Sample records for variability improves expression

  1. Incorporation of gene-specific variability improves expression analysis using high-density DNA microarrays

    Directory of Open Access Journals (Sweden)

    Spitznagel Edward


    Full Text Available Abstract Background The assessment of data reproducibility is essential for application of microarray technology to exploration of biological pathways and disease states. Technical variability in data analysis largely depends on signal intensity. Within that context, the reproducibility of individual probe sets has not been hitherto addressed. Results We used an extraordinarily large replicate data set derived from human placental trophoblast to analyze probe-specific contribution to variability of gene expression. We found that signal variability, in addition to being signal-intensity dependant, is probe set-specific. Importantly, we developed a novel method to quantify the contribution of this probe set-specific variability. Furthermore, we devised a formula that incorporates a priori-computed, replicate-based information on probe set- and intensity-specific variability in determination of expression changes even without technical replicates. Conclusion The strategy of incorporating probe set-specific variability is superior to analysis based on arbitrary fold-change thresholds. We recommend its incorporation to any computation of gene expression changes using high-density DNA microarrays. A Java application implementing our T-score is available at

  2. Xeroderma Pigmentosum: Variable Expressions among Three Siblings

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    M Srinivasa Raju


    Full Text Available Xeroderma pigmentosum is a rare disorder transmitted in an autosomal recessive manner. It is characterized by photosensitivity, pigmentary changes, premature skin aging, and malignant tumor development. The frequency of this disorder is approximately 1 case per 250.000 population. Two important causes of mortality are metastatic malignant melanoma and squamous cell carcinoma. Here xeroderma pigmentosum in three siblings presenting with variable expressions is reported. The seventy of the condition was more in one of the more sun exposed sibling and had more signs of malignant lesions. Intraoral pigmentation was also present in all the three siblings.

  3. Genetic Variants Contribute to Gene Expression Variability in Humans (United States)

    Hulse, Amanda M.; Cai, James J.


    Expression quantitative trait loci (eQTL) studies have established convincing relationships between genetic variants and gene expression. Most of these studies focused on the mean of gene expression level, but not the variance of gene expression level (i.e., gene expression variability). In the present study, we systematically explore genome-wide association between genetic variants and gene expression variability in humans. We adapt the double generalized linear model (dglm) to simultaneously fit the means and the variances of gene expression among the three possible genotypes of a biallelic SNP. The genomic loci showing significant association between the variances of gene expression and the genotypes are termed expression variability QTL (evQTL). Using a data set of gene expression in lymphoblastoid cell lines (LCLs) derived from 210 HapMap individuals, we identify cis-acting evQTL involving 218 distinct genes, among which 8 genes, ADCY1, CTNNA2, DAAM2, FERMT2, IL6, PLOD2, SNX7, and TNFRSF11B, are cross-validated using an extra expression data set of the same LCLs. We also identify ∼300 trans-acting evQTL between >13,000 common SNPs and 500 randomly selected representative genes. We employ two distinct scenarios, emphasizing single-SNP and multiple-SNP effects on expression variability, to explain the formation of evQTL. We argue that detecting evQTL may represent a novel method for effectively screening for genetic interactions, especially when the multiple-SNP influence on expression variability is implied. The implication of our results for revealing genetic mechanisms of gene expression variability is discussed. PMID:23150607

  4. [Effects of situational and individual variables on critical thinking expression]. (United States)

    Tanaka, Yuko; Kusumi, Takashi


    The present study examined when people decide to choose an expression that is based on critical thinking, and how situational and individual variables affect such a decision process. Given a conversation scenario including overgeneralization with two friends, participants decided whether to follow the conversation by a critical-thinking expression or not. The authors controlled purpose and topic as situational variables, and measured critical-thinking ability, critical-thinking disposition, and self-monitoring as individual variables. We conducted an experiment in which the situational variables were counterbalanced in a within-subject design with 60 university students. The results of logistic regression analysis showed differences within individuals in the decision process whether to choose a critical-thinking expression, and that some situational factors and some subscales of the individual measurements were related to the differences.

  5. Capturing heterogeneity in gene expression studies by surrogate variable analysis.

    Directory of Open Access Journals (Sweden)

    Jeffrey T Leek


    Full Text Available It has unambiguously been shown that genetic, environmental, demographic, and technical factors may have substantial effects on gene expression levels. In addition to the measured variable(s of interest, there will tend to be sources of signal due to factors that are unknown, unmeasured, or too complicated to capture through simple models. We show that failing to incorporate these sources of heterogeneity into an analysis can have widespread and detrimental effects on the study. Not only can this reduce power or induce unwanted dependence across genes, but it can also introduce sources of spurious signal to many genes. This phenomenon is true even for well-designed, randomized studies. We introduce "surrogate variable analysis" (SVA to overcome the problems caused by heterogeneity in expression studies. SVA can be applied in conjunction with standard analysis techniques to accurately capture the relationship between expression and any modeled variables of interest. We apply SVA to disease class, time course, and genetics of gene expression studies. We show that SVA increases the biological accuracy and reproducibility of analyses in genome-wide expression studies.

  6. MicroRNA expression variability in human cervical tissues.

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    Patrícia M Pereira

    Full Text Available MicroRNAs (miRNAs are short (approximately 22 nt non-coding regulatory RNAs that control gene expression at the post-transcriptional level. Deregulation of miRNA expression has been discovered in a wide variety of tumours and it is now clear that they contribute to cancer development and progression. Cervical cancer is one of the most common cancers in women worldwide and there is a strong need for a non-invasive, fast and efficient method to diagnose the disease. We investigated miRNA expression profiles in cervical cancer using a microarray platform containing probes for mature miRNAs. We have evaluated miRNA expression profiles of a heterogeneous set of cervical tissues from 25 different patients. This set included 19 normal cervical tissues, 4 squamous cell carcinoma, 5 high-grade squamous intraepithelial lesion (HSIL and 9 low-grade squamous intraepithelial lesion (LSIL samples. We observed high variability in miRNA expression especially among normal cervical samples, which prevented us from obtaining a unique miRNA expression signature for this tumour type. However, deregulated miRNAs were identified in malignant and pre-malignant cervical tissues after tackling the high expression variability observed. We were also able to identify putative target genes of relevant candidate miRNAs. Our results show that miRNA expression shows natural variability among human samples, which complicates miRNA data profiling analysis. However, such expression noise can be filtered and does not prevent the identification of deregulated miRNAs that play a role in the malignant transformation of cervical squamous cells. Deregulated miRNAs highlight new candidate gene targets allowing for a better understanding of the molecular mechanism underlying the development of this tumour type.

  7. Quantifying intrinsic and extrinsic variability in stochastic gene expression models. (United States)

    Singh, Abhyudai; Soltani, Mohammad


    Genetically identical cell populations exhibit considerable intercellular variation in the level of a given protein or mRNA. Both intrinsic and extrinsic sources of noise drive this variability in gene expression. More specifically, extrinsic noise is the expression variability that arises from cell-to-cell differences in cell-specific factors such as enzyme levels, cell size and cell cycle stage. In contrast, intrinsic noise is the expression variability that is not accounted for by extrinsic noise, and typically arises from the inherent stochastic nature of biochemical processes. Two-color reporter experiments are employed to decompose expression variability into its intrinsic and extrinsic noise components. Analytical formulas for intrinsic and extrinsic noise are derived for a class of stochastic gene expression models, where variations in cell-specific factors cause fluctuations in model parameters, in particular, transcription and/or translation rate fluctuations. Assuming mRNA production occurs in random bursts, transcription rate is represented by either the burst frequency (how often the bursts occur) or the burst size (number of mRNAs produced in each burst). Our analysis shows that fluctuations in the transcription burst frequency enhance extrinsic noise but do not affect the intrinsic noise. On the contrary, fluctuations in the transcription burst size or mRNA translation rate dramatically increase both intrinsic and extrinsic noise components. Interestingly, simultaneous fluctuations in transcription and translation rates arising from randomness in ATP abundance can decrease intrinsic noise measured in a two-color reporter assay. Finally, we discuss how these formulas can be combined with single-cell gene expression data from two-color reporter experiments for estimating model parameters.

  8. Building prognostic models for breast cancer patients using clinical variables and hundreds of gene expression signatures

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    Liu Yufeng


    Full Text Available Abstract Background Multiple breast cancer gene expression profiles have been developed that appear to provide similar abilities to predict outcome and may outperform clinical-pathologic criteria; however, the extent to which seemingly disparate profiles provide additive prognostic information is not known, nor do we know whether prognostic profiles perform equally across clinically defined breast cancer subtypes. We evaluated whether combining the prognostic powers of standard breast cancer clinical variables with a large set of gene expression signatures could improve on our ability to predict patient outcomes. Methods Using clinical-pathological variables and a collection of 323 gene expression "modules", including 115 previously published signatures, we build multivariate Cox proportional hazards models using a dataset of 550 node-negative systemically untreated breast cancer patients. Models predictive of pathological complete response (pCR to neoadjuvant chemotherapy were also built using this approach. Results We identified statistically significant prognostic models for relapse-free survival (RFS at 7 years for the entire population, and for the subgroups of patients with ER-positive, or Luminal tumors. Furthermore, we found that combined models that included both clinical and genomic parameters improved prognostication compared with models with either clinical or genomic variables alone. Finally, we were able to build statistically significant combined models for pathological complete response (pCR predictions for the entire population. Conclusions Integration of gene expression signatures and clinical-pathological factors is an improved method over either variable type alone. Highly prognostic models could be created when using all patients, and for the subset of patients with lymph node-negative and ER-positive breast cancers. Other variables beyond gene expression and clinical-pathological variables, like gene mutation status or DNA

  9. Improving transition between power optimization and power limitation of variable speed/variable pitch wind turbines

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, A D; Bindner, H [Risoe National Lab., Wind Energy and Atmospheric Physics Dept., Roskilde (Denmark); Rebsdorf, A [Vestas Wind Systems A/S, Lem (Denmark)


    The paper summarises and describes the main results of a recently performed study of improving the transition between power optimization and power limitation for variable speed/variable pitch wind turbines. The results show that the capability of varying the generator speed also can be exploited in the transition stage to improve the quality of the generated power. (au)


    Manning, James M.; Popowicz, Anthony M.; Padovan, Julio C.; Chait, Brian T.; Manning, Lois R.


    SUMMARY The expression of the six types of human hemoglobin subunits over time is currently considered to be regulated mainly by transcription factors that bind to upstream control regions of the gene (the “extrinsic” component of regulation). Here we describe how subunit pairing and further assembly to tetramers in the liganded state is influenced by the affinity of subunits for one another (the “intrinsic” component of regulation). The adult hemoglobin dimers have the strongest subunit interfaces and the embryonic hemoglobins are the weakest with fetal hemoglobins of intermediate strength, corresponding to the temporal order of their expression. These variable subunit binding strengths and the attenuating effects of acetylation contribute to the differences with which these hemoglobin types form functional O2-binding tetramers consistent with gene switching. PMID:22129306

  11. Variable expression of molecular markers in juvenile nasopharyngeal angiofibroma. (United States)

    Mishra, A; Pandey, A; Mishra, S C


    Molecular categorisation may explain the wide variation in the clinical characteristics of juvenile nasopharyngeal angiofibroma. Variations in molecular markers in juvenile nasopharyngeal angiofibroma in an Indian population were investigated and compared with global reports. Variable molecular marker expression was demonstrated at the regional and global levels. A wide variation in molecular characteristics is evident. Molecular data have been reported for only 11 countries, indicating a clear geographical bias. Only 58 markers have been studied, and most are yet to be validated. Research into the molecular epidemiology of juvenile nasopharyngeal angiofibroma is still in its infancy. Although the molecular variation is not well understood, data obtained so far have prompted important research questions. Hence, multicentre collaborative molecular studies are needed to establish the aetiopathogenesis and establish molecular surrogates for clinical characteristics.

  12. Variability in personality expression across contexts: a social network approach. (United States)

    Clifton, Allan


    The current research investigated how the contextual expression of personality differs across interpersonal relationships. Two related studies were conducted with college samples (Study 1: N = 52, 38 female; Study 2: N = 111, 72 female). Participants in each study completed a five-factor measure of personality and constructed a social network detailing their 30 most important relationships. Participants used a brief Five-Factor Model scale to rate their personality as they experience it when with each person in their social network. Multiple informants selected from each social network then rated the target participant's personality (Study 1: N = 227, Study 2: N = 777). Contextual personality ratings demonstrated incremental validity beyond standard global self-report in predicting specific informants' perceptions. Variability in these contextualized personality ratings was predicted by the position of the other individuals within the social network. Across both studies, participants reported being more extraverted and neurotic, and less conscientious, with more central members of their social networks. Dyadic social network-based assessments of personality provide incremental validity in understanding personality, revealing dynamic patterns of personality variability unobservable with standard assessment techniques. © 2013 Wiley Periodicals, Inc.


    Directory of Open Access Journals (Sweden)

    B.P. Mahesh


    Full Text Available Quality has become one of the most important customer decision factors in the selection among the competing product and services. Consequently, understanding and improving quality is a key factor leading to business success, growth and an enhanced competitive position. Hence quality improvement program should be an integral part of the overall business strategy. According to TQM, the effective way to improve the Quality of the product or service is to improve the process used to build the product. Hence, TQM focuses on process, rather than results as the results are driven by the processes. Many techniques are available for quality improvement. Statistical Process Control (SPC is one such TQM technique which is widely accepted for analyzing quality problems and improving the performance of the production process. This article illustrates the step by step procedure adopted at a soap manufacturing company to improve the Quality by reducing process variability using Statistical Process Control.

  14. Gene expression variability in human hepatic drug metabolizing enzymes and transporters.

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    Lun Yang

    Full Text Available Interindividual variability in the expression of drug-metabolizing enzymes and transporters (DMETs in human liver may contribute to interindividual differences in drug efficacy and adverse reactions. Published studies that analyzed variability in the expression of DMET genes were limited by sample sizes and the number of genes profiled. We systematically analyzed the expression of 374 DMETs from a microarray data set consisting of gene expression profiles derived from 427 human liver samples. The standard deviation of interindividual expression for DMET genes was much higher than that for non-DMET genes. The 20 DMET genes with the largest variability in the expression provided examples of the interindividual variation. Gene expression data were also analyzed using network analysis methods, which delineates the similarities of biological functionalities and regulation mechanisms for these highly variable DMET genes. Expression variability of human hepatic DMET genes may affect drug-gene interactions and disease susceptibility, with concomitant clinical implications.

  15. Facial expression recognition based on improved deep belief networks (United States)

    Wu, Yao; Qiu, Weigen


    In order to improve the robustness of facial expression recognition, a method of face expression recognition based on Local Binary Pattern (LBP) combined with improved deep belief networks (DBNs) is proposed. This method uses LBP to extract the feature, and then uses the improved deep belief networks as the detector and classifier to extract the LBP feature. The combination of LBP and improved deep belief networks is realized in facial expression recognition. In the JAFFE (Japanese Female Facial Expression) database on the recognition rate has improved significantly.

  16. Dynamic Vehicle Routing Using an Improved Variable Neighborhood Search Algorithm

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    Yingcheng Xu


    Full Text Available In order to effectively solve the dynamic vehicle routing problem with time windows, the mathematical model is established and an improved variable neighborhood search algorithm is proposed. In the algorithm, allocation customers and planning routes for the initial solution are completed by the clustering method. Hybrid operators of insert and exchange are used to achieve the shaking process, the later optimization process is presented to improve the solution space, and the best-improvement strategy is adopted, which make the algorithm can achieve a better balance in the solution quality and running time. The idea of simulated annealing is introduced to take control of the acceptance of new solutions, and the influences of arrival time, distribution of geographical location, and time window range on route selection are analyzed. In the experiment, the proposed algorithm is applied to solve the different sizes' problems of DVRP. Comparing to other algorithms on the results shows that the algorithm is effective and feasible.

  17. Improving Expression Power in Modeling OLAP Hierarchies (United States)

    Malinowski, Elzbieta

    Data warehouses and OLAP systems form an integral part of modern decision support systems. In order to exploit both systems to their full capabilities hierarchies must be clearly defined. Hierarchies are important in analytical applications, since they provide users with the possibility to represent data at different abstraction levels. However, even though there are different kinds of hierarchies in real-world applications and some are already implemented in commercial tools, there is still a lack of a well-accepted conceptual model that allows decision-making users express their analysis needs. In this paper, we show how the conceptual multidimensional model can be used to facilitate the representation of complex hierarchies in comparison to their representation in the relational model and commercial OLAP tool, using as an example Microsoft Analysis Services.

  18. Model for expressing leaf photosynthesis in terms of weather variables

    African Journals Online (AJOL)

    A theoretical mathematical model for describing photosynthesis in individual leaves in terms of weather variables is proposed. The model utilizes a series of efficiency parameters, each of which reflect the fraction of potential photosynthetic rate permitted by the different environmental elements. These parameters are useful ...

  19. Can biomechanical variables predict improvement in crouch gait? (United States)

    Hicks, Jennifer L.; Delp, Scott L.; Schwartz, Michael H.


    Many patients respond positively to treatments for crouch gait, yet surgical outcomes are inconsistent and unpredictable. In this study, we developed a multivariable regression model to determine if biomechanical variables and other subject characteristics measured during a physical exam and gait analysis can predict which subjects with crouch gait will demonstrate improved knee kinematics on a follow-up gait analysis. We formulated the model and tested its performance by retrospectively analyzing 353 limbs of subjects who walked with crouch gait. The regression model was able to predict which subjects would demonstrate ‘improved’ and ‘unimproved’ knee kinematics with over 70% accuracy, and was able to explain approximately 49% of the variance in subjects’ change in knee flexion between gait analyses. We found that improvement in stance phase knee flexion was positively associated with three variables that were drawn from knowledge about the biomechanical contributors to crouch gait: i) adequate hamstrings lengths and velocities, possibly achieved via hamstrings lengthening surgery, ii) normal tibial torsion, possibly achieved via tibial derotation osteotomy, and iii) sufficient muscle strength. PMID:21616666

  20. Molecular characterization, tissue expression and sequence variability of the barramundi (Lates calcarifer myostatin gene

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    Smith-Keune Carolyn


    Full Text Available Abstract Background Myostatin (MSTN is a member of the transforming growth factor-β superfamily that negatively regulates growth of skeletal muscle tissue. The gene encoding for the MSTN peptide is a consolidate candidate for the enhancement of productivity in terrestrial livestock. This gene potentially represents an important target for growth improvement of cultured finfish. Results Here we report molecular characterization, tissue expression and sequence variability of the barramundi (Lates calcarifer MSTN-1 gene. The barramundi MSTN-1 was encoded by three exons 379, 371 and 381 bp in length and translated into a 376-amino acid peptide. Intron 1 and 2 were 412 and 819 bp in length and presented typical GT...AG splicing sites. The upstream region contained cis-regulatory elements such as TATA-box and E-boxes. A first assessment of sequence variability suggested that higher mutation rates are found in the 5' flanking region with several SNP's present in this species. A putative micro RNA target site has also been observed in the 3'UTR (untranslated region and is highly conserved across teleost fish. The deduced amino acid sequence was conserved across vertebrates and exhibited characteristic conserved putative functional residues including a cleavage motif of proteolysis (RXXR, nine cysteines and two glycosilation sites. A qualitative analysis of the barramundi MSTN-1 expression pattern revealed that, in adult fish, transcripts are differentially expressed in various tissues other than skeletal muscles including gill, heart, kidney, intestine, liver, spleen, eye, gonad and brain. Conclusion Our findings provide valuable insights such as sequence variation and genomic information which will aid the further investigation of the barramundi MSTN-1 gene in association with growth. The finding for the first time in finfish MSTN of a miRNA target site in the 3'UTR provides an opportunity for the identification of regulatory mutations on the

  1. An improved Lobatto discrete variable representation by a phase optimisation and variable mapping method

    International Nuclear Information System (INIS)

    Yu, Dequan; Cong, Shu-Lin; Sun, Zhigang


    Highlights: • An optimised finite element discrete variable representation method is proposed. • The method is tested by solving one and two dimensional Schrödinger equations. • The method is quite efficient in solving the molecular Schrödinger equation. • It is very easy to generalise the method to multidimensional problems. - Abstract: The Lobatto discrete variable representation (LDVR) proposed by Manoloupolos and Wyatt (1988) has unique features but has not been generally applied in the field of chemical dynamics. Instead, it has popular application in solving atomic physics problems, in combining with the finite element method (FE-DVR), due to its inherent abilities for treating the Coulomb singularity in spherical coordinates. In this work, an efficient phase optimisation and variable mapping procedure is proposed to improve the grid efficiency of the LDVR/FE-DVR method, which makes it not only be competing with the popular DVR methods, such as the Sinc-DVR, but also keep its advantages for treating with the Coulomb singularity. The method is illustrated by calculations for one-dimensional Coulomb potential, and the vibrational states of one-dimensional Morse potential, two-dimensional Morse potential and two-dimensional Henon–Heiles potential, which prove the efficiency of the proposed scheme and promise more general applications of the LDVR/FE-DVR method

  2. An improved Lobatto discrete variable representation by a phase optimisation and variable mapping method

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Dequan [School of Physics and Optoelectronic Technology, Dalian University of Technology, Dalian 116024 (China); State Key Laboratory of Molecular Reaction Dynamics and Center for Theoretical and Computational Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Science, Dalian 116023 (China); Cong, Shu-Lin, E-mail: [School of Physics and Optoelectronic Technology, Dalian University of Technology, Dalian 116024 (China); Sun, Zhigang, E-mail: [State Key Laboratory of Molecular Reaction Dynamics and Center for Theoretical and Computational Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Science, Dalian 116023 (China); Center for Advanced Chemical Physics and 2011 Frontier Center for Quantum Science and Technology, University of Science and Technology of China, 96 Jinzhai Road, Hefei 230026 (China)


    Highlights: • An optimised finite element discrete variable representation method is proposed. • The method is tested by solving one and two dimensional Schrödinger equations. • The method is quite efficient in solving the molecular Schrödinger equation. • It is very easy to generalise the method to multidimensional problems. - Abstract: The Lobatto discrete variable representation (LDVR) proposed by Manoloupolos and Wyatt (1988) has unique features but has not been generally applied in the field of chemical dynamics. Instead, it has popular application in solving atomic physics problems, in combining with the finite element method (FE-DVR), due to its inherent abilities for treating the Coulomb singularity in spherical coordinates. In this work, an efficient phase optimisation and variable mapping procedure is proposed to improve the grid efficiency of the LDVR/FE-DVR method, which makes it not only be competing with the popular DVR methods, such as the Sinc-DVR, but also keep its advantages for treating with the Coulomb singularity. The method is illustrated by calculations for one-dimensional Coulomb potential, and the vibrational states of one-dimensional Morse potential, two-dimensional Morse potential and two-dimensional Henon–Heiles potential, which prove the efficiency of the proposed scheme and promise more general applications of the LDVR/FE-DVR method.

  3. Heart rate variability biofeedback improves cardiorespiratory resting function during sleep. (United States)

    Sakakibara, Masahito; Hayano, Junichiro; Oikawa, Leo O; Katsamanis, Maria; Lehrer, Paul


    The present study was designed to examine the effect of heart rate variability (HRV) biofeedback on the cardiorespiratory resting function during sleep in daily life. Forty-five healthy young adults were randomly assigned to one of three groups: HRV biofeedback, Autogenic Training(AT), and no-treatment control. Participants in the HRV biofeedback were instructed to use a handheld HRV biofeedback device before their habitual bedtime, those in the AT were asked to listen to an audiotaped instruction before bedtime,and those in the control were asked to engage in their habitual activity before bedtime. Pulse wave signal during sleep at their own residences was measured continuously with a wrist watch-type transdermal photoelectric sensor for three time points. Baseline data were collected on the first night of measurements, followed by two successive nights for HRV biofeedback, AT, or control. Cardiorespiratory resting function was assessed quantitatively as the amplitude of high frequency(HF) component of pulse rate variability, a surrogate measure of respiratory sinus arrhythmia. HF component increased during sleep in the HRV biofeedback group,although it remained unchanged in the AT and control groups. These results suggest that HRV biofeedback before sleep may improve cardiorespiratory resting function during sleep.

  4. [TSA improve transgenic porcine cloned embryo development and transgene expression]. (United States)

    Kong, Qing-Ran; Zhu, Jiang; Huang, Bo; Huan, Yan-Jun; Wang, Feng; Shi, Yong-Qian; Liu, Zhong-Feng; Wu, Mei-Ling; Liu, Zhong-Hua


    Uncompleted epigenetic reprogramming is attributed to the low efficiency of producing transgenic cloned animals. Histone modification associated with epigenetics can directly influence the embryo development and transgene expression. Trichostatin A (TSA), as an inhibitor of histone deacetylase, can change the status of histone acetylation, improve somatic cell reprogramming, and enhance cloning efficiency. TSA prevents the chromatin structure from being condensed, so that transcription factor could binds to DNA sequence easily and enhance transgene expression. Our study established the optimal TSA treatment on porcine donor cells and cloned embryos, 250 nmol/L, 24 h and 40 nmol/L, 24 h, respectively. Furthermore, we found that both the cloned embryo and the donor cell treated by TSA resulted in the highest development efficiency. Meanwhile, TSA can improve transgene expression in donor cell and cloned embryo. In summary, TSA can significantly improve porcine reconstructed embryo development and transgene expression.

  5. Exercise training improves heart rate variability after methamphetamine dependency. (United States)

    Dolezal, Brett Andrew; Chudzynski, Joy; Dickerson, Daniel; Mooney, Larissa; Rawson, Richard A; Garfinkel, Alan; Cooper, Christopher B


    Heart rate variability (HRV) reflects a healthy autonomic nervous system and is increased with physical training. Methamphetamine dependence (MD) causes autonomic dysfunction and diminished HRV. We compared recently abstinent methamphetamine-dependent participants with age-matched, drug-free controls (DF) and also investigated whether HRV can be improved with exercise training in the methamphetamine-dependent participants. In 50 participants (MD = 28; DF = 22), resting heart rate (HR; R-R intervals) was recorded over 5 min while seated using a monitor affixed to a chest strap. Previously reported time domain (SDNN, RMSSD, pNN50) and frequency domain (LFnu, HFnu, LF/HF) parameters of HRV were calculated with customized software. MD were randomized to thrice-weekly exercise training (ME = 14) or equal attention without training (MC = 14) over 8 wk. Groups were compared using paired and unpaired t-tests. Statistical significance was set at P ≤ 0.05. Participant characteristics were matched between groups (mean ± SD): age = 33 ± 6 yr; body mass = 82.7 ± 12 kg, body mass index = 26.8 ± 4.1 kg·min. Compared with DF, the MD group had significantly higher resting HR (P HRV indices were similar between ME and MC groups. However, after training, the ME group significantly (all P HRV, based on several conventional indices, was diminished in recently abstinent, methamphetamine-dependent individuals. Moreover, physical training yielded a marked increase in HRV, representing increased vagal modulation or improved autonomic balance.

  6. Correlation of mRNA Expression and Signal Variability in Chronic Intracortical Electrodes. (United States)

    Falcone, Jessica D; Carroll, Sheridan L; Saxena, Tarun; Mandavia, Dev; Clark, Alexus; Yarabarla, Varun; Bellamkonda, Ravi V


    The goal for this research was to identify molecular mechanisms that explain animal-to-animal variability in chronic intracortical recordings. Microwire electrodes were implanted into Sprague Dawley rats at an acute (1 week) and a chronic (14 weeks) time point. Weekly recordings were conducted, and action potentials were evoked in the barrel cortex by deflecting the rat's whiskers. At 1 and 14 weeks, tissue was collected, and mRNA was extracted. mRNA expression was compared between 1 and 14 weeks using a high throughput multiplexed qRT-PCR. Pearson correlation coefficients were calculated between mRNA expression and signal-to-noise ratios at 14 weeks. At 14 weeks, a positive correlation between signal-to-noise ratio (SNR) and NeuN and GFAP mRNA expression was observed, indicating a relationship between recording strength and neuronal population, as well as reactive astrocyte activity. The inflammatory state around the electrode interface was evaluated using M1-like and M2-like markers. Expression for both M1-like and M2-like mRNA markers remained steady from 1 to 14 weeks. Anti-inflammatory markers, CD206 and CD163, however, demonstrated a significant positive correlation with SNR quality at 14 weeks. VE-cadherin, a marker for adherens junctions, and PDGFR-β, a marker for pericytes, both partial representatives of blood-brain barrier health, had a positive correlation with SNR at 14 weeks. Endothelial adhesion markers revealed a significant increase in expression at 14 weeks, while CD45, a pan-leukocyte marker, significantly decreased at 14 weeks. No significant correlation was found for either the endothelial adhesion or pan-leukocyte markers. A positive correlation between anti-inflammatory and blood-brain barrier health mRNA markers with electrophysiological efficacy of implanted intracortical electrodes has been demonstrated. These data reveal potential mechanisms for further evaluation to determine potential target mechanisms to improve

  7. Expression and production of llama variable heavy-chain antibody fragments (VHHs) by Aspergillus awamori

    NARCIS (Netherlands)

    Joosten, V.; Gouka, R.J.; Hondel, C.A.M.J.J. van den; Verrips, C.T.; Lokman, B.C.


    We report the expression and production of llama variable heavy-chain antibody fragments (VHHs) by Aspergillus awamori. Fragments encoding VHHs were cloned in a suitable Aspergillus expression vector and transformants secreting VHH fragments were analysed for integrated gene copy-numbers, mRNA

  8. Variable geometry turbocharging for lower emissions and improved torque characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Hawley, J.G.; Wallace, F.J.; Cox, A. [Bath Univ., Dept. of Mechanical Engineering, Bath (United Kingdom); Horrocks, R.W.; Bird, G.L. [Ford Motor Company Ltd., Engineering Centre for Advanced Vehicle Technology (Diesels), Dunton (United Kingdom)


    Currently, 80 per cent of european diesel passenger cars are turbocharged and, as emission standards become more stringent, this figure is expected to approach 100 per cent in the near future. One major focus that has emerged of the high-speed diesel engine is the application of variable geometry turbocharging (VGT). An extensive steady state experimental investigation has been undertaken on a prototype 1.8 L direct injection (DI) diesel engine to compare the potential benefits of VGT relative to the standard build of the engine with a wastegated fixed geometry turbocharger (FGT). Under part load operation, where emission production is significant in the European drive cycle, independent control of both VCT vane position and exhaust gas recirculation (EGR) value position was used to optimise emission levels. A reduction in the levels of nitrogen oxides (NO{sub x}) of up to 45 per cent was observed at discrete operating points without compromising FGT levels of fuel consumption or smoke. Under limiting torque conditions a 10 per cent improvement was achieved with the VGT over and above the figures of the baseline FGT build within the limiting criteria set for maximum cylinder pressure, smoke level and pre-turbine temperature. (Author)

  9. Immunomodulators targeting MARCO expression improve resistance to postinfluenza bacterial pneumonia. (United States)

    Wu, Muzo; Gibbons, John G; DeLoid, Glen M; Bedugnis, Alice S; Thimmulappa, Rajesh K; Biswal, Shyam; Kobzik, Lester


    Downregulation of the alveolar macrophage (AM) receptor with collagenous structure (MARCO) leads to susceptibility to postinfluenza bacterial pneumonia, a major cause of morbidity and mortality. We sought to determine whether immunomodulation of MARCO could improve host defense and resistance to secondary bacterial pneumonia. RNAseq analysis identified a striking increase in MARCO expression between days 9 and 11 after influenza infection and indicated important roles for Akt and Nrf2 in MARCO recovery. In vitro, primary human AM-like monocyte-derived macrophages (AM-MDMs) and THP-1 macrophages were treated with IFNγ to model influenza effects. Activators of Nrf2 (sulforaphane) or Akt (SC79) caused increased MARCO expression and a MARCO-dependent improvement in phagocytosis in IFNγ-treated cells and improved survival in mice with postinfluenza pneumococcal pneumonia. Transcription factor analysis also indicated a role for transcription factor E-box (TFEB) in MARCO recovery. Overexpression of TFEB in THP-1 cells led to marked increases in MARCO. The ability of Akt activation to increase MARCO expression in IFNγ-treated AM-MDMs was abrogated in TFEB-knockdown cells, indicating Akt increases MARCO expression through TFEB. Increasing MARCO expression by targeting Nrf2 signaling or the Akt-TFEB-MARCO pathway are promising strategies to improve bacterial clearance and survival in postinfluenza bacterial pneumonia. Copyright © 2017 the American Physiological Society.

  10. Improved Variable Window Kernel Estimates of Probability Densities


    Hall, Peter; Hu, Tien Chung; Marron, J. S.


    Variable window width kernel density estimators, with the width varying proportionally to the square root of the density, have been thought to have superior asymptotic properties. The rate of convergence has been claimed to be as good as those typical for higher-order kernels, which makes the variable width estimators more attractive because no adjustment is needed to handle the negativity usually entailed by the latter. However, in a recent paper, Terrell and Scott show that these results ca...

  11. Variability in individual activity bursts improves ant foraging success. (United States)

    Campos, Daniel; Bartumeus, Frederic; Méndez, Vicenç; Andrade, José S; Espadaler, Xavier


    Using experimental and computational methods, we study the role of behavioural variability in activity bursts (or temporal activity patterns) for individual and collective regulation of foraging in A. senilis ants. First, foraging experiments were carried out under special conditions (low densities of ants and food and absence of external cues or stimuli) where individual-based strategies are most prevalent. By using marked individuals and recording all foraging trajectories, we were then able to precisely quantify behavioural variability among individuals. Our main conclusions are that (i) variability of ant trajectories (turning angles, speed, etc.) is low compared with variability of temporal activity profiles, and (ii) this variability seems to be driven by plasticity of individual behaviour through time, rather than the presence of fixed behavioural stereotypes or specialists within the group. The statistical measures obtained from these experimental foraging patterns are then used to build a general agent-based model (ABM) which includes the most relevant properties of ant foraging under natural conditions, including recruitment through pheromone communication. Using the ABM, we are able to provide computational evidence that the characteristics of individual variability observed in our experiments can provide a functional advantage (in terms of foraging success) to the group; thus, we propose the biological basis underpinning our observations. Altogether, our study reveals the potential utility of experiments under simplified (laboratory) conditions for understanding information-gathering in biological systems. © 2016 The Author(s).

  12. Efficiency improvement of variable speed electrical drives for HVAC applications

    Energy Technology Data Exchange (ETDEWEB)

    Abrahamsen, F.; Blaabjerg, F.; Pedersen, J.K. [Aalborg Univ., Inst. of Energy Technology, Aalborg East (Denmark)


    A large part of the produced electrical energy is consumed by ventilators, pumps and compressors, the so-called HVAC applications. A lot of this energy can be saved by speed control, but even with the large saving obtained alone by introduction of variable speed, it is still essential to optimise the control of the variable speed drive and to optimise the electrical machine with respect to efficiency. Experiments are made with energy optimal induction motor control on a 2.2 kW variable speed pump system. It is demonstrated that 10% of the consumed energy can typically be saved by energy optimal motor control compared with constant V/Hz control. In a comparison of induction motors and permanent magnet synchronous motors for a variable speed pump application it is shown that for 2.2 kW motors an investment in high-efficiency or PM motors are typically paid back within 2.5 years and 7 years respectively. For a 90 kW PM motor the pay-back time would be 24 years. It is today not profitable to use PM motors for variable speed HVAC applications above 2 kW rated motor power. A further study is required to determine this limit in power rating more precisely. (orig.)

  13. Improved sample size determination for attributes and variables sampling

    International Nuclear Information System (INIS)

    Stirpe, D.; Picard, R.R.


    Earlier INMM papers have addressed the attributes/variables problem and, under conservative/limiting approximations, have reported analytical solutions for the attributes and variables sample sizes. Through computer simulation of this problem, we have calculated attributes and variables sample sizes as a function of falsification, measurement uncertainties, and required detection probability without using approximations. Using realistic assumptions for uncertainty parameters of measurement, the simulation results support the conclusions: (1) previously used conservative approximations can be expensive because they lead to larger sample sizes than needed; and (2) the optimal verification strategy, as well as the falsification strategy, are highly dependent on the underlying uncertainty parameters of the measurement instruments. 1 ref., 3 figs

  14. Sensitivity and fidelity of DNA microarray improved with integration of Amplified Differential Gene Expression (ADGE

    Directory of Open Access Journals (Sweden)

    Ile Kristina E


    Full Text Available Abstract Background The ADGE technique is a method designed to magnify the ratios of gene expression before detection. It improves the detection sensitivity to small change of gene expression and requires small amount of starting material. However, the throughput of ADGE is low. We integrated ADGE with DNA microarray (ADGE microarray and compared it with regular microarray. Results When ADGE was integrated with DNA microarray, a quantitative relationship of a power function between detected and input ratios was found. Because of ratio magnification, ADGE microarray was better able to detect small changes in gene expression in a drug resistant model cell line system. The PCR amplification of templates and efficient labeling reduced the requirement of starting material to as little as 125 ng of total RNA for one slide hybridization and enhanced the signal intensity. Integration of ratio magnification, template amplification and efficient labeling in ADGE microarray reduced artifacts in microarray data and improved detection fidelity. The results of ADGE microarray were less variable and more reproducible than those of regular microarray. A gene expression profile generated with ADGE microarray characterized the drug resistant phenotype, particularly with reference to glutathione, proliferation and kinase pathways. Conclusion ADGE microarray magnified the ratios of differential gene expression in a power function, improved the detection sensitivity and fidelity and reduced the requirement for starting material while maintaining high throughput. ADGE microarray generated a more informative expression pattern than regular microarray.

  15. Student Engagement and Classroom Variables in Improving Mathematics Achievement (United States)

    Park, So-Young


    The study explored how much student engagement and classroom variables predicted student achievement in mathematics. Since students were nested within a classroom, hierarchical linear modeling (HLM) was employed for the analysis. The results indicated that student engagement had positive effects on student academic growth per month in math after…

  16. Improved variable reduction in partial least squares modelling by Global-Minimum Error Uninformative-Variable Elimination. (United States)

    Andries, Jan P M; Vander Heyden, Yvan; Buydens, Lutgarde M C


    The calibration performance of Partial Least Squares regression (PLS) can be improved by eliminating uninformative variables. For PLS, many variable elimination methods have been developed. One is the Uninformative-Variable Elimination for PLS (UVE-PLS). However, the number of variables retained by UVE-PLS is usually still large. In UVE-PLS, variable elimination is repeated as long as the root mean squared error of cross validation (RMSECV) is decreasing. The set of variables in this first local minimum is retained. In this paper, a modification of UVE-PLS is proposed and investigated, in which UVE is repeated until no further reduction in variables is possible, followed by a search for the global RMSECV minimum. The method is called Global-Minimum Error Uninformative-Variable Elimination for PLS, denoted as GME-UVE-PLS or simply GME-UVE. After each iteration, the predictive ability of the PLS model, built with the remaining variable set, is assessed by RMSECV. The variable set with the global RMSECV minimum is then finally selected. The goal is to obtain smaller sets of variables with similar or improved predictability than those from the classical UVE-PLS method. The performance of the GME-UVE-PLS method is investigated using four data sets, i.e. a simulated set, NIR and NMR spectra, and a theoretical molecular descriptors set, resulting in twelve profile-response (X-y) calibrations. The selective and predictive performances of the models resulting from GME-UVE-PLS are statistically compared to those from UVE-PLS and 1-step UVE, one-sided paired t-tests. The results demonstrate that variable reduction with the proposed GME-UVE-PLS method, usually eliminates significantly more variables than the classical UVE-PLS, while the predictive abilities of the resulting models are better. With GME-UVE-PLS, a lower number of uninformative variables, without a chemical meaning for the response, may be retained than with UVE-PLS. The selectivity of the classical UVE method

  17. Improvement of the variable storage coefficient method with water surface gradient as a variable (United States)

    The variable storage coefficient (VSC) method has been used for streamflow routing in continuous hydrological simulation models such as the Agricultural Policy/Environmental eXtender (APEX) and the Soil and Water Assessment Tool (SWAT) for more than 30 years. APEX operates on a daily time step and ...

  18. Improved expression of recombinant plant-made hEGF. (United States)

    Thomas, David Rhys; Walmsley, Amanda Maree


    The yield of recombinant hEGF was increased approximately tenfold through a range of optimisations. Further, the recombinant protein was found to have biological activity comparable to commercial hEGF. Human epidermal growth factor (hEGF) is a powerful mitogen that can enhance the healing of a wide range of injuries, including burns, cuts, diabetic ulcers and gastric ulcers. However, despite its clinical value, hEGF is only consistently used for the treatment of chronic diabetic ulcers due to its high cost. In this study, hEGF was transiently expressed in Nicotiana benthamiana plants and targeted to the apoplast, ER and vacuole. Several other approaches were also included in a stepwise fashion to identify the optimal conditions for the expression of recombinant hEGF. Expression was found to be highest in the vacuole, while targeting hEGF to the ER caused a decrease in total soluble protein (TSP). Using a codon optimised sequence was found to increase vacuolar targeted hEGF yield by ~34 %, while it was unable to increase the yield of ER targeted hEGF. The use of the P19 silencing inhibitor was able to further increase expression by over threefold, and using 5-week-old plants significantly increased expression compared to 4- or 6-week-old-plants. The combined effect of these optimisations increased expression tenfold over the initial apoplast targeted construct to an average yield of 6.24 % of TSP. The plant-made hEGF was then shown to be equivalent to commercial E. coli derived hEGF in its ability to promote the proliferation of mouse keratinocytes. This study supports the potential for plants to be used for the commercial production of hEGF, and identifies a potential limitation for the further improvement of recombinant protein yields.

  19. Genome engineering for improved recombinant protein expression in Escherichia coli. (United States)

    Mahalik, Shubhashree; Sharma, Ashish K; Mukherjee, Krishna J


    A metabolic engineering perspective which views recombinant protein expression as a multistep pathway allows us to move beyond vector design and identify the downstream rate limiting steps in expression. In E.coli these are typically at the translational level and the supply of precursors in the form of energy, amino acids and nucleotides. Further recombinant protein production triggers a global cellular stress response which feedback inhibits both growth and product formation. Countering this requires a system level analysis followed by a rational host cell engineering to sustain expression for longer time periods. Another strategy to increase protein yields could be to divert the metabolic flux away from biomass formation and towards recombinant protein production. This would require a growth stoppage mechanism which does not affect the metabolic activity of the cell or the transcriptional or translational efficiencies. Finally cells have to be designed for efficient export to prevent buildup of proteins inside the cytoplasm and also simplify downstream processing. The rational and the high throughput strategies that can be used for the construction of such improved host cell platforms for recombinant protein expression is the focus of this review.

  20. Masked expression of life-history traits in a highly variable environment (United States)

    DeBoer, Jason A.; Fontaine, Joseph J.; Chizinski, Christopher J.; Pope, Kevin L.


    Differing life-history strategies may act as a constraint on reproductive expression that ultimately limits the ability of individual species to respond to changes in the magnitude or frequency of environmental variation, and potentially underlies the variation often inherent in phenotypic and evolved responses to anthropogenic change. Alternatively, if there are environmental cues that predict reproductive potential, differential expression of life-history strategies may represent differences in the adaptive capacity to optimize current reproductive value given variation in environmental conditions. We compared several aspects of walleye Sander vitreus spawning ecology at two reservoirs that differ in environmental variability (i.e., annual water-level fluctuation) to identify the capacity of phenotypic expression and the corresponding association with age. Despite significant differences in female body and liver masses between reservoirs that differ in environmental variability, we found no difference in reproductive investment measured by egg size and fecundity. Walleye in a highly variable environment appear to exhibit reproductive traits more typical of a short-lived life-history strategy, which may be resultant from the interaction of environmental and anthropogenic pressures. This finding emphasizes the need to identify the degree to which life-history expression represents physiological constraints versus ecological optimization, particularly as anthropogenic change continues to alter environmental conditions. 

  1. Acute Effects of Plyometric Intervention—Performance Improvement and Related Changes in Sprinting Gait Variability. (United States)

    Maćkała, Krzysztof; Fostiak, Marek


    The purpose of this study was to examine the effect of a short high-intensity plyometric program on the improvement of explosive power of lower extremities and sprint performance as well as changes in sprinting stride variability in male sprinters. Fourteen healthy male sprinters (mean ± SD: age: 18.07 ± 0.73 years, body mass: 73 ± 9.14 kg, height: 180.57 ± 8.16 cm, and best 100 m: 10.89 ± 0.23) participated in the experiment. The experimental protocol included vertical jumping such as squat jump, countermovement jump, and horizontal jumps; standing long jump and standing triple jumps to assess lower-body power, maximal running velocity; a 20-m flying start sprint that evaluated variability of 10 running steps and 60-m starting block sprint. All analyzed parameters were obtained using the new technology of OptoJump-Microgate (OptoJump, Italy). The short-term plyometric training program significantly increased the explosive power of lower extremities, both vertical and horizontal jumping improvement. However, the vertical jumps increased much more than the horizontal. The 20-m improvements were derived from an increase of stride frequency from 4.31 to 4.39 Hz because of a decrease of ground contact time from 138 to 133 milliseconds. This did not translate into step length changes. Therefore, the significantly increased frequency of stride (1.8%), which is a specific expression of ground contact time reduction during support phase, resulted in an increase of speed. The training volume of 2 weeks (with 6 sessions) using high-intensity (between 180 and 250 jumps per session) plyometric exercises can be recommended as the short-term strategy that will optimize one's probability of reaching strong improvements in explosive power and sprint velocity performance.

  2. Utilizing the Vertical Variability of Precipitation to Improve Radar QPE (United States)

    Gatlin, Patrick N.; Petersen, Walter A.


    Characteristics of the melting layer and raindrop size distribution can be exploited to further improve radar quantitative precipitation estimation (QPE). Using dual-polarimetric radar and disdrometers, we found that the characteristic size of raindrops reaching the ground in stratiform precipitation often varies linearly with the depth of the melting layer. As a result, a radar rainfall estimator was formulated using D(sub m) that can be employed by polarimetric as well as dual-frequency radars (e.g., space-based radars such as the GPM DPR), to lower the bias and uncertainty of conventional single radar parameter rainfall estimates by as much as 20%. Polarimetric radar also suffers from issues associated with sampling the vertical distribution of precipitation. Hence, we characterized the vertical profile of polarimetric parameters (VP3)-a radar manifestation of the evolving size and shape of hydrometeors as they fall to the ground-on dual-polarimetric rainfall estimation. The VP3 revealed that the profile of ZDR in stratiform rainfall can bias dual-polarimetric rainfall estimators by as much as 50%, even after correction for the vertical profile of reflectivity (VPR). The VP3 correction technique that we developed can improve operational dual-polarimetric rainfall estimates by 13% beyond that offered by a VPR correction alone.

  3. What to use to express the variability of data: Standard deviation or standard error of mean?


    Barde, Mohini P.; Barde, Prajakt J.


    Statistics plays a vital role in biomedical research. It helps present data precisely and draws the meaningful conclusions. While presenting data, one should be aware of using adequate statistical measures. In biomedical journals, Standard Error of Mean (SEM) and Standard Deviation (SD) are used interchangeably to express the variability; though they measure different parameters. SEM quantifies uncertainty in estimate of the mean whereas SD indicates dispersion of the data from mean. As reade...

  4. EPSPS variability, gene expression, and enzymatic activity in glyphosate-resistant biotypes of Digitaria insularis. (United States)

    Galeano, E; Barroso, A A M; Vasconcelos, T S; López-Rubio, A; Albrecht, A J P; Victoria Filho, R; Carrer, H


    Weed resistance to herbicides is a natural phenomenon that exerts selection on individuals in a population. In Brazil, glyphosate resistance was recently detected in Digitaria insularis. The objective of this study was to elucidate mechanisms of weed resistance in this plant, including genetic variability, allelism, amino acid substitutions, gene expression, and enzymatic activity levels. Most of these have not previously been studied in this species. D. insularis DNA sequences were used to analyze genetic variability. cDNA from resistant and susceptible plants was used to identify mutations, alleles, and 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) expression, using real-time quantitative reverse transcription-polymerase chain reaction. In addition, EPSPS activity was measured. We found a decrease in genetic variability between populations related to glyphosate application. Substitutions from proline to threonine and tyrosine to cysteine led to a decrease in EPSPS affinity for the glyphosate. In addition, the EPSPS enzymatic activity was slightly higher in resistant plants, whereas EPSPS gene expression was almost identical in both biotypes, suggesting feedback regulation at different levels. To conclude, our results suggest new molecular mechanisms used by D. insularis to increase glyphosate resistance.

  5. Dissecting Time- from Tumor-Related Gene Expression Variability in Bilateral Breast Cancer

    Directory of Open Access Journals (Sweden)

    Maurizio Callari


    Full Text Available Metachronous (MBC and synchronous bilateral breast tumors (SBC are mostly distinct primaries, whereas paired primaries and their local recurrences (LRC share a common origin. Intra-pair gene expression variability in MBC, SBC, and LRC derives from time/tumor microenvironment-related and tumor genetic background-related factors and pairs represents an ideal model for trying to dissect tumor-related from microenvironment-related variability. Pairs of tumors derived from women with SBC (n = 18, MBC (n = 11, and LRC (n = 10 undergoing local-regional treatment were profiled for gene expression; similarity between pairs was measured using an intraclass correlation coefficient (ICC computed for each gene and compared using analysis of variance (ANOVA. When considering biologically unselected genes, the highest correlations were found for primaries and paired LRC, and the lowest for MBC pairs. By instead limiting the analysis to the breast cancer intrinsic genes, correlations between primaries and paired LRC were enhanced, while lower similarities were observed for SBC and MBC. Focusing on stromal-related genes, the ICC values decreased for MBC and were significantly different from SBC. These findings indicate that it is possible to dissect intra-pair gene expression variability into components that are associated with genetic origin or with time and microenvironment by using specific gene subsets.

  6. Higher resting heart rate variability predicts skill in expressing some emotions. (United States)

    Tuck, Natalie L; Grant, Rosemary C I; Sollers, John J; Booth, Roger J; Consedine, Nathan S


    Vagally mediated heart rate variability (vmHRV) is a measure of cardiac vagal tone, and is widely viewed as a physiological index of the capacity to regulate emotions. However, studies have not directly tested whether vmHRV is associated with the ability to facially express emotions. In extending prior work, the current report tested links between resting vmHRV and the objectively assessed ability to facially express emotions, hypothesizing that higher vmHRV would predict greater expressive skill. Eighty healthy women completed self-reported measures, before attending a laboratory session in which vmHRV and the ability to express six emotions in the face were assessed. A repeated measures analysis of variance revealed a marginal main effect for vmHRV on skill overall; individuals with higher resting vmHRV were only better able to deliberately facially express anger and interest. Findings suggest that differences in resting vmHRV are associated with the objectively assessed ability to facially express some, but not all, emotions, with potential implications for health and well-being. © 2016 Society for Psychophysiological Research.

  7. Expression analysis of the Theileria parva subtelomere-encoded variable secreted protein gene family.

    Directory of Open Access Journals (Sweden)

    Jacqueline Schmuckli-Maurer

    Full Text Available The intracellular protozoan parasite Theileria parva transforms bovine lymphocytes inducing uncontrolled proliferation. Proteins released from the parasite are assumed to contribute to phenotypic changes of the host cell and parasite persistence. With 85 members, genes encoding subtelomeric variable secreted proteins (SVSPs form the largest gene family in T. parva. The majority of SVSPs contain predicted signal peptides, suggesting secretion into the host cell cytoplasm.We analysed SVSP expression in T. parva-transformed cell lines established in vitro by infection of T or B lymphocytes with cloned T. parva parasites. Microarray and quantitative real-time PCR analysis revealed mRNA expression for a wide range of SVSP genes. The pattern of mRNA expression was largely defined by the parasite genotype and not by host background or cell type, and found to be relatively stable in vitro over a period of two months. Interestingly, immunofluorescence analysis carried out on cell lines established from a cloned parasite showed that expression of a single SVSP encoded by TP03_0882 is limited to only a small percentage of parasites. Epitope-tagged TP03_0882 expressed in mammalian cells was found to translocate into the nucleus, a process that could be attributed to two different nuclear localisation signals.Our analysis reveals a complex pattern of Theileria SVSP mRNA expression, which depends on the parasite genotype. Whereas in cell lines established from a cloned parasite transcripts can be found corresponding to a wide range of SVSP genes, only a minority of parasites appear to express a particular SVSP protein. The fact that a number of SVSPs contain functional nuclear localisation signals suggests that proteins released from the parasite could contribute to phenotypic changes of the host cell. This initial characterisation will facilitate future studies on the regulation of SVSP gene expression and the potential biological role of these enigmatic

  8. Expression patterns of the aquaporin gene family during renal development: influence of genetic variability. (United States)

    Parreira, Kleber S; Debaix, Huguette; Cnops, Yvette; Geffers, Lars; Devuyst, Olivier


    High-throughput analyses have shown that aquaporins (AQPs) belong to a cluster of genes that are differentially expressed during kidney organogenesis. However, the spatiotemporal expression patterns of the AQP gene family during tubular maturation and the potential influence of genetic variation on these patterns and on water handling remain unknown. We investigated the expression patterns of all AQP isoforms in fetal (E13.5 to E18.5), postnatal (P1 to P28), and adult (9 weeks) kidneys of inbred (C57BL/6J) and outbred (CD-1) mice. Using quantitative polymerase chain reaction (PCR), we evidenced two mRNA patterns during tubular maturation in C57 mice. The AQPs 1-7-11 showed an early (from E14.5) and progressive increase to adult levels, similar to the mRNA pattern observed for proximal tubule markers (Megalin, NaPi-IIa, OAT1) and reflecting the continuous increase in renal cortical structures during development. By contrast, AQPs 2-3-4 showed a later (E15.5) and more abrupt increase, with transient postnatal overexpression. Most AQP genes were expressed earlier and/or stronger in maturing CD-1 kidneys. Furthermore, adult CD-1 kidneys expressed more AQP2 in the collecting ducts, which was reflected by a significant delay in excreting a water load. The expression patterns of proximal vs. distal AQPs and the earlier expression in the CD-1 strain were confirmed by immunoblotting and immunostaining. These data (1) substantiate the clustering of important genes during tubular maturation and (2) demonstrate that genetic variability influences the regulation of the AQP gene family during tubular maturation and water handling by the mature kidney.

  9. Von recklinghausens disease: a series of four cases with variable expression. (United States)

    Arun, K P; Thomas Joseph, P; Jaishankar, H P; Abhinethra, M S


    Though neurofibromatosis type I (NFI) is a fairly common condition, it has a variable expressivity and penetrance. Here we present a series of cases with striking differences in the presentation especially in the oral cavity. NFI, also known as von Recklinghausen's neurofibromatosis, is an autosomal dominantly inherited neurogenetic disorder affecting 1:3000 newborn (Bongiorno et al., Oral Dis 12:125-129, 2006). About 50 % of NFI patients have no family history of the disease. There is no prevalence for gender or race in NFI. Expressivity in NFI is tremendously variable, but subtle phenotypic patterns may exist within subgroups of affected patients. Furthermore, 50 % of cases are sporadic and arise from germ cell mutation (Bongiorno et al., Oral Dis 12:125-129, 2006). The precise constellation of findings in any one individual is extremely variable, both within a family and between different families (Batsakis, Tumors of the head and neck: clinical and pathological considerations, 2nd edn. Williams and Wilkins, Baltimore, pp 313-333, 1979). Only 4-7 % of patients affected by neurofibromatosis exhibit oral manifestations (Güneri et al., Turk J Pediatr 48(2):155-158, 2006).

  10. A new efficient statistical test for detecting variability in the gene expression data. (United States)

    Mathur, Sunil; Dolo, Samuel


    DNA microarray technology allows researchers to monitor the expressions of thousands of genes under different conditions. The detection of differential gene expression under two different conditions is very important in microarray studies. Microarray experiments are multi-step procedures and each step is a potential source of variance. This makes the measurement of variability difficult because approach based on gene-by-gene estimation of variance will have few degrees of freedom. It is highly possible that the assumption of equal variance for all the expression levels may not hold. Also, the assumption of normality of gene expressions may not hold. Thus it is essential to have a statistical procedure which is not based on the normality assumption and also it can detect genes with differential variance efficiently. The detection of differential gene expression variance will allow us to identify experimental variables that affect different biological processes and accuracy of DNA microarray measurements.In this article, a new nonparametric test for scale is developed based on the arctangent of the ratio of two expression levels. Most of the tests available in literature require the assumption of normal distribution, which makes them inapplicable in many situations, and it is also hard to verify the suitability of the normal distribution assumption for the given data set. The proposed test does not require the assumption of the distribution for the underlying population and hence makes it more practical and widely applicable. The asymptotic relative efficiency is calculated under different distributions, which show that the proposed test is very powerful when the assumption of normality breaks down. Monte Carlo simulation studies are performed to compare the power of the proposed test with some of the existing procedures. It is found that the proposed test is more powerful than commonly used tests under almost all the distributions considered in the study. A

  11. What to use to express the variability of data: Standard deviation or standard error of mean? (United States)

    Barde, Mohini P; Barde, Prajakt J


    Statistics plays a vital role in biomedical research. It helps present data precisely and draws the meaningful conclusions. While presenting data, one should be aware of using adequate statistical measures. In biomedical journals, Standard Error of Mean (SEM) and Standard Deviation (SD) are used interchangeably to express the variability; though they measure different parameters. SEM quantifies uncertainty in estimate of the mean whereas SD indicates dispersion of the data from mean. As readers are generally interested in knowing the variability within sample, descriptive data should be precisely summarized with SD. Use of SEM should be limited to compute CI which measures the precision of population estimate. Journals can avoid such errors by requiring authors to adhere to their guidelines.

  12. Amino-Terminal Microdeletion within the CNTNAP2 Gene Associated with Variable Expressivity of Speech Delay

    Directory of Open Access Journals (Sweden)

    Amel Al-Murrani


    Full Text Available The contactin-associated protein-like 2 (CNTNAP2 gene is highly expressed in the frontal lobe circuits in the developing human brain. Mutations in this gene have been associated with several neurodevelopmental disorders such as autism and specific language impairment. Here we describe a 450 kb deletion within the CNTNAP2 gene that is maternally inherited in two male siblings, but with a variable clinical phenotype. This variability is described in the context of a limited number of other cases reported in the literature. The in-frame intragenic deletion removes a critical domain of the CNTNAP2 protein, and this case also highlights the challenges of correlating genotype and phenotype.

  13. Amino-Terminal Microdeletion within the CNTNAP2 Gene Associated with Variable Expressivity of Speech Delay (United States)

    Al-Murrani, Amel; Ashton, Fern; Aftimos, Salim; George, Alice M.; Love, Donald R.


    The contactin-associated protein-like 2 (CNTNAP2) gene is highly expressed in the frontal lobe circuits in the developing human brain. Mutations in this gene have been associated with several neurodevelopmental disorders such as autism and specific language impairment. Here we describe a 450 kb deletion within the CNTNAP2 gene that is maternally inherited in two male siblings, but with a variable clinical phenotype. This variability is described in the context of a limited number of other cases reported in the literature. The in-frame intragenic deletion removes a critical domain of the CNTNAP2 protein, and this case also highlights the challenges of correlating genotype and phenotype. PMID:23074684


    Directory of Open Access Journals (Sweden)

    Aleksandra Sudarić


    Full Text Available The aim of this research was to determine the genetic variability of chosen soybean lines in seed quality by determining diversity in phenotypic expression of 1000 seed weight, as well as protein and oil concentrations in the seed. Field trials were set up in a randomized, complete block design with two replications, at the Agricultural Institute Osijek during three growing seasons (2010-2012. Each year, after harvest, 1000 seed weight, and protein and oil concentrations in the seed were determined. Statistical analyses of the results included: calculating basic measures of variation and analysis of variance. The analyzed data showed the existence of plant material's diversity in phenotypic expression of investigated seed quality traits, as well as the existence of statistically significant genotype and year effects.

  15. Network-based group variable selection for detecting expression quantitative trait loci (eQTL

    Directory of Open Access Journals (Sweden)

    Zhang Xuegong


    Full Text Available Abstract Background Analysis of expression quantitative trait loci (eQTL aims to identify the genetic loci associated with the expression level of genes. Penalized regression with a proper penalty is suitable for the high-dimensional biological data. Its performance should be enhanced when we incorporate biological knowledge of gene expression network and linkage disequilibrium (LD structure between loci in high-noise background. Results We propose a network-based group variable selection (NGVS method for QTL detection. Our method simultaneously maps highly correlated expression traits sharing the same biological function to marker sets formed by LD. By grouping markers, complex joint activity of multiple SNPs can be considered and the dimensionality of eQTL problem is reduced dramatically. In order to demonstrate the power and flexibility of our method, we used it to analyze two simulations and a mouse obesity and diabetes dataset. We considered the gene co-expression network, grouped markers into marker sets and treated the additive and dominant effect of each locus as a group: as a consequence, we were able to replicate results previously obtained on the mouse linkage dataset. Furthermore, we observed several possible sex-dependent loci and interactions of multiple SNPs. Conclusions The proposed NGVS method is appropriate for problems with high-dimensional data and high-noise background. On eQTL problem it outperforms the classical Lasso method, which does not consider biological knowledge. Introduction of proper gene expression and loci correlation information makes detecting causal markers more accurate. With reasonable model settings, NGVS can lead to novel biological findings.

  16. Situational Variability of Means of Expression of Positive Emotions in Modern English

    Directory of Open Access Journals (Sweden)

    Alina K. Kisil


    Full Text Available The article investigates situational variability of means of expression of positive emotions in Modern English. This problem is topical for linguistics of emotions, pragma- and sociolinguistics. The author analyzes verbal, paraverbal and nonverbal means of expressing positive emotions of joy and surprise in three communicative registers: official, neutral and unofficial. These registers are singled out on the basis of situational context and participants of the situation. The investigation gave the author the opportunity to come to the conclusion that in the official register emotions are controlled and very often are subject to strategic purposes. They implement the upgrading strategy the aim of which is to give a high evaluation of the addressee and of everything what is happening. It stipulates the use of corresponding expressive words and word combinations, exclamatory sentences, repetitions and rhetorical questions. Paraverbal means include only light laughter and nonverbal – a smile, the expression of the eyes, nods and tangled breath. The range of the means in question is wider in the neutral register where the speaker can use such verbal means as interjections with long sounds, expletives, pauses, descriptions of own emotions. Such paraverbal means as the emotional color of the voice and its volume, intonation, different kinds of laughter and such nonverbal means as different kinds of smile, the expression of the face, gestures and movements are also used. Unofficial register is especially rich in means of expressing positive emotions. Besides means typical of other registers such verbal means as obscene lexicon, phrasal words and graphical means are used here. Paraverbal means include numerous verbs reflecting the volume of voice and nonverbal – rich mimic, friendly hugs and kisses.

  17. The use of vector bootstrapping to improve variable selection precision in Lasso models

    NARCIS (Netherlands)

    Laurin, C.; Boomsma, D.I.; Lubke, G.H.


    The Lasso is a shrinkage regression method that is widely used for variable selection in statistical genetics. Commonly, K-fold cross-validation is used to fit a Lasso model. This is sometimes followed by using bootstrap confidence intervals to improve precision in the resulting variable selections.

  18. Improved Genetic Algorithm with Two-Level Approximation for Truss Optimization by Using Discrete Shape Variables

    Directory of Open Access Journals (Sweden)

    Shen-yan Chen


    Full Text Available This paper presents an Improved Genetic Algorithm with Two-Level Approximation (IGATA to minimize truss weight by simultaneously optimizing size, shape, and topology variables. On the basis of a previously presented truss sizing/topology optimization method based on two-level approximation and genetic algorithm (GA, a new method for adding shape variables is presented, in which the nodal positions are corresponding to a set of coordinate lists. A uniform optimization model including size/shape/topology variables is established. First, a first-level approximate problem is constructed to transform the original implicit problem to an explicit problem. To solve this explicit problem which involves size/shape/topology variables, GA is used to optimize individuals which include discrete topology variables and shape variables. When calculating the fitness value of each member in the current generation, a second-level approximation method is used to optimize the continuous size variables. With the introduction of shape variables, the original optimization algorithm was improved in individual coding strategy as well as GA execution techniques. Meanwhile, the update strategy of the first-level approximation problem was also improved. The results of numerical examples show that the proposed method is effective in dealing with the three kinds of design variables simultaneously, and the required computational cost for structural analysis is quite small.

  19. An improved and explicit surrogate variable analysis procedure by coefficient adjustment. (United States)

    Lee, Seunggeun; Sun, Wei; Wright, Fred A; Zou, Fei


    Unobserved environmental, demographic, and technical factors can negatively affect the estimation and testing of the effects of primary variables. Surrogate variable analysis, proposed to tackle this problem, has been widely used in genomic studies. To estimate hidden factors that are correlated with the primary variables, surrogate variable analysis performs principal component analysis either on a subset of features or on all features, but weighting each differently. However, existing approaches may fail to identify hidden factors that are strongly correlated with the primary variables, and the extra step of feature selection and weight calculation makes the theoretical investigation of surrogate variable analysis challenging. In this paper, we propose an improved surrogate variable analysis using all measured features that has a natural connection with restricted least squares, which allows us to study its theoretical properties. Simulation studies and real data analysis show that the method is competitive to state-of-the-art methods.

  20. Expression profiling of interindividual variability following xenobiotic exposures in primary human hepatocyte cultures

    International Nuclear Information System (INIS)

    Goyak, Katy M.O.; Johnson, Mary C.; Strom, Stephen C.; Omiecinski, Curtis J.


    To examine the magnitude of human variability across the entire transcriptome after chemical challenge, we profiled gene expression responses to three different prototypic chemical inducers in primary human hepatocyte cultures from ten independent donors. Correlation between basal expression in any two hepatocyte donors ranged from r 2 values of 0.967 to 0.857, and chemical treatment tended to negatively impact correlation between donors. Including anticipated target genes, 10,812, 8373, and 7847 genes were changed in at least one donor by Aroclor 1254 (A1254), di(2-ethylhexyl) phthalate (DEHP), and phenobarbital (PB), respectively. A subset of these gene targets (n = 41) were altered with a high level of reproducibility in at least 9 donors, gene responses that correlated well with literature-reported mechanism of action. Filtering responses to the level of gene subsets clarified the biological impact associated with the respective chemical effectors, in lieu of substantial interindividual variation among donor responses. In these respects, the use of hierarchical clustering methods successfully grouped seven of the ten donors into chemical-specific rather than donor-specific clusters. However, at the whole-genome level, the magnitude of conserved gene expression changes among donors was surprisingly small, with fewer than 50% of the gene responses altered by a single chemical conserved in more than one donor. The use of higher level descriptors, such as those defined by the PANTHER classification system, may enable more consistent categorization of gene expression changes across individuals, as increased reproducibility was identified using this method

  1. A Decline in Response Variability Improves Neural Signal Detection during Auditory Task Performance. (United States)

    von Trapp, Gardiner; Buran, Bradley N; Sen, Kamal; Semple, Malcolm N; Sanes, Dan H


    The detection of a sensory stimulus arises from a significant change in neural activity, but a sensory neuron's response is rarely identical to successive presentations of the same stimulus. Large trial-to-trial variability would limit the central nervous system's ability to reliably detect a stimulus, presumably affecting perceptual performance. However, if response variability were to decrease while firing rate remained constant, then neural sensitivity could improve. Here, we asked whether engagement in an auditory detection task can modulate response variability, thereby increasing neural sensitivity. We recorded telemetrically from the core auditory cortex of gerbils, both while they engaged in an amplitude-modulation detection task and while they sat quietly listening to the identical stimuli. Using a signal detection theory framework, we found that neural sensitivity was improved during task performance, and this improvement was closely associated with a decrease in response variability. Moreover, units with the greatest change in response variability had absolute neural thresholds most closely aligned with simultaneously measured perceptual thresholds. Our findings suggest that the limitations imposed by response variability diminish during task performance, thereby improving the sensitivity of neural encoding and potentially leading to better perceptual sensitivity. The detection of a sensory stimulus arises from a significant change in neural activity. However, trial-to-trial variability of the neural response may limit perceptual performance. If the neural response to a stimulus is quite variable, then the response on a given trial could be confused with the pattern of neural activity generated when the stimulus is absent. Therefore, a neural mechanism that served to reduce response variability would allow for better stimulus detection. By recording from the cortex of freely moving animals engaged in an auditory detection task, we found that variability

  2. Facial expression recognition based on improved local ternary pattern and stacked auto-encoder (United States)

    Wu, Yao; Qiu, Weigen


    In order to enhance the robustness of facial expression recognition, we propose a method of facial expression recognition based on improved Local Ternary Pattern (LTP) combined with Stacked Auto-Encoder (SAE). This method uses the improved LTP extraction feature, and then uses the improved depth belief network as the detector and classifier to extract the LTP feature. The combination of LTP and improved deep belief network is realized in facial expression recognition. The recognition rate on CK+ databases has improved significantly.

  3. Improved gene expression signature of testicular carcinoma in situ

    DEFF Research Database (Denmark)

    Almstrup, Kristian; Leffers, Henrik; Lothe, Ragnhild A


    on global gene expression in testicular CIS have been previously published. We have merged the two data sets on CIS samples (n = 6) and identified the shared gene expression signature in relation to expression in normal testis. Among the top-20 highest expressed genes, one-third was transcription factors...... development' were significantly altered and could collectively affect cellular pathways like the WNT signalling cascade, which thus may be disrupted in testicular CIS. The merged CIS data from two different microarray platforms, to our knowledge, provide the most precise CIS gene expression signature to date....

  4. Genetic variability in MCF-7 sublines: evidence of rapid genomic and RNA expression profile modifications

    International Nuclear Information System (INIS)

    Nugoli, Mélanie; Theillet, Charles; Chuchana, Paul; Vendrell, Julie; Orsetti, Béatrice; Ursule, Lisa; Nguyen, Catherine; Birnbaum, Daniel; Douzery, Emmanuel JP; Cohen, Pascale


    Both phenotypic and cytogenetic variability have been reported for clones of breast carcinoma cell lines but have not been comprehensively studied. Despite this, cell lines such as MCF-7 cells are extensively used as model systems. In this work we documented, using CGH and RNA expression profiles, the genetic variability at the genomic and RNA expression levels of MCF-7 cells of different origins. Eight MCF-7 sublines collected from different sources were studied as well as 3 subclones isolated from one of the sublines by limit dilution. MCF-7 sublines showed important differences in copy number alteration (CNA) profiles. Overall numbers of events ranged from 28 to 41. Involved chromosomal regions varied greatly from a subline to another. A total of 62 chromosomal regions were affected by either gains or losses in the 11 sublines studied. We performed a phylogenetic analysis of CGH profiles using maximum parsimony in order to reconstruct the putative filiation of the 11 MCF-7 sublines. The phylogenetic tree obtained showed that the MCF-7 clade was characterized by a restricted set of 8 CNAs and that the most divergent subline occupied the position closest to the common ancestor. Expression profiles of 8 MCF-7 sublines were analyzed along with those of 19 unrelated breast cancer cell lines using home made cDNA arrays comprising 720 genes. Hierarchical clustering analysis of the expression data showed that 7/8 MCF-7 sublines were grouped forming a cluster while the remaining subline clustered with unrelated breast cancer cell lines. These data thus showed that MCF-7 sublines differed at both the genomic and phenotypic levels. The analysis of CGH profiles of the parent subline and its three subclones supported the heteroclonal nature of MCF-7 cells. This strongly suggested that the genetic plasticity of MCF-7 cells was related to their intrinsic capacity to generate clonal heterogeneity. We propose that MCF-7, and possibly the breast tumor it was derived from, evolved

  5. Improvement of SET variability in TaO x based resistive RAM devices (United States)

    Schönhals, Alexander; Waser, Rainer; Wouters, Dirk J.


    Improvement or at least control of variability is one of the key challenges for Redox based resistive switching memory technology. In this paper, we investigate the impact of a serial resistor as a voltage divider on the SET variability in Pt/Ta2O5/Ta/Pt nano crossbar devices. A partial RESET in a competing complementary switching (CS) mode is identified as a possible failure mechanism of bipolar switching SET in our devices. Due to a voltage divider effect, serial resistance value shows unequal impact on switching voltages of both modes which allows for a selective suppression of the CS mode. The impact of voltage divider on SET variability is demonstrated. A combination of appropriate write voltage and serial resistance allows for a significant improvement of the SET variability.

  6. Cultural variability in Expressed Emotion among families of adolescents with anorexia nervosa. (United States)

    Hoste, Renee Rienecke; Labuschagne, Zandre; Lock, James; Le Grange, Daniel


    To examine the cultural variability in Expressed Emotion (EE) among families of white and ethnic minority adolescents with anorexia nervosa (AN). One-hundred and eighty-nine AN patients and their parents completed the Eating Disorder Examination and the Structured Clinical Family Interview, from which EE ratings were made. No differences were found in the number of white and minority families classified as high EE. White families were higher on warmth (W) and tended to be higher on positive remarks (PR) than minority families. High EE was associated with a longer duration of illness, but was not related to eating disorder pathology. Few differences were found between white and ethnic minority families on the EE dimensions of CC, hostility (H), or EOI. Differences between families on W and PR, however, may have important treatment implications. Copyright © 2010 Wiley Periodicals, Inc.

  7. Unpredictable Variable Prenatal Stress Programs Expression of Genes Involved in Appetite Control and Energy Expenditure (United States)

    Moyer, E. L.; Al-Shayeb, B.; Baer, L. A.; Ronca, A. E.


    Exposure to stress in the womb shapes neurobiological and physiological outcomes of offspring in later life, including body weight regulation and metabolic profiles. Our previous work utilizing a centrifugation-induced hyper-gravity demonstrated significantly increased (8-15%) body mass in male, but not female, rats exposed throughout gestation to chronic 2-g from conception to birth. We reported a similar outcome in adult offspring exposed throughout gestation to Unpredictable Variable Prenatal Stress (UVPS). Here we examine gene expression changes and the plasma of animals treated with our UVPS model to identify a potential role for prenatal stress in this hypergravity programming effect. Specifically we focused on appetite control and energy expenditure pathways in prenatally stressed adult (90-day-old) male Sprague-Dawley rats.

  8. Novel Sonic Hedgehog Mutation in a Couple with Variable Expression of Holoprosencephaly

    Directory of Open Access Journals (Sweden)

    M. Aguinaga


    Full Text Available Holoprosencephaly (HPE is the most common developmental defect of the forebrain and midface in humans. sporadic and inherited mutations in the human sonic hedgehog (SHH gene cause 37% of familial HPE. A couple was referred to our unit with a family history of two spontaneous first trimester miscarriages and a daughter with HPE who presented early neonatal death. The father had a repaired median cleft lip, absence of central incisors, facial medial hypoplasia, and cleft palate. Intelligence and a brain CT scan were normal. Direct paternal sequencing analysis showed a novel nonsense mutation (W127X. Facial characteristics are considered as HPE microforms, and the pedigree suggested autosomal dominant inheritance with a variable expression of the phenotype. This study reinforces the importance of an exhaustive evaluation of couples with a history of miscarriages and neonatal deaths with structural defects.

  9. Probabilistic Requirements (Partial) Verification Methods Best Practices Improvement. Variables Acceptance Sampling Calculators: Empirical Testing. Volume 2 (United States)

    Johnson, Kenneth L.; White, K. Preston, Jr.


    The NASA Engineering and Safety Center was requested to improve on the Best Practices document produced for the NESC assessment, Verification of Probabilistic Requirements for the Constellation Program, by giving a recommended procedure for using acceptance sampling by variables techniques as an alternative to the potentially resource-intensive acceptance sampling by attributes method given in the document. In this paper, the results of empirical tests intended to assess the accuracy of acceptance sampling plan calculators implemented for six variable distributions are presented.

  10. Size and Topology Optimization for Trusses with Discrete Design Variables by Improved Firefly Algorithm

    Directory of Open Access Journals (Sweden)

    Yue Wu


    Full Text Available Firefly Algorithm (FA, for short is inspired by the social behavior of fireflies and their phenomenon of bioluminescent communication. Based on the fundamentals of FA, two improved strategies are proposed to conduct size and topology optimization for trusses with discrete design variables. Firstly, development of structural topology optimization method and the basic principle of standard FA are introduced in detail. Then, in order to apply the algorithm to optimization problems with discrete variables, the initial positions of fireflies and the position updating formula are discretized. By embedding the random-weight and enhancing the attractiveness, the performance of this algorithm is improved, and thus an Improved Firefly Algorithm (IFA, for short is proposed. Furthermore, using size variables which are capable of including topology variables and size and topology optimization for trusses with discrete variables is formulated based on the Ground Structure Approach. The essential techniques of variable elastic modulus technology and geometric construction analysis are applied in the structural analysis process. Subsequently, an optimization method for the size and topological design of trusses based on the IFA is introduced. Finally, two numerical examples are shown to verify the feasibility and efficiency of the proposed method by comparing with different deterministic methods.

  11. The Use of Variable Q1 Isolation Windows Improves Selectivity in LC-SWATH-MS Acquisition. (United States)

    Zhang, Ying; Bilbao, Aivett; Bruderer, Tobias; Luban, Jeremy; Strambio-De-Castillia, Caterina; Lisacek, Frédérique; Hopfgartner, Gérard; Varesio, Emmanuel


    As tryptic peptides and metabolites are not equally distributed along the mass range, the probability of cross fragment ion interference is higher in certain windows when fixed Q1 SWATH windows are applied. We evaluated the benefits of utilizing variable Q1 SWATH windows with regards to selectivity improvement. Variable windows based on equalizing the distribution of either the precursor ion population (PIP) or the total ion current (TIC) within each window were generated by an in-house software, swathTUNER. These two variable Q1 SWATH window strategies outperformed, with respect to quantification and identification, the basic approach using a fixed window width (FIX) for proteomic profiling of human monocyte-derived dendritic cells (MDDCs). Thus, 13.8 and 8.4% additional peptide precursors, which resulted in 13.1 and 10.0% more proteins, were confidently identified by SWATH using the strategy PIP and TIC, respectively, in the MDDC proteomic sample. On the basis of the spectral library purity score, some improvement warranted by variable Q1 windows was also observed, albeit to a lesser extent, in the metabolomic profiling of human urine. We show that the novel concept of "scheduled SWATH" proposed here, which incorporates (i) variable isolation windows and (ii) precursor retention time segmentation further improves both peptide and metabolite identifications.

  12. What variables influence the ability of an AFO to improve function and when are they indicated? (United States)

    Malas, Bryan S


    Children with spina bifida often present with functional deficits of the lower limb associated with neurosegmental lesion levels and require orthotic management. The most used orthosis for children with spina bifida is the ankle-foot orthosis (AFO). The AFO improves ambulation and reduces energy cost while walking. Despite the apparent benefits of using an AFO, limited evidence documents the influence of factors predicting the ability of an AFO to improve function and when they are indicated. These variables include AFO design, footwear, AFO-footwear combination, and data acquisition. When these variables are not adequately considered in clinical decision-making, there is a risk the AFO will be abandoned prematurely or the patient's stability, function, and safety compromised. The purposes of this study are to (1) describe the functional deficits based on lesion levels; (2) identify and describe variables that influence the ability of an AFO to control deformities; and (3) describe what variables are indicated for the AFO to control knee flexion during stance, hyperpronation, and valgus stress at the knee. A selective literature review was undertaken searching MEDLINE and Cochrane databases using terms related to "orthosis" and "spina bifida." Based on previous studies and gait analysis data, suggestions can be made regarding material selection/geometric configuration, sagittal alignment, footplate length, and trim lines of an AFO for reducing knee flexion, hyperpronation, and valgus stress at the knee. Further research is required to determine what variables allow an AFO to improve function.

  13. Novel redox nanomedicine improves gene expression of polyion complex vector

    Directory of Open Access Journals (Sweden)

    Kazuko Toh, Toru Yoshitomi, Yutaka Ikeda and Yukio Nagasaki


    Full Text Available Gene therapy has generated worldwide attention as a new medical technology. While non-viral gene vectors are promising candidates as gene carriers, they have several issues such as toxicity and low transfection efficiency. We have hypothesized that the generation of reactive oxygen species (ROS affects gene expression in polyplex supported gene delivery systems. The effect of ROS on the gene expression of polyplex was evaluated using a nitroxide radical-containing nanoparticle (RNP as an ROS scavenger. When polyethyleneimine (PEI/pGL3 or PEI alone was added to the HeLa cells, ROS levels increased significantly. In contrast, when (PEI/pGL3 or PEI was added with RNP, the ROS levels were suppressed. The luciferase expression was increased by the treatment with RNP in a dose-dependent manner and the cellular uptake of pDNA was also increased. Inflammatory cytokines play an important role in ROS generation in vivo. In particular, tumor necrosis factor (TNF-α caused intracellular ROS generation in HeLa cells and decreased gene expression. RNP treatment suppressed ROS production even in the presence of TNF-α and increased gene expression. This anti-inflammatory property of RNP suggests that it may be used as an effective adjuvant for non-viral gene delivery systems.

  14. Chest associated to motor physiotherapy improves cardiovascular variables in newborns with respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    de Abreu Luiz


    Full Text Available Abstract Background We aimed to evaluate the effects of chest and motor physiotherapy treatment on hemodynamic variables in preterm newborns with respiratory distress syndrome. Methods We evaluated heart rate (HR, respiratory rate (RR, systolic (SAP, mean (MAP and diastolic arterial pressure (DAP, temperature and oxygen saturation (SO2% in 44 newborns with respiratory distress syndrome. We compared all variables between before physiotherapy treatment vs. after the last physiotherapy treatment. Newborns were treated during 11 days. Variables were measured 2 minutes before and 5 minutes after each physiotherapy treatment. We applied paired Student t test to compare variables between the two periods. Results HR (148.5 ± 8.5 bpm vs. 137.1 ± 6.8 bpm - p 2%. Conclusions Chest and motor physiotherapy improved cardiovascular parameters in respiratory distress syndrome newborns.

  15. Improved method for solving the neutron transport problem by discretization of space and energy variables

    International Nuclear Information System (INIS)

    Bosevski, T.


    The polynomial interpolation of neutron flux between the chosen space and energy variables enabled transformation of the integral transport equation into a system of linear equations with constant coefficients. Solutions of this system are the needed values of flux for chosen values of space and energy variables. The proposed improved method for solving the neutron transport problem including the mathematical formalism is simple and efficient since the number of needed input data is decreased both in treating the spatial and energy variables. Mathematical method based on this approach gives more stable solutions with significantly decreased probability of numerical errors. Computer code based on the proposed method was used for calculations of one heavy water and one light water reactor cell, and the results were compared to results of other very precise calculations. The proposed method was better concerning convergence rate, decreased computing time and needed computer memory. Discretization of variables enabled direct comparison of theoretical and experimental results

  16. Size and Topology Optimization for Trusses with Discrete Design Variables by Improved Firefly Algorithm

    NARCIS (Netherlands)

    Wu, Yue; Li, Q.; Hu, Qingjie; Borgart, A.


    Firefly Algorithm (FA, for short) is inspired by the social behavior of fireflies and their phenomenon of bioluminescent communication. Based on the fundamentals of FA, two improved strategies are proposed to conduct size and topology optimization for trusses with discrete design variables. Firstly,

  17. An Improved Estimation Using Polya-Gamma Augmentation for Bayesian Structural Equation Models with Dichotomous Variables (United States)

    Kim, Seohyun; Lu, Zhenqiu; Cohen, Allan S.


    Bayesian algorithms have been used successfully in the social and behavioral sciences to analyze dichotomous data particularly with complex structural equation models. In this study, we investigate the use of the Polya-Gamma data augmentation method with Gibbs sampling to improve estimation of structural equation models with dichotomous variables.…

  18. Induction of mutation: Improvement of genetic variability of wheat (Triticum sp.)

    International Nuclear Information System (INIS)

    Parodi, P.C.P.


    The malnutrition problem in developing countries can be solved by increased production of foods with high proteic content. This paper discusses the application of mutagenesis by radiation in the development of an improved wheat variability with high content of proteins and amino acids. Wheat is the staple food of developing countries

  19. Improved means and methods for expressing recombinant proteins

    NARCIS (Netherlands)

    Poolman, Berend; Martinez Linares, Daniel; Gul, Nadia


    The invention relates to the field of genetic engineering and the production of recombinant proteins in microbial host cells. Provided is a method for enhanced expression of a recombinant protein of interest in a microbial host cell, comprising providing a microbial host cell wherein the function of

  20. Cellular variability of RpoS expression underlies subpopulation activation of an integrative and conjugative element.

    Directory of Open Access Journals (Sweden)

    Ryo Miyazaki

    Full Text Available Conjugative transfer of the integrative and conjugative element ICEclc in the bacterium Pseudomonas knackmussii is the consequence of a bistable decision taken in some 3% of cells in a population during stationary phase. Here we study the possible control exerted by the stationary phase sigma factor RpoS on the bistability decision. The gene for RpoS in P. knackmussii B13 was characterized, and a loss-of-function mutant was produced and complemented. We found that, in absence of RpoS, ICEclc transfer rates and activation of two key ICEclc promoters (P(int and P(inR decrease significantly in cells during stationary phase. Microarray and gene reporter analysis indicated that the most direct effect of RpoS is on P(inR, whereas one of the gene products from the P(inR-controlled operon (InrR transmits activation to P(int and other ICEclc core genes. Addition of a second rpoS copy under control of its native promoter resulted in an increase of the proportion of cells expressing the P(int and P(inR promoters to 18%. Strains in which rpoS was replaced by an rpoS-mcherry fusion showed high mCherry fluorescence of individual cells that had activated P(int and P(inR, whereas a double-copy rpoS-mcherry-containing strain displayed twice as much mCherry fluorescence. This suggested that high RpoS levels are a prerequisite for an individual cell to activate P(inR and thus ICEclc transfer. Double promoter-reporter fusions confirmed that expression of P(inR is dominated by extrinsic noise, such as being the result of cellular variability in RpoS. In contrast, expression from P(int is dominated by intrinsic noise, indicating it is specific to the ICEclc transmission cascade. Our results demonstrate how stochastic noise levels of global transcription factors can be transduced to a precise signaling cascade in a subpopulation of cells leading to ICE activation.

  1. Improved Sleep in Military Personnel is Associated with Changes in the Expression of Inflammatory Genes and Improvement in Depression Symptoms

    Directory of Open Access Journals (Sweden)

    Whitney S. Livingston


    Full Text Available Study Objectives: Sleep disturbances are common in military personnel and are associated with increased risk for psychiatric morbidity, including posttraumatic stress disorder and depression, as well as inflammation. Improved sleep quality is linked to reductions in inflammatory bio-markers; however, the underlying mechanisms remain elusive. Methods: In this study we examine whole genome expression changes related to improved sleep in 68 military personnel diagnosed with insomnia. Subjects were classified into the following groups and then compared: improved sleep (n=46, or non-improved sleep (n=22 following three months of standard of care treatment for insomnia. Within subject differential expression was determined from microarray data using the Partek Genomics Suite analysis program and the interactive pathway analysis was used to determine key regulators of observed expression changes. Changes in symptoms of depression and posttraumatic stress disorder were also compared. Results: At baseline both groups were similar in demographics, clinical characteristics, and gene-expression profiles. The microarray data revealed that 217 coding genes were differentially expressed at the follow-up-period compared to baseline in the participants with improved sleep. Expression of inflammatory cytokines were reduced including IL-1β, IL-6, IL-8 and IL-13, with fold changes ranging from -3.19 to -2.1, and there were increases in the expression of inflammatory regulatory genes including toll-like receptors 1, 4, 7, and 8 in the improved sleep group. Interactive pathway analysis revealed 6 gene networks, including ubiquitin which was a major regulator in these gene-expression changes. The improved sleep group also had a significant reduction in the severity of depressive symptoms.Conclusions: Interventions that restore sleep likely reduce the expression of inflammatory genes, which relate to ubiquitin genes and relate to reductions in depressive symptoms.

  2. Variability in Cadence During Forced Cycling Predicts Motor Improvement in Individuals With Parkinson’s Disease (United States)

    Ridgel, Angela L.; Abdar, Hassan Mohammadi; Alberts, Jay L.; Discenzo, Fred M.; Loparo, Kenneth A.


    Variability in severity and progression of Parkinson’s disease symptoms makes it challenging to design therapy interventions that provide maximal benefit. Previous studies showed that forced cycling, at greater pedaling rates, results in greater improvements in motor function than voluntary cycling. The precise mechanism for differences in function following exercise is unknown. We examined the complexity of biomechanical and physiological features of forced and voluntary cycling and correlated these features to improvements in motor function as measured by the Unified Parkinson’s Disease Rating Scale (UPDRS). Heart rate, cadence, and power were analyzed using entropy signal processing techniques. Pattern variability in heart rate and power were greater in the voluntary group when compared to forced group. In contrast, variability in cadence was higher during forced cycling. UPDRS Motor III scores predicted from the pattern variability data were highly correlated to measured scores in the forced group. This study shows how time series analysis methods of biomechanical and physiological parameters of exercise can be used to predict improvements in motor function. This knowledge will be important in the development of optimal exercise-based rehabilitation programs for Parkinson’s disease. PMID:23144045

  3. Improving stability and curving passing performance for railway vehicles with a variable stiffness MRF rubber joint (United States)

    Harris, B. J.; Sun, S. S.; Li, W. H.


    With the growing need for effective intercity transport, the need for more advanced rail vehicle technology has never been greater. The conflicting primary longitudinal suspension requirements of high speed stability and curving performance limit the development of rail vehicle technology. This paper presents a novel magnetorheological fluid based joint with variable stiffness characteristics for the purpose of overcoming this parameter conflict. Firstly, the joint design and working principle is developed. Following this, a prototype is tested by MTS to characterize its variable stiffness properties under a range of conditions. Lastly, the performance of the proposed MRF rubber joint with regard to improving train stability and curving performance is numerically evaluated.

  4. Good days and bad days in dementia: a qualitative chart review of variable symptom expression. (United States)

    Rockwood, Kenneth; Fay, Sherri; Hamilton, Laura; Ross, Elyse; Moorhouse, Paige


    Despite its importance in the lived experience of dementia, symptom fluctuation has been little studied outside Lewy body dementia. We aimed to characterize symptom fluctuation in patients with Alzheimer's disease (AD) and mixed dementia. A qualitative analysis of health records that included notations on good days and bad days yielded 52 community-dwelling patients (women, n = 30; aged 39-91 years; mild dementia, n = 26, chiefly AD, n = 36). Good days/bad days were most often described as changes in the same core set of symptoms (e.g. less/more verbal repetition). In other cases, only good or only bad days were described (e.g., no bad days, better sense of humor on good days). Good days were typically associated with improved global cognition, function, interest, and initiation. Bad days were associated with frequent verbal repetition, poor memory, increased agitation and other disruptive behaviors. Clinically important variability in symptoms appears common in AD and mixed dementia. Even so, what makes a day "good" is not simply more (or less) of what makes a day "bad". Further investigation of the factors that facilitate or encourage good days and mitigate bad days may help improve quality of life for patients and caregivers.


    International Nuclear Information System (INIS)

    Fruth, T.; Cabrera, J.; Csizmadia, Sz.; Eigmüller, P.; Erikson, A.; Kirste, S.; Pasternacki, T.; Rauer, H.; Titz-Weider, R.; Kabath, P.; Chini, R.; Lemke, R.; Murphy, M.


    The CoRoT field LRa02 has been observed with the Berlin Exoplanet Search Telescope II (BEST II) during the southern summer 2007/2008. A first analysis of stellar variability led to the publication of 345 newly discovered variable stars. Now, a deeper analysis of this data set was used to optimize the variability search procedure. Several methods and parameters have been tested in order to improve the selection process compared to the widely used J index for variability ranking. This paper describes an empirical approach to treat systematic trends in photometric data based upon the analysis of variance statistics that can significantly decrease the rate of false detections. Finally, the process of reanalysis and method improvement has virtually doubled the number of variable stars compared to the first analysis by Kabath et al. A supplementary catalog of 272 previously unknown periodic variables plus 52 stars with suspected variability is presented. Improved ephemerides are given for 19 known variables in the field. In addition, the BEST II results are compared with CoRoT data and its automatic variability classification.

  6. Bayesian nonparametric variable selection as an exploratory tool for discovering differentially expressed genes. (United States)

    Shahbaba, Babak; Johnson, Wesley O


    High-throughput scientific studies involving no clear a priori hypothesis are common. For example, a large-scale genomic study of a disease may examine thousands of genes without hypothesizing that any specific gene is responsible for the disease. In these studies, the objective is to explore a large number of possible factors (e.g., genes) in order to identify a small number that will be considered in follow-up studies that tend to be more thorough and on smaller scales. A simple, hierarchical, linear regression model with random coefficients is assumed for case-control data that correspond to each gene. The specific model used will be seen to be related to a standard Bayesian variable selection model. Relatively large regression coefficients correspond to potential differences in responses for cases versus controls and thus to genes that might 'matter'. For large-scale studies, and using a Dirichlet process mixture model for the regression coefficients, we are able to find clusters of regression effects of genes with increasing potential effect or 'relevance', in relation to the outcome of interest. One cluster will always correspond to genes whose coefficients are in a neighborhood that is relatively close to zero and will be deemed least relevant. Other clusters will correspond to increasing magnitudes of the random/latent regression coefficients. Using simulated data, we demonstrate that our approach could be quite effective in finding relevant genes compared with several alternative methods. We apply our model to two large-scale studies. The first study involves transcriptome analysis of infection by human cytomegalovirus. The second study's objective is to identify differentially expressed genes between two types of leukemia. Copyright © 2012 John Wiley & Sons, Ltd.

  7. A hypothesis on improving foreign accents by optimizing variability in vocal learning brain circuits


    Simmonds, Anna J.


    Rapid vocal motor learning is observed when acquiring a language in early childhood, or learning to speak another language later in life. Accurate pronunciation is one of the hardest things for late learners to master and they are almost always left with a non-native accent. Here, I propose a novel hypothesis that this accent could be improved by optimizing variability in vocal learning brain circuits during learning. Much of the neurobiology of human vocal motor learning has been inferred fr...

  8. A hypothesis on improving foreign accents by optimizing variability in vocal learning brain circuits. (United States)

    Simmonds, Anna J


    Rapid vocal motor learning is observed when acquiring a language in early childhood, or learning to speak another language later in life. Accurate pronunciation is one of the hardest things for late learners to master and they are almost always left with a non-native accent. Here, I propose a novel hypothesis that this accent could be improved by optimizing variability in vocal learning brain circuits during learning. Much of the neurobiology of human vocal motor learning has been inferred from studies on songbirds. Jarvis (2004) proposed the hypothesis that as in songbirds there are two pathways in humans: one for learning speech (the striatal vocal learning pathway), and one for production of previously learnt speech (the motor pathway). Learning new motor sequences necessary for accurate non-native pronunciation is challenging and I argue that in late learners of a foreign language the vocal learning pathway becomes inactive prematurely. The motor pathway is engaged once again and learners maintain their original native motor patterns for producing speech, resulting in speaking with a foreign accent. Further, I argue that variability in neural activity within vocal motor circuitry generates vocal variability that supports accurate non-native pronunciation. Recent theoretical and experimental work on motor learning suggests that variability in the motor movement is necessary for the development of expertise. I propose that there is little trial-by-trial variability when using the motor pathway. When using the vocal learning pathway variability gradually increases, reflecting an exploratory phase in which learners try out different ways of pronouncing words, before decreasing and stabilizing once the "best" performance has been identified. The hypothesis proposed here could be tested using behavioral interventions that optimize variability and engage the vocal learning pathway for longer, with the prediction that this would allow learners to develop new motor

  9. Heterologous transporter expression for improved fatty alcohol secretion in yeast

    DEFF Research Database (Denmark)

    Hu, Yating; Zhu, Zhiwei; Nielsen, Jens


    The yeast Saccharomyces cerevisiae is an attractive host for industrial scale production of biofuels including fatty alcohols due to its robustness and tolerance towards harsh fermentation conditions. Many metabolic engineering strategies have been applied to generate high fatty alcohol production...... transporters tested, human FATP1 was shown to mediate fatty alcohol export in a high fatty alcohol production yeast strain. An approximately five-fold increase of fatty alcohol secretion was achieved. The results indicate that the overall cell fitness benefited from fatty alcohol secretion and that the acyl......-CoA synthase activity of FATP1 contributed to increased cell growth as well. This is the first study that enabled an increased cell fitness for fatty alcohol production by heterologous transporter expression in yeast, and this investigation indicates a new potential function of FATP1, which has been known...

  10. Shared Gaussian Process Latent Variable Model for Multi-view Facial Expression Recognition

    NARCIS (Netherlands)

    Eleftheriadis, Stefanos; Rudovic, Ognjen; Pantic, Maja

    Facial-expression data often appear in multiple views either due to head-movements or the camera position. Existing methods for multi-view facial expression recognition perform classification of the target expressions either by using classifiers learned separately for each view or by using a single

  11. Improved variable reduction in partial least squares modelling based on predictive-property-ranked variables and adaptation of partial least squares complexity. (United States)

    Andries, Jan P M; Vander Heyden, Yvan; Buydens, Lutgarde M C


    The calibration performance of partial least squares for one response variable (PLS1) can be improved by elimination of uninformative variables. Many methods are based on so-called predictive variable properties, which are functions of various PLS-model parameters, and which may change during the variable reduction process. In these methods variable reduction is made on the variables ranked in descending order for a given variable property. The methods start with full spectrum modelling. Iteratively, until a specified number of remaining variables is reached, the variable with the smallest property value is eliminated; a new PLS model is calculated, followed by a renewed ranking of the variables. The Stepwise Variable Reduction methods using Predictive-Property-Ranked Variables are denoted as SVR-PPRV. In the existing SVR-PPRV methods the PLS model complexity is kept constant during the variable reduction process. In this study, three new SVR-PPRV methods are proposed, in which a possibility for decreasing the PLS model complexity during the variable reduction process is build in. Therefore we denote our methods as PPRVR-CAM methods (Predictive-Property-Ranked Variable Reduction with Complexity Adapted Models). The selective and predictive abilities of the new methods are investigated and tested, using the absolute PLS regression coefficients as predictive property. They were compared with two modifications of existing SVR-PPRV methods (with constant PLS model complexity) and with two reference methods: uninformative variable elimination followed by either a genetic algorithm for PLS (UVE-GA-PLS) or an interval PLS (UVE-iPLS). The performance of the methods is investigated in conjunction with two data sets from near-infrared sources (NIR) and one simulated set. The selective and predictive performances of the variable reduction methods are compared statistically using the Wilcoxon signed rank test. The three newly developed PPRVR-CAM methods were able to retain

  12. Physical Exercise Improves Heart Rate Variability in Patients with Type 2 Diabetes: A Systematic Review. (United States)

    Villafaina, Santos; Collado-Mateo, Daniel; Fuentes, Juan Pedro; Merellano-Navarro, Eugenio; Gusi, Narcis


    The aim of the present systematic review is to provide an up-to-date analysis of the research on the effects of exercise programs on heart rate variability (HRV) in individuals with type 2 diabetes mellitus (T2DM). An electronic search of the literature (PubMed, PEDro and Web of Science) was performed. "HRV", "heart rate variability", "exercise", "physical" and "diabetes" were the terms used for article retrieval. Lastly, 15 articles were selected. PRISMA methodology was employed and data were extracted according to the PICOS approach. Although HRV is not routinely measured in the management of T2DM, it is an important measure due to its relation with mortality and diabetic neuropathy. Physical exercise has become a therapy for T2DM, because it improves physical fitness and functional capacity, enhances metabolic control and insulin sensitivity, reduces inflammatory markers and neuropathy symptoms and can increase the regenerative capacity of cutaneous axons, slowing or preventing neuropathy progression. However, it is not clear to what extent physical exercise can improve HRV in this population. Participation in the 15 selected studies was similar in men and women (48.01% men and 51.99% women). All the intervention programs included aerobic training, and it was complemented by strength training in four studies. Duration of physical exercise sessions ranged between 30 and 75 min, the frequency being between 2 and 7 days/week. Statistically significant improvements in groups with diabetes, relative to baseline, were observed in nine studies. More than 3 days per week of aerobic training, complemented by strength training, during at least 3 months seems to improve HRV in T2DM. Weekly frequency might be the most important factor to improve HRV. These aspects could help to design better programs based in scientific evidence, incorporating HRV as an important variable associated with diabetic neuropathy and mortality.

  13. Understanding Variability in Beach Slope to Improve Forecasts of Storm-induced Water Levels (United States)

    Doran, K. S.; Stockdon, H. F.; Long, J.


    The National Assessment of Hurricane-Induced Coastal Erosion Hazards combines measurements of beach morphology with storm hydrodynamics to produce forecasts of coastal change during storms for the Gulf of Mexico and Atlantic coastlines of the United States. Wave-induced water levels are estimated using modeled offshore wave height and period and measured beach slope (from dune toe to shoreline) through the empirical parameterization of Stockdon et al. (2006). Spatial and temporal variability in beach slope leads to corresponding variability in predicted wave setup and swash. Seasonal and storm-induced changes in beach slope can lead to differences on the order of a meter in wave runup elevation, making accurate specification of this parameter essential to skillful forecasts of coastal change. Spatial variation in beach slope is accounted for through alongshore averaging, but temporal variability in beach slope is not included in the final computation of the likelihood of coastal change. Additionally, input morphology may be years old and potentially very different than the conditions present during forecast storm. In order to improve our forecasts of hurricane-induced coastal erosion hazards, the temporal variability of beach slope must be included in the final uncertainty of modeled wave-induced water levels. Frequently collected field measurements of lidar-based beach morphology are examined for study sites in Duck, North Carolina, Treasure Island, Florida, Assateague Island, Virginia, and Dauphin Island, Alabama, with some records extending over a period of 15 years. Understanding the variability of slopes at these sites will help provide estimates of associated water level uncertainty which can then be applied to other areas where lidar observations are infrequent, and improve the overall skill of future forecasts of storm-induced coastal change. Stockdon, H. F., Holman, R. A., Howd, P. A., and Sallenger Jr, A. H. (2006). Empirical parameterization of setup

  14. Improving Surgical Safety and Nontechnical Skills in Variable-Resource Contexts: A Novel Educational Curriculum. (United States)

    Lin, Yihan; Scott, John W; Yi, Sojung; Taylor, Kathryn K; Ntakiyiruta, Georges; Ntirenganya, Faustin; Banguti, Paulin; Yule, Steven; Riviello, Robert


    A substantial proportion of adverse intraoperative events are attributed to failures in nontechnical skills. To strengthen these skills and improve surgical safety, the Non-Technical Skills for Surgeons (NOTSS) taxonomy was developed as a common framework. The NOTSS taxonomy was adapted for low- and middle-income countries, where variable resources pose a significant challenge to safe surgery. The NOTSS for variable-resource contexts (VRC) curriculum was developed and implemented in Rwanda, with the aim of enhancing knowledge and attitudes about nontechnical skills and promoting surgical safety. The NOTSS-VRC curriculum was developed through a rigorous process of integrating contextually appropriate values. It was implemented as a 1-day training course for surgical and anesthesia postgraduate trainees. The curriculum comprises lectures, videos, and group discussions. A pretraining and posttraining questionnaire was administered to compare knowledge and attitudes regarding nontechnical skills, and their potential to improve surgical safety. The setting of this study was in the tertiary teaching hospital of Kigali, Rwanda. Participants were residents of the University of Kigali. A total of 55 residents participated from general surgery (31.4%), obstetrics (25.5%), anesthesia (17.6%), and other surgical specialties (25.5%). In a paired analysis, understanding of NOTSS improved significantly (55.6% precourse, 80.9% postcourse, pskills would improve patient outcomes. Nontechnical skills must be highlighted in surgical training in low- and middle-income countries. The NOTSS-VRC curriculum can be implemented without additional technology or significant financial cost. Its deliberate design for resource-constrained settings allows it to be used both as an educational course and a quality improvement strategy. Our research demonstrates it is feasible to improve knowledge and attitudes about NOTSS through a 1-day course, and represents a novel approach to improving global

  15. Environmental interaction, additive and non-additive genetic variability is involved in the expression of tissue and whole-plant heat tolerance in upland cotton (Gossypium hirsutum. L

    Directory of Open Access Journals (Sweden)



    Full Text Available Heat tolerance is measured at tissue level by cellular membrane thermostability (CMT and at the whole plant level by the heat tolerance index (HTI. Eight upland cotton cultivars and 15 crosses were used to determine the type and extent of genetic variability associated with the expression of these traits between and within environments. Heat stress and non-stress conditions were used as the CMT environments and years for HTI. The wide variation in heterotic expression and combining ability effects observed for CMT and HTI suggest multigenic inheritance of these traits. Significant genetic variability across environments was evident but the traits were not highly heritable because of substantial environmental interaction. The available genetic variability included both additive and non-additive components, but the proportion of additive genetic variability was high for HTI. The parental cultivars CRIS-19 and CIM-448 were good donor parents for high CMT under heat-stressed conditions, and MNH-552 and N-Karishma under non-stressed conditions. Cultivar FH-634 was a good donor parent for HTI. The results show two types of general combining ability (GCA inheritance among high CMT parents: positive GCA inheritance expressed by CRIS-19 in the presence of heat stress and MNH-552 and N-Karishma in the absence of heat stress; and negative GCA inheritance expressed by FH-900 in the presence of heat stress. It was also evident that genes controlling high CMT in cultivar CRIS-19 were different from those present in the MNH-552, N-Karishma and FH-900 cultivars. Similarly, among high HTI parents, FH-634 showed positive and CIM-443 negative GCA inheritance. No significant relationship due to genetic causes existed between tissue and whole plant heat tolerance, diminishing the likelihood of simultaneous improvement and selection of the two traits.

  16. Induced Mutation on Jatropha (Jatropha Curcas L.) for Improvement of Agronomic Characters Variability

    International Nuclear Information System (INIS)

    Ita-Dwimahyani; Ishak


    Induced mutation can be used for improving quality in term of seed production, oil content in seed and early maturity of Jatropha with the aim for bio d iesel in Indonesia. The doses of 10, 15, 20, and 25 Gy of gamma applied to cuttings was able to increase genetic variability in vegetatively propagated plants of Jatropha at M1V1 (mutant-1 vegetative-1) generation. Selection for desirable trait will be done at M1V2 (mutant-1 and vegetative-2) generation until homogenous plants obtained. Gamma rays at dose of 20 to 25 Gy damaged several genes controlling growth and development on Jatropha which was shown by dwarf and poor plant growth compared to control (plant without irradiation). Irradiation with the dose of 10 Gy raised genetic variability on plant development which was identified with early maturity. 100 seeds weight was 30% over control, and the number of branch growth was good. (author)

  17. Expressing Environment Assumptions and Real-time Requirements for a Distributed Embedded System with Shared Variables

    DEFF Research Database (Denmark)

    Tjell, Simon; Fernandes, João Miguel


    In a distributed embedded system, it is often necessary to share variables among its computing nodes to allow the distribution of control algorithms. It is therefore necessary to include a component in each node that provides the service of variable sharing. For that type of component, this paper...

  18. Intratumoral heterogeneity of Ki67 expression in early breast cancers exceeds variability between individual tumours

    NARCIS (Netherlands)

    Focke, Cornelia M.; Decker, Thomas; van Diest, Paul J.


    Aims: Regional differences in proliferative activity are commonly seen within breast cancers, but little is known on the extent of intratumoral heterogeneity of Ki67 expression. Our aim was to study the intratumoral heterogeneity of Ki67 expression in early breast cancers and its association with

  19. Variable tidal volumes improve lung protective ventilation strategies in experimental lung injury. (United States)

    Spieth, Peter M; Carvalho, Alysson R; Pelosi, Paolo; Hoehn, Catharina; Meissner, Christoph; Kasper, Michael; Hübler, Matthias; von Neindorff, Matthias; Dassow, Constanze; Barrenschee, Martina; Uhlig, Stefan; Koch, Thea; de Abreu, Marcelo Gama


    Noisy ventilation with variable Vt may improve respiratory function in acute lung injury. To determine the impact of noisy ventilation on respiratory function and its biological effects on lung parenchyma compared with conventional protective mechanical ventilation strategies. In a porcine surfactant depletion model of lung injury, we randomly combined noisy ventilation with the ARDS Network protocol or the open lung approach (n = 9 per group). Respiratory mechanics, gas exchange, and distribution of pulmonary blood flow were measured at intervals over a 6-hour period. Postmortem, lung tissue was analyzed to determine histological damage, mechanical stress, and inflammation. We found that, at comparable minute ventilation, noisy ventilation (1) improved arterial oxygenation and reduced mean inspiratory peak airway pressure and elastance of the respiratory system compared with the ARDS Network protocol and the open lung approach, (2) redistributed pulmonary blood flow to caudal zones compared with the ARDS Network protocol and to peripheral ones compared with the open lung approach, (3) reduced histological damage in comparison to both protective ventilation strategies, and (4) did not increase lung inflammation or mechanical stress. Noisy ventilation with variable Vt and fixed respiratory frequency improves respiratory function and reduces histological damage compared with standard protective ventilation strategies.

  20. Quality Improvement Initiative to Decrease Variability of Emergency Physician Opioid Analgesic Prescribing

    Directory of Open Access Journals (Sweden)

    John H. Burton


    Full Text Available Introduction: Addressing pain is a crucial aspect of emergency medicine. Prescription opioids are commonly prescribed for moderate to severe pain in the emergency department (ED; unfortunately, prescribing practices are variable. High variability of opioid prescribing decisions suggests a lack of consensus and an opportunity to improve care. This quality improvement (QI initiative aimed to reduce variability in ED opioid analgesic prescribing. Methods: We evaluated the impact of a three-part QI initiative on ED opioid prescribing by physicians at seven sites. Stage 1: Retrospective baseline period (nine months. Stage 2: Physicians were informed that opioid prescribing information would be prospectively collected and feedback on their prescribing and that of the group would be shared at the end of the stage (three months. Stage 3: After physicians received their individual opioid prescribing data with blinded comparison to the group means (from Stage 2 they were informed that individual prescribing data would be unblinded and shared with the group after three months. The primary outcome was variability of the standard error of the mean and standard deviation of the opioid prescribing rate (defined as number of patients discharged with an opioid divided by total number of discharges for each provider. Secondary observations included mean quantity of pills per opioid prescription, and overall frequency of opioid prescribing. Results: The study group included 47 physicians with 149,884 ED patient encounters. The variability in prescribing decreased through each stage of the initiative as represented by the distributions for the opioid prescribing rate: Stage 1 mean 20%; Stage 2 mean 13% (46% reduction, p<0.01, and Stage 3 mean 8% (60% reduction, p<0.01. The mean quantity of pills prescribed per prescription was 16 pills in Stage 1, 14 pills in Stage 2 (18% reduction, p<0.01, and 13 pills in Stage 3 (18% reduction, p<0.01. The group mean

  1. An Improved Biclustering Algorithm and Its Application to Gene Expression Spectrum Analysis


    Qu, Hua; Wang, Liu-Pu; Liang, Yan-Chun; Wu, Chun-Guo


    Cheng and Church algorithm is an important approach in biclustering algorithms. In this paper, the process of the extended space in the second stage of Cheng and Church algorithm is improved and the selections of two important parameters are discussed. The results of the improved algorithm used in the gene expression spectrum analysis show that, compared with Cheng and Church algorithm, the quality of clustering results is enhanced obviously, the mining expression models are better, and the d...

  2. Improving Fault Ride-Through Capability of Variable Speed Wind Turbines in Distribution Networks

    DEFF Research Database (Denmark)

    Mokryani, Geev; Siano, P.; Piccolo, Antonio


    In this paper, a fuzzy controller for improving the fault ride-through (FRT) capability of variable speed wind turbines (WTs) equipped with a doubly fed induction generator (DFIG) is presented. DFIGs can be used as reactive power sources to control the voltage at the point of common coupling (PCC......). The controller is designed to compensate for the voltage at the PCC by simultaneously regulating the reactive and active power generated by WTs. The performance of the controller is evaluated in different case studies considering a different number of wind farms in different locations. Simulations carried out...

  3. Exploring Expressive Vocabulary Variability in Two-Year-Olds: The Role of Working Memory. (United States)

    Newbury, Jayne; Klee, Thomas; Stokes, Stephanie F; Moran, Catherine


    This study explored whether measures of working memory ability contribute to the wide variation in 2-year-olds' expressive vocabulary skills. Seventy-nine children (aged 24-30 months) were assessed by using standardized tests of vocabulary and visual cognition, a processing speed measure, and behavioral measures of verbal working memory and phonological short-term memory. Strong correlations were observed between phonological short-term memory, verbal working memory, and expressive vocabulary. Speed of spoken word recognition showed a moderate significant correlation with expressive vocabulary. In a multivariate regression model for expressive vocabulary, the most powerful predictor was a measure of phonological short-term memory (accounting for 66% unique variance), followed by verbal working memory (6%), sex (2%), and age (1%). Processing speed did not add significant unique variance. These findings confirm previous research positing a strong role for phonological short-term memory in early expressive vocabulary acquisition. They also extend previous research in two ways. First, a unique association between verbal working memory and expressive vocabulary in 2-year-olds was observed. Second, processing speed was not a unique predictor of variance in expressive vocabulary when included alongside measures of working memory.

  4. Baseline Chromatin Modification Levels May Predict Interindividual Variability in Ozone-Induced Gene Expression (United States)

    Traditional toxicological paradigms have relied on factors such as age, genotype, and disease status to explain variability in responsiveness to toxicant exposure; however, these are neither sufficient to faithfully identify differentially responsive individuals nor are they modi...

  5. Improvement of two-way continuous-variable quantum key distribution using optical amplifiers

    International Nuclear Information System (INIS)

    Zhang, Yi-Chen; Yu, Song; Gu, Wanyi; Li, Zhengyu; Sun, Maozhu; Peng, Xiang; Guo, Hong; Weedbrook, Christian


    The imperfections of a receiver's detector affect the performance of two-way continuous-variable (CV) quantum key distribution (QKD) protocols and are difficult to adjust in practical situations. We propose a method to improve the performance of two-way CV-QKD by adding a parameter-adjustable optical amplifier at the receiver. A security analysis is derived against a two-mode collective entangling cloner attack. Our simulations show that the proposed method can improve the performance of protocols as long as the inherent noise of the amplifier is lower than a critical value, defined as the tolerable amplifier noise. Furthermore, the optimal performance can approach the scenario where a perfect detector is used. (paper)

  6. Improved integrability of the gradients of solutions of elliptic equations with variable nonlinearity exponent

    International Nuclear Information System (INIS)

    Zhikov, Vasilii V; Pastukhova, Svetlana E


    Elliptic equations of p(x)-Laplacian type are investigated. There is a well-known logarithmic condition on the modulus of continuity of the nonlinearity exponent p(x), which ensures that a Laplacian with variable order of nonlinearity inherits many properties of the usual p-Laplacian of constant order. One of these is the so-called improved integrability of the gradient of the solution. It is proved in this paper that this property holds also under a slightly more general condition on the exponent p(x), although then the improvement of integrability is logarithmic rather than power-like. The method put forward is based on a new generalization of Gehring's lemma, which relies upon the reverse Hoelder inequality 'with increased support and exponent on the right-hand side'. A counterexample is constructed that reveals the extent to which the condition on the modulus of continuity obtained is sharp. Bibliography: 28 titles.

  7. Reducing variability of workforce as a tool to improve plan reliability

    DEFF Research Database (Denmark)

    Wandahl, Søren; Yicheng, S.; Zygmunt, K. J.

    Variability of flow is recognized as the greatest obstacle to production management. Since the work flow and labour flow are two dominators of work performance, it is important to manage them simultaneously. The objective of this paper is to examine whether by reducing the variance of a labour flow......, a plan reliability can be improved, therefore, three different construction labour data sets have been examined by utilizing Monte Carlo Simulation, to analyze the probability to finish simulated projects within a certain time. The research findings revealed that reducing variance in the workforce flow...... does not necessarily shorten the project length, nevertheless it increases probability to finish the tasks within a critical path duration. Additionally, it was concluded, that reducing the variance of crew allocation can improve the productivity....

  8. Vector Control Algorithm for Electric Vehicle AC Induction Motor Based on Improved Variable Gain PID Controller

    Directory of Open Access Journals (Sweden)

    Gang Qin


    Full Text Available The acceleration performance of EV, which affects a lot of performances of EV such as start-up, overtaking, driving safety, and ride comfort, has become increasingly popular in recent researches. An improved variable gain PID control algorithm to improve the acceleration performance is proposed in this paper. The results of simulation with Matlab/Simulink demonstrate the effectiveness of the proposed algorithm through the control performance of motor velocity, motor torque, and three-phase current of motor. Moreover, it is investigated that the proposed controller is valid by comparison with the other PID controllers. Furthermore, the AC induction motor experiment set is constructed to verify the effect of proposed controller.

  9. Why weight? Modelling sample and observational level variability improves power in RNA-seq analyses. (United States)

    Liu, Ruijie; Holik, Aliaksei Z; Su, Shian; Jansz, Natasha; Chen, Kelan; Leong, Huei San; Blewitt, Marnie E; Asselin-Labat, Marie-Liesse; Smyth, Gordon K; Ritchie, Matthew E


    Variations in sample quality are frequently encountered in small RNA-sequencing experiments, and pose a major challenge in a differential expression analysis. Removal of high variation samples reduces noise, but at a cost of reducing power, thus limiting our ability to detect biologically meaningful changes. Similarly, retaining these samples in the analysis may not reveal any statistically significant changes due to the higher noise level. A compromise is to use all available data, but to down-weight the observations from more variable samples. We describe a statistical approach that facilitates this by modelling heterogeneity at both the sample and observational levels as part of the differential expression analysis. At the sample level this is achieved by fitting a log-linear variance model that includes common sample-specific or group-specific parameters that are shared between genes. The estimated sample variance factors are then converted to weights and combined with observational level weights obtained from the mean-variance relationship of the log-counts-per-million using 'voom'. A comprehensive analysis involving both simulations and experimental RNA-sequencing data demonstrates that this strategy leads to a universally more powerful analysis and fewer false discoveries when compared to conventional approaches. This methodology has wide application and is implemented in the open-source 'limma' package. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  10. Improving breast cancer classification with mammography, supported on an appropriate variable selection analysis (United States)

    Pérez, Noel; Guevara, Miguel A.; Silva, Augusto


    This work addresses the issue of variable selection within the context of breast cancer classification with mammography. A comprehensive repository of feature vectors was used including a hybrid subset gathering image-based and clinical features. It aimed to gather experimental evidence of variable selection in terms of cardinality, type and find a classification scheme that provides the best performance over the Area Under Receiver Operating Characteristics Curve (AUC) scores using the ranked features subset. We evaluated and classified a total of 300 subsets of features formed by the application of Chi-Square Discretization, Information-Gain, One-Rule and RELIEF methods in association with Feed-Forward Backpropagation Neural Network (FFBP), Support Vector Machine (SVM) and Decision Tree J48 (DTJ48) Machine Learning Algorithms (MLA) for a comparative performance evaluation based on AUC scores. A variable selection analysis was performed for Single-View Ranking and Multi-View Ranking groups of features. Features subsets representing Microcalcifications (MCs), Masses and both MCs and Masses lesions achieved AUC scores of 0.91, 0.954 and 0.934 respectively. Experimental evidence demonstrated that classification performance was improved by combining image-based and clinical features. The most important clinical and image-based features were StromaDistortion and Circularity respectively. Other less important but worth to use due to its consistency were Contrast, Perimeter, Microcalcification, Correlation and Elongation.

  11. Variable RNA expression from recently acquired, endogenous viral elements (EVE) of white spot syndrome virus (WSSV) in shrimp. (United States)

    Utari, Heny Budi; Soowannayan, Chumporn; Flegel, Timothy W; Whityachumnarnkul, Boonsirm; Kruatrachue, Maleeya


    The viral accommodation hypothesis proposes that endogenous viral elements (EVE) from both RNA and DNA viruses are being continually integrated into the shrimp genome by natural host processes and that they can result in tolerance to viral infection by fortuitous production of antisense, immunospecific RNA (imRNA). Thus, we hypothesized that previously reported microarray results for the presence of white spot syndrome virus (WSSV) open reading frames (ORFs) formerly called 151, 366 and 427 in a domesticated giant tiger shrimp (Penaeus monodon) breeding stock might have represented expression from EVE, since the stock had shown uninterrupted freedom from white spot disease (WSD) for many generations. To test this hypothesis, 128 specimens from a current stock generation were confirmed for freedom from WSSV infection using two nested PCR detection methods. Subsequent nested-PCR testing revealed 33/128 specimens (26%) positive for at least one of the ORF at very high sequence identity (95-99%) to extant WSSV. Positive results for ORF 366 (now known to be a fragment of the WSSV capsid protein gene) dominated (28/33 = 84.8%), so 9 arbitrarily selected 366-positive specimens were tested by strand-specific, nested RT-PCR using DNase-treated RNA templates. This revealed variable RNA expression in individual shrimp including no RNA transcripts (n = 1), sense transcripts only (n = 1), antisense transcripts only (n = 2) or transcripts of both sense (n = 5). The latter 7 expression products indicated specimens producing putative imRNA. The variable types and numbers of the EVE and the variable RNA expression (including potential imRNA) support predictions of the viral accommodation hypothesis that EVE are randomly produced and expressed. Positive nested PCR test results for EVE of ORF 366 using DNA templates derived from shrimp sperm (germ cells), indicated that they were heritable. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Improving evapotranspiration in a land surface model using biophysical variables derived from MSG/SEVIRI satellite

    Directory of Open Access Journals (Sweden)

    N. Ghilain


    Full Text Available Monitoring evapotranspiration over land is highly dependent on the surface state and vegetation dynamics. Data from spaceborn platforms are desirable to complement estimations from land surface models. The success of daily evapotranspiration monitoring at continental scale relies on the availability, quality and continuity of such data. The biophysical variables derived from SEVIRI on board the geostationary satellite Meteosat Second Generation (MSG and distributed by the Satellite Application Facility on Land surface Analysis (LSA-SAF are particularly interesting for such applications, as they aimed at providing continuous and consistent daily time series in near-real time over Africa, Europe and South America. In this paper, we compare them to monthly vegetation parameters from a database commonly used in numerical weather predictions (ECOCLIMAP-I, showing the benefits of the new daily products in detecting the spatial and temporal (seasonal and inter-annual variability of the vegetation, especially relevant over Africa. We propose a method to handle Leaf Area Index (LAI and Fractional Vegetation Cover (FVC products for evapotranspiration monitoring with a land surface model at 3–5 km spatial resolution. The method is conceived to be applicable for near-real time processes at continental scale and relies on the use of a land cover map. We assess the impact of using LSA-SAF biophysical variables compared to ECOCLIMAP-I on evapotranspiration estimated by the land surface model H-TESSEL. Comparison with in-situ observations in Europe and Africa shows an improved estimation of the evapotranspiration, especially in semi-arid climates. Finally, the impact on the land surface modelled evapotranspiration is compared over a north–south transect with a large gradient of vegetation and climate in Western Africa using LSA-SAF radiation forcing derived from remote sensing. Differences are highlighted. An evaluation against remote sensing derived land

  13. Reasoning about variables in 11 to 18 year olds: informal, schooled and formal expression in learning about functions (United States)

    Ayalon, Michal; Watson, Anne; Lerman, Steve


    This study examines expressions of reasoning by some higher achieving 11 to 18 year-old English students responding to a survey consisting of function tasks developed in collaboration with their teachers. We report on 70 students, 10 from each of English years 7-13. Iterative and comparative analysis identified capabilities and difficulties of students and suggested conjectures concerning links between the affordances of the tasks, the curriculum, and students' responses. The paper focuses on five of the survey tasks and highlights connections between informal and formal expressions of reasoning about variables in learning. We introduce the notion of `schooled' expressions of reasoning, neither formal nor informal, to emphasise the role of the formatting tools introduced in school that shape future understanding and reasoning.

  14. Improving plot- and regional-scale crop models for simulating impacts of climate variability and extremes (United States)

    Tao, F.; Rötter, R.


    Many studies on global climate report that climate variability is increasing with more frequent and intense extreme events1. There are quite large uncertainties from both the plot- and regional-scale models in simulating impacts of climate variability and extremes on crop development, growth and productivity2,3. One key to reducing the uncertainties is better exploitation of experimental data to eliminate crop model deficiencies and develop better algorithms that more adequately capture the impacts of extreme events, such as high temperature and drought, on crop performance4,5. In the present study, in a first step, the inter-annual variability in wheat yield and climate from 1971 to 2012 in Finland was investigated. Using statistical approaches the impacts of climate variability and extremes on wheat growth and productivity were quantified. In a second step, a plot-scale model, WOFOST6, and a regional-scale crop model, MCWLA7, were calibrated and validated, and applied to simulate wheat growth and yield variability from 1971-2012. Next, the estimated impacts of high temperature stress, cold damage, and drought stress on crop growth and productivity based on the statistical approaches, and on crop simulation models WOFOST and MCWLA were compared. Then, the impact mechanisms of climate extremes on crop growth and productivity in the WOFOST model and MCWLA model were identified, and subsequently, the various algorithm and impact functions were fitted against the long-term crop trial data. Finally, the impact mechanisms, algorithms and functions in WOFOST model and MCWLA model were improved to better simulate the impacts of climate variability and extremes, particularly high temperature stress, cold damage and drought stress for location-specific and large area climate impact assessments. Our studies provide a good example of how to improve, in parallel, the plot- and regional-scale models for simulating impacts of climate variability and extremes, as needed for

  15. Expressing Environment Assumptions and Real-time Requirements for a Distributed Embedded System with Shared Variables

    DEFF Research Database (Denmark)

    Tjell, Simon; Fernandes, João Miguel


    In a distributed embedded system, it is often necessary to share variables among its computing nodes to allow the distribution of control algorithms. It is therefore necessary to include a component in each node that provides the service of variable sharing. For that type of component, this paper...... for the component. The CPN model can be used to validate the environment assumptions and the requirements. The validation is performed by execution of the model during which traces of events and states are automatically generated and evaluated against the requirements....

  16. Improved classification of Alzheimer's disease data via removal of nuisance variability.

    Directory of Open Access Journals (Sweden)

    Juha Koikkalainen

    Full Text Available Diagnosis of Alzheimer's disease is based on the results of neuropsychological tests and available supporting biomarkers such as the results of imaging studies. The results of the tests and the values of biomarkers are dependent on the nuisance features, such as age and gender. In order to improve diagnostic power, the effects of the nuisance features have to be removed from the data. In this paper, four types of interactions between classification features and nuisance features were identified. Three methods were tested to remove these interactions from the classification data. In stratified analysis, a homogeneous subgroup was generated from a training set. Data correction method utilized linear regression model to remove the effects of nuisance features from data. The third method was a combination of these two methods. The methods were tested using all the baseline data from the Alzheimer's Disease Neuroimaging Initiative database in two classification studies: classifying control subjects from Alzheimer's disease patients and discriminating stable and progressive mild cognitive impairment subjects. The results show that both stratified analysis and data correction are able to statistically significantly improve the classification accuracy of several neuropsychological tests and imaging biomarkers. The improvements were especially large for the classification of stable and progressive mild cognitive impairment subjects, where the best improvements observed were 6% units. The data correction method gave better results for imaging biomarkers, whereas stratified analysis worked well with the neuropsychological tests. In conclusion, the study shows that the excess variability caused by nuisance features should be removed from the data to improve the classification accuracy, and therefore, the reliability of diagnosis making.

  17. Exploring Expressive Vocabulary Variability in Two-Year-Olds: The Role of Working Memory (United States)

    Newbury, Jayne; Klee, Thomas; Stokes, Stephanie F.; Moran, Catherine


    Purpose: This study explored whether measures of working memory ability contribute to the wide variation in 2-year-olds' expressive vocabulary skills. Method: Seventy-nine children (aged 24-30 months) were assessed by using standardized tests of vocabulary and visual cognition, a processing speed measure, and behavioral measures of verbal working…

  18. A Variable Interval Rescheduling Strategy for Dynamic Flexible Job Shop Scheduling Problem by Improved Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Lei Wang


    Full Text Available In real-world manufacturing systems, production scheduling systems are often implemented under random or dynamic events like machine failure, unexpected processing times, stochastic arrival of the urgent orders, cancellation of the orders, and so on. These dynamic events will lead the initial scheduling scheme to be nonoptimal and/or infeasible. Hence, appropriate dynamic rescheduling approaches are needed to overcome the dynamic events. In this paper, we propose a dynamic rescheduling method based on variable interval rescheduling strategy (VIRS to deal with the dynamic flexible job shop scheduling problem considering machine failure, urgent job arrival, and job damage as disruptions. On the other hand, an improved genetic algorithm (GA is proposed for minimizing makespan. In our improved GA, a mix of random initialization population by combining initialization machine and initialization operation with random initialization is designed for generating high-quality initial population. In addition, the elitist strategy (ES and improved population diversity strategy (IPDS are used to avoid falling into the local optimal solution. Experimental results for static and several dynamic events in the FJSP show that our method is feasible and effective.

  19. An adaptive sampling method for variable-fidelity surrogate models using improved hierarchical kriging (United States)

    Hu, Jiexiang; Zhou, Qi; Jiang, Ping; Shao, Xinyu; Xie, Tingli


    Variable-fidelity (VF) modelling methods have been widely used in complex engineering system design to mitigate the computational burden. Building a VF model generally includes two parts: design of experiments and metamodel construction. In this article, an adaptive sampling method based on improved hierarchical kriging (ASM-IHK) is proposed to refine the improved VF model. First, an improved hierarchical kriging model is developed as the metamodel, in which the low-fidelity model is varied through a polynomial response surface function to capture the characteristics of a high-fidelity model. Secondly, to reduce local approximation errors, an active learning strategy based on a sequential sampling method is introduced to make full use of the already required information on the current sampling points and to guide the sampling process of the high-fidelity model. Finally, two numerical examples and the modelling of the aerodynamic coefficient for an aircraft are provided to demonstrate the approximation capability of the proposed approach, as well as three other metamodelling methods and two sequential sampling methods. The results show that ASM-IHK provides a more accurate metamodel at the same simulation cost, which is very important in metamodel-based engineering design problems.

  20. Exploring total cardiac variability in healthy and pathophysiological subjects using improved refined multiscale entropy. (United States)

    Marwaha, Puneeta; Sunkaria, Ramesh Kumar


    Multiscale entropy (MSE) and refined multiscale entropy (RMSE) techniques are being widely used to evaluate the complexity of a time series across multiple time scales 't'. Both these techniques, at certain time scales (sometimes for the entire time scales, in the case of RMSE), assign higher entropy to the HRV time series of certain pathologies than that of healthy subjects, and to their corresponding randomized surrogate time series. This incorrect assessment of signal complexity may be due to the fact that these techniques suffer from the following limitations: (1) threshold value 'r' is updated as a function of long-term standard deviation and hence unable to explore the short-term variability as well as substantial variability inherited in beat-to-beat fluctuations of long-term HRV time series. (2) In RMSE, entropy values assigned to different filtered scaled time series are the result of changes in variance, but do not completely reflect the real structural organization inherited in original time series. In the present work, we propose an improved RMSE (I-RMSE) technique by introducing a new procedure to set the threshold value by taking into account the period-to-period variability inherited in a signal and evaluated it on simulated and real HRV database. The proposed I-RMSE assigns higher entropy to the age-matched healthy subjects than that of patients suffering from atrial fibrillation, congestive heart failure, sudden cardiac death and diabetes mellitus, for the entire time scales. The results strongly support the reduction in complexity of HRV time series in female group, old-aged, patients suffering from severe cardiovascular and non-cardiovascular diseases, and in their corresponding surrogate time series.

  1. Do cooperative learning and family involvement improve variables linked to academic performance? (United States)

    Santos Rego, Miguel A; Ferraces Otero, María J; Godas Otero, Agustín; Lorenzo Moledo, María M


    One of the most serious problems in the Spanish education system is the high percentage of school failure in Compulsory Secondary Education. The aim of this study is to analyze the influence of a socio-educational program based on cooperative learning and family involvement on a series of variables related to academic performance, paying particular attention to the differences between retained and non-retained students. A two-group quasi-experimental design incorporating pre-testing and post-testing was used. The study involved 146 students in the experimental group and 123 in the control group, 8 teachers, and 89 parents or other family members. The program was observed to have a positive effect on self-image, study habits, satisfaction with the subject, maternal support and control, and opinions about the school. In addition, the results for non-retained students are better. Cooperative work and family involvement in education affect the variables which research links to improving school performance.

  2. Reducing Variability of Workforce as a Tool to Improve Plan Reliability

    DEFF Research Database (Denmark)

    Shen, Yicheng; Zygmunt, Katarzyna Julia; Wandahl, Søren


    Variability of flow is recognized as one of the greatest obstacles to production management. Since the work flow and labour flow are two dominators of work performance, it is important to manage them simultaneously. The objective of this paper is to examine if an increased plan reliability could...... of the workforce flow does not necessarily shorten the project length, nevertheless it increases probability to finish the tasks within a critical path duration. Additionally, it was concluded, that reducing the variance of crew allocation can improve the productivity....... be reached by reducing the variance of a labour flow. Therefore, three different construction labour data sets have been examined by utilizing Monte Carlo Simulation, to analyze the probability to finish simulated projects within a certain time. The research findings revealed that reducing variance...

  3. Logic Learning Machine and standard supervised methods for Hodgkin's lymphoma prognosis using gene expression data and clinical variables. (United States)

    Parodi, Stefano; Manneschi, Chiara; Verda, Damiano; Ferrari, Enrico; Muselli, Marco


    This study evaluates the performance of a set of machine learning techniques in predicting the prognosis of Hodgkin's lymphoma using clinical factors and gene expression data. Analysed samples from 130 Hodgkin's lymphoma patients included a small set of clinical variables and more than 54,000 gene features. Machine learning classifiers included three black-box algorithms ( k-nearest neighbour, Artificial Neural Network, and Support Vector Machine) and two methods based on intelligible rules (Decision Tree and the innovative Logic Learning Machine method). Support Vector Machine clearly outperformed any of the other methods. Among the two rule-based algorithms, Logic Learning Machine performed better and identified a set of simple intelligible rules based on a combination of clinical variables and gene expressions. Decision Tree identified a non-coding gene ( XIST) involved in the early phases of X chromosome inactivation that was overexpressed in females and in non-relapsed patients. XIST expression might be responsible for the better prognosis of female Hodgkin's lymphoma patients.

  4. Environmental variables influencing the expression of morphological characteristics in clones of the forage cactus

    Directory of Open Access Journals (Sweden)

    Marcela Lúcia Barbosa

    Full Text Available ABSTRACT The environmental factors that affect the morphological characteristics of different genera of cacti are little known. The aim of this study therefore was to analyse the contribution of environmental variables to growth in cladodes and plant of forage cactus clones of the genera Nopalea and Opuntia. The data used in this study were obtained from an experiment conducted in Serra Talhada, Pernambuco, Brazil, between 2012 and 2013, where the clones 'IPA Sertânia' (Nopalea, 'Miúda' (Nopalea and 'Orelha de Elefante Mexicana' (Opuntia were submitted to different irrigation depths (2.5, 5.0 and 7.5 mm and fixed irrigation intervals (7, 14 and 28 days. Morphological characteristics of the cladodes and plants and weather variables were obtained over time. Pearson's correlation, followed by multicollinearity, canonical and path analysis were applied. The minimum temperature, maximum and minimum relative humidity, wind speed and solar radiation were the variables that most affected growth in the cactus. The genus Opuntia showed less sensitivity to variations in air temperature compared to the genus Nopalea. The higher intensities of global solar radiation affected clones of the genus Nopalea more than the genus Opuntia. It can be concluded that there are different environmental requirements between forage cacti of the genera Nopalea and Opuntia.

  5. Collaborative Research: Improving Decadal Prediction of Arctic Climate Variability and Change Using a Regional Arctic

    Energy Technology Data Exchange (ETDEWEB)

    Gutowski, William J. [Iowa State Univ., Ames, IA (United States)


    This project developed and applied a regional Arctic System model for enhanced decadal predictions. It built on successful research by four of the current PIs with support from the DOE Climate Change Prediction Program, which has resulted in the development of a fully coupled Regional Arctic Climate Model (RACM) consisting of atmosphere, land-hydrology, ocean and sea ice components. An expanded RACM, a Regional Arctic System Model (RASM), has been set up to include ice sheets, ice caps, mountain glaciers, and dynamic vegetation to allow investigation of coupled physical processes responsible for decadal-scale climate change and variability in the Arctic. RASM can have high spatial resolution (~4-20 times higher than currently practical in global models) to advance modeling of critical processes and determine the need for their explicit representation in Global Earth System Models (GESMs). The pan-Arctic region is a key indicator of the state of global climate through polar amplification. However, a system-level understanding of critical arctic processes and feedbacks needs further development. Rapid climate change has occurred in a number of Arctic System components during the past few decades, including retreat of the perennial sea ice cover, increased surface melting of the Greenland ice sheet, acceleration and thinning of outlet glaciers, reduced snow cover, thawing permafrost, and shifts in vegetation. Such changes could have significant ramifications for global sea level, the ocean thermohaline circulation and heat budget, ecosystems, native communities, natural resource exploration, and commercial transportation. The overarching goal of the RASM project has been to advance understanding of past and present states of arctic climate and to improve seasonal to decadal predictions. To do this the project has focused on variability and long-term change of energy and freshwater flows through the arctic climate system. The three foci of this research are: - Changes

  6. Cohort-specific imputation of gene expression improves prediction of warfarin dose for African Americans. (United States)

    Gottlieb, Assaf; Daneshjou, Roxana; DeGorter, Marianne; Bourgeois, Stephane; Svensson, Peter J; Wadelius, Mia; Deloukas, Panos; Montgomery, Stephen B; Altman, Russ B


    Genome-wide association studies are useful for discovering genotype-phenotype associations but are limited because they require large cohorts to identify a signal, which can be population-specific. Mapping genetic variation to genes improves power and allows the effects of both protein-coding variation as well as variation in expression to be combined into "gene level" effects. Previous work has shown that warfarin dose can be predicted using information from genetic variation that affects protein-coding regions. Here, we introduce a method that improves dose prediction by integrating tissue-specific gene expression. In particular, we use drug pathways and expression quantitative trait loci knowledge to impute gene expression-on the assumption that differential expression of key pathway genes may impact dose requirement. We focus on 116 genes from the pharmacokinetic and pharmacodynamic pathways of warfarin within training and validation sets comprising both European and African-descent individuals. We build gene-tissue signatures associated with warfarin dose in a cohort-specific manner and identify a signature of 11 gene-tissue pairs that significantly augments the International Warfarin Pharmacogenetics Consortium dosage-prediction algorithm in both populations. Our results demonstrate that imputed expression can improve dose prediction and bridge population-specific compositions. MATLAB code is available at

  7. Orienting to face expression during encoding improves men's recognition of own gender faces. (United States)

    Fulton, Erika K; Bulluck, Megan; Hertzog, Christopher


    It is unclear why women have superior episodic memory of faces, but the benefit may be partially the result of women engaging in superior processing of facial expressions. Therefore, we hypothesized that orienting instructions to attend to facial expression at encoding would significantly improve men's memory of faces and possibly reduce gender differences. We directed 203 college students (122 women) to study 120 faces under instructions to orient to either the person's gender or their emotional expression. They later took a recognition test of these faces by either judging whether they had previously studied the same person or that person with the exact same expression; the latter test evaluated recollection of specific facial details. Orienting to facial expressions during encoding significantly improved men's recognition of own-gender faces and eliminated the advantage that women had for male faces under gender orienting instructions. Although gender differences in spontaneous strategy use when orienting to faces cannot fully account for gender differences in face recognition, orienting men to facial expression during encoding is one way to significantly improve their episodic memory for male faces. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Intravenous immunoglobulin treatment of the post-polio syndrome: sustained effects on quality of life variables and cytokine expression after one year follow up

    Directory of Open Access Journals (Sweden)

    Gonzalez Henrik


    Full Text Available Abstract Background Expression of inflammatory cytokines in cerebrospinal fluid (CSF has led to the hypothesis of intrathecal chronic inflammation to explain the denervation observed in post-polio syndrome (PPS. It has been shown that therapy with intravenous immunoglobulin (IVIG improves physical performance and dampens down the inflammatory process at 6 months in PPS patients. We here examined the effects of IVIG on cytokine expression and clinical outcome one year after IVIG treatment. Methods From a previous study with 135 PPS patients included, 41 patients were further evaluated before un-blinding for one year (21 placebo and 20 treated with IVIG, Xepol® 50 mg/ml, and were assessed for clinical variables by performing the Short Form-36 survey (SF-36 questionnaire assessment, the 6 minute walk distance test (6MWT and registering pain level by Visual Analogue Scale (VAS after IVIG treatment. A separate cohort of 37 PPS patients went through lumbar puncture (LP at baseline and 20 patients, treated with IVIG, repeated the LP one year later. Thirty patients affected with other neurological diseases (OND were used as control group. Inflammatory cytokines TNF, TGFβ, IFNγ, IL-23, IL-13 and IL-10 were measured in blood cells and CSF cells with RT-PCR. Results Scores of the physical components of SF-36 were significantly higher at the one year follow up time-point in the IVIG-treated patients when compared to baseline as well as to the control subjects. Pain VAS score and 6MWT improved significantly in the IVIG-treated patients when compared with baseline Relative expression of TNF and IFN-γ in both PBMCs and CSF from PPS patients were increased compared to OND subjects at baseline (p  Conclusions IVIG has effects on relevant QoL variables and inflammatory cytokines up to one year in patients with PPS. This gives a basis for scheduling IVIG in upcoming trials with this therapy.

  9. Improving the Accuracy of Laplacian Estimation with Novel Variable Inter-Ring Distances Concentric Ring Electrodes

    Directory of Open Access Journals (Sweden)

    Oleksandr Makeyev


    Full Text Available Noninvasive concentric ring electrodes are a promising alternative to conventional disc electrodes. Currently, the superiority of tripolar concentric ring electrodes over disc electrodes, in particular, in accuracy of Laplacian estimation, has been demonstrated in a range of applications. In our recent work, we have shown that accuracy of Laplacian estimation can be improved with multipolar concentric ring electrodes using a general approach to estimation of the Laplacian for an (n + 1-polar electrode with n rings using the (4n + 1-point method for n ≥ 2. This paper takes the next step toward further improving the Laplacian estimate by proposing novel variable inter-ring distances concentric ring electrodes. Derived using a modified (4n + 1-point method, linearly increasing and decreasing inter-ring distances tripolar (n = 2 and quadripolar (n = 3 electrode configurations are compared to their constant inter-ring distances counterparts. Finite element method modeling and analytic results are consistent and suggest that increasing inter-ring distances electrode configurations may decrease the truncation error resulting in more accurate Laplacian estimates compared to respective constant inter-ring distances configurations. For currently used tripolar electrode configuration, the truncation error may be decreased more than two-fold, while for the quadripolar configuration more than a six-fold decrease is expected.

  10. Improving the Accuracy of Laplacian Estimation with Novel Variable Inter-Ring Distances Concentric Ring Electrodes (United States)

    Makeyev, Oleksandr; Besio, Walter G.


    Noninvasive concentric ring electrodes are a promising alternative to conventional disc electrodes. Currently, the superiority of tripolar concentric ring electrodes over disc electrodes, in particular, in accuracy of Laplacian estimation, has been demonstrated in a range of applications. In our recent work, we have shown that accuracy of Laplacian estimation can be improved with multipolar concentric ring electrodes using a general approach to estimation of the Laplacian for an (n + 1)-polar electrode with n rings using the (4n + 1)-point method for n ≥ 2. This paper takes the next step toward further improving the Laplacian estimate by proposing novel variable inter-ring distances concentric ring electrodes. Derived using a modified (4n + 1)-point method, linearly increasing and decreasing inter-ring distances tripolar (n = 2) and quadripolar (n = 3) electrode configurations are compared to their constant inter-ring distances counterparts. Finite element method modeling and analytic results are consistent and suggest that increasing inter-ring distances electrode configurations may decrease the truncation error resulting in more accurate Laplacian estimates compared to respective constant inter-ring distances configurations. For currently used tripolar electrode configuration, the truncation error may be decreased more than two-fold, while for the quadripolar configuration more than a six-fold decrease is expected. PMID:27294933

  11. Improving Simulated Annealing by Replacing Its Variables with Game-Theoretic Utility Maximizers (United States)

    Wolpert, David H.; Bandari, Esfandiar; Tumer, Kagan


    The game-theory field of Collective INtelligence (COIN) concerns the design of computer-based players engaged in a non-cooperative game so that as those players pursue their self-interests, a pre-specified global goal for the collective computational system is achieved as a side-effect. Previous implementations of COIN algorithms have outperformed conventional techniques by up to several orders of magnitude, on domains ranging from telecommunications control to optimization in congestion problems. Recent mathematical developments have revealed that these previously developed algorithms were based on only two of the three factors determining performance. Consideration of only the third factor would instead lead to conventional optimization techniques like simulated annealing that have little to do with non-cooperative games. In this paper we present an algorithm based on all three terms at once. This algorithm can be viewed as a way to modify simulated annealing by recasting it as a non-cooperative game, with each variable replaced by a player. This recasting allows us to leverage the intelligent behavior of the individual players to substantially improve the exploration step of the simulated annealing. Experiments are presented demonstrating that this recasting significantly improves simulated annealing for a model of an economic process run over an underlying small-worlds topology. Furthermore, these experiments reveal novel small-worlds phenomena, and highlight the shortcomings of conventional mechanism design in bounded rationality domains.

  12. Variable Speed Limits: Strategies to Improve Safety and Traffic Parameters for a Bottleneck

    Directory of Open Access Journals (Sweden)

    M. Z. Hasanpour


    Full Text Available The primary purpose of the speed limit system is to enforce reasonable and safe speed. To reduce secondary problems such as accidents and queuing, Variable Speed Limits (VSL has been suggested. In this paper VSL is used to better safety and traffic parameters. Traffic parameters including speed, queue length and stopping time have been pondering. For VLS, an optimization decision tree algorithm with the function of microscopic simulation was used. The results in case of sub saturated, saturated and supersaturated at a bottleneck are examined and compared with the Allaby logic tree. The results show that the proposed decision tree shows an improved performance in terms of safety and comfort along the highway. The VSL pilot project is part of the Road Safety Improvement Program included in Iran’s road safety action plan that is in the research process in the BHRC Research Institute, Road and Housing & Urban Development Research that is planned for next 10-year Transportation safety view Plan.

  13. Improving RNA-Seq expression estimates by correcting for fragment bias (United States)


    The biochemistry of RNA-Seq library preparation results in cDNA fragments that are not uniformly distributed within the transcripts they represent. This non-uniformity must be accounted for when estimating expression levels, and we show how to perform the needed corrections using a likelihood based approach. We find improvements in expression estimates as measured by correlation with independently performed qRT-PCR and show that correction of bias leads to improved replicability of results across libraries and sequencing technologies. PMID:21410973

  14. Improvements in Key Cardiopulmonary Exercise Testing Variables Following Cardiac Rehabilitation in Patients With Coronary Artery Disease. (United States)

    Popovic, Dejana; Kumar, Nikhil; Chaudhry, Sundeep; Bagai, Akshay; Arena, Ross; Kumar, Naresh


    Improvements in cardiorespiratory fitness (VO2peak) post-cardiac rehabilitation (post-CR) are used to gauge therapeutic efficacy. The aim of the present study was to assess the effect of supervised CR on other cardiopulmonary exercise testing (CPX) variables, specifically those that reflect ventilatory efficiency and VO2 changes in relation to changes in work rate (WR). Patients (n = 142; mean age 63 ± 9 y; 23% female) with coronary artery disease (CAD) participated in supervised CR for 3 to 6 mo completing 60 ± 17 sessions (range: 32-96 sessions), with intensity derived from the baseline CPX. CPX was completed at baseline and post-CR on a cycle ergometer. The minimum heart rate (HR) during cycling was set 5 to 10 beats/min above the HR at ventilatory anaerobic threshold (VAT) while the maximum HR remained below the ischemic threshold observed during CPX, and this intensity was maintained for 25 min. VO2peak, peak O2 pulse, the minute ventilation/carbon dioxide production (VE/VCO2) slope, the oxygen uptake efficiency slope (OUES), and the ΔVO2/ΔWR slope were determined at baseline and post-CR. Following CR, there were significant improvements (all P < .001) in VO2peak (17.7 ± 4.7 mL/kg/min vs 20.9 ± 5.4 mL/kg/min), peak O2 pulse (11.6 ± 3.2 mL/beat vs 13.4 ± 3.6 mL/beat), VE/VCO2 slope (28.4 ± 5.3 vs 27.5 ± 4.7), OUES (1.8 ± 0.5 vs 2.0 ± 0.6), and ΔVO2/ΔWR slope (9.1 ± 1.2 mL/min/W vs 9.6 ± 1.1 mL/min/W). Key markers of ventilatory efficiency and VO2 kinetics during CPX significantly improve following CR. Expanding the list of variables assessed via CPX may provide better resolution in validation of CR therapeutic efficacy in patients with CAD.

  15. Fibroblast growth factor receptor 1 and cytokeratin 20 expressions and their relation to prognostic variables in bladder cancer. (United States)

    Abdul-Maksoud, Rehab S; Shalaby, Sally M; Elsayed, Walid S H; Elkady, Saad


    Tumor grade and stage are currently the most important prognostic variables in bladder cancer but establishing additional criteria is still needed for effective treatment. The aim of the study was to assess the expression of fibroblast growth factor receptor 1 (FGFR1) and cytokeratin 20 (CK20) in cancer bladder (CB) and to evaluate their association with the clinicopathological features of the disease. The study included 80 patients diagnosed as bladder cancer of different stages and grades and 80 patients with nonmalignant urothelial diseases of matched age and sex to the malignant group. The expressions of FGFR1 and CK20 in tissue samples were determined by RT-PCR and immunohistochemistry. The expression levels of FGFR1 and CK20 were increased in the malignant group when compared to the control group (Pbladder cancer reached 97.5% and 92.5%, respectively. Our results determined overexpression of both FGFR1 and CK20 in CB specimens. The alterations in the expression of FGFR1 and CK20 were associated with disease stage and grade. Lastly, combined detection of FGFR1 and CK20 had a high predictive prognostic value in differentiating invasive from non-invasive carcinoma. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Expressed prostatic secretion biomarkers improve stratification of NCCN active surveillance candidates: performance of secretion capacity and TMPRSS2:ERG models. (United States)

    Whelan, Christopher; Kawachi, Mark; Smith, David D; Linehan, Jennifer; Babilonia, Gail; Mejia, Rosa; Wilson, Timothy; Smith, Steven S


    Active surveillance is a viable patient option for prostate cancer provided that a clinical determination of low risk and presumably organ confined disease can be made. To standardize risk stratification schemes the NCCN (National Comprehensive Cancer Network®) provides guidelines for the active surveillance option. We determined the effectiveness of expressed prostatic secretion biomarkers for detecting occult risk factors in NCCN active surveillance candidates. Expressed prostatic secretion specimens were obtained before robot-assisted radical prostatectomy. Secretion capacity biomarkers, including total RNA and expressed prostatic secretion specimen volume, were measured by standard techniques. RNA expression biomarkers, including TXNRD1 mRNA, prostate specific antigen mRNA, TMPRSS2:ERG fusion mRNA and PCA3 mRNA, were measured by quantitative reverse-transcription polymerase chain reaction. Of the 528 patients from whom expressed prostatic secretions were collected 216 were eligible for active surveillance under NCCN guidelines. Variable selection on logistic regression identified 2 models, including one featuring types III and VI TMPRSS2:ERG variants, and one featuring 2 secretion capacity biomarkers. Of the 2 high performing models the secretion capacity model was most effective for detecting cases in this group that were up-staged or up-staged plus upgraded. It decreased the risk of up-staging in patients with a negative test almost eightfold and decreased the risk of up-staging plus upgrading about fivefold while doubling the prevalence of up-staging in the positive test group. Noninvasive expressed prostatic secretion testing may improve patient acceptance of active surveillance by dramatically reducing the presence of occult risk factors among those eligible for active surveillance under NCCN guidelines. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  17. Improving the knowledge about dissolved oxygen and chlorophyll variability at ESTOC by using autonomous vehicles. (United States)

    Cianca, A.; Caudet, E.; Vega, D.; Barrera, C.; Hernandez Brito, J.


    The European Station for Time Series in the Ocean, Canary Islands "ESTOC" is located in the Eastern Subtropical North Atlantic Gyre (29'10ºN, 15'30ºW). ESTOC started operations in 1994 based on a monthly ship-based sampling, in addition to hydrographic and sediment trap moorings. Since 2002, ESTOC is part of the European network for deep sea ocean observatories through several projects, among others ANIMATE (Atlantic Network of Interdisciplinary Moorings and Time-series for Europe), EuroSITES (European Ocean Observatory Network) and Fixed point Open Ocean Observatory network (FixO3). The main purpose of these projects was to improve the time-resolution of the biogeochemical measurements through moored biogeochemical sensors. Additionally, ESTOC is included in the Marine-Maritime observational network of the Macaronesian region, which is supported by the European overseas territories programs since 2009. This network aims to increase the quantity and quality of marine environmental observations. The goal is to understand phenomena which impact in the environment, and consequently at the socio-economy of the region to attempt their prediction. With this purpose, ESTOC has included the use of autonomous vehicles "glider" in order to increase the observational resolution and, by comparison with the parallel observational programs, to study the biogeochemical processes at different time scale resolutions. This study investigates the time variability of the dissolved oxygen and chlorophyll distributions in the water column focusing on the diel cycle, looking at the relevance of this variability in the already known seasonal distributions. Our interest is assessing net community production and remineralization rates through the use of oxygen variations, establishing the relationship between the DO anomalies values and those from the chlorophyll distribution in the water column.

  18. Variability of flax characters, associated with fibre formation, and environmental influence on their expression

    Directory of Open Access Journals (Sweden)

    Nina B Brach


    Full Text Available In this work the results of long-term evaluation of lines of flax genetic collection created in VIR are generalized. A wide variability of fibre productivity and quality characters, and also stability of their manifestation in varying environment is revealed. The genotypes possessing contrast traits of productivity, quality and stability of their display in different years are distinguished. Dependence of correlations between the evaluated characters on the environment parameters is detected. The described lines can serve as a material for profound studying of physiological processes of fibre formation, for the analysis of traits inheritance and successful breeding.

  19. Characterization and Improvement of RNA-Seq Precision in Quantitative Transcript Expression Profiling

    Energy Technology Data Exchange (ETDEWEB)

    Labaj, Pawel P.; Leparc, German G.; Linggi, Bryan E.; Markillie, Lye Meng; Wiley, H. S.; Kreil, David P.


    Measurement precision determines the power of any analysis to reliably identify significant signals, such as in screens for differential expression, independent of whether the experimental design incorporates replicates or not. With the compilation of large scale RNA-Seq data sets with technical replicate samples, however, we can now, for the first time, perform a systematic analysis of the precision of expression level estimates from massively parallel sequencing technology. This then allows considerations for its improvement by computational or experimental means. Results: We report on a comprehensive study of target coverage and measurement precision, including their dependence on transcript expression levels, read depth and other parameters. In particular, an impressive target coverage of 84% of the estimated true transcript population could be achieved with 331 million 50 bp reads, with diminishing returns from longer read lengths and even less gains from increased sequencing depths. Most of the measurement power (75%) is spent on only 7% of the known transcriptome, however, making less strongly expressed transcripts harder to measure. Consequently, less than 30% of all transcripts could be quantified reliably with a relative error < 20%. Based on established tools, we then introduce a new approach for mapping and analyzing sequencing reads that yields substantially improved performance in gene expression profiling, increasing the number of transcripts that can reliably be quantified to over 40%. Extrapolations to higher sequencing depths highlight the need for efficient complementary steps. In discussion we outline possible experimental and computational strategies for further improvements in quantification precision.

  20. Cohort-specific imputation of gene expression improves prediction of warfarin dose for African Americans

    Directory of Open Access Journals (Sweden)

    Assaf Gottlieb


    Full Text Available Abstract Background Genome-wide association studies are useful for discovering genotype–phenotype associations but are limited because they require large cohorts to identify a signal, which can be population-specific. Mapping genetic variation to genes improves power and allows the effects of both protein-coding variation as well as variation in expression to be combined into “gene level” effects. Methods Previous work has shown that warfarin dose can be predicted using information from genetic variation that affects protein-coding regions. Here, we introduce a method that improves dose prediction by integrating tissue-specific gene expression. In particular, we use drug pathways and expression quantitative trait loci knowledge to impute gene expression—on the assumption that differential expression of key pathway genes may impact dose requirement. We focus on 116 genes from the pharmacokinetic and pharmacodynamic pathways of warfarin within training and validation sets comprising both European and African-descent individuals. Results We build gene-tissue signatures associated with warfarin dose in a cohort-specific manner and identify a signature of 11 gene-tissue pairs that significantly augments the International Warfarin Pharmacogenetics Consortium dosage-prediction algorithm in both populations. Conclusions Our results demonstrate that imputed expression can improve dose prediction and bridge population-specific compositions. MATLAB code is available at

  1. Cellulase variants with improved expression, activity and stability, and use thereof (United States)

    Aehle, Wolfgang; Bott, Richard R; Bower, Benjamin; Caspi, Jonathan; Estell, David A; Goedegebuur, Frits; Hommes, Ronaldus W.J.; Kaper, Thijs; Kelemen, Bradley; Kralj, Slavko; Van Lieshout, Johan; Nikolaev, Igor; Van Stigt Thans, Sander; Wallace, Louise; Vogtentanz, Gudrun; Sandgren, Mats


    The present disclosure relates to cellulase variants. In particular the present disclosure relates to cellulase variants having improved expression, activity and/or stability. Also described are nucleic acids encoding the cellulase variants, compositions comprising the cellulase variants, and methods of use thereof.

  2. Cellulase variants with improved expression, activity and stability, and use thereof

    Energy Technology Data Exchange (ETDEWEB)

    Aehle, Wolfgang; Bott, Richard R.; Bower, Benjamin S.; Caspi, Jonathan; Goedegebuur, Frits; Hommes, Ronaldus Wilhelmus Joannes; Kaper, Thijs; Kelemen, Bradley R.; Kralj, Slavko; Van Lieshout, Johannes Franciscus Thomas; Nikolaev, Igor; Wallace, Louise; Van Stigt Thans, Sander; Vogtentanz, Gudrun; Sandgren, Mats


    The present disclosure relates to cellulase variants. In particular the present disclosure relates to cellulase variants having improved expression, activity and/or stability. Also described are nucleic acids encoding the cellulase variants, compositions comprising the cellulase variants, and methods of use thereof.

  3. Variable expressivity of FGF3 mutations associated with deafness and LAMM syndrome

    Directory of Open Access Journals (Sweden)

    Griffith Andrew J


    Full Text Available Abstract Background Recessive mutations of fibroblast growth factor 3 (FGF3 can cause LAMM syndrome (OMIM 610706, characterized by fully penetrant complete labyrinthine aplasia, microtia and microdontia. Methods We performed a prospective molecular genetic and clinical study of families segregating hearing loss linked to FGF3 mutations. Ten affected individuals from three large Pakistani families segregating FGF3 mutations were imaged with CT, MRI, or both to detect inner ear abnormalities. We also modeled the three dimensional structure of FGF3 to better understand the structural consequences of the three missense mutations. Results Two families segregated reported mutations (p.R104X and p.R95W and one family segregated a novel mutation (p.R132GfsX26 of FGF3. All individuals homozygous for p.R104X or p.R132GfsX26 had fully penetrant features of LAMM syndrome. However, recessive p.R95W mutations were associated with nearly normal looking auricles and variable inner ear structural phenotypes, similar to that reported for a Somali family also segregating p.R95W. This suggests that the mild phenotype is not entirely due to genetic background. Molecular modeling result suggests a less drastic effect of p.R95W on FGF3 function compared with known missense mutations detected in fully penetrant LAMM syndrome. Since we detected significant intrafamilial variability of the inner ear structural phenotype in the family segregating p.R95W, we also sequenced FGF10 as a likely candidate for a modifier. However, we did not find any sequence variation, pointing out that a larger sample size will be needed to map and identify a modifier. We also observed a mild to moderate bilateral conductive hearing loss in three carriers of p.R95W, suggesting either a semi-dominant effect of this mutant allele of FGF3, otitis media, or a consequence of genetic background in these three family members. Conclusions We noted a less prominent dental and external ear phenotype in

  4. Procedures for expressing natural or induced variability in carnation (Dianthus Caryophyllus L.)

    International Nuclear Information System (INIS)

    Simard, M.H.


    Mutagenesis (gamma rays) and in vitro organogenesis are used separately or both to diversify carnation varieties by revealing and creating variability. As regards to in vivo mutagenesis, an important diversification of the flower colour is obtained by applying a 60 Gray dose to two hundred rooted cuttings. The organogenesis ability has been tested among different types of explants. The petal of young floral bud shows the best caulogenesis capacities. The organogenesis region is located at the petal base. Histological studies reveal that neoformations are originated from epidermic and sub-epidermic cellular layers. The morphogenetic evolution of neoformations depends on growth factors imbalance. Isolated neoformations can grow in a vegetative way (vitrous plantlets) or in a reproductive one (petaloid structures). Modifications of the petal and neoformations culture conditions induce a normal development by preventing and suppressing vitrification. Histological studies show strong anatomic differences between vitrous and petaloid forms when compared to the normal ones. A method combining in vitro organogenesis and mutagenesis has been investigated. To avoid chimera, petals are irradiated the second day of culture (differentiated cells). A 20 or 40 Gray dose can be applied [fr

  5. Variability in surface antigen expression on neuroblastoma cells as revealed by monoclonal antibodies

    International Nuclear Information System (INIS)

    Malpas, J.S.; Kemshead, J.T.; Pritchard, J.; Greaves, M.F.


    In treatment programmes for neuroblastoma involving autologous bone marrow transplantation, a problem exists in the identification of small numbers of metastatic tumour cells present in the marrow aspirates. Reinfusion of tumour cells along with normal bone marrow may reseed the tumour within a patient who has received high dose chemotherapy. Formalin-induced fluorescence in neuroblastoma is a possible diagnostic aid, but this method has no therapeutic potential. Other methods of detecting tumour relying on gross physiological changes in the patient are not suitable for diagnosis of minimal metastatic disease. As an immunological approach to the problem, rabbit antisera to neuroblastoma have been raised but these reagents suffer from low titre after absorption to make them specific. The authors have used the technique of somatic cell hybridisation to raise monoclonal antibodies which bind to neuroblastoma cells and not to normal haemopoietic progenitors. A panel of such reagents to demonstrate heterogeneity in antigen expression amongst metastatic neuroblastoma cells was employed in a radioimmunoassay as diagnostic aid for this problem. (Auth.)

  6. Chronic variable stress improves glucose tolerance in rats with sucrose-induced prediabetes (United States)

    Packard, Amy E. B.; Ghosal, Sriparna; Herman, James P.; Woods, Stephen C.; Ulrich-Lai, Yvonne M.


    The incidence of type-2 diabetes (T2D) and the burden it places on individuals, as well as society as a whole, compels research into the causes, factors and progression of this disease. Epidemiological studies suggest that chronic stress exposure may contribute to the development and progression of T2D in human patients. To address the interaction between chronic stress and the progression of T2D, we developed a dietary model of the prediabetic state in rats utilizing unlimited access to 30% sucrose solution (in addition to unlimited access to normal chow and water), which led to impaired glucose tolerance despite elevated insulin levels. We then investigated the effects of a chronic variable stress paradigm (CVS; twice daily exposure to an unpredictable stressor for 2 weeks) on metabolic outcomes in this prediabetic model. Chronic stress improved glucose tolerance in prediabetic rats following a glucose challenge. Importantly, pair-fed control groups revealed that the beneficial effect of chronic stress did not result from the decreased food intake or body weight gain that occurred during chronic stress. The present work suggests that chronic stress in rodents can ameliorate the progression of diet-induced prediabetic disease independent of chronic stress-induced decreases in food intake and body weight. PMID:25001967

  7. Phage exposure causes dynamic shifts in the expression states of specific phase-variable genes of Campylobacter jejuni

    DEFF Research Database (Denmark)

    Aidley, Jack; Holst Sørensen, Martine C.; Bayliss, Christopher D.


    Phase variation (PV) creates phenotypic heterogeneity at high frequencies and in a reversible manner. This phenomenon allows bacteria to adapt to a variety of different environments and selective pressures. In Campylobacter jejuni this reversible adaptive process is mediated by mutations in homop......Phase variation (PV) creates phenotypic heterogeneity at high frequencies and in a reversible manner. This phenomenon allows bacteria to adapt to a variety of different environments and selective pressures. In Campylobacter jejuni this reversible adaptive process is mediated by mutations...... in homopolymeric G/C tracts. Many C. jejuni-specific phages are dependent on phase-variable surface structures for successful infection. We previously identified the capsular polysaccharide (CPS) moiety, MeOPN-GalfNAc, as a receptor for phage F336 and showed that phase-variable expression of the transferase...... for this CPS modification, cj1421, and two other phase-variable CPS genes generated phage resistance in C. jejuni. Here we investigate the population dynamics of C. jejuni NCTC11168 when exposed to phage F336 in vitro using a newly described method - the 28-locus-CJ11168 PV analysis. Dynamic switching...

  8. Variable Ventilation Improved Respiratory System Mechanics and Ameliorated Pulmonary Damage in a Rat Model of Lung Ischemia-Reperfusion. (United States)

    Soluri-Martins, André; Moraes, Lillian; Santos, Raquel S; Santos, Cintia L; Huhle, Robert; Capelozzi, Vera L; Pelosi, Paolo; Silva, Pedro L; de Abreu, Marcelo Gama; Rocco, Patricia R M


    Lung ischemia-reperfusion injury remains a major complication after lung transplantation. Variable ventilation (VV) has been shown to improve respiratory function and reduce pulmonary histological damage compared to protective volume-controlled ventilation (VCV) in different models of lung injury induced by endotoxin, surfactant depletion by saline lavage, and hydrochloric acid. However, no study has compared the biological impact of VV vs. VCV in lung ischemia-reperfusion injury, which has a complex pathophysiology different from that of other experimental models. Thirty-six animals were randomly assigned to one of two groups: (1) ischemia-reperfusion (IR), in which the left pulmonary hilum was completely occluded and released after 30 min; and (2) Sham, in which animals underwent the same surgical manipulation but without hilar clamping. Immediately after surgery, the left (IR-injured) and right (contralateral) lungs from 6 animals per group were removed, and served as non-ventilated group (NV) for molecular biology analysis. IR and Sham groups were further randomized to one of two ventilation strategies: VCV ( n = 6/group) [tidal volume (V T ) = 6 mL/kg, positive end-expiratory pressure (PEEP) = 2 cmH 2 O, fraction of inspired oxygen (FiO 2 ) = 0.4]; or VV, which was applied on a breath-to-breath basis as a sequence of randomly generated V T values ( n = 1200; mean V T = 6 mL/kg), with a 30% coefficient of variation. After 5 min of ventilation and at the end of a 2-h period (Final), respiratory system mechanics and arterial blood gases were measured. At Final, lungs were removed for histological and molecular biology analyses. Respiratory system elastance and alveolar collapse were lower in VCV than VV (mean ± SD, VCV 3.6 ± 1.3 cmH 2 0/ml and 2.0 ± 0.8 cmH 2 0/ml, p = 0.005; median [interquartile range], VCV 20.4% [7.9-33.1] and VV 5.4% [3.1-8.8], p = 0.04, respectively). In left lungs of IR animals, VCV increased the expression of interleukin-6 and

  9. Variable Ventilation Improved Respiratory System Mechanics and Ameliorated Pulmonary Damage in a Rat Model of Lung Ischemia-Reperfusion

    Directory of Open Access Journals (Sweden)

    Patricia R. M. Rocco


    Full Text Available Lung ischemia-reperfusion injury remains a major complication after lung transplantation. Variable ventilation (VV has been shown to improve respiratory function and reduce pulmonary histological damage compared to protective volume-controlled ventilation (VCV in different models of lung injury induced by endotoxin, surfactant depletion by saline lavage, and hydrochloric acid. However, no study has compared the biological impact of VV vs. VCV in lung ischemia-reperfusion injury, which has a complex pathophysiology different from that of other experimental models. Thirty-six animals were randomly assigned to one of two groups: (1 ischemia-reperfusion (IR, in which the left pulmonary hilum was completely occluded and released after 30 min; and (2 Sham, in which animals underwent the same surgical manipulation but without hilar clamping. Immediately after surgery, the left (IR-injured and right (contralateral lungs from 6 animals per group were removed, and served as non-ventilated group (NV for molecular biology analysis. IR and Sham groups were further randomized to one of two ventilation strategies: VCV (n = 6/group [tidal volume (VT = 6 mL/kg, positive end-expiratory pressure (PEEP = 2 cmH2O, fraction of inspired oxygen (FiO2 = 0.4]; or VV, which was applied on a breath-to-breath basis as a sequence of randomly generated VT values (n = 1200; mean VT = 6 mL/kg, with a 30% coefficient of variation. After 5 min of ventilation and at the end of a 2-h period (Final, respiratory system mechanics and arterial blood gases were measured. At Final, lungs were removed for histological and molecular biology analyses. Respiratory system elastance and alveolar collapse were lower in VCV than VV (mean ± SD, VCV 3.6 ± 1.3 cmH20/ml and 2.0 ± 0.8 cmH20/ml, p = 0.005; median [interquartile range], VCV 20.4% [7.9–33.1] and VV 5.4% [3.1–8.8], p = 0.04, respectively. In left lungs of IR animals, VCV increased the expression of interleukin-6 and intercellular

  10. Ivabradine Improves Heart Rate Variability in Patients with Nonischemic Dilated Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Ertugrul Kurtoglu


    Full Text Available Background: Ivabradine is a novel specific heart rate (HR-lowering agent that improves event-free survival in patients with heart failure (HF. Objectives: We aimed to evaluate the effect of ivabradine on time domain indices of heart rate variability (HRV in patients with HF. Methods: Forty-eight patients with compensated HF of nonischemic origin were included. Ivabradine treatment was initiated according to the latest HF guidelines. For HRV analysis, 24-h Holter recording was obtained from each patient before and after 8 weeks of treatment with ivabradine. Results: The mean RR interval, standard deviation of all normal to normal RR intervals (SDNN, the standard deviation of 5-min mean RR intervals (SDANN, the mean of the standard deviation of all normal-to-normal RR intervals for all 5-min segments (SDNN index, the percentage of successive normal RR intervals exceeding 50 ms (pNN50, and the square root of the mean of the squares of the differences between successive normal to normal RR intervals (RMSSD were low at baseline before treatment with ivabradine. After 8 weeks of treatment with ivabradine, the mean HR (83.6 ± 8.0 and 64.6 ± 5.8, p < 0.0001, mean RR interval (713 ± 74 and 943 ± 101 ms, p < 0.0001, SDNN (56.2 ± 15.7 and 87.9 ± 19.4 ms, p < 0.0001, SDANN (49.5 ± 14.7 and 76.4 ± 19.5 ms, p < 0.0001, SDNN index (24.7 ± 8.8 and 38.3 ± 13.1 ms, p < 0.0001, pNN50 (2.4 ± 1.6 and 3.2 ± 2.2 %, p < 0.0001, and RMSSD (13.5 ± 4.6 and 17.8 ± 5.4 ms, p < 0.0001 substantially improved, which sustained during both when awake and while asleep. Conclusion: Our findings suggest that treatment with ivabradine improves HRV in nonischemic patients with HF.

  11. Advanced technologies for improved expression of recombinant proteins in bacteria: perspectives and applications. (United States)

    Gupta, Sanjeev K; Shukla, Pratyoosh


    Prokaryotic expression systems are superior in producing valuable recombinant proteins, enzymes and therapeutic products. Conventional microbial technology is evolving gradually and amalgamated with advanced technologies in order to give rise to improved processes for the production of metabolites, recombinant biopharmaceuticals and industrial enzymes. Recently, several novel approaches have been employed in a bacterial expression platform to improve recombinant protein expression. These approaches involve metabolic engineering, use of strong promoters, novel vector elements such as inducers and enhancers, protein tags, secretion signals, high-throughput devices for cloning and process screening as well as fermentation technologies. Advancement of the novel technologies in E. coli systems led to the production of "difficult to express" complex products including small peptides, antibody fragments, few proteins and full-length aglycosylated monoclonal antibodies in considerable large quantity. Wacker's secretion technologies, Pfenex system, inducers, cell-free systems, strain engineering for post-translational modification, such as disulfide bridging and bacterial N-glycosylation, are still under evaluation for the production of complex proteins and peptides in E. coli in an efficient manner. This appraisal provides an impression of expression technologies developed in recent times for enhanced production of heterologous proteins in E. coli which are of foremost importance for diverse applications in microbiology and biopharmaceutical production.

  12. Methods for Using Small Non-Coding RNAs to Improve Recombinant Protein Expression in Mammalian Cells

    Directory of Open Access Journals (Sweden)

    Sarah Inwood


    Full Text Available The ability to produce recombinant proteins by utilizing different “cell factories” revolutionized the biotherapeutic and pharmaceutical industry. Chinese hamster ovary (CHO cells are the dominant industrial producer, especially for antibodies. Human embryonic kidney cells (HEK, while not being as widely used as CHO cells, are used where CHO cells are unable to meet the needs for expression, such as growth factors. Therefore, improving recombinant protein expression from mammalian cells is a priority, and continuing effort is being devoted to this topic. Non-coding RNAs are RNA segments that are not translated into a protein and often have a regulatory role. Since their discovery, major progress has been made towards understanding their functions. Non-coding RNA has been investigated extensively in relation to disease, especially cancer, and recently they have also been used as a method for engineering cells to improve their protein expression capability. In this review, we provide information about methods used to identify non-coding RNAs with the potential of improving recombinant protein expression in mammalian cell lines.

  13. Expression of activation-induced cytidine deaminase gene in B lymphocytes of patients with common variable immunodeficiency. (United States)

    Abolhassani, Hassan; Farrokhi, Amir Salek; Pourhamdi, Shabnam; Mohammadinejad, Payam; Sadeghi, Bamdad; Moazzeni, Seyed-Mohammad; Aghamohammadi, Asghar


    Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by reduced serum level of IgG, IgA or IgM and recurrent bacterial infections. Class switch recombination (CSR) as a critical process in immunoglobulin production is defective in a group of CVID patients. Activation-induced cytidine deaminase (AID) protein is an important molecule involving CSR process. The aim of this study was to investigate the AID gene mRNA production in a group of CVID patients indicating possible role of this molecule in this disorder. Peripheral blood mononuclear cells (PBMC) of 29 CVID patients and 21 healthy controls were isolated and stimulated by CD40L and IL-4 to induce AID gene expression. After 5 days AID gene mRNA production was investigated by real time polymerase chain reaction. AID gene was expressed in all of the studied patients. However the mean density of extracted AID mRNA showed higher level in CVID patients (230.95±103.04 ng/ml) rather than controls (210.00±44.72 ng/ml; P=0.5). CVID cases with lower level of AID had decreased total level of IgE (P=0.04) and stimulated IgE production (P=0.02); while cases with increased level of AID presented higher level of IgA (P=0.04) and numbers of B cells (P=0.02) and autoimmune disease (P=0.02). Different levels of AID gene expression may have important roles in dysregulation of immune system and final clinical presentation in CVID patients. Therefore investigating the expression of AID gene can help in classifying CVID patients.

  14. Cheetah interspecific SCNT followed by embryo aggregation improves in vitro development but not pluripotent gene expression. (United States)

    Moro, L N; Hiriart, M I; Buemo, C; Jarazo, J; Sestelo, A; Veraguas, D; Rodriguez-Alvarez, L; Salamone, D F


    The aim of this study was to evaluate the capacity of domestic cat (Dc, Felis silvestris) oocytes to reprogram the nucleus of cheetah (Ch, Acinonyx jubatus) cells by interspecies SCNT (iSCNT), by using embryo aggregation. Dc oocytes were in vitro matured and subjected to zona pellucida free (ZP-free) SCNT or iSCNT, depending on whether the nucleus donor cell was of Dc or Ch respectively. ZP-free reconstructed embryos were then cultured in microwells individually (Dc1X and Ch1X groups) or in couples (Dc2X and Ch2X groups). Embryo aggregation improved in vitro development obtaining 27.4, 47.7, 16.7 and 28.3% of blastocyst rates in the Dc1X, Dc2X, Ch1X and Ch2X groups, respectively (P<0.05). Moreover, aggregation improved the morphological quality of blastocysts from the Dc2X over the Dc1X group. Gene expression analysis revealed that Ch1X and Ch2X blastocysts had significantly lower relative expression of OCT4, CDX2 and NANOG than the Dc1X, Dc2X and IVF control groups. The OCT4, NANOG, SOX2 and CDX2 genes were overexpressed in Dc1X blastocysts, but the relative expression of these four genes decreased in the Dc2X, reaching similar relative levels to those of Dc IVF blastocysts. In conclusion, Ch blastocysts were produced using Dc oocytes, but with lower relative expression of pluripotent and trophoblastic genes, indicating that nuclear reprogramming could be still incomplete. Despite this, embryo aggregation improved the development of Ch and Dc embryos, and normalized Dc gene expression, which suggests that this strategy could improve full-term developmental efficiency of cat and feline iSCNT embryos. © 2015 Society for Reproduction and Fertility.

  15. Clinicopathological variables of sporadic schwannomas of peripheral nerve in 291 patients and expression of biologically relevant markers. (United States)

    Young, Eric D; Ingram, Davis; Metcalf-Doetsch, William; Khan, Dilshad; Al Sannaa, Ghadah; Le Loarer, Francois; Lazar, Alexander J F; Slopis, John; Torres, Keila E; Lev, Dina; Pollock, Raphael E; McCutcheon, Ian E


    OBJECTIVE While sporadic peripheral schwannomas (SPSs) are generally well treated with surgery, their biology is not well understood. Consequently, treatment options are limited. The aim of this study was to provide a comprehensive description of SPS. The authors describe clinicopathological features and treatment outcomes of patients harboring these tumors, and they assess expression of biomarkers using a clinically annotated tissue microarray. Together, these data give new insight into the biology and management of SPS. METHODS Patients presenting with a primary SPS between 1993 and 2011 (n = 291) were selected from an institutional registry to construct a clinical database. All patients underwent follow-up, and short- and long-term outcomes were assessed. Expression of relevant biomarkers was assessed using a new tissue microarray (n = 121). RESULTS SPSs were generally large (mean 5.5 cm) and frequently painful at presentation (55%). Most patients were treated with surgery (80%), the majority of whom experienced complete resolution (52%) or improvement (18%) of their symptoms. Tumors that were completely resected (85%) did not recur. Some patients experienced short-term (16%) and long-term (4%) complications postoperatively. Schwannomas expressed higher levels of platelet-derived growth factor receptor-β (2.1) than malignant peripheral nerve sheath tumors (MPNSTs) (1.5, p = 0.004) and neurofibromas (1.33, p = 0.007). Expression of human epidermal growth factor receptor-2 was greater in SPSs (0.91) than in MPNSTs (0.33, p = 0.002) and neurofibromas (0.33, p = 0.026). Epidermal growth factor receptor was expressed in far fewer SPS cells (10%) than in MPNSTs (58%, p SPSs more frequently expressed cytoplasmic survivin (66% of tumor cells) than normal nerve (46% of cells), but SPS expressed nuclear survivin in fewer tumor cells than in MPNSTs (24% and 50%, respectively; p = 0.018). CONCLUSIONS Complete resection is curative for SPS. Left untreated, however, these

  16. Mode choice models' ability to express intention to change travel behaviour considering non-compensatory rules and latent variables

    Directory of Open Access Journals (Sweden)

    Nobuhiro Sanko


    Full Text Available Disaggregate behaviour choice models have been improved in many aspects, but they are rarely evaluated from the viewpoint of their ability to express intention to change travel behaviour. This study compared various models, including objective and latent models and compensatory and non-compensatory decision-making models. Latent models contain latent factors calculated using the LISREL (linear structural relations model. Non-compensatory models are based on a lexicographic-semiorder heuristic. This paper proposes ‘probability increment’ and ‘joint probability increment’ as indicators for evaluating the ability of these models to express intention to change travel behaviour. The application to commuting travel data in the Chukyo metropolitan area in Japan showed that the appropriate non-compensatory and latent models outperform other models.

  17. Improving seasonal forecasts of hydroclimatic variables through the state of multiple large-scale climate signals (United States)

    Castelletti, A.; Giuliani, M.; Block, P. J.


    Increasingly uncertain hydrologic regimes combined with more frequent and intense extreme events are challenging water systems management worldwide, emphasizing the need of accurate medium- to long-term predictions to timely prompt anticipatory operations. Despite modern forecasts are skillful over short lead time (from hours to days), predictability generally tends to decrease on longer lead times. Global climate teleconnection, such as El Niño Southern Oscillation (ENSO), may contribute in extending forecast lead times. However, ENSO teleconnection is well defined in some locations, such as Western USA and Australia, while there is no consensus on how it can be detected and used in other regions, particularly in Europe, Africa, and Asia. In this work, we generalize the Niño Index Phase Analysis (NIPA) framework by contributing the Multi Variate Niño Index Phase Analysis (MV-NIPA), which allows capturing the state of multiple large-scale climate signals (i.e. ENSO, North Atlantic Oscillation, Pacific Decadal Oscillation, Atlantic Multi-decadal Oscillation, Indian Ocean Dipole) to forecast hydroclimatic variables on a seasonal time scale. Specifically, our approach distinguishes the different phases of the considered climate signals and, for each phase, identifies relevant anomalies in Sea Surface Temperature (SST) that influence the local hydrologic conditions. The potential of the MV-NIPA framework is demonstrated through an application to the Lake Como system, a regulated lake in northern Italy which is mainly operated for flood control and irrigation supply. Numerical results show high correlations between seasonal SST values and one season-ahead precipitation in the Lake Como basin. The skill of the resulting MV-NIPA forecast outperforms the one of ECMWF products. This information represents a valuable contribution to partially anticipate the summer water availability, especially during drought events, ultimately supporting the improvement of the Lake Como

  18. Variable corneal compensation improves discrimination between normal and glaucomatous eyes with the scanning laser polarimeter. (United States)

    Tannenbaum, Dana P; Hoffman, Douglas; Lemij, Hans G; Garway-Heath, David F; Greenfield, David S; Caprioli, Joseph


    The presently available scanning laser polarimeter (SLP) has a fixed corneal compensator (FCC) that neutralizes corneal birefringence only in eyes with birefringence that matches the population mode. A prototype variable corneal compensator (VCC) provides neutralization of individual corneal birefringence based on individual macular retardation patterns. The aim of this study was to evaluate the relative ability of the SLP with the FCC and with the VCC to discriminate between normal and glaucomatous eyes. Prospective, nonrandomized, comparative case series. Algorithm-generating set consisting of 56 normal eyes and 55 glaucomatous eyes and an independent data set consisting of 83 normal eyes and 56 glaucomatous eyes. Sixteen retardation measurements were obtained with the SLP with the FCC and the VCC from all subjects. Dependency of parameters on age, gender, ethnic origin, and eye side was sought. Logistic regression was used to evaluate how well the various parameters could detect glaucoma. Discriminant functions were generated, and the area under the receiver operating characteristic (ROC) curve was determined. Discrimination between normal and glaucomatous eyes on the basis of single parameters was significantly better with the VCC than with the FCC for 6 retardation parameters: nasal average (P = 0.0003), superior maximum (P = 0.0003), ellipse average (P = 0.002), average thickness (P = 0.003), superior average (P = 0.010), and inferior average (P = 0.010). Discriminant analysis identified the optimal combination of parameters for the FCC and for the VCC. When the discriminant functions were applied to the independent data set, areas under the ROC curve were 0.84 for the FCC and 0.90 for the VCC (PFCC and 0.90 for the VCC (P<0.016). Individual correction for corneal birefringence with the VCC significantly improved the ability of the SLP to distinguish between normal and glaucomatous eyes and enabled detection of patients with early glaucoma.

  19. Gene expression during blow fly development: improving the precision of age estimates in forensic entomology. (United States)

    Tarone, Aaron M; Foran, David R


    Forensic entomologists use size and developmental stage to estimate blow fly age, and from those, a postmortem interval. Since such estimates are generally accurate but often lack precision, particularly in the older developmental stages, alternative aging methods would be advantageous. Presented here is a means of incorporating developmentally regulated gene expression levels into traditional stage and size data, with a goal of more precisely estimating developmental age of immature Lucilia sericata. Generalized additive models of development showed improved statistical support compared to models that did not include gene expression data, resulting in an increase in estimate precision, especially for postfeeding third instars and pupae. The models were then used to make blind estimates of development for 86 immature L. sericata raised on rat carcasses. Overall, inclusion of gene expression data resulted in increased precision in aging blow flies. © 2010 American Academy of Forensic Sciences.

  20. Benazepril hydrochloride improves diabetic nephropathy and decreases proteinuria by decreasing ANGPTL-4 expression. (United States)

    Xue, Lingyu; Feng, Xiaoqing; Wang, Chuanhai; Zhang, Xuebin; Sun, Wenqiang; Yu, Kebo


    This study aimed to investigate the effects of benazepril hydrochloride (BH) on proteinuria and ANGPTL-4 expression in a diabetic nephropathy (DN) rat model. A total of 72 Wistar male rats were randomly divided into three groups: normal control (NC), DN group and BH treatment (BH) groups. The DN model was induced by streptozotocin (STZ). Weight, glucose, proteinuria, biochemical indicators and the kidney weight index were examined at 8, 12 and 16 weeks. In addition, ANGPTL-4 protein and mRNA expressions were assessed by immunohistochemistry and qRT-PCR, respectively. Relationships between ANGPTL-4 and biochemical indicators were investigated using Spearman analysis. Weight was significantly lower but glucose levels were significantly higher in both the DN and BH groups than in the NC group (P Benazepril hydrochloride improves DN and decreases proteinuria by decreasing ANGPTL-4 expression.

  1. Globular Cluster Variable Stars—Atlas and Coordinate Improvement using AAVSOnet Telescopes (Abstract) (United States)

    Welch, D.; Henden, A.; Bell, T.; Suen, C.; Fare, I.; Sills, A.


    (Abstract only) The variable stars of globular clusters have played and continue to play a significant role in our understanding of certain classes of variable stars. Since all stars associated with a cluster have the same age, metallicity, distance and usually very similar (if not identical reddenings), such variables can produce uniquely powerful constraints on where certain types of pulsation behaviors are excited. Advanced amateur astronomers are increasingly well-positioned to provide long-term CCD monitoring of globular cluster variable star but are hampered by a long history of poor or inaccessible finder charts and coordinates. Many of variable-rich clusters have published photographic finder charts taken in relatively poor seeing with blue-sensitive photographic plates. While useful signal-to-noise ratios are relatively straightforward to achieve for RR Lyrae, Type 2 Cepheids, and red giant variables, correct identification remains a difficult issue—particularly when images are taken at V or longer wavelengths. We describe the project and report its progress using the OC61, TMO61, and SRO telescopes of AAVSOnet after the first year of image acquisition and demonstrate several of the data products being developed for globular cluster variables.

  2. Improving preparedness of farmers to Climate Variability: A case study of Vidarbha region of Maharashtra, India (United States)

    Swami, D.; Parthasarathy, D.; Dave, P.


    A key objective of the ongoing research is to understand the risk and vulnerability of agriculture and farming communities with respect to multiple climate change attributes, particularly monsoon variability and hydrology such as ground water availability. Climate Variability has always been a feature affecting Indian agriculture but the nature and characteristics of this variability is not well understood. Indian monsoon patterns are highly variable and most of the studies focus on larger domain such as Central India or Western coast (Ghosh et al., 2009) but district level analysis is missing i.e. the linkage between agriculture and climate variables at finer scale has not been investigated comprehensively. For example, Eastern Vidarbha region in Maharashtra is considered as one of the most agriculturally sensitive region in India, where every year a large number of farmers commit suicide. The main reasons for large number of suicides are climate related stressors such as droughts, hail storms, and monsoon variability aggravated with poor socio-economic conditions. Present study has tried to explore the areas in Vidarbha region of Maharashtra where famers and crop productivity, specifically cotton, sorghum, is highly vulnerable to monsoon variability, hydrological and socio-economic variables which are further modelled to determine the maximal contributing factor towards crops and farmers' vulnerability. After analysis using primary and secondary data, it will aid in decision making regarding field operations such as time of sowing, harvesting and irrigation requirements by optimizing the cropping pattern with climatic, hydrological and socio-economic variables. It also suggests the adaptation strategies to farmers regarding different types of cropping and water harvesting practices, optimized dates and timings for harvesting, sowing, water and nutrient requirements of particular crops according to the specific region. Primarily along with secondary analysis

  3. Acupuncture Alters Expression of Insulin Signaling Related Molecules and Improves Insulin Resistance in OLETF Rats

    Directory of Open Access Journals (Sweden)

    Xin-Yu Huang


    Full Text Available To determine effect of acupuncture on insulin resistance in Otsuka Long-Evans Tokushima Fatty (OLETF rats and to evaluate expression of insulin signaling components. Rats were divided into three groups: Sprague-Dawley (SD rats, OLETF rats, and acupuncture+OLETF rats. Acupuncture was subcutaneously applied to Neiguan (PC6, Zusanli (ST36, and Sanyinjiao (SP6; in contrast, acupuncture to Shenshu (BL23 was administered perpendicularly. For Neiguan (PC6 and Zusanli (ST36, needles were connected to an electroacupuncture (EA apparatus. Fasting blood glucose (FPG was measured by glucose oxidase method. Plasma fasting insulin (FINS and serum C peptide (C-P were determined by ELISA. Protein and mRNA expressions of insulin signaling molecules were determined by Western blot and real-time RT-PCR, respectively. OLETF rats exhibit increased levels of FPG, FINS, C-P, and homeostasis model assessment-estimated insulin resistance (HOMA-IR, which were effectively decreased by acupuncture treatment. mRNA expressions of several insulin signaling related molecules IRS1, IRS2, Akt2, aPKCζ, and GLUT4 were decreased in OLETF rats compared to SD controls. Expression of these molecules was restored back to normal levels upon acupuncture administration. PI3K-p85α was increased in OLETF rats; this increase was also reversed by acupuncture treatment. Acupuncture improves insulin resistance in OLETF rats, possibly via regulating expression of key insulin signaling related molecules.

  4. Relating Linear and Volumetric Variables Through Body Scanning to Improve Human Interfaces in Space (United States)

    Margerum, Sarah E.; Ferrer, Mike A.; Young, Karen S.; Rajulu, Sudhakar


    Designing space suits and vehicles for the diverse human population present unique challenges for the methods of traditional anthropometry. Space suits are bulky and allow the operator to shift position within the suit and inhibit the ability to identify body landmarks. Limited suit sizing options also cause variability in fit and performance between similarly sized individuals. Space vehicles are restrictive in volume in both the fit and the ability to collect data. NASA's Anthropometric and Biomechanics Facility (ABF) has utilized 3D scanning to shift from traditional linear anthropometry to explore and examine volumetric capabilities to provide anthropometric solutions for design. Overall, the key goals are to improve the human-system performance and develop new processes to aid in the design and evaluation of space systems. Four case studies are presented that illustrate the shift from purely linear analyses to an augmented volumetric toolset to predict and analyze the human within the space suit and vehicle. The first case study involves the calculation of maximal head volume to estimate total free volume in the helmet for proper air exchange. Traditional linear measurements resulted in an inaccurate representation of the head shape, yet limited data exists for the determination of a large head volume. Steps were first taken to identify and classify a maximum head volume and the resulting comparisons to the estimate are presented in this paper. This study illustrates the gap between linear components of anthropometry and the need for overall volume metrics in order to provide solutions. A second case study examines the overlay of the space suit scans and components onto scanned individuals to quantify fit and clearance to aid in sizing the suit to the individual. Restrictions in space suit size availability present unique challenges to optimally fit the individual within a limited sizing range while maintaining performance. Quantification of the clearance and

  5. Improved innate and adaptive immunostimulation by genetically modified HIV-1 protein expressing NYVAC vectors.

    Directory of Open Access Journals (Sweden)

    Esther D Quakkelaar

    Full Text Available Attenuated poxviruses are safe and capable of expressing foreign antigens. Poxviruses are applied in veterinary vaccination and explored as candidate vaccines for humans. However, poxviruses express multiple genes encoding proteins that interfere with components of the innate and adaptive immune response. This manuscript describes two strategies aimed to improve the immunogenicity of the highly attenuated, host-range restricted poxvirus NYVAC: deletion of the viral gene encoding type-I interferon-binding protein and development of attenuated replication-competent NYVAC. We evaluated these newly generated NYVAC mutants, encoding HIV-1 env, gag, pol and nef, for their ability to stimulate HIV-specific CD8 T-cell responses in vitro from blood mononuclear cells of HIV-infected subjects. The new vectors were evaluated and compared to the parental NYVAC vector in dendritic cells (DCs, RNA expression arrays, HIV gag expression and cross-presentation assays in vitro. Deletion of type-I interferon-binding protein enhanced expression of interferon and interferon-induced genes in DCs, and increased maturation of infected DCs. Restoration of replication competence induced activation of pathways involving antigen processing and presentation. Also, replication-competent NYVAC showed increased Gag expression in infected cells, permitting enhanced cross-presentation to HIV-specific CD8 T cells and proliferation of HIV-specific memory CD8 T-cells in vitro. The recombinant NYVAC combining both modifications induced interferon-induced genes and genes involved in antigen processing and presentation, as well as increased Gag expression. This combined replication-competent NYVAC is a promising candidate for the next generation of HIV vaccines.

  6. Protein expression and genetic variability of canine Can f 1 in golden and Labrador retriever service dogs. (United States)

    Breitenbuecher, Christina; Belanger, Janelle M; Levy, Kerinne; Mundell, Paul; Fates, Valerie; Gershony, Liza; Famula, Thomas R; Oberbauer, Anita M


    Valued for trainability in diverse tasks, dogs are the primary service animal used to assist individuals with disabilities. Despite their utility, many people in need of service dogs are sensitive to the primary dog allergen, Can f 1, encoded by the Lipocalin 1 gene (LCN1). Several organizations specifically breed service dogs to meet special needs and would like to reduce allergenic potential if possible. In this study, we evaluated the expression of Can f 1 protein and the inherent variability of LCN1 in two breeds used extensively as service dogs. Saliva samples from equal numbers of male and female Labrador retrievers (n = 12), golden retrievers (n = 12), and Labrador-golden crosses (n = 12) were collected 1 h after the morning meal. Can f 1 protein concentrations in the saliva were measured by ELISA, and the LCN1 5' and 3' UTRs and exons sequenced. There was no sex effect (p > 0.2) nor time-of-day effect; however, Can f 1 protein levels varied by breed with Labrador retrievers being lower than golden retrievers (3.18 ± 0.51 and 5.35 ± 0.52 μg/ml, respectively, p < 0.0075), and the Labrador-golden crosses having intermediate levels (3.77 ± 0.48 μg/ml). Although several novel SNPs were identified in LCN1, there were no significant breed-specific sequence differences in the gene and no association of LCN1 genotypes with Can f 1 expression. As service dogs, Labrador retrievers likely have lower allergenic potential and, though there were no DNA sequence differences identified, classical genetic selection on the estimated breeding values associated with salivary Can f 1 expression may further reduce that potential.

  7. Improved capacitance sensor with variable operating frequency for scanning capacitance microscopy

    International Nuclear Information System (INIS)

    Kwon, Joonhyung; Kim, Joonhui; Jeong, Jong-Hwa; Lee, Euy-Kyu; Seok Kim, Yong; Kang, Chi Jung; Park, Sang-il


    Scanning capacitance microscopy (SCM) has been gaining attention for its capability to measure local electrical properties in doping profile, oxide thickness, trapped charges and charge dynamics. In many cases, stray capacitance produced by different samples and measurement conditions affects the resonance frequency of a capacitance sensor. The applications of conventional SCM are critically limited by the fixed operating frequency and lack of tunability in its SCM sensor. In order to widen SCM application to various samples, we have developed a novel SCM sensor with variable operating frequency. By performing variable frequency sweep over the band of 160 MHz, the SCM sensor is tuned to select the best and optimized resonance frequency and quality factor for each sample measurement. The fundamental advantage of the new variable frequency SCM sensor was demonstrated in the SCM imaging of silicon oxide nano-crystals. Typical sensitivity of the variable frequency SCM sensor was found to be 10 -19 F/V

  8. Improvement of two-way continuous variable quantum cryptography by using additional noise

    International Nuclear Information System (INIS)

    Wang Minjie; Pan Wei


    The performance of quantum key distribution such as one-way continuous variable protocols, can be increased by adding some noise on the reference side of error correction in the error-correction phase. For this reason, we here study this possibility in the case of two-way continuous variable system. Finally, the numerical results show that the using of additional noise gives two-way schemes better security performance in terms of secret key rates and resistance to channel excess noise.

  9. Reliability-Based Design Optimization of Trusses with Linked-Discrete Design Variables using the Improved Firefly Algorithm

    Directory of Open Access Journals (Sweden)

    N. M. Okasha


    Full Text Available In this paper, an approach for conducting a Reliability-Based Design Optimization (RBDO of truss structures with linked-discrete design variables is proposed. The sections of the truss members are selected from the AISC standard tables and thus the design variables that represent the properties of each section are linked. Latin hypercube sampling is used in the evaluation of the structural reliability. The improved firefly algorithm is used for the optimization solution process. It was found that in order to use the improved firefly algorithm for efficiently solving problems of reliability-based design optimization with linked-discrete design variables; it needs to be modified as proposed in this paper to accelerate its convergence.

  10. Resistance controllability and variability improvement in a TaO{sub x}-based resistive memory for multilevel storage application

    Energy Technology Data Exchange (ETDEWEB)

    Prakash, A., E-mail:, E-mail:, E-mail:; Song, J.; Hwang, H., E-mail:, E-mail:, E-mail: [Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang, 790-784 (Korea, Republic of); Deleruyelle, D.; Bocquet, M. [Im2np, UMR CNRS 7334, Aix-Marseille Université, Marseille (France)


    In order to obtain reliable multilevel cell (MLC) characteristics, resistance controllability between the different resistance levels is required especially in resistive random access memory (RRAM), which is prone to resistance variability mainly due to its intrinsic random nature of defect generation and filament formation. In this study, we have thoroughly investigated the multilevel resistance variability in a TaO{sub x}-based nanoscale (<30 nm) RRAM operated in MLC mode. It is found that the resistance variability not only depends on the conductive filament size but also is a strong function of oxygen vacancy concentration in it. Based on the gained insights through experimental observations and simulation, it is suggested that forming thinner but denser conductive filament may greatly improve the temporal resistance variability even at low operation current despite the inherent stochastic nature of resistance switching process.

  11. A Spreadsheet-Based Visualized Mindtool for Improving Students' Learning Performance in Identifying Relationships between Numerical Variables (United States)

    Lai, Chiu-Lin; Hwang, Gwo-Jen


    In this study, a spreadsheet-based visualized Mindtool was developed for improving students' learning performance when finding relationships between numerical variables by engaging them in reasoning and decision-making activities. To evaluate the effectiveness of the proposed approach, an experiment was conducted on the "phenomena of climate…

  12. The loss of NDRG2 expression improves depressive behavior through increased phosphorylation of GSK3β. (United States)

    Ichikawa, Tomonaga; Nakahata, Shingo; Tamura, Tomohiro; Manachai, Nawin; Morishita, Kazuhiro


    N-myc downstream-regulated gene 2 (NDRG2) is one of the important stress-inducible genes and plays a critical role in negatively regulating PI3K/AKT signaling during hypoxia and inflammation. Through recruitment of PP2A phosphatase, NDRG2 maintains the dephosphorylated status of PTEN to suppress excessive PI3K/AKT signaling, and loss of NDRG2 expression is frequently seen in various types of cancer with enhanced activation of PI3K/AKT signaling. Because NDRG2 is highly expressed in the nervous system, we investigated whether NDRG2 plays a functional role in the nervous system using Ndrg2-deficient mice. Ndrg2-deficient mice do not display any gross abnormalities in the nervous system, but they have a diminished behavioral response associated with anxiety. Ndrg2-deficient mice exhibited decreased immobility and increased head-dipping and rearing behavior in two behavioral models, indicating an improvement of emotional anxiety-like behavior. Moreover, treatment of wild-type mice with the antidepressant drug imipramine reduced the expression of Ndrg2 in the frontal cortex, which was due to the degradation of HIF-1α through reduced expression of HSP90 protein. Furthermore, we found that the down-regulation of Ndrg2 in Ndrg2-deficient mice and imipramine treatment improved mood behavior with enhanced phosphorylation of GSK3β through activation of PI3K/AKT signaling, suggesting that the expression level of NDRG2 has a causal influence on mood-related phenotypes. Collectively, these results suggest that NDRG2 may be a potential target for mood disorders such as depression and anxiety. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Expression of Root Genes in Arabidopsis Seedlings Grown by Standard and Improved Growing Methods. (United States)

    Qu, Yanli; Liu, Shuai; Bao, Wenlong; Xue, Xian; Ma, Zhengwen; Yokawa, Ken; Baluška, František; Wan, Yinglang


    Roots of Arabidopsis thaliana seedlings grown in the laboratory using the traditional plant-growing culture system (TPG) were covered to maintain them in darkness. This new method is based on a dark chamber and is named the improved plant-growing method (IPG). We measured the light conditions in dark chambers, and found that the highest light intensity was dramatically reduced deeper in the dark chamber. In the bottom and side parts of dark chambers, roots were almost completely shaded. Using the high-throughput RNA sequencing method on the whole RNA extraction from roots, we compared the global gene expression levels in roots of seedlings from these two conditions and identified 141 differently expressed genes (DEGs) between them. According to the KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment, the flavone and flavonol biosynthesis and flavonoid biosynthesis pathways were most affected among all annotated pathways. Surprisingly, no genes of known plant photoreceptors were identified as DEGs by this method. Considering that the light intensity was decreased in the IPG system, we collected four sections (1.5 cm for each) of Arabidopsis roots grown in TPG and IPG conditions, and the spatial-related differential gene expression levels of plant photoreceptors and polar auxin transporters, including CRY1 , CRY2 , PHYA , PHYB , PHOT1 , PHOT2 , and UVR8 were analyzed by qRT-PCR. Using these results, we generated a map of the spatial-related expression patterns of these genes under IPG and TPG conditions. The expression levels of light-related genes in roots is highly sensitive to illumination and it provides a background reference for selecting an improved culture method for laboratory-maintained Arabidopsis seedlings.

  14. pEPito: a significantly improved non-viral episomal expression vector for mammalian cells

    Directory of Open Access Journals (Sweden)

    Ogris Manfred


    Full Text Available Abstract Background The episomal replication of the prototype vector pEPI-1 depends on a transcription unit starting from the constitutively expressed Cytomegalovirus immediate early promoter (CMV-IEP and directed into a 2000 bp long matrix attachment region sequence (MARS derived from the human β-interferon gene. The original pEPI-1 vector contains two mammalian transcription units and a total of 305 CpG islands, which are located predominantly within the vector elements necessary for bacterial propagation and known to be counterproductive for persistent long-term transgene expression. Results Here, we report the development of a novel vector pEPito, which is derived from the pEPI-1 plasmid replicon but has considerably improved efficacy both in vitro and in vivo. The pEPito vector is significantly reduced in size, contains only one transcription unit and 60% less CpG motives in comparison to pEPI-1. It exhibits major advantages compared to the original pEPI-1 plasmid, including higher transgene expression levels and increased colony-forming efficiencies in vitro, as well as more persistent transgene expression profiles in vivo. The performance of pEPito-based vectors was further improved by replacing the CMV-IEP with the human CMV enhancer/human elongation factor 1 alpha promoter (hCMV/EF1P element that is known to be less affected by epigenetic silencing events. Conclusions The novel vector pEPito can be considered suitable as an improved vector for biotechnological applications in vitro and for non-viral gene delivery in vivo.

  15. A New Strain Collection for Improved Expression of Outer Membrane Proteins

    Directory of Open Access Journals (Sweden)

    Ina Meuskens


    Full Text Available Almost all integral membrane proteins found in the outer membranes of Gram-negative bacteria belong to the transmembrane β-barrel family. These proteins are not only important for nutrient uptake and homeostasis, but are also involved in such processes as adhesion, protein secretion, biofilm formation, and virulence. As surface exposed molecules, outer membrane β-barrel proteins are also potential drug and vaccine targets. High production levels of heterologously expressed proteins are desirable for biochemical and especially structural studies, but over-expression and subsequent purification of membrane proteins, including outer membrane proteins, can be challenging. Here, we present a set of deletion mutants derived from E. coli BL21(DE3 designed for the over-expression of recombinant outer membrane proteins. These strains harbor deletions of four genes encoding abundant β-barrel proteins in the outer membrane (OmpA, OmpC, OmpF, and LamB, both single and in all combinations of double, triple, and quadruple knock-outs. The sequences encoding these outer membrane proteins were deleted completely, leaving only a minimal scar sequence, thus preventing the possibility of genetic reversion. Expression tests in the quadruple mutant strain with four test proteins, including a small outer membrane β-barrel protein and variants thereof as well as two virulence-related autotransporters, showed significantly improved expression and better quality of the produced proteins over the parent strain. Differences in growth behavior and aggregation in the presence of high salt were observed, but these phenomena did not negatively influence the expression in the quadruple mutant strain when handled as we recommend. The strains produced in this study can be used for outer membrane protein production and purification, but are also uniquely useful for labeling experiments for biophysical measurements in the native membrane environment.

  16. A novel methodology improves reservoir characterization models using geologic fuzzy variables

    Energy Technology Data Exchange (ETDEWEB)

    Soto B, Rodolfo [DIGITOIL, Maracaibo (Venezuela); Soto O, David A. [Texas A and M University, College Station, TX (United States)


    One of the research projects carried out in Cusiana field to explain its rapid decline during the last years was to get better permeability models. The reservoir of this field has a complex layered system that it is not easy to model using conventional methods. The new technique included the development of porosity and permeability maps from cored wells following the same trend of the sand depositions for each facie or layer according to the sedimentary facie and the depositional system models. Then, we used fuzzy logic to reproduce those maps in three dimensions as geologic fuzzy variables. After multivariate statistical and factor analyses, we found independence and a good correlation coefficient between the geologic fuzzy variables and core permeability and porosity. This means, the geologic fuzzy variable could explain the fabric, the grain size and the pore geometry of the reservoir rock trough the field. Finally, we developed a neural network permeability model using porosity, gamma ray and the geologic fuzzy variable as input variables. This model has a cross-correlation coefficient of 0.873 and average absolute error of 33% compared with the actual model with a correlation coefficient of 0.511 and absolute error greater than 250%. We tested different methodologies, but this new one showed dramatically be a promiser way to get better permeability models. The use of the models have had a high impact in the explanation of well performance and workovers, and reservoir simulation models. (author)

  17. Genetic engineering of human NK cells to express CXCR2 improves migration to renal cell carcinoma. (United States)

    Kremer, Veronika; Ligtenberg, Maarten A; Zendehdel, Rosa; Seitz, Christina; Duivenvoorden, Annet; Wennerberg, Erik; Colón, Eugenia; Scherman-Plogell, Ann-Helén; Lundqvist, Andreas


    Adoptive natural killer (NK) cell transfer is being increasingly used as cancer treatment. However, clinical responses have so far been limited to patients with hematological malignancies. A potential limiting factor in patients with solid tumors is defective homing of the infused NK cells to the tumor site. Chemokines regulate the migration of leukocytes expressing corresponding chemokine receptors. Various solid tumors, including renal cell carcinoma (RCC), readily secrete ligands for the chemokine receptor CXCR2. We hypothesize that infusion of NK cells expressing high levels of the CXCR2 chemokine receptor will result in increased influx of the transferred NK cells into tumors, and improved clinical outcome in patients with cancer. Blood and tumor biopsies from 14 primary RCC patients were assessed by flow cytometry and chemokine analysis. Primary NK cells were transduced with human CXCR2 using a retroviral system. CXCR2 receptor functionality was determined by Calcium flux and NK cell migration was evaluated in transwell assays. We detected higher concentrations of CXCR2 ligands in tumors compared with plasma of RCC patients. In addition, CXCL5 levels correlated with the intratumoral infiltration of CXCR2-positive NK cells. However, tumor-infiltrating NK cells from RCC patients expressed lower CXCR2 compared with peripheral blood NK cells. Moreover, healthy donor NK cells rapidly lost their CXCR2 expression upon in vitro culture and expansion. Genetic modification of human primary NK cells to re-express CXCR2 improved their ability to specifically migrate along a chemokine gradient of recombinant CXCR2 ligands or RCC tumor supernatants compared with controls. The enhanced trafficking resulted in increased killing of target cells. In addition, while their functionality remained unchanged compared with control NK cells, CXCR2-transduced NK cells obtained increased adhesion properties and formed more conjugates with target cells. To increase the success of NK

  18. Constitutive expression of Vitreoscilla haemoglobin in Sphingomonas elodea to improve gellan gum production. (United States)

    Wu, X C; Chen, Y M; Li, Y D; Li, O; Zhu, L; Qian, C D; Tao, X L; Teng, Y


    To improve a commercially used strain for gellan production by exogenous Vitreoscilla haemoglobin (VHb). VHb gene was expressed in Sphingomonas elodea under the control of constitutive bla promoter. Biochemical activity of expressed VHb was confirmed by CO-difference spectra analysis that exhibited a characteristic absorption maximum at 419 nm. During cultivation, not only enhanced cell growth was detected, but also 20% improvement in gellan production was observed after 48 h of incubation, with a maximum yield of 16·82 g l(-1). Moreover, maximum sucrose conversion efficiency (g gellan per g sucrose) was 57·8, 20% higher than that of the parental strain. We further examined the polysaccharide production of VHb-expressing strain at different aeration levels in Erlenmeyer flasks. Again, in all cases, a significant enhancement of gellan production was observed, and the enhancement was more significant under oxygen-limiting conditions (up to 26·8%). VHb exhibited positive effect on cell growth and gellan yield of S. elodea, especially under hypoxic conditions. This is the first application of VHb as an effective metabolic engineering strategy in S. elodea to regulate cell growth and optimize gellan yield. © 2010 The Authors. Journal of Applied Microbiology © 2010 The Society for Applied Microbiology.

  19. Stochastic weather inputs for improved urban water demand forecasting: application of nonlinear input variable selection and machine learning methods (United States)

    Quilty, J.; Adamowski, J. F.


    Urban water supply systems are often stressed during seasonal outdoor water use as water demands related to the climate are variable in nature making it difficult to optimize the operation of the water supply system. Urban water demand forecasts (UWD) failing to include meteorological conditions as inputs to the forecast model may produce poor forecasts as they cannot account for the increase/decrease in demand related to meteorological conditions. Meteorological records stochastically simulated into the future can be used as inputs to data-driven UWD forecasts generally resulting in improved forecast accuracy. This study aims to produce data-driven UWD forecasts for two different Canadian water utilities (Montreal and Victoria) using machine learning methods by first selecting historical UWD and meteorological records derived from a stochastic weather generator using nonlinear input variable selection. The nonlinear input variable selection methods considered in this work are derived from the concept of conditional mutual information, a nonlinear dependency measure based on (multivariate) probability density functions and accounts for relevancy, conditional relevancy, and redundancy from a potential set of input variables. The results of our study indicate that stochastic weather inputs can improve UWD forecast accuracy for the two sites considered in this work. Nonlinear input variable selection is suggested as a means to identify which meteorological conditions should be utilized in the forecast.

  20. Improved installation approach for variable spring setting on a pipe yet to be insulated

    International Nuclear Information System (INIS)

    Shah, H.H.; Chitnis, S.S.; Rencher, D.


    This paper provides an approach in setting of variable spring supports for noninsulated or partially insulated piping systems so that resetting these supports is not required when the insulation is fully installed. This approach shows a method of deriving the spring coldload setting tolerance values that can be readily utilized by craft personnel. This method is based on the percentage of the weight of the insulation compared to the total weight of the pipe and the applicable tolerance. Use of these setting tolerances eliminates reverification of the original cold-load settings, for the majority of variable springs when the insulation is fully installed

  1. Understanding hydrological variability for improved water management in the Semi-Arid Karkheh basin, Iran

    NARCIS (Netherlands)

    Masih, I.


    This study provides a hydrology based assessment of (surface) water resources and its continuum of variability and change at different spatio-temporal scales in the semi-arid Karkheh Basin, Iran, where water is scarce, competition among users is high and massive water resources development is under

  2. Improved theory of time domain reflectometry with variable coaxial cable length for electrical conductivity measurements (United States)

    Although empirical models have been developed previously, a mechanistic model is needed for estimating electrical conductivity (EC) using time domain reflectometry (TDR) with variable lengths of coaxial cable. The goals of this study are to: (1) derive a mechanistic model based on multisection tra...

  3. Novel gene sets improve set-level classification of prokaryotic gene expression data. (United States)

    Holec, Matěj; Kuželka, Ondřej; Železný, Filip


    Set-level classification of gene expression data has received significant attention recently. In this setting, high-dimensional vectors of features corresponding to genes are converted into lower-dimensional vectors of features corresponding to biologically interpretable gene sets. The dimensionality reduction brings the promise of a decreased risk of overfitting, potentially resulting in improved accuracy of the learned classifiers. However, recent empirical research has not confirmed this expectation. Here we hypothesize that the reported unfavorable classification results in the set-level framework were due to the adoption of unsuitable gene sets defined typically on the basis of the Gene ontology and the KEGG database of metabolic networks. We explore an alternative approach to defining gene sets, based on regulatory interactions, which we expect to collect genes with more correlated expression. We hypothesize that such more correlated gene sets will enable to learn more accurate classifiers. We define two families of gene sets using information on regulatory interactions, and evaluate them on phenotype-classification tasks using public prokaryotic gene expression data sets. From each of the two gene-set families, we first select the best-performing subtype. The two selected subtypes are then evaluated on independent (testing) data sets against state-of-the-art gene sets and against the conventional gene-level approach. The novel gene sets are indeed more correlated than the conventional ones, and lead to significantly more accurate classifiers. The novel gene sets are indeed more correlated than the conventional ones, and lead to significantly more accurate classifiers. Novel gene sets defined on the basis of regulatory interactions improve set-level classification of gene expression data. The experimental scripts and other material needed to reproduce the experiments are available at

  4. Expression of a bacterial 3-dehydroshikimate dehydratase reduces lignin content and improves biomass saccharification efficiency. (United States)

    Eudes, Aymerick; Sathitsuksanoh, Noppadon; Baidoo, Edward E K; George, Anthe; Liang, Yan; Yang, Fan; Singh, Seema; Keasling, Jay D; Simmons, Blake A; Loqué, Dominique


    Lignin confers recalcitrance to plant biomass used as feedstocks in agro-processing industries or as source of renewable sugars for the production of bioproducts. The metabolic steps for the synthesis of lignin building blocks belong to the shikimate and phenylpropanoid pathways. Genetic engineering efforts to reduce lignin content typically employ gene knockout or gene silencing techniques to constitutively repress one of these metabolic pathways. Recently, new strategies have emerged offering better spatiotemporal control of lignin deposition, including the expression of enzymes that interfere with the normal process for cell wall lignification. In this study, we report that expression of a 3-dehydroshikimate dehydratase (QsuB from Corynebacterium glutamicum) reduces lignin deposition in Arabidopsis cell walls. QsuB was targeted to the plastids to convert 3-dehydroshikimate - an intermediate of the shikimate pathway - into protocatechuate. Compared to wild-type plants, lines expressing QsuB contain higher amounts of protocatechuate, p-coumarate, p-coumaraldehyde and p-coumaryl alcohol, and lower amounts of coniferaldehyde, coniferyl alcohol, sinapaldehyde and sinapyl alcohol. 2D-NMR spectroscopy and pyrolysis-gas chromatography/mass spectrometry (pyro-GC/MS) reveal an increase of p-hydroxyphenyl units and a reduction of guaiacyl units in the lignin of QsuB lines. Size-exclusion chromatography indicates a lower degree of lignin polymerization in the transgenic lines. Therefore, our data show that the expression of QsuB primarily affects the lignin biosynthetic pathway. Finally, biomass from these lines exhibits more than a twofold improvement in saccharification efficiency. We conclude that the expression of QsuB in plants, in combination with specific promoters, is a promising gain-of-function strategy for spatiotemporal reduction of lignin in plant biomass. © 2015 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The

  5. Wide Variability in Caloric Density of Expressed Human Milk Can Lead to Major Underestimation or Overestimation of Nutrient Content. (United States)

    Sauer, Charles W; Boutin, Mallory A; Kim, Jae H


    Very-low-birth-weight infants continue to face significant difficulties with postnatal growth. Human milk is the optimal form of nutrition for infants but may exhibit variation in nutrient content. This study aimed to perform macronutrient analysis on expressed human milk from mothers whose babies are hospitalized in the neonatal intensive care unit. Up to five human milk samples per participant were analyzed for protein, carbohydrate, and fat content using reference chemical analyses (Kjeldahl for protein, high pressure liquid chromatography for carbohydrates, and Mojonnier for fat). Calorie content was calculated. A total of 64 samples from 24 participants was analyzed. Wide variability was found in calorie, protein, carbohydrate, and fat composition. The authors found an average of 17.9 kcal/ounce, with only 34% of samples falling within 10% of the expected caloric density. The assumption that human milk contains 20 kcal/ounce is no longer supported based on this study. This supports promoting an individualized nutrition strategy as a crucial aspect to optimal nutrition.

  6. Gene expression in response to Cotton Leaf Curl Virus infection in Gossypium hirsutum under variable environmental conditions

    Directory of Open Access Journals (Sweden)

    Rehman Iqra


    Full Text Available Cotton Leaf Curl Disease (CLCuD is one of the threatening constrains of cotton production in Pakistan for which no adequate remedy is available until now. Local variety of Gossypium hirsutum (FH-142 was grown in field and infected naturally by CLCuV under variable range of temperature and humidity. Plants showed thickening of veins in lower leaf surface at 34°C and 60% relative humidity at 15days post infection (dpi and curling of leaf margins at 33°C with 58% relative humidity at 30dpi. Remarkable leaf darkening was observed with reduced boll formation at 45dpi at 26°C and 41% relative humidity. Enation developed, severe thickening and curling of leaves intensified and plants showed dwarf growth at 60dpi at 24°C with 52% relative humidity. PCR amplification of Rep associated gene confirmed the presence of CLCuD-associated begomovirus in the infected samples. Quantitative RT-PCR confirmed the amplification and differential expression of a number of pathogen stress responsive genes at different levels of temperature and humidity. This observation predicts that Cotton Leaf Curl Virus (CLCuV interacts with several host genes that are upregulated to make plants susceptible or suppress other genes to overcome host defense responses.

  7. Using Variable Precision Rough Set for Selection and Classification of Biological Knowledge Integrated in DNA Gene Expression

    Directory of Open Access Journals (Sweden)

    Calvo-Dmgz D.


    Full Text Available DNA microarrays have contributed to the exponential growth of genomic and experimental data in the last decade. This large amount of gene expression data has been used by researchers seeking diagnosis of diseases like cancer using machine learning methods. In turn, explicit biological knowledge about gene functions has also grown tremendously over the last decade. This work integrates explicit biological knowledge, provided as gene sets, into the classication process by means of Variable Precision Rough Set Theory (VPRS. The proposed model is able to highlight which part of the provided biological knowledge has been important for classification. This paper presents a novel model for microarray data classification which is able to incorporate prior biological knowledge in the form of gene sets. Based on this knowledge, we transform the input microarray data into supergenes, and then we apply rough set theory to select the most promising supergenes and to derive a set of easy interpretable classification rules. The proposed model is evaluated over three breast cancer microarrays datasets obtaining successful results compared to classical classification techniques. The experimental results shows that there are not significat differences between our model and classical techniques but it is able to provide a biological-interpretable explanation of how it classifies new samples.

  8. Improved flux calculations for viscous incompressible flow by the variable penalty method

    International Nuclear Information System (INIS)

    Kheshgi, H.; Luskin, M.


    The Navier-Stokes system for viscous, incompressible flow is considered, taking into account a replacement of the continuity equation by the perturbed continuity equation. The introduction of the approximation allows the pressure variable to be eliminated to obtain the system of equations for the approximate velocity. The penalty approximation is often applied to numerical discretizations since it provides a reduction in the size and band-width of the system of equations. Attention is given to error estimates, and to two numerical experiments which illustrate the error estimates considered. It is found that the variable penalty method provides an accurate solution for a much wider range of epsilon than the classical penalty method. 8 references

  9. Variable-speed wind power system with improved energy capture via multilevel conversion (United States)

    Erickson, Robert W.; Al-Naseem, Osama A.; Fingersh, Lee Jay


    A system and method for efficiently capturing electrical energy from a variable-speed generator are disclosed. The system includes a matrix converter using full-bridge, multilevel switch cells, in which semiconductor devices are clamped to a known constant DC voltage of a capacitor. The multilevel matrix converter is capable of generating multilevel voltage wave waveform of arbitrary magnitude and frequencies. The matrix converter can be controlled by using space vector modulation.

  10. Improving the maximum transmission distance of continuous-variable quantum key distribution with noisy coherent states using a noiseless amplifier

    International Nuclear Information System (INIS)

    Wang, Tianyi; Yu, Song; Zhang, Yi-Chen; Gu, Wanyi; Guo, Hong


    By employing a nondeterministic noiseless linear amplifier, we propose to increase the maximum transmission distance of continuous-variable quantum key distribution with noisy coherent states. With the covariance matrix transformation, the expression of secret key rate under reverse reconciliation is derived against collective entangling cloner attacks. We show that the noiseless linear amplifier can compensate the detrimental effect of the preparation noise with an enhancement of the maximum transmission distance and the noise resistance. - Highlights: • Noiseless amplifier is applied in noisy coherent state quantum key distribution. • Negative effect of preparation noise is compensated by noiseless amplification. • Maximum transmission distance and noise resistance are both enhanced

  11. Combining landscape variables and species traits can improve the utility of climate change vulnerability assessments (United States)

    Nadeau, Christopher P.; Fuller, Angela K.


    Conservation organizations worldwide are investing in climate change vulnerability assessments. Most vulnerability assessment methods focus on either landscape features or species traits that can affect a species vulnerability to climate change. However, landscape features and species traits likely interact to affect vulnerability. We compare a landscape-based assessment, a trait-based assessment, and an assessment that combines landscape variables and species traits for 113 species of birds, herpetofauna, and mammals in the northeastern United States. Our aim is to better understand which species traits and landscape variables have the largest influence on assessment results and which types of vulnerability assessments are most useful for different objectives. Species traits were most important for determining which species will be most vulnerable to climate change. The sensitivity of species to dispersal barriers and the species average natal dispersal distance were the most important traits. Landscape features were most important for determining where species will be most vulnerable because species were most vulnerable in areas where multiple landscape features combined to increase vulnerability, regardless of species traits. The interaction between landscape variables and species traits was important when determining how to reduce climate change vulnerability. For example, an assessment that combines information on landscape connectivity, climate change velocity, and natal dispersal distance suggests that increasing landscape connectivity may not reduce the vulnerability of many species. Assessments that include landscape features and species traits will likely be most useful in guiding conservation under climate change.

  12. Expression

    Directory of Open Access Journals (Sweden)

    Wang-Xia Wang


    Full Text Available The miR-15/107 family comprises a group of 10 paralogous microRNAs (miRNAs, sharing a 5′ AGCAGC sequence. These miRNAs have overlapping targets. In order to characterize the expression of miR-15/107 family miRNAs, we employed customized TaqMan Low-Density micro-fluid PCR-array to investigate the expression of miR-15/107 family members, and other selected miRNAs, in 11 human tissues obtained at autopsy including the cerebral cortex, frontal cortex, primary visual cortex, thalamus, heart, lung, liver, kidney, spleen, stomach and skeletal muscle. miR-103, miR-195 and miR-497 were expressed at similar levels across various tissues, whereas miR-107 is enriched in brain samples. We also examined the expression patterns of evolutionarily conserved miR-15/107 miRNAs in three distinct primary rat brain cell preparations (enriched for cortical neurons, astrocytes and microglia, respectively. In primary cultures of rat brain cells, several members of the miR-15/107 family are enriched in neurons compared to other cell types in the central nervous system (CNS. In addition to mature miRNAs, we also examined the expression of precursors (pri-miRNAs. Our data suggested a generally poor correlation between the expression of mature miRNAs and their precursors. In summary, we provide a detailed study of the tissue and cell type-specific expression profile of this highly expressed and phylogenetically conserved family of miRNA genes.

  13. Statistical Analysis of Automatic Seed Word Acquisition to Improve Harmful Expression Extraction in Cyberbullying Detection

    Directory of Open Access Journals (Sweden)

    Suzuha Hatakeyama


    Full Text Available We study the social problem of cyberbullying, defined as a new form of bullying that takes place in the Internet space. This paper proposes a method for automatic acquisition of seed words to improve performance of the original method for the cyberbullying detection by Nitta et al. [1]. We conduct an experiment exactly in the same settings to find out that the method based on a Web mining technique, lost over 30% points of its performance since being proposed in 2013. Thus, we hypothesize on the reasons for the decrease in the performance and propose a number of improvements, from which we experimentally choose the best one. Furthermore, we collect several seed word sets using different approaches, evaluate and their precision. We found out that the influential factor in extraction of harmful expressions is not the number of seed words, but the way the seed words were collected and filtered.

  14. Brief Communication: Upper Air Relaxation in RACMO2 Significantly Improves Modelled Interannual Surface Mass Balance Variability in Antarctica (United States)

    van de Berg, W. J.; Medley, B.


    The Regional Atmospheric Climate Model (RACMO2) has been a powerful tool for improving surface mass balance (SMB) estimates from GCMs or reanalyses. However, new yearly SMB observations for West Antarctica show that the modelled interannual variability in SMB is poorly simulated by RACMO2, in contrast to ERA-Interim, which resolves this variability well. In an attempt to remedy RACMO2 performance, we included additional upper-air relaxation (UAR) in RACMO2. With UAR, the correlation to observations is similar for RACMO2 and ERA-Interim. The spatial SMB patterns and ice-sheet-integrated SMB modelled using UAR remain very similar to the estimates of RACMO2 without UAR. We only observe an upstream smoothing of precipitation in regions with very steep topography like the Antarctic Peninsula. We conclude that UAR is a useful improvement for regional climate model simulations, although results in regions with steep topography should be treated with care.

  15. Overexpression of pucC improves the heterologous protein expression level in a Rhodobacter sphaeroides expression system. (United States)

    Cheng, L; Chen, G; Ding, G; Zhao, Z; Dong, T; Hu, Z


    The Rhodobacter sphaeroides system has been used to express membrane proteins. However, its low yield has substantially limited its application. In order to promote the protein expression capability of this system, the pucC gene, which plays a crucial role in assembling the R. sphaeroides light-harvesting 2 complex (LH2), was overexpressed. To build a pucC overexpression strain, a pucC overexpression vector was constructed and transformed into R. sphaeroides CQU68. The overexpression efficiency was evaluated by quantitative real-time polymerase chain reaction. A well-used reporter β-glucuronidase (GUS) was fusion-expressed with LH2 to evaluate the heterologous protein expression level. As a result, the cell culture and protein in the pucC overexpression strain showed much higher typical spectral absorption peaks at 800 and 850 nm compared with the non-overexpression strain, suggesting a higher expression level of LH2-GUS fusion protein in the pucC overexpression strain. This result was further confirmed by Western blot, which also showed a much higher level of heterologous protein expression in the pucC overexpression strain. We further compared GUS activity in pucC overexpression and non-overexpression strains, the results of which showed that GUS activity in the pucC overexpression strain was approximately ten-fold that in the non-overexpression strain. These results demonstrate that overexpressed pucC can promote heterologous protein expression levels in R. sphaeroides.

  16. Variable cross-section windings for efficiency improvement of electric machines (United States)

    Grachev, P. Yu; Bazarov, A. A.; Tabachinskiy, A. S.


    Implementation of energy-saving technologies in industry is impossible without efficiency improvement of electric machines. The article considers the ways of efficiency improvement and mass and dimensions reduction of electric machines with electronic control. Features of compact winding design for stators and armatures are described. Influence of compact winding on thermal and electrical process is given. Finite element method was used in computer simulation.

  17. Improving the Classification Accuracy for Near-Infrared Spectroscopy of Chinese Salvia miltiorrhiza Using Local Variable Selection

    Directory of Open Access Journals (Sweden)

    Lianqing Zhu


    Full Text Available In order to improve the classification accuracy of Chinese Salvia miltiorrhiza using near-infrared spectroscopy, a novel local variable selection strategy is thus proposed. Combining the strengths of the local algorithm and interval partial least squares, the spectra data have firstly been divided into several pairs of classes in sample direction and equidistant subintervals in variable direction. Then, a local classification model has been built, and the most proper spectral region has been selected based on the new evaluation criterion considering both classification error rate and best predictive ability under the leave-one-out cross validation scheme for each pair of classes. Finally, each observation can be assigned to belong to the class according to the statistical analysis of classification results of the local classification model built on selected variables. The performance of the proposed method was demonstrated through near-infrared spectra of cultivated or wild Salvia miltiorrhiza, which are collected from 8 geographical origins in 5 provinces of China. For comparison, soft independent modelling of class analogy and partial least squares discriminant analysis methods are, respectively, employed as the classification model. Experimental results showed that classification performance of the classification model with local variable selection was obvious better than that without variable selection.

  18. Probabilistic Requirements (Partial) Verification Methods Best Practices Improvement. Variables Acceptance Sampling Calculators: Derivations and Verification of Plans. Volume 1 (United States)

    Johnson, Kenneth L.; White, K, Preston, Jr.


    The NASA Engineering and Safety Center was requested to improve on the Best Practices document produced for the NESC assessment, Verification of Probabilistic Requirements for the Constellation Program, by giving a recommended procedure for using acceptance sampling by variables techniques. This recommended procedure would be used as an alternative to the potentially resource-intensive acceptance sampling by attributes method given in the document. This document contains the outcome of the assessment.

  19. Expression of variable viruses as herpes simplex glycoprotein D and varicella zoster gE glycoprotein using a novel plasmid based expression system in insect cell

    Directory of Open Access Journals (Sweden)

    A.M. Al-Sulaiman


    Full Text Available Several prokaryotic and eukaryotic expression systems have been used for in vitro production of viruses’ proteins. However eukaryotic expression system was always the first choice for production of proteins that undergo post-translational modification such as glycosylation. Recombinant baculoviruses have been widely used as safe vectors to express heterologous genes in the culture of insect cells, but the manipulation involved in creating, titrating, and amplifying viral stocks make it time consuming and laborious. Therefore, to facilitate rapid expression in insect cell, a plasmid based expression system was used to express herpes simplex type 1 glycoprotein D (HSV-1 gD and varicella zoster glycoprotein E (VZV gE. Recombinant plasmids were generated, transfected into insect cells (SF9, and both glycoproteins were expressed 48 h post-infection. A protein with approximately molecular weight of 64-kDa and 98-kDa for HSV-1 gD and VZV gE respectively was expressed and confirmed by SDS. Proteins were detected in insect cells cytoplasm and outer membrane by immunofluorescence. The antigenicity and immunoreactivity of each protein were confirmed by immunoblot and ELISA. Results suggest that this system can be an alternative to the traditional baculovirus expression for small scale expression system in insect cells.

  20. Atorvastatin Improves Inflammatory Response in Atherosclerosis by Upregulating the Expression of GARP (United States)

    Zhao, Xiaoqi; Liu, Yuzhou; Zhong, Yucheng; Liu, Bo; Yu, Kunwu; Shi, Huairui; Zhu, Ruirui; Meng, Kai; Zhang, Wei; Wu, Bangwei


    Regulatory T cells play an important role in the progression of atherosclerosis. GARP is a newly biological membrane molecule existed on activated Tregs, which is related to the release of TGF-β. The antiatherosclerosis effects of statins partly depend on their multiple immune modulatory potencies. In this paper, we present that atorvastatin could upregulate the expression of GARP and TGF-β in CD4+ T cells and increase the numbers of CD4+LAP+ and CD4+Foxp3+ regulatory T cells in ApoE−/− mice. Also, we indicate that atorvastatin promotes the aggregation of GARP+ and Foxp3+ cells and secretory of the TGF-β1 in atherosclerotic plaques. Furthermore, we prove that atorvastatin could delay the procession of atherosclerosis and improve the stability of atherosclerotic plaques. Interestingly, we report that inhibition of GARP distinctly inhibits the anti-inflammatory effects of atorvastatin. We conclude that atorvastatin improves the inflammatory response in atherosclerosis partly by upregulating the expression of GARP on regulatory T cells. PMID:26063978

  1. Ethnicity moderates the outcomes of self-enhancement and self-improvement themes in expressive writing. (United States)

    Tsai, William; Lau, Anna S; Niles, Andrea N; Coello, Jordan; Lieberman, Matthew D; Ko, Ahra C; Hur, Christopher; Stanton, Annette L


    The current study examined whether writing content related to self-enhancing (viz., downward social comparison and situational attributions) and self-improving (viz., upward social comparison and persistence) motivations were differentially related to expressive writing outcomes among 17 Asian American and 17 European American participants. Content analysis of the essays revealed no significant cultural group differences in the likelihood of engaging in self-enhancing versus self-improving reflections on negative personal experiences. However, cultural group differences were apparent in the relation between self-motivation processes and changes in anxiety and depressive symptoms at 3-month follow-up. Among European Americans, writing that reflected downward social comparison predicted positive outcomes, whereas persistence writing themes were related to poorer outcomes. For Asian Americans, writing about persistence was related to positive outcomes, whereas downward social comparison and situational attributions predicted poorer outcomes. Findings provide evidence suggesting culturally distinct mechanisms for the effects of expressive disclosure. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

  2. Modest weight loss in moderately overweight postmenopausal women improves heart rate variability

    DEFF Research Database (Denmark)

    Mouridsen, Mette Rauhe; Bendsen, Nathalie Tommerup; Astrup, Arne


    Purpose: To evaluate the effects of weight loss on heart rate (HR) and heart rate variability (HRV) parameters in overweight postmenopausal women. Design and Methods: Forty-nine overweight postmenopausal women with an average body mass index of 28.8 1.9 kg/m2 underwent a 12-week dietary weight......-to-normal intervals for each 5-min period (SDNNindex). Baseline body fat mass (FM%) and changes in body composition was determined by dual X-ray absorptiometry. Before and after the weight-loss period, total abdominal fat, intra-abdominal fat (IAAT), and subcutaneous abdominal fat (SCAT) were measured by single...

  3. Improved protein quality in transgenic soybean expressing a de novo synthetic protein, MB-16. (United States)

    Zhang, Yunfang; Schernthaner, Johann; Labbé, Natalie; Hefford, Mary A; Zhao, Jiping; Simmonds, Daina H


    To improve soybean [Glycine max (L.) Merrill] seed nutritional quality, a synthetic gene, MB-16 was introduced into the soybean genome to boost seed methionine content. MB-16, an 11 kDa de novo protein enriched in the essential amino acids (EAAs) methionine, threonine, lysine and leucine, was originally developed for expression in rumen bacteria. For efficient seed expression, constructs were designed using the soybean codon bias, with and without the KDEL ER retention sequence, and β-conglycinin or cruciferin seed specific protein storage promoters. Homozygous lines, with single locus integrations, were identified for several transgenic events. Transgene transmission and MB-16 protein expression were confirmed to the T5 and T7 generations, respectively. Quantitative RT-PCR analysis of developing seed showed that the transcript peaked in growing seed, 5-6 mm long, remained at this peak level to the full-sized green seed and then was significantly reduced in maturing yellow seed. Transformed events carrying constructs with the rumen bacteria codon preference showed the same transcription pattern as those with the soybean codon preference, but the transcript levels were lower at each developmental stage. MB-16 protein levels, as determined by immunoblots, were highest in full-sized green seed but the protein virtually disappeared in mature seed. However, amino acid analysis of mature seed, in the best transgenic line, showed a significant increase of 16.2 and 65.9 % in methionine and cysteine, respectively, as compared to the parent. This indicates that MB-16 elevated the sulfur amino acids, improved the EAA seed profile and confirms that a de novo synthetic gene can enhance the nutritional quality of soybean.

  4. PTEN overexpression improves cisplatin-resistance of human ovarian cancer cells through upregulating KRT10 expression

    International Nuclear Information System (INIS)

    Wu, Huijuan; Wang, Ke; Liu, Wenxin; Hao, Quan


    Highlights: • Overexpression of PTEN enhanced the sensitivity of C13K cells to cisplatin. • KRT10 is a downstream molecule of PTEN involved in the resistance-reversing effect. • Overexpression of KRT10 enhanced the chemosensitivity of C13K cells to cisplatin. - Abstract: Multi-drug resistance (MDR) is a common cause of the failure of chemotherapy in ovarian cancer. PTEN, a tumor suppressor gene, has been demonstrated to be able to reverse cisplatin-resistance in ovarian cancer cell line C13K. However, the downstream molecules of PTEN involved in the resistance-reversing effect have not been completely clarified. Therefore, we screened the downstream molecules of PTEN and studied their interactions in C13K ovarian cancer cells using a 3D culture model. Firstly, we constructed an ovarian cancer cell line stably expressing PTEN, C13K/PTEN. MTT assay showed that overexpression of PTEN enhanced the sensitivity of C13K cells to cisplatin, but not to paclitaxel. Then we examined the differently expressed proteins that interacted with PTEN in C13K/PTEN cells with or without cisplatin treatment by co-immunoprecipitation. KRT10 was identified as a differently expressed protein in cisplatin-treated C13K/PTEN cells. Further study confirmed that cisplatin could induce upregulation of KRT10 mRNA and protein in C13K/PTEN cells and there was a directly interaction between KRT10 and PTEN. Forced expression of KRT10 in C13K cells also enhanced cisplatin-induced proliferation inhibition and apoptosis of C13K cells. In addition, KRT10 siRNA blocked cisplatin-induced proliferation inhibition of C13K/PTEN cells. In conclusion, our data demonstrate that KRT10 is a downstream molecule of PTEN which improves cisplatin-resistance of ovarian cancer and forced KRT10 overexpression may also act as a therapeutic method for overcoming MDR in ovarian cancer

  5. Improved adhesive properties of recombinant bifidobacteria expressing the Bifidobacterium bifidum-specific lipoprotein BopA

    Directory of Open Access Journals (Sweden)

    Gleinser Marita


    Full Text Available Abstract Background Bifidobacteria belong to one of the predominant bacterial groups in the intestinal microbiota of infants and adults. Several beneficial effects on the health status of their human hosts have been demonstrated making bifidobacteria interesting candidates for probiotic applications. Adhesion of probiotics to the intestinal epithelium is discussed as a prerequisite for colonisation of and persistence in the gastrointestinal tract. Results In the present study, 15 different strains of bifidobacteria were tested for adhesion. B. bifidum was identified as the species showing highest adhesion to all tested intestinal epithelial cell (IEC lines. Adhesion of B. bifidum S17 to IECs was strongly reduced after treatment of bacteria with pronase. These results strongly indicate that a proteinaceous cell surface component mediates adhesion of B. bifidum S17 to IECs. In silico analysis of the currently accessible Bifidobacterium genomes identified bopA encoding a lipoprotein as a B. bifidum-specific gene previously shown to function as an adhesin of B. bifidum MIMBb75. The in silico results were confirmed by Southern Blot analysis. Furthermore, Northern Blot analysis demonstrated that bopA is expressed in all B. bifidum strains tested under conditions used to cultivate bacteria for adhesion assays. The BopA gene was successfully expressed in E. coli and purified by Ni-NTA affinity chromatography as a C-terminal His6-fusion. Purified BopA had an inhibitory effect on adhesion of B. bifidum S17 to IECs. Moreover, bopA was successfully expressed in B. bifidum S17 and B. longum/infantis E18. Strains overexpressing bopA showed enhanced adhesion to IECs, clearly demonstrating a role of BopA in adhesion of B. bifidum strains. Conclusions BopA was identified as a B. bifidum-specific protein involved in adhesion to IECs. Bifidobacterium strains expressing bopA show enhanced adhesion. Our results represent the first report on recombinant



    Çağatay Dereceli; Hüseyin Kırımoğlu; Mehmet Dallı


    This study focused on reviewing trait anger and level of anger expression styles of students who studied at School of Physical Education and Sports of Adnan Menderes University during 2016-2017 academic year in terms of some variables. As data collection tools; “Personal Information Form” and “Trait Anger and Anger Expression Scale” –designed by Spielberger et al. (1988) and adapted by Özer (1994) into Turkish- were employed. Participants’ trait anger and anger expression styles were compared...

  7. Improved detection of congestive heart failure via probabilistic symbolic pattern recognition and heart rate variability metrics. (United States)

    Mahajan, Ruhi; Viangteeravat, Teeradache; Akbilgic, Oguz


    A timely diagnosis of congestive heart failure (CHF) is crucial to evade a life-threatening event. This paper presents a novel probabilistic symbol pattern recognition (PSPR) approach to detect CHF in subjects from their cardiac interbeat (R-R) intervals. PSPR discretizes each continuous R-R interval time series by mapping them onto an eight-symbol alphabet and then models the pattern transition behavior in the symbolic representation of the series. The PSPR-based analysis of the discretized series from 107 subjects (69 normal and 38 CHF subjects) yielded discernible features to distinguish normal subjects and subjects with CHF. In addition to PSPR features, we also extracted features using the time-domain heart rate variability measures such as average and standard deviation of R-R intervals. An ensemble of bagged decision trees was used to classify two groups resulting in a five-fold cross-validation accuracy, specificity, and sensitivity of 98.1%, 100%, and 94.7%, respectively. However, a 20% holdout validation yielded an accuracy, specificity, and sensitivity of 99.5%, 100%, and 98.57%, respectively. Results from this study suggest that features obtained with the combination of PSPR and long-term heart rate variability measures can be used in developing automated CHF diagnosis tools. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Data-Driven User Feedback: An Improved Neurofeedback Strategy considering the Interindividual Variability of EEG Features

    Directory of Open Access Journals (Sweden)

    Chang-Hee Han


    Full Text Available It has frequently been reported that some users of conventional neurofeedback systems can experience only a small portion of the total feedback range due to the large interindividual variability of EEG features. In this study, we proposed a data-driven neurofeedback strategy considering the individual variability of electroencephalography (EEG features to permit users of the neurofeedback system to experience a wider range of auditory or visual feedback without a customization process. The main idea of the proposed strategy is to adjust the ranges of each feedback level using the density in the offline EEG database acquired from a group of individuals. Twenty-two healthy subjects participated in offline experiments to construct an EEG database, and five subjects participated in online experiments to validate the performance of the proposed data-driven user feedback strategy. Using the optimized bin sizes, the number of feedback levels that each individual experienced was significantly increased to 139% and 144% of the original results with uniform bin sizes in the offline and online experiments, respectively. Our results demonstrated that the use of our data-driven neurofeedback strategy could effectively increase the overall range of feedback levels that each individual experienced during neurofeedback training.

  9. The effect of biomechanical variables on force sensitive resistor error: Implications for calibration and improved accuracy. (United States)

    Schofield, Jonathon S; Evans, Katherine R; Hebert, Jacqueline S; Marasco, Paul D; Carey, Jason P


    Force Sensitive Resistors (FSRs) are commercially available thin film polymer sensors commonly employed in a multitude of biomechanical measurement environments. Reasons for such wide spread usage lie in the versatility, small profile, and low cost of these sensors. Yet FSRs have limitations. It is commonly accepted that temperature, curvature and biological tissue compliance may impact sensor conductance and resulting force readings. The effect of these variables and degree to which they interact has yet to be comprehensively investigated and quantified. This work systematically assesses varying levels of temperature, sensor curvature and surface compliance using a full factorial design-of-experiments approach. Three models of Interlink FSRs were evaluated. Calibration equations under 12 unique combinations of temperature, curvature and compliance were determined for each sensor. Root mean squared error, mean absolute error, and maximum error were quantified as measures of the impact these thermo/mechanical factors have on sensor performance. It was found that all three variables have the potential to affect FSR calibration curves. The FSR model and corresponding sensor geometry are sensitive to these three mechanical factors at varying levels. Experimental results suggest that reducing sensor error requires calibration of each sensor in an environment as close to its intended use as possible and if multiple FSRs are used in a system, they must be calibrated independently. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. A Real-Time Analysis Method for Pulse Rate Variability Based on Improved Basic Scale Entropy

    Directory of Open Access Journals (Sweden)

    Yongxin Chou


    Full Text Available Base scale entropy analysis (BSEA is a nonlinear method to analyze heart rate variability (HRV signal. However, the time consumption of BSEA is too long, and it is unknown whether the BSEA is suitable for analyzing pulse rate variability (PRV signal. Therefore, we proposed a method named sliding window iterative base scale entropy analysis (SWIBSEA by combining BSEA and sliding window iterative theory. The blood pressure signals of healthy young and old subjects are chosen from the authoritative international database MIT/PhysioNet/Fantasia to generate PRV signals as the experimental data. Then, the BSEA and the SWIBSEA are used to analyze the experimental data; the results show that the SWIBSEA reduces the time consumption and the buffer cache space while it gets the same entropy as BSEA. Meanwhile, the changes of base scale entropy (BSE for healthy young and old subjects are the same as that of HRV signal. Therefore, the SWIBSEA can be used for deriving some information from long-term and short-term PRV signals in real time, which has the potential for dynamic PRV signal analysis in some portable and wearable medical devices.

  11. Data-Driven User Feedback: An Improved Neurofeedback Strategy considering the Interindividual Variability of EEG Features. (United States)

    Han, Chang-Hee; Lim, Jeong-Hwan; Lee, Jun-Hak; Kim, Kangsan; Im, Chang-Hwan


    It has frequently been reported that some users of conventional neurofeedback systems can experience only a small portion of the total feedback range due to the large interindividual variability of EEG features. In this study, we proposed a data-driven neurofeedback strategy considering the individual variability of electroencephalography (EEG) features to permit users of the neurofeedback system to experience a wider range of auditory or visual feedback without a customization process. The main idea of the proposed strategy is to adjust the ranges of each feedback level using the density in the offline EEG database acquired from a group of individuals. Twenty-two healthy subjects participated in offline experiments to construct an EEG database, and five subjects participated in online experiments to validate the performance of the proposed data-driven user feedback strategy. Using the optimized bin sizes, the number of feedback levels that each individual experienced was significantly increased to 139% and 144% of the original results with uniform bin sizes in the offline and online experiments, respectively. Our results demonstrated that the use of our data-driven neurofeedback strategy could effectively increase the overall range of feedback levels that each individual experienced during neurofeedback training.

  12. Impact of Narrative Expressive Writing on Heart Rate, Heart Rate Variability, and Blood Pressure After Marital Separation. (United States)

    Bourassa, Kyle J; Allen, John J B; Mehl, Matthias R; Sbarra, David A

    Divorce is a common stressor that is associated with increased risk for poor long-term physical and mental health. Using an experimental design, the current study examined the impact of expressive writing (EW) on average heart rate (HR), HR variability (HRV), and blood pressure (BP) 7.5 months later. Participants from a community sample of recently separated adults (N = 109) were assigned to one of three conditions: traditional EW, narrative EW, or a control writing condition, and were assessed three times for an average of 7.5 months. Each study visit included 27 minutes of physiological assessment; the primary outcomes at each assessment were mean-level HR, HRV, BP scores averaged across six different tasks. Participants in the traditional EW condition did not significantly differ from control participants in their later HR, HRV, or BP. However, relative to control participants, those in the narrative EW condition had significantly lower HR (B = -3.41, 95% confidence interval = -5.76 to -1.06, p = .004) and higher HRV 7.5 months later (B = 0.41, 95% confidence interval = 0.16 to 0.74, p = .001). When comparing narrative EW participants to those in the traditional EW and control writing as a single group, these effects remained and were moderately sized, Cohen d values of -0.61 and 0.60, respectively, and durable across all task conditions when analyzed in independent models. The writing condition groups did not differ in their later BP. Narrative EW decreased HR and increased HRV after marital separation but did not affect BP. We discuss the possible disconnect between psychology and physiology in response to EW, as well as possible future clinical applications after marital separation.

  13. Does the ability to express different emotions predict different indices of physical health? A skill-based study of physical symptoms and heart rate variability. (United States)

    Tuck, Natalie L; Adams, Kathryn S; Consedine, Nathan S


    The outward expression of emotion has been frequently associated with better health outcomes, whereas suppressing emotion is thought to contribute to worse physical health. However, work has typically focused on trait expressive tendencies and the possibility that individual differences in the ability to express specific emotions may also be associated with health has not been widely tested. A cross-sectional study of community dwelling adults. One hundred and twenty-eight participants aged 18-88 years completed questionnaires assessing demographics and health status, before attending a testing session in which resting heart rate variability (HRV) was assessed. Participants then completed a performance-based test of expressive regulatory skill in which they were instructed to enhance and suppress their emotional expressions while they watched film clips validated to elicit amusement, sadness, and anger. Participants rated subjective emotional experience before and after each clip, and their degree of expressivity was scored using FACS-based Noldus FaceReader. Missing data resulted in a final sample size of 117. Linear regressions controlling for age, sex, diagnoses, and trait emotion revealed that greater ability to enhance sad expressions was associated with higher HRV while the ability to enhance expressions of joy was associated with lower symptom interference. In parallel models, the ability to flexibly regulate (both enhance and suppress) expressions of joy and sadness was also associated with lower symptom interference. Findings suggest that the ability to regulate expressions of both sadness and joy is associated with health indices even when controlling for trait affect and potential confounds. The present findings offer early evidence that individual differences in the ability to regulate the outward expression of emotion may be relevant to health and suggest that expressive regulatory skills offer a novel avenue for research and intervention. Statement

  14. Suppression of Tla1 gene expression for improved solar conversion efficiency and photosynthetic productivity in plants and algae (United States)

    Melis, Anastasios; Mitra, Mautusi


    The invention provides method and compositions to minimize the chlorophyll antenna size of photosynthesis by decreasing TLA1 gene expression, thereby improving solar conversion efficiencies and photosynthetic productivity in plants, e.g., green microalgae, under bright sunlight conditions.

  15. Improved methods and resources for paramecium genomics: transcription units, gene annotation and gene expression. (United States)

    Arnaiz, Olivier; Van Dijk, Erwin; Bétermier, Mireille; Lhuillier-Akakpo, Maoussi; de Vanssay, Augustin; Duharcourt, Sandra; Sallet, Erika; Gouzy, Jérôme; Sperling, Linda


    The 15 sibling species of the Paramecium aurelia cryptic species complex emerged after a whole genome duplication that occurred tens of millions of years ago. Given extensive knowledge of the genetics and epigenetics of Paramecium acquired over the last century, this species complex offers a uniquely powerful system to investigate the consequences of whole genome duplication in a unicellular eukaryote as well as the genetic and epigenetic mechanisms that drive speciation. High quality Paramecium gene models are important for research using this system. The major aim of the work reported here was to build an improved gene annotation pipeline for the Paramecium lineage. We generated oriented RNA-Seq transcriptome data across the sexual process of autogamy for the model species Paramecium tetraurelia. We determined, for the first time in a ciliate, candidate P. tetraurelia transcription start sites using an adapted Cap-Seq protocol. We developed TrUC, multi-threaded Perl software that in conjunction with TopHat mapping of RNA-Seq data to a reference genome, predicts transcription units for the annotation pipeline. We used EuGene software to combine annotation evidence. The high quality gene structural annotations obtained for P. tetraurelia were used as evidence to improve published annotations for 3 other Paramecium species. The RNA-Seq data were also used for differential gene expression analysis, providing a gene expression atlas that is more sensitive than the previously established microarray resource. We have developed a gene annotation pipeline tailored for the compact genomes and tiny introns of Paramecium species. A novel component of this pipeline, TrUC, predicts transcription units using Cap-Seq and oriented RNA-Seq data. TrUC could prove useful beyond Paramecium, especially in the case of high gene density. Accurate predictions of 3' and 5' UTR will be particularly valuable for studies of gene expression (e.g. nucleosome positioning, identification of cis

  16. Improving inter-observer variability in the evaluation of ultrasonographic features of polycystic ovaries

    Directory of Open Access Journals (Sweden)

    Leswick David A


    Full Text Available Abstract Background We recently reported poor inter-observer agreement in identifying and quantifying individual ultrasonographic features of polycystic ovaries. Our objective was to determine the effect of a training workshop on reducing inter-observer variation in the ultrasonographic evaluation of polycystic ovaries. Methods Transvaginal ultrasound recordings from thirty women with polycystic ovary syndrome (PCOS were evaluated by three radiologists and three reproductive endocrinologists both before and after an ultrasound workshop. The following endpoints were assessed: 1 follicle number per ovary (FNPO, 2 follicle number per single cross-section (FNPS, 3 largest follicle diameter, 4 ovarian volume, 5 follicle distribution pattern and 6 presence of a corpus luteum (CL. Lin's concordance correlation coefficients (rho and kappa statistics for multiple raters (kappa were used to assess level of inter-observer agreement (>0.80 good, 0.60 – 0.80 moderate/fair, Results Following the workshop, inter-observer agreement improved for the evaluation of FNPS (rho = 0.70, delta rho = +0.11, largest follicle diameter (rho = 0.77, delta rho = +0.10, ovarian volume (rho = 0.84, delta rho = +0.12, follicle distribution pattern (kappa = 0.80, delta kappa = +0.21 and presence of a CL (kappa = 0.87, delta kappa = +0.05. No improvement was evident for FNPO (rho = 0.54, delta rho = -0.01. Both radiologists and reproductive endocrinologists demonstrated improvement in scores (p Conclusion Reliability in evaluating ultrasonographic features of polycystic ovaries can be significantly improved following participation in a training workshop. If ultrasonographic evidence of polycystic ovaries is to be used as an objective measure in the diagnosis of PCOS, then standardized training modules should be implemented to unify the approach to evaluating polycystic ovarian morphology.

  17. Improving understanding of controls on spatial variability in methane fluxes in Arctic tundra (United States)

    Davidson, Scott J.; Sloan, Victoria; Phoenix, Gareth; Wagner, Robert; Oechel, Walter; Zona, Donatella


    The Arctic is experiencing rapid climate change relative to the rest of the globe, and this increase in temperature has feedback effects across hydrological and thermal regimes, plant community distribution and carbon stocks within tundra soils. Arctic wetlands account for a significant amount of methane emissions from natural ecosystems to the atmosphere and with further permafrost degradation under a warming climate, these emissions are expected to increase. Methane (CH4) is an extremely important component of the global carbon cycle with a global warming potential 28.5 times greater than carbon dioxide over a 100 year time scale (IPCC, 2013). In order to validate carbon cycle models, modelling methane at broader landscape scales is needed. To date direct measurements of methane have been sporadic in time and space which, while capturing some key controls on the spatial heterogeneity, make it difficult to accurately upscale methane emissions to the landscape and regional scales. This study investigates what is controlling the spatial heterogeneity of methane fluxes across Arctic tundra. We combined over 300 portable chamber observations from 13 micro-topographic positions (with multiple vegetation types) across three locations spanning a 300km latitudinal gradient in Northern Alaska from Barrow to Ivotuk with synchronous measurements of environmental (soil temperature, soil moisture, water table, active layer thaw depth, pH) and vegetation (plant community composition, height, sedge tiller counts) variables to evaluate key controls on methane fluxes. To assess the diurnal variation in CH4 fluxes, we also performed automated chamber measurements in one study site (Barrow) location. Multiple statistical approaches (regression tree and multiple linear regression) were used to identify key controlling variables and their interactions. Methane emissions across all sites ranged from -0.08 to 15.3 mg C-CH4 m-2 hr-1. As expected, soil moisture was the main control

  18. Cross-platform analysis of cancer microarray data improves gene expression based classification of phenotypes

    Directory of Open Access Journals (Sweden)

    Eils Roland


    Full Text Available Abstract Background The extensive use of DNA microarray technology in the characterization of the cell transcriptome is leading to an ever increasing amount of microarray data from cancer studies. Although similar questions for the same type of cancer are addressed in these different studies, a comparative analysis of their results is hampered by the use of heterogeneous microarray platforms and analysis methods. Results In contrast to a meta-analysis approach where results of different studies are combined on an interpretative level, we investigate here how to directly integrate raw microarray data from different studies for the purpose of supervised classification analysis. We use median rank scores and quantile discretization to derive numerically comparable measures of gene expression from different platforms. These transformed data are then used for training of classifiers based on support vector machines. We apply this approach to six publicly available cancer microarray gene expression data sets, which consist of three pairs of studies, each examining the same type of cancer, i.e. breast cancer, prostate cancer or acute myeloid leukemia. For each pair, one study was performed by means of cDNA microarrays and the other by means of oligonucleotide microarrays. In each pair, high classification accuracies (> 85% were achieved with training and testing on data instances randomly chosen from both data sets in a cross-validation analysis. To exemplify the potential of this cross-platform classification analysis, we use two leukemia microarray data sets to show that important genes with regard to the biology of leukemia are selected in an integrated analysis, which are missed in either single-set analysis. Conclusion Cross-platform classification of multiple cancer microarray data sets yields discriminative gene expression signatures that are found and validated on a large number of microarray samples, generated by different laboratories and

  19. Chain-loaded variable resistance warm-up improves free-weight maximal back squat performance. (United States)

    Mina, Minas A; Blazevich, Anthony J; Giakas, Giannis; Seitz, Laurent B; Kay, Anthony D


    The acute influence of chain-loaded variable resistance exercise on subsequent free-weight one-repetition maximum (1-RM) back squat performance was examined in 16 recreationally active men. The participants performed either a free-weight resistance (FWR) or chain-loaded resistance (CLR) back squat warm-up at 85% 1-RM on two separate occasions. After a 5-min rest, the participants attempted a free-weight 1-RM back squat; if successful, subsequent 5% load additions were made until participants failed to complete the lift. During the 1-RM trials, 3D knee joint kinematics and knee extensor and flexor electromyograms (EMG) were recorded simultaneously. Significantly greater 1-RM (6.2 ± 5.0%; p  .05) was found in concentric EMG, eccentric or concentric knee angular velocity, or peak knee flexion angle. Performing a CLR warm-up enhanced subsequent free-weight 1-RM performance without changes in knee flexion angle or eccentric and concentric knee angular velocities; thus a real 1-RM increase was achieved as the mechanics of the lift were not altered. These results are indicative of a potentiating effect of CLR in a warm-up, which may benefit athletes in tasks where high-level strength is required.

  20. Improving risk estimates of runoff producing areas: formulating variable source areas as a bivariate process. (United States)

    Cheng, Xiaoya; Shaw, Stephen B; Marjerison, Rebecca D; Yearick, Christopher D; DeGloria, Stephen D; Walter, M Todd


    Predicting runoff producing areas and their corresponding risks of generating storm runoff is important for developing watershed management strategies to mitigate non-point source pollution. However, few methods for making these predictions have been proposed, especially operational approaches that would be useful in areas where variable source area (VSA) hydrology dominates storm runoff. The objective of this study is to develop a simple approach to estimate spatially-distributed risks of runoff production. By considering the development of overland flow as a bivariate process, we incorporated both rainfall and antecedent soil moisture conditions into a method for predicting VSAs based on the Natural Resource Conservation Service-Curve Number equation. We used base-flow immediately preceding storm events as an index of antecedent soil wetness status. Using nine sub-basins of the Upper Susquehanna River Basin, we demonstrated that our estimated runoff volumes and extent of VSAs agreed with observations. We further demonstrated a method for mapping these areas in a Geographic Information System using a Soil Topographic Index. The proposed methodology provides a new tool for watershed planners for quantifying runoff risks across watersheds, which can be used to target water quality protection strategies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Utilizing multiple state variables to improve the dynamic range of analog switching in a memristor

    International Nuclear Information System (INIS)

    Jeong, YeonJoo; Kim, Sungho; Lu, Wei D.


    Memristors and memristive systems have been extensively studied for data storage and computing applications such as neuromorphic systems. To act as synapses in neuromorphic systems, the memristor needs to exhibit analog resistive switching (RS) behavior with incremental conductance change. In this study, we show that the dynamic range of the analog RS behavior can be significantly enhanced in a tantalum-oxide-based memristor. By controlling different state variables enabled by different physical effects during the RS process, the gradual filament expansion stage can be selectively enhanced without strongly affecting the abrupt filament length growth stage. Detailed physics-based modeling further verified the observed experimental effects and revealed the roles of oxygen vacancy drift and diffusion processes, and how the diffusion process can be selectively enhanced during the filament expansion stage. These findings lead to more desirable and reliable memristor behaviors for analog computing applications. Additionally, the ability to selectively control different internal physical processes demonstrated in the current study provides guidance for continued device optimization of memristor devices in general

  2. Improved radiological/nuclear source localization in variable NORM background: An MLEM approach with segmentation data

    Energy Technology Data Exchange (ETDEWEB)

    Penny, Robert D., E-mail: [Leidos Inc., 10260 Campus Point Road, San Diego, CA (United States); Crowley, Tanya M.; Gardner, Barbara M.; Mandell, Myron J.; Guo, Yanlin; Haas, Eric B.; Knize, Duane J.; Kuharski, Robert A.; Ranta, Dale; Shyffer, Ryan [Leidos Inc., 10260 Campus Point Road, San Diego, CA (United States); Labov, Simon; Nelson, Karl; Seilhan, Brandon [Lawrence Livermore National Laboratory, Livermore, CA (United States); Valentine, John D. [Lawrence Berkeley National Laboratory, Berkeley, CA (United States)


    A novel approach and algorithm have been developed to rapidly detect and localize both moving and static radiological/nuclear (R/N) sources from an airborne platform. Current aerial systems with radiological sensors are limited in their ability to compensate for variable naturally occurring radioactive material (NORM) background. The proposed approach suppresses the effects of NORM background by incorporating additional information to segment the survey area into regions over which the background is likely to be uniform. The method produces pixelated Source Activity Maps (SAMs) of both target and background radionuclide activity over the survey area. The task of producing the SAMs requires (1) the development of a forward model which describes the transformation of radionuclide activity to detector measurements and (2) the solution of the associated inverse problem. The inverse problem is ill-posed as there are typically fewer measurements than unknowns. In addition the measurements are subject to Poisson statistical noise. The Maximum-Likelihood Expectation-Maximization (MLEM) algorithm is used to solve the inverse problem as it is well suited for under-determined problems corrupted by Poisson noise. A priori terrain information is incorporated to segment the reconstruction space into regions within which we constrain NORM background activity to be uniform. Descriptions of the algorithm and examples of performance with and without segmentation on simulated data are presented.

  3. Improved energy performance of air cooled centrifugal chillers with variable chilled water flow

    International Nuclear Information System (INIS)

    Yu, F.W.; Chan, K.T.


    This paper considers how to apply optimum condensing temperature control and variable chilled water flow to increase the coefficient of performance (COP) of air cooled centrifugal chillers. A thermodynamic model for the chillers was developed and validated using a wide range of operating data and specifications. The model considers real process phenomena, including capacity control by the inlet guide vanes of the compressor and an algorithm to determine the number and speed of condenser fans staged based on a set point of condensing temperature. Based on the validated model, it was found that optimizing the control of condensing temperature and varying the evaporator's chilled water flow rate enable the COP to increase by 0.8-191.7%, depending on the load and ambient conditions. A cooling load profile of an office building in a subtropical climate was considered to assess the potential electricity savings resulting from the increased chiller COP and optimum staging of chillers and pumps. There is 16.3-21.0% reduction in the annual electricity consumption of the building's chiller plant. The results of this paper provide useful information on how to implement a low energy chiller plant

  4. Improving Continuous-Variable Measurement-Device-Independent Multipartite Quantum Communication with Optical Amplifiers* (United States)

    Guo, Ying; Zhao, Wei; Li, Fei; Huang, Duan; Liao, Qin; Xie, Cai-Lang


    The developing tendency of continuous-variable (CV) measurement-device-independent (MDI) quantum cryptography is to cope with the practical issue of implementing scalable quantum networks. Up to now, most theoretical and experimental researches on CV-MDI QKD are focused on two-party protocols. However, we suggest a CV-MDI multipartite quantum secret sharing (QSS) protocol use the EPR states coupled with optical amplifiers. More remarkable, QSS is the real application in multipartite CV-MDI QKD, in other words, is the concrete implementation method of multipartite CV-MDI QKD. It can implement a practical quantum network scheme, under which the legal participants create the secret correlations by using EPR states connecting to an untrusted relay via insecure links and applying the multi-entangled Greenberger-Horne-Zeilinger (GHZ) state analysis at relay station. Even if there is a possibility that the relay may be completely tampered, the legal participants are still able to extract a secret key from network communication. The numerical simulation indicates that the quantum network communication can be achieved in an asymmetric scenario, fulfilling the demands of a practical quantum network. Additionally, we illustrate that the use of optical amplifiers can compensate the partial inherent imperfections of detectors and increase the transmission distance of the CV-MDI quantum system.

  5. Omega-3 Fatty Acid Supplementation Improves Heart Rate Variability in Obese Children

    Directory of Open Access Journals (Sweden)

    Christoph Baumann


    Full Text Available Obese children and adolescents are at high risk of developing cardiovascular diseases later in life. We hypothesized that cardiovascular prophylaxis with omega-3 fatty acids could benefit them. In our study, 20 children and adolescents (mean body mass index percentile: 99.1; mean age: 11.0 years underwent two ambulatory 24 h Holter electrocardiography (ECG recordings (before and after at least 3 months of omega-3 fatty acid supplementation. Time domain heart rate variability (HRV and heart rate (HR were examined for these patients. As a control, we used 24 h Holter ECG recordings of 94 nonobese children and adolescents. Time domain HRV parameters, which are indicators of vagal stimulation, were significantly lower in obese patients than in healthy controls, but HR was higher (standard deviation of the normal-to-normal [SDNN] interbeat intervals: −34.02%; root mean square of successive differences [RMSSD] between normal heartbeats: −40.66%; percentage of consecutive RR intervals [pNN50]: −60.24%; HR: +13.37%. After omega-3 fatty acid supplementation, time domain HRV parameters and HR of obese patients were similar to the values of healthy controls (SDNN interbeat intervals: −21.73%; RMSSD: −19.56%; pNN50: −25.59%; HR: +3.94%. Therefore, omega-3 fatty acid supplementation may be used for cardiovascular prophylaxis in obese children and adolescents.

  6. Inulin Improves Postprandial Hypertriglyceridemia by Modulating Gene Expression in the Small Intestine

    Directory of Open Access Journals (Sweden)

    Sophie Hiel


    Full Text Available Postprandial hyperlipidemia is an important risk factor for cardiovascular diseases in the context of obesity. Inulin is a non-digestible carbohydrate, known for its beneficial properties in metabolic disorders. We investigated the impact of inulin on postprandial hypertriglyceridemia and on lipid metabolism in a mouse model of diet-induced obesity. Mice received a control or a western diet for 4 weeks and were further supplemented or not with inulin for 2 weeks (0.2 g/day per mouse. We performed a lipid tolerance test, measured mRNA expression of genes involved in postprandial lipid metabolism, assessed post-heparin plasma and muscle lipoprotein lipase activity and measured lipid accumulation in the enterocytes and fecal lipid excretion. Inulin supplementation in western diet-fed mice decreases postprandial serum triglycerides concentration, decreases the mRNA expression levels of Cd36 (fatty acid receptor involved in lipid uptake and sensing and apolipoprotein C3 (Apoc3, inhibitor of lipoprotein lipase in the jejunum and increases fecal lipid excretion. In conclusion, inulin improves postprandial hypertriglyceridemia by targeting intestinal lipid metabolism. This work confirms the interest of using inulin supplementation in the management of dyslipidemia linked to obesity and cardiometabolic risk.

  7. Inulin Improves Postprandial Hypertriglyceridemia by Modulating Gene Expression in the Small Intestine. (United States)

    Hiel, Sophie; Neyrinck, Audrey M; Rodriguez, Julie; Pachikian, Barbara D; Bouzin, Caroline; Thissen, Jean-Paul; Cani, Patrice D; Bindels, Laure B; Delzenne, Nathalie M


    Postprandial hyperlipidemia is an important risk factor for cardiovascular diseases in the context of obesity. Inulin is a non-digestible carbohydrate, known for its beneficial properties in metabolic disorders. We investigated the impact of inulin on postprandial hypertriglyceridemia and on lipid metabolism in a mouse model of diet-induced obesity. Mice received a control or a western diet for 4 weeks and were further supplemented or not with inulin for 2 weeks (0.2 g/day per mouse). We performed a lipid tolerance test, measured mRNA expression of genes involved in postprandial lipid metabolism, assessed post-heparin plasma and muscle lipoprotein lipase activity and measured lipid accumulation in the enterocytes and fecal lipid excretion. Inulin supplementation in western diet-fed mice decreases postprandial serum triglycerides concentration, decreases the mRNA expression levels of Cd36 (fatty acid receptor involved in lipid uptake and sensing) and apolipoprotein C3 ( Apoc3 , inhibitor of lipoprotein lipase) in the jejunum and increases fecal lipid excretion. In conclusion, inulin improves postprandial hypertriglyceridemia by targeting intestinal lipid metabolism. This work confirms the interest of using inulin supplementation in the management of dyslipidemia linked to obesity and cardiometabolic risk.

  8. A Link-Based Cluster Ensemble Approach For Improved Gene Expression Data Analysis

    Directory of Open Access Journals (Sweden)



    Full Text Available Abstract It is difficult from possibilities to select a most suitable effective way of clustering algorithm and its dataset for a defined set of gene expression data because we have a huge number of ways and huge number of gene expressions. At present many researchers are preferring to use hierarchical clustering in different forms this is no more totally optimal. Cluster ensemble research can solve this type of problem by automatically merging multiple data partitions from a wide range of different clusterings of any dimensions to improve both the quality and robustness of the clustering result. But we have many existing ensemble approaches using an association matrix to condense sample-cluster and co-occurrence statistics and relations within the ensemble are encapsulated only at raw level while the existing among clusters are totally discriminated. Finding these missing associations can greatly expand the capability of those ensemble methodologies for microarray data clustering. We propose general K-means cluster ensemble approach for the clustering of general categorical data into required number of partitions.

  9. A novel joint analysis framework improves identification of differentially expressed genes in cross disease transcriptomic analysis

    Directory of Open Access Journals (Sweden)

    Wenyi Qin


    Full Text Available Abstract Motivation Detecting differentially expressed (DE genes between disease and normal control group is one of the most common analyses in genome-wide transcriptomic data. Since most studies don’t have a lot of samples, researchers have used meta-analysis to group different datasets for the same disease. Even then, in many cases the statistical power is still not enough. Taking into account the fact that many diseases share the same disease genes, it is desirable to design a statistical framework that can identify diseases’ common and specific DE genes simultaneously to improve the identification power. Results We developed a novel empirical Bayes based mixture model to identify DE genes in specific study by leveraging the shared information across multiple different disease expression data sets. The effectiveness of joint analysis was demonstrated through comprehensive simulation studies and two real data applications. The simulation results showed that our method consistently outperformed single data set analysis and two other meta-analysis methods in identification power. In real data analysis, overall our method demonstrated better identification power in detecting DE genes and prioritized more disease related genes and disease related pathways than single data set analysis. Over 150% more disease related genes are identified by our method in application to Huntington’s disease. We expect that our method would provide researchers a new way of utilizing available data sets from different diseases when sample size of the focused disease is limited.

  10. Can accelerometry data improve estimates of heart rate variability from wrist pulse PPG sensors?* (United States)

    Kos, Maciej; Li, Xuan; Khaghani-Far, Iman; Gordon, Christine M.; Pavel, Misha; Jimison Member, Holly B.


    A key prerequisite for precision medicine is the ability to assess metrics of human behavior objectively, unobtrusively and continuously. This capability serves as a framework for the optimization of tailored, just-in-time precision health interventions. Mobile unobtrusive physiological sensors, an important prerequisite for realizing this vision, show promise in implementing this quality of physiological data collection. However, first we must trust the collected data. In this paper, we present a novel approach to improving heart rate estimates from wrist pulse photoplethysmography (PPG) sensors. We also discuss the impact of sensor movement on the veracity of collected heart rate data. PMID:29060185

  11. Can accelerometry data improve estimates of heart rate variability from wrist pulse PPG sensors? (United States)

    Kos, Maciej; Xuan Li; Khaghani-Far, Iman; Gordon, Christine M; Pavel, Misha; Jimison, Holly B


    A key prerequisite for precision medicine is the ability to assess metrics of human behavior objectively, unobtrusively and continuously. This capability serves as a framework for the optimization of tailored, just-in-time precision health interventions. Mobile unobtrusive physiological sensors, an important prerequisite for realizing this vision, show promise in implementing this quality of physiological data collection. However, first we must trust the collected data. In this paper, we present a novel approach to improving heart rate estimates from wrist pulse photoplethysmography (PPG) sensors. We also discuss the impact of sensor movement on the veracity of collected heart rate data.

  12. Variable geometry gas turbines for improving the part-load performance of marine combined cycles - Combined cycle performance

    DEFF Research Database (Denmark)

    Haglind, Fredrik


    The part-load performance of combined cycles intended for naval use is of great importance, and it is influenced by the gas turbine configuration and load control strategy. This paper is aimed at quantifying the effects of variable geometry gas turbines on the part-load efficiency for combined...... cycles used for ship propulsion. Moreover, the paper is aimed at developing methodologies and deriving models for part-load simulations suitable for energy system analysis of various components within combined cycle power plants. Two different gas turbine configurations are studied, a two-shaft aero......-derivative configuration and a single-shaft industrial configuration. The results suggest that by the use of variable geometry gas turbines, the combined cycle part-load performance can be improved. In order to minimise the voyage fuel consumption, a combined cycle featuring two-shaft gas turbines with VAN control...

  13. Using Improved Entropy-Cloud Model to Select High-Speed Railway Express Freight Train Service Sites

    Directory of Open Access Journals (Sweden)

    Wencheng Huang


    Full Text Available High-speed railway (HSR express freight train service sites selection is critical to the development of China’s Third Party Logistics market. In this paper, we formulate an improved entropy-cloud model based approach to solve the HSR express sites selection problem for the first time. The basic data of the indicators, for example, existing railway network conditions, traffic environment, express freight market demand, and policy, will be used as the inputs. We apply improved entropy method to obtain each subindicator’s weight. The cloud model will be used to select and classify each station under evaluation.

  14. Modeling and Performance Improvement of the Constant Power Regulator Systems in Variable Displacement Axial Piston Pump (United States)

    Park, Sung Hwan; Lee, Ji Min; Kim, Jong Shik


    An irregular performance of a mechanical-type constant power regulator is considered. In order to find the cause of an irregular discharge flow at the cut-off pressure area, modeling and numerical simulations are performed to observe dynamic behavior of internal parts of the constant power regulator system for a swashplate-type axial piston pump. The commercial numerical simulation software AMESim is applied to model the mechanical-type regulator with hydraulic pump and simulate the performance of it. The validity of the simulation model of the constant power regulator system is verified by comparing simulation results with experiments. In order to find the cause of the irregular performance of the mechanical-type constant power regulator system, the behavior of main components such as the spool, sleeve, and counterbalance piston is investigated using computer simulation. The shape modification of the counterbalance piston is proposed to improve the undesirable performance of the mechanical-type constant power regulator. The performance improvement is verified by computer simulation using AMESim software. PMID:24282389

  15. Modeling and Performance Improvement of the Constant Power Regulator Systems in Variable Displacement Axial Piston Pump

    Directory of Open Access Journals (Sweden)

    Sung Hwan Park


    Full Text Available An irregular performance of a mechanical-type constant power regulator is considered. In order to find the cause of an irregular discharge flow at the cut-off pressure area, modeling and numerical simulations are performed to observe dynamic behavior of internal parts of the constant power regulator system for a swashplate-type axial piston pump. The commercial numerical simulation software AMESim is applied to model the mechanical-type regulator with hydraulic pump and simulate the performance of it. The validity of the simulation model of the constant power regulator system is verified by comparing simulation results with experiments. In order to find the cause of the irregular performance of the mechanical-type constant power regulator system, the behavior of main components such as the spool, sleeve, and counterbalance piston is investigated using computer simulation. The shape modification of the counterbalance piston is proposed to improve the undesirable performance of the mechanical-type constant power regulator. The performance improvement is verified by computer simulation using AMESim software.

  16. Modeling and performance improvement of the constant power regulator systems in variable displacement axial piston pump. (United States)

    Park, Sung Hwan; Lee, Ji Min; Kim, Jong Shik


    An irregular performance of a mechanical-type constant power regulator is considered. In order to find the cause of an irregular discharge flow at the cut-off pressure area, modeling and numerical simulations are performed to observe dynamic behavior of internal parts of the constant power regulator system for a swashplate-type axial piston pump. The commercial numerical simulation software AMESim is applied to model the mechanical-type regulator with hydraulic pump and simulate the performance of it. The validity of the simulation model of the constant power regulator system is verified by comparing simulation results with experiments. In order to find the cause of the irregular performance of the mechanical-type constant power regulator system, the behavior of main components such as the spool, sleeve, and counterbalance piston is investigated using computer simulation. The shape modification of the counterbalance piston is proposed to improve the undesirable performance of the mechanical-type constant power regulator. The performance improvement is verified by computer simulation using AMESim software.

  17. Variability in colonization of arbuscular mycorrhizal fungi and its effect on mycorrhizal dependency of improved and unimproved soybean cultivars. (United States)

    Salloum, M S; Guzzo, M C; Velazquez, M S; Sagadin, M B; Luna, C M


    Breeding selection of germplasm under fertilized conditions may reduce the frequency of genes that promote mycorrhizal associations. This study was developed to compare variability in mycorrhizal colonization and its effect on mycorrhizal dependency (MD) in improved soybean genotypes (I-1 and I-2) with differential tolerance to drought stress, and in unimproved soybean genotypes (UI-3 and UI-4). As inoculum, a mixed native arbuscular mycorrhizal fungi (AMF) was isolated from soybean roots, showing spores mostly of the species Funneliformis mosseae. At 20 days, unimproved genotypes followed by I-2, showed an increase in arbuscule formation, but not in I-1. At 40 days, mycorrhizal plants showed an increase in nodulation, this effect being more evident in unimproved genotypes. Mycorrhizal dependency, evaluated as growth and biochemical parameters from oxidative stress was increased in unimproved and I-2 since 20 days, whereas in I-1, MD increased at 40 days. We cannot distinguish significant differences in AMF colonization and MD between unimproved and I-2. However, variability among improved genotypes was observed. Our results suggest that selection for improved soybean genotypes with good and rapid AMF colonization, particularly high arbuscule/hyphae ratio could be a useful strategy for the development of genotypes that optimize AMF contribution to cropping systems.

  18. Variability in the Use of Simulation for Procedural Training in Radiology Residency: Opportunities for Improvement. (United States)

    Matalon, Shanna A; Chikarmane, Sona A; Yeh, Eren D; Smith, Stacy E; Mayo-Smith, William W; Giess, Catherine S


    Increased attention to quality and safety has led to a re-evaluation of the classic apprenticeship model for procedural training. Many have proposed simulation as a supplementary teaching tool. The purpose of this study was to assess radiology resident exposure to procedural training and procedural simulation. An IRB-exempt online survey was distributed to current radiology residents in the United States by e-mail. Survey results were summarized using frequency and percentages. Chi-square tests were used for statistical analysis where appropriate. A total of 353 current residents completed the survey. 37% (n = 129/353) of respondents had never used procedure simulation. Of the residents who had used simulation, most did not do so until after having already performed procedures on patients (59%, n = 132/223). The presence of a dedicated simulation center was reported by over half of residents (56%, n = 196/353) and was associated with prior simulation experience (P = 0.007). Residents who had not had procedural simulation were somewhat likely or highly likely (3 and 4 on a 4-point Likert-scale) to participate if it were available (81%, n = 104/129). Simulation training was associated with higher comfort levels in performing procedures (P simulation training is associated with higher comfort levels when performing procedures, there is variable use in radiology resident training and its use is not currently optimized. Given the increased emphasis on patient safety, these results suggest the need to increase procedural simulation use during residency, including an earlier introduction to simulation before patient exposure. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Variable Pitch Approach for Performance Improving of Straight-Bladed VAWT at Rated Tip Speed Ratio

    Directory of Open Access Journals (Sweden)

    Zhenzhou Zhao


    Full Text Available This paper presents a new variable pitch (VP approach to increase the peak power coefficient of the straight-bladed vertical-axis wind turbine (VAWT, by widening the azimuthal angle band of the blade with the highest aerodynamic torque, instead of increasing the highest torque. The new VP-approach provides a curve of pitch angle designed for the blade operating at the rated tip speed ratio (TSR corresponding to the peak power coefficient of the fixed pitch (FP-VAWT. The effects of the new approach are exploited by using the double multiple stream tubes (DMST model and Prandtl’s mathematics to evaluate the blade tip loss. The research describes the effects from six aspects, including the lift, drag, angle of attack (AoA, resultant velocity, torque, and power output, through a comparison between VP-VAWTs and FP-VAWTs working at four TSRs: 4, 4.5, 5, and 5.5. Compared with the FP-blade, the VP-blade has a wider azimuthal zone with the maximum AoA, lift, drag, and torque in the upwind half-cycle, and yields the two new larger maximum values in the downwind half-cycle. The power distribution in the swept area of the turbine changes from an arched shape of the FP-VAWT into the rectangular shape of the VP-VAWT. The new VP-approach markedly widens the highest-performance zone of the blade in a revolution, and ultimately achieves an 18.9% growth of the peak power coefficient of the VAWT at the optimum TSR. Besides achieving this growth, the new pitching method will enhance the performance at TSRs that are higher than current optimal values, and an increase of torque is also generated.

  20. Uncovering methods for the prevention of protein aggregation and improvement of product quality in a transient expression system. (United States)

    Estes, Bram; Hsu, Yueh-Rong; Tam, Lei-Ting; Sheng, Jackie; Stevens, Jennitte; Haldankar, Raj


    Mammalian expression systems are used routinely for the production of recombinant proteins as therapeutic molecules as well as research tools. Transient expression has become increasingly popular in recent years due to its rapid timeline and improvements in expression level. While improvements to transient expression systems have focused mainly on the level of protein expression, the aspect of protein quality has received little attention. The removal of undesirable products, such as aggregation, depends primarily on purification, requiring additional cumbersome steps, which can lead to a lower product yield and longer timelines. In this study, we show that reducing the level of transcription by transfecting at a lower gene dose improves the quality of secreted molecules prone to aggregation. For gene dosing to have this effect, it is critical for the carrier DNA to be an empty vector containing the same elements as the gene containing plasmid. This approach can be used in combination with a temperature shift to hypothermic conditions during production to enhance the effect. The observed improvements not only minimized aggregation levels, but also generated products with overall superior quality, including more homogeneous signal peptide cleavage and N-linked glycosylation profiles. These techniques have produced a similar improvement in product quality with a variety of other molecules, suggesting that this may be a general approach to enhance product quality from transient expression systems. © 2014 The Authors. Published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers.

  1. Improvement of field matching in segmented-field electron conformal therapy using a variable-SCD applicator

    Energy Technology Data Exchange (ETDEWEB)

    Richert, John D [Department of Physics and Astronomy, Louisiana State University, 202 Nicholson Hall, Baton Rouge, LA 70803-4001 (United States); Hogstrom, Kenneth R [Department of Physics and Astronomy, Louisiana State University, 202 Nicholson Hall, Baton Rouge, LA 70803-4001 (United States); Fields, Robert S [Mary Bird Perkins Cancer Center, 4950 Essen Lane, Baton Rouge, LA 70809-3482 (United States); II, Kenneth L Matthews [Department of Physics and Astronomy, Louisiana State University, 202 Nicholson Hall, Baton Rouge, LA 70803-4001 (United States); Boyd, Robert A [Department of Physics and Astronomy, Louisiana State University, 202 Nicholson Hall, Baton Rouge, LA 70803-4001 (United States)


    The purpose of the present study is to demonstrate that the use of an electron applicator with energy-dependent source-to-collimator distances (SCDs) will significantly improve the dose homogeneity for abutted electron fields in segmented-field electron conformal therapy (ECT). Multiple Coulomb scattering theory was used to calculate and study the P{sub 80-20} penumbra width of off-axis dose profiles as a function of air gap and depth. Collimating insert locations with air gaps (collimator-to-isocenter distance) of 5.0, 7.5, 11.5, 17.5 and 19.5 cm were selected to provide equal P{sub 80-20} at a depth of 1.5 cm in water for energies of 6, 9, 12, 16 and 20 MeV, respectively, for a Varian 2100EX radiation therapy accelerator. A 15 x 15 cm{sup 2} applicator was modified accordingly, and collimating inserts used in the variable-SCD applicator for segmented-field ECT were constructed with diverging edges using a computer-controlled hot-wire cutter, which resulted in 0.27 mm accuracy in the abutted edges. The resulting electron beams were commissioned for the pencil-beam algorithm (PBA) on the Pinnacle{sup 3} treatment planning system. Four hypothetical planning target volumes (PTVs) and one patient were planned for segmented-field ECT using the new variable-SCD applicator, and the resulting dose distributions were compared with those calculated for the identical plans using the conventional 95 cm SCD applicator. Also, a method for quality assurance of segmented-field ECT dose plans using the variable-SCD applicator was evaluated by irradiating a polystyrene phantom using the treatment plans for the hypothetical PTVs. Treatment plans for all four of the hypothetical PTVs using the variable-SCD applicator showed significantly improved dose homogeneity in the abutment regions of the segmented-field ECT plans. This resulted in the dose spread (maximum dose-minimum dose), {sigma}, and D{sub 90-10} in the PTV being reduced by an average of 32%, 29% and 32%, respectively

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

    International Nuclear Information System (INIS)

    Hallahan, Dennis; Kataoka, Yasushi; Kuchibhotla, Jaya; Virudachalam, Subbu; Weichselbaum, Ralph


    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

  3. Improving xylitol production at elevated temperature with engineered Kluyveromyces marxianus through over-expressing transporters. (United States)

    Zhang, Jia; Zhang, Biao; Wang, Dongmei; Gao, Xiaolian; Hong, Jiong


    Three transporter genes including Kluyveromyces marxianus aquaglyceroporin gene (KmFPS1), Candida intermedia glucose/xylose facilitator gene (CiGXF1) or glucose/xylose symporter gene (CiGXS1) were over-expressed in K. marxianus YZJ017 to improve xylitol production at elevated temperatures. The xylitol production of YZJ074 that harbored CiGXF1 was improved to 147.62g/L in Erlenmeyer flask at 42°C. In fermenter, 99.29 and 149.60g/L xylitol were produced from 99.55 and 151.91g/L xylose with productivity of 4.14 and 3.40g/L/h respectively at 42°C. Even at 45°C, YZJ074 could produce 101.30g/L xylitol from 101.41g/L xylose with productivity of 2.81g/L/h. Using fed-batch fermentation through repeatedly adding non-sterilized substrate directly, YZJ074 could produce 312.05g/L xylitol which is the highest yield reported to date. The engineered strains YZJ074 which can produce xylitol at elevated temperatures is an excellent foundation for xylitol bioconversion. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Homozygous Familial Hypercholesterolemia Patients With Identical Mutations Variably Express the LDLR (Low-Density Lipoprotein Receptor): Implications for the Efficacy of Evolocumab. (United States)

    Thedrez, Aurélie; Blom, Dirk J; Ramin-Mangata, Stéphane; Blanchard, Valentin; Croyal, Mikaël; Chemello, Kévin; Nativel, Brice; Pichelin, Matthieu; Cariou, Bertrand; Bourane, Steeve; Tang, Lihua; Farnier, Michel; Raal, Frederick J; Lambert, Gilles


    Evolocumab, a PCSK9 (proprotein convertase subtilisin kexin type 9)-neutralizing antibody, lowers low-density lipoprotein cholesterol (LDL-C) in homozygous familial hypercholesterolemic (HoFH) patients with reduced LDLR (low-density lipoprotein receptor) function. However, their individual responses are highly variable, even among carriers of identical LDLR genetic defects. We aimed to elucidate why HoFH patients variably respond to PCSK9 inhibition. Lymphocytes were isolated from 22 HoFH patients enrolled in the TAUSSIG trial (Trial Assessing Long Term Use of PCSK9 Inhibition in Subjects With Genetic LDL Disorders). Ten patients were true homozygotes (FH1/FH1) and 5 identical compound heterozygotes (FH1/FH2). Lymphocytes were plated with or without mevastatin, recombinant PCSK9 (rPCSK9), or a PCSK9-neutralizing antibody. Cell surface LDLR expression was analyzed by flow cytometry. All HoFH lymphocytes had reduced cell surface LDLR expression compared with non-FH lymphocytes, for each treatment modality. Lymphocytes from FH1/FH2 patients (LDLR defective/negative) displayed the lowest LDLR expression levels followed by lymphocytes from FH1/FH1 patients (defective/defective). Mevastatin increased, whereas rPCSK9 reduced LDLR expression. The PCSK9-neutralizing antibody restored LDLR expression. Lymphocytes displaying higher LDLR expression levels were those isolated from patients presenting with lowest levels of LDL-C and apolipoprotein B, before and after 24 weeks of evolocumab treatment. These negative correlations remained significant in FH1/FH1 patients and appeared more pronounced when patients with apolipoprotein E3/E3 genotypes were analyzed separately. Significant positive correlations were found between the levels of LDLR expression and the percentage reduction in LDL-C on evolocumab treatment. Residual LDLR expression in HoFH is a major determinant of LDL-C levels and seems to drive their individual response to evolocumab. © 2017 American Heart Association

  5. Fulfilling the law of a single independent variable and improving the result of mathematical educational research (United States)

    Pardimin, H.; Arcana, N.


    Many types of research in the field of mathematics education apply the Quasi-Experimental method and statistical analysis use t-test. Quasi-experiment has a weakness that is difficult to fulfil “the law of a single independent variable”. T-test also has a weakness that is a generalization of the conclusions obtained is less powerful. This research aimed to find ways to reduce the weaknesses of the Quasi-experimental method and improved the generalization of the research results. The method applied in the research was a non-interactive qualitative method, and the type was concept analysis. Concepts analysed are the concept of statistics, research methods of education, and research reports. The result represented a way to overcome the weaknesses of quasi-Experiments and T-test. In addition, the way was to apply a combination of Factorial Design and Balanced Design, which the authors refer to as Factorial-Balanced Design. The advantages of this design are: (1) almost fulfilling “the low of single independent variable” so no need to test the similarity of the academic ability, (2) the sample size of the experimental group and the control group became larger and equal; so it becomes robust to deal with violations of the assumptions of the ANOVA test.

  6. Variable sampling-time technique for improving count rate performance of scintillation detectors

    International Nuclear Information System (INIS)

    Tanaka, E.; Nohara, N.; Murayama, H.


    A new technique is presented to improve the count rate capability of a scintillation spectrometer or a position sensitive detector with minimum loss of resolution. The technique is based on the combination of pulse shortening and selective integration in which the integration period is not fixed but shortened by the arrival of the following pulse. Theoretical analysis of the degradation of the statiscal component of resolution is made for the proposed system with delay line pulse shortening, and the factor of resolution loss is formulated as a function of the input pulse rate. A new method is also presented for determining the statistical component of resolution separately from the non-statistical system resolution. Preliminary experiments with a NaI(Tl) detector have been carried out, the results of which are consistent with the theoretical prediction. However, due to the non-exponential scintillation decay of the NaI(Tl) crystal, a simple delay line clipping is not satisfactory, and an RC high-pass filter has been added, which results in further degradation of the statistical resolution. (Auth.)

  7. Beyond clay: Towards an improved set of variables for predicting soil organic matter content (United States)

    Rasmussen, Craig; Heckman, Katherine; Wieder, William R.; Keiluweit, Marco; Lawrence, Corey R.; Berhe, Asmeret Asefaw; Blankinship, Joseph C.; Crow, Susan E.; Druhan, Jennifer; Hicks Pries, Caitlin E.; Marin-Spiotta, Erika; Plante, Alain F.; Schadel, Christina; Schmiel, Joshua P.; Sierra, Carlos A.; Thompson, Aaron; Wagai, Rota


    Improved quantification of the factors controlling soil organic matter (SOM) stabilization at continental to global scales is needed to inform projections of the largest actively cycling terrestrial carbon pool on Earth, and its response to environmental change. Biogeochemical models rely almost exclusively on clay content to modify rates of SOM turnover and fluxes of climate-active CO2 to the atmosphere. Emerging conceptual understanding, however, suggests other soil physicochemical properties may predict SOM stabilization better than clay content. We addressed this discrepancy by synthesizing data from over 5,500 soil profiles spanning continental scale environmental gradients. Here, we demonstrate that other physicochemical parameters are much stronger predictors of SOM content, with clay content having relatively little explanatory power. We show that exchangeable calcium strongly predicted SOM content in water-limited, alkaline soils, whereas with increasing moisture availability and acidity, iron- and aluminum-oxyhydroxides emerged as better predictors, demonstrating that the relative importance of SOM stabilization mechanisms scales with climate and acidity. These results highlight the urgent need to modify biogeochemical models to better reflect the role of soil physicochemical properties in SOM cycling.

  8. Individuals with Type 1 and Type 2 Diabetes Mellitus Trade Increased Hyperglycemia for Decreased Hypoglycemia When Glycemic Variability is not Improved. (United States)

    Jangam, Sujit R; Hayter, Gary; Dunn, Timothy C


    Glycemic variability refers to oscillations in blood glucose within a day and differences in blood glucose at the same time on different days. Glycemic variability is linked to hypoglycemia and hyperglycemia. The relationship among these three important metrics is examined here, specifically to show how reduction in both hypo- and hyperglycemia risk is dependent on changes in variability. To understand the importance of glycemic variability in the simultaneous reduction of hypoglycemia and hyperglycemia risk, we introduce the glycemic risk plot-estimated HbA1c % (eA1c) vs. minutes below 70 mg/dl (MB70) with constant variability contours for predicting post-intervention risks in the absence of a change in glycemic variability. The glycemic risk plot illustrates that individuals who do not reduce glycemic variability improve one of the two metrics (hypoglycemia risk or hyperglycemia risk) at the cost of the other. It is important to reduce variability to improve both risks. These results were confirmed by data collected in a randomized controlled trial consisting of individuals with type 1 and type 2 diabetes on insulin therapy. For type 1, a total of 28 individuals out of 35 (80%) showed improvement in at least one of the risks (hypo and/or hyper) during the 100-day course of the study. Seven individuals (20%) showed improvement in both. Similar data were observed for type 2 where a total of 36 individuals out of 43 (84%) showed improvement in at least one risk and 8 individuals (19%) showed improvement in both. All individuals in the study who showed improvement in both hypoglycemia and hyperglycemia risk also showed a reduction in variability. Therapy changes intended to improve an individual's hypoglycemia or hyperglycemia risk often result in the reduction of one risk at the expense of another. It is important to improve glucose variability to reduce both risks or at least maintain one risk while reducing the other. Abbott Diabetes Care.

  9. Variable-speed belt conveyor systems improve economy in operation; Drehzahlgeregelte Bandanlagen verbessern die betriebswirtschaftlichen Kennzahlen

    Energy Technology Data Exchange (ETDEWEB)

    Keller, C.; Neuffer, I.; Weber, D. [Siemens AG, Erlangen (Germany). Bereich Anlagenbau und Technische Dienstleistungen (ATD)


    Previous large conveyor system solutions were a compromise between mechanical design and electrical drive technology, usually based on slipring motors for cost reasons. Today`s power electronics systems now make it possible to use medium-voltage frequency converters in large conveyor systems. This new technology opens up design solutions with torque control that yield distinctly better behaviour under load fluctuation conditions, thereby reducing wear and tear. Experience gained from completed projects has shown that a higher-level load-dependent conveyor speed control can achieve energy savings of up to 20%, since material flows tend to be stochastic rather than constant. Maximum speed is required for short periods only and can therefore be obtained by means of field weakening, a higher gear ratio and short-time overshooting of the rated motor current. This permits the use of motors with smaller frame sizes. Furthermore, in view of the controlled torque and shorter belt runs, it is conceivable that built-in safety margins could be reduced. The solution presented here shows how a distinct improvement in cost efficiency can be attained. (orig.) [Deutsch] Bisherige Loesungen fuer grosse Bandanlagen sind ein Kompromiss zwischen mechanischer Konstruktion und elektrischer Antriebstechnik, bei der aus Kostengruenden meist Schleifringlaeufermotoren eingesetzt werden. Aufgrund der Moeglichkeiten, die die Leistungselektronik heute bietet, ist ein Einsatz von Mittelspannungsumrichtern auch auf diesem Gebiet realisierbar. Damit sind Loesungen moeglich, die besonders durch ein gefuehrtes Moment ein deutlich verbessertes Verhalten bei Momenten- oder Lastaenderungen herbeifuehren und damit eine materialschonende Betriebsweise ermoeglichen. Ausserdem hat sich bei ausgefuehrten Anlagen gezeigt, dass sich durch eine uebergeordnete foerderleistungsabhaengige Bandgeschwindigkeitsregelung auch Energie bis zu 20% einsparen laesst, da der Materialfluss nicht stetig, sondern eher

  10. Codon optimisation to improve expression of a Mycobacterium avium ssp. paratuberculosis-specific membrane-associated antigen by Lactobacillus salivarius. (United States)

    Johnston, Christopher; Douarre, Pierre E; Soulimane, Tewfik; Pletzer, Daniel; Weingart, Helge; MacSharry, John; Coffey, Aidan; Sleator, Roy D; O'Mahony, Jim


    Subunit and DNA-based vaccines against Mycobacterium avium ssp. paratuberculosis (MAP) attempt to overcome inherent issues associated with whole-cell formulations. However, these vaccines can be hampered by poor expression of recombinant antigens from a number of disparate hosts. The high G+C content of MAP invariably leads to a codon bias throughout gene expression. To investigate if the codon bias affects recombinant MAP antigen expression, the open reading frame of a MAP-specific antigen MptD (MAP3733c) was codon optimised for expression against a Lactobacillus salivarius host. Of the total 209 codons which constitute MAP3733c, 172 were modified resulting in a reduced G+C content from 61% for the native gene to 32.7% for the modified form. Both genes were placed under the transcriptional control of the PnisA promoter; allowing controlled heterologous expression in L. salivarius. Expression was monitored using fluorescence microscopy and microplate fluorometry via GFP tags translationally fused to the C-termini of the two MptD genes. A > 37-fold increase in expression was observed for the codon-optimised MAP3733synth variant over the native gene. Due to the low cost and improved expression achieved, codon optimisation significantly improves the potential of L. salivarius as an oral vaccine stratagem against Johne's disease. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  11. Improvement of the R-SWAT-FME framework to support multiple variables and multi-objective functions (United States)

    Wu, Yiping; Liu, Shu-Guang


    Application of numerical models is a common practice in the environmental field for investigation and prediction of natural and anthropogenic processes. However, process knowledge, parameter identifiability, sensitivity, and uncertainty analyses are still a challenge for large and complex mathematical models such as the hydrological/water quality model, Soil and Water Assessment Tool (SWAT). In this study, the previously developed R program language-SWAT-Flexible Modeling Environment (R-SWAT-FME) was improved to support multiple model variables and objectives at multiple time steps (i.e., daily, monthly, and annually). This expansion is significant because there is usually more than one variable (e.g., water, nutrients, and pesticides) of interest for environmental models like SWAT. To further facilitate its easy use, we also simplified its application requirements without compromising its merits, such as the user-friendly interface. To evaluate the performance of the improved framework, we used a case study focusing on both streamflow and nitrate nitrogen in the Upper Iowa River Basin (above Marengo) in the United States. Results indicated that the R-SWAT-FME performs well and is comparable to the built-in auto-calibration tool in multi-objective model calibration. Overall, the enhanced R-SWAT-FME can be useful for the SWAT community, and the methods we used can also be valuable for wrapping potential R packages with other environmental models.

  12. Collaborative Proposal: Improving Decadal Prediction of Arctic Climate Variability and Change Using a Regional Arctic System Model (RASM)

    Energy Technology Data Exchange (ETDEWEB)

    Maslowski, Wieslaw [Naval Postgraduate School, Monterey, CA (United States)


    This project aims to develop, apply and evaluate a regional Arctic System model (RASM) for enhanced decadal predictions. Its overarching goal is to advance understanding of the past and present states of arctic climate and to facilitate improvements in seasonal to decadal predictions. In particular, it will focus on variability and long-term change of energy and freshwater flows through the arctic climate system. The project will also address modes of natural climate variability as well as extreme and rapid climate change in a region of the Earth that is: (i) a key indicator of the state of global climate through polar amplification and (ii) which is undergoing environmental transitions not seen in instrumental records. RASM will readily allow the addition of other earth system components, such as ecosystem or biochemistry models, thus allowing it to facilitate studies of climate impacts (e.g., droughts and fires) and of ecosystem adaptations to these impacts. As such, RASM is expected to become a foundation for more complete Arctic System models and part of a model hierarchy important for improving climate modeling and predictions.

  13. A simple optimization can improve the performance of single feature polymorphism detection by Affymetrix expression arrays

    Directory of Open Access Journals (Sweden)

    Fujisawa Hironori


    Full Text Available Abstract Background High-density oligonucleotide arrays are effective tools for genotyping numerous loci simultaneously. In small genome species (genome size: Results We compared the single feature polymorphism (SFP detection performance of whole-genome and transcript hybridizations using the Affymetrix GeneChip® Rice Genome Array, using the rice cultivars with full genome sequence, japonica cultivar Nipponbare and indica cultivar 93-11. Both genomes were surveyed for all probe target sequences. Only completely matched 25-mer single copy probes of the Nipponbare genome were extracted, and SFPs between them and 93-11 sequences were predicted. We investigated optimum conditions for SFP detection in both whole genome and transcript hybridization using differences between perfect match and mismatch probe intensities of non-polymorphic targets, assuming that these differences are representative of those between mismatch and perfect targets. Several statistical methods of SFP detection by whole-genome hybridization were compared under the optimized conditions. Causes of false positives and negatives in SFP detection in both types of hybridization were investigated. Conclusions The optimizations allowed a more than 20% increase in true SFP detection in whole-genome hybridization and a large improvement of SFP detection performance in transcript hybridization. Significance analysis of the microarray for log-transformed raw intensities of PM probes gave the best performance in whole genome hybridization, and 22,936 true SFPs were detected with 23.58% false positives by whole genome hybridization. For transcript hybridization, stable SFP detection was achieved for highly expressed genes, and about 3,500 SFPs were detected at a high sensitivity (> 50% in both shoot and young panicle transcripts. High SFP detection performances of both genome and transcript hybridizations indicated that microarrays of a complex genome (e.g., of Oryza sativa can be


    International Nuclear Information System (INIS)

    Ancelin, C.; Le, P.; DeSaint-Quentin, S.; Villatte, N.


    This paper presents EXPRESS, an expert system developed for the automation of reliability studies. The first part consists in the description of the method for static thermohydraulic systems. In this step, the authors define the knowledge representation based on the two inference engines - ALOUETTE and LCR developed by EDF. They explain all the process to construct a fault tree from a topological and functional description of the system. Numerous examples are exhibited in illustration of the method. This is followed by the lessons derived from the studies performed on some safety systems of the PALUEL nuclear plant. The development of the same approach for electric power systems is described, insisting on the difference resulting from the sequential nature of these systems. Finally, they show the main advantages identified during the studies

  15. Quantifying the sources of variability in equine faecal egg counts: implications for improving the utility of the method. (United States)

    Denwood, M J; Love, S; Innocent, G T; Matthews, L; McKendrick, I J; Hillary, N; Smith, A; Reid, S W J


    The faecal egg count (FEC) is the most widely used means of quantifying the nematode burden of horses, and is frequently used in clinical practice to inform treatment and prevention. The statistical process underlying the FEC is complex, comprising a Poisson counting error process for each sample, compounded with an underlying continuous distribution of means between samples. Being able to quantify the sources of variability contributing to this distribution of means is a necessary step towards providing estimates of statistical power for future FEC and FECRT studies, and may help to improve the usefulness of the FEC technique by identifying and minimising unwanted sources of variability. Obtaining such estimates require a hierarchical statistical model coupled with repeated FEC observations from a single animal over a short period of time. Here, we use this approach to provide the first comparative estimate of multiple sources of within-horse FEC variability. The results demonstrate that a substantial proportion of the observed variation in FEC between horses occurs as a result of variation in FEC within an animal, with the major sources being aggregation of eggs within faeces and variation in egg concentration between faecal piles. The McMaster procedure itself is associated with a comparatively small coefficient of variation, and is therefore highly repeatable when a sufficiently large number of eggs are observed to reduce the error associated with the counting process. We conclude that the variation between samples taken from the same animal is substantial, but can be reduced through the use of larger homogenised faecal samples. Estimates are provided for the coefficient of variation (cv) associated with each within animal source of variability in observed FEC, allowing the usefulness of individual FEC to be quantified, and providing a basis for future FEC and FECRT studies. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Can survival prediction be improved by merging gene expression data sets?

    Directory of Open Access Journals (Sweden)

    Haleh Yasrebi

    Full Text Available BACKGROUND: High-throughput gene expression profiling technologies generating a wealth of data, are increasingly used for characterization of tumor biopsies for clinical trials. By applying machine learning algorithms to such clinically documented data sets, one hopes to improve tumor diagnosis, prognosis, as well as prediction of treatment response. However, the limited number of patients enrolled in a single trial study limits the power of machine learning approaches due to over-fitting. One could partially overcome this limitation by merging data from different studies. Nevertheless, such data sets differ from each other with regard to technical biases, patient selection criteria and follow-up treatment. It is therefore not clear at all whether the advantage of increased sample size outweighs the disadvantage of higher heterogeneity of merged data sets. Here, we present a systematic study to answer this question specifically for breast cancer data sets. We use survival prediction based on Cox regression as an assay to measure the added value of merged data sets. RESULTS: Using time-dependent Receiver Operating Characteristic-Area Under the Curve (ROC-AUC and hazard ratio as performance measures, we see in overall no significant improvement or deterioration of survival prediction with merged data sets as compared to individual data sets. This apparently was due to the fact that a few genes with strong prognostic power were not available on all microarray platforms and thus were not retained in the merged data sets. Surprisingly, we found that the overall best performance was achieved with a single-gene predictor consisting of CYB5D1. CONCLUSIONS: Merging did not deteriorate performance on average despite (a The diversity of microarray platforms used. (b The heterogeneity of patients cohorts. (c The heterogeneity of breast cancer disease. (d Substantial variation of time to death or relapse. (e The reduced number of genes in the merged data

  17. Modelos de regresión para variables expresadas como una proporción continua Regression models for variables expressed as a continuous proportion

    Directory of Open Access Journals (Sweden)

    Aarón Salinas-Rodríguez


    Full Text Available OBJETIVO: Describir algunas de las alternativas estadísticas disponibles para el estudio de proporciones continuas y comparar los distintos modelos que existen para evidenciar sus ventajas y desventajas, mediante su aplicación a un ejemplo práctico del ámbito de la salud pública. MATERIAL Y MÉTODOS: Con base en la Encuesta Nacional de Salud Reproductiva realizada en el año 2003, se modeló la proporción de cobertura individual en el programa de planificación familiar -propuesta en un estudio previo realizado en el Instituto Nacional de Salud Pública en Cuernavaca, Morelos, México (2005- mediante el uso de los modelos de regresión normal, gama, beta y de quasi-verosimilitud. La variante del criterio de información de Akaike (AIC que propusieron McQuarrie y Tsai se utilizó para definir el mejor modelo. A continuación, y mediante simulación (enfoque Monte Carlo/cadenas de Markov, se generó una variable con distribución beta para evaluar el comportamiento de los cuatro modelos al variar el tamaño de la muestra desde 100 hasta 18 000 observaciones. RESULTADOS: Los resultados muestran que la mejor opción estadística para el análisis de proporciones continuas es el modelo de regresión beta, de acuerdo con sus supuestos y el valor de AIC. La simulación mostró que a medida que aumenta el tamaño de la muestra, el modelo gama y, en especial, el modelo de quasi-verosimilitud se aproximan en grado significativo al modelo beta. CONCLUSIONES: Para la modelación de proporciones continuas se recomienda emplear el enfoque paramétrico de la regresión beta y evitar el uso del modelo normal. Si se tiene un tamaño de muestra grande, el uso del enfoque de quasi-verosimilitud representa una buena alternativa.OBJECTIVE: To describe some of the statistical alternatives available for studying continuous proportions and to compare them in order to show their advantages and disadvantages by means of their application in a practical example of

  18. Effective non-denaturing purification method for improving the solubility of recombinant actin-binding proteins produced by bacterial expression. (United States)

    Chung, Jeong Min; Lee, Sangmin; Jung, Hyun Suk


    Bacterial expression is commonly used to produce recombinant and truncated mutant eukaryotic proteins. However, heterologous protein expression may render synthesized proteins insoluble. The conventional method used to express a poorly soluble protein, which involves denaturation and refolding, is time-consuming and inefficient. There are several non-denaturing approaches that can increase the solubility of recombinant proteins that include using different bacterial cell strains, altering the time of induction, lowering the incubation temperature, and employing different detergents for purification. In this study, we compared several non-denaturing protocols to express and purify two insoluble 34 kDa actin-bundling protein mutants. The solubility of the mutant proteins was not affected by any of the approaches except for treatment with the detergent sarkosyl. These results indicate that sarkosyl can effectively improve the solubility of insoluble proteins during bacterial expression. Copyright © 2016. Published by Elsevier Inc.

  19. Over-expression of zmarg encoding an arginase improves grain production in maize

    International Nuclear Information System (INIS)

    Hong, D.; Tian, Y.; Meng, X.; Zhang, P.


    Arginase, as one of the three key enzymes in nitrogen catabolism, the physiological role of Arg catabolism in cereal crops has not been fully clarified. Studies have shown that arginase-encoding genes play a key role in providing nitrogen to developing seedlings in many plant species.Yield is a primary trait in many crop breeding programs, which can be increased by modification of genes related to photosynthesis, nitrogen assimilation, carbon distribution, plant architecture, and transcriptional networks controlling plant development. In the present study, a maize arginase gene ZmARG was cloned and introduced into maize inbred lines by Agrobacterium tumefaciens- mediated transformation. Putative transgenic plants were confirmed by PCR, Southern blotting RT-PCR analysis. The expression of the ZmARG gene increased arginase activity in several tissues in transgenic lines. Transgenic maize plants had significantly higher ear weight and 100-seed weight as compared with wild-type control. Our results suggested that ZmARG was a potential target gene for crop yield improvement. (author)

  20. Optical Molecular Imaging of Epidermal Growth Factor Receptor Expression to Improve Detection of Oral Neoplasia

    Directory of Open Access Journals (Sweden)

    Nitin Nitin


    Full Text Available Background: The development of noninvasive molecular imaging approaches has the potential to improve management of cancer. Methods: In this study, we demonstrate the potential of noninvasive topical delivery of an epidermal growth factor-Alexa 647 (EGF-Alexa 647 conjugate to image changes in epidermal growth factor receptor expression associated with oral neoplasia. We report a series of preclinical analyses to evaluate the optical contrast achieved after topical delivery of EGF-Alexa 647 in a variety of model systems, including cells, three-dimensional tissue cultures, and intact human tissue specimens using wide-field and high-resolution fluorescence imaging. Data were collected from 17 different oral cancer patients: eight pairs of normal and abnormal biopsies and nine resected tumors were examined. Results: The EGF-dye conjugate can be uniformly delivered throughout the oral epithelium with a penetration depth exceeding 500 µm and incubation time of less than 30 minutes. After EGF-Alexa 647 incubation, the presence of oral neoplasia is associated with a 1.5- to 6.9-fold increase in fluorescence contrast compared with grossly normal mucosa from the same patient with both wide-field and high-resolution fluorescence imaging. Conclusions: Results illustrate the potential of EGF-targeted fluorescent agents for in vivo molecular imaging, a technique that may aid in the diagnosis and characterization of oral neoplasia and allow real-time detection of tumor margins.

  1. The expression of glycerol facilitators from various yeast species improves growth on glycerol of Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Mathias Klein


    Full Text Available Glycerol is an abundant by-product during biodiesel production and additionally has several assets compared to sugars when used as a carbon source for growing microorganisms in the context of biotechnological applications. However, most strains of the platform production organism Saccharomyces cerevisiae grow poorly in synthetic glycerol medium. It has been hypothesized that the uptake of glycerol could be a major bottleneck for the utilization of glycerol in S. cerevisiae. This species exclusively relies on an active transport system for glycerol uptake. This work demonstrates that the expression of predicted glycerol facilitators (Fps1 homologues from superior glycerol-utilizing yeast species such as Pachysolen tannophilus, Komagataella pastoris, Yarrowia lipolytica and Cyberlindnera jadinii significantly improves the growth performance on glycerol of the previously selected glycerol-consuming S. cerevisiae wild-type strain (CBS 6412-13A. The maximum specific growth rate increased from 0.13 up to 0.18 h−1 and a biomass yield coefficient of 0.56 gDW/gglycerol was observed. These results pave the way for exploiting the assets of glycerol in the production of fuels, chemicals and pharmaceuticals based on baker's yeast. Keywords: Yeast, Saccharomyces cerevisiae, Glycerol, Transport, Glycerol facilitator, Fps1, Stl1

  2. Development and application of a T7 RNA polymerase-dependent expression system for antibiotic production improvement in Streptomyces. (United States)

    Wei, Junhong; Tian, Jinjin; Pan, Guoqing; Xie, Jie; Bao, Jialing; Zhou, Zeyang


    To develop a reliable and easy to use expression system for antibiotic production improvement of Streptomyces. A two-compound T7 RNA polymerase-dependent gene expression system was developed to fulfill this demand. In this system, the T7 RNA polymerase coding sequence was optimized based on the codon usage of Streptomyces coelicolor. To evaluate the functionality of this system, we constructed an activator gene overexpression strain for enhancement of actinorhodin production. By overexpression of the positive regulator actII-ORF4 with this system, the maximum actinorhodin yield of engineered strain was 15-fold higher and the fermentation time was decreased by 48 h. The modified two-compound T7 expression system improves both antibiotic production and accelerates the fermentation process in Streptomyces. This provides a general and useful strategy for strain improvement of important antibiotic producing Streptomyces strains.

  3. Analysis of the diversity of murine antibodies to dextran B1355. II. Demonstration of multiple idiotypes with variable expression in several strains

    International Nuclear Information System (INIS)

    Hansburg, D.; Briles, D.E.; Davie, J.M.


    We have developed radioimmunoassays that detect idiotypic (variable region) differences among the α(1 → 3) dextran-binding myeloma proteins U102, J558, and M104 as well as an assay that detects variable region determinants common to all three proteins. Using these assays, we have examined 7S and 19S anti-α(1 → 3) dextran antibodies induced in five murine strains of the a 1 I/sub g/C/sub H/ linkage group and the recombinant strain BAB/14. All idiotypes were expressed in both 19S and 7S antibodies from all strains, but with considerable strain-specific variability in penetrance. In two strains, one additional type of antibody, which lacked all four idiotypic determinants, generally constituted the bulk of total anti-α(1 → 3) dextran antibodies

  4. BCL-2, in combination with MVP and IGF-1R expression, improves prediction of clinical outcome in complete response cervical carcinoma patients treated by radiochemotherapy. (United States)

    Henríquez-Hernández, Luis Alberto; Lloret, Marta; Pinar, Beatriz; Bordón, Elisa; Rey, Agustín; Lubrano, Amina; Lara, Pedro Carlos


    To investigate whether BCL-2 expression would improve MVP/IGF-1R prediction of clinical outcome in cervix carcinoma patients treated by radiochemotherapy, and suggest possible mechanisms behind this effect. Fifty consecutive patients, who achieved complete response to treatment, from a whole series of 60 cases suffering from non-metastatic localized cervical carcinoma, were prospectively included in this study from July 1999 to December 2003. Follow-up was closed in January 2011. All patients received pelvic radiation (45-64.80 Gy in 1.8-2 Gy fractions) with concomitant cisplatin at 40 mg/m2/week doses followed by brachytherapy. Oncoprotein expression was studied by immunohistochemistry in paraffin-embedded tumour tissue. No relation was found between BCL-2 and clinicopathological variables. High MVP/IGF-1R/BCL-2 tumour expression was strongly related to poor local and regional disease-free survival (PMVP, and IGF-1R overexpression were related to poorer clinical outcome in cervical cancer patients who achieved clinical complete response to radiochemotherapy. The NHEJ repair protein Ku70/80 expression could be involved in the regulation of these oncoproteins. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Reduced Penetrance and Variable Expression of SCN5A Mutations and the Importance of Co-inherited Genetic Variants: Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    T. Robyns, MD.


    Full Text Available Mutations in the SCN5A gene are responsible for multiple phenotypical presentations including Brugada syndrome, long QT syndrome, progressive familial heart block, sick sinus syndrome, dilated cardiomyopathy, lone atrial fibrillation and multiple overlap syndromes. These different phenotypic expressions of a mutation in a single gene can be explained by variable expression and reduced penetrance. One of the possible explanations of these phenomena is the co-inheritance of genetic variants. We describe a family where the individuals exhibit a compound heterozygosity in the SCN5A gene including a mutation (R1632H and a new variant (M858L. Individuals with both the mutation and new variant present with a more severe phenotype including spontaneous atrial tachyarrhythmia at young age. We give an overview of the different phenotypes of "SCN5A disease" and discuss the importance of co-inherited genetic variants in the expression of SCN5A disease.

  6. Determination of supplier-to-supplier and lot-to-lot variability in glycation of recombinant human serum albumin expressed in Oryza sativa.

    Directory of Open Access Journals (Sweden)

    Grant E Frahm

    Full Text Available The use of different expression systems to produce the same recombinant human protein can result in expression-dependent chemical modifications (CMs leading to variability of structure, stability and immunogenicity. Of particular interest are recombinant human proteins expressed in plant-based systems, which have shown particularly high CM variability. In studies presented here, recombinant human serum albumins (rHSA produced in Oryza sativa (Asian rice (OsrHSA from a number of suppliers have been extensively characterized and compared to plasma-derived HSA (pHSA and rHSA expressed in yeast (Pichia pastoris and Saccharomyces cerevisiae. The heterogeneity of each sample was evaluated using size exclusion chromatography (SEC, reversed-phase high-performance liquid chromatography (RP-HPLC and capillary electrophoresis (CE. Modifications of the samples were identified by liquid chromatography-mass spectrometry (LC-MS. The secondary and tertiary structure of the albumin samples were assessed with far U/V circular dichroism spectropolarimetry (far U/V CD and fluorescence spectroscopy, respectively. Far U/V CD and fluorescence analyses were also used to assess thermal stability and drug binding. High molecular weight aggregates in OsrHSA samples were detected with SEC and supplier-to-supplier variability and, more critically, lot-to-lot variability in one manufactures supplied products were identified. LC-MS analysis identified a greater number of hexose-glycated arginine and lysine residues on OsrHSA compared to pHSA or rHSA expressed in yeast. This analysis also showed supplier-to-supplier and lot-to-lot variability in the degree of glycation at specific lysine and arginine residues for OsrHSA. Both the number of glycated residues and the degree of glycation correlated positively with the quantity of non-monomeric species and the chromatographic profiles of the samples. Tertiary structural changes were observed for most OsrHSA samples which

  7. MYT1L mutations cause intellectual disability and variable obesity by dysregulating gene expression and development of the neuroendocrine hypothalamus.

    Directory of Open Access Journals (Sweden)

    Patricia Blanchet


    Full Text Available Deletions at chromosome 2p25.3 are associated with a syndrome consisting of intellectual disability and obesity. The smallest region of overlap for deletions at 2p25.3 contains PXDN and MYT1L. MYT1L is expressed only within the brain in humans. We hypothesized that single nucleotide variants (SNVs in MYT1L would cause a phenotype resembling deletion at 2p25.3. To examine this we sought MYT1L SNVs in exome sequencing data from 4, 296 parent-child trios. Further variants were identified through a genematcher-facilitated collaboration. We report 9 patients with MYT1L SNVs (4 loss of function and 5 missense. The phenotype of SNV carriers overlapped with that of 2p25.3 deletion carriers. To identify the transcriptomic consequences of MYT1L loss of function we used CRISPR-Cas9 to create a knockout cell line. Gene Ontology analysis in knockout cells demonstrated altered expression of genes that regulate gene expression and that are localized to the nucleus. These differentially expressed genes were enriched for OMIM disease ontology terms "mental retardation". To study the developmental effects of MYT1L loss of function we created a zebrafish knockdown using morpholinos. Knockdown zebrafish manifested loss of oxytocin expression in the preoptic neuroendocrine area. This study demonstrates that MYT1L variants are associated with syndromic obesity in humans. The mechanism is related to dysregulated expression of neurodevelopmental genes and altered development of the neuroendocrine hypothalamus.

  8. Improving actuation efficiency through variable recruitment hydraulic McKibben muscles: modeling, orderly recruitment control, and experiments. (United States)

    Meller, Michael; Chipka, Jordan; Volkov, Alexander; Bryant, Matthew; Garcia, Ephrahim


    Hydraulic control systems have become increasingly popular as the means of actuation for human-scale legged robots and assistive devices. One of the biggest limitations to these systems is their run time untethered from a power source. One way to increase endurance is by improving actuation efficiency. We investigate reducing servovalve throttling losses by using a selective recruitment artificial muscle bundle comprised of three motor units. Each motor unit is made up of a pair of hydraulic McKibben muscles connected to one servovalve. The pressure and recruitment state of the artificial muscle bundle can be adjusted to match the load in an efficient manner, much like the firing rate and total number of recruited motor units is adjusted in skeletal muscle. A volume-based effective initial braid angle is used in the model of each recruitment level. This semi-empirical model is utilized to predict the efficiency gains of the proposed variable recruitment actuation scheme versus a throttling-only approach. A real-time orderly recruitment controller with pressure-based thresholds is developed. This controller is used to experimentally validate the model-predicted efficiency gains of recruitment on a robot arm. The results show that utilizing variable recruitment allows for much higher efficiencies over a broader operating envelope.

  9. An improved two-way continuous-variable quantum key distribution protocol with added noise in homodyne detection

    International Nuclear Information System (INIS)

    Sun Maozhu; Peng Xiang; Guo Hong


    We propose an improved two-way continuous-variable quantum key distribution (CV QKD) protocol by adding proper random noise on the receiver’s homodyne detection, the security of which is analysed against general collective attacks. The simulation result under the collective entangling cloner attack indicates that despite the correlation between two-way channels decreasing the secret key rate relative to the uncorrelated channels slightly, the performance of the two-way protocol is still far beyond that of the one-way protocols. Importantly, the added noise in detection is beneficial for the secret key rate and the tolerable excess noise of this two-way protocol. With the reasonable reconciliation efficiency of 90%, the two-way CV QKD with added noise allows the distribution of secret keys over 60 km fibre distance. (paper)

  10. Options to Improve the Quality of Wind Generation Output Forecasting with the Use of Available Information as Explanatory Variables

    Directory of Open Access Journals (Sweden)

    Rafał Magulski


    Full Text Available Development of wind generation, besides its positive aspects related to the use of renewable energy, is a challenge from the point of view of power systems’ operational security and economy. The uncertain and variable nature of wind generation sources entails the need for the for the TSO to provide adequate reserves of power, necessary to maintain the grid’s stable operation, and the actors involved in the trading of energy from these sources incur additional of balancing unplanned output deviations. The paper presents the results of analyses concerning the options to forecast a selected wind farm’s output exercised by means of different methods of prediction, using a different range of measurement and forecasting data available on the farm and its surroundings. The analyses focused on the evaluation of forecast errors, and selection of input data for forecasting models and assessment of their impact on prediction quality improvement.

  11. iHeartLift: a closed loop system with bio-feedback that uses music tempo variability to improve heart rate variability. (United States)

    Ho, Thomas C T; Chen, Xiang


    "Musica delenit bestiam feram" translates into "Music soothes the savage beast". There is a hidden truth in this ancient quip passed down from generations. Besides soothing the heart, it also incites the heart to a healthier level of heart rate variability (HRV). In this paper, an approach to use and test music and biofeedback to increase the heart rate variability for people facing daily stress is discussed. By determining the music tempo variability (MTV) of a piece of music and current heart rate variability, iHeartLift is able to compare the 2 trends and locate a musical piece that is suited to increase the user's heart rate variability to a healthier level. With biofeedback, the 2 trends are continuously compared in real-time and the musical piece is changed in accordance with the current comparisons. A study was conducted and it was generally found that HRV can be uplifted by music regardless of language and meaning of musical lyrics but with limitations to musical genre.

  12. Mediation of social cognitive theory variables in the relationship of exercise and improved eating in sedentary adults with severe obesity. (United States)

    Annesi, James J; Tennant, Gisèle A


    Results from behavioral treatments for obesity have been disappointing due to an inability to sustain healthy eating. The concurrent use of theory, research, and practical application has the potential of reducing overeating through innovative treatments. When overweight individuals begin an exercise program their eating tends to improve, however, the basis of this relationship is not determined. If the psychosocial mediators of the relationship between exercise and improved eating are better understood, supported exercise may be a key component for improving the efficacy of behavioral weight management treatments. In Phase 1 of this research, psychosocial variables derived from social cognitive theory were tested as possible mediators of the relationship of exercise participation with increased fruit and vegetable intake in severely obese adults initiating a 26-week treatment of supported exercise and standard nutrition education (n = 161). Change in self-regulation for healthy eating and self-regulation at treatment end was a strong mediator; with the addition of mood and self-efficacy for healthy eating being additional mediators that notably increased effect ratios. In Phase 2, participants in a cognitive-behavioral nutrition treatment tailored to improve the identified mediators (n = 163) were contrasted with the original group. The cognitive-behavioral nutrition treatment was associated with significantly greater increases than standard nutrition education in self-regulation, p = 0.023, CIs [4.69, 6.48], and [3.19, 5.02], respectively; self-efficacy, p = 0.013, CIs [19.72, 29.41], and [11.70, 20.71], respectively; and a marginally significant decrease in negative mood, p = 0.062, CIs [-14.26, -9.36], and [-10.90, -6.45], respectively. Findings served to inform treatment designs concerning the use of supported exercise and cognitive-behavioral means to derive better outcomes related to nutrition and weight loss in individuals with severe

  13. Executive Summary of the NHLBI Workshop Report: Leveraging Current Scientific Advancements to Understand Sarcoidosis Variability and Improve Outcomes. (United States)

    Maier, Lisa A; Crouser, Elliott D; Martin, William J; Eu, Jerry


    Sarcoidosis is a systemic granulomatous disease that primarily affects the lung; it is associated with significant disparities, more commonly impacting those in the prime of their lives (age 20-50 yr, with a second peak after age 60 yr), black individuals, and women. However, the burden of disease, the ability to diagnose and prognose organ involvement and course, as well as specific treatment options, management options, and disease pathogenesis remain poorly understood. As a result, the National Heart, Lung, and Blood Institute undertook a sarcoidosis workshop, "Leveraging Current Scientific Advancements to Understand Sarcoidosis Variability and Improve Outcomes," to help address these issues by defining the scientific and clinical priorities to improve sarcoidosis care. The overarching recommendations from this workshop are outlined in the following summary and detailed in the accompanying articles. The recommendations included establishing collaborations and networks to conduct research based on consensus definitions of disease phenotypes and standards of care, and to provide clinical outreach to areas with a burden of disease to improve care. These collaborative networks would also serve as the hub to conduct clinical trials of devastating phenotypes (e.g., cardiac, neurologic, and fibrotic disease) not only for treatment but to enhance our understanding of the burden of disease. In addition, the networks would be used to leverage state-of-the-art "omics" and systems biology research, as well as other studies to advance understanding of disease pathogenesis, and development of biomarkers and therapeutic targets, with a goal to translate this information to improve care of individuals with sarcoidosis.

  14. Changes in heart rate variability are associated with expression of short-term and long-term contextual and cued fear memories.

    Directory of Open Access Journals (Sweden)

    Jun Liu

    Full Text Available Heart physiology is a highly useful indicator for measuring not only physical states, but also emotional changes in animals. Yet changes of heart rate variability during fear conditioning have not been systematically studied in mice. Here, we investigated changes in heart rate and heart rate variability in both short-term and long-term contextual and cued fear conditioning. We found that while fear conditioning could increase heart rate, the most significant change was the reduction in heart rate variability which could be further divided into two distinct stages: a highly rhythmic phase (stage-I and a more variable phase (stage-II. We showed that the time duration of the stage-I rhythmic phase were sensitive enough to reflect the transition from short-term to long-term fear memories. Moreover, it could also detect fear extinction effect during the repeated tone recall. These results suggest that heart rate variability is a valuable physiological indicator for sensitively measuring the consolidation and expression of fear memories in mice.

  15. Improvements in force variability and structure from vision- to memory-guided submaximal isometric knee extension in subacute stroke. (United States)

    Chow, John W; Stokic, Dobrivoje S


    We examined changes in variability, accuracy, frequency composition, and temporal regularity of force signal from vision-guided to memory-guided force-matching tasks in 17 subacute stroke and 17 age-matched healthy subjects. Subjects performed a unilateral isometric knee extension at 10, 30, and 50% of peak torque [maximum voluntary contraction (MVC)] for 10 s (3 trials each). Visual feedback was removed at the 5-s mark in the first two trials (feedback withdrawal), and 30 s after the second trial the subjects were asked to produce the target force without visual feedback (force recall). The coefficient of variation and constant error were used to quantify force variability and accuracy. Force structure was assessed by the median frequency, relative spectral power in the 0-3-Hz band, and sample entropy of the force signal. At 10% MVC, the force signal in subacute stroke subjects became steadier, more broadband, and temporally more irregular after the withdrawal of visual feedback, with progressively larger error at higher contraction levels. Also, the lack of modulation in the spectral frequency at higher force levels with visual feedback persisted in both the withdrawal and recall conditions. In terms of changes from the visual feedback condition, the feedback withdrawal produced a greater difference between the paretic, nonparetic, and control legs than the force recall. The overall results suggest improvements in force variability and structure from vision- to memory-guided force control in subacute stroke despite decreased accuracy. Different sensory-motor memory retrieval mechanisms seem to be involved in the feedback withdrawal and force recall conditions, which deserves further study. NEW & NOTEWORTHY We demonstrate that in the subacute phase of stroke, force signals during a low-level isometric knee extension become steadier, more broadband in spectral power, and more complex after removal of visual feedback. Larger force errors are produced when recalling

  16. Lupanine Improves Glucose Homeostasis by Influencing KATP Channels and Insulin Gene Expression

    Directory of Open Access Journals (Sweden)

    Mats Wiedemann


    Full Text Available The glucose-lowering effects of lupin seeds involve the combined action of several components. The present study investigates the influence of one of the main quinolizidine alkaloids, lupanine, on pancreatic beta cells and in an animal model of type-2 diabetes mellitus. In vitro studies were performed with insulin-secreting INS-1E cells or islets of C57BL/6 mice. In the in vivo experiments, hyperglycemia was induced in rats by injecting streptozotocin (65 mg/kg body weight. In the presence of 15 mmol/L glucose, insulin secretion was significantly elevated by 0.5 mmol/L lupanine, whereas the alkaloid did not stimulate insulin release with lower glucose concentrations. In islets treated with l-arginine, the potentiating effect of lupanine already occurred at 8 mmol/L glucose. Lupanine increased the expression of the Ins-1 gene. The potentiating effect on secretion was correlated to membrane depolarization and an increase in the frequency of Ca2+ action potentials. Determination of the current through ATP-dependent K+ channels (KATP channels revealed that lupanine directly inhibited the channel. The effect was dose-dependent but, even with a high lupanine concentration of 1 mmol/L or after a prolonged exposure time (12 h, the KATP channel block was incomplete. Oral administration of lupanine did not induce hypoglycemia. By contrast, lupanine improved glycemic control in response to an oral glucose tolerance test in streptozotocin-diabetic rats. In summary, lupanine acts as a positive modulator of insulin release obviously without a risk for hypoglycemic episodes.

  17. Truncation of a mannanase from Trichoderma harzianum improves its enzymatic properties and expression efficiency in Trichoderma reesei. (United States)

    Wang, Juan; Zeng, Desheng; Liu, Gang; Wang, Shaowen; Yu, Shaowen


    To obtain high expression efficiency of a mannanase gene, ThMan5A, cloned from Trichoderma harzianum MGQ2, both the full-length gene and a truncated gene (ThMan5AΔCBM) that contains only the catalytic domain, were expressed in Trichoderma reesei QM9414 using the strong constitutive promoter of the gene encoding pyruvate decarboxylase (pdc), and purified to homogeneity, respectively. We found that truncation of the gene improved its expression efficiency as well as the enzymatic properties of the encoded protein. The recombinant strain expressing ThMan5AΔCBM produced 2,460 ± 45.1 U/ml of mannanase activity in the culture supernatant; 2.3-fold higher than when expressing the full-length ThMan5A gene. In addition, the truncated mannanase had superior thermostability compared with the full-length enzyme and retained 100 % of its activity after incubation at 60 °C for 48 h. Our results clearly show that the truncated ThMan5A enzyme exhibited improved characteristics both in expression efficiency and in its thermal stability. These characteristics suggest that ThMan5AΔCBM has potential applications in the food, feed, paper, and pulp industries.

  18. Improvements on a simple muscle-based 3D face for realistic facial expressions

    NARCIS (Netherlands)

    Bui, T.D.; Heylen, Dirk K.J.; Nijholt, Antinus; Badler, N.; Thalmann, D.


    Facial expressions play an important role in face-to-face communication. With the development of personal computers capable of rendering high quality graphics, computer facial animation has produced more and more realistic facial expressions to enrich human-computer communication. In this paper, we

  19. Design-Based Learning for Biology: Genetic Engineering Experience Improves Understanding of Gene Expression (United States)

    Ellefson, Michelle R.; Brinker, Rebecca A.; Vernacchio, Vincent J.; Schunn, Christian D.


    Gene expression is a difficult topic for students to learn and comprehend, at least partially because it involves various biochemical structures and processes occurring at the microscopic level. Designer Bacteria, a design-based learning (DBL) unit for high-school students, applies principles of DBL to the teaching of gene expression. Throughout…

  20. IMP3 expression in human ovarian cancer is associated with improved survival

    DEFF Research Database (Denmark)

    Noske, Aurelia; Faggad, Areeg; Wirtz, Ralph


    The insulin-like growth factor-II mRNA-binding protein IMP3 plays an important role in embryogenesis and recent reports suggest an involvement in tumorigenesis. Although IMP3 expression has been well studied in mouse and human fetal and adult gonads, its role in ovarian cancer is unknown. We...... investigated the expression of IMP3 at protein and mRNA levels in a cohort of primary ovarian carcinomas and in 11 ovarian cancer cell lines. Western blot analysis revealed an expression of IMP3 in all ovarian cancer cell lines and immunohistochemistry demonstrated a positive cytoplasmic staining in 32 of 68...... carcinomas (47%). In contrast, epithelium of borderline tumors, as well as, benign ovarian lesions and normal ovaries exhibited only weak or no IMP3 expression. In univariate Kaplan-Meier analysis, IMP3 protein expression was significantly associated with better overall survival (P=0.048). To confirm...

  1. Investment of Vehicle Fixed Asset Investment on improving profitability (Case study of Parahyangan Express Karawang Branch

    Directory of Open Access Journals (Sweden)

    Sri Suartini


    Full Text Available The purpose of this study is to determine how much influence has fixed asset investment in profitability of Parahyangan Express Karawang Branch. This research uses the descriptive method with primary data source of Parahyangan Express Karawang Branch between 2007 - 2016. The result of this research is r average investment value of Parahyangan Express in the period 2007 until 2016. Parahyangan Express in the period 2007 to 2016 tends to decline. Based on test results t comparison t arithmetic with t table showing 2.840> 2.093 t count more than t table. The percentage of influence of fixed asset investment of 30% means 30 % development of profitability. Parahyangan Express is influenced by in-kind fixed assets while 70 % is influenced by other factors not examined in this study.

  2. Benefits and costs of improved cookstoves: assessing the implications of variability in health, forest and climate impacts.

    Directory of Open Access Journals (Sweden)

    Marc A Jeuland

    Full Text Available Current attention to improved cook stoves (ICS focuses on the "triple benefits" they provide, in improved health and time savings for households, in preservation of forests and associated ecosystem services, and in reducing emissions that contribute to global climate change. Despite the purported economic benefits of such technologies, however, progress in achieving large-scale adoption and use has been remarkably slow. This paper uses Monte Carlo simulation analysis to evaluate the claim that households will always reap positive and large benefits from the use of such technologies. Our analysis allows for better understanding of the variability in economic costs and benefits of ICS use in developing countries, which depend on unknown combinations of numerous uncertain parameters. The model results suggest that the private net benefits of ICS will sometimes be negative, and in many instances highly so. Moreover, carbon financing and social subsidies may help enhance incentives to adopt, but will not always be appropriate. The costs and benefits of these technologies are most affected by their relative fuel costs, time and fuel use efficiencies, the incidence and cost-of-illness of acute respiratory illness, and the cost of household cooking time. Combining these results with the fact that households often find these technologies to be inconvenient or culturally inappropriate leads us to understand why uptake has been disappointing. Given the current attention to the scale up of ICS, this analysis is timely and important for highlighting some of the challenges for global efforts to promote ICS.

  3. Whole-Body Vibration Training Improves Heart Rate Variability and Body Fat Percentage in Obese Hispanic Postmenopausal Women. (United States)

    Severino, Gregory; Sanchez-Gonzalez, Marcos; Walters-Edwards, Michelle; Nordvall, Michael; Chernykh, Oksana; Adames, Jason; Wong, Alexei


    The present study examined the effects of a 6-week whole-body vibration training (WBVT) regimen on heart rate variability (HRV) and body composition in obese Hispanic postmenopausal women. Participants were randomly assigned to either WBVT (n = 13) or a nonexercising control group (n = 14). HRV and body composition were measured before and after 6 weeks. There was a significant group by time interaction (P < .05) for heart rate, sympathovagal balance, and body fat percentage (BF%) such that all significantly decreased (P < .05); and R-R intervals significantly increased (P < .05) following WBVT compared to no changes after control. The changes in sympathovagal balance were correlated with changes in BF% (r = .63, P < .05). Our findings indicate that WBVT improves HRV and BF% in obese Hispanic postmenopausal women. The improvement in BF% partially explained the decrease in sympathovagal balance. Since obese and older individuals are at increased risk of developing cardiovascular diseases, they could potentially benefit from WBVT.

  4. RepSox improves viability and regulates gene expression in rhesus monkey-pig interspecies cloned embryos. (United States)

    Zhu, Hai-Ying; Jin, Long; Guo, Qing; Luo, Zhao-Bo; Li, Xiao-Chen; Zhang, Yu-Chen; Xing, Xiao-Xu; Xuan, Mei-Fu; Zhang, Guang-Lei; Luo, Qi-Rong; Wang, Jun-Xia; Cui, Cheng-Du; Li, Wen-Xue; Cui, Zheng-Yun; Yin, Xi-Jun; Kang, Jin-Dan


    To investigate the effect of the small molecule, RepSox, on the expression of developmentally important genes and the pre-implantation development of rhesus monkey-pig interspecies somatic cell nuclear transfer (iSCNT) embryos. Rhesus monkey cells expressing the monomeric red fluorescent protein 1 which have a normal (42) chromosome complement, were used as donor cells to generate iSCNT embryos. RepSox increased the expression levels of the pluripotency-related genes, Oct4 and Nanog (p  0.05), this was not significant. RepSox can improve the developmental potential of rhesus monkey-pig iSCNT embryos by regulating the expression of pluripotency-related genes.

  5. Advanced Design of Dumbbell-shaped Genetic Minimal Vectors Improves Non-coding and Coding RNA Expression. (United States)

    Jiang, Xiaoou; Yu, Han; Teo, Cui Rong; Tan, Genim Siu Xian; Goh, Sok Chin; Patel, Parasvi; Chua, Yiqiang Kevin; Hameed, Nasirah Banu Sahul; Bertoletti, Antonio; Patzel, Volker


    Dumbbell-shaped DNA minimal vectors lacking nontherapeutic genes and bacterial sequences are considered a stable, safe alternative to viral, nonviral, and naked plasmid-based gene-transfer systems. We investigated novel molecular features of dumbbell vectors aiming to reduce vector size and to improve the expression of noncoding or coding RNA. We minimized small hairpin RNA (shRNA) or microRNA (miRNA) expressing dumbbell vectors in size down to 130 bp generating the smallest genetic expression vectors reported. This was achieved by using a minimal H1 promoter with integrated transcriptional terminator transcribing the RNA hairpin structure around the dumbbell loop. Such vectors were generated with high conversion yields using a novel protocol. Minimized shRNA-expressing dumbbells showed accelerated kinetics of delivery and transcription leading to enhanced gene silencing in human tissue culture cells. In primary human T cells, minimized miRNA-expressing dumbbells revealed higher stability and triggered stronger target gene suppression as compared with plasmids and miRNA mimics. Dumbbell-driven gene expression was enhanced up to 56- or 160-fold by implementation of an intron and the SV40 enhancer compared with control dumbbells or plasmids. Advanced dumbbell vectors may represent one option to close the gap between durable expression that is achievable with integrating viral vectors and short-term effects triggered by naked RNA.

  6. GR and ER co-activation alters the expression of differentiation genes and associates with improved ER+ breast cancer outcome (United States)

    West, Diana C.; Pan, Deng; Tonsing-Carter, Eva Y.; Hernandez, Kyle M.; Pierce, Charles F.; Styke, Sarah C.; Bowie, Kathleen R.; Garcia, Tzintzuni I.; Kocherginsky, Masha; Conzen, Suzanne D.


    In estrogen receptor (ER)-negative breast cancer (BC), high tumor glucocorticoid receptor (GR) expression has been associated with a relatively poor outcome. In contrast, using a meta-analysis of several genomic datasets, here we find that tumor GR mRNA expression is associated with improved ER+ relapse-free survival (RFS) (independently of progesterone receptor (PR) expression). To understand the mechanism by which GR expression is associated with a better ER+ BC outcome, the global effect of GR-mediated transcriptional activation in ER+ BC cells was studied. Analysis of GR chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) in ER+/GR+ MCF-7 cells revealed that upon co-activation of GR and ER, GR chromatin association became enriched at proximal promoter regions. Furthermore, following ER activation, increased GR chromatin association was observed at ER, FOXO, and AP1 response elements. In addition, ER associated with GR response elements, suggesting that ER and GR interact in a complex. Co-activation of GR and ER resulted in increased expression (relative to ER activation alone) of transcripts that encode proteins promoting cellular differentiation (e.g. KDM4B, VDR) and inhibiting the Wnt-signaling pathway (IGFBP4). Finally, expression of these individual pro-differentiation genes was associated with significantly improved RFS in ER+ BC patients. Together, these data suggest that the co-expression and subsequent activity of tumor cell GR and ER contribute to the less aggressive natural history of early-stage BC by coordinating the altered expression of genes favoring differentiation. Implications The interaction between estrogen and glucocorticoid receptor activity highlights the importance of context-dependent nuclear receptor function in cancer. PMID:27141101

  7. Multi-scale enhancement of climate prediction over land by improving the model sensitivity to vegetation variability (United States)

    Alessandri, A.; Catalano, F.; De Felice, M.; Hurk, B. V. D.; Doblas-Reyes, F. J.; Boussetta, S.; Balsamo, G.; Miller, P. A.


    Here we demonstrate, for the first time, that the implementation of a realistic representation of vegetation in Earth System Models (ESMs) can significantly improve climate simulation and prediction across multiple time-scales. The effective sub-grid vegetation fractional coverage vary seasonally and at interannual time-scales in response to leaf-canopy growth, phenology and senescence. Therefore it affects biophysical parameters such as the surface resistance to evapotranspiration, albedo, roughness lenght, and soil field capacity. To adequately represent this effect in the EC-Earth ESM, we included an exponential dependence of the vegetation cover on the Leaf Area Index.By comparing two sets of simulations performed with and without the new variable fractional-coverage parameterization, spanning from centennial (20th Century) simulations and retrospective predictions to the decadal (5-years), seasonal (2-4 months) and weather (4 days) time-scales, we show for the first time a significant multi-scale enhancement of vegetation impacts in climate simulation and prediction over land. Particularly large effects at multiple time scales are shown over boreal winter middle-to-high latitudes over Canada, West US, Eastern Europe, Russia and eastern Siberia due to the implemented time-varying shadowing effect by tree-vegetation on snow surfaces. Over Northern Hemisphere boreal forest regions the improved representation of vegetation-cover consistently correct the winter warm biases, improves the climate change sensitivity, the decadal potential predictability as well as the skill of forecasts at seasonal and weather time-scales. Significant improvements of the prediction of 2m temperature and rainfall are also shown over transitional land surface hot spots. Both the potential predictability at decadal time-scale and seasonal-forecasts skill are enhanced over Sahel, North American Great Plains, Nordeste Brazil and South East Asia, mainly related to improved performance in

  8. Using Variable-Length Aligned Fragment Pairs and an Improved Transition Function for Flexible Protein Structure Alignment. (United States)

    Cao, Hu; Lu, Yonggang


    With the rapid growth of known protein 3D structures in number, how to efficiently compare protein structures becomes an essential and challenging problem in computational structural biology. At present, many protein structure alignment methods have been developed. Among all these methods, flexible structure alignment methods are shown to be superior to rigid structure alignment methods in identifying structure similarities between proteins, which have gone through conformational changes. It is also found that the methods based on aligned fragment pairs (AFPs) have a special advantage over other approaches in balancing global structure similarities and local structure similarities. Accordingly, we propose a new flexible protein structure alignment method based on variable-length AFPs. Compared with other methods, the proposed method possesses three main advantages. First, it is based on variable-length AFPs. The length of each AFP is separately determined to maximally represent a local similar structure fragment, which reduces the number of AFPs. Second, it uses local coordinate systems, which simplify the computation at each step of the expansion of AFPs during the AFP identification. Third, it decreases the number of twists by rewarding the situation where nonconsecutive AFPs share the same transformation in the alignment, which is realized by dynamic programming with an improved transition function. The experimental data show that compared with FlexProt, FATCAT, and FlexSnap, the proposed method can achieve comparable results by introducing fewer twists. Meanwhile, it can generate results similar to those of the FATCAT method in much less running time due to the reduced number of AFPs.

  9. A combined supplementation of vitamin B12 and omega-3 fatty acids across two generations improves cardiometabolic variables in rats. (United States)

    Khaire, Amrita; Rathod, Richa; Randhir, Karuna; Kale, Anvita; Joshi, Sadhana


    Our earlier studies indicate that micronutrients (vitamin B12, folic acid) and omega-3 fatty acids especially docosahexaenoic acid (DHA) are interlinked in one carbon cycle. The present study examines the effects of a sustained vitamin B12 deficiency/supplementation in the presence of omega-3 fatty acids across two generations on the pregnancy outcome and cardiometabolic profile [blood pressure, plasma lipid profile (cholesterol and triglycerides), plasma/liver fatty acid profile and hepatic lipid metabolism] in the second generation adult Wistar rat offspring. Two generations of animals were fed the following diets: control; vitamin B12 deficient; vitamin B12 supplemented; vitamin B12 deficient diet supplemented with omega-3 fatty acids; vitamin B12 and omega-3 fatty acid supplemented diets. Male offspring were sacrificed at 3 months of age. Vitamin B12 deficiency lowered the weight gain (p blood pressure, and lowered the levels of plasma/liver DHA (p lipid profile. Vitamin B12 supplementation showed weight gain, blood pressure and the fatty acid profile similar to the control. However, it increased (p acid supplementation to the vitamin B12 deficient group lowered the weight gain although the levels of cardiometabolic variables were comparable to the control. Omega-3 fatty acid supplementation in the presence of vitamin B12 improved the pregnancy outcome and all cardio-metabolic variables. Our study highlights the adverse effects of sustained vitamin B12 deficiency across two generations on the pregnancy outcome, fatty acid profile and blood pressure while a combined supplementation of vitamin B12 and omega-3 fatty acids is beneficial.

  10. Loss of hMSH2 gene expression correlates with improved survival in ...

    Indian Academy of Sciences (India)

    1Department of General and Colorectal Surgery, Medical University of Lodz, pl. Hallera 1 ... expression and clinical parameters but our studies showed ... Journal of Genetics, Vol. .... cancer, further investigation of genetic alterations caused by.

  11. MYT1L mutations cause intellectual disability and variable obesity by dysregulating gene expression and development of the neuroendocrine hypothalamus


    Blanchet, P.; Bebin, M.; Bruet, S,; Cooper, G.M.; Thompson, M.L.; Duban-Bedu, B.; Gerard, B.; Piton, A.; Suckno, S.; Deshpande, C.; Clowes, V.; Vogt, J.; Turnpenny, P.; Williamson, M.P.; Alembik, Y.


    Deletions at chromosome 2p25.3 are associated with a syndrome consisting of intellectual disability and obesity. The smallest region of overlap for deletions at 2p25.3 contains PXDN and MYT1L. MYT1L is expressed only within the brain in humans. We hypothesized that single nucleotide variants (SNVs) in MYT1L would cause a phenotype resembling deletion at 2p25.3. To examine this we sought MYT1L SNVs in exome sequencing data from 4, 296 parent-child trios. Further variants were identified throug...

  12. The variability of Scots pine from Piekielna Góra as expressed by morphological and anatomical traits of needles

    Directory of Open Access Journals (Sweden)

    Maria A. Bobowicz


    Full Text Available Two-year old needles were collected from 30 standing Scots pine trees on Piekielna Góra. These needles were analysed in respect to 13 morphological and anatomical traits. The data so obtained was subjected to a whole range of multi-trait analytical methods in an attempt to determine the variability among the randomly chosen trees. Multivariate analysis of variance and canonical analysis were done as well as calculation of Mahalanobis distances between each pair of trees and their significance was tested by the Hotelling T2 statistics. Aminimum spanning tree was constructed on the basis of the shortest Mahalanobis distances, while a dendrogram (cluster analysis was compiled on the basis of Euclidean distances. It was found that in spite of the fact that the studied population sample of pines did not form internal, significantly differentiated groups, the variability among particular trees was large and depended on the given trait. The number of resin canals best differentiated the studied trees, while the Marcet coefficient did not significantly differentia­te any pair of trees.

  13. Patient-Specific Tailored Intervention Improves INR Time in Therapeutic Range and INR Variability in Heart Failure Patients. (United States)

    Gotsman, Israel; Ezra, Orly; Hirsh Raccah, Bruria; Admon, Dan; Lotan, Chaim; Dekeyser Ganz, Freda


    Many patients with heart failure need anticoagulants, including warfarin. Good control is particularly challenging in heart failure patients, with range, thereby increasing the risk of complications. This study aimed to evaluate the effect of a patient-specific tailored intervention on anticoagulation control in patients with heart failure. Patients with heart failure taking warfarin therapy (n = 145) were randomized to either standard care or a 1-time intervention assessing potential risk factors for lability of INR, in which they received patient-specific instructions. Time in therapeutic range (TTR) using Rosendaal's linear model was assessed 3 months before and after the intervention. The patient-tailored intervention significantly increased anticoagulation control. The median TTR levels before intervention were suboptimal in the interventional and control groups (53% vs 45%, P = .14). After intervention the median TTR increased significantly in the interventional group compared with the control group (80% [interquartile range, 62%-93%] vs 44% [29%-61%], P <.0001). The intervention resulted in a significant improvement in the interventional group before versus after intervention (53% vs 80%, P <.0001) but not in the control group (45% vs 44%, P = .95). The percentage of patients with a TTR ≥60%, considered therapeutic, was substantially higher in the interventional group: 79% versus 25% (P <.0001). The INR variability (standard deviation of each patient's INR measurements) decreased significantly in the interventional group, from 0.53 to 0.32 (P <.0001) after intervention but not in the control group. Patient-specific tailored intervention significantly improves anticoagulation therapy in patients with heart failure. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. The verbal facilitation effect: re-reading person descriptions as a system variable to improve identification performance. (United States)

    Sporer, Siegfried L; Kaminski, Kristina S; Davids, Maike C; McQuiston, Dawn


    When witnesses report a crime, police usually ask for a description of the perpetrator. Several studies suggested that verbalising faces leads to a detriment in identification performance (verbal overshadowing effect [VOE]) but the effect has been difficult to replicate. Here, we sought to reverse the VOE by inducing context reinstatement as a system variable through re-reading one's own description before an identification task. Participants (N = 208) watched a video film and were then dismissed (control group), only described the perpetrator, or described and later re-read their own descriptions before identification in either target-present or target-absent lineups after a 2-day or a 5-week delay. Identification accuracy was significantly higher after re-reading (85.0%) than in the no description control group (62.5%) irrespective of target presence. Data were internally replicated using a second target and corroborated by several small meta-analyses. Identification accuracy was related to description quality. Moreover, there was a tendency towards a verbal facilitation effect (VFE) rather than a VOE. Receiver operating characteristic (ROC) curve analyses confirm that our findings are not due to a shift in response bias but truly reflect improvement of recognition performance. Differences in the ecological validity of study paradigms are discussed.

  15. Estimating annoyance to calculated wind turbine shadow flicker is improved when variables associated with wind turbine noise exposure are considered. (United States)

    Voicescu, Sonia A; Michaud, David S; Feder, Katya; Marro, Leonora; Than, John; Guay, Mireille; Denning, Allison; Bower, Tara; van den Berg, Frits; Broner, Norm; Lavigne, Eric


    The Community Noise and Health Study conducted by Health Canada included randomly selected participants aged 18-79 yrs (606 males, 632 females, response rate 78.9%), living between 0.25 and 11.22 km from operational wind turbines. Annoyance to wind turbine noise (WTN) and other features, including shadow flicker (SF) was assessed. The current analysis reports on the degree to which estimating high annoyance to wind turbine shadow flicker (HAWTSF) was improved when variables known to be related to WTN exposure were also considered. As SF exposure increased [calculated as maximum minutes per day (SFm)], HAWTSF increased from 3.8% at 0 ≤ SFm wind turbine-related features, concern for physical safety, and noise sensitivity. Reported dizziness was also retained in the final model at p = 0.0581. Study findings add to the growing science base in this area and may be helpful in identifying factors associated with community reactions to SF exposure from wind turbines.

  16. Variable selection based on clustering analysis for improvement of polyphenols prediction in green tea using synchronous fluorescence spectra (United States)

    Shan, Jiajia; Wang, Xue; Zhou, Hao; Han, Shuqing; Riza, Dimas Firmanda Al; Kondo, Naoshi


    Synchronous fluorescence spectra, combined with multivariate analysis were used to predict flavonoids content in green tea rapidly and nondestructively. This paper presented a new and efficient spectral intervals selection method called clustering based partial least square (CL-PLS), which selected informative wavelengths by combining clustering concept and partial least square (PLS) methods to improve models’ performance by synchronous fluorescence spectra. The fluorescence spectra of tea samples were obtained and k-means and kohonen-self organizing map clustering algorithms were carried out to cluster full spectra into several clusters, and sub-PLS regression model was developed on each cluster. Finally, CL-PLS models consisting of gradually selected clusters were built. Correlation coefficient (R) was used to evaluate the effect on prediction performance of PLS models. In addition, variable influence on projection partial least square (VIP-PLS), selectivity ratio partial least square (SR-PLS), interval partial least square (iPLS) models and full spectra PLS model were investigated and the results were compared. The results showed that CL-PLS presented the best result for flavonoids prediction using synchronous fluorescence spectra.

  17. Expression profiling of hypothetical genes in Desulfovibrio vulgaris leads to improved functional annotation

    Energy Technology Data Exchange (ETDEWEB)

    Elias, Dwayne A.; Mukhopadhyay, Aindrila; Joachimiak, Marcin P.; Drury, Elliott C.; Redding, Alyssa M.; Yen, Huei-Che B.; Fields, Matthew W.; Hazen, Terry C.; Arkin, Adam P.; Keasling, Jay D.; Wall, Judy D.


    Hypothetical and conserved hypothetical genes account for>30percent of sequenced bacterial genomes. For the sulfate-reducing bacterium Desulfovibrio vulgaris Hildenborough, 347 of the 3634 genes were annotated as conserved hypothetical (9.5percent) along with 887 hypothetical genes (24.4percent). Given the large fraction of the genome, it is plausible that some of these genes serve critical cellular roles. The study goals were to determine which genes were expressed and provide a more functionally based annotation. To accomplish this, expression profiles of 1234 hypothetical and conserved genes were used from transcriptomic datasets of 11 environmental stresses, complemented with shotgun LC-MS/MS and AMT tag proteomic data. Genes were divided into putatively polycistronic operons and those predicted to be monocistronic, then classified by basal expression levels and grouped according to changes in expression for one or multiple stresses. 1212 of these genes were transcribed with 786 producing detectable proteins. There was no evidence for expression of 17 predicted genes. Except for the latter, monocistronic gene annotation was expanded using the above criteria along with matching Clusters of Orthologous Groups. Polycistronic genes were annotated in the same manner with inferences from their proximity to more confidently annotated genes. Two targeted deletion mutants were used as test cases to determine the relevance of the inferred functional annotations.

  18. Transcript-level annotation of Affymetrix probesets improves the interpretation of gene expression data

    Directory of Open Access Journals (Sweden)

    Tu Kang


    Full Text Available Abstract Background The wide use of Affymetrix microarray in broadened fields of biological research has made the probeset annotation an important issue. Standard Affymetrix probeset annotation is at gene level, i.e. a probeset is precisely linked to a gene, and probeset intensity is interpreted as gene expression. The increased knowledge that one gene may have multiple transcript variants clearly brings up the necessity of updating this gene-level annotation to a refined transcript-level. Results Through performing rigorous alignments of the Affymetrix probe sequences against a comprehensive pool of currently available transcript sequences, and further linking the probesets to the International Protein Index, we generated transcript-level or protein-level annotation tables for two popular Affymetrix expression arrays, Mouse Genome 430A 2.0 Array and Human Genome U133A Array. Application of our new annotations in re-examining existing expression data sets shows increased expression consistency among synonymous probesets and strengthened expression correlation between interacting proteins. Conclusion By refining the standard Affymetrix annotation of microarray probesets from the gene level to the transcript level and protein level, one can achieve a more reliable interpretation of their experimental data, which may lead to discovery of more profound regulatory mechanism.

  19. Face or body? Oxytocin improves perception of emotions from facial expressions in incongruent emotional body context. (United States)

    Perry, Anat; Aviezer, Hillel; Goldstein, Pavel; Palgi, Sharon; Klein, Ehud; Shamay-Tsoory, Simone G


    The neuropeptide oxytocin (OT) has been repeatedly reported to play an essential role in the regulation of social cognition in humans in general, and specifically in enhancing the recognition of emotions from facial expressions. The later was assessed in different paradigms that rely primarily on isolated and decontextualized emotional faces. However, recent evidence has indicated that the perception of basic facial expressions is not context invariant and can be categorically altered by context, especially body context, at early perceptual levels. Body context has a strong effect on our perception of emotional expressions, especially when the actual target face and the contextually expected face are perceptually similar. To examine whether and how OT affects emotion recognition, we investigated the role of OT in categorizing facial expressions in incongruent body contexts. Our results show that in the combined process of deciphering emotions from facial expressions and from context, OT gives an advantage to the face. This advantage is most evident when the target face and the contextually expected face are perceptually similar. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. An additional k-means clustering step improves the biological features of WGCNA gene co-expression networks. (United States)

    Botía, Juan A; Vandrovcova, Jana; Forabosco, Paola; Guelfi, Sebastian; D'Sa, Karishma; Hardy, John; Lewis, Cathryn M; Ryten, Mina; Weale, Michael E


    Weighted Gene Co-expression Network Analysis (WGCNA) is a widely used R software package for the generation of gene co-expression networks (GCN). WGCNA generates both a GCN and a derived partitioning of clusters of genes (modules). We propose k-means clustering as an additional processing step to conventional WGCNA, which we have implemented in the R package km2gcn (k-means to gene co-expression network, ). We assessed our method on networks created from UKBEC data (10 different human brain tissues), on networks created from GTEx data (42 human tissues, including 13 brain tissues), and on simulated networks derived from GTEx data. We observed substantially improved module properties, including: (1) few or zero misplaced genes; (2) increased counts of replicable clusters in alternate tissues (x3.1 on average); (3) improved enrichment of Gene Ontology terms (seen in 48/52 GCNs) (4) improved cell type enrichment signals (seen in 21/23 brain GCNs); and (5) more accurate partitions in simulated data according to a range of similarity indices. The results obtained from our investigations indicate that our k-means method, applied as an adjunct to standard WGCNA, results in better network partitions. These improved partitions enable more fruitful downstream analyses, as gene modules are more biologically meaningful.

  1. Variable expression of GFP in different populations of peripheral cholinergic neurons of ChATBAC-eGFP transgenic mice. (United States)

    Brown, T Christopher; Bond, Cherie E; Hoover, Donald B


    Immunohistochemistry is used widely to identify cholinergic neurons, but this approach has some limitations. To address these problems, investigators developed transgenic mice that express enhanced green fluorescent protein (GFP) directed by the promoter for choline acetyltransferase (ChAT), the acetylcholine synthetic enzyme. Although, it was reported that these mice express GFP in all cholinergic neurons and non-neuronal cholinergic cells, we could not detect GFP in cardiac cholinergic nerves in preliminary experiments. Our goals for this study were to confirm our initial observation and perform a qualitative screen of other representative autonomic structures for the presences of GFP in cholinergic innervation of effector tissues. We evaluated GFP fluorescence of intact, unfixed tissues and the cellular localization of GFP and vesicular acetylcholine transporter (VAChT), a specific cholinergic marker, in tissue sections and intestinal whole mounts. Our experiments identified two major tissues where cholinergic neurons and/or nerve fibers lacked GFP: 1) most cholinergic neurons of the intrinsic cardiac ganglia and all cholinergic nerve fibers in the heart and 2) most cholinergic nerve fibers innervating airway smooth muscle. Most cholinergic neurons in airway ganglia stained for GFP. Cholinergic systems in the bladder and intestines were fully delineated by GFP staining. GFP labeling of input to ganglia with long preganglionic projections (vagal) was sparse or weak, while that to ganglia with short preganglionic projections (spinal) was strong. Total absence of GFP might be due to splicing out of the GFP gene. Lack of GFP in nerve projections from GFP-positive cell bodies might reflect a transport deficiency. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Two novel MYH7 proline substitutions cause Laing Distal Myopathy-like phenotypes with variable expressivity and neck extensor contracture. (United States)

    Feinstein-Linial, Miora; Buvoli, Massimo; Buvoli, Ada; Sadeh, Menachem; Dabby, Ron; Straussberg, Rachel; Shelef, Ilan; Dayan, Daniel; Leinwand, Leslie Anne; Birk, Ohad S


    Human skeletal muscles express three major myosin heavy chain (MyHC) isoforms: MyHCIIx (MYH1) in fast type 2B muscle fibers, MyHCIIa (MYH2) in fast type 2A fibers and MyHCI/β-cardiac MyHC (MYH7) in slow type I skeletal fibers and cardiac ventricles. In line with its expression pattern, MYH7 mutations have been reported in association with hypertrophic or dilated cardiomyopathy, skeletal myopathies or a combination of both. We analyzed the clinical and molecular phenotype of two unrelated families of Jewish Moroccan ancestry that presented with apparently autosomal dominant inheritance of progressive Laing-like distal myopathy with non-specific myopathic changes, but uncommon marked contractures and wasting of the neck extensors. Clinical phenotyping, whole exome sequencing and restriction analysis, generation of mutants followed by cell culture transfection and imaging. Using whole exome sequencing we identified in both families two novel heterozygous proline substitutions located in exon 31 of MYH7 within its rod domain: c.4309G>C (p.Ala1437Pro) and c.4301G>C (p.Arg1434Pro). Here we show that the phenotype caused by these mutations includes marked cervical muscle contracture, and report that the severity of the phenotype varies significantly, to the extent of non-penetrance in one of the families. Finally, we provide evidence that both proline substitutions impair myosin self-assembly in non-muscle cells transfected with β-myosin constructs carrying the mutations, but do not prevent incorporation of the mutant molecules into the sarcomere. This study expands our clinical and molecular knowledge of MYH7 rod mutations causing skeletal myopathies, and underscores the importance of discussing disease penetrance during genetic counseling.

  3. Unchanged gene expression of glycogen synthase in muscle from patients with NIDDM following sulphonylurea-induced improvement of glycaemic control

    DEFF Research Database (Denmark)

    Vestergaard, H; Lund, S; Bjørbaek, C


    We have previously shown that the mRNA expression of muscle glycogen synthase is decreased in non-insulin-dependent diabetic (NIDDM) patients; the objective of the present protocol was to examine whether the gene expression of muscle glycogen synthase in NIDDM is affected by chronic sulphonylurea...... as enhanced beta-cell responses to an oral glucose load. During euglycaemic, hyperinsulinaemic clamp (2 mU x kg-1 x min-1) in combination with indirect calorimetry, a 35% (p=0.005) increase in whole-body insulin-stimulated glucose disposal rate, predominantly due to an increased non-oxidative glucose....... In conclusion, improved blood glucose control in gliclazide-treated obese NIDDM patients has no impact on the gene expression of muscle glycogen synthase....

  4. A new mouse model for marfan syndrome presents phenotypic variability associated with the genetic background and overall levels of Fbn1 expression.

    Directory of Open Access Journals (Sweden)

    Bruno L Lima


    Full Text Available Marfan syndrome is an autosomal dominant disease of connective tissue caused by mutations in the fibrillin-1 encoding gene FBN1. Patients present cardiovascular, ocular and skeletal manifestations, and although being fully penetrant, MFS is characterized by a wide clinical variability both within and between families. Here we describe a new mouse model of MFS that recapitulates the clinical heterogeneity of the syndrome in humans. Heterozygotes for the mutant Fbn1 allele mgΔloxPneo, carrying the same internal deletion of exons 19-24 as the mgΔ mouse model, present defective microfibrillar deposition, emphysema, deterioration of aortic wall and kyphosis. However, the onset of a clinical phenotypes is earlier in the 129/Sv than in C57BL/6 background, indicating the existence of genetic modifiers of MFS between these two mouse strains. In addition, we characterized a wide clinical variability within the 129/Sv congenic heterozygotes, suggesting involvement of epigenetic factors in disease severity. Finally, we show a strong negative correlation between overall levels of Fbn1 expression and the severity of the phenotypes, corroborating the suggested protective role of normal fibrillin-1 in MFS pathogenesis, and supporting the development of therapies based on increasing Fbn1 expression.

  5. Phase variable O antigen biosynthetic genes control expression of the major protective antigen and bacteriophage receptor in Vibrio cholerae O1.

    Directory of Open Access Journals (Sweden)

    Kimberley D Seed


    Full Text Available The Vibrio cholerae lipopolysaccharide O1 antigen is a major target of bacteriophages and the human immune system and is of critical importance for vaccine design. We used an O1-specific lytic bacteriophage as a tool to probe the capacity of V. cholerae to alter its O1 antigen and identified a novel mechanism by which this organism can modulate O antigen expression and exhibit intra-strain heterogeneity. We identified two phase variable genes required for O1 antigen biosynthesis, manA and wbeL. manA resides outside of the previously recognized O1 antigen biosynthetic locus, and encodes for a phosphomannose isomerase critical for the initial step in O1 antigen biosynthesis. We determined that manA and wbeL phase variants are attenuated for virulence, providing functional evidence to further support the critical role of the O1 antigen for infectivity. We provide the first report of phase variation modulating O1 antigen expression in V. cholerae, and show that the maintenance of these phase variable loci is an important means by which this facultative pathogen can generate the diverse subpopulations of cells needed for infecting the host intestinal tract and for escaping predation by an O1-specific phage.

  6. Variable expression of cerebral cavernous malformations in carriers of a premature termination codon in exon 17 of the Krit1 gene

    Directory of Open Access Journals (Sweden)

    Gamero Miguel A


    Full Text Available Abstract Background Cerebral cavernous malformations (CCM present as either sporadic or autosomal dominant conditions with incomplete penetrance of symptoms. Differences in genetic and environmental factors might be minimized among first-degree relatives. We therefore studied clinical expression in a family with several affected members. Methods We studied a three-generation family with the onset of CCM as a cerebral haemorrhage in the younger (four-year-old sibling. Identification and enumeration of CCMs were performed in T2-weighted or gradient-echo MRIs of the whole brains. Genetic analysis comprised SCCP, sequencing and restriction polymorphism of the Krit1 gene in the proband and at risk relatives. Results The phenotypes of cerebral cavernous malformations (CCMs in carriers of Krit1 mutations were very variable. We identified a novel frameshift mutation caused by a 1902A insertion in exon 17 of the Krit1 gene, which leads to a premature TAA triplet and predicts the truncating phenotype Y634X. A very striking finding was the absence of both clinical symptoms and CCMs in the eldest sibling harbouring the 1902insA. Conclusions Patients in this family, harbouring the same mutation, illustrate the very variable clinical and radiological expression of a Krit1 mutation. The early and critical onset in the proband contrasts with minor clinical findings in affected relatives. This consideration is important in genetic counselling.

  7. The estimation of soil parameters using observations on crop biophysical variables and the crop model STICS improve the predictions of agro environmental variables. (United States)

    Varella, H.-V.


    Dynamic crop models are very useful to predict the behavior of crops in their environment and are widely used in a lot of agro-environmental work. These models have many parameters and their spatial application require a good knowledge of these parameters, especially of the soil parameters. These parameters can be estimated from soil analysis at different points but this is very costly and requires a lot of experimental work. Nevertheless, observations on crops provided by new techniques like remote sensing or yield monitoring, is a possibility for estimating soil parameters through the inversion of crop models. In this work, the STICS crop model is studied for the wheat and the sugar beet and it includes more than 200 parameters. After a previous work based on a large experimental database for calibrate parameters related to the characteristics of the crop, a global sensitivity analysis of the observed variables (leaf area index LAI and absorbed nitrogen QN provided by remote sensing data, and yield at harvest provided by yield monitoring) to the soil parameters is made, in order to determine which of them have to be estimated. This study was made in different climatic and agronomic conditions and it reveals that 7 soil parameters (4 related to the water and 3 related to the nitrogen) have a clearly influence on the variance of the observed variables and have to be therefore estimated. For estimating these 7 soil parameters, a Bayesian data assimilation method is chosen (because of available prior information on these parameters) named Importance Sampling by using observations, on wheat and sugar beet crop, of LAI and QN at various dates and yield at harvest acquired on different climatic and agronomic conditions. The quality of parameter estimation is then determined by comparing the result of parameter estimation with only prior information and the result with the posterior information provided by the Bayesian data assimilation method. The result of the

  8. Treatment with escitalopram improves the attentional bias toward negative facial expressions in patients with major depressive disorders. (United States)

    Zhou, Zhenhe; Cao, Suxia; Li, Hengfen; Li, Youhui


    We hypothesized that treatment with escitalopram would improve cognitive bias and contribute to the recovery process for patients with major depressive disorder (MDD). Many previous studies have established that patients with MDD tend to pay selective attention to negative stimuli. The assessment of the level of cognitive bias is regarded as a crucial dimension of treatment outcomes for MDD. To our knowledge, no prior studies have been reported on the effects of treatment with escitalopram on attentional bias in MDD, employing a dot probe task of facial expression. We studied 25 patients with MDD and 25 controls, and used a dot probe task of facial expression to measure cognitive bias. The patients' psychopathologies were rated using the Hamilton Depression Scale (HAMD) at baseline and after 8 weeks of treatment with escitalopram. All participants performed the facial expression dot probe task. The results revealed that the 8 week escitalopram treatment decreased the HAMD scores. The patients with MDD at baseline exhibited an attentional bias towards negative faces, however, no significant bias toward either negative or happy faces were observed in the controls. After the 8 week escitalopram treatment, no significant bias toward negative faces was observed in the patient group. In conclusion, patients with MDD pay more attention to negative facial expressions, and treatment with escitalopram improves this attentional bias toward negative facial expressions. This is the first study, to our knowledge, on the effects of treatment with escitalopram on attentional bias in patients with MDD that has employed a dot probe task of facial expression. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Hepatic Expression of Adenovirus 36 E4ORF1 Improves Glycemic Control and Promotes Glucose Metabolism Through AKT Activation. (United States)

    McMurphy, Travis B; Huang, Wei; Xiao, Run; Liu, Xianglan; Dhurandhar, Nikhil V; Cao, Lei


    Considering that impaired proximal insulin signaling is linked with diabetes, approaches that enhance glucose disposal independent of insulin signaling are attractive. In vitro data indicate that the E4ORF1 peptide derived from human adenovirus 36 (Ad36) interacts with cells from adipose tissue, skeletal muscle, and liver to enhance glucose disposal, independent of proximal insulin signaling. Adipocyte-specific expression of Ad36E4ORF1 improves hyperglycemia in mice. To determine the hepatic interaction of Ad36E4ORF1 in enhancing glycemic control, we expressed E4ORF1 of Ad36 or Ad5 or fluorescent tag alone by using recombinant adeno-associated viral vector in the liver of three mouse models. In db/db or diet-induced obesity (DIO) mice, hepatic expression of Ad36E4ORF1 but not Ad5E4ORF1 robustly improved glycemic control. In normoglycemic wild-type mice, hepatic expression of Ad36E4ORF1 lowered nonfasting blood glucose at a high dose of expression. Of note, Ad36E4ORF1 significantly reduced insulin levels in db/db and DIO mice. The improvement in glycemic control was observed without stimulation of the proximal insulin signaling pathway. Collectively, these data indicate that Ad36E4ORF1 is not a typical sensitizer, mimetic, or secretagogue of insulin. Instead, it may have insulin-sparing action, which seems to reduce the need for insulin and, hence, to reduce insulin levels. © 2017 by the American Diabetes Association.

  10. Improving the expression of recombinant pullulanase by increasing mRNA stability in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Tao Li


    Conclusion: The addition of the 5′ SD sequence at the 5′ UTR and a 3′ stem-loop structure at the 3′ UTR of the pulA gene is an effective approach to increase pulA gene expression and fermentation enzyme activity.

  11. Improved methodology for the affinity isolation of human protein complexes expressed at near endogenous levels

    DEFF Research Database (Denmark)

    Domanski, Michal; Molloy, Kelly; Jiang, Hua


    An efficient and reliable procedure for the capture of affinity-tagged proteins and associated complexes from human cell lines is reported. Through multiple optimizations, high yield and low background affinity-purifications are achieved from modest quantities of human cells expressing endogenous...

  12. Improved ethanol production from cheese whey, whey powder, and sugar beet molasses by "Vitreoscilla hemoglobin expressing" Escherichia coli. (United States)

    Akbas, Meltem Yesilcimen; Sar, Taner; Ozcelik, Busra


    This work investigated the improvement of ethanol production by engineered ethanologenic Escherichia coli to express the hemoglobin from the bacterium Vitreoscilla (VHb). Ethanologenic E. coli strain FBR5 and FBR5 transformed with the VHb gene in two constructs (strains TS3 and TS4) were grown in cheese whey (CW) medium at small and large scales, at both high and low aeration, or with whey powder (WP) or sugar beet molasses hydrolysate (SBMH) media at large scale and low aeration. Culture pH, cell growth, VHb levels, and ethanol production were evaluated after 48 h. VHb expression in TS3 and TS4 enhanced their ethanol production in CW (21-419%), in WP (17-362%), or in SBMH (48-118%) media. This work extends the findings that "VHb technology" may be useful for improving the production of ethanol from waste and byproducts of various sources.

  13. Forecasting nonlinear chaotic time series with function expression method based on an improved genetic-simulated annealing algorithm. (United States)

    Wang, Jun; Zhou, Bi-hua; Zhou, Shu-dao; Sheng, Zheng


    The paper proposes a novel function expression method to forecast chaotic time series, using an improved genetic-simulated annealing (IGSA) algorithm to establish the optimum function expression that describes the behavior of time series. In order to deal with the weakness associated with the genetic algorithm, the proposed algorithm incorporates the simulated annealing operation which has the strong local search ability into the genetic algorithm to enhance the performance of optimization; besides, the fitness function and genetic operators are also improved. Finally, the method is applied to the chaotic time series of Quadratic and Rossler maps for validation. The effect of noise in the chaotic time series is also studied numerically. The numerical results verify that the method can forecast chaotic time series with high precision and effectiveness, and the forecasting precision with certain noise is also satisfactory. It can be concluded that the IGSA algorithm is energy-efficient and superior.

  14. Codon Optimization Significantly Improves the Expression Level of α-Amylase Gene from Bacillus licheniformis in Pichia pastoris

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    Jian-Rong Wang


    Full Text Available α-Amylase as an important industrial enzyme has been widely used in starch processing, detergent, and paper industries. To improve expression efficiency of recombinant α-amylase from Bacillus licheniformis (B. licheniformis, the α-amylase gene from B. licheniformis was optimized according to the codon usage of Pichia pastoris (P. pastoris and expressed in P. pastoris. Totally, the codons encoding 305 amino acids were optimized in which a total of 328 nucleotides were changed and the G+C content was increased from 47.6 to 49.2%. The recombinants were cultured in 96-deep-well microplates and screened by a new plate assay method. Compared with the wild-type gene, the optimized gene is expressed at a significantly higher level in P. pastoris after methanol induction for 168 h in 5- and 50-L bioreactor with the maximum activity of 8100 and 11000 U/mL, which was 2.31- and 2.62-fold higher than that by wild-type gene. The improved expression level makes the enzyme a good candidate for α-amylase production in industrial use.

  15. Improving nutritional quality and fungal tolerance in soya bean and grass pea by expressing an oxalate decarboxylase. (United States)

    Kumar, Vinay; Chattopadhyay, Arnab; Ghosh, Sumit; Irfan, Mohammad; Chakraborty, Niranjan; Chakraborty, Subhra; Datta, Asis


    Soya bean (Glycine max) and grass pea (Lathyrus sativus) seeds are important sources of dietary proteins; however, they also contain antinutritional metabolite oxalic acid (OA). Excess dietary intake of OA leads to nephrolithiasis due to the formation of calcium oxalate crystals in kidneys. Besides, OA is also a known precursor of β-N-oxalyl-L-α,β-diaminopropionic acid (β-ODAP), a neurotoxin found in grass pea. Here, we report the reduction in OA level in soya bean (up to 73%) and grass pea (up to 75%) seeds by constitutive and/or seed-specific expression of an oxalate-degrading enzyme, oxalate decarboxylase (FvOXDC) of Flammulina velutipes. In addition, β-ODAP level of grass pea seeds was also reduced up to 73%. Reduced OA content was interrelated with the associated increase in seeds micronutrients such as calcium, iron and zinc. Moreover, constitutive expression of FvOXDC led to improved tolerance to the fungal pathogen Sclerotinia sclerotiorum that requires OA during host colonization. Importantly, FvOXDC-expressing soya bean and grass pea plants were similar to the wild type with respect to the morphology and photosynthetic rates, and seed protein pool remained unaltered as revealed by the comparative proteomic analysis. Taken together, these results demonstrated improved seed quality and tolerance to the fungal pathogen in two important legume crops, by the expression of an oxalate-degrading enzyme. © 2016 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  16. Knocking out Ornithine Decarboxylase Antizyme 1 (OAZ1 Improves Recombinant Protein Expression in the HEK293 Cell Line

    Directory of Open Access Journals (Sweden)

    Laura Abaandou


    Full Text Available Creating efficient cell lines is a priority for the biopharmaceutical industry, which produces biologicals for various uses. A recent approach to achieving this goal is the use of non-coding RNAs, microRNA (miRNA and small interfering RNA (siRNA, to identify key genes that can potentially improve production or growth. The ornithine decarboxylase antizyme 1 (OAZ1 gene, a negative regulator of polyamine biosynthesis, was identified in a genome-wide siRNA screen as a potential engineering target, because its knock down by siRNA increased recombinant protein expression from human embryonic kidney 293 (HEK293 cells by two-fold. To investigate this further, the OAZ1 gene in HEK293 cells was knocked out using CRISPR genome editing. The OAZ1 knockout cell lines displayed up to four-fold higher expression of both stably and transiently expressed proteins, with comparable growth and metabolic activity to the parental cell line; and an approximately three-fold increase in intracellular polyamine content. The results indicate that genetic inactivation of OAZ1 in HEK293 cells is an effective strategy to improve recombinant protein expression in HEK293 cells.

  17. Variable phenotypic expression and onset in MYH14 distal hereditary motor neuropathy phenotype in a large, multigenerational North American family. (United States)

    Iyadurai, Stanley; Arnold, W David; Kissel, John T; Ruhno, Corey; Mcgovern, Vicki L; Snyder, Pamela J; Prior, Thomas W; Roggenbuck, Jennifer; Burghes, Arthur H; Kolb, Stephen J


    Distal hereditary motor neuropathy (dHMN) causes distal-predominant weakness without prominent sensory loss. Myosin heavy chain disorders most commonly result in distal myopathy and cardiomyopathy with or without hearing loss, but a complex phenotype with dHMN, myopathy, hoarseness, and hearing loss was reported in a Korean family with a c.2822G>T mutation in MYH14. In this study we report phenotypic features in a North American family with the c.2822G>T in MYH14. Clinical and molecular characterization was performed in a large, 6-generation, Caucasian family with MYH14 dHMN. A total of 11 affected and 7 unaffected individuals were evaluated and showed varying age of onset and severity of weakness. Genotypic concordance was confirmed with molecular analysis. Electrophysiological studies demonstrated distal motor axonal degeneration without myopathy in all affected subjects tested. Mutation of MYH14 can result in a range of neuromuscular phenotypes that includes a dHMN and hearing loss phenotype with variable age of onset. Muscle Nerve 56: 341-345, 2017. © 2016 Wiley Periodicals, Inc.

  18. Variability of silver fir (Abies alba Mill. progeny from the Tisovik Reserve expressed in needle traits and chloroplast microsatellite DNA

    Directory of Open Access Journals (Sweden)

    Pawlaczyk Ewa M.


    Full Text Available Progeny from nineteen family lines of silver fir (Abies alba Mill. from the Tisovik Reserve growing in an experimental plot were analyzed based on 4 chloroplast microsatellite DNA loci and 12 morphological and anatomical needle traits. The Tisovik Reserve is located in Białowieża Primeval Forest, 120 km north of the natural range limit of this species, and embraces a small and isolated natural population of silver fir. The aim of this study was to determine genetic variation within and between progeny lines. Analysis of phenotypic variation showed that the traits which differed most among individuals were the needle width and the distance from resin canals to vascular bundle. Those traits, which differed most between the progeny lines, were the number of endodermic cells around the vascular bund and the weight of hypodermic cells. In Tisovik progeny, we detected 107 different haplotypes. In progeny lines, we detected more haplotypes than in maternal trees, and most haplotypes did not exist in maternal trees. This may be the result of pollen influx from other silver fir stands. Progeny from Tisovik showed a higher level of variability in comparison with maternal trees.

  19. Marginal level dystrophin expression improves clinical outcome in a strain of dystrophin/utrophin double knockout mice.

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    Dejia Li


    Full Text Available Inactivation of all utrophin isoforms in dystrophin-deficient mdx mice results in a strain of utrophin knockout mdx (uko/mdx mice. Uko/mdx mice display severe clinical symptoms and die prematurely as in Duchenne muscular dystrophy (DMD patients. Here we tested the hypothesis that marginal level dystrophin expression may improve the clinical outcome of uko/mdx mice. It is well established that mdx3cv (3cv mice express a near-full length dystrophin protein at ∼5% of the normal level. We crossed utrophin-null mutation to the 3cv background. The resulting uko/3cv mice expressed the same level of dystrophin as 3cv mice but utrophin expression was completely eliminated. Surprisingly, uko/3cv mice showed a much milder phenotype. Compared to uko/mdx mice, uko/3cv mice had significantly higher body weight and stronger specific muscle force. Most importantly, uko/3cv outlived uko/mdx mice by several folds. Our results suggest that a threshold level dystrophin expression may provide vital clinical support in a severely affected DMD mouse model. This finding may hold clinical implications in developing novel DMD therapies.

  20. Acid or erythromycin stress significantly improves transformation efficiency through regulating expression of DNA binding proteins in Lactococcus lactis F44. (United States)

    Wang, Binbin; Zhang, Huawei; Liang, Dongmei; Hao, Panlong; Li, Yanni; Qiao, Jianjun


    Lactococcus lactis is a gram-positive bacterium used extensively in the dairy industry and food fermentation, and its biological characteristics are usually improved through genetic manipulation. However, poor transformation efficiency was the main restriction factor for the construction of engineered strains. In this study, the transformation efficiency of L. lactis F44 showed a 56.1-fold increase in acid condition (pH 5.0); meanwhile, erythromycin stress (0.04 μg/mL) promoted the transformation efficiency more significantly (76.9-fold). Notably, the transformation efficiency of F44e (L. lactis F44 harboring empty pLEB124) increased up to 149.1-fold under the synergistic stresses of acid and erythromycin. In addition, the gene expression of some DNA binding proteins (DprA, RadA, RadC, RecA, RecQ, and SsbA) changed correspondingly. Especially for radA, 25.1-fold improvement was detected when F44e was exposed to pH 5.0. Overexpression of some DNA binding proteins could improve the transformation efficiency. The results suggested that acid or erythromycin stress could improve the transformation efficiency of L. lactis through regulating gene expression of DNA binding proteins. We have proposed a simple but promising strategy for improving the transformation efficiency of L. lactis and other hard-transformed microorganisms. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  1. Traditional Mongolian medicine Eerdun Wurile improves stroke recovery through regulation of gene expression in rat brain. (United States)

    Gaowa, Saren; Bao, Narisi; Da, Man; Qiburi, Qiburi; Ganbold, Tsogzolmaa; Chen, Lu; Altangerel, Altanzul; Temuqile, Temuqile; Baigude, Huricha


    Eerdun Wurile (EW) is one of the key Mongolian medicines for treatment of neurological and cardiological disorders. EW is ranked most regularly used Mongolian medicine in clinic. Components of EW which mainly originate from natural products are well defined and are unique to Mongolian medicine. Although the recipe of EW contains known neuroactive chemicals originated from plants, its mechanism of action has never been elucidated at molecular level. The objective of the present study is to explore the mechanism of neuroregenerative activity of EW by focusing on the regulation of gene expression in the brain of rat model of stroke. Rat middle cerebral artery occlusion (MCAO) models were treated with EW for 15 days. Then, total RNAs from the cerebral cortex of rat MCAO models treated with either EW or control (saline) were extracted and analyzed by transcriptome sequencing. Differentially expressed genes were analyzed for their functions during the recovery of ischemic stroke. The expression level of significantly differentially expressed genes such as growth factors, microglia markers and secretive enzymes in the lesion was further validated by RT-qPCR and immunohistochemistry. Previously identified neuroactive compounds, such as geniposide (Yu et al., 2009), myristicin (Shin et al., 1988), costunolide (Okugawa et al., 1996), toosendanin (Shi and Chen, 1999) were detected in EW formulation. Bederson scale indicated that the treatment of rat MCAO models with EW showed significantly lowered neurological deficits (p < 0.01). The regional cerebral blood circulation was also remarkably higher in rat MCAO models treated with EW compared to the control group. A total of 186 genes were upregulated in the lesion of rat MCAO models treated with EW compared to control group. Among them, growth factors such as Igf1 (p < 0.05), Igf2 (p < 0.01), Grn (p < 0.01) were significantly upregulated in brain after treatment of rat MCAO models with EW. Meanwhile, greatly

  2. New Frontiers in Heart Rate Variability and Social Coherence Research: Techniques, Technologies, and Implications for Improving Group Dynamics and Outcomes

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    Rollin McCraty


    Full Text Available Concepts embraced by the term coherence have been identified as central to fields such as quantum physics, physiology, and social science. There are different types of coherence, although the term always implies a harmonious relationship, correlations and connections between the various parts of a system. A specific measure derived from heart rate variability (HRV provides a measure of physiological coherence. Another type of coherence, social coherence, relates to the harmonious alignment between couples or pairs, family units, small groups, or larger organizations in which a network of relationships exists among individuals who share common interests and objectives. A high degree of social coherence is reflected by stable and harmonious relationships, which allows for the efficient flow and utilization of energy and communication required for optimal collective cohesion and action. Social coherence requires that group members are attuned and are emotionally connected with each other, and that the group’s emotional energy is organized and regulated by the group as a whole. A number of studies are reviewed which have explored various types of synchronization in infants, pairs and groups, indicating that feelings of cooperation, trust, compassion and increased prosocial behaviors depends largely on the establishment of a spontaneous synchronization of various physiological rhythms between individuals. This article discusses a new application using HRV monitoring in social coherence research and the importance of physiological synchronization in group developmental processes and dynamics. Building on the extensive body of research showing that providing feedback of HRV coherence level at the individual level can improve self-regulation, we suggest the following hypotheses: (1 providing feedback of individual and collective HRV coherence and the degree of heart rhythm synchronization will increase group coherence, and heart rhythm synchronization

  3. Improving sensitivity of linear regression-based cell type-specific differential expression deconvolution with per-gene vs. global significance threshold. (United States)

    Glass, Edmund R; Dozmorov, Mikhail G


    The goal of many human disease-oriented studies is to detect molecular mechanisms different between healthy controls and patients. Yet, commonly used gene expression measurements from blood samples suffer from variability of cell composition. This variability hinders the detection of differentially expressed genes and is often ignored. Combined with cell counts, heterogeneous gene expression may provide deeper insights into the gene expression differences on the cell type-specific level. Published computational methods use linear regression to estimate cell type-specific differential expression, and a global cutoff to judge significance, such as False Discovery Rate (FDR). Yet, they do not consider many artifacts hidden in high-dimensional gene expression data that may negatively affect linear regression. In this paper we quantify the parameter space affecting the performance of linear regression (sensitivity of cell type-specific differential expression detection) on a per-gene basis. We evaluated the effect of sample sizes, cell type-specific proportion variability, and mean squared error on sensitivity of cell type-specific differential expression detection using linear regression. Each parameter affected variability of cell type-specific expression estimates and, subsequently, the sensitivity of differential expression detection. We provide the R package, LRCDE, which performs linear regression-based cell type-specific differential expression (deconvolution) detection on a gene-by-gene basis. Accounting for variability around cell type-specific gene expression estimates, it computes per-gene t-statistics of differential detection, p-values, t-statistic-based sensitivity, group-specific mean squared error, and several gene-specific diagnostic metrics. The sensitivity of linear regression-based cell type-specific differential expression detection differed for each gene as a function of mean squared error, per group sample sizes, and variability of the proportions

  4. Expression of cocoa genes in Saccharomyces cerevisiae improves cocoa butter production

    DEFF Research Database (Denmark)

    Wei, Yongjun; Bergenholm, David; Gossing, Michael


    Background: Cocoa butter (CB) extracted from cocoa beans (Theobroma cacao) is the main raw material for chocolate production, but CB supply is insufficient due to the increased chocolate demand and limited CB production. CB is mainly composed of three different kinds of triacylglycerols (TAGs), 1......), and it is essential to modulate the yeast TAG biosynthetic pathway for higher CBL production.Results: We cloned seven GPAT genes and three LPAT genes from cocoa cDNA, in order to screen for CBL biosynthetic gene candidates. By expressing these cloned cocoa genes and two synthesized cocoa DGAT genes in S. cerevisiae......, we successfully increased total fatty acid production, TAG production and CBL production in some of the strains. In the best producer, the potential CBL content was eightfold higher than the control strain, suggesting the cocoa genes expressed in this strain were functional and might be responsible...

  5. Beetle (Ulomoides dermestoides) fat improves diabetes: effect on liver and pancreatic architecture and on PPARγ expression


    Jasso-Villagomez, E.I.; Garcia-Lorenzana, M.; Almanza-Perez, J.C.; Fortis-Barrera, M.A.; Blancas-Flores, G.; Roman-Ramos, R.; Prado-Barragan, L.A.; Alarcon-Aguilar, F.J.


    Ulomoides dermestoides is a beetle traditionally consumed to treat diabetes. In this study, we performed a composition analysis of U. dermestoides to obtain the principal fractions, which were used to assess the effect on glycemia, liver and pancreatic architecture, and PPARγ and GLUT4 expression. Normal mice and alloxan-induced diabetic mice were administered fractions of chitin, protein or fat, and the acute hypoglycemic effect was evaluated. A subacute study involving daily administration ...

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

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    Kenzie M Birse

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

  7. Ultrasound-targeted microbubble destruction improves the low density lipoprotein receptor gene expression in HepG2 cells

    International Nuclear Information System (INIS)

    Guo Dongping; Li Xiaoyu; Sun, Ping; Tang Yibo; Chen Xiuying; Chen Qi; Fan Leming; Zang Bin; Shao Lizheng; Li Xiaorong


    Ultrasound-targeted microbubble destruction had been employed in gene delivery and promised great potential. Liver has unique features that make it attractive for gene therapy. However, it poses formidable obstacles to hepatocyte-specific gene delivery. This study was designed to test the efficiency of therapeutic gene transfer and expression mediated by ultrasound/microbubble strategy in HepG 2 cell line. Air-filled albumin microbubbles were prepared and mixed with plasmid DNA encoding low density lipoprotein receptor (LDLR) and green fluorescent protein. The mixture of the DNA and microbubbles was administer to cultured HepG 2 cells under variable ultrasound conditions. Transfection rate of the transferred gene and cell viability were assessed by FACS analysis, confocal laser scanning microscopy, Western blot analysis and Trypan blue staining. The result demonstrated that microbubbles with ultrasound irradiation can significantly elevate exogenous LDLR gene expression and the expressed LDLRs were functional and active to uptake their ligands. We conclude that ultrasound-targeted microbubble destruction has the potential to promote safe and efficient LDLR gene transfer into hepatocytes. With further refinement, it may represent an effective nonviral avenue of gene therapy for liver-involved genetic diseases

  8. Laying traits and underlying transcripts, expressed in the hypothalamus and pituitary gland, that were associated with egg production variability in chickens. (United States)

    Chen, Chih-Feng; Shiue, Yow-Ling; Yen, Cheng-Ju; Tang, Pin-Chi; Chang, Hui-Chiu; Lee, Yen-Pai


    The objective was to characterize the potential laying traits and underlying transcripts expressed in the hypothalamus and pituitary gland that were associated with egg production variability in five genetic stocks of chickens: two commercial lines, Red- (n=12) and Black-feather (n=14) Taiwan country chickens (TCCs); two selected lines of TCCs, B (high body weight/comb size; n=17) and L2 (high-egg production; n=14); and a commercial single comb White Leghorn (WL; n=17). Six laying traits, age at first egg, clutch length, pause length, oviposition lag within clutch, follicle rapid growth period, and rate of yolk accumulation were measured. The significance of differential values among five chicken stocks and correlation coefficients between laying traits and number of eggs to 50 weeks of age or laying rate after first egg, and the expression level of 33 transcripts were determined. Longer clutch length and shorter oviposition lag within clutch contributed to a higher number of eggs to 50 weeks of age or laying rate after first egg in L2 (Pdifferent, indicating the accumulation of different alleles after long-term, independent selection. Across all five strains, numbers of eggs to 50 weeks of age were positive correlated with average clutch length (P<0.05) as well as the rate of yolk accumulation (P<0.05). Expressions of PLAG1, STMN2, PGDS, PARK7, ANP32A, PCDHA@, SCG2, BDH and SAR1A transcripts contributed to number of eggs to 50 weeks of age (P<0.05) or laying rate after first egg (P<0.05). Analysis of correlation coefficients indicated that PLAG1 additionally played roles in decreasing average pause length. Two transcripts, PRL and GARNL1, specifically contributed to number of eggs to 50 weeks of age or laying rate after first egg by reducing oviposition lag within clutch (P<0.05) and/or increasing average clutch length (P<0.05), respectively. Expression level of NCAM1, contributed to laying rate after first egg by association with a shorter oviposition lag within

  9. Quantifying Temporal Autocorrelations for the Expression of Geobacter species mRNA Gene Transcripts at Variable Ammonium Levels during in situ U(VI) Bioremediation (United States)

    Mouser, P. J.


    In order to develop decision-making tools for the prediction and optimization of subsurface bioremediation strategies, we must be able to link the molecular-scale activity of microorganisms involved in remediation processes with biogeochemical processes observed at the field-scale. This requires the ability to quantify changes in the in situ metabolic condition of dominant microbes and associate these changes to fluctuations in nutrient levels throughout the bioremediation process. It also necessitates a need to understand the spatiotemporal variability of the molecular-scale information to develop meaningful parameters and constraint ranges in complex bio-physio-chemical models. The expression of three Geobacter species genes (ammonium transporter (amtB), nitrogen fixation (nifD), and a housekeeping gene (recA)) were tracked at two monitoring locations that differed significantly in ammonium (NH4+) concentrations during a field-scale experiment where acetate was injected into the subsurface to simulate Geobacteraceae in a uranium-contaminated aquifer. Analysis of amtB and nifD mRNA transcript levels indicated that NH4+ was the primary form of fixed nitrogen during bioremediation. Overall expression levels of amtB were on average 8-fold higher at NH4+ concentrations of 300 μM or more than at lower NH4+ levels (average 60 μM). The degree of temporal correlation in Geobacter species mRNA expression levels was calculated at both locations using autocorrelation methods that describe the relationship between sample semi-variance and time lag. At the monitoring location with lower NH4+, a temporal correlation lag of 8 days was observed for both amtB and nifD transcript patterns. At the location where higher NH4+ levels were observed, no discernable temporal correlation lag above the sampling frequency (approximately every 2 days) was observed for amtB or nifD transcript fluctuations. Autocorrelation trends in recA expression levels at both locations indicated that

  10. Beetle (Ulomoides dermestoides fat improves diabetes: effect on liver and pancreatic architecture and on PPARγ expression

    Directory of Open Access Journals (Sweden)

    E.I. Jasso-Villagomez


    Full Text Available Ulomoides dermestoides is a beetle traditionally consumed to treat diabetes. In this study, we performed a composition analysis of U. dermestoides to obtain the principal fractions, which were used to assess the effect on glycemia, liver and pancreatic architecture, and PPARγ and GLUT4 expression. Normal mice and alloxan-induced diabetic mice were administered fractions of chitin, protein or fat, and the acute hypoglycemic effect was evaluated. A subacute study involving daily administration of these fractions to diabetic mice was also performed over 30 days, after which the liver and pancreas were processed by conventional histological techniques and stained with hematoxylin and eosin to evaluate morphological changes. The most active fraction, the fat fraction, was analyzed by gas chromatography-mass spectrometry (GC-MS, and PPARγ and GLUT4 mRNA expressions were determined in 3T3-L1 adipocytes. The protein and fat fractions exhibited hypoglycemic effects in the acute as well as in the 30-day study. Only the fat fraction led to elevated insulin levels and reduced glycemia, as well as lower intake of water and food. In the liver, we observed recovery of close hepatic cords in the central lobule vein following treatment with the fat fraction, while in the pancreas there was an increased density and percentage of islets and number of cells per islet, suggesting cellular regeneration. The GC-MS analysis of fat revealed three fatty acids as the major components. Finally, increased expression of PPARγ and GLUT4 was observed in 3T3-L1 adipocytes, indicating an antidiabetic effect.

  11. Constitutive expression of a fungus-inducible carboxylesterase improves disease resistance in transgenic pepper plants. (United States)

    Ko, Moonkyung; Cho, Jung Hyun; Seo, Hyo-Hyoun; Lee, Hyun-Hwa; Kang, Ha-Young; Nguyen, Thai Son; Soh, Hyun Cheol; Kim, Young Soon; Kim, Jeong-Il


    Resistance against anthracnose fungi was enhanced in transgenic pepper plants that accumulated high levels of a carboxylesterase, PepEST in anthracnose-susceptible fruits, with a concurrent induction of antioxidant enzymes and SA-dependent PR proteins. A pepper esterase gene (PepEST) is highly expressed during the incompatible interaction between ripe fruits of pepper (Capsicum annuum L.) and a hemibiotrophic anthracnose fungus (Colletotrichum gloeosporioides). In this study, we found that exogenous application of recombinant PepEST protein on the surface of the unripe pepper fruits led to a potentiated state for disease resistance in the fruits, including generation of hydrogen peroxide and expression of pathogenesis-related (PR) genes that encode mostly small proteins with antimicrobial activity. To elucidate the role of PepEST in plant defense, we further developed transgenic pepper plants overexpressing PepEST under the control of CaMV 35S promoter. Molecular analysis confirmed the establishment of three independent transgenic lines carrying single copy of transgenes. The level of PepEST protein was estimated to be approximately 0.002 % of total soluble protein in transgenic fruits. In response to the anthracnose fungus, the transgenic fruits displayed higher expression of PR genes, PR3, PR5, PR10, and PepThi, than non-transgenic control fruits did. Moreover, immunolocalization results showed concurrent localization of ascorbate peroxidase (APX) and PR3 proteins, along with the PepEST protein, in the infected region of transgenic fruits. Disease rate analysis revealed significantly low occurrence of anthracnose disease in the transgenic fruits, approximately 30 % of that in non-transgenic fruits. Furthermore, the transgenic plants also exhibited resistance against C. acutatum and C. coccodes. Collectively, our results suggest that overexpression of PepEST in pepper confers enhanced resistance against the anthracnose fungi by activating the defense signaling

  12. Renal denervation improves cardiac function in rats with chronic heart failure: Effects on expression of β-adrenoceptors (United States)

    Zheng, Hong; Liu, Xuefei; Sharma, Neeru M.


    Chronic activation of the sympathetic drive contributes to cardiac remodeling and dysfunction during chronic heart failure (HF). The present study was undertaken to assess whether renal denervation (RDN) would abrogate the sympathoexcitation in HF and ameliorate the adrenergic dysfunction and cardiac damage. Ligation of the left coronary artery was used to induce HF in Sprague-Dawley rats. Four weeks after surgery, RDN was performed, 1 wk before the final measurements. At the end of the protocol, cardiac function was assessed by measuring ventricular hemodynamics. Rats with HF had an average infarct area >30% of the left ventricle and left ventricular end-diastolic pressure (LVEDP) >20 mmHg. β1- and β2-adrenoceptor proteins in the left ventricle were reduced by 37 and 49%, respectively, in the rats with HF. RDN lowered elevated levels of urinary excretion of norepinephrine and brain natriuretic peptide levels in the hearts of rats with HF. RDN also decreased LVEDP to 10 mmHg and improved basal dP/dt to within the normal range in rats with HF. RDN blunted loss of β1-adrenoceptor (by 47%) and β2-adrenoceptor (by 100%) protein expression and improved isoproterenol (0.5 μg/kg)-induced increase in +dP/dt (by 71%) and −dP/dt (by 62%) in rats with HF. RDN also attenuated the increase in collagen 1 expression in the left ventricles of rats with HF. These findings demonstrate that RDN initiated in chronic HF condition improves cardiac function mediated by adrenergic agonist and blunts β-adrenoceptor expression loss, providing mechanistic insights for RDN-induced improvements in cardiac function in the HF condition. PMID:27288440

  13. Expression of PprI from Deinococcus radiodurans Improves Lactic Acid Production and Stress Tolerance in Lactococcus lactis.

    Directory of Open Access Journals (Sweden)

    Xiangrong Dong

    Full Text Available PprI is a general switch protein that regulates the expression of certain proteins involved in pathways of cellular resistance in the extremophilic bacterium Deinococcus radiodurans. In this study, we transformed pprI into Lactococcus lactis strain MG1363 using the lactococcal shuttle vector pMG36e and investigated its effects on the tolerance and lactic acid production of L. lactis while under stress. PprI was stably expressed in L. lactis as confirmed by western blot assays. L. lactis expressing PprI exhibited significantly improved resistance to oxidative stress and high osmotic pressure. This enhanced cellular tolerance to stressors might be due to the regulation of resistance-related genes (e.g., recA, recO, sodA, and nah by pprI. Moreover, transformed L. lactis demonstrated increased lactic acid production, attributed to enhanced lactate dehydrogenase activity. These results suggest that pprI can improve the tolerance of L. lactis to environmental stresses, and this transformed bacterial strain is a promising candidate for industrial applications of lactic acid production.

  14. Expression of PprI from Deinococcus radiodurans Improves Lactic Acid Production and Stress Tolerance in Lactococcus lactis. (United States)

    Dong, Xiangrong; Tian, Bing; Dai, Shang; Li, Tao; Guo, Linna; Tan, Zhongfang; Jiao, Zhen; Jin, Qingsheng; Wang, Yanping; Hua, Yuejin


    PprI is a general switch protein that regulates the expression of certain proteins involved in pathways of cellular resistance in the extremophilic bacterium Deinococcus radiodurans. In this study, we transformed pprI into Lactococcus lactis strain MG1363 using the lactococcal shuttle vector pMG36e and investigated its effects on the tolerance and lactic acid production of L. lactis while under stress. PprI was stably expressed in L. lactis as confirmed by western blot assays. L. lactis expressing PprI exhibited significantly improved resistance to oxidative stress and high osmotic pressure. This enhanced cellular tolerance to stressors might be due to the regulation of resistance-related genes (e.g., recA, recO, sodA, and nah) by pprI. Moreover, transformed L. lactis demonstrated increased lactic acid production, attributed to enhanced lactate dehydrogenase activity. These results suggest that pprI can improve the tolerance of L. lactis to environmental stresses, and this transformed bacterial strain is a promising candidate for industrial applications of lactic acid production.

  15. Heterologous expression of VHb can improve the yield and quality of biocontrol fungus Paecilomyces lilacinus, during submerged fermentation. (United States)

    Zhang, Shumeng; Wang, Jieping; Wei, Yale; Tang, Qing; Ali, Maria Kanwal; He, Jin


    Paecilomyces lilacinus is an egg-parasitic fungus which is effective against plant-parasitic nematodes and it has been successfully commercialized for the control of many plant-parasitic nematodes. However, during the large-scale industrial fermentation process of the filamentous fungus, the dissolved oxygen supply is a limiting factor, which influences yield, product quality and production cost. To solve this problem, we intended to heterologously express VHb in P. lilacinus ACSS. After optimizing the vgb gene, we fused it with a selection marker gene nptII, a promoter PgpdA and a terminator TtrpC. The complete expression cassette PgpdA-nptII-vgb-TtrpC was transferred into P. lilacinus ACSS by Agrobacterium tumefaciens-mediated transformation. Consequently, we successfully screened an applicable fungus strain PNVT8 which efficiently expressed VHb. The submerged fermentation experiments demonstrated that the expression of VHb not only increased the production traits of P. lilacinus such as biomass and spore production, but also improved the beneficial product quality and application value, due to the secretion of more protease and chitinase. It can be speculated that the recombinant strain harboring vgb gene will have a growth advantage over the original strain under anaerobic conditions in soil and therefore will possess higher biocontrol efficiency against plant-parasitic nematodes. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Transgenic Cotton Plants Expressing the HaHR3 Gene Conferred Enhanced Resistance to Helicoverpa armigera and Improved Cotton Yield. (United States)

    Han, Qiang; Wang, Zhenzhen; He, Yunxin; Xiong, Yehui; Lv, Shun; Li, Shupeng; Zhang, Zhigang; Qiu, Dewen; Zeng, Hongmei


    RNA interference (RNAi) has been developed as an efficient technology. RNAi insect-resistant transgenic plants expressing double-stranded RNA (dsRNA) that is ingested into insects to silence target genes can affect the viability of these pests or even lead to their death. HaHR3 , a molt-regulating transcription factor gene, was previously selected as a target expressed in bacteria and tobacco plants to control Helicoverpa armigera by RNAi technology. In this work, we selected the dsRNA- HaHR3 fragment to silence HaHR3 in cotton bollworm for plant mediated-RNAi research. A total of 19 transgenic cotton lines expressing HaHR3 were successfully cultivated, and seven generated lines were used to perform feeding bioassays. Transgenic cotton plants expressing ds HaHR3 were shown to induce high larval mortality and deformities of pupation and adult eclosion when used to feed the newly hatched larvae, and 3rd and 5th instar larvae of H. armigera . Moreover, HaHR3 transgenic cotton also demonstrated an improved cotton yield when compared with controls.

  17. Phase variable expression of a single phage receptor in Campylobacter jejuni NCTC12662 influences sensitivity toward several diverse CPS-dependent phages

    DEFF Research Database (Denmark)

    Gencay, Yilmaz Emre; Sørensen, Martine C.H.; Wenzel, Cory Q.


    Campylobacter jejuni NCTC12662 is sensitive to infection by many Campylobacter bacteriophages. Here we used this strain to investigate the molecular mechanism behind phage resistance development when exposed to a single phage and demonstrate how phase variable expression of one surface component...... influences phage sensitivity against many diverse C. jejuni phages. When C. jejuni NCTC12662 was exposed to phage F207 overnight, 25% of the bacterial cells were able to grow on a lawn of phage F207, suggesting that resistance develops at a high frequency. One resistant variant, 12662R, was further...... characterized and shown to be an adsorption mutant. Plaque assays using our large phage collection showed that seven out of 36 diverse capsular polysaccharide (CPS)-dependent phages could not infect 12662R, whereas the remaining phages formed plaques on 12662R with reduced efficiencies. Analysis of the CPS...

  18. Improving the scaling normalization for high-density oligonucleotide GeneChip expression microarrays

    Directory of Open Access Journals (Sweden)

    Lu Chao


    Full Text Available Abstract Background Normalization is an important step for microarray data analysis to minimize biological and technical variations. Choosing a suitable approach can be critical. The default method in GeneChip expression microarray uses a constant factor, the scaling factor (SF, for every gene on an array. The SF is obtained from a trimmed average signal of the array after excluding the 2% of the probe sets with the highest and the lowest values. Results Among the 76 U34A GeneChip experiments, the total signals on each array showed 25.8% variations in terms of the coefficient of variation, although all microarrays were hybridized with the same amount of biotin-labeled cRNA. The 2% of the probe sets with the highest signals that were normally excluded from SF calculation accounted for 34% to 54% of the total signals (40.7% ± 4.4%, mean ± sd. In comparison with normalization factors obtained from the median signal or from the mean of the log transformed signal, SF showed the greatest variation. The normalization factors obtained from log transformed signals showed least variation. Conclusions Eliminating 40% of the signal data during SF calculation failed to show any benefit. Normalization factors obtained with log transformed signals performed the best. Thus, it is suggested to use the mean of the logarithm transformed data for normalization, rather than the arithmetic mean of signals in GeneChip gene expression microarrays.

  19. Improved cellulolytic efficacy in Penicilium decumbens via heterologous expression of Hypocrea jecorina endoglucanase II

    Directory of Open Access Journals (Sweden)

    Qin Yuqi


    Full Text Available Hypocrea jecorina endoglucanase II (Hjegl2 was heterologously expressed in Penicillium decumbens (yielding strain Pd::Hjegl2. After induction in cellulose containing media, strain Pd::Hjeg2 displayed increased carboxymethylcellulase activity (CMCase, 5.77 IU/ml, representing a 21% increase and cellulose degradation determined with a filter paper assay (FPA, 0.40 IU/ml, 67% increase, as compared to the parent strain. In media supplemented with glucose (2%, Pd::Hjegl2, displayed 51.2-fold and 3-fold higher CMCase and FPA activities, respectively, as compared to the parent strain. No changes in the expression levels of the four main native cellulase genes of P. decumbens (Pdegl1, Pdegl2, Pdcbh1, and Pdcbh2 were noted between the transformant and wild-type strains. These data support the idea that Hjegl2 cleaves both internal and terminal glycosidic residues, in a relatively random and processive manner. In situ polyacrylamide gelactivity staining of extracts derived from wild-type and Pd::Hjegl2 revealed two additional active fractions in the latter strain; one with a molecular mass ~50-65 KDa and another ~80-116 kDa.

  20. Improving retting of fibre through genetic modification of flax to express pectinases. (United States)

    Musialak, Magdalena; Wróbel-Kwiatkowska, Magdalena; Kulma, Anna; Starzycka, Eligia; Szopa, Jan


    Flax (Linum usitatissimum L.) is a raw material used for important industrial products. Linen has very high quality textile properties, such as its strength, water absorption, comfort and feel. However, it occupies less than 1% of the total textile market. The major reason for this is the long and difficult retting process by which linen fibres are obtained. In retting, bast fibre bundles are separated from the core, the epidermis and the cuticle. This is accomplished by the cleavage of pectins and hemicellulose in the flax cell wall, a process mainly carried out by plant pathogens like filamentous fungi. The remaining bast fibres are mainly composed of cellulose and lignin. The aim of this study was to generate plants that could be retted more efficiently. To accomplish this, we employed the novel approach of transgenic flax plant generation with increased polygalacturonase (PGI ) and rhamnogalacturonase (RHA) activities. The constitutive expression of Aspergillus aculeatus genes resulted in a significant reduction in the pectin content in tissue-cultured and field-grown plants. This pectin content reduction was accompanied by a significantly higher (more than 2-fold) retting efficiency of the transgenic plant fibres as measured by a modified Fried's test. No alteration in the lignin or cellulose content was observed in the transgenic plants relative to the control. This indicates that the over-expression of the two enzymes does not affect flax fibre composition. The growth rate and soluble sugar and starch contents were in the range of the control levels. It is interesting to note that the RHA and PGI plants showed higher resistance to Fusarium culmorum and F. oxysporum attack, which correlates with the increased phenolic acid level. In this report, we demonstrate for the first time that over-expression of the A. aculeatus genes results in flax plants more readily usable for fibre production. The biochemical parameters of the cell wall components indicated that

  1. The shunt from the cyclooxygenase to lipoxygenase pathway in human osteoarthritic subchondral osteoblasts is linked with a variable expression of the 5-lipoxygenase-activating protein. (United States)

    Maxis, Kelitha; Delalandre, Aline; Martel-Pelletier, Johanne; Pelletier, Jean-Pierre; Duval, Nicolas; Lajeunesse, Daniel


    Osteoarthritis (OA) is characterized by articular cartilage degradation and hypertrophic bone changes with osteophyte formation and abnormal bone remodeling. Two groups of OA patients were identified via the production of variable and opposite levels of prostaglandin E2 (PGE2) or leukotriene B4 (LTB4) by subchondral osteoblasts, PGE2 levels discriminating between low and high subgroups. We studied whether the expression of 5-lipoxygenase (5-LO) or 5-LO-activating protein (FLAP) is responsible for the shunt from prostaglandins to leukotrienes. FLAP mRNA levels varied in low and high OA groups compared with normal, whereas mRNA levels of 5-LO were similar in all osteoblasts. Selective inhibition of cyclooxygenase-2 (COX-2) with NS-398-stimulated FLAP expression in the high OA osteoblasts subgroup, whereas it was without effect in the low OA osteoblasts subgroup. The addition of PGE2 to the low OA osteoblasts subgroup decreased FLAP expression but failed to affect it in the high OA osteoblasts subgroup. LTB4 levels in OA osteoblasts were stimulated about twofold by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) plus transforming growth factor-beta (TGF-beta), a situation corresponding to their effect on FLAP mRNA levels. Treatments with 1,25(OH)2D3 and TGF-beta also modulated PGE2 production. TGF-beta stimulated PGE2 production in both OA osteoblast groups, whereas 1,25(OH)2D3 alone had a limited effect but decreased the effect of TGF-beta in the low OA osteoblasts subgroup. This modulation of PGE2 production was mirrored by the synthesis of COX-2. IL-18 levels were only slightly increased in a subgroup of OA osteoblasts compared with normal; however, no relationship was observed overall between IL-18 and PGE2 levels in normal and OA osteoblasts. These results suggest that the shunt from the production of PGE2 to LTB4 is through regulation of the expression of FLAP, not 5-LO, in OA osteoblasts. The expression of FLAP in OA osteoblasts is also modulated differently by 1,25(OH

  2. A safer, urea-based in situ hybridization method improves detection of gene expression in diverse animal species. (United States)

    Sinigaglia, Chiara; Thiel, Daniel; Hejnol, Andreas; Houliston, Evelyn; Leclère, Lucas


    In situ hybridization is a widely employed technique allowing spatial visualization of gene expression in fixed specimens. It has greatly advanced our understanding of biological processes, including developmental regulation. In situ protocols are today routinely followed in numerous laboratories, and although details might change, they all include a hybridization step, where specific antisense RNA or DNA probes anneal to the target nucleic acid sequence. This step is generally carried out at high temperatures and in a denaturing solution, called hybridization buffer, commonly containing 50% (v/v) formamide - a hazardous chemical. When applied to the soft-bodied hydrozoan medusa Clytia hemisphaerica, we found that this traditional hybridization approach was not fully satisfactory, causing extensive deterioration of morphology and tissue texture which compromised our observation and interpretation of results. We thus tested alternative solutions for in situ detection of gene expression and, inspired by optimized protocols for Northern and Southern blot analysis, we substituted the 50% formamide with an equal volume of 8M urea solution in the hybridization buffer. Our new protocol not only yielded better morphologies and tissue consistency, but also notably improved the resolution of the signal, allowing more precise localization of gene expression and reducing aspecific staining associated with problematic areas. Given the improved results and reduced manipulation risks, we tested the urea protocol on other metazoans, two brachiopod species (Novocrania anomala and Terebratalia transversa) and the priapulid worm Priapulus caudatus, obtaining a similar reduction of aspecific probe binding. Overall, substitution of formamide by urea during in situ hybridization offers a safer alternative, potentially of widespread use in research, medical and teaching contexts. We encourage other workers to test this approach on their study organisms, and hope that they will also

  3. Yield improvement of heterologous peptides expressed in yps1-disrupted Saccharomyces cerevisiae strains. (United States)

    Egel-Mitani; Andersen; Diers; Hach; Thim; Hastrup; Vad


    Heterologous protein expression levels in Saccharomyces cerevisiae fermentations are highly dependent on the susceptibility to endogenous yeast proteases. Small peptides, such as glucagon and glucagon-like-peptides (GLP-1 and GLP-2), featuring an open structure are particularly accessible for proteolytic degradation during fermentation. Therefore, homogeneous products cannot be obtained. The most sensitive residues are found at basic amino acid residues in the peptide sequence. These heterologous peptides are degraded mainly by the YPS1-encoded aspartic protease, yapsin1, when produced in the yeast. In this article, distinct degradation products were analyzed by HPLC and mass spectrometry, and high yield of the heterologous peptide production has been achieved by the disruption of the YPS1 gene (previously called YAP3). By this technique, high yield continuous fermentation of glucagon in S. cerevisiae is now possible.

  4. Transgene expression, but not gene delivery, is improved by adhesion-assisted lipofection of hematopoietic cells. (United States)

    Keller, H; Yunxu, C; Marit, G; Pla, M; Reiffers, J; Thèze, J; Froussard, P


    In contrast to adherent cells, cells growing in suspension and particularly hematopoietic cells, are notoriously difficult to transfect in vitro using nonviral approaches. In the present study, the effect of cell adhesion on gene transfer efficacy was investigated by allowing hematopoietic cells to bind to an adherent cell monolayer (ACM) before being subjected to cationic liposome-mediated DNA transfer. Human CD34 and T CD4 cell lines were cultivated on an ACM constituted of murine fibroblast NIH3T3 cells and transfected with a plasmid carrying the beta-galactosidase gene. X-gal staining showed that up to 27% of the cells expressed the transgene. In contrast, less than 0.1% of these cells were positively transfected in suspension. This adhesion-assisted lipofection (AAL) procedure was also successfully tested on blood lymphocytes, since it resulted in up to 30% of transfected human primary T lymphocytes. Flow cytometry analysis performed on T lymphocyte subsets revealed that 8 and 9%, respectively, of CD4 and CD8 cells could be transfected with a plasmid carrying the green fluorescent protein gene. Other adherent cells, such as MS5 murine stromal cells or HeLa epithelial cells, were also a compatible matrix for AAL. Moreover, the pCMV beta plasmid was present in similar amounts in the nuclei of TF1 cells transfected in suspension or with the AAL procedure. These data raise the possibility that cell matrix/hematopoietic cell interactions might govern expression of the transgene in hematopoietic cells growing usually in suspension, but not endocytosis of liposome/DNA particles and plasmid migration ot the cell nucleus.

  5. Hybrid robust model based on an improved functional link neural network integrating with partial least square (IFLNN-PLS) and its application to predicting key process variables. (United States)

    He, Yan-Lin; Xu, Yuan; Geng, Zhi-Qiang; Zhu, Qun-Xiong


    In this paper, a hybrid robust model based on an improved functional link neural network integrating with partial least square (IFLNN-PLS) is proposed. Firstly, an improved functional link neural network with small norm of expanded weights and high input-output correlation (SNEWHIOC-FLNN) was proposed for enhancing the generalization performance of FLNN. Unlike the traditional FLNN, the expanded variables of the original inputs are not directly used as the inputs in the proposed SNEWHIOC-FLNN model. The original inputs are attached to some small norm of expanded weights. As a result, the correlation coefficient between some of the expanded variables and the outputs is enhanced. The larger the correlation coefficient is, the more relevant the expanded variables tend to be. In the end, the expanded variables with larger correlation coefficient are selected as the inputs to improve the performance of the traditional FLNN. In order to test the proposed SNEWHIOC-FLNN model, three UCI (University of California, Irvine) regression datasets named Housing, Concrete Compressive Strength (CCS), and Yacht Hydro Dynamics (YHD) are selected. Then a hybrid model based on the improved FLNN integrating with partial least square (IFLNN-PLS) was built. In IFLNN-PLS model, the connection weights are calculated using the partial least square method but not the error back propagation algorithm. Lastly, IFLNN-PLS was developed as an intelligent measurement model for accurately predicting the key variables in the Purified Terephthalic Acid (PTA) process and the High Density Polyethylene (HDPE) process. Simulation results illustrated that the IFLNN-PLS could significant improve the prediction performance. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

  6. Locomotor activity of rats with SCI is improved by dexmedetomidine by targeting the expression of inflammatory factors. (United States)

    Wang, Wei-Guo; Wang, Lin; Jiao, Zhen-Hua; Xue, Bin; Xu, Zhan-Wang


    Dexmedetomidine, a well‑known selective α‑2 adrenoceptor agonist, inhibits the apoptosis of neurons and protects other organs from oxidative damage. In the present study, the effect of dexmedetomidine on spinal cord injury (SCI) in a rat model was investigated. The SCI rat model was prepared using the weight‑drop method, and the effect of dexmedetomidine on locomotor activity was analyzed using the Basso, Beattie and Bresnahan (BBB) rating scale. Western blot analysis was used to observe changes in the expression of apoptosis‑related proteins, including B‑cell lymphoma 2 (Bcl‑2) and Bcl‑2‑associated X protein (Bax). The results revealed that treatment of the SCI rats with dexmedetomidine at a dose of 50 mg/kg significantly prevented the formation of edema in the tissues of the spinal cord. Dexmedetomidine also inhibited the SCI‑induced accumulation of neutrophils in the spinal cord. The BBB scores were significantly increased (PSCI treated with dexmedetomidine after 10 days. The results of grid walking test revealed a marked decrease in the number of missteps following 10 days of dexmedetomidine treatment. The expression levels of tumor necrosis factor (TNF)‑α and interleukin (IL)‑1β were significantly reduced (PSCI exerted an inhibitory effect on the SCI‑induced increase in the expression of Bax. The expression of Bcl‑2 was increased in the dexmedetomidine treated rats, compared with that in the control group. Taken together, dexmedetomidine improved the locomotor activity of the rats through the inhibition of edema, reduction in the expression levels of TNF‑α and IL‑1β, and inhibition of the induction of apoptosis. Therefore, dexmedetomidine may be of therapeutic importance for patients with SCI.

  7. Lycium chinense Improves Post-Menopausal Obesity via Regulation of PPAR-γ and Estrogen Receptor-α/β Expressions. (United States)

    Kim, Mi Hye; Kim, Eun-Jung; Choi, You Yeon; Hong, Jongki; Yang, Woong Mo


    The fruit of Lycium chinense Miller (Solanaceae) is used as a functional food and a medicinal herb for treating many specific health concerns. Weight gain induced by estrogen deficiency is a problem for post-menopausal women around the globe. The present study investigates the effects of aqueous extract of L. chinense (LC) on post-menopausal obesity. Female C57BL/6 mice were ovariectomized and fed on high-fat diet (HFD) for 12 weeks to induce post-menopausal obesity. LC extract (1[Formula: see text]mg/kg and 10[Formula: see text]mg/kg) was orally administrated for 6 weeks with continuous HFD feeding. Ovarian adipose tissues and uterus were weighed. Serum triglyceride, cholesterol, LDL-cholesterol and fasting glucose levels were analyzed. The expressions of adipocyte-specific factors and estrogen receptors (ERs) were investigated. Additionally, lipid accumulation was confirmed in differentiated 3T3-L1 adipocytes. Increased body weight due to post-menopausal obesity was ameliorated about 14.7% and 17.76% by treatment of 1[Formula: see text]mg/kg and 10[Formula: see text]mg/kg LC, respectively. LC treatment reduced both of serum lipid and fasting blood glucose levels. Adipocyte hypertrophy and fatty liver were ameliorated in LC-treated groups. In LC-treated adipocyte cells, lipid accumulation was significantly inhibited. The expression of perilipin in adipose tissues was decreased by LC. In addition, expression of PPAR-[Formula: see text] protein was down-regulated in adipose tissues and differentiated adipocytes, while GLUT4 expression was increased in adipose tissues by LC treatment. Moreover, LC treatment up-regulated the expressions of ER-[Formula: see text]/[Formula: see text] accompanied with increased uterine weight. These results showed the ameliorative effects of LC on overweight after menopause. Post-menopausal obesity may be improved by LC treatment.

  8. Linnorm: improved statistical analysis for single cell RNA-seq expression data. (United States)

    Yip, Shun H; Wang, Panwen; Kocher, Jean-Pierre A; Sham, Pak Chung; Wang, Junwen


    Linnorm is a novel normalization and transformation method for the analysis of single cell RNA sequencing (scRNA-seq) data. Linnorm is developed to remove technical noises and simultaneously preserve biological variations in scRNA-seq data, such that existing statistical methods can be improved. Using real scRNA-seq data, we compared Linnorm with existing normalization methods, including NODES, SAMstrt, SCnorm, scran, DESeq and TMM. Linnorm shows advantages in speed, technical noise removal and preservation of cell heterogeneity, which can improve existing methods in the discovery of novel subtypes, pseudo-temporal ordering of cells, clustering analysis, etc. Linnorm also performs better than existing DEG analysis methods, including BASiCS, NODES, SAMstrt, Seurat and DESeq2, in false positive rate control and accuracy. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  9. Renin-angiotensin-aldosterone system inhibitors improve membrane stability and change gene-expression profiles in dystrophic skeletal muscles. (United States)

    Chadwick, Jessica A; Bhattacharya, Sayak; Lowe, Jeovanna; Weisleder, Noah; Rafael-Fortney, Jill A


    Angiotensin-converting enzyme inhibitors (ACEi) and mineralocorticoid receptor (MR) antagonists are FDA-approved drugs that inhibit the renin-angiotensin-aldosterone system (RAAS) and are used to treat heart failure. Combined treatment with the ACEi lisinopril and the nonspecific MR antagonist spironolactone surprisingly improves skeletal muscle, in addition to heart function and pathology in a Duchenne muscular dystrophy (DMD) mouse model. We recently demonstrated that MR is present in all limb and respiratory muscles and functions as a steroid hormone receptor in differentiated normal human skeletal muscle fibers. The goals of the current study were to begin to define cellular and molecular mechanisms mediating the skeletal muscle efficacy of RAAS inhibitor treatment. We also compared molecular changes resulting from RAAS inhibition with those resulting from the current DMD standard-of-care glucocorticoid treatment. Direct assessment of muscle membrane integrity demonstrated improvement in dystrophic mice treated with lisinopril and spironolactone compared with untreated mice. Short-term treatments of dystrophic mice with specific and nonspecific MR antagonists combined with lisinopril led to overlapping gene-expression profiles with beneficial regulation of metabolic processes and decreased inflammatory gene expression. Glucocorticoids increased apoptotic, proteolytic, and chemokine gene expression that was not changed by RAAS inhibitors in dystrophic mice. Microarray data identified potential genes that may underlie RAAS inhibitor treatment efficacy and the side effects of glucocorticoids. Direct effects of RAAS inhibitors on membrane integrity also contribute to improved pathology of dystrophic muscles. Together, these data will inform clinical development of MR antagonists for treating skeletal muscles in DMD. Copyright © 2017 the American Physiological Society.

  10. Uphill running improves rat Achilles tendon tissue mechanical properties and alters gene expression without inducing pathological changes

    DEFF Research Database (Denmark)

    Heinemeier, K M; Skovgaard, D; Bayer, M L


    was increased, while collagen I was unchanged, and decreases were seen in noncollagen matrix components (fibromodulin and biglycan), matrix degrading enzymes, transforming growth factor-ß1, and connective tissue growth factor. In conclusion, the tested model could not be validated as a model for Achilles...... tendinopathy, as the rats were able to adapt to 12 wk of uphill running without any signs of tendinopathy. Improved mechanical properties were observed, as well as changes in gene-expression that were distinctly different from what is seen in tendinopathy and in response to short-term tendon loading....

  11. Reduction of liver fructokinase expression and improved hepatic inflammation and metabolism in liquid fructose-fed rats after atorvastatin treatment

    Energy Technology Data Exchange (ETDEWEB)

    Vila, Laia; Rebollo, Alba; Adalsteisson, Gunnar S [Pharmacology Unit, Department of Pharmacology and Therapeutic Chemistry, School of Pharmacy, University of Barcelona, Barcelona (Spain); Alegret, Marta; Merlos, Manuel; Roglans, Nuria [Pharmacology Unit, Department of Pharmacology and Therapeutic Chemistry, School of Pharmacy, University of Barcelona, Barcelona (Spain); IBUB - Institute of Biomedicine, University of Barcelona, Barcelona (Spain); CIBERobn, [Center for Biomedical Investigation Network in Obesity and Nutrition Physiopathology; Spain; Laguna, Juan C., E-mail: [Pharmacology Unit, Department of Pharmacology and Therapeutic Chemistry, School of Pharmacy, University of Barcelona, Barcelona (Spain); IBUB -Institute of Biomedicine, University of Barcelona, Barcelona (Spain); CIBERobn, [Center for Biomedical Investigation Network in Obesity and Nutrition Physiopathology; Spain


    Consumption of beverages that contain fructose favors the increasing prevalence of metabolic syndrome alterations in humans, including non-alcoholic fatty liver disease (NAFLD). Although the only effective treatment for NAFLD is caloric restriction and weight loss, existing data show that atorvastatin, a hydroxymethyl-glutaryl-CoA reductase inhibitor, can be used safely in patients with NAFLD and improves hepatic histology. To gain further insight into the molecular mechanisms of atorvastatin's therapeutic effect on NAFLD, we used an experimental model that mimics human consumption of fructose-sweetened beverages. Control, fructose (10% w/v solution) and fructose + atorvastatin (30 mg/kg/day) Sprague-Dawley rats were sacrificed after 14 days. Plasma and liver tissue samples were obtained to determine plasma analytes, liver histology, and the expression of liver proteins that are related to fatty acid synthesis and catabolism, and inflammatory processes. Fructose supplementation induced hypertriglyceridemia and hyperleptinemia, hepatic steatosis and necroinflammation, increased the expression of genes related to fatty acid synthesis and decreased fatty acid {beta}-oxidation activity. Atorvastatin treatment completely abolished histological signs of necroinflammation, reducing the hepatic expression of metallothionein-1 and nuclear factor kappa B binding. Furthermore, atorvastatin reduced plasma (x 0.74) and liver triglyceride (x 0.62) concentrations, decreased the liver expression of carbohydrate response element binding protein transcription factor (x0.45) and its target genes, and increased the hepatic activity of the fatty acid {beta}-oxidation system (x 1.15). These effects may be related to the fact that atorvastatin decreased the expression of fructokinase (x 0.6) in livers of fructose-supplemented rats, reducing the metabolic burden on the liver that is imposed by continuous fructose ingestion. - Graphical Abstract: Display Omitted Research Highlights

  12. Reduction of liver fructokinase expression and improved hepatic inflammation and metabolism in liquid fructose-fed rats after atorvastatin treatment

    International Nuclear Information System (INIS)

    Vila, Laia; Rebollo, Alba; Adalsteisson, Gunnar S.; Alegret, Marta; Merlos, Manuel; Roglans, Nuria; Laguna, Juan C.


    Consumption of beverages that contain fructose favors the increasing prevalence of metabolic syndrome alterations in humans, including non-alcoholic fatty liver disease (NAFLD). Although the only effective treatment for NAFLD is caloric restriction and weight loss, existing data show that atorvastatin, a hydroxymethyl-glutaryl-CoA reductase inhibitor, can be used safely in patients with NAFLD and improves hepatic histology. To gain further insight into the molecular mechanisms of atorvastatin's therapeutic effect on NAFLD, we used an experimental model that mimics human consumption of fructose-sweetened beverages. Control, fructose (10% w/v solution) and fructose + atorvastatin (30 mg/kg/day) Sprague-Dawley rats were sacrificed after 14 days. Plasma and liver tissue samples were obtained to determine plasma analytes, liver histology, and the expression of liver proteins that are related to fatty acid synthesis and catabolism, and inflammatory processes. Fructose supplementation induced hypertriglyceridemia and hyperleptinemia, hepatic steatosis and necroinflammation, increased the expression of genes related to fatty acid synthesis and decreased fatty acid β-oxidation activity. Atorvastatin treatment completely abolished histological signs of necroinflammation, reducing the hepatic expression of metallothionein-1 and nuclear factor kappa B binding. Furthermore, atorvastatin reduced plasma (x 0.74) and liver triglyceride (x 0.62) concentrations, decreased the liver expression of carbohydrate response element binding protein transcription factor (x0.45) and its target genes, and increased the hepatic activity of the fatty acid β-oxidation system (x 1.15). These effects may be related to the fact that atorvastatin decreased the expression of fructokinase (x 0.6) in livers of fructose-supplemented rats, reducing the metabolic burden on the liver that is imposed by continuous fructose ingestion. - Graphical Abstract: Display Omitted Research Highlights:

  13. Spatial Scaling of Environmental Variables Improves Species-Habitat Models of Fishes in a Small, Sand-Bed Lowland River.

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    Johannes Radinger

    Full Text Available Habitat suitability and the distinct mobility of species depict fundamental keys for explaining and understanding the distribution of river fishes. In recent years, comprehensive data on river hydromorphology has been mapped at spatial scales down to 100 m, potentially serving high resolution species-habitat models, e.g., for fish. However, the relative importance of specific hydromorphological and in-stream habitat variables and their spatial scales of influence is poorly understood. Applying boosted regression trees, we developed species-habitat models for 13 fish species in a sand-bed lowland river based on river morphological and in-stream habitat data. First, we calculated mean values for the predictor variables in five distance classes (from the sampling site up to 4000 m up- and downstream to identify the spatial scale that best predicts the presence of fish species. Second, we compared the suitability of measured variables and assessment scores related to natural reference conditions. Third, we identified variables which best explained the presence of fish species. The mean model quality (AUC = 0.78, area under the receiver operating characteristic curve significantly increased when information on the habitat conditions up- and downstream of a sampling site (maximum AUC at 2500 m distance class, +0.049 and topological variables (e.g., stream order were included (AUC = +0.014. Both measured and assessed variables were similarly well suited to predict species' presence. Stream order variables and measured cross section features (e.g., width, depth, velocity were best-suited predictors. In addition, measured channel-bed characteristics (e.g., substrate types and assessed longitudinal channel features (e.g., naturalness of river planform were also good predictors. These findings demonstrate (i the applicability of high resolution river morphological and instream-habitat data (measured and assessed variables to predict fish presence, (ii the

  14. Expression microarray reproducibility is improved by optimising purification steps in RNA amplification and labelling

    Directory of Open Access Journals (Sweden)

    Brenton James D


    Full Text Available Abstract Background Expression microarrays have evolved into a powerful tool with great potential for clinical application and therefore reliability of data is essential. RNA amplification is used when the amount of starting material is scarce, as is frequently the case with clinical samples. Purification steps are critical in RNA amplification and labelling protocols, and there is a lack of sufficient data to validate and optimise the process. Results Here the purification steps involved in the protocol for indirect labelling of amplified RNA are evaluated and the experimentally determined best method for each step with respect to yield, purity, size distribution of the transcripts, and dye coupling is used to generate targets tested in replicate hybridisations. DNase treatment of diluted total RNA samples followed by phenol extraction is the optimal way to remove genomic DNA contamination. Purification of double-stranded cDNA is best achieved by phenol extraction followed by isopropanol precipitation at room temperature. Extraction with guanidinium-phenol and Lithium Chloride precipitation are the optimal methods for purification of amplified RNA and labelled aRNA respectively. Conclusion This protocol provides targets that generate highly reproducible microarray data with good representation of transcripts across the size spectrum and a coefficient of repeatability significantly better than that reported previously.

  15. Research on the Rural Express Alliance based on ANP improved profit Allocation (United States)

    Zhuang, Yufeng; Zhang, Bin


    Online shopping platform in rural distribution difficulties, leading to rural online shopping market and logistics market development is slow. At present, China Post and other private courier companies are not possible to do. So we need to build distribution alliances. Reasonable profit allocation mechanism is the key to the stable development of this distribution alliance. So we proposed the Shapley Value Method and the ANP Improved Model to allocate profits. Finally, the rationality of the method is proved by numerical analysis before and after using the corrected Shapley Value.

  16. Enhanced leptin sensitivity and improved glucose homeostasis in mice lacking suppressor of cytokine signaling-3 in POMC-expressing cells. (United States)

    Kievit, Paul; Howard, Jane K; Badman, Michael K; Balthasar, Nina; Coppari, Roberto; Mori, Hiroyuki; Lee, Charlotte E; Elmquist, Joel K; Yoshimura, Akihiko; Flier, Jeffrey S


    Suppressor of cytokine signaling-3 (Socs-3) negatively regulates the action of various cytokines, as well as the metabolic hormones leptin and insulin. Mice with haploinsufficiency of Socs-3, or those with neuronal deletion of Socs-3, are lean and more leptin and insulin sensitive. To examine the role of Socs-3 within specific neurons critical to energy balance, we created mice with selective deletion of Socs-3 within pro-opiomelanocortin (POMC)-expressing cells. These mice had enhanced leptin sensitivity, measured by weight loss and food intake after leptin infusion. On chow diet, glucose homeostasis was improved despite normal weight gain. On a high-fat diet, the rate of weight gain was reduced, due to increased energy expenditure rather than decreased food intake; glucose homeostasis and insulin sensitivity were substantially improved. These studies demonstrate that Socs-3 within POMC neurons regulates leptin sensitivity and glucose homeostasis, and plays a key role in linking high-fat diet to disordered metabolism.

  17. An improved synchronous reference frame phase-locked loop for stand-alone variable speed constant frequency power generation systems

    DEFF Research Database (Denmark)

    Liu, Yi; Xu, Wei; Ke, Longzhang


    The phase-locked loop (PLL) based on conventional synchronous reference frame, i.e. dqPLL, is usually employed in grid-connected variable speed constant frequency (VSCF) power generation systems (PGSs). However, the voltage amplitude drop of stand-alone PGSs is often greater than that of the grid...

  18. Collaborative Proposal: Improving Decadal Prediction of Arctic Climate Variability and Change Using a Regional Arctic System Model (RASM)

    Energy Technology Data Exchange (ETDEWEB)

    Maslowski, Wieslaw [Naval Postgraduate School, Monterey, CA (United States). Dept. of Oceanography; Cassano, John J. [Univ. of Colorado, Boulder, CO (United States); Gutowski, Jr., William J. [Iowa State Univ., Ames, IA (United States); Lipscomb, William H. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Nijssen, Bart [Univ. of Washington, Seattle, WA (United States); Roberts, Andrew [Naval Postgraduate School, Monterey, CA (United States). Dept. of Oceanography; Robertson, William [Univ. of Texas, El Paso, TX (United States); Tulaczyk, Slawek [Univ. of California, Santa Cruz, CA (United States); Zeng, Xubin [Univ. of Arizona, Tucson, AZ (United States)


    The primary outcome of the project was the development of the Regional Arctic System Model (RASM) and evaluation of its individual model components, coupling among them and fully coupled model results. Overall, we have demonstrated that RASM produces realistic mean and seasonal surface climate as well as its interannual and decadal variability and trends.

  19. Improvement of enzymatic saccharification yield in Arabidopsis thaliana by ectopic expression of the rice SUB1A-1 transcription factor

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    Lizeth Núñez-López


    Full Text Available Saccharification of polysaccharides releases monosaccharides that can be used by ethanol-producing microorganisms in biofuel production. To improve plant biomass as a raw material for saccharification, factors controlling the accumulation and structure of carbohydrates must be identified. Rice SUB1A-1 is a transcription factor that represses the turnover of starch and postpones energy-consuming growth processes under submergence stress. Arabidopsis was employed to test if heterologous expression of SUB1A-1 or SUB1C-1 (a related gene can be used to improve saccharification. Cellulolytic and amylolytic enzymatic treatments confirmed that SUB1A-1 transgenics had better saccharification yield than wild-type (Col-0, mainly from accumulated starch. This improved saccharification yield was developmentally controlled; when compared to Col-0, young transgenic vegetative plants yielded 200–300% more glucose, adult vegetative plants yielded 40–90% more glucose and plants in reproductive stage had no difference in yield. We measured photosynthetic parameters, starch granule microstructure, and transcript abundance of genes involved in starch degradation (SEX4, GWD1, juvenile transition (SPL3-5 and meristematic identity (FUL, SOC1 but found no differences to Col-0, indicating that starch accumulation may be controlled by down-regulation of CONSTANS and FLOWERING LOCUS T by SUB1A-1 as previously reported. SUB1A-1 transgenics also offered less resistance to deformation than wild-type concomitant to up-regulation of AtEXP2 expansin and BGL2 glucan-1,3,-beta-glucosidase. We conclude that heterologous SUB1A-1 expression can improve saccharification yield and softness, two traits needed in bioethanol production.

  20. A Moderate Low-Carbohydrate Low-Calorie Diet Improves Lipid Profile, Insulin Sensitivity and Adiponectin Expression in Rats

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    Jie-Hua Chen


    Full Text Available Calorie restriction (CR via manipulating dietary carbohydrates has attracted increasing interest in the prevention and treatment of metabolic syndrome. There is little consensus about the extent of carbohydrate restriction to elicit optimal results in controlling metabolic parameters. Our study will identify a better carbohydrate-restricted diet using rat models. Rats were fed with one of the following diets for 12 weeks: Control diet, 80% energy (34% carbohydrate-reduced and 60% energy (68% carbohydrate-reduced of the control diet. Changes in metabolic parameters and expressions of adiponectin and peroxisome proliferator activator receptor γ (PPARγ were identified. Compared to the control diet, 68% carbohydrate-reduced diet led to a decrease in serum triglyceride and increases inlow density lipoprotein-cholesterol (LDL-C, high density lipoprotein-cholesterol (HDL-C and total cholesterol; a 34% carbohydrate-reduced diet resulted in a decrease in triglycerides and an increase in HDL-cholesterol, no changes however, were shown in LDL-cholesterol and total cholesterol; reductions in HOMA-IR were observed in both CR groups. Gene expressions of adiponectin and PPARγ in adipose tissues were found proportionally elevated with an increased degree of energy restriction. Our study for the first time ever identified that a moderate-carbohydrate restricted diet is not only effective in raising gene expressions of adiponectin and PPARγ which potentially lead to better metabolic conditions but is better at improving lipid profiles than a low-carbohydrate diet in rats.

  1. Prostate Cancer Cells Express More Androgen Receptor (AR) Following Androgen Deprivation, Improving Recognition by AR-Specific T Cells. (United States)

    Olson, Brian M; Gamat, Melissa; Seliski, Joseph; Sawicki, Thomas; Jeffery, Justin; Ellis, Leigh; Drake, Charles G; Weichert, Jamey; McNeel, Douglas G


    Androgen deprivation is the primary therapy for recurrent prostate cancer, and agents targeting the androgen receptor (AR) pathway continue to be developed. Because androgen-deprivation therapy (ADT) has immmunostimulatory effects as well as direct antitumor effects, AR-targeted therapies have been combined with other anticancer therapies, including immunotherapies. Here, we sought to study whether an antigen-specific mechanism of resistance to ADT (overexpression of the AR) may result in enhanced AR-specific T-cell immune recognition, and whether this might be strategically combined with an antitumor vaccine targeting the AR. Androgen deprivation increased AR expression in human and murine prostate tumor cells in vitro and in vivo The increased expression persisted over time. Increased AR expression was associated with recognition and cytolytic activity by AR-specific T cells. Furthermore, ADT combined with vaccination, specifically a DNA vaccine encoding the ligand-binding domain of the AR, led to improved antitumor responses as measured by tumor volumes and delays in the emergence of castrate-resistant prostate tumors in two murine prostate cancer models (Myc-CaP and prostate-specific PTEN-deficient mice). Together, these data suggest that ADT combined with AR-directed immunotherapy targets a major mechanism of resistance, overexpression of the AR. This combination may be more effective than ADT combined with other immunotherapeutic approaches. Cancer Immunol Res; 5(12); 1074-85. ©2017 AACR . ©2017 American Association for Cancer Research.

  2. The porcine circovirus type 1 capsid gene promoter improves antigen expression and immunogenicity in a HIV-1 plasmid vaccine

    Directory of Open Access Journals (Sweden)

    Burger Marieta


    Full Text Available Abstract Background One of the promising avenues for development of vaccines against Human immunodeficiency virus type 1 (HIV-1 and other human pathogens is the use of plasmid-based DNA vaccines. However, relatively large doses of plasmid must be injected for a relatively weak response. We investigated whether genome elements from Porcine circovirus type 1 (PCV-1, an apathogenic small ssDNA-containing virus, had useful expression-enhancing properties that could allow dose-sparing in a plasmid vaccine. Results The linearised PCV-1 genome inserted 5' of the CMV promoter in the well-characterised HIV-1 plasmid vaccine pTHgrttnC increased expression of the polyantigen up to 2-fold, and elicited 3-fold higher CTL responses in mice at 10-fold lower doses than unmodified pTHgrttnC. The PCV-1 capsid gene promoter (Pcap alone was equally effective. Enhancing activity was traced to a putative composite host transcription factor binding site and a "Conserved Late Element" transcription-enhancing sequence previously unidentified in circoviruses. Conclusions We identified a novel PCV-1 genome-derived enhancer sequence that significantly increased antigen expression from plasmids in in vitro assays, and improved immunogenicity in mice of the HIV-1 subtype C vaccine plasmid, pTHgrttnC. This should allow significant dose sparing of, or increased responses to, this and other plasmid-based vaccines. We also report investigations of the potential of other circovirus-derived sequences to be similarly used.

  3. Weight-loss changes PPAR expression, reduces atherosclerosis and improves cardiovascular function in obese insulin-resistant mice

    Energy Technology Data Exchange (ETDEWEB)

    Verreth, Wim; Verhamme, Peter; Pelat, Michael; Ganame, Javier; Bielicki, John K.; Mertens, Ann; Quarck, Rozenn; Benhabiles, Nora; Marguerie, Gerard; Mackness, Bharti; Mackness, Mike; Ninio, Ewa; Herregods, Marie-Christine; Balligand, Jean-Luc; Holvoet, Paul


    Weight-loss in obese insulin-resistant, but not in insulin-sensitive, persons reduces CHD risk. It is not known to what extent changes in the adipose gene expression profile are important for reducing CHD risk. We studied the effect of diet restriction-induced weight-loss on gene expression in adipose tissue, atherosclerosis and cardiovascular function in mice with combined leptin and LDL-receptor deficiency. Obesity, hypertriglyceridemia and insulin-resistance are associated with hypertension, impaired left ventricle function and accelerated atherosclerosis in those mice. Diet restriction during 12 weeks caused a 45% weight-loss and changes in the gene expression in adipose tissue of PPARa and PPAR? and of key genes regulating glucose transport and insulin sensitivity, lipid metabolism, oxidative stress and inflammation, most of which are under the transcriptional control of PPARs. These changes were associated with increased insulin-sensitivity, decreased hypertriglyceridemia, reduced mean 24-hour blood pressure and heart rate, restored circadian variations of blood pressure and heart rate, increased ejection fraction, and reduced atherosclerosis. Thus, induction of PPARa and PPAR? in adipose tissue is a key mechanism for reducing atherosclerosis and improving cardiovascular function resulting from weight-loss. Our observations point to the critical role of PPARs in the pathogenesis of cardiovascular features of the metabolic syndrome.

  4. The accuracy of survival time prediction for patients with glioma is improved by measuring mitotic spindle checkpoint gene expression.

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    Li Bie

    Full Text Available Identification of gene expression changes that improve prediction of survival time across all glioma grades would be clinically useful. Four Affymetrix GeneChip datasets from the literature, containing data from 771 glioma samples representing all WHO grades and eight normal brain samples, were used in an ANOVA model to screen for transcript changes that correlated with grade. Observations were confirmed and extended using qPCR assays on RNA derived from 38 additional glioma samples and eight normal samples for which survival data were available. RNA levels of eight major mitotic spindle assembly checkpoint (SAC genes (BUB1, BUB1B, BUB3, CENPE, MAD1L1, MAD2L1, CDC20, TTK significantly correlated with glioma grade and six also significantly correlated with survival time. In particular, the level of BUB1B expression was highly correlated with survival time (p<0.0001, and significantly outperformed all other measured parameters, including two standards; WHO grade and MIB-1 (Ki-67 labeling index. Measurement of the expression levels of a small set of SAC genes may complement histological grade and other clinical parameters for predicting survival time.

  5. A simple and accurate two-step long DNA sequences synthesis strategy to improve heterologous gene expression in pichia.

    Directory of Open Access Journals (Sweden)

    Jiang-Ke Yang

    Full Text Available In vitro gene chemical synthesis is a powerful tool to improve the expression of gene in heterologous system. In this study, a two-step gene synthesis strategy that combines an assembly PCR and an overlap extension PCR (AOE was developed. In this strategy, the chemically synthesized oligonucleotides were assembled into several 200-500 bp fragments with 20-25 bp overlap at each end by assembly PCR, and then an overlap extension PCR was conducted to assemble all these fragments into a full length DNA sequence. Using this method, we de novo designed and optimized the codon of Rhizopus oryzae lipase gene ROL (810 bp and Aspergillus niger phytase gene phyA (1404 bp. Compared with the original ROL gene and phyA gene, the codon-optimized genes expressed at a significantly higher level in yeasts after methanol induction. We believe this AOE method to be of special interest as it is simple, accurate and has no limitation with respect to the size of the gene to be synthesized. Combined with de novo design, this method allows the rapid synthesis of a gene optimized for expression in the system of choice and production of sufficient biological material for molecular characterization and biotechnological application.

  6. Ablation of neurons expressing melanin-concentrating hormone (MCH) in adult mice improves glucose tolerance independent of MCH signaling. (United States)

    Whiddon, Benjamin B; Palmiter, Richard D


    Melanin-concentrating hormone (MCH)-expressing neurons have been ascribed many roles based on studies of MCH-deficient mice. However, MCH neurons express other neurotransmitters, including GABA, nesfatin, and cocaine-amphetamine-regulated transcript. The importance of these other signaling molecules made by MCH neurons remains incompletely characterized. To determine the roles of MCH neurons in vivo, we targeted expression of the human diphtheria toxin receptor (DTR) to the gene for MCH (Pmch). Within 2 weeks of diphtheria toxin injection, heterozygous Pmch(DTR/+) mice lost 98% of their MCH neurons. These mice became lean but ate normally and were hyperactive, especially during a fast. They also responded abnormally to psychostimulants. For these phenotypes, ablation of MCH neurons recapitulated knock-out of MCH, so MCH appears to be the critical neuromodulator released by these neurons. In contrast, MCH-neuron-ablated mice showed improved glucose tolerance when compared with MCH-deficient mutant mice and wild-type mice. We conclude that MCH neurons regulate glucose tolerance through signaling molecules other than MCH.

  7. Expression of angiotensin II receptors in the caprine ovary and improvement of follicular viability in vitro. (United States)

    Bruno, J B; Lima-Verde, I B; Celestino, J J H; Lima, L F; Matos, M H T; Faustino, L R; Donato, M A M; Peixoto, C A; Campello, C C; Silva, J R V; Figueiredo, J R


    This study aimed to evaluate mRNA levels of angiotensin II (ANG II) receptors (AGTR1 and AGTR2) in caprine follicles and to investigate the influence of ANG II on the viability and in vitro growth of preantral follicles. Real-time polymerase chain reaction (PCR) was used to quantify AGTR1 and AGTR2 mRNA levels in the different follicular stages. For culture, caprine ovaries were collected, cut into 13 fragments and then either directly fixed for histological and ultrastructural analysis (fresh control) or placed in culture for 1 or 7 days in α-minumum essential medium plus (α-MEM+) with 0, 1, 5, 10, 50 or 100 ng/ml ANG II. Then, the fragments were destined to morphological, viability and ultrastructural analysis. The results showed that primordial follicles had higher levels of AGTR1 and AGTR2 mRNA than secondary follicles. Granulosa/theca cells from antral follicles had higher levels of AGTR1 mRNA than their respective cumulus-oocyte complex (COCs). After 7 days of culture, ANG II (10 or 50 ng/ml) maintained the percentages of normal follicles compared with α-MEM+. Fluorescence and ultrastructural microscopy confirmed follicular integrity in ANG II (10 ng/ml). In conclusion, a high expression of AGTR1 and AGTR2 is observed in primordial follicles. Granulosa/theca cells from antral follicles had higher levels of AGTR1 mRNA. Finally, 10 ng/ml ANG II maintained the viability of caprine preantral follicles after in vitro culture.

  8. MO-DE-207B-03: Improved Cancer Classification Using Patient-Specific Biological Pathway Information Via Gene Expression Data

    Energy Technology Data Exchange (ETDEWEB)

    Young, M; Craft, D [Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States)


    Purpose: To develop an efficient, pathway-based classification system using network biology statistics to assist in patient-specific response predictions to radiation and drug therapies across multiple cancer types. Methods: We developed PICS (Pathway Informed Classification System), a novel two-step cancer classification algorithm. In PICS, a matrix m of mRNA expression values for a patient cohort is collapsed into a matrix p of biological pathways. The entries of p, which we term pathway scores, are obtained from either principal component analysis (PCA), normal tissue centroid (NTC), or gene expression deviation (GED). The pathway score matrix is clustered using both k-means and hierarchical clustering, and a clustering is judged by how well it groups patients into distinct survival classes. The most effective pathway scoring/clustering combination, per clustering p-value, thus generates various ‘signatures’ for conventional and functional cancer classification. Results: PICS successfully regularized large dimension gene data, separated normal and cancerous tissues, and clustered a large patient cohort spanning six cancer types. Furthermore, PICS clustered patient cohorts into distinct, statistically-significant survival groups. For a suboptimally-debulked ovarian cancer set, the pathway-classified Kaplan-Meier survival curve (p = .00127) showed significant improvement over that of a prior gene expression-classified study (p = .0179). For a pancreatic cancer set, the pathway-classified Kaplan-Meier survival curve (p = .00141) showed significant improvement over that of a prior gene expression-classified study (p = .04). Pathway-based classification confirmed biomarkers for the pyrimidine, WNT-signaling, glycerophosphoglycerol, beta-alanine, and panthothenic acid pathways for ovarian cancer. Despite its robust nature, PICS requires significantly less run time than current pathway scoring methods. Conclusion: This work validates the PICS method to improve

  9. Collaborative Proposal: Improving Decadal Prediction of Arctic Climate Variability and Change Using a Regional Arctic System Model (RASM)

    Energy Technology Data Exchange (ETDEWEB)

    Robertson, William [Univ. of Texas, El Paso, TX (United States)


    RASM is a multi-disciplinary project, which brings together researchers from six state universities, one military postgraduate school, and one DoE laboratory to address the core modeling objectives of the arctic research community articulated in the Arctic System Modeling report by Roberts et al. (2010b). This report advocates the construction of a regional downscaling tool to generate probabilistic decadal projections of Greenland ice sheet retreat, evolution of arctic sea ice cover, changes in land surface vegetation, and regional processes leading to arctic amplification. Unified coupled models such as RASM are ideal for this purpose because they simulate fine-scale physics, essential for the realistic representation of intra-annual variability, in addition to processes fundamental to long term climatic shifts (Hurrell et al. 2009). By using RASM with boundary conditions from a global model, we can generate many-member ensembles essential for understanding uncertainty in regional climate projections (Hawkins and Sutton 2009). This probabilistic approach is computationally prohibitive for high-resolution global models in the foreseeable future, and also for regional models interactively nested within global simulations. Yet it is fundamental for quantifying uncertainty in decadal forecasts to make them useful for decision makers (Doherty et al. 2009). For this reason, we have targeted development of ensemble generation techniques as a core project task (Task 4.5). Environmental impact assessment specialists need high-fidelity regional ensemble projections to improve the accuracy of their work (Challinor et al. 2009; Moss et al. 2010). This is especially true of the Arctic, where economic, social and national interests are rapidly reshaping the high north in step with regional climate change. During the next decade, considerable oil and gas discoveries are expected across many parts of the marine and terrestrial Arctic (Gautier et al. 2009), the economics of the

  10. Autologous implantation of BMP2-expressing dermal fibroblasts to improve bone mineral density and architecture in rabbit long bones. (United States)

    Ishihara, Akikazu; Weisbrode, Steve E; Bertone, Alicia L


    Cell-mediated gene therapy may treat bone fragility disorders. Dermal fibroblasts (DFb) may be an alternative cell source to stem cells for orthopedic gene therapy because of their rapid cell yield and excellent plasticity with bone morphogenetic protein-2 (BMP2) gene transduction. Autologous DFb or BMP2-expressing autologous DFb were administered in twelve rabbits by two delivery routes; a transcortical intra-medullar infusion into tibiae and delayed intra-osseous injection into femoral drill defects. Both delivery methods of DFb-BMP2 resulted in a successful cell engraftment, increased bone volume, bone mineral density, improved trabecular bone microarchitecture, greater bone defect filling, external callus formation, and trabecular surface area, compared to non-transduced DFb or no cells. Cell engraftment within trabecular bone and bone marrow tissue was most efficiently achieved by intra-osseous injection of DFb-BMP2. Our results suggested that BMP2-expressing autologous DFb have enhanced efficiency of engraftment in target bones resulting in a measurable biologic response by the bone of improved bone mineral density and bone microarchitecture. These results support that autologous implantation of DFb-BMP2 warrants further study on animal models of bone fragility disorders, such as osteogenesis imperfecta and osteoporosis to potentially enhance bone quality, particularly along with other gene modification of these diseases. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  11. Curcumin upregulates S100 expression and improves regeneration of the sciatic nerve following its complete amputation in mice

    Directory of Open Access Journals (Sweden)

    Guo-min Liu


    Full Text Available The repair of peripheral nerve injury after complete amputation is difficult, and even with anastomosis, the rapid recovery of nerve function remains challenging. Curcumin, extracted from plants of the genus Curcuma, has been shown to have anti-oxidant and anti-inflammatory properties and to improve sciatic nerve crush injury in rats. Here, we determined whether curcumin had neuroprotective effects following complete peripheral nerve amputation injury. BALB/c mice underwent complete sciatic nerve amputation, followed by an immediate epineurium anastomosis. Mice were intragastrically administered curcumin at doses of 40 (high, 20 (moderate, and 10 mg/kg/d (low for 1 week. We found that myelin in the mice of the high- and moderate-dose curcumin groups appeared with regular shape, uniform thickness, clear boundary, and little hyperplasia surrounding the myelin. High and moderate doses of curcumin markedly improved both action potential amplitude of the sciatic nerves and the conduction velocity of the corresponding motor neurons, and upregulated mRNA and protein expression of S100, a marker for Schwann cell proliferation, in L4–6 spinal cord segments. These results suggest that curcumin is effective in promoting the repair of complete sciatic nerve amputation injury and that the underlying mechanism may be associated with upregulation of S100 expression.

  12. Orphan nuclear receptor TR3/Nur77 improves wound healing by upregulating the expression of integrin β4. (United States)

    Niu, Gengming; Ye, Taiyang; Qin, Liuliang; Bourbon, Pierre M; Chang, Cheng; Zhao, Shengqiang; Li, Yan; Zhou, Lei; Cui, Pengfei; Rabinovitz, Issac; Mercurio, Arthur M; Zhao, Dezheng; Zeng, Huiyan


    Tissue repair/wound healing, in which angiogenesis plays an important role, is a critical step in many diseases including chronic wound, myocardial infarction, stroke, cancer, and inflammation. Recently, we were the first to report that orphan nuclear receptor TR3/Nur77 is a critical mediator of angiogenesis and its associated microvessel permeability. Tumor growth and angiogenesis induced by VEGF-A, histamine, and serotonin are almost completely inhibited in Nur77 knockout mice. However, it is not known whether TR3/Nur77 plays any roles in wound healing. In these studies, skin wound-healing assay was performed in 3 types of genetically modified mice having various Nur77 activities. We found that ectopic induction of Nur77 in endothelial cells of mice is sufficient to improve skin wound healing. Although skin wound healing in Nur77 knockout mice is comparable to the wild-type control mice, the process is significantly delayed in the EC-Nur77-DN mice, in which a dominant negative Nur77 mutant is inducibly and specifically expressed in mouse endothelial cells. By a loss-of-function assay, we elucidate a novel feed-forward signaling pathway, integrin β4 → PI3K → Akt → FAK, by which TR3 mediates HUVEC migration. Furthermore, TR3/Nur77 regulates the expression of integrin β4 by targeting its promoter activity. In conclusion, expression of TR3/Nur77 improves wound healing by targeting integrin β4. TR3/Nur77 is a potential candidate for proangiogenic therapy. The results further suggest that TR3/Nur77 is required for pathologic angiogenesis but not for developmental/physiologic angiogenesis and that Nur77 and its family members play a redundant role in normal skin wound healing. © FASEB.

  13. Melatonin improves placental efficiency and birth weight and increases the placental expression of antioxidant enzymes in undernourished pregnancy. (United States)

    Richter, Hans G; Hansell, Jeremy A; Raut, Shruti; Giussani, Dino A


    Melatonin participates in circadian, seasonal and reproductive physiology. Melatonin also acts as a potent endogenous antioxidant by scavenging free radicals and upregulating antioxidant pathways. The placenta expresses melatonin receptors and melatonin protects against oxidative damage induced in rat placenta by ischemia-reperfusion. One of the most common complications in pregnancy is a reduction in fetal nutrient delivery, which is known to promote oxidative stress. However, whether melatonin protects placental function and fetal development in undernourished pregnancy is unknown. Here, we investigated the effects of maternal treatment with melatonin on placental efficiency, fetal growth, birth weight and protein expression of placental oxidative stress markers in undernourished pregnancy. On day 15 of pregnancy, rats were divided into control and undernourished pregnancy (35% reduction in food intake), with and without melatonin treatment (5 microg/mL drinking water). On day 20 of gestation, fetal biometry was carried out, the placenta was weighed and subsequently analyzed by Western blot for xanthine oxidase, heat shock protein (HSP) 27 and 70, catalase, manganese superoxide dismutase (Mn-SOD) and glutathione peroxidase 1 (GPx-1). A separate cohort was allowed to deliver to assess effects on birth weight. Maternal undernutrition led to a fall in placental efficiency, disproportionate intrauterine growth retardation and a reduction in birth weight. Maternal treatment with melatonin in undernourished pregnancy improved placental efficiency and restored birth weight, and it increased the expression of placental Mn-SOD and catalase. The data show that in pregnancy complicated by undernutrition, melatonin may improve placental efficiency and birth weight by upregulating placental antioxidant enzymes.

  14. Central coast designs: The Eightball Express. Taking off with convention, cruising with improvements and landing with absolute success (United States)

    Davis, Ryan Edwin; Dawson, Anne Marie; Fecht, Paul Hans; Fry, Roman Zyabash; Vantriet, Robert; Macabantad, Dominique Dujale; Miller, Robert Glenn; Perez, Gustavo, Jr.; Weise, Timothy Michael


    The airline industry is very competitive, resulting in most U.S. and many international airlines being unprofitable. Because of this competition the airlines have been engaging in fare wars (which reduce revenue generated by transporting passengers) while inflation has increased. This situation of course is not developing revenue for the airlines. To revive the airlines to profitability, the difference between revenue received and airline operational cost must be improved. To solve these extreme conditions, the Eightball Express was designed with the main philosophy of developing an aircraft with a low direct operating cost and acquisition cost. Central Coast Designs' (CCD) aircraft utilizes primarily aluminum in the structure to minimize manufacturing cost, supercritical airfoil sections to minimize drag, and fuel efficient engines to minimize fuel burn. Furthermore, the aircraft was designed using Total Quality Management and Integrated Product Development to minimize development and manufacturing costs. Using these primary cost reduction techniques, the Eightball Express was designed to meet the Lockheed/AIAA Request for Proposal (RFP) requirements of a low cost, 153 passenger, 3000 nm. range transport. The Eightball Express is able to takeoff on less than a 7000 ft. runway, cruise at Mach 0.82 at an altitude of 36,000 ft. for a range of 3,000 nm., and lands on a 5,000 ft. runway. lt is able to perform this mission at a direct operating cost of 3.51 cents/available seat mile in 1992 dollars while the acquisition cost is only $28 million in 1992 dollars. By utilizing and improving on proven technologies, CCD has produced an efficient low cost commercial transport for the future.

  15. Nanopolymers improve delivery of exon skipping oligonucleotides and concomitant dystrophin expression in skeletal muscle of mdx mice

    Directory of Open Access Journals (Sweden)

    Sirsi Shashank R


    Full Text Available Abstract Background Exon skipping oligonucleotides (ESOs of 2'O-Methyl (2'OMe and morpholino chemistry have been shown to restore dystrophin expression in muscle fibers from the mdx mouse, and are currently being tested in phase I clinical trials for Duchenne Muscular Dystrophy (DMD. However, ESOs remain limited in their effectiveness because of an inadequate delivery profile. Synthetic cationic copolymers of poly(ethylene imine (PEI and poly(ethylene glycol (PEG are regarded as effective agents for enhanced delivery of nucleic acids in various applications. Results We examined whether PEG-PEI copolymers can facilitate ESO-mediated dystrophin expression after intramuscular injections into tibialis anterior (TA muscles of mdx mice. We utilized a set of PEG-PEI copolymers containing 2 kDa PEI and either 550 Da or 5 kDa PEG, both of which bind 2'OMe ESOs with high affinity and form stable nanoparticulates with a relatively low surface charge. Three weekly intramuscular injections of 5 μg of ESO complexed with PEI2K-PEG550 copolymers resulted in about 500 dystrophin-positive fibers and about 12% of normal levels of dystrophin expression at 3 weeks after the initial injection, which is significantly greater than for injections of ESO alone, which are known to be almost completely ineffective. In an effort to enhance biocompatibility and cellular uptake, the PEI2K-PEG550 and PEI2K-PEG5K copolymers were functionalized by covalent conjugation with nanogold (NG or adsorbtion of colloidal gold (CG, respectively. Surprisingly, using the same injection and dosing regimen, we found no significant difference in dystrophin expression by Western blot between the NG-PEI2K-PEG550, CG-PEI2K-PEG5K, and non-functionalized PEI2K-PEG550 copolymers. Dose-response experiments using the CG-PEI2K-PEG5K copolymer with total ESO ranging from 3–60 μg yielded a maximum of about 15% dystrophin expression. Further improvements in dystrophin expression up to 20% of normal

  16. Phosphodiesterase-4 inhibition alters gene expression and improves isoniazid-mediated clearance of Mycobacterium tuberculosis in rabbit lungs.

    Directory of Open Access Journals (Sweden)

    Selvakumar Subbian


    Full Text Available Tuberculosis (TB treatment is hampered by the long duration of antibiotic therapy required to achieve cure. This indolent response has been partly attributed to the ability of subpopulations of less metabolically active Mycobacterium tuberculosis (Mtb to withstand killing by current anti-TB drugs. We have used immune modulation with a phosphodiesterase-4 (PDE4 inhibitor, CC-3052, that reduces tumor necrosis factor alpha (TNF-α production by increasing intracellular cAMP in macrophages, to examine the crosstalk between host and pathogen in rabbits with pulmonary TB during treatment with isoniazid (INH. Based on DNA microarray, changes in host gene expression during CC-3052 treatment of Mtb infected rabbits support a link between PDE4 inhibition and specific down-regulation of the innate immune response. The overall pattern of host gene expression in the lungs of infected rabbits treated with CC-3052, compared to untreated rabbits, was similar to that described in vitro in resting Mtb infected macrophages, suggesting suboptimal macrophage activation. These alterations in host immunity were associated with corresponding down-regulation of a number of Mtb genes that have been associated with a metabolic shift towards dormancy. Moreover, treatment with CC-3052 and INH resulted in reduced expression of those genes associated with the bacterial response to INH. Importantly, CC-3052 treatment of infected rabbits was associated with reduced ability of Mtb to withstand INH killing, shown by improved bacillary clearance, from the lungs of co-treated animals compared to rabbits treated with INH alone. The results of our study suggest that changes in Mtb gene expression, in response to changes in the host immune response, can alter the responsiveness of the bacteria to antimicrobial agents. These findings provide a basis for exploring the potential use of adjunctive immune modulation with PDE4 inhibitors to enhance the efficacy of existing anti-TB treatment.

  17. Estradiol improves cardiac and hepatic function after trauma-hemorrhage: role of enhanced heat shock protein expression. (United States)

    Szalay, László; Shimizu, Tomoharu; Suzuki, Takao; Yu, Huang-Ping; Choudhry, Mashkoor A; Schwacha, Martin G; Rue, Loring W; Bland, Kirby I; Chaudry, Irshad H


    Although studies indicate that 17beta-estradiol administration after trauma-hemorrhage (T-H) improves cardiac and hepatic functions, the underlying mechanisms remain unclear. Because the induction of heat shock proteins (HSPs) can protect cardiac and hepatic functions, we hypothesized that these proteins contribute to the salutary effects of estradiol after T-H. To test this hypothesis, male Sprague-Dawley rats ( approximately 300 g) underwent laparotomy and hemorrhagic shock (35-40 mmHg for approximately 90 min) followed by resuscitation with four times the shed blood volume in the form of Ringer lactate. 17beta-estradiol (1 mg/kg body wt) was administered at the end of the resuscitation. Five hours after T-H and resuscitation there was a significant decrease in cardiac output, positive and negative maximal rate of left ventricular pressure. Liver function as determined by bile production and indocyanine green clearance was also compromised after T-H and resuscitation. This was accompanied by an increase in plasma alanine aminotransferase (ALT) levels and liver perfusate lactic dehydrogenase levels. Furthermore, circulating levels of TNF-alpha, IL-6, and IL-10 were also increased. In addition to decreased cardiac and hepatic function, there was an increase in cardiac HSP32 expression and a reduction in HSP60 expression after T-H. In the liver, HSP32 and HSP70 were increased after T-H. There was no change in heart HSP70 and liver HSP60 after T-H and resuscitation. Estradiol administration at the end of T-H and resuscitation increased heart/liver HSPs expression, ameliorated the impairment of heart/liver functions, and significantly prevented the increase in plasma levels of ALT, TNF-alpha, and IL-6. The ability of estradiol to induce HSPs expression in the heart and the liver suggests that HSPs, in part, mediate the salutary effects of 17beta-estradiol on organ functions after T-H.

  18. Variable geometry gas turbines for improving the part-load performance of marine combined cycles - Gas turbine performance

    DEFF Research Database (Denmark)

    Haglind, Fredrik


    The part-load performance of gas and steam turbine combined cycles intended for naval use is of great importance, and it is influenced by the gas turbine configuration and load control strategy. This paper is aimed at quantifying the effects of variable geometry on the gas turbine part...... of various components within gas turbines. Two different gas turbine configurations are studied, a two-shaft aero-derivative configuration and a single-shaft industrial configuration. When both gas turbine configurations are running in part-load using fuel flow control, the results indicate better part......-load performance for the two-shaft gas turbine. Reducing the load this way is accompanied by a much larger decrease in exhaust gas temperature for the single-shaft gas turbine than for the two-shaft configuration. As used here, the results suggest that variable geometry generally deteriorates the gas turbine part...

  19. Fumarate Production by Torulopsis glabrata: Engineering Heterologous Fumarase Expression and Improving Acid Tolerance.

    Directory of Open Access Journals (Sweden)

    Xiulai Chen

    Full Text Available Fumarate is a well-known biomass building block compound. However, the poor catalytic efficiency of fumarase is one of the major factors preventing its widespread production. To address this issue, we selected residues 159HPND162 of fumarase from Rhizopus oryzae as targets for site-directed mutagenesis based on molecular docking analysis. Twelve mutants were generated and characterized in detail. Kinetic studies showed that the Km values of the P160A, P160T, P160H, N161E, and D162W mutants were decreased, whereas Km values of H159Y, H159V, H159S, N161R, N161F, D162K, and D162M mutants were increased. In addition, all mutants displayed decreased catalytic efficiency except for the P160A mutant, whose kcat/Km was increased by 33.2%. Moreover, by overexpressing the P160A mutant, the engineered strain T.G-PMS-P160A was able to produce 5.2 g/L fumarate. To further enhance fumarate production, the acid tolerance of T.G-PMS-P160A was improved by deleting ade12, a component of the purine nucleotide cycle, and the resulting strain T.G(△ade12-PMS-P160A produced 9.2 g/L fumarate. The strategy generated in this study opens up new avenues for pathway optimization and efficient production of natural products.

  20. Mirror-drawing skill in children with specific language impairment: Improving generalization by incorporating variability into the practice session. (United States)

    Desmottes, Lise; Maillart, Christelle; Meulemans, Thierry


    This study aimed to investigate the procedural deficit hypothesis (PDH) in children with specific language impairment (SLI) by using a mirror-drawing task, a sensorimotor adaptation paradigm that does not involve sequence learning and has never before been used in SLI. A total of 30 school-aged children with SLI matched to 30 typically developing (TD) control children had to trace several figures seen only in mirror-reversed view in two practice sessions separated by a one-week interval. Two practice conditions were compared: a constant condition in which children had to trace the same figure throughout the learning trials, and a variable one in which they had to trace different figures in each trial. The results revealed a similar learning pattern between SLI and TD children in both practice conditions, suggesting that initial learning for a non-sequential procedural task is preserved in SLI. However, the children with SLI generalized the mirror-drawing skill in the same way as the TD children only if there was variability in the way the material was trained (variable practice). No significant schedule effects were observed in the control group.

  1. Efficient heterologous expression and secretion in Aspergillus oryzae of a llama variable heavy-chain antibody fragment V(HH) against EGFR. (United States)

    Okazaki, Fumiyoshi; Aoki, Jun-ichi; Tabuchi, Soichiro; Tanaka, Tsutomu; Ogino, Chiaki; Kondo, Akihiko


    We have constructed a filamentous fungus Aspergillus oryzae that secretes a llama variable heavy-chain antibody fragment (V(HH)) that binds specifically to epidermal growth factor receptor (EGFR) in a culture medium. A major improvement in yield was achieved by fusing the V(HH) with a Taka-amylase A signal sequence (sTAA) and a segment of 28 amino acids from the N-terminal region of Rhizopus oryzae lipase (N28). The yields of secreted, immunologically active anti-EGFR V(HH) reached 73.8 mg/1 in a Sakaguchi flask. The V(HH) fragments were released from the sTAA or N28 proteins by an indigenous A. oryzae protease during cultivation. The purified recombinant V(HH) fragment was specifically recognized and could bind to the EGFR with a high affinity.

  2. Efforts to find a better measuring system for climatic gas discharges. CICERO in a new EU project which aims to improve GWP and radiation contribution expressions

    International Nuclear Information System (INIS)

    Fuglestvedt, Jan


    The article describes the problems with the present system used by the Kyoto protocol and the project efforts for improving the formulas and models of expressing climatic gas discharge measurements through a common measuring unit

  3. Integrated cell and process engineering for improved transient production of a "difficult-to-express" fusion protein by CHO cells. (United States)

    Johari, Yusuf B; Estes, Scott D; Alves, Christina S; Sinacore, Marty S; James, David C


    Based on an optimized electroporation protocol, we designed a rapid, milliliter-scale diagnostic transient production assay to identify limitations in the ability of Chinese hamster ovary (CHO) cells to produce a model "difficult-to-express" homodimeric Fc-fusion protein, Sp35Fc, that exhibited very low volumetric titer and intracellular formation of disulfide-bonded oligomeric aggregates post-transfection. As expression of Sp35Fc induced an unfolded protein response in transfected host cells, we utilized the transient assay to compare, in parallel, multiple functionally diverse strategies to engineer intracellular processing of Sp35Fc in order to increase production and reduce aggregation as two discrete design objectives. Specifically, we compared the effect of (i) co-expression of ER-resident molecular chaperones (BiP, PDI, CypB) or active forms of UPR transactivators (ATF6c, XBP1s) at varying recombinant gene load, (ii) addition of small molecules known to act as chemical chaperones (PBA, DMSO, glycerol, betaine, TMAO) or modulate UPR signaling (PERK inhibitor GSK2606414) at varying concentration, (iii) a reduction in culture temperature to 32°C. Using this information, we designed a biphasic, Sp35Fc-specific transient manufacturing process mediated by lipofection that utilized CypB co-expression at an optimal Sp35Fc:CypB gene ratio of 5:1 to initially maximize transfected cell proliferation, followed by addition of a combination of PBA (0.5 mM) and glycerol (1% v/v) at the onset of stationary phase to maximize cell specific production and eliminate Sp35Fc aggregation. Using this optimal, engineered process transient Sp35Fc production was significantly increased sixfold over a 12 day production process with no evidence of disulfide-bonded aggregates. Finally, transient production in clonally derived sub-populations (derived from parental CHO host) screened for a heritably improved capability to produce Sp35Fc was also significantly improved by the optimized

  4. Development of sensor-less control strategies for grid connected PMSG based variable speed wind energy conversion system with improved power quality features

    Energy Technology Data Exchange (ETDEWEB)

    Chandra, A. [Quebec Univ., Montreal, PQ (Canada). Dept. of Electrical Engineering


    Interest in renewable energy sources has grown in recent years in response to concerns of increasing pollution levels and depleting fossil fuels. Among renewable energy sources, wind energy generation is the fastest growing technology and one of the most cost-effective and environmental friendly means to generate electricity from renewable sources. Modern wind turbines are ready to be deployed in large scale as a result of recent developments in wind power technology. Variable speed permanent magnet synchronous generators (PMSG) based wind energy conversion systems (WECS) are becoming more popular. The use of a permanent magnet reduces size, cost and weight of overall WECS. In addition, the absence of field winding and its excitation system avoids heat dissipation in the rotor winding, thereby improving overall efficiency of the WECS. This type of configuration is more appropriate for remote locations, particularly for off-shore wind application, where the geared doubly fed induction generator usually requires regular maintenance due to tearing-wearing in brushes, windings and gear box. This presentation discussed the development of sensor-less control strategies for grid connected PMSG based variable speed wind energy conversion system with improved power quality features. A novel adaptive network-based fuzzy inference system was used to estimate the speed and position of variable speed PMSG under fluctuating wind conditions. A novel control strategy was developed for the grid interfacing inverter incorporating power quality improvement features at point of common coupling.

  5. Climate SPHINX: High-resolution present-day and future climate simulations with an improved representation of small-scale variability (United States)

    Davini, Paolo; von Hardenberg, Jost; Corti, Susanna; Subramanian, Aneesh; Weisheimer, Antje; Christensen, Hannah; Juricke, Stephan; Palmer, Tim


    The PRACE Climate SPHINX project investigates the sensitivity of climate simulations to model resolution and stochastic parameterization. The EC-Earth Earth-System Model is used to explore the impact of stochastic physics in 30-years climate integrations as a function of model resolution (from 80km up to 16km for the atmosphere). The experiments include more than 70 simulations in both a historical scenario (1979-2008) and a climate change projection (2039-2068), using RCP8.5 CMIP5 forcing. A total amount of 20 million core hours will be used at end of the project (March 2016) and about 150 TBytes of post-processed data will be available to the climate community. Preliminary results show a clear improvement in the representation of climate variability over the Euro-Atlantic following resolution increase. More specifically, the well-known atmospheric blocking negative bias over Europe is definitely resolved. High resolution runs also show improved fidelity in representation of tropical variability - such as the MJO and its propagation - over the low resolution simulations. It is shown that including stochastic parameterization in the low resolution runs help to improve some of the aspects of the MJO propagation further. These findings show the importance of representing the impact of small scale processes on the large scale climate variability either explicitly (with high resolution simulations) or stochastically (in low resolution simulations).

  6. Locomotor training with body weight support in SCI: EMG improvement is more optimally expressed at a low testing speed. (United States)

    Meyns, P; Van de Crommert, H W A A; Rijken, H; van Kuppevelt, D H J M; Duysens, J


    Case series. To determine the optimal testing speed at which the recovery of the EMG (electromyographic) activity should be assessed during and after body weight supported (BWS) locomotor training. Tertiary hospital, Sint Maartenskliniek, Nijmegen, The Netherlands. Four participants with incomplete chronic SCI were included for BWS locomotor training; one AIS-C and three AIS-D (according to the ASIA (American Spinal Injury Association) Impairment Scale or AIS). All were at least 5 years after injury. The SCI participants were trained three times a week for a period of 6 weeks. They improved their locomotor function in terms of higher walking speed, less BWS and less assistance needed. To investigate which treadmill speed for EMG assessment reflects the functional improvement most adequately, all participants were assessed weekly using the same two speeds (0.5 and 1.5 km h(-1), referred to as low and high speed, respectively) for 6 weeks. The change in root mean square EMG (RMS EMG) was assessed in four leg muscles; biceps femoris, rectus femoris, gastrocnemius medialis and tibialis anterior. The changes in RMS EMG occurred at similar phases of the step cycle for both walking conditions, but these changes were larger when the treadmill was set at a low speed (0.5 km h(-1)). Improvement in gait is feasible with BWS treadmill training even long after injury. The EMG changes after treadmill training are more optimally expressed using a low rather than a high testing treadmill speed.

  7. Engineering Aspergillus oryzae A-4 through the chromosomal insertion of foreign cellulase expression cassette to improve conversion of cellulosic biomass into lipids.

    Directory of Open Access Journals (Sweden)

    Hui Lin

    Full Text Available A genetic modification scheme was designed for Aspergillus oryzae A-4, a natural cellulosic lipids producer, to enhance its lipid production from biomass by putting the spotlight on improving cellulase secretion. Four cellulase genes were separately expressed in A-4 under the control of hlyA promoter, with the help of the successful development of a chromosomal genetic manipulation system. Comparison of cellulase activities of PCR-positive transformants showed that these transformants integrated with celA gene and with celC gene had significantly (p<0.05 higher average FPAase activities than those strains integrated with celB gene and with celD gene. Through the assessment of cellulosic lipids accumulating abilities, celA transformant A2-2 and celC transformant D1-B1 were isolated as promising candidates, which could yield 101%-133% and 35.22%-59.57% higher amount of lipids than the reference strain A-4 (WT under submerged (SmF conditions and solid-state (SSF conditions, respectively. Variability in metabolism associated to the introduction of cellulase gene in A2-2 and D1-B1 was subsequently investigated. It was noted that cellulase expression repressed biomass formation but enhanced lipid accumulation; whereas the inhibitory effect on cell growth would be shielded during cellulosic lipids production owing to the essential role of cellulase in substrate utilization. Different metabolic profiles also existed between A2-2 and D1-B1, which could be attributed to not only different transgene but also biological impacts of different integration. Overall, both simultaneous saccharification and lipid accumulation were enhanced in A2-2 and D1-B1, resulting in efficient conversion of cellulose into lipids. A regulation of cellulase secretion in natural cellulosic lipids producers could be a possible strategy to enhance its lipid production from lignocellulosic biomass.

  8. The Role of the Process and Design Variables in Improving the Performance of Heat Exchanger Tube Expansion

    Directory of Open Access Journals (Sweden)

    Changwan Han


    Full Text Available In the expansion process of a fin-tube heat exchanger, the process variables and shape of the expansion ball affect the deformation of the tube’s inner grooves, the adhesion, and the expansion force. These factors influence the efficiency of heat transfer and the lifetime of the expansion equipment. Therefore, this study analyzed the influential variables of the tube expansion process as well as the expansion ball design through experiments and simulations. A new method was proposed to determine the severity of adhesion in the tube’s inner grooves using the expansion force rate. Expansion experiments with Al tubes show that the expansion force decreases when using a lubricant with high viscosity and when the lubricant remains on the expansion ball for a longer duration. Finite element analysis was also performed to examine the expansion of Cu tubes, which showed that the expansion force was higher when using expansion ball shapes that have higher contact area between the ball and tube surface. The radius of curvature of the expansion ball also influenced the expansion force. However, increasing the ratio of the radial force to the expansion force increased the deformation of the tube’s inner grooves.

  9. Eugenosedin-A improves glucose metabolism and inhibits MAPKs expression in streptozotocin/nicotinamide-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Kuo-Ping Shen


    Full Text Available This study examined the effects of eugenosedin-A (Eu-A in a streptozotocin (STZ/nicotinamide-induced rat model of type II diabetes mellitus (T2DM. Six-week-old Sprague–Dawley rats were randomly divided into three groups: (1 RD group, normal rats fed a regular diet (RD, (2 DM group, T2DM rats fed a high-fat diet, and (3 Eu-A group, T2DM rats fed a high fat diet plus oral Eu-A (5 mg/kg/day. After 30 days, the DM group had higher body weight, higher blood glucose and lower insulin levels than the RD group. The DM group also had increased protein expression of glycogen synthase kinase (GSK in liver and skeletal muscle and decreased protein expression of insulin receptor (IR, insulin receptor substrate-1 (IRS-1, IRS-2, AMP-activated protein kinase (AMPK, glucose transporter-4 (GLUT-4, glucokinase (GCK, and peroxisome proliferator-activated receptor γ (PPAR-γ. STZ/nicotinamide-induced T2DM increased the expression of mitogen-activated protein kinases (MAPKs: p38, ERK, JNK and inflammatory p65 protein. In the Eu-A treated T2DM rats, however, blood glucose was attenuated and the insulin concentration stimulated. Changes in IR, IRS-1 and IRS-2 proteins as well as AMPK, GLUT-4, GCK, GSK, PPAR-γ, MAPKs, and inflammatory p65 proteins were ameliorated. These results suggested that Eu-A alleviates STZ/nicotinamide-induced hyperglycemia by improving insulin levels and glucose metabolism, and inhibiting the MAPKs- and p65-mediated inflammatory pathway.

  10. Ectopic Expression of Pumpkin NAC Transcription Factor CmNAC1 Improves Multiple Abiotic Stress Tolerance in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Haishun Cao


    Full Text Available Drought, cold and salinity are the major environmental stresses that limit agricultural productivity. NAC transcription factors regulate the stress response in plants. Pumpkin (Cucurbita moschata is an important cucurbit vegetable crop and it has strong resistance to abiotic stress; however, the biological functions of stress-related NAC genes in this crop are largely unknown. This study reports the function of CmNAC1, a stress-responsive pumpkin NAC domain protein. The CmNAC1-GFP fusion protein was transiently expressed in tobacco leaves for subcellular localization analysis, and we found that CmNAC1 is localized in the nucleus. Transactivation assay in yeast cells revealed that CmNAC1 functions as a transcription activator, and its transactivation domain is located in the C-terminus. CmNAC1 was ubiquitously expressed in different organs, and its transcript was induced by salinity, cold, dehydration, H2O2, and abscisic acid (ABA treatment. Furthermore, the ectopic expression (EE of CmNAC1 in Arabidopsis led to ABA hypersensitivity and enhanced tolerance to salinity, drought and cold stress. In addition, five ABA-responsive elements were enriched in CmNAC1 promoter. The CmNAC1-EE plants exhibited different root architecture, leaf morphology, and significantly high concentration of ABA compared with WT Arabidopsis under normal conditions. Our results indicated that CmNAC1 is a critical factor in ABA signaling pathways and it can be utilized in transgenic breeding to improve the abiotic stress tolerance of crops.

  11. Over-expression of Follistatin-like 3 attenuates fat accumulation and improves insulin sensitivity in mice

    DEFF Research Database (Denmark)

    Brandt, Claus; Hansen, Rasmus Hvass; Hansen, Jakob Bondo


    -fat feeding. Body weight, food intake, fat accumulation by MR scanning, and glucose, insulin and glucagon tolerance were evaluated, as was the response in body weight and metabolic parameters to 24h fasting. Effects of fstl3 on pancreatic insulin and glucagon content, and pancreatic islet morphology were......OBJECTIVE: Follistatin-like 3 (fstl3), a natural inhibitor of members of the TGF-β family, increases during resistance training in human plasma. Fstl3 primarily binds myostatin and activin A, and thereby inhibits their functions. We hypothesize that blocking myostatin and activin A signalling....../glucagon ratio. Accordingly, fstl3 transfection improved counter-regulation to 24h fasting. CONCLUSION: Fstl3 over-expression regulates insulin and glucagon sensitivities through increased muscular insulin action, as well as increased hepatic glucagon sensitivity and pancreatic glucagon content....

  12. Improved exogenous DNA uptake in bovine spermatozoa and gene expression in embryos using membrane destabilizing agents in ICSI-SMGT. (United States)

    Sánchez-Villalba, Esther; Arias, María Elena; Zambrano, Fabiola; Loren, Pía; Felmer, Ricardo


    Sperm-mediated gene transfer (SMGT) is a simple, fast, and economical biotechnological tool for producing transgenic animals. However, transgene expression with this technique in bovine embryos is still inefficient due to low uptake and binding of exogenous DNA in spermatozoa. The present study evaluated the effects of sperm membrane destabilization on the binding capacity, location and quantity of bound exogenous DNA in cryopreserved bovine spermatozoa using Triton X-100 (TX-100), lysolecithin (LL) and sodium hydroxide (NaOH). Effects of these treatments were also evaluated by intracytoplasmic sperm injection (ICSI)-SMGT. Results showed that all treatments bound exogenous DNA to spermatozoa including the control. Spermatozoa treated with different membrane destabilizing agents bound the exogenous DNA throughout the head and tail of spermatozoa, compared with the control, in which binding occurred mainly in the post-acrosomal region and tail. The amount of exogenous DNA bound to spermatozoa was much higher for the different sperm treatments than the control (P Exogenous gene expression in embryos was also improved by these treatments. These results demonstrated that sperm membrane destabilization could be a novel strategy in bovine SMGT protocols for the generation of transgenic embryos by ICSI.

  13. Improved gene expression in resting macrophages using an oligopeptide derived from Vpr of human immunodeficiency virus type-1

    International Nuclear Information System (INIS)

    Mizoguchi, Izuru; Ooe, Yoshihiro; Hoshino, Shigeki; Shimura, Mari; Kasahara, Tadashi; Kano, Shigeyuki; Ohta, Toshiko; Takaku, Fumimaro; Nakayama, Yasuhide; Ishizaka, Yukihito


    Vpr, an accessory gene product of human immunodeficiency virus type-1, is thought to transport a viral DNA from the cytoplasm to the nucleus in resting macrophages. Previously, we reported that a peptide encompassing amino acids 52-78 of Vpr (C45D18) promotes the nuclear trafficking of recombinant proteins that are conjugated with C45D18. Here, we present evidence that C45D18, when conjugated with a six-branched cationic polymer of poly(N,N-dimethylaminopropylacrylamide)-block-oligo(4-aminostyrene) (SV: star vector), facilitates gene expression in resting macrophages. Although there was no difference between SV alone and C45D18-SV with respect to gene transduction into growing cells, C45D18-SV resulted in more than 40-fold greater expression of the exogenous gene upon transduction into chemically differentiated macrophages and human quiescent monocyte-derived macrophages. The data suggest that C45D18 contributes to improving the ability of a non-viral vector to transduce macrophages with exogenous genes and we discuss its further application

  14. Improved Variable Selection Algorithm Using a LASSO-Type Penalty, with an Application to Assessing Hepatitis B Infection Relevant Factors in Community Residents (United States)

    Guo, Pi; Zeng, Fangfang; Hu, Xiaomin; Zhang, Dingmei; Zhu, Shuming; Deng, Yu; Hao, Yuantao


    Objectives In epidemiological studies, it is important to identify independent associations between collective exposures and a health outcome. The current stepwise selection technique ignores stochastic errors and suffers from a lack of stability. The alternative LASSO-penalized regression model can be applied to detect significant predictors from a pool of candidate variables. However, this technique is prone to false positives and tends to create excessive biases. It remains challenging to develop robust variable selection methods and enhance predictability. Material and methods Two improved algorithms denoted the two-stage hybrid and bootstrap ranking procedures, both using a LASSO-type penalty, were developed for epidemiological association analysis. The performance of the proposed procedures and other methods including conventional LASSO, Bolasso, stepwise and stability selection models were evaluated using intensive simulation. In addition, methods were compared by using an empirical analysis based on large-scale survey data of hepatitis B infection-relevant factors among Guangdong residents. Results The proposed procedures produced comparable or less biased selection results when compared to conventional variable selection models. In total, the two newly proposed procedures were stable with respect to various scenarios of simulation, demonstrating a higher power and a lower false positive rate during variable selection than the compared methods. In empirical analysis, the proposed procedures yielding a sparse set of hepatitis B infection-relevant factors gave the best predictive performance and showed that the procedures were able to select a more stringent set of factors. The individual history of hepatitis B vaccination, family and individual history of hepatitis B infection were associated with hepatitis B infection in the studied residents according to the proposed procedures. Conclusions The newly proposed procedures improve the identification of

  15. Exercise improves cognitive responses to psychological stress through enhancement of epigenetic mechanisms and gene expression in the dentate gyrus.

    Directory of Open Access Journals (Sweden)

    Andrew Collins

    Full Text Available We have shown previously that exercise benefits stress resistance and stress coping capabilities. Furthermore, we reported recently that epigenetic changes related to gene transcription are involved in memory formation of stressful events. In view of the enhanced coping capabilities in exercised subjects we investigated epigenetic, gene expression and behavioral changes in 4-weeks voluntarily exercised rats.Exercised and control rats coped differently when exposed to a novel environment. Whereas the control rats explored the new cage for the complete 30-min period, exercised animals only did so during the first 15 min after which they returned to sleeping or resting behavior. Both groups of animals showed similar behavioral responses in the initial forced swim session. When re-tested 24 h later however the exercised rats showed significantly more immobility behavior and less struggling and swimming. If rats were killed at 2 h after novelty or the initial swim test, i.e. at the peak of histone H3 phospho-acetylation and c-Fos induction, then the exercised rats showed a significantly higher number of dentate granule neurons expressing the histone modifications and immediate-early gene induction.Thus, irrespective of the behavioral response in the novel cage or initial forced swim session, the impact of the event at the dentate gyrus level was greater in exercised rats than in control animals. Furthermore, in view of our concept that the neuronal response in the dentate gyrus after forced swimming is involved in memory formation of the stressful event, the observations in exercised rats of enhanced neuronal responses as well as higher immobility responses in the re-test are consistent with the reportedly improved cognitive performance in these animals. Thus, improved stress coping in exercised subjects seems to involve enhanced cognitive capabilities possibly resulting from distinct epigenetic mechanisms in dentate gyrus neurons.

  16. Improving the phenotypic expression of rice genotypes: Rethinking “intensification” for production systems and selection practices for rice breeding

    Directory of Open Access Journals (Sweden)

    Norman Uphoff


    Full Text Available Intensification in rice crop production is generally understood as requiring increased use of material inputs: water, inorganic fertilizers, and agrochemicals. However, this is not the only kind of intensification available. More productive crop phenotypes, with traits such as more resistance to biotic and abiotic stresses and shorter crop cycles, are possible through modifications in the management of rice plants, soil, water, and nutrients, reducing rather than increasing material inputs. Greater factor productivity can be achieved through the application of new knowledge and more skill, and (initially more labor, as seen from the System of Rice Intensification (SRI, whose practices are used in various combinations by as many as 10 million farmers on about 4 million hectares in over 50 countries. The highest yields achieved with these management methods have come from hybrids and improved rice varieties, confirming the importance of making genetic improvements. However, unimproved varieties are also responsive to these changes, which induce better growth and functioning of rice root systems and more abundance, diversity, and activity of beneficial soil organisms. Some of these organisms as symbiotic endophytes can affect and enhance the expression of rice plants' genetic potential as well as their phenotypic resilience to multiple stresses, including those of climate change. SRI experience and data suggest that decades of plant breeding have been selecting for the best crop genetic endowments under suboptimal growing conditions, with crowding of plants that impedes their photosynthesis and growth, flooding of rice paddies that causes roots to degenerate and forgoes benefits derived from aerobic soil organisms, and overuse of agrochemicals that adversely affect these organisms as well as soil and human health. This review paper reports evidence from research in India and Indonesia that changes in crop and water management can improve the


    Directory of Open Access Journals (Sweden)

    Lukman Hakim


    Full Text Available Information on the variability and correlation between agronomic characters of mungbean accessions with their yield are important for supporting breeding program of the plant. A total of 350 mungbean accessions were evaluated at Muara Experimental Farm, Indonesian Center for Food Crops Research and Development, Bogor, during the dry season of 2005. The experiment was conducted in a completely randomized block design with three replications. Each accession was planted in two rows of 5 m long. Plant spacing was 40 cm x 20 cm, two plants per hill. Correlation and path coefficient analyses were used to quantifythe magnitude of the relationship between yield components and grain yield. The variability among the accessions was significant for most of the characters studied, especially for days to maturity, plant height, pods per plant, and seed size. Among the yield components, the number of pods per plant and plant height positively correlated with the grain yield, but theseed size negatively correlated with grain yield. The direct effects of the number of pods per plant and plant height on seed yield as indicated by path coefficient were the highest, while other causal effects were small or negative. Yield variation (1- R2 attributable to the nine yield component variables was slightly high (61.23%, which means that mungbean accessions with high grain yield should have sufficient plant height and high number of pods per plant. Therefore, these parameters (number of pods per plant and plant height can be used as the selection criteria in mungbean breeding program. These criteria can be visualized during bulk selection on the early generation stage of F2 to F4, and subsequently on line development of individual plant (pedigree of F5.

  18. Genetic improvement of fiber length and coarseness based on paper product performance and material variability - a review (United States)

    Brian K. Via; Michael Stine; Todd F. Shupe; Chi-Leung So; Leslie Groom


    Improvement of specific gravity through tree breeding was an early choice made in the mid 20th century due to its ease of measurement and impact on pulp yield and lumber strength and stiffness. This was often the first, and in many cases, the only wood quality trait selected for. However, from a product standpoint, increased specific gravity has shown to lower many...

  19. Estimating Composite Curve Number Using an Improved SCS-CN Method with Remotely Sensed Variables in Guangzhou, China

    Directory of Open Access Journals (Sweden)

    Qihao Weng


    Full Text Available The rainfall and runoff relationship becomes an intriguing issue as urbanization continues to evolve worldwide. In this paper, we developed a simulation model based on the soil conservation service curve number (SCS-CN method to analyze the rainfall-runoff relationship in Guangzhou, a rapid growing metropolitan area in southern China. The SCS-CN method was initially developed by the Natural Resources Conservation Service (NRCS of the United States Department of Agriculture (USDA, and is one of the most enduring methods for estimating direct runoff volume in ungauged catchments. In this model, the curve number (CN is a key variable which is usually obtained by the look-up table of TR-55. Due to the limitations of TR-55 in characterizing complex urban environments and in classifying land use/cover types, the SCS-CN model cannot provide more detailed runoff information. Thus, this paper develops a method to calculate CN by using remote sensing variables, including vegetation, impervious surface, and soil (V-I-S. The specific objectives of this paper are: (1 To extract the V-I-S fraction images using Linear Spectral Mixture Analysis; (2 To obtain composite CN by incorporating vegetation types, soil types, and V-I-S fraction images; and (3 To simulate direct runoff under the scenarios with precipitation of 57mm (occurred once every five years by average and 81mm (occurred once every ten years. Our experiment shows that the proposed method is easy to use and can derive composite CN effectively.

  20. Age differences in coupling of intraindividual variability in mnemonic strategies and practice-related associative recall improvements. (United States)

    Hertzog, Christopher; Lövdén, Martin; Lindenberger, Ulman; Schmiedek, Florian


    The importance of encoding strategies for associative recall is well established, but there have been no studies of aging and intraindividual variability (IAV) in strategy use during extended practice. We observed strategy use and cued-recall test performance over 101 days of practice in 101 younger adults (M = 25.6 years) and 103 older adults (M = 71.3 years) sandwiched by a pretest and posttest battery including an associative recall test. Each practice session included 2 lists of 12 number-noun paired-associate (PA) items (e.g., 23-DOGS), presented for brief exposures titrated to maintain below-ceiling performance throughout practice. Participants reported strategy use (e.g., rote repetition, imagery) after each test. Substantial IAV in strategy use was detected that was coupled with performance; lists studied with normatively effective strategies (e.g., imagery) generated higher PA recall than lists studied with less effective strategies (e.g., rote repetition). In comparison to younger adults, older adults' practice (a) relied more on repetition and less on effective strategies, (b) showed lower levels of IAV in effective strategy use, and (c) had lower within-person strategy-recall coupling, especially late in practice. Individual differences in pretest-posttest gains in PA recall were predicted by average level of effective strategy use in young adults but by strategy-recall coupling in older adults. Results are consistent with the hypothesis that experiencing variability in strategic outcomes during practice helps hone the effectiveness of strategic encoding behavior, and that older adults' reduced degree of pretest-posttest gains is influenced by lower likelihood of using and optimizing effective strategies through practice. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  1. Estimation of Paddy Rice Variables with a Modified Water Cloud Model and Improved Polarimetric Decomposition Using Multi-Temporal RADARSAT-2 Images

    Directory of Open Access Journals (Sweden)

    Zhi Yang


    Full Text Available Rice growth monitoring is very important as rice is one of the staple crops of the world. Rice variables as quantitative indicators of rice growth are critical for farming management and yield estimation, and synthetic aperture radar (SAR has great advantages for monitoring rice variables due to its all-weather observation capability. In this study, eight temporal RADARSAT-2 full-polarimetric SAR images were acquired during rice growth cycle and a modified water cloud model (MWCM was proposed, in which the heterogeneity of the rice canopy in the horizontal direction and its phenological changes were considered when the double-bounce scattering between the rice canopy and the underlying surface was firstly considered as well. Then, three scattering components from an improved polarimetric decomposition were coupled with the MWCM, instead of the backscattering coefficients. Using a genetic algorithm, eight rice variables were estimated, such as the leaf area index (LAI, rice height (h, and the fresh and dry biomass of ears (Fe and De. The accuracy validation showed the MWCM was suitable for the estimation of rice variables during the whole growth season. The validation results showed that the MWCM could predict the temporal behaviors of the rice variables well during the growth cycle (R2 > 0.8. Compared with the original water cloud model (WCM, the relative errors of rice variables with the MWCM were much smaller, especially in the vegetation phase (approximately 15% smaller. Finally, it was discussed that the MWCM could be used, theoretically, for extensive applications since the empirical coefficients in the MWCM were determined in general cases, but more applications of the MWCM are necessary in future work.

  2. Effects of limited concentrate feeding on growth and blood and serum variables, and on nutrient digestibility and gene expression of hepatic gluconeogenic enzymes in dairy calves. (United States)

    Lohakare, J D; van de Sand, H; Gerlach, K; Hosseini, A; Mielenz, M; Sauerwein, H; Pries, M; Südekum, K-H


    This study elucidated the effects of limited concentrate feeding on growth, nutrient digestibility, blood profile and gene expression of gluconeogenic enzymes in the liver of dairy calves. The study utilized 36 German Holstein dairy calves (5-7 days of age) divided into two groups of 18 calves each for 150 days. Control group calves received 2 kg/(calf × day) of concentrate, whereas calves in the restricted group received only 1 kg/(calf × day). Good quality forage (mixture of maize and grass silages) was available for ad libitum consumption to both groups. The intake of milk replacer before weaning, and of concentrate were recorded daily per calf; however, the consumption of forages was quantified as daily average of the group. Body weights (BW) were recorded at start and on days 35, 70, 112 and 150. Blood and serum samples and spot urinary and faecal samples were also collected at similar time points. On days 70 and 150, liver biopsies were collected from seven animals in each group. The BW was not different between the groups at all times. Total BW gain in the control group was 124 kg as opposed to 111 kg in restricted group that led to average BW gain of 827 g/day and 739 g/day in respective groups, and the differences were significant (p = 0.018). As planned, the control group had higher concentrate and lower forage intake than the restricted group. The blood haemoglobin, haematocrit and serum variables (glucose, total protein, albumin and urea) were within the normal range in both groups, but serum glucose was higher (p < 0.05) in control than in restricted group at 70 days. There was no difference between groups in organic matter (OM) digestibility which declined (p < 0.001) with increasing age in both groups. Microbial crude protein (MCP) synthesis estimated from urinary allantoin excretion increased (p < 0.001) in both groups with increasing age but was not different between groups. The mRNA expressions for the gluconeogenic enzymes, cytosolic and

  3. Improvement in latent variable indirect response modeling of multiple categorical clinical endpoints: application to modeling of guselkumab treatment effects in psoriatic patients. (United States)

    Hu, Chuanpu; Randazzo, Bruce; Sharma, Amarnath; Zhou, Honghui


    Exposure-response modeling plays an important role in optimizing dose and dosing regimens during clinical drug development. The modeling of multiple endpoints is made possible in part by recent progress in latent variable indirect response (IDR) modeling for ordered categorical endpoints. This manuscript aims to investigate the level of improvement achievable by jointly modeling two such endpoints in the latent variable IDR modeling framework through the sharing of model parameters. This is illustrated with an application to the exposure-response of guselkumab, a human IgG1 monoclonal antibody in clinical development that blocks IL-23. A Phase 2b study was conducted in 238 patients with psoriasis for which disease severity was assessed using Psoriasis Area and Severity Index (PASI) and Physician's Global Assessment (PGA) scores. A latent variable Type I IDR model was developed to evaluate the therapeutic effect of guselkumab dosing on 75, 90 and 100% improvement of PASI scores from baseline and PGA scores, with placebo effect empirically modeled. The results showed that the joint model is able to describe the observed data better with fewer parameters compared with the common approach of separately modeling the endpoints.

  4. ATF3 expression improves motor function in the ALS mouse model by promoting motor neuron survival and retaining muscle innervation. (United States)

    Seijffers, Rhona; Zhang, Jiangwen; Matthews, Jonathan C; Chen, Adam; Tamrazian, Eric; Babaniyi, Olusegun; Selig, Martin; Hynynen, Meri; Woolf, Clifford J; Brown, Robert H


    ALS is a fatal neurodegenerative disease characterized by a progressive loss of motor neurons and atrophy of distal axon terminals in muscle, resulting in loss of motor function. Motor end plates denervated by axonal retraction of dying motor neurons are partially reinnervated by remaining viable motor neurons; however, this axonal sprouting is insufficient to compensate for motor neuron loss. Activating transcription factor 3 (ATF3) promotes neuronal survival and axonal growth. Here, we reveal that forced expression of ATF3 in motor neurons of transgenic SOD1(G93A) ALS mice delays neuromuscular junction denervation by inducing axonal sprouting and enhancing motor neuron viability. Maintenance of neuromuscular junction innervation during the course of the disease in ATF3/SOD1(G93A) mice is associated with a substantial delay in muscle atrophy and improved motor performance. Although disease onset and mortality are delayed, disease duration is not affected. This study shows that adaptive axonal growth-promoting mechanisms can substantially improve motor function in ALS and importantly, that augmenting viability of the motor neuron soma and maintaining functional neuromuscular junction connections are both essential elements in therapy for motor neuron disease in the SOD1(G93A) mice. Accordingly, effective protection of optimal motor neuron function requires restitution of multiple dysregulated cellular pathways.

  5. Genetic diversity analysis in Malaysian giant prawns using expressed sequence tag microsatellite markers for stock improvement program. (United States)

    Atin, K H; Christianus, A; Fatin, N; Lutas, A C; Shabanimofrad, M; Subha, B


    The Malaysian giant prawn is among the most commonly cultured species of the genus Macrobrachium. Stocks of giant prawns from four rivers in Peninsular Malaysia have been used for aquaculture over the past 25 years, which has led to repeated harvesting, restocking, and transplantation between rivers. Consequently, a stock improvement program is now important to avoid the depletion of wild stocks and the loss of genetic diversity. However, the success of such an improvement program depends on our knowledge of the genetic variation of these base populations. The aim of the current study was to estimate genetic variation and differentiation of these riverine sources using novel expressed sequence tag-microsatellite (EST-SSR) markers, which not only are informative on genetic diversity but also provide information on immune and metabolic traits. Our findings indicated that the tested stocks have inbreeding depression due to a significant deficiency in heterozygotes, and F IS was estimated as 0.15538 to 0.31938. An F-statistics analysis suggested that the stocks are composed of one large panmictic population. Among the four locations, stocks from Johor, in the southern region of the peninsular, showed higher allelic and genetic diversity than the other stocks. To overcome inbreeding problems, the Johor population could be used as a base population in a stock improvement program by crossing to the other populations. The study demonstrated that EST-SSR markers can be incorporated in future marker assisted breeding to aid the proper management of the stocks by breeders and stakeholders in Malaysia.

  6. An improved procedure to accurately assess the variability of the exposure to electromagnetic radiation emitted by GSM base station antennas

    International Nuclear Information System (INIS)

    Bechet, Paul; Miclaus, Simona


    Long-term human exposure around Global System for Mobile Communications (GSM) base station antennas has not yet been precisely established; this is of interest from human health and epidemiological perspectives. Actual exposure is difficult to assess accurately, mainly because there is a lack of technical information directly from the GSM operators. The in situ measurement standards available at present provide only a worst-case prediction method; the present work goes beyond this and proposes a methodology that, without the need for data from operators, allows a reliable way to express real exposure with a greater accuracy than all other methods proposed to date. The method is based on dual measurements of the signal strengths in the frequency domain and the time domain and takes into consideration the instantaneous traffic in GSM channels. In addition, it allows a channel-individualized exposure assessement, by making possible the separate analysis of the electric field level in the two types of channel of the GSM standard—the traffic channels and the control channels. (paper)

  7. Improved estimation of heavy rainfall by weather radar after reflectivity correction and accounting for raindrop size distribution variability (United States)

    Hazenberg, Pieter; Leijnse, Hidde; Uijlenhoet, Remko


    Between 25 and 27 August 2010 a long-duration mesoscale convective system was observed above the Netherlands, locally giving rise to rainfall accumulations exceeding 150 mm. Correctly measuring the amount of precipitation during such an extreme event is important, both from a hydrological and meteorological perspective. Unfortunately, the operational weather radar measurements were affected by multiple sources of error and only 30% of the precipitation observed by rain gauges was estimated. Such an underestimation of heavy rainfall, albeit generally less strong than in this extreme case, is typical for operational weather radar in The Netherlands. In general weather radar measurement errors can be subdivided into two groups: (1) errors affecting the volumetric reflectivity measurements (e.g. ground clutter, radar calibration, vertical profile of reflectivity) and (2) errors resulting from variations in the raindrop size distribution that in turn result in incorrect rainfall intensity and attenuation estimates from observed reflectivity measurements. A stepwise procedure to correct for the first group of errors leads to large improvements in the quality of the estimated precipitation, increasing the radar rainfall accumulations to about 65% of those observed by gauges. To correct for the second group of errors, a coherent method is presented linking the parameters of the radar reflectivity-rain rate (Z-R) and radar reflectivity-specific attenuation (Z-k) relationships to the normalized drop size distribution (DSD). Two different procedures were applied. First, normalized DSD parameters for the whole event and for each precipitation type separately (convective, stratiform and undefined) were obtained using local disdrometer observations. Second, 10,000 randomly generated plausible normalized drop size distributions were used for rainfall estimation, to evaluate whether this Monte Carlo method would improve the quality of weather radar rainfall products. Using the

  8. Design method of a power management strategy for variable battery capacities range-extended electric vehicles to improve energy efficiency and cost-effectiveness

    International Nuclear Information System (INIS)

    Du, Jiuyu; Chen, Jingfu; Song, Ziyou; Gao, Mingming; Ouyang, Minggao


    Energy management strategy and battery capacity are the primary factors for the energy efficiency of range-extended electric buses (REEBs). To improve the energy efficiency of REEBs developed by Tsinghua University, an optimal design method of global optimization-based strategy is investigated. It is real-time and adaptive to variable traction battery capacities of series REEBs. For simulation, the physical model of REEB and key components are established. The optimal strategy is first extracted by the power split ratio (PSR) from REEB simulation result with dynamic program (DP) algorithm. The power distribution map is obtained by series simulations for variable battery capacity options. The control law for developing optimal strategy are achieved by cluster regression for power distribution data. To verify the effect of the proposed energy management strategy, characteristics of powertrain, energy efficiency, operating cost, and computing time are ultimately analyzed. Simulation results show that the energy efficiency of the global optimization-based strategy presented in this paper is similar to that of the DP strategy. Therefore, the overall energy efficiency can be significantly improved compared with that of the CDCS strategy, and operating costs can be substantially reduced. The feasibility of candidate control strategies is thereby assessed via the employment of variable parameters. - Highlights: • Analysis method of powertrain energy efficiency and power distribution is proposed. • The power distribution rules of strategy with variable battery capacities are achieved. • The parametric method of proposed PSR-RB strategy is presented. • The energy efficiency of powertrain is analysis by flow analysis method. • The energy management strategy is global optimization-based and real-time.

  9. Exclusion of Patients with a Severe T-Cell Defect Improves the Definition of Common Variable Immunodeficiency. (United States)

    Bertinchamp, Rémi; Gérard, Laurence; Boutboul, David; Malphettes, Marion; Fieschi, Claire; Oksenhendler, Eric

    In 2014, the European Society for Immune Deficiencies (ESID) revised the common variable immunodeficiency (CVID) diagnosis criteria by incorporating new clinical and biological markers. The new definition appeared more restrictive but had not yet been evaluated in a large cohort of patients. The objective of this study was to evaluate the impact of this new definition in a large cohort of patients with primary hypogammaglobulinemia. Evaluation of 3 different CVID definitions (ESID/Pan-American Group for Immunodeficiency [PAGID] 1999, ESID 2014, DEFI 2015) in 521 patients included in the French DEFI study with a diagnosis of primary hypogammaglobulinemia. Using the ESID/PAGID 1999 definition, 351 patients were classified as CVID. The new ESID 2014 definition excluded 62 (18%) patients. Most of them (n = 56; 90%) had a less severe disease, whereas 6 (10%) presented with a severe disease with major T-cell defect. We propose different criteria (occurrence of opportunistic infection or very low naive CD4+ T-cell count) to define this population with severe T-cell defect. Sixty-two patients fulfilled these criteria, represented 20% of the initial CVID population but accounted for 77% of the deaths, with a 5-year overall survival of 67.6% (95% confidence interval, 51.0-79.6), and were considered as late onset combined immunodeficiency (LOCID). The new ESID definition for CVID still fails to exclude a large number of patients with severe T-cell defect. We propose a new definition (DEFI 2015) that excluded more patients with a T-cell defect and consider these patients as LOCID. This population has a poor outcome and should be considered as a distinct group requiring specific care. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  10. Freight railway transport: Critical variables to improve the transport applied to infrastructure costs and its associated traffic flow

    Energy Technology Data Exchange (ETDEWEB)

    Zakowska, L.; Pulawska-Obiedowska, S.


    The developed societies have as challenge, among others, to achieve a mobility development based on economic models of low carbon and energy efficient, making it accessible to the entire population. In this context, the sustainable mobility seems to meet the economic, social and environmental needs, minimizing their negative impact. There are three factors that are relevant: (1) infrastructures; (2) modes of transport more ecological and safe, and (3) operations and services for passengers and freights.The objective of this research is to provide guidance to investment in sustainable transport infrastructures that are truly useful and effective. In particular we have studied the case of the railway, using the following information: details of the infrastructure; cost of construction (per kilometre); maintenance cost, and life cycle. This information may be relevant to consider their possible business models.The methodology of this research was focused in the detailed analysis of the infrastructure use and maintenance criteria, the market opportunities for freight development and the available data to validate the obtained results from the software tool reached in this work. Our research includes the different following aspects:• Evaluation of the supported traffic by the rail line.• Relevant items to be considered in the rail infrastructure. Defining the track, we can group items in two sets: civil and rail installations.• Rolling stock available. Locomotives and wagons are modelled to introduce the data as convenience for the user.Besides our research includes the development of software, Decision System Tool (DST), for studying the construction and maintenance cost of railway infrastructure. It is developed in a common and open source program, providing the user the interaction with the critical variable of the line. It has been adjusted using the following references: MOM PlanCargorail; EcoTransIT, and Projects funded by Framework Program of EU (New

  11. Reco level Smin and subsystem Smin: improved global inclusive variables for measuring the new physics mass scale in MET events at hadron colliders

    Energy Technology Data Exchange (ETDEWEB)

    Konar, Partha; /Florida U.; Kong, Kyoungchul; /SLAC; Matchev, Konstantin T.; Park, Myeonghun; /Florida U.


    The variable {radical}s{sub min} was originally proposed in [1] as a model-independent, global and fully inclusive measure of the new physics mass scale in missing energy events at hadron colliders. In the original incarnation of {radical}s{sub min}, however, the connection to the new physics mass scale was blurred by the effects of the underlying event, most notably initial state radiation and multiple parton interactions. In this paper we advertize two improved variants of the {radical}s{sub min} variable, which overcome this problem. First we show that by evaluating the {radical}s{sub min} variable at the RECO level, in terms of the reconstructed objects in the event, the effects from the underlying event are significantly diminished and the nice correlation between the peak in the {radical}s{sub min}{sup (reco)} distribution and the new physics mass scale is restored. Secondly, the underlying event problem can be avoided altogether when the {radical}s{sub min} concept is applied to a subsystem of the event which does not involve any QCD jets. We supply an analytic formula for the resulting subsystem {radical}s{sub min}{sup (sub)} variable and show that its peak exhibits the usual correlation with the mass scale of the particles produced in the subsystem. Finally, we contrast {radical}s{sub min} to other popular inclusive variables such as H{sub T}, M{sub Tgen} and M{sub TTgen}. We illustrate our discussion with several examples from supersymmetry, and with dilepton events from top quark pair production.

  12. The HER4 isoform JM-a/CYT2 relates to improved survival in bladder cancer patients but only if the estrogen receptor α is not expressed

    DEFF Research Database (Denmark)

    Munk, Mathias; Memon, Ashfaque Ahmed; Poulsen, Steen Seier


    Abstract Bladder cancer tumors expressing human epidermal growth factor receptor 4 (HER4) demonstrate improved patient survival. HER4 isoforms and estrogen receptor alpha (ER-α) can form chaperone complexes causing cell-proliferation. We wanted to explore if HER4 isoforms and ER-α could correlate...... to poor prognosis in bladder cancers. We developed mRNA assays for HER4 isoforms (JM-a, JM-b, CYT1, and CYT2) and for ER-α. Expression was analyzed in tumors from 85 bladder cancer patients and compared to overall survival (median follow-up of 5.1 years). ER-α was expressed in 38% (n = 32) of tumors...... and half of those (18/36) expressed both isoforms. JM-a/CYT2 expression correlated to improved survival (p = 0.004), but not when ER-α was co-expressed (p = 0.897). Immunohistochemistry revealed protein expression of HER4 and ER-α in tumor cells. Growth of RT4 bladder cancer cells, expressing both JM...

  13. Improvement of In Vivo Expression of Genes Delivered by Self-Amplifying RNA Using Vaccinia Virus Immune Evasion Proteins (United States)

    Beissert, Tim; Koste, Lars; Perkovic, Mario; Walzer, Kerstin C.; Erbar, Stephanie; Selmi, Abderraouf; Diken, Mustafa; Kreiter, Sebastian; Türeci, Özlem; Sahin, Ugur


    Among nucleic acid–based delivery platforms, self-amplifying RNA (saRNA) vectors are of increasing interest for applications such as transient expression of recombinant proteins and vaccination. saRNA is safe and, due to its capability to amplify intracellularly, high protein levels can be produced from even minute amounts of transfected templates. However, it is an obstacle to full exploitation of this platform that saRNA induces a strong innate host immune response. In transfected cells, pattern recognition receptors sense double-stranded RNA intermediates and via activation of protein kinase R (PKR) and interferon signaling initiate host defense measures including a translational shutdown. To reduce pattern recognition receptor stimulation and unleash suppressed saRNA translation, this study co-delivered non-replicating mRNA encoding vaccinia virus immune evasion proteins E3, K3, and B18. It was shown that E3 is far superior to K3 or B18 as a highly potent blocker of PKR activation and of interferon (IFN)-β upregulation. B18, in contrast, is superior in controlling OAS1, a key IFN-inducible gene involved in viral RNA degradation. By combining all three vaccinia proteins, the study achieved significant suppression of PKR and IFN pathway activation in vitro and enhanced expression of saRNA-encoded genes of interest both in vitro and in vivo. This approach promises to overcome key hurdles of saRNA gene delivery. Its application may improve the bioavailability of the encoded protein, and reduce the effective dose and correspondingly the cost of goods of manufacture in the various fields where saRNA utilization is envisioned. PMID:28877647

  14. Curcumin Increase the Expression of Neural Stem/Progenitor Cells and Improves Functional Recovery after Spinal Cord Injury (United States)

    Bang, Woo-Seok; Kim, Kyoung-Tae; Seo, Ye Jin; Cho, Dae-Chul; Sung, Joo-Kyung; Kim, Chi Heon


    Objective To investigates the effect of curcumin on proliferation of spinal cord neural stem/progenitor cells (SC-NSPCs) and functional outcome in a rat spinal cord injury (SCI) model. Methods Sixty adult male Sprague-Dawley rats were randomly and blindly allocated into three groups (sham control group; curcumin treated group after SCI; vehicle treated group after SCI). Functional recovery was evaluated by the Basso, Beattie, and Bresnahan (BBB) scale during 6 weeks after SCI. The expression of SC-NSPC proliferation and astrogliosis were analyzed by nestin/Bromodeoxyuridine (BrdU) and Glial fibrillary acidic protein (GFAP) staining. The injured spinal cord was then examined histologically, including quantification of cavitation. Results The BBB score of the SCI-curcumin group was better than that of SCI-vehicle group up to 14 days (p<0.05). The co-immunoreactivity of nestin/BrdU in the SCI-curcumin group was much higher than that of the SCI-vehicle group 1 week after surgery (p<0.05). The GFAP immunoreactivity of the SCI-curcumin group was remarkably lower than that of the SCI-vehicle group 4 weeks after surgery (p<0.05). The lesion cavity was significantly reduced in the curcumin group as compared to the control group (p<0.05). Conclusion These results indicate that curcumin could increase the expression of SC-NSPCs, and reduce the activity of reactive astrogliosis and lesion cavity. Consequently curcumin could improve the functional recovery after SCI via SC-NSPC properties. PMID:29354231

  15. Heterologous expression of Spathaspora passalidarum xylose reductase and xylitol dehydrogenase genes improved xylose fermentation ability of Aureobasidium pullulans. (United States)

    Guo, Jian; Huang, Siyao; Chen, Yefu; Guo, Xuewu; Xiao, Dongguang


    Aureobasidium pullulans is a yeast-like fungus that can ferment xylose to generate high-value-added products, such as pullulan, heavy oil, and melanin. The combinatorial expression of two xylose reductase (XR) genes and two xylitol dehydrogenase (XDH) genes from Spathaspora passalidarum and the heterologous expression of the Piromyces sp. xylose isomerase (XI) gene were induced in A. pullulans to increase the consumption capability of A. pullulans on xylose. The overexpression of XYL1.2 (encoding XR) and XYL2.2 (encoding XDH) was the most beneficial for xylose utilization, resulting in a 17.76% increase in consumed xylose compared with the parent strain, whereas the introduction of the Piromyces sp. XI pathway failed to enhance xylose utilization efficiency. Mutants with superior xylose fermentation performance exhibited increased intracellular reducing equivalents. The fermentation performance of all recombinant strains was not affected when glucose or sucrose was utilized as the carbon source. The strain with overexpression of XYL1.2 and XYL2.2 exhibited excellent fermentation performance with mimicked hydrolysate, and pullulan production increased by 97.72% compared with that of the parent strain. The present work indicates that the P4 mutant (using the XR/XDH pathway) with overexpressed XYL1.2 and XYL2.2 exhibited the best xylose fermentation performance. The P4 strain showed the highest intracellular reducing equivalents and XR and XDH activity, with consequently improved pullulan productivity and reduced melanin production. This valuable development in aerobic fermentation by the P4 strain may provide guidance for the biotransformation of xylose to high-value products by A. pullulans through genetic approach.

  16. Variable effectiveness of stepwise implementation of nudge-type interventions to improve provider compliance with intraoperative low tidal volume ventilation. (United States)

    O'Reilly-Shah, Vikas N; Easton, George S; Jabaley, Craig S; Lynde, Grant C


    Identifying mechanisms to improve provider compliance with quality metrics is a common goal across medical disciplines. Nudge interventions are minimally invasive strategies that can influence behavioural changes and are increasingly used within healthcare settings. We hypothesised that nudge interventions may improve provider compliance with lung-protective ventilation (LPV) strategies during general anaesthesia. We developed an audit and feedback dashboard that included information on both provider-level and department-level compliance with LPV strategies in two academic hospitals, two non-academic hospitals and two academic surgery centres affiliated with a single healthcare system. Dashboards were emailed to providers four times over the course of the 9-month study. Additionally, the default setting on anaesthesia machines for tidal volume was decreased from 700 mL to 400 mL. Data on surgical cases performed between 1 September 2016 and 31 May 2017 were examined for compliance with LPV. The impact of the interventions was assessed via pairwise logistic regression analysis corrected for multiple comparisons. A total of 14 793 anaesthesia records were analysed. Absolute compliance rates increased from 59.3% to 87.8%preintervention to postintervention. Introduction of attending physician dashboards resulted in a 41% increase in the odds of compliance (OR 1.41, 95% CI 1.17 to 1.69, p=0.002). Subsequently, the addition of advanced practice provider and resident dashboards lead to an additional 93% increase in the odds of compliance (OR 1.93, 95% CI 1.52 to 2.46, p<0.001). Lastly, modifying ventilator defaults led to a 376% increase in the odds of compliance (OR 3.76, 95% CI 3.1 to 4.57, p<0.001). Audit and feedback tools in conjunction with default changes improve provider compliance. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise

  17. Combination of Bcl-2 and MYC protein expression improves high-risk stratification in diffuse large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Wang J


    Full Text Available Jing Wang,* Min Zhou,* Jing-Yan Xu,* Bing Chen, Jian OuyangDepartment of Hematology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this work and should be considered as cofirst authorsPurpose: To evaluate whether the addition of two biological markers (MYC and BCL-2 protein overexpression improves the stratification of high-risk patients with diffuse large B-cell lymphoma (DLBCL.Method: Seven risk factors were identified at diagnosis, and a maximum of 7 points were assigned to each patient. The patients were classified according to four risk groups: low (0–1, low-intermediate (2–3, high-intermediate (4, and high (5–7. Only high-risk patients with DLBCL were included in this analysis. We retrospectively examined 20 cases from 2008 to 2013 at the Nanjing Drum Tower Hospital.Results: The median expression of MYC protein was 60%, and 17 of 20 (65% evaluable cases overexpressed MYC. The median expression of BCL-2 protein was also 60%. Eighteen of 20 (90% evaluable cases showed BCL-2 overexpression. Additionally, 12 out of 20 cases (60% demonstrated coexpression of MYC and BCL-2 proteins. The percentages of overall survival and progression-free survival at the median follow-up time (36 months were 33.3%±16.1% and 16.9%±13.5%, respectively. By comparison, nine, four, and 20 patients were classified as high risk based on the International Prognostic Index (IPI, National Comprehensive Cancer Network(NCCN-IPI, and revised IPI criteria, respectively. According to the IPI and NCCN-IPI stratification, the risk groups demonstrated closely overlapping survival curves. In addition, four out of 20 cases were identified as low-intermediate risk according to the NCCN-IPI criteria.Conclusion: The addition of MYC and BCL-2 protein expression to the IPI could identify a subset of DLBCL patients with high-risk clinicopathological characteristics and

  18. Improved electronic interfaces for AT-cut quartz crystal microbalance sensors under variable damping and parallel capacitance conditions. (United States)

    Arnau, A; García, J V; Jimenez, Y; Ferrari, V; Ferrari, M


    A new configuration of automatic capacitance compensation (ACC) technique based on an oscillatorlike working interface, which permits the tracking of the series resonant frequency and the monitoring of the motional resistance and the parallel capacitance of a thickness-shear mode quartz crystal microbalance sensor, is introduced. The new configuration permits an easier calibration of the system which, in principle, improves the accuracy. Experimental results are reported with 9 and 10 MHz crystals in liquids with different parallel capacitances which demonstrate the effectiveness of the capacitance compensation. Some frequency deviations from the exact series resonant frequency, measured by an impedance analyzer, are explained by the specific nonideal behavior of the circuit components. A tentative approach is proposed to solve this problem that is also common to previous ACC systems.

  19. Improved electronic interfaces for AT-cut quartz crystal microbalance sensors under variable damping and parallel capacitance conditions

    International Nuclear Information System (INIS)

    Arnau, A.; Garcia, J. V.; Jimenez, Y.; Ferrari, V.; Ferrari, M.


    A new configuration of automatic capacitance compensation (ACC) technique based on an oscillatorlike working interface, which permits the tracking of the series resonant frequency and the monitoring of the motional resistance and the parallel capacitance of a thickness-shear mode quartz crystal microbalance sensor, is introduced. The new configuration permits an easier calibration of the system which, in principle, improves the accuracy. Experimental results are reported with 9 and 10 MHz crystals in liquids with different parallel capacitances which demonstrate the effectiveness of the capacitance compensation. Some frequency deviations from the exact series resonant frequency, measured by an impedance analyzer, are explained by the specific nonideal behavior of the circuit components. A tentative approach is proposed to solve this problem that is also common to previous ACC systems

  20. Study on the essential variables for pipe outer surface irradiated laser stress improvement process (L-SIP). Development of pipe outer surface irradiated laser stress improvement process (L-SIP)

    International Nuclear Information System (INIS)

    Ohta, Takahiro; Kamo, Kazuhiko; Muroya, Itaru; Asada, Seiji; Nakamura, Yasuo


    The new process called L-SIP (outer surface irradiated Laser Stress Improvement Process) is developed to improve the tensile residual stress of the inner surface near the butt welded joints of pipes in the compression stress. The temperature gradient occurs in the thickness of pipes in heating the outer surface rapidly by laser beam. By the thermal expansion difference between the inner surface and the outer surface, the compression stress occurs near the inner surface of pipes. In this paper, the essential variables for L-SIP is studied by experimental and FEM analysis. The range of the essential variables for L-SIP, which are defined by thermo-elastic FEM analysis, are Tmax=550 - 650degC, L Q /√rh ≥ 3, W Q /√rh ≥ 1.7, and, 0.04 ≤ F 0 ≤ 0.10 where Tmax is maximum temperature on the monitor point of the outer surface, F 0 is k x τ 0 /h 2 , k is thermal diffusivity coefficient, τ 0 is the temperature rise time from 100degC to maximum temperature on the monitor point of the outer surface, W Q is τ 0 x v, υ is moving velocity, L Q is the uniform temperature length in the axial direction, h is thickness of the pipe, and r is average radius of the pipe. It is showed by thermo-elastic-plastic FEM analysis that the residual stresses near the inner surface of pipes are improved in 4 different size pipes under the same essential variables. L-SIP is actually applied to welding joints of 4B x Sch160 and 2B x Sch80 SUS304 type stainless steel pipes within the defined range of the essential variables. The measured welding residual stresses on the inner surface near the welding joints are tensile. The residual stresses on the inner surface change to compression in all joints by L-SIP. (author)

  1. A new adenovirus based vaccine vector expressing an Eimeria tenella derived TLR agonist improves cellular immune responses to an antigenic target.

    Directory of Open Access Journals (Sweden)

    Daniel M Appledorn


    Full Text Available Adenoviral based vectors remain promising vaccine platforms for use against numerous pathogens, including HIV. Recent vaccine trials utilizing Adenovirus based vaccines expressing HIV antigens confirmed induction of cellular immune responses, but these responses failed to prevent HIV infections in vaccinees. This illustrates the need to develop vaccine formulations capable of generating more potent T-cell responses to HIV antigens, such as HIV-Gag, since robust immune responses to this antigen correlate with improved outcomes in long-term non-progressor HIV infected individuals.In this study we designed a novel vaccine strategy utilizing an Ad-based vector expressing a potent TLR agonist derived from Eimeria tenella as an adjuvant to improve immune responses from a [E1-]Ad-based HIV-Gag vaccine. Our results confirm that expression of rEA elicits significantly increased TLR mediated innate immune responses as measured by the influx of plasma cytokines and chemokines, and activation of innate immune responding cells. Furthermore, our data show that the quantity and quality of HIV-Gag specific CD8(+ and CD8(- T-cell responses were significantly improved when coupled with rEA expression. These responses also correlated with a significantly increased number of HIV-Gag derived epitopes being recognized by host T cells. Finally, functional assays confirmed that rEA expression significantly improved antigen specific CTL responses, in vivo. Moreover, we show that these improved responses were dependent upon improved TLR pathway interactions.The data presented in this study illustrate the potential utility of Ad-based vectors expressing TLR agonists to improve clinical outcomes dependent upon induction of robust, antigen specific immune responses.

  2. Improvement of Systematic Bias of mean state and the intraseasonal variability of CFSv2 through superparameterization and revised cloud-convection-radiation parameterization (United States)

    Mukhopadhyay, P.; Phani Murali Krishna, R.; Goswami, Bidyut B.; Abhik, S.; Ganai, Malay; Mahakur, M.; Khairoutdinov, Marat; Dudhia, Jimmy


    Inspite of significant improvement in numerical model physics, resolution and numerics, the general circulation models (GCMs) find it difficult to simulate realistic seasonal and intraseasonal variabilities over global tropics and particularly over Indian summer monsoon (ISM) region. The bias is mainly attributed to the improper representation of physical processes. Among all the processes, the cloud and convective processes appear to play a major role in modulating model bias. In recent times, NCEP CFSv2 model is being adopted under Monsoon Mission for dynamical monsoon forecast over Indian region. The analyses of climate free run of CFSv2 in two resolutions namely at T126 and T382, show largely similar bias in simulating seasonal rainfall, in capturing the intraseasonal variability at different scales over the global tropics and also in capturing tropical waves. Thus, the biases of CFSv2 indicate a deficiency in model's parameterization of cloud and convective processes. Keeping this in background and also for the need to improve the model fidelity, two approaches have been adopted. Firstly, in the superparameterization, 32 cloud resolving models each with a horizontal resolution of 4 km are embedded in each GCM (CFSv2) grid and the conventional sub-grid scale convective parameterization is deactivated. This is done to demonstrate the role of resolving cloud processes which otherwise remain unresolved. The superparameterized CFSv2 (SP-CFS) is developed on a coarser version T62. The model is integrated for six and half years in climate free run mode being initialised from 16 May 2008. The analyses reveal that SP-CFS simulates a significantly improved mean state as compared to default CFS. The systematic bias of lesser rainfall over Indian land mass, colder troposphere has substantially been improved. Most importantly the convectively coupled equatorial waves and the eastward propagating MJO has been found to be simulated with more fidelity in SP-CFS. The reason of

  3. Variable importance in latent variable regression models

    NARCIS (Netherlands)

    Kvalheim, O.M.; Arneberg, R.; Bleie, O.; Rajalahti, T.; Smilde, A.K.; Westerhuis, J.A.


    The quality and practical usefulness of a regression model are a function of both interpretability and prediction performance. This work presents some new graphical tools for improved interpretation of latent variable regression models that can also assist in improved algorithms for variable

  4. Improvement in Simulation of Eurasian Winter Climate Variability with a Realistic Arctic Sea Ice Condition in an Atmospheric GCM (United States)

    Lim, Young-Kwon; Ham, Yoo-Geun; Jeong, Jee-Hoon; Kug, Jong-Seong


    The present study investigates how much a realistic Arctic sea ice condition can contribute to improve simulation of the winter climate variation over the Eurasia region. Model experiments are set up using different sea ice boundary conditions over the past 24 years (i.e., 1988-2011). One is an atmospheric model inter-comparison (AMIP) type of run forced with observed sea-surface temperature (SST), sea ice, and greenhouse gases (referred to as Exp RSI), and the other is the same as Exp RSI except for the sea ice forcing, which is a repeating climatological annual cycle (referred to as Exp CSI). Results show that Exp RSI produces the observed dominant pattern of Eurasian winter temperatures and their interannual variation better than Exp CSI (correlation difference up to approx. 0.3). Exp RSI captures the observed strong relationship between the sea ice concentration near the Barents and Kara seas and the temperature anomaly across Eurasia, including northeastern Asia, which is not well captured in Exp CSI. Lagged atmospheric responses to sea ice retreat are examined using observations to understand atmospheric processes for the Eurasian cooling response including the Arctic temperature increase, sea-level pressure increase, upper-level jet weakening and cold air outbreak toward the mid-latitude. The reproducibility of these lagged responses by Exp RSI is also evaluated.

  5. Global Optimization of Ventricular Myocyte Model to Multi-Variable Objective Improves Predictions of Drug-Induced Torsades de Pointes

    Directory of Open Access Journals (Sweden)

    Trine Krogh-Madsen


    Full Text Available In silico cardiac myocyte models present powerful tools for drug safety testing and for predicting phenotypical consequences of ion channel mutations, but their accuracy is sometimes limited. For example, several models describing human ventricular electrophysiology perform poorly when simulating effects of long QT mutations. Model optimization represents one way of obtaining models with stronger predictive power. Using a recent human ventricular myocyte model, we demonstrate that model optimization to clinical long QT data, in conjunction with physiologically-based bounds on intracellular calcium and sodium concentrations, better constrains model parameters. To determine if the model optimized to congenital long QT data better predicts risk of drug-induced long QT arrhythmogenesis, in particular Torsades de Pointes risk, we tested the optimized model against a database of known arrhythmogenic and non-arrhythmogenic ion channel blockers. When doing so, the optimized model provided an improved risk assessment. In particular, we demonstrate an elimination of false-positive outcomes generated by the baseline model, in which simulations of non-torsadogenic drugs, in particular verapamil, predict action potential prolongation. Our results underscore the importance of currents beyond those directly impacted by a drug block in determining torsadogenic risk. Our study also highlights the need for rich data in cardiac myocyte model optimization and substantiates such optimization as a method to generate models with higher accuracy of predictions of drug-induced cardiotoxicity.

  6. Improvement in simulation of Eurasian winter climate variability with a realistic Arctic sea ice condition in an atmospheric GCM

    International Nuclear Information System (INIS)

    Lim, Young-Kwon; Ham, Yoo-Geun; Jeong, Jee-Hoon; Kug, Jong-Seong


    The present study investigates how much a realistic Arctic sea ice condition can contribute to improve simulation of the winter climate variation over the Eurasia region. Model experiments are set up using different sea ice boundary conditions over the past 24 years (i.e., 1988–2011). One is an atmospheric model inter-comparison (AMIP) type of run forced with observed sea-surface temperature (SST), sea ice, and greenhouse gases (referred to as Exp RSI), and the other is the same as Exp RSI except for the sea ice forcing, which is a repeating climatological annual cycle (referred to as Exp CSI). Results show that Exp RSI produces the observed dominant pattern of Eurasian winter temperatures and their interannual variation better than Exp CSI (correlation difference up to ∼0.3). Exp RSI captures the observed strong relationship between the sea ice concentration near the Barents and Kara seas and the temperature anomaly across Eurasia, including northeastern Asia, which is not well captured in Exp CSI. Lagged atmospheric responses to sea ice retreat are examined using observations to understand atmospheric processes for the Eurasian cooling response including the Arctic temperature increase, sea-level pressure increase, upper-level jet weakening and cold air outbreak toward the mid-latitude. The reproducibility of these lagged responses by Exp RSI is also evaluated. (letter)

  7. Heterologous Expression of Two Jatropha Aquaporins Imparts Drought and Salt Tolerance and Improves Seed Viability in Transgenic Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Kasim Khan

    Full Text Available Drought and high salinity are environmental conditions that cause adverse effects on the growth and productivity of crops. Aquaporins are small integral membrane proteins that belong to the family of the major intrinsic proteins (MIPs, with members in animals, plants and microbes, where they facilitate the transport of water and/or small neutral solutes thereby affecting water balance. In this study we characterized two aquaporin genes namely, plasma membrane intrinsic protein (PIP2;7 and tonoplast intrinsic protein TIP1;3 from Jatropha curcas that are localised to the plasma membrane and vacuole respectively. Transgenic Arabidopsis thaliana lines over-expressing JcPIP2;7 and JcTIP1;3 under a constitutive promoter show improved germination under high salt and mannitol compared to control seeds. These transgenic plants also show increased root length under abiotic stress conditions compared to wild type Col-0 plants. Transgenic lines exposed to drought conditions by withholding water for 20 days, were able to withstand water stress and attained normal growth after re-watering unlike control plants which could not survive. Transgenic lines also had better seed yield than control under salt stress. Importantly, seed viability of transgenic plants grown under high salt concentration was 35%-45% compared to less than 5% for control seeds obtained from plants growing under salt stress. The effect of JcPIP2;7 and JcTIP1;3 on improving germination and seed viability in drought and salinity make these important candidates for genetic manipulation of plants for growth in saline soils.

  8. Combining biological and psychosocial baseline variables did not improve prediction of outcome of a very-low-energy diet in a clinic referral population. (United States)

    Sumithran, P; Purcell, K; Kuyruk, S; Proietto, J; Prendergast, L A


    Consistent, strong predictors of obesity treatment outcomes have not been identified. It has been suggested that broadening the range of predictor variables examined may be valuable. We explored methods to predict outcomes of a very-low-energy diet (VLED)-based programme in a clinically comparable setting, using a wide array of pre-intervention biological and psychosocial participant data. A total of 61 women and 39 men (mean ± standard deviation [SD] body mass index: 39.8 ± 7.3 kg/m 2 ) underwent an 8-week VLED and 12-month follow-up. At baseline, participants underwent a blood test and assessment of psychological, social and behavioural factors previously associated with treatment outcomes. Logistic regression, linear discriminant analysis, decision trees and random forests were used to model outcomes from baseline variables. Of the 100 participants, 88 completed the VLED and 42 attended the Week 60 visit. Overall prediction rates for weight loss of ≥10% at weeks 8 and 60, and attrition at Week 60, using combined data were between 77.8 and 87.6% for logistic regression, and lower for other methods. When logistic regression analyses included only baseline demographic and anthropometric variables, prediction rates were 76.2-86.1%. In this population, considering a wide range of biological and psychosocial data did not improve outcome prediction compared to simply-obtained baseline characteristics. © 2017 World Obesity Federation.

  9. Chronic aerobic exercise associated to dietary modification improve endothelial function and eNOS expression in high fat fed hamsters.

    Directory of Open Access Journals (Sweden)

    Beatriz C S Boa

    reactivity was similar between groups, suggesting that only endothelial damage had occurred. Our results indicate that an aerobic routine and/or dietary modification may cause significant improvements to high fat fed animals, diminishing visceral depots, increasing eNOS expression and reducing microcirculatory dysfunction.

  10. The supplementation of low-P diets with microbial 6-phytase expressed in Aspergillus oryzae improves P digestibility in sows. (United States)

    Torrallardona, D; Llauradó, L; Broz, J


    Two trials were conducted to evaluate a novel microbial 6-phytase expressed in Aspergillus oryzae (Ronozyme HiPhos; DSM Nutritional Products, Basel, Switzerland) in gestating and lactating sows. In the first trial, 24 sows (Duroc × Landrace; 223 kg BW) were offered, at 16 d of gestation, a low-P control diet (formulated to provide 4.0 g total P/kg; 1.5 g digestible P/kg) supplemented with 0, 500, or 1000 phytase activity (FYT)/kg of phytase. Two weeks later, fresh feces were sampled from all sows and the apparent total tract digestibility of P was measured using TiO(2) as indigestible marker. Phytase supplementation did not (P > 0.10) affect the total tract digestibility of P but reduced (P phytase. After 2 wk, fresh feces were sampled from all sows and the apparent total tract digestibility of P was measured using TiO(2) as indigestible marker. Phytase supplementation improved (P phytase tested increased the apparent total tract digestibility of P in sows and reduced P excretion in feces.

  11. siRNA associated with immunonanoparticles directed against cd99 antigen improves gene expression inhibition in vivo in Ewing's sarcoma. (United States)

    Ramon, A L; Bertrand, J R; de Martimprey, H; Bernard, G; Ponchel, G; Malvy, C; Vauthier, C


    Ewing's sarcoma is a rare, mostly pediatric bone cancer that presents a chromosome abnormality called EWS/Fli-1, responsible for the development of the tumor. In vivo, tumor growth can be inhibited specifically by delivering small interfering RNA (siRNA) associated with nanoparticles. The aim of the work was to design targeted nanoparticles against the cell membrane glycoprotein cd99, which is overexpressed in Ewing's sarcoma cells to improve siRNA delivery to tumor cells. Biotinylated poly(isobutylcyanoacrylate) nanoparticles were conceived as a platform to design targeted nanoparticles with biotinylated ligands and using the biotin-streptavidin coupling method. The targeted nanoparticles were validated in vivo for the targeted delivery of siRNA after systemic administration to mice bearing a tumor model of the Ewing's sarcoma. The expression of the gene responsible of Ewing's sarcoma was inhibited at 78% ± 6% by associating the siRNA with the cd99-targeted nanoparticles compared with an inhibition of only 41% ± 9% achieved with the nontargeted nanoparticles. Copyright © 2013 John Wiley & Sons, Ltd.

  12. Variable wide range of lens power and its improvement in a liquid-crystal lens using highly resistive films divided into two regions with different diameters (United States)

    Kawamura, Marenori; Sato, Susumu


    The variable range of lens power of a liquid-crystal (LC) lens driven by two voltages is discussed on the basis of calculated and experimental results. The LC lens has two electrodes, which are a circularly hole-patterned electrode and a circular electrode, in addition to a common electrode, and highly resistive transparent films. The variable range of lens power increases with increasing driving voltage applied across the circularly hole-patterned electrode and the common electrode, and with decreasing diameter of highly resistive films. However, the optical-phase retardation profile tends to deviate from a parabolic curve in these cases. As a method to improve the trade-off properties, the highly resistive film is divided into two regions with different diameters, where the sheet resistance of an outer film is larger than that of an inner one. The improved LC lens has a lens power that varies in a wide range, and it exhibits a good parabolic phase retardation profile.

  13. An exploratory, large-scale study of pain and quality of life outcomes in cancer patients with moderate or severe pain, and variables predicting improvement. (United States)

    Maximiano, Constanza; López, Iker; Martín, Cristina; Zugazabeitia, Luis; Martí-Ciriquián, Juan L; Núñez, Miguel A; Contreras, Jorge; Herdman, Michael; Traseira, Susana; Provencio, Mariano


    There have been few large-scale, real world studies in Spain to assess change in pain and quality of life (QOL) outcomes in cancer patients with moderate to severe pain. This study aimed to assess changes on both outcomes after 3 months of usual care and to investigate factors associated with change in QoL. Large, multi-centre, observational study in patients with lung, head and neck, colorectal or breast cancer experiencing a first episode of moderate to severe pain while attending one of the participating centres. QoL was assessed using the EuroQol-5D questionnaire and pain using the Brief Pain Inventory (BPI). Instruments were administered at baseline and after 3 months of follow up. Multivariate analyses were used to assess the impact of treatment factors, demographic and clinical variables, pain and other symptoms on QoL scores. 1711 patients were included for analysis. After 3 months of usual care, a significant improvement was observed in pain and QoL in all four cancer groups (pbreast cancer patients showed the largest gains. Poorer baseline performance status (ECOG) and the presence of anxiety/depression were associated with significantly poorer QOL outcomes. Improvements in BPI pain scores were associated with improved QoL. In the four cancer types studied, pain and QoL outcomes improved considerably after 3 months of usual care. Improvements in pain made a substantial contribution to QoL gains whilst the presence of anxiety and depression and poor baseline performance status significantly constrained improvement.

  14. Expression and Purification of Glycosyltransferases in Pichia Pastoris: Towards Improving the Migration of Stem Cells by Enhancing Surface Expression of Sialyl Lewis X

    KAUST Repository

    Al-Amoodi, Asma S.


    Recruitment of circulating cells towards target sites is primarily dependent on E-selectin receptor/ligand adhesive interactions. Glycosyltransferase (GTs) are involved in the creation of E-selectin ligands. A sialofucosylated terminal tetrasaccharide like glycan structure known as sialyl Lewis x (sLex), is the most recognized ligand by selectins. This structure is found on the surface of cancer cells and leukocytes but is often absent on the surface of many adult stem cell populations. In order to synthesize sLex, GTs must be endogenously expressed and remain active within the cells. Generally, these stem cells express terminal sialylated lactosamine structures on their glycoproteins which require the addition of alpha-(1,3)-fucose to be converted into an E-selectin ligand. There are a number of fucosyltransferases (FUTs) that are able to modify terminal lactosamine structures to create sLex such as FUT6. In this work we focused on expressing and purifying active recombinant FUTs as a tool to help create sLex structures on the surface of adult stem cells in order to enhance their migration.

  15. Endoglucanase enzyme protein engineering by site-directed mutagenesis to improve the enzymatic properties and its expression in yeast

    Directory of Open Access Journals (Sweden)

    Farnaz Nikzad Jamnani


    Full Text Available Introduction: Fossil fuel is an expensive and finite energy source. Therefore, the use of renewable energy and biofuels production has been taken into consideration. One of the most suitable raw materials for biofuels is cellulosic compounds. Only microorganisms that contain cellulose enzymes can decompose cellulose and fungus of Trichodermareesei is the most important producer of this enzyme. Methods: In this study the nucleotide sequence of endoglucanase II, which is the starter of attack to cellulose chains, synthesized from amino acid sequence of this enzyme in fungus T.reesei and based on codon usage in the host; yeast Pichiapastoris. To produce optimized enzyme and to decrease the production time and enzyme price, protein engineering will be used. There are some methods to improve the enzymatic properties like site-directed mutagenesis in which amino-acid replacement occur. In this study two mutations were induced in endoglucanase enzyme gene by PCR in which free syctein positions 169 and 393 were switched to valine and histidine respectively. Then this gene was inserted into the pPinka expression vector and cloned in Escherichia coli. The recombinant plasmids were transferred into P.pastoris competent cells with electroporation, recombinant yeasts were cultured in BMMY medium and induced with methanol. Results: The sequencing of gene proved the induction of the two mutations and the presence of recombinant enzyme was confirmed by dinitrosalicilic acid method and SDS-PAGE. Conclusion: Examination of biochemical properties revealed that the two mutations simultaneously decreased catalytic power, thermal stability and increased the affinity of enzyme and substrate.

  16. Reduction-sensitive lipopolyamines as a novel nonviral gene delivery system for modulated release of DNA with improved transgene expression. (United States)

    Byk, G; Wetzer, B; Frederic, M; Dubertret, C; Pitard, B; Jaslin, G; Scherman, D


    We have designed and synthesized original cationic lipids for modulated release of DNA from cationic lipid/DNA complexes. Our rationale was that modulated degradation of the lipids during or after penetration into the cell could improve the trafficking of DNA to the nucleus resulting in increased transgene expression. The new reduction-sensitive lipopolyamines (RSL) harbor a disulfide bridge within different positions in the backbone of the lipids as biosensitive function. A useful synthetic method was developed to obtain, with very good yields and reproducibility, unsymmetrical disulfide-bridged molecules, starting from symmetrical disulfides and thiols. The new lipopolyamines are good candidates as carriers of therapeutic genes for in vivo gene delivery. To optimize the transfection efficiency in these novel series, we have carried out structure-activity relationship studies by placing the disulfide bridge at different positions in the backbone of the cationic lipid and by systematic variation of lipid chain length. Results indicate that the transfection level can be modulated as a function of the location of the disulfide bridge in the molecule. We suggest that an early release of DNA during or after penetration into the cell, probably promoted by reduction of a disulfide bridge placed between the polyamine and the lipid, implies a total loss of transfection efficiency. On the other hand, proper modulation of DNA release by inserting the disulfide bridge between one lipid chain and the rest of the molecule brings about increased transfection efficiency as compared to previously described nondegradable lipopolyamine analogues. Finally, preliminary physicochemical characterization of the complexes demonstrates that DNA release from complexes can be modulated as a function of the surrounding reducing conditions of the complexes and of the localization of the disulfide bridge within the lipopolyamine. Our results suggest that RSL is a promising new approach for gene

  17. Winner's Curse Correction and Variable Thresholding Improve Performance of Polygenic Risk Modeling Based on Genome-Wide Association Study Summary-Level Data.

    Directory of Open Access Journals (Sweden)

    Jianxin Shi


    Full Text Available Recent heritability analyses have indicated that genome-wide association studies (GWAS have the potential to improve genetic risk prediction for complex diseases based on polygenic risk score (PRS, a simple modelling technique that can be implemented using summary-level data from the discovery samples. We herein propose modifications to improve the performance of PRS. We introduce threshold-dependent winner's-curse adjustments for marginal association coefficients that are used to weight the single-nucleotide polymorphisms (SNPs in PRS. Further, as a way to incorporate external functional/annotation knowledge that could identify subsets of SNPs highly enriched for associations, we propose variable thresholds for SNPs selection. We applied our methods to GWAS summary-level data of 14 complex diseases. Across all diseases, a simple winner's curse correction uniformly led to enhancement of performance of the models, whereas incorporation of functional SNPs was beneficial only for selected diseases. Compared to the standard PRS algorithm, the proposed methods in combination led to notable gain in efficiency (25-50% increase in the prediction R2 for 5 of 14 diseases. As an example, for GWAS of type 2 diabetes, winner's curse correction improved prediction R2 from 2.29% based on the standard PRS to 3.10% (P = 0.0017 and incorporating functional annotation data further improved R2 to 3.53% (P = 2×10-5. Our simulation studies illustrate why differential treatment of certain categories of functional SNPs, even when shown to be highly enriched for GWAS-heritability, does not lead to proportionate improvement in genetic risk-prediction because of non-uniform linkage disequilibrium structure.

  18. Expression of Aspergillus hemoglobin domain activities in Aspergillus oryzae grown on solid substrates improves growth rate and enzyme production

    NARCIS (Netherlands)

    Biesebeke, te R.; Boussier, A.; Biezen van, N.; Braaksma, M.; Hondel, van den C.A.M.J.J.; Vos, de W.M.; Punt, P.J.


    DNA fragments coding for hemoglobin domains (HBD) were isolated from Aspergillus oryzae and Aspergillus niger. The HBD activities were expressed in A. oryzae by introduction of HBD gene fragments under the control of the promoter of the constitutively expressed gpdA gene. In the transformants,

  19. Tide Gauge Records Reveal Improved Processing of Gravity Recovery and Climate Experiment Time-Variable Mass Solutions over the Coastal Ocean (United States)

    Piecuch, Christopher G.; Landerer, Felix W.; Ponte, Rui M.


    Monthly ocean bottom pressure solutions from the Gravity Recovery and Climate Experiment (GRACE), derived using surface spherical cap mass concentration (MC) blocks and spherical harmonics (SH) basis functions, are compared to tide gauge (TG) monthly averaged sea level data over 2003-2015 to evaluate improved gravimetric data processing methods near the coast. MC solutions can explain ≳ 42% of the monthly variance in TG time series over broad shelf regions and in semi-enclosed marginal seas. MC solutions also generally explain ˜5-32 % more TG data variance than SH estimates. Applying a coastline resolution improvement algorithm in the GRACE data processing leads to ˜ 31% more variance in TG records explained by the MC solution on average compared to not using this algorithm. Synthetic observations sampled from an ocean general circulation model exhibit similar patterns of correspondence between modeled TG and MC time series and differences between MC and SH time series in terms of their relationship with TG time series, suggesting that observational results here are generally consistent with expectations from ocean dynamics. This work demonstrates the improved quality of recent MC solutions compared to earlier SH estimates over the coastal ocean, and suggests that the MC solutions could be a useful tool for understanding contemporary coastal sea level variability and change.

  20. Does social trust increase willingness to pay taxes to improve public healthcare? Cross-sectional cross-country instrumental variable analysis. (United States)

    Habibov, Nazim; Cheung, Alex; Auchynnikava, Alena


    The purpose of this paper is to investigate the effect of social trust on the willingness to pay more taxes to improve public healthcare in post-communist countries. The well-documented association between higher levels of social trust and better health has traditionally been assumed to reflect the notion that social trust is positively associated with support for public healthcare system through its encouragement of cooperative behaviour, social cohesion, social solidarity, and collective action. Hence, in this paper, we have explicitly tested the notion that social trust contributes to an increase in willingness to financially support public healthcare. We use micro data from the 2010 Life-in-Transition survey (N = 29,526). Classic binomial probit and instrumental variables ivprobit regressions are estimated to model the relationship between social trust and paying more taxes to improve public healthcare. We found that an increase in social trust is associated with a greater willingness to pay more taxes to improve public healthcare. From the perspective of policy-making, healthcare administrators, policy-makers, and international donors should be aware that social trust is an important factor in determining the willingness of the population to provide much-needed financial resources to supporting public healthcare. From a theoretical perspective, we found that estimating the effect of trust on support for healthcare without taking confounding and measurement error problems into consideration will likely lead to an underestimation of the true effect of trust. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Improved imaging of cochlear nerve hypoplasia using a 3-Tesla variable flip-angle turbo spin-echo sequence and a 7-cm surface coil. (United States)

    Giesemann, Anja M; Raab, Peter; Lyutenski, Stefan; Dettmer, Sabine; Bültmann, Eva; Frömke, Cornelia; Lenarz, Thomas; Lanfermann, Heinrich; Goetz, Friedrich


    Magnetic resonance imaging of the temporal bone has an important role in decision making with regard to cochlea implantation, especially in children with cochlear nerve deficiency. The purpose of this study was to evaluate the usefulness of the combination of an advanced high-resolution T2-weighted sequence with a surface coil in a 3-Tesla magnetic resonance imaging scanner in cases of suspected cochlear nerve aplasia. Prospective study. Seven patients with cochlear nerve hypoplasia or aplasia were prospectively examined using a high-resolution three-dimensional variable flip-angle turbo spin-echo sequence using a surface coil, and the images were compared with the same sequence in standard resolution using a standard head coil. Three neuroradiologists evaluated the magnetic resonance images independently, rating the visibility of the nerves in diagnosing hypoplasia or aplasia. Eight ears in seven patients with hypoplasia or aplasia of the cochlear nerve were examined. The average age was 2.7 years (range, 9 months-5 years). Seven ears had accompanying malformations. The inter-rater reliability in diagnosing hypoplasia or aplasia was greater using the high-resolution three-dimensional variable flip-angle turbo spin-echo sequence (fixed-marginal kappa: 0.64) than with the same sequence in lower resolution (fixed-marginal kappa: 0.06). Examining cases of suspected cochlear nerve aplasia using the high-resolution three-dimensional variable flip-angle turbo spin-echo sequence in combination with a surface coil shows significant improvement over standard methods. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

  2. An Improved Collocation Meshless Method Based on the Variable Shaped Radial Basis Function for the Solution of the Interior Acoustic Problems

    Directory of Open Access Journals (Sweden)

    Shuang Wang


    Full Text Available As an efficient tool, radial basis function (RBF has been widely used for the multivariate approximation, interpolating continuous, and the solution of the particle differential equations. However, ill-conditioned interpolation matrix may be encountered when the interpolation points are very dense or irregularly arranged. To avert this problem, RBFs with variable shape parameters are introduced, and several new variation strategies are proposed. Comparison with the RBF with constant shape parameters are made, and the results show that the condition number of the interpolation matrix grows much slower with our strategies. As an application, an improved collocation meshless method is formulated by employing the new RBF. In addition, the Hermite-type interpolation is implemented to handle the Neumann boundary conditions and an additional sine/cosine basis is introduced for the Helmlholtz equation. Then, two interior acoustic problems are solved with the presented method; the results demonstrate the robustness and effectiveness of the method.

  3. Ectopic expression of Arabidopsis broad-spectrum resistance gene RPW8.2 improves the resistance to powdery mildew in grapevine (Vitis vinifera). (United States)

    Hu, Yang; Li, Yajuan; Hou, Fengjuan; Wan, Dongyan; Cheng, Yuan; Han, Yongtao; Gao, Yurong; Liu, Jie; Guo, Ye; Xiao, Shunyuan; Wang, Yuejin; Wen, Ying-Qiang


    Powdery mildew is the most economically important disease of cultivated grapevines worldwide. Here, we report that the Arabidopsis broad-spectrum disease resistance gene RPW8.2 could improve resistance to powdery mildew in Vitis vinifera cv. Thompson Seedless. The RPW8.2-YFP fusion gene was stably expressed in grapevines from either the constitutive 35S promoter or the native promoter (NP) of RPW8.2. The grapevine shoots and plantlets transgenic for 35S::RPW8.2-YFP showed reduced rooting and reduced growth at later development stages in the absence of any pathogens. Infection tests with an adapted grapevine powdery mildew isolate En NAFU1 showed that hyphal growth and sporulation were significantly restricted in transgenic grapevines expressing either of the two constructs. The resistance appeared to be attributable to the ectopic expression of RPW8.2, and associated with the enhanced encasement of the haustorial complex (EHC) and onsite accumulation of H 2 O 2 . In addition, the RPW8.2-YFP fusion protein showed focal accumulation around the fungal penetration sites. Transcriptome analysis revealed that ectopic expression of RPW8.2 in grapevines not only significantly enhanced salicylic acid-dependent defense signaling, but also altered expression of other phytohormone-associated genes. Taken together, our results indicate that RPW8.2 could be utilized as a transgene for improving resistance against powdery mildew in grapevines. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. High RBM3 expression is associated with an improved survival and oxaliplatin response in patients with metastatic colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Christina Siesing

    Full Text Available High expression of the RNA-binding motif protein 3 (RBM3 has been shown to correlate, with prolonged survival in several malignant diseases and with the benefit of platinum-based chemotherapy in ovarian cancer. The aim of this study was to evaluate RBM3 in metastatic colorectal cancer (mCRC as a prognostic factor for overall survival and in relation to benefit of first-line chemotherapy.Immunohistochemical staining was conducted and evaluated in tumours from 455 mCRC patients. Kaplan-Meier analysis and Cox regression proportional hazards models were used to access the impact of RBM3 expression on overall survival (OS and progression-free survival (PFS.High RBM3 expression, both nuclear and cytoplasmic, was an independent prognostic factor for prolonged OS (hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.50-0.90 and HR 0.66, 95% CI 0.48-0.91, respectively. PFS was significantly longer in patients with high RBM3 expression who had received first-line oxaliplatin based treatment, compared to those who had received irinotecan based treatment, both regarding nuclear and cytoplasmic expression (p-value 0.020 and 0.022 respectively.High RBM3 expression is an independent predictor of prolonged survival in mCRC patients, in particular in patients treated with first-line oxaliplatin based chemotherapy.

  5. Expression of the Arabidopsis vacuolar H+-pyrophosphatase gene (AVP1) improves the shoot biomass of transgenic barley and increases grain yield in a saline field

    KAUST Repository

    Schilling, Rhiannon K.


    Cereal varieties with improved salinity tolerance are needed to achieve profitable grain yields in saline soils. The expression of AVP1, an Arabidopsis gene encoding a vacuolar proton pumping pyrophosphatase (H+-PPase), has been shown to improve the salinity tolerance of transgenic plants in greenhouse conditions. However, the potential for this gene to improve the grain yield of cereal crops in a saline field has yet to be evaluated. Recent advances in high-throughput nondestructive phenotyping technologies also offer an opportunity to quantitatively evaluate the growth of transgenic plants under abiotic stress through time. In this study, the growth of transgenic barley expressing AVP1 was evaluated under saline conditions in a pot experiment using nondestructive plant imaging and in a saline field trial. Greenhouse-grown transgenic barley expressing AVP1 produced a larger shoot biomass compared to segregants, as determined by an increase in projected shoot area, when grown in soil with 150 mm NaCl. This increase in shoot biomass of transgenic AVP1 barley occurred from an early growth stage and also in nonsaline conditions. In a saline field, the transgenic barley expressing AVP1 also showed an increase in shoot biomass and, importantly, produced a greater grain yield per plant compared to wild-type plants. Interestingly, the expression of AVP1 did not alter barley leaf sodium concentrations in either greenhouse- or field-grown plants. This study validates our greenhouse-based experiments and indicates that transgenic barley expressing AVP1 is a promising option for increasing cereal crop productivity in saline fields. © 2013 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  6. JBP485 improves gentamicin-induced acute renal failure by regulating the expression and function of Oat1 and Oat3 in rats

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Xinjin [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian (China); Meng, Qiang; Liu, Qi; Wang, Changyuan; Sun, Huijun; Peng, Jinyong; Ma, Xiaochi [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Dalian Medical University, Liaoning (China); Kaku, Taiichi [Japan Bioproducts Industry Co. Ltd., Tomigaya, Shibuya-ku, Tokyo (Japan); Liu, Kexin, E-mail: [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Dalian Medical University, Liaoning (China)


    We investigated the effects of JBP485 (an anti-inflammatory dipeptide and a substrate of OAT) on regulation of the expression and function of renal Oat1 and Oat3, which can accelerate the excretion of accumulated uremic toxins (e.g. indoxyl sulfate) in the kidney to improve gentamicin-induced ARF in rats. JBP485 caused a significant decrease in the accumulation of endogenous substances (creatinine, blood urea nitrogen and indoxyl sulfate) in vivo, an increase in the excretion of exogenous compounds (lisinopril and inulin) into urine, and up-regulation of the expressions of renal Oat1 and Oat3 in the kidney tissues and slices via substrate induction. To determine the effect of JBP485 on the accelerated excretion of uremic toxins mediated by Oat1 and Oat3, the mRNA and protein expression levels of renal basolateral Oats were assessed by quantitative real-time PCR, western blot, immunohistochemical analysis and an immunofluorescence method. Gentamicin down-regulated the expression of Oats mRNA and protein in rat kidney, and these effects were reversed after administration of JBP485. In addition, JBP485 caused a significant decrease in MPO and MDA levels in the kidney, and improved the pathological condition of rat kidney. These results indicated that JBP485 improved acute renal failure by increasing the expression and function of Oat1 and Oat3, and by decreasing overoxidation of the kidney in gentamicin-induced ARF rats. - Highlights: • JBP485 could up-regulate function and expression of Oat1 and Oat3 in kidney. • Effects of JBP485 on ARF are mediated by stimulating excretion of uremic toxins. • JBP485 protected against gentamicin-induced ARF by decreasing MPO and MDA.

  7. Expression of the Arabidopsis vacuolar H+-pyrophosphatase gene (AVP1) improves the shoot biomass of transgenic barley and increases grain yield in a saline field

    KAUST Repository

    Schilling, Rhiannon K.; Marschner, Petra; Shavrukov, Yuri N.; Berger, Bettina; Tester, Mark A.; Roy, Stuart John; Plett, Darren Craig


    Cereal varieties with improved salinity tolerance are needed to achieve profitable grain yields in saline soils. The expression of AVP1, an Arabidopsis gene encoding a vacuolar proton pumping pyrophosphatase (H+-PPase), has been shown to improve the salinity tolerance of transgenic plants in greenhouse conditions. However, the potential for this gene to improve the grain yield of cereal crops in a saline field has yet to be evaluated. Recent advances in high-throughput nondestructive phenotyping technologies also offer an opportunity to quantitatively evaluate the growth of transgenic plants under abiotic stress through time. In this study, the growth of transgenic barley expressing AVP1 was evaluated under saline conditions in a pot experiment using nondestructive plant imaging and in a saline field trial. Greenhouse-grown transgenic barley expressing AVP1 produced a larger shoot biomass compared to segregants, as determined by an increase in projected shoot area, when grown in soil with 150 mm NaCl. This increase in shoot biomass of transgenic AVP1 barley occurred from an early growth stage and also in nonsaline conditions. In a saline field, the transgenic barley expressing AVP1 also showed an increase in shoot biomass and, importantly, produced a greater grain yield per plant compared to wild-type plants. Interestingly, the expression of AVP1 did not alter barley leaf sodium concentrations in either greenhouse- or field-grown plants. This study validates our greenhouse-based experiments and indicates that transgenic barley expressing AVP1 is a promising option for increasing cereal crop productivity in saline fields. © 2013 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  8. Expression profiling analysis: Uncoupling protein 2 deficiency improves hepatic glucose, lipid profiles and insulin sensitivity in high-fat diet-fed mice by modulating expression of genes in peroxisome proliferator-activated receptor signaling pathway. (United States)

    Zhou, Mei-Cen; Yu, Ping; Sun, Qi; Li, Yu-Xiu


    Uncoupling protein 2 (UCP2), which was an important mitochondrial inner membrane protein associated with glucose and lipid metabolism, widely expresses in all kinds of tissues including hepatocytes. The present study aimed to explore the impact of UCP2 deficiency on glucose and lipid metabolism, insulin sensitivity and its effect on the liver-associated signaling pathway by expression profiling analysis. Four-week-old male UCP2-/- mice and UCP2+/+ mice were randomly assigned to four groups: UCP2-/- on a high-fat diet, UCP2-/- on a normal chow diet, UCP2+/+ on a high-fat diet and UCP2+/+ on a normal chow diet. The differentially expressed genes in the four groups on the 16th week were identified by Affymetrix gene array. The results of intraperitoneal glucose tolerance test and insulin tolerance showed that blood glucose and β-cell function were improved in the UCP2-/- group on high-fat diet. Enhanced insulin sensitivity was observed in the UCP2-/- group. The differentially expressed genes were mapped to 23 pathways (P high-fat diet. The upregulation of genes in the PPAR signaling pathway could explain our finding that UCP2 deficiency ameliorated insulin sensitivity. The manipulation of UCP2 protein expression could represent a new strategy for the prevention and treatment of diabetes.

  9. Can the Five Factor Model of Personality Account for the Variability of Autism Symptom Expression? Multivariate Approaches to Behavioral Phenotyping in Adult Autism Spectrum Disorder (United States)

    Schwartzman, Benjamin C.; Wood, Jeffrey J.; Kapp, Steven K.


    The present study aimed to: determine the extent to which the five factor model of personality (FFM) accounts for variability in autism spectrum disorder (ASD) symptomatology in adults, examine differences in average FFM personality traits of adults with and without ASD and identify distinct behavioral phenotypes within ASD. Adults (N = 828;…

  10. A breast cancer meta-analysis of two expression measures of chromosomal instability reveals a relationship with younger age at diagnosis and high risk histopathological variables

    DEFF Research Database (Denmark)

    Endesfelder, David; McGranahan, Nicholas; Birkbak, Nicolai Juul


    Breast cancer in younger patients often presents with adverse histopathological features, including increased frequency of estrogen receptor negative and lymph node positive disease status. Chromosomal instability (CIN) is increasingly recognised as an important prognostic variable in solid tumours...... may be a defining feature of breast cancer biology and clinical outcome....

  11. Multi variable control of a switched ignition device: efficiency improvement under various constraints; Commande multivariable d`un moteur a allumage commande: Amelioration du rendement sous differentes contraintes

    Energy Technology Data Exchange (ETDEWEB)

    Chaumerliac, V


    Spark-ignition engine control needs substantial improvement for various reasons: a non-linear and multivariable process, the strictness of anti-pollution constraints, the necessity of fuel economy, the variable running conditions, the aging, the reliability and the cost. The improvement of engine efficiency will be involved in this context and with the pollution constraints. This work develops a system approach and its philosophy is based on a suitable description of the main dynamics. A compartmentalized model of a spark-ignition engine and the dynamic of the vehicle is presented. The aim of this modeling is to have a good representativeness in transients and to describe the behavior of the outputs useful for control. The multivariable control is split in two independent systems. The first one controls the spark advance control to obtain the maximum torque. The second one controls the throttle and the electronic fuel injection device to have lower pollutant emissions. The spark advance closed loop control uses information measured with either a cylinder pressure sensor or a torque sensor. These studies have achieved to an adaptive tuning on engine bench. A new actuator, the electronic throttle control, can provide a higher degree of precision for the fuel/air ratio regulation system, particularly during fast accelerations and decelerations. An intake manifold pressure control is developed to coordinate the air and fuel flows. A delay strategy and a simple compensation of fuel supply dynamics allow to obtain good results on engine bench. Uncoupling the acceleration pedal and the throttle command is a promising way to improve engine efficiency and reduce exhaust emission during transient phases. (author) 59 refs.

  12. Social Anxiety and Positive Emotions: A Prospective Examination of a Self-Regulatory Model with Tendencies to Suppress or Express Emotions as a Moderating Variable (United States)

    Kashdan, Todd B.; Breen, William E.


    The purpose of the present study was to examine social anxiety as a predictor of positive emotions using a short-term prospective design. We examined whether the effects of social anxiety on positive emotions are moderated by tendencies to openly express or suppress emotions. Over the course of a 3-month interval, people with excessive social…

  13. Chance-constrained overland flow modeling for improving conceptual distributed hydrologic simulations based on scaling representation of sub-daily rainfall variability

    International Nuclear Information System (INIS)

    Han, Jing-Cheng; Huang, Guohe; Huang, Yuefei; Zhang, Hua; Li, Zhong; Chen, Qiuwen


    Lack of hydrologic process representation at the short time-scale would lead to inadequate simulations in distributed hydrological modeling. Especially for complex mountainous watersheds, surface runoff simulations are significantly affected by the overland flow generation, which is closely related to the rainfall characteristics at a sub-time step. In this paper, the sub-daily variability of rainfall intensity was considered using a probability distribution, and a chance-constrained overland flow modeling approach was proposed to capture the generation of overland flow within conceptual distributed hydrologic simulations. The integrated modeling procedures were further demonstrated through a watershed of China Three Gorges Reservoir area, leading to an improved SLURP-TGR hydrologic model based on SLURP. Combined with rainfall thresholds determined to distinguish various magnitudes of daily rainfall totals, three levels of significance were simultaneously employed to examine the hydrologic-response simulation. Results showed that SLURP-TGR could enhance the model performance, and the deviation of runoff simulations was effectively controlled. However, rainfall thresholds were so crucial for reflecting the scaling effect of rainfall intensity that optimal levels of significance and rainfall threshold were 0.05 and 10 mm, respectively. As for the Xiangxi River watershed, the main runoff contribution came from interflow of the fast store. Although slight differences of overland flow simulations between SLURP and SLURP-TGR were derived, SLURP-TGR was found to help improve the simulation of peak flows, and would improve the overall modeling efficiency through adjusting runoff component simulations. Consequently, the developed modeling approach favors efficient representation of hydrological processes and would be expected to have a potential for wide applications. - Highlights: • We develop an improved hydrologic model considering the scaling effect of rainfall. • A

  14. Chance-constrained overland flow modeling for improving conceptual distributed hydrologic simulations based on scaling representation of sub-daily rainfall variability

    Energy Technology Data Exchange (ETDEWEB)

    Han, Jing-Cheng [State Key Laboratory of Hydroscience & Engineering, Department of Hydraulic Engineering, Tsinghua University, Beijing 100084 (China); Huang, Guohe, E-mail: [Institute for Energy, Environment and Sustainable Communities, University of Regina, Regina, Saskatchewan S4S 0A2 (Canada); Huang, Yuefei [State Key Laboratory of Hydroscience & Engineering, Department of Hydraulic Engineering, Tsinghua University, Beijing 100084 (China); Zhang, Hua [College of Science and Engineering, Texas A& M University — Corpus Christi, Corpus Christi, TX 78412-5797 (United States); Li, Zhong [Institute for Energy, Environment and Sustainable Communities, University of Regina, Regina, Saskatchewan S4S 0A2 (Canada); Chen, Qiuwen [Center for Eco-Environmental Research, Nanjing Hydraulics Research Institute, Nanjing 210029 (China)


    Lack of hydrologic process representation at the short time-scale would lead to inadequate simulations in distributed hydrological modeling. Especially for complex mountainous watersheds, surface runoff simulations are significantly affected by the overland flow generation, which is closely related to the rainfall characteristics at a sub-time step. In this paper, the sub-daily variability of rainfall intensity was considered using a probability distribution, and a chance-constrained overland flow modeling approach was proposed to capture the generation of overland flow within conceptual distributed hydrologic simulations. The integrated modeling procedures were further demonstrated through a watershed of China Three Gorges Reservoir area, leading to an improved SLURP-TGR hydrologic model based on SLURP. Combined with rainfall thresholds determined to distinguish various magnitudes of daily rainfall totals, three levels of significance were simultaneously employed to examine the hydrologic-response simulation. Results showed that SLURP-TGR could enhance the model performance, and the deviation of runoff simulations was effectively controlled. However, rainfall thresholds were so crucial for reflecting the scaling effect of rainfall intensity that optimal levels of significance and rainfall threshold were 0.05 and 10 mm, respectively. As for the Xiangxi River watershed, the main runoff contribution came from interflow of the fast store. Although slight differences of overland flow simulations between SLURP and SLURP-TGR were derived, SLURP-TGR was found to help improve the simulation of peak flows, and would improve the overall modeling efficiency through adjusting runoff component simulations. Consequently, the developed modeling approach favors efficient representation of hydrological processes and would be expected to have a potential for wide applications. - Highlights: • We develop an improved hydrologic model considering the scaling effect of rainfall. • A

  15. Improving the performance of industrial ethanol-producing yeast by expressing the aspartyl protease on the cell surface. (United States)

    Guo, Zhong-peng; Zhang, Liang; Ding, Zhong-yang; Wang, Zheng-Xiang; Shi, Gui-Yang


    The yeasts used in fuel ethanol manufacture are unable to metabolize soluble proteins. The PEP4 gene, encoding a vacuolar aspartyl protease in Saccharomyces cerevisiae, was either secretively or cell-surface anchored expressed in industrial ethanol-producing S. cerevisiae. The obtained recombinant strains APA (expressing the protease secretively) and APB (expressing the protease on the cell wall) were studied under ethanol fermentation conditions in feed barley cultures. The effects of expression of the protease on product formation, growth and cell protein content were measured. The biomass yield of the wild-type was clearly lower than that of the recombinant strains (0.578 ± 0.12 g biomass/g glucose for APA and 0.582 ± 0.08 g biomass/g glucose for APB). In addition, nearly 98-99% of the theoretical maximum level of ethanol yield was achieved (relative to the amount of substrate consumed) for the recombinant strains, while limiting the nitrogen source resulted in dissatisfactory fermentation for the wild-type and more than 30 g/l residual sugar was detected at the end of fermentation. In addition, higher growth rate, viability and lower yields of byproducts such as glycerol and pyruvic acid for recombinant strains were observed. Expressing acid protease can be expected to lead to a significant increase in ethanol productivity. Copyright © 2010 John Wiley & Sons, Ltd.

  16. Abnormal histopathology, fat percent and hepatic apolipoprotein A I and apolipoprotein B100 mRNA expression in fatty liver hemorrhagic syndrome and their improvement by soybean lecithin. (United States)

    Song, Yalu; Ruan, Jiming; Luo, Junrong; Wang, Tiancheng; Yang, Fei; Cao, Huabin; Huang, Jianzhen; Hu, Guoliang


    To investigate the etiopathogenesis of fatty liver hemorrhagic syndrome (FLHS) and the protective effects of soybean lecithin against FLHS in laying hens, 135 healthy 300-day-old Hyline laying hens were randomly divided into groups: control (group 1), diseased (group 2), and protected (group 3). Each group contained 45 layers with 3 replicates. The birds in these 3 groups were fed a control diet, a high-energy/low-protein (HELP) diet or the HELP diet supplemented with 3% soybean lecithin instead of maize. The fat percent in the liver was calculated. Histopathological changes in the liver were determined by staining, and the mRNA expression levels of apolipoproteinA I (apoA I) and apolipoprotein B100 (apoB100) in the liver were determined by RT-PCR. The results showed that the fat percent in the liver of group 2 was much higher (P steatosis in the liver cell on d 30 and 60. The mRNA expression levels of apoA I and apoB100 in the livers were variable throughout the experiment. The expression level of apoA I in group 2 significantly decreased on d 60 (P < 0.05); the expression level of apoB100 slightly increased on d 30 in group 2, while it sharply decreased on d 60. Compared to group 1, the expression level of apoB100 showed no significant difference in group 3 (P < 0.05). This study indicated that FLHS induced pathological changes and abnormal expression of apoA I and apoB100 in the livers of laying hens and that soybean lecithin alleviated these abnormal changes. © 2017 Poultry Science Association Inc.

  17. Modification of the Creator recombination system for proteomics applications – improved expression by addition of splice sites (United States)

    Colwill, Karen; Wells, Clark D; Elder, Kelly; Goudreault, Marilyn; Hersi, Kadija; Kulkarni, Sarang; Hardy, W Rod; Pawson, Tony; Morin, Gregg B


    Background Recombinational systems have been developed to rapidly shuttle Open Reading Frames (ORFs) into multiple expression vectors in order to analyze the large number of cDNAs available in the post-genomic era. In the Creator system, an ORF introduced into a donor vector can be transferred with Cre recombinase to a library of acceptor vectors optimized for different applications. Usability of the Creator system is impacted by the ability to easily manipulate DNA, the number of acceptor vectors for downstream applications, and the level of protein expression from Creator vectors. Results To date, we have developed over 20 novel acceptor vectors that employ a variety of promoters and epitope tags commonly employed for proteomics applications and gene function analysis. We also made several enhancements to the donor vectors including addition of different multiple cloning sites to allow shuttling from pre-existing vectors and introduction of the lacZ alpha reporter gene to allow for selection. Importantly, in order to ameliorate any effects on protein expression of the loxP site between a 5' tag and ORF, we introduced a splicing event into our expression vectors. The message produced from the resulting 'Creator Splice' vector undergoes splicing in mammalian systems to remove the loxP site. Upon analysis of our Creator Splice constructs, we discovered that protein expression levels were also significantly increased. Conclusion The development of new donor and acceptor vectors has increased versatility during the cloning process and made this system compatible with a wider variety of downstream applications. The modifications introduced in our Creator Splice system were designed to remove extraneous sequences due to recombination but also aided in downstream analysis by increasing protein expression levels. As a result, we can now employ epitope tags that are detected less efficiently and reduce our assay scale to allow for higher throughput. The Creator Splice

  18. Modification of the Creator recombination system for proteomics applications--improved expression by addition of splice sites. (United States)

    Colwill, Karen; Wells, Clark D; Elder, Kelly; Goudreault, Marilyn; Hersi, Kadija; Kulkarni, Sarang; Hardy, W Rod; Pawson, Tony; Morin, Gregg B


    Recombinational systems have been developed to rapidly shuttle Open Reading Frames (ORFs) into multiple expression vectors in order to analyze the large number of cDNAs available in the post-genomic era. In the Creator system, an ORF introduced into a donor vector can be transferred with Cre recombinase to a library of acceptor vectors optimized for different applications. Usability of the Creator system is impacted by the ability to easily manipulate DNA, the number of acceptor vectors for downstream applications, and the level of protein expression from Creator vectors. To date, we have developed over 20 novel acceptor vectors that employ a variety of promoters and epitope tags commonly employed for proteomics applications and gene function analysis. We also made several enhancements to the donor vectors including addition of different multiple cloning sites to allow shuttling from pre-existing vectors and introduction of the lacZ alpha reporter gene to allow for selection. Importantly, in order to ameliorate any effects on protein expression of the loxP site between a 5' tag and ORF, we introduced a splicing event into our expression vectors. The message produced from the resulting 'Creator Splice' vector undergoes splicing in mammalian systems to remove the loxP site. Upon analysis of our Creator Splice constructs, we discovered that protein expression levels were also significantly increased. The development of new donor and acceptor vectors has increased versatility during the cloning process and made this system compatible with a wider variety of downstream applications. The modifications introduced in our Creator Splice system were designed to remove extraneous sequences due to recombination but also aided in downstream analysis by increasing protein expression levels. As a result, we can now employ epitope tags that are detected less efficiently and reduce our assay scale to allow for higher throughput. The Creator Splice system appears to be an extremely

  19. The Survivin −31 Snp in Human Colorectal Cancer Correlates with Survivin Splice Variant Expression and Improved Overall Survival

    Directory of Open Access Journals (Sweden)

    Anna G. Antonacopoulou


    Full Text Available Background: Survivin is involved in the regulation of