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Sample records for multidimensional phenotypic profiling

  1. Profile Analysis: Multidimensional Scaling Approach.

    ERIC Educational Resources Information Center

    Ding, Cody S.

    2001-01-01

    Outlines an exploratory multidimensional scaling-based approach to profile analysis called Profile Analysis via Multidimensional Scaling (PAMS) (M. Davison, 1994). The PAMS model has the advantages of being applied to samples of any size easily, classifying persons on a continuum, and using person profile index for further hypothesis studies, but…

  2. Estimating Cognitive Profiles Using Profile Analysis via Multidimensional Scaling (PAMS).

    PubMed

    Kim, Se-Kang; Frisby, Craig L; Davison, Mark L

    2004-10-01

    Two of the most popular methods of profile analysis, cluster analysis and modal profile analysis, have limitations. First, neither technique is adequate when the sample size is large. Second, neither method will necessarily provide profile information in terms of both level and pattern. A new method of profile analysis, called Profile Analysis via Multidimensional Scaling (PAMS; Davison, 1996), is introduced to meet the challenge. PAMS extends the use of simple multidimensional scaling methods to identify latent profiles in a multi-test battery. Application of PAMS to profile analysis is described. The PAMS model is then used to identify latent profiles from a subgroup (N = 357) within the sample of the Woodcock-Johnson Psychoeducational Battery-Revised (WJ-R; McGrew, Werder, & Woodcock, 1991; Woodcock & Johnson, 1989), followed by a discussion of procedures for interpreting participants' observed score profiles from the latent PAMS profiles. Finally, advantages and limitations of the PAMS technique are discussed.

  3. Confirmatory Factor Analysis and Profile Analysis via Multidimensional Scaling

    ERIC Educational Resources Information Center

    Kim, Se-Kang; Davison, Mark L.; Frisby, Craig L.

    2007-01-01

    This paper describes the Confirmatory Factor Analysis (CFA) parameterization of the Profile Analysis via Multidimensional Scaling (PAMS) model to demonstrate validation of profile pattern hypotheses derived from multidimensional scaling (MDS). Profile Analysis via Multidimensional Scaling (PAMS) is an exploratory method for identifying major…

  4. Multidimensional Clinical Phenotyping of an Adult Cystic Fibrosis Patient Population

    PubMed Central

    Conrad, Douglas J.; Bailey, Barbara A.

    2015-01-01

    Background Cystic Fibrosis (CF) is a multi-systemic disease resulting from mutations in the Cystic Fibrosis Transmembrane Regulator (CFTR) gene and has major manifestations in the sino-pulmonary, and gastro-intestinal tracts. Clinical phenotypes were generated using 26 common clinical variables to generate classes that overlapped quantiles of lung function and were based on multiple aspects of CF systemic disease. Methods The variables included age, gender, CFTR mutations, FEV1% predicted, FVC% predicted, height, weight, Brasfield chest xray score, pancreatic sufficiency status and clinical microbiology results. Complete datasets were compiled on 211 subjects. Phenotypes were identified using a proximity matrix generated by the unsupervised Random Forests algorithm and subsequent clustering by the Partitioning around Medoids (PAM) algorithm. The final phenotypic classes were then characterized and compared to a similar dataset obtained three years earlier. Findings Clinical phenotypes were identified using a clustering strategy that generated four and five phenotypes. Each strategy identified 1) a low lung health scores phenotype, 2) a younger, well-nourished, male-dominated class, 3) various high lung health score phenotypes that varied in terms of age, gender and nutritional status. This multidimensional clinical phenotyping strategy identified classes with expected microbiology results and low risk clinical phenotypes with pancreatic sufficiency. Interpretation This study demonstrated regional adult CF clinical phenotypes using non-parametric, continuous, ordinal and categorical data with a minimal amount of subjective data to identify clinically relevant phenotypes. These studies identified the relative stability of the phenotypes, demonstrated specific phenotypes consistent with published findings and identified others needing further study. PMID:25822311

  5. Multidimensional Neuropathic Pain Phenotypes after Spinal Cord Injury.

    PubMed

    Widerström-Noga, Eva; Felix, Elizabeth R; Adcock, James P; Escalona, Maydelis; Tibbett, Jacqueline

    2016-03-01

    Identifying clinical neuropathic pain phenotypes is a first step to better understand the underlying pain mechanisms after spinal cord injury (SCI). The primary purpose of the present study was to characterize multidimensional neuropathic pain phenotypes based on quantitative sensory testing (QST), pain intensity, and utilization of catastrophizing coping strategies. Thermal perception, thermal pain, and vibratory perception thresholds were assessed above and below the level of injury (LOI) in 101 persons with SCI and neuropathic pain, 18 persons with SCI and no neuropathic pain, and 50 able-bodied, pain-free controls. Cluster analysis of QST z-scores below the LOI, pain intensity ratings, and the Coping Strategies Questionnaire (CSQ) catastrophizing subscale scores in subjects with neuropathic pain resulted in two phenotypes: severe neuropathic pain (SNP) with greater pain intensity (7.39 ± 1.57) and thermal and vibratory sensitivity compared with the moderate neuropathic pain (MNP; 5.40 ± 1.43). A factor analysis including all CSQ subscales, the Neuropathic Pain Symptom Inventory (NPSI) total score, and thermal pain sensitivity above and below the LOI resulted in three factors: (1) adaptive pain coping including increasing activities, diverting attention, and reinterpreting pain sensations; (2) catastrophizing, neuropathic pain, and thermal sensitivity including greater NPSI total score, thermal pain sensitivity below the LOI, and catastrophizing; and (3) general pain sensitivity including greater thermal pain sensitivity above the LOI and lower catastrophizing. Our results suggest that neuropathic pain symptom severity post-SCI is significantly associated with residual spinothalamic tract function below the LOI and catastrophizing pain coping.

  6. Multidimensional profiles of health locus of control in Hispanic Americans.

    PubMed

    Champagne, Brian R; Fox, Rina S; Mills, Sarah D; Sadler, Georgia Robins; Malcarne, Vanessa L

    2016-10-01

    Latent profile analysis identified health locus of control profiles among 436 Hispanic Americans who completed the Multidimensional Health Locus of Control scales. Results revealed four profiles: Internally Oriented-Weak, -Moderate, -Strong, and Externally Oriented. The profile groups were compared on sociocultural and demographic characteristics, health beliefs and behaviors, and physical and mental health outcomes. The Internally Oriented-Strong group had less cancer fatalism, religiosity, and equity health attributions, and more alcohol consumption than the other three groups; the Externally Oriented group had stronger equity health attributions and less alcohol consumption. Deriving multidimensional health locus of control profiles through latent profile analysis allows examination of the relationships of health locus of control subtypes to health variables.

  7. Multidimensional profiling of cell surface proteins and nuclear markers

    SciTech Connect

    Han, Ju; Chang, Hang; Andarawewa, Kumari; Yaswen, Paul; Helen Barcellos-Hoff, Mary; Parvin, Bahram

    2009-01-30

    Cell membrane proteins play an important role in tissue architecture and cell-cell communication. We hypothesize that segmentation and multidimensional characterization of the distribution of cell membrane proteins, on a cell-by-cell basis, enable improved classification of treatment groups and identify important characteristics that can otherwise be hidden. We have developed a series of computational steps to (i) delineate cell membrane protein signals and associate them with a specific nucleus; (ii) compute a coupled representation of the multiplexed DNA content with membrane proteins; (iii) rank computed features associated with such a multidimensional representation; (iv) visualize selected features for comparative evaluation through heatmaps; and (v) discriminate between treatment groups in an optimal fashion. The novelty of our method is in the segmentation of the membrane signal and the multidimensional representation of phenotypic signature on a cell-by-cell basis. To test the utility of this method, the proposed computational steps were applied to images of cells that have been irradiated with different radiation qualities in the presence and absence of other small molecules. These samples are labeled for their DNA content and E-cadherin membrane proteins. We demonstrate that multidimensional representations of cell-by-cell phenotypes improve predictive and visualization capabilities among different treatment groups, and identify hidden variables.

  8. Confirmatory Factor Analysis and Profile Analysis via Multidimensional Scaling.

    PubMed

    Kim, Se-Kang; Davison, Mark L; Frisby, Craig L

    2007-01-01

    This paper describes the Confirmatory Factor Analysis (CFA) parameterization of the Profile Analysis via Multidimensional Scaling (PAMS) model to demonstrate validation of profile pattern hypotheses derived from multidimensional scaling (MDS). Profile Analysis via Multidimensional Scaling (PAMS) is an exploratory method for identifying major profiles in a multi-subtest test battery. Major profile patterns are represented as dimensions extracted from a MDS analysis. PAMS represents an individual observed score as a linear combination of dimensions where the dimensions are the most typical profile patterns present in a population. While the PAMS approach was initially developed for exploratory purposes, its results can later be confirmed in a different sample by CFA. Since CFA is often used to verify results from an exploratory factor analysis, the present paper makes the connection between a factor model and the PAMS model, and then illustrates CFA with a simulated example (that was generated by the PAMS model) and at the same time with a real example. The real example demonstrates confirmation of PAMS exploratory results by using a different sample. Fit indexes can be used to indicate whether the CFA reparameterization as a confirmatory approach works for the PAMS exploratory results.

  9. Using Profile Analysis via Multidimensional Scaling (PAMS) to Identify Core Profiles from the WMS-III

    ERIC Educational Resources Information Center

    Frisby, Craig L.; Kim, Se-Kang

    2008-01-01

    Profile Analysis via Multidimensional Scaling (PAMS) is a procedure for extracting latent core profiles in a multitest data set. The PAMS procedure offers several advantages compared with other profile analysis procedures. Most notably, PAMS estimates individual profile weights that reflect the degree to which an individual's observed profile…

  10. Estimating Cognitive Profiles Using Profile Analysis via Multidimensional Scaling (PAMS)

    ERIC Educational Resources Information Center

    Kim, Se-Kang; Frisby, Craig L.; Davison, Mark L.

    2004-01-01

    Two of the most popular methods of profile analysis, cluster analysis and modal profile analysis, have limitations. First, neither technique is adequate when the sample size is large. Second, neither method will necessarily provide profile information in terms of both level and pattern. A new method of profile analysis, called Profile Analysis via…

  11. Evaluating the Invariance of Cognitive Profile Patterns Derived from Profile Analysis via Multidimensional Scaling (PAMS): A Bootstrapping Approach

    ERIC Educational Resources Information Center

    Kim, Se-Kang

    2010-01-01

    The aim of the current study is to validate the invariance of major profile patterns derived from multidimensional scaling (MDS) by bootstrapping. Profile Analysis via Multidimensional Scaling (PAMS) was employed to obtain profiles and bootstrapping was used to construct the sampling distributions of the profile coordinates and the empirical…

  12. Evolution of cooperation in a multidimensional phenotype space.

    PubMed

    Kroumi, Dhaker; Lessard, Sabin

    2015-06-01

    The emergence of cooperation in populations of selfish individuals is a fascinating topic that has inspired much theoretical work. An important model to study cooperation is the phenotypic model, where individuals are characterized by phenotypic properties that are visible to others. The phenotype of an individual can be represented for instance by a vector x = (x1,…,xn), where x1,…,xn are integers. The population can be well mixed in the sense that everyone is equally likely to interact with everyone else, but the behavioral strategies of the individuals can depend on their distance in the phenotype space. A cooperator can choose to help other individuals exhibiting the same phenotype and defects otherwise. Cooperation is said to be favored by selection if it is more abundant than defection in the stationary state. This means that the average frequency of cooperators in the stationary state strictly exceeds 1/2. Antal et al. (2009c) found conditions that ensure that cooperation is more abundant than defection in a one-dimensional (i.e. n = 1) and an infinite-dimensional (i.e. n = ∞) phenotype space in the case of the Prisoner's Dilemma under weak selection. However, reality lies between these two limit cases. In this paper, we derive the corresponding condition in the case of a phenotype space of any finite dimension. This is done by applying a perturbation method to study a mutation-selection equilibrium under weak selection. This condition is obtained in the limit of a large population size by using the ancestral process. The best scenario for cooperation to be more likely to evolve is found to be a high population-scaled phenotype mutation rate, a low population-scaled strategy mutation rate and a high phenotype space dimension. The biological intuition is that a high population-scaled phenotype mutation rate reduces the quantity of interactions between cooperators and defectors, while a high population-scaled strategy mutation rate introduces newly

  13. Multidimensional Dyspnea Profile: an instrument for clinical and laboratory research

    PubMed Central

    O'Donnell, Carl R.; Guilfoyle, Tegan E.; Parshall, Mark B.; Schwartzstein, Richard M.; Meek, Paula M.; Gracely, Richard H.; Lansing, Robert W.

    2015-01-01

    There is growing awareness that dyspnoea, like pain, is a multidimensional experience, but measurement instruments have not kept pace. The Multidimensional Dyspnea Profile (MDP) assesses overall breathing discomfort, sensory qualities, and emotional responses in laboratory and clinical settings. Here we provide the MDP, review published evidence regarding its measurement properties and discuss its use and interpretation. The MDP assesses dyspnoea during a specific time or a particular activity (focus period) and is designed to examine individual items that are theoretically aligned with separate mechanisms. In contrast, other multidimensional dyspnoea scales assess recalled recent dyspnoea over a period of days using aggregate scores. Previous psychophysical and psychometric studies using the MDP show that: 1) subjects exposed to different laboratory stimuli could discriminate between air hunger and work/effort sensation, and found air hunger more unpleasant; 2) the MDP immediate unpleasantness scale (A1) was convergent with common dyspnoea scales; 3) in emergency department patients, two domains were distinguished (immediate perception, emotional response); 4) test–retest reliability over hours was high; 5) the instrument responded to opioid treatment of experimental dyspnoea and to clinical improvement; 6) convergent validity with common instruments was good; and 7) items responded differently from one another as predicted for multiple dimensions. PMID:25792641

  14. Using Profile Analysis via Multidimensional Scaling (PAMS) to identify core profiles from the WMS-III.

    PubMed

    Frisby, Craig L; Kim, Se-Kang

    2008-03-01

    Profile Analysis via Multidimensional Scaling (PAMS) is a procedure for extracting latent core profiles in a multitest data set. The PAMS procedure offers several advantages compared with other profile analysis procedures. Most notably, PAMS estimates individual profile weights that reflect the degree to which an individual's observed profile approximates the shape and scatter of latent core profiles. The PAMS procedure was applied to index scores of nonreplicated participants from the standardization sample (N = 1,033) for the Wechsler Memory Scale--Third Edition (D. Tulsky, J. Zhu, & M. F. Ledbetter, 2002). PAMS extracted discrepant visual memory and auditory memory versus working memory core profiles for the complete 16- to 89-year-old sample and discrepant working memory and auditory memory versus working memory core profiles for the 75- to 89-year-old cohort. Implications for use of PAMS in future research are discussed.

  15. Target deconvolution techniques in modern phenotypic profiling.

    PubMed

    Lee, Jiyoun; Bogyo, Matthew

    2013-02-01

    The past decade has seen rapid growth in the use of diverse compound libraries in classical phenotypic screens to identify modulators of a given process. The subsequent process of identifying the molecular targets of active hits, also called 'target deconvolution', is an essential step for understanding compound mechanism of action and for using the identified hits as tools for further dissection of a given biological process. Recent advances in 'omics' technologies, coupled with in silico approaches and the reduced cost of whole genome sequencing, have greatly improved the workflow of target deconvolution and have contributed to a renaissance of 'modern' phenotypic profiling. In this review, we will outline how both new and old techniques are being used in the difficult process of target identification and validation as well as discuss some of the ongoing challenges remaining for phenotypic screening.

  16. Bifactor Approach to Modeling Multidimensionality of Physical Self-Perception Profile

    ERIC Educational Resources Information Center

    Chung, ChihMing; Liao, Xiaolan; Song, Hairong; Lee, Taehun

    2016-01-01

    The multi-dimensionality of Physical Self-Perception Profile (PSPP) has been acknowledged by the use of correlated-factor model and second-order model. In this study, the authors critically endorse the bifactor model, as a substitute to address the multi-dimensionality of PSPP. To cross-validate the models, analyses are conducted first in…

  17. Multidimensional Profiling Platforms Reveal Metabolic Dysregulation caused by Organophosphorus Pesticides

    PubMed Central

    Medina-Cleghorn, Daniel; Heslin, Ann; Morris, Patrick J.; Mulvihill, Melinda M.; Nomura, Daniel K.

    2014-01-01

    We are environmentally exposed to countless synthetic chemicals on a daily basis with an increasing number of these chemical exposures linked to adverse health effects. However, our understanding of the (patho)physiological effects of these chemicals remains poorly understood, due in-part to a general lack of effort to systematically and comprehensively identify the direct interactions of environmental chemicals with biological macromolecules in mammalian systems in vivo. Here, we have used functional chemoproteomic and metabolomic platforms to broadly identify direct enzyme targets that are inhibited by widely used organophosphorus (OP) pesticides in vivo in mice and to determine metabolic alterations that are caused by these chemicals. We find that these pesticides directly inhibit over 20 serine hydrolases in vivo leading to widespread disruptions in lipid metabolism. Through identifying direct biological targets of OP pesticides, we show heretofore unrecognized modes of toxicity that may be associated with these agents and underscore the utility of utilizing multidimensional profiling approaches to obtain a more complete understanding of toxicities associated with environmental chemicals. PMID:24205821

  18. Multi-dimensional phenotyping: towards a new taxonomy for airway disease.

    PubMed

    Wardlaw, A J; Silverman, M; Siva, R; Pavord, I D; Green, R

    2005-10-01

    All the real knowledge which we possess, depends on methods by which we distinguish the similar from the dissimilar. The greater the number of natural distinctions this method comprehends the clearer becomes our idea of things. The more numerous the objects which employ our attention the more difficult it becomes to form such a method and the more necessary. Classification is a fundamental part of medicine. Diseases are often categorized according to pre-20th century descriptions and concepts of disease based on symptoms, signs and functional abnormalities rather than on underlying pathogenesis. Where the aetiology of disease has been revealed (for example in the infectious diseases) a more precise classification has become possible, but in the chronic inflammatory diseases, and in the inflammatory airway diseases in particular, where pathogenesis has been stubbornly difficult to elucidate, we still use broad descriptive terms such as asthma and chronic obstructive pulmonary disease, which defy precise definition because they encompass a wide spectrum of presentations and physiological and cellular abnormalities. It is our contention that these broad-brush terms have outlived their usefulness and that we should be looking to create a new taxonomy of airway disease-a taxonomy that more closely reflects the spectrum of phenotypes that are encompassed within the term airway inflammatory diseases, and that gives full recognition to late 20th and 21st century insights into the disordered physiology and cell biology that characterizes these conditions in the expectation that these will map more closely to both aetiology and response to treatment. Development of this taxonomy will require a much more complete and sophisticated correlation of the many variables that make up a condition than has been usual to employ in an approach that encompasses multi-dimensional phenotyping and uses complex statistical tools such as cluster analysis.

  19. Ameloblastoma Phenotypes Reflected in Distinct Transcriptome Profiles

    PubMed Central

    Hu, Shijia; Parker, Joel; Divaris, Kimon; Padilla, Ricardo; Murrah, Valerie; Wright, John Timothy

    2016-01-01

    Ameloblastoma is a locally invasive benign neoplasm derived from odontogenic epithelium and presents with diverse phenotypes yet to be characterized molecularly. High recurrence rates of 50–80% with conservative treatment in some sub-types warrants radical surgical resections resulting in high morbidity. The objective of the study was to characterize the transcriptome of ameloblastoma and identify relevant genes and molecular pathways using normal odontogenic tissue (human “dentome”) for comparison. Laser capture microdissection was used to obtain neoplastic epithelial tissue from 17 tumors which were examined using the Agilent 44 k whole genome microarray. Ameloblastoma separated into 2 distinct molecular clusters that were associated with pre-secretory ameloblast and odontoblast. Within the pre-secretory cluster, 9/10 of samples were of the follicular type while 6/7 of the samples in the odontoblast cluster were of the plexiform type (p < 0.05). Common pathways altered in both clusters included cell-cycle regulation, inflammatory and MAPkinase pathways, specifically known cancer-driving genes such as TP53 and members of the MAPkinase pathways. The pre-secretory ameloblast cluster exhibited higher activation of inflammatory pathways while the odontoblast cluster showed greater disturbances in transcription regulators. Our results are suggestive of underlying inter-tumor molecular heterogeneity of ameloblastoma sub-types and have implications for the use of tailored treatment. PMID:27491308

  20. The Impact of Time Perspective Latent Profiles on College Drinking: A Multidimensional Approach

    PubMed Central

    Braitman, Abby L.; Henson, James M.

    2015-01-01

    Background Zimbardo and Boyd’s1 time perspective, or the temporal framework individuals use to process information, has been shown to predict health behaviors such as alcohol use. Previous studies supported the predictive validity of individual dimensions of time perspective, with some dimensions acting as protective factors and others as risk factors. However, some studies produced findings contrary to the general body of literature. In addition, time perspective is a multidimensional construct, and the combination of perspectives may be more predictive than individual dimensions in isolation; consequently, multidimensional profiles are a more accurate measure of individual differences and more appropriate for predicting health behaviors. Objectives The current study identified naturally occurring profiles of time perspective and examined their association with risky alcohol use. Methods Data were collected from a college student sample (n = 431, mean age = 20.41 years) using an online survey. Time perspective profiles were identified using latent profile analysis. Results Bootstrapped regression models identified a protective class that engaged in significantly less overall drinking (β = −0.254) as well as engaging in significantly less episodic high risk drinking (β = −0.274). There was also emerging evidence of a high risk time perspective profile that was linked to more overall drinking (β = 0.198) and engaging in more high risk drinking (β = 0.245), though these differences were not significant. Conclusions/Importance These findings support examining time perspective in a multidimensional framework rather than individual dimensions in isolation. Implications include identifying students most in need of interventions, and tailoring interventions to target temporal framing in decision-making. PMID:25607806

  1. An examination of obsessive-compulsive symptoms and dimensions using profile analysis via multidimensional scaling (PAMS).

    PubMed

    McKay, Dean; Kim, Se-Kang; Taylor, Steven; Abramowitz, Jonathan S; Tolin, David; Coles, Meredith; Timpano, Kiara R; Olatunji, Bunmi

    2014-05-01

    Contemporary cognitive models of obsessive-compulsive disorder (OCD) emphasize the importance of various types of dysfunctional beliefs in contributing to OC symptoms, such as beliefs about excessive personal responsibility, perfectionism, and intolerance for uncertainty. The present study seeks to further our understanding of the role of these beliefs by identifying the common profiles of such beliefs, using profile analysis via multidimensional scaling (PAMS). In Study 1, a large student sample (N=4079) completed the 44-item obsessive beliefs questionnaire. One major profile, control of thoughts and perfectionism, was extracted. Study 2 examined profiles of the 87-item obsessive beliefs questionnaire in people with obsessive-compulsive disorder (OCD; n=398), other anxiety disorders (n=104), and a sample of undergraduate students (n=285). Inflated responsibility was a prominent subscale in the profiles of all three groups. Only control over thoughts was a unique subscale in the profile obtained for the OCD group, with this group having lower scores compared to the other groups. The results suggest that while inflated responsibility is a significant subscale in the profile of individuals with OCD, it is not a unique contributor; instead, control over thoughts is unique to OCD. The data, as well as recent research investigating obsessive beliefs, suggest the need to revise the contemporary cognitive model of OCD.

  2. Phenotype microarray profiling of Zymomonas mobilis ZM4.

    PubMed

    Bochner, Barry; Gomez, Vanessa; Ziman, Michael; Yang, Shihui; Brown, Steven D

    2010-05-01

    In this study, we developed a Phenotype MicroArray (PM) protocol to profile cellular phenotypes in Zymomonas mobilis, which included a standard set of nearly 2,000 assays for carbon, nitrogen, phosphorus and sulfur source utilization, nutrient stimulation, pH and osmotic stresses, and chemical sensitivities with 240 inhibitory chemicals. We observed two positive assays for C-source utilization (fructose and glucose) using the PM screen, which uses redox chemistry and cell respiration as a universal reporter to profile growth phenotypes in a high-throughput 96-well plate-based format. For nitrogen metabolism, the bacterium showed a positive test results for ammonia, aspartate, asparagine, glutamate, glutamine, and peptides. Z. mobilis appeared to use a diverse array of P-sources with two exceptions being pyrophosphate and tripolyphosphate. The assays suggested that Z. mobilis uses both inorganic and organic compounds as S-sources. No stimulation by nutrients was detected; however, there was evidence of partial inhibition by purines and pyrimidines, NAD, and deferoxamine. Z. mobilis was relatively resistant to acid pH, tolerating a pH down to about 4.0. It also tolerated phosphate, sulfate, and nitrate, but was rather sensitive to chloride and nitrite. Z. mobilis showed resistance to a large number of diverse chemicals that inhibit most bacteria. The information from PM analysis provides an overview of Z. mobilis physiology and a foundation for future comparisons of other wild-type and mutant Z. mobilis strains.

  3. Phenotype Microarray Profiling of Zymomonas mobilis ZM4

    SciTech Connect

    Bochner, Barry; Gomez, Vanessa; Ziman, michael; Yang, Shihui; Brown, Steven D

    2009-01-01

    In this study, we developed a Phenotype MicroArray{trademark} (PM) protocol to profile cellular phenotypes in Zymomonas mobilis, which included a standard set of nearly 2,000 assays for carbon, nitrogen, phosphorus and sulfur source utilization, nutrient stimulation, pH and osmotic stresses, and chemical sensitivities with 240 inhibitory chemicals. We observed two positive assays for C-source utilization (fructose and glucose) using the PM screen, which uses redox chemistry and cell respiration as a universal reporter to profile growth phenotypes in a high-throughput 96-well plate-based format. For nitrogen metabolism, the bacterium showed a positive test results for ammonia, aspartate, asparagine, glutamate, glutamine, and peptides. Z. mobilis appeared to use a diverse array of P-sources with two exceptions being pyrophosphate and tripolyphosphate. The assays suggested that Z. mobilis uses both inorganic and organic compounds as S-sources. No stimulation by nutrients was detected; however, there was evidence of partial inhibition by purines and pyrimidines, NAD, and deferoxamine. Z. mobilis was relatively resistant to acid pH, tolerating a pH down to about 4.0. It also tolerated phosphate, sulfate, and nitrate, but was rather sensitive to chloride and nitrite. Z. mobilis showed resistance to a large number of diverse chemicals that inhibit most bacteria. The information from PM analysis provides an overview of Z. mobilis physiology and a foundation for future comparisons of other wild-type and mutant Z. mobilis strains.

  4. Examining Work Ethic across Populations: A Comparison of the Multidimensional Work Ethic Profile across Three Diverse Cultures

    ERIC Educational Resources Information Center

    Woehr, David J.; Arciniega, Luis M.; Lim, Doo H.

    2007-01-01

    The authors examined the measurement equivalence of the Multidimensional Work Ethic Profile (MWEP) across the diverse cultures of Korea, Mexico, and the United States. Korean- and Spanish-language versions of the MWEP were developed and evaluated relative to the original English version of the measure. Confirmatory factor analytic results…

  5. A Phenotypic Profile of the Candida albicans Regulatory Network

    PubMed Central

    Homann, Oliver R.; Dea, Jeanselle; Noble, Suzanne M.; Johnson, Alexander D.

    2009-01-01

    Candida albicans is a normal resident of the gastrointestinal tract and also the most prevalent fungal pathogen of humans. It last shared a common ancestor with the model yeast Saccharomyces cerevisiae over 300 million years ago. We describe a collection of 143 genetically matched strains of C. albicans, each of which has been deleted for a specific transcriptional regulator. This collection represents a large fraction of the non-essential transcription circuitry. A phenotypic profile for each mutant was developed using a screen of 55 growth conditions. The results identify the biological roles of many individual transcriptional regulators; for many, this work represents the first description of their functions. For example, a quarter of the strains showed altered colony formation, a phenotype reflecting transitions among yeast, pseudohyphal, and hyphal cell forms. These transitions, which have been closely linked to pathogenesis, have been extensively studied, yet our work nearly doubles the number of transcriptional regulators known to influence them. As a second example, nearly a quarter of the knockout strains affected sensitivity to commonly used antifungal drugs; although a few transcriptional regulators have previously been implicated in susceptibility to these drugs, our work indicates many additional mechanisms of sensitivity and resistance. Finally, our results inform how transcriptional networks evolve. Comparison with the existing S. cerevisiae data (supplemented by additional S. cerevisiae experiments reported here) allows the first systematic analysis of phenotypic conservation by orthologous transcriptional regulators over a large evolutionary distance. We find that, despite the many specific wiring changes documented between these species, the general phenotypes of orthologous transcriptional regulator knockouts are largely conserved. These observations support the idea that many wiring changes affect the detailed architecture of the circuit, but

  6. Multidimensional analysis of particle size fractal characteristics in a farmland soil profile

    NASA Astrophysics Data System (ADS)

    Du, Y. C.; Han, J. C.; Zhang, S. W.; Huang, Y. F.; Wang, H. Y.; Luo, L. T.; Zhang, W. H.

    2017-01-01

    Soil particle size distribution (PSD) is a basic soil property, closely related to soil erosion, soil moisture, and so on. The multidimensional fractal method has been proved to be a better description of soil PSD. By choosing the four fractal parameters of Δa, ΔaR/ΔaL, D1/D0 and, Δf(a)R/Δf(a)L, and using the multifractal spectrum, this paper analyzed one- and two-dimensional fractal characteristics of the soil profile (A, B, and C layers from top to bottom) PSD and their relationship on a field scale. The results showed that the PSD characteristics of different soil profiles were more heterogeneous in the east and west (WE) than the north and south (NS) in the study area, and the A layer soil PSD was the most uneven, with a larger degree of dispersion. With the soil layer depth, the soil PSD tended to be uniform. Regardless of one-dimensional or two-dimensional characteristics, the proportion of the low value of soil particle mass percent was relatively larger. The results of this study will not only provide a reference method for analyses of the fractal characteristics of soil PSD on a field scale, but also provide guidance in further understanding the soil structure and soil forming process.

  7. Comparing Longitudinal Profile Patterns of Mathematics and Reading in Early Child Longitudinal Study, Kindergarten: The Profile Analysis via Multidimensional Scaling (PAMS) Approach

    ERIC Educational Resources Information Center

    Kim, Se-Kang

    2010-01-01

    The aim of the study is to compare longitudinal patterns from Mathematics and Reading data from the direct child assessment of Early Child Longitudinal Study, Kindergarten (ECLS-K, US Department of Education, National Center for Education Statistics 2006), utilizing Profile Analysis via Multidimensional Scaling (PAMS). PAMS has been used initially…

  8. Extracting body image symptom dimensions among eating disorder patients: the Profile Analysis via Multidimensional Scaling (PAMS) approach.

    PubMed

    Olatunji, Bunmi O; Kim, Se-Kang; Wall, David

    2015-09-01

    The present study employs Profile Analysis via Multidimensional Scaling (PAMS), a procedure for extracting dimensions, in order to identify core eating disorder symptoms in a clinical sample. A large sample of patients with eating disorders (N=5193) presenting for treatment completed the Eating Disorders Inventory-2 (EDI-2; Garner, 1991), and PAMS was then employed to estimate individual profile weights that reflect the degree to which an individual's observed symptom profile approximates the pattern of the dimensions. The findings revealed three symptom dimensions: Body Thinness, Body Perfectionism, and Body Awareness. Subsequent analysis using individual level data illustrate that the PAMS profiles properly operate as prototypical profiles that encapsulate all individuals' response patterns. The implications of these dimensional findings for the assessment and diagnosis of eating disorders are discussed.

  9. Transcriptional Profiling of Egg Allergy and Relationship to Disease Phenotype

    PubMed Central

    Kosoy, Roman; Agashe, Charuta; Grishin, Alexander; Leung, Donald Y.; Wood, Robert A.; Sicherer, Scott H.; Jones, Stacie M.; Burks, A. Wesley; Davidson, Wendy F.; Lindblad, Robert W.; Dawson, Peter; Merad, Miriam; Kidd, Brian A.; Dudley, Joel T.; Sampson, Hugh A.

    2016-01-01

    Background Egg allergy is one of the most common food allergies of childhood. There is a lack of information on the immunologic basis of egg allergy beyond the role of IgE. Objective To use transcriptional profiling as a novel approach to uncover immunologic processes associated with different phenotypes of egg allergy. Methods Peripheral blood mononuclear cells (PBMCs) were obtained from egg-allergic children who were defined as reactive (BER) or tolerant (BET) to baked egg, and from food allergic controls (AC) who were egg non-allergic. PBMCs were stimulated with egg white protein. Gene transcription was measured by microarray after 24 h, and cytokine secretion by multiplex assay after 5 days. Results The transcriptional response of PBMCs to egg protein differed between BER and BET versus AC subjects. Compared to the AC group, the BER group displayed increased expression of genes associated with allergic inflammation as well as corresponding increased secretion of IL-5, IL-9 and TNF-α. A similar pattern was observed for the BET group. Further similarities in gene expression patterns between BER and BET groups, as well as some important differences, were revealed using a novel Immune Annotation resource developed for this project. This approach identified several novel processes not previously associated with egg allergy, including positive associations with TLR4-stimulated myeloid cells and activated NK cells, and negative associations with an induced Treg signature. Further pathway analysis of differentially expressed genes comparing BER to BET subjects showed significant enrichment of IFN-α and IFN-γ response genes, as well as genes associated with virally-infected DCs. Conclusions Transcriptional profiling identified several novel pathways and processes that differed when comparing the response to egg allergen in BET, BER, and AC groups. We conclude that this approach is a useful hypothesis-generating mechanism to identify novel immune processes associated

  10. Unique DNA methylome profiles in CpG island methylator phenotype colon cancers

    PubMed Central

    Xu, Yaomin; Hu, Bo; Choi, Ae-Jin; Gopalan, Banu; Lee, Byron H.; Kalady, Matthew F.; Church, James M.; Ting, Angela H.

    2012-01-01

    A subset of colorectal cancers was postulated to have the CpG island methylator phenotype (CIMP), a higher propensity for CpG island DNA methylation. The validity of CIMP, its molecular basis, and its prognostic value remain highly controversial. Using MBD-isolated genome sequencing, we mapped and compared genome-wide DNA methylation profiles of normal, non-CIMP, and CIMP colon specimens. Multidimensional scaling analysis revealed that each specimen could be clearly classified as normal, non-CIMP, and CIMP, thus signifying that these three groups have distinctly different global methylation patterns. We discovered 3780 sites in various genomic contexts that were hypermethylated in both non-CIMP and CIMP colon cancers when compared with normal colon. An additional 2026 sites were found to be hypermethylated in CIMP tumors only; and importantly, 80% of these sites were located in CpG islands. These data demonstrate on a genome-wide level that the additional hypermethylation seen in CIMP tumors occurs almost exclusively at CpG islands and support definitively that these tumors were appropriately named. When these sites were examined more closely, we found that 25% were adjacent to sites that were also hypermethylated in non-CIMP tumors. Thus, CIMP is also characterized by more extensive methylation of sites that are already prone to be hypermethylated in colon cancer. These observations indicate that CIMP tumors have specific defects in controlling both DNA methylation seeding and spreading and serve as an important first step in delineating molecular mechanisms that control these processes. PMID:21990380

  11. Large-scale image-based screening and profiling of cellular phenotypes.

    PubMed

    Bougen-Zhukov, Nicola; Loh, Sheng Yang; Lee, Hwee Kuan; Loo, Lit-Hsin

    2017-02-01

    Cellular phenotypes are observable characteristics of cells resulting from the interactions of intrinsic and extrinsic chemical or biochemical factors. Image-based phenotypic screens under large numbers of basal or perturbed conditions can be used to study the influences of these factors on cellular phenotypes. Hundreds to thousands of phenotypic descriptors can also be quantified from the images of cells under each of these experimental conditions. Therefore, huge amounts of data can be generated, and the analysis of these data has become a major bottleneck in large-scale phenotypic screens. Here, we review current experimental and computational methods for large-scale image-based phenotypic screens. Our focus is on phenotypic profiling, a computational procedure for constructing quantitative and compact representations of cellular phenotypes based on the images collected in these screens. © 2016 International Society for Advancement of Cytometry.

  12. Heat Survival and Phenotype Microarray Profiling of Salmonella Typhimurium Mutants.

    PubMed

    Dawoud, Turki M; Khatiwara, Anita; Park, Si Hong; Davis, Morgan L; Baker, Christopher A; Ricke, Steven C; Kwon, Young Min

    2017-02-01

    Contamination of food products by pathogenic microorganisms continues to be a major public health and food industry concern. Non-typhoidal Salmonella species have led to numerous outbreaks associated with various foods. A wide variety of methods have been applied and introduced for treatment of fresh foods to eliminate pathogenic as well as spoilage microorganisms. Salmonella can become exposed to elevated temperatures while associated with hosts such as poultry. In addition, heat treatment is also applied at various stages of processing to retain the shelf life of food products. Despite this, these microorganisms may overcome exposure to such treatments through the efficient expression of stress response mechanisms and result in illness following consumption. Thermal stress induces a range of destructive exposures to bacterial cells such as protein damage and DNA damage caused by reactive oxygen species. In this study, we chose three genes (∆recD, ∆STM14_5307, and ∆aroD) associated with conditionally essential genes required for different aspects of optimal growth at 42 °C and evaluated the responses of wild type and mutant Salmonella Typhimurium strains to uncover potential mechanisms that may enable survival and resistance under thermal stress. The RecBCD complex that initiates repair of double-stranded DNA breaks through homologous recombination. STM14_5307 is a transcriptional regulator involved in stationary phase growth and inositol metabolism. The gene aroD is involved in metabolism and stationary phase growth. These strains were characterized via high throughput phenotypic profiling in response to two different growth temperatures (37 °C (human host temperature) and 42 °C (poultry host temperature)). The ∆aroD strain exhibited the highest sensitivity to the various temperatures followed by the ∆recD and ∆STM14_5307 strains, respectively. Achieving more understanding of the molecular mechanisms of heat survival may lead to the development

  13. Large-scale Phenotypic Profiling of Gene Deletion Mutants in Candida glabrata

    PubMed Central

    Tscherner, Michael; Kuchler, Karl

    2016-01-01

    Here, we describe a method enabling the phenotypic profiling of genome-scale deletion collections of fungal mutants to detect phenotypes for various stress conditions. These stress conditions include among many others antifungal drug susceptibility, temperature-induced and osmotic as well as heavy metal or oxidative stress. The protocol was extensively used to phenotype a collection of gene deletion mutants in the human fungal pathogen Candida glabrata (C. glabrata) (Schwarzmüller et al., 2014). PMID:27774498

  14. CEBPA-double-mutated acute myeloid leukemia displays a unique phenotypic profile: a reliable screening method and insight into biological features.

    PubMed

    Mannelli, Francesco; Ponziani, Vanessa; Bencini, Sara; Bonetti, Maria Ida; Benelli, Matteo; Cutini, Ilaria; Gianfaldoni, Giacomo; Scappini, Barbara; Pancani, Fabiana; Piccini, Matteo; Rondelli, Tommaso; Caporale, Roberto; Gelli, Anna Maria Grazia; Peruzzi, Benedetta; Chiarini, Marco; Borlenghi, Erika; Spinelli, Orietta; Giupponi, Damiano; Zanghì, Pamela; Bassan, Renato; Rambaldi, Alessandro; Rossi, Giuseppe; Bosi, Alberto

    2017-03-01

    Mutations in CCAAT/enhancer binding protein α (CEBPA) occur in 5-10% of cases of acute myeloid leukemia. CEBPA-double-mutated cases usually bear biallelic N- and C-terminal mutations and are associated with a favorable clinical outcome. Identification of CEBPA mutants is challenging because of the variety of mutations, intrinsic characteristics of the gene and technical issues. Several screening methods (fragment-length analysis, gene expression array) have been proposed especially for large-scale clinical use; although efficient, they are limited by specific concerns. We investigated the phenotypic profile of blast and maturing bone marrow cell compartments at diagnosis in 251 cases of acute myeloid leukemia. In this cohort, 16 (6.4%) patients had two CEBPA mutations, whereas ten (4.0%) had a single mutation. First, we highlighted that the CEBPA-double-mutated subset displays recurrent phenotypic abnormalities in all cell compartments. By mutational analysis after cell sorting, we demonstrated that this common phenotypic signature depends on CEBPA-double-mutated multi-lineage involvement. From a multidimensional study of phenotypic data, we developed a classifier including ten core and widely available parameters. The selected markers on blasts (CD34, CD117, CD7, CD15, CD65), neutrophil (SSC, CD64), monocytic (CD14, CD64) and erythroid (CD117) compartments were able to cluster CEBPA-double-mutated cases. In a validation set of 259 AML cases from three independent centers, our classifier showed excellent performance with 100% specificity and 100% sensitivity. We have, therefore, established a reliable screening method, based upon multidimensional analysis of widely available phenotypic parameters. This method provides early results and is suitable for large-scale detection of CEBPA-double-mutated status, allowing gene sequencing to be focused in selected cases.

  15. Bacterial profiling of soil using genus-specific markers and multidimensional scaling.

    PubMed

    Lenz, Erin J; Foran, David R

    2010-11-01

    Forensic identification of soil based on microbial DNA fingerprinting has met with mixed success, with research efforts rarely considering temporal variability or local heterogeneity in soil's microbial makeup. In the research presented, the nitrogen fixing bacteria rhizobia were specifically examined. Soils were collected monthly from five habitats for 1 year, and quarterly in each cardinal direction from the main collection site. When all habitats were compared simultaneously using Terminal Restriction Fragment Length Polymorphism analysis of the rhizobial recA gene and multidimensional scaling, only two were differentiated over a year's time, however pairwise comparisons allowed four of five soils to be effectively differentiated. Adding in 10-foot distant soils as "questioned" samples correctly grouped them in 40-70% of cases, depending on restriction enzyme used. The results indicate that the technique has potential for forensic soil identification, although extensive anthropogenic manipulation of a soil makes such identification much more tentative.

  16. Phenotypic and functional profiling of mouse intestinal antigen presenting cells

    PubMed Central

    Harusato, Akihito; Flannigan, Kyle L.; Geem, Duke; Denning, Timothy L.

    2015-01-01

    The microbiota that populates the mammalian intestine consists of hundreds of trillions of bacteria that are separated from underlying immune cells by a single layer of epithelial cells. The intestinal immune system effectively tolerates components of the microbiota that provide benefit to the host while remaining poised to eliminate those that are harmful. Antigen presenting cells, especially macrophages and dendritic cells, play important roles in maintaining intestinal homeostasis via their ability to orchestrate appropriate responses to the microbiota. Paramount to elucidating intestinal macrophage- and dendritic cell-mediated functions is the ability to effectively isolate and identify these cells from a complex cellular environment. In this review, we summarize methodology for the isolation and phenotypic characterization of macrophages and DCs from the mouse intestine and discuss how this may be useful for gaining insight into the mechanisms by which mucosal immune tolerance is maintained. PMID:25891794

  17. Phenotypic profiling of antibiotic response signatures in Escherichia coli using Raman spectroscopy.

    PubMed

    Athamneh, A I M; Alajlouni, R A; Wallace, R S; Seleem, M N; Senger, R S

    2014-01-01

    Identifying the mechanism of action of new potential antibiotics is a necessary but time-consuming and costly process. Phenotypic profiling has been utilized effectively to facilitate the discovery of the mechanism of action and molecular targets of uncharacterized drugs. In this research, Raman spectroscopy was used to profile the phenotypic response of Escherichia coli to applied antibiotics. The use of Raman spectroscopy is advantageous because it is noninvasive, label free, and prone to automation, and its results can be obtained in real time. In this research, E. coli cultures were subjected to three times the MICs of 15 different antibiotics (representing five functional antibiotic classes) with known mechanisms of action for 30 min before being analyzed by Raman spectroscopy (using a 532-nm excitation wavelength). The resulting Raman spectra contained sufficient biochemical information to distinguish between profiles induced by individual antibiotics belonging to the same class. The collected spectral data were used to build a discriminant analysis model that identified the effects of unknown antibiotic compounds on the phenotype of E. coli cultures. Chemometric analysis showed the ability of Raman spectroscopy to predict the functional class of an unknown antibiotic and to identify individual antibiotics that elicit similar phenotypic responses. Results of this research demonstrate the power of Raman spectroscopy as a cellular phenotypic profiling methodology and its potential impact on antibiotic drug development research.

  18. Data sources for in vivo molecular profiling of human phenotypes.

    PubMed

    Cardozo, Timothy; Gupta, Priyanka; Ni, Eric; Young, Lauren M; Tivon, Doreen; Felsovalyi, Klara

    2016-11-01

    Molecular profiling of human diseases has been approached at the genetic (DNA), expression (RNA), and proteomic (protein) levels. An important goal of these efforts is to map observed molecular patterns to specific, mechanistic organic entities, such as loci in the genome, individual RNA molecules or defined proteins or protein assemblies. Importantly, such maps have been historically approached in the more intuitive context of a theoretical individual cell, but diseases are better described in reality using an in vivo framework, namely a library of several tissue-specific maps. In this article, we review the existing data atlases that can be used for this purpose and identify critical gaps that could move the field forward from cellular to in vivo dimensions. WIREs Syst Biol Med 2016, 8:472-484. doi: 10.1002/wsbm.1354 For further resources related to this article, please visit the WIREs website.

  19. Adolescent Risk Behaviors: Studying Typical and Atypical Individuals via Multidimensional Scaling Profile Analysis

    ERIC Educational Resources Information Center

    Dong, Yang; Ding, Cody

    2012-01-01

    Within the framework of problem behavior theory, the purpose of this study was to examine risk behavior profiles of typical and atypical adolescents and the differential outcomes of well-beings for these individuals in the United States. Based on the data from the survey of Health Behavior of School-Aged Children by World Health Organization,…

  20. Phenotypic and ionome profiling of Triticum aestivum x Aegiolps tauschii introgression lines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Eighty-four single homozygous introgressions of the Aegilops tauschii D-genome in the ‘Chinese Spring’ genetic background were used to study phenotypic and ionome profiles during two years of field experiments. An augmented design was used with a repeated check of a local bread wheat cultivar was im...

  1. Computational Models for Prediction of Yeast Strain Potential for Winemaking from Phenotypic Profiles

    PubMed Central

    Umek, Lan; Fonseca, Elza; Drumonde-Neves, João; Dequin, Sylvie; Zupan, Blaz; Schuller, Dorit

    2013-01-01

    Saccharomyces cerevisiae strains from diverse natural habitats harbour a vast amount of phenotypic diversity, driven by interactions between yeast and the respective environment. In grape juice fermentations, strains are exposed to a wide array of biotic and abiotic stressors, which may lead to strain selection and generate naturally arising strain diversity. Certain phenotypes are of particular interest for the winemaking industry and could be identified by screening of large number of different strains. The objective of the present work was to use data mining approaches to identify those phenotypic tests that are most useful to predict a strain's potential for winemaking. We have constituted a S. cerevisiae collection comprising 172 strains of worldwide geographical origins or technological applications. Their phenotype was screened by considering 30 physiological traits that are important from an oenological point of view. Growth in the presence of potassium bisulphite, growth at 40°C, and resistance to ethanol were mostly contributing to strain variability, as shown by the principal component analysis. In the hierarchical clustering of phenotypic profiles the strains isolated from the same wines and vineyards were scattered throughout all clusters, whereas commercial winemaking strains tended to co-cluster. Mann-Whitney test revealed significant associations between phenotypic results and strain's technological application or origin. Naïve Bayesian classifier identified 3 of the 30 phenotypic tests of growth in iprodion (0.05 mg/mL), cycloheximide (0.1 µg/mL) and potassium bisulphite (150 mg/mL) that provided most information for the assignment of a strain to the group of commercial strains. The probability of a strain to be assigned to this group was 27% using the entire phenotypic profile and increased to 95%, when only results from the three tests were considered. Results show the usefulness of computational approaches to simplify strain selection

  2. Computational models for prediction of yeast strain potential for winemaking from phenotypic profiles.

    PubMed

    Mendes, Inês; Franco-Duarte, Ricardo; Umek, Lan; Fonseca, Elza; Drumonde-Neves, João; Dequin, Sylvie; Zupan, Blaz; Schuller, Dorit

    2013-01-01

    Saccharomyces cerevisiae strains from diverse natural habitats harbour a vast amount of phenotypic diversity, driven by interactions between yeast and the respective environment. In grape juice fermentations, strains are exposed to a wide array of biotic and abiotic stressors, which may lead to strain selection and generate naturally arising strain diversity. Certain phenotypes are of particular interest for the winemaking industry and could be identified by screening of large number of different strains. The objective of the present work was to use data mining approaches to identify those phenotypic tests that are most useful to predict a strain's potential for winemaking. We have constituted a S. cerevisiae collection comprising 172 strains of worldwide geographical origins or technological applications. Their phenotype was screened by considering 30 physiological traits that are important from an oenological point of view. Growth in the presence of potassium bisulphite, growth at 40 °C, and resistance to ethanol were mostly contributing to strain variability, as shown by the principal component analysis. In the hierarchical clustering of phenotypic profiles the strains isolated from the same wines and vineyards were scattered throughout all clusters, whereas commercial winemaking strains tended to co-cluster. Mann-Whitney test revealed significant associations between phenotypic results and strain's technological application or origin. Naïve Bayesian classifier identified 3 of the 30 phenotypic tests of growth in iprodion (0.05 mg/mL), cycloheximide (0.1 µg/mL) and potassium bisulphite (150 mg/mL) that provided most information for the assignment of a strain to the group of commercial strains. The probability of a strain to be assigned to this group was 27% using the entire phenotypic profile and increased to 95%, when only results from the three tests were considered. Results show the usefulness of computational approaches to simplify strain selection

  3. Active Learning Strategies for Phenotypic Profiling of High-Content Screens.

    PubMed

    Smith, Kevin; Horvath, Peter

    2014-06-01

    High-content screening is a powerful method to discover new drugs and carry out basic biological research. Increasingly, high-content screens have come to rely on supervised machine learning (SML) to perform automatic phenotypic classification as an essential step of the analysis. However, this comes at a cost, namely, the labeled examples required to train the predictive model. Classification performance increases with the number of labeled examples, and because labeling examples demands time from an expert, the training process represents a significant time investment. Active learning strategies attempt to overcome this bottleneck by presenting the most relevant examples to the annotator, thereby achieving high accuracy while minimizing the cost of obtaining labeled data. In this article, we investigate the impact of active learning on single-cell-based phenotype recognition, using data from three large-scale RNA interference high-content screens representing diverse phenotypic profiling problems. We consider several combinations of active learning strategies and popular SML methods. Our results show that active learning significantly reduces the time cost and can be used to reveal the same phenotypic targets identified using SML. We also identify combinations of active learning strategies and SML methods which perform better than others on the phenotypic profiling problems we studied.

  4. Shade Avoidance Components and Pathways in Adult Plants Revealed by Phenotypic Profiling

    PubMed Central

    Nozue, Kazunari; Tat, An V.; Kumar Devisetty, Upendra; Robinson, Matthew; Mumbach, Maxwell R.; Ichihashi, Yasunori; Lekkala, Saradadevi; Maloof, Julin N.

    2015-01-01

    Shade from neighboring plants limits light for photosynthesis; as a consequence, plants have a variety of strategies to avoid canopy shade and compete with their neighbors for light. Collectively the response to foliar shade is called the shade avoidance syndrome (SAS). The SAS includes elongation of a variety of organs, acceleration of flowering time, and additional physiological responses, which are seen throughout the plant life cycle. However, current mechanistic knowledge is mainly limited to shade-induced elongation of seedlings. Here we use phenotypic profiling of seedling, leaf, and flowering time traits to untangle complex SAS networks. We used over-representation analysis (ORA) of shade-responsive genes, combined with previous annotation, to logically select 59 known and candidate novel mutants for phenotyping. Our analysis reveals shared and separate pathways for each shade avoidance response. In particular, auxin pathway components were required for shade avoidance responses in hypocotyl, petiole, and flowering time, whereas jasmonic acid pathway components were only required for petiole and flowering time responses. Our phenotypic profiling allowed discovery of seventeen novel shade avoidance mutants. Our results demonstrate that logical selection of mutants increased success of phenotypic profiling to dissect complex traits and discover novel components. PMID:25874869

  5. Association of immunological cell profiles with specific clinical phenotypes of scleroderma disease.

    PubMed

    López-Cacho, José Manuel; Gallardo, Soledad; Posada, Manuel; Aguerri, Miriam; Calzada, David; Mayayo, Teodoro; González-Rodríguez, María Luisa; Rabasco, Antonio María; Lahoz, Carlos; Cárdaba, Blanca

    2014-01-01

    This study aimed to search the correlation among immunological profiles and clinical phenotypes of scleroderma in well-characterized groups of scleroderma patients, comparing forty-nine scleroderma patients stratified according to specific clinical phenotypes with forty-nine healthy controls. Five immunological cell subpopulations (B, CD4(+) and CD8(+) T-cells, NK, and monocytes) and their respective stages of apoptosis and activation were analyzed by flow cytometry, in samples of peripheral blood mononuclear cells (PBMCs). Analyses of results were stratified according to disease stage, time since the diagnosis, and visceral damage (pulmonary fibrosis, pulmonary hypertension, and cardiac affliction) and by time of treatment with corticosteroids. An increase in the percentages of monocytes and a decrease in the B cells were mainly related to the disease progression. A general apoptosis decrease was found in all phenotypes studied, except in localized scleroderma. An increase of B and NK cells activation was found in patients diagnosed more than 10 years ago. Specific cell populations like monocytes, NK, and B cells were associated with the type of affected organ. This study shows how, in a heterogeneous disease, proper patient's stratification according to clinical phenotypes allows finding specific cellular profiles. Our data may lead to improvements in the knowledge of prognosis factors and to aid in the analysis of future specific therapies.

  6. Association of Immunological Cell Profiles with Specific Clinical Phenotypes of Scleroderma Disease

    PubMed Central

    Calzada, David; Mayayo, Teodoro; González-Rodríguez, María Luisa; Rabasco, Antonio María; Lahoz, Carlos

    2014-01-01

    This study aimed to search the correlation among immunological profiles and clinical phenotypes of scleroderma in well-characterized groups of scleroderma patients, comparing forty-nine scleroderma patients stratified according to specific clinical phenotypes with forty-nine healthy controls. Five immunological cell subpopulations (B, CD4+ and CD8+ T-cells, NK, and monocytes) and their respective stages of apoptosis and activation were analyzed by flow cytometry, in samples of peripheral blood mononuclear cells (PBMCs). Analyses of results were stratified according to disease stage, time since the diagnosis, and visceral damage (pulmonary fibrosis, pulmonary hypertension, and cardiac affliction) and by time of treatment with corticosteroids. An increase in the percentages of monocytes and a decrease in the B cells were mainly related to the disease progression. A general apoptosis decrease was found in all phenotypes studied, except in localized scleroderma. An increase of B and NK cells activation was found in patients diagnosed more than 10 years ago. Specific cell populations like monocytes, NK, and B cells were associated with the type of affected organ. This study shows how, in a heterogeneous disease, proper patient's stratification according to clinical phenotypes allows finding specific cellular profiles. Our data may lead to improvements in the knowledge of prognosis factors and to aid in the analysis of future specific therapies. PMID:24818126

  7. Multidimensional spectrometer

    DOEpatents

    Zanni, Martin Thomas; Damrauer, Niels H.

    2010-07-20

    A multidimensional spectrometer for the infrared, visible, and ultraviolet regions of the electromagnetic spectrum, and a method for making multidimensional spectroscopic measurements in the infrared, visible, and ultraviolet regions of the electromagnetic spectrum. The multidimensional spectrometer facilitates measurements of inter- and intra-molecular interactions.

  8. Pre-clinical cognitive phenotypes for Alzheimer's disease: a latent profile approach

    PubMed Central

    Hayden, Kathleen M.; Kuchibhatla, Maragatha; Romero, Heather R.; Plassman, Brenda L.; Burke, James R.; Browndyke, Jeffrey N.; Welsh-Bohmer, Kathleen A.

    2013-01-01

    Background Cognitive profiles for pre-clinical Alzheimer's disease (AD) can be used to identify groups of individuals at risk for disease and better characterize pre-clinical disease. Profiles or patterns of performance as pre-clinical phenotypes may be more useful than individual test scores or measures of global decline. Objective(s) The aim of this work is to evaluate patterns of cognitive performance in cognitively normal individuals to derive latent profiles associated with later onset of disease using a combination of factor analysis and latent profile analysis. Methods The National Alzheimer's Coordinating Centers collect data, including a battery of neuropsychological tests, from participants at 29 NIA funded Alzheimer's Disease Centers across the United States. Prior factor analyses of this battery demonstrated a four-factor structure comprising memory, attention, language, and executive function. Factor scores from these analyses were used in a latent profile approach to characterize cognition among a group of cognitively normal participants (n=3,911). Associations between latent profiles and disease outcomes an average of 3 years later were evaluated with multinomial regression models. Similar analyses were used to determine predictors of profile membership. Results Four groups were identified; each with distinct characteristics and significantly associated with later disease outcomes. Two groups were significantly associated with development of cognitive impairment. In post-hoc analyses, both the Trail Making Test Part B, and a contrast score (Delayed Recall - Trails B), significantly predicted group membership and later cognitive impairment. Conclusions Latent profile analysis is a useful method to evaluate patterns of cognition in large samples for the identification of preclinical AD phenotypes; however comparable results can be achieved with very sensitive tests and contrast scores. PMID:24080384

  9. Immune Neuroendocrine Phenotypes in Coturnix coturnix: Do Avian Species Show LEWIS/FISCHER-Like Profiles?

    PubMed Central

    Nazar, F. Nicolas; Barrios, Bibiana E.; Kaiser, Pete; Marin, Raul H.; Correa, Silvia G.

    2015-01-01

    Immunoneuroendocrinology studies have identified conserved communicational paths in birds and mammals, e.g. the Hypothalamus-Pituitary-Adrenal axis with anti-inflammatory activity mediated by glucocorticoids. Immune neuroendocrine phenotypes (INPs) have been proposed for mammals implying the categorization of a population in subgroups underlying divergent immune-neuroendocrine interactions. These phenotypes were studied in the context of the LEWIS/FISCHER paradigm (rats expressing high or low pro-inflammatory profiles, respectively). Although avian species have some common immunological mechanisms with mammals, they have also evolved some distinct strategies and, until now, it has not been studied whether birds may also share with mammals similar INPs. Based on corticosterone levels we determined the existence of two divergent groups in Coturnix coturnix that also differed in other immune-neuroendocrine responses. Quail with lowest corticosterone showed higher lymphoproliferative and antibody responses, interferon-γ and interleukin-1β mRNA expression levels and lower frequencies of leukocyte subpopulations distribution and interleukin-13 levels, than their higher corticosterone counterparts. Results suggest the existence of INPs in birds, comparable to mammalian LEWIS/FISCHER profiles, where basal corticosterone also underlies responses of comparable variables associated to the phenotypes. Concluding, INP may not be a mammalian distinct feature, leading to discuss whether these profiles represent a parallel phenomenon evolved in birds and mammals, or a common feature inherited from a reptilian ancestor millions of years ago. PMID:25793369

  10. Phenotypic Characterization of Retinoic Acid Differentiated SH-SY5Y Cells by Transcriptional Profiling

    PubMed Central

    Korecka, Joanna A.; van Kesteren, Ronald E.; Blaas, Eva; Spitzer, Sonia O.; Kamstra, Jorke H.; Smit, August B.; Swaab, Dick F.; Verhaagen, Joost; Bossers, Koen

    2013-01-01

    Multiple genetic and environmental factors play a role in the development and progression of Parkinson’s disease (PD). The main neuropathological hallmark of PD is the degeneration of dopaminergic (DAergic) neurons in the substantia nigra pars compacta. To study genetic and molecular contributors to the disease process, there is a great need for readily accessible cells with prominent DAergic features that can be used for reproducible in vitro cellular screening. Here, we investigated the molecular phenotype of retinoic acid (RA) differentiated SH-SY5Y cells using genome wide transcriptional profiling combined with gene ontology, transcription factor and molecular pathway analysis. We demonstrated that RA induces a general neuronal differentiation program in SH-SY5Y cells and that these cells develop a predominantly mature DAergic-like neurotransmitter phenotype. This phenotype is characterized by increased dopamine levels together with a substantial suppression of other neurotransmitter phenotypes, such as those for noradrenaline, acetylcholine, glutamate, serotonin and histamine. In addition, we show that RA differentiated SH-SY5Y cells express the dopamine and noradrenalin neurotransmitter transporters that are responsible for uptake of MPP(+), a well known DAergic cell toxicant. MPP(+) treatment alters mitochondrial activity according to its proposed cytotoxic effect in DAergic neurons. Taken together, RA differentiated SH-SY5Y cells have a DAergic-like phenotype, and provide a good cellular screening tool to find novel genes or compounds that affect cytotoxic processes that are associated with PD. PMID:23724009

  11. Evaluation of drug toxicity profiles based on the phenotypes of ascidian Ciona intestinalis.

    PubMed

    Mizotani, Yuji; Itoh, Shun; Hotta, Kohji; Tashiro, Etsu; Oka, Kotaro; Imoto, Masaya

    2015-08-07

    In vivo toxicity evaluation using model organisms is an important step for the development of new drugs. Here, we report that Ciona intestinalis, a chordate invertebrate, is beneficial to drug toxicity evaluation for the following reasons: rapid embryonic and larval development, resemblance to vertebrates, ease of management, low cost, transparent body, and low risk of ethical issues. The dynamic phenotypic change of Ciona larvae during metamorphosis prompted us to examine the effect of cytotoxic drugs on its development by quantifying six toxicity endpoints: degenerated tail size, ampulla length, rotation of body axis, stomach size, heart rate, and body size. As a result, mitochondrial respiratory inhibitors, tubulin polymerization/depolymerization inhibitors, or DNA/RNA synthesis inhibitors showed distinct toxicity profiles against these six endpoints, but drugs with the same targets showed a similar toxicity profile in Ciona. Our results suggest Ciona is an effective animal model for profiling drug toxicity and exploring the mechanisms of drugs with unknown targets.

  12. Metabolic profiles to define the genome: can we hear the phenotypes?

    PubMed Central

    Griffin, Julian L

    2004-01-01

    There is an increased reliance on genetically modified organisms as a functional genomic tool to elucidate the role of genes and their protein products. Despite this, many models do not express the expected phenotype thought to be associated with the gene or protein. There is thus an increased need to further define the phenotype resultant from a genetic modification to understand how the transcriptional or proteomic network may conspire to alter the expected phenotype. This is best typified by the description of the silent phenotype in genetic manipulations of yeast. High-resolution proton nuclear magnetic resonance ((1)H NMR) spectroscopy provides an ideal mechanism for the profiling of metabolites within biofluids, tissue extracts or, with recent advances, intact tissues. These metabolic datasets can be readily mined using a range of pattern recognition techniques, including hierarchical cluster analysis, principal components analysis, partial least squares and neural networks, with the combined approach being termed metabolomics. This review describes the application of NMR-based metabolomics or metabonomics to genetic and chemical interventions in a number of different species, demonstrating the versatility of such an approach, as well as suggesting how it may be integrated with other "omic" technologies. PMID:15306403

  13. Cancer RNA-Seq Nexus: a database of phenotype-specific transcriptome profiling in cancer cells.

    PubMed

    Li, Jian-Rong; Sun, Chuan-Hu; Li, Wenyuan; Chao, Rou-Fang; Huang, Chieh-Chen; Zhou, Xianghong Jasmine; Liu, Chun-Chi

    2016-01-04

    The genome-wide transcriptome profiling of cancerous and normal tissue samples can provide insights into the molecular mechanisms of cancer initiation and progression. RNA Sequencing (RNA-Seq) is a revolutionary tool that has been used extensively in cancer research. However, no existing RNA-Seq database provides all of the following features: (i) large-scale and comprehensive data archives and analyses, including coding-transcript profiling, long non-coding RNA (lncRNA) profiling and coexpression networks; (ii) phenotype-oriented data organization and searching and (iii) the visualization of expression profiles, differential expression and regulatory networks. We have constructed the first public database that meets these criteria, the Cancer RNA-Seq Nexus (CRN, http://syslab4.nchu.edu.tw/CRN). CRN has a user-friendly web interface designed to facilitate cancer research and personalized medicine. It is an open resource for intuitive data exploration, providing coding-transcript/lncRNA expression profiles to support researchers generating new hypotheses in cancer research and personalized medicine.

  14. Empirically Based Phenotypic Profiles of Children with Pervasive Developmental Disorders: Interpretation in the Light of the DSM-5

    ERIC Educational Resources Information Center

    Greaves-Lord, Kirstin; Eussen, Mart L. J. M.; Verhulst, Frank C.; Minderaa, Ruud B.; Mandy, William; Hudziak, James J.; Steenhuis, Mark Peter; de Nijs, Pieter F.; Hartman, Catharina A.

    2013-01-01

    This study aimed to contribute to the Diagnostic and Statistical Manual (DSM) debates on the conceptualization of autism by investigating (1) whether empirically based distinct phenotypic profiles could be distinguished within a sample of mainly cognitively able children with pervasive developmental disorder (PDD), and (2) how profiles related to…

  15. Phenotypic Profiles of Enterotoxigenic Escherichia coli Associated with Early Childhood Diarrhea in Rural Egypt

    PubMed Central

    Shaheen, Hind I.; Khalil, Sami B.; Rao, Malla R.; Elyazeed, Remon Abu; Wierzba, Thomas F.; Peruski, Leonard F.; Putnam, Shannon; Navarro, Armando; Morsy, Badria Z.; Cravioto, Alejandro; Clemens, John D.; Svennerholm, Ann-Mari; Savarino, Stephen J.

    2004-01-01

    Enterotoxigenic Escherichia coli (ETEC) causes substantial diarrheal morbidity and mortality in young children in countries with limited resources. We determined the phenotypic profiles of 915 ETEC diarrheal isolates derived from Egyptian children under 3 years of age who participated in a 3-year population-based study. For each strain, we ascertained enterotoxin and colonization factor (CF) expression, the O:H serotype, and antimicrobial susceptibility. Sixty-one percent of the strains expressed heat-stable enterotoxin (ST) only, 26% expressed heat-labile enterotoxin (LT) alone, and 12% expressed both toxins. The most common CF phenotypes were colonization factor antigen I (CFA/I) (10%), coli surface antigen 6 (CS6) (9%), CS14 (6%), and CS1 plus CS3 (4%). Fifty-nine percent of the strains did not express any of the 12 CFs included in our test panel. Resistance of ETEC strains to ampicillin (63%), trimethoprim-sulfamethoxazole (52%), and tetracycline (43%) was common, while resistance to quinolone antibiotics was rarely detected. As for the distribution of observed serotypes, there was an unusually wide diversity of O antigens and H types represented among the 915 ETEC strains. The most commonly recognized composite ETEC phenotypes were ST CS14 O78:H18 (4%), ST (or LTST) CFA/I O128:H12 (3%), ST CS1+CS3 O6:H16 (2%), and ST CFA/I O153:H45 (1.5%). Temporal plots of diarrheal episodes associated with ETEC strains bearing common composite phenotypes were consistent with discrete community outbreaks either within a single or over successive warm seasons. These data suggest that a proportion of the disease that is endemic to young children in rural Egypt represents the confluence of small epidemics by clonally related ETEC strains that are transiently introduced or that persist in a community reservoir. PMID:15583286

  16. High-resolution phenotypic profiling defines genes essential for mycobacterial growth and cholesterol catabolism.

    PubMed

    Griffin, Jennifer E; Gawronski, Jeffrey D; Dejesus, Michael A; Ioerger, Thomas R; Akerley, Brian J; Sassetti, Christopher M

    2011-09-01

    The pathways that comprise cellular metabolism are highly interconnected, and alterations in individual enzymes can have far-reaching effects. As a result, global profiling methods that measure gene expression are of limited value in predicting how the loss of an individual function will affect the cell. In this work, we employed a new method of global phenotypic profiling to directly define the genes required for the growth of Mycobacterium tuberculosis. A combination of high-density mutagenesis and deep-sequencing was used to characterize the composition of complex mutant libraries exposed to different conditions. This allowed the unambiguous identification of the genes that are essential for Mtb to grow in vitro, and proved to be a significant improvement over previous approaches. To further explore functions that are required for persistence in the host, we defined the pathways necessary for the utilization of cholesterol, a critical carbon source during infection. Few of the genes we identified had previously been implicated in this adaptation by transcriptional profiling, and only a fraction were encoded in the chromosomal region known to encode sterol catabolic functions. These genes comprise an unexpectedly large percentage of those previously shown to be required for bacterial growth in mouse tissue. Thus, this single nutritional change accounts for a significant fraction of the adaption to the host. This work provides the most comprehensive genetic characterization of a sterol catabolic pathway to date, suggests putative roles for uncharacterized virulence genes, and precisely maps genes encoding potential drug targets.

  17. Phenotypic Variations in the Foliar Chemical Profile of Persea americana Mill. cv. Hass.

    PubMed

    García-Rodríguez, Yolanda Magdalena; Torres-Gurrola, Guadalupe; Meléndez-González, Claudio; Espinosa-García, Francisco J

    2016-12-01

    The Hass avocado tree Persea americana cv. Hass was derived from a single hybrid tree of P. americana var. drymifolia and P. americana var. guatemalensis, and it is propagated clonally by grafting. This cultivar is the most widely planted in the world but its profile of secondary metabolites has been studied rarely despite of its importance in plant protection. We illustrate the variability of the volatilome of mature leaves by describing the average chemical composition and the phenotypic variability found in 70 trees. Contrary to the uniformity expected in the Hass cultivar, high variability coefficients were found for most of the 36 detected foliar volatile compounds; furthermore we found six chemotypes grouping the foliar phenotypes of the sampled trees using hierarchical cluster analysis. About 48% of trees were grouped in one chemotype; five chemotypes grouped the remaining trees. The compounds that determined these chemotypes were: estragole, α-farnesene, β-caryophyllene, germacrene D, α-cubebene and eugenol. This striking variation in a cultivar propagated clonally is discussed in terms of somatic mutation.

  18. Genomic and phenotypic profiles of two Brazilian breast cancer cell lines derived from primary human tumors

    PubMed Central

    CORRÊA, NATÁSSIA C.R.; KUASNE, HELLEN; FARIA, JERUSA A.Q.A.; SEIXAS, CIÇA C.S.; SANTOS, IRIA G.D.; ABREU, FRANCINE B.; NONOGAKI, SUELY; ROCHA, RAFAEL M.; SILVA, GERLUZA APARECIDA BORGES; GOBBI, HELENICE; ROGATTO, SILVIA R.; GOES, ALFREDO M.; GOMES, DAWIDSON A.

    2013-01-01

    Breast cancer is the most common type of cancer among women worldwide. Research using breast cancer cell lines derived from primary tumors may provide valuable additional knowledge regarding this type of cancer. Therefore, the aim of this study was to investigate the phenotypic profiles of MACL-1 and MGSO-3, the only Brazilian breast cancer cell lines available for comparative studies. We evaluated the presence of hormone receptors, proliferation, differentiation and stem cell markers, using immunohistochemical staining of the primary tumor, cultured cells and xenografts implanted in immunodeficient mice. We also investigated the ability of the cell lines to form colonies and copy number alterations by array comparative genomic hybridization. Histopathological analysis showed that the invasive primary tumor from which the MACL-1 cell line was derived, was a luminal A subtype carcinoma, while the ductal carcinoma in situ (DCIS) that gave rise to the MGSO-3 cell line was a HER2 subtype tumor, both showing different proliferation levels. The cell lines and the tumor xenografts in mice preserved their high proliferative potential, but did not maintain the expression of the other markers assessed. This shift in expression may be due to the selection of an ‘establishment’ phenotype in vitro. Whole-genome DNA evaluation showed a large amount of copy number alterations (CNAs) in the two cell lines. These findings render MACL-1 and MGSO-3 the first characterized Brazilian breast cancer cell lines to be potentially used for comparative research. PMID:23404580

  19. Time series modeling of live-cell shape dynamics for image-based phenotypic profiling.

    PubMed

    Gordonov, Simon; Hwang, Mun Kyung; Wells, Alan; Gertler, Frank B; Lauffenburger, Douglas A; Bathe, Mark

    2016-01-01

    Live-cell imaging can be used to capture spatio-temporal aspects of cellular responses that are not accessible to fixed-cell imaging. As the use of live-cell imaging continues to increase, new computational procedures are needed to characterize and classify the temporal dynamics of individual cells. For this purpose, here we present the general experimental-computational framework SAPHIRE (Stochastic Annotation of Phenotypic Individual-cell Responses) to characterize phenotypic cellular responses from time series imaging datasets. Hidden Markov modeling is used to infer and annotate morphological state and state-switching properties from image-derived cell shape measurements. Time series modeling is performed on each cell individually, making the approach broadly useful for analyzing asynchronous cell populations. Two-color fluorescent cells simultaneously expressing actin and nuclear reporters enabled us to profile temporal changes in cell shape following pharmacological inhibition of cytoskeleton-regulatory signaling pathways. Results are compared with existing approaches conventionally applied to fixed-cell imaging datasets, and indicate that time series modeling captures heterogeneous dynamic cellular responses that can improve drug classification and offer additional important insight into mechanisms of drug action. The software is available at http://saphire-hcs.org.

  20. Muscle transcriptomic profiles in pigs with divergent phenotypes for fatness traits

    PubMed Central

    2010-01-01

    Background Selection for increasing intramuscular fat content would definitively improve the palatability and juiciness of pig meat as well as the sensorial and organoleptic properties of cured products. However, evidences obtained in human and model organisms suggest that high levels of intramuscular fat might alter muscle lipid and carbohydrate metabolism. We have analysed this issue by determining the transcriptomic profiles of Duroc pigs with divergent phenotypes for 13 fatness traits. The strong aptitude of Duroc pigs to have high levels of intramuscular fat makes them a valuable model to analyse the mechanisms that regulate muscle lipid metabolism, an issue with evident implications in the elucidation of the genetic basis of human metabolic diseases such as obesity and insulin resistance. Results Muscle gene expression profiles of 68 Duroc pigs belonging to two groups (HIGH and LOW) with extreme phenotypes for lipid deposition and composition traits have been analysed. Microarray and quantitative PCR analysis showed that genes related to fatty acid uptake, lipogenesis and triacylglycerol synthesis were upregulated in the muscle tissue of HIGH pigs, which are fatter and have higher amounts of intramuscular fat than their LOW counterparts. Paradoxically, lipolytic genes also showed increased mRNA levels in the HIGH group suggesting the existence of a cycle where triacylglycerols are continuously synthesized and degraded. Several genes related to the insulin-signalling pathway, that is usually impaired in obese humans, were also upregulated. Finally, genes related to antigen-processing and presentation were downregulated in the HIGH group. Conclusion Our data suggest that selection for increasing intramuscular fat content in pigs would lead to a shift but not a disruption of the metabolic homeostasis of muscle cells. Future studies on the post-translational changes affecting protein activity or expression as well as information about protein location within the

  1. Mitochondria Biogenesis and Bioenergetics Gene Profiles in Isogenic Prostate Cells with Different Malignant Phenotypes

    PubMed Central

    Burch, Tanya C.; Rhim, Johng S.

    2016-01-01

    Background. The most significant hallmarks of cancer are directly or indirectly linked to deregulated mitochondria. In this study, we sought to profile mitochondria associated genes in isogenic prostate cell lines with different tumorigenic phenotypes from the same patient. Results. Two isogenic human prostate cell lines RC77N/E (nonmalignant cells) and RC77T/E (malignant cells) were profiled for expression of mitochondrial biogenesis and energy metabolism genes by qRT-PCR using the Human Mitochondria and the Mitochondrial Energy Metabolism RT2 PCR arrays. Forty-seven genes were differentially regulated between the two cell lines. The interaction and regulatory networks of these genes were generated by Ingenuity Pathway Analysis. UCP2 was the most significantly upregulated gene in primary adenocarcinoma cells in the current study. The overexpression of UCP2 upon malignant transformation was further validated using human prostatectomy clinical specimens. Conclusions. This study demonstrates the overexpression of multiple genes that are involved in mitochondria biogenesis, bioenergetics, and modulation of apoptosis. These genes may play a role in malignant transformation and disease progression. The upregulation of some of these genes in clinical samples indicates that some of the differentially transcribed genes could be the potential targets for therapeutic interventions. PMID:27478826

  2. Insomnia Phenotypes Based on Objective Sleep Duration in Adolescents: Depression Risk and Differential Behavioral Profiles

    PubMed Central

    Fernandez-Mendoza, Julio; Calhoun, Susan L.; Vgontzas, Alexandros N.; Li, Yun; Gaines, Jordan; Liao, Duanping; Bixler, Edward O.

    2016-01-01

    Based on previous studies on the role of objective sleep duration in predicting morbidity in individuals with insomnia, we examined the role of objective sleep duration in differentiating behavioral profiles in adolescents with insomnia symptoms. Adolescents from the Penn State Child Cohort (n = 397, ages 12–23, 54.7% male) underwent a nine-hour polysomnography (PSG), clinical history, physical examination and psychometric testing, including the Child or Adult Behavior Checklist and Pediatric Behavior Scale. Insomnia symptoms were defined as a self-report of difficulty falling and/or staying asleep and objective “short” sleep duration as a PSG total sleep time ≤7 h. A significant interaction showed that objective short sleep duration modified the association of insomnia symptoms with internalizing problems. Consistently, adolescents with insomnia symptoms and short sleep duration were characterized by depression, rumination, mood dysregulation and social isolation, while adolescents with insomnia symptoms and normal sleep duration were characterized by rule-breaking and aggressive behaviors and, to a lesser extent, rumination. These findings indicate that objective sleep duration is useful in differentiating behavioral profiles among adolescents with insomnia symptoms. The insomnia with objective short sleep duration phenotype is associated with an increased risk of depression earlier in the lifespan than previously believed. PMID:27983580

  3. Correlation of Lactobacillus rhamnosus Genotypes and Carbohydrate Utilization Signatures Determined by Phenotype Profiling

    PubMed Central

    Lambert, Jolanda; van Limpt, Kees; Wels, Michiel; Smokvina, Tamara; Knol, Jan; Kleerebezem, Michiel

    2015-01-01

    Lactobacillus rhamnosus is a bacterial species commonly colonizing the gastrointestinal (GI) tract of humans and also frequently used in food products. While some strains have been studied extensively, physiological variability among isolates of the species found in healthy humans or their diet is largely unexplored. The aim of this study was to characterize the diversity of carbohydrate utilization capabilities of human isolates and food-derived strains of L. rhamnosus in relation to their niche of isolation and genotype. We investigated the genotypic and phenotypic diversity of 25 out of 65 L. rhamnosus strains from various niches, mainly human feces and fermented dairy products. Genetic fingerprinting of the strains by amplified fragment length polymorphism (AFLP) identified 11 distinct subgroups at 70% similarity and suggested niche enrichment within particular genetic clades. High-resolution carbohydrate utilization profiling (OmniLog) identified 14 carbon sources that could be used by all of the strains tested for growth, while the utilization of 58 carbon sources differed significantly between strains, enabling the stratification of L. rhamnosus strains into three metabolic clusters that partially correlate with the genotypic clades but appear uncorrelated with the strain's origin of isolation. Draft genome sequences of 8 strains were generated and employed in a gene-trait matching (GTM) analysis together with the publicly available genomes of L. rhamnosus GG (ATCC 53103) and HN001 for several carbohydrates that were distinct for the different metabolic clusters: l-rhamnose, cellobiose, l-sorbose, and α-methyl-d-glucoside. From the analysis, candidate genes were identified that correlate with l-sorbose and α-methyl-d-glucoside utilization, and the proposed function of these genes could be confirmed by heterologous expression in a strain lacking the genes. This study expands our insight into the phenotypic and genotypic diversity of the species L. rhamnosus

  4. Metabolomics profiling in plasma samples from glioma patients correlates with tumor phenotypes

    PubMed Central

    Zhao, Hua; Heimberger, Amy B.; Lu, Zhimin; Wu, Xifeng; Hodges, Tiffany R.; Song, Renduo; Shen, Jie

    2016-01-01

    Background Tumor-based molecular biomarkers have redefined in the classification gliomas. However, the association of systemic metabolomics with glioma phenotype has not been explored yet. Methods In this study, we conducted two-step (discovery and validation) metabolomic profiling in plasma samples from 87 glioma patients. The metabolomics data were tested for correlation with glioma grade (high vs low), glioblastoma (GBM) versus malignant gliomas, and IDH mutation status. Results Five metabolites, namely uracil, arginine, lactate, cystamine, and ornithine, significantly differed between high- and low-grade glioma patients in both the discovery and validation cohorts. When the discovery and validation cohorts were combined, we identified 29 significant metabolites with 18 remaining significant after adjusting for multiple comparisons. Those 18 significant metabolites separated high- from low-grade glioma patients with 91.1% accuracy. In the pathway analysis, a total of 18 significantly metabolic pathways were identified. Similarly, we identified 2 and 6 metabolites that significantly differed between GBM and non-GBM, and IDH mutation positive and negative patients after multiple comparison adjusting. Those 6 significant metabolites separated IDH1 mutation positive from negative glioma patients with 94.4% accuracy. Three pathways were identified to be associated with IDH mutation status. Within arginine and proline metabolism, levels of intermediate metabolites in creatine pathway were all significantly lower in IDH mutation positive than in negative patients, suggesting an increased activity of creatine pathway in IDH mutation positive tumors. Conclusion Our findings identified metabolites and metabolic pathways that differentiated tumor phenotypes. These may be useful as host biomarker candidates to further help glioma molecular classification. PMID:26967252

  5. Robust Classification of Small-Molecule Mechanism of Action Using a Minimalist High-Content Microscopy Screen and Multidimensional Phenotypic Trajectory Analysis.

    PubMed

    Twarog, Nathaniel R; Low, Jonathan A; Currier, Duane G; Miller, Greg; Chen, Taosheng; Shelat, Anang A

    2016-01-01

    Phenotypic screening through high-content automated microscopy is a powerful tool for evaluating the mechanism of action of candidate therapeutics. Despite more than a decade of development, however, high content assays have yielded mixed results, identifying robust phenotypes in only a small subset of compound classes. This has led to a combinatorial explosion of assay techniques, analyzing cellular phenotypes across dozens of assays with hundreds of measurements. Here, using a minimalist three-stain assay and only 23 basic cellular measurements, we developed an analytical approach that leverages informative dimensions extracted by linear discriminant analysis to evaluate similarity between the phenotypic trajectories of different compounds in response to a range of doses. This method enabled us to visualize biologically-interpretable phenotypic tracks populated by compounds of similar mechanism of action, cluster compounds according to phenotypic similarity, and classify novel compounds by comparing them to phenotypically active exemplars. Hierarchical clustering applied to 154 compounds from over a dozen different mechanistic classes demonstrated tight agreement with published compound mechanism classification. Using 11 phenotypically active mechanism classes, classification was performed on all 154 compounds: 78% were correctly identified as belonging to one of the 11 exemplar classes or to a different unspecified class, with accuracy increasing to 89% when less phenotypically active compounds were excluded. Importantly, several apparent clustering and classification failures, including rigosertib and 5-fluoro-2'-deoxycytidine, instead revealed more complex mechanisms or off-target effects verified by more recent publications. These results show that a simple, easily replicated, minimalist high-content assay can reveal subtle variations in the cellular phenotype induced by compounds and can correctly predict mechanism of action, as long as the appropriate

  6. A Person-Centered Perspective on Multidimensional Perfectionism in Canadian and Chinese University Students: A Multigroup Latent Profile Analysis

    ERIC Educational Resources Information Center

    Smith, Martin M.; Saklofske, Donald H.; Yan, Gonggu; Sherry, Simon B.

    2016-01-01

    This study investigated the generalizability of the tripartite model of perfectionism across Canadian and Chinese university students. Using latent profile analysis and indicators of perfectionistic strivings, perfectionistic concerns, and neuroticism in both groups, the authors derived a 3-profile solution: adaptive perfectionists, maladaptive…

  7. Local Context Finder (LCF) reveals multidimensional relationships among mRNA expression profiles of Arabidopsis responding to pathogen infection.

    PubMed

    Katagiri, Fumiaki; Glazebrook, Jane

    2003-09-16

    A major task in computational analysis of mRNA expression profiles is definition of relationships among profiles on the basis of similarities among them. This is generally achieved by pattern recognition in the distribution of data points representing each profile in a high-dimensional space. Some drawbacks of commonly used pattern recognition algorithms stem from their use of a globally linear space and/or limited degrees of freedom. A pattern recognition method called Local Context Finder (LCF) is described here. LCF uses nonlinear dimensionality reduction for pattern recognition. Then it builds a network of profiles based on the nonlinear dimensionality reduction results. LCF was used to analyze mRNA expression profiles of the plant host Arabidopsis interacting with the bacterial pathogen Pseudomonas syringae. In one case, LCF revealed two dimensions essential to explain the effects of the NahG transgene and the ndr1 mutation on resistant and susceptible responses. In another case, plant mutants deficient in responses to pathogen infection were classified on the basis of LCF analysis of their profiles. The classification by LCF was consistent with the results of biological characterization of the mutants. Thus, LCF is a powerful method for extracting information from expression profile data.

  8. Temporal expression profiling identifies pathways mediating effect of causal variant on phenotype.

    PubMed

    Gupta, Saumya; Radhakrishnan, Aparna; Raharja-Liu, Pandu; Lin, Gen; Steinmetz, Lars M; Gagneur, Julien; Sinha, Himanshu

    2015-06-01

    Even with identification of multiple causal genetic variants for common human diseases, understanding the molecular processes mediating the causal variants' effect on the disease remains a challenge. This understanding is crucial for the development of therapeutic strategies to prevent and treat disease. While static profiling of gene expression is primarily used to get insights into the biological bases of diseases, it makes differentiating the causative from the correlative effects difficult, as the dynamics of the underlying biological processes are not monitored. Using yeast as a model, we studied genome-wide gene expression dynamics in the presence of a causal variant as the sole genetic determinant, and performed allele-specific functional validation to delineate the causal effects of the genetic variant on the phenotype. Here, we characterized the precise genetic effects of a functional MKT1 allelic variant in sporulation efficiency variation. A mathematical model describing meiotic landmark events and conditional activation of MKT1 expression during sporulation specified an early meiotic role of this variant. By analyzing the early meiotic genome-wide transcriptional response, we demonstrate an MKT1-dependent role of novel modulators, namely, RTG1/3, regulators of mitochondrial retrograde signaling, and DAL82, regulator of nitrogen starvation, in additively effecting sporulation efficiency. In the presence of functional MKT1 allele, better respiration during early sporulation was observed, which was dependent on the mitochondrial retrograde regulator, RTG3. Furthermore, our approach showed that MKT1 contributes to sporulation independent of Puf3, an RNA-binding protein that steady-state transcription profiling studies have suggested to mediate MKT1-pleiotropic effects during mitotic growth. These results uncover interesting regulatory links between meiosis and mitochondrial retrograde signaling. In this study, we highlight the advantage of analyzing allele

  9. Methotrexate modulates folate phenotype and inflammatory profile in EA.hy 926 cells.

    PubMed

    Summers, Carolyn M; Hammons, Andrea L; Arora, Jasbir; Zhang, Suhong; Jochems, Jeanine; Blair, Ian A; Whitehead, Alexander S

    2014-06-05

    EA.hy 926 cells grown under low folate conditions adopt a "pro-atherosclerotic" morphology and biochemical phenotype. Pharmacologically relevant doses of the antifolate drug methotrexate (MTX) were applied to EA.hy 926 cells maintained in normal (Hi) and low (Lo) folate culture media. Under both folate conditions, MTX caused inhibition of cell proliferation without significantly compromising metabolic activity. MTX treated Hi cells were depleted of folate derivatives, which were present in altered proportions relative to untreated cells. Transcript profiling using microarrays indicated that MTX treatment modified the transciptome in similar ways for both Hi and Lo cells. Many inflammation-related genes, most prominently those encoding C3 and IL-8, were up-regulated, whereas many genes involved in cell division were down-regulated. The results for C3 and IL-8 were confirmed by quantitative RT-PCR and ELISA. MTX appears to modify the inflammatory potential of EA.hy 926 cells such that its therapeutic properties may, at least under some conditions, be accompanied by the induction of a subset of gene products that promote and/or maintain comorbid pathologies.

  10. Characterization of CADASIL among the Han Chinese in Taiwan: Distinct Genotypic and Phenotypic Profiles

    PubMed Central

    Fuh, Jong-Ling; Chern, Chang-Ming; Lee, Wei-Ju; Guo, Yuh-Cherng; Wang, Shuu-Jiun; Lee, I-Hui; Liu, Yo-Tsen; Wang, Yen-Feng; Chang, Feng-Chi; Chang, Ming-Hung; Soong, Bing-Wen; Lee, Yi-Chung

    2015-01-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is originally featured with a strong clustering of mutations in NOTCH3 exons 3–6 and leukoencephalopathy with frequent anterior temporal pole involvement. The present study aims at characterizing the genotypic and phenotypic profiles of CADASIL in Taiwan. One hundred and twelve patients with CADASIL from 95 families of Chinese descents in Taiwan were identified by Sanger sequencing of exons 2 to 24 of NOTCH3. Twenty different mutations in NOTCH3 were uncovered, including 3 novel ones, and R544C in exon 11 was the most common mutation, accounting for 70.5% of the pedigrees. Haplotype analyses were conducted in 14 families harboring NOTCH3 R544C mutation and demonstrated a common haplotype linked to NOTCH3 R544C at loci D19S929 and D19S411. Comparing with CADASIL in most Caucasian populations, CADASIL in Taiwan has several distinct features, including less frequent anterior temporal involvement, older age at symptom onset, higher incidence of intracerebral hemorrhage, and rarer occurrence of migraine. Subgroup analyses revealed that the R544C mutation is associated with lower frequency of anterior temporal involvement, later age at onset and higher frequency of cognitive dysfunction. In conclusion, the present study broadens the spectrum of NOTCH3 mutations and provides additional insights for the clinical and molecular characteristics of CADASIL patients of Han-Chinese descents. PMID:26308724

  11. Characterization of CADASIL among the Han Chinese in Taiwan: Distinct Genotypic and Phenotypic Profiles.

    PubMed

    Liao, Yi-Chu; Hsiao, Cheng-Tsung; Fuh, Jong-Ling; Chern, Chang-Ming; Lee, Wei-Ju; Guo, Yuh-Cherng; Wang, Shuu-Jiun; Lee, I-Hui; Liu, Yo-Tsen; Wang, Yen-Feng; Chang, Feng-Chi; Chang, Ming-Hung; Soong, Bing-Wen; Lee, Yi-Chung

    2015-01-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is originally featured with a strong clustering of mutations in NOTCH3 exons 3-6 and leukoencephalopathy with frequent anterior temporal pole involvement. The present study aims at characterizing the genotypic and phenotypic profiles of CADASIL in Taiwan. One hundred and twelve patients with CADASIL from 95 families of Chinese descents in Taiwan were identified by Sanger sequencing of exons 2 to 24 of NOTCH3. Twenty different mutations in NOTCH3 were uncovered, including 3 novel ones, and R544C in exon 11 was the most common mutation, accounting for 70.5% of the pedigrees. Haplotype analyses were conducted in 14 families harboring NOTCH3 R544C mutation and demonstrated a common haplotype linked to NOTCH3 R544C at loci D19S929 and D19S411. Comparing with CADASIL in most Caucasian populations, CADASIL in Taiwan has several distinct features, including less frequent anterior temporal involvement, older age at symptom onset, higher incidence of intracerebral hemorrhage, and rarer occurrence of migraine. Subgroup analyses revealed that the R544C mutation is associated with lower frequency of anterior temporal involvement, later age at onset and higher frequency of cognitive dysfunction. In conclusion, the present study broadens the spectrum of NOTCH3 mutations and provides additional insights for the clinical and molecular characteristics of CADASIL patients of Han-Chinese descents.

  12. Correlation of Phenotypic Profiles Using Targeted Proteomics Identifies Mycobacterial Esx-1 Substrates

    PubMed Central

    2015-01-01

    The Esx/WXG-100 (ESAT-6/Wss) exporters are multiprotein complexes that promote protein translocation across the cytoplasmic membrane in a diverse range of pathogenic and nonpathogenic bacterial species. The Esx-1 (ESAT-6 System-1) system mediates virulence factor translocation in mycobacterial pathogens, including the human pathogen Mycobacterium tuberculosis. Although several genes have been associated with Esx-1-mediated transport and virulence, the contribution of individual Esx-1 genes to export is largely undefined. A unique aspect of Esx-1 export is that several substrates require each other for export/stability. We exploited substrate “codependency” to identify Esx-1 substrates. We simultaneously quantified changes in the levels of 13 Esx-1 proteins from both secreted and cytosolic protein fractions generated from 16 Esx-1-deficient Mycobacterium marinum strains in a single experiment using MRM/SRM targeted mass spectrometry. This expansion of measurable Esx-1 proteins allowed us to define statistical rules for assigning novel substrates using phenotypic profiles of known Esx-1 substrates. Using this approach, we identified three additional Esx-1 substrates encoded by the esx-1 region. Our studies begin to address how disruption of specific genes affects several proteins in the Esx-1 complex. Overall, our findings illuminate relationships between Esx-1 proteins and create a framework for the identification of secreted substrates applicable to other protein exporters and pathways. PMID:25106450

  13. Correlation of phenotypic profiles using targeted proteomics identifies mycobacterial esx-1 substrates.

    PubMed

    Champion, Matthew M; Williams, Emily A; Pinapati, Richard S; Champion, Patricia A DiGiuseppe

    2014-11-07

    The Esx/WXG-100 (ESAT-6/Wss) exporters are multiprotein complexes that promote protein translocation across the cytoplasmic membrane in a diverse range of pathogenic and nonpathogenic bacterial species. The Esx-1 (ESAT-6 System-1) system mediates virulence factor translocation in mycobacterial pathogens, including the human pathogen Mycobacterium tuberculosis. Although several genes have been associated with Esx-1-mediated transport and virulence, the contribution of individual Esx-1 genes to export is largely undefined. A unique aspect of Esx-1 export is that several substrates require each other for export/stability. We exploited substrate "codependency" to identify Esx-1 substrates. We simultaneously quantified changes in the levels of 13 Esx-1 proteins from both secreted and cytosolic protein fractions generated from 16 Esx-1-deficient Mycobacterium marinum strains in a single experiment using MRM/SRM targeted mass spectrometry. This expansion of measurable Esx-1 proteins allowed us to define statistical rules for assigning novel substrates using phenotypic profiles of known Esx-1 substrates. Using this approach, we identified three additional Esx-1 substrates encoded by the esx-1 region. Our studies begin to address how disruption of specific genes affects several proteins in the Esx-1 complex. Overall, our findings illuminate relationships between Esx-1 proteins and create a framework for the identification of secreted substrates applicable to other protein exporters and pathways.

  14. Toxin profile, antibiotic resistance, and phenotypic and molecular characterization of Bacillus cereus in Sunsik.

    PubMed

    Chon, Jung-Whan; Kim, Jong-Hyun; Lee, Sun-Jin; Hyeon, Ji-Yeon; Seo, Kun-Ho

    2012-10-01

    Sunsik, a ready-to-eat food in Korea, is comprised of various agricultural and marine products, and has been an important concern in Bacillus cereus food poisoning. The aim of this study was to investigate the toxin profiles, genotypic and phenotypic patterns as well as antibiotic resistance of B. cereus strains isolated from Sunsik. A subtyping method known as automated repetitive sequence-based PCR system (DiversiLab™) was used to assess the intraspecific biodiversity of these isolates. Thirty-five B. cereus strains were isolated from 100 commercial Sunsik samples, all of which harbored at least 1 enterotoxin gene. The detection rates of nheABC, hblCDA, cytK, and entFM enterotoxin gene among all isolates were 97%, 86%, 77%, and 100%, respectively. Most strains also produced corresponding enterotoxins such as HBL (83%) and NHE (94%). One strain (2.9%) carried the emetic toxin genes, including ces and EM1, and was positive for the HEp-2 cell emetic toxin assay. Most strains were positive for various biochemical tests such as salicin hydrolysis (86%), starch fermentation (89%), hemolysis (89%), motility test (100%) and lecithinase hydrolysis (89%). All isolates were susceptible to most antibiotics although they were highly resistant to β-lactam antibiotics. By using the automated rep-PCR system, all isolates were successfully differentiated, indicating the diversity of B. cereus strains present in Sunsik.

  15. Multi-dimensional TOF-SIMS analysis for effective profiling of disease-related ions from the tissue surface

    NASA Astrophysics Data System (ADS)

    Park, Ji-Won; Jeong, Hyobin; Kang, Byeongsoo; Kim, Su Jin; Park, Sang Yoon; Kang, Sokbom; Kim, Hark Kyun; Choi, Joon Sig; Hwang, Daehee; Lee, Tae Geol

    2015-06-01

    Time-of-flight secondary ion mass spectrometry (TOF-SIMS) emerges as a promising tool to identify the ions (small molecules) indicative of disease states from the surface of patient tissues. In TOF-SIMS analysis, an enhanced ionization of surface molecules is critical to increase the number of detected ions. Several methods have been developed to enhance ionization capability. However, how these methods improve identification of disease-related ions has not been systematically explored. Here, we present a multi-dimensional SIMS (MD-SIMS) that combines conventional TOF-SIMS and metal-assisted SIMS (MetA-SIMS). Using this approach, we analyzed cancer and adjacent normal tissues first by TOF-SIMS and subsequently by MetA-SIMS. In total, TOF- and MetA-SIMS detected 632 and 959 ions, respectively. Among them, 426 were commonly detected by both methods, while 206 and 533 were detected uniquely by TOF- and MetA-SIMS, respectively. Of the 426 commonly detected ions, 250 increased in their intensities by MetA-SIMS, whereas 176 decreased. The integrated analysis of the ions detected by the two methods resulted in an increased number of discriminatory ions leading to an enhanced separation between cancer and normal tissues. Therefore, the results show that MD-SIMS can be a useful approach to provide a comprehensive list of discriminatory ions indicative of disease states.

  16. Multi-dimensional TOF-SIMS analysis for effective profiling of disease-related ions from the tissue surface.

    PubMed

    Park, Ji-Won; Jeong, Hyobin; Kang, Byeongsoo; Kim, Su Jin; Park, Sang Yoon; Kang, Sokbom; Kim, Hark Kyun; Choi, Joon Sig; Hwang, Daehee; Lee, Tae Geol

    2015-06-05

    Time-of-flight secondary ion mass spectrometry (TOF-SIMS) emerges as a promising tool to identify the ions (small molecules) indicative of disease states from the surface of patient tissues. In TOF-SIMS analysis, an enhanced ionization of surface molecules is critical to increase the number of detected ions. Several methods have been developed to enhance ionization capability. However, how these methods improve identification of disease-related ions has not been systematically explored. Here, we present a multi-dimensional SIMS (MD-SIMS) that combines conventional TOF-SIMS and metal-assisted SIMS (MetA-SIMS). Using this approach, we analyzed cancer and adjacent normal tissues first by TOF-SIMS and subsequently by MetA-SIMS. In total, TOF- and MetA-SIMS detected 632 and 959 ions, respectively. Among them, 426 were commonly detected by both methods, while 206 and 533 were detected uniquely by TOF- and MetA-SIMS, respectively. Of the 426 commonly detected ions, 250 increased in their intensities by MetA-SIMS, whereas 176 decreased. The integrated analysis of the ions detected by the two methods resulted in an increased number of discriminatory ions leading to an enhanced separation between cancer and normal tissues. Therefore, the results show that MD-SIMS can be a useful approach to provide a comprehensive list of discriminatory ions indicative of disease states.

  17. Inherited erythromelalgia due to mutations in SCN9A: natural history, clinical phenotype and somatosensory profile.

    PubMed

    McDonnell, Aoibhinn; Schulman, Betsy; Ali, Zahid; Dib-Hajj, Sulayman D; Brock, Fiona; Cobain, Sonia; Mainka, Tina; Vollert, Jan; Tarabar, Sanela; Waxman, Stephen G

    2016-04-01

    Inherited erythromelalgia, the first human pain syndrome linked to voltage-gated sodium channels, is widely regarded as a genetic model of human pain. Because inherited erythromelalgia was linked to gain-of-function changes of sodium channel Na(v)1.7 only a decade ago, the literature has mainly consisted of reports of genetic and/or clinical characterization of individual patients. This paper describes the pattern of pain, natural history, somatosensory profile, psychosocial status and olfactory testing of 13 subjects with primary inherited erythromelalgia with mutations of SCN9A, the gene encoding Na(v)1.7. Subjects were clinically profiled using questionnaires, quantitative sensory testing and olfaction testing during the in-clinic phase of the study. In addition, a detailed pain phenotype for each subject was obtained over a 3-month period at home using diaries, enabling subjects to self-report pain attacks, potential triggers, duration and severity of pain. All subjects reported pain and heat in the extremities (usually feet and/or hands), with pain attacks triggered by heat or exercise and relieved mainly by non-pharmacological manoeuvres such as cooling. A large proportion of pain attacks (355/1099; 32%) did not involve a specific trigger. There was considerable variability in the number, duration and severity of pain attacks between subjects, even those carrying the same mutation within a family, and within individuals over the 12-13 week observation period. Most subjects (11/13) had pain between attacks. For these subjects, mean pain severity between pain attacks was usually lower than that during an attack. Olfaction testing using the Sniffin'T test did not demonstrate hyperosmia. One subject had evidence of orthostatic hypotension. Overall, there was a statistically significant correlation between total Hospital Anxiety and Depression Scale scores (P= 0.005) and pain between attacks and for Hospital Anxiety and Depression Scale Depression scores and pain

  18. Exploring the Lean Phenotype of Glutathione-Depleted Mice: Thiol, Amino Acid and Fatty Acid Profiles

    PubMed Central

    Elshorbagy, Amany K.; Jernerén, Fredrik; Scudamore, Cheryl L.; McMurray, Fiona; Cater, Heather; Hough, Tertius; Cox, Roger; Refsum, Helga

    2016-01-01

    Background Although reduced glutathione (rGSH) is decreased in obese mice and humans, block of GSH synthesis by buthionine sulfoximine (BSO) results in a lean, insulin-sensitive phenotype. Data is lacking about the effect of BSO on GSH precursors, cysteine and glutamate. Plasma total cysteine (tCys) is positively associated with stearoyl-coenzyme A desaturase (SCD) activity and adiposity in humans and animal models. Objective To explore the phenotype, amino acid and fatty acid profiles in BSO-treated mice. Design Male C3H/HeH mice aged 11 weeks were fed a high-fat diet with or without BSO in drinking water (30 mmol/L) for 8 weeks. Amino acid and fatty acid changes were assessed, as well as food consumption, energy expenditure, locomotor activity, body composition and liver vacuolation (steatosis). Results Despite higher food intake, BSO decreased particularly fat mass but also lean mass (both P<0.001), and prevented fatty liver vacuolation. Physical activity increased during the dark phase. BSO decreased plasma free fatty acids and enhanced insulin sensitivity. BSO did not alter liver rGSH, but decreased plasma total GSH (tGSH) and rGSH (by ~70%), and liver tGSH (by 82%). Glutamate accumulated in plasma and liver. Urine excretion of cysteine and its precursors was increased by BSO. tCys, rCys and cystine decreased in plasma (by 23–45%, P<0.001 for all), but were maintained in liver, at the expense of decreased taurine. Free and total plasma concentrations of the SCD products, oleic and palmitoleic acids were decreased (by 27–38%, P <0.001 for all). Conclusion Counterintuitively, block of GSH synthesis decreases circulating tCys, raising the question of whether the BSO-induced obesity-resistance is linked to cysteine depletion. Cysteine-supplementation of BSO-treated mice is warranted to dissect the effects of cysteine and GSH depletion on energy metabolism. PMID:27788147

  19. A Systematic Framework for Drug Repositioning from Integrated Omics and Drug Phenotype Profiles Using Pathway-Drug Network

    PubMed Central

    Jadamba, Erkhembayar

    2016-01-01

    Drug repositioning offers new clinical indications for old drugs. Recently, many computational approaches have been developed to repurpose marketed drugs in human diseases by mining various of biological data including disease expression profiles, pathways, drug phenotype expression profiles, and chemical structure data. However, despite encouraging results, a comprehensive and efficient computational drug repositioning approach is needed that includes the high-level integration of available resources. In this study, we propose a systematic framework employing experimental genomic knowledge and pharmaceutical knowledge to reposition drugs for a specific disease. Specifically, we first obtain experimental genomic knowledge from disease gene expression profiles and pharmaceutical knowledge from drug phenotype expression profiles and construct a pathway-drug network representing a priori known associations between drugs and pathways. To discover promising candidates for drug repositioning, we initialize node labels for the pathway-drug network using identified disease pathways and known drugs associated with the phenotype of interest and perform network propagation in a semisupervised manner. To evaluate our method, we conducted some experiments to reposition 1309 drugs based on four different breast cancer datasets and verified the results of promising candidate drugs for breast cancer by a two-step validation procedure. Consequently, our experimental results showed that the proposed framework is quite useful approach to discover promising candidates for breast cancer treatment. PMID:28127549

  20. Peruvian Maca (Lepidium peruvianum): (II) Phytochemical Profiles of Four Prime Maca Phenotypes Grown in Two Geographically-Distant Locations.

    PubMed

    O Meissner, Henry; Mscisz, Alina; Piatkowska, Ewa; Baraniak, Marek; Mielcarek, Sebastian; Kedzia, Bogdan; Holderna-Kedzia, Elzbieta; Pisulewski, Pawel

    2016-03-01

    Peruvian Maca crops (Lepidium peruvianum), grown in two geographically-distant cultivation sites located at similar altitudes in the highlands of the Peruvian Andes (Junin at 4,200 m a.s.l. and Ancash 4,150 m a.s.l.), were used in the study. Four prime Maca phenotypes, distinguished by hypocotyl colours labelled as "Yellow", "Purple", "Red" and "Black" were selected to determine distribution in levels and corresponding ratios between individual Glucosinolates (Glucotropaeolin and m-methylglucotropaeolin) in an attempt to identify four Peruvian Maca phenotypes from analyses of powdered hypocotyls. There were highly significant differences (P<0.01) in hypocotyl weight/size of four Maca phenotypes harvested in two locations. The Junin crop represented a mostly "large" class (13.3 g) with "small" size hypocotyls (7.2 g), while a "small" class was predominant in Ancash (3.5 g). Powdered Yellow Maca showed significantly higher (P<0.001) microbial contamination than the other three, with Black Maca being the least infected. Only minor, statistically-confirmed differences were detected in nutritive characteristics between the four Maca phenotypes grown in Junin, however highly significant differences (P<0.01) in Glucosinolates existed between the Red and Black Maca grown in Junin and Ancash. Irrespective of the cultivation location, Red phenotypes showed the highest content of Total Glucosinolates, followed by Black and Purple, with the Yellow phenotype showing consistently lower levels. Highly significant P<0.01) differences determined in ratios of individual Glucosinolates between four Maca phenotypes grown in two locations, confirms an earlier assumption that sums of individual Glucosinolates, their ratios and profiles, may be feasible to explore in analytically identifying individual Maca phenotypes in pulverised marketed Maca products.

  1. Peruvian Maca (Lepidium peruvianum): (II) Phytochemical Profiles of Four Prime Maca Phenotypes Grown in Two Geographically-Distant Locations

    PubMed Central

    O. Meissner, Henry; Mscisz, Alina; Piatkowska, Ewa; Baraniak, Marek; Mielcarek, Sebastian; Kedzia, Bogdan; Holderna-Kedzia, Elzbieta; Pisulewski, Pawel

    2016-01-01

    Peruvian Maca crops (Lepidium peruvianum), grown in two geographically-distant cultivation sites located at similar altitudes in the highlands of the Peruvian Andes (Junin at 4,200 m a.s.l. and Ancash 4,150 m a.s.l.), were used in the study. Four prime Maca phenotypes, distinguished by hypocotyl colours labelled as “Yellow”, “Purple”, “Red” and “Black” were selected to determine distribution in levels and corresponding ratios between individual Glucosinolates (Glucotropaeolin and m-methylglucotropaeolin) in an attempt to identify four Peruvian Maca phenotypes from analyses of powdered hypocotyls. There were highly significant differences (P<0.01) in hypocotyl weight/size of four Maca phenotypes harvested in two locations. The Junin crop represented a mostly “large” class (13.3 g) with “small” size hypocotyls (7.2 g), while a “small” class was predominant in Ancash (3.5 g). Powdered Yellow Maca showed significantly higher (P<0.001) microbial contamination than the other three, with Black Maca being the least infected. Only minor, statistically-confirmed differences were detected in nutritive characteristics between the four Maca phenotypes grown in Junin, however highly significant differences (P<0.01) in Glucosinolates existed between the Red and Black Maca grown in Junin and Ancash. Irrespective of the cultivation location, Red phenotypes showed the highest content of Total Glucosinolates, followed by Black and Purple, with the Yellow phenotype showing consistently lower levels. Highly significant P<0.01) differences determined in ratios of individual Glucosinolates between four Maca phenotypes grown in two locations, confirms an earlier assumption that sums of individual Glucosinolates, their ratios and profiles, may be feasible to explore in analytically identifying individual Maca phenotypes in pulverised marketed Maca products. PMID:27127450

  2. Phenotypic profiling of keloid scars using FT-IR microspectroscopy reveals a unique spectral signature.

    PubMed

    Hollywood, Katherine A; Maatje, Marlies; Shadi, Iqbal T; Henderson, Alex; McGrouther, Duncan Angus; Goodacre, Royston; Bayat, Ardeshir

    2010-12-01

    Keloid disease (KD) is a quasineoplastic fibroproliferative tumour of unknown origin causing a progressive, recurrent dermal lesion. KD is not homogeneous in nature and shows phenotypic structural differences between its distinct peripheral margins compared to its centre. The keloid margin is often symptomatically more active with increased dermal cellularity, compared to a symptomatically dormant and hypocellular centre of lesion. The aim of this study was to delineate the morphological components of a keloid scar tissue by measuring the differences between various anatomical locations within the keloid tissue, such as the margin and the centre of the lesion compared to its surrounding normal skin using Fourier transform infrared (FT-IR) microspectroscopy. FT-IR microspectroscopy is a technique that produces spectra with detailed molecular biochemical information inherent of the chemical structure. Chemical maps were constructed on extralesional cross sections taken from six keloid scars. H&E stained sections were used to confirm diagnosis of keloid and orientate the experimental cross sections prior to FT-IR. Spectral band assignment and principal components analysis were conducted. Distinct vibrational bands (100 spectra) were observed using FT-IR spectroscopy. Partial least squares discriminant analysis, with bootstrapping (10,000 analyses), identified whether a spectrum was from the keloid or normal tissue showing an average accuracy of 84.8%, precision of 80.4%, specificity of 76.2%, and sensitivity of 92.9%. FT-IR microspectroscopy showed significant differences in spectral profiles in keloid tissue in different anatomical locations within the cross section. We believe that this proof-of-concept study may help substantiate the use of FTIR spectroscopy in keloid diagnosis and prognosis.

  3. Lipid mediator metabolic profiling demonstrates differences in eicosanoid patterns in two phenotypically distinct mast cell populations[S

    PubMed Central

    Lundström, Susanna L.; Saluja, Rohit; Adner, Mikael; Haeggström, Jesper Z.; Nilsson, Gunnar; Wheelock, Craig E.

    2013-01-01

    Mast cells are inflammatory cells that play key roles in health and disease. They are distributed in all tissues and appear in two main phenotypes, connective tissue and mucosal mast cells, with differing capacities to release inflammatory mediators. A metabolic profiling approach was used to obtain a more comprehensive understanding of the ability of mast cell phenotypes to produce eicosanoids and other lipid mediators. A total of 90 lipid mediators (oxylipins) were characterized using liquid chromatography-tandem mass spectrometry (LC-MS/MS), representing the cyclooxygenase (COX), lipoxygenase (LO), and cytochrome P450 (CYP) metabolic pathways. In vitro-derived murine mucosal-like mast cells (MLMC) and connective tissue-like mast cells (CTLMC) exhibited distinct mRNA expression patterns of enzymes involved in oxylipin biosynthesis. Oxylipins produced by 5-LO and COX pathways were the predominant species in both phenotypes, with 5-LO products constituting 90 ± 2% of the CTLMCs compared with 58 ± 8% in the MLMCs. Multivariate analyses demonstrated that CTLMCs and MLMCs secrete differing oxylipin profiles at baseline and following calcium ionophore stimulation, evidencing specificity in both a time- and biosynthetic pathway-dependent manner. In addition to the COX-regulated prostaglandin PGD2 and 5-LO-regulated cysteinyl-leukotrienes (e.g., LTC4), several other mediators evidenced phenotype-specificity, which may have biological implications in mast cell-mediated regulation of inflammatory responses. PMID:23034214

  4. High-content analysis to leverage a robust phenotypic profiling approach to vascular modulation.

    PubMed

    Isherwood, Beverley J; Walls, Rebecca E; Roberts, Mark E; Houslay, Thomas M; Brave, Sandra R; Barry, Simon T; Carragher, Neil O

    2013-12-01

    Phenotypic screening seeks to identify substances that modulate phenotypes in a desired manner with the aim of progressing first-in-class agents. Successful campaigns require physiological relevance, robust screening, and an ability to deconvolute perturbed pathways. High-content analysis (HCA) is increasingly used in cell biology and offers one approach to prosecution of phenotypic screens, but challenges exist in exploitation where data generated are high volume and complex. We combine development of an organotypic model with novel HCA tools to map phenotypic responses to pharmacological perturbations. We describe implementation for angiogenesis, a process that has long been a focus for therapeutic intervention but has lacked robust models that recapitulate more completely mechanisms involved. The study used human primary endothelial cells in co-culture with stromal fibroblasts to model multiple aspects of angiogenic signaling: cell interactions, proliferation, migration, and differentiation. Multiple quantitative descriptors were derived from automated microscopy using custom-designed algorithms. Data were extracted using a bespoke informatics platform that integrates processing, statistics, and feature display into a streamlined workflow for building and interrogating fingerprints. Ninety compounds were characterized, defining mode of action by phenotype. Our approach for assessing phenotypic outcomes in complex assay models is robust and capable of supporting a range of phenotypic screens at scale.

  5. Profiling the extended phenotype of plant pathogens: Challenges in Bacterial Molecular Plant Pathology.

    PubMed

    Preston, Gail M

    2017-04-01

    One of the most fundamental questions in plant pathology is what determines whether a pathogen grows within a plant? This question is frequently studied in terms of the role of elicitors and pathogenicity factors in the triggering or overcoming of host defences. However, this focus fails to address the basic question of how the environment in host tissues acts to support or restrict pathogen growth. Efforts to understand this aspect of host-pathogen interactions are commonly confounded by several issues, including the complexity of the plant environment, the artificial nature of many experimental infection systems and the fact that the physiological properties of a pathogen growing in association with a plant can be very different from the properties of the pathogen in culture. It is also important to recognize that the phenotype and evolution of pathogen and host are inextricably linked through their interactions, such that the environment experienced by a pathogen within a host, and its phenotype within the host, is a product of both its interaction with its host and its evolutionary history, including its co-evolution with host plants. As the phenotypic properties of a pathogen within a host cannot be defined in isolation from the host, it may be appropriate to think of pathogens as having an 'extended phenotype' that is the product of their genotype, host interactions and population structure within the host environment. This article reflects on the challenge of defining and studying this extended phenotype, in relation to the questions posed below, and considers how knowledge of the phenotype of pathogens in the host environment could be used to improve disease control. What determines whether a pathogen grows within a plant? What aspects of pathogen biology should be considered in describing the extended phenotype of a pathogen within a host? How can we study the extended phenotype in ways that provide insights into the phenotypic properties of pathogens

  6. Phenotypic profile of expanded NK cells in chronic lymphoproliferative disorders: a surrogate marker for NK-cell clonality

    PubMed Central

    Bárcena, Paloma; Jara-Acevedo, María; Tabernero, María Dolores; López, Antonio; Sánchez, María Luz; García-Montero, Andrés C.; Muñoz-García, Noemí; Vidriales, María Belén; Paiva, Artur; Lecrevisse, Quentin; Lima, Margarida; Langerak, Anton W.; Böttcher, Sebastian; van Dongen, Jacques J.M.

    2015-01-01

    Currently, the lack of a universal and specific marker of clonality hampers the diagnosis and classification of chronic expansions of natural killer (NK) cells. Here we investigated the utility of flow cytometric detection of aberrant/altered NK-cell phenotypes as a surrogate marker for clonality, in the diagnostic work-up of chronic lymphoproliferative disorders of NK cells (CLPD-NK). For this purpose, a large panel of markers was evaluated by multiparametric flow cytometry on peripheral blood (PB) CD56low NK cells from 60 patients, including 23 subjects with predefined clonal (n = 9) and polyclonal (n = 14) CD56low NK-cell expansions, and 37 with CLPD-NK of undetermined clonality; also, PB samples from 10 healthy adults were included. Clonality was established using the human androgen receptor (HUMARA) assay. Clonal NK cells were found to show decreased expression of CD7, CD11b and CD38, and higher CD2, CD94 and HLADR levels vs. normal NK cells, together with a restricted repertoire of expression of the CD158a, CD158b and CD161 killer-associated receptors. In turn, NK cells from both clonal and polyclonal CLPD-NK showed similar/overlapping phenotypic profiles, except for high and more homogeneous expression of CD94 and HLADR, which was restricted to clonal CLPD-NK. We conclude that the CD94hi/HLADR+ phenotypic profile proved to be a useful surrogate marker for NK-cell clonality. PMID:26556869

  7. Phenotypic profile of expanded NK cells in chronic lymphoproliferative disorders: a surrogate marker for NK-cell clonality.

    PubMed

    Bárcena, Paloma; Jara-Acevedo, María; Tabernero, María Dolores; López, Antonio; Sánchez, María Luz; García-Montero, Andrés C; Muñoz-García, Noemí; Vidriales, María Belén; Paiva, Artur; Lecrevisse, Quentin; Lima, Margarida; Langerak, Anton W; Böttcher, Sebastian; van Dongen, Jacques J M; Orfao, Alberto; Almeida, Julia

    2015-12-15

    Currently, the lack of a universal and specific marker of clonality hampers the diagnosis and classification of chronic expansions of natural killer (NK) cells. Here we investigated the utility of flow cytometric detection of aberrant/altered NK-cell phenotypes as a surrogate marker for clonality, in the diagnostic work-up of chronic lymphoproliferative disorders of NK cells (CLPD-NK). For this purpose, a large panel of markers was evaluated by multiparametric flow cytometry on peripheral blood (PB) CD56(low) NK cells from 60 patients, including 23 subjects with predefined clonal (n = 9) and polyclonal (n = 14) CD56(low) NK-cell expansions, and 37 with CLPD-NK of undetermined clonality; also, PB samples from 10 healthy adults were included. Clonality was established using the human androgen receptor (HUMARA) assay. Clonal NK cells were found to show decreased expression of CD7, CD11b and CD38, and higher CD2, CD94 and HLADR levels vs. normal NK cells, together with a restricted repertoire of expression of the CD158a, CD158b and CD161 killer-associated receptors. In turn, NK cells from both clonal and polyclonal CLPD-NK showed similar/overlapping phenotypic profiles, except for high and more homogeneous expression of CD94 and HLADR, which was restricted to clonal CLPD-NK. We conclude that the CD94(hi)/HLADR+ phenotypic profile proved to be a useful surrogate marker for NK-cell clonality.

  8. Latent profile analysis of healthy schizotypy within the extended psychosis phenotype

    PubMed Central

    Tabak, Naomi Tuchman; de Mamani, Amy Gina Weisman

    2014-01-01

    Converging evidence suggests that psychosis exists on a continuum, and that even mentally “healthy” individuals may experience subclinical psychotic experiences. However, little research has examined the subjective and psychological well-being of individuals in the putatively healthy end of the continuum. This study explored the latent profile structure of schizotypy in a non-clinical sample and compared subjective and psychological well-being across schizotypy profiles. Latent profile analysis was conducted on participants’ responses (N=420) to the Oxford-Liverpool Inventory of Feelings and Experiences. Six latent profiles emerged: Low Schizotypy, Average, High Schizotypy, High Unusual Experiences (UE), High Introvertive Anhedonia, and High Introvertive Anhedonia/Cognitive Disorganization. Individuals in the profile characterized by high UE without negative, disorganized or impulsive features tended to endorse similar levels of well-being as the Average and Low Schizotypy profiles. With some exceptions, all three profiles also demonstrated significantly greater subjective and psychological well-being when compared to negative/disorganized schizotypy profiles. The UE profile most closely aligns with previous conceptualizations of “healthy schizotypy.” Future research should investigate how individuals in this profile make sense of unusual or ambiguous experiences that may lead to distress in clinical populations. PMID:24001585

  9. Recycling Behavior: A Multidimensional Approach

    ERIC Educational Resources Information Center

    Meneses, Gonzalo Diaz; Palacio, Asuncion Beerli

    2005-01-01

    This work centers on the study of consumer recycling roles to examine the sociodemographic and psychographic profile of the distribution of recycling tasks and roles within the household. With this aim in mind, an empirical work was carried out, the results of which suggest that recycling behavior is multidimensional and comprises the undertaking…

  10. Multidimensional scaling

    PubMed Central

    Papesh, Megan H.; Goldinger, Stephen D.

    2012-01-01

    The concept of similarity, or a sense of "sameness" among things, is pivotal to theories in the cognitive sciences and beyond. Similarity, however, is a difficult thing to measure. Multidimensional scaling (MDS) is a tool by which researchers can obtain quantitative estimates of similarity among groups of items. More formally, MDS refers to a set of statistical techniques that are used to reduce the complexity of a data set, permitting visual appreciation of the underlying relational structures contained therein. The current paper provides an overview of MDS. We discuss key aspects of performing this technique, such as methods that can be used to collect similarity estimates, analytic techniques for treating proximity data, and various concerns regarding interpretation of the MDS output. MDS analyses of two novel data sets are also included, highlighting in step-by-step fashion how MDS is performed, and key issues that may arise during analysis. PMID:23359318

  11. Label-free cell phenotypic profiling decodes the composition and signaling of an endogenous ATP-sensitive potassium channel

    PubMed Central

    Sun, Haiyan; Wei, Ying; Deng, Huayun; Xiong, Qiaojie; Li, Min; Lahiri, Joydeep; Fang, Ye

    2014-01-01

    Current technologies for studying ion channels are fundamentally limited because of their inability to functionally link ion channel activity to cellular pathways. Herein, we report the use of label-free cell phenotypic profiling to decode the composition and signaling of an endogenous ATP-sensitive potassium ion channel (KATP) in HepG2C3A, a hepatocellular carcinoma cell line. Label-free cell phenotypic agonist profiling showed that pinacidil triggered characteristically similar dynamic mass redistribution (DMR) signals in A431, A549, HT29 and HepG2C3A, but not in HepG2 cells. Reverse transcriptase PCR, RNAi knockdown, and KATP blocker profiling showed that the pinacidil DMR is due to the activation of SUR2/Kir6.2 KATP channels in HepG2C3A cells. Kinase inhibition and RNAi knockdown showed that the pinacidil activated KATP channels trigger signaling through Rho kinase and Janus kinase-3, and cause actin remodeling. The results are the first demonstration of a label-free methodology to characterize the composition and signaling of an endogenous ATP-sensitive potassium ion channel. PMID:24816792

  12. Redefining phenotypes in eating disorders based on personality: a latent profile analysis.

    PubMed

    Krug, Isabel; Root, Tammy; Bulik, Cynthia; Granero, Roser; Penelo, Eva; Jiménez-Murcia, Susana; Fernández-Aranda, Fernando

    2011-08-15

    To conduct a latent profile analysis (LPA) in eating disorder (ED) patients using temperament and character (TCI-R) measures as indicators. 1312 ED patients including those with anorexia nervosa (AN), bulimia nervosa (BN) and EDNOS were assessed. The final LPA solution was validated using demographics, clinical variables, ED symptomatology (EDI-2) and impulsive behaviors. The best-fitting model consisted of a six-profile solution using the seven subscales of the TCI-R. These profiles were labeled: "self-focused", "inhibited", "average", "impulsive", "adaptive" and "maladaptive". Validation analyses indicated that the "inhibited" and "maladaptive" profiles generally presented with the highest values for ED symptomatology and impulsive behaviors. Whereas high levels of Harm Avoidance and low levels of Novelty Seeking and Persistence characterized the "inhibited" profile, the "maladaptive" profile presented with low levels of Reward Dependence, Self-Directedness and Cooperativeness. The most favorable results on the other hand were exhibited by the "adaptive" profile, characterized by high scores on Reward Dependence, Self-Directedness, Cooperativeness and low levels on Novelty Seeking. Finally, when our six-profile solution was compared with the DSM-IV ED diagnoses, significant differences among profiles and ED diagnoses were observed. Our study shows that ED patients can be meaningfully grouped according to temperament and character.

  13. High-resolution phenotypic profiling of natural products-induced effects on the single-cell level

    PubMed Central

    Kremb, Stephan; Voolstra, Christian R.

    2017-01-01

    Natural products (NPs) are highly evolved molecules making them a valuable resource for new therapeutics. Here we demonstrate the usefulness of broad-spectrum phenotypic profiling of NP-induced perturbations on single cells with imaging-based High-Content Screening to inform on physiology, mechanisms-of-actions, and multi-level toxicity. Our technology platform aims at broad applicability using a comprehensive marker panel with standardized settings streamlined towards an easy implementation in laboratories dedicated to natural products research. PMID:28295057

  14. Adaptation of the Biolog Phenotype MicroArrayTM Technology to Profile the Obligate Anaerobe Geobacter metallireducens

    SciTech Connect

    Joyner, Dominique; Fortney, Julian; Chakraborty, Romy; Hazen, Terry

    2010-05-17

    The Biolog OmniLog? Phenotype MicroArray (PM) plate technology was successfully adapted to generate a select phenotypic profile of the strict anaerobe Geobacter metallireducens (G.m.). The profile generated for G.m. provides insight into the chemical sensitivity of the organism as well as some of its metabolic capabilities when grown with a basal medium containing acetate and Fe(III). The PM technology was developed for aerobic organisms. The reduction of a tetrazolium dye by the test organism represents metabolic activity on the array which is detected and measured by the OmniLog(R) system. We have previously adapted the technology for the anaerobic sulfate reducing bacterium Desulfovibrio vulgaris. In this work, we have taken the technology a step further by adapting it for the iron reducing obligate anaerobe Geobacter metallireducens. In an osmotic stress microarray it was determined that the organism has higher sensitivity to impermeable solutes 3-6percent KCl and 2-5percent NaNO3 that result in osmotic stress by osmosis to the cell than to permeable non-ionic solutes represented by 5-20percent ethylene glycol and 2-3percent urea. The osmotic stress microarray also includes an array of osmoprotectants and precursor molecules that were screened to identify substrates that would provide osmotic protection to NaCl stress. None of the substrates tested conferred resistance to elevated concentrations of salt. Verification studies in which G.m. was grown in defined medium amended with 100mM NaCl (MIC) and the common osmoprotectants betaine, glycine and proline supported the PM findings. Further verification was done by analysis of transcriptomic profiles of G.m. grown under 100mM NaCl stress that revealed up-regulation of genes related to degradation rather than accumulation of the above-mentioned osmoprotectants. The phenotypic profile, supported by additional analysis indicates that the accumulation of these osmoprotectants as a response to salt stress does not

  15. Multidimensional heritability analysis of neuroanatomical shape

    PubMed Central

    Ge, Tian; Reuter, Martin; Winkler, Anderson M.; Holmes, Avram J.; Lee, Phil H.; Tirrell, Lee S.; Roffman, Joshua L.; Buckner, Randy L.; Smoller, Jordan W.; Sabuncu, Mert R.

    2016-01-01

    In the dawning era of large-scale biomedical data, multidimensional phenotype vectors will play an increasing role in examining the genetic underpinnings of brain features, behaviour and disease. For example, shape measurements derived from brain MRI scans are multidimensional geometric descriptions of brain structure and provide an alternate class of phenotypes that remains largely unexplored in genetic studies. Here we extend the concept of heritability to multidimensional traits, and present the first comprehensive analysis of the heritability of neuroanatomical shape measurements across an ensemble of brain structures based on genome-wide SNP and MRI data from 1,320 unrelated, young and healthy individuals. We replicate our findings in an extended twin sample from the Human Connectome Project (HCP). Our results demonstrate that neuroanatomical shape can be significantly heritable, above and beyond volume, and can serve as a complementary phenotype to study the genetic determinants and clinical relevance of brain structure. PMID:27845344

  16. Phenotypic and genotypic profile of human tympanic membrane derived cultured cells.

    PubMed

    Redmond, Sharon L; Levin, Brett; Heel, Kathryn A; Atlas, Marcus D; Marano, Robert J

    2011-02-01

    The human tympanic membrane (hTM), known more commonly as the eardrum, is a thin, multi-layered membrane that is unique in the body as it is suspended in air. When perforated, the hTM's primary function of sound-pressure transmission is compromised. For the purposes of TM reconstruction, we investigated the phenotype and genotype of cultured primary cells derived from hTM tissue explants, compared to epithelial (HaCaT cells) and mesenchymal (human dermal fibroblasts (HDF)) reference cells. Epithelium-specific ets-1 (ESE-1), E-cadherin, keratinocyte growth factor-1 (KGF-1/FGF-7), keratinocyte growth factor-2 (KGF-2/FGF10), fibroblast growth factor receptor 1 (FGFR1), variants of fibroblast growth factor receptor 2 (FGFR2), fibroblast surface protein (FSP), and vimentin proteins were used to assess the phenotypes of all cultured cells. Wholemount and paraffin-embedded hTM tissues were stained with ESE-1 and E-cadherin proteins to establish normal epithelial-specific expression patterns within the epithelial layers. Immunofluorescent (IF) cell staining of hTM epithelial cells (hTMk) demonstrated co-expression of both epithelial- and mesenchymal-specific proteins. Flow cytometry (FCM) analysis further demonstrated co-expression of these epithelial and mesenchymal-specific proteins, indicating the subcultured hTMk cells possessed a transitional phenotype. Gene transcript analysis of hTMk cells by reverse transcriptase polymerase chain reaction (RT-PCR) revealed a down regulation of ESE-1, E-cadherin, FGFR2, variant 1 and variant 2 (FGFR2v1 and FGFR2v2) between low and high passages, and up-regulation of KGF-1, KGF-2, and FGFR1. All results indicate a gradual shift in cell phenotype of hTMk-derived cells from epithelial to mesenchymal.

  17. Comparison of phenotypic and genotypic profiles among caprine and ovine Mycoplasma ovipneumoniae strains.

    PubMed

    Maksimović, Z; De la Fe, C; Amores, J; Gómez-Martín, Á; Rifatbegović, M

    2017-02-18

    Mycoplasma ovipneumoniae (Movp) is considered to be one of the most important mycoplasmas causing respiratory disease in small ruminants. Most epidemiologic and characterisation studies have been conducted on strains collected from sheep. Information on the presence and characteristics of Movp in healthy and pneumonic goats is limited. Phenotypic or genotypic differences between sheep and goat isolates have never been studied. The objective of our study was to characterise and compare the similarities and differences between caprine and ovine Movp strains isolated from affected and asymptomatic animals in order to elucidate phenotypic and genotypic variability. Four different techniques were used on a set of 23 Movp isolates. These included SDS-PAGE, Western blotting, random amplified polymorphic DNA and the heat shock protein 70 gene sequence-based method. A high degree of phenotypic and genotypic heterogeneity among Movp strains was demonstrated in this study. Our results demonstrated differences between goat and sheep strains, revealing not only a link between strains and host ruminant species, but by geographical origin as well. However, the finding of immunodominant antigens of molecular masses 36, 38, 40 and 70 kDa (±3 kDa) in Movp isolates from sheep and goats foretells their potential use in the development of serological diagnostic tests and vaccines.

  18. Common Variable Immunodeficiency patients with a phenotypic profile of immunosenescence present with thrombocytopenia

    PubMed Central

    Stuchlý, Jan; Kanderová, Veronika; Vlková, Marcela; Heřmanová, Ivana; Slámová, Lucie; Pelák, Ondřej; Taraldsrud, Eli; Jílek, Dalibor; Králíčková, Pavlína; Fevang, Børre; Trková, Marie; Hrušák, Ondřej; Froňková, Eva; Šedivá, Anna; Litzman, Jiří; Kalina, Tomáš

    2017-01-01

    Common variable immunodeficiency (CVID) is a heterogeneous group of diseases. Our aim was to define sub-groups of CVID patients with similar phenotypes and clinical characteristics. Using eight-color flow cytometry, we analyzed both B- and T-cell phenotypes in a cohort of 88 CVID patients and 48 healthy donors. A hierarchical clustering of probability binning “bins” yielded a separate cluster of 22 CVID patients with an abnormal phenotype. We showed coordinated proportional changes in naïve CD4+ T-cells (decreased), intermediate CD27− CD28+ CD4+ T-cells (increased) and CD21low B-cells (increased) that were stable for over three years. Moreover, the lymphocytes’ immunophenotype in this patient cluster exhibited features of profound immunosenescence and chronic activation. Thrombocytopenia was only found in this cluster (36% of cases, manifested as Immune Thrombocytopenia (ITP) or Evans syndrome). Clinical complications more frequently found in these patients include lung fibrosis (in 59% of cases) and bronchiectasis (55%). The degree of severity of these symptoms corresponded to more deviation from normal levels with respect to CD21low B-cells, naïve CD4+ and CD27− CD28+ over three years. Moreover, th-cells. Next-generation sequencing did not reveal any common genetic background. We delineate a subgroup of CVID patients with activated and immunosenescent immunophenotype of lymphocytes and distinct set of clinical complications without common genetic background. PMID:28054583

  19. Antibiotic resistance profiling and phenotyping of Aeromonas species isolated from aquatic sources.

    PubMed

    Odeyemi, Olumide A; Ahmad, Asmat

    2017-01-01

    This study aimed to investigate antibiotics resistance pattern and phenotyping of Aeromonas species isolated from different aquatic sources in Melaka, Malaysia. A total of 53 Aeromonas species were isolated from the following sources: sediment (n = 13), bivalve (n = 10), sea cucumber (n = 16) and sea water (n = 14) and resistance to 12 antibiotics - Tetracycline (30 μg), Kanamycin (30 μg), Oxytetracycline (30 μg), Ampicillin (10 μg), Streptomycin (10 μg), Gentamicin (10 μg), Sulphamethoxazole (25 μg), Nalixidic acid (30 μg), Trimethoprim (1.25 μg), Novobiocin (5 μg), Penicilin (10 μg) and Chloramphenicol (10 μg) was tested. The results obtained from this study reveal multi drug resistance pattern among the isolates. All the isolates were completely resistant to Ampicillin, Novobiocin, Sulphamethoxazole and Trimethoprim, respectively but susceptible to Tetracycline (100%), Kanamycin (5.7%), Gentamicin (5.7%) and Oxytetracycline (24.5%). Antibiotics phenotyping of the bacteria revealed 21 different phenotypes among the isolates.

  20. Sensory ciliogenesis in Caenorhabditis elegans: assignment of IFT components into distinct modules based on transport and phenotypic profiles.

    PubMed

    Ou, Guangshuo; Koga, Makato; Blacque, Oliver E; Murayama, Takashi; Ohshima, Yasumi; Schafer, Jenny C; Li, Chunmei; Yoder, Bradley K; Leroux, Michel R; Scholey, Jonathan M

    2007-05-01

    Sensory cilium biogenesis within Caenorhabditis elegans neurons depends on the kinesin-2-dependent intraflagellar transport (IFT) of ciliary precursors associated with IFT particles to the axoneme tip. Here we analyzed the molecular organization of the IFT machinery by comparing the in vivo transport and phenotypic profiles of multiple proteins involved in IFT and ciliogenesis. Based on their motility in wild-type and bbs (Bardet-Biedl syndrome) mutants, IFT proteins were classified into groups with similar transport profiles that we refer to as "modules." We also analyzed the distribution and transport of fluorescent IFT particles in multiple known ciliary mutants and 49 new ciliary mutants. Most of the latter mutants were snip-SNP mapped and one, namely dyf-14(ks69), was cloned and found to encode a conserved protein essential for ciliogenesis. The products of these ciliogenesis genes could also be assigned to the aforementioned set of modules or to specific aspects of ciliogenesis, based on IFT particle dynamics and ciliary mutant phenotypes. Although binding assays would be required to confirm direct physical interactions, the results are consistent with the hypothesis that the C. elegans IFT machinery has a modular design, consisting of modules IFT-subcomplex A, IFT-subcomplex B, and a BBS protein complex, in addition to motor and cargo modules, with each module contributing to distinct functional aspects of IFT or ciliogenesis.

  1. Phenotypic Space and Variation of Floral Scent Profiles during Late Flower Development in Antirrhinum

    PubMed Central

    Weiss, Julia; Mühlemann, Joëlle K.; Ruiz-Hernández, Victoria; Dudareva, Natalia; Egea-Cortines, Marcos

    2016-01-01

    The genus Antirrhinum comprises about 28 species with a center of origin in the Iberian Peninsula. They show an important diversity of growing niches. We have performed a comprehensive analysis of scent profiles in eight wild species, Antirrhinum linkianum, A. tortuosum, A. cirrigherum, A. latifolium, A. meonanthum, A. braun-blanquetii, A. barrelieri, and A. graniticum. We used also two laboratory inbred lines A. majus, 165E and Sippe50. We identified 63 volatile organic compounds (VOCs) belonging to phenylpropanoids, benzenoids, mono- and sesquiterpenes, nitrogen-containing compounds, and aliphatic alcohols previously described in plants. Twenty-four VOCs were produced at levels higher than 2% of total VOC emission, while other VOCs were emitted in trace amounts. The absolute scent emission varied during flower maturation and species. The lowest emitting was A. meonanthum while A. tortuosum had the largest emissions. Species were clustered according to their scent profiles and the resulting dendrogram matched the current species phylogeny. However, two accessions, A. majus Sippe 50 and A. braun-blanquetii, showed development-specific changes in their VOC composition, suggesting a precise control and fine tuning of scent profiles. Cluster analysis of the different scent components failed to identify a specific synthesis pathway, indicating a key role of scent profiles as blends. There is considerable degree of chemodiversity in scent profiles in Antirrhinum. The specific developmental stage plays an important role in scent quantitative emissions. The relative robustness of the bouquets could be an adaptation to local pollinators. PMID:28066463

  2. Characteristic DNA methylation profiles in peripheral blood monocytes are associated with inflammatory phenotypes of asthma

    PubMed Central

    Gunawardhana, Lakshitha P; Gibson, Peter G; Simpson, Jodie L; Benton, Miles C; Lea, Rodney A; Baines, Katherine J

    2014-01-01

    Epigenetic changes including DNA methylation caused by environmental exposures may contribute to the heterogeneous inflammatory response in asthma. Here we investigate alterations in DNA methylation of purified blood monocytes that are associated with inflammatory phenotypes of asthma. Peripheral blood was collected from adults with eosinophilic asthma (EA; n = 21), paucigranulocytic asthma (PGA; n = 22), neutrophilic asthma (NA; n = 9), and healthy controls (n = 10). Blood monocytes were isolated using ficoll density gradient and immuno-magnetic cell separation. Bisulfite converted genomic DNA was hybridized to Illumina Infinium Methylation27 arrays and analyzed for differential methylation using R/Bioconductor packages; networks of gene interactions were identified using the STRING database. Compared with healthy controls, differentially methylated CpG loci were identified in EA (n = 413), PGA (n = 495), and NA (n = 89). We found that 223, 237, and 72 loci were significantly hypermethylated in EA, PGA, and NA, respectively. Nine genes were common to all three phenotypes and showed increased methylation in asthma. Three pathway networks were identified in EA, involved in purine metabolism, calcium signaling, and ECM-receptor interaction. In PGA, two networks were identified, involved in neuroactive ligand-receptor interaction and ubiquitin mediated proteolysis. In NA, one network was identified involving sFRP1 as a key node, over representing the Wnt signaling pathway. We have identified characteristic alterations in DNA methylation that are associated with inflammatory phenotypes of asthma and may contribute to the disease mechanisms. This network-based characterization may help in the development of epigenetic biomarkers and therapeutic targets for asthma. PMID:25147914

  3. Liver transcriptome profile in pigs with extreme phenotypes of intramuscular fatty acid composition

    PubMed Central

    2012-01-01

    Background New advances in high-throughput technologies have allowed for the massive analysis of genomic data, providing new opportunities for the characterization of the transcriptome architectures. Recent studies in pigs have employed RNA-Seq to explore the transcriptome of different tissues in a reduced number of animals. The main goal of this study was the identification of differentially-expressed genes in the liver of Iberian x Landrace crossbred pigs showing extreme phenotypes for intramuscular fatty acid composition using RNA-Seq. Results The liver transcriptomes of two female groups (H and L) with phenotypically extreme intramuscular fatty acid composition were sequenced using RNA-Seq. A total of 146 and 180 unannotated protein-coding genes were identified in intergenic regions for the L and H groups, respectively. In addition, a range of 5.8 to 7.3% of repetitive elements was found, with SINEs being the most abundant elements. The expression in liver of 186 (L) and 270 (H) lncRNAs was also detected. The higher reproducibility of the RNA-Seq data was validated by RT-qPCR and porcine expression microarrays, therefore showing a strong correlation between RT-qPCR and RNA-Seq data (ranking from 0.79 to 0.96), as well as between microarrays and RNA-Seq (r=0.72). A differential expression analysis between H and L animals identified 55 genes differentially-expressed between groups. Pathways analysis revealed that these genes belong to biological functions, canonical pathways and three gene networks related to lipid and fatty acid metabolism. In concordance with the phenotypic classification, the pathways analysis inferred that linolenic and arachidonic acids metabolism was altered between extreme individuals. In addition, a connection was observed among the top three networks, hence suggesting that these genes are interconnected and play an important role in lipid and fatty acid metabolism. Conclusions In the present study RNA-Seq was used as a tool to explore

  4. Development of a 3D Tissue Culture-Based High-Content Screening Platform That Uses Phenotypic Profiling to Discriminate Selective Inhibitors of Receptor Tyrosine Kinases.

    PubMed

    Booij, Tijmen H; Klop, Maarten J D; Yan, Kuan; Szántai-Kis, Csaba; Szokol, Balint; Orfi, Laszlo; van de Water, Bob; Keri, Gyorgy; Price, Leo S

    2016-10-01

    3D tissue cultures provide a more physiologically relevant context for the screening of compounds, compared with 2D cell cultures. Cells cultured in 3D hydrogels also show complex phenotypes, increasing the scope for phenotypic profiling. Here we describe a high-content screening platform that uses invasive human prostate cancer cells cultured in 3D in standard 384-well assay plates to study the activity of potential therapeutic small molecules and antibody biologics. Image analysis tools were developed to process 3D image data to measure over 800 phenotypic parameters. Multiparametric analysis was used to evaluate the effect of compounds on tissue morphology. We applied this screening platform to measure the activity and selectivity of inhibitors of the c-Met and epidermal growth factor (EGF) receptor (EGFR) tyrosine kinases in 3D cultured prostate carcinoma cells. c-Met and EGFR activity was quantified based on the phenotypic profiles induced by their respective ligands, hepatocyte growth factor and EGF. The screening method was applied to a novel collection of 80 putative inhibitors of c-Met and EGFR. Compounds were identified that induced phenotypic profiles indicative of selective inhibition of c-Met, EGFR, or bispecific inhibition of both targets. In conclusion, we describe a fully scalable high-content screening platform that uses phenotypic profiling to discriminate selective and nonselective (off-target) inhibitors in a physiologically relevant 3D cell culture setting.

  5. Development of a 3D Tissue Culture–Based High-Content Screening Platform That Uses Phenotypic Profiling to Discriminate Selective Inhibitors of Receptor Tyrosine Kinases

    PubMed Central

    Booij, Tijmen H.; Klop, Maarten J. D.; Yan, Kuan; Szántai-Kis, Csaba; Szokol, Balint; Orfi, Laszlo; van de Water, Bob; Keri, Gyorgy; Price, Leo S.

    2016-01-01

    3D tissue cultures provide a more physiologically relevant context for the screening of compounds, compared with 2D cell cultures. Cells cultured in 3D hydrogels also show complex phenotypes, increasing the scope for phenotypic profiling. Here we describe a high-content screening platform that uses invasive human prostate cancer cells cultured in 3D in standard 384-well assay plates to study the activity of potential therapeutic small molecules and antibody biologics. Image analysis tools were developed to process 3D image data to measure over 800 phenotypic parameters. Multiparametric analysis was used to evaluate the effect of compounds on tissue morphology. We applied this screening platform to measure the activity and selectivity of inhibitors of the c-Met and epidermal growth factor (EGF) receptor (EGFR) tyrosine kinases in 3D cultured prostate carcinoma cells. c-Met and EGFR activity was quantified based on the phenotypic profiles induced by their respective ligands, hepatocyte growth factor and EGF. The screening method was applied to a novel collection of 80 putative inhibitors of c-Met and EGFR. Compounds were identified that induced phenotypic profiles indicative of selective inhibition of c-Met, EGFR, or bispecific inhibition of both targets. In conclusion, we describe a fully scalable high-content screening platform that uses phenotypic profiling to discriminate selective and nonselective (off-target) inhibitors in a physiologically relevant 3D cell culture setting. PMID:27412535

  6. Phenotypic profiling of Scedosporium aurantiacum, an opportunistic pathogen colonizing human lungs.

    PubMed

    Kaur, Jashanpreet; Duan, Shu Yao; Vaas, Lea A I; Penesyan, Anahit; Meyer, Wieland; Paulsen, Ian T; Nevalainen, Helena

    2015-01-01

    Genotyping studies of Australian Scedosporium isolates have revealed the strong prevalence of a recently described species: Scedosporium aurantiacum. In addition to occurring in the environment, this fungus is also known to colonise the respiratory tracts of cystic fibrosis (CF) patients. A high throughput Phenotype Microarray (PM) analysis using 94 assorted substrates (sugars, amino acids, hexose-acids and carboxylic acids) was carried out for four isolates exhibiting different levels of virulence, determined using a Galleria mellonella infection model. A significant difference was observed in the substrate utilisation patterns of strains displaying differential virulence. For example, certain sugars such as sucrose (saccharose) were utilised only by low virulence strains whereas some sugar derivatives such as D-turanose promoted respiration only in the more virulent strains. Strains with a higher level of virulence also displayed flexibility and metabolic adaptability at two different temperature conditions tested (28 and 37°C). Phenotype microarray data were integrated with the whole-genome sequence data of S. aurantiacum to reconstruct a pathway map for the metabolism of selected substrates to further elucidate differences between the strains.

  7. Short communication: Cytokine profiles from blood mononuclear cells of dairy cows classified with divergent immune response phenotypes.

    PubMed

    Martin, C E; Paibomesai, M A; Emam, S M; Gallienne, J; Hine, B C; Thompson-Crispi, K A; Mallard, B A

    2016-03-01

    Genetic selection for enhanced immune response has been shown to decrease disease occurrence in dairy cattle. Cows can be classified as high (H), average, or low responders based on antibody-mediated immune response (AMIR), predominated by type-2 cytokine production, and cell-mediated immune response (CMIR) through estimated breeding values for these traits. The purpose of this study was to identify in vitro tests that correlate with in vivo immune response phenotyping in dairy cattle. Blood mononuclear cells (BMC) isolated from cows classified as H-AMIR and H-CMIR through estimated breeding values for immune response traits were stimulated with concanavalin A (ConA; Sigma Aldrich, St. Louis, MO) and gene expression, cytokine production, and cell proliferation was determined at multiple time points. A repeated measures model, which included the effects of immune response group, parity, and stage of lactation, was used to compare differences between immune response phenotype groups. The H-AMIR cows produced more IL-4 protein than H-CMIR cows at 48 h; however, no difference in gene expression of type-2 transcription factor GATA3 or IL4 was noted. The BMC from H-CMIR cows had increased production of IFN-γ protein at 48, 72, and 96 h compared with H-AMIR animals. Further, H-CMIR cows had increased expression of the IFNG gene at 16, 24, and 48 h post-treatment with ConA, although expression of the type-1 transcription factor gene TBX21 did not differ between immune response groups. Although proliferation of BMC increased from 24 to 72 h after ConA stimulation, no differences were found between the immune response groups. Overall, stimulation of H-AMIR and H-CMIR bovine BMC with ConA resulted in distinct cytokine production profiles according to genetically defined groups. These distinct cytokine profiles could be used to define disease resistance phenotypes in dairy cows according to stimulation in vitro; however, other immune response phenotypes should be assessed.

  8. Fibroblasts from phenotypically normal palmar fascia exhibit molecular profiles highly similar to fibroblasts from active disease in Dupuytren's Contracture

    PubMed Central

    2012-01-01

    Background Dupuytren's contracture (DC) is a fibroproliferative disorder characterized by the progressive development of a scar-like collagen-rich cord that affects the palmar fascia of the hand and leads to digital flexion contractures. DC is most commonly treated by surgical resection of the diseased tissue, but has a high reported recurrence rate ranging from 27% to 80%. We sought to determine if the transcriptomic profiles of fibroblasts derived from DC-affected palmar fascia, adjacent phenotypically normal palmar fascia, and non-DC palmar fascial tissues might provide mechanistic clues to understanding the puzzle of disease predisposition and recurrence in DC. Methods To achieve this, total RNA was obtained from fibroblasts derived from primary DC-affected palmar fascia, patient-matched unaffected palmar fascia, and palmar fascia from non-DC patients undergoing carpal tunnel release (6 patients in each group). These cells were grown on a type-1 collagen substrate (to better mimic their in vivo environments). Microarray analyses were subsequently performed using Illumina BeadChip arrays to compare the transcriptomic profiles of these three cell populations. Data were analyzed using Significance Analysis of Microarrays (SAM v3.02), hierarchical clustering, concordance mapping and Venn diagram. Results We found that the transcriptomic profiles of DC-disease fibroblasts and fibroblasts from unaffected fascia of DC patients exhibited a much greater overlap than fibroblasts derived from the palmar fascia of patients undergoing carpal tunnel release. Quantitative real time RT-PCR confirmed the differential expression of select genes validating the microarray data analyses. These data are consistent with the hypothesis that predisposition and recurrence in DC may stem, at least in part, from intrinsic similarities in the basal gene expression of diseased and phenotypically unaffected palmar fascia fibroblasts. These data also demonstrate that a collagen

  9. Microbial forensics: predicting phenotypic characteristics and environmental conditions from large-scale gene expression profiles.

    PubMed

    Kim, Minseung; Zorraquino, Violeta; Tagkopoulos, Ilias

    2015-03-01

    A tantalizing question in cellular physiology is whether the cellular state and environmental conditions can be inferred by the expression signature of an organism. To investigate this relationship, we created an extensive normalized gene expression compendium for the bacterium Escherichia coli that was further enriched with meta-information through an iterative learning procedure. We then constructed an ensemble method to predict environmental and cellular state, including strain, growth phase, medium, oxygen level, antibiotic and carbon source presence. Results show that gene expression is an excellent predictor of environmental structure, with multi-class ensemble models achieving balanced accuracy between 70.0% (±3.5%) to 98.3% (±2.3%) for the various characteristics. Interestingly, this performance can be significantly boosted when environmental and strain characteristics are simultaneously considered, as a composite classifier that captures the inter-dependencies of three characteristics (medium, phase and strain) achieved 10.6% (±1.0%) higher performance than any individual models. Contrary to expectations, only 59% of the top informative genes were also identified as differentially expressed under the respective conditions. Functional analysis of the respective genetic signatures implicates a wide spectrum of Gene Ontology terms and KEGG pathways with condition-specific information content, including iron transport, transferases, and enterobactin synthesis. Further experimental phenotypic-to-genotypic mapping that we conducted for knock-out mutants argues for the information content of top-ranked genes. This work demonstrates the degree at which genome-scale transcriptional information can be predictive of latent, heterogeneous and seemingly disparate phenotypic and environmental characteristics, with far-reaching applications.

  10. Gene Expression Profiling of H9c2 Myoblast Differentiation towards a Cardiac-Like Phenotype

    PubMed Central

    Branco, Ana F.; Pereira, Susana P.; Gonzalez, Susana; Gusev, Oleg; Rizvanov, Albert A.; Oliveira, Paulo J.

    2015-01-01

    H9c2 myoblasts are a cell model used as an alternative for cardiomyocytes. H9c2 cells have the ability to differentiate towards a cardiac phenotype when the media serum is reduced in the presence of all-trans-retinoic acid (RA), creating multinucleated cells with low proliferative capacity. In the present study, we performed for the first time a transcriptional analysis of the H9c2 cell line in two differentiation states, i.e. embryonic cells and differentiated cardiac-like cells. The results show that RA-induced H9c2 differentiation increased the expression of genes encoding for cardiac sarcomeric proteins such as troponin T, or calcium transporters and associated machinery, including SERCA2, ryanodine receptor and phospholamban as well as genes associated with mitochondrial energy production including respiratory chain complexes subunits, mitochondrial creatine kinase, carnitine palmitoyltransferase I and uncoupling proteins. Undifferentiated myoblasts showed increased gene expression of pro-survival proteins such as Bcl-2 as well as cell cycle-regulating proteins. The results indicate that the differentiation of H9c2 cells lead to an increase of transcripts and protein levels involved in calcium handling, glycolytic and mitochondrial metabolism, confirming that H9c2 cell differentiation induced by RA towards a more cardiac-like phenotype involves remodeled mitochondrial function. PI3K, PDK1 and p-CREB also appear to be involved on H9c2 differentiation. Furthermore, complex analysis of differently expressed transcripts revealed significant up-regulation of gene expression related to cardiac muscle contraction, dilated cardiomyopathy and other pathways specific for the cardiac tissue. Metabolic and gene expression remodeling impacts cell responses to different stimuli and determine how these cells are used for biochemical assays. PMID:26121149

  11. Stereomicroscopic 3D-pattern profiling of murine and human intestinal inflammation reveals unique structural phenotypes

    PubMed Central

    Rodriguez-Palacios, Alex; Kodani, Tomohiro; Kaydo, Lindsey; Pietropaoli, Davide; Corridoni, Daniele; Howell, Scott; Katz, Jeffry; Xin, Wei; Pizarro, Theresa T.; Cominelli, Fabio

    2015-01-01

    Histology is fundamental to assess two-dimensional intestinal inflammation; however, inflammatory bowel diseases (IBDs) are often indistinguishable microscopically on the basis of mucosal biopsies. Here, we use stereomicroscopy (SM) to rapidly profile the entire intestinal topography and assess inflammation. We examine the mucosal surface of >700 mice (encompassing >16 strains and various IBD-models), create a profiling catalogue of 3D-stereomicroscopic abnormalities and demonstrate that mice with comparable histological scores display unique sub-clusters of 3D-structure-patterns of IBD pathology, which we call 3D-stereoenterotypes, and which are otherwise indiscernible histologically. We show that two ileal IBD-stereoenterotypes (‘cobblestones' versus ‘villous mini-aggregation') cluster separately within two distinct mouse lines of spontaneous ileitis, suggesting that host genetics drive unique and divergent inflammatory 3D-structural patterns in the gut. In humans, stereomicroscopy reveals ‘liquefaction' lesions and hierarchical fistulous complexes, enriched with clostridia/segmented filamentous bacteria, running under healthy mucosa in Crohn's disease. We suggest that stereomicroscopic (3D-SMAPgut) profiling can be easily implemented and enable the comprehensive study of inflammatory 3D structures, genetics and flora in IBD. PMID:26154811

  12. Shift in polyphenol profile and sublethal phenotype caused by silencing of anthocyanidin synthase in apple (Malus sp.).

    PubMed

    Szankowski, Iris; Flachowsky, Henryk; Li, Houhua; Halbwirth, Heidrun; Treutter, Dieter; Regos, Ionela; Hanke, Magda-Viola; Stich, Karl; Fischer, Thilo C

    2009-02-01

    We have investigated the consequences of blocking anthocyanin biosynthesis by silencing a key enzyme, anthocyanidin synthase, in transgenic plants of a red-leaved apple cultivar. This is complementary to a previous study of induction of anthocyanin biosynthesis by overexpressing a heterologous transcription factor. Analysis of these opposite phenotypes allows one to study anthocyanin functions in apple and to test the influence of the genetic manipulation on other, related metabolites. As expected, anthocyanin biosynthesis was almost completely blocked and this was accompanied by a shift in the profile of flavonoids and related polyphenols. Most interestingly, a rise in epicatechin was found. A severe reduction of viability by necrotic leaf lesions was also observed, suggesting an essential function of anthocyanins in apple.

  13. Human Adult Stem Cells Maintain a Constant Phenotype Profile Irrespective of Their Origin, Basal Media, and Long Term Cultures

    PubMed Central

    Somasundaram, Indumathi; Mishra, Rashmi; Radhakrishnan, Harikrishnan; Sankaran, Rajkumar; Garikipati, Venkata Naga Srikanth

    2015-01-01

    The study aims to identify the phenotypic marker expressions of different human adult stem cells derived from, namely, bone marrow, subcutaneous fat, and omentum fat, cultured in different media, namely, DMEM-Low Glucose, Alpha-MEM, DMEM-F12 and DMEM-KO and under long term culture conditions (>P20). We characterized immunophenotype by using various hematopoietic, mesenchymal, endothelial markers, and cell adhesion molecules in the long term cultures (Passages-P1, P3, P5, P9, P12, P15, and P20.) Interestingly, data revealed similar marker expression profiles irrespective of source, basal media, and extensive culturing. This demonstrates that all adult stem cell sources mentioned in this study share similar phenotypic marker and all media seem appropriate for culturing these sources. However, a disparity was observed in the markers such as CD49d, CD54, CD117, CD29, and CD106, thereby warranting further research on these markers. Besides the aforesaid objective, it is understood from the study that immunophenotyping acts as a valuable tool to identify inherent property of each cell, thereby leading to a valuable cell based therapy. PMID:25688272

  14. Molecular and phenotypic profiling from the base to the crown in maritime pine wood-forming tissue.

    PubMed

    Paiva, Jorge A P; Garcés, Marcelo; Alves, Ana; Garnier-Géré, Pauline; Rodrigues, José Carlos; Lalanne, Céline; Porcon, Stéphane; Le Provost, Grégoire; Perez, Denilson da Silva; Brach, Jean; Frigerio, Jean-Marc; Claverol, Stéphane; Barré, Aurélien; Fevereiro, Pedro; Plomion, Christophe

    2008-01-01

    Environmental, developmental and genetic factors affect variation in wood properties at the chemical, anatomical and physical levels. Here, the phenotypic variation observed along the tree stem was explored and the hypothesis tested that this variation could be the result of the differential expression of genes/proteins during wood formation. Differentiating xylem samples of maritime pine (Pinus pinaster) were collected from the top (crown wood, CW) to the bottom (base wood, BW) of adult trees. These samples were characterized by Fourier transform infrared spectroscopy (FTIR) and analytical pyrolysis. Two main groups of samples, corresponding to CW and BW, could be distinguished from cell wall chemical composition. A genomic approach, combining large-scale production of expressed sequence tags (ESTs), gene expression profiling and quantitative proteomics analysis, allowed identification of 262 unigenes (out of 3512) and 231 proteins (out of 1372 spots) that were differentially expressed along the stem. A good relationship was found between functional categories from transcriptomic and proteomic data. A good fit between the molecular mechanisms involved in CW-BW formation and these two types of wood phenotypic differences was also observed. This work provides a list of candidate genes for wood properties that will be tested in forward genetics.

  15. Phenotypic and allelic profile of ABO and Rhésus D blood group system among blood donor in Antananarivo.

    PubMed

    Randriamanantany, Z A; Rajaonatahina, D H; Razafimanantsoa, F E; Rasamindrakotroka, M T; Andriamahenina, R; Rasoarilalamanarivo, F B; Hanitriniala, S P; Herisoa, F R; Rasamindrakotroka, A; Rakoto Alson, O A

    2012-12-01

    This study assessed the phenotypic and allelic profiles of ABO and Rhesus D blood group system among first time blood donors at the National Centre of Blood Supply of Antananarivo. We collected through this retrospective study all data registered during 7 years of practice (from 2003 to 2009). Age and sex were analysed with the result of ABO and RhD screening. They were tested both with Beth Vincent and Simonin tests which were performed in a plate, by using commercial monoclonal antibody (Diaclone(®) et Eryclone(®)), and home-made red cells tests. The Rh D was performed with the same commercial kits. The frequencies of alleles were calculated by using Bernstein method. Data about 45,857 donors were obtained. A male predominance (80.46%) was found and most of our donors were aged <40 (74.92%). 98.90% of the donors were Rh D positive. Phenotypic distribution of each ABO antigen was, respectively, 22.61, 29.66, 6.13 and 41.60% for A, B, AB and O antigen. Allelic frequencies of A, B and O were 0.1559, 0.1987 and 0.6454. These results confirmed the fact that Madagascan population had admixed ethnic origin.

  16. Phenotypic and metabolic profiling of colony morphology variants evolved from Pseudomonas fluorescens biofilms.

    PubMed

    Workentine, Matthew L; Harrison, Joe J; Weljie, Aalim M; Tran, Vy A; Stenroos, Pernilla U; Tremaroli, Valentina; Vogel, Hans J; Ceri, Howard; Turner, Raymond J

    2010-06-01

    Colony morphology variants isolated from natural and laboratory-grown biofilms represent subpopulations of biofilm cells that may be important for multiple aspects of the sessile lifestyle, from surface colonization to stress resistance. There are many genetic and environmental factors that determine the frequency at which colony morphology variants are recovered from biofilms. One of these factors involves an increased selection for variants in biofilms of Pseudomonas species bearing inactivating mutations in the global activator of cyanide biosynthesis/regulator of secondary metabolism (gac/rsm) signal transduction pathway. Here we characterize two distinct colony morphology variants isolated from biofilms of Pseudomonas fluorescens missing the gacS sensor kinase. These variants produced more biofilm cell mass, and in one case, this was likely due to overproduction of the exopolysaccharide cellulose. Nuclear magnetic resonance (NMR) metabolomics revealed distinct metabolic changes for each of the two phenotypic variants, and these changes involved amino acids and metabolites produced through glutathione biochemistry. Some of these metabolites are hypothesized to play a role in redox and metal homeostasis, and corresponding to this, we show that biofilm populations grown from each of these variants had a different ability to survive when exposed to toxic doses of metal ions. These data suggest that colony morphology variants that evolve during growth of P. fluorescens as a biofilm may have distinct metabolic capacities that contribute to their individual abilities to withstand environmental stress.

  17. Phenotypic side effects prediction by optimizing correlation with chemical and target profiles of drugs.

    PubMed

    Kanji, Rakesh; Sharma, Abhinav; Bagler, Ganesh

    2015-11-01

    Despite technological progresses and improved understanding of biological systems, discovery of novel drugs is an inefficient, arduous and expensive process. Research and development cost of drugs is unreasonably high, largely attributed to the high attrition rate of candidate drugs due to adverse drug reactions. Computational methods for accurate prediction of drug side effects, rooted in empirical data of drugs, have the potential to enhance the efficacy of the drug discovery process. Identification of features critical for specifying side effects would facilitate efficient computational procedures for their prediction. We devised a generalized ordinary canonical correlation model for prediction of drug side effects based on their chemical properties as well as their target profiles. While the former is based on 2D and 3D chemical features, the latter enumerates a systems-level property of drugs. We find that the model incorporating chemical features outperforms that incorporating target profiles. Furthermore we identified the 2D and 3D chemical properties that yield best results, thereby implying their relevance in specifying adverse drug reactions.

  18. Endometrial gene expression profile of pregnant sows with extreme phenotypes for reproductive efficiency

    PubMed Central

    Córdoba, S.; Balcells, I.; Castelló, A.; Ovilo, C.; Noguera, J. L.; Timoneda, O.; Sánchez, A.

    2015-01-01

    Prolificacy can directly impact porcine profitability, but large genetic variation and low heritability have been found regarding litter size among porcine breeds. To identify key differences in gene expression associated to swine reproductive efficiency, we performed a transcriptome analysis of sows’ endometrium from an Iberian x Meishan F2 population at day 30–32 of gestation, classified according to their estimated breeding value (EBV) as high (H, EBV > 0) and low (L, EBV < 0) prolificacy phenotypes. For each sample, mRNA and small RNA libraries were RNA-sequenced, identifying 141 genes and 10 miRNAs differentially expressed between H and L groups. We selected four miRNAs based on their role in reproduction, and five genes displaying the highest differences and a positive mapping into known reproductive QTLs for RT-qPCR validation on the whole extreme population. Significant differences were validated for genes: PTGS2 (p = 0.03; H/L ratio = 3.50), PTHLH (p = 0.03; H/L ratio = 3.69), MMP8 (p = 0.01; H/L ratio = 4.41) and SCNN1G (p = 0.04; H/L ratio = 3.42). Although selected miRNAs showed similar expression levels between H and L groups, significant correlation was found between the expression level of ssc-miR-133a (p < 0.01) and ssc-miR-92a (p < 0.01) and validated genes. These results provide a better understanding of the genetic architecture of prolificacy-related traits and embryo implantation failure in pigs. PMID:26435523

  19. Phenotypic heterogeneity, novel diagnostic markers, and target expression profiles in normal and neoplastic human mast cells.

    PubMed

    Valent, Peter; Cerny-Reiterer, Sabine; Herrmann, Harald; Mirkina, Irina; George, Tracy I; Sotlar, Karl; Sperr, Wolfgang R; Horny, Hans-Peter

    2010-09-01

    Mast cells (MC) are specialized immune cells that play a key role in anaphylactic reactions. Growth, differentiation, and function of these cells are regulated by a complex network of cytokines, surface receptors, signaling molecules, the microenvironment, and the genetic background. A number of previous and more recent data suggest that MC are heterogeneous in terms of cytokine-regulation, expression of cytoplasmic and cell surface antigens, and response to ligands. MC heterogeneity is often organ-specific and is considered to be related to MC plasticity, disease-associated factors, and the maturation stage of the cells. The stem cell factor (SCF) receptor KIT (CD117) is expressed on all types of MC independent of maturation and activation-status. In systemic mastocytosis (SM), KIT is often expressed in MC in a mutated and constitutively activated form. In these patients, MC aberrantly display CD2 and CD25, diagnostic markers of neoplastic MC in all SM variants. In advanced SM, MC co-express substantial amounts of CD30, whereas CD2 expression on MC may be decreased compared to indolent SM. Other surface molecules, such as CD63 or CD203c, are overexpressed on neoplastic MC in SM, and are further upregulated upon cross-linking of the IgE receptor. Some of the cell surface antigens expressed on MC or their progenitors may serve as therapeutic targets in the future. These targets include CD25, CD30, CD33, CD44, and CD117/KIT. The current article provides an overview on cell surface antigens and target receptors expressed by MC in physiologic and reactive tissues, and in patients with SM, with special reference to phenotypic heterogeneity and clinical implications.

  20. Whole blood gene expression profiles distinguish clinical phenotypes of venous thromboembolism☆

    PubMed Central

    Lewis, Deborah A.; Suchindran, Sunil; Beckman, Michele G.; Hooper, W. Craig; Grant, Althea M.; Heit, John A.; Manco-Johnson, Marilyn; Moll, Stephan; Philipp, Claire S.; Kenney, Kristy; De Staercke, Christine; Pyle, Meredith E.; Chi, Jen-Tsan; Ortel, Thomas L.

    2015-01-01

    Introduction Recurrent venous thromboembolism (VTE) occurs infrequently following a provoked event but occurs in up to 30% of individuals following an initial unprovoked event. There is limited understanding of the biological mechanisms that predispose patients to recurrent VTE. Objectives To identify whole blood gene expression profiles that distinguished patients with clinically distinct patterns of VTE. Patients/Methods We studied 107 patients with VTE separated into 3 groups: (1) ‘low-risk’ patients had one or more provoked VTE; (2) ‘moderate-risk’ patients had a single unprovoked VTE; (3) ‘high-risk’ patients had ≥2 unprovoked VTE. Each patient group was also compared to twenty-five individuals with no personal history of VTE. Total RNA from whole blood was isolated and hybridized to Illumina HT-12 V4 Beadchips to assay whole genome expression. Results Using class prediction analysis, we distinguished high-risk patients from low-risk patients and healthy controls with good receiver operating curve characteristics (AUC = 0.81 and 0.84, respectively). We also distinguished moderate-risk individuals and low-risk individuals from healthy controls with AUC’s of 0.69 and 0.80, respectively. Using differential expression analysis, we identified several genes previously implicated in thrombotic disorders by genetic analyses, including SELP, KLKB1, ANXA5, and CD46. Protein levels for several of the identified genes were not significantly different between the different groups. Conclusion Gene expression profiles are capable of distinguishing patients with different clinical presentations of VTE, and genes relevant to VTE risk are frequently differentially expressed in these comparisons. PMID:25684211

  1. Phenotypic profiling and gene expression analyses for aromatic and volatile compounds in Chamoes (Cucumis melo).

    PubMed

    Lee, Jeongyeo; Kim, Min Keun; Hwang, Seung Hwan; Kim, Jungeun; Ahn, Jong Moon; Min, Sung Ran; Park, Sang Un; Lim, Soon Sung; Kim, HyeRan

    2014-05-01

    Gotgam chamoe (GgC), a native oriental melon in Korea, is known to possess the aroma of a dried persimmon, an agronomic relevance for melon breeding program. The volatile compounds and the transcript levels of aromatic compound genes in cultivar (Ohbokggul chamoe [OC]) and GgC were profiled. A total of 62 volatile compounds were identified and quantified. Twenty-eight volatile compounds were specific to either the OC or the GgC. The amounts of volatile alcohol, saturated hydrocarbon, and unsaturated hydrocarbon compounds were 2.2, 2.7, and 1.1 times higher in OC, respectively. The amounts of ketone volatiles were 1.2 times higher in GgC, whereas the total amounts of esters were similar. In the shikimate pathway, transcriptional patterns with the fruit parts were different between the two chamoes for CmDAHPS, CmDHD/SDH, and CmEPSPS. The expression levels of all six genes investigated, especially CmCS, were highest in the peel of both chamoes compared to the other parts. The transcript levels of the aromatic amino acid biosynthesis genes demonstrate that phenylalanine and tyrosine are present more in edible parts of the chamoe, while tryptophan may be accumulated low in the chamoe. In addition, phenylalanine and tryptophan are synthesized more in GgC than the OC.

  2. Characterisation of Phenotypic and Genotypic Antibiotic Resistance Profile of Enterococci from Cheeses in Turkey

    PubMed Central

    Yipel, Mustafa; Aslantaş, Özkan; Gündoğdu, Aycan

    2016-01-01

    The aim of this study was to determine the prevalence of enterococci in cheese samples and to characterize their antimicrobial resistance profiles as well as the associated resistance genes. A total of 139 enterococci were isolated from 99 cheese samples, the isolates were identified as E. faecalis (61.2%), E. faecium (15.1%), E. gallinarum (12.9%), E. durans (5.0%), E. casseliflavis (2.9%) and E. avium (2.9%). The most frequent antimicrobial resistance observed in enterococci isolates was to lincomycin (88.5%), followed by kanamycin (84.2%), gentamycin (low level, 51.1%), rifampin (46.8%) and tetracycline (33.8%). Among the isolates, the frequencies of high level gentamycin and streptomycin resistant enterococci strains were 2.2% and 5.8%, respectively. Apart from the mentioned antibiotics, low levels of resistance to ciprofloxacin, erythromycin and chloramphenicol were found. Moreover no resistance was observed against penicillin and ampicillin. The antimicrobial resistance genes including tetM, tetL, ermB, cat, aph(3’)-IIIa, ant(6)-Ia and aac(6’)-Ieaph(2”)-Ia were found in enterococci from Turkish cheese samples. In the current study, we provided data for antibiotic resistance and the occurrence of resistance genes among enterococci. Regulatory and quality control programs for milk and other dairy products from farms to retail outlets has to be established and strengthened to monitor trends in antimicrobial resistance among emerging food borne pathogens in Turkey. PMID:27433106

  3. Childhood-onset systemic lupus erythematosus in Singapore: clinical phenotypes, disease activity, damage, and autoantibody profiles.

    PubMed

    Tan, J H T; Hoh, S F; Win, M T M; Chan, Y H; Das, L; Arkachaisri, T

    2015-08-01

    Childhood-onset systemic lupus erythematosus (cSLE) is a multisystem autoimmune disease characterized by immune dysregulation affecting patients less than 18 years old. One-fifth of SLE cases are diagnosed during childhood. cSLE presents differently from adults and has a more severe and aggressive course. We describe the clinical and antibody profiles in our cSLE Singapore cohort. All cSLE patients who satisfied the 1997 American College of Rheumatology diagnostic criteria were captured in our lupus registry from January 2009 to January 2014. Data including demographic, cumulative clinical, serologic data, and damage indices were collected. Adjusted mean SLEDAI-2K (AMS) was used to summarize disease activity over multiple visits. Cluster analysis using non-hierarchical K-means procedure was performed on eight selected antibodies. The 64 patients (female:male ratio 5:1; Chinese 45.3%, Malay 28.1%, Indian 9.4%, and other races 17.2%) had a mean onset age of 11.5 years (range 2.1-16.7) and mean age at diagnosis was 11.9 years (range 2.6-18.0). Our study demonstrated differences in clinical manifestations for which hematologic involvement was the most common manifestation with less renal disease and uncommon neurologic manifestation as compared to other cSLE cohorts reported in our region. Antibody clusters were identified in our cohort but their clinical association/discrimination and outcome prediction required further validation study. Outcomes of our cohort in regard to disease activity after therapy and organ damages were comparable if not better to other cSLE cohorts elsewhere. Steroid-related damage, including symptomatic multifocal avascular necrosis and cataract, were not uncommon locally. Infection remains the major cause of death for the continent. Nevertheless, the five year survival rate of our cohort (98.4%) was high.

  4. Proteomic and transcriptomic profiling of Staphylococcus aureus surface LPXTG-proteins: correlation with agr genotypes and adherence phenotypes.

    PubMed

    Ythier, Mathilde; Resch, Grégory; Waridel, Patrice; Panchaud, Alexandre; Gfeller, Aurélie; Majcherczyk, Paul; Quadroni, Manfredo; Moreillon, Philippe

    2012-11-01

    Staphylococcus aureus infections involve numerous adhesins and toxins, which expression depends on complex regulatory networks. Adhesins include a family of surface proteins covalently attached to the peptidoglycan via a conserved LPXTG motif. Here we determined the protein and mRNA expression of LPXTG-proteins of S. aureus Newman in time-course experiments, and their relation to fibrinogen adherence in vitro. Experiments were performed with mutants in the global accessory-gene regulator (agr), surface protein A (Spa), and fibrinogen-binding protein A (ClfA), as well as during growth in iron-rich or iron-poor media. Surface proteins were recovered by trypsin-shaving of live bacteria. Released peptides were analyzed by liquid chromatography coupled to tandem mass-spectrometry. To unambiguously identify peptides unique to LPXTG-proteins, the analytical conditions were refined using a reference library of S. aureus LPXTG-proteins heterogeneously expressed in surrogate Lactococcus lactis. Transcriptomes were determined by microarrays. Sixteen of the 18 LPXTG-proteins present in S. aureus Newman were detected by proteomics. Nine LPXTG-proteins showed a bell-shape agr-like expression that was abrogated in agr-negative mutants including Spa, fibronectin-binding protein A (FnBPA), ClfA, iron-binding IsdA, and IsdB, immunomodulator SasH, functionally uncharacterized SasD, biofilm-related SasG and methicillin resistance-related FmtB. However, only Spa and SasH modified their proteomic and mRNA profiles in parallel in the parent and its agr- mutant, whereas all other LPXTG-proteins modified their proteomic profiles independently of their mRNA. Moreover, ClfA became highly transcribed and active in fibrinogen-adherence tests during late growth (24 h), whereas it remained poorly detected by proteomics. On the other hand, iron-regulated IsdA-B-C increased their protein expression by >10-times in iron-poor conditions. Thus, proteomic, transcriptomic, and adherence-phenotype

  5. Comparative Proteomic Profiling of Divergent Phenotypes for Water Holding Capacity across the Post Mortem Ageing Period in Porcine Muscle Exudate

    PubMed Central

    Di Luca, Alessio; Hamill, Ruth M.; Mullen, Anne Maria; Slavov, Nikolai; Elia, Giuliano

    2016-01-01

    Two dimensional Difference Gel Electrophoresis (2-D DIGE) and mass spectrometry were applied to investigate the changes in metabolic proteins that occur over a seven day (day 1, 3 and 7) post mortem ageing period in porcine centrifugal exudate from divergent meat quality phenotypes. The objectives of the research were to enhance our understanding of the phenotype (water holding capacity) and search for biomarkers of this economically significant pork quality attribute. Major changes in protein abundance across nine phenotype-by-time conditions were observed. Proteomic patterns were dominated by post mortem ageing timepoint. Using a machine learning algorithm (l1-regularized logistic regression), a model was derived with the ability to discriminate between high drip and low drip phenotypes using a subset of 25 proteins with an accuracy of 63%. Models discriminating between divergent phenotypes with accuracy of 72% and 73% were also derived comparing respectively, high drip plus intermediate phenotype (considered as one phenotype) versus low drip and comparing low drip plus intermediate phenotype (considered as one phenotype) versus high drip. In all comparisons, the general classes of discriminatory proteins identified include metabolic enzymes, stress response, transport and structural proteins. In this research we have enhanced our understanding of the protein related processes underpinning this phenotype and provided strong data to work toward development of protein biomarkers for water holding capacity. PMID:26950297

  6. Metabolite profiling of Camellia sinensis by automated sequential, multidimensional gas chromatography/mass spectrometry reveals strong monsoon effects on tea constituents.

    PubMed

    Kowalsick, Amanda; Kfoury, Nicole; Robbat, Albert; Ahmed, Selena; Orians, Colin; Griffin, Timothy; Cash, Sean B; Stepp, John Richard

    2014-11-28

    Seasonal variation in tea (Camellia sinensis (L.) Kuntze; Theaceae) chemistry was investigated using automated sequential, multidimensional gas chromatography/mass spectrometry (GC-GC/MS). Metabolite libraries were produced for teas harvested from the Bulang Mountains in Yunnan, China before and after the onset of the East Asian Monsoon. A total of 201 spring and 196 monsoon metabolites were identified, with 169 common and 59 seasonally unique compounds. An additional 163 metabolites were detected but their identity could not be confirmed. Spectral deconvolution of GC/MS data was used to measure the relative concentrations in the teas. Within each family individual metabolite concentrations increased, decreased and stayed the same. The major constituents in both teas were linalool (28%), geraniol (13%), α-terpineol (10%), hotrienol (4%) and nerol (3%). This work provides the foundation to monitor seasonal variations of tea chemistry.

  7. Gender differences in the T-cell profiles of the airways in COPD patients associated with clinical phenotypes

    PubMed Central

    Forsslund, Helena; Yang, Mingxing; Mikko, Mikael; Karimi, Reza; Nyrén, Sven; Engvall, Benita; Grunewald, Johan; Merikallio, Heta; Kaarteenaho, Riitta; Wahlström, Jan; Wheelock, Åsa M; Sköld, C Magnus

    2017-01-01

    T lymphocytes are believed to play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). How T cells are recruited to the lungs and contribute to the inflammatory process is largely unknown. COPD is a heterogeneous disease, and discriminating disease phenotypes based on distinct molecular and cellular pathways may provide new approaches for individualized diagnosis and therapies. Bronchoalveolar lavage (BAL) and blood samples were obtained from 40 never-smokers, 40 smokers with normal lung function, and 38 COPD patients. T-cell chemokine receptor expression was analyzed with flow cytometry, and soluble BAL cytokines and chemokines were measured using a cytokine multiplex assay. Correlations with gender and clinical characteristics including lung imaging were investigated using multivariate modeling. Th1/Tc1- and Th2/Tc2-associated soluble analytes and T-cell chemokine receptors were analyzed as cumulative Th1/Tc1 and Th2/Tc2 immune responses. A higher expression of chemokine receptor CCR5 on CD8+ T cells in BAL and higher percentage of CXCR3+CD8+ T cells in blood was found in female smokers with COPD compared to those without COPD. CCR5 expression on CD4+ and CD8+ T cells was lower in BAL from male smokers with COPD compared to those without COPD. Among female smokers with COPD, Th1/Tc1 immune response was linked to BAL macrophage numbers and goblet cell density, and Th2/Tc2 response was associated with the measures of emphysema on high-resolution computed tomography. The highly gender-dependent T-cell profile in COPD indicates different links between cellular events and clinical manifestations in females compared to males. Our findings may reveal mechanisms of importance for the difference in clinical course in female COPD patients compared to males. PMID:28053515

  8. Expanding the phenotypic profile of Kleefstra syndrome: A female with low-average intelligence and childhood apraxia of speech.

    PubMed

    Samango-Sprouse, Carole; Lawson, Patrick; Sprouse, Courtney; Stapleton, Emily; Sadeghin, Teresa; Gropman, Andrea

    2016-05-01

    Kleefstra syndrome (KS) is a rare neurogenetic disorder most commonly caused by deletion in the 9q34.3 chromosomal region and is associated with intellectual disabilities, severe speech delay, and motor planning deficits. To our knowledge, this is the first patient (PQ, a 6-year-old female) with a 9q34.3 deletion who has near normal intelligence, and developmental dyspraxia with childhood apraxia of speech (CAS). At 6, the Wechsler Preschool and Primary Intelligence testing (WPPSI-III) revealed a Verbal IQ of 81 and Performance IQ of 79. The Beery Buktenica Test of Visual Motor Integration, 5th Edition (VMI) indicated severe visual motor deficits: VMI = 51; Visual Perception = 48; Motor Coordination < 45. On the Receptive One Word Picture Vocabulary Test-R (ROWPVT-R), she had standard scores of 96 and 99 in contrast to an Expressive One Word Picture Vocabulary-R (EOWPVT-R) standard scores of 73 and 82, revealing a discrepancy in vocabulary domains on both evaluations. Preschool Language Scale-4 (PLS-4) on PQ's first evaluation reveals a significant difference between auditory comprehension and expressive communication with standard scores of 78 and 57, respectively, further supporting the presence of CAS. This patient's near normal intelligence expands the phenotypic profile as well as the prognosis associated with KS. The identification of CAS in this patient provides a novel explanation for the previously reported speech delay and expressive language disorder. Further research is warranted on the impact of CAS on intelligence and behavioral outcome in KS. Therapeutic and prognostic implications are discussed.

  9. Phenotypic, antimicrobial susceptibility profile and virulence factors of Klebsiella pneumoniae isolated from buffalo and cow mastitic milk

    PubMed Central

    Osman, Kamelia M; Hassan, Hany M; Orabi, Ahmed; Abdelhafez, Ahmed S T

    2014-01-01

    Studies on the prevalence and virulence genes of Klebsiella mastitis pathogens in a buffalo population are undocumented. Also, the association of rmpA kfu, uge, magA, Aerobactin, K1 and K2 virulent factors with K. pneumoniae buffalo, and cow mastitis is unreported. The virulence of K. pneumoniae was evaluated through both phenotypic and molecular assays. In vivo virulence was assessed by the Vero cell cytotoxicity, suckling mouse assay and mice lethality test. Antimicrobial susceptibility was tested by disk diffusion method. The 45 K. pneumoniae isolates from buffalo (n = 10/232) and cow (n = 35/293) milk were isolated (45/525; 8.6%) and screened via PCR for seven virulence genes encoding uridine diphosphate galactose 4 epimerase encoding gene responsible for capsule and smooth lipopolysaccharide synthesis (uge), siderophores (kfu and aerobactin), protectines or invasins (rmpA and magA), and the capsule and hypermucoviscosity (K1 and K2). The most common virulence genes were rmpA, kfu, uge, and magA (77.8% each). Aerobactin and K1 genes were found at medium rates of 66.7% each and K2 (55.6%). The Vero cell cytotoxicity and LD (50) in mice were found in 100% of isolates. A multidrug resistance pattern was observed for 40% of the antimicrobials. The distribution of virulence profiles indicate a role of rmpA, kfu, uge, magA, Aerobactin, and K1 and K2 in pathogenicity of K. pneumoniae in udder infections and invasiveness, and constitutes a threat for vulnerable animals, even more if they are in combination with antibiotic resistance. PMID:24915048

  10. Phenotypic Transition as a Survival Strategy of Glioma.

    PubMed

    Ichikawa, Tomotsugu; Otani, Yoshihiro; Kurozumi, Kazuhiko; Date, Isao

    2016-07-15

    Malignant glioma is characterized by rapid proliferation, invasion into surrounding central nervous system tissues, and aberrant vascularization. There is increasing evidence that shows gliomas are more complex than previously thought, as each tumor comprises considerable intratumoral heterogeneity with mixtures of genetically and phenotypically distinct subclones. Heterogeneity within and across tumors is recognized as a critical factor that limits therapeutic progress for malignant glioma. Recent genotyping and expression profiling of gliomas has allowed for the creation of classification schemes that assign tumors to subtypes based on similarity to defined expression signatures. Also, malignant gliomas frequently shift their biological features upon recurrence and progression. The ability of glioma cells to resist adverse conditions such as hypoxia and metabolic stress is necessary for sustained tumor growth and strongly influences tumor behaviors. In general, glioma cells are in one of two phenotypic categories: higher proliferative activity with angiogenesis, or higher migratory activity with attenuated proliferative ability. Further, they switch phenotypic categories depending on the situation. To date, a multidimensional approach has been employed to clarify the mechanisms of phenotypic shift of glioma. Various molecular and signaling pathways are involved in phenotypic shifts of glioma, possibly with crosstalk between them. In this review, we discuss molecular and phenotypic heterogeneity of glioma cells and mechanisms of phenotypic shifts in regard to the glioma proliferation, angiogenesis, and invasion. A better understanding of the molecular mechanisms that underlie phenotypic shifts of glioma may provide new insights into targeted therapeutic strategies.

  11. Multidimensional Liquid Chromatography Platform for Profiling Alterations of Clusterin N-Glycosylation in the Plasma of Patients with Renal Cell Carcinoma

    PubMed Central

    Tousi, Fateme; Bones, Jonathan; Iliopoulos, Othon; Hancock, William S.; Hincapie, Marina

    2012-01-01

    Identification of potential changes in the glycosylation of existing cancer biomarkers can result in a higher level of diagnostic sensitivity and specificity. Clusterin (Apolipoprotein J) has been implicated in renal cell carcinoma (RCC) and other types of malignancy as potential biomarker. In the present work, an automated multidimensional HPLC platform enabling high throughput affinity enrichment of clusterin from plasma samples was developed. Integrated with two dimensional gel electrophoresis, high purity clusterin in microgram quantities suitable for glycan characterization was isolated. The analytical platform was applied to study clusterin glycosylation in a small group of RCC patients before and after nephrectopy as a pilot study to evaluate the performance of the platform. A statistically significant decrease was observed in the levels of a bi-antennary digalactosyl disialylated (A2G2S(3)2) glycans while the levels of a core fucosylated bi-antennary digalactosyl disialylated glycan (FA2G2S(6)2) and a tri-antennary trigalactosyl disialylated glycan (A3G3S(6)2) were increased in the post-surgery plasma samples. PMID:22885037

  12. Metabolic parameters linked by Phenotype MicroArray to acid resistance profiles of poultry-associated Salmonella enterica

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phenotype microarrays were analyzed for 51 datasets derived from Salmonella enterica. The top 4 serovars associated with poultry products and one associated with turkey, respectively Typhimurium, Enteritidis, Heidelberg, Infantis and Senftenberg, were represented. Datasets were clustered into two ...

  13. Computational Typologies of Multidimensional End-of-Primary-School Performance Profiles from an Educational Perspective of Large-Scale TIMSS and PIRLS Surveys

    ERIC Educational Resources Information Center

    Unlu, Ali; Schurig, Michael

    2015-01-01

    Recently, performance profiles in reading, mathematics and science were created using the data collectively available in the Trends in International Mathematics and Science Study (TIMSS) and the Progress in International Reading Literacy Study (PIRLS) 2011. In addition, a classification of children to the end of their primary school years was…

  14. Multidimensional Risk Analysis: MRISK

    NASA Technical Reports Server (NTRS)

    McCollum, Raymond; Brown, Douglas; O'Shea, Sarah Beth; Reith, William; Rabulan, Jennifer; Melrose, Graeme

    2015-01-01

    Multidimensional Risk (MRISK) calculates the combined multidimensional score using Mahalanobis distance. MRISK accounts for covariance between consequence dimensions, which de-conflicts the interdependencies of consequence dimensions, providing a clearer depiction of risks. Additionally, in the event the dimensions are not correlated, Mahalanobis distance reduces to Euclidean distance normalized by the variance and, therefore, represents the most flexible and optimal method to combine dimensions. MRISK is currently being used in NASA's Environmentally Responsible Aviation (ERA) project o assess risk and prioritize scarce resources.

  15. Genetic Polymorphisms and Phenotypic Profiles of Sulfadiazine-Resistant and Sensitive Toxoplasma gondii Isolates Obtained from Newborns with Congenital Toxoplasmosis in Minas Gerais, Brazil

    PubMed Central

    Silva, Letícia Azevedo; Reis-Cunha, João Luís; Bartholomeu, Daniella Castanheira; Vítor, Ricardo Wagner Almeida

    2017-01-01

    Background Previous Toxoplasma gondii studies revealed that mutations in the dhps (dihydropteroate synthase) gene are associated with resistance to sulfonamides. Although Brazilian strains are genotypically different, very limited data are available regarding the susceptibility of strains obtained from human to sulfonamides. The aim of this study was to evaluate the efficacy of sulfadiazine (SDZ) against Brazilian isolates of T. gondii and verify whether isolates present polymorphisms in the dhps gene. We also investigated whether the virulence-phenotype and/or genotype were associated with the profile of susceptibility to SDZ. Methods Five T. gondii isolates obtained from newborns with congenital toxoplasmosis were used to verify susceptibility. Mice were infected with 104 tachyzoites and orally treated with different doses of SDZ. The mortality curve was evaluated by the Log-rank test. The presence of polymorphisms in the dhps gene was verified using sequencing. A descriptive analysis for 11 Brazilian isolates was used to assess the association between susceptibility, genotype, and virulence-phenotype. Results Statistical analysis showed that TgCTBr03, 07, 08, and 16 isolates were susceptible to SDZ, whereas TgCTBr11 isolate presented a profile of resistance to SDZ. Nineteen polymorphisms were identified in dhps exons. Seven polymorphisms corresponded to non-synonymous mutations, with four being new mutations, described for the first time in this study. No association was found between the profile of susceptibility and the virulence-phenotype or genotype of the parasite. Conclusions There is a high variability in the susceptibilities of Brazilian T. gondii strains to SDZ, with evidence of drug resistance. Despite the large number of polymorphisms identified, the profile of susceptibility to SDZ was not associated with any of the dhps variants identified in this study. Other genetic factors, not yet determined, may be associated with the resistance to SDZ; thus

  16. Effects of a weight loss program on body composition and the metabolic profile in obese postmenopausal women displaying various obesity phenotypes: a MONET group study.

    PubMed

    Normandin, Eve; Doucet, Eric; Rabasa-Lhoret, Rémi; Brochu, Martin

    2015-07-01

    Obesity is a heterogeneous condition, since the metabolic profile may differ greatly from one individual to another. The objective of this study was to compare the effect of a 6-month diet-induced weight loss program on body composition and the metabolic profile in obese individuals displaying different obesity phenotypes. Secondary analyses were done on 129 obese (% body fat: 46% ± 4%) postmenopausal women (age: 57 ± 4 years). Outcome measures included body composition, body fat distribution, glucose homeostasis, fasting lipids, and blood pressure. Obesity phenotypes were determined based on lean body mass (LBM) index (LBMI = LBM/height(2)) and visceral fat (VF) accumulation, as follows: 1, lower VF and lower LBMI (n = 35); 2, lower VF and higher LBMI (n = 19); 3, higher VF and lower LBMI (n = 14); and 4, higher VF and higher LBMI (n = 61). All groups had significantly improved measures of body composition after the intervention (P < 0.0001). Greater decreases in LBM and LBMI were observed in the higher LBMI groups than in the lower LBMI groups (P < 0.0001). Similarly, decreases in VF were greater in the higher VF groups than in the lower VF groups (P < 0.05). Overall, fasting insulin levels and glucose disposal improved following the intervention, with higher LBMI groups showing a trend for greater improvements (P = 0.06 and 0.07, respectively). Overall, no difference was observed among the different obesity phenotypes regarding improvements in the metabolic profile in response to weight loss. Individuals displaying higher VF or higher LBMI at baseline experienced significantly greater decreases for these variables after the intervention.

  17. Global nutrient profiling by Phenotype MicroArrays: a tool complementing genomic and proteomic studies in conidial fungi*

    PubMed Central

    Atanasova, Lea; Druzhinina, Irina S.

    2010-01-01

    Conidial fungi or molds and mildews are widely used in modern biotechnology as producers of antibiotics and other secondary metabolites, industrially important enzymes, chemicals and food. They are also important pathogens of animals including humans and agricultural crops. These various applications and extremely versatile natural phenotypes have led to the constantly growing list of complete genomes which are now available. Functional genomics and proteomics widely exploit the genomic information to study the cell-wide impact of altered genes on the phenotype of an organism and its function. This allows for global analysis of the information flow from DNA to RNA to protein, but it is usually not sufficient for the description of the global phenotype of an organism. More recently, Phenotype MicroArray (PM) technology has been introduced as a tool to characterize the metabolism of a (wild) fungal strain or a mutant. In this article, we review the background of PM applications for fungi and the methodic requirements to obtain reliable results. We also report examples of the versatility of this tool. PMID:20205302

  18. Numerical approaches for multidimensional simulations of stellar explosions

    NASA Astrophysics Data System (ADS)

    Chen, Ke-Jung; Heger, Alexander; Almgren, Ann S.

    2013-11-01

    We introduce numerical algorithms for initializing multidimensional simulations of stellar explosions with 1D stellar evolution models. The initial mapping from 1D profiles onto multidimensional grids can generate severe numerical artifacts, one of the most severe of which is the violation of conservation laws for physical quantities. We introduce a numerical scheme for mapping 1D spherically-symmetric data onto multidimensional meshes so that these physical quantities are conserved. We verify our scheme by porting a realistic 1D Lagrangian stellar profile to the new multidimensional Eulerian hydro code CASTRO. Our results show that all important features in the profiles are reproduced on the new grid and that conservation laws are enforced at all resolutions after mapping. We also introduce a numerical scheme for initializing multidimensional supernova simulations with realistic perturbations predicted by 1D stellar evolution models. Instead of seeding 3D stellar profiles with random perturbations, we imprint them with velocity perturbations that reproduce the Kolmogorov energy spectrum expected for highly turbulent convective regions in stars. Our models return Kolmogorov energy spectra and vortex structures like those in turbulent flows before the modes become nonlinear. Finally, we describe approaches to determining the resolution for simulations required to capture fluid instabilities and nuclear burning. Our algorithms are applicable to multidimensional simulations besides stellar explosions that range from astrophysics to cosmology.

  19. Multidimensional spectral load balancing

    SciTech Connect

    Hendrickson, B.; Leland, R.

    1993-01-01

    We describe an algorithm for the static load balancing of scientific computations that generalizes and improves upon spectral bisection. Through a novel use of multiple eigenvectors, our new spectral algorithm can divide a computation into 4 or 8 pieces at once. These multidimensional spectral partitioning algorithms generate balanced partitions that have lower communication overhead and are less expensive to compute than those produced by spectral bisection. In addition, they automatically work to minimize message contention on a hypercube or mesh architecture. These spectral partitions are further improved by a multidimensional generalization of the Kernighan-Lin graph partitioning algorithm. Results on several computational grids are given and compared with other popular methods.

  20. Comparison of phenotypic and genotypic antimicrobial profiles in Eschericia coli and Salmonella enterica from the same dairy cattle farms

    PubMed Central

    Scaria, Joy; Warnick, Lorin D; Kaneene, John B.; May, Katherine; Teng, Ching-Hao; Chang, Yung-Fu

    2010-01-01

    Transmission of antimicrobial drug resistance from resistant bacteria to non-resistant strains is an important public health issue. In this study, we have examined the possibility of multiple resistance gene transfer between Escherichia coli and Salmonella in the natural setting. Bacteria isolated from calves concurrently shedding E. coli and Salmonella showed similar antimicrobial drug resistance patterns as measured by a broth dilution method. However, microarray analysis of the antibiotic resistance at the gene level revealed several differences in resistance gene profile. Resistance profiles of E. coli isolated from different farms were closer than the profile of E. coli and Salmonella isolated from the same farm. This shows that the chance of multiple resistance gene transfers between these species is unlikely. PMID:20688154

  1. Saccular Transcriptome Profiles of the Seasonal Breeding Plainfin Midshipman Fish (Porichthys notatus), a Teleost with Divergent Sexual Phenotypes

    PubMed Central

    Faber-Hammond, Joshua; Samanta, Manoj P.; Whitchurch, Elizabeth A.; Manning, Dustin; Sisneros, Joseph A.; Coffin, Allison B.

    2015-01-01

    Acoustic communication is essential for the reproductive success of the plainfin midshipman fish (Porichthys notatus). During the breeding season, type I males use acoustic cues to advertise nest location to potential mates, creating an audible signal that attracts reproductive females. Type II (sneaker) males also likely use this social acoustic signal to find breeding pairs from which to steal fertilizations. Estrogen-induced changes in the auditory system of breeding females are thought to enhance neural encoding of the advertisement call, and recent anatomical data suggest the saccule (the main auditory end organ) as one possible target for this seasonal modulation. Here we describe saccular transcriptomes from all three sexual phenotypes (females, type I and II males) collected during the breeding season as a first step in understanding the mechanisms underlying sexual phenotype-specific and seasonal differences in auditory function. We used RNA-Seq on the Ion Torrent platform to create a combined transcriptome dataset containing over 79,000 assembled transcripts representing almost 9,000 unique annotated genes. These identified genes include several with known inner ear function and multiple steroid hormone receptors. Transcripts most closely matched to published genomes of nile tilapia and large yellow croaker, inconsistent with the phylogenetic relationship between these species but consistent with the importance of acoustic communication in their life-history strategies. We then compared the RNA-Seq results from the saccules of reproductive females with a separate transcriptome from the non-reproductive female phenotype and found over 700 differentially expressed transcripts, including members of the Wnt and Notch signaling pathways that mediate cell proliferation and hair cell addition in the inner ear. These data constitute a valuable resource for furthering our understanding of the molecular basis for peripheral auditory function as well as a range of

  2. Saccular Transcriptome Profiles of the Seasonal Breeding Plainfin Midshipman Fish (Porichthys notatus), a Teleost with Divergent Sexual Phenotypes.

    PubMed

    Faber-Hammond, Joshua; Samanta, Manoj P; Whitchurch, Elizabeth A; Manning, Dustin; Sisneros, Joseph A; Coffin, Allison B

    2015-01-01

    Acoustic communication is essential for the reproductive success of the plainfin midshipman fish (Porichthys notatus). During the breeding season, type I males use acoustic cues to advertise nest location to potential mates, creating an audible signal that attracts reproductive females. Type II (sneaker) males also likely use this social acoustic signal to find breeding pairs from which to steal fertilizations. Estrogen-induced changes in the auditory system of breeding females are thought to enhance neural encoding of the advertisement call, and recent anatomical data suggest the saccule (the main auditory end organ) as one possible target for this seasonal modulation. Here we describe saccular transcriptomes from all three sexual phenotypes (females, type I and II males) collected during the breeding season as a first step in understanding the mechanisms underlying sexual phenotype-specific and seasonal differences in auditory function. We used RNA-Seq on the Ion Torrent platform to create a combined transcriptome dataset containing over 79,000 assembled transcripts representing almost 9,000 unique annotated genes. These identified genes include several with known inner ear function and multiple steroid hormone receptors. Transcripts most closely matched to published genomes of nile tilapia and large yellow croaker, inconsistent with the phylogenetic relationship between these species but consistent with the importance of acoustic communication in their life-history strategies. We then compared the RNA-Seq results from the saccules of reproductive females with a separate transcriptome from the non-reproductive female phenotype and found over 700 differentially expressed transcripts, including members of the Wnt and Notch signaling pathways that mediate cell proliferation and hair cell addition in the inner ear. These data constitute a valuable resource for furthering our understanding of the molecular basis for peripheral auditory function as well as a range of

  3. Appropriately differentiated ARPE-19 cells regain phenotype and gene expression profiles similar to those of native RPE cells

    PubMed Central

    Jaworski, Cynthia; Postnikova, Olga. A.; Kutty, R. Krishnan; Duncan, Todd; Tan, Li Xuan; Poliakov, Eugenia; Lakkaraju, Aparna; Redmond, T. Michael

    2017-01-01

    Purpose The RPE cell line ARPE-19 provides a dependable and widely used alternative to native RPE. However, replication of the native RPE phenotype becomes more difficult because these cells lose their specialized phenotype after multiple passages. Compounding this problem is the widespread use of ARPE-19 cells in an undifferentiated state to attempt to model RPE functions. We wished to determine whether suitable culture conditions and differentiation could restore the RPE-appropriate expression of genes and proteins to ARPE-19, along with a functional and morphological phenotype resembling native RPE. We compared the transcriptome of ARPE-19 cells kept in long-term culture with those of primary and other human RPE cells to assess the former’s inherent plasticity relative to the latter. Methods ARPE-19 cells at passages 9 to 12 grown in DMEM containing high glucose and pyruvate with 1% fetal bovine serum were differentiated for up to 4 months. Immunocytochemistry was performed on ARPE-19 cells grown on filters. Total RNA extracted from ARPE-19 cells cultured for either 4 days or 4 months was used for RNA sequencing (RNA-Seq) analysis using a 2 × 50 bp paired end protocol. The RNA-Seq data were analyzed to identify the affected pathways and recognize shared ontological classification among differentially expressed genes. RPE-specific mRNAs and miRNAs were assessed with quantitative real-time (RT)–PCR, and proteins with western blotting. Results ARPE-19 cells grown for 4 months developed the classic native RPE phenotype with heavy pigmentation. RPE-expressed genes, including RPE65, RDH5, and RDH10, as well as miR-204/211, were greatly increased in the ARPE-19 cells maintained at confluence for 4 months. The RNA-Seq analysis provided a comprehensive view of the relative abundance and differential expression of the genes in the differentiated ARPE-19 cells. Of the 16,757 genes with detectable signals, nearly 1,681 genes were upregulated, and 1,629 genes were

  4. CDH23 Mutation and Phenotype Heterogeneity: A Profile of 107 Diverse Families with Usher Syndrome and Nonsyndromic Deafness

    PubMed Central

    Astuto, L. M.; Bork, J. M.; Weston, M. D.; Askew, J. W.; Fields, R. R.; Orten, D. J.; Ohliger, S. J.; Riazuddin, S.; Morell, R. J.; Khan, S.; Riazuddin, S.; Kremer, H.; van Hauwe, P.; Moller, C. G.; Cremers, C. W. R. J.; Ayuso, C.; Heckenlively, J. R.; Rohrschneider, K.; Spandau, U.; Greenberg, J.; Ramesar, R.; Reardon, W.; Bitoun, P.; Millan, J.; Legge, R.; Friedman, T. B.; Kimberling, W. J.

    2002-01-01

    Usher syndrome type I is characterized by congenital hearing loss, retinitis pigmentosa (RP), and variable vestibular areflexia. Usher syndrome type ID, one of seven Usher syndrome type I genetic localizations, have been mapped to a chromosomal interval that overlaps with a nonsyndromic-deafness localization, DFNB12. Mutations in CDH23, a gene that encodes a putative cell-adhesion protein with multiple cadherin-like domains, are responsible for both Usher syndrome and DFNB12 nonsyndromic deafness. Specific CDH23 mutational defects have been identified that differentiate these two phenotypes. Only missense mutations of CDH23 have been observed in families with nonsyndromic deafness, whereas nonsense, frameshift, splice-site, and missense mutations have been identified in families with Usher syndrome. In the present study, a panel of 69 probands with Usher syndrome and 38 probands with recessive nonsyndromic deafness were screened for the presence of mutations in the entire coding region of CDH23, by heteroduplex, single-strand conformation polymorphism, and direct sequence analyses. A total of 36 different CDH23 mutations were detected in 45 families; 33 of these mutations were novel, including 18 missense, 3 nonsense, 5 splicing defects, 5 microdeletions, and 2 insertions. A total of seven mutations were common to more than one family. Numerous exonic and intronic polymorphisms also were detected. Results of ophthalmologic examinations of the patients with nonsyndromic deafness have found asymptomatic RP–like manifestations, indicating that missense mutations may have a subtle effect in the retina. Furthermore, patients with mutations in CDH23 display a wide range of hearing loss and RP phenotypes, differing in severity, age at onset, type, and the presence or absence of vestibular areflexia. PMID:12075507

  5. Multidimensional capillary electrophoresis.

    PubMed

    Grochocki, Wojciech; Markuszewski, Michał J; Quirino, Joselito P

    2015-01-01

    Multidimensional separation where two or more orthogonal displacement mechanisms are combined is a promising approach to increase peak capacity in CE. The combinations allow dramatic improvement of analytical performance since the total peak capacity is given by a product of the peak capacities of all methods. The initial reports were concentrated on the construction of effective connections between capillaries for 2D analysis. Today, 2D and 3D CE systems are now able to separate real complex biological or environmental mixtures with good repeatability, improved resolution with minimal loss of sample. This review will present the developments in the field of multidimensional CE during the last 15 years. The endeavors in this specific field were on the development of interfaces, interface-free techniques including integrated separations, microdevices, and on-line sample concentration techniques to improve detection sensitivity.

  6. Multidimensional diffusion MRI

    NASA Astrophysics Data System (ADS)

    Topgaard, Daniel

    2017-02-01

    Principles from multidimensional NMR spectroscopy, and in particular solid-state NMR, have recently been transferred to the field of diffusion MRI, offering non-invasive characterization of heterogeneous anisotropic materials, such as the human brain, at an unprecedented level of detail. Here we revisit the basic physics of solid-state NMR and diffusion MRI to pinpoint the origin of the somewhat unexpected analogy between the two fields, and provide an overview of current diffusion MRI acquisition protocols and data analysis methods to quantify the composition of heterogeneous materials in terms of diffusion tensor distributions with size, shape, and orientation dimensions. While the most advanced methods allow estimation of the complete multidimensional distributions, simpler methods focus on various projections onto lower-dimensional spaces as well as determination of means and variances rather than actual distributions. Even the less advanced methods provide simple and intuitive scalar parameters that are directly related to microstructural features that can be observed in optical microscopy images, e.g. average cell eccentricity, variance of cell density, and orientational order - properties that are inextricably entangled in conventional diffusion MRI. Key to disentangling all these microstructural features is MRI signal acquisition combining isotropic and directional dimensions, just as in the field of multidimensional solid-state NMR from which most of the ideas for the new methods are derived.

  7. Development of a three-dimensional multiscale agent-based tumor model: simulating gene-protein interaction profiles, cell phenotypes and multicellular patterns in brain cancer.

    PubMed

    Zhang, Le; Athale, Chaitanya A; Deisboeck, Thomas S

    2007-01-07

    Experimental evidence suggests that epidermal growth factor receptor (EGFR)-mediated activation of the signaling protein phospholipase Cgamma plays a critical role in a cancer cell's phenotypic decision to either proliferate or to migrate at a given point in time. Here, we present a novel three-dimensional multiscale agent-based model to simulate this cellular decision process in the context of a virtual brain tumor. Each tumor cell is equipped with an EGFR gene-protein interaction network module that also connects to a simplified cell cycle description. The simulation results show that over time proliferative and migratory cell populations not only oscillate but also directly impact the spatio-temporal expansion patterns of the entire cancer system. The percentage change in the concentration of the sub-cellular interaction network's molecular components fluctuates, and, for the 'proliferation-to-migration' switch we find that the phenotype triggering molecular profile to some degree varies as the tumor system grows and the microenvironment changes. We discuss potential implications of these findings for experimental and clinical cancer research.

  8. mRNA and methylation profiling of radioresistant esophageal cancer cells: the involvement of Sall2 in acquired aggressive phenotypes

    PubMed Central

    Luo, Judong; Wang, Wenjie; Tang, Yiting; Zhou, Dandan; Gao, Yi; Zhang, Qi; Zhou, Xifa; Zhu, Hui; Xing, Ligang; Yu, Jinming

    2017-01-01

    Esophageal squamous cell carcinoma (ESCC) is one of the deadliest malignancies worldwide. Radiotherapy plays a critical role in the curative management of inoperable ESCC patients. However, radioresistance restricts the efficacy of radiotherapy for ESCC patients. The molecules involved in radioresistance remain largely unknown, and new approaches to sensitize cells to irradiation are in demand. Technical advances in analysis of mRNA and methylation have enabled the exploration of the etiology of diseases and have the potential to broaden our understanding of the molecular pathways of ESCC radioresistance. In this study, we constructed radioresistant TE-1 and Eca-109 cell lines (TE-1/R and Eca-109/R, respectively). The radioresistant cells showed an increased migration ability but reduced apoptosis and cisplatin sensitivity compared with their parent cells. mRNA and methylation profiling by microarray revealed 1192 preferentially expressed mRNAs and 8841 aberrantly methylated regions between TE-1/R and TE-1 cells. By integrating the mRNA and methylation profiles, we related the decreased expression of transcription factor Sall2 with a corresponding increase in its methylation in TE-1/R cells, indicating its involvement in radioresistance. Upregulation of Sall2 decreased the growth and migration advantage of radioresistant ESCC cells. Taken together, our present findings illustrate the mRNA and DNA methylation changes during the radioresistance of ESCC and the important role of Sall2 in esophageal cancer malignancy. PMID:28367244

  9. Cervical Cancer Cell Supernatants Induce a Phenotypic Switch from U937-Derived Macrophage-Activated M1 State into M2-Like Suppressor Phenotype with Change in Toll-Like Receptor Profile

    PubMed Central

    Sánchez-Reyes, Karina; Bravo-Cuellar, Alejandro; Hernández-Flores, Georgina; Lerma-Díaz, José Manuel; Jave-Suárez, Luis Felipe; Gómez-Lomelí, Paulina; de Celis, Ruth; Aguilar-Lemarroy, Adriana; Domínguez-Rodríguez, Jorge Ramiro; Ortiz-Lazareno, Pablo Cesar

    2014-01-01

    Cervical cancer (CC) is the second most common cancer among women worldwide. Infection with human papillomavirus (HPV) is the main risk factor for developing CC. Macrophages are important immune effector cells; they can be differentiated into two phenotypes, identified as M1 (classically activated) and M2 (alternatively activated). Macrophage polarization exerts profound effects on the Toll-like receptor (TLR) profile. In this study, we evaluated whether the supernatant of human CC cells HeLa, SiHa, and C-33A induces a shift of M1 macrophage toward M2 macrophage in U937-derived macrophages. Results. The results showed that soluble factors secreted by CC cells induce a change in the immunophenotype of macrophages from macrophage M1 into macrophage M2. U937-derived macrophages M1 released proinflammatory cytokines and nitric oxide; however, when these cells were treated with the supernatant of CC cell lines, we observed a turnover of M1 toward M2. These cells increased CD163 and IL-10 expression. The expression of TLR-3, -7, and -9 is increased when the macrophages were treated with the supernatant of CC cells. Conclusions. Our result strongly suggests that CC cells may, through the secretion of soluble factors, induce a change of immunophenotype M1 into M2 macrophages. PMID:25309919

  10. Sex-Related Cognitive Profile in Autism Spectrum Disorders Diagnosed Late in Life: Implications for the Female Autistic Phenotype.

    PubMed

    Lehnhardt, Fritz-Georg; Falter, Christine Michaela; Gawronski, Astrid; Pfeiffer, Kathleen; Tepest, Ralf; Franklin, Jeremy; Vogeley, Kai

    2016-01-01

    Females with high-functioning ASD are known to camouflage their autistic symptoms better than their male counterparts, making them prone to being under-ascertained and delayed in diagnostic assessment. Thus far the underlying cognitive processes that enable such successful socio-communicative adaptation are not well understood. The current results show sex-related differences in the cognitive profile of ASD individuals, which were diagnosed late in life exclusively. Higher verbal abilities were found in males (n = 69) as opposed to higher processing speed and better executive functions in females with ASD (n = 38). Since both sexes remained unidentified during childhood and adolescence, these results are suggestive for sex-distinctive cognitive strategies as an alternative to typically-developed reciprocal social behavior and social mimicry in high functioning ASD.

  11. Influence of blood pressure profile on frailty phenotype in community-dwelling elders in Brazil - FIBRA study.

    PubMed

    Fattori, A; Santimaria, M R; Alves, R M A; Guariento, M E; Neri, A L

    2013-01-01

    Frailty is a clinical condition associated with pathological aging and biological vulnerability. In the spectrum of events related to frailty, aging of the cardiocirculatory system and abnormalities in arterial blood pressure (BP) partly explain the changes in tissue perfusion and, potentially, the decrease in physiological reserves. This study investigated the relationship between BP levels, systemic arterial hypertension (SAH) and the frailty phenotype by analyzing frailty criteria in a cross-sectional model into the FIBRA network, a populational sample of community-dwelling elders in Southeastern Brazil. Study participants with ≥65 years were selected by probabilistic sampling of residents in the urban area of the municipality of Campinas (n=900). Considering frailty as a whole and the difference between genders, there was a greater proportion of frail or pre-frail individuals among women than men. Analysis of individual frailty criteria showed that weight loss and fatigue were more common among women (18.3% vs. 12.5%, p=0.034 and 22.5% vs. 11.9%, p<0.001, respectively). Comparison of individuals with or without SAH failed to reveal any differences related to frailty criteria. Nevertheless, averages of diastolic blood pressure (DBP) and mean arterial blood pressure values were lower among elderly individuals with reduced grip strength, physical activity and the frailty classification as a whole (OR 0.986, IC 0.975-0.997) (for every 1 mmHg reduction in MBP values, the likelihood of being frail increased 1.4%). Our findings corroborate the relationship between BP values and frailty in the elderly and contribute to an understanding of the pathophysiological mechanisms of the syndrome.

  12. Phenotypic Profiling Reveals that Candida albicans Opaque Cells Represent a Metabolically Specialized Cell State Compared to Default White Cells

    PubMed Central

    Ene, Iuliana V.; Lohse, Matthew B.; Vladu, Adrian V.; Morschhäuser, Joachim; Johnson, Alexander D.

    2016-01-01

    ABSTRACT The white-opaque switch is a bistable, epigenetic transition affecting multiple traits in Candida albicans including mating, immunogenicity, and niche specificity. To compare how the two cell states respond to external cues, we examined the fitness, phenotypic switching, and filamentation properties of white cells and opaque cells under 1,440 different conditions at 25°C and 37°C. We demonstrate that white and opaque cells display striking differences in their integration of metabolic and thermal cues, so that the two states exhibit optimal fitness under distinct conditions. White cells were fitter than opaque cells under a wide range of environmental conditions, including growth at various pHs and in the presence of chemical stresses or antifungal drugs. This difference was exacerbated at 37°C, consistent with white cells being the default state of C. albicans in the mammalian host. In contrast, opaque cells showed greater fitness than white cells under select nutritional conditions, including growth on diverse peptides at 25°C. We further demonstrate that filamentation is significantly rewired between the two states, with white and opaque cells undergoing filamentous growth in response to distinct external cues. Genetic analysis was used to identify signaling pathways impacting the white-opaque transition both in vitro and in a murine model of commensal colonization, and three sugar sensing pathways are revealed as regulators of the switch. Together, these findings establish that white and opaque cells are programmed for differential integration of metabolic and thermal cues and that opaque cells represent a more metabolically specialized cell state than the default white state. PMID:27879329

  13. Phenotypes and gene expression profiles of Saccharopolyspora erythraea rifampicin-resistant (rif) mutants affected in erythromycin production

    PubMed Central

    Carata, Elisabetta; Peano, Clelia; Tredici, Salvatore M; Ferrari, Francesco; Talà, Adelfia; Corti, Giorgio; Bicciato, Silvio; De Bellis, Gianluca; Alifano, Pietro

    2009-01-01

    Background There is evidence from previous works that bacterial secondary metabolism may be stimulated by genetic manipulation of RNA polymerase (RNAP). In this study we have used rifampicin selection as a strategy to genetically improve the erythromycin producer Saccharopolyspora erythraea. Results Spontaneous rifampicin-resistant (rif) mutants were isolated from the parental strain NRRL2338 and two rif mutations mapping within rpoB, S444F and Q426R, were characterized. With respect to the parental strain, S444F mutants exhibited higher respiratory performance and up to four-fold higher final erythromycin yields; in contrast, Q426R mutants were slow-growing, developmental-defective and severely impaired in erythromycin production. DNA microarray analysis demonstrated that these rif mutations deeply changed the transcriptional profile of S. erythraea. The expression of genes coding for key enzymes of carbon (and energy) and nitrogen central metabolism was dramatically altered in turn affecting the flux of metabolites through erythromycin feeder pathways. In particular, the valine catabolic pathway that supplies propionyl-CoA for biosynthesis of the erythromycin precursor 6-deoxyerythronolide B was strongly up-regulated in the S444F mutants, while the expression of the biosynthetic gene cluster of erythromycin (ery) was not significantly affected. In contrast, the ery cluster was down-regulated (<2-fold) in the Q426R mutants. These strains also exhibited an impressive stimulation of the nitrogen regulon, which may contribute to lower erythromycin yields as erythromycin production was strongly inhibited by ammonium. Conclusion Rifampicin selection is a simple and reliable tool to investigate novel links between primary and secondary metabolism and morphological differentiation in S. erythraea and to improve erythromycin production. At the same time genome-wide analysis of expression profiles using DNA microarrays allowed information to be gained about the mechanisms

  14. Profiles.

    ERIC Educational Resources Information Center

    School Arts, 1979

    1979-01-01

    Profiles seven Black, Native American, and Chicano artists and art teachers: Hale A. Woodruff, Allan Houser, Luis Jimenez, Betrand D. Phillips, James E. Pate, I, and Fernando Navarro. This article is part of a theme issue on multicultural art. (SJL)

  15. Proteomic and Glycoproteomic Profilings Reveal That Post-translational Modifications of Toxins Contribute to Venom Phenotype in Snakes.

    PubMed

    Andrade-Silva, Débora; Zelanis, André; Kitano, Eduardo S; Junqueira-de-Azevedo, Inácio L M; Reis, Marcelo S; Lopes, Aline S; Serrano, Solange M T

    2016-08-05

    Snake venoms are biological weapon systems composed of secreted proteins and peptides that are used for immobilizing or killing prey. Although post-translational modifications are widely investigated because of their importance in many biological phenomena, we currently still have little understanding of how protein glycosylation impacts the variation and stability of venom proteomes. To address these issues, here we characterized the venom proteomes of seven Bothrops snakes using a shotgun proteomics strategy. Moreover, we compared the electrophoretic profiles of native and deglycosylated venoms and, in order to assess their subproteomes of glycoproteins, we identified the proteins with affinity for three lectins with different saccharide specificities and their putative glycosylation sites. As proteinases are abundant glycosylated toxins, we examined the effect of N-deglycosylation on their catalytic activities and show that the proteinases of the seven venoms were similarly affected by removal of N-glycans. Moreover, we prospected putative glycosylation sites of transcripts of a B. jararaca venom gland data set and detected toxin family related patterns of glycosylation. Based on our global analysis, we report that Bothrops venom proteomes and glycoproteomes contain a core of components that markedly define their composition, which is conserved upon evolution in parallel to other molecular markers that determine their phylogenetic classification.

  16. MicroRNA-499 Expression Distinctively Correlates to Target Genes sox6 and rod1 Profiles to Resolve the Skeletal Muscle Phenotype in Nile Tilapia

    PubMed Central

    Carvalho, Robson F.; Martins, Cesar; Pinhal, Danillo

    2015-01-01

    A class of small non-coding RNAs, the microRNAs (miRNAs), has been shown to be essential for the regulation of specific cell pathways, including skeletal muscle development, maintenance and homeostasis in vertebrates. However, the relative contribution of miRNAs for determining the red and white muscle cell phenotypes is far from being fully comprehended. To better characterize the role of miRNA in skeletal muscle cell biology, we investigated muscle-specific miRNA (myomiR) signatures in Nile tilapia fish. Quantitative (RT-qPCR) and spatial (FISH) expression analyses revealed a highly differential expression (forty-four-fold) of miR-499 in red skeletal muscle compared to white skeletal muscle, whereas the remaining known myomiRs were equally expressed in both muscle cell types. Detailed examination of the miR-499 targets through bioinformatics led us to the sox6 and rod1 genes, which had low expression in red muscle cells according to RT-qPCR, FISH, and protein immunofluorescence profiling experiments. Interestingly, we verified that the high expression of miR-499 perfectly correlates with a low expression of sox6 and rod1 target genes, as verified by a distinctive predominance of mRNA destabilization and protein translational decay to these genes, respectively. Through a genome-wide comparative analysis of SOX6 and ROD1 protein domains and through an in silico gene regulatory network, we also demonstrate that both proteins are essentially similar in vertebrate genomes, suggesting their gene regulatory network may also be widely conserved. Overall, our data shed light on the potential regulation of targets by miR-499 associated with the slow-twitch muscle fiber type phenotype. Additionally the results provide novel insights into the evolutionary dynamics of miRNA and target genes enrolled in a putative constrained molecular pathway in the skeletal muscle cells of vertebrates. PMID:25793727

  17. Multidimensional sexual perfectionism.

    PubMed

    Stoeber, Joachim; Harvey, Laura N; Almeida, Isabel; Lyons, Emma

    2013-11-01

    Perfectionism is a multidimensional personality characteristic that can affect all areas of life. This article presents the first systematic investigation of multidimensional perfectionism in the domain of sexuality exploring the unique relationships that different forms of sexual perfectionism show with positive and negative aspects of sexuality. A sample of 272 university students (52 male, 220 female) completed measures of four forms of sexual perfectionism: self-oriented, partner-oriented, partner-prescribed, and socially prescribed. In addition, they completed measures of sexual esteem, sexual self-efficacy, sexual optimism, sex life satisfaction (capturing positive aspects of sexuality) and sexual problem self-blame, sexual anxiety, sexual depression, and negative sexual perfectionism cognitions during sex (capturing negative aspects). Results showed unique patterns of relationships for the four forms of sexual perfectionism, suggesting that partner-prescribed and socially prescribed sexual perfectionism are maladaptive forms of sexual perfectionism associated with negative aspects of sexuality whereas self-oriented and partner-oriented sexual perfectionism emerged as ambivalent forms associated with positive and negative aspects.

  18. Multidimensional Potential Burgers Turbulence

    NASA Astrophysics Data System (ADS)

    Boritchev, Alexandre

    2016-03-01

    We consider the multidimensional generalised stochastic Burgers equation in the space-periodic setting: partial {u}/partial t+(nabla f({u}) \\cdot nabla) {u}-ν Δ {u}= nabla η, quad t ≥ 0, {x} in{T}^d=({R}/ {Z})^d, under the assumption that u is a gradient. Here f is strongly convex and satisfies a growth condition, ν is small and positive, while η is a random forcing term, smooth in space and white in time. For solutions u of this equation, we study Sobolev norms of u averaged in time and in ensemble: each of these norms behaves as a given negative power of ν. These results yield sharp upper and lower bounds for natural analogues of quantities characterising the hydrodynamical turbulence, namely the averages of the increments and of the energy spectrum. These quantities behave as a power of the norm of the relevant parameter, which is respectively the separation ℓ in the physical space and the wavenumber k in the Fourier space. Our bounds do not depend on the initial condition and hold uniformly in {ν}. We generalise the results obtained for the one-dimensional case in [10], confirming the physical predictions in [4, 30]. Note that the form of the estimates does not depend on the dimension: the powers of {ν, |{{k}}|, ℓ} are the same in the one- and the multi-dimensional setting.

  19. Elevated paternal glucocorticoid exposure alters the small noncoding RNA profile in sperm and modifies anxiety and depressive phenotypes in the offspring

    PubMed Central

    Short, A K; Fennell, K A; Perreau, V M; Fox, A; O'Bryan, M K; Kim, J H; Bredy, T W; Pang, T Y; Hannan, A J

    2016-01-01

    Recent studies have suggested that physiological and behavioral traits may be transgenerationally inherited through the paternal lineage, possibly via non-genomic signals derived from the sperm. To investigate how paternal stress might influence offspring behavioral phenotypes, a model of hypothalamic–pituitary–adrenal (HPA) axis dysregulation was used. Male breeders were administered water supplemented with corticosterone (CORT) for 4 weeks before mating with untreated female mice. Female, but not male, F1 offspring of CORT-treated fathers displayed altered fear extinction at 2 weeks of age. Only male F1 offspring exhibited altered patterns of ultrasonic vocalization at postnatal day 3 and, as adults, showed decreased time in open on the elevated-plus maze and time in light on the light–dark apparatus, suggesting a hyperanxiety-like behavioral phenotype due to paternal CORT treatment. Interestingly, expression of the paternally imprinted gene Igf2 was increased in the hippocampus of F1 male offspring but downregulated in female offspring. Male and female F2 offspring displayed increased time spent in the open arm of the elevated-plus maze, suggesting lower levels of anxiety compared with control animals. Only male F2 offspring showed increased immobility time on the forced-swim test and increased latency to feed on the novelty-supressed feeding test, suggesting a depression-like phenotype in these animals. Collectively, these data provide evidence that paternal CORT treatment alters anxiety and depression-related behaviors across multiple generations. Analysis of the small RNA profile in sperm from CORT-treated males revealed marked effects on the expression of small noncoding RNAs. Sperm from CORT-treated males contained elevated levels of three microRNAs, miR-98, miR-144 and miR-190b, which are predicted to interact with multiple growth factors, including Igf2 and Bdnf. Sustained elevation of glucocorticoids is therefore involved in the transmission of

  20. Multidimensional Perfectionism and the Self

    ERIC Educational Resources Information Center

    Ward, Andrew M.; Ashby, Jeffrey S.

    2008-01-01

    This study examined multidimensional perfectionism and self-development. Two hundred seventy-one undergraduates completed a measure of multidimensional perfectionism and two Kohutian measures designed to measure aspects of self-development including social connectedness, social assurance, goal instability (idealization), and grandiosity. The…

  1. Theta vocabulary II. Multidimensional case

    NASA Astrophysics Data System (ADS)

    Kharchev, S.; Zabrodin, A.

    2016-06-01

    It is shown that the Jacobi and Riemann identities of degree four for the multidimensional theta functions as well as the Weierstrass identities emerge as algebraic consequences of the fundamental multidimensional binary identities connecting the theta functions with Riemann matrices τ and 2 τ.

  2. Seten: A tool for systematic identification and comparison of processes, phenotypes and diseases associated with RNA-binding proteins from condition-specific CLIP-seq profiles.

    PubMed

    Budak, Gungor; Srivastava, Rajneesh; Janga, Sarath Chandra

    2017-03-23

    RNA-binding proteins (RBPs) control the regulation of gene expression in eukaryotic genomes at post-transcriptional level by binding to their cognate RNAs. Although several variants of CLIP (crosslinking and immunoprecipitation) protocols are currently available to study the global protein-RNA interaction landscape at single nucleotide resolution in a cell, currently there are very few tools which can facilitate understanding and dissecting the functional associations of RBPs from the resulting binding maps. Here, we present Seten, a web-based and a command line tool, which can identify and compare processes, phenotypes and diseases associated with RBPs from condition-specific CLIP-seq profiles. Seten uses BED files resulting from most peak calling algorithms which include scores reflecting the extent of binding of an RBP on the target transcript, to provide both traditional functional enrichment as well as gene set enrichment results for a number of gene set collections including BioCarta, KEGG, Reactome, Gene Ontology (GO), Human Phenotype Ontology (HPO) and MalaCards Disease Ontology for several organisms including fruit fly, human, mouse, rat, worm, and yeast. It also provides an option to dynamically compare the associated gene sets across datasets as bubble charts, to facilitate comparative analysis. Benchmarking of Seten using eCLIP data for IGF2BP1, SRSF7 and PTBP1 against their corresponding CRISPR RNA-seq in K562 cells as well as randomized negative controls, demonstrated that its gene set enrichment method outperforms functional enrichment, with scores significantly contributing to the discovery of true annotations. Comparative performance analysis using these CRISPR control datasets revealed significantly higher precision and comparable recall to that observed using ChIP-Enrich. Seten's web interface currently provides precomputed results for about 200 CLIP-seq datasets and both command line as well as web interfaces can be used to analyze CLIP

  3. Deriving Stopping Rules for Multidimensional Computerized Adaptive Testing

    ERIC Educational Resources Information Center

    Wang, Chun; Chang, Hua-Hua; Boughton, Keith A.

    2013-01-01

    Multidimensional computerized adaptive testing (MCAT) is able to provide a vector of ability estimates for each examinee, which could be used to provide a more informative profile of an examinee's performance. The current literature on MCAT focuses on the fixed-length tests, which can generate less accurate results for those examinees whose…

  4. Linear and Nonlinear Thinking: A Multidimensional Model and Measure

    ERIC Educational Resources Information Center

    Groves, Kevin S.; Vance, Charles M.

    2015-01-01

    Building upon previously developed and more general dual-process models, this paper provides empirical support for a multidimensional thinking style construct comprised of linear thinking and multiple dimensions of nonlinear thinking. A self-report assessment instrument (Linear/Nonlinear Thinking Style Profile; LNTSP) is presented and…

  5. Suicide: a multidimensional malaise.

    PubMed

    Leenaars, A A

    1996-01-01

    No one really knows why human beings commit suicide. The goal of this paper is to provide a psychological point of view on the topic, among the many other perspectives that are needed. It addresses the question by providing a theory of suicide, arguing that it is theory that allows us to sort out the booming buzzing mess of experience (Wm. James). Suicide is a multi-dimensional malaise. Metaphorically speaking, it is an intrapsychic drama on an interpersonal stage. As sound theory must be empirically observable, the theory is next applied to research of suicide notes, studying such factors as age, sex, and method of suicide, cross-culture and cross-time. Next, because all theory must have clinical applicability, a clinical case study of Goethe's Werther is provided. Overall, it is concluded that we need to continue to develop models to understand the suicidal mind.

  6. Spectral multidimensional scaling

    PubMed Central

    Aflalo, Yonathan; Kimmel, Ron

    2013-01-01

    An important tool in information analysis is dimensionality reduction. There are various approaches for large data simplification by scaling its dimensions down that play a significant role in recognition and classification tasks. The efficiency of dimension reduction tools is measured in terms of memory and computational complexity, which are usually a function of the number of the given data points. Sparse local operators that involve substantially less than quadratic complexity at one end, and faithful multiscale models with quadratic cost at the other end, make the design of dimension reduction procedure a delicate balance between modeling accuracy and efficiency. Here, we combine the benefits of both and propose a low-dimensional multiscale modeling of the data, at a modest computational cost. The idea is to project the classical multidimensional scaling problem into the data spectral domain extracted from its Laplace–Beltrami operator. There, embedding into a small dimensional Euclidean space is accomplished while optimizing for a small number of coefficients. We provide a theoretical support and demonstrate that working in the natural eigenspace of the data, one could reduce the process complexity while maintaining the model fidelity. As examples, we efficiently canonize nonrigid shapes by embedding their intrinsic metric into , a method often used for matching and classifying almost isometric articulated objects. Finally, we demonstrate the method by exposing the style in which handwritten digits appear in a large collection of images. We also visualize clustering of digits by treating images as feature points that we map to a plane. PMID:24108352

  7. Relationship of inflammatory profile of elderly patients serum and senescence-associated secretory phenotype with human breast cancer cells proliferation: Role of IL6/IL8 ratio.

    PubMed

    Barajas-Gómez, Bertha Alicia; Rosas-Carrasco, Oscar; Morales-Rosales, Sandra Lisbeth; Pedraza Vázquez, Gibrán; González-Puertos, Viridiana Yazmín; Juárez-Cedillo, Teresa; García-Álvarez, Jorge Antonio; López-Diazguerrero, Norma Edith; Damián-Matsumura, Pablo; Königsberg, Mina; Luna-López, Armando

    2017-03-01

    Aging is considered a systemic, chronic and low-grade inflammatory state, called "inflammaging", which has been contemplated as a risk factor for cancer development and progression in the elderly population. Cellular senescence is a multifactorial phenomenon of growth arrest and distorted function, which has been recognized as a contributor to aging. Senescent cells have an altered secretion pattern called Senescent Associated Secretory Phenotype (SASP), that comprise a complex mix of factors including cytokines, growth factors, chemokines and matrix metalloproteinases among others. The SASP secreted by accumulated senescent cells during old age has been related to local inflammation that leads to cellular transformation and therefore may be supporting the inflammaging process. Here, we evaluated if the pro-inflammatory profile within the serum obtained from elderly patients (EPS) was able to induce cellular proliferation in the breast cancer transformed cell line (MCF-7), in a similar way to the proliferation stimulated by the SASP obtained from WI-38 primary cells prematurely induced to senescence by oxidative stress (SIPS). At the same time, the participation of IL-6/IL-8 ratio was determined. Our results showed that not all the EPS increased MCF-7 proliferation. However, there was an interesting relationship between IL-6 and IL-8 concentrations, when the IL-6 was higher than IL-8. Similar results were found with SASP from SIPS-WI-38 on the MCF-7 proliferation. Although it is known that those cytokines are fundamental factors to induce proliferation; the occurrence of other components in the cellular microenvironment is necessary to carry out this effect.

  8. Multidimensional persistence in biomolecular data

    PubMed Central

    Xia, Kelin; Wei, Guo-Wei

    2015-01-01

    Persistent homology has emerged as a popular technique for the topological simplification of big data, including biomolecular data. Multidimensional persistence bears considerable promise to bridge the gap between geometry and topology. However, its practical and robust construction has been a challenge. We introduce two families of multidimensional persistence, namely pseudo-multidimensional persistence and multiscale multidimensional persistence. The former is generated via the repeated applications of persistent homology filtration to high dimensional data, such as results from molecular dynamics or partial differential equations. The latter is constructed via isotropic and anisotropic scales that create new simiplicial complexes and associated topological spaces. The utility, robustness and efficiency of the proposed topological methods are demonstrated via protein folding, protein flexibility analysis, the topological denoising of cryo-electron microscopy data, and the scale dependence of nano particles. Topological transition between partial folded and unfolded proteins has been observed in multidimensional persistence. The separation between noise topological signatures and molecular topological fingerprints is achieved by the Laplace-Beltrami flow. The multiscale multidimensional persistent homology reveals relative local features in Betti-0 invariants and the relatively global characteristics of Betti-1 and Betti-2 invariants. PMID:26032339

  9. A Multidimensional Partial Credit Model with Associated Item and Test Statistics: An Application to Mixed-Format Tests

    ERIC Educational Resources Information Center

    Yao, Lihua; Schwarz, Richard D.

    2006-01-01

    Multidimensional item response theory (IRT) models have been proposed for better understanding the dimensional structure of data or to define diagnostic profiles of student learning. A compensatory multidimensional two-parameter partial credit model (M-2PPC) for constructed-response items is presented that is a generalization of those proposed to…

  10. Noncommutative accelerated multidimensional universe dominated by quintessence

    NASA Astrophysics Data System (ADS)

    El-Nabulsi, Ahmad Rami

    2010-04-01

    Noncommutative Geometry recently attracted growing interest of cosmologists, mainly after the greatest success of unifying the forces of nature into a single gravitational spectral action in a purely algebraic way, rather than as being an entirely new formalism. In the present work, we discuss a multidimensional Friedmann-Robertson-Walker flat universe in which the perfect fluid has a Gaussian profile in time and depends on a fundamental minimal length sqrt{θ} like ρ= ρ(0)exp (- t 2/4 θ) for some positive constant ρ(0). This special form is motivated by a more recent noncommutative inflationary cosmological model, which was found to be able to drive the universe through a bounce without the need of any scalar field. Furthermore, we conjecture that the generalized equation of state has the special form p= ω a m ρ- ρ,( ω, m)∈ℝ where a( t) is the scale factor. It was found that the expansion of the multidimensional universe accelerates in time and is dominated for very large time by quintessence. Many additional consequences are revealed and discussed in some detail.

  11. Multidimensional Learner Model In Intelligent Learning System

    NASA Astrophysics Data System (ADS)

    Deliyska, B.; Rozeva, A.

    2009-11-01

    The learner model in an intelligent learning system (ILS) has to ensure the personalization (individualization) and the adaptability of e-learning in an online learner-centered environment. ILS is a distributed e-learning system whose modules can be independent and located in different nodes (servers) on the Web. This kind of e-learning is achieved through the resources of the Semantic Web and is designed and developed around a course, group of courses or specialty. An essential part of ILS is learner model database which contains structured data about learner profile and temporal status in the learning process of one or more courses. In the paper a learner model position in ILS is considered and a relational database is designed from learner's domain ontology. Multidimensional modeling agent for the source database is designed and resultant learner data cube is presented. Agent's modules are proposed with corresponding algorithms and procedures. Multidimensional (OLAP) analysis guidelines on the resultant learner module for designing dynamic learning strategy have been highlighted.

  12. Multidimensional peptide separations in proteomics.

    PubMed

    Link, Andrew J

    2002-12-01

    Multidimensional peptide separation will play an increasingly important role in the drive to identify and quantitate the proteome. By increasing the peak and load capacity, multidimensional approaches increase the number and dynamic range of peptides that can be analyzed in a complex biological organism. Separation methods using different physical properties of peptides have been combined with varying degrees of success. The ultimate goal is a rapid separation strategy that can be coupled with analytical methods, such as mass spectrometry, to provide comprehensive monitoring of the changing concentration, interactions, and structures of proteins in the proteome.

  13. Comparative Phenotypic and Molecular Genetic Profiling of Wild Lactococcus lactis subsp. lactis Strains of the L. lactis subsp. lactis and L. lactis subsp. cremoris Genotypes, Isolated from Starter-Free Cheeses Made of Raw Milk▿

    PubMed Central

    Fernández, Elena; Alegría, Ángel; Delgado, Susana; Martín, M. Cruz; Mayo, Baltasar

    2011-01-01

    Twenty Lactococcus lactis strains with an L. lactis subsp. lactis phenotype isolated from five traditional cheeses made of raw milk with no added starters belonging to the L. lactis subsp. lactis and L. lactis subsp. cremoris genotypes (lactis and cremoris genotypes, respectively; 10 strains each) were subjected to a series of phenotypic and genetic typing methods, with the aims of determining their phylogenetic relationships and suitability as starters. Pulsed-field gel electrophoresis (PFGE) analysis of intact genomes digested with SalI and SmaI proved that all strains were different except for three isolates of the cremoris genotype, which showed identical PFGE profiles. Multilocus sequence typing (MLST) analysis using internal sequences of seven loci (namely, atpA, rpoA, pheS, pepN, bcaT, pepX, and 16S rRNA gene) revealed considerable intergenotype nucleotide polymorphism, although deduced amino acid changes were scarce. Analysis of the MLST data for the present strains and others from other dairy and nondairy sources showed that all of them clustered into the cremoris or lactis genotype group, by using both independent and combined gene sequences. These two groups of strains also showed distinctive carbohydrate fermentation and enzyme activity profiles, with the strains in the cremoris group showing broader profiles. However, the profiles of resistance/susceptibility to 16 antibiotics were very similar, showing no atypical resistance, except for tetracycline resistance in three identical cremoris genotype isolates. The numbers and concentrations of volatile compounds produced in milk by the strains belonging to these two groups were clearly different, with the cremoris genotype strains producing higher concentrations of more branched-chain, derived compounds. Together, the present results support the idea that the lactis and cremoris genotypes of phenotypic Lactococcus lactis subsp. lactis actually represent true subspecies. Some strains of the two subspecies

  14. On the Need for Multidimensional Stirling Simulations

    NASA Technical Reports Server (NTRS)

    Dyson, Rodger W.; Wilson, Scott D.; Tew, Roy C.; Demko, Rikako

    2005-01-01

    Given the cost and complication of simulating Stirling convertors, do we really need multidimensional modeling when one-dimensional capabilities exist? This paper provides a comprehensive description of when and why multidimensional simulation is needed.

  15. Bioimaging for quantitative phenotype analysis.

    PubMed

    Chen, Weiyang; Xia, Xian; Huang, Yi; Chen, Xingwei; Han, Jing-Dong J

    2016-06-01

    With the development of bio-imaging techniques, an increasing number of studies apply these techniques to generate a myriad of image data. Its applications range from quantification of cellular, tissue, organismal and behavioral phenotypes of model organisms, to human facial phenotypes. The bio-imaging approaches to automatically detect, quantify, and profile phenotypic changes related to specific biological questions open new doors to studying phenotype-genotype associations and to precisely evaluating molecular changes associated with quantitative phenotypes. Here, we review major applications of bioimage-based quantitative phenotype analysis. Specifically, we describe the biological questions and experimental needs addressable by these analyses, computational techniques and tools that are available in these contexts, and the new perspectives on phenotype-genotype association uncovered by such analyses.

  16. A log-linear multidimensional Rasch model for capture-recapture.

    PubMed

    Pelle, E; Hessen, D J; van der Heijden, P G M

    2016-02-20

    In this paper, a log-linear multidimensional Rasch model is proposed for capture-recapture analysis of registration data. In the model, heterogeneity of capture probabilities is taken into account, and registrations are viewed as dichotomously scored indicators of one or more latent variables that can account for correlations among registrations. It is shown how the probability of a generic capture profile is expressed under the log-linear multidimensional Rasch model and how the parameters of the traditional log-linear model are derived from those of the log-linear multidimensional Rasch model. Finally, an application of the model to neural tube defects data is presented.

  17. Profiling functions of ectomycorrhizal diversity and root structuring in seedlings of Norway spruce (Picea abies) with fast- and slow-growing phenotypes.

    PubMed

    Velmala, Sannakajsa M; Rajala, Tiina; Heinonsalo, Jussi; Taylor, Andy F S; Pennanen, Taina

    2014-01-01

    We studied the role of taxonomical and functional ectomycorrhizal (ECM) fungal diversity in root formation and nutrient uptake by Norway spruce (Picea abies) seedlings with fast- and slow-growing phenotypes. Seedlings were grown with an increasing ECM fungal diversity gradient from one to four species and sampled before aboveground growth differences between the two phenotypes were apparent. ECM fungal colonization patterns were determined and functional diversity was assayed via measurements of potential enzyme activities of eight exoenzymes probably involved in nutrient mobilization. Phenotypes did not vary in their receptiveness to different ECM fungal species. However, seedlings of slow-growing phenotypes had higher fine-root density and thus more condensed root systems than fast-growing seedlings, but the potential enzyme activities of ectomycorrhizas did not differ qualitatively or quantitatively. ECM species richness increased host nutrient acquisition potential by diversifying the exoenzyme palette. Needle nitrogen content correlated positively with high chitinase activity of ectomycorrhizas. Rather than fast- and slow-growing phenotypes exhibiting differing receptiveness to ECM fungi, our results suggest that distinctions in fine-root structuring and in the belowground growth strategy already apparent at early stages of seedling development may explain later growth differences between fast- and slow-growing families.

  18. Multidimensional Perfectionism and Ego Defenses

    ERIC Educational Resources Information Center

    Dickinson, Wendy L.; Ashby, Jeffrey S.

    2005-01-01

    This study examined the relationship between multidimensional perfectionism and ego defense style among 130 college students. Cluster analysis results facilitated the identification of groups of adaptive perfectionists, maladaptive perfectionists, and non-perfectionists. The researchers found that identified maladaptive perfectionists used…

  19. Multidimensional Scaling of Video Surrogates.

    ERIC Educational Resources Information Center

    Goodrum, Abby A.

    2001-01-01

    Four types of video surrogates were compared under two tasks. Multidimensional scaling was used to map dimensional dispersions of users' judgments of similarity between videos and surrogates. Congruence between these maps was used to evaluate representativeness of each surrogate type. Congruence was greater for image-based than for text-based…

  20. A Multidimensional Software Engineering Course

    ERIC Educational Resources Information Center

    Barzilay, O.; Hazzan, O.; Yehudai, A.

    2009-01-01

    Software engineering (SE) is a multidimensional field that involves activities in various areas and disciplines, such as computer science, project management, and system engineering. Though modern SE curricula include designated courses that address these various subjects, an advanced summary course that synthesizes them is still missing. Such a…

  1. Characterization of the Drug Resistance Profiles of Patients Infected with CRF07_BC Using Phenotypic Assay and Ultra-Deep Pyrosequencing

    PubMed Central

    Huang, Szu-Wei; Li, Wei-You; Wang, Wen-Hung; Lin, Yu-Ting; Chou, Chih-Hung; Chen, Marcelo; Huang, Hsien-Da; Chen, Yen-Hsu; Lu, Po-Liang; Wang, Sheng-Fan; Oka, Shinichi; Chen, Yi-Ming Arthur

    2017-01-01

    The usefulness of ultra-deep pyrosequencing (UDPS) for the diagnosis of HIV-1 drug resistance (DR) remains to be determined. Previously, we reported an explosive outbreak of HIV-1 circulating recombinant form (CRF) 07_BC among injection drug users (IDUs) in Taiwan in 2004. The goal of this study was to characterize the DR of CRF07_BC strains using different assays including UDPS. Seven CRF07_BC isolates including 4 from early epidemic (collected in 2004–2005) and 3 from late epidemic (collected in 2008) were obtained from treatment-naïve patient’s peripheral blood mononuclear cells. Viral RNA was extracted directly from patient’s plasma or from cultural supernatant and the pol sequences were determined using RT-PCR sequencing or UDPS. For comparison, phenotypic drug susceptibility assay using MAGIC-5 cells (in-house phenotypic assay) and Antivirogram were performed. In-house phenotypic assay showed that all the early epidemic and none of the late epidemic CRF07_BC isolates were resistant to most protease inhibitors (PIs) (4.4–47.3 fold). Neither genotypic assay nor Antivirogram detected any DR mutations. UDPS showed that early epidemic isolates contained 0.01–0.08% of PI DR major mutations. Furthermore, the combinations of major and accessory PI DR mutations significantly correlated with the phenotypic DR. The in-house phenotypic assay is superior to other conventional phenotypic assays in the detection of DR variants with a frequency as low as 0.01%. PMID:28107423

  2. A combined analysis of the Frost Multidimensional Perfectionism Scale (FMPS), Child and Adolescent Perfectionism Scale (CAPS), and Almost Perfect Scale-Revised (APS-R): Different perfectionist profiles in adolescent high school students.

    PubMed

    Sironic, Amanda; Reeve, Robert A

    2015-12-01

    To investigate differences and similarities in the dimensional constructs of the Frost Multidimensional Perfectionism Scale (FMPS; Frost, Marten, Lahart, & Rosenblate, 1990), Child and Adolescent Perfectionism Scale (CAPS; Flett, Hewitt, Boucher, Davidson, & Munro, 2000), and Almost Perfect Scale-Revised (APS-R; Slaney, Rice, Mobley, Trippi, & Ashby, 2001), 938 high school students completed the 3 perfectionism questionnaires, as well as the Depression Anxiety Stress Scales (DASS; Lovibond & Lovibond, 1995). Preliminary analyses revealed commonly observed factor structures for each perfectionism questionnaire. Exploratory factor analysis of item responses from the questionnaires (combined) yielded a 4-factor solution (factors were labeled High Personal Standards, Concerns, Doubts and Discrepancy, Externally Motivated Perfectionism, and Organization and Order). A latent class analysis of individuals' mean ratings on each of the 4 factors yielded a 6-class solution. Three of the 6 classes represented perfectionist subgroups (labeled adaptive perfectionist, externally motivated maladaptive perfectionist, and mixed maladaptive perfectionist), and 3 represented nonperfectionist subgroups (labeled nonperfectionist A, nonperfectionist B, and order and organization nonperfectionist). Each of the 6 subgroups was meaningfully associated with the DASS. Findings showed that 3 out of 10 students were classified as maladaptive perfectionists, and maladaptive perfectionists were more prevalent than adaptive perfectionists. In sum, it is evident that combined ratings from the FMPS, CAPS, and APS-R offer a meaningful characterization of perfectionism.

  3. Cuba: Multidimensional numerical integration library

    NASA Astrophysics Data System (ADS)

    Hahn, Thomas

    2016-08-01

    The Cuba library offers four independent routines for multidimensional numerical integration: Vegas, Suave, Divonne, and Cuhre. The four algorithms work by very different methods, and can integrate vector integrands and have very similar Fortran, C/C++, and Mathematica interfaces. Their invocation is very similar, making it easy to cross-check by substituting one method by another. For further safeguarding, the output is supplemented by a chi-square probability which quantifies the reliability of the error estimate.

  4. Multidimensional bioseparation with modular microfluidics

    DOEpatents

    Chirica, Gabriela S.; Renzi, Ronald F.

    2013-08-27

    A multidimensional chemical separation and analysis system is described including a prototyping platform and modular microfluidic components capable of rapid and convenient assembly, alteration and disassembly of numerous candidate separation systems. Partial or total computer control of the separation system is possible. Single or multiple alternative processing trains can be tested, optimized and/or run in parallel. Examples related to the separation and analysis of human bodily fluids are given.

  5. Comprehensive multi-dimensional liquid chromatographic separation in biomedical and pharmaceutical analysis: a review.

    PubMed

    Dixon, Steven P; Pitfield, Ian D; Perrett, David

    2006-01-01

    'Multi-dimensional' liquid separations have a history almost as long as chromatography. In multi-dimensional chromatography the sample is subjected to more than one separation mechanism; each mechanism is considered an independent separation dimension. The separations can be carried out either offline via fraction collection, or directly coupled online. Early multi-dimensional separations using combinations of paper chromatography, electrophoresis and gels, in both planar and columnar modes are reviewed. Developments in HPLC have increased the number of measurable analytes in ever more complex matrices, and this has led to the concept of 'global metabolite profiling'. This review focuses on the theory and practice of modern 'comprehensive' multi-dimensional liquid chromatography when applied to biomedical and pharmaceutical analysis.

  6. Cytomegalovirus infection modulates the phenotype and functional profile of the T-cell immune response to mycobacterial antigens in older life☆

    PubMed Central

    Terrazzini, Nadia; Bajwa, Martha; Vita, Serena; Thomas, David; Smith, Helen; Vescovini, Rosanna; Sansoni, Paolo; Kern, Florian

    2014-01-01

    Infection with Cytomegalovirus is associated with accelerated immunosenescence. Expansions of CMV-specific T cell responses have previously been demonstrated to affect the ability of T cells to respond to other infections. Most people above 60 years of age display M. tuberculosis-specific immunity because of vaccination, exposure, or both. T-cell responses can be assessed by measuring intracellular IFN-γ in vitro after tuberculin stimulation. Here we investigated tuberculin-specific CD4 T-cell responses in independently living healthy older people in the South of England using flow-cytometry. Individuals were investigated for tuberculin and CMV-specific T-cell immunity using in vitro antigen stimulation followed by intracellular staining for IFN-γ, TNF-α, IL2, as well as degranulation and CD154 upregulation. We also examined a control group of younger individuals (20–35 years of age). There was no significant difference between older and young people in regards to tuberculin responsiveness of CD4 T-cells; however, older people seemed to show more outliers. Increased responsiveness to tuberculin was significantly correlated to CMV responsiveness but not age. In older donors, the memory phenotype of tuberculin-induced T-cells was significantly skewed towards a more terminal differentiation phenotype in CMV-infected compared to uninfected individuals and the degree of skewing correlated quantitatively with the size of the CMV-specific CD4 T-cell response. This is a fundamental advance over previous reports of changes of the tuberculin-specific CD4 T-cell response with CMV serostatus. Our results show that how the immune system responds to CMV has a fundamental impact on the phenotype and function of the immune response to mycobacterial antigens in older life. PMID:24370373

  7. Multidimensionality in host manipulation mimicked by serotonin injection

    PubMed Central

    Perrot-Minnot, Marie-Jeanne; Sanchez-Thirion, Kevin; Cézilly, Frank

    2014-01-01

    Manipulative parasites often alter the phenotype of their hosts along multiple dimensions. ‘Multidimensionality’ in host manipulation could consist in the simultaneous alteration of several physiological pathways independently of one another, or proceed from the disruption of some key physiological parameter, followed by a cascade of effects. We compared multidimensionality in ‘host manipulation’ between two closely related amphipods, Gammarus fossarum and Gammarus pulex, naturally and experimentally infected with Pomphorhynchus laevis (Acanthocephala), respectively. To that end, we calculated in each host–parasite association the effect size of the difference between infected and uninfected individuals for six different traits (activity, phototaxis, geotaxis, attraction to conspecifics, refuge use and metabolic rate). The effects sizes were highly correlated between host–parasite associations, providing evidence for a relatively constant ‘infection syndrome’. Using the same methodology, we compared the extent of phenotypic alterations induced by an experimental injection of serotonin (5-HT) in uninfected G. pulex to that induced by experimental or natural infection with P. laevis. We observed a significant correlation between effect sizes across the six traits, indicating that injection with 5-HT can faithfully mimic the ‘infection syndrome’. This is, to our knowledge, the first experimental evidence that multidimensionality in host manipulation can proceed, at least partly, from the disruption of some major physiological mechanism. PMID:25339729

  8. Phenotype, hormonal profile and genotype of subjects with partial androgen insensitivity syndrome: report of a family with four adult males and one child with disorder of sexual differentiation.

    PubMed

    Kulshreshtha, B; Philibert, P; Eunice, M; Audran, F; Paris, F; Khurana, M L; Ammini, A C; Charles, S

    2009-08-01

    There is little information on the molecular basis of intrafamilial and inter-familial phenotypic heterogeneity with the same androgen receptor (AR) mutation in patients with partial androgen insensitivity syndrome. A genetic analysis was performed in a large kindred with ambiguous genitalia and the genotype-phenotype correlations were analysed. The index case was brought for sex assignment. Family history revealed four other affected members who had hypospadias and varying degrees of virilisation. All the affected males had hemizygous mutations in the third exon of the AR gene (A596T). One was also found to have a heterozygous mutation in the fourth exon of the 5 alpha reductase type 2 gene (G196S). This affected male with double mutations was better virilised compared with the other affected members with a single mutation. The degree of virilisation correlated with serum testosterone levels. Gynaecomastia was not present in any of these subjects. It is concluded that the subject with dual gene defects also had higher levels of testosterone and pubertal virilsation. Testosterone levels possibly govern the degree of pubertal virilisation in subjects with A596T gene defects. It is not clear whether the better pubertal virilsation and higher testosterone are in any way causally related to the SRD5A2 gene defect.

  9. Gene Expression Profiling Differentiates Autism Case–Controls and Phenotypic Variants of Autism Spectrum Disorders: Evidence for Circadian Rhythm Dysfunction in Severe Autism

    PubMed Central

    Hu, Valerie W.; Sarachana, Tewarit; Kim, Kyung Soon; Nguyen, AnhThu; Kulkarni, Shreya; Steinberg, Mara E.; Luu, Truong; Lai, Yinglei; Lee, Norman H.

    2009-01-01

    Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by delayed/abnormal language development, deficits in social interaction, repetitive behaviors and restricted interests. The heterogeneity in clinical presentation of ASD, likely due to different etiologies, complicates genetic/biological analyses of these disorders. DNA microarray analyses were conducted on 116 lymphoblastoid cell lines (LCL) from individuals with idiopathic autism who are divided into three phenotypic subgroups according to severity scores from the commonly used Autism Diagnostic Interview-Revised questionnaire and age-matched, nonautistic controls. Statistical analyses of gene expression data from control LCL against that of LCL from ASD probands identify genes for which expression levels are either quantitatively or qualitatively associated with phenotypic severity. Comparison of the significant differentially expressed genes from each subgroup relative to the control group reveals differentially expressed genes unique to each subgroup as well as genes in common across subgroups. Among the findings unique to the most severely affected ASD group are 15 genes that regulate circadian rhythm, which has been shown to have multiple effects on neurological as well as metabolic functions commonly dysregulated in autism. Among the genes common to all three subgroups of ASD are 20 novel genes mostly in putative noncoding regions, which appear to associate with androgen sensitivity and which may underlie the strong 4:1 bias toward affected males. PMID:19418574

  10. Gene expression profiling and phenotype analyses of S. cerevisiae in response to changing copper reveals six genes with new roles in copper and iron metabolism.

    PubMed

    van Bakel, Harm; Strengman, Eric; Wijmenga, Cisca; Holstege, Frank C P

    2005-08-11

    Exhaustive microarray time course analyses of Saccharomyces cerevisiae during copper starvation and copper excess reveal new aspects of metal-induced gene regulation. Aside from identifying targets of established copper- and iron-responsive transcription factors, we find that genes encoding mitochondrial proteins are downregulated and that copper-independent iron transport genes are preferentially upregulated, both during prolonged copper deprivation. The experiments also suggest the presence of a small regulatory iron pool that links copper and iron responses. One hundred twenty-eight genes with putative roles in metal metabolism were further investigated by several systematic phenotype screens. Of the novel phenotypes uncovered, hsp12-Delta and arn1-Delta display increased sensitivity to copper, cyc1-Delta and crr1-Delta show resistance to high copper, vma13-Delta exhibits increased sensitivity to iron deprivation, and pep12-Delta results in reduced growth in high copper and low iron. Besides revealing new components of eukaryotic metal trafficking pathways, the results underscore the previously determined intimate links between iron and copper metabolism and mitochondrial and vacuolar function in metal trafficking. The analyses further suggest that copper starvation can specifically lead to downregulation of respiratory function to preserve iron and copper for other cellular processes.

  11. Bioactive Potential of Marine Macroalgae from the Central Red Sea (Saudi Arabia) Assessed by High-Throughput Imaging-Based Phenotypic Profiling

    PubMed Central

    Kremb, Stephan; Müller, Constanze; Schmitt-Kopplin, Philippe; Voolstra, Christian R.

    2017-01-01

    Marine algae represent an important source of novel natural products. While their bioactive potential has been studied to some extent, limited information is available on marine algae from the Red Sea. This study aimed at the broad discovery of new bioactivities from a collection of twelve macroalgal species from the Central Red Sea. We used imaging-based High-Content Screening (HCS) with a diverse spectrum of cellular markers for detailed cytological profiling of fractionated algal extracts. The cytological profiles for 3 out of 60 algal fractions clustered closely to reference inhibitors and showed strong inhibitory activities on the HIV-1 reverse transcriptase in a single-enzyme biochemical assay, validating the suggested biological target. Subsequent chemical profiling of the active fractions of two brown algal species by ultra-high resolution mass spectrometry (FT-ICR-MS) revealed possible candidate molecules. A database query of these molecules led us to groups of compounds with structural similarities, which are suggested to be responsible for the observed activity. Our work demonstrates the versatility and power of cytological profiling for the bioprospecting of unknown biological resources and highlights Red Sea algae as a source of bioactives that may serve as a starting point for further studies. PMID:28335513

  12. Measures for a multidimensional multiverse

    NASA Astrophysics Data System (ADS)

    Chung, Hyeyoun

    2015-04-01

    We explore the phenomenological implications of generalizing the causal patch and fat geodesic measures to a multidimensional multiverse, where the vacua can have differing numbers of large dimensions. We consider a simple model in which the vacua are nucleated from a D -dimensional parent spacetime through dynamical compactification of the extra dimensions, and compute the geometric contribution to the probability distribution of observations within the multiverse for each measure. We then study how the shape of this probability distribution depends on the time scales for the existence of observers, for vacuum domination, and for curvature domination (tobs,tΛ , and tc, respectively.) In this work we restrict ourselves to bubbles with positive cosmological constant, Λ . We find that in the case of the causal patch cutoff, when the bubble universes have p +1 large spatial dimensions with p ≥2 , the shape of the probability distribution is such that we obtain the coincidence of time scales tobs˜tΛ˜tc . Moreover, the size of the cosmological constant is related to the size of the landscape. However, the exact shape of the probability distribution is different in the case p =2 , compared to p ≥3 . In the case of the fat geodesic measure, the result is even more robust: the shape of the probability distribution is the same for all p ≥2 , and we once again obtain the coincidence tobs˜tΛ˜tc . These results require only very mild conditions on the prior probability of the distribution of vacua in the landscape. Our work shows that the observed double coincidence of time scales is a robust prediction even when the multiverse is generalized to be multidimensional; that this coincidence is not a consequence of our particular Universe being (3 +1 )-dimensional; and that this observable cannot be used to preferentially select one measure over another in a multidimensional multiverse.

  13. The influence of aging and estradiol to progesterone ratio on rat macrophage phenotypic profile and NO and TNF-α production.

    PubMed

    Dimitrijević, Mirjana; Stanojević, Stanislava; Kuštrimović, Nataša; Mitić, Katarina; Vujić, Vesna; Aleksić, Iva; Radojević, Katarina; Leposavić, Gordana

    2013-11-01

    The phenotype and function of tissue macrophages substantially depend on the cellular milieu and biological effector molecules, such as steroid hormones, to which they are exposed. Furthermore, in female rats, aging is associated with the altered macrophage functioning and the increased estrogen level is followed by a decrease in that of progesterone. Therefore, the present study aimed to investigate the influence of estradiol/progesterone balance on rat macrophage function and phenotype throughout whole adult lifespan. We ovariectomized rats at the late prepubertal age or at the very end of reproductive lifespan, and examined the expression of ED2 (CD163, a marker of mature resident macrophages related to secretion of inflammatory mediators) on peritoneal macrophages and their ability to produce TNF-α and NO upon LPS-stimulation at different age points. In addition, to delineate direct and indirect effects of estrogen, we assessed the in vitro influence of different concentrations of 17β-estradiol on LPS-induced macrophage TNF-α and NO production. Results showed that: (a) the low frequency of ED2(high) cells amongst peritoneal macrophages of aged rats was accompanied with the reduced TNF-α, but not NO production; (b) estradiol level gradually increased following ovariectomy; (c) macrophage ED2 expression and TNF-α production were dependent on estradiol/progesterone balance and they changed in the same direction; (d) changes in estradiol/progesterone balance differentially affected macrophages TNF-α and NO production; and (e) estradiol exerted pro-inflammatory and anti-inflammatory effects on macrophages in vivo and in vitro, respectively. Overall, our study discloses that estradiol/progesterone balance contributes to the fine-tuning of rat macrophage secretory capacity, and adds to a better understanding of the ovarian steroid hormone role in the regulation of macrophage function, and its significance for the age-associated changes in innate immunity.

  14. On Compensation in Multidimensional Response Modeling

    ERIC Educational Resources Information Center

    van der Linden, Wim J.

    2012-01-01

    The issue of compensation in multidimensional response modeling is addressed. We show that multidimensional response models are compensatory in their ability parameters if and only if they are monotone. In addition, a minimal set of assumptions is presented under which the MLEs of the ability parameters are also compensatory. In a recent series of…

  15. Robustness of Adaptive Testing to Multidimensionality.

    ERIC Educational Resources Information Center

    Weiss, David J.; Suhadolnik, Debra

    The present monte carlo simulation study was designed to examine the effects of multidimensionality during the administration of computerized adaptive testing (CAT). It was assumed that multidimensionality existed in the individuals to whom test items were being administered, i.e., that the correct or incorrect responses given by an individual…

  16. Phenotype markers and cytokine intracellular production by CD8+ gammadelta T lymphocytes do not support a regulatory T profile in Behçet's disease patients and healthy controls.

    PubMed

    Clemente, Antonio; Cambra, Ana; Munoz-Saá, Iván; Crespí, Catalina; Pallarés, Lucio; Juan, Antonio; Matamoros, Núria; Julià, Maria Rosa

    2010-04-08

    gammadelta T lymphocytes (GD) have been suggested as one of the causes of cytokine dysregulation that results in neutrophils hyperactivation in Behçet's disease (BD) patients. In addition, GD can provoke cytotoxic lesions in autoimmune diseases by interaction with MICA (MHC class I chain-related A) molecules, through NKG2D receptor on its surface. In contrast, the CD8+ subset of gammadelta T lymphocytes (GDCD8+) has been related to regulatory T activity. The aim of this study was to determine the phenotype and the intracellular cytokine profile in GD from peripheral blood, to discern if they were skewed to an effector or regulatory pattern in BD. We performed phenotype analysis, by three-colour flow cytometry, in 28 BD, 15 healthy controls (HC) and 14 patients with recurrent bucal ulcers (RBU). We studied intracellular cytokine production in 10 BD and 14 HC, after polyclonal stimulation. In addition, we analysed serum IL-15 and soluble MICA, by ELISA, in 27 BD, 21 HC and 40 rheumatoid arthritis patients. The hallmark in BD was a specific increase in CD8 expression by GD, and in GDCD8+ absolute numbers. Most of GDCD8+ presented CD8 alphaalpha homodimers and were negative for CD103, Foxp3 and CTLA-4. GDCD8+ and GDCD8- were high IFNgamma-, but poor IL-2, IL-10, TGFbeta and IL-4-producing cells, with no differences between BD and HC. NKG2D expression on CD8+ T cells, serum IL-15 and soluble MICA were not significantly increased in BD. Our results do not suggest a T regulatory profile for GDCD8+ neither in HC, nor in BD. We cannot rule out other suppression mechanisms or some heterogeneity within this subset that could contribute to regulatory function.

  17. An Introduction to Coherent Multidimensional Spectroscopy.

    PubMed

    Chen, Peter C

    2016-12-01

    Coherent multidimensional spectroscopy is a field that has drawn much attention as an optical analogue to multidimensional nuclear magnetic resonance imaging. Coherent multidimensional spectroscopic techniques produce spectra that show the magnitude of an optical signal as a function of two or more pulsed laser frequencies. Spectra can be collected in either the frequency or the time domain. In addition to improving resolution and overcoming spectral congestion, coherent multidimensional spectroscopy provides the ability to investigate and conduct studies based upon the relationship between different peaks. The purpose of this paper is to provide a general introduction to the area of coherent multidimensional spectroscopy, to provide a brief overview of current experimental approaches, and to discuss some emerging developments in this relatively young field.

  18. Exhaustive screening of the acid beta-glucosidase gene, by fluorescence-assisted mismatch analysis using universal primers: mutation profile and genotype/phenotype correlations in Gaucher disease.

    PubMed Central

    Germain, D P; Puech, J P; Caillaud, C; Kahn, A; Poenaru, L

    1998-01-01

    Gaucher disease (GD) is one of the most prevalent lysosomal storage disorders and one of the rare genetic diseases now accessible to therapy. Outside the Ashkenazi Jewish community, a high molecular diversity is observed, leaving approximately 30% of alleles undetected. Nevertheless, very few exhaustive methods have been developed for extensive gene screening of a large series of patients. Our approach for a complete search of mutations was the association of fluorescent chemical cleavage of mismatches with a universal strand-specific labeling system. The glucocerebrosidase (GBA) gene was scanned by use of a set of six amplicons, comprising 11 exons, all exon/intron boundaries, and the promoter region. By use of this screening strategy, the difficulties due to the existence of a highly homologous pseudogene were easily overcome, and both GD mutant alleles were identified in all 25 patients studied, thus attesting to a sensitivity that approaches 100%. A total of 18 different mutations and a new glucocerebrosidase haplotype were detected. The mutational spectrum included eight novel acid beta-glucosidase mutations: IVS2 G(+1)-->T, I119T, R170P, N188K, S237P, K303I, L324P, and A446P. These data further indicate the genetic heterogeneity of the lesions causing GD. Established genotype/phenotype correlations generally were confirmed, but notable disparities were disclosed in several cases, thus underlining the limitation in the prognostic value of genotyping. The observed influence of multifactorial control on this monogenic disease is discussed. PMID:9683600

  19. Physical Self-Concept in Adolescence: Generalizability of a Multidimensional, Hierarchical Model Across Gender and Grade

    ERIC Educational Resources Information Center

    Hagger, Martin S.; Biddle, Stuart J. H.; John Wang, C. K.

    2005-01-01

    This study tests the generalizability of the factor pattern, structural parameters, and latent mean structure of a multidimensional, hierarchical model of physical self-concept in adolescents across gender and grade. A children's version of the Physical Self-Perception Profile (C-PSPP) was administered to seventh-, eighth- and ninth-grade high…

  20. Physical Self-Perceptions in Adolescence: Generalizability of a Hierarchical Multidimensional Model across Three Cultures.

    ERIC Educational Resources Information Center

    Hagger, Martin S.; Biddle, Stuart J. H.; Chow, Edward W.; Stambulova, Natalia; Kavussanu, Maria

    2003-01-01

    Examined the generalizability of the form, structural parameters, and latent means of a hierarchical multidimensional model of physical self-perceptions in adolescents from three cultures. A children's version of the physical self-perception profile was administered to British, Hong Kong, and Russian students. Tests of cross-cultural…

  1. Multidimensional Adaptation in MAS Organizations.

    PubMed

    Alberola, Juan M; Julian, Vicente; Garcia-Fornes, Ana

    2013-04-01

    Organization adaptation requires determining the consequences of applying changes not only in terms of the benefits provided but also measuring the adaptation costs as well as the impact that these changes have on all of the components of the organization. In this paper, we provide an approach for adaptation in multiagent systems based on a multidimensional transition deliberation mechanism (MTDM). This approach considers transitions in multiple dimensions and is aimed at obtaining the adaptation with the highest potential for improvement in utility based on the costs of adaptation. The approach provides an accurate measurement of the impact of the adaptation since it determines the organization that is to be transitioned to as well as the changes required to carry out this transition. We show an example of adaptation in a service provider network environment in order to demonstrate that the measurement of the adaptation consequences taken by the MTDM improves the organization performance more than the other approaches.

  2. Minimal Models of Multidimensional Computations

    PubMed Central

    Fitzgerald, Jeffrey D.; Sincich, Lawrence C.; Sharpee, Tatyana O.

    2011-01-01

    The multidimensional computations performed by many biological systems are often characterized with limited information about the correlations between inputs and outputs. Given this limitation, our approach is to construct the maximum noise entropy response function of the system, leading to a closed-form and minimally biased model consistent with a given set of constraints on the input/output moments; the result is equivalent to conditional random field models from machine learning. For systems with binary outputs, such as neurons encoding sensory stimuli, the maximum noise entropy models are logistic functions whose arguments depend on the constraints. A constraint on the average output turns the binary maximum noise entropy models into minimum mutual information models, allowing for the calculation of the information content of the constraints and an information theoretic characterization of the system's computations. We use this approach to analyze the nonlinear input/output functions in macaque retina and thalamus; although these systems have been previously shown to be responsive to two input dimensions, the functional form of the response function in this reduced space had not been unambiguously identified. A second order model based on the logistic function is found to be both necessary and sufficient to accurately describe the neural responses to naturalistic stimuli, accounting for an average of 93% of the mutual information with a small number of parameters. Thus, despite the fact that the stimulus is highly non-Gaussian, the vast majority of the information in the neural responses is related to first and second order correlations. Our results suggest a principled and unbiased way to model multidimensional computations and determine the statistics of the inputs that are being encoded in the outputs. PMID:21455284

  3. MicroRNA Expression Profile Identifies High Grade, Non-Muscle-Invasive Bladder Tumors at Elevated Risk to Progress to an Invasive Phenotype

    PubMed Central

    Lenherr, Sara M.; Tsai, Sheaumei; Silva Neto, Brasil; Sullivan, Travis B.; Cimmino, Cara B.; Logvinenko, Tanya; Gee, Jason; Huang, Wei; Libertino, John A.; Summerhayes, Ian C.; Rieger-Christ, Kimberly M.

    2017-01-01

    The objective of this study was to identify a panel of microRNAs (miRNAs) differentially expressed in high-grade non-muscle invasive (NMI; TaG3–T1G3) urothelial carcinoma that progress to muscle-invasive disease compared to those that remain non-muscle invasive, whether recurrence happens or not. Eighty-nine high-grade NMI urothelial carcinoma lesions were identified and total RNA was extracted from paraffin-embedded tissue. Patients were categorized as either having a non-muscle invasive lesion with no evidence of progression over a 3-year period or as having a similar lesion showing progression to muscle invasion over the same period. In addition, comparison of miRNA expression levels between patients with and without prior intravesical therapy was performed. Total RNA was pooled for microarray analysis in each group (non-progressors and progressors), and qRT-PCR of individual samples validated differential expression between non-progressive and progressive lesions. MiR-32-5p, -224-5p, and -412-3p were associated with cancer-specific survival. Downregulation of miR-203a-3p and miR-205-5p were significantly linked to progression in non-muscle invasive bladder tumors. These miRNAs include those implicated in epithelial mesenchymal transition, previously identified as members of a panel characterizing transition from the non-invasive to invasive phenotype in bladder tumors. Furthermore, we were able to identify specific miRNAs that are linked to postoperative outcome in patients with high grade NMI urothelial carcinoma of the bladder (UCB) that progressed to muscle-invasive (MI) disease. PMID:28218662

  4. Adulthood dietary exposure to a common pesticide leads to an obese-like phenotype and a diabetic profile in apoE3 mice.

    PubMed

    Peris-Sampedro, Fiona; Cabré, Maria; Basaure, Pia; Reverte, Ingrid; Domingo, José L; Teresa Colomina, Maria

    2015-10-01

    Increasing evidence links the widespread exposure to organophosphate (OP) pesticides to the global epidemics of type 2 diabetes and obesity. Our recent data highlighted gene×environment interactions: mice expressing the human apolipoprotein E3 (apoE3) isoform were more prone to develop obesity than those expressing apoE2 or apoE4 upon dietary challenge with chlorpyrifos (CPF), the most used OP worldwide. Thus, we aimed to further explore the contribution of the APOE3 genotype on the emergence of obesity and related metabolic dysfunctions upon subchronic exposure to CPF. Seven-month-old targeted replacement apoE3 and C57BL/6N male mice were orally exposed to CPF at 0 or 2mg/kg body weight/day for 8 consecutive weeks. We examined body weight status, food and water intake, lipid and glucose homeostasis, metabolic biomarkers concentrations, insulin levels and insulin resistance, and leptin and ghrelin profiles. CPF exposure generally increased food ingestion, glucose and total cholesterol concentrations, and tended to elevate acyl ghrelin levels. Nonetheless, excess weight gain and increased leptin levels were inherent to apoE3 mice. Moreover, the propensity towards a diabetic profile was markedly higher in these animals than in C57BL/6N, as they showed a higher homeostatic model assessment for insulin resistance index and higher insulin levels. Although both genotypes were metabolically affected by CPF, the results of the present investigation revealed that apoE3 mice were the most vulnerable to developing obesity and related disturbances following CPF administration through the diet. Since the APOE3 genotype is the most prevalent worldwide, current findings have particular implications for human health.

  5. Development of a Multidimensional Thinking Styles Scale Based on Theory of Mental Self-Government for Sixth Grade Students

    ERIC Educational Resources Information Center

    Chaiyapornpattana, Niorn; Wongwanich, Suwimon

    2013-01-01

    This study designed 1) to develop a multidimensional thinking styles scale based on theory of mental self-government for sixth grade student 2) to investigate quality of the developed scale 3) to study profile of styles of sixth grade student and a relation of profile of styles of student in each dimension and background of gender and grade with…

  6. Memory CD8(+) T cells elicited by HIV-1 lipopeptide vaccines display similar phenotypic profiles but differences in term of magnitude and multifunctionality compared with FLU- or EBV-specific memory T cells in humans.

    PubMed

    Figueiredo, Suzanne; Charmeteau, Benedicte; Surenaud, Mathieu; Salmon, Dominique; Launay, Odile; Guillet, Jean-Gérard; Hosmalin, Anne; Gahery, Hanne

    2014-01-16

    Differentiation marker, multifunctionality and magnitude analyses of specific-CD8(+) memory T cells are crucial to improve development of HIV vaccines designed to generate cell-mediated immunity. Therefore, we fully characterized the HIV-specific CD8(+) T cell responses induced in volunteers vaccinated with HIV lipopeptide vaccines for phenotypic markers, tetramer staining, cytokine secretion, and cytotoxic activities. The frequency of ex vivo CD8(+) T cells elicited by lipopeptide vaccines is very rare and central-memory phenotype and functions of these cells were been shown to be important in AIDS immunity. So, we expanded them using specific peptides to compare the memory T cell responses induced in volunteers by HIV vaccines with responses to influenza (FLU) or Epstein Barr virus (EBV). By analyzing the differentiation state of IFN-γ-secreting CD8(+) T cells, we found a CCR7(-)CD45RA(-)CD28(+int)/CD28(-) profile (>85%) belonging to a subset of intermediate-differentiated effector T cells for HIV, FLU, and EBV. We then assessed the quality of the response by measuring various T cell functions. The percentage of single IFN-γ T cell producers in response to HIV was 62% of the total of secreting T cells compared with 35% for FLU and EBV, dual and triple (IFN-γ/IL-2/CD107a) T cell producers could also be detected but at lower levels (8% compared with 37%). Finally, HIV-specific T cells secreted IFN-γ and TNF-α, but not the dual combination like FLU- and EBV-specific T cells. Thus, we found that the functional profile and magnitude of expanded HIV-specific CD8(+) T precursors were more limited than those of to FLU- and EBV-specific CD8(+) T cells. These data show that CD8(+) T cells induced by these HIV vaccines have a similar differentiation profile to FLU and EBV CD8(+) T cells, but that the vaccine potency to induce multifunctional T cells needs to be increased in order to improve vaccination strategies.

  7. Multidimensional text classification for drug information.

    PubMed

    Lertnattee, Verayuth; Theeramunkong, Thanaruk

    2004-09-01

    This paper proposes a multidimensional model for classifying drug information text documents. The concept of multidimensional category model is introduced for representing classes. In contrast with traditional flat and hierarchical category models, the multidimensional category model classifies each document using multiple predefined sets of categories, where each set corresponds to a dimension. Since a multidimensional model can be converted to flat and hierarchical models, three classification approaches are possible, i.e., classifying directly based on the multidimensional model and classifying with the equivalent flat or hierarchical models. The efficiency of these three approaches is investigated using drug information collection with two different dimensions: 1) drug topics and 2) primary therapeutic classes. In the experiments, k-nearest neighbor, naive Bayes, and two centroid-based methods are selected as classifiers. The comparisons among three approaches of classification are done using two-way analysis of variance, followed by the Scheffé's test for post hoc comparison. The experimental results show that multidimensional-based classification performs better than the others, especially in the presence of a relatively small training set. As one application, a category-based search engine using the multidimensional category concept was developed to help users retrieve drug information.

  8. Transcriptional Profiling in Experimental Visceral Leishmaniasis Reveals a Broad Splenic Inflammatory Environment that Conditions Macrophages toward a Disease-Promoting Phenotype.

    PubMed

    Kong, Fanping; Saldarriaga, Omar A; Spratt, Heidi; Osorio, E Yaneth; Travi, Bruno L; Luxon, Bruce A; Melby, Peter C

    2017-01-01

    Visceral Leishmaniasis (VL), caused by the intracellular protozoan Leishmania donovani, is characterized by relentlessly increasing visceral parasite replication, cachexia, massive splenomegaly, pancytopenia and ultimately death. Progressive disease is considered to be due to impaired effector T cell function and/or failure of macrophages to be activated to kill the intracellular parasite. In previous studies, we used the Syrian hamster (Mesocricetus auratus) as a model because it mimics the progressive nature of active human VL. We demonstrated previously that mixed expression of macrophage-activating (IFN-γ) and regulatory (IL-4, IL-10, IL-21) cytokines, parasite-induced expression of macrophage arginase 1 (Arg1), and decreased production of nitric oxide are key immunopathologic factors. Here we examined global changes in gene expression to define the splenic environment and phenotype of splenic macrophages during progressive VL. We used RNA sequencing coupled with de novo transcriptome assembly, because the Syrian hamster does not have a fully sequenced and annotated reference genome. Differentially expressed transcripts identified a highly inflammatory spleen environment with abundant expression of type I and type II interferon response genes. However, high IFN-γ expression was ineffective in directing exclusive M1 macrophage polarization, suppressing M2-associated gene expression, and restraining parasite replication and disease. While many IFN-inducible transcripts were upregulated in the infected spleen, fewer were induced in splenic macrophages in VL. Paradoxically, IFN-γ enhanced parasite growth and induced the counter-regulatory molecules Arg1, Ido1 and Irg1 in splenic macrophages. This was mediated, at least in part, through IFN-γ-induced activation of STAT3 and expression of IL-10, which suggests that splenic macrophages in VL are conditioned to respond to macrophage activation signals with a counter-regulatory response that is ineffective and even

  9. Transcriptional Profiling in Experimental Visceral Leishmaniasis Reveals a Broad Splenic Inflammatory Environment that Conditions Macrophages toward a Disease-Promoting Phenotype

    PubMed Central

    Spratt, Heidi; Travi, Bruno L.; Luxon, Bruce A.

    2017-01-01

    Visceral Leishmaniasis (VL), caused by the intracellular protozoan Leishmania donovani, is characterized by relentlessly increasing visceral parasite replication, cachexia, massive splenomegaly, pancytopenia and ultimately death. Progressive disease is considered to be due to impaired effector T cell function and/or failure of macrophages to be activated to kill the intracellular parasite. In previous studies, we used the Syrian hamster (Mesocricetus auratus) as a model because it mimics the progressive nature of active human VL. We demonstrated previously that mixed expression of macrophage-activating (IFN-γ) and regulatory (IL-4, IL-10, IL-21) cytokines, parasite-induced expression of macrophage arginase 1 (Arg1), and decreased production of nitric oxide are key immunopathologic factors. Here we examined global changes in gene expression to define the splenic environment and phenotype of splenic macrophages during progressive VL. We used RNA sequencing coupled with de novo transcriptome assembly, because the Syrian hamster does not have a fully sequenced and annotated reference genome. Differentially expressed transcripts identified a highly inflammatory spleen environment with abundant expression of type I and type II interferon response genes. However, high IFN-γ expression was ineffective in directing exclusive M1 macrophage polarization, suppressing M2-associated gene expression, and restraining parasite replication and disease. While many IFN-inducible transcripts were upregulated in the infected spleen, fewer were induced in splenic macrophages in VL. Paradoxically, IFN-γ enhanced parasite growth and induced the counter-regulatory molecules Arg1, Ido1 and Irg1 in splenic macrophages. This was mediated, at least in part, through IFN-γ-induced activation of STAT3 and expression of IL-10, which suggests that splenic macrophages in VL are conditioned to respond to macrophage activation signals with a counter-regulatory response that is ineffective and even

  10. Differentiation of Shewanella putrefaciens and Shewanella alga on the basis of whole-cell protein profiles, ribotyping, phenotypic characterization, and 16S rRNA gene sequence analysis.

    PubMed

    Vogel, B F; Jørgensen, K; Christensen, H; Olsen, J E; Gram, L

    1997-06-01

    Seventy-six presumed Shewanella putrefaciens isolates from fish, oil drillings, and clinical specimens, the type strain of Shewanella putrefaciens (ATCC 8071), the type strain of Shewanella alga (IAM 14159), and the type strain of Shewanella hanedai (ATCC 33224) were compared by several typing methods. Numerical analysis of sodium dodecyl sulfate-polyacrylamide gel electrophoresis of whole-cell protein and ribotyping patterns showed that the strains were separated into two distinct clusters with 56% +/- 10% and 40% +/- 14% similarity for whole-cell protein profiling and ribotyping, respectively. One cluster consisted of 26 isolates with 52 to 55 mol% G + C and included 15 human isolates, mostly clinical specimens, 8 isolates from marine waters, and the type strain of S. alga. This homogeneous cluster of mesophilic, halotolerant strains was by all analyses identical to the recently defined species S. alga (U. Simidu et al., Int. J. Syst. Bacteriol, 40:331-336, 1990). Fifty-two typically psychrotolerant strains formed the other, more heterogeneous major cluster, with 43 to 47 mol% G + C. The type strain of S. putrefaciens was included in this group. The two groups were confirmed by 16S rRNA gene sequence analysis. It is concluded that the isolates must be considered two different species, S. alga and S. putrefaciens, and that most mesophilic isolates formerly identified as S. putrefaciens belong to S. alga. The ecological role and potential pathogenicity of S. alga can be evaluated only if the organism is correctly identified.

  11. Analytical chemistry, multidimensional spectral signatures, and the future of coherent multidimensional spectroscopy

    NASA Astrophysics Data System (ADS)

    Wright, John C.

    2016-10-01

    Spectroscopy is a dominant measurement methodology because it resolves molecular level details over a wide concentration range. Its limitations, however, become challenged when applied to complex materials. Coherent multidimensional spectroscopy (CMDS) is the optical analogue of multidimensional NMR and like NMR, its multidimensionality promises to increase the spectral selectivity of vibrational and electronic spectroscopy. This article explores whether this promise can make CMDS a dominant spectroscopic method throughout the sciences. In order for CMDS to become a dominant methodology, it must create multidimensional spectral fingerprints that provide the selectivity required for probing complex samples. Pump-CMDS probe methods separate the pump's measurement of dynamics from a multidimensional and selective probe. Fully coherent CMDS methods are ideal multidimensional probes because they avoid relaxation effects, spectrally isolate the output signals, and provide unique and invariant spectral signatures using any combination of vibrational and electronic quantum states.

  12. Using Multidimensional Scaling for Curricular Goal Analysis.

    ERIC Educational Resources Information Center

    Leitzman, David F.; And Others

    1980-01-01

    Reports research that utilized multidimensional scaling and related analytic procedures to validate the curricular goals of a graduate therapeutic recreation program. Data analysis includes the use of the two-dimensional KYST and PREFMAP spaces. (Author/JD)

  13. Multi-dimensional edge detection operators

    NASA Astrophysics Data System (ADS)

    Youn, Sungwook; Lee, Chulhee

    2014-05-01

    In remote sensing, modern sensors produce multi-dimensional images. For example, hyperspectral images contain hundreds of spectral images. In many image processing applications, segmentation is an important step. Traditionally, most image segmentation and edge detection methods have been developed for one-dimensional images. For multidimensional images, the output images of spectral band images are typically combined under certain rules or using decision fusions. In this paper, we proposed a new edge detection algorithm for multi-dimensional images using secondorder statistics. First, we reduce the dimension of input images using the principal component analysis. Then we applied multi-dimensional edge detection operators that utilize second-order statistics. Experimental results show promising results compared to conventional one-dimensional edge detectors such as Sobel filter.

  14. Identifying neurocognitive phenotypes in autism.

    PubMed Central

    Tager-Flusberg, Helen; Joseph, Robert M

    2003-01-01

    Autism is a complex disorder that is heterogeneous both in its phenotypic expression and its etiology. The search for genes associated with autism and the neurobiological mechanisms that underlie its behavioural symptoms has been hampered by this heterogeneity. Recent studies indicate that within autism, there may be distinct subgroups that can be defined based on differences in neurocognitive profiles. This paper presents evidence for two kinds of subtypes in autism that are defined on the basis of language profiles and on the basis of cognitive profiles. The implications for genetic and neurobiological studies of these subgroups are discussed, with special reference to evidence relating these cognitive phenotypes to volumetric studies of brain size and organization in autism. PMID:12639328

  15. Multidimensional Data Modeling for Business Process Analysis

    NASA Astrophysics Data System (ADS)

    Mansmann, Svetlana; Neumuth, Thomas; Scholl, Marc H.

    The emerging area of business process intelligence attempts to enhance the analytical capabilities of business process management systems by employing data warehousing and mining technologies. This paper presents an approach to re-engineering the business process modeling in conformity with the multidimensional data model. Since the business process and the multidimensional model are driven by rather different objectives and assumptions, there is no straightforward solution to converging these models.

  16. Multidimensional imaging using compressive Fresnel holography.

    PubMed

    Horisaki, Ryoichi; Tanida, Jun; Stern, Adrian; Javidi, Bahram

    2012-06-01

    We propose a generalized framework for single-shot acquisition of multidimensional objects using compressive Fresnel holography. A multidimensional object with spatial, spectral, and polarimetric information is propagated with the Fresnel diffraction, and the propagated signal of each channel is observed by an image sensor with randomly arranged optical elements for filtering. The object data are reconstructed using a compressive sensing algorithm. This scheme is verified with numerical experiments. The proposed framework can be applied to imageries for spectrum, polarization, and so on.

  17. Multidimensionally encoded magnetic resonance imaging.

    PubMed

    Lin, Fa-Hsuan

    2013-07-01

    Magnetic resonance imaging (MRI) typically achieves spatial encoding by measuring the projection of a q-dimensional object over q-dimensional spatial bases created by linear spatial encoding magnetic fields (SEMs). Recently, imaging strategies using nonlinear SEMs have demonstrated potential advantages for reconstructing images with higher spatiotemporal resolution and reducing peripheral nerve stimulation. In practice, nonlinear SEMs and linear SEMs can be used jointly to further improve the image reconstruction performance. Here, we propose the multidimensionally encoded (MDE) MRI to map a q-dimensional object onto a p-dimensional encoding space where p > q. MDE MRI is a theoretical framework linking imaging strategies using linear and nonlinear SEMs. Using a system of eight surface SEM coils with an eight-channel radiofrequency coil array, we demonstrate the five-dimensional MDE MRI for a two-dimensional object as a further generalization of PatLoc imaging and O-space imaging. We also present a method of optimizing spatial bases in MDE MRI. Results show that MDE MRI with a higher dimensional encoding space can reconstruct images more efficiently and with a smaller reconstruction error when the k-space sampling distribution and the number of samples are controlled.

  18. Multidimensional stochastic approximation Monte Carlo

    NASA Astrophysics Data System (ADS)

    Zablotskiy, Sergey V.; Ivanov, Victor A.; Paul, Wolfgang

    2016-06-01

    Stochastic Approximation Monte Carlo (SAMC) has been established as a mathematically founded powerful flat-histogram Monte Carlo method, used to determine the density of states, g (E ) , of a model system. We show here how it can be generalized for the determination of multidimensional probability distributions (or equivalently densities of states) of macroscopic or mesoscopic variables defined on the space of microstates of a statistical mechanical system. This establishes this method as a systematic way for coarse graining a model system, or, in other words, for performing a renormalization group step on a model. We discuss the formulation of the Kadanoff block spin transformation and the coarse-graining procedure for polymer models in this language. We also apply it to a standard case in the literature of two-dimensional densities of states, where two competing energetic effects are present g (E1,E2) . We show when and why care has to be exercised when obtaining the microcanonical density of states g (E1+E2) from g (E1,E2) .

  19. Vector fields in multidimensional cosmology

    NASA Astrophysics Data System (ADS)

    Meierovich, Boris E.

    2011-09-01

    Vector fields in the expanding Universe are considered within the multidimensional theory of general relativity. Vector fields in general relativity form a three-parametric variety. Our consideration includes the fields with a nonzero covariant divergence. Depending on the relations between the particular parameters and the symmetry of a problem, the vector fields can be longitudinal and/or transverse, ultrarelativistic (i.e. massless) or nonrelativistic (massive), and so on. The longitudinal and transverse vector fields are considered separately in detail in the background of the de Sitter cosmological metric. In most cases the field equations reduce to Bessel equations, and their temporal evolution is analyzed analytically. The energy-momentum tensor of the most simple zero-mass longitudinal vector fields enters the Einstein equations as an additive to the cosmological constant. In this case the de Sitter metric is the exact solution of the Einstein equations. Hence, the most simple zero-mass longitudinal vector field pretends to be an adequate tool for macroscopic description of dark energy as a source of the expansion of the Universe at a constant rate. The zero-mass vector field does not vanish in the process of expansion. On the contrary, massive fields vanish with time. Though their amplitude is falling down, the massive fields make the expansion accelerated.

  20. Automated genome-wide visual profiling of cellular proteins involved in HIV infection.

    PubMed

    Genovesio, Auguste; Kwon, Yong-Jun; Windisch, Marc P; Kim, Nam Youl; Choi, Seo Yeon; Kim, Hi Chul; Jung, Sungyong; Mammano, Fabrizio; Perrin, Virginie; Boese, Annette S; Casartelli, Nicoletta; Schwartz, Olivier; Nehrbass, Ulf; Emans, Neil

    2011-10-01

    Recent genome-wide RNAi screens have identified >842 human genes that affect the human immunodeficiency virus (HIV) cycle. The list of genes implicated in infection differs between screens, and there is minimal overlap. A reason for this variance is the interdependence of HIV infection and host cell function, producing a multitude of indirect or pleiotropic cellular effects affecting the viral infection during RNAi screening. To overcome this, the authors devised a 15-dimensional phenotypic profile to define the viral infection block induced by CD4 silencing in HeLa cells. They demonstrate that this phenotypic profile excludes nonspecific, RNAi-based side effects and viral replication defects mediated by silencing of housekeeping genes. To achieve statistical robustness, the authors used automatically annotated RNAi arrays for seven independent genome-wide RNAi screens. This identified 56 host genes, which reliably reproduced CD4-like phenotypes upon HIV infection. The factors include 11 known HIV interactors and 45 factors previously not associated with HIV infection. As proof of concept, the authors confirmed that silencing of PAK1, Ku70, and RNAseH2A impaired HIV replication in Jurkat cells. In summary, multidimensional, visual profiling can identify genes required for HIV infection.

  1. RNA: State Memory and Mediator of Cellular Phenotype

    PubMed Central

    Kim, Junhyong; Eberwine, James

    2010-01-01

    It has become increasingly clear that the genome is dynamic and exquisitely sensitive, changing expression patterns in response to age, environmental stimuli and pharmacological and physiological manipulations. Similarly, cellular phenotype, traditionally viewed as a stable end-state, should be viewed as versatile and changeable. The phenotype of a cell is better defined as a “homeostatic phenotype” implying plasticity resulting from a dynamically-changing yet characteristic pattern of gene/protein expression. A stable change in phenotype is the result of the movement of a cell between different multi-dimensional identity spaces. Here, we describe a key driver of this transition and the stabilizer of phenotype: the relative abundances of the cellular RNAs. We argue that the quantitative state of RNA can be likened to a state memory, that when transferred between cells, alters the phenotype in a predictable manner. PMID:20382532

  2. New integrative computational approaches unveil the Saccharomyces cerevisiae pheno-metabolomic fermentative profile and allow strain selection for winemaking.

    PubMed

    Franco-Duarte, Ricardo; Umek, Lan; Mendes, Inês; Castro, Cristiana C; Fonseca, Nuno; Martins, Rosa; Silva-Ferreira, António C; Sampaio, Paula; Pais, Célia; Schuller, Dorit

    2016-11-15

    During must fermentation by Saccharomyces cerevisiae strains thousands of volatile aroma compounds are formed. The objective of the present work was to adapt computational approaches to analyze pheno-metabolomic diversity of a S. cerevisiae strain collection with different origins. Phenotypic and genetic characterization together with individual must fermentations were performed, and metabolites relevant to aromatic profiles were determined. Experimental results were projected onto a common coordinates system, revealing 17 statistical-relevant multi-dimensional modules, combining sets of most-correlated features of noteworthy biological importance. The present method allowed, as a breakthrough, to combine genetic, phenotypic and metabolomic data, which has not been possible so far due to difficulties in comparing different types of data. Therefore, the proposed computational approach revealed as successful to shed light into the holistic characterization of S. cerevisiae pheno-metabolome in must fermentative conditions. This will allow the identification of combined relevant features with application in selection of good winemaking strains.

  3. Multidimensional Analysis of Nuclear Detonations

    DTIC Science & Technology

    2015-09-17

    reconstructions and temperature distributions of the early time nuclear fireballs. Initial developments have resulted in the first 2-dimensional... temperature distribution of a nuclear fireball using digitized film. This temperature analysis underwent verification using the Digital Imaging and Remote... temperature profile of the nuclear fireball as a function of optical path length. A 3-dimensional reconstruction was performed using a variation of a

  4. Quantification of Microbial Phenotypes

    PubMed Central

    Martínez, Verónica S.; Krömer, Jens O.

    2016-01-01

    Metabolite profiling technologies have improved to generate close to quantitative metabolomics data, which can be employed to quantitatively describe the metabolic phenotype of an organism. Here, we review the current technologies available for quantitative metabolomics, present their advantages and drawbacks, and the current challenges to generate fully quantitative metabolomics data. Metabolomics data can be integrated into metabolic networks using thermodynamic principles to constrain the directionality of reactions. Here we explain how to estimate Gibbs energy under physiological conditions, including examples of the estimations, and the different methods for thermodynamics-based network analysis. The fundamentals of the methods and how to perform the analyses are described. Finally, an example applying quantitative metabolomics to a yeast model by 13C fluxomics and thermodynamics-based network analysis is presented. The example shows that (1) these two methods are complementary to each other; and (2) there is a need to take into account Gibbs energy errors. Better estimations of metabolic phenotypes will be obtained when further constraints are included in the analysis. PMID:27941694

  5. Resonance beyond frequency-matching: multidimensional resonance

    NASA Astrophysics Data System (ADS)

    Wang, Zhenyu; Li, Mingzhe; Wang, Ruifang

    2017-03-01

    Resonance, conventionally defined as the oscillation of a system when the temporal frequency of an external stimulus matches a natural frequency of the system, is important in both fundamental physics and applied disciplines. However, the spatial character of oscillation is not considered in this definition. We reveal the creation of spatial resonance when the stimulus matches the space pattern of a normal mode in an oscillating system. The complete resonance, which we call multidimensional resonance, should be a combination of both the temporal and the spatial resonance. We further elucidate that the spin wave produced by multidimensional resonance drives considerably faster reversal of the vortex core in a magnetic nanodisc. Multidimensional resonance provides insight into the nature of wave dynamics and opens the door to novel applications.

  6. Multidimensional energy operator for image processing

    NASA Astrophysics Data System (ADS)

    Maragos, Petros; Bovik, Alan C.; Quatieri, Thomas F.

    1992-11-01

    The 1-D nonlinear differential operator (Psi) (f) equals (f')2 - ff' has been recently introduced to signal processing and has been found very useful for estimating the parameters of sinusoids and the modulating signals of AM-FM signals. It is called an energy operator because it can track the energy of an oscillator source generating a sinusoidal signal. In this paper we introduce the multidimensional extension (Phi) (f) equals (parallel)DELf(parallel)2 - fDEL2f of the 1-D energy operator and briefly outline some of its applications to image processing. We discuss some interesting properties of the multidimensional operator and develop demodulation algorithms to estimate the amplitude envelope and instantaneous frequencies of 2-D spatially-varying AM-FM signals, which can model image texture. The attractive features of the multidimensional operator and the related amplitude/frequency demodulation algorithms are their simplicity, efficiency, and ability to track instantaneously- varying spatial modulation patterns.

  7. Preface: Special Topic on Multidimensional Spectroscopy

    NASA Astrophysics Data System (ADS)

    Mukamel, Shaul; Bakker, Huib J.

    2015-06-01

    Multidimensional signals are generated by subjecting molecules to sequences of short optical pulses and recording correlation plots related to the various controlled delay periods. These techniques which span all the way from the THz to the x-ray regimes provide qualitatively new structural and dynamical molecular information not available from conventional one-dimensional techniques. This issue surveys the recent experimental and theoretical progresses in this rapidly developing 20 year old field which illustrates the novel insights provided by multidimensional techniques into electronic and nuclear motions. It should serve as a valuable source for experts in the field and help introduce newcomers to this exciting and challenging branch of nonlinear spectroscopy.

  8. A field-grown transgenic tomato line expressing higher levels of polyamines reveals legume cover crop mulch-specific perturbations in fruit phenotype at the levels of metabolite profiles, gene expression, and agronomic characteristics.

    PubMed

    Neelam, Anil; Cassol, Tatiana; Mehta, Roshni A; Abdul-Baki, Aref A; Sobolev, Anatoli P; Goyal, Ravinder K; Abbott, Judith; Segre, Anna L; Handa, Avtar K; Mattoo, Autar K

    2008-01-01

    Genetic modification of crop plants to introduce desirable traits such as nutritional enhancement, disease and pest resistance, and enhanced crop productivity is increasingly seen as a promising technology for sustainable agriculture and boosting food production in the world. Independently, cultural practices that utilize alternative agriculture strategies including organic cultivation subscribe to sustainable agriculture by limiting chemical usage and reduced tillage. How the two together affect fruit metabolism or plant growth in the field or whether they are compatible has not yet been tested. Fruit-specific yeast S-adenosylmethionine decarboxylase (ySAMdc) line 579HO, and a control line 556AZ were grown in leguminous hairy vetch (Vicia villosa Roth) (HV) mulch and conventional black polyethylene (BP) mulch, and their fruit analysed. Significant genotypexmulch-dependent interactions on fruit phenotype were exemplified by differential profiles of 20 fruit metabolites such as amino acids, sugars, and organic acids. Expression patterns of the ySAMdc transgene, and tomato SAMdc, E8, PEPC, and ICDHc genes were compared between the two lines as a function of growth on either BP or HV mulch. HV mulch significantly stimulated the accumulation of asparagine, glutamate, glutamine, choline, and citrate concomitant with a decrease in glucose in the 556AZ fruits during ripening as compared to BP. It enables a metabolic system in tomato somewhat akin to the one in higher polyamine-accumulating transgenic fruit that have higher phytonutrient content. Finally, synergism was found between HV mulch and transgenic tomato in up-regulating N:C indicator genes PEPC and ICDHc in the fruit.

  9. Diagnose Test-Taker's Profile in Terms of Core Profile Patterns: Principal Component (PC) vs. Profile Analysis via MDS (PAMS) Approaches.

    ERIC Educational Resources Information Center

    Kim, Se-Kang; Davison, Mark L.

    A study was conducted to examine how principal components analysis (PCA) and Profile Analysis via Multidimensional Scaling (PAMS) can be used to diagnose individuals observed score profiles in terms of core profile patterns identified by each method. The standardization sample from the Wechsler Intelligence Scale for Children, Third Edition…

  10. The Efficacy of Multidimensional Constraint Keys in Database Query Performance

    ERIC Educational Resources Information Center

    Cardwell, Leslie K.

    2012-01-01

    This work is intended to introduce a database design method to resolve the two-dimensional complexities inherent in the relational data model and its resulting performance challenges through abstract multidimensional constructs. A multidimensional constraint is derived and utilized to implement an indexed Multidimensional Key (MK) to abstract a…

  11. A combined multidimensional scaling and hierarchical clustering view for the exploratory analysis of multidimensional data

    NASA Astrophysics Data System (ADS)

    Craig, Paul; Roa-Seïler, Néna

    2013-01-01

    This paper describes a novel information visualization technique that combines multidimensional scaling and hierarchical clustering to support the exploratory analysis of multidimensional data. The technique displays the results of multidimensional scaling using a scatter plot where the proximity of any two items' representations is approximate to their similarity according to a Euclidean distance metric. The results of hierarchical clustering are overlaid onto this view by drawing smoothed outlines around each nested cluster. The difference in similarity between successive cluster combinations is used to colour code clusters and make stronger natural clusters more prominent in the display. When a cluster or group of items is selected, multidimensional scaling and hierarchical clustering are re-applied to a filtered subset of the data, and animation is used to smooth the transition between successive filtered views. As a case study we demonstrate the technique being used to analyse survey data relating to the appropriateness of different phrases to different emotionally charged situations.

  12. Multidimensional Perspectives on Principal Leadership Effectiveness

    ERIC Educational Resources Information Center

    Beycioglu, Kadir, Ed.; Pashiardis, Petros, Ed.

    2015-01-01

    Exceptional management skills are crucial to success in educational environments. As school leaders, principals are expected to effectively supervise the school system while facing a multitude of issues and demands. "Multidimensional Perspectives on Principal Leadership Effectiveness" combines best practices and the latest approaches in…

  13. A New Heterogeneous Multidimensional Unfolding Procedure

    ERIC Educational Resources Information Center

    Park, Joonwook; Rajagopal, Priyali; DeSarbo, Wayne S.

    2012-01-01

    A variety of joint space multidimensional scaling (MDS) methods have been utilized for the spatial analysis of two- or three-way dominance data involving subjects' preferences, choices, considerations, intentions, etc. so as to provide a parsimonious spatial depiction of the underlying relevant dimensions, attributes, stimuli, and/or subjects'…

  14. Multidimensional neural growing networks and computer intelligence

    SciTech Connect

    Yashchenko, V.A.

    1995-03-01

    This paper examines information-computation processes in time and in space and some aspects of computer intelligence using multidimensional matrix neural growing networks. In particular, issues of object-oriented {open_quotes}thinking{close_quotes} of computers are considered.

  15. Multidimensional Treatment of Fear of Death.

    ERIC Educational Resources Information Center

    Hoelter, Jon W.

    1979-01-01

    Presents a multidimensional conception of fear of death and provides subscales for measuring suggested dimensions (fear of the dying process, of the dead, of being destroyed, for significant others, of the unknown, of conscious death, for body after death, and of premature death). Evidence for construct validity is provided. (Author/BEF)

  16. Multidimensional IRT Models for Composite Scores

    ERIC Educational Resources Information Center

    Yen, Shu Jing; Walker, Leah

    2007-01-01

    Tests of English Language Proficiency are often designed such that each section of the test measures a single latent ability. For instance an English Proficiency Assessment might consist of sections measuring Speaking, Listening, and Reading ability. However, Overall English Proficiency and composite abilities are naturally multidimensional. This…

  17. Multidimensional Screening as a Pharmacology Laboratory Experience.

    ERIC Educational Resources Information Center

    Malone, Marvin H.; And Others

    1979-01-01

    A multidimensional pharmacodynamic screening experiment that addresses drug interaction is included in the pharmacology-toxicology laboratory experience of pharmacy students at the University of the Pacific. The student handout with directions for the procedure is reproduced, drug compounds tested are listed, and laboratory evaluation results are…

  18. DICON: interactive visual analysis of multidimensional clusters.

    PubMed

    Cao, Nan; Gotz, David; Sun, Jimeng; Qu, Huamin

    2011-12-01

    Clustering as a fundamental data analysis technique has been widely used in many analytic applications. However, it is often difficult for users to understand and evaluate multidimensional clustering results, especially the quality of clusters and their semantics. For large and complex data, high-level statistical information about the clusters is often needed for users to evaluate cluster quality while a detailed display of multidimensional attributes of the data is necessary to understand the meaning of clusters. In this paper, we introduce DICON, an icon-based cluster visualization that embeds statistical information into a multi-attribute display to facilitate cluster interpretation, evaluation, and comparison. We design a treemap-like icon to represent a multidimensional cluster, and the quality of the cluster can be conveniently evaluated with the embedded statistical information. We further develop a novel layout algorithm which can generate similar icons for similar clusters, making comparisons of clusters easier. User interaction and clutter reduction are integrated into the system to help users more effectively analyze and refine clustering results for large datasets. We demonstrate the power of DICON through a user study and a case study in the healthcare domain. Our evaluation shows the benefits of the technique, especially in support of complex multidimensional cluster analysis.

  19. Career Success: Constructing a Multidimensional Model

    ERIC Educational Resources Information Center

    Dries, Nicky; Pepermans, Roland; Carlier, Olivier

    2008-01-01

    A multidimensional model of career success was developed aiming to be more inclusive than existing models. In a first study, 22 managers were asked to tell the story of their careers. At the end of each interview, idiosyncratic career success "construct ladders" were constructed for each interviewee through an interactive process with the…

  20. White Dialectics as Multidimensional, Contextual, and Transformational

    ERIC Educational Resources Information Center

    Abrams, Elizabeth M.; Todd, Nathan R.

    2011-01-01

    This rejoinder provides a response to reactions by Ponterotto, Sue, and Toporek to the White dialectics framework presented in Todd and Abrams's article. The present response focuses on incorporating multidimensionality, the multilevel nature of context, and the potential for transformation in the White dialectics framework. The authors expand…

  1. A Multidimensional Construct of Self-Esteem

    ERIC Educational Resources Information Center

    Norem-Hebeisen, Ardyth A.

    1976-01-01

    Evidence for construct validity of this multi-dimensional concept of self esteem includes the relative congruence of the factor structure with the theoretical construct, the stability of the structure when subjected to a series of empirical tests, increasingly positive self-referent responses with increasing age, willingness to become more…

  2. Uncertainty of Comparative Judgments and Multidimensional Structure

    ERIC Educational Resources Information Center

    Sjoberg, Lennart

    1975-01-01

    An analysis of preferences with respect to silhouette drawings of nude females is presented. Systematic intransitivities were discovered. The dispersions of differences (comparatal dispersons) were shown to reflect the multidimensional structure of the stimuli, a finding expected on the basis of prior work. (Author)

  3. Multidimensional Tauberian theorems for generalized functions

    NASA Astrophysics Data System (ADS)

    Drozhzhinov, Yu N.

    2016-12-01

    This is a brief survey of multidimensional Tauberian theorems for generalized functions. Included are theorems of Hardy-Littlewood type, Tauberian and Abelian comparison theorems of Keldysh type, theorems of Wiener type, and Tauberian theorems for generalized functions with values in Banach spaces. Bibliography: 58 titles.

  4. Multidimensional Human Dynamics in Mobile Phone Communications

    PubMed Central

    Quadri, Christian; Zignani, Matteo; Capra, Lorenzo; Gaito, Sabrina; Rossi, Gian Paolo

    2014-01-01

    In today's technology-assisted society, social interactions may be expressed through a variety of techno-communication channels, including online social networks, email and mobile phones (calls, text messages). Consequently, a clear grasp of human behavior through the diverse communication media is considered a key factor in understanding the formation of the today's information society. So far, all previous research on user communication behavior has focused on a sole communication activity. In this paper we move forward another step on this research path by performing a multidimensional study of human sociality as an expression of the use of mobile phones. The paper focuses on user temporal communication behavior in the interplay between the two complementary communication media, text messages and phone calls, that represent the bi-dimensional scenario of analysis. Our study provides a theoretical framework for analyzing multidimensional bursts as the most general burst category, that includes one-dimensional bursts as the simplest case, and offers empirical evidence of their nature by following the combined phone call/text message communication patterns of approximately one million people over three-month period. This quantitative approach enables the design of a generative model rooted in the three most significant features of the multidimensional burst - the number of dimensions, prevalence and interleaving degree - able to reproduce the main media usage attitude. The other findings of the paper include a novel multidimensional burst detection algorithm and an insight analysis of the human media selection process. PMID:25068479

  5. Multidimensional stochastic approximation using locally contractive functions

    NASA Technical Reports Server (NTRS)

    Lawton, W. M.

    1975-01-01

    A Robbins-Monro type multidimensional stochastic approximation algorithm which converges in mean square and with probability one to the fixed point of a locally contractive regression function is developed. The algorithm is applied to obtain maximum likelihood estimates of the parameters for a mixture of multivariate normal distributions.

  6. Examination of the Structure and Grade-Related Differentiation of Multidimensional Self-Concept Instruments for Children Using ESEM

    ERIC Educational Resources Information Center

    Arens, A. Katrin; Morin, Alexandre J. S.

    2016-01-01

    This study is a substantive-methodological synergy in which exploratory structural equation modeling is applied to investigate the factor structure of multidimensional self-concept instruments. On the basis of a sample of German students (N = 1958) who completed the Self-Description Questionnaire I and the Self-Perception Profile for Children, the…

  7. Sex Differences in the Multidimensional Self-Concepts of African American Adolescents: The Mediating Role of Gender Identity

    ERIC Educational Resources Information Center

    Thomson, Nicole Renick; Zand, Debra H.

    2007-01-01

    The present study investigates whether the gender identities of African American adolescents mediate sex differences found in their multidimensional self-concepts. The sample included 174 African American adolescents who completed the 21-item Children's Personal Attributes Questionnaire and the Self-Perception Profile for Adolescents. Results…

  8. Bronchiectasis: Phenotyping a Complex Disease.

    PubMed

    Chalmers, James D

    2017-03-15

    Bronchiectasis is a long-neglected disease currently experiencing a surge in interest. It is a highly complex condition with numerous aetiologies, co-morbidities and a heterogeneous disease presentation and clinical course. The past few years have seen major advances in our understanding of the disease, primarily through large real-life cohort studies. The main outcomes of interest in bronchiectasis are symptoms, exacerbations, treatment response, disease progression and death. We are now more able to identify clearly the radiological, clinical, microbiological and inflammatory contributors to these outcomes. Over the past couple of years, multidimensional scoring systems such as the Bronchiectasis Severity Index have been introduced to predict disease severity and mortality. Although there are currently no licensed therapies for bronchiectasis, an increasing number of clinical trials are planned or ongoing. While this emerging evidence is awaited, bronchiectasis guidelines will continue to be informed largely by real-life evidence from observational studies and patient registries. Key developments in the bronchiectasis field include the establishment of international disease registries and characterisation of disease phenotypes using cluster analysis and biological data.

  9. Effective Friedmann model from multidimensional cosmologies

    NASA Astrophysics Data System (ADS)

    Zhuk, A.

    2006-10-01

    We investigate the possibility of the construction of the conventional Friedmann cosmology for our observable Universe if the underlying theory is the multidimensional Kaluza-Klein model. We show that the effective Friedmann model obtained by dynamic compactification of the multidimensional model is faced with too strong variations in the fundamental constants. On the other hand, models with stable compactification of the internal space are free from this problem and also result in conventional four-dimensonal cosmological behaviour for our Universe. We prove a no-go theorem, which shows that stable compactification of the internal spaces is possible only if the equations of state in the external and internal spaces are properly adjusted to each other. With a proper choice of parameters (fine tuning), the effective cosmological constant in this model provides the late-time acceleration of the Universe.

  10. Visualization of Multidimensional Data in Nursing Science.

    PubMed

    Docherty, Sharron L; Vorderstrasse, Allison; Brandon, Debra; Johnson, Constance

    2016-10-18

    Nursing scientists have long been interested in complex, context-dependent questions addressing individual- and population-level challenges in health and illness. These critical questions require multilevel data (e.g., genetic, physiologic, biologic, behavioral, affective, and social). Advances in data-gathering methods have resulted in the collection of large sets of complex, multifaceted, and often non-comparable data. Scientific visualization is a powerful methodological tool for facilitating understanding of these multidimensional data sets. Our purpose is to demonstrate the utility of scientific visualization as a method for identifying associations, patterns, and trends in multidimensional data as exemplified in two studies. We describe a brief history of visual analysis, processes involved in scientific visualization, and opportunities and challenges in the use of visualization methods. Scientific visualization can play a crucial role in helping nurse scientists make sense of the structure and underlying patterns in their data to answer vital questions in the field.

  11. Multidimensional X-Space Magnetic Particle Imaging

    PubMed Central

    Conolly, Steven M.

    2012-01-01

    Magnetic particle imaging (MPI) is a promising new medical imaging tracer modality with potential applications in human angiography, cancer imaging, in vivo cell tracking, and inflammation imaging. Here we demonstrate both theoretically and experimentally that multidimensional MPI is a linear shift-in-variant imaging system with an analytic point spread function. We also introduce a fast image reconstruction method that obtains the intrinsic MPI image with high signal-to-noise ratio via a simple gridding operation in x-space. We also demonstrate a method to reconstruct large field-of-view (FOV) images using partial FOV scanning, despite the loss of first harmonic image information due to direct feedthrough contamination. We conclude with the first experimental test of multidimensional x-space MPI. PMID:21402508

  12. Multidimensional x-space magnetic particle imaging.

    PubMed

    Goodwill, Patrick W; Conolly, Steven M

    2011-09-01

    Magnetic particle imaging (MPI) is a promising new medical imaging tracer modality with potential applications in human angiography, cancer imaging, in vivo cell tracking, and inflammation imaging. Here we demonstrate both theoretically and experimentally that multidimensional MPI is a linear shift-invariant imaging system with an analytic point spread function. We also introduce a fast image reconstruction method that obtains the intrinsic MPI image with high signal-to-noise ratio via a simple gridding operation in x-space. We also demonstrate a method to reconstruct large field-of-view (FOV) images using partial FOV scanning, despite the loss of first harmonic image information due to direct feedthrough contamination. We conclude with the first experimental test of multidimensional x-space MPI.

  13. Plant phenomics and the need for physiological phenotyping across scales to narrow the genotype-to-phenotype knowledge gap.

    PubMed

    Großkinsky, Dominik K; Svensgaard, Jesper; Christensen, Svend; Roitsch, Thomas

    2015-09-01

    Plants are affected by complex genome×environment×management interactions which determine phenotypic plasticity as a result of the variability of genetic components. Whereas great advances have been made in the cost-efficient and high-throughput analyses of genetic information and non-invasive phenotyping, the large-scale analyses of the underlying physiological mechanisms lag behind. The external phenotype is determined by the sum of the complex interactions of metabolic pathways and intracellular regulatory networks that is reflected in an internal, physiological, and biochemical phenotype. These various scales of dynamic physiological responses need to be considered, and genotyping and external phenotyping should be linked to the physiology at the cellular and tissue level. A high-dimensional physiological phenotyping across scales is needed that integrates the precise characterization of the internal phenotype into high-throughput phenotyping of whole plants and canopies. By this means, complex traits can be broken down into individual components of physiological traits. Since the higher resolution of physiological phenotyping by 'wet chemistry' is inherently limited in throughput, high-throughput non-invasive phenotyping needs to be validated and verified across scales to be used as proxy for the underlying processes. Armed with this interdisciplinary and multidimensional phenomics approach, plant physiology, non-invasive phenotyping, and functional genomics will complement each other, ultimately enabling the in silico assessment of responses under defined environments with advanced crop models. This will allow generation of robust physiological predictors also for complex traits to bridge the knowledge gap between genotype and phenotype for applications in breeding, precision farming, and basic research.

  14. Progress in Multi-Dimensional Upwind Differencing

    DTIC Science & Technology

    1992-09-01

    advances in each of these components are discussed; putting them all together is the present focus of a worldwide research effort. Some numerical results ...as 1983 by Phil Roe [1]. A study of discrete multi-dimensional wave models by Roe followed in 1985 (ICASE Report 85-18, also [21), but it took until...consider the numerical results shown in Figure :3 and 4, taken from [:34] and [35], respectively. In Figure 3a the exact and discrete Mach-number

  15. On the Need for Multidimensional Stirling Analysis

    NASA Technical Reports Server (NTRS)

    Dyson, Rodger; Wilson, Scott; Tew, Roy; Demko, Rikako

    2006-01-01

    Contents include the following: Dual opposed convertors. High efficiency. Low mass space power. One-dimensional analysis. Fast computation. Design optimizations are easily done. Need for multidimensional modeling. Axisymmetric simulation. Flow characteristics. Low mach number. Laminar, transitional, and turbulent flow. Conjugate heat transfer. Third order analysis. Recent whole engine modeling. Regenerator geometry. Turbulence modeling. Flat head heater not 1-D. Empirical coefficients needed. Experiment design. Flow distribution. Sensor placement. Calibration. Validation.

  16. Elements Of Theory Of Multidimensional Complex Variables

    NASA Technical Reports Server (NTRS)

    Martin, E. Dale

    1993-01-01

    Two reports describe elements of theory of multidimensional complex variables, with emphasis on three dimensions. First report introduces general theory. Second, presents further developments in theory of analytic functions of single three-dimensional variable and applies theory to representation of ideal flows. Results of preliminary studies suggest analytic functions of new three-dimensional complex variables useful in numerous applications, including representing of three-dimensional flows and potentials.

  17. Multidimensional reaction rate theory with anisotropic diffusion.

    PubMed

    Berezhkovskii, Alexander M; Szabo, Attila; Greives, Nicholas; Zhou, Huan-Xiang

    2014-11-28

    An analytical expression is derived for the rate constant that describes diffusive transitions between two deep wells of a multidimensional potential. The expression, in contrast to the Kramers-Langer formula for the rate constant, is valid even when the diffusion is highly anisotropic. Our approach is based on a variational principle for the reactive flux and uses a trial function for the splitting probability or commitor. The theoretical result is validated by Brownian dynamics simulations.

  18. Relevance in the science classroom: A multidimensional analysis

    NASA Astrophysics Data System (ADS)

    Hartwell, Matthew F.

    While perceived relevance is considered a fundamental component of adaptive learning, the experience of relevance and its conceptual definition have not been well described. The mixed-methods research presented in this dissertation aimed to clarify the conceptual meaning of relevance by focusing on its phenomenological experience from the students' perspective. Following a critical literature review, I propose an identity-based model of perceived relevance that includes three components: a contextual target, an identity target, and a connection type, or lens. An empirical investigation of this model that consisted of two general phases was implemented in four 9th grade-biology classrooms. Participants in Phase 1 (N = 118) completed a series of four open-ended writing activities focused on eliciting perceived personal connections to academic content. Exploratory qualitative content analysis of a 25% random sample of the student responses was used to identify the main meaning-units of the proposed model as well as different dimensions of student relevance perceptions. These meaning-units and dimensions provided the basis for the construction of a conceptual mapping sentence capturing students' perceived relevance, which was then applied in a confirmatory analysis to all other student responses. Participants in Phase 2 (N = 139) completed a closed survey designed based on the mapping sentence to assess their perceived relevance of a biology unit. The survey also included scales assessing other domain-level motivational processes. Exploratory factor analysis and non-metric multidimensional scaling indicated a coherent conceptual structure, which included a primary interpretive relevance dimension. Comparison of the conceptual structure across various groups (randomly-split sample, gender, academic level, domain-general motivational profiles) provided support for its ubiquity and insight into variation in the experience of perceived relevance among students of different

  19. Trellis coding with multidimensional QAM signal sets

    NASA Technical Reports Server (NTRS)

    Pietrobon, Steven S.; Costello, Daniel J.

    1993-01-01

    Trellis coding using multidimensional QAM signal sets is investigated. Finite-size 2D signal sets are presented that have minimum average energy, are 90-deg rotationally symmetric, and have from 16 to 1024 points. The best trellis codes using the finite 16-QAM signal set with two, four, six, and eight dimensions are found by computer search (the multidimensional signal set is constructed from the 2D signal set). The best moderate complexity trellis codes for infinite lattices with two, four, six, and eight dimensions are also found. The minimum free squared Euclidean distance and number of nearest neighbors for these codes were used as the selection criteria. Many of the multidimensional codes are fully rotationally invariant and give asymptotic coding gains up to 6.0 dB. From the infinite lattice codes, the best codes for transmitting J, J + 1/4, J + 1/3, J + 1/2, J + 2/3, and J + 3/4 bit/sym (J an integer) are presented.

  20. Multidimensional Homophily in Friendship Networks1

    PubMed Central

    Block, Per; Grund, Thomas

    2014-01-01

    Homophily – the tendency for individuals to associate with similar others – is one of the most persistent findings in social network analysis. Its importance is established along the lines of a multitude of sociologically relevant dimensions, e.g. sex, ethnicity and social class. Existing research, however, mostly focuses on one dimension at a time. But people are inherently multidimensional, have many attributes and are members of multiple groups. In this article, we explore such multidimensionality further in the context of network dynamics. Are friendship ties increasingly likely to emerge and persist when individuals have an increasing number of attributes in common? We analyze eleven friendship networks of adolescents, draw on stochastic actor-oriented network models and focus on the interaction of established homophily effects. Our results indicate that main effects for homophily on various dimensions are positive. At the same time, the interaction of these homophily effects is negative. There seems to be a diminishing effect for having more than one attribute in common. We conclude that studies of homophily and friendship formation need to address such multidimensionality further. PMID:25525503

  1. Serum Biochemical Phenotypes in the Domestic Dog.

    PubMed

    Chang, Yu-Mei; Hadox, Erin; Szladovits, Balazs; Garden, Oliver A

    2016-01-01

    The serum or plasma biochemical profile is essential in the diagnosis and monitoring of systemic disease in veterinary medicine, but current reference intervals typically take no account of breed-specific differences. Breed-specific hematological phenotypes have been documented in the domestic dog, but little has been published on serum biochemical phenotypes in this species. Serum biochemical profiles of dogs in which all measurements fell within the existing reference intervals were retrieved from a large veterinary database. Serum biochemical profiles from 3045 dogs were retrieved, of which 1495 had an accompanying normal glucose concentration. Sixty pure breeds plus a mixed breed control group were represented by at least 10 individuals. All analytes, except for sodium, chloride and glucose, showed variation with age. Total protein, globulin, potassium, chloride, creatinine, cholesterol, total bilirubin, ALT, CK, amylase, and lipase varied between sexes. Neutering status significantly impacted all analytes except albumin, sodium, calcium, urea, and glucose. Principal component analysis of serum biochemical data revealed 36 pure breeds with distinctive phenotypes. Furthermore, comparative analysis identified 23 breeds with significant differences from the mixed breed group in all biochemical analytes except urea and glucose. Eighteen breeds were identified by both principal component and comparative analysis. Tentative reference intervals were generated for breeds with a distinctive phenotype identified by comparative analysis and represented by at least 120 individuals. This is the first large-scale analysis of breed-specific serum biochemical phenotypes in the domestic dog and highlights potential genetic components of biochemical traits in this species.

  2. Serum Biochemical Phenotypes in the Domestic Dog

    PubMed Central

    Chang, Yu-Mei; Hadox, Erin; Szladovits, Balazs; Garden, Oliver A.

    2016-01-01

    The serum or plasma biochemical profile is essential in the diagnosis and monitoring of systemic disease in veterinary medicine, but current reference intervals typically take no account of breed-specific differences. Breed-specific hematological phenotypes have been documented in the domestic dog, but little has been published on serum biochemical phenotypes in this species. Serum biochemical profiles of dogs in which all measurements fell within the existing reference intervals were retrieved from a large veterinary database. Serum biochemical profiles from 3045 dogs were retrieved, of which 1495 had an accompanying normal glucose concentration. Sixty pure breeds plus a mixed breed control group were represented by at least 10 individuals. All analytes, except for sodium, chloride and glucose, showed variation with age. Total protein, globulin, potassium, chloride, creatinine, cholesterol, total bilirubin, ALT, CK, amylase, and lipase varied between sexes. Neutering status significantly impacted all analytes except albumin, sodium, calcium, urea, and glucose. Principal component analysis of serum biochemical data revealed 36 pure breeds with distinctive phenotypes. Furthermore, comparative analysis identified 23 breeds with significant differences from the mixed breed group in all biochemical analytes except urea and glucose. Eighteen breeds were identified by both principal component and comparative analysis. Tentative reference intervals were generated for breeds with a distinctive phenotype identified by comparative analysis and represented by at least 120 individuals. This is the first large-scale analysis of breed-specific serum biochemical phenotypes in the domestic dog and highlights potential genetic components of biochemical traits in this species. PMID:26919479

  3. Cluster Analysis and Clinical Asthma Phenotypes

    PubMed Central

    Shaw, Dominic E.; Berry, Michael A.; Thomas, Michael; Brightling, Christopher E.; Wardlaw, Andrew J.

    2014-01-01

    Rationale Heterogeneity in asthma expression is multidimensional, including variability in clinical, physiologic, and pathologic parameters. Classification requires consideration of these disparate domains in a unified model. Objectives To explore the application of a multivariate mathematical technique, k-means cluster analysis, for identifying distinct phenotypic groups. Methods We performed k-means cluster analysis in three independent asthma populations. Clusters of a population managed in primary care (n = 184) with predominantly mild to moderate disease, were compared with a refractory asthma population managed in secondary care (n = 187). We then compared differences in asthma outcomes (exacerbation frequency and change in corticosteroid dose at 12 mo) between clusters in a third population of 68 subjects with predominantly refractory asthma, clustered at entry into a randomized trial comparing a strategy of minimizing eosinophilic inflammation (inflammation-guided strategy) with standard care. Measurements and Main Results Two clusters (early-onset atopic and obese, noneosinophilic) were common to both asthma populations. Two clusters characterized by marked discordance between symptom expression and eosinophilic airway inflammation (early-onset symptom predominant and late-onset inflammation predominant) were specific to refractory asthma. Inflammation-guided management was superior for both discordant subgroups leading to a reduction in exacerbation frequency in the inflammation-predominant cluster (3.53 [SD, 1.18] vs. 0.38 [SD, 0.13] exacerbation/patient/yr, P = 0.002) and a dose reduction of inhaled corticosteroid in the symptom-predominant cluster (mean difference, 1,829 μg beclomethasone equivalent/d [95% confidence interval, 307–3,349 μg]; P = 0.02). Conclusions Cluster analysis offers a novel multidimensional approach for identifying asthma phenotypes that exhibit differences in clinical response to treatment algorithms. PMID:18480428

  4. Nuclear Forensic Inferences Using Iterative Multidimensional Statistics

    SciTech Connect

    Robel, M; Kristo, M J; Heller, M A

    2009-06-09

    Nuclear forensics involves the analysis of interdicted nuclear material for specific material characteristics (referred to as 'signatures') that imply specific geographical locations, production processes, culprit intentions, etc. Predictive signatures rely on expert knowledge of physics, chemistry, and engineering to develop inferences from these material characteristics. Comparative signatures, on the other hand, rely on comparison of the material characteristics of the interdicted sample (the 'questioned sample' in FBI parlance) with those of a set of known samples. In the ideal case, the set of known samples would be a comprehensive nuclear forensics database, a database which does not currently exist. In fact, our ability to analyze interdicted samples and produce an extensive list of precise materials characteristics far exceeds our ability to interpret the results. Therefore, as we seek to develop the extensive databases necessary for nuclear forensics, we must also develop the methods necessary to produce the necessary inferences from comparison of our analytical results with these large, multidimensional sets of data. In the work reported here, we used a large, multidimensional dataset of results from quality control analyses of uranium ore concentrate (UOC, sometimes called 'yellowcake'). We have found that traditional multidimensional techniques, such as principal components analysis (PCA), are especially useful for understanding such datasets and drawing relevant conclusions. In particular, we have developed an iterative partial least squares-discriminant analysis (PLS-DA) procedure that has proven especially adept at identifying the production location of unknown UOC samples. By removing classes which fell far outside the initial decision boundary, and then rebuilding the PLS-DA model, we have consistently produced better and more definitive attributions than with a single pass classification approach. Performance of the iterative PLS-DA method

  5. Multidimensional voice analysis of reflux laryngitis patients.

    PubMed

    Pribuisienë, Rûta; Uloza, Virgilijus; Saferis, Viktoras

    2005-01-01

    The aim of the study was to analyze and quantify the voice characteristics of reflux laryngitis (RL) patients and to determine the most important voice tests and voice-quality parameters in the functional diagnostics of RL. The voices of 83 RL patients and 31 persons in the control group were evaluated. Vocal function was assessed using a multidimensional set of video laryngostroboscopic, perceptual, acoustic, aerodynamic and subjective measurements according to the protocol elaborated by the Committee on Phoniatrics of the European Laryngological Society. The mean values of the hoarseness visual analogue scale assessment and voice handicap index were significantly higher (P<0.05) in the group of RL patients as compared to the controls. Objective voice assessment revealed a significant increase in mean values of jitter, shimmer and normalized noise energy (NNE), along with a significant decrease in pitch range, maximum frequency, phonetogram area (S) and maximum phonation time (MPT) in RL patients, both in the male and female subgroups. According to the results of discriminant analysis, the NNE, MPT, S and intensity range were determined as an optimum set for functional diagnostics of RL. The derived function (equation) makes it possible to assign the person to the group of RL patients with an accuracy of 86.7%. The sensitivity and specificity of eight voice parameters were found to be higher than 50%. The results of the present study demonstrate a reduction of phonation capabilities and voice quality in RL patients. Multidimensional voice evaluation makes it possible to detect significant differences in mean values of perceptual, subjective and objective voice quality parameters between RL patients and controls groups. Therefore, multidimensional voice analysis is an important tool in the functional diagnostics of RL.

  6. Construct continuity in the presence of multidimensionality

    NASA Astrophysics Data System (ADS)

    Staniewska, Dorota

    Unidimensionality -- a condition, under which only one dominant construct is being measured by the test, is a fundamental assumption of most modern day psychometric models. However, some tests are multidimensional by design. A test, for instance, might measure physics, biology and chemistry subscales combined to measure a "general science" composite. The relative magnitudes of those subscales sometimes shift from administration to administration, which results in an altered composite. This study examined the conditions under which two different forms of a multidimensional test measure the same composite construct to a degree that allows them to be equated, i.e. used interchangeably. IRT true-score equating was used in a simulation study to assess the closeness of the scores on the forms. Conditions examined included the correlations between subscales, varying number of items per subscale form to form, and different subpopulation ability estimates on the subscales. Differences in the equating errors due to generating model (1PL or 3PL) were also examined. A way of calculating a unidimensional composite from a two-dimensional ability was devised and compared to the unidimensional composite obtained from Parscale. It was found that in general, the errors increase with decreasing correlation between traits and increased divergence of the two forms to be equated, with the later being the main predictor of the equating errors. However, the magnitude of those errors was small for the population as a whole especially when all examinee abilities are drawn from the same distribution. It was concluded that IRT true score equating is relatively robust to multidimensionality for the conditions examined, especially if the overall population score is desired. However, when accurate estimate of the equated score for individuals at the extremes of the population is needed, or whenever population abilities are drawn from more than one distribution, the unidimensional true score

  7. A Multidimensional Scaling Approach to Dimensionality Assessment for Measurement Instruments Modeled by Multidimensional Item Response Theory

    ERIC Educational Resources Information Center

    Toro, Maritsa

    2011-01-01

    The statistical assessment of dimensionality provides evidence of the underlying constructs measured by a survey or test instrument. This study focuses on educational measurement, specifically tests comprised of items described as multidimensional. That is, items that require examinee proficiency in multiple content areas and/or multiple cognitive…

  8. A multidimensional representation model of geographic features

    USGS Publications Warehouse

    Usery, E. Lynn; Timson, George; Coletti, Mark

    2016-01-28

    A multidimensional model of geographic features has been developed and implemented with data from The National Map of the U.S. Geological Survey. The model, programmed in C++ and implemented as a feature library, was tested with data from the National Hydrography Dataset demonstrating the capability to handle changes in feature attributes, such as increases in chlorine concentration in a stream, and feature geometry, such as the changing shoreline of barrier islands over time. Data can be entered directly, from a comma separated file, or features with attributes and relationships can be automatically populated in the model from data in the Spatial Data Transfer Standard format.

  9. Multidimensional world, inflation, and modern acceleration

    SciTech Connect

    Bronnikov, K. A.; Rubin, S. G.; Svadkovsky, I. V.

    2010-04-15

    Starting from pure multidimensional gravity with curvature-nonlinear terms but no matter fields in the initial action, we obtain a cosmological model with two effective scalar fields related to the size of two extra factor spaces. The model includes both an early inflationary stage and that of modern accelerated expansion and satisfies the observational data. There are no small parameters; the effective inflaton mass depends on the initial conditions which explain its small value as compared to the Planck mass. At the modern stage, the size of extra dimensions slowly increases, therefore this model predicts drastic changes in the physical laws of our Universe in the remote future.

  10. Multidimensional world, inflation, and modern acceleration

    NASA Astrophysics Data System (ADS)

    Bronnikov, K. A.; Rubin, S. G.; Svadkovsky, I. V.

    2010-04-01

    Starting from pure multidimensional gravity with curvature-nonlinear terms but no matter fields in the initial action, we obtain a cosmological model with two effective scalar fields related to the size of two extra factor spaces. The model includes both an early inflationary stage and that of modern accelerated expansion and satisfies the observational data. There are no small parameters; the effective inflaton mass depends on the initial conditions which explain its small value as compared to the Planck mass. At the modern stage, the size of extra dimensions slowly increases, therefore this model predicts drastic changes in the physical laws of our Universe in the remote future.

  11. Evolution of multidimensional flat anisotropic cosmological models

    SciTech Connect

    Beloborodov, A. ); Demianski, M. Nicolaus Copernicus Astronomical Center, Bartycka 18, 00-716 Warsaw International Center for Relativistic Astrophysics , Universita di Roma I, La Sapienza, Rome ); Ivanov, P.; Polnarev, A.G. )

    1993-07-15

    We study the dynamics of a flat multidimensional anisotropic cosmological model filled with an anisotropic fluidlike medium. By an appropriate choice of variables, the dynamical equations reduce to a two-dimensional dynamical system. We present a detailed analysis of the time evolution of this system and the conditions of the existence of spacetime singularities. We investigate the conditions under which violent, exponential, and power-law inflation is possible. We show that dimensional reduction cannot proceed by anti-inflation (rapid contraction of internal space). Our model indicates that it is very difficult to achieve dimensional reduction by classical means.

  12. Multi-dimensional MHD simple waves

    SciTech Connect

    Webb, G. M.; Ratkiewicz, R.; Brio, M.; Zank, G. P.

    1996-07-20

    In this paper we consider a formalism for multi-dimensional simple MHD waves using ideas developed by Boillat. For simple wave solutions one assumes that all the physical variables (the density {rho}, gas pressure p, fluid velocity u, gas entropy S, and magnetic induction B in the MHD case) depend on a single phase function {phi}(r,t). The simple wave solution ansatz and the MHD equations then require that the phase function {phi} satisfies an implicit equation of the form f({phi})=r{center_dot}n({phi})-{lambda}({phi})t, where n({phi})={nabla}{phi}/|{nabla}{phi}| is the wave normal, {lambda}({phi})={omega}/k=-{phi}{sub t}/|{nabla}{phi}| is the normal speed of the wave front, and f({phi}) is an arbitrary differentiable function of {phi}. The formalism allows for more general simple waves than that usually dealt with in which n({phi}) is a constant unit vector that does not vary along the wave front. The formalism has implications for shock formation and wave breaking for multi-dimensional waves.

  13. Multi-dimensional MHD simple waves

    NASA Technical Reports Server (NTRS)

    Webb, G. M.; Ratkiewicz, R.; Brio, M.; Zank, G. P.

    1995-01-01

    In this paper we consider a formalism for multi-dimensional simple MHD waves using ideas developed by Boillat. For simple wave solutions one assumes that all the physical variables (the density rho, gas pressure p, fluid velocity V, gas entropy S, and magnetic induction B in the MHD case) depend on a single phase function phi(r,t). The simple wave solution ansatz and the MHD equations then require that the phase function has the form phi = r x n(phi) - lambda(phi)t, where = n(phi) = Delta phi / (absolute value of Delta phi) is the wave normal and lambda(phi) = omega/k = -phi t / (absolute value of Delta phi) is the normal speed of the wave front. The formalism allows for more general simple waves than that usually dealt with in which n(phi) is a constant unit vector that does not vary along the wave front. The formalism has implications for shock formation for multi-dimensional waves.

  14. Testlet-Based Multidimensional Adaptive Testing.

    PubMed

    Frey, Andreas; Seitz, Nicki-Nils; Brandt, Steffen

    2016-01-01

    Multidimensional adaptive testing (MAT) is a highly efficient method for the simultaneous measurement of several latent traits. Currently, no psychometrically sound approach is available for the use of MAT in testlet-based tests. Testlets are sets of items sharing a common stimulus such as a graph or a text. They are frequently used in large operational testing programs like TOEFL, PISA, PIRLS, or NAEP. To make MAT accessible for such testing programs, we present a novel combination of MAT with a multidimensional generalization of the random effects testlet model (MAT-MTIRT). MAT-MTIRT compared to non-adaptive testing is examined for several combinations of testlet effect variances (0.0, 0.5, 1.0, and 1.5) and testlet sizes (3, 6, and 9 items) with a simulation study considering three ability dimensions with simple loading structure. MAT-MTIRT outperformed non-adaptive testing regarding the measurement precision of the ability estimates. Further, the measurement precision decreased when testlet effect variances and testlet sizes increased. The suggested combination of the MTIRT model therefore provides a solution to the substantial problems of testlet-based tests while keeping the length of the test within an acceptable range.

  15. Testlet-Based Multidimensional Adaptive Testing

    PubMed Central

    Frey, Andreas; Seitz, Nicki-Nils; Brandt, Steffen

    2016-01-01

    Multidimensional adaptive testing (MAT) is a highly efficient method for the simultaneous measurement of several latent traits. Currently, no psychometrically sound approach is available for the use of MAT in testlet-based tests. Testlets are sets of items sharing a common stimulus such as a graph or a text. They are frequently used in large operational testing programs like TOEFL, PISA, PIRLS, or NAEP. To make MAT accessible for such testing programs, we present a novel combination of MAT with a multidimensional generalization of the random effects testlet model (MAT-MTIRT). MAT-MTIRT compared to non-adaptive testing is examined for several combinations of testlet effect variances (0.0, 0.5, 1.0, and 1.5) and testlet sizes (3, 6, and 9 items) with a simulation study considering three ability dimensions with simple loading structure. MAT-MTIRT outperformed non-adaptive testing regarding the measurement precision of the ability estimates. Further, the measurement precision decreased when testlet effect variances and testlet sizes increased. The suggested combination of the MTIRT model therefore provides a solution to the substantial problems of testlet-based tests while keeping the length of the test within an acceptable range. PMID:27917132

  16. MULTIDIMENSIONAL MODELING OF CORONAL RAIN DYNAMICS

    SciTech Connect

    Fang, X.; Xia, C.; Keppens, R.

    2013-07-10

    We present the first multidimensional, magnetohydrodynamic simulations that capture the initial formation and long-term sustainment of the enigmatic coronal rain phenomenon. We demonstrate how thermal instability can induce a spectacular display of in situ forming blob-like condensations which then start their intimate ballet on top of initially linear force-free arcades. Our magnetic arcades host a chromospheric, transition region, and coronal plasma. Following coronal rain dynamics for over 80 minutes of physical time, we collect enough statistics to quantify blob widths, lengths, velocity distributions, and other characteristics which directly match modern observational knowledge. Our virtual coronal rain displays the deformation of blobs into V-shaped features, interactions of blobs due to mostly pressure-mediated levitations, and gives the first views of blobs that evaporate in situ or are siphoned over the apex of the background arcade. Our simulations pave the way for systematic surveys of coronal rain showers in true multidimensional settings to connect parameterized heating prescriptions with rain statistics, ultimately allowing us to quantify the coronal heating input.

  17. Temporal masking of multidimensional tactual stimuli

    NASA Astrophysics Data System (ADS)

    Tan, Hong Z.; Reed, Charlotte M.; Delhorne, Lorraine A.; Durlach, Nathaniel I.; Wan, Natasha

    2003-12-01

    Experiments were performed to examine the temporal masking properties of multidimensional tactual stimulation patterns delivered to the left index finger. The stimuli consisted of fixed-frequency sinusoidal motions in the kinesthetic (2 or 4 Hz), midfrequency (30 Hz), and cutaneous (300 Hz) frequency ranges. Seven stimuli composed of one, two, or three spectral components were constructed at each of two signal durations (125 or 250 ms). Subjects identified target signals under three different masking paradigms: forward masking, backward masking, and sandwiched masking (in which the target is presented between two maskers). Target identification was studied as a function of interstimulus interval (ISI) in the range 0 to 640 ms. For both signal durations, percent-correct scores increased with ISI for each of the three masking paradigms. Scores with forward and backward masking were similar and significantly higher than scores obtained with sandwiched masking. Analyses of error trials revealed that subjects showed a tendency to respond, more often than chance, with the masker, the composite of the masker and target, or the combination of the target and a component of the masker. The current results are compared to those obtained in previous studies of tactual recognition masking with brief cutaneous spatial patterns. The results are also discussed in terms of estimates of information transfer (IT) and IT rate, are compared to previous studies with multidimensional tactual signals, and are related to research on the development of tactual aids for the deaf.

  18. Multidimensional Conservation Laws and Low Regularity Solutions

    SciTech Connect

    Barbara Lee Keyfitz

    2007-06-16

    This is the concluding report for the project, a continuation of research by Keyfitz and co-workers on multidimensional conservation laws, and applications of nonhyperbolic conservation laws in the two-fluid model for multiphase flow. The multidimensional research project was started with Suncica Canic, at the University of Houston and with Eun Heui Kim, now at California State University Long Beach. Two postdoctoral researchers, Katarina Jegdic and Allen Tesdall, also worked on this research. Jegdic's research was supported (for a total of one year) by this grant. Work on nonhyperbolic models for two-phase flows is being pursued jointly with Michael Sever, Hebrew University. Background for the project is contained in earlier reports. Note that in 2006, the project received a one-year no-cost extension that will end in September, 2007. A new proposal, for continuation of the research and for new projects, will be submitted in the Fall of 2007, with funding requested to begin in the summer of 2008. The reason for the 'funding gap' is Keyfitz's four-year stint as Director of the Fields Institute in Toronto, Canada. The research has continued, but has been supported by Canadian grant funds, as seems appropriate during this period.

  19. Multidimensional Modeling of Coronal Rain Dynamics

    NASA Astrophysics Data System (ADS)

    Fang, X.; Xia, C.; Keppens, R.

    2013-07-01

    We present the first multidimensional, magnetohydrodynamic simulations that capture the initial formation and long-term sustainment of the enigmatic coronal rain phenomenon. We demonstrate how thermal instability can induce a spectacular display of in situ forming blob-like condensations which then start their intimate ballet on top of initially linear force-free arcades. Our magnetic arcades host a chromospheric, transition region, and coronal plasma. Following coronal rain dynamics for over 80 minutes of physical time, we collect enough statistics to quantify blob widths, lengths, velocity distributions, and other characteristics which directly match modern observational knowledge. Our virtual coronal rain displays the deformation of blobs into V-shaped features, interactions of blobs due to mostly pressure-mediated levitations, and gives the first views of blobs that evaporate in situ or are siphoned over the apex of the background arcade. Our simulations pave the way for systematic surveys of coronal rain showers in true multidimensional settings to connect parameterized heating prescriptions with rain statistics, ultimately allowing us to quantify the coronal heating input.

  20. Benchmarking the Multidimensional Stellar Implicit Code MUSIC

    NASA Astrophysics Data System (ADS)

    Goffrey, T.; Pratt, J.; Viallet, M.; Baraffe, I.; Popov, M. V.; Walder, R.; Folini, D.; Geroux, C.; Constantino, T.

    2017-03-01

    We present the results of a numerical benchmark study for the MUltidimensional Stellar Implicit Code (MUSIC) based on widely applicable two- and three-dimensional compressible hydrodynamics problems relevant to stellar interiors. MUSIC is an implicit large eddy simulation code that uses implicit time integration, implemented as a Jacobian-free Newton Krylov method. A physics based preconditioning technique which can be adjusted to target varying physics is used to improve the performance of the solver. The problems used for this benchmark study include the Rayleigh-Taylor and Kelvin-Helmholtz instabilities, and the decay of the Taylor-Green vortex. Additionally we show a test of hydrostatic equilibrium, in a stellar environment which is dominated by radiative effects. In this setting the flexibility of the preconditioning technique is demonstrated. This work aims to bridge the gap between the hydrodynamic test problems typically used during development of numerical methods and the complex flows of stellar interiors. A series of multidimensional tests were performed and analysed. Each of these test cases was analysed with a simple, scalar diagnostic, with the aim of enabling direct code comparisons. As the tests performed do not have analytic solutions, we verify MUSIC by comparing it to established codes including ATHENA and the PENCIL code. MUSIC is able to both reproduce behaviour from established and widely-used codes as well as results expected from theoretical predictions. This benchmarking study concludes a series of papers describing the development of the MUSIC code and provides confidence in future applications.

  1. Heterogeneous multidimensional scaling for complex networks

    NASA Astrophysics Data System (ADS)

    Xuan, Qi; Ma, Xiaodi; Fu, Chenbo; Dong, Hui; Zhang, Guijun; Yu, Li

    2015-07-01

    Many real-world networks are essentially heterogeneous, where the nodes have different abilities to gain connections. Such networks are difficult to be embedded into low-dimensional Euclidean space if we ignore the heterogeneity and treat all the nodes equally. In this paper, based on a newly defined heterogeneous distance and a generalized network distance under the constraints of network and triangle inequalities, respectively, we propose a new heterogeneous multidimensional scaling method (HMDS) to embed different networks into proper Euclidean spaces. We find that HMDS behaves much better than the traditional multidimensional scaling method (MDS) in embedding different artificial and real-world networks into Euclidean spaces. Besides, we also propose a method to estimate the appropriate dimensions of Euclidean spaces for different networks, and find that the estimated dimensions are quite close to the real dimensions for those geometrical networks under study. These methods thus can help to better understand the evolution of real-world networks, and have practical importance in network visualization, community detection, link prediction and localization of wireless sensors.

  2. Connecting SEM Analysis and Profile Analysis via MDS.

    ERIC Educational Resources Information Center

    Kim, Se-Kang; Davison, Mark L.

    This study was designed to explain how Profile Analysis via Multidimensional Scaling (PAMS) could be viewed as a structural equations model (SEM). The study replicated the major profiles extracted from PAMS in the context of the latent variables in SEM. Data involved the Basic Theme Scales of the Strong Campbell Interest Inventory (Campbell and…

  3. Multidimensional Approximation Operators Generated by Lebesgue-Stieltjes Measures

    NASA Astrophysics Data System (ADS)

    Volkov, Yu I.

    1984-06-01

    A general class of sequences of multidimensional positive linear operators is defined and studied; it includes, in particular, sequences of multidimensional Berstein polynomials. The main asymptotic term is obtained in the remainder when derivatives of functions in certain classes are approximated by derivatives of the values of the operators on these functions. Bibliography: 10 titles.

  4. Multidimensional Linking for Tests with Mixed Item Types

    ERIC Educational Resources Information Center

    Yao, Lihua; Boughton, Keith

    2009-01-01

    Numerous assessments contain a mixture of multiple choice (MC) and constructed response (CR) item types and many have been found to measure more than one trait. Thus, there is a need for multidimensional dichotomous and polytomous item response theory (IRT) modeling solutions, including multidimensional linking software. For example,…

  5. Multidimensional Computerized Adaptive Testing for Indonesia Junior High School Biology

    ERIC Educational Resources Information Center

    Kuo, Bor-Chen; Daud, Muslem; Yang, Chih-Wei

    2015-01-01

    This paper describes a curriculum-based multidimensional computerized adaptive test that was developed for Indonesia junior high school Biology. In adherence to the Indonesian curriculum of different Biology dimensions, 300 items was constructed, and then tested to 2238 students. A multidimensional random coefficients multinomial logit model was…

  6. Entropic uncertainty relations in multidimensional position and momentum spaces

    SciTech Connect

    Huang Yichen

    2011-05-15

    Commutator-based entropic uncertainty relations in multidimensional position and momentum spaces are derived, twofold generalizing previous entropic uncertainty relations for one-mode states. They provide optimal lower bounds and imply the multidimensional variance-based uncertainty principle. The article concludes with an open conjecture.

  7. Multidimensional Physical Self-Concept of Athletes with Physical Disabilities

    ERIC Educational Resources Information Center

    Shapiro, Deborah R.; Martin, Jeffrey J.

    2010-01-01

    The purposes of this investigation were first to predict reported PA (physical activity) behavior and self-esteem using a multidimensional physical self-concept model and second to describe perceptions of multidimensional physical self-concept (e.g., strength, endurance, sport competence) among athletes with physical disabilities. Athletes (N =…

  8. Heteronuclear Multidimensional Protein NMR in a Teaching Laboratory

    ERIC Educational Resources Information Center

    Wright, Nathan T.

    2016-01-01

    Heteronuclear multidimensional NMR techniques are commonly used to study protein structure, function, and dynamics, yet they are rarely taught at the undergraduate level. Here, we describe a senior undergraduate laboratory where students collect, process, and analyze heteronuclear multidimensional NMR experiments using an unstudied Ig domain (Ig2…

  9. The Concept of Aptitude and Multidimensional Validity Revisited.

    ERIC Educational Resources Information Center

    Roeser, Robert W.; Shavelson, Richard J.; Kupermintz, Haggai; Lau, Shun; Ayala, Carlos; Haydel, Angela; Schultz, Susan; Gallagher, Larry; Quihuis, Gisell

    2002-01-01

    Provides an overview of the approach of Richard E. Snow to the concept of aptitude and multidimensional validity and summarizes the studies in this special issue. Overall, studies confirmed the multidimensional structure of science achievement scores, the validity of some key motivational constructs for predicting achievement, and other ideas…

  10. Evaluating Item Fit for Multidimensional Item Response Models

    ERIC Educational Resources Information Center

    Zhang, Bo; Stone, Clement A.

    2008-01-01

    This research examines the utility of the s-x[superscript 2] statistic proposed by Orlando and Thissen (2000) in evaluating item fit for multidimensional item response models. Monte Carlo simulation was conducted to investigate both the Type I error and statistical power of this fit statistic in analyzing two kinds of multidimensional test…

  11. ICM: a web server for integrated clustering of multi-dimensional biomedical data

    PubMed Central

    He, Song; He, Haochen; Xu, Wenjian; Huang, Xin; Jiang, Shuai; Li, Fei; He, Fuchu; Bo, Xiaochen

    2016-01-01

    Large-scale efforts for parallel acquisition of multi-omics profiling continue to generate extensive amounts of multi-dimensional biomedical data. Thus, integrated clustering of multiple types of omics data is essential for developing individual-based treatments and precision medicine. However, while rapid progress has been made, methods for integrated clustering are lacking an intuitive web interface that facilitates the biomedical researchers without sufficient programming skills. Here, we present a web tool, named Integrated Clustering of Multi-dimensional biomedical data (ICM), that provides an interface from which to fuse, cluster and visualize multi-dimensional biomedical data and knowledge. With ICM, users can explore the heterogeneity of a disease or a biological process by identifying subgroups of patients. The results obtained can then be interactively modified by using an intuitive user interface. Researchers can also exchange the results from ICM with collaborators via a web link containing a Project ID number that will directly pull up the analysis results being shared. ICM also support incremental clustering that allows users to add new sample data into the data of a previous study to obtain a clustering result. Currently, the ICM web server is available with no login requirement and at no cost at http://biotech.bmi.ac.cn/icm/. PMID:27131784

  12. Distribution of phenotypes among Bacillus thuringiensis strains.

    PubMed

    Martin, Phyllis A W; Gundersen-Rindal, Dawn E; Blackburn, Michael B

    2010-06-01

    An extensive collection of Bacillus thuringiensis isolates from around the world were phenotypically profiled using standard biochemical tests. Six phenotypic traits occurred in 20-86% of the isolates and were useful in distinguishing isolates: production of urease (U; 20.5% of isolates), hydrolysis of esculin (E; 32.3% of isolates), acid production from salicin (A; 37.4% of isolates), acid production from sucrose (S; 34.0% of isolates), production of phospholipase C or lecithinase (L; 79.7% of isolates), and hydrolysis of starch (T; 85.8% of isolates). With the exception of acid production from salicin and hydrolysis of esculin, which were associated, the traits assorted independently. Of the 64 possible combinations of these six phenotypic characteristics, 15 combinations accounted for ca. 80% of all isolates, with the most common phenotype being TL (23.6% of isolates). Surprisingly, while the biochemical traits generally assorted independently, certain phenotypic traits associated with the parasporal crystal were correlated with certain combinations of biochemical traits. Crystals that remained attached to spores (which tended to be non-toxic to insects) were highly correlated with the phenotypes that included both L and S. Among the 15 most abundant phenotypes characterizing B. thuringiensis strains, amorphous crystals were associated with TLE, TL, T, and Ø (the absence of positive tested biochemical traits). Amorphous crystal types displayed a distinct bias toward toxicity to dipteran insects. Although all common phenotypes included B. thuringiensis isolates producing bipyramidal crystals toxic to lepidopteran insects, those with the highest abundance of these toxic crystals displayed phenotypes TLU, TLUA, TLUAE, and TLAE.

  13. Modeling and multidimensional optimization of a tapered free electron laser

    NASA Astrophysics Data System (ADS)

    Jiao, Y.; Wu, J.; Cai, Y.; Chao, A. W.; Fawley, W. M.; Frisch, J.; Huang, Z.; Nuhn, H.-D.; Pellegrini, C.; Reiche, S.

    2012-05-01

    Energy extraction efficiency of a free electron laser (FEL) can be greatly increased using a tapered undulator and self-seeding. However, the extraction rate is limited by various effects that eventually lead to saturation of the peak intensity and power. To better understand these effects, we develop a model extending the Kroll-Morton-Rosenbluth, one-dimensional theory to include the physics of diffraction, optical guiding, and radially resolved particle trapping. The predictions of the model agree well with that of the GENESIS single-frequency numerical simulations. In particular, we discuss the evolution of the electron-radiation interaction along the tapered undulator and show that the decreasing of refractive guiding is the major cause of the efficiency reduction, particle detrapping, and then saturation of the radiation power. With this understanding, we develop a multidimensional optimization scheme based on GENESIS simulations to increase the energy extraction efficiency via an improved taper profile and variation in electron beam radius. We present optimization results for hard x-ray tapered FELs, and the dependence of the maximum extractable radiation power on various parameters of the initial electron beam, radiation field, and the undulator system. We also study the effect of the sideband growth in a tapered FEL. Such growth induces increased particle detrapping and thus decreased refractive guiding that together strongly limit the overall energy extraction efficiency.

  14. Phenotype definition in epilepsy.

    PubMed

    Winawer, Melodie R

    2006-05-01

    Phenotype definition consists of the use of epidemiologic, biological, molecular, or computational methods to systematically select features of a disorder that might result from distinct genetic influences. By carefully defining the target phenotype, or dividing the sample by phenotypic characteristics, we can hope to narrow the range of genes that influence risk for the trait in the study population, thereby increasing the likelihood of finding them. In this article, fundamental issues that arise in phenotyping in epilepsy and other disorders are reviewed, and factors complicating genotype-phenotype correlation are discussed. Methods of data collection, analysis, and interpretation are addressed, focusing on epidemiologic studies. With this foundation in place, the epilepsy subtypes and clinical features that appear to have a genetic basis are described, and the epidemiologic studies that have provided evidence for the heritability of these phenotypic characteristics, supporting their use in future genetic investigations, are reviewed. Finally, several molecular approaches to phenotype definition are discussed, in which the molecular defect, rather than the clinical phenotype, is used as a starting point.

  15. First insights into the genotype–phenotype map of phenotypic stability in rye

    PubMed Central

    Wang, Yu; Mette, Michael Florian; Miedaner, Thomas; Wilde, Peer; Reif, Jochen C.; Zhao, Yusheng

    2015-01-01

    Improving phenotypic stability of crops is pivotal for coping with the detrimental impacts of climate change. The goal of this study was to gain first insights into the genetic architecture of phenotypic stability in cereals. To this end, we determined grain yield, thousand kernel weight, test weight, falling number, and both protein and soluble pentosan content for two large bi-parental rye populations connected through one common parent and grown in multi-environmental field trials involving more than 15 000 yield plots. Based on these extensive phenotypic data, we calculated parameters for static and dynamic phenotypic stability of the different traits and applied linkage mapping using whole-genome molecular marker profiles. While we observed an absence of large-effect quantitative trait loci (QTLs) underlying yield stability, large and stable QTLs were found for phenotypic stability of test weight, soluble pentosan content, and falling number. Applying genome-wide selection, which in contrast to marker-assisted selection also takes into account loci with small-effect sizes, considerably increased the accuracy of prediction of phenotypic stability for all traits by exploiting both genetic relatedness and linkage between single-nucleotide polymorphisms and QTLs. We conclude that breeding for crop phenotypic stability can be improved in related populations using genomic selection approaches established upon extensive phenotypic data. PMID:25873667

  16. Physical properties of multidimensional and multiferroic composites

    NASA Astrophysics Data System (ADS)

    Mori, Kiyotaka

    The properties of multidimensional and multiferroic composite systems consisting of smart materials are investigated for the intended use in microelectromechanical systems (MEMS) sensor and actuator applications. A multidimensional composite system combines within it different dimensionalities such as 1-D, 2-D, and 3-D constituents. A multiferroic composite system, meanwhile, consists of different ferroics such as ferroelastic, ferromagnetic and ferroelectric materials. We demonstrate effects of dimensionality on thermoelastic properties of NiTi/Si cantilevers for MEMS actuators. The stress state of the bimorph cantilevers is controlled by the dimensionality of the Si cantilever surface (2-D or 1-D corrugated) or the NiTi thin film (2-D or 1-D patterned). Compared to single dimensional NiTi/Si cantilevers the multidimensional device features an improved actuation performance, that is, it combines a small thermoelastic with a large martensitic transformational deflection. We also demonstrate magnetoelectric effects as examples of multiferroic composite systems for novel sensor applications. An example is the magnetic field induced magnetoelectric effect, MEH, in a ferroelectric/ferromagnetic composite PVDF/Terfenol-D. Here, an applied magnetic field induces a piezomagnetic strain in Terfenol-D, which couples to PVDF and induces a piezoelectric charge or voltage. We obtained a MEH coefficient of 1.43 V/cm Oe in agreement with an analytical calculation. The magnetoelastic coupling coefficient of the PVDF/Terfenol-D composite is estimated as 11%. Further, we demonstrate an electrical field induced magnetoelectric effect, MEE, in the ferromagnetic/ferroelectric composites CoB/PZT and PZT/Metglas/PZT. In this case the application of an electric field induces a piezoelectric strain in the PZT ceramic. The strain couples to piezomagnetic CoB or Metglas. Hence, the magnetization of the ferromagnetic materials changes with the electrical field applied to the ferroelectric

  17. Multidimensional scaling of musical time estimations.

    PubMed

    Cocenas-Silva, Raquel; Bueno, José Lino Oliveira; Molin, Paul; Bigand, Emmanuel

    2011-06-01

    The aim of this study was to identify the psycho-musical factors that govern time evaluation in Western music from baroque, classic, romantic, and modern repertoires. The excerpts were previously found to represent variability in musical properties and to induce four main categories of emotions. 48 participants (musicians and nonmusicians) freely listened to 16 musical excerpts (lasting 20 sec. each) and grouped those that seemed to have the same duration. Then, participants associated each group of excerpts to one of a set of sine wave tones varying in duration from 16 to 24 sec. Multidimensional scaling analysis generated a two-dimensional solution for these time judgments. Musical excerpts with high arousal produced an overestimation of time, and affective valence had little influence on time perception. The duration was also overestimated when tempo and loudness were higher, and to a lesser extent, timbre density. In contrast, musical tension had little influence.

  18. AMADA-Analysis of multidimensional astronomical datasets

    NASA Astrophysics Data System (ADS)

    de Souza, R. S.; Ciardi, B.

    2015-09-01

    We present AMADA, an interactive web application to analyze multidimensional datasets. The user uploads a simple ASCII file and AMADA performs a number of exploratory analysis together with contemporary visualizations diagnostics. The package performs a hierarchical clustering in the parameter space, and the user can choose among linear, monotonic or non-linear correlation analysis. AMADA provides a number of clustering visualization diagnostics such as heatmaps, dendrograms, chord diagrams, and graphs. In addition, AMADA has the option to run a standard or robust principal components analysis, displaying the results as polar bar plots. The code is written in R and the web interface was created using the SHINY framework. AMADA source-code is freely available at https://goo.gl/KeSPue, and the shiny-app at http://goo.gl/UTnU7I.

  19. Multidimensional Multiphysics Simulation of TRISO Particle Fuel

    SciTech Connect

    J. D. Hales; R. L. Williamson; S. R. Novascone; D. M. Perez; B. W. Spencer; G. Pastore

    2013-11-01

    Multidimensional multiphysics analysis of TRISO-coated particle fuel using the BISON finite-element based nuclear fuels code is described. The governing equations and material models applicable to particle fuel and implemented in BISON are outlined. Code verification based on a recent IAEA benchmarking exercise is described, and excellant comparisons are reported. Multiple TRISO-coated particles of increasing geometric complexity are considered. It is shown that the code's ability to perform large-scale parallel computations permits application to complex 3D phenomena while very efficient solutions for either 1D spherically symmetric or 2D axisymmetric geometries are straightforward. Additionally, the flexibility to easily include new physical and material models and uncomplicated ability to couple to lower length scale simulations makes BISON a powerful tool for simulation of coated-particle fuel. Future code development activities and potential applications are identified.

  20. Multidimensional multiphysics simulation of TRISO particle fuel

    NASA Astrophysics Data System (ADS)

    Hales, J. D.; Williamson, R. L.; Novascone, S. R.; Perez, D. M.; Spencer, B. W.; Pastore, G.

    2013-11-01

    Multidimensional multiphysics analysis of TRISO-coated particle fuel using the BISON finite element nuclear fuels code is described. The governing equations and material models applicable to particle fuel and implemented in BISON are outlined. Code verification based on a recent IAEA benchmarking exercise is described, and excellent comparisons are reported. Multiple TRISO-coated particles of increasing geometric complexity are considered. The code's ability to use the same algorithms and models to solve problems of varying dimensionality from 1D through 3D is demonstrated. The code provides rapid solutions of 1D spherically symmetric and 2D axially symmetric models, and its scalable parallel processing capability allows for solutions of large, complex 3D models. Additionally, the flexibility to easily include new physical and material models and straightforward ability to couple to lower length scale simulations makes BISON a powerful tool for simulation of coated-particle fuel. Future code development activities and potential applications are identified.

  1. Biological evolution in a multidimensional fitness landscape

    NASA Astrophysics Data System (ADS)

    Saakian, David B.; Kirakosyan, Zara; Hu, Chin-Kun

    2012-09-01

    We considered a multiblock molecular model of biological evolution, in which fitness is a function of the mean types of alleles located at different parts (blocks) of the genome. We formulated an infinite population model with selection and mutation, and calculated the mean fitness. For the case of recombination, we formulated a model with a multidimensional fitness landscape (the dimension of the space is equal to the number of blocks) and derived a theorem about the dynamics of initially narrow distribution. We also considered the case of lethal mutations. We also formulated the finite population version of the model in the case of lethal mutations. Our models, derived for the virus evolution, are interesting also for the statistical mechanics and the Hamilton-Jacobi equation as well.

  2. Masking failures of multidimensional sensors (extended abstract)

    NASA Technical Reports Server (NTRS)

    Chew, Paul; Marzullo, Keith

    1990-01-01

    When a computer monitors a physical process, the computer uses sensors to determine the values of the physical variables that represent the state of the process. A sensor can sometimes fail, however, and in the worst case report a value completely unrelated to the true physical value. The work described is motivated by a methodology for transforming a process control program that can not tolerate sensor failure into one that can. In this methodology, a reliable abstract sensor is created by combining information from several real sensors that measure the same physical value. To be useful, an abstract sensor must deliver reasonably accurate information at reasonable computational cost. Sensors are considered that deliver multidimensional values (e.g., location or velocity in three dimensions, or both temperature and pressure). Geometric techniques are used to derive upper bounds on abstract sensor accuracy and to develop efficient algorithms for implementing abstract sensors.

  3. Biological evolution in a multidimensional fitness landscape.

    PubMed

    Saakian, David B; Kirakosyan, Zara; Hu, Chin-Kun

    2012-09-01

    We considered a multiblock molecular model of biological evolution, in which fitness is a function of the mean types of alleles located at different parts (blocks) of the genome. We formulated an infinite population model with selection and mutation, and calculated the mean fitness. For the case of recombination, we formulated a model with a multidimensional fitness landscape (the dimension of the space is equal to the number of blocks) and derived a theorem about the dynamics of initially narrow distribution. We also considered the case of lethal mutations. We also formulated the finite population version of the model in the case of lethal mutations. Our models, derived for the virus evolution, are interesting also for the statistical mechanics and the Hamilton-Jacobi equation as well.

  4. Multidimensional gas chromatography beyond simple volatiles separation.

    PubMed

    Chin, Sung-Tong; Marriott, Philip J

    2014-08-18

    Multidimensional separation in gas chromatography (MDGC) plays an important role in chemical analysis. This review presents selected literature on MDGC development and examples of the range of functionality reported for MDGC methods over the past 2 decades. With the most obvious advantage of providing much greater capacity for resolving constituents of a sample, MDGC extends analytical efficiency to a more substantial molecular coverage, combined with operational flexibility. But by judicious choice of implementation method, important chemical information relating to the sample, its components, potentially physico-chemical properties, and improved capacity for absolute identification may be realised. Sample-to-sample comparison is improved, and sample characterisation is facilitated especially when MDGC is combined with the informing power of modern mass spectrometry. Innovative MDGC arrangements allow high resolution coupled with spectroscopy and alternative bioassays, and delivers molecular elucidation in ways that are beyond just simple analysis of volatiles.

  5. Multidimensional integrable models of gravitation and cosmology

    NASA Astrophysics Data System (ADS)

    Ivashchuk, V. D.; Melnikov, V. N.

    Review of the motivation and main results in multidimentional gravitation and cosmology is presented. Special attention is devoted to results within the model with scalar fields and fields of forms in the billiard approach for obtaining cosmological solutions with branes and integrable configurations with fluxand black branes. In case of the quantum billiard with branes it is shown that the basis solutions for wave functions vanish in the limit of the formation of billiard walls (i.e., at the singularity) for the D = 11 model which mimics the D = 11 supergravitational cosmology. Another fruitful approach - to multidimensional gravity with higher derivatives is mentioned, which leads to a unified description of inflation and the present accelerated expansion of the Universe. Some of these models explain possible spatial and temporal variations of the fine structure and the gravitational constants.

  6. Quantum effects in homogeneous multidimensional cosmologies

    SciTech Connect

    Szydlowski, M.; Szczesny, J.

    1988-12-15

    In the present paper we determine quantum distribution functions for a wide class of multidimensional cosmological models. The exact formulas for quantum distribution functions are given and their universal character at high and low temperatures shown. The obtained formulas provide us with the possibility to investigate the metric back reaction and to discuss the dimensional reduction problem. The assumption of the low-temperature approximation gives us the possibility to discuss the dynamics by using the methods of dynamical systems. Stable solutions, within the class FRW x S/sup 3/ x S/sup 3/ models, where FRW denotes Friedmann, Robertson and Walker, are discussed, and it is shown that only a zero-measure set of trajectories in the phase space leads to a solution with a static microspace. This analysis shows that, insofar as quantum effects lead to solutions with a static microspace, these solutions are unstable.

  7. DRACO---A New Multidimensional Hydrocode

    NASA Astrophysics Data System (ADS)

    Keller, D.; Collins, T. J. B.; Delettrez, J. A.; McKenty, P. W.; Radha, P. B.; Town, R. P. J.; Whitney, B.; Moses, G. A.

    1999-11-01

    A program to develop a new multidimensional hydrocode is underway at LLE. DRACO is an arbitrary Lagrange-Eulerian (ALE) code designed to run in 1, 2, and 3 dimensions in planar (cartesian), cylindrical, and spherical geometries. The basic hydroportion of DRACO employs second-order rezoning and interface tracking. A mixed-material equation of state (EOS) using SESAME or Wisconsin table lookups has recently been incorporated. One of the main objectives of the program is to fully exploit the parallel capabilities of the 32-processor SGI Origin-2000. This paper will describe the basic code, present results of our parallel work, and show results of recent burnthrough calculations. This work was supported by the U.S. Department of Energy Office of Inertial Confinement Fusion under Cooperative Agreement No. DE-FC03-92SF19460, the University of Rochester, and the New York State Energy Research and Development Authority.

  8. Multidimensional student skills with collaborative filtering

    NASA Astrophysics Data System (ADS)

    Bergner, Yoav; Rayyan, Saif; Seaton, Daniel; Pritchard, David E.

    2013-01-01

    Despite the fact that a physics course typically culminates in one final grade for the student, many instructors and researchers believe that there are multiple skills that students acquire to achieve mastery. Assessment validation and data analysis in general may thus benefit from extension to multidimensional ability. This paper introduces an approach for model determination and dimensionality analysis using collaborative filtering (CF), which is related to factor analysis and item response theory (IRT). Model selection is guided by machine learning perspectives, seeking to maximize the accuracy in predicting which students will answer which items correctly. We apply the CF to response data for the Mechanics Baseline Test and combine the results with prior analysis using unidimensional IRT.

  9. Multidimensional Scaling Visualization Using Parametric Entropy

    NASA Astrophysics Data System (ADS)

    Lopes, António M.; Tenreiro Machado, J. A.; Galhano, Alexandra M.

    2015-12-01

    This paper studies complex systems using a generalized multidimensional scaling (MDS) technique. Complex systems are characterized by time-series responses, interpreted as a manifestation of their dynamics. Two types of time-series are analyzed, namely 18 stock markets and the gross domestic product per capita of 18 countries. For constructing the MDS charts, indices based on parametric entropies are adopted. Multiparameter entropies allow the variation of the parameters leading to alternative sets of charts. The final MDS maps are then assembled by means of Procrustes’ method that maximizes the fit between the individual charts. Therefore, the proposed method can be interpreted as a generalization to higher dimensions of the standard technique that represents (and discretizes) items by means of single “points” (i.e. zero-dimensional “objects”). The MDS plots, involving one-, two- and three-dimensional “objects”, reveal a good performance in capturing the correlations between data.

  10. Testing for uniformity in multidimensional data.

    PubMed

    Smith, S P; Jain, A K

    1984-01-01

    Testing for uniformity in multidimensional data is important in exploratory pattern analysis, statistical pattern recognition, and image processing. The goal of this paper is to determine whether the data follow the uniform distribution over some compact convex set in K-dimensional space, called the sampling window. We first provide a simple, computationally efficient method for generating a uniformly distributed sample over a set which approximates the convex hul of the data. We then test for uniformity by comparing this generated sample to the data by using Friedman-Rafsky's minimal spanning tree (MST) based test. Experiments with both simulated and real data indicate that this MST-based test is useful in deciding if data are uniform.

  11. Multidimensional numerical modeling of heat exchangers

    NASA Astrophysics Data System (ADS)

    Sha, W. T.; Yang, C. I.; Kao, T. T.; Cho, S. M.

    A comprehensive, multidimensional, thermal-hydraulic model is developed for the analysis of shell-and-tube heat exchangers for liquid-metal services. For the shellside fluid, the conservation equations of mass, momentum, and energy for continuum fluids are modified using the concept of porosity, surface permeability and distributed resistance to account for the blockage effects due to the presence of heat-transfer tubes, flow baffles/shrouds, the support plates, etc. On the tubeside, the heat-transfer tubes are connected in parallel between the inlet and outlet plenums, and tubeside flow distribution is calculated based on the plenum-to-plenum pressure difference being equal for all tubes. It is assumed that the fluid remains single-phase on the shell side and may undergo phase-change on the tube side, thereby simulating the conditions of Liquid Metal Fast Breeder Reactor (LMFBR) intermediate heat exchangers (IHX) and steam generators (SG).

  12. Transonic Shocks in Multidimensional Divergent Nozzles

    NASA Astrophysics Data System (ADS)

    Bae, Myoungjean; Feldman, Mikhail

    2011-07-01

    We establish existence, uniqueness and stability of transonic shocks for a steady compressible non-isentropic potential flow system in a multidimensional divergent nozzle with an arbitrary smooth cross-section, for a prescribed exit pressure. The proof is based on solving a free boundary problem for a system of partial differential equations consisting of an elliptic equation and a transport equation. In the process, we obtain unique solvability for a class of transport equations with velocity fields of weak regularity (non-Lipschitz), an infinite dimensional weak implicit mapping theorem which does not require continuous Fréchet differentiability, and regularity theory for a class of elliptic partial differential equations with discontinuous oblique boundary conditions.

  13. The Phenotype of Spontaneous Preterm Birth: Application of a Clinical Phenotyping Tool

    PubMed Central

    Manuck, Tracy A.; Esplin, M. Sean; Biggio, Joseph; Bukowski, Radek; Parry, Samuel; Zhang, Heping; Varner, Michael W.; Andrews, William; Saade, George; Sadovsky, Yoel; Reddy, Uma M.; Ilekis, John

    2015-01-01

    Objective Spontaneous preterm birth (SPTB) is a complex condition that is likely a final common pathway with multiple possible etiologies. We hypothesized that a comprehensive classification system could appropriately group women with similar STPB etiologies, and provide an explanation, at least in part, for the disparities in SPTB associated with race and gestational age at delivery. Study Design Planned analysis of a multicenter, prospective study of singleton SPTB. Women with SPTB < 34 weeks were included. We defined 9 potential SPTB phenotypes based on clinical data, including infection/inflammation, maternal stress, decidual hemorrhage, uterine distention, cervical insufficiency, placental dysfunction, premature rupture of the membranes, maternal comorbidities, and familial factors. Each woman was evaluated for each phenotype. Delivery gestational age was compared between those with and without each phenotype. Phenotype profiles were also compared between women with very early (20.0–27.9 weeks) SPTB vs. those with early SPTB (28.0–34.0 weeks), and between African-American and Caucasian women. Statistical analysis was by t-test and chi-square as appropriate. Results The phenotyping tool was applied to 1025 women with SPTB who delivered at a mean 30.0 (+/− 3.2) weeks gestation. Of these, 800 (78%) had ≥2 phenotypes. Only 43 (4.2%) had no phenotypes. The 281 women with early SPTB were more likely to have infection/inflammation, decidual hemorrhage, and cervical insufficiency phenotypes (all p≤0.001). African-American women had more maternal stress and cervical insufficiency but less decidual hemorrhage and placental dysfunction compared to Caucasian women (all p<0.05). Gestational age at delivery decreased as the number of phenotypes present increased. Conclusions Precise SPTB phenotyping classifies women with SPTB and identifies specific differences between very early and early SPTB and between African-Americans and Caucasians. PMID:25687564

  14. Identifying Major Profile Patterns in a Population: An Exploratory Study of WAIS and GATB Patterns.

    ERIC Educational Resources Information Center

    Davison, Mark L.; And Others

    1996-01-01

    Results of profile analysis via multidimensional scaling (PAMS), a technique for studying the most prominent profiles in a battery of measures, are reported for the Wechsler Adult Intelligence Scale--Revised (WAIS) and the General Aptitude Test Battery (GATB). PAMS profiles and the methodological features of the PAMS approach are discussed. (SLD)

  15. Towards recommendations for metadata and data handling in plant phenotyping.

    PubMed

    Krajewski, Paweł; Chen, Dijun; Ćwiek, Hanna; van Dijk, Aalt D J; Fiorani, Fabio; Kersey, Paul; Klukas, Christian; Lange, Matthias; Markiewicz, Augustyn; Nap, Jan Peter; van Oeveren, Jan; Pommier, Cyril; Scholz, Uwe; van Schriek, Marco; Usadel, Björn; Weise, Stephan

    2015-09-01

    Recent methodological developments in plant phenotyping, as well as the growing importance of its applications in plant science and breeding, are resulting in a fast accumulation of multidimensional data. There is great potential for expediting both discovery and application if these data are made publicly available for analysis. However, collection and storage of phenotypic observations is not yet sufficiently governed by standards that would ensure interoperability among data providers and precisely link specific phenotypes and associated genomic sequence information. This lack of standards is mainly a result of a large variability of phenotyping protocols, the multitude of phenotypic traits that are measured, and the dependence of these traits on the environment. This paper discusses the current situation of standardization in the area of phenomics, points out the problems and shortages, and presents the areas that would benefit from improvement in this field. In addition, the foundations of the work that could revise the situation are proposed, and practical solutions developed by the authors are introduced.

  16. Macrophage phenotypes in atherosclerosis.

    PubMed

    Colin, Sophie; Chinetti-Gbaguidi, Giulia; Staels, Bart

    2014-11-01

    Initiation and progression of atherosclerosis depend on local inflammation and accumulation of lipids in the vascular wall. Although many cells are involved in the development and progression of atherosclerosis, macrophages are fundamental contributors. For nearly a decade, the phenotypic heterogeneity and plasticity of macrophages has been studied. In atherosclerotic lesions, macrophages are submitted to a large variety of micro-environmental signals, such as oxidized lipids and cytokines, which influence the phenotypic polarization and activation of macrophages resulting in a dynamic plasticity. The macrophage phenotype spectrum is characterized, at the extremes, by the classical M1 macrophages induced by T-helper 1 (Th-1) cytokines and by the alternative M2 macrophages induced by Th-2 cytokines. M2 macrophages can be further classified into M2a, M2b, M2c, and M2d subtypes. More recently, additional plaque-specific macrophage phenotypes have been identified, termed as Mox, Mhem, and M4. Understanding the mechanisms and functional consequences of the phenotypic heterogeneity of macrophages will contribute to determine their potential role in lesion development and plaque stability. Furthermore, research on macrophage plasticity could lead to novel therapeutic approaches to counteract cardiovascular diseases such as atherosclerosis. The present review summarizes our current knowledge on macrophage subsets in atherosclerotic plaques and mechanism behind the modulation of the macrophage phenotype.

  17. A study of multidimensional modeling approaches for data warehouse

    NASA Astrophysics Data System (ADS)

    Yusof, Sharmila Mat; Sidi, Fatimah; Ibrahim, Hamidah; Affendey, Lilly Suriani

    2016-08-01

    Data warehouse system is used to support the process of organizational decision making. Hence, the system must extract and integrate information from heterogeneous data sources in order to uncover relevant knowledge suitable for decision making process. However, the development of data warehouse is a difficult and complex process especially in its conceptual design (multidimensional modeling). Thus, there have been various approaches proposed to overcome the difficulty. This study surveys and compares the approaches of multidimensional modeling and highlights the issues, trend and solution proposed to date. The contribution is on the state of the art of the multidimensional modeling design.

  18. A Conceptual Model for Multidimensional Analysis of Documents

    NASA Astrophysics Data System (ADS)

    Ravat, Franck; Teste, Olivier; Tournier, Ronan; Zurlfluh, Gilles

    Data warehousing and OLAP are mainly used for the analysis of transactional data. Nowadays, with the evolution of Internet, and the development of semi-structured data exchange format (such as XML), it is possible to consider entire fragments of data such as documents as analysis sources. As a consequence, an adapted multidimensional analysis framework needs to be provided. In this paper, we introduce an OLAP multidimensional conceptual model without facts. This model is based on the unique concept of dimensions and is adapted for multidimensional document analysis. We also provide a set of manipulation operations.

  19. NASA Multidimensional Stirling Convertor Code Developed

    NASA Technical Reports Server (NTRS)

    Tew, Roy C.; Thieme, Lanny G.

    2004-01-01

    A high-efficiency Stirling Radioisotope Generator (SRG) for use on potential NASA Space Science missions is being developed by the Department of Energy, Lockheed Martin, Stirling Technology Company, and the NASA Glenn Research Center. These missions may include providing spacecraft onboard electric power for deep space missions or power for unmanned Mars rovers. Glenn is also developing advanced technology for Stirling convertors, aimed at substantially improving the specific power and efficiency of the convertor and the overall power system. Performance and mass improvement goals have been established for second- and third-generation Stirling radioisotope power systems. Multiple efforts are underway to achieve these goals, both in house at Glenn and under various grants and contracts. These efforts include the development of a multidimensional Stirling computational fluid dynamics code, high-temperature materials, advanced controllers, an end-to-end system dynamics model, low-vibration techniques, advanced regenerators, and a lightweight convertor. Under a NASA grant, Cleveland State University (CSU) and its subcontractors, the University of Minnesota (UMN) and Gedeon Associates, have developed a twodimensional computer simulation of a CSUmod Stirling convertor. The CFD-ACE commercial software developed by CFD Research Corp. of Huntsville, Alabama, is being used. The CSUmod is a scaled version of the Stirling Technology Demonstrator Convertor (TDC), which was designed and fabricated by the Stirling Technology Company and is being tested by NASA. The schematic illustrates the structure of this model. Modeled are the fluid-flow and heat-transfer phenomena that occur in the expansion space, the heater, the regenerator, the cooler, the compression space, the surrounding walls, and the moving piston and displacer. In addition, the overall heat transfer, the indicated power, and the efficiency can be calculated. The CSUmod model is being converted to a two

  20. Exploring multidimensional free energy surfaces of peptides

    NASA Astrophysics Data System (ADS)

    Wang, Yan; Kuczera, Krzysztof

    1997-03-01

    A new statistical mechanics thermodynamic integration method is presented, enabling exploration of multidimensional conformational free energy surfaces of large flexible molecules. In this approach a single molecular dynamics simulation in which a set of coordinates has been constrained to fixed values yields the free energy gradient with respect to all coordinates in the set. The availability of the multidimensional gradient opens new possibilities for exploration of molecular conformational free energy surfaces, including free energy optimization to locate free energy minima, calculation of higher free energy derivatives, and finding optimal free energy paths between states. Additionally, choosing of all "soft" degrees of freedom as the constrained set leads to accelerated convergence of averages, effectively overcoming the sampling problem of free energy simulations. Two applications of the method are presented: Helical states of model peptides. For model peptides (Ala)n and (Aib)n where n=6,8,10 and Aib is α-methylalanine in vacuum, free energy maps and free energy optimization in φ-ψ space are used to locate free energy minima corresponding to α-, π- and 3_10-helical structures. The stability of the minima is characterized by calculating numerical second derivatives of the free energy. Free energy decomposition is employed to reveal the molecular mechanism for the improved stability of the 3_10h relative to the ah in Aib-containing peptides. DPDPE peptide pre-organization. For the linear form of the opioid peptide DPDPE in aqueous solution, the effective local sampling made possible by fixing all soft degrees of freedom is used to calculate the free energy difference between the open and cyclic-like structures, providing an estimate of the free energy of pre-organizing the peptide for disulfide bond formation. The open structure was found to be more stable by 4.0 ± 0.8 kcal/mol. The cyclic-like conformation was much better solvated than the open

  1. Adaptive free energy sampling in multidimensional collective variable space using boxed molecular dynamics.

    PubMed

    O'Connor, Mike; Paci, Emanuele; McIntosh-Smith, Simon; Glowacki, David R

    2016-12-22

    The past decade has seen the development of a new class of rare event methods in which molecular configuration space is divided into a set of boundaries/interfaces, and then short trajectories are run between boundaries. For all these methods, an important concern is how to generate boundaries. In this paper, we outline an algorithm for adaptively generating boundaries along a free energy surface in multi-dimensional collective variable (CV) space, building on the boxed molecular dynamics (BXD) rare event algorithm. BXD is a simple technique for accelerating the simulation of rare events and free energy sampling which has proven useful for calculating kinetics and free energy profiles in reactive and non-reactive molecular dynamics (MD) simulations across a range of systems, in both NVT and NVE ensembles. Two key developments outlined in this paper make it possible to automate BXD, and to adaptively map free energy and kinetics in complex systems. First, we have generalized BXD to multidimensional CV space. Using strategies from rigid-body dynamics, we have derived a simple and general velocity-reflection procedure that conserves energy for arbitrary collective variable definitions in multiple dimensions, and show that it is straightforward to apply BXD to sampling in multidimensional CV space so long as the Cartesian gradients ∇CV are available. Second, we have modified BXD to undertake on-the-fly statistical analysis during a trajectory, harnessing the information content latent in the dynamics to automatically determine boundary locations. Such automation not only makes BXD considerably easier to use; it also guarantees optimal boundaries, speeding up convergence. We have tested the multidimensional adaptive BXD procedure by calculating the potential of mean force for a chemical reaction recently investigated using both experimental and computational approaches - i.e., F + CD3CN → DF + D2CN in both the gas phase and a strongly coupled explicit CD3CN solvent

  2. A Scalar Product Model for the Multidimensional Scaling of Choice

    ERIC Educational Resources Information Center

    Bechtel, Gordon G.; And Others

    1971-01-01

    Contains a solution for the multidimensional scaling of pairwise choice when individuals are represented as dimensional weights. The analysis supplies an exact least squares solution and estimates of group unscalability parameters. (DG)

  3. The Measurement of Self-Rated Depression: A Multidimensional Approach.

    ERIC Educational Resources Information Center

    Bolon, Kevin; Barling, Julian

    1980-01-01

    Investigates the capacity of the Zung Self-Rating Depression Scale for providing specific multidimensional descriptors of depressive behavior. Ideational, physiological and behavioral depression factors were evident in data from 96 normal, white university student volunteers. (Author/RH)

  4. Design of Multidimensional Shinnar-Le Roux RF Pulses

    PubMed Central

    Ma, Chao; Liang, Zhi-Pei

    2014-01-01

    Purpose To generalize the conventional Shinnar-Le Roux (SLR) method for the design of multidimensional RF pulses. Methods Using echo-planar gradients, the multidimensional RF pulse design problem was converted into a series of 1D polynomial design problems. Each of the 1D polynomial design problems was solved efficiently. B0 inhomogeneity compensation and design of spatial-spectral pulses were also considered. Results The proposed method was used to design 2D excitation and refocusing pulses. The results were validated through Bloch equation simulation and experiments on a 3.0 T scanner. Large-tip-angle, equiripple-error, multidimensional excitation was achieved with ripple levels closely matching the design specifications. Conclusion The conventional SLR method can be extended to design multidimensional RF pulses. The proposed method achieves almost equiripple excitation errors, allows easy control of the tradeoff among design parameters, and is computationally efficient. PMID:24578212

  5. A multidimensional subdiffusion model: An arbitrage-free market

    NASA Astrophysics Data System (ADS)

    Li, Guo-Hua; Zhang, Hong; Luo, Mao-Kang

    2012-12-01

    To capture the subdiffusive characteristics of financial markets, the subordinated process, directed by the inverse α-stale subordinator Sα(t) for 0 < α < 1, has been employed as the model of asset prices. In this article, we introduce a multidimensional subdiffusion model that has a bond and K correlated stocks. The stock price process is a multidimensional subdiffusion process directed by the inverse α-stable subordinator. This model describes the period of stagnation for each stock and the behavior of the dependency between multiple stocks. Moreover, we derive the multidimensional fractional backward Kolmogorov equation for the subordinated process using the Laplace transform technique. Finally, using a martingale approach, we prove that the multidimensional subdiffusion model is arbitrage-free, and also gives an arbitrage-free pricing rule for contingent claims associated with the martingale measure.

  6. The space transformation in the simulation of multidimensional random fields

    USGS Publications Warehouse

    Christakos, G.

    1987-01-01

    Space transformations are proposed as a mathematically meaningful and practically comprehensive approach to simulate multidimensional random fields. Within this context the turning bands method of simulation is reconsidered and improved in both the space and frequency domains. ?? 1987.

  7. Development and Validation of Triarchic Psychopathy Scales from the Multidimensional Personality Questionnaire

    PubMed Central

    Brislin, Sarah J.; Drislane, Laura E.; Smith, Shannon Toney; Edens, John F.; Patrick, Christopher J.

    2015-01-01

    Psychopathy is conceptualized by the triarchic model as encompassing three distinct phenotypic constructs: boldness, meanness, and disinhibition. In the current study, the Multidimensional Personality Questionnaire (MPQ), a normal-range personality measure, was evaluated for representation of these three constructs. Consensus ratings were used to identify MPQ items most related to each triarchic (Tri) construct. Scale measures were developed from items indicative of each construct, and scores for these scales were evaluated for convergent and discriminant validity in community (N = 176) and incarcerated samples (N = 240). A cross the two samples, MPQ-Tri scale scores demonstrated good internal consistencies and relationships with criterion measures of various types consistent with predictions based on the triarchic model. Findings are discussed in terms of their implications for further investigation of the triarchic model constructs in preexisting datasets that include the MPQ, in particular longitudinal and genetically informative datasets. PMID:25642934

  8. Overeating phenotypes in overweight and obese children.

    PubMed

    Boutelle, Kerri N; Peterson, Carol B; Crosby, Ross D; Rydell, Sarah A; Zucker, Nancy; Harnack, Lisa

    2014-05-01

    The purpose of this study was to identify overeating phenotypes and their correlates in overweight and obese children. One hundred and seventeen treatment-seeking overweight and obese 8-12year-old children and their parents completed the study. Children completed an eating in the absence of hunger (EAH) paradigm, the Eating Disorder Examination interview, and measurements of height and weight. Parents and children completed questionnaires that evaluated satiety responsiveness, food responsiveness, negative affect eating, external eating and eating in the absence of hunger. Latent profile analysis was used to identify heterogeneity in overeating phenotypes in the child participants. Latent classes were then compared on measures of demographics, obesity status and nutritional intake. Three latent classes of overweight and obese children were identified: High Satiety Responsive, High Food Responsive, and Moderate Satiety and Food Responsive. Results indicated that the High Food Responsive group had higher BMI and BMI-Z scores compared to the High Satiety Responsive group. No differences were found among classes in demographics or nutritional intake. This study identified three overeating phenotypes, supporting the heterogeneity of eating patterns associated with overweight and obesity in treatment-seeking children. These finding suggest that these phenotypes can potentially be used to identify high risk groups, inform prevention and intervention targets, and develop specific treatments for these behavioral phenotypes.

  9. Central Schemes for Multi-Dimensional Hamilton-Jacobi Equations

    NASA Technical Reports Server (NTRS)

    Bryson, Steve; Levy, Doron; Biegel, Bryan (Technical Monitor)

    2002-01-01

    We present new, efficient central schemes for multi-dimensional Hamilton-Jacobi equations. These non-oscillatory, non-staggered schemes are first- and second-order accurate and are designed to scale well with an increasing dimension. Efficiency is obtained by carefully choosing the location of the evolution points and by using a one-dimensional projection step. First-and second-order accuracy is verified for a variety of multi-dimensional, convex and non-convex problems.

  10. Multidimensional Programming Methods for Energy Facility Siting: Alternative Approaches

    NASA Technical Reports Server (NTRS)

    Solomon, B. D.; Haynes, K. E.

    1982-01-01

    The use of multidimensional optimization methods in solving power plant siting problems, which are characterized by several conflicting, noncommensurable objectives is addressed. After a discussion of data requirements and exclusionary site screening methods for bounding the decision space, classes of multiobjective and goal programming models are discussed in the context of finite site selection. Advantages and limitations of these approaches are highlighted and the linkage of multidimensional methods with the subjective, behavioral components of the power plant siting process is emphasized.

  11. Towards a genuinely multi-dimensional upwind scheme

    NASA Technical Reports Server (NTRS)

    Powell, Kenneth G.; Vanleer, Bram; Roe, Philip L.

    1990-01-01

    Methods of incorporating multi-dimensional ideas into algorithms for the solution of Euler equations are presented. Three schemes are developed and tested: a scheme based on a downwind distribution, a scheme based on a rotated Riemann solver and a scheme based on a generalized Riemann solver. The schemes show an improvement over first-order, grid-aligned upwind schemes, but the higher-order performance is less impressive. An outlook for the future of multi-dimensional upwind schemes is given.

  12. Multidimensional Hybridization of Dark Surface Plasmons.

    PubMed

    Yankovich, Andrew B; Verre, Ruggero; Olsén, Erik; Persson, Anton E O; Trinh, Viet; Dovner, Gudrun; Käll, Mikael; Olsson, Eva

    2017-04-07

    Synthetic three-dimensional (3D) nanoarchitectures are providing more control over light-matter interactions and rapidly progressing photonic-based technology. These applications often utilize the strong synergy between electromagnetic fields and surface plasmons (SPs) in metallic nanostructures. However, many of the SP interactions hosted by complex 3D nanostructures are poorly understood because they involve dark hybridized states that are typically undetectable with far-field optical spectroscopy. Here, we use experimental and theoretical electron energy loss spectroscopy to elucidate dark SPs and their interactions in layered metal-insulator-metal disc nanostructures. We go beyond the established dipole SP hybridization analysis by measuring breathing and multipolar SP hybridization. In addition, we reveal multidimensional SP hybridization that simultaneously utilizes in-plane and out-of-plane SP coupling. Near-field classic electrodynamics calculations provide excellent agreement with all experiments. These results advance the fundamental understanding of SP hybridization in 3D nanostructures and provide avenues to further tune the interaction between electromagnetic fields and matter.

  13. Multidimensional In Vivo Hazard Assessment Using Zebrafish

    PubMed Central

    Tanguay, Robert L.

    2014-01-01

    There are tens of thousands of man-made chemicals in the environment; the inherent safety of most of these chemicals is not known. Relevant biological platforms and new computational tools are needed to prioritize testing of chemicals with limited human health hazard information. We describe an experimental design for high-throughput characterization of multidimensional in vivo effects with the power to evaluate trends relating to commonly cited chemical predictors. We evaluated all 1060 unique U.S. EPA ToxCast phase 1 and 2 compounds using the embryonic zebrafish and found that 487 induced significant adverse biological responses. The utilization of 18 simultaneously measured endpoints means that the entire system serves as a robust biological sensor for chemical hazard. The experimental design enabled us to describe global patterns of variation across tested compounds, evaluate the concordance of the available in vitro and in vivo phase 1 data with this study, highlight specific mechanisms/value-added/novel biology related to notochord development, and demonstrate that the developmental zebrafish detects adverse responses that would be missed by less comprehensive testing strategies. PMID:24136191

  14. Multidimensional indexing tools for the virtual observatory

    NASA Astrophysics Data System (ADS)

    Csabai, I.; Dobos, L.; Trencséni, M.; Herczegh, G.; Józsa, P.; Purger, N.; Budavári, T.; Szalay, A. S.

    2007-10-01

    The last decade has seen a dramatic change in the way astronomy is carried out. The dawn of the the new microelectronic devices, like CCDs has dramatically extended the amount of observed data. Large, in some cases all sky surveys emerged in almost all the wavelength ranges of the observable spectrum of electromagnetic waves. This large amount of data has to be organized, published electronically and a new style of data retrieval is essential to exploit all the hidden information in the multiwavelength data. Many statistical algorithms required for these tasks run reasonably fast when using small sets of in-memory data, but take noticeable performance hits when operating on large databases that do not fit into memory. We utilize new software technologies to develop and evaluate fast multidimensional indexing schemes that inherently follow the underlying, highly non-uniform distribution of the data: they are layered uniform indices, hierarchical binary space partitioning, and sampled flat Voronoi tessellation of the data. These techniques can dramatically speed up operations such as finding similar objects by example, classifying objects or comparing extensive simulation sets with observations.

  15. Correlative visualization techniques for multidimensional data

    NASA Technical Reports Server (NTRS)

    Treinish, Lloyd A.; Goettsche, Craig

    1989-01-01

    Critical to the understanding of data is the ability to provide pictorial or visual representation of those data, particularly in support of correlative data analysis. Despite the advancement of visualization techniques for scientific data over the last several years, there are still significant problems in bringing today's hardware and software technology into the hands of the typical scientist. For example, there are other computer science domains outside of computer graphics that are required to make visualization effective such as data management. Well-defined, flexible mechanisms for data access and management must be combined with rendering algorithms, data transformation, etc. to form a generic visualization pipeline. A generalized approach to data visualization is critical for the correlative analysis of distinct, complex, multidimensional data sets in the space and Earth sciences. Different classes of data representation techniques must be used within such a framework, which can range from simple, static two- and three-dimensional line plots to animation, surface rendering, and volumetric imaging. Static examples of actual data analyses will illustrate the importance of an effective pipeline in data visualization system.

  16. Multi-dimensional cosmology and GUP

    SciTech Connect

    Zeynali, K.; Motavalli, H.; Darabi, F. E-mail: f.darabi@azaruniv.edu

    2012-12-01

    We consider a multidimensional cosmological model with FRW type metric having 4-dimensional space-time and d-dimensional Ricci-flat internal space sectors with a higher dimensional cosmological constant. We study the classical cosmology in commutative and GUP cases and obtain the corresponding exact solutions for negative and positive cosmological constants. It is shown that for negative cosmological constant, the commutative and GUP cases result in finite size universes with smaller size and longer ages, and larger size and shorter age, respectively. For positive cosmological constant, the commutative and GUP cases result in infinite size universes having late time accelerating behavior in good agreement with current observations. The accelerating phase starts in the GUP case sooner than the commutative case. In both commutative and GUP cases, and for both negative and positive cosmological constants, the internal space is stabilized to the sub-Planck size, at least within the present age of the universe. Then, we study the quantum cosmology by deriving the Wheeler-DeWitt equation, and obtain the exact solutions in the commutative case and the perturbative solutions in GUP case, to first order in the GUP small parameter, for both negative and positive cosmological constants. It is shown that good correspondence exists between the classical and quantum solutions.

  17. Multidimensional imaging of the thorax: practical applications.

    PubMed

    Ravenel, J G; McAdams, H P; Remy-Jardin, M; Remy, J

    2001-10-01

    Over the past decade, faster CT scan times, thinner collimation, and the development of multirow detectors, coupled with the increasing capability of computers to process large amounts of data in short periods of time, have lead to an expansion in the ability to create diagnostically useful two-dimensional (2D) and three-dimensional (3D) images within the thorax. Applications within the thorax include, but are not limited to, evaluation of pulmonary and systemic vasculature, evaluation of the tracheobronchial tree, and delineation of diffuse lung disease. Pulmonary nodule volume and growth can be more accurately predicted, and represents an improvement in the evaluation of the solitary pulmonary nodule. Multiplanar images increase our understanding of thoracic anatomy and can help to guide bronchoscopic procedures. Because there are strengths and weaknesses to all the reconstruction algorithms, the utility of any given technique is dependent on the clinical question to be answered. For instance, although maximum intensity projection imaging (MIP) is helpful in the evaluation of micronodular lung disease, it is of little value in the diagnosis of aortic dissection. As the ability to generate faster and more precise multidimensional images grow, the demand for such imaging is likely to increase. In this review, the authors discuss the various reconstruction techniques available, followed by a discussion of the clinical applications.

  18. Outstanding Phenotypic Differences in the Profile of Amyloid-β between Tg2576 and APPswe/PS1dE9 Transgenic Mouse Models of Alzheimer’s Disease

    PubMed Central

    Allué, José Antonio; Sarasa, Leticia; Izco, María; Pérez-Grijalba, Virginia; Fandos, Noelia; Pascual-Lucas, María; Ogueta, Samuel; Pesini, Pedro; Sarasa, Manuel

    2016-01-01

    APPswe/PS1dE9 and Tg2576 are very common transgenic mouse models of Alzheimer’s disease (AD), used in many laboratories as tools to research the mechanistic process leading to the disease. In order to augment our knowledge about the amyloid-β (Aβ) isoforms present in both transgenic mouse models, we have developed two chromatographic methods, one acidic and the other basic, for the characterization of the Aβ species produced in the brains of the two transgenic mouse models. After immunoprecipitation and micro-liquid chromatography-electrospray ionization mass spectrometry/mass spectrometry, 10 species of Aβ, surprisingly all of human origin, were detected in the brain of Tg2576 mouse, whereas 39 species, of both murine and human origin, were detected in the brain of the APP/PS1 mouse. To the best of our knowledge, this is the first study showing the identification of such a high number of Aβ species in the brain of the APP/PS1 transgenic mouse, whereas, in contrast, a much lower number of Aβ species were identified in the Tg2576 mouse. Therefore, this study brings to light a relevant phenotypic difference between these two popular mice models of AD. PMID:27258422

  19. Versatile lipid profiling by liquid chromatography-high resolution mass spectrometry using all ion fragmentation and polarity switching. Preliminary application for serum samples phenotyping related to canine mammary cancer.

    PubMed

    Gallart-Ayala, H; Courant, F; Severe, S; Antignac, J-P; Morio, F; Abadie, J; Le Bizec, B

    2013-09-24

    Lipids represent an extended class of substances characterized by such high variety and complexity that makes their unified analyses by liquid chromatography coupled to either high resolution or tandem mass spectrometry (LC-HRMS or LC-MS/MS) a real challenge. In the present study, a new versatile methodology associating ultra high performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-HRMS/MS) have been developed for a comprehensive analysis of lipids. The use of polarity switching and "all ion fragmentation" (AIF) have been two action levels particularly exploited to finally permit the detection and identification of a multi-class and multi-analyte extended range of lipids in a single run. For identification purposes, both higher energy collision dissociation (HCD) and in-source CID (collision induced dissociation) fragmentation were evaluated in order to obtain information about the precursor and product ions in the same spectra. This approach provides both class-specific and lipid-specific fragments, enhancing lipid identification. Finally, the developed method was applied for differential phenotyping of serum samples collected from pet dogs developing spontaneous malignant mammary tumors and health controls. A biological signature associated with the presence of cancer was then successfully revealed from this lipidome analysis, which required to be further investigated and confirmed at larger scale.

  20. Stem cells isolated from adipose tissue of obese patients show changes in their transcriptomic profile that indicate loss in stemcellness and increased commitment to an adipocyte-like phenotype

    PubMed Central

    2013-01-01

    Background The adipose tissue is an endocrine regulator and a risk factor for atherosclerosis and cardiovascular disease when by excessive accumulation induces obesity. Although the adipose tissue is also a reservoir for stem cells (ASC) their function and “stemcellness” has been questioned. Our aim was to investigate the mechanisms by which obesity affects subcutaneous white adipose tissue (WAT) stem cells. Results Transcriptomics, in silico analysis, real-time polymerase chain reaction (PCR) and western blots were performed on isolated stem cells from subcutaneous abdominal WAT of morbidly obese patients (ASCmo) and of non-obese individuals (ASCn). ASCmo and ASCn gene expression clustered separately from each other. ASCmo showed downregulation of “stemness” genes and upregulation of adipogenic and inflammatory genes with respect to ASCn. Moreover, the application of bioinformatics and Ingenuity Pathway Analysis (IPA) showed that the transcription factor Smad3 was tentatively affected in obese ASCmo. Validation of this target confirmed a significantly reduced Smad3 nuclear translocation in the isolated ASCmo. Conclusions The transcriptomic profile of the stem cells reservoir in obese subcutaneous WAT is highly modified with significant changes in genes regulating stemcellness, lineage commitment and inflammation. In addition to body mass index, cardiovascular risk factor clustering further affect the ASC transcriptomic profile inducing loss of multipotency and, hence, capacity for tissue repair. In summary, the stem cells in the subcutaneous WAT niche of obese patients are already committed to adipocyte differentiation and show an upregulated inflammatory gene expression associated to their loss of stemcellness. PMID:24040759

  1. Down Syndrome: Cognitive Phenotype

    ERIC Educational Resources Information Center

    Silverman, Wayne

    2007-01-01

    Down syndrome is the most prevalent cause of intellectual impairment associated with a genetic anomaly, in this case, trisomy of chromosome 21. It affects both physical and cognitive development and produces a characteristic phenotype, although affected individuals vary considerably with respect to severity of specific impairments. Studies…

  2. Global Langevin model of multidimensional biomolecular dynamics

    NASA Astrophysics Data System (ADS)

    Schaudinnus, Norbert; Lickert, Benjamin; Biswas, Mithun; Stock, Gerhard

    2016-11-01

    Molecular dynamics simulations of biomolecular processes are often discussed in terms of diffusive motion on a low-dimensional free energy landscape F ( 𝒙 ) . To provide a theoretical basis for this interpretation, one may invoke the system-bath ansatz á la Zwanzig. That is, by assuming a time scale separation between the slow motion along the system coordinate x and the fast fluctuations of the bath, a memory-free Langevin equation can be derived that describes the system's motion on the free energy landscape F ( 𝒙 ) , which is damped by a friction field and driven by a stochastic force that is related to the friction via the fluctuation-dissipation theorem. While the theoretical formulation of Zwanzig typically assumes a highly idealized form of the bath Hamiltonian and the system-bath coupling, one would like to extend the approach to realistic data-based biomolecular systems. Here a practical method is proposed to construct an analytically defined global model of structural dynamics. Given a molecular dynamics simulation and adequate collective coordinates, the approach employs an "empirical valence bond"-type model which is suitable to represent multidimensional free energy landscapes as well as an approximate description of the friction field. Adopting alanine dipeptide and a three-dimensional model of heptaalanine as simple examples, the resulting Langevin model is shown to reproduce the results of the underlying all-atom simulations. Because the Langevin equation can also be shown to satisfy the underlying assumptions of the theory (such as a delta-correlated Gaussian-distributed noise), the global model provides a correct, albeit empirical, realization of Zwanzig's formulation. As an application, the model can be used to investigate the dependence of the system on parameter changes and to predict the effect of site-selective mutations on the dynamics.

  3. Information theoretic approaches to multidimensional neural computations

    NASA Astrophysics Data System (ADS)

    Fitzgerald, Jeffrey D.

    Many systems in nature process information by transforming inputs from their environments into observable output states. These systems are often difficult to study because they are performing computations on multidimensional inputs with many degrees of freedom using highly nonlinear functions. The work presented in this dissertation deals with some of the issues involved with characterizing real-world input/output systems and understanding the properties of idealized systems using information theoretic methods. Using the principle of maximum entropy, a family of models are created that are consistent with certain measurable correlations from an input/output dataset but are maximally unbiased in all other respects, thereby eliminating all unjustified assumptions about the computation. In certain cases, including spiking neurons, we show that these models also minimize the mutual information. This property gives one the advantage of being able to identify the relevant input/output statistics by calculating their information content. We argue that these maximum entropy models provide a much needed quantitative framework for characterizing and understanding sensory processing neurons that are selective for multiple stimulus features. To demonstrate their usefulness, these ideas are applied to neural recordings from macaque retina and thalamus. These neurons, which primarily respond to two stimulus features, are shown to be well described using only first and second order statistics, indicating that their firing rates encode information about stimulus correlations. In addition to modeling multi-feature computations in the relevant feature space, we also show that maximum entropy models are capable of discovering the relevant feature space themselves. This technique overcomes the disadvantages of two commonly used dimensionality reduction methods and is explored using several simulated neurons, as well as retinal and thalamic recordings. Finally, we ask how neurons in a

  4. Multidimensional seismic data reconstruction using tensor analysis

    NASA Astrophysics Data System (ADS)

    Kreimer, Nadia

    Exploration seismology utilizes the seismic wavefield for prospecting oil and gas. The seismic reflection experiment consists on deploying sources and receivers in the surface of an area of interest. When the sources are activated, the receivers measure the wavefield that is reflected from different subsurface interfaces and store the information as time-series called traces or seismograms. The seismic data depend on two source coordinates, two receiver coordinates and time (a 5D volume). Obstacles in the field, logistical and economical factors constrain seismic data acquisition. Therefore, the wavefield sampling is incomplete in the four spatial dimensions. Seismic data undergoes different processes. In particular, the reconstruction process is responsible for correcting sampling irregularities of the seismic wavefield. This thesis focuses on the development of new methodologies for the reconstruction of multidimensional seismic data. This thesis examines techniques based on tensor algebra and proposes three methods that exploit the tensor nature of the seismic data. The fully sampled volume is low-rank in the frequency-space domain. The rank increases when we have missing traces and/or noise. The methods proposed perform rank reduction on frequency slices of the 4D spatial volume. The first method employs the Higher-Order Singular Value Decomposition (HOSVD) immersed in an iterative algorithm that reinserts weighted observations. The second method uses a sequential truncated SVD on the unfoldings of the tensor slices (SEQ-SVD). The third method formulates the rank reduction problem as a convex optimization problem. The measure of the rank is replaced by the nuclear norm of the tensor and the alternating direction method of multipliers (ADMM) minimizes the cost function. All three methods have the interesting property that they are robust to curvature of the reflections, unlike many reconstruction methods. Finally, we present a comparison between the methods

  5. SAGE - MULTIDIMENSIONAL SELF-ADAPTIVE GRID CODE

    NASA Technical Reports Server (NTRS)

    Davies, C. B.

    1994-01-01

    SAGE, Self Adaptive Grid codE, is a flexible tool for adapting and restructuring both 2D and 3D grids. Solution-adaptive grid methods are useful tools for efficient and accurate flow predictions. In supersonic and hypersonic flows, strong gradient regions such as shocks, contact discontinuities, shear layers, etc., require careful distribution of grid points to minimize grid error and produce accurate flow-field predictions. SAGE helps the user obtain more accurate solutions by intelligently redistributing (i.e. adapting) the original grid points based on an initial or interim flow-field solution. The user then computes a new solution using the adapted grid as input to the flow solver. The adaptive-grid methodology poses the problem in an algebraic, unidirectional manner for multi-dimensional adaptations. The procedure is analogous to applying tension and torsion spring forces proportional to the local flow gradient at every grid point and finding the equilibrium position of the resulting system of grid points. The multi-dimensional problem of grid adaption is split into a series of one-dimensional problems along the computational coordinate lines. The reduced one dimensional problem then requires a tridiagonal solver to find the location of grid points along a coordinate line. Multi-directional adaption is achieved by the sequential application of the method in each coordinate direction. The tension forces direct the redistribution of points to the strong gradient region. To maintain smoothness and a measure of orthogonality of grid lines, torsional forces are introduced that relate information between the family of lines adjacent to one another. The smoothness and orthogonality constraints are direction-dependent, since they relate only the coordinate lines that are being adapted to the neighboring lines that have already been adapted. Therefore the solutions are non-unique and depend on the order and direction of adaption. Non-uniqueness of the adapted grid is

  6. Phenotypic approaches to drought in cassava: review.

    PubMed

    Okogbenin, Emmanuel; Setter, Tim L; Ferguson, Morag; Mutegi, Rose; Ceballos, Hernan; Olasanmi, Bunmi; Fregene, Martin

    2013-01-01

    Cassava is an important crop in Africa, Asia, Latin America, and the Caribbean. Cassava can be produced adequately in drought conditions making it the ideal food security crop in marginal environments. Although cassava can tolerate drought stress, it can be genetically improved to enhance productivity in such environments. Drought adaptation studies in over three decades in cassava have identified relevant mechanisms which have been explored in conventional breeding. Drought is a quantitative trait and its multigenic nature makes it very challenging to effectively manipulate and combine genes in breeding for rapid genetic gain and selection process. Cassava has a long growth cycle of 12-18 months which invariably contributes to a long breeding scheme for the crop. Modern breeding using advances in genomics and improved genotyping, is facilitating the dissection and genetic analysis of complex traits including drought tolerance, thus helping to better elucidate and understand the genetic basis of such traits. A beneficial goal of new innovative breeding strategies is to shorten the breeding cycle using minimized, efficient or fast phenotyping protocols. While high throughput genotyping have been achieved, this is rarely the case for phenotyping for drought adaptation. Some of the storage root phenotyping in cassava are often done very late in the evaluation cycle making selection process very slow. This paper highlights some modified traits suitable for early-growth phase phenotyping that may be used to reduce drought phenotyping cycle in cassava. Such modified traits can significantly complement the high throughput genotyping procedures to fast track breeding of improved drought tolerant varieties. The need for metabolite profiling, improved phenomics to take advantage of next generation sequencing technologies and high throughput phenotyping are basic steps for future direction to improve genetic gain and maximize speed for drought tolerance breeding.

  7. Phenotypic approaches to drought in cassava: review

    PubMed Central

    Okogbenin, Emmanuel; Setter, Tim L.; Ferguson, Morag; Mutegi, Rose; Ceballos, Hernan; Olasanmi, Bunmi; Fregene, Martin

    2012-01-01

    Cassava is an important crop in Africa, Asia, Latin America, and the Caribbean. Cassava can be produced adequately in drought conditions making it the ideal food security crop in marginal environments. Although cassava can tolerate drought stress, it can be genetically improved to enhance productivity in such environments. Drought adaptation studies in over three decades in cassava have identified relevant mechanisms which have been explored in conventional breeding. Drought is a quantitative trait and its multigenic nature makes it very challenging to effectively manipulate and combine genes in breeding for rapid genetic gain and selection process. Cassava has a long growth cycle of 12–18 months which invariably contributes to a long breeding scheme for the crop. Modern breeding using advances in genomics and improved genotyping, is facilitating the dissection and genetic analysis of complex traits including drought tolerance, thus helping to better elucidate and understand the genetic basis of such traits. A beneficial goal of new innovative breeding strategies is to shorten the breeding cycle using minimized, efficient or fast phenotyping protocols. While high throughput genotyping have been achieved, this is rarely the case for phenotyping for drought adaptation. Some of the storage root phenotyping in cassava are often done very late in the evaluation cycle making selection process very slow. This paper highlights some modified traits suitable for early-growth phase phenotyping that may be used to reduce drought phenotyping cycle in cassava. Such modified traits can significantly complement the high throughput genotyping procedures to fast track breeding of improved drought tolerant varieties. The need for metabolite profiling, improved phenomics to take advantage of next generation sequencing technologies and high throughput phenotyping are basic steps for future direction to improve genetic gain and maximize speed for drought tolerance breeding. PMID

  8. Revealing potential molecular targets bridging colitis and colorectal cancer based on multidimensional integration strategy

    PubMed Central

    Hu, Yongfei; Li, Xiaobo; Wang, Xishan; Fan, Huihui; Wang, Guiyu; Wang, Dong

    2015-01-01

    Chronic inflammation may play a vital role in the pathogenesis of inflammation-associated tumors. However, the underlying mechanisms bridging ulcerative colitis (UC) and colorectal cancer (CRC) remain unclear. Here, we integrated multidimensional interaction resources, including gene expression profiling, protein-protein interactions (PPIs), transcriptional and post-transcriptional regulation data, and virus-host interactions, to tentatively explore potential molecular targets that functionally link UC and CRC at a systematic level. In this work, by deciphering the overlapping genes, crosstalking genes and pivotal regulators of both UC- and CRC-associated functional module pairs, we revealed a variety of genes (including FOS and DUSP1, etc.), transcription factors (including SMAD3 and ETS1, etc.) and miRNAs (including miR-155 and miR-196b, etc.) that may have the potential to complete the connections between UC and CRC. Interestingly, further analyses of the virus-host interaction network demonstrated that several virus proteins (including EBNA-LP of EBV and protein E7 of HPV) frequently inter-connected to UC- and CRC-associated module pairs with their validated targets significantly enriched in both modules of the host. Together, our results suggested that multidimensional integration strategy provides a novel approach to discover potential molecular targets that bridge the connections between UC and CRC, which could also be extensively applied to studies on other inflammation-related cancers. PMID:26461477

  9. The scheme and research of TV series multidimensional comprehensive evaluation on cross-platform

    NASA Astrophysics Data System (ADS)

    Chai, Jianping; Bai, Xuesong; Zhou, Hongjun; Yin, Fulian

    2016-10-01

    As for shortcomings of the comprehensive evaluation system on traditional TV programs such as single data source, ignorance of new media as well as the high time cost and difficulty of making surveys, a new evaluation of TV series is proposed in this paper, which has a perspective in cross-platform multidimensional evaluation after broadcasting. This scheme considers the data directly collected from cable television and the Internet as research objects. It's based on TOPSIS principle, after preprocessing and calculation of the data, they become primary indicators that reflect different profiles of the viewing of TV series. Then after the process of reasonable empowerment and summation by the six methods(PCA, AHP, etc.), the primary indicators form the composite indices on different channels or websites. The scheme avoids the inefficiency and difficulty of survey and marking; At the same time, it not only reflects different dimensions of viewing, but also combines TV media and new media, completing the multidimensional comprehensive evaluation of TV series on cross-platform.

  10. [Multidimensional diagnosis in general medicine. Comparative study of the use of various instruments].

    PubMed

    Becchi, M A; Franzelli, A; Moscardelli, S; De Pieri, P; Zeni, L; Paccagnella, B

    1994-10-01

    This study was performed to test three instruments for functional status assessment in General Practice: the Dartmouth Coop Charts (COOP Charts), the Functional Status Questionnaire (FSQ) and the Duke University Health Profile (DUHP). All the instruments covered a score of functional aspects in physical, mental and social areas, providing a multidimensional measure of health status. We used these three instruments, validated by international studies, to acquire information concerning their feasibility and acceptability among patients from rural communities needing primary care and to test their validity in differentiating between patient subgroups. The COOP Charts, the FSQ and the DUHP were administered by physicians respectively to 98, 100 and 97 patients, waiting for a visit in the ambulatories of their General Practitioner. Answers relating to each instrument were analyzed according to sex, age and education of patients. All the instruments seemed to be feasible and acceptable, but only the COOP Charts and the FSQ were able to discriminate between different sex, age and scolarity groups. Taking into account the need to elaborate answers according to a formula when using the FSQ, we concluded that the best instrument for General Practice to provide a multidimensional measure of health status seems to be the COOP Charts.

  11. Single cell dynamic phenotyping

    PubMed Central

    Patsch, Katherin; Chiu, Chi-Li; Engeln, Mark; Agus, David B.; Mallick, Parag; Mumenthaler, Shannon M.; Ruderman, Daniel

    2016-01-01

    Live cell imaging has improved our ability to measure phenotypic heterogeneity. However, bottlenecks in imaging and image processing often make it difficult to differentiate interesting biological behavior from technical artifact. Thus there is a need for new methods that improve data quality without sacrificing throughput. Here we present a 3-step workflow to improve dynamic phenotype measurements of heterogeneous cell populations. We provide guidelines for image acquisition, phenotype tracking, and data filtering to remove erroneous cell tracks using the novel Tracking Aberration Measure (TrAM). Our workflow is broadly applicable across imaging platforms and analysis software. By applying this workflow to cancer cell assays, we reduced aberrant cell track prevalence from 17% to 2%. The cost of this improvement was removing 15% of the well-tracked cells. This enabled detection of significant motility differences between cell lines. Similarly, we avoided detecting a false change in translocation kinetics by eliminating the true cause: varied proportions of unresponsive cells. Finally, by systematically seeking heterogeneous behaviors, we detected subpopulations that otherwise could have been missed, including early apoptotic events and pre-mitotic cells. We provide optimized protocols for specific applications and step-by-step guidelines for adapting them to a variety of biological systems. PMID:27708391

  12. RPPA-based protein profiling reveals eIF4G overexpression and 4E-BP1 serine 65 phosphorylation as molecular events that correspond with a pro-survival phenotype in chronic lymphocytic leukemia

    PubMed Central

    Shull, Austin Y.; Noonepalle, Satish K.; Awan, Farrukh T.; Liu, Jimei; Pei, Lirong; Bollag, Roni J.; Salman, Huda; Ding, Zhiyong; Shi, Huidong

    2015-01-01

    Chronic lymphocytic leukemia (CLL), the most common adult leukemia, remains incurable despite advancements in treatment regimens over the past decade. Several expression profile studies have been pursued to better understand CLL pathogenesis. However, these large-scale studies only provide information at the transcriptional level. To better comprehend the differential protein changes that take place in CLL, we performed a reverse-phase protein array (RPPA) analysis using 167 different antibodies on B-cell lysates from 18 CLL patients and 6 normal donors. From our analysis, we discovered an enrichment of protein alterations involved with mRNA translation, specifically upregulation of the translation initiator eIF4G and phosphorylation of the cap-dependent translation inhibitor 4E-BP1 at serine 65. Interestingly, 4E-BP1 phosphorylation occurred independently of AKT phosphorylation, suggesting a disconnect between PI3K/AKT pathway activation and 4E-BP1 phosphorylation. Based on these results, we treated primary CLL samples with NVP-BEZ235, a PI3K/mTOR dual inhibitor, and compared its apoptotic-inducing potential against the BTK inhibitor Ibrutinib and the PI3Kδ inhibitor Idelalisib. We demonstrated that treatment with NVP-BEZ235 caused greater apoptosis, greater apoptotic cleavage of eIF4G, and greater dephosphorylation of 4E-BP1 in primary CLL cells. Taken together, these results highlight the potential dependence of eIF4G overexpression and 4E-BP1 phosphorylation in CLL survival. PMID:25999352

  13. Multidimensional Integrative Genomics Approaches to Dissecting Cardiovascular Disease

    PubMed Central

    Arneson, Douglas; Shu, Le; Tsai, Brandon; Barrere-Cain, Rio; Sun, Christine; Yang, Xia

    2017-01-01

    Elucidating the mechanisms of complex diseases such as cardiovascular disease (CVD) remains a significant challenge due to multidimensional alterations at molecular, cellular, tissue, and organ levels. To better understand CVD and offer insights into the underlying mechanisms and potential therapeutic strategies, data from multiple omics types (genomics, epigenomics, transcriptomics, metabolomics, proteomics, microbiomics) from both humans and model organisms have become available. However, individual omics data types capture only a fraction of the molecular mechanisms. To address this challenge, there have been numerous efforts to develop integrative genomics methods that can leverage multidimensional information from diverse data types to derive comprehensive molecular insights. In this review, we summarize recent methodological advances in multidimensional omics integration, exemplify their applications in cardiovascular research, and pinpoint challenges and future directions in this incipient field. PMID:28289683

  14. Fast Packet Classification Using Multi-Dimensional Encoding

    NASA Astrophysics Data System (ADS)

    Huang, Chi Jia; Chen, Chien

    Internet routers need to classify incoming packets quickly into flows in order to support features such as Internet security, virtual private networks and Quality of Service (QoS). Packet classification uses information contained in the packet header, and a predefined rule table in the routers. Packet classification of multiple fields is generally a difficult problem. Hence, researchers have proposed various algorithms. This study proposes a multi-dimensional encoding method in which parameters such as the source IP address, destination IP address, source port, destination port and protocol type are placed in a multi-dimensional space. Similar to the previously best known algorithm, i.e., bitmap intersection, multi-dimensional encoding is based on the multi-dimensional range lookup approach, in which rules are divided into several multi-dimensional collision-free rule sets. These sets are then used to form the new coding vector to replace the bit vector of the bitmap intersection algorithm. The average memory storage of this encoding is Θ (L · N · log N) for each dimension, where L denotes the number of collision-free rule sets, and N represents the number of rules. The multi-dimensional encoding practically requires much less memory than bitmap intersection algorithm. Additionally, the computation needed for this encoding is as simple as bitmap intersection algorithm. The low memory requirement of the proposed scheme means that it not only decreases the cost of packet classification engine, but also increases the classification performance, since memory represents the performance bottleneck in the packet classification engine implementation using a network processor.

  15. [Phenotype specific therapy of COPD].

    PubMed

    Rothe, Thomas

    2014-12-10

    COPD is not a homogenous disease but consists of at least four different phenotypes: Emphysema, COPD with chronic bronchitis, asthma-COPD overlap syndrome (ACOS), and COPD with recurrent exacerbations. With differentiation, treatment can be designed phenotype-specific. Some modern drugs are not indicated in all phenotypes.

  16. Multidimensional structure of employee motivation - Clustering approach

    NASA Astrophysics Data System (ADS)

    Gąsior, Marcin; Skowron, Łukasz; Sak-Skowron, Monika

    2014-12-01

    Employees' motivation along with their satisfaction with work is one of the most significant factors determining functioning and the success of an organization on the market. The purpose of this article is to demonstrate that motivation to work is a phenomenon whose nature is different among subsequent employees not only in terms of its general level, but also internal structure, and checking whether among various possible structures of motivation there is repeatability which could prove the existence of specific regularities and enabling possible classification of employees. Reasoning with regard to internal structure of motivation was conducted on the basis of the designated 14 variables expressing it, which included both internal factors (feelings) and external (actions), both positive and negative in its meaning. The conducted research consisted in segmentation of the surveyed employees using the generalized method of k-means, in order to separate groups with the same subsequent intensity profiles, so designated variables. By way of research, five various groups of employees were found. Each has a unique, different profile of motivation, at the same time, in each of them a different satisfaction level of the employed was observed. The analysis leads to a conclusion that the motivation profile itself is not completely connected with the perceived satisfaction with work. While signs of motivation positive in nature are usually stronger among satisfied employees, and the weaker - among dissatisfied ones, we cannot speak about a similar regularity when it comes to factors of negative nature. Furthermore, the presented research shows that within negative factors, larger intensification can be observed among ones of internal nature, while among these of external nature - it is smaller.

  17. Genotypic and phenotypic profiles of Escherichia coli isolates belonging to clinical sequence type 131 (ST131), clinical non-ST131, and fecal non-ST131 lineages from India.

    PubMed

    Hussain, Arif; Ranjan, Amit; Nandanwar, Nishant; Babbar, Anshu; Jadhav, Savita; Ahmed, Niyaz

    2014-12-01

    In view of the epidemiological success of CTX-M-15-producing lineages of Escherichia coli and particularly of sequence type 131 (ST131), it is of significant interest to explore its prevalence in countries such as India and to determine if antibiotic resistance, virulence, metabolic potential, and/or the genetic architecture of the ST131 isolates differ from those of non-ST131 isolates. A collection of 126 E. coli isolates comprising 43 ST131 E. coli, 40 non-ST131 E. coli, and 43 fecal E. coli isolates collected from a tertiary care hospital in India was analyzed. These isolates were subjected to enterobacterial repetitive intergenic consensus (ERIC)-based fingerprinting, O typing, phylogenetic grouping, antibiotic sensitivity testing, and virulence and antimicrobial resistance gene (VAG) detection. Representative isolates from this collection were also analyzed by multilocus sequence typing (MLST), conjugation, metabolic profiling, biofilm production assay, and zebra fish lethality assay. All of the 43 ST131 E. coli isolates were exclusively associated with phylogenetic group B2 (100%), while most of the clinical non-ST131 and stool non-ST131 E. coli isolates were affiliated with the B2 (38%) and A (58%) phylogenetic groups, respectively. Significantly greater proportions of ST131 isolates (58%) than non-ST131 isolates (clinical and stool E. coli isolates, 5% each) were technically identified to be extraintestinal pathogenic E. coli (ExPEC). The clinical ST131, clinical non-ST131, and stool non-ST131 E. coli isolates exhibited high rates of multidrug resistance (95%, 91%, and 91%, respectively), extended-spectrum-β-lactamase (ESBL) production (86%, 83%, and 91%, respectively), and metallo-β-lactamase (MBL) production (28%, 33%, and 0%, respectively). CTX-M-15 was strongly linked with ESBL production in ST131 isolates (93%), whereas CTX-M-15 plus TEM were present in clinical and stool non-ST131 E. coli isolates. Using MLST, we confirmed the presence of two NDM-1

  18. Genotypic and Phenotypic Profiles of Escherichia coli Isolates Belonging to Clinical Sequence Type 131 (ST131), Clinical Non-ST131, and Fecal Non-ST131 Lineages from India

    PubMed Central

    Hussain, Arif; Ranjan, Amit; Nandanwar, Nishant; Babbar, Anshu; Jadhav, Savita

    2014-01-01

    In view of the epidemiological success of CTX-M-15-producing lineages of Escherichia coli and particularly of sequence type 131 (ST131), it is of significant interest to explore its prevalence in countries such as India and to determine if antibiotic resistance, virulence, metabolic potential, and/or the genetic architecture of the ST131 isolates differ from those of non-ST131 isolates. A collection of 126 E. coli isolates comprising 43 ST131 E. coli, 40 non-ST131 E. coli, and 43 fecal E. coli isolates collected from a tertiary care hospital in India was analyzed. These isolates were subjected to enterobacterial repetitive intergenic consensus (ERIC)-based fingerprinting, O typing, phylogenetic grouping, antibiotic sensitivity testing, and virulence and antimicrobial resistance gene (VAG) detection. Representative isolates from this collection were also analyzed by multilocus sequence typing (MLST), conjugation, metabolic profiling, biofilm production assay, and zebra fish lethality assay. All of the 43 ST131 E. coli isolates were exclusively associated with phylogenetic group B2 (100%), while most of the clinical non-ST131 and stool non-ST131 E. coli isolates were affiliated with the B2 (38%) and A (58%) phylogenetic groups, respectively. Significantly greater proportions of ST131 isolates (58%) than non-ST131 isolates (clinical and stool E. coli isolates, 5% each) were technically identified to be extraintestinal pathogenic E. coli (ExPEC). The clinical ST131, clinical non-ST131, and stool non-ST131 E. coli isolates exhibited high rates of multidrug resistance (95%, 91%, and 91%, respectively), extended-spectrum-β-lactamase (ESBL) production (86%, 83%, and 91%, respectively), and metallo-β-lactamase (MBL) production (28%, 33%, and 0%, respectively). CTX-M-15 was strongly linked with ESBL production in ST131 isolates (93%), whereas CTX-M-15 plus TEM were present in clinical and stool non-ST131 E. coli isolates. Using MLST, we confirmed the presence of two NDM-1

  19. Multidimensional assessment of perceived treatment-entry pressures among substance abusers.

    PubMed

    Marlowe, D B; Merikle, E P; Kirby, K C; Festinger, D S; McLellan, A T

    2001-06-01

    Motivational assessment instruments typically measure clients' attributions about their readiness to change problem behaviors. They do not indicate why a client may be motivated to change, or provide guidance on how to retain an unmotivated client in treatment. The authors interviewed 415 substance abuse clients about their reasons for entering treatment and scored their responses along the dimensions of (a) negative versus positive treatment-entry pressures, (b) internal versus external sources of those pressures, and (c) the life domain from which the pressures emanated. Exploratory cluster analysis yielded 5 types of clients characterized by different profiles of perceived treatment-entry pressures. Cluster membership was predictive of treatment outcomes, and the clusters differed by demographic variables. These data support the discriminative and predictive utility of performing a multidimensional assessment of pressures to enter treatment.

  20. Multi-dimensional, non-contact metrology using trilateration and high resolution FMCW ladar.

    PubMed

    Mateo, Ana Baselga; Barber, Zeb W

    2015-07-01

    Here we propose, describe, and provide experimental proof-of-concept demonstrations of a multidimensional, non-contact-length metrology system design based on high resolution (millimeter to sub-100 micron) frequency modulated continuous wave (FMCW) ladar and trilateration based on length measurements from multiple, optical fiber-connected transmitters. With an accurate FMCW ladar source, the trilateration-based design provides 3D resolution inherently independent of standoff range and allows self-calibration to provide flexible setup of a field system. A proof-of-concept experimental demonstration was performed using a highly stabilized, 2 THz bandwidth chirped laser source, two emitters, and one scanning emitter/receiver providing 1D surface profiles (2D metrology) of diffuse targets. The measured coordinate precision of <200 microns was determined to be limited by laser speckle issues caused by diffuse scattering of the targets.

  1. Phylogenetic distribution of phenotypic traits in Bacillus thuringiensis determined by multilocus sequence analysis.

    PubMed

    Blackburn, Michael B; Martin, Phyllis A W; Kuhar, Daniel; Farrar, Robert R; Gundersen-Rindal, Dawn E

    2013-01-01

    Diverse isolates from a world-wide collection of Bacillus thuringiensis were classified based on phenotypic profiles resulting from six biochemical tests; production of amylase (T), lecithinase (L), urease (U), acid from sucrose (S) and salicin (A), and the hydrolysis of esculin (E). Eighty two isolates representing the 15 most common phenotypic profiles were subjected to phylogenetic analysis by multilocus sequence typing; these were found to be distributed among 19 sequence types, 8 of which were novel. Approximately 70% of the isolates belonged to sequence types corresponding to the classical B. thuringiensis varieties kurstaki (20 isolates), finitimus (15 isolates), morrisoni (11 isolates) and israelensis (11 isolates). Generally, there was little apparent correlation between phenotypic traits and phylogenetic position, and phenotypic variation was often substantial within a sequence type. Isolates of the sequence type corresponding to kurstaki displayed the greatest apparent phenotypic variation with 6 of the 15 phenotypic profiles represented. Despite the phenotypic variation often observed within a given sequence type, certain phenotypes appeared highly correlated with particular sequence types. Isolates with the phenotypic profiles TLUAE and LSAE were found to be exclusively associated with sequence types associated with varieties kurstaki and finitimus, respectively, and 7 of 8 TS isolates were found to be associated with the morrisoni sequence type. Our results suggest that the B. thuringiensis varieties israelensis and kurstaki represent the most abundant varieties of Bt in soil.

  2. Multivariate phenotype association analysis by marker-set kernel machine regression.

    PubMed

    Maity, Arnab; Sullivan, Patrick F; Tzeng, Jun-Ying

    2012-11-01

    Genetic studies of complex diseases often collect multiple phenotypes relevant to the disorders. As these phenotypes can be correlated and share common genetic mechanisms, jointly analyzing these traits may bring more power to detect genes influencing individual or multiple phenotypes. Given the advancement brought by the multivariate phenotype approaches and the multimarker kernel machine regression, we construct a multivariate regression based on kernel machine to facilitate the joint evaluation of multimarker effects on multiple phenotypes. The kernel machine serves as a powerful dimension-reduction tool to capture complex effects among markers. The multivariate framework incorporates the potentially correlated multidimensional phenotypic information and accommodates common or different environmental covariates for each trait. We derive the multivariate kernel machine test based on a score-like statistic, and conduct simulations to evaluate the validity and efficacy of the method. We also study the performance of the commonly adapted strategies for kernel machine analysis on multiple phenotypes, including the multiple univariate kernel machine tests with original phenotypes or with their principal components. Our results suggest that none of these approaches has the uniformly best power, and the optimal test depends on the magnitude of the phenotype correlation and the effect patterns. However, the multivariate test retains to be a reasonable approach when the multiple phenotypes have none or mild correlations, and gives the best power once the correlation becomes stronger or when there exist genes that affect more than one phenotype. We illustrate the utility of the multivariate kernel machine method through the Clinical Antipsychotic Trails of Intervention Effectiveness antibody study.

  3. `Weak A' phenotypes

    PubMed Central

    Cartron, J. P.; Gerbal, A.; Hughes-Jones, N. C.; Salmon, C.

    1974-01-01

    Thirty-five weak A samples including fourteen A3, eight Ax, seven Aend, three Am and three Ae1 were studied in order to determine their A antigen site density, using an IgG anti-A labelled with 125I. The values obtained ranged between 30,000 A antigen sites for A3 individuals, and 700 sites for the Ae1 red cells. The hierarchy of values observed made it possible to establish a quantitative relationship between the red cell agglutinability of these phenotypes measured under standard conditions, and their antigen site density. PMID:4435836

  4. Cognitive Profile of Turner Syndrome

    ERIC Educational Resources Information Center

    Hong, David; Kent, Jamie Scaletta; Kesler, Shelli

    2009-01-01

    Turner syndrome (TS) is a relatively common neurogenetic disorder characterized by complete or partial monosomy-X in a phenotypic female. TS is associated with a cognitive profile that typically includes intact intellectual function and verbal abilities with relative weaknesses in visual-spatial, executive, and social cognitive domains. In this…

  5. Multidimensional Measurement of Poverty among Women in Sub-Saharan Africa

    ERIC Educational Resources Information Center

    Batana, Yele Maweki

    2013-01-01

    Since the seminal work of Sen, poverty has been recognized as a multidimensional phenomenon. The recent availability of relevant databases renewed the interest in this approach. This paper estimates multidimensional poverty among women in fourteen Sub-Saharan African countries using the Alkire and Foster multidimensional poverty measures, whose…

  6. Best Design for Multidimensional Computerized Adaptive Testing with the Bifactor Model

    ERIC Educational Resources Information Center

    Seo, Dong Gi; Weiss, David J.

    2015-01-01

    Most computerized adaptive tests (CATs) have been studied using the framework of unidimensional item response theory. However, many psychological variables are multidimensional and might benefit from using a multidimensional approach to CATs. This study investigated the accuracy, fidelity, and efficiency of a fully multidimensional CAT algorithm…

  7. Using Multidimensional Scaling to Explore Value Issues in Counseling.

    ERIC Educational Resources Information Center

    Richards, P. Scott; Davison, Mark L.

    It is widely agreed that counselors' and clients' values influence every phase of psychotherapy. A preliminary appraisal of the usefulness of multidimensional scaling (MDS) for investigating the effects of values on counseling process and outcome was done. MDS was used to investigate how theistic or atheistic values of a counselor, when revealed,…

  8. Assessing Multidimensional Energy Literacy of Secondary Students Using Contextualized Assessment

    ERIC Educational Resources Information Center

    Chen, Kuan-Li; Liu, Shiang-Yao; Chen, Po-Hsi

    2015-01-01

    Energy literacy is multidimensional, comprising broad content knowledge as well as affect and behavior. Our previous study has defined four core dimensions for the assessment framework, including energy concepts, reasoning on energy issues, low-carbon lifestyle, and civic responsibility for a sustainable society. The present study compiled a…

  9. The Multidimensionality of Calling: Conceptualization, Measurement and a Bicultural Perspective

    ERIC Educational Resources Information Center

    Hagmaier, Tamara; Abele, Andrea E.

    2012-01-01

    The experience of a calling may be seen as the ultimate form of subjective career success that has many positive consequences for individuals and organizations. We are here concerned with the conceptualization of a new multidimensional measure of calling, the MCM. In the first two studies we employed a qualitative approach and came up with five…

  10. The Relationship between Anxiety and Stuttering: A Multidimensional Approach

    ERIC Educational Resources Information Center

    Ezrati-Vinacour, Ruth; Levin, Iris

    2004-01-01

    The relationship between anxiety and stuttering is equivocal from both clinical and empirical perspectives. This study examined the relationship within the framework of the multidimensional interaction model of anxiety that includes an approach to general anxiety in specific situations [J. Pers. Soc. Psychol. 60 (1991) 919]. Ninety-four males aged…

  11. Individual and Institutional Determinants of Multidimensional Poverty: A European Comparison

    ERIC Educational Resources Information Center

    Dewilde, Caroline

    2008-01-01

    In this article we evaluate to what extent between-country differences in the probability of being "multidimensional" poor can be explained by a range of "domain-specific" indicators of welfare regime arrangements. To this end, a so-called micro-macro model is estimated, testing the "independent" effect of…

  12. Multidimensional Collaboration: Reflections on Action Research in a Clinical Context

    ERIC Educational Resources Information Center

    Gregory, Sheila; Poland, Fiona; Spalding, Nicola J.; Sargen, Kevin; McCulloch, Jane; Vicary, Penny

    2011-01-01

    This paper reflects on the challenges and benefits of multidimensional collaboration in an action research study to evaluate and improve preoperative education for patients awaiting colorectal surgery. Three cycles of planning, acting, observing and reflecting were designed to evaluate practice and implement change in this interactive setting,…

  13. A Multidimensional Approach to E-Learning Sustainability

    ERIC Educational Resources Information Center

    Trentin, Guglielmo, Ed.

    2007-01-01

    The aim of the article is to outline the possible key elements related to the sustainability of e-learning. After analyzing trends in e-learning diffusion, a multidimensional model for sustainability of e-learning innovations is presented. The proposed model is characterized by eight dimensions that are closely and mutually interrelated:…

  14. Multidimensional Scaling of High School Students' Perceptions of Academic Dishonesty

    ERIC Educational Resources Information Center

    Schmelkin, Liora Pedhazur; Gilbert, Kimberly A.; Silva, Rebecca

    2010-01-01

    Although cheating on tests and other forms of academic dishonesty are considered rampant, no standard definition of academic dishonesty exists. The current study was conducted to investigate the perceptions of academic dishonesty in high school students, utilizing an innovative methodology, multidimensional scaling (MDS). Two methods were used to…

  15. Development and Validation of the Multidimensional State Boredom Scale

    ERIC Educational Resources Information Center

    Fahlman, Shelley A.; Mercer-Lynn, Kimberley B.; Flora, David B.; Eastwood, John D.

    2013-01-01

    This article describes the development and validation of the Multidimensional State Boredom Scale (MSBS)--the first and only full-scale measure of state boredom. It was developed based on a theoretically and empirically grounded definition of boredom. A five-factor structure of the scale (Disengagement, High Arousal, Low Arousal, Inattention, and…

  16. Reporting of Subscores Using Multidimensional Item Response Theory

    ERIC Educational Resources Information Center

    Haberman, Shelby J.; Sinharay, Sandip

    2010-01-01

    Recently, there has been increasing interest in reporting subscores. This paper examines reporting of subscores using multidimensional item response theory (MIRT) models (e.g., Reckase in "Appl. Psychol. Meas." 21:25-36, 1997; C.R. Rao and S. Sinharay (Eds), "Handbook of Statistics, vol. 26," pp. 607-642, North-Holland, Amsterdam, 2007; Beguin &…

  17. Interactive Multidimensional Scaling of Cognitive Structure Underlying Person Perception

    ERIC Educational Resources Information Center

    Kehoe, Jerard; Reynolds, Thomas J.

    1977-01-01

    A computer-interactive multidimensional scaling program was used together with free response methods to represent and label dimensions of individual cognitive structure underlying persons' perceptions. The dimensional structures derived were predictive of semantic differential, paired comparison, and Repertory Grid Test triad judgments.…

  18. Multidimensional Adaptive Testing with Optimal Design Criteria for Item Selection

    ERIC Educational Resources Information Center

    Mulder, Joris; van der Linden, Wim J.

    2009-01-01

    Several criteria from the optimal design literature are examined for use with item selection in multidimensional adaptive testing. In particular, it is examined what criteria are appropriate for adaptive testing in which all abilities are intentional, some should be considered as a nuisance, or the interest is in the testing of a composite of the…

  19. Best Practices Inquiry: A Multidimensional, Value-Critical Framework

    ERIC Educational Resources Information Center

    Petr, Christopher G.; Walter, Uta M.

    2005-01-01

    This article offers a multidimensional framework that broadens current approaches to "best practices" inquiry to include (1) the perspectives of both the consumers of services and professional practitioners and (2) a value-based critique. The predominant empirical approach to best practices inquiry is a necessary, but not sufficient, component of…

  20. The Multi-Dimensional Demands of Reading in the Disciplines

    ERIC Educational Resources Information Center

    Lee, Carol D.

    2014-01-01

    This commentary addresses the complexities of reading comprehension with an explicit focus on reading in the disciplines. The author proposes reading as entailing multi-dimensional demands of the reader and posing complex challenges for teachers. These challenges are intensified by restrictive conceptions of relevant prior knowledge and experience…

  1. Bayesian Multidimensional IRT Models with a Hierarchical Structure

    ERIC Educational Resources Information Center

    Sheng, Yanyan; Wikle, Christopher K.

    2008-01-01

    As item response models gain increased popularity in large-scale educational and measurement testing situations, many studies have been conducted on the development and applications of unidimensional and multidimensional models. Recently, attention has been paid to IRT-based models with an overall ability dimension underlying several ability…

  2. Examining the Reliability of Student Growth Percentiles Using Multidimensional IRT

    ERIC Educational Resources Information Center

    Monroe, Scott; Cai, Li

    2015-01-01

    Student growth percentiles (SGPs, Betebenner, 2009) are used to locate a student's current score in a conditional distribution based on the student's past scores. Currently, following Betebenner (2009), quantile regression (QR) is most often used operationally to estimate the SGPs. Alternatively, multidimensional item response theory (MIRT) may…

  3. Extending Validity Evidence for Multidimensional Measures of Coaching Competency

    ERIC Educational Resources Information Center

    Myers, Nicholas D.; Wolfe, Edward W.; Maier, Kimberly S.; Feltz, Deborah L.; Reckase, Mark D.

    2006-01-01

    This study extended validity evidence for multidimensional measures of coaching competency derived from the Coaching Competency Scale (CCS; Myers, Feltz, Maier, Wolfe, & Reckase, 2006) by examining use of the original rating scale structure and testing how measures related to satisfaction with the head coach within teams and between teams.…

  4. A Multidimensional Test of Self-Concept: Further Findings.

    ERIC Educational Resources Information Center

    Lathrop, Richard G.

    The Multidimensional Test of Self-Concept (MTS) is based on the assumption that an individual's perception of his/her well-being is related to the difference between the current state of that individual and the desired state. This difference between the two states may be directly measured, and a single self-concept score generated. The MTS…

  5. Parentification of Adult Children of Divorce: A Multidimensional Analysis.

    ERIC Educational Resources Information Center

    Jurkovic, Gregory J.; Thirkield, Alison; Morrell, Richard

    2001-01-01

    Compared the responses of 381 late adolescent and young adult children of divorce and nondivorce on a new multidimensional measure of parentification assessing the extent and fairness of past and present family caregiving. Evidence that problematic forms of parentification in children of divorce continue into late adolescence and young adulthood…

  6. Image matrix processor for fast multi-dimensional computations

    DOEpatents

    Roberson, G.P.; Skeate, M.F.

    1996-10-15

    An apparatus for multi-dimensional computation is disclosed which comprises a computation engine, including a plurality of processing modules. The processing modules are configured in parallel and compute respective contributions to a computed multi-dimensional image of respective two dimensional data sets. A high-speed, parallel access storage system is provided which stores the multi-dimensional data sets, and a switching circuit routes the data among the processing modules in the computation engine and the storage system. A data acquisition port receives the two dimensional data sets representing projections through an image, for reconstruction algorithms such as encountered in computerized tomography. The processing modules include a programmable local host, by which they may be configured to execute a plurality of different types of multi-dimensional algorithms. The processing modules thus include an image manipulation processor, which includes a source cache, a target cache, a coefficient table, and control software for executing image transformation routines using data in the source cache and the coefficient table and loading resulting data in the target cache. The local host processor operates to load the source cache with a two dimensional data set, loads the coefficient table, and transfers resulting data out of the target cache to the storage system, or to another destination. 10 figs.

  7. The Structure and Validity of the Multidimensional Social Support Questionnaire

    ERIC Educational Resources Information Center

    Hardesty, Patrick H.; Richardson, George B.

    2012-01-01

    The factor structure and concurrent validity of the Multidimensional Social Support Questionnaire, a brief measure of perceived social support for use with adolescents, was examined. Findings suggest that four dimensions of perceived social support may yield more information than assessments of the unitary construct of support. (Contains 8 tables…

  8. Multidimensional Scoring of Abilities: The Ordered Polytomous Response Case

    ERIC Educational Resources Information Center

    de la Torre, Jimmy

    2008-01-01

    Recent work has shown that multidimensionally scoring responses from different tests can provide better ability estimates. For educational assessment data, applications of this approach have been limited to binary scores. Of the different variants, the de la Torre and Patz model is considered more general because implementing the scoring procedure…

  9. Multidimensional Poverty in China: Findings Based on the CHNS

    ERIC Educational Resources Information Center

    Yu, Jiantuo

    2013-01-01

    This paper estimates multidimensional poverty in China by applying the Alkire-Foster methodology to the China Health and Nutrition Survey 2000-2009 data. Five dimensions are included: income, living standard, education, health and social security. Results suggest that rapid economic growth has resulted not only in a reduction in income poverty but…

  10. Five Evils: Multidimensional Poverty and Race in America

    ERIC Educational Resources Information Center

    Reeves, Richard; Rodrigue, Edward; Kneebone, Elizabeth

    2016-01-01

    Poverty is about a lack of money, but it's not only about that. As a lived experience, poverty is also characterized by ill health, insecurity, discomfort, isolation, and more. To put it another way: Poverty is multidimensional, and its dimensions often cluster together to intensify the negative effects of being poor. In this first of a two-part…

  11. Income Tax Preparation Assistance Service Learning Program: A Multidimensional Assessment

    ERIC Educational Resources Information Center

    Aldridge, Richard; Callahan, Richard A.; Chen, Yining; Wade, Stacy R.

    2015-01-01

    The authors present a multidimensional assessment of the outcomes and benefits of an income tax preparation assistance (ITPA) service learning program. They measure the perceived proximate benefits at the delivery of the service program, the actual learning outcome benefits prior to graduation, and the perceived long-term benefits from a…

  12. Turkish Validity Examination of the Multidimensional Students' Life Satisfaction Scale

    ERIC Educational Resources Information Center

    Irmak, Sezgin; Kuruuzum, Ayse

    2009-01-01

    The validation studies of the Multidimensional Students' Life Satisfaction Scale (MSLSS) have been conducted with samples from different nations but mostly from western individualistic cultures. Life satisfaction and its constructs could differ depending on cultural characteristics and life satisfaction scales should be validated in different…

  13. Posterior Predictive Model Checking for Multidimensionality in Item Response Theory

    ERIC Educational Resources Information Center

    Levy, Roy; Mislevy, Robert J.; Sinharay, Sandip

    2009-01-01

    If data exhibit multidimensionality, key conditional independence assumptions of unidimensional models do not hold. The current work pursues posterior predictive model checking, a flexible family of model-checking procedures, as a tool for criticizing models due to unaccounted for dimensions in the context of item response theory. Factors…

  14. Scoring and modeling psychological measures in the presence of multidimensionality.

    PubMed

    Reise, Steven P; Bonifay, Wes E; Haviland, Mark G

    2013-01-01

    Confirmatory factor analytic studies of psychological measures showing item responses to be multidimensional do not provide sufficient guidance for applied work. Demonstrating that item response data are multifactorial in this way does not necessarily (a) mean that a total scale score is an inadequate indicator of the intended construct, (b) demand creating and scoring subscales, or (c) require specifying a multidimensional measurement model in research using structural equation modeling (SEM). To better inform these important decisions, more fine-grained psychometric analyses are necessary. We describe 3 established, but seldom used, psychometric approaches that address 4 distinct questions: (a) To what degree do total scale scores reflect reliable variation on a single construct? (b) Is the scoring and reporting of subscale scores justified? (c) If justified, how much reliable variance do subscale scores provide after controlling for a general factor? and (d) Can multidimensional item response data be represented by a unidimensional measurement model in SEM, or are multidimensional measurement models (e.g., second-order, bifactor) necessary to achieve unbiased structural coefficients? In the discussion, we provide guidance for applied researchers on how best to interpret the results from applying these methods and review their limitations.

  15. Mental Models of Text and Film: A Multidimensional Scaling Analysis.

    ERIC Educational Resources Information Center

    Rowell, Jack A.; Moss, Peter D.

    1986-01-01

    Reports results of experiment to determine whether mental models are constructed of interrelationships and cross-relationships of character attributions drawn in themes of novels and films. The study used "Animal Farm" in print and cartoon forms. Results demonstrated validity of multidimensional scaling for representing both media.…

  16. Image matrix processor for fast multi-dimensional computations

    DOEpatents

    Roberson, George P.; Skeate, Michael F.

    1996-01-01

    An apparatus for multi-dimensional computation which comprises a computation engine, including a plurality of processing modules. The processing modules are configured in parallel and compute respective contributions to a computed multi-dimensional image of respective two dimensional data sets. A high-speed, parallel access storage system is provided which stores the multi-dimensional data sets, and a switching circuit routes the data among the processing modules in the computation engine and the storage system. A data acquisition port receives the two dimensional data sets representing projections through an image, for reconstruction algorithms such as encountered in computerized tomography. The processing modules include a programmable local host, by which they may be configured to execute a plurality of different types of multi-dimensional algorithms. The processing modules thus include an image manipulation processor, which includes a source cache, a target cache, a coefficient table, and control software for executing image transformation routines using data in the source cache and the coefficient table and loading resulting data in the target cache. The local host processor operates to load the source cache with a two dimensional data set, loads the coefficient table, and transfers resulting data out of the target cache to the storage system, or to another destination.

  17. Identity Status and Empathic Response Patterns: A Multidimensional Investigation.

    ERIC Educational Resources Information Center

    Erlanger, David M.

    1998-01-01

    The multidimensional empathic response patterns of late adolescent undergraduate students (N=153) was examined according to their identity status. Subjects completed self-report measures of empathic response style and identity development. Findings for empathic concern, cognitive empathy, and empathic distress are related to identity status…

  18. Stabilization of Internal Space in Noncommutative Multidimensional Cosmology

    NASA Astrophysics Data System (ADS)

    Khosravi, N.; Jalalzadeh, S.; Sepangi, H. R.

    We study the cosmological aspects of a noncommutative, multidimensional universe where the matter source is assumed to be a scalar field which does not commute with the internal scale factor. We show that such noncommutativity results in the internal dimensions being stabilized.

  19. Multidimensional linearizable system of n-wave-type equations

    NASA Astrophysics Data System (ADS)

    Zenchuk, A. I.

    2017-01-01

    We propose a linearizable version of a multidimensional system of n-wave-type nonlinear partial differential equations ( PDEs). We derive this system using the spectral representation of its solution via a procedure similar to the dressing method for nonlinear PDEs integrable by the inverse scattering transform method. We show that the proposed system is completely integrable and construct a particular solution.

  20. A Multidimensional Analysis of a Written L2 Spanish Corpus

    ERIC Educational Resources Information Center

    Asencion-Delaney, Yuly; Collentine, Joseph

    2011-01-01

    The present study adds to our understanding of how learners employ lexical and grammatical phenomena to communicate in writing in different types of interlanguage discourse. A multidimensional (factor) analysis of a corpus of L2 Spanish writing (202,241 words) generated by second- and third-year, university-level learners was performed. The…

  1. Science Concepts in Semantic Space--A Multidimensional Scaling Study

    ERIC Educational Resources Information Center

    Preece, P. F. W.

    1976-01-01

    Data on the semantic proximity of classical mechanics concepts, obtained by means of a cross-sectional investigation (100 subjects) using a continued word association test, were analyzed by individual difference multidimensional scaling to permit the mapping of semantic space for individual subjects. (JC)

  2. A MULTIDIMENSIONAL AND MULTIPHYSICS APPROACH TO NUCLEAR FUEL BEHAVIOR SIMULATION

    SciTech Connect

    R. L. Williamson; J. D. Hales; S. R. Novascone; M. R. Tonks; D. R. Gaston; C. J. Permann; D. Andrs; R. C. Martineau

    2012-04-01

    Important aspects of fuel rod behavior, for example pellet-clad mechanical interaction (PCMI), fuel fracture, oxide formation, non-axisymmetric cooling, and response to fuel manufacturing defects, are inherently multidimensional in addition to being complicated multiphysics problems. Many current modeling tools are strictly 2D axisymmetric or even 1.5D. This paper outlines the capabilities of a new fuel modeling tool able to analyze either 2D axisymmetric or fully 3D models. These capabilities include temperature-dependent thermal conductivity of fuel; swelling and densification; fuel creep; pellet fracture; fission gas release; cladding creep; irradiation growth; and gap mechanics (contact and gap heat transfer). The need for multiphysics, multidimensional modeling is then demonstrated through a discussion of results for a set of example problems. The first, a 10-pellet rodlet, demonstrates the viability of the solution method employed. This example highlights the effect of our smeared cracking model and also shows the multidimensional nature of discrete fuel pellet modeling. The second example relies on our the multidimensional, multiphysics approach to analyze a missing pellet surface problem. As a final example, we show a lower-length-scale simulation coupled to a continuum-scale simulation.

  3. BMDS: A Collection of R Functions for Bayesian Multidimensional Scaling

    ERIC Educational Resources Information Center

    Okada, Kensuke; Shigemasu, Kazuo

    2009-01-01

    Bayesian multidimensional scaling (MDS) has attracted a great deal of attention because: (1) it provides a better fit than do classical MDS and ALSCAL; (2) it provides estimation errors of the distances; and (3) the Bayesian dimension selection criterion, MDSIC, provides a direct indication of optimal dimensionality. However, Bayesian MDS is not…

  4. Implementation and Measurement Efficiency of Multidimensional Computerized Adaptive Testing

    ERIC Educational Resources Information Center

    Wang, Wen-Chung; Chen, Po-Hsi

    2004-01-01

    Multidimensional adaptive testing (MAT) procedures are proposed for the measurement of several latent traits by a single examination. Bayesian latent trait estimation and adaptive item selection are derived. Simulations were conducted to compare the measurement efficiency of MAT with those of unidimensional adaptive testing and random…

  5. A General Multidimensional Model for the Measurement of Cultural Differences.

    ERIC Educational Resources Information Center

    Olmedo, Esteban L.; Martinez, Sergio R.

    A multidimensional model for measuring cultural differences (MCD) based on factor analytic theory and techniques is proposed. The model assumes that a cultural space may be defined by means of a relatively small number of orthogonal dimensions which are linear combinations of a much larger number of cultural variables. Once a suitable,…

  6. The Multidimensional Structure of Verbal Comprehension Test Items.

    ERIC Educational Resources Information Center

    Peled, Zimra

    1984-01-01

    The multidimensional structure of verbal comprehension test items was investigated. Empirical evidence was provided to support the theory that item tasks are multivariate-multiordered composites of faceted components: language, contextual knowledge, and cognitive operation. Linear and circular properties of cylindrical manifestation were…

  7. Evaluation of Linking Methods for Multidimensional IRT Calibrations

    ERIC Educational Resources Information Center

    Min, Kyung-Seok

    2007-01-01

    Most researchers agree that psychological/educational tests are sensitive to multiple traits, implying the need for a multidimensional item response theory (MIRT). One limitation of applying a MIRT in practice is the difficulty in establishing equivalent scales of multiple traits. In this study, a new MIRT linking method was proposed and evaluated…

  8. Positivity-preserving numerical schemes for multidimensional advection

    NASA Technical Reports Server (NTRS)

    Leonard, B. P.; Macvean, M. K.; Lock, A. P.

    1993-01-01

    This report describes the construction of an explicit, single time-step, conservative, finite-volume method for multidimensional advective flow, based on a uniformly third-order polynomial interpolation algorithm (UTOPIA). Particular attention is paid to the problem of flow-to-grid angle-dependent, anisotropic distortion typical of one-dimensional schemes used component-wise. The third-order multidimensional scheme automatically includes certain cross-difference terms that guarantee good isotropy (and stability). However, above first-order, polynomial-based advection schemes do not preserve positivity (the multidimensional analogue of monotonicity). For this reason, a multidimensional generalization of the first author's universal flux-limiter is sought. This is a very challenging problem. A simple flux-limiter can be found; but this introduces strong anisotropic distortion. A more sophisticated technique, limiting part of the flux and then restoring the isotropy-maintaining cross-terms afterwards, gives more satisfactory results. Test cases are confined to two dimensions; three-dimensional extensions are briefly discussed.

  9. The Multidimensionality of Child Poverty: Evidence from Afghanistan

    ERIC Educational Resources Information Center

    Trani, Jean-Francois; Biggeri, Mario; Mauro, Vincenzo

    2013-01-01

    This paper examines multidimensional poverty among children in Afghanistan using the Alkire-Foster method. Several previous studies have underlined the need to separate children from their adult nexus when studying poverty and treat them according to their own specificities. From the capability approach, child poverty is understood to be the lack…

  10. Multidimensional Treatment of Attention Deficit Disorder: A Family Oriented Approach.

    ERIC Educational Resources Information Center

    Erk, Robert R.

    1997-01-01

    Counseling that involves the entire family has the potential to motivate children with Attention Deficit Disorder (ADD), improve the children's self-concept, and help them improve social skills or functioning. Probable causes, family patterns, effects of ADD on family interactions, counseling issues, and a multidimensional treatment approach are…

  11. Income and beyond: Multidimensional Poverty in Six Latin American Countries

    ERIC Educational Resources Information Center

    Battiston, Diego; Cruces, Guillermo; Lopez-Calva, Luis Felipe; Lugo, Maria Ana; Santos, Maria Emma

    2013-01-01

    This paper studies multidimensional poverty for Argentina, Brazil, Chile, El Salvador, Mexico and Uruguay for the period 1992-2006. The approach overcomes the limitations of the two traditional methods of poverty analysis in Latin America (income-based and unmet basic needs) by combining income with five other dimensions: school attendance for…

  12. A Framework for Dimensionality Assessment for Multidimensional Item Response Models

    ERIC Educational Resources Information Center

    Svetina, Dubravka; Levy, Roy

    2014-01-01

    A framework is introduced for considering dimensionality assessment procedures for multidimensional item response models. The framework characterizes procedures in terms of their confirmatory or exploratory approach, parametric or nonparametric assumptions, and applicability to dichotomous, polytomous, and missing data. Popular and emerging…

  13. Conditional Covariance-based Representation of Multidimensional Test Structure.

    ERIC Educational Resources Information Center

    Bolt, Daniel M.

    2001-01-01

    Presents a new nonparametric method for constructing a spatial representation of multidimensional test structure, the Conditional Covariance-based SCALing (CCSCAL) method. Describes an index to measure the accuracy of the representation. Uses simulation and real-life data analyses to show that the method provides a suitable approximation to…

  14. Teacher Self-Regulation: Examining a Multidimensional Construct

    ERIC Educational Resources Information Center

    Capa-Aydin, Yesim; Sungur, Semra; Uzuntiryaki, Esen

    2009-01-01

    This study aimed to develop and validate an instrument to assess the multidimensional nature of teacher self-regulation. A nine-factor structure was proposed: goal setting, intrinsic interest, performance goal orientation, mastery goal orientation, self-instruction, emotional control, self-evaluation, self-reaction, and help-seeking. Through a…

  15. Gender and Attitudes toward People Using Wheelchairs: A Multidimensional Perspective

    ERIC Educational Resources Information Center

    Vilchinsky, Noa; Werner, Shirli; Findler, Liora

    2010-01-01

    This study aims to investigate the effect of observer's gender and target's gender on attitudes toward people who use wheelchairs due to a physical disability. Four hundred four Jewish Israeli students without disabilities completed the "Multidimensional Attitudes Scale Toward Persons With Disabilities" (MAS). Initially, confirmatory…

  16. Educational Mismatch of Graduates: A Multidimensional and Fuzzy Indicator

    ERIC Educational Resources Information Center

    Betti, Gianni; D'Agostino, Antonella; Neri, Laura

    2011-01-01

    In this paper we attempt to measure the educational mismatch, seen as a problem of overeducation, using a multidimensional and fuzzy methodology. Educational mismatch can be difficult to measure because many factors can converge to its definition and the traditional unidimensional indicators presented in literature can offer a restricted view of…

  17. On the Solution of NBVP for Multidimensional Hyperbolic Equations

    PubMed Central

    Ashyralyev, Allaberen

    2014-01-01

    We are interested in studying multidimensional hyperbolic equations with nonlocal integral and Neumann or nonclassical conditions. For the approximate solution of this problem first and second order of accuracy difference schemes are presented. Stability estimates for the solution of these difference schemes are established. Some numerical examples illustrating applicability of these methods to hyperbolic problems are given. PMID:24983006

  18. The Phenotype of Loneliness

    PubMed Central

    Cacioppo, John T.; Cacioppo, Stephanie

    2012-01-01

    Goossens’ (in press) review nicely maps the progression of scientific research from its early focus on loneliness as a dysphoric state that results from the discrepancy between a person's ideal and actual social relationships to its current emphasis on the centrality of loneliness to our very nature as a social species, and he argues that developmental science throughout Europe has a great deal to contribute to our understanding of this construct. He concludes that psychologists should care about research on loneliness for five reasons: (i) it is a well-defined phenotype, (ii) it shows both high stability and individual differences in rates of change across years, (iii) it has adaptive value and evolutionary significance, (iv) it has a genetic substrate that is moderated by social environments, and (v) it has self-maintaining features that can lead to adverse mental health outcomes. Goossen's (2012) review is rife with information and ideas. We focus here on two additional important reasons and on the phenotype of loneliness. PMID:23024688

  19. From Phenotype to Genotype

    PubMed Central

    2014-01-01

    The progress in phenotype descriptions, measurements, and analyses has been remarkable in the last 50 years. Biomarkers (proteins, carbohydrates, lipids, hormones, various RNAs and cDNAs, microarrays) have been discovered and correlated with diseases and disorders, as well as physiological responses to disease, injury, stress, within blood, urine, and saliva. Three-dimensional digital imaging advanced how we “see” and utilize phenotypes toward diagnosis, treatment, and prognosis. In each example, scientific discovery led to inform clinical health care. In tandem, genetics evolved from Mendelian inheritance (single gene mutations) to include Complex Human Diseases (multiple gene-gene and gene-environment interactions). In addition, epigenetics blossomed with new insights about gene modifiers (e.g., histone and non-histone chromosomal protein methylation, acetylation, sulfation, phosphorylation). We are now at the beginning of a new era using human and microbial whole-genome sequencing to make significant healthcare decisions as to risk, stratification of patients, diagnosis, treatments, and outcomes. Are we as clinicians, scientists, and educators prepared to expand our scope of practice, knowledge base, integration into primary health care (medicine, pharmacy, nursing, and allied health science professions), and clinical approaches to craniofacial-oral-dental health care? The time is now. PMID:24799423

  20. Language Phenotypes and Intervention Planning: Bridging Research and Practice

    ERIC Educational Resources Information Center

    Fidler, Deborah J.; Philofsky, Amy; Hepburn, Susan L.

    2007-01-01

    This paper focuses on the communication and language phenotypes associated with three genetic disorders: Down syndrome, Williams syndrome, and fragile X syndrome. It is argued that there is empirical evidence that these disorders predispose children to specific profiles of strength and weakness in some areas of speech, language, and communication,…

  1. Designing Multichannel, Multidimensional, Arbitrary Flip Angle RF Pulses Using an Optimal Control Approach

    PubMed Central

    Xu, Dan; King, Kevin F.; Zhu, Yudong; McKinnon, Graeme C.; Liang, Zhi-Pei

    2009-01-01

    The vast majority of parallel transmission RF pulse designs so far are based on small-tip-angle (STA) approximation of the Bloch equation. These methods can design only excitation pulses with small flip angles (e.g., 30°). The linear class large-tip-angle (LCLTA) method is able to design large-tip-angle parallel transmission pulses through concatenating a sequence of small-excitation pulses when certain k-space trajectories are used. However, both STA and LCLTA are linear approximations of the nonlinear Bloch equation. Therefore, distortions from the ideal magnetization profiles due to the higher order terms can appear in the final magnetization profiles. This issue is addressed in this work by formulating the multidimensional multichannel RF pulse design as an optimal control problem with multiple controls based directly on the Bloch equation. Necessary conditions for the optimal solution are derived and a first-order gradient optimization algorithm is used to iteratively solve the optimal control problem, where an existing pulse is used as an initial “guess.” A systematic design procedure is also presented. Bloch simulation and phantom experimental results using various parallel transmission pulses (excitation, inversion, and refocusing) are shown to illustrate the effectiveness of the optimal control method in improving the spatial localization or homogeneity of the magnetization profiles. PMID:18306407

  2. Second order multidimensional sign-preserving remapping for ALE methods

    SciTech Connect

    Hill, Ryan N; Szmelter, J.

    2010-12-15

    A second-order conservative sign-preserving remapping scheme for Arbitrary Lagrangian-Eulerian (ALE) methods is developed utilising concepts of the Multidimensional Positive Definite Advection Transport Algorithm (MPDATA). The algorithm is inherently multidimensional, and so does not introduce splitting errors. The remapping is implemented in a two-dimensional, finite element ALE solver employing staggered quadrilateral meshes. The MPDATA remapping uses a finite volume discretization developed for volume coordinates. It is applied for the remapping of density and internal energy arranged as cell centered, and velocity as nodal, dependent variables. In the paper, the advection of scalar fields is examined first for test cases with prescribed mesh movement. A direct comparison of MPDATA with the performance of the van Leer MUSCL scheme indicates advantages of a multidimensional approach. Furthermore, distinctly different performance between basic MPDATA and the infinite gauge option is illustrated using benchmarks involving transport of a sign changing velocity field. Further development extends the application of MPDATA remapping to the full ALE solver with a staggered mesh arrangement for density, internal energy and momentum using volume coordinates. At present, two options of the algorithm - basic and infinite gauge - are implemented. To ensure a meaningful assessment, an identical Lagrangian solver and computational mesh update routines are used with either MPDATA or van Leer MUSCL remapping. The evaluation places particular focus on the abilities of both schemes to accurately model multidimensional problems. Theoretical considerations are supported with numerical examples. In addition to the prescribed mesh movement cases for advection of scalars, the demonstrations include two-dimensional Eulerian and ALE flow simulations on quadrilateral meshes with both fixed and variable timestep control. The key comparisons include the standard test cases of Sod and Noh

  3. A multifaceted analysis of HIV-1 protease multidrug resistance phenotypes

    PubMed Central

    2011-01-01

    Background Great strides have been made in the effective treatment of HIV-1 with the development of second-generation protease inhibitors (PIs) that are effective against historically multi-PI-resistant HIV-1 variants. Nevertheless, mutation patterns that confer decreasing susceptibility to available PIs continue to arise within the population. Understanding the phenotypic and genotypic patterns responsible for multi-PI resistance is necessary for developing PIs that are active against clinically-relevant PI-resistant HIV-1 variants. Results In this work, we use globally optimal integer programming-based clustering techniques to elucidate multi-PI phenotypic resistance patterns using a data set of 398 HIV-1 protease sequences that have each been phenotyped for susceptibility toward the nine clinically-approved HIV-1 PIs. We validate the information content of the clusters by evaluating their ability to predict the level of decreased susceptibility to each of the available PIs using a cross validation procedure. We demonstrate the finding that as a result of phenotypic cross resistance, the considered clinical HIV-1 protease isolates are confined to ~6% or less of the clinically-relevant phenotypic space. Clustering and feature selection methods are used to find representative sequences and mutations for major resistance phenotypes to elucidate their genotypic signatures. We show that phenotypic similarity does not imply genotypic similarity, that different PI-resistance mutation patterns can give rise to HIV-1 isolates with similar phenotypic profiles. Conclusion Rather than characterizing HIV-1 susceptibility toward each PI individually, our study offers a unique perspective on the phenomenon of PI class resistance by uncovering major multidrug-resistant phenotypic patterns and their often diverse genotypic determinants, providing a methodology that can be applied to understand clinically-relevant phenotypic patterns to aid in the design of novel inhibitors that

  4. Psychometric Properties of the Frost Multidimensional Perfectionism Scale with Australian Adolescent Girls: Clarification of Multidimensionality and Perfectionist Typology

    ERIC Educational Resources Information Center

    Hawkins, Colleen C.; Watt, Helen M. G.; Sinclair, Kenneth E.

    2006-01-01

    The psychometric properties of the Frost, Marten, Lahart, and Rosenblate Multidimensional Perfectionism Scale (1990) are investigated to determine its usefulness as a measurement of perfectionism with Australian secondary school girls and to find empirical support for the existence of both healthy and unhealthy types of perfectionist students.…

  5. Racial Identity, Phenotype, and Self-Esteem among Biracial Polynesian/White Individuals

    ERIC Educational Resources Information Center

    Allen, G. E. Kawika; Garriott, Patton O.; Reyes, Carla J.; Hsieh, Catherine

    2013-01-01

    This study examined racial identity, self-esteem, and phenotype among biracial Polynesian/White adults. Eighty-four Polynesian/White persons completed the Biracial Identity Attitude Scale, the Rosenberg Self-Esteem Inventory, and a Polynesian phenotype scale. Profile analyses showed participants identified more with their Polynesian parent. A…

  6. Distinct metabolic network states manifest in the gene expression profiles of pediatric inflammatory bowel disease patients and controls

    PubMed Central

    Knecht, Carolin; Fretter, Christoph; Rosenstiel, Philip; Krawczak, Michael; Hütt, Marc-Thorsten

    2016-01-01

    Information on biological networks can greatly facilitate the function-orientated interpretation of high-throughput molecular data. Genome-wide metabolic network models of human cells, in particular, can be employed to contextualize gene expression profiles of patients with the goal of both, a better understanding of individual etiologies and an educated reclassification of (clinically defined) phenotypes. We analyzed publicly available expression profiles of intestinal tissues from treatment-naive pediatric inflammatory bowel disease (IBD) patients and age-matched control individuals, using a reaction-centric metabolic network derived from the Recon2 model. By way of defining a measure of ‘coherence’, we quantified how well individual patterns of expression changes matched the metabolic network. We observed a bimodal distribution of metabolic network coherence in both patients and controls, albeit at notably different mixture probabilities. Multidimensional scaling analysis revealed a bisectional pattern as well that overlapped widely with the metabolic network-based results. Expression differences driving the observed bimodality were related to cellular transport of thiamine and bile acid metabolism, thereby highlighting the crosstalk between metabolism and other vital pathways. We demonstrated how classical data mining and network analysis can jointly identify biologically meaningful patterns in gene expression data. PMID:27585741

  7. Gingival Tissue Transcriptomes Identify Distinct Periodontitis Phenotypes

    PubMed Central

    Kebschull, M.; Demmer, R.T.; Grün, B.; Guarnieri, P.; Pavlidis, P.; Papapanou, P.N.

    2014-01-01

    The currently recognized principal forms of periodontitis—chronic and aggressive—lack an unequivocal, pathobiology-based foundation. We explored whether gingival tissue transcriptomes can serve as the basis for an alternative classification of periodontitis. We used cross-sectional whole-genome gene expression data from 241 gingival tissue biopsies obtained from sites with periodontal pathology in 120 systemically healthy nonsmokers with periodontitis, with available data on clinical periodontal status, subgingival microbial profiles, and serum IgG antibodies to periodontal microbiota. Adjusted model-based clustering of transcriptomic data using finite mixtures generated two distinct clusters of patients that did not align with the current classification of chronic and aggressive periodontitis. Differential expression profiles primarily related to cell proliferation in cluster 1 and to lymphocyte activation and unfolded protein responses in cluster 2. Patients in the two clusters did not differ with respect to age but presented with distinct phenotypes (statistically significantly different whole-mouth clinical measures of extent/severity, subgingival microbial burden by several species, and selected serum antibody responses). Patients in cluster 2 showed more extensive/severe disease and were more often male. The findings suggest that distinct gene expression signatures in pathologic gingival tissues translate into phenotypic differences and can provide a basis for a novel classification. PMID:24646639

  8. High-throughput mouse phenotyping.

    PubMed

    Gates, Hilary; Mallon, Ann-Marie; Brown, Steve D M

    2011-04-01

    Comprehensive phenotyping will be required to reveal the pleiotropic functions of a gene and to uncover the wider role of genetic loci within diverse biological systems. The challenge will be to devise phenotyping approaches to characterise the thousands of mutants that are being generated as part of international efforts to acquire a mutant for every gene in the mouse genome. In order to acquire robust datasets of broad based phenotypes from mouse mutants it is necessary to design and implement pipelines that incorporate standardised phenotyping platforms that are validated across diverse mouse genetics centres or mouse clinics. We describe here the rationale and methodology behind one phenotyping pipeline, EMPReSSslim, that was designed as part of the work of the EUMORPHIA and EUMODIC consortia, and which exemplifies some of the challenges facing large-scale phenotyping. EMPReSSslim captures a broad range of data on diverse biological systems, from biochemical to physiological amongst others. Data capture and dissemination is pivotal to the operation of large-scale phenotyping pipelines, including the definition of parameters integral to each phenotyping test and the associated ontological descriptions. EMPReSSslim data is displayed within the EuroPhenome database, where a variety of tools are available to allow the user to search for interesting biological or clinical phenotypes.

  9. EHR Big Data Deep Phenotyping

    PubMed Central

    Lenert, L.; Lopez-Campos, G.

    2014-01-01

    Summary Objectives Given the quickening speed of discovery of variant disease drivers from combined patient genotype and phenotype data, the objective is to provide methodology using big data technology to support the definition of deep phenotypes in medical records. Methods As the vast stores of genomic information increase with next generation sequencing, the importance of deep phenotyping increases. The growth of genomic data and adoption of Electronic Health Records (EHR) in medicine provides a unique opportunity to integrate phenotype and genotype data into medical records. The method by which collections of clinical findings and other health related data are leveraged to form meaningful phenotypes is an active area of research. Longitudinal data stored in EHRs provide a wealth of information that can be used to construct phenotypes of patients. We focus on a practical problem around data integration for deep phenotype identification within EHR data. The use of big data approaches are described that enable scalable markup of EHR events that can be used for semantic and temporal similarity analysis to support the identification of phenotype and genotype relationships. Conclusions Stead and colleagues’ 2005 concept of using light standards to increase the productivity of software systems by riding on the wave of hardware/processing power is described as a harbinger for designing future healthcare systems. The big data solution, using flexible markup, provides a route to improved utilization of processing power for organizing patient records in genotype and phenotype research. PMID:25123744

  10. Multidimensional and comprehensive two-dimensional gas chromatography of dichloromethane soluble products from a high sulfur Jordanian oil shale.

    PubMed

    Amer, Mohammad W; Mitrevski, Blagoj; Jackson, W Roy; Chaffee, Alan L; Marriott, Philip J

    2014-03-01

    A high sulfur Jordanian oil shale was converted into liquid hydrocarbons by reaction at 390 °C under N2, and the dichloromethane soluble fraction of the products was isolated then analyzed by using gas chromatography (GC). Comprehensive two-dimensional GC (GC×GC) and multidimensional GC (MDGC) were applied for component separation on a polar - non-polar column set. Flame-ionization detection (FID) was used with GC×GC for general sample profiling, and mass spectrometry (MS) for component identification in MDGC. Multidimensional GC revealed a range of thiophenes (th), benzothiophenes (bth) and small amounts of dibenzothiophenes (dbth) and benzonaphthothiophenes (bnth). In addition, a range of aliphatic alkanes and cycloalkanes, ethers, polar single ring aromatic compounds and small amounts of polycyclic aromatics were also identified. Some of these compound classes were not uniquely observable by conventional 1D GC, and certainly this is true for many of their minor constituent members. The total number of distinct compounds was very large (ca.>1000). GC×GC was shown to be appropriate for general sample profiling, and MDGC-MS proved to be a powerful technique for the separation and identification of sulfur-containing components and other polar compounds.

  11. Autism Spectrum and Obsessive–Compulsive Disorders: OC Behaviors, Phenotypes and Genetics

    PubMed Central

    Jacob, Suma; Landeros-Weisenberger, Angeli; Leckman, James F.

    2014-01-01

    Autism spectrum disorders (ASDs) are a phenotypically and etiologically heterogeneous set of disorders that include obsessive–compulsive behaviors (OCB) that partially overlap with symptoms associated with obsessive–compulsive disorder (OCD). The OCB seen in ASD vary depending on the individual’s mental and chronological age as well as the etiology of their ASD. Although progress has been made in the measurement of the OCB associated with ASD, more work is needed including the potential identification of heritable endophenotypes. Likewise, important progress toward the understanding of genetic influences in ASD has been made by greater refinement of relevant phenotypes using a broad range of study designs, including twin and family-genetic studies, parametric and nonparametric linkage analyses, as well as candidate gene studies and the study of rare genetic variants. These genetic analyses could lead to the refinement of the OCB phenotypes as larger samples are studied and specific associations are replicated. Like ASD, OCB are likely to prove to be multidimensional and polygenic. Some of the vulnerability genes may prove to be generalist genes influencing the phenotypic expression of both ASD and OCD while others will be specific to subcomponents of the ASD phenotype. In order to discover molecular and genetic mechanisms, collaborative approaches need to generate shared samples, resources, novel genomic technologies, as well as more refined phenotypes and innovative statistical approaches. There is a growing need to identify the range of molecular pathways involved in OCB related to ASD in order to develop novel treatment interventions. PMID:20029829

  12. An object-oriented multidimensional model for data warehouse

    NASA Astrophysics Data System (ADS)

    Gosain, Anjana; Mann, Suman

    2011-12-01

    Organizations, to have a competitive edge upon each other, resort to business intelligence which refers to information available for enterprise to make strategic decisions. Data warehouse being the repository of data provides the backend for achieving business intelligence. The design of data warehouse, thereby, forms the key, to extract and obtain the relevant information facilitating to make strategic decisions. The initial focus for the design had been upon the conceptual models but now object oriented multidimensional modelling has emerged as the foundation for the designing of data warehouse. Several proposals have been put forth for object oriented multidimensional modelling, each incorporating some or other features, but not all. This paper consolidates all the features previously introduced and the new introduced, thus, proposing a new model having features to be incorporated while designing the data warehouse.

  13. Advanced numerics for multi-dimensional fluid flow calculations

    NASA Technical Reports Server (NTRS)

    Vanka, S. P.

    1984-01-01

    In recent years, there has been a growing interest in the development and use of mathematical models for the simulation of fluid flow, heat transfer and combustion processes in engineering equipment. The equations representing the multi-dimensional transport of mass, momenta and species are numerically solved by finite-difference or finite-element techniques. However despite the multiude of differencing schemes and solution algorithms, and the advancement of computing power, the calculation of multi-dimensional flows, especially three-dimensional flows, remains a mammoth task. The following discussion is concerned with the author's recent work on the construction of accurate discretization schemes for the partial derivatives, and the efficient solution of the set of nonlinear algebraic equations resulting after discretization. The present work has been jointly supported by the Ramjet Engine Division of the Wright Patterson Air Force Base, Ohio, and the NASA Lewis Research Center.

  14. A Multidimensional Data Warehouse for Community Health Centers

    PubMed Central

    Kunjan, Kislaya; Toscos, Tammy; Turkcan, Ayten; Doebbeling, Brad N.

    2015-01-01

    Community health centers (CHCs) play a pivotal role in healthcare delivery to vulnerable populations, but have not yet benefited from a data warehouse that can support improvements in clinical and financial outcomes across the practice. We have developed a multidimensional clinic data warehouse (CDW) by working with 7 CHCs across the state of Indiana and integrating their operational, financial and electronic patient records to support ongoing delivery of care. We describe in detail the rationale for the project, the data architecture employed, the content of the data warehouse, along with a description of the challenges experienced and strategies used in the development of this repository that may help other researchers, managers and leaders in health informatics. The resulting multidimensional data warehouse is highly practical and is designed to provide a foundation for wide-ranging healthcare data analytics over time and across the community health research enterprise. PMID:26958297

  15. Multidimensional nanomaterials for the control of stem cell fate

    NASA Astrophysics Data System (ADS)

    Chueng, Sy-Tsong Dean; Yang, Letao; Zhang, Yixiao; Lee, Ki-Bum

    2016-09-01

    Current stem cell therapy suffers low efficiency in giving rise to differentiated cell lineages, which can replace the original damaged cells. Nanomaterials, on the other hand, provide unique physical size, surface chemistry, conductivity, and topographical microenvironment to regulate stem cell differentiation through multidimensional approaches to facilitate gene delivery, cell-cell, and cell-ECM interactions. In this review, nanomaterials are demonstrated to work both alone and synergistically to guide selective stem cell differentiation. From three different nanotechnology families, three approaches are shown: (1) soluble microenvironmental factors; (2) insoluble physical microenvironment; and (3) nano-topographical features. As regenerative medicine is heavily invested in effective stem cell therapy, this review is inspired to generate discussions in the potential clinical applications of multi-dimensional nanomaterials.

  16. A Multidimensional Data Warehouse for Community Health Centers.

    PubMed

    Kunjan, Kislaya; Toscos, Tammy; Turkcan, Ayten; Doebbeling, Brad N

    2015-01-01

    Community health centers (CHCs) play a pivotal role in healthcare delivery to vulnerable populations, but have not yet benefited from a data warehouse that can support improvements in clinical and financial outcomes across the practice. We have developed a multidimensional clinic data warehouse (CDW) by working with 7 CHCs across the state of Indiana and integrating their operational, financial and electronic patient records to support ongoing delivery of care. We describe in detail the rationale for the project, the data architecture employed, the content of the data warehouse, along with a description of the challenges experienced and strategies used in the development of this repository that may help other researchers, managers and leaders in health informatics. The resulting multidimensional data warehouse is highly practical and is designed to provide a foundation for wide-ranging healthcare data analytics over time and across the community health research enterprise.

  17. Multidimensional Simulations of Thermonuclear Supernovae from The First Stars

    NASA Astrophysics Data System (ADS)

    Chen, Ke-Jung; Heger, Alexander; Almgren, Ann

    2011-04-01

    Current models of the formation of the first stars in the universe suggest that these stars were very massive, having a typical mass scale of hundreds of solar masses. Such stars would explode as pair instability supernovae (PSNe). These supernovae hold the key to understanding the formation of the first heavy elements and the first galaxy formation in the universe. The current theoretical models for PSNe are all based on one-dimensional calculations; until now, multidimensional simulations have been scarce. We present the results from multidimensional numerical studies of PSNe with a new radiation-hydrodynamics code, CASTRO and with realistic nuclear reaction networks. We simulate the fluid instabilities that occur in multiple spatial dimensions and discuss how the resulting mixing affects the explosion, mixing, and nucleosynthesis of these supernovae.

  18. Advanced numerics for multi-dimensional fluid flow calculations

    SciTech Connect

    Vanka, S.P.

    1984-04-01

    In recent years, there has been a growing interest in the development and use of mathematical models for the simulation of fluid flow, heat transfer and combustion processes in engineering equipment. The equations representing the multi-dimensional transport of mass, momenta and species are numerically solved by finite-difference or finite-element techniques. However despite the multiude of differencing schemes and solution algorithms, and the advancement of computing power, the calculation of multi-dimensional flows, especially three-dimensional flows, remains a mammoth task. The following discussion is concerned with the author's recent work on the construction of accurate discretization schemes for the partial derivatives, and the efficient solution of the set of nonlinear algebraic equations resulting after discretization. The present work has been jointly supported by the Ramjet Engine Division of the Wright Patterson Air Force Base, Ohio, and the NASA Lewis Research Center.

  19. Analysis of protein composition using multidimensional chromatography and mass spectrometry.

    PubMed

    Link, Andrew J; Washburn, Michael P

    2014-11-03

    Multidimensional liquid chromatography of peptides produced by protease digestion of complex protein mixtures followed by tandem mass spectrometry can be coupled with automated database searching to identify large numbers of proteins in complex samples. These methods avoid the limitations of gel electrophoresis and in-gel digestions by directly identifying protein mixtures in solution. One method used extensively is named Multidimensional Protein Identification Technology (MudPIT), where reversed-phase chromatography and strong cation-exchange chromatography are coupled directly in a microcapillary column. This column is then placed in line between an HPLC and a mass spectrometer for complex mixture analysis. MudPIT remains a powerful approach for analyzing complex mixtures like whole proteomes and protein complexes. MudPIT is used for quantitative proteomic analysis of complex mixtures to generate novel biological insights.

  20. Plant Phenotype Characterization System

    SciTech Connect

    Daniel W McDonald; Ronald B Michaels

    2005-09-09

    This report is the final scientific report for the DOE Inventions and Innovations Project: Plant Phenotype Characterization System, DE-FG36-04GO14334. The period of performance was September 30, 2004 through July 15, 2005. The project objective is to demonstrate the viability of a new scientific instrument concept for the study of plant root systems. The root systems of plants are thought to be important in plant yield and thus important to DOE goals in renewable energy sources. The scientific study and understanding of plant root systems is hampered by the difficulty in observing root activity and the inadequacy of existing root study instrumentation options. We have demonstrated a high throughput, non-invasive, high resolution technique for visualizing plant root systems in-situ. Our approach is based upon low-energy x-ray radiography and the use of containers and substrates (artificial soil) which are virtually transparent to x-rays. The system allows us to germinate and grow plant specimens in our containers and substrates and to generate x-ray images of the developing root system over time. The same plant can be imaged at different times in its development. The system can be used for root studies in plant physiology, plant morphology, plant breeding, plant functional genomics and plant genotype screening.

  1. State Profiles.

    ERIC Educational Resources Information Center

    State-Federal Information Clearinghouse for Exceptional Children, Reston, VA.

    State-by-state public policy profiles are provided by the Council for Exceptional Children's State-Federal Information Clearinghouse. These profiles summarize the present legal base for the delivery of educational services to handicapped children in the United States. Included in each profile is information from various avenues used to establish…

  2. Multidimensional, multiphysics simulations of core-collapse supernovae

    SciTech Connect

    Messer, Bronson; Mezzacappa, Anthony; Blondin, J. M.; Bruenn, S. W.; Hix, William Raphael

    2008-01-01

    CHIMERA is a multi-dimensional radiation hydrodynamics code designed to study core-collapse supernovae. The code is made up of three essentially independent parts: a hydrodynamics module, a nuclear burning module, and a neutrino transport solver combined within an operator-split approach. We review the code s architecture and some recently improved implementations used in the code. We also briefly discuss preliminary results obtained with the code in three spatial dimensions.

  3. Multidimensional, multiphysics simulations of core-collapse supernovae

    SciTech Connect

    Messer, Bronson; Mezzacappa, Anthony; Blondin, J. M.; Bruenn, S. W.; Hix, William Raphael

    2008-01-01

    CHIMERA is a multi-dimensional radiation hydrodynamics code designed to study core-collapse supernovae. The code is made up of three essentially independent parts: a hydrodynamics module, a nuclear burning module, and a neutrino transport solver combined within an operator-split approach. We review the code's architecture and some recently improved implementations used in the code. We also briefly discuss preliminary results obtained with the code in three spatial dimensions.

  4. Multidimensional scaling analysis of simulated air combat maneuvering performance data.

    PubMed

    Polzella, D J; Reid, G B

    1989-02-01

    This paper describes the decomposition of air combat maneuvering by means of multidimensional scaling (MDS). MDS analyses were applied to performance data obtained from expert and novice pilots during simulated air-to-air combat. The results of these analyses revealed that the performance of expert pilots is characterized by advantageous maneuverability and intelligent energy management. It is argued that MDS, unlike simpler metrics, permits the investigator to achieve greater insights into the underlying structure associated with performance of a complex task.

  5. Application of Multidimensional Spectrum Analysis for Analytical Chemistry

    SciTech Connect

    Hatsukawa, Yuichi; Hayakawa, Takehito; Toh, Yosuke; Shinohara, Nobuo; Oshima, Masumi

    1999-12-31

    Feasibility of application of the multidimensional {gamma} ray spectroscopy for analytical chemistry was examined. Two reference igneous rock (JP-1, JB-1a) samples issued by the Geological Survey of Japan (GSJ) were irradiated at a research reactor with thermal neutrons, and {gamma} rays from the radioisotopes produced by neutron capture reactions were measured using a {gamma}-ray detector array. Simultaneously 27 elements were observed with no chemical separation.

  6. Accelerated expansion of the Universe and multidimensional theory of gravitation

    NASA Astrophysics Data System (ADS)

    Pakhomov, A. G.

    2007-09-01

    A condition for accelerated expansion of the Universe is derived from multidimensional formulas of gravitation, which is a generalization of the general theory of relativity for n dimensions. The model of a one-component ideal isotropic substance with a power-law diagonal metric is used as initial one. Restrictions on the state equations of our 3D space and accompanying additional dimensions are obtained.

  7. In-in formalism on tunneling background: Multidimensional quantum mechanics

    NASA Astrophysics Data System (ADS)

    Sugimura, Kazuyuki

    2013-07-01

    We reformulate quantum tunneling in a multidimensional system where the tunneling sector is nonlinearly coupled to oscillators. The WKB wave function is explicitly constructed under the assumption that the system was in the ground state before tunneling. We find that the quantum state after tunneling can be expressed in the language of the conventional in-in formalism. Some implications of the result to cosmology are discussed.

  8. Analysis of self-similar solutions of multidimensional conservation laws

    SciTech Connect

    Keyfitz, Barbara

    2014-02-15

    This project focused on analysis of multidimensional conservation laws, specifically on extensions to the study of self-siminar solutions, a project initiated by the PI. In addition, progress was made on an approach to studying conservation laws of very low regularity; in this research, the context was a novel problem in chromatography. Two graduate students in mathematics were supported during the grant period, and have almost completed their thesis research.

  9. Probes for multidimensional nanospectroscopic imaging and methods of fabrication thereof

    SciTech Connect

    Weber-Bargioni, Alexander; Cabrini, Stefano; Bao, Wei; Melli, Mauro; Yablonovitch, Eli; Schuck, Peter J

    2015-03-17

    This disclosure provides systems, methods, and apparatus related to probes for multidimensional nanospectroscopic imaging. In one aspect, a method includes providing a transparent tip comprising a dielectric material. A four-sided pyramidal-shaped structure is formed at an apex of the transparent tip using a focused ion beam. Metal layers are deposited over two opposing sides of the four-sided pyramidal-shaped structure.

  10. Unveiling Bacterial Interactions through Multidimensional Scaling and Dynamics Modeling

    PubMed Central

    Dorado-Morales, Pedro; Vilanova, Cristina; P. Garay, Carlos; Martí, Jose Manuel; Porcar, Manuel

    2015-01-01

    We propose a new strategy to identify and visualize bacterial consortia by conducting replicated culturing of environmental samples coupled with high-throughput sequencing and multidimensional scaling analysis, followed by identification of bacteria-bacteria correlations and interactions. We conducted a proof of concept assay with pine-tree resin-based media in ten replicates, which allowed detecting and visualizing dynamical bacterial associations in the form of statistically significant and yet biologically relevant bacterial consortia. PMID:26671778

  11. Application of multidimensional spectrum analysis for analytical chemistry

    SciTech Connect

    Hatsukawa, Yuichi; Hayakawa, Takehito; Toh, Yosuke; Shinohara, Nobuo; Oshima, Masumi

    1999-11-16

    Feasibility of application of the multidimensional {gamma} ray spectroscopy for analytical chemistry was examined. Two reference igneous rock (JP-1, JB-1a) samples issued by the Geological Survey of Japan (GSJ) were irradiated at a research reactor with thermal neutrons, and {gamma} rays from the radioisotopes produced by neutron capture reactions were measured using a {gamma}-ray detector array. Simultaneously 27 elements were observed with no chemical separation.

  12. Multidimensional physical activity: An opportunity not a problem

    PubMed Central

    Thompson, Dylan; Peacock, Oliver; Western, Max; Batterham, Alan M.

    2015-01-01

    Our research shows that no single metric will adequately reflect an individual’s physical activity because multiple biologically-important dimensions are independent and unrelated. We propose that there is an opportunity to exploit this multidimensional characteristic of physical activity in order to improve personalised feedback and offer physical activity options and choices that are tailored to an individual’s needs and preferences. PMID:25607280

  13. Global phenotypic characterization of bacteria

    PubMed Central

    Bochner, Barry R

    2009-01-01

    The measure of the quality of a systems biology model is how well it can reproduce and predict the behaviors of a biological system such as a microbial cell. In recent years, these models have been built up in layers, and each layer has been growing in sophistication and accuracy in parallel with a global data set to challenge and validate the models in predicting the content or activities of genes (genomics), proteins (proteomics), metabolites (metabolomics), and ultimately cell phenotypes (phenomics). This review focuses on the latter, the phenotypes of microbial cells. The development of Phenotype MicroArrays, which attempt to give a global view of cellular phenotypes, is described. In addition to their use in fleshing out and validating systems biology models, there are many other uses of this global phenotyping technology in basic and applied microbiology research, which are also described. PMID:19054113

  14. Are multidimensional social classifications of areas useful in UK health service research?

    PubMed Central

    Reading, R; Openshaw, S; Jarvis, S

    1994-01-01

    OBJECTIVES--To show the advantages and disadvantages of a multi-dimensional small area classification in the analysis of child health data in order to measure social inequalities in health and to identify the types of area that have greater health needs. DESIGN--Health data on children from the district child health information system and a survey of primary school children's height were classified by the census enumeration district of residence using the Super profiles neighbourhood classification. SETTING--County of Northumberland, United Kingdom. SUBJECTS--One cohort comprised 21,702 preschool children age 0-5 years resident in Northumberland, and another cohort 9930 school children aged 5-8.5 years. MAIN OUTCOME MEASURES--Variations between types of area in the proportions of babies with birthweight less than 2.8 kg; births to mothers aged less than 20 years; pertussis immunisation uptake; child health screening uptake; and mean height of school children. RESULTS--Areas with the poorest child health measures were those which were most socially disadvantaged. The most affluent areas tended to have the best measures of health, although rural areas also had good measures. Problems in analysis included examples of the "ecological fallacy", misleading area descriptions, and the identification of the specific factors associated with poor health measures. Advantages included a wider view of social circumstances than simply "deprivation" and the ability to identify characteristic types of areas with increased child health needs. CONCLUSIONS--There is a limited place for multidimensional small area classifications in the analysis of health data for both research and health needs assessment provided the inherent drawbacks of these data are understood in interpreting the results. PMID:8189178

  15. Efficient Subtorus Processor Allocation in a Multi-Dimensional Torus

    SciTech Connect

    Weizhen Mao; Jie Chen; William Watson

    2005-11-30

    Processor allocation in a mesh or torus connected multicomputer system with up to three dimensions is a hard problem that has received some research attention in the past decade. With the recent deployment of multicomputer systems with a torus topology of dimensions higher than three, which are used to solve complex problems arising in scientific computing, it becomes imminent to study the problem of allocating processors of the configuration of a torus in a multi-dimensional torus connected system. In this paper, we first define the concept of a semitorus. We present two partition schemes, the Equal Partition (EP) and the Non-Equal Partition (NEP), that partition a multi-dimensional semitorus into a set of sub-semitori. We then propose two processor allocation algorithms based on these partition schemes. We evaluate our algorithms by incorporating them in commonly used FCFS and backfilling scheduling policies and conducting simulation using workload traces from the Parallel Workloads Archive. Specifically, our simulation experiments compare four algorithm combinations, FCFS/EP, FCFS/NEP, backfilling/EP, and backfilling/NEP, for two existing multi-dimensional torus connected systems. The simulation results show that our algorithms (especially the backfilling/NEP combination) are capable of producing schedules with system utilization and mean job bounded slowdowns comparable to those in a fully connected multicomputer.

  16. The Compactification Problems of Additional Dimensions in Multidimensional Cosmological Theories

    NASA Astrophysics Data System (ADS)

    Saidov, Tamerlan

    2011-11-01

    Multidimensionality of our Universe is one of the most intriguing assumption in modern physics. It follows naturally from theories unifying different fundamental interactions with gravity, e.g. M/string theory. The idea has received a great deal of renewed attention over the last few years. However, it also brings a row of additional questions. According to observations the internal space should be static or nearly static at least from the time of primordial nucleosynthesis, otherwise the fundamental physical constants would vary. This means that at the present evolutionary stage of the Universe there are two possibilities: slow variation or compactification of internal space scale parameters. In many recent studies the problem of extra dimensions stabilization was studied for so-called ADD. Under these approaches a massive scalar fields (gravitons or radions) of external space-time can be presented as conformal excitations. In above mentioned works it was assumed that multidimensional action to be linear with respect to curvature. Although as follows from string theory, the gravity action needs to be extended to nonlinear one. In order to investigate effects of nonlinearity, in this Thesis a multidimensional Lagrangian will be studied, having the form L = f(R), where f(R) is an arbitrary smooth function of the scalar curvature.

  17. Design of integrated and networked multidimensional grating digital readout

    NASA Astrophysics Data System (ADS)

    Chang, Li; Xu, Hui; Xiu, Guoyi

    2008-10-01

    The grating digital readout is the key measurement feedback device of the numerical control system and base of the equipment manufacturing industry. With the development of the complex machining, the multi-axis linkage is a new direction of the numerical control system, which needs the multidimensional measurement. Based on all digital grating moiré fringe subdivision theory, the paper introduces the design of integrated and networked multidimensional grating digital readout with an embedded system-on-chip ZA7V that is a complete field configurable system-on-chip with a 32- bit ARM7TDMI processor core, a programmable logic matrix, a robust memory subsystem and a high-performance dedicated internal bus. Networked functions include Ethernet interface, CAN bus interface, USB bus interface and GPRS interface so that the grating digital readout can access the device network, workshop network, intranet network and Internet. The simulation results and experimental data prove that the realization of the integrated and networked multidimensional grating digital readout. It will be widely used in the numerical control system and machining center.

  18. Igloo-Plot: a tool for visualization of multidimensional datasets.

    PubMed

    Kuntal, Bhusan K; Ghosh, Tarini Shankar; Mande, Sharmila S

    2014-01-01

    Advances in science and technology have resulted in an exponential growth of multivariate (or multi-dimensional) datasets which are being generated from various research areas especially in the domain of biological sciences. Visualization and analysis of such data (with the objective of uncovering the hidden patterns therein) is an important and challenging task. We present a tool, called Igloo-Plot, for efficient visualization of multidimensional datasets. The tool addresses some of the key limitations of contemporary multivariate visualization and analysis tools. The visualization layout, not only facilitates an easy identification of clusters of data-points having similar feature compositions, but also the 'marker features' specific to each of these clusters. The applicability of the various functionalities implemented herein is demonstrated using several well studied multi-dimensional datasets. Igloo-Plot is expected to be a valuable resource for researchers working in multivariate data mining studies. Igloo-Plot is available for download from: http://metagenomics.atc.tcs.com/IglooPlot/.

  19. Theme section: Multi-dimensional modelling, analysis and visualization

    NASA Astrophysics Data System (ADS)

    Guilbert, Éric; Çöltekin, Arzu; Castro, Francesc Antón; Pettit, Chris

    2016-07-01

    Spatial data are now collected and processed in larger amounts, and used by larger populations than ever before. While most geospatial data have traditionally been recorded as two-dimensional data, the evolution of data collection methods and user demands have led to data beyond the two dimensions describing complex multidimensional phenomena. An example of the relevance of multidimensional modelling is seen with the development of urban modelling where several dimensions have been added to the traditional 2D map representation (Sester et al., 2011). These include obviously the third spatial dimension (Biljecki et al., 2015) as well as the temporal, but also the scale dimension (Van Oosterom and Stoter, 2010) or, as mentioned by (Lu et al., 2016), multi-spectral and multi-sensor data. Such a view provides an organisation of multidimensional data around these different axes and it is time to explore each axis as the availability of unprecedented amounts of new data demands new solutions. The availability of such large amounts of data induces an acute need for developing new approaches to assist with their dissemination, visualisation, and analysis by end users. Several issues need to be considered in order to provide a meaningful representation and assist in data visualisation and mining, modelling and analysis; such as data structures allowing representation at different scales or in different contexts of thematic information.

  20. Multidimensional physical self-concept of athletes with physical disabilities.

    PubMed

    Shapiro, Deborah R; Martin, Jeffrey J

    2010-10-01

    The purposes of this investigation were first to predict reported PA (physical activity) behavior and self-esteem using a multidimensional physical self-concept model and second to describe perceptions of multidimensional physical self-concept (e.g., strength, endurance, sport competence) among athletes with physical disabilities. Athletes (N = 36, M age = 16.11, SD age = 2.8) completed the Physical Self-Description Questionnaire. Participants reported mostly positive perceptions of self-esteem, global physical self-concept, endurance, body fat, sport competence, strength, flexibility, and physical activity (Ms ranging from 3.9 to 5.6 out of 6). Correlations indicated a number of significant relationships among self-esteem and reported PA and various dimensions of physical self-concept. Using physical self-concept, strength, endurance, and flexibility in the first regression equation and sport competence and endurance simultaneously in the second equation, 47 and 31% of the variance was accounted for in self-esteem and reported PA, respectively. The findings support the value of examining multidimensional physical self-concept as different aspects of the physical self appear to have different influences on reported PA engagement versus self-esteem.

  1. An improved multidimensional MPA procedure for bidirectional earthquake excitations.

    PubMed

    Wang, Feng; Sun, Jian-Gang; Zhang, Ning

    2014-01-01

    Presently, the modal pushover analysis procedure is extended to multidimensional analysis of structures subjected to multidimensional earthquake excitations. an improved multidimensional modal pushover analysis (IMMPA) method is presented in the paper in order to estimate the response demands of structures subjected to bidirectional earthquake excitations, in which the unidirectional earthquake excitation applied on equivalent SDOF system is replaced by the direct superposition of two components earthquake excitations, and independent analysis in each direction is not required and the application of simplified superposition formulas is avoided. The strength reduction factor spectra based on superposition of earthquake excitations are discussed and compared with the traditional strength reduction factor spectra. The step-by-step procedure is proposed to estimate seismic demands of structures. Two examples are implemented to verify the accuracy of the method, and the results of the examples show that (1) the IMMPA method can be used to estimate the responses of structure subjected to bidirectional earthquake excitations. (2) Along with increase of peak of earthquake acceleration, structural response deviation estimated with the IMMPA method may also increase. (3) Along with increase of the number of total floors of structures, structural response deviation estimated with the IMMPA method may also increase.

  2. An Improved Multidimensional MPA Procedure for Bidirectional Earthquake Excitations

    PubMed Central

    Wang, Feng; Sun, Jian-Gang; Zhang, Ning

    2014-01-01

    Presently, the modal pushover analysis procedure is extended to multidimensional analysis of structures subjected to multidimensional earthquake excitations. an improved multidimensional modal pushover analysis (IMMPA) method is presented in the paper in order to estimate the response demands of structures subjected to bidirectional earthquake excitations, in which the unidirectional earthquake excitation applied on equivalent SDOF system is replaced by the direct superposition of two components earthquake excitations, and independent analysis in each direction is not required and the application of simplified superposition formulas is avoided. The strength reduction factor spectra based on superposition of earthquake excitations are discussed and compared with the traditional strength reduction factor spectra. The step-by-step procedure is proposed to estimate seismic demands of structures. Two examples are implemented to verify the accuracy of the method, and the results of the examples show that (1) the IMMPA method can be used to estimate the responses of structure subjected to bidirectional earthquake excitations. (2) Along with increase of peak of earthquake acceleration, structural response deviation estimated with the IMMPA method may also increase. (3) Along with increase of the number of total floors of structures, structural response deviation estimated with the IMMPA method may also increase. PMID:25140333

  3. Enhancing Privacy in Participatory Sensing Applications with Multidimensional Data

    SciTech Connect

    Groat, Michael; Forrest, Stephanie; Horey, James L; Edwards, Benjamin; He, Wenbo

    2012-01-01

    Participatory sensing applications rely on individuals to share local and personal data with others to produce aggregated models and knowledge. In this setting, privacy is an important consideration, and lack of privacy could discourage widespread adoption of many exciting applications. We present a privacy-preserving participatory sensing scheme for multidimensional data which uses negative surveys. Multidimensional data, such as vectors of attributes that include location and environment fields, pose a particular challenge for privacy protection and are common in participatory sensing applications. When reporting data in a negative survey, an individual participant randomly selects a value from the set complement of the sensed data value, once for each dimension, and returns the negative values to a central collection server. Using algorithms described in this paper, the server can reconstruct the probability density functions of the original distributions of sensed values, without knowing the participants actual data. As a consequence, complicated encryption and key management schemes are avoided, conserving energy. We study trade-offs between accuracy and privacy, and their relationships to the number of dimensions, categories, and participants. We introduce dimensional adjustment, a method that reduces the magnification of error associated with earlier work. Two simulation scenarios illustrate how the approach can protect the privacy of a participant's multidimensional data while allowing useful population information to be aggregated.

  4. Interdisciplinary hospice team processes and multidimensional pain: a qualitative study.

    PubMed

    Dugan Day, Michele

    2012-01-01

    Hospice teams may address multidimensional pain through the synergistic interaction of team members from various professional disciplines during regularly scheduled team meetings. However, the occurrence of that critical exchange has not been adequately described or documented. The purpose of this qualitative study was to explore two processes in team pain palliation: communication and collaboration. Data were gathered through individual interviews and a 1-year observation of team members from two hospices (physicians, nurses, aides, chaplains, social workers). Utilizing constant comparison, 14 final thematic categories were discovered. Use of biopsychosocial/spiritual terms by all team members meant that the team had the common language needed to communicate about multidimensional pain. Interviews and observation revealed a gap in translating multidisciplinary communication in team meetings into collaborative acts for pain treatment. In addition, structural influences inhibited creativity in pain palliation. There was no mutual understanding of the purpose for team meetings, no recognition of the need to reflect on team process, or common definition of leadership. Social work roles in hospice should include leadership that moves teams toward interdisciplinary care for multidimensional pain.

  5. POLARIZED LINE FORMATION IN MULTI-DIMENSIONAL MEDIA. III. HANLE EFFECT WITH PARTIAL FREQUENCY REDISTRIBUTION

    SciTech Connect

    Anusha, L. S.; Nagendra, K. N.

    2011-09-01

    In two previous papers, we solved the polarized radiative transfer (RT) equation in multi-dimensional (multi-D) geometries with partial frequency redistribution as the scattering mechanism. We assumed Rayleigh scattering as the only source of linear polarization (Q/I, U/I) in both these papers. In this paper, we extend these previous works to include the effect of weak oriented magnetic fields (Hanle effect) on line scattering. We generalize the technique of Stokes vector decomposition in terms of the irreducible spherical tensors T{sup K}{sub Q}, developed by Anusha and Nagendra, to the case of RT with Hanle effect. A fast iterative method of solution (based on the Stabilized Preconditioned Bi-Conjugate-Gradient technique), developed by Anusha et al., is now generalized to the case of RT in magnetized three-dimensional media. We use the efficient short-characteristics formal solution method for multi-D media, generalized appropriately to the present context. The main results of this paper are the following: (1) a comparison of emergent (I, Q/I, U/I) profiles formed in one-dimensional (1D) media, with the corresponding emergent, spatially averaged profiles formed in multi-D media, shows that in the spatially resolved structures, the assumption of 1D may lead to large errors in linear polarization, especially in the line wings. (2) The multi-D RT in semi-infinite non-magnetic media causes a strong spatial variation of the emergent (Q/I, U/I) profiles, which is more pronounced in the line wings. (3) The presence of a weak magnetic field modifies the spatial variation of the emergent (Q/I, U/I) profiles in the line core, by producing significant changes in their magnitudes.

  6. Measurement and inference of profile soil-water dynamics at different hillslope positions in a semi-arid agricultural watershed

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dynamics of profile soil water vary in relation to terrain, soil and plant characteristics. The objectives of this study are to quantify dynamic soil-water content over a range of slope positions, infer soil profile water fluxes, and identify locations most likely influenced by multidimensional flo...

  7. Parasitic manipulation of hosts' phenotype, or how to make a zombie--an introduction to the symposium.

    PubMed

    Weinersmith, Kelly; Faulkes, Zen

    2014-07-01

    Nearly all animals in nature are infected by at least one parasite, and many of those parasites can significantly change the phenotype of their hosts, often in ways that increase the parasite's likelihood of transmission. Hosts' phenotypic changes are multidimensional, and manipulated traits include behavior, neurotransmission, coloration, morphology, and hormone levels. The field of parasitic manipulation of hosts' phenotype has now accrued many examples of systems where parasites manipulate the phenotypes of their hosts and focus has shifted to answering three main questions. First, through what mechanisms do parasites manipulate the hosts' phenotype? Parasites often induce changes in the hosts' phenotypes that neuroscientists are unable to recreate under laboratory conditions, suggesting that parasites may have much to teach us about links between the brain, immune system, and the expression of phenotype. Second, what are the ecological implications of phenotypic manipulation? Manipulated hosts are often abundant, and changes in their phenotype may have important population, community, and ecosystem-level implications. Finally, how did parasitic manipulation of hosts' phenotype evolve? The selective pressures faced by parasites are extremely complex, often with multiple hosts that are actively resisting infection, both in physiological and evolutionary time-scales. Here, we provide an overview of how the work presented in this special issue contributes to tackling these three main questions. Studies on parasites' manipulation of their hosts' phenotype are undertaken largely by parasitologists, and a major goal of this symposium is to recruit researchers from other fields to the study of these phenomena. Our ability to answer the three questions outlined above would be greatly enhanced by participation from individuals trained in the fields of, for example, neurobiology, physiology, immunology, ecology, evolutionary biology, and invertebrate biology. Conversely

  8. Exploring and linking biomedical resources through multidimensional semantic spaces

    PubMed Central

    2012-01-01

    Background The semantic integration of biomedical resources is still a challenging issue which is required for effective information processing and data analysis. The availability of comprehensive knowledge resources such as biomedical ontologies and integrated thesauri greatly facilitates this integration effort by means of semantic annotation, which allows disparate data formats and contents to be expressed under a common semantic space. In this paper, we propose a multidimensional representation for such a semantic space, where dimensions regard the different perspectives in biomedical research (e.g., population, disease, anatomy and protein/genes). Results This paper presents a novel method for building multidimensional semantic spaces from semantically annotated biomedical data collections. This method consists of two main processes: knowledge and data normalization. The former one arranges the concepts provided by a reference knowledge resource (e.g., biomedical ontologies and thesauri) into a set of hierarchical dimensions for analysis purposes. The latter one reduces the annotation set associated to each collection item into a set of points of the multidimensional space. Additionally, we have developed a visual tool, called 3D-Browser, which implements OLAP-like operators over the generated multidimensional space. The method and the tool have been tested and evaluated in the context of the Health-e-Child (HeC) project. Automatic semantic annotation was applied to tag three collections of abstracts taken from PubMed, one for each target disease of the project, the Uniprot database, and the HeC patient record database. We adopted the UMLS Meta-thesaurus 2010AA as the reference knowledge resource. Conclusions Current knowledge resources and semantic-aware technology make possible the integration of biomedical resources. Such an integration is performed through semantic annotation of the intended biomedical data resources. This paper shows how these annotations

  9. Bridging the genotype–phenotype gap: what does it take?

    PubMed Central

    Gjuvsland, Arne B; Vik, Jon Olav; Beard, Daniel A; Hunter, Peter J; Omholt, Stig W

    2013-01-01

    The genotype–phenotype map (GP map) concept applies to any time point in the ontogeny of a living system. It is the outcome of very complex dynamics that include environmental effects, and bridging the genotype–phenotype gap is synonymous with understanding these dynamics. The context for this understanding is physiology, and the disciplinary goals of physiology do indeed demand the physiological community to seek this understanding. We claim that this task is beyond reach without use of mathematical models that bind together genetic and phenotypic data in a causally cohesive way. We provide illustrations of such causally cohesive genotype–phenotype models where the phenotypes span from gene expression profiles to development of whole organs. Bridging the genotype–phenotype gap also demands that large-scale biological (‘omics’) data and associated bioinformatics resources be more effectively integrated with computational physiology than is currently the case. A third major element is the need for developing a phenomics technology way beyond current state of the art, and we advocate the establishment of a Human Phenome Programme solidly grounded on biophysically based mathematical descriptions of human physiology. PMID:23401613

  10. Integrating Clinical Phenotype and Gene Expression Data to Prioritize Novel Drug Uses

    PubMed Central

    Paik, H; Chen, B; Sirota, M; Hadley, D

    2016-01-01

    Drug repositioning has been based largely on genomic signatures of drugs and diseases. One challenge in these efforts lies in connecting the molecular signatures of drugs into clinical responses, including therapeutic and side effects, to the repurpose of drugs. We addressed this challenge by evaluating drug‐drug relationships using a phenotypic and molecular‐based approach that integrates therapeutic indications, side effects, and gene expression profiles induced by each drug. Using cosine similarity, relationships between 445 drugs were evaluated based on high‐dimensional spaces consisting of phenotypic terms of drugs and genomic signatures, respectively. One hundred fifty‐one of 445 drugs comprising 450 drug pairs displayed significant similarities in both phenotypic and genomic signatures (P value < 0.05). We also found that similar gene expressions of drugs do indeed yield similar clinical phenotypes. We generated similarity matrixes of drugs using the expression profiles they induce in a cell line and phenotypic effects. PMID:27860440

  11. Syndromic (phenotypic) diarrhea in early infancy.

    PubMed

    Goulet, Olivier; Vinson, Christine; Roquelaure, Bertrand; Brousse, Nicole; Bodemer, Christine; Cézard, Jean-Pierre

    2008-02-28

    Syndromic diarrhea (SD), also known as phenotypic diarrhea (PD) or tricho-hepato-enteric syndrome (THE), is a congenital enteropathy presenting with early-onset of severe diarrhea requiring parenteral nutrition (PN). To date, no epidemiological data are available. The estimated prevalence is approximately 1/300,000-400,000 live births in Western Europe. Ethnic origin does not appear to be associated with SD. Infants are born small for gestational age and present with facial dysmorphism including prominent forehead and cheeks, broad nasal root and hypertelorism. Hairs are woolly, easily removed and poorly pigmented. Severe and persistent diarrhea starts within the first 6 months of life (profile, though a functional T-cell immune deficiency with defective antibody production was reported. Microscopic analysis of the hair show twisted hair (pili torti), aniso- and poilkilotrichosis, and trichorrhexis nodosa. Histopathological analysis of small intestine biopsy shows non-specific villous atrophy with low or no mononuclear cell infiltration of the lamina propria, and no specific histological abnormalities involving the epithelium. The etiology remains unknown. The frequent association of the disorder with parental consanguinity and/or affected siblings suggests a genetic origin with an autosomal recessive mode of transmission. Early management consists of total PN. Some infants have a rather milder phenotype with partial PN dependency or require only enteral feeding. Prognosis of this syndrome is poor, but most patients now survive, and about half of the patients may be weaned from PN at adolescence, but experience failure to thrive and final short stature. DISEASE NAME AND SYNONYMS: Syndromic

  12. Neuroproteomic profiling of human brain tissue using multidimensional separation techniques and selective enrichment of membrane proteins.

    PubMed

    Musunuri, Sravani; Shevchenko, Ganna; Bergquist, Jonas

    2012-12-01

    Hydrophobic membrane proteins (MPs) occupy a unique niche in the brain proteome research due to their important physiological roles. Therefore, the extraction, separation, and identification of MPs are of great interest in proteomic analysis. We applied various proteomic techniques to enrich, separate, and analyze the human brain proteome, including membrane proteome. Temperature-induced phase fractionation with the nonionic surfactant Triton X-114 was used to simultaneously extract, separate, and concentrate low abundant hydrophobic and high abundant hydrophilic proteins from human brain tissue. The extracted and delipidated proteins were analyzed by two-dimensional gel electrophoresis (2DE). Approximately 600 spots were detected in the gels. In-solution digestion was performed on 3 kDa spin filters. Tryptic peptides were separated using RP nano-LC and analyzed using two different high performance mass spectrometers, linear ion trap-Fourier transform and a linear ion trap-Orbitrap to reveal the low abundant MPs. In total, 837 and 780 unique proteins were identified by using linear ion trap-Fourier transform and linear ion trap-Orbitrap mass spectrometers, respectively. More than 29% of the identified proteins were classified as MPs with significant biological functions such as ion channels and transporters. Our study establishes a simple and rapid shotgun approach for the characterization of the brain proteome, and allows comprehensive analysis of brain membrane proteomes.

  13. From Career Decision-Making Styles to Career Decision-Making Profiles: A Multidimensional Approach

    ERIC Educational Resources Information Center

    Gati, Itamar; Landman, Shiri; Davidovitch, Shlomit; Asulin-Peretz, Lisa; Gadassi, Reuma

    2010-01-01

    Previous research on individual differences in career decision-making processes has often focused on classifying individuals into a few types of decision-making "styles" based on the most dominant trait or characteristic of their approach to the decision process (e.g., rational, intuitive, dependent; Harren, 1979). In this research, an…

  14. Profile Analysis via Multidimensional Scaling for the "Revised Two-Factor Learning Process Questionnaire"

    ERIC Educational Resources Information Center

    Socha, Alan; Sigler, Ellen A.

    2011-01-01

    The "Revised Learning Process Questionnaire" has been part of the development of a conceptual understanding of how students learn and what motivates them to engage in particular tasks. We obtained responses from 329 student volunteers at a mid-sized public university in the southeast United States. While looking at the psychometric…

  15. Multi-Dimensional Structure of Crystalline Chiral Condensates in Quark Matter

    NASA Astrophysics Data System (ADS)

    Lee, Tong-Gyu; Nishiyama, Kazuya; Yasutake, Nobutoshi; Maruyama, Toshiki; Tatsumi, Toshitaka

    We explore the multi-dimensional structure of inhomogeneous chiral condensates in quark matter. For a one-dimensional structure, the system becomes unstable at finite temperature due to the Nambu-Goldstone excitations. However, inhomogeneous chiral condensates with multi-dimensional modulations may be realized as a true long-range order at any temperature, as inferred from the Landau-Peierls theorem. We here present some possible strategies for searching the multi-dimensional structure of chiral crystals.

  16. Finding Our Way through Phenotypes

    PubMed Central

    Deans, Andrew R.; Lewis, Suzanna E.; Huala, Eva; Anzaldo, Salvatore S.; Ashburner, Michael; Balhoff, James P.; Blackburn, David C.; Blake, Judith A.; Burleigh, J. Gordon; Chanet, Bruno; Cooper, Laurel D.; Courtot, Mélanie; Csösz, Sándor; Cui, Hong; Dahdul, Wasila; Das, Sandip; Dececchi, T. Alexander; Dettai, Agnes; Diogo, Rui; Druzinsky, Robert E.; Dumontier, Michel; Franz, Nico M.; Friedrich, Frank; Gkoutos, George V.; Haendel, Melissa; Harmon, Luke J.; Hayamizu, Terry F.; He, Yongqun; Hines, Heather M.; Ibrahim, Nizar; Jackson, Laura M.; Jaiswal, Pankaj; James-Zorn, Christina; Köhler, Sebastian; Lecointre, Guillaume; Lapp, Hilmar; Lawrence, Carolyn J.; Le Novère, Nicolas; Lundberg, John G.; Macklin, James; Mast, Austin R.; Midford, Peter E.; Mikó, István; Mungall, Christopher J.; Oellrich, Anika; Osumi-Sutherland, David; Parkinson, Helen; Ramírez, Martín J.; Richter, Stefan; Robinson, Peter N.; Ruttenberg, Alan; Schulz, Katja S.; Segerdell, Erik; Seltmann, Katja C.; Sharkey, Michael J.; Smith, Aaron D.; Smith, Barry; Specht, Chelsea D.; Squires, R. Burke; Thacker, Robert W.; Thessen, Anne; Fernandez-Triana, Jose; Vihinen, Mauno; Vize, Peter D.; Vogt, Lars; Wall, Christine E.; Walls, Ramona L.; Westerfeld, Monte; Wharton, Robert A.; Wirkner, Christian S.; Woolley, James B.; Yoder, Matthew J.; Zorn, Aaron M.; Mabee, Paula

    2015-01-01

    Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility. PMID:25562316

  17. Finding our way through phenotypes.

    PubMed

    Deans, Andrew R; Lewis, Suzanna E; Huala, Eva; Anzaldo, Salvatore S; Ashburner, Michael; Balhoff, James P; Blackburn, David C; Blake, Judith A; Burleigh, J Gordon; Chanet, Bruno; Cooper, Laurel D; Courtot, Mélanie; Csösz, Sándor; Cui, Hong; Dahdul, Wasila; Das, Sandip; Dececchi, T Alexander; Dettai, Agnes; Diogo, Rui; Druzinsky, Robert E; Dumontier, Michel; Franz, Nico M; Friedrich, Frank; Gkoutos, George V; Haendel, Melissa; Harmon, Luke J; Hayamizu, Terry F; He, Yongqun; Hines, Heather M; Ibrahim, Nizar; Jackson, Laura M; Jaiswal, Pankaj; James-Zorn, Christina; Köhler, Sebastian; Lecointre, Guillaume; Lapp, Hilmar; Lawrence, Carolyn J; Le Novère, Nicolas; Lundberg, John G; Macklin, James; Mast, Austin R; Midford, Peter E; Mikó, István; Mungall, Christopher J; Oellrich, Anika; Osumi-Sutherland, David; Parkinson, Helen; Ramírez, Martín J; Richter, Stefan; Robinson, Peter N; Ruttenberg, Alan; Schulz, Katja S; Segerdell, Erik; Seltmann, Katja C; Sharkey, Michael J; Smith, Aaron D; Smith, Barry; Specht, Chelsea D; Squires, R Burke; Thacker, Robert W; Thessen, Anne; Fernandez-Triana, Jose; Vihinen, Mauno; Vize, Peter D; Vogt, Lars; Wall, Christine E; Walls, Ramona L; Westerfeld, Monte; Wharton, Robert A; Wirkner, Christian S; Woolley, James B; Yoder, Matthew J; Zorn, Aaron M; Mabee, Paula

    2015-01-01

    Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility.

  18. Large-scale integration of small molecule-induced genome-wide transcriptional responses, Kinome-wide binding affinities and cell-growth inhibition profiles reveal global trends characterizing systems-level drug action.

    PubMed

    Vidović, Dušica; Koleti, Amar; Schürer, Stephan C

    2014-01-01

    The Library of Integrated Network-based Cellular Signatures (LINCS) project is a large-scale coordinated effort to build a comprehensive systems biology reference resource. The goals of the program include the generation of a very large multidimensional data matrix and informatics and computational tools to integrate, analyze, and make the data readily accessible. LINCS data include genome-wide transcriptional signatures, biochemical protein binding profiles, cellular phenotypic response profiles and various other datasets for a wide range of cell model systems and molecular and genetic perturbations. Here we present a partial survey of this data facilitated by data standards and in particular a robust compound standardization workflow; we integrated several types of LINCS signatures and analyzed the results with a focus on mechanism of action (MoA) and chemical compounds. We illustrate how kinase targets can be related to disease models and relevant drugs. We identified some fundamental trends that appear to link Kinome binding profiles and transcriptional signatures to chemical information and biochemical binding profiles to transcriptional responses independent of chemical similarity. To fill gaps in the datasets we developed and applied predictive models. The results can be interpreted at the systems level as demonstrated based on a large number of signaling pathways. We can identify clear global relationships, suggesting robustness of cellular responses to chemical perturbation. Overall, the results suggest that chemical similarity is a useful measure at the systems level, which would support phenotypic drug optimization efforts. With this study we demonstrate the potential of such integrated analysis approaches and suggest prioritizing further experiments to fill the gaps in the current data.

  19. Scaling Laws for the Multidimensional Burgers Equation with Quadratic External Potential

    NASA Astrophysics Data System (ADS)

    Leonenko, N. N.; Ruiz-Medina, M. D.

    2006-07-01

    The reordering of the multidimensional exponential quadratic operator in coordinate-momentum space (see X. Wang, C.H. Oh and L.C. Kwek (1998). J. Phys. A.: Math. Gen. 31:4329-4336) is applied to derive an explicit formulation of the solution to the multidimensional heat equation with quadratic external potential and random initial conditions. The solution to the multidimensional Burgers equation with quadratic external potential under Gaussian strongly dependent scenarios is also obtained via the Hopf-Cole transformation. The limiting distributions of scaling solutions to the multidimensional heat and Burgers equations with quadratic external potential are then obtained under such scenarios.

  20. The digital revolution in phenotyping

    PubMed Central

    Oellrich, Anika; Collier, Nigel; Groza, Tudor; Rebholz-Schuhmann, Dietrich; Shah, Nigam; Bodenreider, Olivier; Boland, Mary Regina; Georgiev, Ivo; Liu, Hongfang; Livingston, Kevin; Luna, Augustin; Mallon, Ann-Marie; Manda, Prashanti; Robinson, Peter N.; Rustici, Gabriella; Simon, Michelle; Wang, Liqin; Winnenburg, Rainer; Dumontier, Michel

    2016-01-01

    Phenotypes have gained increased notoriety in the clinical and biological domain owing to their application in numerous areas such as the discovery of disease genes and drug targets, phylogenetics and pharmacogenomics. Phenotypes, defined as observable characteristics of organisms, can be seen as one of the bridges that lead to a translation of experimental findings into clinical applications and thereby support ‘bench to bedside’ efforts. However, to build this translational bridge, a common and universal understanding of phenotypes is required that goes beyond domain-specific definitions. To achieve this ambitious goal, a digital revolution is ongoing that enables the encoding of data in computer-readable formats and the data storage in specialized repositories, ready for integration, enabling translational research. While phenome research is an ongoing endeavor, the true potential hidden in the currently available data still needs to be unlocked, offering exciting opportunities for the forthcoming years. Here, we provide insights into the state-of-the-art in digital phenotyping, by means of representing, acquiring and analyzing phenotype data. In addition, we provide visions of this field for future research work that could enable better applications of phenotype data. PMID:26420780

  1. Meloidogyne partityla on Pecan Isozyme Phenotypes and Other Host.

    PubMed

    Starr, J L; Tomaszewski, E K; Mundo-Ocampo, M; Baldwin, J G

    1996-12-01

    Meloidogyne sp. from five pecan (Carya illinoensis) orchards in Texas were distinctive in host range and iszoyme profiles from common species of Meloidogyne but were morphologically congruent with Meloidogyne partityla Kleynhans, a species previously known only in South Africa. In addition to pecan, species of walnut (Juglans hindsii and J. regia) and hickory (C. ovata) also were hosts. No reproduction was observed on 15 other plant species from nine families, including several common hosts of other Meloidogyne spp. Three esterase phenotypes and two malate dehydrogenase phenotypes of M. partityla were identified by polyacrylamide gel electrophoresis. Each of these isozyme phenotypes was distinct from those of the more common species M. arenaria, M. hapla, M. incognita, and M. javanica.

  2. Meloidogyne partityla on Pecan Isozyme Phenotypes and Other Host

    PubMed Central

    Starr, J. L.; Tomaszewski, E. K.; Mundo-Ocampo, M.; Baldwin, J. G.

    1996-01-01

    Meloidogyne sp. from five pecan (Carya illinoensis) orchards in Texas were distinctive in host range and iszoyme profiles from common species of Meloidogyne but were morphologically congruent with Meloidogyne partityla Kleynhans, a species previously known only in South Africa. In addition to pecan, species of walnut (Juglans hindsii and J. regia) and hickory (C. ovata) also were hosts. No reproduction was observed on 15 other plant species from nine families, including several common hosts of other Meloidogyne spp. Three esterase phenotypes and two malate dehydrogenase phenotypes of M. partityla were identified by polyacrylamide gel electrophoresis. Each of these isozyme phenotypes was distinct from those of the more common species M. arenaria, M. hapla, M. incognita, and M. javanica. PMID:19277175

  3. Hierarchical phenotypic and epigenetic variation in cloned swine.

    PubMed

    Archer, Greg S; Dindot, Scott; Friend, Ted H; Walker, Shawn; Zaunbrecher, Gretchen; Lawhorn, Bruce; Piedrahita, Jorge A

    2003-08-01

    Cloning by somatic cell nuclear transfer can result in the birth of animals with phenotypic and gene expression abnormalities. We compared adult cloned pigs and adult pigs from naturally bred control females using a series of physiological and genetic parameters, including detailed methylation profiles of selected genomic regions. Phenotypic and genetic analyses indicated that there are two classes of traits, one in which the cloned pigs have less variation than controls and another characterized by variation that is equally high in cloned and control pigs. Although cloning creates animals within the normal phenotypic range, it increases the variability associated with some traits. This finding is contrary to the expectation that cloning can be used to reduce the size of groups involved in animal experimentation and to reproduce an animal, including a pet, with a homogenous set of desired traits.

  4. Efficient and direct generation of multidimensional free energy surfaces via adiabatic dynamics without coordinate transformations.

    PubMed

    Abrams, Jerry B; Tuckerman, Mark E

    2008-12-11

    Adiabatic free energy dynamics (AFED) was introduced by Rosso et al. [J. Chem. Phys. 2002, 116, 4389] for computing free energy profiles quickly and accurately using a dynamical adiabatic separation between a set of collective variables or reaction coordinates and the remaining degrees of freedom of a system. This approach has been shown to lead to a significant gain in efficiency versus traditional methods such as umbrella sampling, thermodynamic integration, and free energy perturbation for generating one-dimensional free energy profiles. More importantly, AFED is able to generate multidimensional free energy surfaces efficiently via full sweeps of the surface that rapidly map out the locations of the free energy minima. The most significant drawback to the AFED approach is the need to transform the coordinates into a generalized coordinate system that explicitly contains the collective variables of interest. Recently, Maragliano and Vanden-Eijnden built upon the AFED approach by introducing a set of extended phase-space variables, to which the adiabatic decoupling and high temperature are applied [Chem. Phys. Lett. 2006, 426, 168]. In this scheme, which the authors termed "temperature accelerated molecular dynamics" or TAMD, the need for explicit coordinate transformations is circumvented. The ability of AFED and TAMD to generate free energy surfaces efficiently depends on the thermostatting mechanism employed, since both approaches are inherently nonequilibrium due to the adiabatic decoupling. Indeed, Maragliano and Vanden-Eijnden did not report any direct generation of free energy surfaces within the overdamped Langevin dynamics employed by these authors. Here, we show that by formulating TAMD in a manner that is closer to the original AFED approach, including the generalized Gaussian moment thermostat (GGMT) and multiple time-scale integration, multidimensional free energy surfaces for complex systems can be generated directly from the probability

  5. Phenotypic Landscape of a Bacterial Cell

    PubMed Central

    Nichols, Robert J.; Sen, Saunak; Choo, Yoe Jin; Beltrao, Pedro; Zietek, Matylda; Chaba, Rachna; Lee, Sueyoung; Kazmierczak, Krystyna M.; Lee, Karis J.; Wong, Angela; Shales, Michael; Lovett, Susan; Winkler, Malcolm E.; Krogan, Nevan J.; Typas, Athanasios; Gross, Carol A.

    2011-01-01

    Summary The explosion of sequence information in bacteria makes developing high-throughput, cost-effective approaches to matching genes with phenotypes imperative. Using E. coli as proof of principle, we show that combining large-scale chemical genomics with quantitative fitness measurements provides a high-quality data set rich in discovery. Probing growth profiles of a mutant library in hundreds of conditions in parallel yielded > 10,000 phenotypes that allowed us to study gene essentiality, discover leads for gene function and drug action, and understand higher-order organization of the bacterial chromosome. We highlight new information derived from the study, including insights into a gene involved in multiple antibiotic resistance and the synergy between a broadly used combinatory antibiotic therapy, trimethoprim and sulfonamides. This data set, publicly available at http://ecoliwiki.net/tools/chemgen/, is a valuable resource for both the microbiological and bioinformatic communities, as it provides high-confidence associations between hundreds of annotated and uncharacterized genes as well as inferences about the mode of action of several poorly understood drugs. PMID:21185072

  6. The renal microenvironment modifies dendritic cell phenotype.

    PubMed

    Chessa, Federica; Mathow, Daniel; Wang, Shijun; Hielscher, Thomas; Atzberger, Ann; Porubsky, Stefan; Gretz, Norbert; Burgdorf, Sven; Gröne, Hermann-Josef; Popovic, Zoran V

    2016-01-01

    Renal dendritic cells are a major component of the renal mononuclear phagocytic system. In the renal interstitium, these cells are exposed to an osmotic gradient, mainly sodium, whose concentration progressively increases towards inner medulla. Renal allograft rejection affects predominantly the cortex, suggesting a protective role of the renal medullary micromilieu. Whether osmolar variations can modulate the function of renal dendritic cells is currently undefined. Considering the central role of dendritic cells in promoting allorejection, we tested whether the biophysical micromilieu, particularly the interstitial osmotic gradient, influences their alloreactivity. There was a progressive depletion of leukocytes towards the medulla of homeostatic kidney. Only macrophages opposed this tendency. Flow cytometry of homeostatic and post-transplant medullary dendritic cells revealed a switch towards a macrophage-like phenotype. Similarly, bone marrow-derived dendritic cells developed ex vivo in sodium chloride-enriched medium acquired a M2-like signature. Microarray analysis of allotransplant dendritic cells posed a medullary downregulation of genes mainly involved in alloantigen recognition. Gene expression profiles of both medullary dendritic cells and bone marrow-derived dendritic cells matured in hyperosmolar medium had an overlap with the macrophage M2 signature. Thus, the medullary environment inhibits an alloimmune response by modulating the phenotype and function of dendritic cells.

  7. Phenotypic landscape of a bacterial cell.

    PubMed

    Nichols, Robert J; Sen, Saunak; Choo, Yoe Jin; Beltrao, Pedro; Zietek, Matylda; Chaba, Rachna; Lee, Sueyoung; Kazmierczak, Krystyna M; Lee, Karis J; Wong, Angela; Shales, Michael; Lovett, Susan; Winkler, Malcolm E; Krogan, Nevan J; Typas, Athanasios; Gross, Carol A

    2011-01-07

    The explosion of sequence information in bacteria makes developing high-throughput, cost-effective approaches to matching genes with phenotypes imperative. Using E. coli as proof of principle, we show that combining large-scale chemical genomics with quantitative fitness measurements provides a high-quality data set rich in discovery. Probing growth profiles of a mutant library in hundreds of conditions in parallel yielded > 10,000 phenotypes that allowed us to study gene essentiality, discover leads for gene function and drug action, and understand higher-order organization of the bacterial chromosome. We highlight new information derived from the study, including insights into a gene involved in multiple antibiotic resistance and the synergy between a broadly used combinatory antibiotic therapy, trimethoprim and sulfonamides. This data set, publicly available at http://ecoliwiki.net/tools/chemgen/, is a valuable resource for both the microbiological and bioinformatic communities, as it provides high-confidence associations between hundreds of annotated and uncharacterized genes as well as inferences about the mode of action of several poorly understood drugs.

  8. Column-coupling strategies for multidimensional electrophoretic separation techniques.

    PubMed

    Kler, Pablo A; Sydes, Daniel; Huhn, Carolin

    2015-01-01

    Multidimensional electrophoretic separations represent one of the most common strategies for dealing with the analysis of complex samples. In recent years we have been witnessing the explosive growth of separation techniques for the analysis of complex samples in applications ranging from life sciences to industry. In this sense, electrophoretic separations offer several strategic advantages such as excellent separation efficiency, different methods with a broad range of separation mechanisms, and low liquid consumption generating less waste effluents and lower costs per analysis, among others. Despite their impressive separation efficiency, multidimensional electrophoretic separations present some drawbacks that have delayed their extensive use: the volumes of the columns, and consequently of the injected sample, are significantly smaller compared to other analytical techniques, thus the coupling interfaces between two separations components must be very efficient in terms of providing geometrical precision with low dead volume. Likewise, very sensitive detection systems are required. Additionally, in electrophoretic separation techniques, the surface properties of the columns play a fundamental role for electroosmosis as well as the unwanted adsorption of proteins or other complex biomolecules. In this sense the requirements for an efficient coupling for electrophoretic separation techniques involve several aspects related to microfluidics and physicochemical interactions of the electrolyte solutions and the solid capillary walls. It is interesting to see how these multidimensional electrophoretic separation techniques have been used jointly with different detection techniques, for intermediate detection as well as for final identification and quantification, particularly important in the case of mass spectrometry. In this work we present a critical review about the different strategies for coupling two or more electrophoretic separation techniques and the

  9. Multidimensional Sexual Perfectionism and Female Sexual Function: A Longitudinal Investigation.

    PubMed

    Stoeber, Joachim; Harvey, Laura N

    2016-11-01

    Research on multidimensional sexual perfectionism differentiates four forms: self-oriented, partner-oriented, partner-prescribed, and socially prescribed. Self-oriented sexual perfectionism reflects perfectionistic standards people apply to themselves as sexual partners; partner-oriented sexual perfectionism reflects perfectionistic standards people apply to their sexual partner; partner-prescribed sexual perfectionism reflects people's beliefs that their sexual partner imposes perfectionistic standards on them; and socially prescribed sexual perfectionism reflects people's beliefs that society imposes such standards on them. Previous studies found partner-prescribed and socially prescribed sexual perfectionism to be maladaptive forms of sexual perfectionism associated with a negative sexual self-concept and problematic sexual behaviors, but only examined cross-sectional relationships. The present article presents the first longitudinal study examining whether multidimensional sexual perfectionism predicts changes in sexual self-concept and sexual function over time. A total of 366 women aged 17-69 years completed measures of multidimensional sexual perfectionism, sexual esteem, sexual anxiety, sexual problem self-blame, and sexual function (cross-sectional data). Three to six months later, 164 of the women completed the same measures again (longitudinal data). Across analyses, partner-prescribed sexual perfectionism emerged as the most maladaptive form of sexual perfectionism. In the cross-sectional data, partner-prescribed sexual perfectionism showed positive relationships with sexual anxiety, sexual problem self-blame, and intercourse pain, and negative relationships with sexual esteem, desire, arousal, lubrication, and orgasmic function. In the longitudinal data, partner-prescribed sexual perfectionism predicted increases in sexual anxiety and decreases in sexual esteem, arousal, and lubrication over time. The findings suggest that partner-prescribed sexual

  10. Analysis of world economic variables using multidimensional scaling.

    PubMed

    Machado, J A Tenreiro; Mata, Maria Eugénia

    2015-01-01

    Waves of globalization reflect the historical technical progress and modern economic growth. The dynamics of this process are here approached using the multidimensional scaling (MDS) methodology to analyze the evolution of GDP per capita, international trade openness, life expectancy, and education tertiary enrollment in 14 countries. MDS provides the appropriate theoretical concepts and the exact mathematical tools to describe the joint evolution of these indicators of economic growth, globalization, welfare and human development of the world economy from 1977 up to 2012. The polarization dance of countries enlightens the convergence paths, potential warfare and present-day rivalries in the global geopolitical scene.

  11. Enhancing Privacy in Participatory Sensing Applications with Multidimensional Data

    SciTech Connect

    Forrest, Stephanie; He, Wenbo; Groat, Michael; Edwards, Benjamin; Horey, James L

    2013-01-01

    Participatory sensing applications rely on individuals to share personal data to produce aggregated models and knowledge. In this setting, privacy concerns can discourage widespread adoption of new applications. We present a privacy-preserving participatory sensing scheme based on negative surveys for both continuous and multivariate categorical data. Without relying on encryption, our algorithms enhance the privacy of sensed data in an energy and computation efficient manner. Simulations and implementation on Android smart phones illustrate how multidimensional data can be aggregated in a useful and privacy-enhancing manner.

  12. Multidimensional electronic spectroscopy of phycobiliproteins from cryptophyte algae

    NASA Astrophysics Data System (ADS)

    Turner, Daniel

    2011-03-01

    We describe new spectroscopic measurements which reveal additional information regarding the observed quantum coherences in proteins extracted from photosynthetic algae. The proteins we investigate are the phycobiliproteins phycoerythrin 545 and phycocyanin 645. Two new avenues have been explored. We describe how changes to the chemical and biological environment impact the quantum coherence present in the 2D electronic correlation spectrum. We also use new multidimensional spectroscopic techniques to reveal insights into the nature of the quantum coherence and the nature of the participating states.

  13. Intrinsic irreversibility limits the efficiency of multidimensional molecular motors

    NASA Astrophysics Data System (ADS)

    Jack, M. W.; Tumlin, C.

    2016-05-01

    We consider the efficiency limits of Brownian motors able to extract work from the temperature difference between reservoirs or from external thermodynamic forces. These systems can operate in a variety of modes, including as isothermal engines, heat engines, refrigerators, and heat pumps. We derive analytical results showing that certain classes of multidimensional Brownian motor, including the Smoluchowski-Feynman ratchet, are unable to attain perfect efficiency (Carnot efficiency for heat engines). This demonstrates the presence of intrinsic irreversibilities in their operating mechanism. We present numerical simulations showing that in some cases the loss process that limits efficiency is associated with vortices in the probability current.

  14. Unobtrusive interferometer tracking by path length oscillation for multidimensional spectroscopy.

    PubMed

    Lee, Kevin F; Bonvalet, Adeline; Nuernberger, Patrick; Joffre, Manuel

    2009-07-20

    We track the path difference between interferometer arms with few-nanometer accuracy without adding optics to the beam path. We measure the interference of a helium-neon beam that copropagates through the interferometer with midinfrared pulses used for multidimensional spectroscopy. This can indicate motion, but not direction. By oscillating the path length of one arm with a mirror on a piezoelectric stack and monitoring the oscillations of the recombined helium-neon beam, the direction can be calculated, and the path delay can be continuously tracked.

  15. Indexing of multidimensional lookup tables in embedded systems.

    PubMed

    Vrhel, Michael J

    2004-10-01

    The proliferation of color devices and the desire to have them accurately communicate color information has led to a need for embedded systems that perform color conversions. A common method for performing color space conversions is to characterize the device with a multidimensional lookup table (MLUT). To reduce cost, many of the embedded systems have limited computational abilities. This leads to a need for the design of efficient methods for performing MLUT indexing and interpolation. This paper examines and compares two methods of MLUT indexing within embedded systems. The comparison is made in terms of colorimetric accuracy and computational cost.

  16. Multidimensional master equation and its Monte-Carlo simulation.

    PubMed

    Pang, Juan; Bai, Zhan-Wu; Bao, Jing-Dong

    2013-02-28

    We derive an integral form of multidimensional master equation for a markovian process, in which the transition function is obtained in terms of a set of discrete Langevin equations. The solution of master equation, namely, the probability density function is calculated by using the Monte-Carlo composite sampling method. In comparison with the usual Langevin-trajectory simulation, the present approach decreases effectively coarse-grained error. We apply the master equation to investigate time-dependent barrier escape rate of a particle from a two-dimensional metastable potential and show the advantage of this approach in the calculations of quantities that depend on the probability density function.

  17. Overview of the BISON Multidimensional Fuel Performance Code

    SciTech Connect

    R. L. Williamson; J. D. Hales; S. R. Novascone; B. W. Spencer; D. M. Perez; G. Pastore; R. C. Martineau

    2013-10-01

    BISON is a modern multidimensional multiphysics finite-element based nuclear fuel performance code that has been under development at the Idaho National Laboratory (USA) since 2009. A brief background is provided on the code’s computational framework (MOOSE), governing equations, and material and behavioral models. Ongoing code verification and validation work is outlined, and comparative results are provided for select validation cases. Recent applications are discussed, including specific description of two applications where 3D treatment is important. A summary of future code development and validation activities is given. Numerous references to published work are provided where interested readers can find more complete information.

  18. Adaptive multidimensional modulation and multiplexing for next generation optical networks

    NASA Astrophysics Data System (ADS)

    Cvijetic, Milorad

    2015-01-01

    The overall spectral efficiency in optical transmission systems needs to be enhanced by employment of advanced modulation, multiplexing, and coding schemes, as well as the advanced detection techniques. In parallel, novel networking concepts with the griddles and elastic bandwidth allocation are needed to increase the network dynamics and flexibility. In this paper we discuss multidimensional modulation, multiplexing, and coding schemes, which are enablers not only of the information capacity increase, but also for the next generation elastic high-speed optical networking and outline possible future directions and application scenario in different networking segments.

  19. A multi-dimensional sampling method for locating small scatterers

    NASA Astrophysics Data System (ADS)

    Song, Rencheng; Zhong, Yu; Chen, Xudong

    2012-11-01

    A multiple signal classification (MUSIC)-like multi-dimensional sampling method (MDSM) is introduced to locate small three-dimensional scatterers using electromagnetic waves. The indicator is built with the most stable part of signal subspace of the multi-static response matrix on a set of combinatorial sampling nodes inside the domain of interest. It has two main advantages compared to the conventional MUSIC methods. First, the MDSM is more robust against noise. Second, it can work with a single incidence even for multi-scatterers. Numerical simulations are presented to show the good performance of the proposed method.

  20. Analysis of World Economic Variables Using Multidimensional Scaling

    PubMed Central

    Machado, J.A. Tenreiro; Mata, Maria Eugénia

    2015-01-01

    Waves of globalization reflect the historical technical progress and modern economic growth. The dynamics of this process are here approached using the multidimensional scaling (MDS) methodology to analyze the evolution of GDP per capita, international trade openness, life expectancy, and education tertiary enrollment in 14 countries. MDS provides the appropriate theoretical concepts and the exact mathematical tools to describe the joint evolution of these indicators of economic growth, globalization, welfare and human development of the world economy from 1977 up to 2012. The polarization dance of countries enlightens the convergence paths, potential warfare and present-day rivalries in the global geopolitical scene. PMID:25811177