Tissue Complication Probability Estimation by the Lyman-Kutcher-Burman Method Does Not Accurately Predict Spinal Cord Tolerance to Stereotactic Radiosurgery

    Purpose: To determine whether normal tissue complication probability (NTCP) analyses of the human spinal cord by use of the Lyman-Kutcher-Burman (LKB) model, supplemented by linear–quadratic modeling to account for the effect of fractionation, predict the risk of myelopathy from stereotactic radiosurgery (SRS). Methods and Materials: From November 2001 to July 2008, 24 spinal hemangioblastomas in 17 patients were treated with SRS. Of the tumors, 17 received 1 fraction with a median dose of 20 Gy (range, 18–30 Gy) and 7 received 20 to 25 Gy in 2 or 3 sessions, with cord maximum doses of 22.7 Gy (range, 17.8–30.9 Gy) and 22.0 Gy (range, 20.2–26.6 Gy), respectively. By use of conventional values for α/β, volume parameter n, 50% complication probability dose TD50, and inverse slope parameter m, a computationally simplified implementation of the LKB model was used to calculate the biologically equivalent uniform dose and NTCP for each treatment. Exploratory calculations were performed with alternate values of α/β and n. Results: In this study 1 case (4%) of myelopathy occurred. The LKB model using radiobiological parameters from Emami and the logistic model with parameters from Schultheiss overestimated complication rates, predicting 13 complications (54%) and 18 complications (75%), respectively. An increase in the volume parameter (n), to assume greater parallel organization, improved the predictive value of the models. Maximum-likelihood LKB fitting of α/β and n yielded better predictions (0.7 complications), with n = 0.023 and α/β = 17.8 Gy. Conclusions: The spinal cord tolerance to the dosimetry of SRS is higher than predicted by the LKB model using any set of accepted parameters. Only a high α/β value in the LKB model and only a large volume effect in the logistic model with Schultheiss data could explain the low number of complications observed. This finding emphasizes that radiobiological models traditionally used to estimate spinal cord NTCP

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

    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

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

    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

  17. 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

    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.

  18. Tissue-specific calibration of extracellular matrix material properties by transforming growth factor-β and Runx2 in bone is required for hearing

    Chang, Jolie L; Brauer, Delia S.; Johnson, Jacob; Chen, Carol G.; Akil, Omar; Balooch, Guive; Humphrey, Mary Beth; Chin, Emily N.; Porter, Alexandra E.; Butcher, Kristin; Ritchie, Robert O.; Schneider, Richard A; Lalwani, Anil; Derynck, Rik; Marshall, Grayson W.

    2010-01-01

    By investigating the role of bone quality in hearing, this study provides evidence that signaling pathways and lineage-specific transcription factors cooperate to define the tissue-specific and functionally essential material properties of the extracellular matrix.

  19. Differences between liver gap junction protein and lens MIP 26 from rat: implications for tissue specificity of gap junctions.

    Nicholson, B J; Takemoto, L J; Hunkapiller, M W; Hood, L E; Revel, J P

    1983-03-01

    Liver gap junctions and gap-junction-like structures from eye lenses are each comprised of a single major protein (Mr 28,000 and 26,000, respectively). These proteins display different two-dimensional peptide fingerprints, distinct amino acid compositions, nonhomologous N-terminal amino acid sequences and different sensitivities to proteases when part of the intact junction. However, the junctional protein of each tissue is well conserved between species, as demonstrated previously for lens and now for liver in several mammalian species. The possiblity of tissue-specific gap junction proteins is discussed in the light of data suggesting that rat heart gap junctions are comprised of yet a third protein. PMID:6299583

  20. A High-Dimensional Atlas of Human T Cell Diversity Reveals Tissue-Specific Trafficking and Cytokine Signatures.

    Wong, Michael Thomas; Ong, David Eng Hui; Lim, Frances Sheau Huei; Teng, Karen Wei Weng; McGovern, Naomi; Narayanan, Sriram; Ho, Wen Qi; Cerny, Daniela; Tan, Henry Kun Kiaang; Anicete, Rosslyn; Tan, Bien Keem; Lim, Tony Kiat Hon; Chan, Chung Yip; Cheow, Peng Chung; Lee, Ser Yee; Takano, Angela; Tan, Eng-Huat; Tam, John Kit Chung; Tan, Ern Yu; Chan, Jerry Kok Yen; Fink, Katja; Bertoletti, Antonio; Ginhoux, Florent; Curotto de Lafaille, Maria Alicia; Newell, Evan William

    2016-08-16

    Depending on the tissue microenvironment, T cells can differentiate into highly diverse subsets expressing unique trafficking receptors and cytokines. Studies of human lymphocytes have primarily focused on a limited number of parameters in blood, representing an incomplete view of the human immune system. Here, we have utilized mass cytometry to simultaneously analyze T cell trafficking and functional markers across eight different human tissues, including blood, lymphoid, and non-lymphoid tissues. These data have revealed that combinatorial expression of trafficking receptors and cytokines better defines tissue specificity. Notably, we identified numerous T helper cell subsets with overlapping cytokine expression, but only specific cytokine combinations are secreted regardless of tissue type. This indicates that T cell lineages defined in mouse models cannot be clearly distinguished in humans. Overall, our data uncover a plethora of tissue immune signatures and provide a systemic map of how T cell phenotypes are altered throughout the human body. PMID:27521270

  1. Gambogic Acid Is a Tissue-Specific Proteasome Inhibitor In Vitro and In Vivo

    Xiaofen Li

    2013-01-01

    Full Text Available Gambogic acid (GA is a natural compound derived from Chinese herbs that has been approved by the Chinese Food and Drug Administration for clinical trials in cancer patients; however, its molecular targets have not been thoroughly studied. Here, we report that GA inhibits tumor proteasome activity, with potency comparable to bortezomib but much less toxicity. First, GA acts as a prodrug and only gains proteasome-inhibitory function after being metabolized by intracellular CYP2E1. Second, GA-induced proteasome inhibition is a prerequisite for its cytotoxicity and anticancer effect without off-targets. Finally, because expression of the CYP2E1 gene is very high in tumor tissues but low in many normal tissues, GA could therefore produce tissue-specific proteasome inhibition and tumor-specific toxicity, with clinical significance for designing novel strategies for cancer treatment.

  2. Tissue-specific down-regulation of RIPK 2 in Mycobacterium leprae-infected nu/nu mice

    Gue-Tae Chae

    1992-01-01

    Full Text Available RIPK 2 is adapter molecule in the signal pathway involved in Toll-like receptors. However, there has been no reported association between receptor-interacting serine/threonine kinase 2 (RIPK 2 expression and the infectious diseases involving mycobacterial infection. This study found that its expression was down-regulated in the footpads and skin but was up-regulated in the liver of Mycobacterium leprae-infected nu/nu mice compared with those of the M. leprae non-infected nu/nu mice. It was observed that the interlukin-12p40 and interferon-γ genes involved in the susceptibility of M. leprae were down-regulated in the skin but were up-regulated in the liver. Overall, this suggests that regulation of RIPK 2 expression is tissue-specifically associated with M. leprae infection.

  3. Medullary Epithelial Cells of the Human Thymus Express a Highly Diverse Selection of Tissue-specific Genes Colocalized in Chromosomal Clusters

    Gotter, Jörn; Brors, Benedikt; Hergenhahn, Manfred; Kyewski, Bruno

    2004-01-01

    Promiscuous expression of tissue-specific self-antigens in the thymus imposes T cell tolerance and protects from autoimmune diseases, as shown in animal studies. Analysis of promiscuous gene expression in purified stromal cells of the human thymus at the single and global gene level documents the species conservation of this phenomenon. Medullary thymic epithelial cells overexpress a highly diverse set of genes (>400) including many tissue-specific antigens, disease-associated autoantigens, a...

  4. Topological and organizational properties of the products of house-keeping and tissue-specific genes in protein-protein interaction networks

    Liu Wei-chung; Lin Wen-hsien; Hwang Ming-jing

    2009-01-01

    Abstract Background Human cells of various tissue types differ greatly in morphology despite having the same set of genetic information. Some genes are expressed in all cell types to perform house-keeping functions, while some are selectively expressed to perform tissue-specific functions. In this study, we wished to elucidate how proteins encoded by human house-keeping genes and tissue-specific genes are organized in human protein-protein interaction networks. We constructed protein-protein ...

  5. De novo assembly and characterization of tissue-specific transcriptome in the endangered golden mahseer, Tor putitora.

    Barat, Ashoktaru; Kumar, Rohit; Goel, Chirag; Singh, Atul Kumar; Sahoo, Prabhati Kumari

    2016-02-01

    The golden mahseer (Tor putitora) graces most of the Himalayan Rivers of India and neighboring South Asian countries. Despite its several importance as a research model, as food, and in sport fishing, knowledge on transcriptome database is nil. Therefore, it was targeted to develop reference transcriptome databases of the species using next-generation sequencing. In the present study, 100,540,130 high-quality paired-end reads were obtained from six cDNA libraries of spleen, liver, gill, kidney, muscle, and brain with 28.4 GB data using Illumina paired-end sequencing technology. Tissue-specific transcriptomes as well as complete transcriptome assembly were analyzed for concise representation of the study. In brief, the de novo assembly of individual tissue resulted in an average of 31,829 (18,512-46,348) contigs per sample, while combined transcriptome comprised 77,907 unique transcript fragments (unigenes) assembled from reads of six tissues. Approximately 75,407 (96.8%) unigenes could be annotated according to their homology matches in the nr, SwisseProt, GO, or KEGG databases. Comparative analysis showed that 84% of the unigenes have significant similarity to zebra fish RefSeq proteins. Tissue-specific-dominated genes were also identified to hypothesize their localization and expression in individual tissue. In addition, 2485 simple sequence repeats (SSRs) were detected from 77,907 transcripts in the combined transcriptome of the golden mahseer. This study has generated organ-specific transcriptome profiles, which will be helpful to understand the local adaptation, genome evolution, and also future functional studies on immune system of the golden mahseer. PMID:26702399

  6. Tissue specific diurnal rhythms of metabolites and their regulation during herbivore attack in a native tobacco, Nicotiana attenuata.

    Sang-Gyu Kim

    Full Text Available Ecological performance is all about timing and the endogenous clock that allows the entrainment of rhythms and anticipation of fitness-determining events is being rapidly characterized. How plants anticipate daily abiotic stresses, such as cold in early mornings and drought at noon, as well as biotic stresses, such as the timing of pathogen infections, is being explored, but little is known about the clock's role in regulating responses to insect herbivores and mutualists, whose behaviors are known to be strongly diurnally regulated and whose attack is known to reconfigure plant metabolomes. We developed a liquid chromatography-mass spectrometry procedure and analyzed its output with model-based peak picking algorithms to identify metabolites with diurnal accumulation patterns in sink/source leaves and roots in an unbiased manner. The response of metabolites with strong diurnal patterns to simulated attack from the specialist herbivore, Manduca sexta larvae was analyzed and annotated with in-house and public databases. Roots and leaves had largely different rhythms and only 10 ions of 182 oscillating ions in leaves and 179 oscillating ions in roots were rhythmic in both tissues: root metabolites mainly peaked at dusk or night, while leaf metabolites peaked during the day. Many oscillating metabolites showed tissue-specific regulation by simulated herbivory of which systemic responses in unattacked tissues were particularly pronounced. Diurnal and herbivory-elicited accumulation patterns of disaccharide, phenylalanine, tyrosine, lyciumoside I, coumaroyl tyramine, 12-oxophytodienoic acid and jasmonic acid and those of their related biosynthetic transcripts were examined in detail. We conclude that oscillating metabolites of N. attenuata accumulate in a highly tissue-specific manner and the patterns reveal pronounced diurnal rhythms in the generalized and specialized metabolism that mediates the plant's responses to herbivores and mutualists. We

  7. Tissue-specific cytochrome c oxidase assembly defects due to mutations in SCO2 and SURF1.

    Stiburek, Lukas; Vesela, Katerina; Hansikova, Hana; Pecina, Petr; Tesarova, Marketa; Cerna, Leona; Houstek, Josef; Zeman, Jiri

    2005-12-15

    The biogenesis of eukaryotic COX (cytochrome c oxidase) requires several accessory proteins in addition to structural subunits and prosthetic groups. We have analysed the assembly state of COX and SCO2 protein levels in various tissues of six patients with mutations in SCO2 and SURF1. SCO2 is a copper-binding protein presumably involved in formation of the Cu(A) centre of the COX2 subunit. The function of SURF1 is unknown. Immunoblot analysis of native gels demonstrated that COX holoenzyme is reduced to 10-20% in skeletal muscle and brain of SCO2 and SURF1 patients and to 10-30% in heart of SCO2 patients, whereas liver of SCO2 patients' contained normal holoenzyme levels. The steady-state levels of mutant SCO2 protein ranged from 0 to 20% in different SCO2 patient tissues. In addition, eight distinct COX subcomplexes and unassembled subunits were found, some of them identical with known assembly intermediates of the human enzyme. Heart, brain and skeletal muscle of SCO2 patients contained accumulated levels of the COX1.COX4.COX5A subcomplex, three COX1-containing subcomplexes, a COX4.COX5A subcomplex and two subcomplexes composed of only COX4 or COX5A. The accumulation of COX1.COX4.COX5A subcomplex, along with the virtual absence of free COX2, suggests that the lack of the Cu(A) centre may result in decreased stability of COX2. The appearance of COX4.COX5A subcomplex indicates that association of these nucleus-encoded subunits probably precedes their addition to COX1 during the assembly process. Finally, the consequences of SCO2 and SURF1 mutations suggest the existence of tissue-specific functional differences of these proteins that may serve different tissue-specific requirements for the regulation of COX biogenesis. PMID:16083427

  8. Involvement of an ent-copalyl diphosphate synthase in tissue-specific accumulation of specialized diterpenes in Andrographis paniculata.

    Misra, Rajesh Chandra; Garg, Anchal; Roy, Sudeep; Chanotiya, Chandan Singh; Vasudev, Prema G; Ghosh, Sumit

    2015-11-01

    Ent-labdane-related diterpene (ent-LRD) specialized (i.e. secondary) metabolites of the medicinal plant kalmegh (Andrographis paniculata) have long been known for several pharmacological activities. However, our understanding of the ent-LRD biosynthetic pathway has remained largely incomplete. Since ent-LRDs accumulate in leaves, we carried out a comparative transcriptional analysis using leaf and root tissues, and identified 389 differentially expressed transcripts, including 223 transcripts that were preferentially expressed in leaf tissue. Analysis of the transcripts revealed various specialized metabolic pathways, including transcripts of the ent-LRD biosynthetic pathway. Two class II diterpene synthases (ApCPS1 and ApCPS2) along with one (ApCPS1') and two (ApCPS2' and ApCPS2″) transcriptional variants that were the outcomes of alternative splicing of the precursor mRNA and alternative transcriptional termination, respectively, were identified. ApCPS1 and ApCPS2 encode for 832- and 817-amino acids proteins, respectively, and are phylogenetically related to the dicotyledons ent-copalyl diphosphate synthases (ent-CPSs). The spatio-temporal patterns of ent-LRD metabolites accumulation and gene expression suggested a likely role for ApCPS1 in general (i.e. primary) metabolism, perhaps by providing precursor for the biosynthesis of phytohormone gibberellin (GA). However, ApCPS2 is potentially involved in tissue-specific accumulation of ent-LRD specialized metabolites. Bacterially expressed recombinant ApCPS2 catalyzed the conversion of (E,E,E)-geranylgeranyl diphosphate (GGPP), the general precursor of diterpenes to ent-copalyl diphosphate (ent-CPP), the precursor of ent-LRDs. Taken together, these results advance our understanding of the tissue-specific accumulation of specialized ent-LRDs of medicinal importance. PMID:26475187

  9. Lack of global meiotic sex chromosome inactivation, and paucity of tissue-specific gene expression on the Drosophila X chromosome

    Nurminsky Dmitry I

    2011-05-01

    Full Text Available Abstract Background Paucity of male-biased genes on the Drosophila X chromosome is a well-established phenomenon, thought to be specifically linked to the role of these genes in reproduction and/or their expression in the meiotic male germline. In particular, meiotic sex chromosome inactivation (MSCI has been widely considered a driving force behind depletion of spermatocyte-biased X-linked genes in Drosophila by analogy with mammals, even though the existence of global MCSI in Drosophila has not been proven. Results Microarray-based study and qRT-PCR analyses show that the dynamics of gene expression during testis development are very similar between X-linked and autosomal genes, with both showing transcriptional activation concomitant with meiosis. However, the genes showing at least ten-fold expression bias toward testis are significantly underrepresented on the X chromosome. Intriguingly, the genes with similar expression bias toward tissues other than testis, even those not apparently associated with reproduction, are also strongly underrepresented on the X. Bioinformatics analysis shows that while tissue-specific genes often bind silencing-associated factors in embryonic and cultured cells, this trend is less prominent for the X-linked genes. Conclusions Our data show that the global meiotic inactivation of the X chromosome does not occur in Drosophila. Paucity of testis-biased genes on the X appears not to be linked to reproduction or germline-specific events, but rather reflects a general underrepresentation of tissue-biased genes on this chromosome. Our analyses suggest that the activation/repression switch mechanisms that probably orchestrate the highly-biased expression of tissue-specific genes are generally not efficient on the X chromosome. This effect, probably caused by dosage compensation counteracting repression of the X-linked genes, may be the cause of the exodus of highly tissue-biased genes to the autosomes.

  10. Tissue-specific populations of leukocytes in semen-producing organs of the normal, hemicastrated, and vasectomized mouse.

    Mullen, Thomas E; Kiessling, Rachel L; Kiessling, Ann A

    2003-03-01

    Semen HIV is separate and distinct from blood HIV and work has revealed that seminal plasma HIV particles do not arise from infected cells in semen. These findings indicate that semen-producing organs contain multiple, separate populations of HIV host cells. To test this hypothesis, we have examined leukocytes in semen-producing organs of male mice. Cells expressing F4/80 (tissue-specific macrophage marker) were abundant in testicular interstitium and as dendritic-like cells in the lumenal epithelium of the epididymis, especially the initial segment. Cells expressing CD45 (panleukocyte marker) were found rarely in the testicular interstitium, commonly in epididymal epithelium, were most abundant in the interstitium of the epididymis, and were more readily released from minced tissues than were F4/80(+) cells. Unlike the testis and epididymis, F4/80(+) cells in seminal vesicles also appeared to be CD45(+). Seminal vesicle leukocytes were restricted to the epithelium surrounding the lumen and were not released by mincing. CD11b (monocyte/B cell marker) was detected in testicular and seminal vesicle interstitium, but not in the epididymis. Hemicastration and vasectomy caused a limited redistribution of the leukocytes. These findings confirm the existence of tissue-specific populations of leukocytes in semen-producing organs and indicate that some populations are highly tissue adherent. The regionalized, tissue-adherent macrophages in the testicular interstitium, the initial segment of the caput epididymis, and the seminal vesicle epithelium suggest the existence of reservoirs of HIV-infected cells in humans that could contribute virus particles, but not infected cells, to semen and possibly blood. PMID:12689416

  11. De novo assembly and characterization of tissue-specific transcriptome in the endangered golden mahseer, Tor putitora

    Ashoktaru Barat

    2016-02-01

    Full Text Available The golden mahseer (Tor putitora graces most of the Himalayan Rivers of India and neighboring South Asian countries. Despite its several importance as a research model, as food, and in sport fishing, knowledge on transcriptome database is nil. Therefore, it was targeted to develop reference transcriptome databases of the species using next-generation sequencing. In the present study, 100,540,130 high-quality paired-end reads were obtained from six cDNA libraries of spleen, liver, gill, kidney, muscle, and brain with 28.4 GB data using Illumina paired-end sequencing technology. Tissue-specific transcriptomes as well as complete transcriptome assembly were analyzed for concise representation of the study. In brief, the de novo assembly of individual tissue resulted in an average of 31,829 (18,512–46,348 contigs per sample, while combined transcriptome comprised 77,907 unique transcript fragments (unigenes assembled from reads of six tissues. Approximately 75,407 (96.8% unigenes could be annotated according to their homology matches in the nr, SwisseProt, GO, or KEGG databases. Comparative analysis showed that 84% of the unigenes have significant similarity to zebra fish RefSeq proteins. Tissue-specific-dominated genes were also identified to hypothesize their localization and expression in individual tissue. In addition, 2485 simple sequence repeats (SSRs were detected from 77,907 transcripts in the combined transcriptome of the golden mahseer. This study has generated organ-specific transcriptome profiles, which will be helpful to understand the local adaptation, genome evolution, and also future functional studies on immune system of the golden mahseer.

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

    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.

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

    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)

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

    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

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

    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.

  16. Quantitative Assessment of Protein Structural Models by Comparison of H/D Exchange MS Data with Exchange Behavior Accurately Predicted by DXCOREX

    Liu, Tong; Pantazatos, Dennis; Li, Sheng; Hamuro, Yoshitomo; Hilser, Vincent J.; Woods, Virgil L.

    2012-01-01

    Peptide amide hydrogen/deuterium exchange mass spectrometry (DXMS) data are often used to qualitatively support models for protein structure. We have developed and validated a method (DXCOREX) by which exchange data can be used to quantitatively assess the accuracy of three-dimensional (3-D) models of protein structure. The method utilizes the COREX algorithm to predict a protein's amide hydrogen exchange rates by reference to a hypothesized structure, and these values are used to generate a virtual data set (deuteron incorporation per peptide) that can be quantitatively compared with the deuteration level of the peptide probes measured by hydrogen exchange experimentation. The accuracy of DXCOREX was established in studies performed with 13 proteins for which both high-resolution structures and experimental data were available. The DXCOREX-calculated and experimental data for each protein was highly correlated. We then employed correlation analysis of DXCOREX-calculated versus DXMS experimental data to assess the accuracy of a recently proposed structural model for the catalytic domain of a Ca2+-independent phospholipase A2. The model's calculated exchange behavior was highly correlated with the experimental exchange results available for the protein, supporting the accuracy of the proposed model. This method of analysis will substantially increase the precision with which experimental hydrogen exchange data can help decipher challenging questions regarding protein structure and dynamics.

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

    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. Structural evolution and tissue-specific expression of tetrapod-specific second isoform of secretory pathway Ca2+-ATPase

    Highlights: ► Full-length secretory pathway Ca-ATPase (SPCA2) cloned from rat duodenum. ► ATP2C2 gene (encoding SPCA2) exists only in genomes of Tetrapoda. ► Rat and pig SPCA2 are expressed in intestines, lung and some secretory glands. ► Subcellular localization of SPCA2 may depend on tissue type. ► In rat duodenum, SPCA2 is localized in plasma membrane-associated compartments. -- Abstract: Secretory pathway Ca-ATPases are less characterized mammalian calcium pumps than plasma membrane Ca-ATPases and sarco-endoplasmic reticulum Ca-ATPases. Here we report analysis of molecular evolution, alternative splicing, tissue-specific expression and subcellular localization of the second isoform of the secretory pathway Ca-ATPase (SPCA2), the product of the ATP2C2 gene. The primary structure of SPCA2 from rat duodenum deduced from full-length transcript contains 944 amino acid residues, and exhibits 65% sequence identity with known SPCA1. The rat SPCA2 sequence is also highly homologous to putative human protein KIAA0703, however, the latter seems to have an aberrant N-terminus originating from intron 2. The tissue-specificity of SPCA2 expression is different from ubiquitous SPCA1. Rat SPCA2 transcripts were detected predominantly in gastrointestinal tract, lung, trachea, lactating mammary gland, skin and preputial gland. In the newborn pig, the expression profile is very similar with one remarkable exception: porcine bulbourethral gland gave the strongest signal. Upon overexpression in cultured cells, SPCA2 shows an intracellular distribution with remarkable enrichment in Golgi. However, in vivo SPCA2 may be localized in compartments that differ among various tissues: it is intracellular in epidermis, but enriched in plasma membranes of the intestinal epithelium. Analysis of SPCA2 sequences from various vertebrate species argue that ATP2C2 gene radiated from ATP2C1 (encoding SPCA1) during adaptation of tetrapod ancestors to terrestrial habitats.

  19. Tissue-specific B-cell dysfunction and generalized memory B-cell loss during acute SIV infection.

    Sandrine Peruchon

    Full Text Available BACKGROUND: Primary HIV-infected patients display severe and irreversible damage to different blood B-cell subsets which is not restored by highly efficient anti-retroviral therapy (HAART. Because longitudinal investigations of primary HIV-infection is limited by the availability of lymphoid organs, we studied the tissue-specific B-cell dysfunctions in acutely simian immunodeficiency virus (SIV mac251-infected Cynomolgus macaques. METHODS AND FINDINGS: Experiments were performed on three groups of macaques infected for 14, 21 or 28 days and on three groups of animals treated with HAART for two-weeks either initiated at 4 h, 7 or 14 days post-infection (p.i.. We have simultaneously compared changes in B-cell phenotypes and functions and tissue organization of B-cell areas in various lymphoid organs. We showed that SIV induced a steady decline in SIgG-expressing memory (SIgD(-CD27(+ B-cells in spleen and lymph nodes during the first 4 weeks of infection, concomitant to selective homing/sequestration of B-cells to the small intestine and spleen. SIV non-specific Ig production was transiently increased before D14p.i., whereas SIV-specific Ig production was only detectable after D14p.i., coinciding with the presence of CD8(+ T-cells and IgG-expressing plasma cells within germinal centres. Transient B-cell apoptosis on D14p.i. and commitment to terminal differentiation contributed to memory B-cell loss. HAART abrogated B-cell apoptosis, homing to the small intestine and SIV-specific Ig production but had minimal effect on early Ig production, increased B-cell proportions in spleen and loss of memory B-cells. Therefore, virus-B-cell interactions and SIV-induced inflammatory cytokines may differently contribute to early B-cell dysfunction and impaired SIV/HIV-specific antibody response. CONCLUSIONS: These data establish tissue-specific impairments in B-cell trafficking and functions and a generalized and steady memory B-cell loss in secondary lymphoid

  20. Implementing the Effects of Changing Landscape by the Recent Bark Beetle Infestation on Snow Accumulation and Ablation to More Accurately Predict Stream Flow in the Upper Little Laramie River, Wyoming watershed.

    Heward, J.; Ohara, N.

    2014-12-01

    In many alpine regions, especially in the western United States, the snow pack is the cause of the peak discharge and most of the annual flow. A distributed snow melt model with a point-scale snow melt theory is used to estimate the timing and intensity of both snow accumulation and ablation. The type and distribution of vegetation across a watershed influences timing and intensity of snow melt processes. Efforts are being made to understand how a changing landscape will ultimately affect stream flow in a mountainous environment. This study includes an analysis of the effects of the recent bark beetle infestation, using leaf area index (LAI) data acquired from MODIS data sets. These changes were incorporated into the snow model to more accurately predict snow melt timing and intensity. It was observed through the primary model implementation that snowmelt was intensified by the LAI reduction. The radiation change and turbulent flux effects were separately quantified by the vegetation parameterization in the snow model. This distributed snow model will be used to more accurately predict stream flow in the Upper Little Laramie River, Wyoming watershed.

  1. Tissue-specific laser microdissection of the Brassica napus funiculus improves gene discovery and spatial identification of biological processes

    Chan, Ainsley C.; Khan, Deirdre; Girard, Ian J.; Becker, Michael G.; Millar, Jenna L.; Sytnik, David; Belmonte, Mark F.

    2016-01-01

    The three primary tissue systems of the funiculus each undergo unique developmental programs to support the growth and development of the filial seed. To understand the underlying transcriptional mechanisms that orchestrate development of the funiculus at the globular embryonic stage of seed development, we used laser microdissection coupled with RNA-sequencing to produce a high-resolution dataset of the mRNAs present in the epidermis, cortex, and vasculature of the Brassica napus (canola) funiculus. We identified 7761 additional genes in these tissues compared with the whole funiculus organ alone using this technology. Differential expression and enrichment analyses were used to identify several biological processes associated with each tissue system. Our data show that cell wall modification and lipid metabolism are prominent in the epidermis, cell growth and modification occur in the cortex, and vascular tissue proliferation and differentiation occur in the central vascular strand. We provide further evidence that each of the three tissue systems of the globular stage funiculus are involved in specific biological processes that all co-ordinate to support seed development. The identification of genes and gene regulators responsible for tissue-specific developmental processes of the canola funiculus now serves as a valuable resource for seed improvement research. PMID:27194740

  2. Promoter complexity and tissue-specific expression of stress response components in Mytilus galloprovincialis, a sessile marine invertebrate species.

    Chrysa Pantzartzi

    Full Text Available The mechanisms of stress tolerance in sessile animals, such as molluscs, can offer fundamental insights into the adaptation of organisms for a wide range of environmental challenges. One of the best studied processes at the molecular level relevant to stress tolerance is the heat shock response in the genus Mytilus. We focus on the upstream region of Mytilus galloprovincialis Hsp90 genes and their structural and functional associations, using comparative genomics and network inference. Sequence comparison of this region provides novel evidence that the transcription of Hsp90 is regulated via a dense region of transcription factor binding sites, also containing a region with similarity to the Gamera family of LINE-like repetitive sequences and a genus-specific element of unknown function. Furthermore, we infer a set of gene networks from tissue-specific expression data, and specifically extract an Hsp class-associated network, with 174 genes and 2,226 associations, exhibiting a complex pattern of expression across multiple tissue types. Our results (i suggest that the heat shock response in the genus Mytilus is regulated by an unexpectedly complex upstream region, and (ii provide new directions for the use of the heat shock process as a biosensor system for environmental monitoring.

  3. Comprehensive Tissue-Specific Transcriptome Analysis Reveals Distinct Regulatory Programs during Early Tomato Fruit Development1[OPEN

    Pattison, Richard J.; Csukasi, Fabiana; Zheng, Yi; Fei, Zhangjun; van der Knaap, Esther; Catalá, Carmen

    2015-01-01

    Fruit formation and early development involve a range of physiological and morphological transformations of the various constituent tissues of the ovary. These developmental changes vary considerably according to tissue type, but molecular analyses at an organ-wide level inevitably obscure many tissue-specific phenomena. We used laser-capture microdissection coupled to high-throughput RNA sequencing to analyze the transcriptome of ovaries and fruit tissues of the wild tomato species Solanum pimpinellifolium. This laser-capture microdissection-high-throughput RNA sequencing approach allowed quantitative global profiling of gene expression at previously unobtainable levels of spatial resolution, revealing numerous contrasting transcriptome profiles and uncovering rare and cell type-specific transcripts. Coexpressed gene clusters linked specific tissues and stages to major transcriptional changes underlying the ovary-to-fruit transition and provided evidence of regulatory modules related to cell division, photosynthesis, and auxin transport in internal fruit tissues, together with parallel specialization of the pericarp transcriptome in stress responses and secondary metabolism. Analysis of transcription factor expression and regulatory motifs indicated putative gene regulatory modules that may regulate the development of different tissues and hormonal processes. Major alterations in the expression of hormone metabolic and signaling components illustrate the complex hormonal control underpinning fruit formation, with intricate spatiotemporal variations suggesting separate regulatory programs. PMID:26099271

  4. Changes in levels of tissue-specific aldolases following whole-body x-irradiation of rat

    Effects of whole-body X-irradiation (600 R) of rat on the levels of tissue-specific forms of fructose-1, 6-biphosphate (FDP) aldolase have been investigated. Aldolase activities of type A from muscle, heart and spleen were relatively more susceptible than those from brain (A-C), liver (B) and kidney (A-B). While aldolase activities from brain and kidney showed losses after exposure of rat to 1000 R, that from liver remained unaffected. Effects on muscle aldolase were most pronounced. In muscle, though aldolase showed reduction in activity with FDP as substrate, no change was observed towards fructose-1-phosphate (F-1-P); consequently FDP/F-1-P activity ratio was reduced. Post-irradiation structural changes in muscle aldolase were suggested by the appearance of an extra band with aldolase activity in the gel electrophoresis pattern of muscle extract of irradiated rat. Incubation of muscle extract of control rat with that from irradiated animal at pH 6.0 resulted in loss of aldolase activity, and the presence of EDTA and -SH agents enhanced the loss. A similar loss of crystalline rabbit muscle aldolase was also seen upon incubation with muscle extract from irradiated rat and iodoacetamide protected against such loss. The results indicated involvement of catheptic enzymes of lysosomal origin in the inactivation of aldolase in rat muscle. Incorporation of DL-[1-14C] leucine into the muscle proteins of rat was inhibited by 80-90% upon administration of cycloheximide or puromycin. (author)

  5. Tissue-specific expression of insulin-like growth factor II mRNAs with distinct 5' untranslated regions

    The authors have used RNA from human hypothalamus as template for the production of cDNAs encoding insulin-like growth factor II (IGF-II). The prohormone coding sequence of brain IGF-II RNA is identical to that found in liver; however, the 5' untranslated sequence of the brain cDNA has no homology to the 5' untranslated sequence of the previously reported liver cDNAs. By using hybridization to specific probes as well as a method based on the properties of RNase H, they found that the human IGF-II gene has at least three exons that encode alternative 5' untranslated regions and that are expressed in a tissue-specific manner. A probe specific to the brain cDNA 5' untranslated region hybridizes to a 6.0-kilobase transcript present in placenta, hypothalamus, adrenal gland, kidney, Wilms tumor, and a pheochromocytoma. The 5' untranslated sequence of the brain cDNA does not hybridize to a 5.3-kilobase transcript found in liver or to a 5.0-kb transcript found in pheochromocytoma. By using RNase H to specifically fragment the IGF-II transcripts into 3' and 5' fragments, they found that the RNAs vary in size due to differences in the 5' end but not the 3' end

  6. Tissue-specific expression of transfected human insulin genes in pluripotent clonal rat insulinoma lines induced during passage in vivo

    Madsen, O.D.; Andersen, L.C.; Michelsen, B.; Owerbach, D.; Larsson, L.I.; Lernmark, A.; Steiner, D.F. (Hagedorn Research Laboratory, Gentofte (Denmark))

    1988-09-01

    The pluripotent rat islet tumor cell line MSL-G2 expresses primarily glucagon or cholecystokinin and not insulin in vitro but changes phenotype completely after prolonged in vivo cultivation to yield small-sized hypoglycemic tumors composed almost entirely of insulin-producing beta cells. When a genomic DNA fragment containing the coding and upstream regulatory regions of the human insulin gene was stably transfected into MSL-G2 cells no measurable amounts of insulin or insulin mRNA were detected in vitro. However, successive transplantation of two transfected clones resulted in hypoglycemic tumors that efficiently coexpressed human and rat insulin as determined by human C-peptide-specific immunoreagents. These results demonstrate that cis-acting tissue-specific insulin gene enhancer elements are conserved between rat and human insulin genes. The authors propose that the in vivo differentiation of MSL-G2 cells and transfected subclones into insulin-producing cells reflects processes of natural beta-cell ontogeny leading to insulin gene expression.

  7. Tissue-specific expression of transfected human insulin genes in pluripotent clonal rat insulinoma lines induced during passage in vivo

    The pluripotent rat islet tumor cell line MSL-G2 expresses primarily glucagon or cholecystokinin and not insulin in vitro but changes phenotype completely after prolonged in vivo cultivation to yield small-sized hypoglycemic tumors composed almost entirely of insulin-producing beta cells. When a genomic DNA fragment containing the coding and upstream regulatory regions of the human insulin gene was stably transfected into MSL-G2 cells no measurable amounts of insulin or insulin mRNA were detected in vitro. However, successive transplantation of two transfected clones resulted in hypoglycemic tumors that efficiently coexpressed human and rat insulin as determined by human C-peptide-specific immunoreagents. These results demonstrate that cis-acting tissue-specific insulin gene enhancer elements are conserved between rat and human insulin genes. The authors propose that the in vivo differentiation of MSL-G2 cells and transfected subclones into insulin-producing cells reflects processes of natural beta-cell ontogeny leading to insulin gene expression

  8. Long-range looping of a locus control region drives tissue-specific chromatin packing within a multigene cluster.

    Tsai, Yu-Cheng; Cooke, Nancy E; Liebhaber, Stephen A

    2016-06-01

    The relationships of higher order chromatin organization to mammalian gene expression remain incompletely defined. The human Growth Hormone (hGH) multigene cluster contains five gene paralogs. These genes are selectively activated in either the pituitary or the placenta by distinct components of a remote locus control region (LCR). Prior studies have revealed that appropriate activation of the placental genes is dependent not only on the actions of the LCR, but also on the multigene composition of the cluster itself. Here, we demonstrate that the hGH LCR 'loops' over a distance of 28 kb in primary placental nuclei to make specific contacts with the promoters of the two GH genes in the cluster. This long-range interaction sequesters the GH genes from the three hCS genes which co-assemble into a tightly packed 'hCS chromatin hub'. Elimination of the long-range looping, via specific deletion of the placental LCR components, triggers a dramatic disruption of the hCS chromatin hub. These data reveal a higher-order structural pathway by which long-range looping from an LCR impacts on local chromatin architecture that is linked to tissue-specific gene regulation within a multigene cluster. PMID:26893355

  9. Dose-dependence, sex- and tissue-specificity, and persistence of radiation-induced genomic DNA methylation changes

    Radiation is a well-known genotoxic agent and human carcinogen that gives rise to a variety of long-term effects. Its detrimental influence on cellular function is actively studied nowadays. One of the most analyzed, yet least understood long-term effects of ionizing radiation is transgenerational genomic instability. The inheritance of genomic instability suggests the possible involvement of epigenetic mechanisms, such as changes of the methylation of cytosine residues located within CpG dinucleotides. In the current study we evaluated the dose-dependence of the radiation-induced global genome DNA methylation changes. We also analyzed the effects of acute and chronic high dose (5 Gy) exposure on DNA methylation in liver, spleen, and lung tissues of male and female mice and evaluated the possible persistence of the radiation-induced DNA methylation changes. Here we report that radiation-induced DNA methylation changes were sex- and tissue-specific, dose-dependent, and persistent. In parallel we have studied the levels of DNA damage in the exposed tissues. Based on the correlation between the levels of DNA methylation and DNA damage we propose that radiation-induced global genome DNA hypomethylation is DNA repair-related

  10. Systems view of adipogenesis via novel omics-driven and tissue-specific activity scoring of network functional modules

    Nassiri, Isar; Lombardo, Rosario; Lauria, Mario; Morine, Melissa J.; Moyseos, Petros; Varma, Vijayalakshmi; Nolen, Greg T.; Knox, Bridgett; Sloper, Daniel; Kaput, Jim; Priami, Corrado

    2016-07-01

    The investigation of the complex processes involved in cellular differentiation must be based on unbiased, high throughput data processing methods to identify relevant biological pathways. A number of bioinformatics tools are available that can generate lists of pathways ranked by statistical significance (i.e. by p-value), while ideally it would be desirable to functionally score the pathways relative to each other or to other interacting parts of the system or process. We describe a new computational method (Network Activity Score Finder - NASFinder) to identify tissue-specific, omics-determined sub-networks and the connections with their upstream regulator receptors to obtain a systems view of the differentiation of human adipocytes. Adipogenesis of human SBGS pre-adipocyte cells in vitro was monitored with a transcriptomic data set comprising six time points (0, 6, 48, 96, 192, 384 hours). To elucidate the mechanisms of adipogenesis, NASFinder was used to perform time-point analysis by comparing each time point against the control (0 h) and time-lapse analysis by comparing each time point with the previous one. NASFinder identified the coordinated activity of seemingly unrelated processes between each comparison, providing the first systems view of adipogenesis in culture. NASFinder has been implemented into a web-based, freely available resource associated with novel, easy to read visualization of omics data sets and network modules.

  11. A Systematic Phenotypic Screen of F-box Genes Through a Tissue-specific RNAi-based Approach in Drosophila

    Wen Dui; Wei Lu; Jun Ma; Renjie Jiao

    2012-01-01

    F-box proteins are components of the SCF (SkpA-Cullin 1-F-box) E3 ligase complexes,acting as the specificity-determinants in targeting substrate proteins for ubiquitination and degradation.In humans,at least 22 out of 75 F-box proteins have experimentally documented substrates,whereas in Drosophila 12 F-box proteins have been characterized with known substrates.To systematically investigate the genetic and molecular functions of F-box proteins in Drosophila,we performed a survey of the literature and databases.We identified 45 Drosophila genes that encode proteins containing at least one F-box domain.We collected publically available RNAi lines against these genes and used them in a tissue-specific RNAi-based phenotypic screen.Here,we present our systematic phenotypic dataset from the eye,the wing and the notum.This dataset is the first of its kind and represents a useful resource for future studies of the molecular and genetic functions of F-box genes in Drosophila.Our results show that,as expected,F-box genes in Drosophila have regulatory roles in a diverse array of processes including cell proliferation,cell growth,signal transduction,and cellular and animal survival.

  12. Identification and tissue-specific distribution of sulfated glycosaminoglycans in the blood-sucking bug Rhodnius prolixus (Linnaeus).

    Costa-Filho, Adilson; Souza, Maisa L S; Martins, Rita C L; dos Santos, André V F; Silva, Gabriela V; Comaru, Michele W; Moreira, Mônica F; Atella, Georgia C; Allodi, Silvana; Nasciutti, Luiz E; Masuda, Hatisaburo; Silva, Luiz-Claudio F

    2004-03-01

    We have previously characterized heparan sulfate (HS) as the major ovarian sulfated glycosaminoglycan (GAG) in females of Rhodnius prolixus, while chondroitin sulfate (CS) was the minor component. Using histochemical procedures we found that GAGs were concentrated in the ovarian tissue but not found inside the oocytes. Here, we extend our initial observations of GAG expression in R. prolixus by characterizing these molecules in other organs: the fat body, intestinal tract, and the reproductive tracts. Only HS and CS were found in the three organs analyzed, however CS was the major GAG species in these tissues. We also determined the compartmental distribution of GAGs in these organs by histochemical analysis using 1,9-dimethylmethylene blue, and evaluated the specific distribution of CS within both male and female reproductive tracts by immunohistochemistry using an anti-CS antibody. We also determined the GAG composition in eggs at days 0 and 6 of embryonic development. Only HS and CS were found in eggs at day 6, while no sulfated GAGs were detected at day 0. Our results demonstrate that HS and CS are the only sulfated GAG species expressed in the fat body and in the intestinal and reproductive tracts of Rhodnius male and female adults. Both sulfated GAGs were also identified in Rhodnius embryos. Altogether, these results show no qualitative differences in the sulfated GAG composition regarding tissue-specific or development-specific distribution. PMID:14871621

  13. Nonsyntenic Genes Drive Tissue-Specific Dynamics of Differential, Nonadditive, and Allelic Expression Patterns in Maize Hybrids.

    Baldauf, Jutta A; Marcon, Caroline; Paschold, Anja; Hochholdinger, Frank

    2016-06-01

    Distantly related maize (Zea mays) inbred lines display an exceptional degree of genomic diversity. F1 progeny of such inbred lines are often more vigorous than their parents, a phenomenon known as heterosis. In this study, we investigated how the genetic divergence of the maize inbred lines B73 and Mo17 and their F1 hybrid progeny is reflected in differential, nonadditive, and allelic expression patterns in primary root tissues. In pairwise comparisons of the four genotypes, the number of differentially expressed genes between the two parental inbred lines significantly exceeded those of parent versus hybrid comparisons in all four tissues under analysis. No differentially expressed genes were detected between reciprocal hybrids, which share the same nuclear genome. Moreover, hundreds of nonadditive and allelic expression ratios that were different from the expression ratios of the parents were observed in the reciprocal hybrids. The overlap of both nonadditive and allelic expression patterns in the reciprocal hybrids significantly exceeded the expected values. For all studied types of expression - differential, nonadditive, and allelic - substantial tissue-specific plasticity was observed. Significantly, nonsyntenic genes that evolved after the last whole genome duplication of a maize progenitor from genes with synteny to sorghum (Sorghum bicolor) were highly overrepresented among differential, nonadditive, and allelic expression patterns compared with the fraction of these genes among all expressed genes. This observation underscores the role of nonsyntenic genes in shaping the transcriptomic landscape of maize hybrids during the early developmental manifestation of heterosis in root tissues of maize hybrids. PMID:27208302

  14. Tissue-specific expression of GFP reporter gene in germline driven by GATA-2 promoter and enhancers in zebrafish

    2000-01-01

    GATA-2,a transcription factor,is expressed in several types of blood cells and in the central nervous system (CNS),and regulates the differentiation of these cells.We have obtained five zebrafish transgenic germlines that carry and express the green fluorescent protein (GFP) gene ligated to various 5′flanking sequences of zebrafish GATA-2 gene.The spatial pattern of GFP expression varies,mainly depending on which regulatory sequence is used,among the germlines.In some of the germlines,the expression of GFP is restricted to the CNS and the enveloping layer (EVL) cells,while in some other lines GFP is observed only in the CNS.It is noted that the intensity of GFP in the transgenic fish remain unchanged after a six-generation passage of the transgenes.The transgenic fish could find its uses in the future in generating tissue-specific,even cellspecific mutant fish and in functional study of related genes through transgenesis.

  15. 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

    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.

  16. Identification of tissue-specific DNA-protein binding sites by means of two-dimensional electrophoretic mobility shift assay display.

    Chernov, Igor P; Timchenko, Kira A; Akopov, Sergey B; Nikolaev, Lev G; Sverdlov, Eugene D

    2007-05-01

    We developed a technique of differential electrophoretic mobility shift assay (EMSA) display allowing identification of tissue-specific protein-binding sites within long genomic sequences. Using this approach, we identified 10 cell type-specific protein-binding sites (protein target sites [PTSs]) within a 137-kb human chromosome 19 region. In general, tissue-specific binding of proteins from different nuclear extracts by individual PTSs did not follow the all-or-nothing principle. Most often, PTS-protein complexes were formed in all cases, but they were different for different nuclear extracts used. PMID:17359930

  17. Regulation of tissue-specific alternative splicing: exon-specific cis-elements govern the splicing of leukocyte common antigen pre-mRNA.

    Streuli, M; Saito, H

    1989-01-01

    Tissue-specific alternative splicing is an important mechanism for controlling gene expression. Exons 4, 5 and 6 of the human leukocyte common antigen (LCA) gene are included in B cell mRNA but excluded from thymocyte mRNA by differential splicing. In order to study this tissue-specific alternative splicing, we constructed mini-genes that contain only a few of the LCA exons and the SV40 promoter. Mouse B cells and thymocytes were transfected with these mini-gene constructs and the structures ...

  18. A comprehensive gene expression atlas of sex- and tissue-specificity in the malaria vector, Anopheles gambiae

    Crisanti Andrea

    2011-06-01

    Full Text Available Abstract Background The mosquito, Anopheles gambiae, is the primary vector of human malaria, a disease responsible for millions of deaths each year. To improve strategies for controlling transmission of the causative parasite, Plasmodium falciparum, we require a thorough understanding of the developmental mechanisms, physiological processes and evolutionary pressures affecting life-history traits in the mosquito. Identifying genes expressed in particular tissues or involved in specific biological processes is an essential part of this process. Results In this study, we present transcription profiles for ~82% of annotated Anopheles genes in dissected adult male and female tissues. The sensitivity afforded by examining dissected tissues found gene activity in an additional 20% of the genome that is undetected when using whole-animal samples. The somatic and reproductive tissues we examined each displayed patterns of sexually dimorphic and tissue-specific expression. By comparing expression profiles with Drosophila melanogaster we also assessed which genes are well conserved within the Diptera versus those that are more recently evolved. Conclusions Our expression atlas and associated publicly available database, the MozAtlas (http://www.tissue-atlas.org, provides information on the relative strength and specificity of gene expression in several somatic and reproductive tissues, isolated from a single strain grown under uniform conditions. The data will serve as a reference for other mosquito researchers by providing a simple method for identifying where genes are expressed in the adult, however, in addition our resource will also provide insights into the evolutionary diversity associated with gene expression levels among species.

  19. Tissue-specific increases in 11beta-hydroxysteroid dehydrogenase type 1 in normal weight postmenopausal women.

    Therése Andersson

    Full Text Available With age and menopause there is a shift in adipose distribution from gluteo-femoral to abdominal depots in women. Associated with this redistribution of fat are increased risks of type 2 diabetes and cardiovascular disease. Glucocorticoids influence body composition, and 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1 which converts inert cortisone to active cortisol is a putative key mediator of metabolic complications in obesity. Increased 11betaHSD1 in adipose tissue may contribute to postmenopausal central obesity. We hypothesized that tissue-specific 11betaHSD1 gene expression and activity are up-regulated in the older, postmenopausal women compared to young, premenopausal women. Twenty-three pre- and 23 postmenopausal, healthy, normal weight women were recruited. The participants underwent a urine collection, a subcutaneous adipose tissue biopsy and the hepatic 11betaHSD1 activity was estimated by the serum cortisol response after an oral dose of cortisone. Urinary (5alpha-tetrahydrocortisol+5beta-tetrahydrocortisol/tetrahydrocortisone ratios were higher in postmenopausal women versus premenopausal women in luteal phase (P<0.05, indicating an increased whole-body 11betaHSD1 activity. Postmenopausal women had higher 11betaHSD1 gene expression in subcutaneous fat (P<0.05. Hepatic first pass conversion of oral cortisone to cortisol was also increased in postmenopausal women versus premenopausal women in follicular phase of the menstrual cycle (P<0.01, at 30 min post cortisone ingestion, suggesting higher hepatic 11betaHSD1 activity. In conclusion, our results indicate that postmenopausal normal weight women have increased 11betaHSD1 activity in adipose tissue and liver. This may contribute to metabolic dysfunctions with menopause and ageing in women.

  20. Assessment of tissue-specific accumulation and effects of cadmium in a marine fish fed contaminated commercially produced diet

    Commercially produced fish diet is now widely used in fish farming but it often contains elevated levels of cadmium (Cd). However, the adverse effects on fish are poorly understood. In this study, farm-raised marine grunts, Terapon jarbua, were fed Cd-contaminated diet or exposed to waterborne Cd for 4 weeks. Tissue-specific Cd bioaccumulation and its effects were subsequently examined. We found that Cd was accumulated in different fish tissues (digestive tracts, gills or livers). At the end of the exposure, Cd accumulation peaked in the fishes' livers (5.0-6.3 μg g-1), followed by the digestive tracts (0.83-3.16 μg g-1) and gills (0.27-2.74 μg g-1). Endpoints such as the survival rate, specific growth rate, condition factor, and superoxide dismutase activity were not significantly affected by Cd exposure. In contrast, metallothionein (MT) induction and subcellular Cd distribution indicated that there were possible sublethal effects of Cd exposure. MT was induced in response to Cd accumulation, but it returned to the control levels after a longer exposure period, except for hepatic MT induction resulting from waterborne or low dietary Cd exposure. The Cd percentage in the metallothionein-like protein (MTLP) fraction increased over exposure time, and it accounted for more than 57% Cd in the fishes' livers and 80% Cd in their digestive tracts by the end of the exposure period. Overall, although Cd in commercial fish diet did not have significant lethality to T. jarbua, sensitive responses such as hepatic MT induction and subcellular Cd distribution revealed that the Cd-induced storage and detoxification in T. jarbua may increase fish's tolerance to toxic metals.

  1. Tissue-specific expression of a gene encoding a cell wall-localized lipid transfer protein from Arabidopsis.

    Thoma, S; Hecht, U; Kippers, A; Botella, J; De Vries, S; Somerville, C

    1994-05-01

    Nonspecific lipid transfer proteins (LTPs) from plants are characterized by their ability to stimulate phospholipid transfer between membranes in vitro. However, because these proteins are generally located outside of the plasma membrane, it is unlikely that they have a similar role in vivo. As a step toward identifying the function of these proteins, one of several LTP genes from Arabidoposis has been cloned and the expression pattern of the gene has been examined by analysis of the tissue specificity of beta-glucuronidase (GUS) activity in transgenic plants containing LTP promoter-GUS fusions and by in situ mRNA localization. The LTP1 promoter was active early in development in protoderm cells of embryos, vascular tissues, lignified tips of cotyledons, shoot meristem, and stipules. In adult plants, the gene was expressed in epidermal cells of young leaves and the stem. In flowers, expression was observed in the epidermis of all developing influorescence and flower organ primordia, the epidermis of the siliques and the outer ovule wall, the stigma, petal tips, and floral nectaries of mature flowers, and the petal/sepal abscission zone of mature siliques. The presence of GUS activity in guard cells, lateral roots, pollen grains, leaf vascular tissue, and internal cells of stipules and nectaries was not confirmed by in situ hybridizations, supporting previous observations that suggest that the reporter gene is subject to artifactual expression. These results are consistent with a role for the LTP1 gene product in some aspect of secretion or deposition of lipophilic substances in the cell walls of expanding epidermal cells and certain secretory tissues. The LTP1 promoter region contained sequences homologous to putative regulatory elements of genes in the phenylpropanoid biosynthetic pathway, suggesting that the expression of the LTP1 gene may be regulated by the same or similar mechanisms as genes in the phenylpropanoid pathway. PMID:8029357

  2. Assessment of tissue-specific accumulation and effects of cadmium in a marine fish fed contaminated commercially produced diet

    Dang Fei [AMCE and Department of Biology, Hong Kong University of Science and Technology (HKUST), Clear Water Bay, Kowloon (Hong Kong); Wang Wenxiong, E-mail: wwang@ust.hk [AMCE and Department of Biology, Hong Kong University of Science and Technology (HKUST), Clear Water Bay, Kowloon (Hong Kong)

    2009-11-27

    Commercially produced fish diet is now widely used in fish farming but it often contains elevated levels of cadmium (Cd). However, the adverse effects on fish are poorly understood. In this study, farm-raised marine grunts, Terapon jarbua, were fed Cd-contaminated diet or exposed to waterborne Cd for 4 weeks. Tissue-specific Cd bioaccumulation and its effects were subsequently examined. We found that Cd was accumulated in different fish tissues (digestive tracts, gills or livers). At the end of the exposure, Cd accumulation peaked in the fishes' livers (5.0-6.3 {mu}g g{sup -1}), followed by the digestive tracts (0.83-3.16 {mu}g g{sup -1}) and gills (0.27-2.74 {mu}g g{sup -1}). Endpoints such as the survival rate, specific growth rate, condition factor, and superoxide dismutase activity were not significantly affected by Cd exposure. In contrast, metallothionein (MT) induction and subcellular Cd distribution indicated that there were possible sublethal effects of Cd exposure. MT was induced in response to Cd accumulation, but it returned to the control levels after a longer exposure period, except for hepatic MT induction resulting from waterborne or low dietary Cd exposure. The Cd percentage in the metallothionein-like protein (MTLP) fraction increased over exposure time, and it accounted for more than 57% Cd in the fishes' livers and 80% Cd in their digestive tracts by the end of the exposure period. Overall, although Cd in commercial fish diet did not have significant lethality to T. jarbua, sensitive responses such as hepatic MT induction and subcellular Cd distribution revealed that the Cd-induced storage and detoxification in T. jarbua may increase fish's tolerance to toxic metals.

  3. Identification of the interactome between fish plasma proteins and Edwardsiella tarda reveals tissue-specific strategies against bacterial infection.

    Li, Hui; Huang, Xiaoyan; Zeng, Zaohai; Peng, Xuan-Xian; Peng, Bo

    2016-09-01

    Elucidating the complex pathogen-host interaction is essential for a comprehensive understanding of how these remarkable agents invade their hosts and how the hosts defend against these invaders. During the infection, pathogens interact intensively with host to enable their survival, which can be revealed through their interactome. Edwardsiella tarda is a Gram-negative bacterial pathogen causing huge economic loss in aquaculture and a spectrum of intestinal and extraintestinal diseases in humans. E. tarda is an ideal model for host-pathogen investigation as it infects fish in three distinct steps: entering the host, circulating through the blood and establishing infection. We adopted a previous established proteomic approach that inactivated E. tarda cells and covalent crosslink fish plasma proteins were used to capture plasma proteins and bacterial outer membrane proteins, respectively. By the combinatorial use of proteomic and biochemical approaches, six plasma proteins and seven outer membrane proteins (OMPs) were identified. Interactions among these proteins were validated with protein-array, far-Western blotting and co-immunoprecipitation. At last, seventeen plasma protein-bacteria protein-protein interaction were confirmed to be involved in the interaction network, forming a complex interactome. Compared to our previous results, different host proteins were detected, whereas some of the bacterial proteins were similar, which indicates that hosts adopt tissue-specific strategies to cope with the same pathogen during infection. Thus, our results provide a robust demonstration of both bacterial initiators and host receptors or interacting proteins to further explore infection and anti-infective mechanisms between hosts and microbes. PMID:27458055

  4. Common inversion polymorphism at 17q21.31 affects expression of multiple genes in tissue-specific manner

    de Jong Simone

    2012-09-01

    Full Text Available Abstract Background Chromosome 17q21.31 contains a common inversion polymorphism of approximately 900 kb in populations with European ancestry. Two divergent MAPT haplotypes, H1 and H2 are described with distinct linkage disequilibrium patterns across the region reflecting the inversion status at this locus. The MAPT H1 haplotype has been associated with progressive supranuclear palsy, corticobasal degeneration, Parkinson’s disease and Alzheimer’s disease, while the H2 is linked to recurrent deletion events associated with the 17q21.31 microdeletion syndrome, a disease characterized by developmental delay and learning disability. Results In this study, we investigate the effect of the inversion on the expression of genes in the 17q21.31 region. We find the expression of several genes in and at the borders of the inversion to be affected; specific either to whole blood or different regions of the human brain. The H1 haplotype was found to be associated with an increased expression of LRRC37A4, PLEKH1M and MAPT. In contrast, a decreased expression of MGC57346, LRRC37A and CRHR1 was associated with H1. Conclusions Studies thus far have focused on the expression of MAPT in the inversion region. However, our results show that the inversion status affects expression of other genes in the 17q21.31 region as well. Given the link between the inversion status and different neurological diseases, these genes may also be involved in disease pathology, possibly in a tissue-specific manner.

  5. Tissue specific alterations in the Elα subunit of branched-chain ketoacid dehydrogenase (BCKD) in rats

    Polyclonal antibodies (anti-E1E2 IgG) directed against bovine kidney BCKD have been used to examine the metabolic role of this enzyme in the rat. BCKD activity was assayed in detergent-disrupted kidney mitochondria using [1-14C]α-ketoacids. Rates of oxidation of the keto analogs of leucine, valine and isoleucine were 21.6 +/- 1.5, 20.6 +/- 1.3 and 10.2 +/- 0.6 nmol/min/mg protein, respectively. Addition of anti-E1E2 IgG completely inhibited oxidation of all 3 ketoacids. Anti-E1E2 IgG inhibited oxidation of the keto analogs derived from methionine and threonine by 75% and 30%, respectively. It did not inhibit mitochondrial dehydrogenases other than BCKD. Thus, BCKD appears to be important in oxidative metabolism of 5 of the 9 indispensable amino acids. Immunoblots of rat kidneys, liver, muscle and heart mitochondria revealed a tissue specific alteration in the E1α subunit of BCKD. Kidneys and heart each appeared to contain two E1α polypeptides differing by an apparent molecular weight of 900 daltons; the predominant E1α polypeptide in heart was the heavier E1α band whereas in kidney it was the lighter band. Liver and muscle, however, each exhibited a single but different E1α polypeptide. E1α in liver corresponded to the lighter E1α polypeptide of kidney and heart whereas in muscle E1α corresponded to the heavier polypeptide. The E1α subunit differences are associated with differences in basal BCKD activity of these tissues

  6. Combinatorial binding leads to diverse regulatory responses: Lmd is a tissue-specific modulator of Mef2 activity.

    Paulo M F Cunha

    2010-07-01

    Full Text Available Understanding how complex patterns of temporal and spatial expression are regulated is central to deciphering genetic programs that drive development. Gene expression is initiated through the action of transcription factors and their cofactors converging on enhancer elements leading to a defined activity. Specific constellations of combinatorial occupancy are therefore often conceptualized as rigid binding codes that give rise to a common output of spatio-temporal expression. Here, we assessed this assumption using the regulatory input of two essential transcription factors within the Drosophila myogenic network. Mutations in either Myocyte enhancing factor 2 (Mef2 or the zinc-finger transcription factor lame duck (lmd lead to very similar defects in myoblast fusion, yet the underlying molecular mechanism for this shared phenotype is not understood. Using a combination of ChIP-on-chip analysis and expression profiling of loss-of-function mutants, we obtained a global view of the regulatory input of both factors during development. The majority of Lmd-bound enhancers are co-bound by Mef2, representing a subset of Mef2's transcriptional input during these stages of development. Systematic analyses of the regulatory contribution of both factors demonstrate diverse regulatory roles, despite their co-occupancy of shared enhancer elements. These results indicate that Lmd is a tissue-specific modulator of Mef2 activity, acting as both a transcriptional activator and repressor, which has important implications for myogenesis. More generally, this study demonstrates considerable flexibility in the regulatory output of two factors, leading to additive, cooperative, and repressive modes of co-regulation.

  7. A new method to determine tissue specific tissue factor thrombomodulin activities: endotoxin and particulate air pollution induced disbalance

    Gerlofs-Nijland Miriam E

    2008-10-01

    Full Text Available Abstract Background Increase in tissue factor (TF and loss in thrombomodulin (TM antigen levels has been described in various inflammatory disorders. The functional consequences of such changes in antigen concentrations in the coagulation balance are, however, not known. This study was designed to assess the consequences of inflammation-driven organ specific functional properties of the procoagulant response. Methods Tissue specific procoagulant activity was assessed by adding tissue homogenate to normal human pool plasma and recording of the thrombin generation curve. The new technique was subsequently applied on two inflammation driven animal models: 1 mouse lipopolysaccharide (LPS induced endotoxemia and 2 spontaneously hypertensive rats exposed to environmental air pollution (particulate matter (PM. Results Addition of lung tissue from untreated animals to human plasma suppressed the endogenous thrombin potential (ETP (175 ± 61 vs. 1437 ± 112 nM.min for control. This inhibitory effect was due to TM, because a it was absent in protein C deficient plasma and b lungs from TMpro/pro mice allowed full thrombin generation (ETP: 1686 ± 209 nM.min. The inhibitory effect of TM was lost after LPS administration to mice, which induced TF activity in lungs of C57Bl/6 mice as well as increased the ETP (941 ± 523 vs. 194 ± 159 nM.min for control. Another pro-inflammatory stimulus, PM dose-dependently increased TF in the lungs of spontaneously hypertensive rats at 4 and 48 hours after PM exposure. The ETP increased up to 48 hours at the highest concentration of PM (1441 ± 289 nM.min vs. saline: 164 ± 64 nM.min, p Conclusion Inflammation associated procoagulant effects in tissues are dependent on variations in activity of the TF-TM balance. The application of these novel organ specific functional assays is a useful tool to monitor inflammation-driven shifts in the coagulation balance within animal or human tissues.

  8. Dynamic Metabolic Profiles and Tissue-Specific Source Effects on the Metabolome of Developing Seeds of Brassica napus.

    Helin Tan

    Full Text Available Canola (Brassica napus is one of several important oil-producing crops, and the physiological processes, enzymes, and genes involved in oil synthesis in canola seeds have been well characterized. However, relatively little is known about the dynamic metabolic changes that occur during oil accumulation in seeds, as well as the mechanistic origins of metabolic changes. To explore the metabolic changes that occur during oil accumulation, we isolated metabolites from both seed and silique wall and identified and characterized them by using gas chromatography coupled with mass spectrometry (GC-MS. The results showed that a total of 443 metabolites were identified from four developmental stages. Dozens of these metabolites were differentially expressed during seed ripening, including 20 known to be involved in seed development. To investigate the contribution of tissue-specific carbon sources to the biosynthesis of these metabolites, we examined the metabolic changes of silique walls and seeds under three treatments: leaf-detachment (Ld, phloem-peeling (Pe, and selective silique darkening (Sd. Our study demonstrated that the oil content was independent of leaf photosynthesis and phloem transport during oil accumulation, but required the metabolic influx from the silique wall. Notably, Sd treatment resulted in seed senescence, which eventually led to a severe reduction of the oil content. Sd treatment also caused a significant accumulation of fatty acids (FA, organic acids and amino acids. Furthermore, an unexpected accumulation of sugar derivatives and organic acid was observed in the Pe- and Sd-treated seeds. Consistent with this, the expression of a subset of genes involved in FA metabolism, sugar and oil storage was significantly altered in Pe and Sd treated seeds. Taken together, our studies suggest the metabolite profiles of canola seeds dynamically varied during the course of oil accumulation, which may provide a new insight into the mechanisms

  9. Tissue-specific and neural activity-regulated expression of human BDNF gene in BAC transgenic mice

    Palm Kaia

    2009-06-01

    Full Text Available Abstract Background Brain-derived neurotrophic factor (BDNF is a small secreted protein that has important roles in the developing and adult nervous system. Altered expression or changes in the regulation of the BDNF gene have been implicated in a variety of human nervous system disorders. Although regulation of the rodent BDNF gene has been extensively investigated, in vivo studies regarding the human BDNF gene are largely limited to postmortem analysis. Bacterial artificial chromosome (BAC transgenic mice harboring the human BDNF gene and its regulatory flanking sequences constitute a useful tool for studying human BDNF gene regulation and for identification of therapeutic compounds modulating BDNF expression. Results In this study we have generated and analyzed BAC transgenic mice carrying 168 kb of the human BDNF locus modified such that BDNF coding sequence was replaced with the sequence of a fusion protein consisting of N-terminal BDNF and the enhanced green fluorescent protein (EGFP. The human BDNF-BAC construct containing all BDNF 5' exons preceded by different promoters recapitulated the expression of endogenous BDNF mRNA in the brain and several non-neural tissues of transgenic mice. All different 5' exon-specific BDNF-EGFP alternative transcripts were expressed from the transgenic human BDNF-BAC construct, resembling the expression of endogenous BDNF. Furthermore, BDNF-EGFP mRNA was induced upon treatment with kainic acid in a promotor-specific manner, similarly to that of the endogenous mouse BDNF mRNA. Conclusion Genomic region covering 67 kb of human BDNF gene, 84 kb of upstream and 17 kb of downstream sequences is sufficient to drive tissue-specific and kainic acid-induced expression of the reporter gene in transgenic mice. The pattern of expression of the transgene is highly similar to BDNF gene expression in mouse and human. This is the first study to show that human BDNF gene is regulated by neural activity.

  10. Interstitial tissue-specific gene expression in mouse testis by intra-tunica albuguineal injection of recombinant baculovirus

    Hyun Jung Park; Won Young Lee; Jin Hoi Kim; Jae Hwan Kim; Hun Jong Jung; Nam Hyung Kim; Bo Kyung Kim; Hyuk Song

    2009-01-01

    The purpose of this study is to establish a gene delivery system for interstitial tissue-specific protein expression in mice testes using modified recombinant baculovirus. Green fluorescent protein (GFP)-expressing recombinant bacuiovirus (GFP-baculovirus), in which the insect cell-specific polyhedron promoter was replaced by the cytomegalovirus (CMV)-IE promoter, was used to transfect testicular cells in vitro, and for intra-tunica albuguineai injection of the interstitial tissue of the testis. GFP expression was monitored in frozen testes sections by fluorescence microscopy. Expression of GFP in testicular tissues was also assessed by reverse transcription polymerase chain reaction (RT-PCR), and protein expression was assessed by Western blot. Testicular cells in vitro were infected efficiently by modified recombinant GFP-baculovirus. Intra-tunica albuguineal injection of GFP-baculovirus into the mouse testis resulted in a high level of GFP expression in the interstitial tissues. RT-PCR analysis clearly showed GFP gene expression in the testis, particularly interstitial tissues. Intra-tunica albuguineal injection of a modified baculovirus that encoded recombinant rat insulin-like growth factor binding protein (IGFBP)-5 resulted in an increase in IGFBP-5 in testis and semen. In conclusion, we have developed an efficient delivery system for gene expression in vivo in testicular cells, particularly cells of the interstitial tissue using intra-tunica albuguineal injection of a modified recombinant baculovirus. This method will be particularly relevant for application that requires gene delivery and protein expression in the testicular cells of the outer seminiferous tubule of the testis.

  11. [11C]-metformin distribution in the liver and small intestine using dynamic PET in mice demonstrates tissue-specific transporter dependency

    Jensen, Jonas B; Sundelin, Elias I; Jakobsen, Steen;

    2016-01-01

    ) including Multidrug and Toxin Extrusion proteins (MATE) are essential for transport of metformin across membranes, but tissue-specific activity of these transporters in vivo is incompletely understood. Here, we use dynamic PET with C11-labelled metformin ([11C]-metformin) in mice to investigate the role of...

  12. Persistent foot-and-mouth disease virus infection in the nasopharynx of cattle: tissue-specific distribution and local cytokine expression

    Tissues obtained post-mortem from cattle persistently infected with foot-and-mouth disease virus (FMDV) were analyzed to characterize the tissue-specific localization of FMDV and partial transcriptome profiles for selected immunoregulatory cytokines. Analysis of 28 distinct anatomic sites from 21 st...

  13. Complementarity of medium-throughput in situ RNA hybridization and tissue-specific transcriptomics: case study of Arabidopsis seed development kinetics.

    Francoz, Edith; Ranocha, Philippe; Pernot, Clémentine; Ru, Aurélie Le; Pacquit, Valérie; Dunand, Christophe; Burlat, Vincent

    2016-01-01

    The rationale of this study is to compare and integrate two heterologous datasets intended to unravel the spatiotemporal specificities of gene expression in a rapidly growing and complex organ. We implemented medium-throughput RNA in situ hybridization (ISH) for 39 genes mainly corresponding to cell wall proteins for which we have particular interest, selected (i) on their sequence identity (24 class III peroxidase multigenic family members and 15 additional genes used as positive controls) and (ii) on their expression levels in a publicly available Arabidopsis thaliana seed tissue-specific transcriptomics study. The specificity of the hybridization signals was carefully studied, and ISH results obtained for the 39 selected genes were systematically compared with tissue-specific transcriptomics for 5 seed developmental stages. Integration of results illustrates the complementarity of both datasets. The tissue-specific transcriptomics provides high-throughput possibilities whereas ISH provides high spatial resolution. Moreover, depending on the tissues and the developmental stages considered, one or the other technique appears more sensitive than the other. For each tissue/developmental stage, we finally determined tissue-specific transcriptomic threshold values compatible with the spatiotemporally-specific detection limits of ISH for lists of hundreds to tens-of-thousands of genes. PMID:27095274

  14. Regulation of oxytocin receptor gene expression in sheep: tissue specificity, multiple transcripts and mRNA editing.

    Feng, H C; Bhave, M; Fairclough, R J

    2000-09-01

    The increase in uterine oxytocin receptor concentrations over the late luteal phase of the oestrous cycle in sheep is thought to play an important role in the regulation of the duration of the cycle by facilitating the effect of oxytocin on uterine prostaglandin release. Experiments indicated that oxytocin receptor mRNA expression in the endometrium was high at oestrus compared with at days 2, 7 and 12 of the oestrous cycle. The amount of oxytocin receptor mRNA expression in the pituitary gland did not show any significant differences during the oestrous cycle. Oxytocin receptor cDNA was obtained and characterized from ovine uterine endometrium on day 15 of the oestrous cycle, using RT-PCR techniques, to study the mechanisms underlying the resolution of oxytocin receptor expression. The cDNA sequence for the oxytocin receptor gene in sheep was found to be similar to that described previously, except for a difference of seven nucleotides. These nucleotide differences resulted in changes in four of the deduced amino acids in the oxytocin receptor sequence. The heterogeneity of the different sized oxytocin receptor transcripts in sheep is due, at least in part, to the alternative use of polyadenylation sites. Northern hybridization confirmed that the oxytocin receptor gene is expressed in ovine corpus luteum. The investigations on oxytocin receptor gene expression indicate that the patten of oxytocin receptor gene expression in sheep is not only tissue-specific, but also highly function-related. Evidence was obtained of mRNA editing in both the coding and the 3'-untranslated (3'UTR) regions of oxytocin receptor gene transcripts in ovine endometrium; this was the first demonstration of this phenomenon for oxytocin receptor mRNA. The present results indicate that the observed differences in oxytocin receptor mRNA sequences for the different oxytocin receptor populations in endometrium are due to mRNA editing. mRNA editing of oxytocin receptor transcripts may be

  15. EFS shows biallelic methylation in uveal melanoma with poor prognosis as well as tissue-specific methylation

    Uveal melanoma (UM) is a rare eye tumor. There are two classes of UM, which can be discriminated by the chromosome 3 status or global mRNA expression profile. Metastatic progression is predominantly originated from class II tumors or from tumors showing loss of an entire chromosome 3 (monosomy 3). We performed detailed EFS (embryonal Fyn-associated substrate) methylation analyses in UM, cultured uveal melanocytes and normal tissues, to explore the role of the differentially methylated EFS promoter region CpG island in tumor classification and metastatic progression. EFS methylation was determined by direct sequencing of PCR products from bisulfite-treated DNA or by sequence analysis of individual cloned PCR products. The results were associated with clinical features of tumors and tumor-related death of patients. Analysis of 16 UM showed full methylation of the EFS CpG island in 8 (50%), no methylation in 5 (31%) and partial methylation in 3 (19%) tumors. Kaplan-Meier analysis revealed a higher risk of metastatic progression for tumors with EFS methylation (p = 0.02). This correlation was confirmed in an independent set of 24 randomly chosen tumors. Notably, only UM with EFS methylation gave rise to metastases. Real-time quantitative RT-PCR expression analysis revealed a significant inverse correlation of EFS mRNA expression with EFS methylation in UM. We further found that EFS methylation is tissue-specific with full methylation in peripheral blood cells, and no methylation in sperm, cultured primary fibroblasts and fetal muscle, kidney and brain. Adult brain samples, cultured melanocytes from the uveal tract, fetal liver and 3 of 4 buccal swab samples showed partial methylation. EFS methylation always affects both alleles in normal and tumor samples. Biallelic EFS methylation is likely to be the result of a site-directed methylation mechanism. Based on partial methylation as observed in cultured melanocytes we hypothesize that there might be methylated and

  16. Mining tissue specificity, gene connectivity and disease association to reveal a set of genes that modify the action of disease causing genes

    Reverter Antonio

    2008-09-01

    Full Text Available Abstract Background The tissue specificity of gene expression has been linked to a number of significant outcomes including level of expression, and differential rates of polymorphism, evolution and disease association. Recent studies have also shown the importance of exploring differential gene connectivity and sequence conservation in the identification of disease-associated genes. However, no study relates gene interactions with tissue specificity and disease association. Methods We adopted an a priori approach making as few assumptions as possible to analyse the interplay among gene-gene interactions with tissue specificity and its subsequent likelihood of association with disease. We mined three large datasets comprising expression data drawn from massively parallel signature sequencing across 32 tissues, describing a set of 55,606 true positive interactions for 7,197 genes, and microarray expression results generated during the profiling of systemic inflammation, from which 126,543 interactions among 7,090 genes were reported. Results Amongst the myriad of complex relationships identified between expression, disease, connectivity and tissue specificity, some interesting patterns emerged. These include elevated rates of expression and network connectivity in housekeeping and disease-associated tissue-specific genes. We found that disease-associated genes are more likely to show tissue specific expression and most frequently interact with other disease genes. Using the thresholds defined in these observations, we develop a guilt-by-association algorithm and discover a group of 112 non-disease annotated genes that predominantly interact with disease-associated genes, impacting on disease outcomes. Conclusion We conclude that parameters such as tissue specificity and network connectivity can be used in combination to identify a group of genes, not previously confirmed as disease causing, that are involved in interactions with disease causing

  17. Prediction

    Woollard, W.J.

    2006-01-01

    In this chapter we will look at the ways in which you can use ICT in the classroom to support hypothesis and prediction and how modern technology is enabling: pattern seeking, extrapolation and interpolation to meet the challenges of the information explosion of the 21st century.

  18. Multiple POU-binding motifs, recognized by tissue-specific nuclear factors, are important for Dll1 gene expression in neural stem cells

    We cloned the 5'-flanking region of the mouse homolog of the Delta gene (Dll1) and demonstrated that the sequence between nucleotide position -514 and -484 in the 5'-flanking region of Dll1 played a critical role in the regulation of its tissue-specific expression in neural stem cells (NSCs). Further, we showed that multiple POU-binding motifs, located within this short sequence of 30 bp, were essential for transcriptional activation of Dll1 and also that multiple tissue-specific nuclear factors recognized these POU-binding motifs in various combinations through differentiation of NSCs. Thus, POU-binding factors may play an important role in Dll1 expression in developing NSCs

  19. Tissue-specific and plasma microRNA profiles could be promising biomarkers of histological classification and TNM stage in non-small cell lung cancer.

    Pu, Qiang; Huang, Yuchuan; Lu, Yanrong; Peng, Yong; Zhang, Jie; Feng, Guanglin; Wang, Changguo; Liu, Lunxu; Dai, Ya

    2016-04-26

    In a previous study, we determined that plasma miRNAs are potential biomarkers for cigarette smoking-related lung fibrosis. Herein, we determine whether tissue-specific and plasma miRNA profiles could be promising biomarkers for histological classification and TNM stage in non-small cell lung cancer (NSCLC). Plasma miRNA profiling preoperatively and seven days postoperatively, and cancer and normal tissue miRNA profiling were performed in NSCLC patients and matched healthy controls. There was a > twofold change for all signature miRNAs between the NSCLC patients and controls, with P values of staging lung squamous cell carcinoma, and miR-3613-3p, miR-3675-3p, and miR-5571-5p were promising biomarkers of different staging lung adenocarcinoma. These results suggest that tissue-specific and plasma miRNAs could be potential biomarkers of histological classification and TNM stage in NSCLC. PMID:27148421

  20. Tissue-specific activation of mitogen-activated protein kinases for expression of transthyretin by phenylalanine and its metabolite, phenylpyruvic acid

    Park, Joo-Won; Lee, Mi Hee; Choi, Jin-Ok; Park, Hae-Young; Jung, Sung-Chul

    2009-01-01

    Phenylketonuria is an autosomal recessive disorder caused by a deficiency of phenylalanine hydroxylase. Transthyretin has been implicated as an indicator of nutritional status in phenylketonuria patients. In this study, we report that phenylalanine and its metabolite, phenylpyruvic acid, affect MAPK, changing transthyretin expression in a cell- and tissue-specific manner. Treatment of HepG2 cells with phenylalanine or phenylpyruvic acid decreased transcription of the TTR gene and decreased th...

  1. Tissue specific analysis reveals a differential organization and regulation of both ethylene biosynthesis and E8 during climacteric ripening of tomato

    Van de Poel, Bram; Vandenzavel, Nick; Smet, Cindy; Nicolay, Toon; Bulens, Inge; Mellidou, Ifigeneia; Vandoninck, Sandy; Hertog, Maarten LATM; Derua, Rita; Spaepen, Stijn; Vanderleyden, Jos; Waelkens, Etienne; De Proft, Maurice P; Nicolai, Bart M.; Geeraerd, Annemie H

    2014-01-01

    Background: Solanum lycopersicum or tomato is extensively studied with respect to the ethylene metabolism during climacteric ripening, focusing almost exclusively on fruit pericarp. In this work the ethylene biosynthesis pathway was examined in all major tomato fruit tissues: pericarp, septa, columella, placenta, locular gel and seeds. The tissue specific ethylene production rate was measured throughout fruit development, climacteric ripening and postharvest storage. All ethylene intermediate...

  2. Astrocyte- and hepatocyte-specific expression of genes from the distal serpin subcluster at 14q32.1 associates with tissue-specific chromatin structures

    Gopalan, Sunita; Kasza, Aneta; Xu, Weili; Kiss, Daniel L.; Wilczynska, Katarzyna M.; Rydel, Russell E.; Kordula, Tomasz

    2005-01-01

    The distal serpin subcluster contains genes encoding α1-antichymotrypsin (ACT), protein C inhibitor (PCI), kallistatin (KAL), and the KAL-like protein that are expressed in hepatocytes but only the act gene is expressed in astrocytes. We show here that the tissue-specific expression of these genes associates with astrocyte- and hepatocyte-specific chromatin structures. In hepatocytes, we identified twelve DNase I-hypersenitive sites (DHS) that were distributed throughout the entire subcluster...

  3. Distinct repressing modules on the distal region of the SBP2 promoter contribute to its vascular tissue-specific expression in different vegetative organs.

    Freitas, Rejane L; Carvalho, Claudine M; Fietto, Luciano G; Loureiro, Marcelo E; Almeida, Andrea M; Fontes, Elizabeth P B

    2007-11-01

    The Glycine max sucrose binding protein (GmSBP2) promoter directs vascular tissue-specific expression of reporter genes in transgenic tobacco. Here we showed that an SBP2-GFP fusion protein under the control of the GmSBP2 promoter accumulates in the vascular tissues of vegetative organs, which is consistent with the proposed involvement of SBP in sucrose transport-dependent physiological processes. Through gain-of-function experiments we confirmed that the tissue-specific determinants of the SBP2 promoter reside in the distal cis-regulatory domain A, CRD-A (position -2000 to -700) that is organized into a modular configuration to suppress promoter activity in tissues other than vascular tissues. The four analyzed CRD-A sub-modules, designates Frag II (-1785/-1508), Frag III (-1507/-1237), Frag IV (-1236/-971) and Frag V (-970/-700), act independently to alter the constitutive pattern of -92pSBP2-mediated GUS expression in different organs. Frag V fused to -92pSBP2-GUS restored the tissue-specific pattern of the full-length promoter in the shoot apex, but not in other organs. Likewise, Frag IV confined GUS expression to the vascular bundle of leaves, whereas Frag II mediated vascular specific expression in roots. Strong stem expression-repressing elements were located at positions -1485 to -1212, as Frag III limited GUS expression to the inner phloem. We have also mapped a procambium silencer to the consensus sequence CAGTTnCaAccACATTcCT which is located in both distal and proximal upstream modules. Fusion of either repressing element-containing module to the constitutive -92pSBP2 promoter suppresses GUS expression in the elongation zone of roots. Together our results demonstrate the unusual aspect of distal sequences negatively controlling tissue-specificity of a plant promoter. PMID:17710554

  4. Prediction

    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...

  5. Accurate Finite Difference Algorithms

    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.

  6. CXCR6, a newly defined biomarker of tissue-specific stem cell asymmetric self-renewal, identifies more aggressive human melanoma cancer stem cells.

    Rouzbeh Taghizadeh

    Full Text Available A fundamental problem in cancer research is identifying the cell type that is capable of sustaining neoplastic growth and its origin from normal tissue cells. Recent investigations of a variety of tumor types have shown that phenotypically identifiable and isolable subfractions of cells possess the tumor-forming ability. In the present paper, using two lineage-related human melanoma cell lines, primary melanoma line IGR39 and its metastatic derivative line IGR37, two main observations are reported. The first one is the first phenotypic evidence to support the origin of melanoma cancer stem cells (CSCs from mutated tissue-specific stem cells; and the second one is the identification of a more aggressive subpopulation of CSCs in melanoma that are CXCR6+.We defined CXCR6 as a new biomarker for tissue-specific stem cell asymmetric self-renewal. Thus, the relationship between melanoma formation and ABCG2 and CXCR6 expression was investigated. Consistent with their non-metastatic character, unsorted IGR39 cells formed significantly smaller tumors than unsorted IGR37 cells. In addition, ABCG2+ cells produced tumors that had a 2-fold greater mass than tumors produced by unsorted cells or ABCG2- cells. CXCR6+ cells produced more aggressive tumors. CXCR6 identifies a more discrete subpopulation of cultured human melanoma cells with a more aggressive MCSC phenotype than cells selected on the basis of the ABCG2+ phenotype alone.The association of a more aggressive tumor phenotype with asymmetric self-renewal phenotype reveals a previously unrecognized aspect of tumor cell physiology. Namely, the retention of some tissue-specific stem cell attributes, like the ability to asymmetrically self-renew, impacts the natural history of human tumor development. Knowledge of this new aspect of tumor development and progression may provide new targets for cancer prevention and treatment.

  7. hSAGEing: an improved SAGE-based software for identification of human tissue-specific or common tumor markers and suppressors.

    Cheng-Hong Yang

    Full Text Available BACKGROUND: SAGE (serial analysis of gene expression is a powerful method of analyzing gene expression for the entire transcriptome. There are currently many well-developed SAGE tools. However, the cross-comparison of different tissues is seldom addressed, thus limiting the identification of common- and tissue-specific tumor markers. METHODOLOGY/PRINCIPAL FINDINGS: To improve the SAGE mining methods, we propose a novel function for cross-tissue comparison of SAGE data by combining the mathematical set theory and logic with a unique "multi-pool method" that analyzes multiple pools of pair-wise case controls individually. When all the settings are in "inclusion", the common SAGE tag sequences are mined. When one tissue type is in "inclusion" and the other types of tissues are not in "inclusion", the selected tissue-specific SAGE tag sequences are generated. They are displayed in tags-per-million (TPM and fold values, as well as visually displayed in four kinds of scales in a color gradient pattern. In the fold visualization display, the top scores of the SAGE tag sequences are provided, along with cluster plots. A user-defined matrix file is designed for cross-tissue comparison by selecting libraries from publically available databases or user-defined libraries. CONCLUSIONS/SIGNIFICANCE: The hSAGEing tool provides a combination of friendly cross-tissue analysis and an interface for comparing SAGE libraries for the first time. Some up- or down-regulated genes with tissue-specific or common tumor markers and suppressors are identified computationally. The tool is useful and convenient for in silico cancer transcriptomic studies and is freely available at http://bio.kuas.edu.tw/hSAGEing.

  8. Different cis-Regulatory DNA Elements Mediate Developmental Stage- and Tissue-specific Expression of the Human COL2A1 Gene in Transgenic Mice

    Leung, Keith K.H.; Ng, Ling Jim; Ho, Ken K.Y.; Tam, Patrick P L; Cheah, Kathryn S. E.

    1998-01-01

    Expression of the type II collagen gene (human COL2A1, mouse Col2a1) heralds the differentiation of chondrocytes. It is also expressed in progenitor cells of some nonchondrogenic tissues during embryogenesis. DNA sequences in the 5' flanking region and intron 1 are known to control tissue- specific expression in vitro, but the regulation of COL2A1 expression in vivo is not clearly understood. We have tested the regulatory activity of DNA sequences from COL2A1 on the expression of a lacZ repor...

  9. Tissue-Specific Signatures in the Transcriptional Response to Anaplasma phagocytophilum Infection of Ixodes scapularis and Ixodes ricinus Tick Cell Lines

    Alberdi, Pilar; Mansfield, Karen L.; Manzano-Román, Raúl; Cook, Charlotte; Ayllón, Nieves; Villar, Margarita; Johnson, Nicholas; Fooks, Anthony R.; de la Fuente, José

    2016-01-01

    Anaplasma phagocytophilum are transmitted by Ixodes spp. ticks and have become one of the most common and relevant tick-borne pathogens due to their impact on human and animal health. Recent results have increased our understanding of the molecular interactions between Ixodes scapularis and A. phagocytophilum through the demonstration of tissue-specific molecular pathways that ensure pathogen infection, development and transmission by ticks. However, little is known about the Ixodes ricinus genes and proteins involved in the response to A. phagocytophilum infection. The tick species I. scapularis and I. ricinus are evolutionarily closely related and therefore similar responses are expected in A. phagocytophilum-infected cells. However, differences may exist between I. scapularis ISE6 and I. ricinus IRE/CTVM20 tick cells associated with tissue-specific signatures of these cell lines. To address this hypothesis, the transcriptional response to A. phagocytophilum infection was characterized by RNA sequencing and compared between I. scapularis ISE6 and I. ricinus IRE/CTVM20 tick cell lines. The transcriptional response to infection of I. scapularis ISE6 cells resembled that of tick hemocytes while the response in I. ricinus IRE/CTVM20 cells was more closely related to that reported previously in infected tick midguts. The inhibition of cell apoptosis by A. phagocytophilum appears to be a key adaptation mechanism to facilitate infection of both vertebrate and tick cells and was used to investigate further the tissue-specific response of tick cell lines to pathogen infection. The results supported a role for the intrinsic pathway in the inhibition of cell apoptosis by A. phagocytophilum infection of I. scapularis ISE6 cells. In contrast, the results in I. ricinus IRE/CTVM20 cells were similar to those obtained in tick midguts and suggested a role for the JAK/STAT pathway in the inhibition of apoptosis in tick cells infected with A. phagocytophilum. Nevertheless, tick

  10. Impact of tissue specific parameters on the predition of the biological effectiveness for treatment planning in ion beam therapy

    Treatment planning in ion beam therapy requires a reliable estimation of the relative biological effectiveness (RBE) of the irradiated tissue. For the pilot project at GSI Helmholtzzentrum fuer Schwerionenforschung GmbH and at other European ion beam therapy centers RBE prediction is based on a biophysical model, the Local Effect Model (LEM). The model version in use, LEM I, is optimized to give a reliable estimation of RBE in the target volume for carbon ion irradiation. However, systematic deviations are observed for the entrance channel of carbon ions and in general for lighter ions. Thus, the LEM has been continuously developed to improve accuracy. The recent version LEM IV has proven to better describe in-vitro cell experiments. Thus, for the clinical application of LEM IV it is of interest to analyze potential differences compared to LEM I under treatment-like conditions. The systematic analysis presented in this work is aiming at the comparison of RBE-weighted doses resulting from different approaches and model versions for protons and carbon ions. This will facilitate the assessment of consequences for clinical application and the interpretation of clinical results from different institutions. In the course of this thesis it has been shown that the RBE-weighted doses predicted on the basis of LEM IV for typical situations representing chordoma treatments differ on average by less than 10 % to those based on LEM I and thus also allow a consistent interpretation of the clinical results. At Japanese ion beam therapy centers the RBE is estimated using their clinical experience from neutron therapy in combination with in-vitro measurements for carbon ions (HIMAC approach). The methods presented in this work allow direct comparison of the HIMAC approach and the LEM and thus of the clinical results obtained at Japanese and European ion beam therapy centers. Furthermore, the sensitivity of the RBE on the model parameters was evaluated. Among all parameters the

  11. Evolution of tissue-specific keratins as deduced from novel cDNA sequences of the lungfish Protopterus aethiopicus.

    Schaffeld, Michael; Bremer, Miriam; Hunzinger, Christian; Markl, Jürgen

    2005-03-01

    Lungfishes are possibly the closest extant relatives of the land vertebrates (tetrapods). We report here the cDNA and predicted amino acid sequences of 13 different keratins (ten type I and three type II) of the lungfish Protopterus aethiopicus. These keratins include the orthologs of human K8 and K18. The lungfish keratins were also identified in tissue extracts using two-dimensional polyacrylamide gel electrophoresis, keratin blot binding assays and immunoblotting. The identified keratin spots were analyzed by peptide mass fingerprinting which assigned seven sequences (inclusively Protopterus K8 and K18) to their respective protein spot. The peptide mass fingerprints also revealed the fact that the major epidermal type I and type II keratins of this lungfish have not yet been sequenced. Nevertheless, phylogenetic trees constructed from multiple sequence alignments of keratins from lungfish and distantly related vertebrates such as lamprey, shark, trout, frog, and human reveal new insights into the evolution of K8 and K18, and unravel a variety of independent keratin radiation events. PMID:15819414

  12. Differential domain evolution and complex RNA processing in a family of paralogous EPB41 (protein 4.1) genes facilitates expression of diverse tissue-specific isoforms

    Parra, Marilyn; Gee, Sherry; Chan, Nadine; Ryaboy, Dmitriy; Dubchak, Inna; Narla, Mohandas; Gascard, Philippe D.; Conboy, John G.

    2004-07-15

    The EPB41 (protein 4.1) genes epitomize the resourcefulness of the mammalian genome to encode a complex proteome from a small number of genes. By utilizing alternative transcriptional promoters and tissue-specific alternative pre-mRNA splicing, EPB41, EPB41L2, EPB41L3, and EPB41L1 encode a diverse array of structural adapter proteins. Comparative genomic and transcript analysis of these 140kb-240kb genes indicates several unusual features: differential evolution of highly conserved exons encoding known functional domains, interspersed with unique exons whose size and sequence variations contribute substantially to intergenic diversity: alternative first exons, most of which map far upstream of the coding regions; and complex tissue-specific alternative pre-mRNA splicing that facilitates synthesis of functionally different complements of 4.1 proteins in various cells. Understanding the splicing regulatory networks that control protein 4.1 expression will be critical to a full appreciation of the many roles of 4.1 proteins in normal cell biology and their proposed roles in human cancer.

  13. sek-1 is important in tissue-specific regulation of innate immunity during the Xoo infection in the model host Caenorhabditis elegans

    Y Bai

    2014-08-01

    Full Text Available Xanthomonas oryzae pv. Oryzae (Xoo are plant pathogenic bacteria that can cause serious blight of rice. We have demonstrated that Xoo can infect the model organism C. elegans and p38 MAPK pathway plays specific roles in defense against the pathogen in our previous paper. Based on that p38 MAPK pathway can be activated in a range of tissues, it is intriguing to compare the tissue-specific activities of this pathway in host innate immunity. Here, transgenic worms that sek-1 expressed specifically in neurons system, ciliated sensory neurons, and intestine respectively are used to determine the nematode survival and transcriptional levels of immune-related genes. We report that SEK-1 and TOL-1 are not involved in C. elegans avoidance behavior, and ingestion of nematodes is related to the aversion and also the characteristics of bacteria. In addition, tol-1 and sek-1 participate the immune response to the infection by Xoo; sek-1 also exhibits tissue-specific activities in host innate immunity. Our findings suggest that overlapping immune effect may exist between the tol-1 and sek-1.

  14. α-Fetoprotein promoter-driven Cre/LoxP-switched RNA interference for hepatocellular carcinoma tissue-specific target therapy.

    Yuan-Fei Peng

    Full Text Available BACKGROUND: RNA interference (RNAi has recently emerged as a potential treatment modality for hepatocellular carcinoma (HCC therapy, but the lack of cellular targets and sustained efficacy limits its application. The purpose of this study is to develop an HCC tissue-specific RNAi system and investigate its possibility for HCC treatment. METHODS: Two different HCC-specific RNAi systems in which therapeutic miRNA or shRNA against target gene (Beclin 1 was directly or indirectly driven by alpha-fetoprotein promoter (AFP-miRNA and AFP-Cre/LoxP-shRNA were constructed. Human HCC cell lines (HepG2, Hep3B and HCCLM3 and non-HCC cell lines (L-02, Hela and SW1116 were infected with the systems. The effectiveness and tissue-specificity of the systems were examined by Q-PCR and western blot analysis. The efficacy of the systems was further tested in mouse model of HCC by intravenous or intratumoral administration. The feasibility of the system for HCC treatment was evaluated by applying the system as adjuvant therapy to enhance sorafenib treatment. An AFP-Cre/LoxP-shRNA system targeting Atg5 gene (AFP-Cre/LoxP-shRNA-Atg5 was constructed and its efficacy in sensitizing HCC cells (MHCC97L/PLC to sorafenib treatment was examined by apoptosis assay in vitro and tumorigenesis assay in vivo. RESULTS: The AFP-miRNA system could silence target gene (Beclin 1 but required a high titer which was lethal to target cells. The AFP-Cre/LoxP-shRNA system could efficiently knockdown target gene while maintain high HCC specificity. Intratumoral injection of the AFP-Cre/LoxP-shRNA system could efficiently silence target gene (Beclin 1 in vivo while intravenous administration could not. The AFP-Cre/LoxP-shRNA system target Atg5 gene could significantly sensitize MHCC97L/PLC cells to sorafenib-induced apoptosis in vitro and tumor growth suppression in vivo. CONCLUSIONS: An efficient HCC tissue-specific RNAi system (AFP-Cre/LoxP-shRNA was successfully established. The system

  15. {sup 99m}Tc-pertechnetate uptake in hepatoma cells due to tissue-specific human sodium iodide symporter gene expression

    Chen Libo [Department of Nuclear Medicine, Shanghai Sixth People' s Hospital, Shanghai Jiao Tong University, 200233 Shanghai (China); Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center (DKFZ) and Heidelberg University, 69120 Heidelberg (Germany); Altman, Annette [Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center (DKFZ) and Heidelberg University, 69120 Heidelberg (Germany); Mier, Walter [Department of Nuclear Medicine, University of Heidelberg, 69120 Heidelberg (Germany); Lu Hankui [Department of Nuclear Medicine, Shanghai Sixth People' s Hospital, Shanghai Jiao Tong University, 200233 Shanghai (China); Zhu Ruisen [Department of Nuclear Medicine, Shanghai Sixth People' s Hospital, Shanghai Jiao Tong University, 200233 Shanghai (China); Haberkorn, Uwe [Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center (DKFZ) and Heidelberg University, 69120 Heidelberg (Germany) and Department of Nuclear Medicine, University of Heidelberg, 69120 Heidelberg (Germany)]. E-mail: uwe_haberkorn@med.uni-heidelberg.de

    2006-05-15

    The sodium iodide symporter (NIS) gene could be used as an ideal reporter gene as well as a promising therapeutic gene. {sup 99m}Tc-pertechnetate has proven to be more advantageous than {sup 131}I-iodide with respect to image quality, procedure and radiation dose in examination of thyroid uptake and scintigraphy. Herein, we investigated the feasibility of monitoring human sodium iodide symporter (hNIS) gene expression with {sup 99m}Tc-pertechnetate in hepatoma cells (MH3924A) following tissue-specific expression. Methods: MH3924A cells were stably transfected with the recombinant retroviral vector, in which hNIS cDNA was driven by murine albumin enhancer/promoter (mAlb) and coupled to hygromycin resistance gene using an internal ribosomal entry site. Functional NIS expression in hepatoma cells was confirmed by an {sup 125}I{sup -} uptake assay. The dynamic uptake and efflux of {sup 99m}Tc-pertechnetate was determined both in vitro and in vivo. Results: The {sup 99m}Tc-pertechnetate was up to 254-fold higher in stably transfected MH3924A cells than in wild-type cells. However, the in vitro efflux of {sup 99m}Tc-pertechnetate out of recombinant cells was rapid with a half-life of less than 2 min. Further, the in vivo studies yielded clear images and quantitative data of mAlbhNIS-infected tumor xenografts using {sup 99m}Tc-pertechnetate and {gamma} camera. Conclusion: The current study demonstrates enhanced {sup 99m}Tc-pertechnetate uptake in hepatoma cells in vitro and in vivo following tissue-specific gene transfer using a recombinant retrovirus with the albumin enhancer/promoter and the hNIS gene. It is feasible to monitor hNIS gene expression noninvasively and quantitatively using conventional {gamma} camera and {sup 99m}Tc-pertechnetate.

  16. From food to offspring down: tissue-specific discrimination and turn-over of stable isotopes in herbivorous waterbirds and other avian foraging guilds.

    Hahn, Steffen; Hoye, Bethany J; Korthals, Harry; Klaassen, Marcel

    2012-01-01

    Isotopic discrimination and turn-over are fundamental to the application of stable isotope ecology in animals. However, detailed information for specific tissues and species are widely lacking, notably for herbivorous species. We provide details on tissue-specific carbon and nitrogen discrimination and turn-over times from food to blood, feathers, claws, egg tissues and offspring down feathers in four species of herbivorous waterbirds. Source-to-tissue discrimination factors for carbon (δ¹³C) and nitrogen stable isotope ratios (δ¹⁵N) showed little variation across species but varied between tissues. Apparent discrimination factors ranged between -0.5 to 2.5‰ for δ¹³C and 2.8 to 5.2‰ for δ¹⁵N, and were more similar between blood components than between keratinous tissues or egg tissue. Comparing these results with published data from other species we found no effect of foraging guild on discrimination factors for carbon but a significant foraging-guild effect for nitrogen discrimination factors.Turn-over of δ¹³C in tissues was most rapid in blood plasma, with a half-life of 4.3 d, whereas δ¹³C in blood cells had a half-life of approximately 32 d. Turn-over times for albumen and yolk in laying females were similar to those of blood plasma, at 3.2 and 6.0 d respectively. Within yolk, we found decreasing half-life times of δ¹³C from inner yolk (13.3 d) to outer yolk (3.1 d), related to the temporal pattern of tissue formation.We found similarities in tissue-specific turn-over times across all avian species studied to date. Yet, while generalities regarding discrimination factors and tissue turn-over times can be made, a large amount of variation remains unexplained. PMID:22312422

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

    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

  18. 脂肪组织特异性表达载体的构建%Construction of Adipose Tissue - specific Expression Vector

    华晓敏; 许登高; 潘庆杰

    2012-01-01

    采用PCR技术克隆了小鼠脂肪组织特异表达的脂肪酸结合蛋白ap2基因增强子和启动子,通过DNA重组技术将该基因增强子和启动子重组于pEGFP - N1真核表达载体上,构建pEGFP - N1 - ap2重组质粒,通过PCR扩增、酶切电泳分析和测序的方法对重组质粒进行鉴定,并转染小鼠前脂肪细胞,通过荧光素酶活性检测特异性表达强度.结果表明,本实验克隆的ap2基因增强子和启动子的碱基组成与GenBank中的ap2基因序列完全一致,通过DNA重组技术将该基因增强子和启动子重组于pEGFP- N1真核表达载体上,成功构建了脂肪组织特异表达的重组质粒.为以后的转基因动物的研究奠定了基础.%The mouse adipose tissue -specific fatty acid binding protein ap2 gene enhancer /promoter was amplified by PCR amplification, and it was recombined into pEGFP - Nl eukaryotic expression vector by recombinant DNA technology, to obtain pEGFP - Nl - ap2 recombinant plasmid, which was identified by PCR amplification, enzyme digestion and DNA sequencing and infected with mouse pre - adipocytes, and its expression was detected by the fluorescence detection of the enzyme activity specific expression strength. The results showed that, cloned gene enhancer and promoter is consistent with the ap2 gene sequences in GenBank. The enhancer / promoter was recombined into pEGFP - Nl eukaryotic expression vector by recombinant DNA technology. The construction of the adipose tissue - specific expression vector was successfully constructed, which can provide a necessary basis for further study.

  19. Structural evolution and tissue-specific expression of tetrapod-specific second isoform of secretory pathway Ca{sup 2+}-ATPase

    Pestov, Nikolay B., E-mail: korn@mail.ibch.ru [Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117871 (Russian Federation); Dmitriev, Ruslan I.; Kostina, Maria B. [Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117871 (Russian Federation); Korneenko, Tatyana V. [Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117871 (Russian Federation); Department of Physiology and Pharmacology, University of Toledo College of Medicine, 3000 Arlington Ave., Toledo, OH 43614 (United States); Shakhparonov, Mikhail I. [Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117871 (Russian Federation); Modyanov, Nikolai N., E-mail: nikolai.modyanov@utoledo.edu [Department of Physiology and Pharmacology, University of Toledo College of Medicine, 3000 Arlington Ave., Toledo, OH 43614 (United States)

    2012-01-27

    Highlights: Black-Right-Pointing-Pointer Full-length secretory pathway Ca-ATPase (SPCA2) cloned from rat duodenum. Black-Right-Pointing-Pointer ATP2C2 gene (encoding SPCA2) exists only in genomes of Tetrapoda. Black-Right-Pointing-Pointer Rat and pig SPCA2 are expressed in intestines, lung and some secretory glands. Black-Right-Pointing-Pointer Subcellular localization of SPCA2 may depend on tissue type. Black-Right-Pointing-Pointer In rat duodenum, SPCA2 is localized in plasma membrane-associated compartments. -- Abstract: Secretory pathway Ca-ATPases are less characterized mammalian calcium pumps than plasma membrane Ca-ATPases and sarco-endoplasmic reticulum Ca-ATPases. Here we report analysis of molecular evolution, alternative splicing, tissue-specific expression and subcellular localization of the second isoform of the secretory pathway Ca-ATPase (SPCA2), the product of the ATP2C2 gene. The primary structure of SPCA2 from rat duodenum deduced from full-length transcript contains 944 amino acid residues, and exhibits 65% sequence identity with known SPCA1. The rat SPCA2 sequence is also highly homologous to putative human protein KIAA0703, however, the latter seems to have an aberrant N-terminus originating from intron 2. The tissue-specificity of SPCA2 expression is different from ubiquitous SPCA1. Rat SPCA2 transcripts were detected predominantly in gastrointestinal tract, lung, trachea, lactating mammary gland, skin and preputial gland. In the newborn pig, the expression profile is very similar with one remarkable exception: porcine bulbourethral gland gave the strongest signal. Upon overexpression in cultured cells, SPCA2 shows an intracellular distribution with remarkable enrichment in Golgi. However, in vivo SPCA2 may be localized in compartments that differ among various tissues: it is intracellular in epidermis, but enriched in plasma membranes of the intestinal epithelium. Analysis of SPCA2 sequences from various vertebrate species argue that ATP2C2

  20. 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

    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

  1. Fine-mapping analysis revealed complex pleiotropic effect and tissue-specific regulatory mechanism of TNFSF15 in primary biliary cholangitis, Crohn's disease and leprosy.

    Sun, Yonghu; Irwanto, Astrid; Toyo-Oka, Licht; Hong, Myunghee; Liu, Hong; Andiappan, Anand Kumar; Choi, Hyunchul; Hitomi, Yuki; Yu, Gongqi; Yu, Yongxiang; Bao, Fangfang; Wang, Chuan; Fu, Xian; Yue, Zhenhua; Wang, Honglei; Zhang, Huimin; Kawashima, Minae; Kojima, Kaname; Nagasaki, Masao; Nakamura, Minoru; Yang, Suk-Kyun; Ye, Byong Duk; Denise, Yosua; Rotzschke, Olaf; Song, Kyuyoung; Tokunaga, Katsushi; Zhang, Furen; Liu, Jianjun

    2016-01-01

    Genetic polymorphism within the 9q32 locus is linked with increased risk of several diseases, including Crohn's disease (CD), primary biliary cholangitis (PBC) and leprosy. The most likely disease-causing gene within 9q32 is TNFSF15, which encodes the pro-inflammatory cytokine TNF super-family member 15, but it was unknown whether these disparate diseases were associated with the same genetic variance in 9q32, and how variance within this locus might contribute to pathology. Using genetic data from published studies on CD, PBC and leprosy we revealed that bearing a T allele at rs6478108/rs6478109 (r(2) = 1) or rs4979462 was significantly associated with increased risk of CD and decreased risk of leprosy, while the T allele at rs4979462 was associated with significantly increased risk of PBC. In vitro analyses showed that the rs6478109 genotype significantly affected TNFSF15 expression in cells from whole blood of controls, while functional annotation using publicly-available data revealed the broad cell type/tissue-specific regulatory potential of variance at rs6478109 or rs4979462. In summary, we provide evidence that variance within TNFSF15 has the potential to affect cytokine expression across a range of tissues and thereby contribute to protection from infectious diseases such as leprosy, while increasing the risk of immune-mediated diseases including CD and PBC. PMID:27507062

  2. Verification, Characterization and Tissue-specific Expression of UreG, a Urease Accessory Protein Gene, from the Amphioxus Branchiostoma belcheri

    Ji-Yu XUE; Shi-Cui ZHANG; Nai-Guo LIU; Zhen-Hui LIU

    2006-01-01

    UreG genes have been found in bacteria, fungi and plants but have not yet identified in animals,although a putative UreG-like gene has been documented in sea urchin. In the course of a large-scale sequencing of amphioxus gut cDNA library, we have identified a cDNA with high similarity to UreG genes. Both reverse transcription-polymerase chain reaction and nested polymerase chain reaction, as well as in situ hybridization histochemistry, verified that the cDNA represented an amphioxus UreG gene (AmphiUreG) rather than a microbial contaminant of the cDNA library. This is further supported by the presence of urease activity in amphioxus gut, gill and ovary. AmphiUreG encodes a deduced protein of 200 amino acid residues including a highly conserved P-loop, beating approximately 46%-49%, 44%-48%, and 29%-37% similarity to fungal,plant and bacterial UreG proteins, respectively. It shows a tissue-specific expression pattern in amphioxus,and is especially abundant in the digestive system. This is the first UreG gene identified in animal species.

  3. [11C]-Labeled Metformin Distribution in the Liver and Small Intestine Using Dynamic Positron Emission Tomography in Mice Demonstrates Tissue-Specific Transporter Dependency.

    Jensen, Jonas B; Sundelin, Elias I; Jakobsen, Steen; Gormsen, Lars C; Munk, Ole L; Frøkiær, Jørgen; Jessen, Niels

    2016-06-01

    Metformin is the most commonly prescribed oral antidiabetic drug, with well-documented beneficial preventive effects on diabetic complications. Despite being in clinical use for almost 60 years, the underlying mechanisms for metformin action remain elusive. Organic cation transporters (OCT), including multidrug and toxin extrusion proteins (MATE), are essential for transport of metformin across membranes, but tissue-specific activity of these transporters in vivo is incompletely understood. Here, we use dynamic positron emission tomography with [(11)C]-labeled metformin ([(11)C]-metformin) in mice to investigate the role of OCT and MATE in a well-established target tissue, the liver, and a putative target of metformin, the small intestine. Ablation of OCT1 and OCT2 significantly reduced the distribution of metformin in the liver and small intestine. In contrast, inhibition of MATE1 with pyrimethamine caused accumulation of metformin in the liver but did not affect distribution in the small intestine. The demonstration of OCT-mediated transport into the small intestine provides evidence of direct effects of metformin in this tissue. OCT and MATE have important but separate roles in uptake and elimination of metformin in the liver, but this is not due to changes in biliary secretion. [(11)C]-Metformin holds great potential as a tool to determine the pharmacokinetic properties of metformin in clinical studies. PMID:26993065

  4. The tissue-specific Rep8/UBXD6 tethers p97 to the endoplasmic reticulum membrane for degradation of misfolded proteins.

    Louise Madsen

    Full Text Available The protein known as p97 or VCP in mammals and Cdc48 in yeast is a versatile ATPase complex involved in several biological functions including membrane fusion, protein folding, and activation of membrane-bound transcription factors. In addition, p97 plays a central role in degradation of misfolded secretory proteins via the ER-associated degradation pathway. This functional diversity of p97 depends on its association with various cofactors, and to further our understanding of p97 function it is important that these cofactors are identified and analyzed. Here, we isolate and characterize the human protein named Rep8 or Ubxd6 as a new cofactor of p97. Mouse Rep8 is highly tissue-specific and abundant in gonads. In testes, Rep8 is expressed in post-meiotic round spermatids, whereas in ovaries Rep8 is expressed in granulosa cells. Rep8 associates directly with p97 via its UBX domain. We show that Rep8 is a transmembrane protein that localizes to the ER membrane with its UBX domain facing the cytoplasm. Knock-down of Rep8 expression in human cells leads to a decreased association of p97 with the ER membrane and concomitantly a retarded degradation of misfolded ER-derived proteasome substrates. Thus, Rep8 tethers p97 to the ER membrane for efficient ER-associated degradation.

  5. Persistent Foot-and-Mouth Disease Virus Infection in the Nasopharynx of Cattle; Tissue-Specific Distribution and Local Cytokine Expression.

    Juan M Pacheco

    Full Text Available Tissues obtained post-mortem from cattle persistently infected with foot-and-mouth disease virus (FMDV were analyzed to characterize the tissue-specific localization of FMDV and partial transcriptome profiles for selected immunoregulatory cytokines. Analysis of 28 distinct anatomic sites from 21 steers infected with FMDV serotype A, O or SAT2, had the highest prevalence of overall viral detection in the dorsal nasopharynx (80.95% and dorsal soft palate (71.43%. FMDV was less frequently detected in laryngeal mucosal tissues, oropharyngeal mucosal sites, and lymph nodes draining the pharynx. Immunomicroscopy indicated that within persistently infected mucosal tissues, FMDV antigens were rarely detectable within few epithelial cells in regions of mucosa-associated lymphoid tissue (MALT. Transcriptome analysis of persistently infected pharyngeal tissues by qRT-PCR for 14 cytokine genes indicated a general trend of decreased mRNA levels compared to uninfected control animals. Although, statistically significant differences were not observed, greatest suppression of relative expression (RE was identified for IP-10 (RE = 0.198, IFN-β (RE = 0.269, IL-12 (RE = 0.275, and IL-2 (RE = 0.312. Increased relative expression was detected for IL-6 (RE = 2.065. Overall, this data demonstrates that during the FMDV carrier state in cattle, viral persistence is associated with epithelial cells of the nasopharynx in the upper respiratory tract and decreased levels of mRNA for several immunoregulatory cytokines in the infected tissues.

  6. Tissue-specific expression of glutathione S-transferases induced by 2-tridecanone or quercetin in cotton bollworms, Helicoverpa armigera (Hübner)

    TANG Fang; LIANG Pei; GAO Xiwu

    2005-01-01

    The tissue-specific expression of glutathione S-transferases (GSTs) in the cotton bollworm and the expression level induced by 2-tridecanone and quercetin were examined using the methods of biochemistry and the quantitative PCR. The relative expression level of GST mRNA was unanimous with the GSTs activity conjugaging with 1-chloro-2, 4-dimitro-benzene (CDNB) in fat bodies,midguts, heads and integuments of cotton bollworms. The GSTs activity in fat bodies was the highest, then midguts, heads and integuments in turn, which was in consistent with the relative expression level of GST mRNA. The specific activity of GSTs and the relative expression level of GST mRNA could be significantly induced by 2-tridecanone and quercetin, and after the induction the order of the GSTs activity and the relative expression level of GST mRNA in the above four tissues in cotton bollworms was not different from the control.The induction of GSTs by 2-tridecanone was stronger than by quercetin in all four tissues, which was in accordance with the relative expression level of GST mRNA. It suggested that the increase of GSTs activity induced by plant allelochemicals was associated with the elevated expression of GST mRNA in cotton bollworms.

  7. Characterization, Evolution and Tissue-specific Expression of AmphiCalbin, a Novel Gene Encoding EF-hand Calcium-binding Protein in Amphioxus Branchiostoma belcheri

    Jing LUAN; Shicui ZHANG; Zhenhui LIU; Chunxin FAN; Guangdong JI; Lei LI

    2007-01-01

    An amphioxus full-length cDNA, AmphiCalbin, encoding a novel EF-hand calcium-binding protein (EFCaBP), was isolated from the gut cDNA library of amphioxus Branchiostoma belcheri. It consists of 1321 bp with a 636 bp open reading frame encoding a protein of 211 amino acids with a molecular mass of approximately 24.5 kDa. The phylogenetic analysis offers two interesting inferences. First, AmphiCalbin clusters with a group of unnamed EFCaBPs that are differentiated from other identified EFCaBPs. Second,AmphiCalbin falls at the base of the vertebrate unnamed EFCaBPs clade, probably representing their prototype.This is also corroborated by the fact that AmphiCalbin has an exon-intron organization identical to that of vertebrate unnamed EFCaBP genes. Both tissue-section in situ hybridization and whole-mount in situ hybridization prove a tissue-specific expression pattern of AmphiCalbin, with high levels of expression in the digestive system and gonads. It is proposed that AmphiCalbin might play a role in the digestive system and gonads. These observations lay the foundation for further understanding of the function of the unnamed EFCaBPs.

  8. Species-and tissue-specific mercury bioaccumulation in five fish species from Laizhou Bay in the Bohai Sea of China

    LIU Jinhu; CAO Liang; HUANG Wei; DOU Shuozeng

    2013-01-01

    Mercury (Hg) concentrations in the tissues (muscle,stomach,liver,gills,skin,and gonads)of five fish species (mullet Liza haematocheilus,flathead fish Platycephalus indicus,sea bass Lateolabrax japonicus,mackerel Scomberomorus niphonius and silver pomfret Pampus argenteus) collected from Laizhou Bay in the Bohai Sea of China were investigated.The results indicate that Hg bioaccumulation in the five fish was tissue-specific,with the highest levels in the muscle and liver,followed by the stomach and gonads.The lowest levels were found in the gills and skin.Fish at higher trophic levels (flathead fish and sea bass) exhibited higher Hg concentrations than consumers at lower trophic levels.Mercury bioaccumulation tended to be positively correlated with fish length in mullet,silver pomfret,mackerel,and flathead fish,but was negatively correlated with fish length in sea bass.The Hg concentrations in the muscles of all fish species in Laizhou Bay were within the permissible limits of food safety set by national and international criteria.However,the suggesting maximum consumption of sea bass is 263 g per week for human health.

  9. Temporal and tissue specific regulation of RP-associated splicing factor genes PRPF3, PRPF31 and PRPC8--implications in the pathogenesis of RP.

    Huibi Cao

    Full Text Available BACKGROUND: Genetic mutations in several ubiquitously expressed RNA splicing genes such as PRPF3, PRP31 and PRPC8, have been found to cause retina-specific diseases in humans. To understand this intriguing phenomenon, most studies have been focused on testing two major hypotheses. One hypothesis assumes that these mutations interrupt retina-specific interactions that are important for RNA splicing, implying that there are specific components in the retina interacting with these splicing factors. The second hypothesis suggests that these mutations have only a mild effect on the protein function and thus affect only the metabolically highly active cells such as retinal photoreceptors. METHODOLOGY/PRINCIPAL FINDINGS: We examined the second hypothesis using the PRPF3 gene as an example. We analyzed the spatial and temporal expression of the PRPF3 gene in mice and found that it is highly expressed in retinal cells relative to other tissues and its expression is developmentally regulated. In addition, we also found that PRP31 and PRPC8 as well as snRNAs are highly expressed in retinal cells. CONCLUSIONS/SIGNIFICANCE: Our data suggest that the retina requires a relatively high level of RNA splicing activity for optimal tissue-specific physiological function. Because the RP18 mutation has neither a debilitating nor acute effect on protein function, we suggest that retinal degeneration is the accumulative effect of decades of suboptimal RNA splicing due to the mildly impaired protein.

  10. Identification of a proglucagon cDNA from Rana tigrina rugulosa that encodes two GLP-1s and that is alternatively spliced in a tissue-specific manner.

    Yeung, C M; Chow, B K

    2001-11-01

    Glucagon plays a pivotal role in the regulation of metabolism. A glucagon receptor has been previously characterized in the frog, Rana tigrina rugulosa, and the frog and human glucagon receptors have been shown to possess similar binding affinities toward human glucagon. To study the structural evolution of glucagon peptide and its receptor in vertebrates, in the current study, a proglucagon cDNA from the same frog species was cloned. Interestingly, in contrast to the mammalian proglucagons that contain only one GLP-1 peptide, the frog proglucagon cDNA encodes two GLP-1 peptides (GLP-1A and GLP-1B) in addition to a glucagon peptide and a glucagon-like peptide 2 (GLP-2). By reverse transcriptase-PCR (RT-PCR) analysis, the proglucagon gene expression was widely detected in the brain, colon, small intestine, liver, lung, and pancreas, suggesting that the proglucagon-derived peptides have diverse functions in frogs. Moreover, tissue-specific alternative mRNA splicing was observed in the brain, colon, and pancreas. In these tissues, proglucagon transcripts with a 135 bp in frame deletion encoding GLP-1A were found. This splicing event in R. tigrina rugulosa is novel because it deletes a GLP-1 encoding sequence instead of the GLP-2 observed in other vertebrates. These findings should enhance understanding of the proglucagon evolution, structure, and expression in vertebrates. PMID:11703080

  11. Differential gene expression and characterization of tissue-specific cDNA clones in oil palm using mRNA differential display.

    San, Cha Thye; Shah, Farida Habib

    2005-12-01

    The mRNA differential display method was utilized to study the differential expression and regulation of genes in two species of oil palm, the commercially grown variety Elaeis guineensis, var. tenera and the South American species, Elaeis oleifera. We demonstrated the differential expression of genes in the mesocarp and kernel at the week of active oil synthesis (15 week after anthesis) during fruit development as compare to the roots and leaves and the isolation of tissue-specific and species-specific cDNA clones. A total of eight specific cDNA clones were isolated and their specificities were confirmed by Northern hybridization and classified into three groups. Group one contains four clones (KT3, KT4, KT5 and KT6) that are kernel-specific for E. guineensis, tenera and E. oleifera. The second group represents clone FST1, which is mesocarp and kernel-specific for E. guineensis, tenera and E. oleifera. The third group represents clones MLT1, MLT2 and MLO1 that are mesocarp and leaf-specific. Northern analysis showed that their expressions were developmentally regulated. Nucleotide sequencing and homology search in GenBank data revealed that clones KT3 and KT4 encode for the same maturation protein PM3. While clones MLT1 and MLT2 encode for S-ribonuclease binding protein and fibrillin, respectively. The other clones (KT5, KT6, FST1 and MLO1) did not display any significant homology to any known protein. PMID:16328884

  12. Breaking-off tissue specific activity of the oil palm metallothionein-like gene promoter in T(1) seedlings of tomato exposed to metal ions.

    Kamaladini, Hossein; Nor Akmar Abdullah, Siti; Aziz, Maheran Abdul; Ismail, Ismanizan Bin; Haddadi, Fatemeh

    2013-02-15

    Metallothioneins (MTs) are cysteine-rich metal-binding proteins that are involved in cell growth regulation, transportation of metal ions and detoxification of heavy metals. A mesocarp-specific metallothionein-like gene (MT3-A) promoter was isolated from the oil palm (Elaeis guineensis Jacq). A vector construct containing the MT3-A promoter fused to the β-glucuronidase (GUS) gene in the pCAMBIA 1304 vector was produced and used in Agrobacterium-mediated transformation of tomato. Histochemical GUS assay of different tissues of transgenic tomato showed that the MT3-A promoter only drove GUS expression in the reproductive tissues and organs, including the anther, fruit and seed coat. Competitive RT-PCR and GUS fluorometric assay showed changes in the level of GUS mRNA and enzyme activity in the transgenic tomato (T(0)). No GUS mRNA was found in roots and leaves of transgenic tomato. In contrast, the leaves of transgenic tomato seedlings (T(1)) produced the highest GUS activity when treated with 150 μM Cu(2+) compared to the control (without Cu(2+)). However, Zn(2+) and Fe(2+) treatments did not show GUS expression in the leaves of the transgenic tomato seedlings. Interestingly, the results showed a breaking-off tissue-specific activity of the oil palm MT3-A promoter in T(1) seedlings of tomato when subjected to Cu(2+) ions. PMID:23290536

  13. Gene expression anti-profiles as a basis for accurate universal cancer signatures

    Corrada Bravo Héctor

    2012-10-01

    Full Text Available Abstract Background Early screening for cancer is arguably one of the greatest public health advances over the last fifty years. However, many cancer screening tests are invasive (digital rectal exams, expensive (mammograms, imaging or both (colonoscopies. This has spurred growing interest in developing genomic signatures that can be used for cancer diagnosis and prognosis. However, progress has been slowed by heterogeneity in cancer profiles and the lack of effective computational prediction tools for this type of data. Results We developed anti-profiles as a first step towards translating experimental findings suggesting that stochastic across-sample hyper-variability in the expression of specific genes is a stable and general property of cancer into predictive and diagnostic signatures. Using single-chip microarray normalization and quality assessment methods, we developed an anti-profile for colon cancer in tissue biopsy samples. To demonstrate the translational potential of our findings, we applied the signature developed in the tissue samples, without any further retraining or normalization, to screen patients for colon cancer based on genomic measurements from peripheral blood in an independent study (AUC of 0.89. This method achieved higher accuracy than the signature underlying commercially available peripheral blood screening tests for colon cancer (AUC of 0.81. We also confirmed the existence of hyper-variable genes across a range of cancer types and found that a significant proportion of tissue-specific genes are hyper-variable in cancer. Based on these observations, we developed a universal cancer anti-profile that accurately distinguishes cancer from normal regardless of tissue type (ten-fold cross-validation AUC > 0.92. Conclusions We have introduced anti-profiles as a new approach for developing cancer genomic signatures that specifically takes advantage of gene expression heterogeneity. We have demonstrated that anti

  14. Regulation of tissue-specific expression of SPATULA, a bHLH gene involved in carpel development, seedling germination, and lateral organ growth in Arabidopsis.

    Groszmann, Michael; Bylstra, Yasmin; Lampugnani, Edwin R; Smyth, David R

    2010-03-01

    SPATULA is a bHLH transcription factor that promotes growth of tissues arising from the carpel margins, including the septum and transmitting tract. It is also involved in repressing germination of newly harvested seeds, and in inhibiting cotyledon, leaf, and petal expansion. Using a reporter gene construct, its expression profile was fully defined. Consistent with its known functions, SPT was expressed in developing carpel margin tissues, and in the hypocotyls and cotyledons of germinating seedlings, and in developing leaves and petals. It was also strongly expressed in tissues where no functions have been identified to date, including the dehiscence zone of fruits, developing anthers, embryos, and in the epidermal initials and new stele of root tips. The promoter region of SPT was dissected by truncation and deletion, and two main regions occupied by tissue-specific enhancers were identified. These were correlated with eight regions conserved between promoter regions of Arabidopsis, Brassica oleracea, and Brassica rapa. When transformed into Arabidopsis, the B. oleracea promoter drove expression in reproductive tissues mostly comparable to the equivalent Arabidopsis promoter. There is genetic evidence that SPT function in the gynoecium is associated with the perception of auxin. However, site-directed mutagenesis of three putative auxin-response elements had no detectable effect on SPT expression patterns. Even so, disruption of a putative E-box variant adjacent to one of these resulted in a loss of valve dehiscence zone expression. This expression was also specifically lost in mutants of another bHLH gene INDEHISCENT, indicating that IND may directly regulate SPT expression through this variant E-box. PMID:20176890

  15. Tissue-specific root ion profiling reveals essential roles of the CAX and ACA calcium transport systems in response to hypoxia in Arabidopsis.

    Wang, Feifei; Chen, Zhong-Hua; Liu, Xiaohui; Colmer, Timothy David; Zhou, Meixue; Shabala, Sergey

    2016-06-01

    Waterlogging is a major abiotic stress that limits the growth of plants. The crucial role of Ca(2+) as a second messenger in response to abiotic and biotic stimuli has been widely recognized in plants. However, the physiological and molecular mechanisms of Ca(2+) distribution within specific cell types in different root zones under hypoxia is poorly understood. In this work, whole-plant physiological and tissue-specific Ca(2+) changes were studied using several ACA (Ca(2+)-ATPase) and CAX (Ca(2+)/proton exchanger) knock-out Arabidopsis mutants subjected to waterlogging treatment. In the wild-type (WT) plants, several days of hypoxia decreased the expression of ACA8, CAX4, and CAX11 by 33% and 50% compared with the control. The hypoxic treatment also resulted in an up to 11-fold tissue-dependent increase in Ca(2+) accumulation in root tissues as revealed by confocal microscopy. The increase was much higher in stelar cells in the mature zone of Arabidopsis mutants with loss of function for ACA8, ACA11, CAX4, and CAX11 In addition, a significantly increased Ca(2+) concentration was found in the cytosol of stelar cells in the mature zone after hypoxic treatment. Three weeks of waterlogging resulted in dramatic loss of shoot biomass in cax11 plants (67% loss in shoot dry weight), while in the WT and other transport mutants this decline was only 14-22%. These results were also consistent with a decline in leaf chlorophyll fluorescence (F v/F m). It is suggested that CAX11 plays a key role in maintaining cytosolic Ca(2+) homeostasis and/or signalling in root cells under hypoxic conditions. PMID:26889007

  16. Interactive effects of chronic waterborne copper and cadmium exposure on tissue-specific metal accumulation and reproduction in fathead minnow (Pimephales promelas).

    Driessnack, Melissa K; Matthews, Amber L; Raine, Jason C; Niyogi, Som

    2016-01-01

    The present study was carried out to examine the interactive effects of chronic waterborne copper (Cu) and cadmium (Cd) on tissue-specific metal accumulation and reproduction in fathead minnow (Pimephales promelas). Trios (1 male: 2 female; n=5) of fish were exposed for 21days to: (i) control (no added Cu or Cd), (ii) waterborne Cu (75μg/L), (iii) waterborne Cd (5μg/L), and (iv) Cu and Cd mixture (75 and 5μg/L, respectively). Reproductive output (cumulative egg production) was significantly reduced by Cu but not by Cd. Interestingly however, no spawning occurred in fish exposed to the mixture of waterborne Cu and Cd. In general, both Cu and Cd accumulation in target tissues (gill, liver, gonad and carcass) increased significantly in fish exposed to Cu and Cd mixture, and no interaction between Cu and Cd accumulation was observed in any tissues, except in the liver where Cu accumulation was significantly reduced by Cd. The expression of female hepatic estrogen receptor genes (ER-α and ER-β) was most significantly elevated in fish exposed to Cu and Cd mixture, whereas vitellogenin gene expression was reduced maximally in the same exposure. Similarly, the hepatic expression of the metallothionein gene was most significantly upregulated in fish exposed to Cu and Cd mixture. Moreover, the circulating estradiol level in females was significantly decreased only during the co-exposure of waterborne Cu and Cd. Overall, the present study indicates that the interaction of chronic waterborne Cu and Cd exposure may elicit greater than additive effect on reproductive output in fish. PMID:26498072

  17. Tissue-specific differences in the spatial interposition of X-chromosome and 3R chromosome regions in the malaria mosquito Anopheles messeae Fall.

    Gleb Artemov

    Full Text Available Spatial organization of a chromosome in a nucleus is very important in biology but many aspects of it are still generally unresolved. We focused on tissue-specific features of chromosome architecture in closely related malaria mosquitoes, which have essential inter-specific differences in polytene chromosome attachments in nurse cells. We showed that the region responsible for X-chromosome attachment interacts with nuclear lamina stronger in nurse cells, then in salivary glands cells in Anopheles messeae Fall. The inter-tissue differences were demonstrated more convincingly in an experiment of two distinct chromosomes interposition in the nucleus space of cells from four tissues. Microdissected DNA-probes from nurse cells X-chromosome (2BC and 3R chromosomes (32D attachment regions were hybridized with intact nuclei of nurse cells, salivary gland cells, follicle epithelium cells and imaginal disсs cells in 3D-FISH experiments. We showed that only salivary gland cells and follicle epithelium cells have no statistical differences in the interposition of 2BC and 32D. Generally, the X-chromosome and 3R chromosome are located closer to each other in cells of the somatic system in comparison with nurse cells on average. The imaginal disсs cell nuclei have an intermediate arrangement of chromosome interposition, similar to other somatic cells and nurse cells. In spite of species-specific chromosome attachments there are no differences in interposition of nurse cells chromosomes in An. messeae and An. atroparvus Thiel. Nurse cells have an unusual chromosome arrangement without a chromocenter, which could be due to the special mission of generative system cells in ontogenesis and evolution.

  18. Bipartite recognition of DNA by TCF/Pangolin is remarkably flexible and contributes to transcriptional responsiveness and tissue specificity of wingless signaling.

    Hilary C Archbold

    2014-09-01

    Full Text Available The T-cell factor (TCF family of transcription factors are major mediators of Wnt/β-catenin signaling in metazoans. All TCFs contain a High Mobility Group (HMG domain that possesses specific DNA binding activity. In addition, many TCFs contain a second DNA binding domain, the C-clamp, which binds to DNA motifs referred to as Helper sites. While HMG and Helper sites are both important for the activation of several Wnt dependent cis-regulatory modules (W-CRMs, the rules of what constitutes a functional HMG-Helper site pair are unknown. In this report, we employed a combination of in vitro binding, reporter gene analysis and bioinformatics to address this question, using the Drosophila family member TCF/Pangolin (TCF/Pan as a model. We found that while there were constraints for the orientation and spacing of HMG-Helper pairs, the presence of a Helper site near a HMG site in any orientation increased binding and transcriptional response, with some orientations displaying tissue-specific patterns. We found that altering an HMG-Helper site pair from a sub-optimal to optimal orientation/spacing dramatically increased the responsiveness of a W-CRM in several fly tissues. In addition, we used the knowledge gained to bioinformatically identify two novel W-CRMs, one that was activated by Wnt/β-catenin signaling in the prothoracic gland, a tissue not previously connected to this pathway. In sum, this work extends the importance of Helper sites in fly W-CRMs and suggests that the type of HMG-Helper pair is a major factor in setting the threshold for Wnt activation and tissue-responsiveness.

  19. Calcium-insensitive splice variants of mammalian E1 subunit of 2-oxoglutarate dehydrogenase complex with tissue-specific patterns of expression.

    Denton, Richard M; Pullen, Timothy J; Armstrong, Craig T; Heesom, Kate J; Rutter, Guy A

    2016-05-01

    The 2-oxoglutarate dehydrogenase (OGDH) complex is an important control point in vertebrate mitochondrial oxidative metabolism, including in the citrate cycle and catabolism of alternative fuels including glutamine. It is subject to allosteric regulation by NADH and the ATP/ADP ratio, and by Ca(2+) through binding to the E1 subunit. The latter involves a unique Ca(2+)-binding site which includes D(114)ADLD (site 1). Here, we describe three splice variants of E1 in which either the exon expressing this site is replaced with another exon (loss of site 1, LS1) or an additional exon is expressed leading to the insertion of 15 amino acids just downstream of site 1 (Insert), or both changes occur together (LS1/Insert). We show that all three variants are essentially Ca(2+)-insensitive. Comparison of massive parallel sequence (RNA-Seq) databases demonstrates predominant expression of the Ca(2+)-sensitive archetype form in heart and skeletal muscle, but substantial expression of the Ca(2+)-insensitive variants in brain, pancreatic islets and other tissues. Detailed proteomic and activity studies comparing OGDH complexes from rat heart and brain confirmed the substantial difference in expression between these tissues. The evolution of OGDH variants was explored using bioinformatics, and this indicated that Ca(2+)-sensitivity arose with the emergence of chordates. In all species examined, this was associated with the co-emergence of Ca(2+)-insensitive variants suggesting a retained requirement for the latter in some settings. Tissue-specific expression of OGDH splice variants may thus provide a mechanism that tunes the control of the enzyme to the specialized metabolic and signalling needs of individual cell types. PMID:26936970

  20. A novel rat genomic simple repeat DNA with RNA-homology shows triplex (H-DNA)-like structure and tissue-specific RNA expression

    Mammalian genome contains a wide variety of repetitive DNA sequences of relatively unknown function. We report a novel 227 bp simple repeat DNA (3.3 DNA) with a d {(GA) 7A (AG) 7} dinucleotide mirror repeat from the rat (Rattus norvegicus) genome. 3.3 DNA showed 75-85% homology with several eukaryotic mRNAs due to (GA/CU) n dinucleotide repeats by nBlast search and a dispersed distribution in the rat genome by Southern blot hybridization with [32P]3.3 DNA. The d {(GA) 7A (AG) 7} mirror repeat formed a triplex (H-DNA)-like structure in vitro. Two large RNAs of 9.1 and 7.5 kb were detected by [32P]3.3 DNA in rat brain by Northern blot hybridization indicating expression of such simple sequence repeats at RNA level in vivo. Further, several cDNAs were isolated from a rat cDNA library by [32P]3.3 DNA probe. Three such cDNAs showed tissue-specific RNA expression in rat. pRT 4.1 cDNA showed strong expression of a 2.39 kb RNA in brain and spleen, pRT 5.5 cDNA showed strong expression of a 2.8 kb RNA in brain and a 3.9 kb RNA in lungs, and pRT 11.4 cDNA showed weak expression of a 2.4 kb RNA in lungs. Thus, genomic simple sequence repeats containing d (GA/CT) n dinucleotides are transcriptionally expressed and regulated in rat tissues. Such d (GA/CT) n dinucleotide repeats may form structural elements (e.g., triplex) which may be sites for functional regulation of genomic coding sequences as well as RNAs. This may be a general function of such transcriptionally active simple sequence repeats widely dispersed in mammalian genome

  1. Effect of tissue-specific acetylcholinesterase inhibitor C-547 on α3β4 and αβεδ acetylcholine receptors in COS cells.

    Lindovský, Jiří; Petrov, Konstantin; Krůšek, Jan; Reznik, Vladimir S; Nikolsky, Eugeny E; Vyskočil, František

    2012-08-01

    The C-547 is the most effective muscle and tissue-specific anticholinesterase among alkylammonium derivatives of 6-methyluracil (ADEMS) acting in nanomolar concentrations on locomotor muscles but not on respiratory muscles, smooth muscles and heart and brain acetylcholine esterases (AChE). When applied systematically it could influence peripheral acetylcholine receptors. The aim of the present study was to investigate the effect of C-547 on rat α3β4 (ganglionic type) and αβεδ (muscle type) nicotinic receptors expressed in COS cells. Currents evoked by rapid application of acetylcholine or nicotine were recorded in whole-cell mode by electrophysiological patch-clamp technique 2-4 days after cell transfection by plasmids coding the α3β4 or αβεδ combination of receptor subunits. In cells sensitive to acetylcholine, the application of C-547 evoked no responses. When acetylcholine was applied during an already running application of C-547, acetylcholine responses were only inhibited at concentrations higher than 10(-7)M. This inhibition is not voltage-dependent, but is accompanied by an increased rate of desensitization. Thus in both types of receptors, effective doses are approximately 100 times higher than those inhibiting AChE in leg muscles and similar to those inhibiting respiratory diaphragm muscles and external intercostal muscles. These observations show that C-547 can be considered for symptomatic treatment of myasthenia gravis and other congenital myasthenic syndromes as an inhibitor of AChE in leg muscles at concentrations much lower than those inhibiting muscle and ganglion types of acetylcholine receptors. PMID:22634638

  2. Tissue-specific direct microtransfer of nanomaterials into Drosophila embryos as a versatile in vivo test bed for nanomaterial toxicity assessment

    Vega-Alvarez S

    2014-04-01

    Full Text Available Sasha Vega-Alvarez,1 Adriana Herrera,2 Carlos Rinaldi,2–4 Franklin A Carrero-Martínez1,5 1Department of Biology, 2Department of Chemical Engineering, University of Puerto Rico-Mayagüez, Mayagüez, Puerto Rico; 3J Crayton Pruitt Family Department of Biomedical Engineering, 4Department of Chemical Engineering, University of Florida, Gainesville, FL, USA; 5Department of Anatomy and Neuroscience, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico Abstract: Nanomaterials are the subject of intense research, focused on their synthesis, modification, and biomedical applications. Increased nanomaterial production and their wide range of applications imply a higher risk of human and environmental exposure. Unfortunately, neither environmental effects nor toxicity of nanomaterials to organisms are fully understood. Cost-effective, rapid toxicity assays requiring minimal amounts of materials are needed to establish both their biomedical potential and environmental safety standards. Drosophila exemplifies an efficient and cost-effective model organism with a vast repertoire of in vivo tools and techniques, all with high-throughput scalability and screening feasibility throughout its life cycle. Here we report tissue specific nanomaterial assessment through direct microtransfer into target tissues. We tested several nanomaterials with potential biomedical applications such as single-wall carbon nanotubes, multiwall carbon nanotubes, silver, gold, titanium dioxide, and iron oxide nanoparticles. Assessment of nanomaterial toxicity was conducted by evaluating progression through developmental morphological milestones in Drosophila. This cost-effective assessment method is amenable to high-throughput screening. Keywords: nanotoxicity, Drosophila, microtransfer, nanoparticle, iron oxide, silver, gold, titanium dioxide, carbon nanotube

  3. Post-Mortem Stability of RNA in Skeletal Muscle and Adipose Tissue and the Tissue-Specific Expression of Myostatin, Perilipin and Associated Factors in the Horse

    Morrison, Philippa K.; Bing, Chen; Harris, Patricia A.; Maltin, Charlotte A.; Grove-White, Dai; Argo, Caroline McG.

    2014-01-01

    Obesity, a major concern for equine welfare, is highly prevalent in the leisure horse population. Skeletal-muscle and adipose tissues are important determinants of maintenance energy requirements. The myostatin and perilipin pathways play key roles in the regulation of muscle mass and lipolysis respectively and have both been associated with obesity predisposition in other mammalian species. High quality samples, suitable for molecular biology, are an essential prerequisite for detailed investigations of gene and protein expression. Hence, this study has evaluated a) the post-mortem stability of RNA extracted from skeletal-muscle and adipose-tissues collected under commercial conditions and b) the tissue-specific presence of myostatin, the moystatin receptor (activin receptor IIB, ActRIIB), follistatin and perilipin, genes and proteins across a range of equine tissues. Objectives were addressed using tissues from 7 Thoroughbred horses presented for slaughter at a commercial abattoir; a) samples were collected at 7 time-points from Masseter muscle and perirenal adipose from 5 minutes to 6 hours post-mortem. Extracted RN was appraised by Optical Density analysis and agarose-gel electrophoresis. b) Quantitative real time PCR and Western Blotting were used to evaluate gene and protein expression in anatomically-defined samples collected from 17 tissues (6 organs, 4 skeletal muscles and 7 discrete adipose depots). The results indicate that, under the present collection conditions, intact, good quality RNA could be extracted from skeletal-muscle for up to 2 hours post-mortem. However, RNA from adipose tissue may be more susceptible to degradation/contamination and samples should be collected no later than 30 minutes post-mortem. The data also show that myostatin and ActRIIB genes and proteins were almost exclusively expressed in skeletal muscle. The follistatin gene showed a more diverse gene expression profile, with expression evident in several organs, adipose tissue

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

    To investigate whether MRI (RECIST 1.1, WHO criteria and the volumetric approach) or 18F-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 18F-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.)

  5. Accurate backgrounds to Higgs production at the LHC

    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.

  6. 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?

    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.)

  7. Small RNA and degradome deep sequencing reveals drought-and tissue-specific micrornas and their important roles in drought-sensitive and drought-tolerant tomato genotypes.

    Candar-Cakir, Bilgin; Arican, Ercan; Zhang, Baohong

    2016-08-01

    Drought stress has adverse impacts on plant production and productivity. MicroRNAs (miRNAs) are one class of noncoding RNAs regulating gene expression post-transcriptionally. In this study, we employed small RNA and degradome sequencing to systematically investigate the tissue-specific miRNAs responsible to drought stress, which are understudied in tomato. For this purpose, root and upground tissues of two different drought-responsive tomato genotypes (Lycopersicon esculentum as sensitive and L. esculentum var. cerasiforme as tolerant) were subjected to stress with 5% polyethylene glycol for 7 days. A total of 699 conserved miRNAs belonging to 578 families were determined and 688 miRNAs were significantly differentially expressed between different treatments, tissues and genotypes. Using degradome sequencing, 44 target genes were identified associated with 36 miRNA families. Drought-related miRNAs and their targets were enriched functionally by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Totally, 53 miRNAs targeted 23 key drought stress- and tissue development-related genes, including DRP (dehydration-responsive protein), GTs (glycosyltransferases), ERF (ethylene responsive factor), PSII (photosystem II) protein, HD-ZIP (homeodomain-leucine zipper), MYB and NAC-domain transcription factors. miR160, miR165, miR166, miR171, miR398, miR408, miR827, miR9472, miR9476 and miR9552 were the key miRNAs functioning in regulation of these genes and involving in tomato response to drought stress. Additionally, plant hormone signal transduction pathway genes were differentially regulated by miR169, miR172, miR393, miR5641, miR5658 and miR7997 in both tissues of both sensitive and tolerant genotypes. These results provide new insight into the regulatory role of miRNAs in drought response with plant hormone signal transduction and drought-tolerant tomato breeding. PMID:26857916

  8. LIR1基因在水稻中的组织特异性表达%Tissue-specific expression of LIR1 gene in rice

    岳彩黎; 王贵学; 黄俊丽; 胡锋; 秦峰

    2012-01-01

    水稻LIR1是LIR( light-induced rice)蛋白家族的一员,受光与生物钟的调节,在植物光反应及生物节律性调控方面有重要作用.为了研究水稻LIR1的生理功能,利用半定量RT-PCR技术对水稻‘珍汕97B’LIR1基因做了根、叶鞘、叶片及穗的组织特异性表达分析,同时构建了启动子的GUS基因融合表达载体LIR1::GUS转化烟草,利用GUS组织化学染色检测GUS基因在烟草组织器官中的表达情况.研究结果表明:LIR1基因在水稻叶片中的表达量较高,而在叶鞘、穗与根中表达量较低;GUS染色主要集中在叶片组织及茎中,而在植株的根部不显色.%Rice LIR1 ,a member of LrR(light-induced,rice)protein family,regulated by light and the biological clock,plays an important role for photosynthesis and biorhythm. In order to study the physiological functions of LIR1 , the tissue-specific expression analysis of UR1 gene in root, leaf sheath, young leaves, mature leaves and young panicle was carried out by RT-PCR, and the fusion binary expression vector LIR1 :: GUS was constructed to study the expression of GUS in transgenic tobacco plants. The results demonstrated that the expression level of LIR1 gene was much higher in leaf than that in leaf sheath, young panicle and root, and GUS expression was mainly concentrated in the stem,the major veins of leaf and the mesophyll presenting uneven distribution,but not in root.

  9. The role of human cytochrome P4503A4 in biotransformation of tissue-specific derivatives of 7H-dibenzo[c,g]carbazole

    The environmental pollutant 7H-dibenzo[c,g]carbazole (DBC) and its derivative, 5,9-dimethylDBC (DiMeDBC), produced significant and dose-dependent levels of micronuclei followed by a substantial increase in the frequency of apoptotic cells in the V79MZh3A4 cell line stably expressing the human cytochrome P450 (hCYP) 3A4. In contrast, neither micronuclei nor apoptosis were found in cells exposed to the sarcomagenic carcinogen, N-methylDBC (N-MeDBC). A slight but significant level of gene mutations and DNA adducts detected in V79MZh3A4 cells treated with N-MeDBC, only at the highest concentration (30 μM), revealed that this sarcomagenic carcinogen was also metabolized by hCYP3A4. Surprisingly, DBC increased the frequency of 6-thioguanine resistant (6-TGr) mutations only at the highest concentration (30 μM), while DiMeDBC failed to increase the frequency of these mutations. The resistance to 6-thioguanine is caused by the mutations in the hypoxanthine-guanine phosphoribosyltransferase (Hprt) gene. The molecular analysis of the coding region of Hprt gene showed a deletion of the entire exon 8 in DiMeDBC-induced 6-TGr mutants, while no changes in the nucleotide sequences were identified in 6-TGr mutants produced by DBC and N-MeDBC. Based on our results, we suggest that hCYP3A4 is involved in the metabolism of DBC and its tissue-specific derivatives. While hCYP3A4 probably plays an important role in biotransformation of the liver carcinogens, DBC and DiMeDBC, it might only have a marginal function in N-MeDBC metabolism. - Highlights: → DBC activation via CYP3A4 resulted in micronuclei, DNA adduct formation and mutations in V79MZh3A4 cells. → The CYP3A4-mediated DiMeDBC activation caused micronuclei followed by apoptosis in V79MZh3A4 cells. → The genotoxic effects produced by N-MeDBC in V79MZh3A4 cells were negligible. → The hCYP3A4 may play an important role in DBC and DiMeDBC metabolism. → The CYP3A4 might only have a marginal function in N-MeDBC metabolism.

  10. Towards accurate emergency response behavior

    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

  11. Accurate determination of antenna directivity

    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...

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

    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

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

    Andersen, Mikael Rørdam; Nielsen, Jakob Blæsbjerg; Klitgaard, Andreas; Petersen, Lene Maj; Zachariasen, Mia; Hansen, Tilde J; Holberg Blicher, Lene; Gotfredsen, Charlotte Held; Larsen, Thomas Ostenfeld; Nielsen, Kristian Fog; Mortensen, Uffe Hasbro

    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...... used A. nidulans for our method development and validation due to the wealth of available biochemical data, but the method can be applied to any fungus with a sequenced and assembled genome, thus supporting further secondary metabolite pathway elucidation in the fungal kingdom....

  14. An Innovative Imputation and Classification Approach for Accurate Disease Prediction

    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...

  15. Standardized EEG interpretation accurately predicts prognosis after cardiac arrest

    Westhall, Erik; 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...

  16. Modes-of-Action Related to Repeated Dose Toxicity: Tissue-Specific Biological Roles of PPAR γ Ligand-Dependent Dysregulation in Nonalcoholic Fatty Liver Disease

    Merilin Al Sharif; Petko Alov; Vessela Vitcheva; Ilza Pajeva; Ivanka Tsakovska

    2014-01-01

    Comprehensive understanding of the precise mode of action/adverse outcome pathway (MoA/AOP) of chemicals becomes a key step towards superseding the current repeated dose toxicity testing methodology with new generation predictive toxicology tools. The description and characterization of the toxicological MoA leading to non-alcoholic fatty liver disease (NAFLD) are of specific interest, due to its increasing incidence in the modern society. Growing evidence stresses on the PPAR γ ligand-depend...

  17. Toward Accurate and Quantitative Comparative Metagenomics.

    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

  18. Accurate ab initio spin densities

    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...

  19. Accurate Modeling of Advanced Reflectarrays

    Zhou, Min

    of the incident field, the choice of basis functions, and the technique to calculate the far-field. Based on accurate reference measurements of two offset reflectarrays carried out at the DTU-ESA Spherical NearField Antenna Test Facility, it was concluded that the three latter factors are particularly important...... to the conventional phase-only optimization technique (POT), the geometrical parameters of the array elements are directly optimized to fulfill the far-field requirements, thus maintaining a direct relation between optimization goals and optimization variables. As a result, better designs can be obtained compared...... using the GDOT to demonstrate its capabilities. To verify the accuracy of the GDOT, two offset contoured beam reflectarrays that radiate a high-gain beam on a European coverage have been designed and manufactured, and subsequently measured at the DTU-ESA Spherical Near-Field Antenna Test Facility...

  20. Accurate thickness measurement of graphene

    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.

  1. Accurately measuring dynamic coefficient of friction in ultraform finishing

    Briggs, Dennis; Echaves, Samantha; Pidgeon, Brendan; Travis, Nathan; Ellis, Jonathan D.

    2013-09-01

    UltraForm Finishing (UFF) is a deterministic sub-aperture computer numerically controlled grinding and polishing platform designed by OptiPro Systems. UFF is used to grind and polish a variety of optics from simple spherical to fully freeform, and numerous materials from glasses to optical ceramics. The UFF system consists of an abrasive belt around a compliant wheel that rotates and contacts the part to remove material. This work aims to accurately measure the dynamic coefficient of friction (μ), how it changes as a function of belt wear, and how this ultimately affects material removal rates. The coefficient of friction has been examined in terms of contact mechanics and Preston's equation to determine accurate material removal rates. By accurately predicting changes in μ, polishing iterations can be more accurately predicted, reducing the total number of iterations required to meet specifications. We have established an experimental apparatus that can accurately measure μ by measuring triaxial forces during translating loading conditions or while manufacturing the removal spots used to calculate material removal rates. Using this system, we will demonstrate μ measurements for UFF belts during different states of their lifecycle and assess the material removal function from spot diagrams as a function of wear. Ultimately, we will use this system for qualifying belt-wheel-material combinations to develop a spot-morphing model to better predict instantaneous material removal functions.

  2. An intergenic region shared by At4g35985 and At4g35987 in Arabidopsis thaliana is a tissue specific and stress inducible bidirectional promoter analyzed in transgenic arabidopsis and tobacco plants.

    Joydeep Banerjee

    Full Text Available On chromosome 4 in the Arabidopsis genome, two neighboring genes (calmodulin methyl transferase At4g35987 and senescence associated gene At4g35985 are located in a head-to-head divergent orientation sharing a putative bidirectional promoter. This 1258 bp intergenic region contains a number of environmental stress responsive and tissue specific cis-regulatory elements. Transcript analysis of At4g35985 and At4g35987 genes by quantitative real time PCR showed tissue specific and stress inducible expression profiles. We tested the bidirectional promoter-function of the intergenic region shared by the divergent genes At4g35985 and At4g35987 using two reporter genes (GFP and GUS in both orientations in transient tobacco protoplast and Agro-infiltration assays, as well as in stably transformed transgenic Arabidopsis and tobacco plants. In transient assays with GFP and GUS reporter genes the At4g35985 promoter (P85 showed stronger expression (about 3.5 fold compared to the At4g35987 promoter (P87. The tissue specific as well as stress responsive functional nature of the bidirectional promoter was evaluated in independent transgenic Arabidopsis and tobacco lines. Expression of P85 activity was detected in the midrib of leaves, leaf trichomes, apical meristemic regions, throughout the root, lateral roots and flowers. The expression of P87 was observed in leaf-tip, hydathodes, apical meristem, root tips, emerging lateral root tips, root stele region and in floral tissues. The bidirectional promoter in both orientations shows differential up-regulation (2.5 to 3 fold under salt stress. Use of such regulatory elements of bidirectional promoters showing spatial and stress inducible promoter-functions in heterologous system might be an important tool for plant biotechnology and gene stacking applications.

  3. Can clinicians accurately assess esophageal dilation without fluoroscopy?

    Bailey, A D; Goldner, F

    1990-01-01

    This study questioned whether clinicians could determine the success of esophageal dilation accurately without the aid of fluoroscopy. Twenty patients were enrolled with the diagnosis of distal esophageal stenosis, including benign peptic stricture (17), Schatski's ring (2), and squamous cell carcinoma of the esophagus (1). Dilation attempts using only Maloney dilators were monitored fluoroscopically by the principle investigator, the physician and patient being unaware of the findings. Physicians then predicted whether or not their dilations were successful, and they examined various features to determine their usefulness in predicting successful dilation. They were able to predict successful dilation accurately in 97% of the cases studied; however, their predictions of unsuccessful dilation were correct only 60% of the time. Features helpful in predicting passage included easy passage of the dilator (98%) and the patient feeling the dilator in the stomach (95%). Excessive resistance suggesting unsuccessful passage was an unreliable feature and was often due to the dilator curling in the stomach. When Maloney dilators are used to dilate simple distal strictures, if the physician predicts successful passage, he is reliably accurate without the use of fluoroscopy; however, if unsuccessful passage is suspected, fluoroscopy must be used for confirmation. PMID:2210278

  4. Too much data, but little inter-changeability: a lesson learned from mining public data on tissue specificity of gene expression

    Duffin Kevin

    2006-10-01

    investigate the cause for such discrepancies. Our study shows that the exploitation of rich public expression resource requires extensive knowledge about the technologies, and experiment. Informatic methodologies for better interoperability among platforms still remain a gap. One of the areas that can be improved practically is the accurate sequence mapping of SAGE tags and array probes to full-length genes. Reviewers This article was reviewed by Dr. I. King Jordan, Dr. Joel Bader, and Dr. Arcady Mushegian.

  5. A More Accurate Fourier Transform

    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...

  6. Accurately Detecting Students' Lies regarding Relational Aggression by Correctional Instructions

    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…

  7. Isolation, characterization, and tissue-specific expression of GABA A receptor α1 subunit gene of Carassius auratus gibelio after avermectin treatment.

    Zhao, Yini; Sun, Qi; Hu, Kun; Ruan, Jiming; Yang, Xianle

    2016-02-01

    Carassius auratus gibelio has been widely cultivated in fish farms in China, with avermectin (AVM) being used to prevent parasite infection. Recently, AVM was found to pass through the Carassius auratus gibelio blood-brain barrier (BBB). Although AVM acts mainly through a GABA receptor and specifically the α1 subunit gene, the most common isoform of the GABA A receptor, which is widely expressed in brain neurons and has been studied in other fish, Carassius auratus gibelio GABA A receptor α1 subunit gene cloning, and whether AVM passes through the BBB to induce Carassius auratus gibelio GABA A receptor α1 subunit gene expression have not been studied. The aim of this study was to clone, sequence, and phylogenetically analyze the GABA A receptor α1 subunit gene and to investigate the correlation of its expression with neurotoxicity in brain, liver, and kidney after AVM treatment by quantitative real-time reverse transcription polymerase chain reaction. The α1 subunit gene was 1550 bp in length with an open reading frame of 1380 bp encoding a predicted protein with 459 amino acid residues. The gene contained 128 bp of 5' terminal untranslated region (URT) and 72 bp of 3' terminal UTR. The α1 subunit structural features conformed to the Cys-loop ligand-gated ion channels family, which includes a signal peptide, an extracellular domain at the N-terminal, and four transmembrane domains. The established phylogenetic tree indicated that the α1 subunits of Carassius auratus gibelio and Danio rerio were the most closely related to each other. The α1 subunit was found to be highly expressed in brain and ovary, and the α1 mRNA transcription level increased significantly in brain. Moreover, the higher the concentration of AVM was, the higher the GABA A receptor expression was, indicating that AVM can induce significant neurotoxicity to Carassius auratus gibelio. Therefore, the α1 subunit mRNA expression was positively correlated with the neurotoxicity of AVM in

  8. Prediction of Unsteady Transonic Aerodynamics Project

    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...

  9. 38 CFR 4.46 - Accurate measurement.

    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...

  10. Accurate adiabatic correction in the hydrogen molecule

    Pachucki, Krzysztof, E-mail: krp@fuw.edu.pl [Faculty of Physics, University of Warsaw, Pasteura 5, 02-093 Warsaw (Poland); Komasa, Jacek, E-mail: komasa@man.poznan.pl [Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61-614 Poznań (Poland)

    2014-12-14

    A new formalism for the accurate treatment of adiabatic effects in the hydrogen molecule is presented, in which the electronic wave function is expanded in the James-Coolidge basis functions. Systematic increase in the size of the basis set permits estimation of the accuracy. Numerical results for the adiabatic correction to the Born-Oppenheimer interaction energy reveal a relative precision of 10{sup −12} at an arbitrary internuclear distance. Such calculations have been performed for 88 internuclear distances in the range of 0 < R ⩽ 12 bohrs to construct the adiabatic correction potential and to solve the nuclear Schrödinger equation. Finally, the adiabatic correction to the dissociation energies of all rovibrational levels in H{sub 2}, HD, HT, D{sub 2}, DT, and T{sub 2} has been determined. For the ground state of H{sub 2} the estimated precision is 3 × 10{sup −7} cm{sup −1}, which is almost three orders of magnitude higher than that of the best previous result. The achieved accuracy removes the adiabatic contribution from the overall error budget of the present day theoretical predictions for the rovibrational levels.

  11. The DNA binding site of the Dof protein NtBBF1 is essential for tissue-specific and auxin-regulated expression of the rolB oncogene in plants.

    Baumann, K; De Paolis, A; Costantino, P; Gualberti, G

    1999-01-01

    The Dof proteins are a large family of plant transcription factors that share a single highly conserved zinc finger. The tobacco Dof protein NtBBF1 was identified by its ability to bind to regulatory domain B in the promoter of the rolB oncogene. In this study, we show that the ACT T TA target sequence of NtBBF1 in domain B is necessary for tissue-specific expression of rolB. beta-Glucuronidase (GUS) activity of tobacco plants containing a rolB promoter-GUS fusion with a mutated NtBBF1 target sequence within domain B is almost completely suppressed in apical meristems and is severely abated in the vascular system. The ACT T TA motif is shown here also to be one of the cis-regulatory elements involved in auxin induction of rolB. The pattern of NtBBF1 expression in plants is remarkably similar to that of rolB, except in mesophyll cells of mature leaves, in which only NtBBF1 expression could be detected. Ectopic expression of rolB in mesophyll cells was achieved by particle gun delivery if the NtBBF1 binding sequence was intact. These data provide evidence that in the plant, a Dof protein DNA binding sequence acts as a transcriptional regulatory motif, and they point to NtBBF1 as the protein involved in mediating tissue-specific and auxin-inducible expression of rolB. PMID:10072394

  12. Effects of dietary cadmium exposure on tissue-specific cadmium accumulation, iron status and expression of iron-handling and stress-inducible genes in rainbow trout: Influence of elevated dietary iron

    Kwong, Raymond W.M. [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Andres, Jose A. [Department of Biology, University of Saskatchewan, Saskatoon, SK, S7N 5E2 (Canada); Niyogi, Som, E-mail: som.niyogi@usask.ca [Department of Biology, University of Saskatchewan, Saskatoon, SK, S7N 5E2 (Canada)

    2011-03-15

    Recent evidences suggest that dietary cadmium (Cd) uptake likely occurs via the dietary iron (Fe) uptake pathway in freshwater fish, at least in part. The present study investigated the interactive effects of dietary Cd and Fe in juvenile rainbow trout (Oncorhynchus mykiss). Fish were treated for four weeks with four different diets: normal Fe, high Fe, normal Fe plus Cd, and high Fe plus Cd. Physiological parameters, tissue-specific Fe and Cd level, plasma Fe status, and tissue-specific mRNA expression of transferrin, metallothioneins (MT-A and MT-B) and heat shock proteins 70 (HSP70a and HSP70b) were analyzed. Exposure to dietary Cd increased Cd burden in the following order: intestine > kidney > stomach > liver > gill > carcass. Interestingly, high dietary Fe reduced Cd accumulation in the stomach and intestine as well as in the wholebody of fish. Dietary Cd increased hepatic transferrin mRNA expression and total Fe binding capacity in the plasma, indicating the effect of Cd on Fe handling in fish. The mRNA expression of MTs and HSP70s was also increased in various tissues following dietary Cd exposure, however the response profile of different MT and HSP70 genes was not consistent among different tissues. In general, MT-A was more responsive to Cd exposure in the intestine and liver, whereas MT-B was more responsive in the kidney. Similarly, HSP70a expression was more sensitive to Cd exposure than HSP70b, particularly in the intestine. Interestingly, high Fe diet suppressed Cd-induced induction of transferrin, MT and HSP70 genes in various tissues. Overall, our study suggests that elevated dietary Fe can reduce Cd accumulation and ameliorate Cd-induced stress responses in freshwater fish.

  13. Tissue Specific Promoters in Colorectal Cancer

    A. R. Rama

    2015-01-01

    Full Text Available Colorectal carcinoma is the third most prevalent cancer in the world. In the most advanced stages, the use of chemotherapy induces a poor response and is usually accompanied by other tissue damage. Significant progress based on suicide gene therapy has demonstrated that it may potentiate the classical cytotoxic effects in colorectal cancer. The inconvenience still rests with the targeting and the specificity efficiency. The main target of gene therapy is to achieve an effective vehicle to hand over therapeutic genes safely into specific cells. One possibility is the use of tumor-specific promoters overexpressed in cancers. They could induce a specific expression of therapeutic genes in a given tumor, increasing their localized activity. Several promoters have been assayed into direct suicide genes to cancer cells. This review discusses the current status of specific tumor-promoters and their great potential in colorectal carcinoma treatment.

  14. Tissue-specific MR contrast agents

    The purpose of this review is to outline recent trends in contrast agent development for magnetic resonance imaging. Up to now, small molecular weight gadolinium chelates are the workhorse in contrast enhanced MRI. These first generation MR contrast agents distribute into the intravascular and interstitial space, thus allowing the evaluation of physiological parameters, such as the status or existence of the blood-brain-barrier or the renal function. Shortly after the first clinical use of paramagnetic metallochelates in 1983, compounds were suggested for liver imaging and enhancing a cardiac infarct. Meanwhile, liver specific contrast agents based on gadolinium, manganese or iron become reality. Dedicated blood pool agents will be available within the next years. These gadolinium or iron agents will be beneficial for longer lasting MRA procedures, such as cardiac imaging. Contrast enhanced lymphography after interstitial or intravenous injection will be another major step forward in diagnostic imaging. Metastatic involvement will be seen either after the injection of ultrasmall superparamagnetic iron oxides or dedicated gadolinium chelates. The accumulation of both compound classes is triggered by an uptake into macrophages. It is likely that similar agents will augment MRI of atheriosclerotic plaques, a systemic inflammatory disease of the arterial wall. Thrombus-specific agents based on small gadolinium labeled peptides are on the horizon. It is very obvious that the future of cardiovascular MRI will benefit from the development of new paramagnetic and superparamagnetic substances. The expectations for new tumor-, pathology- or receptor-specific agents are high. However, is not likely that such a compound will be available for daily routine MRI within the next decade

  15. Simple and accurate analytical calculation of shortest path lengths

    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.

  16. Accurate multireference study of Si3 electronic manifold

    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...

  17. Predictive modeling of complications.

    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

  18. Influence of elevated alkalinity and natural organic matter (NOM) on tissue-specific metal accumulation and reproductive performance in fathead minnows during chronic, multi-trophic exposures to a metal mine effluent.

    Ouellet, Jacob D; Dubé, Monique G; Niyogi, Som

    2013-09-01

    Metal bioavailability in aquatic organisms is known to be influenced by various water chemistry parameters. The present study examined the influence of alkalinity and natural organic matter (NOM) on tissue-specific metal accumulation and reproductive performance of fathead minnows (Pimephales promelas) during environmentally relevant chronic exposures to a metal mine effluent (MME). Sodium bicarbonate (NaHCO3) or NOM (as commercial humic acid) were added to a Canadian MME [45 percent process water effluent (PWE)] in order to evaluate whether increases in alkalinity (3-4 fold) or NOM (~1.5-3mg/L dissolved organic carbon) would reduce metal accumulation and mitigate reproductive toxicity in fathead minnows during a 21-day multi-trophic exposure. Eleven metals (barium, boron, cobalt, copper, lithium, manganese, molybdenum, nickel, rubidium, selenium, and strontium) were elevated in the 45 percent PWE relative to the reference water. Exposure to the unmodified 45 percent PWE resulted in a decrease of fathead minnow egg production (~300 fewer eggs/pair) relative to the unmodified reference water, over the 21-day exposure period. Water chemistry modifications produced a modest decrease in free ion activity of some metals (as shown by MINTEQ, Version 3) in the 45 percent PWE exposure water, but did not alter the metal burden in the treatment-matched larval Chironomus dilutus (the food source of fish during exposure). The tissue-specific metal accumulation increased in fish exposed to the 45 percent PWE relative to the reference water, irrespective of water chemistry modifications, and the tissue metal concentrations were found to be similar between fish in the unmodified and modified 45 percent PWE (higher alkalinity or NOM) treatments. Interestingly however, increased alkalinity and NOM markedly improved fish egg production both in the reference water (~500 and ~590 additional eggs/pair, respectively) and 45 percent PWE treatments (~570 and ~260 additional eggs

  19. Accurate Measurement of the Relative Abundance of Different DNA Species in Complex DNA Mixtures

    Jeong, Sangkyun; Yu, Hyunjoo; Pfeifer, Karl

    2012-01-01

    A molecular tool that can compare the abundances of different DNA sequences is necessary for comparing intergenic or interspecific gene expression. We devised and verified such a tool using a quantitative competitive polymerase chain reaction approach. For this approach, we adapted a competitor array, an artificially made plasmid DNA in which all the competitor templates for the target DNAs are arranged with a defined ratio, and melting analysis for allele quantitation for accurate quantitation of the fractional ratios of competitively amplified DNAs. Assays on two sets of DNA mixtures with explicitly known compositional structures of the test sequences were performed. The resultant average relative errors of 0.059 and 0.021 emphasize the highly accurate nature of this method. Furthermore, the method's capability of obtaining biological data is demonstrated by the fact that it can illustrate the tissue-specific quantitative expression signatures of the three housekeeping genes G6pdx, Ubc, and Rps27 by using the forms of the relative abundances of their transcripts, and the differential preferences of Igf2 enhancers for each of the multiple Igf2 promoters for the transcription. PMID:22334570

  20. Tissue specificity of methylation of cytosines in regulatory regions of four genes located in the locus FXYD5-COX7A1 of human chromosome 19: correlation with their expression level.

    Chalaya, T V; Akopov, S B; Nikolaev, L G; Sverdlov, E D

    2006-03-01

    In this study, we compared degree of methylation of selected CpG sites in CCGG sequences located in promoter regions of four human genes with expression level of these genes in several human cell lines and tissues. These genes were subdivided into two groups according to the dependence of their expression on CpG methylation in the 5 -regions. The first group, characterized by clear correlation of methylation with the transcription level, includes housekeeping gene COX6B (the absence of methylation unambiguously correlates with expression) and urothelium-specific uroplakin gene (the methylation coincides with absence of expression). The second group includes genes that are expressed in many, but not all tissues and cells. For these genes (LEAP-1 and ATP4A), there was no correlation between methylation and expression. It is possible that methylation provides some basal level of gene repression, which is overcome by binding of tissue-specific transcription factors, whereas lack of methylation gives the opportunity for gene expression in various cells and tissues. PMID:16545066

  1. Beta-adrenergic stimulation of cFOS via protein kinase A is mediated by cAMP regulatory element binding protein (CREB)-dependent and tissue-specific CREB-independent mechanisms in corticotrope cells.

    Boutillier, A L; Barthel, F; Roberts, J L; Loeffler, J P

    1992-11-25

    Catecholamines stimulate proopiomelanocortin (POMC) gene expression in corticotrope cells, but the molecular mechanisms of these effects are not known. While beta-adrenergic receptors stimulate the protein kinase A (PKA) system, the POMC promoter does not have classical cAMP-response elements (CREs). Therefore, we investigated the induction of the c-fos protooncogen, previously shown to increase POMC transcription in AtT20 cells. In this corticotrope-derived cell line, we show that activation of beta-receptors with isoprenaline (Iso) induces a transient rise in c-fos mRNA levels. Gel mobility shift assays with a labeled AP1 consensus sequence (TGACTCA) showed induction of specific binding activity after Iso treatment. Cotransfection experiments with dominant inhibitory PKA mutants and reporter genes containing c-fos promoter sequences showed that c-fos induction by Iso is entirely dependent on a functional PKA activity. Furthermore, we show that beta-receptor induction of c-fos in corticotrophs is mediated by at least two distinct cAMP-responsive sequences. cAMP regulatory element binding (CREB)-dependent induction is observed on the CRE located at -60 bp on the c-fos promoter. A region located in the vicinity of the dyad symetry element (-290) is also found to mediate tissue-specific cAMP induction. Transcriptional activation by this site, although sensitive to PKA antagonism, is not blocked by CREB mutants. PMID:1331087

  2. Laboratory Building for Accurate Determination of Plutonium

    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

  3. Accurate thermoelastic tensor and acoustic velocities of NaCl

    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

  4. Accurate thermoelastic tensor and acoustic velocities of NaCl

    Marcondes, Michel L.; Shukla, Gaurav; da Silveira, Pedro; Wentzcovitch, Renata M.

    2015-12-01

    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.

  5. Accurate thermoelastic tensor and acoustic velocities of NaCl

    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.

  6. Efficient and accurate sound propagation using adaptive rectangular decomposition.

    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

  7. Long Range Aircraft Trajectory Prediction

    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 ...

  8. Method for Accurately Calibrating a Spectrometer Using Broadband Light

    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.

  9. The FLUKA code: An accurate simulation tool for particle therapy

    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...

  10. Invariant Image Watermarking Using Accurate Zernike Moments

    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.

  11. The Cell Death Inhibitor ARC Is Induced in a Tissue-Specific Manner by Deletion of the Tumor Suppressor Gene Men1, but Not Required for Tumor Development and Growth.

    Wendy M McKimpson

    Full Text Available Multiple endocrine neoplasia type 1 (MEN1 is a genetic disorder characterized by tissue-specific tumors in the endocrine pancreas, parathyroid, and pituitary glands. Although tumor development in these tissues is dependent upon genetic inactivation of the tumor suppressor Men1, loss of both alleles of this gene is not sufficient to induce these cancers. Men1 encodes menin, a nuclear protein that influences transcription. A previous ChIP on chip analysis suggested that menin binds promoter sequences of nol3, encoding ARC, which is a cell death inhibitor that has been implicated in cancer pathogenesis. We hypothesized that ARC functions as a co-factor with Men1 loss to induce the tissue-restricted distribution of tumors seen in MEN1. Using mouse models that recapitulate this syndrome, we found that biallelic deletion of Men1 results in selective induction of ARC expression in tissues that develop tumors. Specifically, loss of Men1 in all cells of the pancreas resulted in marked increases in ARC mRNA and protein in the endocrine, but not exocrine, pancreas. Similarly, ARC expression increased in the parathyroid with inactivation of Men1 in that tissue. To test if ARC contributes to MEN1 tumor development in the endocrine pancreas, we generated mice that lacked none, one, or both copies of ARC in the context of Men1 deletion. Studies in a cohort of 126 mice demonstrated that, although mice lacking Men1 developed insulinomas as expected, elimination of ARC in this context did not significantly alter tumor load. Cellular rates of proliferation and death in these tumors were also not perturbed in the absence of ARC. These results indicate that ARC is upregulated by loss Men1 in the tissue-restricted distribution of MEN1 tumors, but that ARC is not required for tumor development in this syndrome.

  12. Targeted Expression of Stromelysin-1 in Mammary Gland Provides Evidence for a Role of Proteinases in Branching Morphogenesis and the Requirement for an Intact Basement Membrane for Tissue-specific Gene Expression

    Sympson, Carolyn J; Talhouk, Rabih S; Alexander, Caroline M; Chin, Jennie R; Cliff, Shirley M; Bissell, Mina J; Werb, Zena

    1994-05-01

    The extracellular matrix (ECM) is an important regulator of the differentiated phenotype of mammary epithelial cells in culture. Despite the fact that ECM-degrading enzymes have been implicated in morphogenesis and tissue remodeling, there is little evidence for a direct role for such regulation in vivo. We generated transgenic mice that express autoactivated isoforms of the matrix metalloproteinase stromelysin-1, under the control of the whey acidic protein gene promoter, to examine the effect of inappropriate expression of this enzyme. Stromelysin-1 is implicated as the primary player in the loss of basement membrane and loss of function in the mammary gland during involution. The transgene was expressed at low levels in mammary glands of virgin female mice, leading to an unexpected phenotype: The primary ducts had supernumerary branches and showed precocious development of alveoli that expressed beta-casein at levels similar to that of an early- to mid-pregnant gland. Lactating glands showed high levels of transgene expression, with accumulation at the basement membrane, and a decrease in laminin and collagen IV, resulting in a loss of basement membrane integrity; this was accompanied by a dramatic alteration of alveolar morphology, with decreased size and shrunken lumina containing little beta-casein. During pregnancy, expression of endogenous whey acidic protein and beta-casein was reduced in transgenic glands, confirming the observed dependence of milk protein transcription of ECM in mammary epithelial cells in culture. These data provide direct evidence that stromelysin-1 activity can be morphogenic for mammary epithelial cells, inducing hyperproliferation and differentiation in virgin animals, and that its lytic activity can, indeed, disrupt membrane integrity and reduce mammary-specific function. We conclude that the balance of ECM-degrading enzymes with their inhibitors, and the associated regulation of ECM structure, is crucial for tissue-specific gene

  13. Accurate method of modeling cluster scaling relations in modified gravity

    He, Jian-hua; Li, Baojiu

    2016-06-01

    We propose a new method to model cluster scaling relations in modified gravity. Using a suite of nonradiative hydrodynamical simulations, we show that the scaling relations of accumulated gas quantities, such as the Sunyaev-Zel'dovich effect (Compton-y parameter) and the x-ray Compton-y parameter, can be accurately predicted using the known results in the Λ CDM model with a precision of ˜3 % . This method provides a reliable way to analyze the gas physics in modified gravity using the less demanding and much more efficient pure cold dark matter simulations. Our results therefore have important theoretical and practical implications in constraining gravity using cluster surveys.

  14. Accurate studies on dissociation energies of diatomic molecules

    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.

  15. Accurate atomic data for industrial plasma applications

    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.

  16. More accurate picture of human body organs

    Computerized tomography and nucler magnetic resonance tomography (NMRT) are revolutionary contributions to radiodiagnosis because they allow to obtain a more accurate image of human body organs. The principles are described of both methods. Attention is mainly devoted to NMRT which has clinically only been used for three years. It does not burden the organism with ionizing radiation. (Ha)

  17. Can blind persons accurately assess body size from the voice?

    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

  18. The economic value of accurate wind power forecasting to utilities

    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)

  19. Downstream prediction using a nonlinear prediction method

    Adenan, N. H.; Noorani, M. S. M.

    2013-11-01

    The estimation of river flow is significantly related to the impact of urban hydrology, as this could provide information to solve important problems, such as flooding downstream. The nonlinear prediction method has been employed for analysis of four years of daily river flow data for the Langat River at Kajang, Malaysia, which is located in a downstream area. The nonlinear prediction method involves two steps; namely, the reconstruction of phase space and prediction. The reconstruction of phase space involves reconstruction from a single variable to the m-dimensional phase space in which the dimension m is based on optimal values from two methods: the correlation dimension method (Model I) and false nearest neighbour(s) (Model II). The selection of an appropriate method for selecting a combination of preliminary parameters, such as m, is important to provide an accurate prediction. From our investigation, we gather that via manipulation of the appropriate parameters for the reconstruction of the phase space, Model II provides better prediction results. In particular, we have used Model II together with the local linear prediction method to achieve the prediction results for the downstream area with a high correlation coefficient. In summary, the results show that Langat River in Kajang is chaotic, and, therefore, predictable using the nonlinear prediction method. Thus, the analysis and prediction of river flow in this area can provide river flow information to the proper authorities for the construction of flood control, particularly for the downstream area.

  20. Programming Useful Life Prediction (PULP) Project

    National Aeronautics and Space Administration — Accurately predicting Remaining Useful Life (RUL) provides significant benefits—it increases safety and reduces financial and labor resource requirements....

  1. Fast and accurate estimation for astrophysical problems in large databases

    Richards, Joseph W.

    2010-10-01

    A recent flood of astronomical data has created much demand for sophisticated statistical and machine learning tools that can rapidly draw accurate inferences from large databases of high-dimensional data. In this Ph.D. thesis, methods for statistical inference in such databases will be proposed, studied, and applied to real data. I use methods for low-dimensional parametrization of complex, high-dimensional data that are based on the notion of preserving the connectivity of data points in the context of a Markov random walk over the data set. I show how this simple parameterization of data can be exploited to: define appropriate prototypes for use in complex mixture models, determine data-driven eigenfunctions for accurate nonparametric regression, and find a set of suitable features to use in a statistical classifier. In this thesis, methods for each of these tasks are built up from simple principles, compared to existing methods in the literature, and applied to data from astronomical all-sky surveys. I examine several important problems in astrophysics, such as estimation of star formation history parameters for galaxies, prediction of redshifts of galaxies using photometric data, and classification of different types of supernovae based on their photometric light curves. Fast methods for high-dimensional data analysis are crucial in each of these problems because they all involve the analysis of complicated high-dimensional data in large, all-sky surveys. Specifically, I estimate the star formation history parameters for the nearly 800,000 galaxies in the Sloan Digital Sky Survey (SDSS) Data Release 7 spectroscopic catalog, determine redshifts for over 300,000 galaxies in the SDSS photometric catalog, and estimate the types of 20,000 supernovae as part of the Supernova Photometric Classification Challenge. Accurate predictions and classifications are imperative in each of these examples because these estimates are utilized in broader inference problems

  2. Non-coplanar polychlorinated biphenyls (PCBs) are direct agonists for the human pregnane-X receptor and constitutive androstane receptor, and activate target gene expression in a tissue-specific manner

    The polychlorinated biphenyl group possesses high environmental persistence, leading to bioaccumulation and a number of adverse effects in mammals. Whilst coplanar PCBs elicit their toxic effects through agonism of the aryl hydrocarbon receptor; however, non-coplanar PCBs are not ligands for AhR, but may be ligands for members of the nuclear receptor family of proteins. To better understand the biological actions of non-coplanar PCBs, we have undertaken a systematic analysis of their ability to activate PXR and CAR-mediated effects. Cells were exposed to a range of non-coplanar PCBs (99, 138, 153, 180 and 194), or the coplanar PCB77: Direct activation of PXR and CAR was measured using a mammalian receptor activation assay in human liver cells, with rifampicin and CITCO used as positive controls ligands for PXR and CAR, respectively; activation of target gene expression was examined using reporter gene plasmids for CYP3A4 and MDR1 transfected into liver, intestine and lung cell lines. Several of the non-coplanar PCBs directly activated PXR and CAR, whilst the coplanar PCB77 did not. Non-coplanar PCBs were also able to activate PXR/CAR target gene expression in a substitution- and tissue-specific manner. Non-coplanar PCBs act as direct activators for the nuclear receptors PXR and CAR, and are able to elicit transcriptional activation of target genes in a substitution- and tissue-dependent manner. Chronic activation of PXR/CAR is linked to adverse effects and must be included in any risk assessment of PCBs. -- Highlights: ► Several Non-coplanar PCBs are able to directly activate both PXR and CAR in vitro. ► PCB153 is the most potent direct activator of PXR and CAR nuclear receptors. ► Non-coplanar PCB activation of CYP3A4/MDR1 reporter genes is structure-dependent. ► Non-coplanar PCB activate CYP3A4/MDR1 reporter genes in a tissue-dependent. ► PCB153 is the most potent activator of PXR/CAR target gene in all tissues.

  3. Non-coplanar polychlorinated biphenyls (PCBs) are direct agonists for the human pregnane-X receptor and constitutive androstane receptor, and activate target gene expression in a tissue-specific manner

    Al-Salman, Fadheela; Plant, Nick, E-mail: N.Plant@Surrey.ac.uk

    2012-08-15

    The polychlorinated biphenyl group possesses high environmental persistence, leading to bioaccumulation and a number of adverse effects in mammals. Whilst coplanar PCBs elicit their toxic effects through agonism of the aryl hydrocarbon receptor; however, non-coplanar PCBs are not ligands for AhR, but may be ligands for members of the nuclear receptor family of proteins. To better understand the biological actions of non-coplanar PCBs, we have undertaken a systematic analysis of their ability to activate PXR and CAR-mediated effects. Cells were exposed to a range of non-coplanar PCBs (99, 138, 153, 180 and 194), or the coplanar PCB77: Direct activation of PXR and CAR was measured using a mammalian receptor activation assay in human liver cells, with rifampicin and CITCO used as positive controls ligands for PXR and CAR, respectively; activation of target gene expression was examined using reporter gene plasmids for CYP3A4 and MDR1 transfected into liver, intestine and lung cell lines. Several of the non-coplanar PCBs directly activated PXR and CAR, whilst the coplanar PCB77 did not. Non-coplanar PCBs were also able to activate PXR/CAR target gene expression in a substitution- and tissue-specific manner. Non-coplanar PCBs act as direct activators for the nuclear receptors PXR and CAR, and are able to elicit transcriptional activation of target genes in a substitution- and tissue-dependent manner. Chronic activation of PXR/CAR is linked to adverse effects and must be included in any risk assessment of PCBs. -- Highlights: ► Several Non-coplanar PCBs are able to directly activate both PXR and CAR in vitro. ► PCB153 is the most potent direct activator of PXR and CAR nuclear receptors. ► Non-coplanar PCB activation of CYP3A4/MDR1 reporter genes is structure-dependent. ► Non-coplanar PCB activate CYP3A4/MDR1 reporter genes in a tissue-dependent. ► PCB153 is the most potent activator of PXR/CAR target gene in all tissues.

  4. How Accurate is inv(A)*b?

    Druinsky, Alex

    2012-01-01

    Several widely-used textbooks lead the reader to believe that solving a linear system of equations Ax = b by multiplying the vector b by a computed inverse inv(A) is inaccurate. Virtually all other textbooks on numerical analysis and numerical linear algebra advise against using computed inverses without stating whether this is accurate or not. In fact, under reasonable assumptions on how the inverse is computed, x = inv(A)*b is as accurate as the solution computed by the best backward-stable solvers. This fact is not new, but obviously obscure. We review the literature on the accuracy of this computation and present a self-contained numerical analysis of it.

  5. Accurate guitar tuning by cochlear implant musicians.

    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.

  6. Accurate guitar tuning by cochlear implant musicians.

    Lu, Thomas; Huang, Juan; Zeng, Fan-Gang

    2014-01-01

    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. PMID:24651081

  7. Accurate Finite Difference Methods for Option Pricing

    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...

  8. Accurate, reproducible measurement of blood pressure.

    Campbell, N. R.; Chockalingam, A; Fodor, J. G.; McKay, D. W.

    1990-01-01

    The diagnosis of mild hypertension and the treatment of hypertension require accurate measurement of blood pressure. Blood pressure readings are altered by various factors that influence the patient, the techniques used and the accuracy of the sphygmomanometer. The variability of readings can be reduced if informed patients prepare in advance by emptying their bladder and bowel, by avoiding over-the-counter vasoactive drugs the day of measurement and by avoiding exposure to cold, caffeine con...

  9. Accurate variational forms for multiskyrmion configurations

    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.

  10. Efficient Accurate Context-Sensitive Anomaly Detection

    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.

  11. Towards accurate modeling of moving contact lines

    Holmgren, Hanna

    2015-01-01

    The present thesis treats the numerical simulation of immiscible incompressible two-phase flows with moving contact lines. The conventional Navier–Stokes equations combined with a no-slip boundary condition leads to a non-integrable stress singularity at the contact line. The singularity in the model can be avoided by allowing the contact line to slip. Implementing slip conditions in an accurate way is not straight-forward and different regularization techniques exist where ad-hoc procedures ...

  12. Accurate phase-shift velocimetry in rock

    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.

  13. High Frequency QRS ECG Accurately Detects Cardiomyopathy

    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

  14. Niche Genetic Algorithm with Accurate Optimization Performance

    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.

  15. How accurately can we calculate thermal systems?

    The objective was to determine how accurately simple reactor lattice integral parameters can be determined, considering user input, differences in the methods, source data and the data processing procedures and assumptions. Three simple square lattice test cases with different fuel to moderator ratios were defined. The effect of the thermal scattering models were shown to be important and much bigger than the spread in the results. Nevertheless, differences of up to 0.4% in the K-eff calculated by continuous energy Monte Carlo codes were observed even when the same source data were used. (author)

  16. Accurate diagnosis is essential for amebiasis

    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.

  17. Investigations on Accurate Analysis of Microstrip Reflectarrays

    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...

  18. Accurate location estimation of moving object with energy constraint & adaptive update algorithms to save data

    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 ...

  19. 猪I-FABP基因的分子克隆与组织特异性表达分析%Molecular Cloning and Tissue-specific Expression of Intestinal-type Fatty Acid Binding Protein in Porcine

    姜延志; 李学伟

    2006-01-01

    小肠型脂肪酸结合蛋白对长链脂肪酸具有高度的亲和力,参与脂肪酸的吸收和细胞内转运.利用cDNA末端快速扩增(RACE)技术并结合同源克隆策略,克隆到了编码猪小肠型脂肪酸结合蛋白基因(I-FABP)的全长cDNA序列(GenBank接受号:AY960624),并对系统发育关系等进行了生物信息学分析.猪I-FABP基因的cDNA序列全长614 bp,其中包括399 bp的开放式读码框(ORF),43 bp的5'末端非编码区(5'URT)和172 bp的3'末端非编码区(3'URT),编码132个氨基酸残基蛋白,在氨基酸水平上与其他物种的I-FABP具有高度的同源性.以邻接法(Neigbor-Joining,NJ)所构建的系统发育关系表明,猪I-FABP与其他物种的I-FABP属于同一类群,且与人的遗传距离最近.Northern杂交和半定量RT-PCR分析发现,猪I-FABP在猪体组织中出现约620 bp大小的转录本,且在猪体组织中广泛存在,但在小肠组织中表达量最为丰富.%The intestinal fatty acid-binding protein (I-FABP) shows binding specificity for long-chain fatty acids and is proposed to be involved in the uptake of dietary fatty acids and their intracellular transport. In this study, the full-length cDNA of I-FABP was cloned from pig intestine by homology cloning approach combined with 3' and 5' RACE. Sequence analysis and bioinformatics study showed that this cDNA contained 614 nucleotides, with a 399 bp open reading frame (ORF) flanked by a 43 bp 5' UTR and a172 bp 3' UTR. The encoded 132 amino acids of pig I-FABP with a molecular weight of approximately 15 kDa shared a high sequence identity of 68%-85% with those of other species. In addition, the phylogenetical analysis also indicated that the pig I-FABP was in the same branch with those of other species. The tissue-specific expression of pig I-FABP was measured by Northern hybridization and semi-quantitative RT-PCR. The results demonstrated that pig I-FABP mRNA was extensively present in various tissues, but I-FABP transcript of

  20. Accurate radiative transfer calculations for layered media.

    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

  1. Accurate basis set truncation for wavefunction embedding

    Barnes, Taylor A.; Goodpaster, Jason D.; Manby, Frederick R.; Miller, Thomas F.

    2013-07-01

    Density functional theory (DFT) provides a formally exact framework for performing embedded subsystem electronic structure calculations, including DFT-in-DFT and wavefunction theory-in-DFT descriptions. In the interest of efficiency, it is desirable to truncate the atomic orbital basis set in which the subsystem calculation is performed, thus avoiding high-order scaling with respect to the size of the MO virtual space. In this study, we extend a recently introduced projection-based embedding method [F. R. Manby, M. Stella, J. D. Goodpaster, and T. F. Miller III, J. Chem. Theory Comput. 8, 2564 (2012)], 10.1021/ct300544e to allow for the systematic and accurate truncation of the embedded subsystem basis set. The approach is applied to both covalently and non-covalently bound test cases, including water clusters and polypeptide chains, and it is demonstrated that errors associated with basis set truncation are controllable to well within chemical accuracy. Furthermore, we show that this approach allows for switching between accurate projection-based embedding and DFT embedding with approximate kinetic energy (KE) functionals; in this sense, the approach provides a means of systematically improving upon the use of approximate KE functionals in DFT embedding.

  2. Accurate pose estimation for forensic identification

    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.

  3. Accurate determination of characteristic relative permeability curves

    Krause, Michael H.; Benson, Sally M.

    2015-09-01

    A recently developed technique to accurately characterize sub-core scale heterogeneity is applied to investigate the factors responsible for flowrate-dependent effective relative permeability curves measured on core samples in the laboratory. The dependency of laboratory measured relative permeability on flowrate has long been both supported and challenged by a number of investigators. Studies have shown that this apparent flowrate dependency is a result of both sub-core scale heterogeneity and outlet boundary effects. However this has only been demonstrated numerically for highly simplified models of porous media. In this paper, flowrate dependency of effective relative permeability is demonstrated using two rock cores, a Berea Sandstone and a heterogeneous sandstone from the Otway Basin Pilot Project in Australia. Numerical simulations of steady-state coreflooding experiments are conducted at a number of injection rates using a single set of input characteristic relative permeability curves. Effective relative permeability is then calculated from the simulation data using standard interpretation methods for calculating relative permeability from steady-state tests. Results show that simplified approaches may be used to determine flowrate-independent characteristic relative permeability provided flow rate is sufficiently high, and the core heterogeneity is relatively low. It is also shown that characteristic relative permeability can be determined at any typical flowrate, and even for geologically complex models, when using accurate three-dimensional models.

  4. Accurate shear measurement with faint sources

    Zhang, Jun; Foucaud, Sebastien [Center for Astronomy and Astrophysics, Department of Physics and Astronomy, Shanghai Jiao Tong University, 955 Jianchuan road, Shanghai, 200240 (China); Luo, Wentao, E-mail: betajzhang@sjtu.edu.cn, E-mail: walt@shao.ac.cn, E-mail: foucaud@sjtu.edu.cn [Key Laboratory for Research in Galaxies and Cosmology, Shanghai Astronomical Observatory, Nandan Road 80, Shanghai, 200030 (China)

    2015-01-01

    For cosmic shear to become an accurate cosmological probe, systematic errors in the shear measurement method must be unambiguously identified and corrected for. Previous work of this series has demonstrated that cosmic shears can be measured accurately in Fourier space in the presence of background noise and finite pixel size, without assumptions on the morphologies of galaxy and PSF. The remaining major source of error is source Poisson noise, due to the finiteness of source photon number. This problem is particularly important for faint galaxies in space-based weak lensing measurements, and for ground-based images of short exposure times. In this work, we propose a simple and rigorous way of removing the shear bias from the source Poisson noise. Our noise treatment can be generalized for images made of multiple exposures through MultiDrizzle. This is demonstrated with the SDSS and COSMOS/ACS data. With a large ensemble of mock galaxy images of unrestricted morphologies, we show that our shear measurement method can achieve sub-percent level accuracy even for images of signal-to-noise ratio less than 5 in general, making it the most promising technique for cosmic shear measurement in the ongoing and upcoming large scale galaxy surveys.

  5. On Prediction of EOP

    Malkin, Z

    2009-01-01

    Two methods of prediction of the Pole coordinates and TAI-UTC were tested -- extrapolation of the deterministic components and ARIMA. It was found that each of these methods is most effective for certain length of prognosis. For short-time prediction ARIMA algorithm yields more accurate prognosis, and for long-time one extrapolation is preferable. So, the combined algorithm is being used in practice of IAA EOP Service. The accuracy of prognosis is close to accuracy of IERS algorithms. For prediction of nutation the program KSV-1996-1 by T. Herring is being used.

  6. The FLUKA Code: An Accurate Simulation Tool for Particle Therapy

    Battistoni, Giuseppe; Bauer, Julia; Boehlen, Till T.; Cerutti, Francesco; Chin, Mary P. W.; Dos Santos Augusto, Ricardo; Ferrari, Alfredo; Ortega, Pablo G.; Kozłowska, Wioletta; 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 both 4He and 12C ion beams. Accurate description of ionization energy losses and of particle scattering and interactions lead to the excellent agreement of calculated depth–dose profiles with those measured at leading European hadron therapy centers, both with proton and ion beams. In order to support the application of FLUKA in hospital-based environments, Flair, the FLUKA graphical interface, has been enhanced with the capability of translating CT DICOM images into voxel-based computational phantoms in a fast and well-structured way. The interface is capable of importing also radiotherapy treatment data described in DICOM RT standard. In addition, the interface is equipped with an intuitive PET scanner geometry generator and automatic recording of coincidence events. Clinically, similar cases will be presented both in terms of absorbed dose and biological dose calculations describing the various available features. PMID:27242956

  7. The FLUKA Code: An Accurate Simulation Tool for Particle Therapy.

    Battistoni, Giuseppe; Bauer, Julia; Boehlen, Till T; Cerutti, Francesco; Chin, Mary P W; Dos Santos Augusto, Ricardo; Ferrari, Alfredo; Ortega, Pablo G; Kozłowska, Wioletta; 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 both (4)He and (12)C ion beams. Accurate description of ionization energy losses and of particle scattering and interactions lead to the excellent agreement of calculated depth-dose profiles with those measured at leading European hadron therapy centers, both with proton and ion beams. In order to support the application of FLUKA in hospital-based environments, Flair, the FLUKA graphical interface, has been enhanced with the capability of translating CT DICOM images into voxel-based computational phantoms in a fast and well-structured way. The interface is capable of importing also radiotherapy treatment data described in DICOM RT standard. In addition, the interface is equipped with an intuitive PET scanner geometry generator and automatic recording of coincidence events. Clinically, similar cases will be presented both in terms of absorbed dose and biological dose calculations describing the various available features. PMID:27242956

  8. Accurate bond dissociation energies (D 0) for FHF- isotopologues

    Stein, Christopher; Oswald, Rainer; Sebald, Peter; Botschwina, Peter; Stoll, Hermann; Peterson, Kirk A.

    2013-09-01

    Accurate bond dissociation energies (D 0) are determined for three isotopologues of the bifluoride ion (FHF-). While the zero-point vibrational contributions are taken from our previous work (P. Sebald, A. Bargholz, R. Oswald, C. Stein, P. Botschwina, J. Phys. Chem. A, DOI: 10.1021/jp3123677), the equilibrium dissociation energy (D e ) of the reaction ? was obtained by a composite method including frozen-core (fc) CCSD(T) calculations with basis sets up to cardinal number n = 7 followed by extrapolation to the complete basis set limit. Smaller terms beyond fc-CCSD(T) cancel each other almost completely. The D 0 values of FHF-, FDF-, and FTF- are predicted to be 15,176, 15,191, and 15,198 cm-1, respectively, with an uncertainty of ca. 15 cm-1.

  9. Accurate characterisation of post moulding shrinkage of polymer parts

    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 was...... used to record the length at a well-defined position on each part continuously, starting from approximately 10 minutes after moulding and covering a time period of 7 days. Two series of shrinkage curves were analysed and length values after stabilisation extracted and compared for all 16 parts. Values...... 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...

  10. Accurate monitoring of large aligned objects with videometric techniques

    Klumb, F; Grussenmeyer, P

    1999-01-01

    This paper describes a new videometric technique designed to monitor the deformations and misalignments of large vital components in the centre of a future particle detector. It relies on a geometrical principle called "reciprocal collimation" of two CCD cameras: the combination of the video devices in pair gives rise to a network of well located reference lines that surround the object to be surveyed. Each observed point, which in practice is a bright point-like light- source, is accurately located with respect to this network of neighbouring axes. Adjustment calculations provide the three- dimensional position of the object fitted with various light-sources. An experimental test-bench, equipped with four cameras, has corroborated the precision predicted by previous simulations of the system. (11 refs).

  11. How accurately can 21cm tomography constrain cosmology?

    Mao, Yi; Tegmark, Max; McQuinn, Matthew; Zaldarriaga, Matias; Zahn, Oliver

    2008-07-01

    There is growing interest in using 3-dimensional neutral hydrogen mapping with the redshifted 21 cm line as a cosmological probe. However, its utility depends on many assumptions. To aid experimental planning and design, we quantify how the precision with which cosmological parameters can be measured depends on a broad range of assumptions, focusing on the 21 cm signal from 6noise, to uncertainties in the reionization history, and to the level of contamination from astrophysical foregrounds. We derive simple analytic estimates for how various assumptions affect an experiment’s sensitivity, and we find that the modeling of reionization is the most important, followed by the array layout. We present an accurate yet robust method for measuring cosmological parameters that exploits the fact that the ionization power spectra are rather smooth functions that can be accurately fit by 7 phenomenological parameters. We find that for future experiments, marginalizing over these nuisance parameters may provide constraints almost as tight on the cosmology as if 21 cm tomography measured the matter power spectrum directly. A future square kilometer array optimized for 21 cm tomography could improve the sensitivity to spatial curvature and neutrino masses by up to 2 orders of magnitude, to ΔΩk≈0.0002 and Δmν≈0.007eV, and give a 4σ detection of the spectral index running predicted by the simplest inflation models.

  12. Accurate location estimation of moving object In Wireless Sensor network

    Vinay Bhaskar Semwal

    2011-12-01

    Full Text Available One of the central issues in wirless 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.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 had shown that our tracking method performs well in terms of energy saving regardless of mobility pattern of the mobile target. We extends the life time of network with less sensor node. Once a new object is detected, a mobile agent will be initiated to track the roaming path of the object.

  13. Accurate Telescope Mount Positioning with MEMS Accelerometers

    Mészáros, László; Pál, András; Csépány, Gergely

    2014-01-01

    This paper describes the advantages and challenges of applying microelectromechanical accelerometer systems (MEMS accelerometers) in order to attain precise, accurate and stateless positioning of telescope mounts. This provides a completely independent method from other forms of electronic, optical, mechanical or magnetic feedback or real-time astrometry. Our goal is to reach the sub-arcminute range which is well smaller than the field-of-view of conventional imaging telescope systems. Here we present how this sub-arcminute accuracy can be achieved with very cheap MEMS sensors and we also detail how our procedures can be extended in order to attain even finer measurements. In addition, our paper discusses how can a complete system design be implemented in order to be a part of a telescope control system.

  14. Accurate estimation of indoor travel times

    Prentow, Thor Siiger; Blunck, Henrik; Stisen, Allan;

    2014-01-01

    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. InTraTime...... allows to specify temporal and other query parameters, such as time-of-day, day-of-week or the identity of the traveling individual. As input the method is designed to take generic position traces and is thus interoperable with a variety of indoor positioning systems. The method's advantages include...... a minimal-effort setup and self-improving operations due to unsupervised learning---as it is able to adapt implicitly to factors influencing indoor travel times such as elevators, rotating doors or changes in building layout. We evaluate and compare the proposed InTraTime method to indoor adaptions...

  15. Accurate sky background modelling for ESO facilities

    Full text: Ground-based measurements like e.g. high resolution spectroscopy are heavily influenced by several physical processes. Amongst others, line absorption/ emission, air glow by OH molecules, and scattering of photons within the earth's atmosphere make observations in particular from facilities like the future European extremely large telescope a challenge. Additionally, emission from unresolved extrasolar objects, the zodiacal light, the moon and even thermal emission from the telescope and the instrument contribute significantly to the broad band background over a wide wavelength range. In our talk we review these influences and give an overview on how they can be accurately modeled for increasing the overall precision of spectroscopic and imaging measurements. (author)

  16. Accurate valence band width of diamond

    An accurate width is determined for the valence band of diamond by imaging photoelectron momentum distributions for a variety of initial- and final-state energies. The experimental result of 23.0±0.2 eV2 agrees well with first-principles quasiparticle calculations (23.0 and 22.88 eV) and significantly exceeds the local-density-functional width, 21.5±0.2 eV2. This difference quantifies effects of creating an excited hole state (with associated many-body effects) in a band measurement vs studying ground-state properties treated by local-density-functional calculations. copyright 1997 The American Physical Society

  17. Accurate Weather Forecasting for Radio Astronomy

    Maddalena, Ronald J.

    2010-01-01

    The NRAO Green Bank Telescope routinely observes at wavelengths from 3 mm to 1 m. As with all mm-wave telescopes, observing conditions depend upon the variable atmospheric water content. The site provides over 100 days/yr when opacities are low enough for good observing at 3 mm, but winds on the open-air structure reduce the time suitable for 3-mm observing where pointing is critical. Thus, to maximum productivity the observing wavelength needs to match weather conditions. For 6 years the telescope has used a dynamic scheduling system (recently upgraded; www.gb.nrao.edu/DSS) that requires accurate multi-day forecasts for winds and opacities. Since opacity forecasts are not provided by the National Weather Services (NWS), I have developed an automated system that takes available forecasts, derives forecasted opacities, and deploys the results on the web in user-friendly graphical overviews (www.gb.nrao.edu/ rmaddale/Weather). The system relies on the "North American Mesoscale" models, which are updated by the NWS every 6 hrs, have a 12 km horizontal resolution, 1 hr temporal resolution, run to 84 hrs, and have 60 vertical layers that extend to 20 km. Each forecast consists of a time series of ground conditions, cloud coverage, etc, and, most importantly, temperature, pressure, humidity as a function of height. I use the Liebe's MWP model (Radio Science, 20, 1069, 1985) to determine the absorption in each layer for each hour for 30 observing wavelengths. Radiative transfer provides, for each hour and wavelength, the total opacity and the radio brightness of the atmosphere, which contributes substantially at some wavelengths to Tsys and the observational noise. Comparisons of measured and forecasted Tsys at 22.2 and 44 GHz imply that the forecasted opacities are good to about 0.01 Nepers, which is sufficient for forecasting and accurate calibration. Reliability is high out to 2 days and degrades slowly for longer-range forecasts.

  18. Predicting Pallet Part Yields From Hardwood Cants

    Mitchell, Hal Lee

    1999-01-01

    Pallet cant quality directly impacts pallet part processing and material costs. By knowing the quality of the cants being processed, pallet manufacturers can predict costs to attain better value from their raw materials and more accurately price their pallets. The study objectives were 1) to develop a procedure for accurately predicting hardwood pallet part yield as a function of raw material geometry and grade, processing equipment, and pallet part geometry, 2) to develop a model for accur...

  19. Approaching system equilibrium with accurate or not accurate feedback information in a two-route system

    Zhao, Xiao-mei; Xie, Dong-fan; Li, Qi

    2015-02-01

    With the development of intelligent transport system, advanced information feedback strategies have been developed to reduce traffic congestion and enhance the capacity. However, previous strategies provide accurate information to travelers and our simulation results show that accurate information brings negative effects, especially in delay case. Because travelers prefer to the best condition route with accurate information, and delayed information cannot reflect current traffic condition but past. Then travelers make wrong routing decisions, causing the decrease of the capacity and the increase of oscillations and the system deviating from the equilibrium. To avoid the negative effect, bounded rationality is taken into account by introducing a boundedly rational threshold BR. When difference between two routes is less than the BR, routes have equal probability to be chosen. The bounded rationality is helpful to improve the efficiency in terms of capacity, oscillation and the gap deviating from the system equilibrium.

  20. Prediction in projection

    Garland, Joshua; Bradley, Elizabeth

    2015-12-01

    Prediction models that capture and use the structure of state-space dynamics can be very effective. In practice, however, one rarely has access to full information about that structure, and accurate reconstruction of the dynamics from scalar time-series data—e.g., via delay-coordinate embedding—can be a real challenge. In this paper, we show that forecast models that employ incomplete reconstructions of the dynamics—i.e., models that are not necessarily true embeddings—can produce surprisingly accurate predictions of the state of a dynamical system. In particular, we demonstrate the effectiveness of a simple near-neighbor forecast technique that works with a two-dimensional time-delay reconstruction of both low- and high-dimensional dynamical systems. Even though correctness of the topology may not be guaranteed for incomplete reconstructions like this, the dynamical structure that they do capture allows for accurate predictions—in many cases, even more accurate than predictions generated using a traditional embedding. This could be very useful in the context of real-time forecasting, where the human effort required to produce a correct delay-coordinate embedding is prohibitive.

  1. Tissue-specific regulatory network extractor (TS-REX): a database and software resource for the tissue and cell type-specific investigation of transcription factor-gene networks.

    Colecchia, Federico; Kottwitz, Denise; Wagner, Mandy; Pfenninger, Cosima V; Thiel, Gerald; Tamm, Ingo; Peterson, Carsten; Nuber, Ulrike A

    2009-06-01

    The prediction of transcription factor binding sites in genomic sequences is in principle very useful to identify upstream regulatory factors. However, when applying this concept to genomes of multicellular organisms such as mammals, one has to deal with a large number of false positive predictions since many transcription factor genes are only expressed in specific tissues or cell types. We developed TS-REX, a database/software system that supports the analysis of tissue and cell type-specific transcription factor-gene networks based on expressed sequence tag abundance of transcription factor-encoding genes in UniGene EST libraries. The use of expression levels of transcription factor-encoding genes according to hierarchical anatomical classifications covering different tissues and cell types makes it possible to filter out irrelevant binding site predictions and to identify candidates of potential functional importance for further experimental testing. TS-REX covers ESTs from H. sapiens and M. musculus, and allows the characterization of both presence and specificity of transcription factors in user-specified tissues or cell types. The software allows users to interactively visualize transcription factor-gene networks, as well as to export data for further processing. TS-REX was applied to predict regulators of Polycomb group genes in six human tumor tissues and in human embryonic stem cells. PMID:19443447

  2. Fast and Provably Accurate Bilateral Filtering.

    Chaudhury, Kunal N; Dabhade, Swapnil D

    2016-06-01

    The bilateral filter is a non-linear filter that uses a range filter along with a spatial filter to perform edge-preserving smoothing of images. A direct computation of the bilateral filter requires O(S) operations per pixel, where S is the size of the support of the spatial filter. In this paper, we present a fast and provably accurate algorithm for approximating the bilateral filter when the range kernel is Gaussian. In particular, for box and Gaussian spatial filters, the proposed algorithm can cut down the complexity to O(1) per pixel for any arbitrary S . The algorithm has a simple implementation involving N+1 spatial filterings, where N is the approximation order. We give a detailed analysis of the filtering accuracy that can be achieved by the proposed approximation in relation to the target bilateral filter. This allows us to estimate the order N required to obtain a given accuracy. We also present comprehensive numerical results to demonstrate that the proposed algorithm is competitive with the state-of-the-art methods in terms of speed and accuracy. PMID:27093722

  3. Accurate fission data for nuclear safety

    Solders, A; Jokinen, A; Kolhinen, V S; Lantz, M; Mattera, A; Penttila, H; Pomp, S; Rakopoulos, V; Rinta-Antila, S

    2013-01-01

    The Accurate fission data for nuclear safety (AlFONS) project aims at high precision measurements of fission yields, using the renewed IGISOL mass separator facility in combination with a new high current light ion cyclotron at the University of Jyvaskyla. The 30 MeV proton beam will be used to create fast and thermal neutron spectra for the study of neutron induced fission yields. Thanks to a series of mass separating elements, culminating with the JYFLTRAP Penning trap, it is possible to achieve a mass resolving power in the order of a few hundred thousands. In this paper we present the experimental setup and the design of a neutron converter target for IGISOL. The goal is to have a flexible design. For studies of exotic nuclei far from stability a high neutron flux (10^12 neutrons/s) at energies 1 - 30 MeV is desired while for reactor applications neutron spectra that resembles those of thermal and fast nuclear reactors are preferred. It is also desirable to be able to produce (semi-)monoenergetic neutrons...

  4. Urolithiasis: how accurate are plain radiographs?

    Chan, V.O.; Buckley, O.; Persaud, T.; Torreggiani, W.C. [Dept. of Radiology, The Adelaide and Meath Hospital, Tallaght, Dublin (Ireland)], E-mail: William.Torreggiani@amnch.ie

    2008-06-15

    To determine the value of the kidneys, ureters, and bladder radiograph (KUB) in the diagnosis of urolithiasis using unenhanced helical computerized tomography (UHCT) as the gold standard. A retrospective study was performed on 100 consecutive patients being investigated for suspected urolithiasis. All patients presented with acute renal colic and had a KUB and UHCT within a 3-hour period. UHCT and KUB pairs were assessed separately by 2 radiologists in consensus who were blinded to the clinical details of the patients and the results of the other tests and examinations. The presence, location, number, and size of stones were recorded. Each UHCT and KUB pair was then compared for concordance on a stone-by-stone basis. KUB was concordant with the gold standard UHCT in only 50% of patients (11 positive, 39 negative), giving a sensitivity of 18.6%, a specificity of 95.1%, a positive predictive value of 84.6%, and a negative predictive value of 44.8%. KUB has a very low sensitivity for the detection of urolithiasis, although specificity is acceptable. (author)

  5. Urolithiasis: how accurate are plain radiographs?

    To determine the value of the kidneys, ureters, and bladder radiograph (KUB) in the diagnosis of urolithiasis using unenhanced helical computerized tomography (UHCT) as the gold standard. A retrospective study was performed on 100 consecutive patients being investigated for suspected urolithiasis. All patients presented with acute renal colic and had a KUB and UHCT within a 3-hour period. UHCT and KUB pairs were assessed separately by 2 radiologists in consensus who were blinded to the clinical details of the patients and the results of the other tests and examinations. The presence, location, number, and size of stones were recorded. Each UHCT and KUB pair was then compared for concordance on a stone-by-stone basis. KUB was concordant with the gold standard UHCT in only 50% of patients (11 positive, 39 negative), giving a sensitivity of 18.6%, a specificity of 95.1%, a positive predictive value of 84.6%, and a negative predictive value of 44.8%. KUB has a very low sensitivity for the detection of urolithiasis, although specificity is acceptable. (author)

  6. ACCURATE FORECAST AS AN EFFECTIVE WAY TO REDUCE THE ECONOMIC RISK OF AGRO-INDUSTRIAL COMPLEX

    Kymratova A. M.

    2014-11-01

    Full Text Available This article discusses the ways of reducing the financial, economic and social risks on the basis of an accurate prediction. We study the importance of natural time series of winter wheat yield, minimum winter, winter-spring daily temperatures. The feature of the time series of this class is disobeying a normal distribution, there is no visible trend

  7. Towards a more accurate concept of fuels

    Full text: The introduction of LEU in Atucha and the approval of CARA show an advancement of the Argentine power stations fuels, which stimulate and show a direction to follow. In the first case, the use of enriched U fuel relax an important restriction related to neutronic economy; that means that it is possible to design less penalized fuels using more Zry. The second case allows a decrease in the lineal power of the rods, enabling a better performance of the fuel in normal and also in accident conditions. In this work we wish to emphasize this last point, trying to find a design in which the surface power of the rod is diminished. Hence, in accident conditions owing to lack of coolant, the cladding tube will not reach temperatures that will produce oxidation, with the corresponding H2 formation and with plasticity enough to form blisters, which will obstruct the reflooding and hydration that will produce fragility and rupture of the cladding tube, with the corresponding radioactive material dispersion. This work is oriented to find rods designs with quasi rectangular geometry to lower the surface power of the rods, in order to obtain a lower central temperature of the rod. Thus, critical temperatures will not be reached in case of lack of coolant. This design is becoming a reality after PPFAE's efforts in search of cladding tubes fabrication with different circumferential values, rectangular in particular. This geometry, with an appropriate pellet design, can minimize the pellet-cladding interaction and, through the accurate width election, non rectified pellets could be used. This means an important economy in pellets production, as well as an advance in the fabrication of fuels in gloves box and hot cells in the future. The sequence to determine critical geometrical parameters is described and some rod dispositions are explored

  8. Accurate orbit propagation with planetary close encounters

    Baù, Giulio; Milani Comparetti, Andrea; Guerra, Francesca

    2015-08-01

    We tackle the problem of accurately propagating the motion of those small bodies that undergo close approaches with a planet. The literature is lacking on this topic and the reliability of the numerical results is not sufficiently discussed. The high-frequency components of the perturbation generated by a close encounter makes the propagation particularly challenging both from the point of view of the dynamical stability of the formulation and the numerical stability of the integrator. In our approach a fixed step-size and order multistep integrator is combined with a regularized formulation of the perturbed two-body problem. When the propagated object enters the region of influence of a celestial body, the latter becomes the new primary body of attraction. Moreover, the formulation and the step-size will also be changed if necessary. We present: 1) the restarter procedure applied to the multistep integrator whenever the primary body is changed; 2) new analytical formulae for setting the step-size (given the order of the multistep, formulation and initial osculating orbit) in order to control the accumulation of the local truncation error and guarantee the numerical stability during the propagation; 3) a new definition of the region of influence in the phase space. We test the propagator with some real asteroids subject to the gravitational attraction of the planets, the Yarkovsky and relativistic perturbations. Our goal is to show that the proposed approach improves the performance of both the propagator implemented in the OrbFit software package (which is currently used by the NEODyS service) and of the propagator represented by a variable step-size and order multistep method combined with Cowell's formulation (i.e. direct integration of position and velocity in either the physical or a fictitious time).

  9. Accurate paleointensities - the multi-method approach

    de Groot, Lennart

    2016-04-01

    The accuracy of models describing rapid changes in the geomagnetic field over the past millennia critically depends on the availability of reliable paleointensity estimates. Over the past decade methods to derive paleointensities from lavas (the only recorder of the geomagnetic field that is available all over the globe and through geologic times) have seen significant improvements and various alternative techniques were proposed. The 'classical' Thellier-style approach was optimized and selection criteria were defined in the 'Standard Paleointensity Definitions' (Paterson et al, 2014). The Multispecimen approach was validated and the importance of additional tests and criteria to assess Multispecimen results must be emphasized. Recently, a non-heating, relative paleointensity technique was proposed -the pseudo-Thellier protocol- which shows great potential in both accuracy and efficiency, but currently lacks a solid theoretical underpinning. Here I present work using all three of the aforementioned paleointensity methods on suites of young lavas taken from the volcanic islands of Hawaii, La Palma, Gran Canaria, Tenerife, and Terceira. Many of the sampled cooling units are <100 years old, the actual field strength at the time of cooling is therefore reasonably well known. Rather intuitively, flows that produce coherent results from two or more different paleointensity methods yield the most accurate estimates of the paleofield. Furthermore, the results for some flows pass the selection criteria for one method, but fail in other techniques. Scrutinizing and combing all acceptable results yielded reliable paleointensity estimates for 60-70% of all sampled cooling units - an exceptionally high success rate. This 'multi-method paleointensity approach' therefore has high potential to provide the much-needed paleointensities to improve geomagnetic field models for the Holocene.

  10. Towards Accurate Application Characterization for Exascale (APEX)

    Hammond, Simon David [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States)

    2015-09-01

    Sandia National Laboratories has been engaged in hardware and software codesign activities for a number of years, indeed, it might be argued that prototyping of clusters as far back as the CPLANT machines and many large capability resources including ASCI Red and RedStorm were examples of codesigned solutions. As the research supporting our codesign activities has moved closer to investigating on-node runtime behavior a nature hunger has grown for detailed analysis of both hardware and algorithm performance from the perspective of low-level operations. The Application Characterization for Exascale (APEX) LDRD was a project concieved of addressing some of these concerns. Primarily the research was to intended to focus on generating accurate and reproducible low-level performance metrics using tools that could scale to production-class code bases. Along side this research was an advocacy and analysis role associated with evaluating tools for production use, working with leading industry vendors to develop and refine solutions required by our code teams and to directly engage with production code developers to form a context for the application analysis and a bridge to the research community within Sandia. On each of these accounts significant progress has been made, particularly, as this report will cover, in the low-level analysis of operations for important classes of algorithms. This report summarizes the development of a collection of tools under the APEX research program and leaves to other SAND and L2 milestone reports the description of codesign progress with Sandia’s production users/developers.

  11. Accurate hydrocarbon estimates attained with radioactive isotope

    To make accurate economic evaluations of new discoveries, an oil company needs to know how much gas and oil a reservoir contains. The porous rocks of these reservoirs are not completely filled with gas or oil, but contain a mixture of gas, oil and water. It is extremely important to know what volume percentage of this water--called connate water--is contained in the reservoir rock. The percentage of connate water can be calculated from electrical resistivity measurements made downhole. The accuracy of this method can be improved if a pure sample of connate water can be analyzed or if the chemistry of the water can be determined by conventional logging methods. Because of the similarity of the mud filtrate--the water in a water-based drilling fluid--and the connate water, this is not always possible. If the oil company cannot distinguish between connate water and mud filtrate, its oil-in-place calculations could be incorrect by ten percent or more. It is clear that unless an oil company can be sure that a sample of connate water is pure, or at the very least knows exactly how much mud filtrate it contains, its assessment of the reservoir's water content--and consequently its oil or gas content--will be distorted. The oil companies have opted for the Repeat Formation Tester (RFT) method. Label the drilling fluid with small doses of tritium--a radioactive isotope of hydrogen--and it will be easy to detect and quantify in the sample

  12. Fast, accurate standardless XRF analysis with IQ+

    Full text: Due to both chemical and physical effects, the most accurate XRF data are derived from calibrations set up using in-type standards, necessitating some prior knowledge of the samples being analysed. Whilst this is often the case for routine samples, particularly in production control, for completely unknown samples the identification and availability of in-type standards can be problematic. Under these circumstances standardless analysis can offer a viable solution. Successful analysis of completely unknown samples requires a complete chemical overview of the speciemen together with the flexibility of a fundamental parameters (FP) algorithm to handle wide-ranging compositions. Although FP algorithms are improving all the time, most still require set-up samples to define the spectrometer response to a particular element. Whilst such materials may be referred to as standards, the emphasis in this kind of analysis is that only a single calibration point is required per element and that the standard chosen does not have to be in-type. The high sensitivities of modern XRF spectrometers, together with recent developments in detector counting electronics that possess a large dynamic range and high-speed data processing capacity bring significant advances to fast, standardless analysis. Illustrated with a tantalite-columbite heavy-mineral concentrate grading use-case, this paper will present the philosophy behind the semi-quantitative IQ+ software and the required hardware. This combination can give a rapid scan-based overview and quantification of the sample in less than two minutes, together with the ability to define channels for specific elements of interest where higher accuracy and lower levels of quantification are required. The accuracy, precision and limitations of standardless analysis will be assessed using certified reference materials of widely differing chemical and physical composition. Copyright (2002) Australian X-ray Analytical Association Inc

  13. Data cache organization for accurate timing analysis

    Schoeberl, Martin; Huber, Benedikt; Puffitsch, Wolfgang

    2013-01-01

    Caches are essential to bridge the gap between the high latency main memory and the fast processor pipeline. Standard processor architectures implement two first-level caches to avoid a structural hazard in the pipeline: an instruction cache and a data cache. For tight worst-case execution times...... it is important to classify memory accesses as either cache hit or cache miss. The addresses of instruction fetches are known statically and static cache hit/miss classification is possible for the instruction cache. The access to data that is cached in the data cache is harder to predict statically. Several...... different data areas, such as stack, global data, and heap allocated data, share the same cache. Some addresses are known statically, other addresses are only known at runtime. With a standard cache organization all those different data areas must be considered by worst-case execution time analysis...

  14. Accurate thermodynamic characterization of a synthetic coal mine methane mixture

    Highlights: • Accurate density data of a 10 components synthetic coal mine methane mixture are presented. • Experimental data are compared with the densities calculated from the GERG-2008 equation of state. • Relative deviations in density were within a 0.2% band at temperatures above 275 K. • Densities at 250 K as well as at 275 K and pressures above 10 MPa showed higher deviations. -- Abstract: In the last few years, coal mine methane (CMM) has gained significance as a potential non-conventional gas fuel. The progressive depletion of common fossil fuels reserves and, on the other hand, the positive estimates of CMM resources as a by-product of mining promote this fuel gas as a promising alternative fuel. The increasing importance of its exploitation makes it necessary to check the capability of the present-day models and equations of state for natural gas to predict the thermophysical properties of gases with a considerably different composition, like CMM. In this work, accurate density measurements of a synthetic CMM mixture are reported in the temperature range from (250 to 400) K and pressures up to 15 MPa, as part of the research project EMRP ENG01 of the European Metrology Research Program for the characterization of non-conventional energy gases. Experimental data were compared with the densities calculated with the GERG-2008 equation of state. Relative deviations between experimental and estimated densities were within a 0.2% band at temperatures above 275 K, while data at 250 K as well as at 275 K and pressures above 10 MPa showed higher deviations

  15. Accurate molecular classification of cancer using simple rules

    Gotoh Osamu

    2009-10-01

    Full Text Available Abstract Background One intractable problem with using microarray data analysis for cancer classification is how to reduce the extremely high-dimensionality gene feature data to remove the effects of noise. Feature selection is often used to address this problem by selecting informative genes from among thousands or tens of thousands of genes. However, most of the existing methods of microarray-based cancer classification utilize too many genes to achieve accurate classification, which often hampers the interpretability of the models. For a better understanding of the classification results, it is desirable to develop simpler rule-based models with as few marker genes as possible. Methods We screened a small number of informative single genes and gene pairs on the basis of their depended degrees proposed in rough sets. Applying the decision rules induced by the selected genes or gene pairs, we constructed cancer classifiers. We tested the efficacy of the classifiers by leave-one-out cross-validation (LOOCV of training sets and classification of independent test sets. Results We applied our methods to five cancerous gene expression datasets: leukemia (acute lymphoblastic leukemia [ALL] vs. acute myeloid leukemia [AML], lung cancer, prostate cancer, breast cancer, and leukemia (ALL vs. mixed-lineage leukemia [MLL] vs. AML. Accurate classification outcomes were obtained by utilizing just one or two genes. Some genes that correlated closely with the pathogenesis of relevant cancers were identified. In terms of both classification performance and algorithm simplicity, our approach outperformed or at least matched existing methods. Conclusion In cancerous gene expression datasets, a small number of genes, even one or two if selected correctly, is capable of achieving an ideal cancer classification effect. This finding also means that very simple rules may perform well for cancerous class prediction.

  16. Accurate state and parameter estimation in nonlinear systems with sparse observations

    Rey, Daniel; Eldridge, Michael; Kostuk, Mark [Department of Physics, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0374 (United States); Abarbanel, Henry D.I., E-mail: habarbanel@ucsd.edu [Department of Physics, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0374 (United States); Marine Physical Laboratory, Scripps Institution of Oceanography, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0374 (United States); Schumann-Bischoff, Jan [Max Planck Institute for Dynamics and Self-Organization, Am Faßberg 17, 37077 Göttingen (Germany); Institute for Nonlinear Dynamics, Georg-August-Universität Göttingen, Am Faßberg 17, 37077 Göttingen (Germany); Parlitz, Ulrich, E-mail: ulrich.parlitz@ds.mpg.de [Max Planck Institute for Dynamics and Self-Organization, Am Faßberg 17, 37077 Göttingen (Germany); Institute for Nonlinear Dynamics, Georg-August-Universität Göttingen, Am Faßberg 17, 37077 Göttingen (Germany)

    2014-02-01

    Transferring information from observations to models of complex systems may meet impediments when the number of observations at any observation time is not sufficient. This is especially so when chaotic behavior is expressed. We show how to use time-delay embedding, familiar from nonlinear dynamics, to provide the information required to obtain accurate state and parameter estimates. Good estimates of parameters and unobserved states are necessary for good predictions of the future state of a model system. This method may be critical in allowing the understanding of prediction in complex systems as varied as nervous systems and weather prediction where insufficient measurements are typical.

  17. Accurate Segmentation for Infrared Flying Bird Tracking

    ZHENG Hong; HUANG Ying; LING Haibin; ZOU Qi; YANG Hao

    2016-01-01

    Bird strikes present a huge risk for air ve-hicles, especially since traditional airport bird surveillance is mainly dependent on inefficient human observation. For improving the effectiveness and efficiency of bird monitor-ing, computer vision techniques have been proposed to detect birds, determine bird flying trajectories, and pre-dict aircraft takeoff delays. Flying bird with a huge de-formation causes a great challenge to current tracking al-gorithms. We propose a segmentation based approach to enable tracking can adapt to the varying shape of bird. The approach works by segmenting object at a region of inter-est, where is determined by the object localization method and heuristic edge information. The segmentation is per-formed by Markov random field, which is trained by fore-ground and background mixture Gaussian models. Exper-iments demonstrate that the proposed approach provides the ability to handle large deformations and outperforms the m ost state-of-the-art tracker in the infrared flying bird tracking problem.

  18. Accurate simulation of optical properties in dyes.

    Jacquemin, Denis; Perpète, Eric A; Ciofini, Ilaria; Adamo, Carlo

    2009-02-17

    Since Antiquity, humans have produced and commercialized dyes. To this day, extraction of natural dyes often requires lengthy and costly procedures. In the 19th century, global markets and new industrial products drove a significant effort to synthesize artificial dyes, characterized by low production costs, huge quantities, and new optical properties (colors). Dyes that encompass classes of molecules absorbing in the UV-visible part of the electromagnetic spectrum now have a wider range of applications, including coloring (textiles, food, paintings), energy production (photovoltaic cells, OLEDs), or pharmaceuticals (diagnostics, drugs). Parallel to the growth in dye applications, researchers have increased their efforts to design and synthesize new dyes to customize absorption and emission properties. In particular, dyes containing one or more metallic centers allow for the construction of fairly sophisticated systems capable of selectively reacting to light of a given wavelength and behaving as molecular devices (photochemical molecular devices, PMDs).Theoretical tools able to predict and interpret the excited-state properties of organic and inorganic dyes allow for an efficient screening of photochemical centers. In this Account, we report recent developments defining a quantitative ab initio protocol (based on time-dependent density functional theory) for modeling dye spectral properties. In particular, we discuss the importance of several parameters, such as the methods used for electronic structure calculations, solvent effects, and statistical treatments. In addition, we illustrate the performance of such simulation tools through case studies. We also comment on current weak points of these methods and ways to improve them. PMID:19113946

  19. Climate prediction and predictability

    Allen, Myles

    2010-05-01

    Climate prediction is generally accepted to be one of the grand challenges of the Geophysical Sciences. What is less widely acknowledged is that fundamental issues have yet to be resolved concerning the nature of the challenge, even after decades of research in this area. How do we verify or falsify a probabilistic forecast of a singular event such as anthropogenic warming over the 21st century? How do we determine the information content of a climate forecast? What does it mean for a modelling system to be "good enough" to forecast a particular variable? How will we know when models and forecasting systems are "good enough" to provide detailed forecasts of weather at specific locations or, for example, the risks associated with global geo-engineering schemes. This talk will provide an overview of these questions in the light of recent developments in multi-decade climate forecasting, drawing on concepts from information theory, machine learning and statistics. I will draw extensively but not exclusively from the experience of the climateprediction.net project, running multiple versions of climate models on personal computers.

  20. Accurate measurement of liquid transport through nanoscale conduits.

    Alibakhshi, Mohammad Amin; Xie, Quan; Li, Yinxiao; Duan, Chuanhua

    2016-01-01

    Nanoscale liquid transport governs the behaviour of a wide range of nanofluidic systems, yet remains poorly characterized and understood due to the enormous hydraulic resistance associated with the nanoconfinement and the resulting minuscule flow rates in such systems. To overcome this problem, here we present a new measurement technique based on capillary flow and a novel hybrid nanochannel design and use it to measure water transport through single 2-D hydrophilic silica nanochannels with heights down to 7 nm. Our results show that silica nanochannels exhibit increased mass flow resistance compared to the classical hydrodynamics prediction. This difference increases with decreasing channel height and reaches 45% in the case of 7 nm nanochannels. This resistance increase is attributed to the formation of a 7-angstrom-thick stagnant hydration layer on the hydrophilic surfaces. By avoiding use of any pressure and flow sensors or any theoretical estimations the hybrid nanochannel scheme enables facile and precise flow measurement through single nanochannels, nanotubes, or nanoporous media and opens the prospect for accurate characterization of both hydrophilic and hydrophobic nanofluidic systems. PMID:27112404